Thursday, December 29, 2011

HCV News Ticker-Cirrhosis Tied to Increased Risk of Liver Cancer in Diabetics

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Management of Hepatitis C Infection

Cirrhosis Tied to Increased Risk of Liver Cancer in Diabetics

By David Douglas

NEW YORK (Reuters Health) Dec 26 - Cirrhosis and hepatitis are associated with the occurrence of hepatocellular carcinoma (HCC) in patients with diabetes, and hepatitis C is of particular importance, Taiwanese researchers report in a November 15 online paper in The American Journal of Gastroenterology.

As Dr. Shih-Wei Lai told Reuters Health by email, "In our study, diabetic patients comorbid with liver cirrhosis, hepatitis B, and hepatitis C were at significantly increased risk of developing hepatocellular carcinoma, and the risk associated with hepatitis C was stronger than that with hepatitis B."

Dr. Lai of China Medical University, Taichung and colleagues note that there is accumulating evidence that patients with diabetes mellitus are more prone to cancer in general and liver cancer in particular. An American study indicated that the risk of HCC in diabetic patients was more than twice that in non-diabetics, and there have been some similar findings in Taiwan.

To clarify the effect of diabetes on HCC risk, the team examined a health insurance database covering the years 2000 to 2005 and used the information to compare 19,349 newly diagnosed diabetes patients with 77,396 matched controls. Where possible, they were followed until the end of 2008.

The HCC incidence was doubled in diabetics compared with controls (21.0 versus 10.4 per 10,000 person-years), which translated to an adjusted hazard ratio of 1.73, the team found. Hazard ratios were also significantly and independently increased by being male (2.32), and having cirrhosis (8.65), hepatitis B (2.52), and hepatitis C (5.61).

Stratified analyses showed that subjects with diabetes and cirrhosis along with hepatitis C had the greatest elevation in risk (hazard ratio, 72.4).

The researchers then went on to examine the association between HCC and anti-diabetic medication. After adjustment, metformin use was associated with significant protection (hazard ratio, 0.49). This was also true of thiazolidinediones (hazard ratio, 0.56). Taking insulin, sulfonylureas, and other agents also reduced the risk, but not significantly.

Overall, given the influence of the studied comorbidities, concluded Dr. Lai, "These observations suggest that patients with these disorders may be the high-risk group that deserves to be closely monitored. The importance of hepatitis C should not be overlooked."


Am J Gastroenterol 2011.

Risk Factors for Hepatocellular Carcinoma in a Cohort Infected With Hepatitis B or C

Scott R Walter; Hla-Hla Thein; Heather F Gidding; Janaki Amin; Matthew G Law; Jacob George; Gregory J Dore

Posted: 12/28/2011; J Gastroenterol Hepatol. 2011;26(12):1757-1764. © 2011 Blackwell Publishing

Discussion Only

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This study identifies sociodemographic and health factors predictive of developing HCC among a cohort of people with chronic HBV or HCV infection in NSW. The incidence of HCC increased with age and comorbidity score, and was higher among males, metropolitan residents, and those with ALD, and particularly cirrhosis. Older age, being male, and having a high comorbidity score were significantly and independently associated with the risk of HCC. Co-infection with HBV and HCV was associated with increased HCC risk in the HCV cohort, and of all risk factors considered, cirrhosis conferred the greatest additional risk, regardless of infection type.

The risk of HCC was observed to increase significantly with age for both HBV- and HCV-infected groups. Such an increase in risk with age has been widely observed,[32] but in some countries, age-specific incidence peaks in the 60s, rather than late 70 s or beyond, possibly due to variation in the prevalence of certain risk factors between regions.[17,21]

Being male is another well-known risk factor for HCC, although there is considerable regional variation in the relative risk compared to females.[21] While relative risks of males compared to females for HCC among the general population range from close to one to almost nine, in most regions in the world, males have two to four times the risk of females,[21] consistent with our results.

A clear increase in the risk of HCC with comorbidity score was observed for both infection groups. Few studies have assessed the association between comorbidity score and HCC risk, as it is often more informative to examine individual health conditions. Each comorbid condition influences the risk of HCC by varying degrees, and multiple conditions might interact in complex ways. However, in terms of identifying high-risk individuals, the comorbidity score quantifies the combined effect of multiple conditions, without the need to interpret risks associated with multiple factors and their interactions.

A number of papers have reported a twofold to threefold increase in HCC risk due to diabetes,[14–16,26] some of which also found an interaction between viral hepatitis and diabetes.[14,16] While including diabetes in the models suggested an increase in the risk of comparable magnitude, the difference was not sufficiently significant to remain in the final model, suggesting that in our cohort, this is a low-risk condition relative to other factors considered.

