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In This Issue:
• Treatment of Acute Hepatitis C
• Impact of Cirrhosis on CD4 Cell Count
• Alcohol Worsens Liver Disease Progression
• HCV Treatment and Outcomes in IDUs
• HCV Treatment after Liver Transplantation
• New Noninvasive Fibrosis Index
Treatment of Acute Hepatitis C
Research has shown that early treatment with interferon-based therapy during the acute phase of hepatitis C Virus (HCV) infection produces high sustained virological response (SVR) rates, but the optimal duration of therapy is unknown. As described in the February 2007 Journal of Viral Hepatitis, G. Calleri and colleagues assessed the benefits of a short course (12 weeks) of 1.0-1.5 mcg/kg/week pegylated interferon alpha-2b (PegIntron) in 46 patients with acute HCV infection (genotype not reported in abstract). After a six-month post-treatment follow-up period, 72% achieved SVR, 17% relapsed after the completion of therapy, and 9% were non-responders. Factors associated with SVR were use of at least 1.2 mcg/kg/week of PegIntron, lower peak HCV viral load, and undetectable HCV RNA at weeks 4 and 12. Treatment was well-tolerated overall, and only one patient stopped therapy prematurely. These results suggest that 12 weeks of pegylated interferon may be adequate for many patients with acute HCV infection.
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Impact of Cirrhosis on CD4 Cell Count
Liver cirrhosis can have a negative effect on immune function, a finding that has particular relevance for HIV-positive individuals. As reported in the February 1, 2007 issue of Clinical Infectious Diseases, B.H. McGovern and colleagues studied 60 HIV-negative outpatients with cirrhosis; 31 had chronic hepatitis C and one had chronic hepatitis B. Well over half (65%) had low CD4 cell counts (below 550 cells/mm3), including 43% with counts below 350 cells/mm3 and 7% below 200 cells/mm3 (the level at which the risk of opportunistic infections begins to rise). However, 95% of patients with a low absolute CD4 cell count still had a normal CD4 cell percentage (the proportion of CD4 cells out of all lymphocytes). Abnormally low CD4 cell counts were associated with portal hypertension, spleen enlargement, thrombocytopenia (low platelet count), and leukopenia (low white blood cell count). The authors concluded that, “Cirrhosis is associated with low CD4 T-cell counts in the absence of HIV infection.” These results suggest that CD4 cell percentage, rather than absolute CD4 cell count, may be a better measure for monitoring HIV disease progression in patients with advanced liver disease.
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Alcohol Worsens Liver Disease Progression
Heavy alcohol use can cause liver damage on its own, accelerate liver disease progression in people with hepatitis C, and interfere with response to therapy. As reported in the February 2007 issue of Alcoholism Clinical & Experimental Research, C.M. Chen and colleagues assessed outcomes associated with alcohol use and HCV infection based on more than seven million death records compiled by the U.S. National Center for Health Statistics. HCV, heavy alcohol use, or both were factors in 132,468 deaths. Patients with HCV-related deaths had a higher prevalence of heavy alcohol use, and the effect was stronger for women. Among HCV-positive men, heavy alcohol use was associated with a decrease in the mean age of death from 55 to 50 years; among women, the decrease was larger, from 61 to 49 years. Compared with HCV positive moderate or non-drinkers, the probability of death before age 65 for heavy drinkers rose from 68% to 91% for men, and from 47% to 88% for women. The researchers concluded that, “This study provides mortality-based evidence to further establish heavy alcohol consumption as one of the key risk factors contributing to premature deaths from HCV in the United States,” and provides the first empirical evidence that “alcohol consumption affects men and women differently in HCV mortality.” In general, HCV-positive women experience slower liver disease progression and longer survival than men, but in this study the advantage was lost with heavy alcohol use.
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HCV Treatment and Outcomes in IDUs
Many patients with a history of injection drug use have been excluded from hepatitis C treatment due to the belief that they are poor candidates for therapy. As reported in the February 2007 Journal of Clinical Gastroenterology, K.H. Seal and colleagues assessed the impact of injection drug use history on HCV treatment candidacy and outcomes in 4,318 patients with hepatitis C seen at 24 Department of Veterans Affairs medical centers between 1999 and 2001. More than half (61%) reported a history of injection drug use. Injection history was not significantly associated with patient acceptance of hepatitis C treatment, early discontinuation of therapy, or rate of virological response. Patients who were not considered candidates for HCV treatment were more likely to have lower incomes and less education, and to consume three or more alcoholic drinks per day. The authors concluded that, “A history of injection drug use was not associated with HCV treatment candidacy or outcomes, supporting national guidelines to evaluate former injection drug users on a case-by-case basis for HCV treatment.”
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HCV Treatment after Liver Transplantation
Two recent studies examined the effect of interferon-based therapy on progression of liver fibrosis. In the first study, reported in the February 15, 2007 issue of Transplantation, M. Bahra and colleagues assessed the rate of fibrosis progression in 28 liver transplant recipients with chronic hepatitis C who achieved SVR after treatment with conventional interferon or pegylated interferon (either Pegasys or PegIntron), both in combination with ribavirin. Liver biopsies performed before and one and three years after treatment showed no significant increase in fibrosis scores (mean 1.8, 2.0, and 2.1, respectively). Five years after completion of therapy, the mean fibrosis score declined to 1.4. The yearly fibrosis progression rate was 0.75 before antiviral therapy and 0.15 after treatment. The researchers concluded that, “Sustained virologic response is associated with a deceleration of fibrosis progression and might therefore play a major role in prevention of graft cirrhosis in hepatitis C virus-infected liver graft recipients.”
In the second study, reported in the March 2007 Journal of Hepatology, F.P. Picciotto and colleagues analyzed the efficacy of antiviral therapy in 61 HCV-infected liver transplant recipients treated with PegIntron plus ribavirin for 24 or 48 weeks; 28 (17%) achieved SVR. During follow-up, sustained responders had a significantly lower rate of death compared with nonresponders and relapsers.
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New Noninvasive Fibrosis Index
In the February 2007 issue of Hepatology, Japanese researchers reported on a new noninvasive index of readily available blood tests to assess liver fibrosis progression. M. Koda and colleagues conducted a study of 402 chronic hepatitis C patients who underwent liver biopsy between April 1994 and March 2004. The investigators identified three blood markers associated with fibrosis progression: platelet count, aspartate aminotransferase (AST) level, and gamma-globulin level. The resulting “FibroIndex” was then verified in a group of 30 patients who underwent a second biopsy more than one year after interferon-based therapy. The FibroIndex was more accurate in predicting significant or severe fibrosis than the Forns index or the AST-to-platelet ratio index (APRI). Using the best cutoff values to identify the absence or presence of significant fibrosis, about one-third of patients could have avoided biopsies. Among the 30 treated patients, changes in FibroIndex score directly correlated with changes in fibrosis as determined by biopsy. The researchers concluded that, “The FibroIndex is a simple and reliable index for predicting significant fibrosis in [patients with] chronic hepatitis C and could also be used as a surrogate marker during anti-fibrotic treatment for chronic hepatitis C.”
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