From Medscape Gastroenterology
Liver Disease: Good News and Bad NewsDigestive Disease Week 2012
William F. Balistreri, MD
Click here to view the new Medscape video with Dr. Bill Balistreri discussing data from last months DDW; including treatment for HCV, and fatty liver disease.
Emerging Data in Liver Disease
Hello, I am Dr. Bill Balistreri, Professor of Pediatrics and Medicine at the University of Cincinnati College of Medicine and Cincinnati Children's Hospital. I am here at Digestive Disease Week (DDW) in San Diego to discuss emerging data on liver disease for Medscape.
Studies presented at DDW 2012 have highlighted 2 major issues that have received attention over the past year. The first issue is new strategies for the treatment of hepatitis C virus (HCV) infection, including the possibility of an interferon-free regimen. The second issue is concern about the rising incidence and impact of obesity-related liver diseases: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)
The Good News: Treatment for HCV Infection
First, the good news: Combination therapy with pegylated interferon and ribavirin has long stood as the standard of care for patients with chronic HCV infection. Although effective in achieving high response rates, this regimen is associated with troublesome side effects. Thus, the development and approval of 2 effective protease inhibitors, telaprevir and boceprevir, was hailed as a new era of therapy for patients with hepatitis C genotype 1 infection.
Several studies were presented to document that these direct-acting antiviral agents allow more effective and shorter durations of treatment. For example, in patients infected with HCV genotype 1, for whom previous standard therapy failed to eliminate the virus, treatment with either of these protease inhibitors was shown to be significantly more effective, with sustained viral response rates 2- to 3-fold higher compared with traditional therapy.
An American Association for the Study of Liver Diseases (AASLD) plenary session presentation[1] reported that when telaprevir was used in combination with peginterferon and ribavirin, the dose of ribavirin was able to be substantially reduced. Ribavirin dose reduction to less than 600 mg/day had no substantial effect on sustained viral response (SVR) rates in patients given telaprevir combination treatment. In another study,[2] when boceprevir was used in combination with peginterferon and ribavirin, SVR was achieved in patients who had been nonresponsive to previous therapy.
Despite the optimism about the prospects for this treatment of HCV, a remaining concern is the fact that telaprevir and boceprevir must be used in combination with peginterferon and ribavirin. This is far from the ideal regimen. In fact, because of poor tolerability, many treatment candidates will decide not to pursue treatment or to defer treatment until a simpler regimen is available.
However, other studies suggest that an interferon-free regimen (and perhaps even a ribavirin-free regimen) is no longer a dream. A number of compounds encompassing several distinct drug classes are currently under development. These drugs bring us one step closer to the long sought-after ideal: the ability to delete interferon injections from treatment strategies.
In the interim, how can we tailor therapy and predict response rates? Investigators noted that patients infected with hepatitis C genotypes 2 and 3 achieve SVR rates between 70% and 80% in clinical trials. However, in real-life settings, lower SVR rates in the range of 55%-65% are reported. In work presented here,[3] predictive factors for nonresponsive patients with genotypes 2 and 3 included daily alcohol intake greater than 40 g, HIV co-infection, low thyroid-stimulating hormone (TSH) levels, the presence of cirrhosis, and the duration of infection. These risk factors should be assessed and may suggest the need for an intensified treatment course.
Further data[4] were presented on a major genetic predictive factor: a single nucleotide polymorphism in the upstream region of the interleukin-28B gene. Genotype CC is the strongest factor predictive of SVR in patients with HCV genotype 1 treated with peginterferon and ribavirin. This CC genotype was also shown to be associated with a significantly higher rate of spontaneous clearance in both white and African American patients with exposure to HCV. This information will be of value when counseling patients.
The Bad News: Fatty Liver Disease on the Rise
Now the bad news: NAFLD has become the leading cause of liver disease in North America, as a result of the rapidly increasing prevalence of obesity. However, accurate population-based data on the incidence of NASH are sparse, in part because the diagnosis requires histopathologic documentation.
In a study presented here,[5] the temporal trend in the prevalence of NASH in one US county over the past 30 years was reported. In this Mayo Clinic review of 555 autopsy records, there was a significant increase between 1981 and 2010 in mean body mass index, as well as in the prevalence of obesity, in this county. There was also a striking increase in the prevalence of steatosis and NASH. Among persons who were obese, the prevalence of steatosis increased from 23% in the 1980s to 49% in the 1990s, and to 60% in the most recent era. Even in nonobese patients, the prevalence of steatosis increased from 12% (1980s) to 27% (1990s) to 36% (today).
In a related study,[6] investigators examined trends in the prevalence of NAFLD in children over the past 2 decades. They used nationally representative data from the National Health and Nutrition Examination Survey (NHANES) data sets, spanning 1988-2008. More than 10,000 adolescents were included in this analysis. The percentage of adolescents who were obese increased from 11% to 21% over this 30-year period. Suspected NAFLD increased from 4% to 10%. Among obese adolescents, the prevalence of elevated aminotransferase levels increased 120%, from 17% to 37%.
The bottom line is that suspected NAFLD in children is increasing in prevalence and affects about 10% of all adolescents. Of note, the increase in NAFLD was not solely defined by the number of overweight children. The increased prevalence of NAFLD was much greater than the increase in the prevalence of obesity. These data strongly support recommendations to screen for NAFLD in obese adolescents. This raises the question as to the best screening and confirmation methods. Specifically, is there a noninvasive way to diagnose NASH?
Several studies[7,8] presented here indicate that this is possible, to a degree, using serum biomarkers of hepatocyte apoptosis and oxidative stress. Circulating markers of hepatic cell death -- cytokeratin 18 fragments and soluble Fas (Fas ligand) -- were shown to be useful for the diagnosis of NAFLD and NASH. A prediction model was also developed.
A combination of these markers had superior diagnostic performance for detecting NASH compared with measurement of the individual markers.
In addition, newer magnetic resonance techniques, such as measurement of the proton-density fat fraction, correlate with histology-determined steatosis grade in adults with NAFLD. However, a study[9] reported here documented that the amount of hepatic steatosis on imaging does not necessarily correlate with the severity of liver disease, and steatosis is not linearly related to disease progression. Future studies will need to explore the natural history of NAFLD, the interplay between hepatic steatosis and fibrosis, and whether novel imaging or MRI techniques can be used as a noninvasive means to study disease progression by fat mapping and changes in fat distribution over time.
Why are we concerned? Obese patients with fatty liver are at increased risk for early morbidity and mortality.
This begins during adolescence. A study presented at DDW 2012[10] evaluated the association among obesity, fatty liver, and cardiovascular risk in pediatric patients. They documented that obesity may in fact confer a cardiovascular disease risk burden that is comparable to that of patients with familial dyslipidemias. Thus, earlier recognition and medical intervention is warranted.
Another study[11] reported that moderately severe obstructive sleep apnea and hypoxia are common in obese patients with biopsy-proven NAFLD. Obstructive sleep apnea and hypoxia were also associated with more advanced fibrosis in pediatric patients. A large multicenter cohort further documented that NAFLD is a predisposing condition for hepatocellular carcinoma. Of concern, NAFLD-associated hepatocellular carcinoma often occurs in the absence of cirrhosis. This may suggest the need to revise current guidelines, which suggest surveillance programs for cancer in patients with cirrhosis.
Finally, one study[12] reported the long-term follow-up of a liver-related death rate in patients with nonalcoholic fatty liver disease and alcoholic-related fatty liver disease. A similar proportion of patients with NAFLD and with alcoholic fatty liver disease developed cirrhosis. However, patients with NAFLD had a worse overall survival than patients with alcoholic-related fatty liver disease. These sobering studies underscore the urgent need to enhance our efforts to reduce the trend in obesity rates and the prevalence of fatty liver disease.
Thank you for listening. This is Bill Balistreri, for Medscape.
Showing posts with label a-DDW 2012 meeting. Show all posts
Showing posts with label a-DDW 2012 meeting. Show all posts
Saturday, June 2, 2012
Saturday, May 26, 2012
May 26 Weekend Reading-Relevant Hepatitis C Research and News
Girl Reading by Pablo Picasso
Greetings,
Most weekends this blog offers up a few substantial links to relevant HCV information, click here for previous "Weekend Reading" articles. Hepatitis C New Drug Research And Liver Health has an article database which includes full-text and abstracts on hepatitis C. View the RSS feed for this weekend of updates.
Meeting Coverage In The News
EASL 2012
EASL: Telaprevir 100% Effective for IL28B CC, Adding VX-222 Overcomes Unfavorable Genes
Meeting Coverage In The News
EASL 2012
EASL: Telaprevir 100% Effective for IL28B CC, Adding VX-222 Overcomes Unfavorable Genes
23 May 2012
Written by Liz Highleyman
Written by Liz Highleyman
Adding telaprevir (Incivek) to pegylated interferon and ribavirin cured all hepatitis C patients with the favorable IL28B gene pattern, researchers reported at the 47th International Liver Congress (EASL 2012) last month in Barcelona. Another study found that adding the experimental HCV protease inhibitor VX-222 raised cure rates even for those with unfavorable IL28B patterns.
DDW, the annual meeting of the American Gastroenterological Association (AGA) Institute, is jointly sponsored by the American Association for the Study of Liver Diseases, the AGA, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract.
Increased mortality observed in patients with HCV and diabetes
Increased mortality observed in patients with HCV and diabetes
May 23, 2012
Those with both hepatitis C and diabetes had a higher mortality rate when compared with those who had either condition alone, according to research presented during Digestive Disease Week 2012.
Those with both hepatitis C and diabetes had a higher mortality rate when compared with those who had either condition alone, according to research presented during Digestive Disease Week 2012.
When we observed the rates for patients who had both hepatitis C and diabetes, we saw that the mortality rate was significantly increased — at least three times the amount of patients died in the group with both hepatitis C and diabetes compared with patients who had neither condition,”
Meira Abramowitz, MD, of the division of internal medicine at SUNY Downstate Medical Center in Brooklyn, N.Y., told Infectious Disease News.
Meira Abramowitz, MD, of the division of internal medicine at SUNY Downstate Medical Center in Brooklyn, N.Y., told Infectious Disease News.
Abramowitz and colleagues conducted a retrospective chart review of patients treated at the VA New York Harbor Healthcare System from 2002 to 2003. Mortality data were collected from 2011.
Patients with HCV were identified from a registry of more than 6,000 patients with HCV. These patients were age-matched with other patients without HCV from the VA system, some of whom had diabetes.
The final cohort included 1,846 patients, of whom 18.8% had neither HCV nor diabetes and 12.8% had both. Of the 579 patients with diabetes, 31.3% died vs. 20.6% of the 1,213 patients without diabetes. Of the 1,141 patients with HCV, 24.5% died vs. 24.1% of the 692 patients without HCV.
Of the 237 patients with both HCV and diabetes, 36.3% died vs. 20.8% of the 867 patients with HCV alone, 27.8% of the 342 patients with diabetes alone and 20.2% of the 346 patients with neither disease. The OR for mortality in patients with diabetes vs. patients without diabetes was 1.7 (95% CI, 1.3-2.24). This increased to 1.89 when the researchers compared patients with both HCV and diabetes to patients with neither disease (95% CI, 1.45-2.46).
Of the 237 patients with both HCV and diabetes, 36.3% died vs. 20.8% of the 867 patients with HCV alone, 27.8% of the 342 patients with diabetes alone and 20.2% of the 346 patients with neither disease. The OR for mortality in patients with diabetes vs. patients without diabetes was 1.7 (95% CI, 1.3-2.24). This increased to 1.89 when the researchers compared patients with both HCV and diabetes to patients with neither disease (95% CI, 1.45-2.46).
“We are not entirely sure why this mortality increase took place because both of these conditions have their own individual complications,” Abramowitz said. “Hepatitis C can develop into hepatocellular carcinoma and hepatic encephalopathy, while diabetes can progress into diabetic nephropathy and diabetic neuropathy with accompanying cardiovascular complications.”