Alcohol consumption has been identified as a key risk factor for HCC, interacting synergistically with chronic viral hepatitis infection,[16,33] but relatively few studies have examined the risk associated with ALD.[34] We observed significant risk associated with hospitalization with this condition, possibly through the combined effects of alcohol-related and hepatitis-related liver injury. The observed increased risk of HCC among those with HBV/HCV co-infection is consistent with other studies, which found that the combined effect of the two infections is more than additive, but less than multiplicative.[17,18,20,35]

Cirrhosis is well known as the precursor for the vast majority of chronic viral hepatitis-related HCC cases.[19,36,37] Not surprisingly, our study identified cirrhosis as the strongest predictor of HCC for both HBV and HCV cohorts. Two studies based in Taiwan found a 12-fold and 50-fold increase in risk due to cirrhosis among a HBV-infected cohort.[25,38] Sherman reports a more than 20-fold increase in HCC incidence in people with HCV and cirrhosis, compared to those with HCV alone.[36] The magnitude of these estimates approximately agrees with the very high risk identified in our study. The combined effects of cirrhosis and ALD indicated further amplified risk of HCC, particularly among those with HCV. Having a hospital record for both conditions likely indicates advanced or rapidly-progressing liver disease.

A limitation of this study was the incompleteness of country of birth information in the viral hepatitis notification data, which inhibited analysis of the differential risk of developing HCC between people born in different regions. This is particularly pertinent, given that more than half of the HBV-infected group have immigrated from HBV-endemic countries, such as China and Vietnam,[39,40] while the majority of those with HCV are Australian born.[41] Region of birth might also confound the association between remoteness and HCC, since there are much higher proportions of Asian born people in metropolitan areas than non-metropolitan areas.[42] This is particularly likely to be a factor among the HBV-infected cohort. More limited access to specific HCC diagnostic services in non-metropolitan areas might also be a factor in producing an apparently lower incidence of HCC.

A further limitation was the availability of cirrhosis data only through hospitalization codes, particularly as liver biopsy and hepatic elastography diagnosis are generally undertaken through outpatient services. Also, linked treatment data were not available for this study, which eliminated the possibility of examining the extent to which antiviral therapy reduces HCC risk; however, this might form the basis of future studies when additional data permit.

HCC screening and surveillance among at-risk groups have only relatively recently been shown to improve survival.[43,44] Cases only presenting when symptomatic often have a poorer prognosis and fewer treatment options than those detected in the asymptomatic stage of disease.[24,45] In light of its ability to detect tumors early and improve treatment eligibility and survival, screening and surveillance play a key role in reducing the burden of HCC. However, it is only practiced by some groups in NSW, with less than 20% of HCC cases being identified via surveillance.[45,46] Identifying and quantifying risk factors specific to a population, as we have done, forms an integral part of targeting cost-effective surveillance and provides motivation for more widespread screening of high-risk groups.

Antiviral therapy has been shown to limit the progression of liver disease, and in some HBV cases, can reverse decompensated cirrhosis, considerably reducing the risk of HCC.[37,47] Thus, antiviral therapy of chronic viral hepatitis represents a pivotal pathway for reducing the burden of HCC. This also bolsters the case for increasing treatment uptake in general among those with chronic viral hepatitis infection, given that currently, approximately 5% of HBV-infected people[48] and 1–2% of HCV-infected people[41] receive antiviral therapy. A combination of surveillance and treatment has been shown to be a more cost-effective way to reduce the burden of liver cancer than surveillance alone.[46]

In summary, this study has identified and quantified important risk factors for HCC within a high-risk, population-based cohort. Several key factors emerged as independent and significant risks for HCC. Although some previously-reported risk factors were not significant in our analysis, those that were identified were largely consistent with studies conducted in other regions of the world. The association with older age highlights the potential impact of HBV and HCV screening of at-risk groups and early clinical assessment. Antiviral therapy for chronic viral hepatitis is an important strategy for preventing HCC, and further research is required to quantify its mitigation of HCC risk at a population level in the Australian context.

If you carry a donor card people like me can have a transplant

A cancer sufferer who has been placed on the transplant waiting list wants her story to raise awareness of the importance of carrying a donor card.

Rhiannon Jeans, 43, from Scunthorpe, has suffered from Primary Billiary Cirrhosis, an incurable liver disease, for ten years and has since been diagnosed with liver cancer.

This has made the need for Rhiannon's surgery more urgent and she has since been placed on the waiting list for a liver transplant.

She said: "My condition is a chronic liver disease that usually affects women. It is quite rare and people don't often know that they have got it.

"I always knew that the cure was a transplant as it is an incurable disease but it depends on how the disease progresses.

"But when I found out I had liver cancer this made the need for a transplant more urgent.".. Continue reading..


Early guidance on use of hepatitis C protease inhibitors in HIV-co-infected patientsMichael Carter

Published: 29 December 2011

Doctors in the US state of Maryland have issued preliminary guidance for the use of hepatitis C protease inhibitors by patients co-infected with HIV. Published in the online edition of Clinical Infectious Diseases, the provisional recommendations support use of the protease inhibitors in selected groups of co-infected patients.

