HEPATOLOGY WATCH®

MARCH 2003

CIRRHOSIS WITH REFRACTORY ASCITES

Transjugular intrahepatic portosystemic shunting (TIPS) vs. paracentesis plus albumin. P. Gines and colleagues from the University of Barcelona randomized 70 patients with cirrhosis and refractory ascites to receive TIPS or repeated paracentesis plus intravenous albumin. The 1- and 2-year probabilities of survival without liver transplantation were similar for patients treated with TIPS (41% and 26%) or paracentesis (35% and 30%). Patients treated with TIPS had lower rates of hepatorenal syndrome and recurrent ascites; however, they also had a higher frequency of severe hepatic encephalopathy. In addition, calculated costs were greater in the TIPS group. These findings show that TIPS therapy was more costly and did not improve survival rates compared to repeated paracenteses in patients with cirrhosis and refractory ascites. (Gines P, et al. Gastroenterology 2002;123:1839-1847)

CHRONIC HEPATITIS C VIRUS (HCV) AND HEPATITIS B VIRUS (HBV) INFECTION

Progression of fibrosis in chronic HCV infection. M. Ghaney et al. from the NIH analyzed data from 123 patients with chronic HCV infection who had undergone 2 liver biopsies at a mean interval of 44 months (range, 4-212 months) without intervening treatment. Hepatic fibrosis was evaluated by a scoring system of 0 (no fibrosis) to 6 (cirrhosis). Progression of fibrosis was found in 48 (39%) patients, with 9% developing cirrhosis; 29 (24%) showed improvement in fibrosis. The rate of fibrosis progression was slow in the overall patient population (only 0.12 fibrosis units per year); however, it was greater in the following patient subgroups: older patients; patients with higher serum alanine and aspartate aminotransferase levels; and patients with extensive periportal necrosis. These results support recommendations that HCV patients with normal serum aminotransferase levels and mild liver histology can initially be observed without treatment. (Ghaney MG, et al. Gastroenterology 2003;124:97-104)

Hepatic iron loading in HCV infection. Hepatic iron loading is common in patients with chronic HCV infection. Bruce Tung et al. at the University of Washington studied 316 patients with chronic hepatitis C. Among 198 patients with compensated liver disease, they found the presence of HFE mutations to be associated with elevations of the hepatic iron index, serum ferritin, iron levels and serum transferrin saturation. Furthermore, after adjustment for duration of HCV infection, HFE mutations were independently associated with bridging fibrosis or cirrhosis. However, an association of HFE mutations with iron loading was not observed in 118 patients with end-stage liver disease. The prevalence of HFE mutations was similar in patients with either compensated or end-stage liver disease. Thus, while HFE mutations may accelerate fibrosis in compensated chronic HCV disease, there is no evidence that HFE mutations cause progression to end-stage liver disease. (Tung BY, et al. Gastroenterology 2003;124:318-326)

Long-term lamivudine therapy in chronic HBV infection. J. Dienstag and coworkers at the Massachusetts General Hospital evaluated the histological outcomes of long-term lamivudine therapy in 63 patients with chronic HBV infection. After 1 year of lamivudine therapy, HAI scores of liver biopsy samples from 36 (57%) patients showed at least a 2-point improvement and 24 (38%) patients had no change. After 2 additional years of treatment, liver histology from 12 (19%) patients continued to improve and 38 (60%) patients remained stable. Patients without YMDD variants were more likely to improve (77% vs. 44%) and less likely to deteriorate (5% vs. 15%). Progression to cirrhosis occurred in only 1 patient (a YMDD variant), and 3 of 34 patients showed progression to bridging fibrosis (all YMDD variants). Furthermore, cirrhosis improved in 8 of 11 patients, and bridging fibrosis improved in 12 of 19 patients. These findings indicate that long-term lamivudine therapy reduces necroinflammatory activity and improves fibrosis in most chronic HBV patients without YMDD variants. (Dienstag JL, et al. Gastroenterology 2003;124:105-117)

PRIMARY BILIARY CIRRHOSIS (PBC)

Methotrexate therapy. Nancy Bach and colleagues treated 110 PBC patients with methotrexate 15 mg weekly. Only half the patients completed 5 years of methotrexate therapy, which did not prevent disease progression or improve survival compared to historical controls (n = 180) treated with either ursodeoxycholic acid or placebo in a previous trial. These results demonstrate that methotrexate is not effective treatment for patients with PBC. (Bach N, et al. Am J Gastroenterol 2003;98:187-193)

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

Association of overweight with elevated serum alanine aminotransferase (ALT) levels. Constance Ruhl and James Everhart reviewed data from the third US National Health and Nutrition Examination Survey (1988-1994) in which adult participants (5,724) underwent anthropometric measurements. Participants with excessive alcohol consumption, HBV, HCV, iron overload, or known diabetes were excluded. Serum ALT levels (a surrogate marker for NAFLD) were elevated in 2.8% of the study population. Multivariate analysis identified central adiposity, serum leptin level, and serum insulin level as the determinants associated with elevated serum ALT activity and higher body weight. An accompanying editorial by Jeanne Clark and Anna Mae Diehl acknowledged that occult liver disease may be more common than previously suspected. They agreed that the association of ALT abnormalities with the metabolic syndrome supports the conclusion that the ALT elevations are due to NAFLD. Clark and Diehl also raised several questions: is serum ALT an adequate marker for NAFLD, is their estimate of the prevalence of NAFLD too low, and is NAFLD a disease or an incidental condition with a benign prognosis? (Ruhl CE, Everhart JE. Gastroenterology 2003;124: 71-79 and Clark JM, Diehl AM. Gastroenterology 2003;124: 248-250)

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