References:
Disclosures:
DDW
DDW-Hepatitis C Patients May Be Able to Delay Therapy
Improved treatment coming for HIV/ HCV co-infection
Improved treatment coming for HIV/ HCV co-infection
View Additional DDW articles..............
Research
ISSUE: MAY 2012 | VOLUME: 63:5
Update on the Diagnosis and Treatment of Hepatitis C
by Arun B. Jesudian, MD and Ira M. Jacobson, MD
Hepatitis C virus (HCV) infection is a national and global public health concern, affecting up to 4 million individuals in the United States and 200 million individuals worldwide. Despite a declining incidence of new HCV infections in the United States, the prevalence of advanced liver disease secondary to chronic HCV infection, including cirrhosis and hepatocellular carcinoma, is expected to rise in the coming years.
Update on the Diagnosis and Treatment of Hepatitis C
by Arun B. Jesudian, MD and Ira M. Jacobson, MD
Hepatitis C virus (HCV) infection is a national and global public health concern, affecting up to 4 million individuals in the United States and 200 million individuals worldwide. Despite a declining incidence of new HCV infections in the United States, the prevalence of advanced liver disease secondary to chronic HCV infection, including cirrhosis and hepatocellular carcinoma, is expected to rise in the coming years.
Download to read this article in PDF document:
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NICE Bites is a monthly bulletin which summarises key prescribing points from NICE guidance. This edition includes two topics; Anaphylaxis and Hepatis C – technology appraisals.
Healthy You
Oregon State University
Like curry? New biological role identified for compound used in ancient medicine
CORVALLIS, Ore. – Scientists have just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.
CORVALLIS, Ore. – Scientists have just identified a new reason why some curry dishes, made with spices humans have used for thousands of years, might be good for you.
New research at Oregon State University has discovered that curcumin, a compound found in the cooking spice turmeric, can cause a modest but measurable increase in levels of a protein that's known to be important in the "innate" immune system, helping to prevent infection in humans and other animals.
This cathelicidin antimicrobial peptide, or CAMP, is part of what helps our immune system fight off various bacteria, viruses or fungi even though they hadn't been encountered before.
Prior to this, it was known that CAMP levels were increased by vitamin D. Discovery of an alternative mechanism to influence or raise CAMP levels is of scientific interest and could open new research avenues in nutrition and pharmacology, scientists said.
Turmeric is a flavorful, orange-yellow spice and an important ingredient in many curries, commonly found in Indian, South Asian and Middle Eastern cuisine. It has also been used for 2,500 years as a medicinal compound in the Ayurvedic system of medicine in India – not to mention being part of some religious and wedding ceremonies. In India, turmeric is treated with reverence.
The newest findings were made by researchers in the Linus Pauling Institute at OSU and published today in the Journal of Nutritional Biochemistry, in collaboration with scientists from the University of Copenhagen in Denmark. The work was supported by the National Institutes of Health.
"This research points to a new avenue for regulating CAMP gene expression," said Adrian Gombart, an associate professor of biochemistry and biophysics in the Linus Pauling Institute. "It's interesting and somewhat surprising that curcumin can do that, and could provide another tool to develop medical therapies."
The newest findings were made by researchers in the Linus Pauling Institute at OSU and published today in the Journal of Nutritional Biochemistry, in collaboration with scientists from the University of Copenhagen in Denmark. The work was supported by the National Institutes of Health.
"This research points to a new avenue for regulating CAMP gene expression," said Adrian Gombart, an associate professor of biochemistry and biophysics in the Linus Pauling Institute. "It's interesting and somewhat surprising that curcumin can do that, and could provide another tool to develop medical therapies."
The impact of curcumin in this role is not nearly as potent as that of vitamin D, Gombart said, but could nonetheless have physiologic value. Curcumin has also been studied for its anti-inflammatory and antioxidant properties.
"Curcumin, as part of turmeric, is generally consumed in the diet at fairly low levels," Gombart said. "However, it's possible that sustained consumption over time may be healthy and help protect against infection, especially in the stomach and intestinal tract."
In this study, Chunxiao Guo, a graduate student, and Gombart looked at the potential of both curcumin and omega-3 fatty acids to increase expression of the CAMP gene. They found no particular value with the omega-3 fatty acids for this purpose, but curcumin did have a clear effect. It caused levels of CAMP to almost triple.
In this study, Chunxiao Guo, a graduate student, and Gombart looked at the potential of both curcumin and omega-3 fatty acids to increase expression of the CAMP gene. They found no particular value with the omega-3 fatty acids for this purpose, but curcumin did have a clear effect. It caused levels of CAMP to almost triple.
There has been intense scientific interest in the vitamin D receptor in recent years because of potential therapeutic benefits in treating infection, cancer, psoriasis and other diseases, the researchers noted in their report. An alternative way to elicit a related biological response could be significant and merits additional research, they said.
The CAMP peptide is the only known antimicrobial peptide of its type in humans, researchers said. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis.
Is coffee good for the liver?
ISIC the Institute for Scientific Information on Coffee©
14th May 2012
Questions patients ask
Q: Is coffee good for the liver?
A: Research suggests that regular, moderate coffee consumption can lower people’s risk of developing a range of liver diseases – including cancer, fibrosis (scar tissue that builds up within the liver) and cirrhosis (the result of a long-term build up of scar tissue within the liver).
Q: How many cups of coffee do I need to drink to see a benefit?
A: It is too early to make specific recommendations concerning the levels of coffee intake that may be beneficial for liver function. Research suggests that regular, moderate coffee consumption may be beneficial
1,2. However certain patients with specific conditions may need to limit their caffeine consumption. For example, pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.
Q: Are the benefits of coffee down to caffeine?
A: While research has suggested that caffeine may slow down the progression of liver fibrosis, alcoholic cirrhosis and liver cancer
3,4,5, the extent to which caffeine is implicated in the reduced risk of developing these diseases remains unclear. Research also suggests that other coffee constituents, including cafestol and kahweol6 (naturally occurring compounds found in the oily part of coffee), and antioxidants may have a beneficial effect on liver function.
Q: Is decaffeinated coffee as good as regular coffee?
A: Research suggests that caffeine might play a role in the relationship between coffee drinking and lower risk of liver disease; however, currently there are no published studies specifically investigating the effects of decaffeinated coffee on liver function.
Q: If I’m a coffee drinker, can I drink more alcohol without increasing my risk of liver disease?
A: No. All medical advice makes clear that excessive alcohol consumption is detrimental to health. Adults, who choose to consume alcohol, should be aware of the recommended advice for safe consumption. While scientific research suggests that coffee drinking may have a beneficial effect on liver function, the risks associated with excessive alcohol consumption are not counter balanced by coffee consumption.
Q: I’ve heard that the effects of alcohol on the liver can be different for women than for men. Is the same true for coffee?
A: Generally, the effect of coffee drinking does not differ between the sexes; however, some groups, such as pregnant women, smokers, or women taking hormone replacement therapy do metabolise caffeine at a different rate to those in the general population. Pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.
Q: Do all types of coffee have the same effect?
A: Studies investigating the relationship between coffee and liver function have demonstrated beneficial effects in various types of coffee preparation, including filtered, instant and espresso coffee.
Q: Is it safe for individuals with liver disease to drink coffee?
A: Yes, there is no evidence to suggest that moderate coffee drinking poses any dangers for individuals with liver disease. In fact, some studies suggest coffee may slow down the progression of liver disease in some patients.
Q: Does coffee have any benefits for individuals with liver disease?
A: Research has shown that individuals with liver disease who regularly drink moderate amounts of coffee tend to display a milder progression of the disease7,8.
Source and References
Is coffee good for the liver?
ISIC the Institute for Scientific Information on Coffee©
14th May 2012
Questions patients ask
Q: Is coffee good for the liver?
A: Research suggests that regular, moderate coffee consumption can lower people’s risk of developing a range of liver diseases – including cancer, fibrosis (scar tissue that builds up within the liver) and cirrhosis (the result of a long-term build up of scar tissue within the liver).
Q: How many cups of coffee do I need to drink to see a benefit?
A: It is too early to make specific recommendations concerning the levels of coffee intake that may be beneficial for liver function. Research suggests that regular, moderate coffee consumption may be beneficial
1,2. However certain patients with specific conditions may need to limit their caffeine consumption. For example, pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.
Q: Are the benefits of coffee down to caffeine?
A: While research has suggested that caffeine may slow down the progression of liver fibrosis, alcoholic cirrhosis and liver cancer
3,4,5, the extent to which caffeine is implicated in the reduced risk of developing these diseases remains unclear. Research also suggests that other coffee constituents, including cafestol and kahweol6 (naturally occurring compounds found in the oily part of coffee), and antioxidants may have a beneficial effect on liver function.
Q: Is decaffeinated coffee as good as regular coffee?
A: Research suggests that caffeine might play a role in the relationship between coffee drinking and lower risk of liver disease; however, currently there are no published studies specifically investigating the effects of decaffeinated coffee on liver function.
Q: If I’m a coffee drinker, can I drink more alcohol without increasing my risk of liver disease?
A: No. All medical advice makes clear that excessive alcohol consumption is detrimental to health. Adults, who choose to consume alcohol, should be aware of the recommended advice for safe consumption. While scientific research suggests that coffee drinking may have a beneficial effect on liver function, the risks associated with excessive alcohol consumption are not counter balanced by coffee consumption.
Q: I’ve heard that the effects of alcohol on the liver can be different for women than for men. Is the same true for coffee?
A: Generally, the effect of coffee drinking does not differ between the sexes; however, some groups, such as pregnant women, smokers, or women taking hormone replacement therapy do metabolise caffeine at a different rate to those in the general population. Pregnant women are advised to limit their caffeine intake to 200-300mg per day – the equivalent amount found in 2-3 regular cups of coffee.
Q: Do all types of coffee have the same effect?
A: Studies investigating the relationship between coffee and liver function have demonstrated beneficial effects in various types of coffee preparation, including filtered, instant and espresso coffee.
Q: Is it safe for individuals with liver disease to drink coffee?
A: Yes, there is no evidence to suggest that moderate coffee drinking poses any dangers for individuals with liver disease. In fact, some studies suggest coffee may slow down the progression of liver disease in some patients.
Q: Does coffee have any benefits for individuals with liver disease?
A: Research has shown that individuals with liver disease who regularly drink moderate amounts of coffee tend to display a milder progression of the disease7,8.
Source and References
May 24
Think you eat a nutritious diet but still find yourself battling sugar cravings, feeling fatigued and struggling to lose weight? Then carve out time today to watch this talk by Stanford internist Nicole Peoples, DO. In this video lecture, she explains what happens once food enters your system, how your body responds to it and why the food choices you’re making could be contributing to these and other symptoms.
Friday, May 25, 2012
Improved treatment coming for HIV/ HCV co-infection
DDW Daily News
Improved treatment coming for HIV/ HCV co-infection
May 22, 2012
Interim results from Phase 2b trials of direct-acting antiviral therapy in patients co-infected with HIV and HCV are showing promising results. So promising, in fact, that it may be time to alter treatment.
“We have tantalizing data from two trials,” said John Vierling, MD, FACP, professor of medicine and surgery at the Baylor College of Medicine, Houston, TX. “I would encourage enrollment in Phase 3 trials that are now open rather than individual, off-label use of these agents.”
Dr. Vierling was the lead speaker for a Monday afternoon symposium on Liver Disease in Patients with HIV Infection sponsored by the AASLD.
HCV has emerged as a significant clinical problem among patients infected with HIV, Dr. Vierling noted. About a third of HIV patients in the U.S. are coinfected with HCV.
“The success of HIV therapy in reducing viral loads and extending life has led to the recognition that liver disease is a significant comorbidity with HIV,” he said. “HCV infection, in particular, is associated with increased morbidity and mortality from liver disease in patients with HIV.”
