HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians

December 1998

HIGHLIGHTS FROM THE 49TH ANNUAL MEETING OF

THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES

NOVEMBER 6-10, 1998

PRIMARY BILIARY CIRRHOSIS/PRIMARY SCLEROSING CHOLANGITIS/AUTOIMMUNE HEPATITIS

Infectious agents and primary biliary cirrhosis (PBC). Previous data suggested that bacterial infections may be associated with the pathogenesis of PBC. Tanaka and colleagues obtained liver tissue from 28 PBC and 20 control patients and found no evidence of an ongoing infectious process by PCR analysis with primers specific for the bacterial 16s rRNA region. (Tanaka A, et al. Hepatology 1998; 28: 238A)

Liver transplantation for primary sclerosing cholangitis (PSC). Kim and colleagues reported that current survival results for PSC patients treated with liver transplantation in the current decade are excellent. Survival for the 225 patients included in the study was 95% at 1 year, 93% at 3 years, and 86% at 5 years. A pretransplant risk score > 3.5 was associated with an increased risk of death and higher resource utilization. (Kim WR, et al. Hepatology 1998; 28: 389A)

Autoimmune liver disease in Alaska Natives. Hurlburt and colleagues investigated the prevalence of autoimmune liver diseases in Alaska Natives and found the rates of autoimmune hepatitis and primary biliary cirrhosis to be among the highest in the world (41.3/100,00 and 13.4/100,000, respectively). Primary sclerosing cholangitis was not identified in this population. (Hurlburt K, et al. Hepatology 1998; 28: 548A)

Tacrolimus vs cyclosporine. Martin and colleagues prospectively evaluated post-transplantation HCV recurrence in 85 patients randomly assigned to receive either cyclosporine or tacrolimus as primary immunosuppression therapy. Their data show no differences in the HCV recurrence rate up to 6 months post-liver transplantation in patients receiving tacrolimus vs cyclosporine. (Martin P, et al. Hepatology 1998; 28: 313A).

Combined lamivudine (LAM) and hepatitis B immunoglobulin (HBIg) therapy. Terrault and coworkers compared the results of long-term HBIg therapy to those of short-term HBIg therapy for six months combined with chronic LAM treatment in recipients transplanted for HBV disease. Survival was similar between the two treatment groups and there was a trend towards a lower HBV recurrence rate in the combined HBIg/LAM group. The implication is that HBIg/LAM therapy is an equally effective and less costly HBV prophylaxis therapy alternative to HBIg monotherapy. (Terrault NE, et al. Hepatology 1998; 28: 389A)

Acetaminophen (APAP) hepatotoxicity and ethanol. Chien and colleagues performed a series of studies investigating the effect of ethanol ingestion on APAP hepatotoxicity in healthy subjects by assessing the formation of the hepatotoxic metabolite NAPQI. Although co-administration of ethanol and APAP was associated with a decrease in the formation of NAPQI, the metabolite’s formation was enhanced (P < 0.03) when the APAP dose was given just after the ethanol was cleared. Thus, ethanol may increase the risk of APAP-induced hepatotoxicity although the clinical relevance of this observation requires further study. (Chien JY, et al, Hepatology 1998; 28: 257A)

Ursodeoxycholic acid (UDCA) and nonalcoholic steatohepatitis (NASH). Ceriani and associates studied the effect of adding UDCA therapy to a low fat diet in the treatment of NASH. They found normalization of liver enzymes to occur more frequently in patients receiving UDCA therapy (p=0.0008). (Ceriani R, et al. Hepatology 1998; 28: 386A)

HFE mutation and alcohol-related cirrhosis. Gordon and colleagues investigated the role of the HFE mutation in determining a predisposition to alcohol-related cirrhosis in a Celtic population. HFE heterozygosity (no homozygotes were identified) was not found to be a predisposing factor for alcoholic liver disease. (Gordon HM, et al. Hepatology 1998; 28: 199A)