“The benefits of including these medications will outweigh the risks for some individuals,” comment the authors.

In May 2011 the protease inhibitors boceprevir and telaprevir were approved in the US for the treatment of chronic hepatitis C genotype 1 infection. In clinical trials, involving hepatitis C-mono-infected individuals, the use of these drugs in combination with pegylated interferon and ribavirin improved rates of sustained virological response by between 25% and 31%.

Clinical trials into the safety and efficacy of these hepatitis C protease inhibitors are currently underway involving patients co-infected with HIV....Continue reading..

Top 10 HIV and hepatitis stories of 2011

HIV prevention garnered the most headlines, with studies showing that antiretroviral therapy prevents transmission and pre-exposure prophylaxis works. On the hepatitis C front, the first new direct-acting antiviral drugs were approved, ushering in a new era of more effective treatment.

In our last issue for 2011, reviews some the year's major news highlights. HIV prevention garnered the most headlines, with studies showing that antiretroviral therapy (ART) prevents transmission and pre-exposure prophylaxis (PrEP) works -- at least for some people some of the time. On the hepatitis C front, the first new direct-acting antiviral drugs were approved, ushering in a new era of more effective treatment.

1. AIDS at 30

An overarching theme of the year was the 30th anniversary of AIDS, an opportunity to take stock of the remarkable progress over the past 3 decades as well as work yet to be done.

The anniversary is dated from the first medical report about the epidemic. The June 5, 1981, issue of Morbidity and Mortality Weekly Report (MMWR) included an article about a strange cluster of Pneumocystis pneumonia (PCP) cases among previously healthy gay men in Los Angeles. The July 4 issue described 2 dozen cases of PCP and a rare cancer, Kaposi sarcoma, in California and New York. The first 2 MMWR reports of AIDS are included in The Body's comprehensive archive of articles on the history of the HIV/AIDS epidemic.

2. Treatment is Prevention

The biggest HIV news of 2011 involved findings that were widely anticipated and already informing clinical practice and personal decisions, but data from a large randomized controlled trial removed any doubt: HIV treatment isHIV prevention....Continue reading..

Clinical Trials

Drug Trials Not Representative, Researchers Charge

By Emily P. Walker, Washington Correspondent, MedPage Today
Published: December 27, 2011

Few major randomized, controlled clinical trials examine the effects of a drug in patients who have multiple chronic conditions, even though more than one-quarter of all Americans are living with at least two chronic health conditions, researchers reported.

The proportion is even greater for older individuals, two out of three of whom are likely to have at least two chronic health conditions, according to Alejandro Jadad, MD, and colleagues from the Centre for Health, Wellness and Cancer Survivorship at the University Health Network in Toronto.

That means that most trials on which the FDA bases its approval of new drugs are not generalizable to the U.S. population, they wrote in a research letter published in the Dec. 28 issue of the Journal of the American Medical Association.

Jadad and his colleagues examined all randomized controlled studies that dealt with an intervention for a long-lasting or chronic disease or condition that were published from January-March in 1995, 2000, 2005, and 2010 in five major peer-reviewed medical journals -- BMJ, CMAJ, JAMA, The Lancet, and the New England Journal of Medicine -- as well as six journals that focus on the most prevalent chronic conditions, including Circulation and Annals of General Psychiatry.

Only six of the 284 published trials analyzed (2.1%) explicitly included patients with multiple chronic conditions, and that percentage didn't change much from 1995 to 2010. In 179 of the randomized controlled trials, patients with multiple medical conditions were explicitly excluded from the trial.

Patients with multiple conditions were mentioned often in trial reports, although not actually included in the trial. About 70% of the published trial reports mentioned multiple coexisting diseases; with general medical journals describing them more often than specialized journals (72% versus 69%; P=0.02).

The letter authors concluded that few randomized controlled clinical trials published in the last 15 years have included patients with multiple chronic conditions.

Although the study was small, the authors said the finding "invites reflection about the risk of unintended harm from inappropriate generalization of trial results conducted in populations with a single disease."

"Given the possible drug-to-drug, drug-to-disease, and disease-to-disease interactions that remain unexamined, most of the evidence gathered to date by [randomized controlled clinical trials] is of limited value to guide decisions," they wrote.

The study authors said it may be useful for the FDA to have drug companies include subgroups of patients with the most common combinations of diseases in their drug development process; to observe safety outcomes of adding a new drug to patients who are already medicated for other conditions; and to have post-marketing studies that include the risk stratification to allow for meta-analyses across populations, such as those with multiple conditions.

Off Topic

Most intriguing ‘Medical Mysteries’ of 2011

Highlights from our series of tough-to-diagnose medical problems.
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