The primary goal in treating these co-infected individuals is to prevent progression to cirrhosis. In patients who already show signs of cirrhosis, the goal is to prevent progression to liver cancer or the need for liver transplantation.
Boceprevir and telaprevir have been approved for the treatment of HCV genotype 1, which is responsible for about 75 percent of HCV infection in the U.S. and about 90 percent of HCV infection among African Americans. Trials for HIV/HCV co-infection are less advanced.
Boceprevir
An interim analysis of boceprevir plus peginterferon/ribavirin (PR) versus PR alone was reported in April. Early trials suggested that the combination is more effective than PR alone, but questions remain about the safety and efficacy of the combination.
The interim analysis assessed treatment results after 12 weeks, Dr. Vierling said. The trial was relatively small — 64 patients randomized to boceprevir/PR and 34 to PR alone. Patients in both arms were in early middle age, he said, predominantly male and white. There was a very low incidence of cirrhosis — just 3 percent in the PR arm and 6 percent in the boceprevir/PR arm.
All of the patients enrolled in the trial received at least one treatment. In the PR arm, 18 patients (53 percent) discontinued and 12 patients (35 percent) completed treatment. The other four patients crossed over to the boceprevir/PR arm after a futility analysis. In the boceprevir/PR arm, 24 patients (38 percent) discontinued and 40 (63 percent) completed treatment.
At four, eight, 12, and 24 weeks, the sustained viral response was higher in the boceprevir/PR arm. The sustained viral response rate at 12 weeks, the intended interim endpoint, was 60.7 percent in the boceprevir/ PR arm and 26.5 percent in the PR arm.
There were also three HIV breakthroughs in the boceprevir/PR arm, all of them at week 24 or later in the trial. Pharmacokinetic data show drug-drug interactions between boceprevir and multiple antiretroviral agents. It may be appropriate to adjust antiretroviral dosing to account for the interactions, Dr. Vierling said.
There were no major differences in safety profiles between the two arms, with no deaths in either arm and adverse events in 100 percent of patients in the PR arm compared to 98 percent in the boceprevir/PR arm. There were some differences in side effects but no surprises, Dr. Vierling said.
“These adverse events are not unique to the co-infected population,” he said. “They are very similar to the adverse events we see in the moninfected population.”
Telaprevir
Telaprevir plus PR showed similarly positive results compared to PR alone. Dr Vierling reviewed interim findings from the Phase 2 Study 110 trial first released in March 2012.
The Study 110 trial included patients who were on antiretroviral therapy (ART) and patients who were not on ART. Of the patients on ART, 74 percent on telaprevir showed sustained viral response at 12 compared to 45 percent of patients on PR alone. The results were similar in patients not on ART — 71 percent in the telaprevir arm showed sustained viral response compared to 33 percent for PR only. Three of the telaprevir patients showed HVC breakthrough, but there were no HIV viral load rebounds in either group.
“The rates of efficacy are quite encouraging for both of these trials, as are safety and tolerability,” Dr. Vierling said.
Improved treatment coming for HIV/ HCV co-infection
May 22, 2012
Interim results from Phase 2b trials of direct-acting antiviral therapy in patients co-infected with HIV and HCV are showing promising results. So promising, in fact, that it may be time to alter treatment.
“We have tantalizing data from two trials,” said John Vierling, MD, FACP, professor of medicine and surgery at the Baylor College of Medicine, Houston, TX. “I would encourage enrollment in Phase 3 trials that are now open rather than individual, off-label use of these agents.”
Dr. Vierling was the lead speaker for a Monday afternoon symposium on Liver Disease in Patients with HIV Infection sponsored by the AASLD.
HCV has emerged as a significant clinical problem among patients infected with HIV, Dr. Vierling noted. About a third of HIV patients in the U.S. are coinfected with HCV.
“The success of HIV therapy in reducing viral loads and extending life has led to the recognition that liver disease is a significant comorbidity with HIV,” he said. “HCV infection, in particular, is associated with increased morbidity and mortality from liver disease in patients with HIV.”
The primary goal in treating these co-infected individuals is to prevent progression to cirrhosis. In patients who already show signs of cirrhosis, the goal is to prevent progression to liver cancer or the need for liver transplantation.
Boceprevir and telaprevir have been approved for the treatment of HCV genotype 1, which is responsible for about 75 percent of HCV infection in the U.S. and about 90 percent of HCV infection among African Americans. Trials for HIV/HCV co-infection are less advanced.
Boceprevir
An interim analysis of boceprevir plus peginterferon/ribavirin (PR) versus PR alone was reported in April. Early trials suggested that the combination is more effective than PR alone, but questions remain about the safety and efficacy of the combination.
The interim analysis assessed treatment results after 12 weeks, Dr. Vierling said. The trial was relatively small — 64 patients randomized to boceprevir/PR and 34 to PR alone. Patients in both arms were in early middle age, he said, predominantly male and white. There was a very low incidence of cirrhosis — just 3 percent in the PR arm and 6 percent in the boceprevir/PR arm.
All of the patients enrolled in the trial received at least one treatment. In the PR arm, 18 patients (53 percent) discontinued and 12 patients (35 percent) completed treatment. The other four patients crossed over to the boceprevir/PR arm after a futility analysis. In the boceprevir/PR arm, 24 patients (38 percent) discontinued and 40 (63 percent) completed treatment.
At four, eight, 12, and 24 weeks, the sustained viral response was higher in the boceprevir/PR arm. The sustained viral response rate at 12 weeks, the intended interim endpoint, was 60.7 percent in the boceprevir/ PR arm and 26.5 percent in the PR arm.
There were also three HIV breakthroughs in the boceprevir/PR arm, all of them at week 24 or later in the trial. Pharmacokinetic data show drug-drug interactions between boceprevir and multiple antiretroviral agents. It may be appropriate to adjust antiretroviral dosing to account for the interactions, Dr. Vierling said.
There were no major differences in safety profiles between the two arms, with no deaths in either arm and adverse events in 100 percent of patients in the PR arm compared to 98 percent in the boceprevir/PR arm. There were some differences in side effects but no surprises, Dr. Vierling said.
“These adverse events are not unique to the co-infected population,” he said. “They are very similar to the adverse events we see in the moninfected population.”
Telaprevir
Telaprevir plus PR showed similarly positive results compared to PR alone. Dr Vierling reviewed interim findings from the Phase 2 Study 110 trial first released in March 2012.
The Study 110 trial included patients who were on antiretroviral therapy (ART) and patients who were not on ART. Of the patients on ART, 74 percent on telaprevir showed sustained viral response at 12 compared to 45 percent of patients on PR alone. The results were similar in patients not on ART — 71 percent in the telaprevir arm showed sustained viral response compared to 33 percent for PR only. Three of the telaprevir patients showed HVC breakthrough, but there were no HIV viral load rebounds in either group.
“The rates of efficacy are quite encouraging for both of these trials, as are safety and tolerability,” Dr. Vierling said.
DDW-Metformin Shows Dose-Dependent Risk Reduction of HCC in Patients With Diabetes
DGDispatch
Metformin Shows Dose-Dependent Risk Reduction of HCC in Patients With Diabetes: Presented at DDW
By Nancy A. Melville
SAN DIEGO -- May 25, 2012 -- Metformin shows a dose-dependent chemopreventive effect in reducing the risk of hepatocellular carcinoma (HCC) at a rate of about 7% per year, researchers said here at the Digestive Disease Week (DDW) 2012.
Metformin has been linked with HCC in past research involving patients with other conditions, said lead author Chun-Ying Wu, MD, Yang-Ming University in Taipei, Taiwan
"Previous studies have shown a relationship between HCC and metformin, and in a prospective cohort of cirrhotic patients with hepatitis C, metformin use was associated with significantly reduced HCC risk," he said on May 21.
Several mechanisms are believed to provide the benefit, Dr. Wu added. "Whereas insulin resistance plays a role in hepatic carcinogenesis via activation of the IGF-1 signalling axis and increased fat accumulation in hepatocytes, metformin has been shown to improve insulin sensitivity, inhibit hepatic gluconeogenesis and decrease glycogenolysis."
In the new study, the research team evaluated 97,430 patients diagnosed with HCC between 1997 and 2008 who were enrolled in Taiwan's National Health Insurance Research Database and 194,860 age, gender, and physician visit date-matched controls.
The patients with diabetes not using metformin showed the highest risk of HCC (adjusted odds ratio [OR] = 1.95). This was followed by patients with diabetes who rarely used metformin (OR = 1.74), and then by those who frequently used metformin (OR = 1.67) and those who regularly used metformin (OR = 1.56).
Each incremental year increase in metformin use resulted in a 6% to 7% reduction in the risk of HCC in patients with diabetes.
"In the nationwide population study, we found that use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner," Dr. Wu concluded. "Using metformin in diabetic patients to decrease the risk of HCC should be recommended."
Digestive Disease Week 2012 is cosponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
[Presentation title: Metformin Decreases Hepatocellular Carcinoma Risk in a Dose-Dependent Manner: Population-Based and in Vitro Studies. Abstract 596]
Metformin Shows Dose-Dependent Risk Reduction of HCC in Patients With Diabetes: Presented at DDW
By Nancy A. Melville
SAN DIEGO -- May 25, 2012 -- Metformin shows a dose-dependent chemopreventive effect in reducing the risk of hepatocellular carcinoma (HCC) at a rate of about 7% per year, researchers said here at the Digestive Disease Week (DDW) 2012.
Metformin has been linked with HCC in past research involving patients with other conditions, said lead author Chun-Ying Wu, MD, Yang-Ming University in Taipei, Taiwan
"Previous studies have shown a relationship between HCC and metformin, and in a prospective cohort of cirrhotic patients with hepatitis C, metformin use was associated with significantly reduced HCC risk," he said on May 21.
Several mechanisms are believed to provide the benefit, Dr. Wu added. "Whereas insulin resistance plays a role in hepatic carcinogenesis via activation of the IGF-1 signalling axis and increased fat accumulation in hepatocytes, metformin has been shown to improve insulin sensitivity, inhibit hepatic gluconeogenesis and decrease glycogenolysis."
In the new study, the research team evaluated 97,430 patients diagnosed with HCC between 1997 and 2008 who were enrolled in Taiwan's National Health Insurance Research Database and 194,860 age, gender, and physician visit date-matched controls.
The patients with diabetes not using metformin showed the highest risk of HCC (adjusted odds ratio [OR] = 1.95). This was followed by patients with diabetes who rarely used metformin (OR = 1.74), and then by those who frequently used metformin (OR = 1.67) and those who regularly used metformin (OR = 1.56).
Each incremental year increase in metformin use resulted in a 6% to 7% reduction in the risk of HCC in patients with diabetes.
"In the nationwide population study, we found that use of metformin is associated with a decreased risk of HCC in diabetic patients in a dose-dependent manner," Dr. Wu concluded. "Using metformin in diabetic patients to decrease the risk of HCC should be recommended."
Digestive Disease Week 2012 is cosponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society for Surgery of the Alimentary Tract (SSAT).
[Presentation title: Metformin Decreases Hepatocellular Carcinoma Risk in a Dose-Dependent Manner: Population-Based and in Vitro Studies. Abstract 596]
Thursday, May 24, 2012
DDW-Many Livers 'Too Fat' For Transplant
• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
• Increases in factors associated with fatty liver disease may be leading clinicians to discard more donated livers.
• Point out that over the past few years there's been a decline in the number of liver transplants done, but that decline isn't explained by flat donation rates alone.
In an analysis of data from the United Organ Sharing Network (UNOS), age, obesity, diabetes, and hypertension were associated with an increased risk of a liver being discarded, Eric Orman, MD, of the University of North Carolina at Chapel Hill, and colleagues reported during a press briefing at Digestive Disease Week here.
