Excess liver-related morbidity of chronic hepatitis C patients, who achieve a sustained viral response, and are discharged from care.
Hepatitis-related Renal Disease
Entry completed for BI 201335 plus pegIFN/RBV Phase III hepatitis C Trial
In The News
Chinese doctors find way to detect liver cancer earlier
SHANGHAI, Dec. 19 (Xinhua) -- A simple test using just one milliliter of a patient's blood can tell whether the patient has liver cancer -- even if the tumor is less than two centimeters in diameter, new medical research in Shanghai shows.
Doctors at the Zhongshan Hospital, a major medical institution affiliated with Fudan University, have found that seven microRNAs, or ribonucleic acid molecules, are strongly related to liver problems. This discovery can raise the accuracy of tests for early-stage liver cancer to almost 90 percent.
Each test will cost a patient only about 100 yuan (15.9 U.S. dollars), said Dr. Fan Jia, vice president of the hospital and one of the country's leading liver surgeons.
The research results have been published on the website of the Journal of Clinical Oncology, the official journal of the American Society of Clinical Oncology.
China sees half of the world's new liver cancer cases each year. More than 60 percent of Chinese liver cancer patients are diagnosed too late to be cured, according to the medical paper written by Fan's team.
Fan said that the current check for liver cancer, which is based on the volume of alpha-fetoprotein (AFP) in blood, was not accurate for some people, including pregnant women and patients with hepatitis, gonadal carcinoma or gastrointestinal cancer, as their AFP levels are also possibly high.
Fan's team examined blood samples from 934 people, including healthy people and those with hepatitis B, cirrhosis or liver cancer between 2008 and 2010. The team found that seven of the more than 130 microRNAs in their blood were closely linked to liver problems, and could, therefore, be used to test the health of a person's liver.
The team is applying for patents for the test in China, the United States, Japan and the European Union, and is still in the process of developing a microchip containing the seven microRNAs before the test will be adopted on a large scale.
New at CCO
CCO Hepatology inPractice™ is now live! Simultaneously search multiple databases offering instant answers to your clinical questions:
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New At NATAP
Impact of HCV protease-inhibitor-based triple therapy for chronic HCV genotype 1 infection - Review -
"Measurement of HCV RNA at week 4 of treatment and at week 8 (if boceprevir is chosen) or week 12 (if telaprevir is chosen) is now mandatory. Adequate laboratory infrastructure and rapid turnaround time will be required to ensure the new treatment algorithms can be implemented effectively. Patient education and adherence are more important than ever.....Controversies that remain to be resolved include whether abbreviated treatment could be used in previous relapsers who achieve an extended RVR, and the optimal treatment duration for patients with cirrhosis and for Black patients."
Intravenous silibinin as 'rescue treatment' for on-treatment non-responders to pegylated interferon/ribavirin combination therapy
from Jules: there are several potential ways to use ivSilibinin: for nonresponders to triple therapy along with continuation of peg/rbv; at the initiation of therapy for cirrhotics or null cirrhotics but the idea of infusion therapy may be difficult for some; as firstline therapy for patients along with triple therapy who have unfavorable TT & CT IL28b polymorphisms.
New At GastroHep
Ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis
This month's issue of Hepatology investigates ultrasonographic surveillance of hepatocellular carcinoma in cirrhosis.
Detection of small hepatocellular carcinoma eligible for curative treatment is increased by surveillance, but its optimal periodicity is still debated.
Dr Jean-Claude Trinchet and colleagues from France conducted a randomized trial comparing 2 ultrasonographic periodicities, at 3 months versus 6 months.
A multicenter randomized trial was conducted in France and Belgium.
Patients with histologically proven compensated cirrhosis were randomized into 2 groups, with ultrasonography every 6 months or 3 months.
Hepatocellular carcinoma was confirmed in only 10%
Hepatology
For each focal lesion detected, diagnostic procedures were performed according to European Association for the Study of the Liver guidelines.
