HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians
October 1998
AUTOIMMUNE LIVER DISEASE
Primary biliary cirrhosis and autoimmune hepatitis overlap. Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) are the two most common immune-mediated liver diseases and their clinical features may overlap in an individual patient (PBC-AIH overlap syndrome). Dr. Olivier Chazouilleres and coworkers reviewed 130 patients diagnosed with PBC to identify those who also had features of AIH. Twelve cases (9.2%) of overlap syndrome were identified as defined by the presence of at least 2 of 3 recognized biochemical, serological, and histological criteria for each disease. Several of these patients required combination therapy with ursodeoxycholic acid (UDCA) and corticosteroids to achieve symptomatic and marked biochemical improvements. The authors conclude that the PBC-AIH overlap syndrome is not rare and that it may represent a cause of resistance to UDCA therapy in PBC patients. (Chazouilleres O, et al. Hepatology 1998; 28: 296-301).Variant syndromes of autoimmune hepatitis. The criteria for autoimmune hepatitis (AIH) have been standardized and a scoring system has been proposed by the International Autoimmune Hepatitis Group (IAHG) which permits quantitative comparison between patients with classical features of AIH and those with atypical variant findings. Dr. Albert Czaja evaluated 225 patients with a diagnosis of an autoimmune liver disease utilizing these standard criteria and a modification of the IAHG scoring system to determine the frequency of variant syndromes and the strength of the original diagnosis. Variant forms were found in 18% of cases and only patients with features of both AIH and PBC responded to corticosteroid therapy as commonly as definite AIH patients. The author concludes that variant forms are common and should be sought in all patients with autoimmune liver diseases. (Czaja A. Hepatology 1998; 28:360-365)
CHRONIC HEPATITIS C
Ribavirin therapy. Interferon (IFN) retreatment of chronic hepatitis C (CHC) patients who initially fail to respond to IFN treatment is generally considered to be an ineffective therapeutic maneuver. Dr. Raffaello Sostegni and colleagues conducted a trial in which 96 nonresponders to IFN-alfa therapy were randomized to one of three treatment groups: Group 1 (33 patients) received ribavirin alone x 6 months (1,000 mg/daily) followed by IFN-alfa n-3 alone (3 MU thrice weekly) x 6 months; group 2 (33 patients) received ribavirin plus IFN-alfa n-3 x 6 months; group 3 (30 patients) received IFN-alfa n-3 alone x 6 months. At the end of treatment more group 2 patients (41%) than group 1 or 3 patients (10% and 17%, respectively) had normal serum alanine aminotransferase levels (P=0.008). In addition, liver biopsies showed an improvement in necroinflammatory scores for only group 2 patients (P=0.01). The authors conclude that concomitant therapy with ribavirin and IFN-alfa n-3 was superior to a sequential schedule or IFN-alfa n-3 monotherapy in CHC patients who had not responded to initial IFN treatments. (Sostegni R, et al. Hepatology 1998; 28:341-346)
Clinical outcome as a function of transmission mode. Dr. Stuart Gordon and colleagues reviewed 627 patients with chronic hepatitis C (CHC) to determine if mode of transmission affects disease outcome. The transmission mode groups consisted of 282 (45%) transfusion recipients, 262 (42%) patients who acquired CHC via other routes of percutaneous exposure, and 83 (13%) patients who were without known risks. Duration of follow-up was 1-25 years (median of 21 years). Cirrhotic patients were more frequently found in the transfusion recipient group than in the other two groups (P<0.001). Univariate analysis showed that viral acquisition by transfusion predicted risk of decompensation with liver failure. The authors conclude that source of CHC infection is a predictor of outcome. (Gordon SC, et al. Hepatology 1998;28:562-567)
HEPATOCELLULAR CARCINOGENESIS
Chronic viral hepatitis disease progression and hepatocellular carcinogenesis. Dr. Kenji Ikeda and coworkers prospectively observed 2,215 patients with chronic viral hepatitis to study characteristics of disease development and carcinogenesis. The chronic viral hepatitis subgroups consisted of hepatitis B virus (HBV, n=610) patients, hepatitis C virus (HCV, n=1,500) patients, patients with both HBV and HCV (n=53), and patients with neither HBV or HCV (n=52). The median observation period was 4.1 years (range of 0.1 to 16.3 years). Cirrhosis occurred in 7.6%, 21.7%, and 32.2% of these patients by the 5th, 10th, and 15th years, respectively. Although progression rates between the HBV and HCV patients were similar, the carcinogenesis rate was higher in the HCV group than in the HBV group (26.0% vs 18.8% by the 15th year, P=0.006). The authors conclude that there are some differences in the mode of disease progression and cancer promotion between HBV and HCV infection. (Ikeda K, et al. Journal of Hepatology 1998; 28:930-938)HEMACHROMATOSIS
Elevated hepatic iron index and end-stage liver disease. Dr. Scott Cotler and colleagues obtained measurements of serum transferrin saturation and ferritin levels in 106 cirrhotic patients prior to liver transplantation. They also calculated the hepatic iron index in the explant liver tissue from these patients and performed genotyping studies in those patients with a hepatic iron index >1.9. Thirty-three (31%) patients had elevated serum iron studies suggesting hereditary hemochromatosis (HHC) and only four of these patients had a hepatic iron index >1.9. None of these four patients was homozygous for the HHC mutation (Cys 282 Tyr). The authors conclude that iron studies are nonspecific for identifying end-stage liver patients with HHC and that genotyping studies should be utilized. (Cotler SJ, et al. Journal of Hepatology 1998; 29:257-262)Hepatology Watch is produced through an educational grant from the marketers of URSO®
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