"We're actually throwing out livers that in the past may have been able to be used ... [because] of all these factors associated with fatty liver disease," Orman explained.
Orman said that over the past few years, there's been a decline in the number of liver transplants done, but that drop isn't explained by flat donation rates alone.
"Although donation rates have decreased overall, they haven't decreased to the same extent as the decline in the number of livers transplanted," he said, adding that one explanation may be an increase in discard rates due to poor quality of organs.
So he and colleagues conducted a retrospective study of data from UNOS between 1994 and 2010 totaling 93,232 organ donors. Living donors, split livers, and donors with a body mass index of less than 14 or more than 50 kg/m were excluded.
Among the nearly 94,000 donors, 75% of livers were transplanted and a quarter of livers were not used.
They found that the number of discarded organs was stable until 2003 (with a total of 1,058 organs discarded in that last year), and then rose to 1,828 by 2010.
In a bivariate analysis, they found that discarded livers more often came from donors who were older (median 49 versus 43 years), obese (35% verses 22% of non-obese donors), diabetic (35% versus 24% of nondiabetics), and hypertensive (31% versus 22% of normotensive patients).
Discard rates were also higher in donation after cardiac death, which is different from standard procurement. In the latter, a patient is declared brain dead but kept on a ventilator to keep the organs perfused (65% versus 22%). In donation after cardiac death, perfusion of blood to the organs is disrupted.
In multivariate analysis, the researchers found that all of the previous factors were associated with a liver being discarded:
The researchers also saw significant increases in median donor age (40 to 46) and the prevalence of obesity (13% to 31%) during the study period, along with significant increases in diabetes (3% to 13%), hypertension (22% to 39%), and donation after cardiac death (2% to 12%).
They estimated that in 2010, 44% of discards were due to increased age, 9% to obesity, 5% to diabetes, and 5% to hypertension. These proportions were stable over time, they said.
On the other hand, the proportion of livers discarded due to donation after cardiac death rose from 0.2% in 2000 to 26% in 2010, suggesting an increasing reluctance to use these grafts, they reported.
Orman said that, overall, the findings are important "because if these trends continue, we're going to see further declines in liver transplant."
Kenneth Andreoni, MD, a UNOS committee member, said the increasing prevalence of comorbidities in donors is a "double-edged sword" because it reflects the fact that public health messages about safety are getting through to younger people, even though that may mean fewer quality donors.
"We're seeing fewer young people dying in traumas, but we're getting less high-quality, excellent organs," Andreoni told MedPage Today. "The question is, how can we make the best use of more middle-age and older donors?"
When it comes to organs with fatty liver disease, some researchers have been trying to better quantify the type of fat in the liver so that surgeons can have a better idea of what's usable and what's not, said Andreoni, who is from Ohio State University in Columbus.
Improvements on the pathology side may also be needed, he said. For instance, pathologists may need to offer a more specific range in terms of the percentage of fat in the organ, so clinicians can more easily recognize if an organ needs to be discarded or not.
Other work has focused on whether there are better ways to protect a fatty liver so it has a better chance of working after it's transplanted. "Is there something you can put in during reperfusion, like an antioxidant, that will lead to better outcomes?" Andreoni said.
A co-author reported a relationship with Salix Pharmaceuticals
Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine
http://www.medpagetoday.com/MeetingCoverage/DDW/32912
• Increases in factors associated with fatty liver disease may be leading clinicians to discard more donated livers.
• Point out that over the past few years there's been a decline in the number of liver transplants done, but that decline isn't explained by flat donation rates alone.
In an analysis of data from the United Organ Sharing Network (UNOS), age, obesity, diabetes, and hypertension were associated with an increased risk of a liver being discarded, Eric Orman, MD, of the University of North Carolina at Chapel Hill, and colleagues reported during a press briefing at Digestive Disease Week here.
"We're actually throwing out livers that in the past may have been able to be used ... [because] of all these factors associated with fatty liver disease," Orman explained.
Orman said that over the past few years, there's been a decline in the number of liver transplants done, but that drop isn't explained by flat donation rates alone.
"Although donation rates have decreased overall, they haven't decreased to the same extent as the decline in the number of livers transplanted," he said, adding that one explanation may be an increase in discard rates due to poor quality of organs.
So he and colleagues conducted a retrospective study of data from UNOS between 1994 and 2010 totaling 93,232 organ donors. Living donors, split livers, and donors with a body mass index of less than 14 or more than 50 kg/m were excluded.
Among the nearly 94,000 donors, 75% of livers were transplanted and a quarter of livers were not used.
They found that the number of discarded organs was stable until 2003 (with a total of 1,058 organs discarded in that last year), and then rose to 1,828 by 2010.
In a bivariate analysis, they found that discarded livers more often came from donors who were older (median 49 versus 43 years), obese (35% verses 22% of non-obese donors), diabetic (35% versus 24% of nondiabetics), and hypertensive (31% versus 22% of normotensive patients).
Discard rates were also higher in donation after cardiac death, which is different from standard procurement. In the latter, a patient is declared brain dead but kept on a ventilator to keep the organs perfused (65% versus 22%). In donation after cardiac death, perfusion of blood to the organs is disrupted.
In multivariate analysis, the researchers found that all of the previous factors were associated with a liver being discarded:
- Age (OR 1.03 for each year increase, 95% CI 1.03 to 1.04)
- Obesity (OR 1.92, 95% CI 1.82 to 2.03)
- Diabetes (OR 1.42, 95% CI 1.32 to 1.53)
- Hypertension (OR 1.15, 95% CI 1.08 to 1.22)
- Donation after cardiac death (OR 12.3, 95% CI 11.3 to 13.4)
The researchers also saw significant increases in median donor age (40 to 46) and the prevalence of obesity (13% to 31%) during the study period, along with significant increases in diabetes (3% to 13%), hypertension (22% to 39%), and donation after cardiac death (2% to 12%).
They estimated that in 2010, 44% of discards were due to increased age, 9% to obesity, 5% to diabetes, and 5% to hypertension. These proportions were stable over time, they said.
On the other hand, the proportion of livers discarded due to donation after cardiac death rose from 0.2% in 2000 to 26% in 2010, suggesting an increasing reluctance to use these grafts, they reported.
Orman said that, overall, the findings are important "because if these trends continue, we're going to see further declines in liver transplant."
Kenneth Andreoni, MD, a UNOS committee member, said the increasing prevalence of comorbidities in donors is a "double-edged sword" because it reflects the fact that public health messages about safety are getting through to younger people, even though that may mean fewer quality donors.
"We're seeing fewer young people dying in traumas, but we're getting less high-quality, excellent organs," Andreoni told MedPage Today. "The question is, how can we make the best use of more middle-age and older donors?"
When it comes to organs with fatty liver disease, some researchers have been trying to better quantify the type of fat in the liver so that surgeons can have a better idea of what's usable and what's not, said Andreoni, who is from Ohio State University in Columbus.
Improvements on the pathology side may also be needed, he said. For instance, pathologists may need to offer a more specific range in terms of the percentage of fat in the organ, so clinicians can more easily recognize if an organ needs to be discarded or not.
Other work has focused on whether there are better ways to protect a fatty liver so it has a better chance of working after it's transplanted. "Is there something you can put in during reperfusion, like an antioxidant, that will lead to better outcomes?" Andreoni said.
A co-author reported a relationship with Salix Pharmaceuticals
Primary source: Digestive Disease Week
Source reference:
Orman ES, et al "The number of grafts available for liver transplantation is decreasing as a result of increasing age, metabolic syndrome, and donation after cardiac death" DDW 2012; Abstract 841.
Kristina Fiore
Staff WriterSource reference:
Orman ES, et al "The number of grafts available for liver transplantation is decreasing as a result of increasing age, metabolic syndrome, and donation after cardiac death" DDW 2012; Abstract 841.
Kristina Fiore
Kristina Fiore joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine
http://www.medpagetoday.com/MeetingCoverage/DDW/32912
Wednesday, May 23, 2012
DDW- People With Diabetes May Need Earlier Colon Screen
From WebMD Health News
People With Diabetes May Need Earlier Colon Screen
That may very well be the case, say researchers who found that people in their 40s with type 2 diabetes are about as likely to have precancerous colon growths called adenomas as people in their 50s without diabetes.
"It's almost as is if having diabetes advances your age by 10 years in this regard," says researcher Susan Hongha Vu, MD, a clinical gastroenterology fellow at Washington University School of Medicine in St. Louis.
If the findings are confirmed in a larger, more robust study, the guidelines should be changed so that people with diabetes start colon cancer screening at age 40, she tells WebMD.
Vu presented the study at the Digestive Disease Week conference in San Diego.
Colon Cancer Screening Guidelines
Current guidelines call for men and women at average risk to undergo regular colon cancer screenings beginning at age 50. Colonoscopy, which allows the doctor to view the entire colon and remove any abnormal growths, is the gold standard. There are several other screening options, though, such as flexible sigmoidoscopy and fecal occult blood tests.
But people at high risk of colon cancer should begin screening earlier, according to the recommendations.
Research suggests diabetes may be another such risk factor, Vu says.
"A lot of studies have shown an association between type 2 diabetes and an increased risk of colon cancer," she says.
"Studies also show that diabetes increases the risk of precancerous lesions in the colon," Vu says.
"But as far as we know, no one had taken the next logical step -- that is, to determine whether people with type 2 diabetes should be screened earlier," she says.
Study: Diabetes Appears to Affect Polyp Risk
So the researchers examined the medical records of three groups of people having a colonoscopy over a six-year period at their institution: 125 people ages 40-49 with type 2 diabetes, 125 people 40-49 without diabetes, and 125 people ages 50-59 without diabetes.
Colonoscopy found at least one precancerous polyp in:
People with diabetes may have other risk factors for adenomas and colon cancer that weren't measured, says John Petrini, MD, a gastroenterologist at the Sansum Clinic in Santa Barbara, Calif.
Vu says there is a possible explanation for a link between diabetes and colon cancer. People with diabetes have abnormally high levels of insulin in their blood, and insulin can fuel the growth of cells, including precancerous and cancer cells, she says.
The findings are intriguing, Petrini says. But until there is a large, well-designed study confirming the finding, it's too early to talk about changing guidelines, he says.
But should people with diabetes in their 40s go in for early screening if they are concerned? They could, Petrini says. But without guidelines, insurers are unlikely to cover the cost of the test -- about $1,000 in the case of colonoscopy, he says.
On the other hand, a person might opt for a less expensive flexible sigmoidoscopy, which is a good way of identifying people who need a full colonoscopy, Petrini says.
About 25 million Americans have diabetes, and that number is expected to double in the next 25 years. Over 1.1 million have colorectal cancer, according to the American Cancer Society.
These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.
SOURCES:
Digestive Disease Week, San Diego, May 19-22, 2012.
Susan Hongha Vu, MD, clinical gastroenterology fellow, Washington University School of Medicine, St. Louis.
John Petrini, MD, gastroenterologist, Sansum Clinic, Santa Barbara, Calif.
Conference News @ Medscape
People With Diabetes May Need Earlier Colon Screen
That may very well be the case, say researchers who found that people in their 40s with type 2 diabetes are about as likely to have precancerous colon growths called adenomas as people in their 50s without diabetes.
"It's almost as is if having diabetes advances your age by 10 years in this regard," says researcher Susan Hongha Vu, MD, a clinical gastroenterology fellow at Washington University School of Medicine in St. Louis.
If the findings are confirmed in a larger, more robust study, the guidelines should be changed so that people with diabetes start colon cancer screening at age 40, she tells WebMD.
Vu presented the study at the Digestive Disease Week conference in San Diego.
Colon Cancer Screening Guidelines
Current guidelines call for men and women at average risk to undergo regular colon cancer screenings beginning at age 50. Colonoscopy, which allows the doctor to view the entire colon and remove any abnormal growths, is the gold standard. There are several other screening options, though, such as flexible sigmoidoscopy and fecal occult blood tests.
