(Summary: Previous studies of taribavirin were not dosed by weight, and trial results in terms of SVR were not impressive. New studies using weight-based dosing not only show that taribavirin in combination with peginterferon is as effective as ribavirin / peginterferon but also that taribavirin causes less anemia and minimizes the need for erythropoiesis-stimulating agents (ESAs), thus proving more cost effective.)
Article: Prevalence of Vitamin D Deficiency in Chronic Liver Disease by, Arteh J, Narra S, Nair S. Department of Internal Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Source: Dig Dis Sci. 2010 Sep;55(9):2624-8. Epub 2009 Dec 4.
Summary by Alan Franciscus
There has been a lot of news about vitamin D deficiency in the general population and in liver disease. There has been some evidence that suggest that cirrhosis interferes with the metabolism of calcium and vitamin D. In the current small study the authors sought to determine the prevalence of vitamin D deficiency.
One hundred and eighteen people—43 people with hepatitis C cirrhosis, 57 people with hepatitis C but who did not have cirrhosis, and 18 people with non-hepatitis C-related cirrhosis—were seen consecutively while attending the University of Tennessee Hepatology Clinic. The study participants had their vitamin D level measured.
The severity of vitamin D deficiency was graded as mild—20-32 ng/ml, moderate—7-19 ng/ml, or severe—32 ng/ml.
Almost all of the patients were found to have some degree of vitamin D deficiency—109 out of 118 patients (92.4%). In the group with cirrhosis 16.3% had mild, 48.8% had moderate, and 30.2% had severe vitamin D deficiency. In the group with no cirrhosis, 22.8% had mild, 52.6% had moderate, and 14% had severe vitamin D deficiency. In the group of those with cirrhosis (but not hepatitis C) 38.9% had mild, 27.8% had moderate, and 27.8% had severe vitamin D deficiency. Patients with cirrhosis were more likely to have severe vitamin D deficiency (
Top-line results from Vertex’s phase III study of telaprevir plus pegylated interferon and ribavirin called the REALIZE trial were released today. The trial treated HCV genotype 1 people who DID NOT achieve a sustained virological response (SVR—HCV RNA undetectable 24 weeks after treatment was completed) with a previous course of pegylated interferon plus ribavirin. The study included people who had a relapse (number = 354 patients), who were partial responders (n= 124 patients) or who had a null response (n=184 patients)*.
An overall sustained virological response of 65% was achieved in the telaprevir based arms compared to 17% of people in the control arm (pegylated interferon/ribavirin – without telaprevir). Breaking it down by type of response and when the first dose of telaprevir was given (simultaneous start arm and delayed start arm), the results showed an SVR rate of 83 and 88% in relapsers, 59 and 54% in partial responders and 29 and 33% in null responders.
HCV Advocate will update once we have analyzed the trial results.
*Definitions of response types (per Vertex press release):
•Relapser – undetectable at the completion of at least 42 weeks of therapy but became detectable during the follow-up period
•Partial responder – people who achieved at least a 2 log 10 reduction in viral load at week 12, but who were never undetectable during therapy
•Null responder – a person who achieved LESS than a 2 log 10 reduction in HCV RNA by week 12
Idenix reported that the Food and Drug Administration (FDA) has put two of its experimental therapies on clinical hold due to safety concerns. The two drugs are:
•IDX182 – HCV polymerase inhibitor (phase I) and,
•IDX320 –HCV protease inhibitor (phase II)
According to published reports, all of the studies have been completed so there are no patients who are currently receiving either medication. The drugs were put on hold by the FDA because of possible liver toxicities.
The next step in the process is for the FDA to review all of the data from the studies and make a determination if the clinical trials can proceed or if they will be canceled altogether.
Idenix has two other HCV drugs in clinical development—IDX375 and IDX184 (HCV polymerase inhibitors) in phase I and phase II studies.
Article: Alpha-fetoprotein above normal levels as a risk factor for the development of hepato-cellular carcinoma in patients infected with hepatitis C virus by Tateyama M, Yatsuhashi H, Taura N, et al. J Source: Gastroenterol. 2010 Aug 14. [Epub ahead of print] http://www.ncbi.nlm.nih.gov/pubmed/20711614
Alfa-fetoprotein (AFP) is a blood test that is used widely to detect abnormalities that may be an indication of the presence of certain types of cancers. In pregnant woman, the test is used to find out if the baby is more likely to have certain birth defects. In viral hepatitis it is a test used to indicate liver cancer. However, it is not always an accurate test so liver imaging is used in conjunction with the test to detect possible liver cancer. In people with chronic hepatitis B the AFP test and a liver imaging test are recommended every 6 to 12 months regardless of how much the liver is damaged. In people with chronic hepatitis C most providers will generally start monitoring for liver cancer using the AFP test and liver imaging once someone has developed severe fibrosis or cirrhosis.
In the current study, a total of 707 patients with chronic hepatitis C were evaluated for liver cancer prior to beginning an HCV clinical trial or before starting interferon treatment. They looked at many factors including age, gender, HCV RNA (viral load), HCV genotype, fibrosis level, liver biochemical levels, platelet counts and alpha-fetoprotein levels. Fibrosis was classified into 4 stages with F0/1 being no or minimal activity up to F4 being severe fibrosis /cirrhosis.
The results found that the increasing rate of liver cancer over 10-years was 2.5% (F0/F1); 12.8 % (F2); 19.3% (F3) and 55.9% (F4). The authors noted that certain factors increased the risk for the development of liver cancer including age 57 years old or older, fibrosis/cirrhosis stage F4, AFP levels of 6 to 20 ng/mL and levels greater than or equal to 20 ng/mL). The authors also reported that the ten-year cumulative incidence rate of liver cancer for patients with AFP levels (ng/mL) lower than 6 was 6.0%; 6 to 20 was 24.6%, and if levels were greater than or equal to 20 it was 47.3%.
The authors concluded that “[N]ot only high (>20 ng/mL) levels, but also even slightly elevated (6-20 ng/mL) AFP levels, could serve as a risk factor for HCC to complement the fibrosis stage.” The authors also noted that the AFP levels of less than 6 ng/mL show a low risk for the development of liver cancer in people with chronic hepatitis regardless of the stage of fibrosis.
The Bottom Line: In people with chronic hepatitis C, frequent monitoring of liver cancer with the AFP test and imaging is needed in people with severe fibrosis or cirrhosis regardless of AFP levels. It is reassuring to know, however, that regardless of HCV disease progression, a person who has an AFP level below 6 ng/mL carries a very low risk for developing liver cancer.