HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians
MAY 1998
HEPATITIS A IN CHRONIC LIVER DISEASE
Hepatitis A virus superinfection in chronic viral hepatitis patients. Dr. Sandro Vento and colleagues collected data concerning the outcome of HAV infection in 163 chronic hepatitis B (HBV) and 432 chronic hepatitis C (HCV) patients. These patients were prospectively followed from June 1990 to July 1997. Ten HBV and 17 HCV patients acquired HAV superinfections. Nine of the 10 HBV patients had an uncomplicated HAV course while fulminant hepatic failure developed in 7 HCV patients (6 of these patients died; fatality rate of 35%). The authors speculate that HAV may trigger an autoimmune mechanism in susceptible HCV patients leading to massive necrosis of hepatocytes and they suggest that patients with chronic HCV be vaccinated against HAV. (Vento S, et al. N Engl J Med 1998; 338: 286-290)
Hepatitis A vaccination of patients with chronic liver disease. Dr. Emmet Keeffe and colleagues performed an open, multicenter study to investigate the safety and immunogenicity of an inactivated hepatitis A vaccine (Havrix™) administered in two doses 6 months apart to patients with chronic liver disease (CLD). The hepatitis A vaccine groups consisted of 188 healthy adults, 104 chronic hepatitis C patients, 46 chronic hepatitis B patients, and 70 patients with CLD not due to a viral hepatitis. An additional 67 chronic hepatitis C patients vaccinated with a recombinant DNA hepatitis B vaccine (Engerix-B™) were also observed as a prospective, parallel comparator to the hepatitis A vaccine patients. The hepatitis A vaccine was well tolerated and more than 94% of all vaccinees became seropositive, thus demonstrating a satisfactory immune response in patients with chronic viral hepatitis and other miscellaneous CLD. (Keeffe E, et al. Hepatology 1998; 27: 881-886)
CHRONIC HEPATITIS C
Kidney transplantation and hepatitis C virus infection. Dr. Christophe Legendre and coworkers at the Necker Hospital in Paris retrospectively studied the impact of HCV infection in 499 hepatitis B virus-negative patients who received an initial cadaver donor kidney transplant and had a graft or patient survival of at least 6 months. Anti-HCV antibodies were detected in 112 (22%) patients at the time of transplantation. Mean follow-up after transplantation was 81 ± 2 months. Kidney transplant recipients with anti-HCV antibodies had a shorter patient survival (p < 0.01) and a shorter graft survival (p < 0.0001) than recipients without anti-HCV antibodies. Increased mortality was caused by liver disease and sepsis. The authors conclude that HCV infection had a harmful impact on patients who had undergone kidney transplantation. (Legendre C, et al. Transplantation 1998; 65: 667-670)
Clinical course of interferon - treated chronic hepatitis C. Dr. Camma Calogero and colleagues examined the clinical course of chronic hepatitis C patients who had a sustained response to a-interferon therapy. Sustained response was defined as normal serum aminotransferase levels 12 months after stopping interferon treatment. The study data base was derived from 426 patients with biopsy proven chronic hepatitis C who had been enrolled in two previously reported randomized clinical trials designed to compare 6 and 12 months of interferon therapy. In the first trial 116 patients were treated with human lymphoblastoid a-n1 interferon (Wellferon) and in the second trial 310 patients received recombinant interferon a-2b (Intron-A). The mean follow-up was 62.1 months (7-109 months) and 62 (15.1%) patients were identified as sustained responders. Late aminotransferase relapses were not observed among the sustained responders and 56 (90.3%) of the sustained responders were serum HCV RNA negative at the end of follow-up. In addition, liver event-free survival was significantly longer in the sustained responders than in all remaining patients (p < 0.01). (Calogero C, et al. Journal of Hepatology 1998; 28: 531-537)
CHOLESTATIC CHRONIC LIVER DISEASE
Epidemiology of autoimmune liver disease. Dr. Kirsten Boberg and coworkers have recently described for the first time the relative frequencies of three autoimmune liver diseases, primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH), in a defined Norwegian population. Patients with PBC, PSC, and AIH were prospectively registered over 10 years from 1986 through 1995. The mean annual incidence per 100,000 inhabitants was 1.6 for PBC, 1.3 for PSC, and 1.9 for AIH. The point prevalence per 100,000 inhabitants was 14.6 for PBC, 8.5 for PSC, and 16.9 for AIH. The authors conclude that these epidemiologic data can be used to plan for liver transplantation requirements. (Boberg KM, et al. Scand J Gastroenterol 1998; 33: 99-103)
Antimitochondrial antibodies in healthy adults. The detection of antimitochondrial antibodies (AMAs) has become a major criterion for the diagnosis of primary biliary cirrhosis (PBC). Dr. Alberti Mattalia and colleagues have utilized a new test based on a recombinant protein (r-MIT 3) containing the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2 to detect the presence of AMA in a cohort of 1,530 healthy people from northern Italy. The sera of 9 (0.5%) people reacted to r-MIT3 by ELISA while only one of the 9 samples were determined to be AMA-positive by indirect immunofluorescence microscopy. It is unknown if this data is indicative of background reactivity or of early presymptomatic PBC. However, the sera of one of the 9 patients had an AMA profile identical to typical PBC and the reactivity of the sera of 8 patients retested had a wider AMA pattern after 8-14 months of follow-up. The authors state that the identification of very early PBC will be a major tool to understand the initial events that lead to disease. (Mattalia A, et al. Hepatology 1998; 27: 656-661)
HEMOCHROMATOSIS
Screening for hemochromatosis. Dr. Claus Niederau and colleagues prospectively screened 3,012 asymptomatic employees and 3,027 outpatients by determining serum ferritin levels and transferrin saturation to estimate the frequency of iron overload and iron deficiency. Gross iron overload indicated by elevated transferrin saturation and ferritin levels was proven by liver biopsy or phlebotomy treatment in 28 study subjects and 6 of their siblings. Thirty of these 34 subjects were precirrhotic. Among male employees, gross iron overload was almost as common as iron deficiency (0.4% and 0.5%, respectively). The authors conclude that the prevalence of hemochromatosis is high and that screening for hemochromatosis in asymptomatic people should be established. (Neiderau C, et al. Ann Intern Med 1998; 128: 337-345)
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