But people at high risk of colon cancer should begin screening earlier, according to the recommendations.
Research suggests diabetes may be another such risk factor, Vu says.
"A lot of studies have shown an association between type 2 diabetes and an increased risk of colon cancer," she says.
"Studies also show that diabetes increases the risk of precancerous lesions in the colon," Vu says.
"But as far as we know, no one had taken the next logical step -- that is, to determine whether people with type 2 diabetes should be screened earlier," she says.
Study: Diabetes Appears to Affect Polyp Risk
So the researchers examined the medical records of three groups of people having a colonoscopy over a six-year period at their institution: 125 people ages 40-49 with type 2 diabetes, 125 people 40-49 without diabetes, and 125 people ages 50-59 without diabetes.
Colonoscopy found at least one precancerous polyp in:
- 14% of those ages 40-49 without diabetes
- 30% of those ages 40-49 with diabetes
- 32% of those ages 50-59 without diabetes
People with diabetes may have other risk factors for adenomas and colon cancer that weren't measured, says John Petrini, MD, a gastroenterologist at the Sansum Clinic in Santa Barbara, Calif.
Vu says there is a possible explanation for a link between diabetes and colon cancer. People with diabetes have abnormally high levels of insulin in their blood, and insulin can fuel the growth of cells, including precancerous and cancer cells, she says.
The findings are intriguing, Petrini says. But until there is a large, well-designed study confirming the finding, it's too early to talk about changing guidelines, he says.
But should people with diabetes in their 40s go in for early screening if they are concerned? They could, Petrini says. But without guidelines, insurers are unlikely to cover the cost of the test -- about $1,000 in the case of colonoscopy, he says.
On the other hand, a person might opt for a less expensive flexible sigmoidoscopy, which is a good way of identifying people who need a full colonoscopy, Petrini says.
About 25 million Americans have diabetes, and that number is expected to double in the next 25 years. Over 1.1 million have colorectal cancer, according to the American Cancer Society.
These findings were presented at a medical conference. They should be considered preliminary as they have not yet undergone the "peer review" process, in which outside experts scrutinize the data prior to publication in a medical journal.
SOURCES:
Digestive Disease Week, San Diego, May 19-22, 2012.
Susan Hongha Vu, MD, clinical gastroenterology fellow, Washington University School of Medicine, St. Louis.
John Petrini, MD, gastroenterologist, Sansum Clinic, Santa Barbara, Calif.
Conference News @ Medscape
- DDWOral Methylnaltrexone for Opioid-Induced Constipation
- DDWPeople With Diabetes May Need Earlier Colon Screen
- DDWRobust, Durable Responses With Vedolizumab for UC
- DDWGolimumab Eases Ulcerative Colitis Symptoms
- DDWCases of C. Diff Increased 12-Fold Among Children
- DDWHigh Altitudes Might Precipitate IBD Flares
- DDWBody-Building Supplements Top List of Hepatotoxic Agents
- DDWStatins Shown to Be Safe in Patients With Cirrhosis
- DDWLandmark US Trial Shows Screening Cuts Colorectal Cancer
- DDWPatients Prefer Colonoscopy Over CT Colonography for Cancer
- DDWPrevalence of GERD is 4 Times Higher Among People With IBS
- DDWComplications Are Emerging for Baby Boomers With HCV
- DDWPrevalence of NAFLD Increasing Among American Adolescents
Medscape Gastroenterology © 2012 WebMD, LLC
DDW-Patients May Receive Too Much Acetaminophen in Hospital
WEDNESDAY, May 23 (HealthDay News)
Roughly 2.5 percent of admitted hospital patients may receive more than the safe daily cumulative dose of the pain-reliever acetaminophen, best known as Tylenol, on at least one day, according to a new U.S. study.
Roughly 2.5 percent of admitted hospital patients may receive more than the safe daily cumulative dose of the pain-reliever acetaminophen, best known as Tylenol, on at least one day, according to a new U.S. study.
Patients on more than one drug containing acetaminophen often consume more than the recommended 4 grams per day of the drug, the researchers from Thomas Jefferson University Hospital in Philadelphia found.
Together, two tablets of extra-strength Tylenol contain 1 gram of acetaminophen, commonly used to relieve pain and reduce fever.
Over the course of two years, researchers led by Dr. Jesse Civan examined 46,000 hospital admissions and the medications those patients were given. They found that on at least one day of hospitalization, roughly 1,100 patients received more than 4 grams of acetaminophen in the form of Tylenol, Percocet and similar drugs.
The study authors also assessed the effects the acetaminophen had on the patients' livers and found only a small minority were given a blood test to check their liver function. The investigators noted that this test is typically used only when a doctor has a specific concern about possible problems with a patient's liver.
In the small number of patients who did have the blood test of liver function, the researchers noted that there were no serious liver injuries. They said there wasn't enough information to determine if abnormal test results were the result of excessive exposure to acetaminophen.
Civan and colleagues concluded that more research is needed to determine if new recommendations for the safe daily dosing of acetaminophen are necessary. They added that patients need better education on acetaminophen safety, particularly for use of the drug after they leave the hospital, when patients may try to duplicate the medications and doses they were given during their admission.
The study was presented Monday at the Digestive Disease Week meeting in San Diego. The data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.
Civan and colleagues concluded that more research is needed to determine if new recommendations for the safe daily dosing of acetaminophen are necessary. They added that patients need better education on acetaminophen safety, particularly for use of the drug after they leave the hospital, when patients may try to duplicate the medications and doses they were given during their admission.
The study was presented Monday at the Digestive Disease Week meeting in San Diego. The data and conclusions should be viewed as preliminary until published in a peer-reviewed journal.
The U.S. Food and Drug Administration has more about acetaminophen.
DDW
DDW
Dr. Orman will present these data on Monday, May 21 at 4 p.m. PT in Halls C-G of the San Diego Convention Center.
Patterns of Usage of Acetaminophen in Excess of Four Grams Daily in a Hospitalized Population at a Tertiary Care Center (Abstract #743)
Hospitalized patients who receive multiple orders of medication containing acetaminophen are likely to receive a higher than intended dose of the drug, even when provided by physicians, according to new research from Thomas Jefferson University Hospital, Philadelphia, PA.
Reviewing 46,000 hospital admissions over a two-year period, investigators led by Jesse Civan, MD, GI fellow, division of gastroenterology, Thomas Jefferson University Hospital, found that about 1,100 individuals received more than 4 grams of acetaminophen on at least one day. In other words, about 2.5 percent of all patients admitted to the hospital received more than what is currently considered the safe cumulative daily dose on at least one calendar day.
Investigators sought to determine exactly how much acetaminophen was being dispensed in a large tertiary-care hospital and how it compared to the generally accepted safe maximum dose. They reviewed a computer database tracking every patient admitted to their hospital and every dose of medicine prescribed and received. This allowed them to calculate exactly how much medication patients were exposed to, including any medication containing acetaminophen, such as Tylenol®, Percocet® and other similar medicines, and to generate a list of all patients who received more than 4 grams of acetaminophen on at least one calendar day.
Researchers also reviewed liver function and injury, which are reported in the same database, to determine potential detrimental effects of acetaminophen use on patients. By reviewing a specific blood test — the alanine amino-transferase (ALT) test, which is generally used to screen for liver injury possibly related to acetaminophen — Dr. Civan and his colleagues found that only a small minority of patients were administered an ALT test. They attribute this finding to the fact that the blood test is only usually checked when a physician is particularly concerned about a possible liver problem.
In the small minority of patients who did have an ALT checked, there was insufficient data to do a “formal cause analysis” to determine whether an abnormal ALT could be blamed on the acetaminophen exposure. Because of the paucity of ALT monitoring, no conclusion could be reached about whether the acetaminophen exposure might have had any detectable detrimental consequences.
Dr. Civan added that these findings could have implications on public health and the need to improve patient education regarding safe dosages at home, since many patients will likely attempt to emulate the medications provided at the hospital once they get home. He concluded that further study in this closely monitored population in which every dose of acetaminophen-containing medication administered is recorded might shed light on the ongoing discussion at the U.S. Food and Drug Administration and elsewhere regarding new recommendations for maximum safe daily dosing. Dr Civan stressed that although it remains unclear whether blood test abnormalities may have resulted from acetaminophen use, he did not find any evidence of any cases of serious liver injury.
Acetaminophen has been under increasing scrutiny in the U.S. — it is the leading cause of acute liver failure and emergent liver transplant, and previous studies have suggested that unintentional overdose is a significant problem. There has also been debate in the medical literature about whether a less severe form of acetaminophen-induced liver injury due to unintentional overdose may be important.
http://hepatitiscnewdrugs.blogspot.com/2012/05/ddw-new-research-examines-impact-of.html
Patterns of Usage of Acetaminophen in Excess of Four Grams Daily in a Hospitalized Population at a Tertiary Care Center (Abstract #743)
Hospitalized patients who receive multiple orders of medication containing acetaminophen are likely to receive a higher than intended dose of the drug, even when provided by physicians, according to new research from Thomas Jefferson University Hospital, Philadelphia, PA.
Reviewing 46,000 hospital admissions over a two-year period, investigators led by Jesse Civan, MD, GI fellow, division of gastroenterology, Thomas Jefferson University Hospital, found that about 1,100 individuals received more than 4 grams of acetaminophen on at least one day. In other words, about 2.5 percent of all patients admitted to the hospital received more than what is currently considered the safe cumulative daily dose on at least one calendar day.
Investigators sought to determine exactly how much acetaminophen was being dispensed in a large tertiary-care hospital and how it compared to the generally accepted safe maximum dose. They reviewed a computer database tracking every patient admitted to their hospital and every dose of medicine prescribed and received. This allowed them to calculate exactly how much medication patients were exposed to, including any medication containing acetaminophen, such as Tylenol®, Percocet® and other similar medicines, and to generate a list of all patients who received more than 4 grams of acetaminophen on at least one calendar day.
Researchers also reviewed liver function and injury, which are reported in the same database, to determine potential detrimental effects of acetaminophen use on patients. By reviewing a specific blood test — the alanine amino-transferase (ALT) test, which is generally used to screen for liver injury possibly related to acetaminophen — Dr. Civan and his colleagues found that only a small minority of patients were administered an ALT test. They attribute this finding to the fact that the blood test is only usually checked when a physician is particularly concerned about a possible liver problem.
In the small minority of patients who did have an ALT checked, there was insufficient data to do a “formal cause analysis” to determine whether an abnormal ALT could be blamed on the acetaminophen exposure. Because of the paucity of ALT monitoring, no conclusion could be reached about whether the acetaminophen exposure might have had any detectable detrimental consequences.
Dr. Civan added that these findings could have implications on public health and the need to improve patient education regarding safe dosages at home, since many patients will likely attempt to emulate the medications provided at the hospital once they get home. He concluded that further study in this closely monitored population in which every dose of acetaminophen-containing medication administered is recorded might shed light on the ongoing discussion at the U.S. Food and Drug Administration and elsewhere regarding new recommendations for maximum safe daily dosing. Dr Civan stressed that although it remains unclear whether blood test abnormalities may have resulted from acetaminophen use, he did not find any evidence of any cases of serious liver injury.
Acetaminophen has been under increasing scrutiny in the U.S. — it is the leading cause of acute liver failure and emergent liver transplant, and previous studies have suggested that unintentional overdose is a significant problem. There has also been debate in the medical literature about whether a less severe form of acetaminophen-induced liver injury due to unintentional overdose may be important.
http://hepatitiscnewdrugs.blogspot.com/2012/05/ddw-new-research-examines-impact-of.html
Tuesday, May 22, 2012
DDW-New research examines impact of liver disease
New research examines impact of liver disease
May 22nd, 2012
New research being presented at Digestive Disease Week® (DDW) offers key insights into the progression of diseases leading to liver damage, which affect diverse populations, including young people. Studies show that the increasing rates of obesity are putting teens at risk for developing nonalcoholic fatty liver disease and are decreasing the availability of healthy livers for organ donations, which are urgently needed as people continue to experience complications from diseases, such as hepatitis C and drug-induced liver toxicity.