Biochemical expression in subjects heterozygous for hemochromatosis. Moirand and colleagues found that C282Y heterozygosity for the HFE mutation does not influence the results of serum iron tests. However, their data did show that alcohol consumption and polymetabolic syndrome (obesity, diabetes, hyperlipidemia) increase the probability of abnormal iron studies. (Moriand R, et al. Hepatology 1998; 28: 419A)

Noninvasive indicators of fibrosis in hemochromatosis. Two abstracts reported predictors of fibrosis in patients with hemochromatosis. Guyader and colleagues evaluated variables linked to severe liver fibrosis in C282Y homozygous hemochromatosis patients by multivariate regression analysis. They found that patients who have all three of the following characteristics have no risk of significant liver fibrosis: serum ferritin level < 1000 m g/L, no hepatomegaly, and a normal serum AST level. Baker and coworkers investigated clinical predictors of fibrosis and cirrhosis in patients diagnosed with hereditary hemochromatosis by genetic testing. They found that patients with serum ferritin levels < 1000 m g/L and minimal alcohol intake are unlikely to have fibrosis or cirrhosis. Hemochromatosis patients with these findings predicting the absence of fibrosis might be spared a liver biopsy. (Guyader D, et al. Hepatology 1998; 28: 419A and Baker ER, et al Hepatology 1998; 28: 421A)

Surveillance for hepatocellular carcinoma in hemochromatosis. Dixon and colleagues analyzed patients with hepatocellular carcinoma (HCC) due to hemochromatosis. Their data showed that regular 6 monthly examinations with serum alpha-fetoprotein and ultrasound allowed for an earlier diagnosis of HCC and thus extended survival. (Dixon JL., et al. Hepatology 1998; 28: 421A)

Interferon alfa-2b (IFNa 2b) and ribavirin. Two abstracts reported results of multicenter studies investigating the efficacy of combining IFNa 2b and ribavirin to treat chronic hepatitis C (McHutchison et al: a U.S. multicenter trial, and Poynard et al; an international trial). Both trials found the combination therapy to more effectively achieve biochemical, virological and histologic improvements than IFNa 2b monotherapy and to have an acceptable safety profile. Genotype 1 patients benefited more from 48 weeks of treatment. (McHutchison J, et al. Hepatology 1998; 28: 387A and Poynard T, et al. Hepatology 1998; 28: 387A)

The future U.S. healthcare burden. Davis and colleagues developed a model based on prevalence data from NANES III and incidence data from the CDC to project the future health care demands due to HCV infection in the U.S. Their model predicts that the prevalence of HCV will remain high for several years and cases with major complications will increases. (Davis GL, et al. Hepatology 1998; 28: 390A)

Impact of interferon alfa-2b (IFNa 2b) and ribavirin on liver fibrosis progression. Poynard and coworkers studied the effect of combed IFNa 2b and ribavirin therapy on liver fibrosis progression in HCV patients. This combination therapy achieved a virological sustained response rate (44%) that was also associated with regression of fibrosis. Moreover, the fibrosis progression rate was reduced four-fold, even in those patients who did not have a sustained response. (Poynard T, et al. Hepatology 1998; 28: 497A)

Lamivudine (LAM) therapy. Two abstracts by Schiff and colleagues reported the use of LAM in treating chronic hepatitis B (CHB) patients. In the first abstract, interim results indicate that HBeAg seroconversion produced by LAM monotherapy is durable (91% maintenance rate with median follow-up of 6 months). In the second study LAM monotherapy was associated with a better histologic response and serum ALT normalization in CHB patients who were interferon alfa-2b non-responders than placebo or combination LAM/interferon alfa-2b treatments. (Schiff E, et al. Hepatology 1998; 28: 163A and Schiff E, et al. Hepatology 1998; 28: 388A)

Hepatocellular carcinoma (HCC) detection. McMahon and coworkers reported data from a population-based study of Alaska Natives in which HBsAg carriers were screened with periodic serum alpha-fetoprotein determinations over a 15-year period. Compared to historical data, serum alpha-fetoprotein screening was found to effectively detect most HCC tumors at a resectable stage and significantly prolong survival. (McMahon BJ, et al. Hepatology 1998; 28: 388A)