HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians

April 1999

HEPATITIS A VIRUS (HAV)
Food-borne outbreak. Yvan Hutin and colleagues investigated a recent large food-borne outbreak of HAV in Michigan involving exposure to frozen strawberries prepared by the same processor. In this study, outbreaks of HAV were linked to a common source of contaminated food by viral genetic analysis. (Hutin YJF, et al. N Engl J Med 1999; 340: 595-602). In an accompanying editorial, Raymond Koff asserts that early childhood (beginning at the age of 2 years) immunization against HAV should be implemented in the United States. He argues that HAV is a frequent cause of acute viral hepatitis which can be associated with serious consequences and that the HAV vaccine is highly effective and safe. In addition, outbreaks of HAV, such as the one described by Hutin et al, are likely to continue because much of the harvesting of foods is done in other countries where U.S. recommendations for HAV prophylaxis with food handlers have no effect. The author concludes that eradication of HAV will not be achievable without a routine childhood vaccination program. (Koff RS, N Engl J Med 1999; 340: 644-645)

Economic analysis of immunization strategies. Ananya Das conducted an economic analysis of HAV immunization programs by comparing 3 different strategies in a cohort of 2-year old healthy children in a developed country. The 3 strategies were universal vaccination, vaccination of only susceptible children (HAV antibody negative), and no vaccination program. Vaccination of susceptible children was found to be the most cost-effective strategy. However, if the cost of vaccination is less than $57/person, universal vaccination would be the preferred strategy. (Das A. Hepatology 1999; 29: 548-552)

HEPATITIS C VIRUS (HCV)
Impact of interferon alfa on hepatic fibrosis. Rodolphe Sobesky and coworkers assessed the impact of interferon alfa (IFN-a) on liver fibrosis progression in 185 chronic HCV patients who had undergone liver biopsies before and after treatment. The fibrosis progression rate was calculated as the ratio of fibrosis stage (METAVIR units) and time. Fewer INF-a treated patients had an increase in fibrosis stage compared to 102 historical controls (P< 0.001). More patients exhibiting an early response to IFN-a therapy had an improvement in fibrosis stage (P=0.03). These data indicate the IFN-a therapy changes the natural progression rate of fibrosis. (Sobesky R, et al. Gastroenterology 1999; 116: 378-386)

Early prediction of response to interferon treatment. Johannes Brouwer et al report on the value of HCV RNA testing to predict whether or not HCV patients will respond to current treatment regimens. A positive HCV RNA test (³ 103 copies/ml) at 4 weeks of interferon alfa-2b monotherapy (336 patients) or interferon-ribavirin combination therapy (40 patients) was highly predictive for identifying patients who did not obtain a sustained response (99% and 100%, respectively). The week 4 HCV RNA testing was more sensitive and specific than serum alanine aminotransferase testing at week 4 (P<0.001), week 8 (P<0.001), or week 12 (P <0.001). The authors conclude that a positive HCV RNA test at 4 weeks is highly predictive for nonresponse to antiviral therapy. (Brouwer JT, et al. J Hepatol 1999; 30: 192-198)

Association with diabetes mellitus. Andrew Mason and associates retrospectively analyzed 1,117 chronic viral hepatitis patients for factors associated with diabetes and conducted a case-control study to determine the seroprevalence of HCV in a cohort of 594 diabetic patients and 377 patients with thyroid disease to investigate a potential relationship between HCV and diabetes. Multivariate analysis of the viral hepatitis data revealed HCV infection is an independent predictor of diabetes (P=0.02) and more patients in the diabetic cohort than in the control thyroid disease cohort were found to have HCV infection (P=0.02). These results suggest an association between HCV and diabetes. (Mason AL, et al. Hepatology 1999; 29: 328-333)

Low-grade non-Hodgkin's lymphoma (NHL). Imran Rasul and coworkers studied 16 patients with chronic HCV and cryoglobulinemia for evidence of NHL. Bone marrow morphology was consistent with NHL in 2 patients and suspicious for NHL in 7 patients. Molecular analysis identified 3 patients with a B-cell monoclonal proliferation. These findings confirm the presence of occult lymphoproliferative disorders in patients with HCV and cryoglobulinemia. (Rasul I, et al. Hepatology 1999; 29: 543-547)

HEMOCHROMATOSIS
Phenotypic expression of HFE mutations. Romain Moirand and colleagues studied two populations of people with iron overload in western France (Brittany) with the primary aim of determining the phenotypic expression of HFE mutations. The two study populations consisted of 531 patients with liver iron overload and 579 relatives of patients with hemochromatosis. C282Y heterozygotes in both populations had lower levels of iron overload and did not have significant iron-related hepatic disease. No differences were found between H63D heterozygotes and homozygotes. Although it is difficult to make general conclusions from a homogenous population, these data show that in patients with iron overload in western France, the hemochromatosis phenotype is associated with C282Y +/+ genotypes and the role of H63D is marginal. (Moirand R, et al. Gastroenterology 1999, 118: 372-377)