"Liver disease often leads to lifelong problems and serious consequences," said Donald M. Jensen, MD, professor of medicine, and director, Center for Liver Diseases, University of Chicago Medical Center, IL. "With increasing incidence, it is more important than ever to investigate the causes, prevention and treatment for conditions like nonalcoholic fatty liver diseases and chronic hepatitis C, as well as to identify obstacles to liver transplantation." DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Prevalence of Suspected NAFLD Is Increasing Among U.S. Adolescents (Abstract #705)
Suspected non-alcoholic fatty liver disease (NAFLD) is increasing in teens, affecting approximately 10 percent of the age group, leading to a host of conditions, including liver damage, diabetes, hypertension and cancer. While the common perception has been that there are an increasing number of children identified with NAFLD, previous studies have not demonstrated the rate of that increase nor whether the increase actually exists. Investigators led by Miriam Vos, MD, assistant professor of pediatrics at Emory University and Children's Healthcare of Atlanta, GA, sought to determine whether rates seem high because people are studying them more closely or whether there really are more cases of teenagers with NAFLD.
Investigators determined that the increase in NAFLD was not defined by the number of overweight children. When comparing the rate of increase in children with fatty liver disease to the rate of increase in overweight children, research showed that the increase in children with fatty liver was much greater than the increase in overweight children. This finding demonstrates that just having overweight kids does not explain the increase in fatty liver. Investigators also looked at cross-sectional data to explain the increase and found a link to increased NAFLD and waist circumference (the measure of the distance around the abdomen half way between the inferior margin in the last rib and the crest of the hip bone).
"We know that if a child is overweight, they are more likely to be overweight as an adult, and we know from national data that teens with fatty liver disease become adults with fatty liver disease, unless they improve their diet and lose a significant amount of weight," said Dr. Vos. She added that adolescents may have an easier time losing weight compared to adults because they have been overweight for a shorter period of time.
To increase the likelihood of weight loss success, Dr. Vos supports a multi-sector approach, including community programs and school programs that steadily support healthy food and exercise. These types of programs are increasing around the country, but need to be uniformly available so that entire communities and children are not excluded from their benefits. She also recommends instituting these supportive programs while children are young so that their parents can help them develop good habits at an early age. Dr. Vos added that she is hopeful that, in the future, we will have medications for the most severe cases of NAFLD to help complement a healthy regimen. This summer, the National Institutes of Health (NIH)-sponsored NASH Clinical Research Network will start a new clinical trial to research the treatment of fatty liver.
Dr. Vos and colleagues are also studying the connection between diet and fat in the liver and increased cardiovascular risk. Data show that cardiovascular disease is very high in adults with NAFLD, and multiple studies have shown that adolescents with NAFLD have markers that show increased risk for cardiovascular disease.
In this study, investigators reviewed nationally representative data of more than 10,000 12- to 18-year-olds from the National Health and Examination Survey datasets, spanning from 1988 to 2008, excluding subjects with missing data and known liver disease. Suspected NAFLD was defined as overweight/obese (those with a body mass index greater than the 85th percentile) with elevated alanine aminotransferase (ALT) levels greater than 25.8 for boys or 22.1 for girls, and also as overweight/obese with ALT levels greater than 30 to allow for comparison with previous studies. ALT is a blood test that is typically used to detect liver injury.
Funding for this study was provided by the NIH.
Dr. Vos will present these data on Monday, May 21 at 11:15 a.m. PT in Room 2 of the San Diego Convention Center.
Current and Future Disease Progression of HCV-Infected Patients Among Different Age Cohorts (Abstract# Sa1084)
Several hundred thousand Americans with chronic hepatitis C virus infection (HCV) are predicted to develop potentially life-threatening liver complications within the next few years, according to a new study from Vertex Pharmaceuticals. Risk was found to be dramatically higher among baby boomers, a segment of the population that accounts for 82 percent of all Americans with HCV.
To assess the future health needs of HCV patients, researchers evaluated medical insurance claims data to determine how many individuals with HCV already have advanced liver disease and how many more will develop complications in time. Researchers found that more than 200,000 HCV patients were suffering from advanced liver disease in 2008 and a projected 300,000 additional patients — mostly baby boomers — are on track to develop advanced liver disease by 2015. Without treatment, the number of patients with advanced liver disease is expected to triple by 2015.
"This alarming finding places additional stress on an already overburdened health-care system, which will need to prepare for an increase in patients suffering from advanced liver disease," said Ann Kwong, PhD, vice president and HCV franchise lead at Vertex. "It is critical to treat HCV patients before they develop costly and irreversible liver complications."
Dr. Kwong recommends that one important course of action is a focus on HCV diagnoses. By screening patients for HCV infection, there is a greater opportunity to identify and potentially cure infection before liver complications occur. Currently approved HCV therapies are most effective in patients without advanced liver disease, so diagnosing the virus earlier offers patients the best chance to be cured.
Researchers stressed that not all patients developing liver complications can be accurately identified with insurance claims data. Individuals with existing liver disease may not be diagnosed and therefore cannot be accounted for in this study. In the future, universal screenings for HCV infection are expected to help diagnose not only more cases of HCV, but also lead to more testing for liver complications.
Up to five million U.S. adults have HCV, and 75 percent of them are unaware of their infection. HCV is commonly called a "silent killer" because it often has no symptoms and can go decades without being detected. Chronic HCV is the leading cause of liver cancer and the most common reason for liver transplantation in the U.S.
This study was funded by Vertex Pharmaceuticals.
Dr. Kwong will present these data on Saturday, May 19 at noon PT in Halls C-G of the San Diego Convention Center.
The Number of Grafts Available for Liver Transplantation is Decreasing as a Result of Increasing Donor Age, Metabolic Syndrome and Donation After Cardiac Death (Abstract #841)
The number of liver transplants has declined in the U.S. since 2006, so investigators led by Eric S. Orman, MD, gastroenterology fellow, the University of North Carolina, Chapel Hill, looked at various donor factors to determine why. By studying the United Network for Organ Sharing (UNOS) database for all donor information, researchers assessed which factors prompted physicians to discard an organ.
With standard donation, a patient is declared brain dead and kept on cardiovascular support so the organs can continue to receive oxygen and blood before being removed for transplant. In recent years, surgeons have also increasingly used the method known as donation after cardiac death, which occurs when patients die and the heart stops on its own. Cardiac death donation is considered an alternative way to donate organs and has been promoted as a way to increase the total number of organ donors. An increasingly large percentage of organ donors are in the donation after cardiac death category; less than 10 years ago, it was fewer than 2 percent, but currently, the rate has increased to more than 12 percent.
However, there is a widespread pattern of health-care professionals becoming increasingly reluctant to use organs donated after cardiac death. In reviewing the UNOS database, researchers found that the total number of donors who have at least one organ recovered for transplant has stopped increasing over the past few years, despite an increasing proportion of donation after cardiac death donors.
Investigators looked at the group of organ donors who had at least one organ recovered for transplant to determine whether the donor liver was a fatty liver. By reviewing donor characteristics that are strongly associated with having a fatty liver, such as diabetes, obesity, older age and high blood pressure, researchers found that these factors were all associated with discarding a liver. "Cardiac death donation is negatively impacting the overall number of liver transplants that we can do," said Dr. Orman.
The next step of the research is to look more closely at why more livers are being discarded, how large of a role donation after cardiac death is playing in those organs discarded, and what is driving the increase in donation after cardiac death.
No pharmaceutical funding was provided for this study.
Dr. Orman will present these data on Monday, May 21 at 4 p.m. PT in Halls C-G of the San Diego Convention Center.
Patterns of Usage of Acetaminophen in Excess of Four Grams Daily in a Hospitalized Population at a Tertiary Care Center (Abstract #743)
Hospitalized patients who receive multiple orders of medication containing acetaminophen are likely to receive a higher than intended dose of the drug, even when provided by physicians, according to new research from Thomas Jefferson University Hospital, Philadelphia, PA.
Reviewing 46,000 hospital admissions over a two-year period, investigators led by Jesse Civan, MD, GI fellow, division of gastroenterology, Thomas Jefferson University Hospital, found that about 1,100 individuals received more than 4 grams of acetaminophen on at least one day. In other words, about 2.5 percent of all patients admitted to the hospital received more than what is currently considered the safe cumulative daily dose on at least one calendar day.
Investigators sought to determine exactly how much acetaminophen was being dispensed in a large tertiary-care hospital and how it compared to the generally accepted safe maximum dose. They reviewed a computer database tracking every patient admitted to their hospital and every dose of medicine prescribed and received. This allowed them to calculate exactly how much medication patients were exposed to, including any medication containing acetaminophen, such as Tylenol®, Percocet® and other similar medicines, and to generate a list of all patients who received more than 4 grams of acetaminophen on at least one calendar day.
Researchers also reviewed liver function and injury, which are reported in the same database, to determine potential detrimental effects of acetaminophen use on patients. By reviewing a specific blood test — the alanine amino-transferase (ALT) test, which is generally used to screen for liver injury possibly related to acetaminophen — Dr. Civan and his colleagues found that only a small minority of patients were administered an ALT test. They attribute this finding to the fact that the blood test is only usually checked when a physician is particularly concerned about a possible liver problem.
In the small minority of patients who did have an ALT checked, there was insufficient data to do a "formal cause analysis" to determine whether an abnormal ALT could be blamed on the acetaminophen exposure. Because of the paucity of ALT monitoring, no conclusion could be reached about whether the acetaminophen exposure might have had any detectable detrimental consequences.
Dr. Civan added that these findings could have implications on public health and the need to improve patient education regarding safe dosages at home, since many patients will likely attempt to emulate the medications provided at the hospital once they get home. He concluded that further study in this closely monitored population in which every dose of acetaminophen-containing medication administered is recorded might shed light on the ongoing discussion at the U.S. Food and Drug Administration and elsewhere regarding new recommendations for maximum safe daily dosing. Dr Civan stressed that although it remains unclear whether blood test abnormalities may have resulted from acetaminophen use, he did not find any evidence of any cases of serious liver injury.
Acetaminophen has been under increasing scrutiny in the U.S. — it is the leading cause of acute liver failure and emergent liver transplant, and previous studies have suggested that unintentional overdose is a significant problem. There has also been debate in the medical literature about whether a less severe form of acetaminophen-induced liver injury due to unintentional overdose may be important.
This study received no pharmaceutical funding.
Dr. Civan will present these data on Monday, May 21 at 2:15 p.m. in 6e, San Diego Convention Center.
Herbal and Dietary Supplement Hepatoxicity in the U.S.A. (Abstract #167)
Dietary supplements used for body building and weight loss are the most common of any supplements to cause liver injury, according to new research from the U.S. Drug Induced Liver Injury Network (DILIN). Dietary supplements include herbal remedies, bodybuilding supplements, health food supplements, or anything that people can buy over the counter or online that is not prescribed by a physician.
Liver injury from medication is the main reason why drugs are taken off the market. While estimates suggest that herbal/dietary supplement products are used by up to 40 percent of the U.S. population, their side effects, including potential toxicity, is not well defined. Researchers led by Victor J. Navarro, MD, an investigator funded by the National Institutes of Health-sponsored DILIN, and professor of medicine, pharmacology and experimental therapeutics, Thomas Jefferson University, Philadelphia, PA, sought to explore liver injury from herbal/dietary supplements by examining the types of products taken, and the severity and outcomes associated with liver injury due to them.
Investigators looked at 109 cases of patients in the DILIN who appeared to have liver damage due to dietary supplements; most were male, white and overweight. They found that the supplements most likely to be the cause of liver injury were those reported for body building and for weight loss.