Cumulative incidence of events was estimated, then compared using Gray's test.
The prevalence of hepatocellular carcinoma 30 mm in diameter was the main endpoint.
A sample size of 1,200 patients was required.
The team randomized a total of 1,278 patients.
The research team detected at least one focal lesion in 28% of patients but hepatocellular carcinoma was confirmed in only 10%.
Focal-lesion incidence was not different between the groups but incidence of lesions 10 mm or less was increased.
No difference in either hepatocellular carcinoma incidence or in prevalence of tumors 30 mm or less in diameter was observed between the randomized groups.
Dr Trinchet's team concluded, "Ultrsonography surveillance, performed every 3 months, detects more small focal lesions than ultrasonography every 6 months, but does not improve detection of small hepatocellular carcinoma, probably because of limitations in recall procedures."
Hepatology 2011: 54(6): 1987–1997
20 December 2011
Serum ferritin concentration and transferrin saturation before liver transplantation
Serum ferritin concentration and transferrin saturation before liver transplantation predict decreased long-term recipient survival, reports December's issue of Hepatology.
Serum ferritin concentration is a widely available parameter used to assess iron homeostasis.
It has been described as a marker to identify high-risk patients awaiting liver transplantation but is also elevated in systemic immune-mediated diseases, metabolic syndrome, and in hemodialysis where it is associated with an inferior prognosis.
Dr Christian Strassburg and colleagues from Germany analyzed whether serum ferritin is not only a predictor of liver-related mortality prior to liver transplantation but also an independent marker of survival following liver transplantation.
In a dual-center, retrospective study, a cohort of 328 consecutive first-liver transplantation patients from Hannover Medical School, Germany, and 82 consecutive liver transplant patients from Regensburg University Hospital, Germany as validation cohort were analyzed.
In patients exhibiting serum ferritin 365 μg/L or more versus less than 365 μg/L prior to liver transplantation, 1-, 3-, and 5-year post-liver transplantation survival was 73% versus 81%, 64% versus 77%, and 61% versus 74%, respectively.
Overall survival with serum ferritin concentrations 365 μg/L or more was 54%
Hepatology
The team confirmed this in the validation cohort.
Multivariate analyses identified serum ferritin of 365 μg/L or more combined with transferrin saturation less than 55%, hepatocellular carcinoma, and the survival after liver transplantation (SALT) score as independent risk factors for death.
In patients with serum ferritin concentrations 365 μg/L or more and transferrin saturation less than 55%, the overall survival was 54% versus 75% in the remaining group.
In the validation cohort, it was 29% versus 72%, respectively.
Dr Strassburg's team concludes, "Serum ferritin concentration 365 μg/L or more in combination with transferrin saturation less than 55% before liver transplantation is an independent risk factor for mortality following liver transplantation."
"Lower transferrin saturation combined with elevated serum ferritin concentrations indicate that acute phase mechanisms beyond iron overload may play a prognostic role."
"Serum ferritin concentration therefore not only predicts pre-liver transplantation mortality but also death following liver transplantation."
Hepatology 2011: 54(6): 2114–2124
19 December 2011
Spike Seen in Transplants for Fatty Liver Disease
By Charles Bankhead, Staff Writer, MedPage Today
Published: December 20, 2011
Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner
The frequency of liver transplantation for nonalcoholic steatohepatitis (NASH) increased six-fold over the past 15 years and recipients live longer compared with other liver transplant patients, a review of a national database showed.
Consistent with the obesity epidemic, the proportion of liver transplants involving patients with nonalcoholic steatohepatitis (NASH) increased from 1.2% from 1997 to 2003 to 7.4% in 2010, making NASH the fourth most common reason for liver transplantation.
Post-transplant survival of NASH patients proved superior to that of all but four other types of recipients: primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and hepatitis B infection (HBV), according to an article published online in Liver Transplantation.
The authors pointed to a reduced mortality from graft failure as a possible explanation for the improved survival of NASH patients after liver transplantation.
