HEPATOLOGY WATCH®
Timely Information for Practicing Physicians

August 1999

PRIMARY BILIARY CIRRHOSIS (PBC)
Long-term follow-up. Two recent reports examined the long-term clinical outcome of patients with PBC. Pardeep Nijhawan et al. observed that a large cohort of 1,692 PBC patients presenting to the Mayo Clinic from 1976 to 1985 had a higher than expected incidence of malignancy (especially hepatobiliary cancers) when compared to a national cancer (SEER) database (P<0.001). In the second study, Renee Poupon and colleagues reported the 10-year survival (without liver transplantation) of 225 PBC patients treated with ursodeoxycholic acid (UDCA) to be greater than that predicted by the Mayo PBC model (P<0.04). An increased frequency of hepatocellular or colon carcinomas in this UDCA-treated population was not observed. PBC patients, particularly those who are untreated and/or with advanced disease, may benefit from screening for hepatobiliary malignancies. (Nijhawan PK, et al. Hepatology 1999; 29:1396-1398 and Poupon RE, et al. Hepatology 1999; 29:1668-1671)

UDCA effects. Burton Combes et al. analyzed bile acid composition in fasting duodenal bile after 2 years of UDCA therapy (55 patients) and found decreases of cholic and chenodeoxycholic acid (CDCA) concentrations, which in turn resulted in a decrease of the hydrophobicity of the bile acids. These observed bile acid changes are consistent with the proposed mechanism of hepatoprotection by UDCA (inhibition of the transport of endogenous hepatotoxic bile acids into hepatocytes). A secondary effect of UDCA is suggested in studies done by Phillippe Podevin and coworkers, who showed that UDCA interferes with endogenous interferon (IFN) signaling pathways in a concentration-dependent manner due to a transuppressor effect on IFN-induced promoter activity. (Combes B, et al. Hepatology 1999; 29:1649-1654 and Podevin P, et al. Hepatology 1999; 29:1840-1847)

HEMOCHROMATOSIS
HFE genotyping. Bruce Bacon and associates studied 66 hereditary hemochromatosis patients and 132 patients with other liver diseases. They determined that HFE genotyping is a useful test for the diagnosis of hemochromatosis and may lead to the identification of unsuspected C282Y homozygotes in patients with liver disease and suspected iron overload, even when previous diagnostic criteria of hepatic iron index >1.9 is absent. This study confirms that the phenotypic expression of hereditary hemochromatosis is highly variable. (Bacon BR, et al. Ann Intern Med 1999; 130:953-962)

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Clinical and pathological findings. Liver biopsy specimens from 132 patients with NAFLD were studied by Christi Matteoni and coworkers and separated into 4 histological types: (1) simple fatty liver, (2) steatohepatitis, (3) steatonecrosis, and (4) steatonecrosis plus Mallory hyaline or fibrosis. They found that outcomes were not uniform across these histological types, cirrhosis was more common in types 2-4 than in type 1 (P£ 0.001) and most liver-related deaths were observed in type 4. (Matteoni CA, et al. Gastroenterology 1999; 116:1413-1419)

ALCOHOLIC LIVER DISEASE
S-adenosylmethionine (Ado Met) therapy. Jose Mato et al. reported results of a double-blind trial in which 123 patients with alcoholic liver cirrhosis were randomized to receive Ado Met (1200 mg/day orally) or placebo for 2 years. Overall mortality/liver transplantation was decreased in the Ado Met group compared to the placebo group (16% vs. 30%) and the 2-year survival curves were significantly different between the 2 groups (P=0.046). In an accompanying editorial, Charles Lieber concluded that Ado Met supplementation may reduce the significant mortality associated with alcoholic liver cirrhosis. (Mato JM, et al. J Hepatol 1999; 30:1081-1089 and Lieber CS, J Hepatol 1999; 30:1155-1159)

CIRRHOTIC PATIENTS WITH GASTROINTESTINAL BLEEDING
Antibiotic prophylaxis. Brigitte Bernard and coworkers performed a meta-analysis of 5 trials (n=534) to assess the efficacy of antibiotic prophylaxis in preventing infections in cirrhotic patients with gastrointestinal bleeding and their effect on survival. Antibiotic therapy was found to increase the mean percentage of patients free of infection (P<0.001) and to increase the mean short-term survival rate (P=0.004). The authors conclude that 7 days of antibiotic prophylaxis should be utilized in cirrhotic patients with gastrointestinal bleeding. (Bernard B, et al. Hepatology 1999; 29:1655-1661)

SURGERY
Risk with liver disease. Lawrence Friedman reviewed the operative risk in patients with liver disease undergoing surgery. His discussion includes the effects of anesthesia and surgery on the liver, estimating operative risk, resection of hepatocellular carcinoma, surgery in patients with obstructive jaundice, preoperative evaluation, and postoperative monitoring. This is a valuable and concise review of the multiple and challenging problems that are encountered when surgical procedures are performed on patients with hepatic dysfunction. (Friedman LS, Hepatology 1999; 29:1617-1623)