"There is so little regulation of the many products on the market; we couldn't possibly begin to figure out which products to target first without doing this research," said Dr. Navarro. He added that now that they know that bodybuilding and weight loss supplements are the most common causes of dietary supplement-induced injury among the products, they can focus their efforts accordingly.
Investigators are also looking at targeted components of herbal/dietary supplements. For example, previous studies have shown that green tea extract, which can be added to herbal/dietary supplements in high concentrations in pill form, can potentially cause damage to the liver. So DILIN investigators have also sought to determine how common the ingredients of green tea are in dietary supplements when the manufacturer has not identified it as such.
They hypothesized that green tea extract is prevalent in many products but is not specifically identified — in fact, their research has shown that it is present in up to 40 percent of products in which it was not listed on the label. For this reason, investigators will always have difficulty linking liver injuries to green tea extract unless they do a careful analysis of each product.
Dr. Navarro cautioned that because it is not well known how common liver injury is due to dietary supplements, it is difficult to suggest how likely it is that someone would suffer liver damage, but that this is another area where investigators are looking to do more research.
Investigators now have many more cases to study and their next step is to understand how the supplements cause injury and why. They are working with the Food and Drug Administration to identify various contaminants and determine which of the products on the market are the most harmful, especially since herbal/dietary supplement are not tightly regulated. They are also studying possible factors that may predispose a consumer of herbal/dietary supplement to liver injury, such as genetic makeup.
Dr. Navarro will present the DILIN's research data on Saturday, May 19 at 2:15 p.m. PT in Halls C-G of the San Diego Convention Center.
Provided by Digestive Disease Week
May 22nd, 2012
New research being presented at Digestive Disease Week® (DDW) offers key insights into the progression of diseases leading to liver damage, which affect diverse populations, including young people. Studies show that the increasing rates of obesity are putting teens at risk for developing nonalcoholic fatty liver disease and are decreasing the availability of healthy livers for organ donations, which are urgently needed as people continue to experience complications from diseases, such as hepatitis C and drug-induced liver toxicity.
"Liver disease often leads to lifelong problems and serious consequences," said Donald M. Jensen, MD, professor of medicine, and director, Center for Liver Diseases, University of Chicago Medical Center, IL. "With increasing incidence, it is more important than ever to investigate the causes, prevention and treatment for conditions like nonalcoholic fatty liver diseases and chronic hepatitis C, as well as to identify obstacles to liver transplantation." DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
Prevalence of Suspected NAFLD Is Increasing Among U.S. Adolescents (Abstract #705)
Suspected non-alcoholic fatty liver disease (NAFLD) is increasing in teens, affecting approximately 10 percent of the age group, leading to a host of conditions, including liver damage, diabetes, hypertension and cancer. While the common perception has been that there are an increasing number of children identified with NAFLD, previous studies have not demonstrated the rate of that increase nor whether the increase actually exists. Investigators led by Miriam Vos, MD, assistant professor of pediatrics at Emory University and Children's Healthcare of Atlanta, GA, sought to determine whether rates seem high because people are studying them more closely or whether there really are more cases of teenagers with NAFLD.
Investigators determined that the increase in NAFLD was not defined by the number of overweight children. When comparing the rate of increase in children with fatty liver disease to the rate of increase in overweight children, research showed that the increase in children with fatty liver was much greater than the increase in overweight children. This finding demonstrates that just having overweight kids does not explain the increase in fatty liver. Investigators also looked at cross-sectional data to explain the increase and found a link to increased NAFLD and waist circumference (the measure of the distance around the abdomen half way between the inferior margin in the last rib and the crest of the hip bone).
"We know that if a child is overweight, they are more likely to be overweight as an adult, and we know from national data that teens with fatty liver disease become adults with fatty liver disease, unless they improve their diet and lose a significant amount of weight," said Dr. Vos. She added that adolescents may have an easier time losing weight compared to adults because they have been overweight for a shorter period of time.
To increase the likelihood of weight loss success, Dr. Vos supports a multi-sector approach, including community programs and school programs that steadily support healthy food and exercise. These types of programs are increasing around the country, but need to be uniformly available so that entire communities and children are not excluded from their benefits. She also recommends instituting these supportive programs while children are young so that their parents can help them develop good habits at an early age. Dr. Vos added that she is hopeful that, in the future, we will have medications for the most severe cases of NAFLD to help complement a healthy regimen. This summer, the National Institutes of Health (NIH)-sponsored NASH Clinical Research Network will start a new clinical trial to research the treatment of fatty liver.
Dr. Vos and colleagues are also studying the connection between diet and fat in the liver and increased cardiovascular risk. Data show that cardiovascular disease is very high in adults with NAFLD, and multiple studies have shown that adolescents with NAFLD have markers that show increased risk for cardiovascular disease.
In this study, investigators reviewed nationally representative data of more than 10,000 12- to 18-year-olds from the National Health and Examination Survey datasets, spanning from 1988 to 2008, excluding subjects with missing data and known liver disease. Suspected NAFLD was defined as overweight/obese (those with a body mass index greater than the 85th percentile) with elevated alanine aminotransferase (ALT) levels greater than 25.8 for boys or 22.1 for girls, and also as overweight/obese with ALT levels greater than 30 to allow for comparison with previous studies. ALT is a blood test that is typically used to detect liver injury.
Funding for this study was provided by the NIH.
Dr. Vos will present these data on Monday, May 21 at 11:15 a.m. PT in Room 2 of the San Diego Convention Center.
Current and Future Disease Progression of HCV-Infected Patients Among Different Age Cohorts (Abstract# Sa1084)
Several hundred thousand Americans with chronic hepatitis C virus infection (HCV) are predicted to develop potentially life-threatening liver complications within the next few years, according to a new study from Vertex Pharmaceuticals. Risk was found to be dramatically higher among baby boomers, a segment of the population that accounts for 82 percent of all Americans with HCV.
To assess the future health needs of HCV patients, researchers evaluated medical insurance claims data to determine how many individuals with HCV already have advanced liver disease and how many more will develop complications in time. Researchers found that more than 200,000 HCV patients were suffering from advanced liver disease in 2008 and a projected 300,000 additional patients — mostly baby boomers — are on track to develop advanced liver disease by 2015. Without treatment, the number of patients with advanced liver disease is expected to triple by 2015.
"This alarming finding places additional stress on an already overburdened health-care system, which will need to prepare for an increase in patients suffering from advanced liver disease," said Ann Kwong, PhD, vice president and HCV franchise lead at Vertex. "It is critical to treat HCV patients before they develop costly and irreversible liver complications."
Dr. Kwong recommends that one important course of action is a focus on HCV diagnoses. By screening patients for HCV infection, there is a greater opportunity to identify and potentially cure infection before liver complications occur. Currently approved HCV therapies are most effective in patients without advanced liver disease, so diagnosing the virus earlier offers patients the best chance to be cured.
Researchers stressed that not all patients developing liver complications can be accurately identified with insurance claims data. Individuals with existing liver disease may not be diagnosed and therefore cannot be accounted for in this study. In the future, universal screenings for HCV infection are expected to help diagnose not only more cases of HCV, but also lead to more testing for liver complications.
Up to five million U.S. adults have HCV, and 75 percent of them are unaware of their infection. HCV is commonly called a "silent killer" because it often has no symptoms and can go decades without being detected. Chronic HCV is the leading cause of liver cancer and the most common reason for liver transplantation in the U.S.
This study was funded by Vertex Pharmaceuticals.
Dr. Kwong will present these data on Saturday, May 19 at noon PT in Halls C-G of the San Diego Convention Center.
The Number of Grafts Available for Liver Transplantation is Decreasing as a Result of Increasing Donor Age, Metabolic Syndrome and Donation After Cardiac Death (Abstract #841)
The number of liver transplants has declined in the U.S. since 2006, so investigators led by Eric S. Orman, MD, gastroenterology fellow, the University of North Carolina, Chapel Hill, looked at various donor factors to determine why. By studying the United Network for Organ Sharing (UNOS) database for all donor information, researchers assessed which factors prompted physicians to discard an organ.
With standard donation, a patient is declared brain dead and kept on cardiovascular support so the organs can continue to receive oxygen and blood before being removed for transplant. In recent years, surgeons have also increasingly used the method known as donation after cardiac death, which occurs when patients die and the heart stops on its own. Cardiac death donation is considered an alternative way to donate organs and has been promoted as a way to increase the total number of organ donors. An increasingly large percentage of organ donors are in the donation after cardiac death category; less than 10 years ago, it was fewer than 2 percent, but currently, the rate has increased to more than 12 percent.
However, there is a widespread pattern of health-care professionals becoming increasingly reluctant to use organs donated after cardiac death. In reviewing the UNOS database, researchers found that the total number of donors who have at least one organ recovered for transplant has stopped increasing over the past few years, despite an increasing proportion of donation after cardiac death donors.
Investigators looked at the group of organ donors who had at least one organ recovered for transplant to determine whether the donor liver was a fatty liver. By reviewing donor characteristics that are strongly associated with having a fatty liver, such as diabetes, obesity, older age and high blood pressure, researchers found that these factors were all associated with discarding a liver. "Cardiac death donation is negatively impacting the overall number of liver transplants that we can do," said Dr. Orman.
The next step of the research is to look more closely at why more livers are being discarded, how large of a role donation after cardiac death is playing in those organs discarded, and what is driving the increase in donation after cardiac death.
No pharmaceutical funding was provided for this study.
Dr. Orman will present these data on Monday, May 21 at 4 p.m. PT in Halls C-G of the San Diego Convention Center.
Patterns of Usage of Acetaminophen in Excess of Four Grams Daily in a Hospitalized Population at a Tertiary Care Center (Abstract #743)
Hospitalized patients who receive multiple orders of medication containing acetaminophen are likely to receive a higher than intended dose of the drug, even when provided by physicians, according to new research from Thomas Jefferson University Hospital, Philadelphia, PA.
Reviewing 46,000 hospital admissions over a two-year period, investigators led by Jesse Civan, MD, GI fellow, division of gastroenterology, Thomas Jefferson University Hospital, found that about 1,100 individuals received more than 4 grams of acetaminophen on at least one day. In other words, about 2.5 percent of all patients admitted to the hospital received more than what is currently considered the safe cumulative daily dose on at least one calendar day.
Investigators sought to determine exactly how much acetaminophen was being dispensed in a large tertiary-care hospital and how it compared to the generally accepted safe maximum dose. They reviewed a computer database tracking every patient admitted to their hospital and every dose of medicine prescribed and received. This allowed them to calculate exactly how much medication patients were exposed to, including any medication containing acetaminophen, such as Tylenol®, Percocet® and other similar medicines, and to generate a list of all patients who received more than 4 grams of acetaminophen on at least one calendar day.
Researchers also reviewed liver function and injury, which are reported in the same database, to determine potential detrimental effects of acetaminophen use on patients. By reviewing a specific blood test — the alanine amino-transferase (ALT) test, which is generally used to screen for liver injury possibly related to acetaminophen — Dr. Civan and his colleagues found that only a small minority of patients were administered an ALT test. They attribute this finding to the fact that the blood test is only usually checked when a physician is particularly concerned about a possible liver problem.
In the small minority of patients who did have an ALT checked, there was insufficient data to do a "formal cause analysis" to determine whether an abnormal ALT could be blamed on the acetaminophen exposure. Because of the paucity of ALT monitoring, no conclusion could be reached about whether the acetaminophen exposure might have had any detectable detrimental consequences.
Dr. Civan added that these findings could have implications on public health and the need to improve patient education regarding safe dosages at home, since many patients will likely attempt to emulate the medications provided at the hospital once they get home. He concluded that further study in this closely monitored population in which every dose of acetaminophen-containing medication administered is recorded might shed light on the ongoing discussion at the U.S. Food and Drug Administration and elsewhere regarding new recommendations for maximum safe daily dosing. Dr Civan stressed that although it remains unclear whether blood test abnormalities may have resulted from acetaminophen use, he did not find any evidence of any cases of serious liver injury.