"Only 8.6% of deaths in patients with NASH were caused by graft failure compared with 16.6% of deaths in patients without NASH," wrote Anita Afzali, MD, of the University of Washington in Seattle, and co-authors. "This is likely due to lower rates of recurrence of NASH and cirrhosis in transplanted livers as compared to recurrence of other diseases such as hepatitis C and hepatitis B."
Detailed screening of transplantation candidates for cardiovascular disease might have excluded more high-risk patients with NASH, they added.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the U.S., affecting almost 30% of the population. In 15% to 20% of cases, NAFLD progresses to NASH, according to the authors.
Central obesity and insulin resistance are the most common factors in NAFLD and NASH. Given the growing prevalence of obesity, as many as 25 million Americans could have NASH, which can progress to cirrhosis, hepatocellular carcinoma, and liver failure.
Some authorities have predicted that NASH will become the leading indication for liver transplantation within 10 to 20 years, surpassing the current leader, hepatitis C virus (HCV) infection.
Patients with NAFLD/NASH have an increased risk of cardiovascular morbidity and mortality because of associated risk factors. The heightened cardiovascular risk could adversely affect post-transplantation survival. However, NASH patients might also have improved survival because of a reduced risk of disease recurrence, the authors continued.
No studies have examined recent national trends in liver transplantation for NASH-related reasons. To address the gap in data, Afzali and colleagues analyzed data from the United Network for Organ Sharing (UNOS).
The investigators sought out all adults who had first-time cadaveric liver transplantations in the U.S. from 1997 to 2010. The analysis yielded 53,738 patients, of whom 1,810 had NASH as the indication for transplantation.
During 1997 to 2003, NASH accounted for 1.2% of all liver transplantations. Thereafter, the proportion of transplantations involving NASH increased until NASH represented the fourth most common reason, trailing only hepatocellular carcinoma (HCC), HCV, and alcohol-related liver disease.
From 2008 to 2010, the proportion of liver transplantations involving patients with NASH exceeded those involving patients with cryptogenic cirrhosis. The proportion of liver transplants performed for NASH was 7.4% in 2010.
The proportion of transplantations for NASH and cryptogenic cirrhosis combined increased steadily after 2003, suggesting the increase in NASH-related indications was not a reflection of "diagnostic transfer," the authors noted.
Patients with NASH or cryptogenic cirrhosis tended to be older, white, female, obese, and diabetic, as compared with transplant recipients with other types of liver disease. Other clinical and laboratory characteristics were similar for patients with and without NASH or cryptogenic cirrhosis, as were donor characteristics.
As compared with liver recipients with other types of liver disease, those with NASH or cryptogenic cirrhosis did not have an increased mortality (HR 0.94 for NASH, HR 0.97 for cryptogenic cirrhosis). Nor did they have increased risk of graft failure (HR 0.89 for NASH and HR 0.95 for cryptogenic cirrhosis).
Adjustment for donor characteristics alone had little impact on survival or graft failure. Adjustment for donor and recipient characteristics resulted in significantly reduced risks of death and graft failure among patients with NASH and cryptogenic cirrhosis:
- NASH death: adjusted HR 0.75, 95% CI 0.66 to 0.85
- NASH graft failure: adjusted HR 0.76, 95% CI 0.68 to 0.85
- Cryptogenic cirrhosis death: adjusted HR 0.86, 95% CI 0.80 to 0.93
- Cryptogenic cirrhosis graft failure: adjusted HR 0.90, 95% CI 0.84 to 0.96
The results did not change significantly in a separate analysis of the years 2004 to 2010.
Patients with NASH or cryptogenic cirrhosis had a one-year survival of 87.6%, three-year survival of 82.2%, and five-year survival of 76.7%. The survival was superior to that of patients with HCC, HCV, alcoholic liver disease, acute hepatic necrosis, hemochromatosis, and cryptogenic liver disease.