Acetaminophen has been under increasing scrutiny in the U.S. — it is the leading cause of acute liver failure and emergent liver transplant, and previous studies have suggested that unintentional overdose is a significant problem. There has also been debate in the medical literature about whether a less severe form of acetaminophen-induced liver injury due to unintentional overdose may be important.
This study received no pharmaceutical funding.
Dr. Civan will present these data on Monday, May 21 at 2:15 p.m. in 6e, San Diego Convention Center.
Herbal and Dietary Supplement Hepatoxicity in the U.S.A. (Abstract #167)
Dietary supplements used for body building and weight loss are the most common of any supplements to cause liver injury, according to new research from the U.S. Drug Induced Liver Injury Network (DILIN). Dietary supplements include herbal remedies, bodybuilding supplements, health food supplements, or anything that people can buy over the counter or online that is not prescribed by a physician.
Liver injury from medication is the main reason why drugs are taken off the market. While estimates suggest that herbal/dietary supplement products are used by up to 40 percent of the U.S. population, their side effects, including potential toxicity, is not well defined. Researchers led by Victor J. Navarro, MD, an investigator funded by the National Institutes of Health-sponsored DILIN, and professor of medicine, pharmacology and experimental therapeutics, Thomas Jefferson University, Philadelphia, PA, sought to explore liver injury from herbal/dietary supplements by examining the types of products taken, and the severity and outcomes associated with liver injury due to them.
Investigators looked at 109 cases of patients in the DILIN who appeared to have liver damage due to dietary supplements; most were male, white and overweight. They found that the supplements most likely to be the cause of liver injury were those reported for body building and for weight loss.
"There is so little regulation of the many products on the market; we couldn't possibly begin to figure out which products to target first without doing this research," said Dr. Navarro. He added that now that they know that bodybuilding and weight loss supplements are the most common causes of dietary supplement-induced injury among the products, they can focus their efforts accordingly.
Investigators are also looking at targeted components of herbal/dietary supplements. For example, previous studies have shown that green tea extract, which can be added to herbal/dietary supplements in high concentrations in pill form, can potentially cause damage to the liver. So DILIN investigators have also sought to determine how common the ingredients of green tea are in dietary supplements when the manufacturer has not identified it as such.
They hypothesized that green tea extract is prevalent in many products but is not specifically identified — in fact, their research has shown that it is present in up to 40 percent of products in which it was not listed on the label. For this reason, investigators will always have difficulty linking liver injuries to green tea extract unless they do a careful analysis of each product.
Dr. Navarro cautioned that because it is not well known how common liver injury is due to dietary supplements, it is difficult to suggest how likely it is that someone would suffer liver damage, but that this is another area where investigators are looking to do more research.
Investigators now have many more cases to study and their next step is to understand how the supplements cause injury and why. They are working with the Food and Drug Administration to identify various contaminants and determine which of the products on the market are the most harmful, especially since herbal/dietary supplement are not tightly regulated. They are also studying possible factors that may predispose a consumer of herbal/dietary supplement to liver injury, such as genetic makeup.
Dr. Navarro will present the DILIN's research data on Saturday, May 19 at 2:15 p.m. PT in Halls C-G of the San Diego Convention Center.
Provided by Digestive Disease Week
DDW-Statins Shown to Be Safe in Patients With Cirrhosis
May 22, 2012
From Medscape Medical News
Statins Shown to Be Safe in Patients With Cirrhosis
Caroline HelwickSan Diego, California) — Statin therapy is not only safe for people with cirrhosis, it might be potentially beneficial, according to research presented here at Digestive Disease Week 2012.
"We found less progression of liver disease in patients taking statins, and a lower mortality rate. This is contrary to prior beliefs that statins may not be safe in patients with cirrhosis; in fact, they may be beneficial," said lead investigator Sonal Kumar, MD, from Brigham and Women's Hospital in Boston, Massachusetts.
Patients with cirrhosis have decreased hepatic clearance, and thus could be at increased risk for complications, specifically hepatic decompensation. Statins lower portal pressure and, therefore, might be protective of the liver, she explained.
Dr. Kumar and colleagues conducted a study to determine the effect of statin therapy on the risk from hepatic decompensation in 82 people with biopsy-proven cirrhosis who had taken statins for at least 3 months for the treatment of dyslipidemia. This group was compared with 162 control subjects who had cirrhosis but were not taking statins and who were matched in a 2:1 ratio by age, sex and Child-Pugh class.
In each group, 70.4% of patients were Child-Pugh A and 29.6% were Child-Pugh B/C. Other relevant disease-related factors were not different between the groups. Median duration of statin use was 25 months. Median follow-up was 36 months for the statin group and 30 months for the control group.
The primary outcomes were hepatic decompensation (defined as the development of ascites, jaundice, hepatic encephalopathy, or variceal hemorrhage) and time to decompensation.
Statins Cut Decompensating Events in Half
In a multivariate analysis, the use of a statin was associated with a 56% reduction in risk for hepatic decompensation (95% confidence interval [CI], 0.27 to 0.71). There were fewer decompensating events in the statin group than in the control group (39.5% vs 55.6%; P = .01), Dr. Kumar reported.
The largest difference was observed for patients who developed jaundice (7.4% vs 20.9%; P = .001) or ascites (20.9% vs 37.0%; P = .009).
Time to decompensation was significantly longer in the statin group. In the control group, half had decompensated at 2.3 years; in the statin group, median time to decompensation was not reached. In Child-Pugh A patients, median time to decompensation was 8.1 years in the control group; again, it was not reached in the statin group.
In addition, overall mortality was significantly lower in the statin group (37.0% vs 50.6%; P = .043). On multivariate analysis, statin use was significantly associated with a 51% reduction in mortality (95% CI, 0.29 to 0.81), Dr. Kumar reported.
Strikingly, in Child-Pugh A patients, time to death was significantly longer in the statin group than in the control group (7.0 vs 14.4 years; P = .005).
Although 29 patients in the control group underwent liver transplantation, only 2 patients in the statin group did, she added.
There were no differences in cause of death, although for one third of patients, cause of death could not be ascertained.
The study has a number of limitations, Dr. Kumar acknowledged. It is a retrospective study of a heterogeneous population with varied duration of statin therapy; compliance with statin use was not well documented; and investigators could not account for a number of potentially contributing factors, including obesity, use of aspirin or other nonsteroidal anti-inflammatory drugs, and active alcohol consumption.
Bruce Sands, MD, MS, the Dr. Burrill B. Crohn professor of medicine at Mount Sinai Medical Center in New York City, moderated a press briefing during which the results were discussed. "This is a wonderful study, but it is retrospective and hypothesis-generating. I would like to see a prospective randomized controlled trial showing there are actually benefits to statin use," he said.
Zobair Younossi, MD, vice president of research and chair of medicine at the Inova Health System in Falls Church, Virginia, explained that his own research has shown that disease-related mortality is similar among statin users and nonusers. "Statins are safe," he maintained. "Don't worry about further liver toxicity."
Dr. Kumar said that this information should be reassuring to physicians, many of whom discontinue statin use in their patients, which puts them at risk for worsening cardiovascular disease.
Dr. Kumar, Dr. Sands, and Dr. Younossi have disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2012: Abstract 595. Presented May 21, 2012.
Medscape Conference News
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DDWStatins Shown to Be Safe in Patients With Cirrhosis
Medscape Medical News, May 22, 2012
DDWLandmark US Trial Shows Screening Cuts Colorectal Cancer
Medscape Medical News, May 22, 2012
DDWPatients Prefer Colonoscopy Over CT Colonography for Cancer
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DDWPrevalence of GERD is 4 Times Higher Among People With IBS
Medscape Medical News, May 20, 2012
DDWComplications Are Emerging for Baby Boomers With HCV
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From Medscape Medical News
Statins Shown to Be Safe in Patients With Cirrhosis
Caroline HelwickSan Diego, California) — Statin therapy is not only safe for people with cirrhosis, it might be potentially beneficial, according to research presented here at Digestive Disease Week 2012.
"We found less progression of liver disease in patients taking statins, and a lower mortality rate. This is contrary to prior beliefs that statins may not be safe in patients with cirrhosis; in fact, they may be beneficial," said lead investigator Sonal Kumar, MD, from Brigham and Women's Hospital in Boston, Massachusetts.
Patients with cirrhosis have decreased hepatic clearance, and thus could be at increased risk for complications, specifically hepatic decompensation. Statins lower portal pressure and, therefore, might be protective of the liver, she explained.
Dr. Kumar and colleagues conducted a study to determine the effect of statin therapy on the risk from hepatic decompensation in 82 people with biopsy-proven cirrhosis who had taken statins for at least 3 months for the treatment of dyslipidemia. This group was compared with 162 control subjects who had cirrhosis but were not taking statins and who were matched in a 2:1 ratio by age, sex and Child-Pugh class.
In each group, 70.4% of patients were Child-Pugh A and 29.6% were Child-Pugh B/C. Other relevant disease-related factors were not different between the groups. Median duration of statin use was 25 months. Median follow-up was 36 months for the statin group and 30 months for the control group.
The primary outcomes were hepatic decompensation (defined as the development of ascites, jaundice, hepatic encephalopathy, or variceal hemorrhage) and time to decompensation.
Statins Cut Decompensating Events in Half
In a multivariate analysis, the use of a statin was associated with a 56% reduction in risk for hepatic decompensation (95% confidence interval [CI], 0.27 to 0.71). There were fewer decompensating events in the statin group than in the control group (39.5% vs 55.6%; P = .01), Dr. Kumar reported.
The largest difference was observed for patients who developed jaundice (7.4% vs 20.9%; P = .001) or ascites (20.9% vs 37.0%; P = .009).
Time to decompensation was significantly longer in the statin group. In the control group, half had decompensated at 2.3 years; in the statin group, median time to decompensation was not reached. In Child-Pugh A patients, median time to decompensation was 8.1 years in the control group; again, it was not reached in the statin group.
In addition, overall mortality was significantly lower in the statin group (37.0% vs 50.6%; P = .043). On multivariate analysis, statin use was significantly associated with a 51% reduction in mortality (95% CI, 0.29 to 0.81), Dr. Kumar reported.
Strikingly, in Child-Pugh A patients, time to death was significantly longer in the statin group than in the control group (7.0 vs 14.4 years; P = .005).
Although 29 patients in the control group underwent liver transplantation, only 2 patients in the statin group did, she added.
There were no differences in cause of death, although for one third of patients, cause of death could not be ascertained.
The study has a number of limitations, Dr. Kumar acknowledged. It is a retrospective study of a heterogeneous population with varied duration of statin therapy; compliance with statin use was not well documented; and investigators could not account for a number of potentially contributing factors, including obesity, use of aspirin or other nonsteroidal anti-inflammatory drugs, and active alcohol consumption.
Bruce Sands, MD, MS, the Dr. Burrill B. Crohn professor of medicine at Mount Sinai Medical Center in New York City, moderated a press briefing during which the results were discussed. "This is a wonderful study, but it is retrospective and hypothesis-generating. I would like to see a prospective randomized controlled trial showing there are actually benefits to statin use," he said.
Zobair Younossi, MD, vice president of research and chair of medicine at the Inova Health System in Falls Church, Virginia, explained that his own research has shown that disease-related mortality is similar among statin users and nonusers. "Statins are safe," he maintained. "Don't worry about further liver toxicity."
Dr. Kumar said that this information should be reassuring to physicians, many of whom discontinue statin use in their patients, which puts them at risk for worsening cardiovascular disease.
Dr. Kumar, Dr. Sands, and Dr. Younossi have disclosed no relevant financial relationships.
Digestive Disease Week (DDW) 2012: Abstract 595. Presented May 21, 2012.
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