"Our study demonstrates that post-transplantation survival in patients with NASH is excellent and comparable to patients with all other liver diseases combined," the authors wrote in conclusion. "Post-transplantation survival in patients with NASH is, in fact, superior to the post-transplantation survival of patients with other common indications for transplantation."
A study limitation was that the diagnosis of liver disease in the UNOS database was based on reporting by the transplantation center so the accuracy of the data could not be confirmed. Also, reported causes of death may have been inaccurate.
FYI
(RTTNews.com) - The U.S. Food and Drug Administration has revised the label of Sanofi's (SNY) heart rhythm drug, Multaq, to include new safety warnings, as the drug has been found to increase the risk of serious cardiovascular events, including death, when used by patients in permanent atrial fibrillation.
Multaq is approved in more than 50 countries, including, the United States, Germany, the United Kingdom, Italy, Spain and France.
In the U.S., Multaq was approved in July 2009 to reduce the risk of cardiovascular hospitalization in patients with atrial fibrillation or atrial flutter. The drug was approved in the European Union in November 2009 for clinically stable adult patients with a history of, or current non-permanent atrial fibrillation to prevent recurrence of atrial fibrillation or to lower ventricular rate.
Multaq has been the subject of safety concerns both before and after its approval.
In one of the clinical trials, before its approval, the drug caused an increased risk of death in high-risk patients with congestive heart failure.
So the FDA approval of Multaq in 2009 came only with a black box warning - the most serious type of warning, against its use by patients with New York Heart Association, or NYHA, Class IV heart failure or NYHA Class II-III heart failure.
Following several reports of hepatocellular liver injury and hepatic failure in patients treated with Multaq, the FDA, in January of this year, alerted healthcare professionals and patients about the severe liver injury associated with the drug, including two cases of acute liver failure, which lead to liver transplantation for the patients. Accordingly, the drug's label was revised to reflect the concerns of liver injury.
Now, after reviewing data from two clinical trials, namely the PALLAS trial and the ATHENA trial, the FDA has provided new information and recommendations for the use of Multaq to manage the potential serious cardiovascular risks with the drug.
According to the new recommendations in the label, Multaq should not be prescribed to patients with atrial fibrillation, or AF, who cannot or will not be converted into normal sinus rhythm (permanent AF), because the drug doubles the rate of cardiovascular death, stroke, and heart failure in such patients. The heart rhythm of patients should be monitored by electrocardiogram at least once every 3 months.
The revised label also recommends that if the patient is in AF, Multaq should be stopped or, if clinically indicated, the patient should be cardioverted. Patients prescribed Multaq should receive appropriate antithrombotic therapy.
The regulatory agency is also reviewing the risk evaluation and mitigation strategy, or REMS, for Multaq to determine the changes necessary to ensure that the benefits of the drug outweigh the risks of cardiovascular death, stroke, and heart failure.
The FDA in its statement said that from approval in July 2009 through October 2011, a total of about 1.3 million Multaq prescriptions were dispensed and roughly 278,000 patients received Multaq prescriptions from U.S. outpatient retail pharmacies.
In September of 2011, the European Medicines Agency recommended restricting use of Multaq following reports of two cases of serious liver injury leading to liver transplantation in patients taking the drug.
Given that Multaq provides a benefit for patients with non-permanent atrial fibrillation, it is necessary that healthcare professionals who prescribe Multaq follow the recommendations in the revised Multaq drug label as recommended by the regulatory agency.
Once hailed as a potential blockbuster, Multaq has been plagued with safety concerns, which have taken a toll on its sales. The drug logged in sales of 172 million euros last year and 131 million euros in the first half of 2011
Big Pharma
10 Biotech Stock Predictions for 2012The Amgen(AMGN_) strategy of returning cash to shareholders in form of share buybacks, Dutch tender offers and dividends is abandoned in favor of ramped up acquisitions i.e. Gilead Sciences(GILD_) buying Pharmasset(VRUS_). Large-cap biotech firms start acting like Big Pharma -- choosing to buy growth instead of seeking it from internal drug development....
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