HEPATOLOGY WATCHTM
Timely Information for Practicing Physicians

FEBRUARY 1999

URSODEOXYCHOLIC ACID THERAPY
Cost-effectiveness of therapy for primary biliary cirrhosis (PBC). Tousif Pasha and coworkers conducted a cost-effectiveness analysis of ursodeoxycholic acid (UDCA) therapy compared to placebo in PBC by assessing the combined data of two previously published studies (the Mayo and Canadian UDCA trials). The authors calculated the incidence of major liver disease complications for the UDCA and placebo groups and estimated the average annual direct medical costs based on literature and institutional data. UDCA therapy resulted in an annual cost savings per patient of $1,372 primarily because of the reduced relative risk of liver transplantation and decreased incidence of esophageal varices. The authors conclude that the use of UDCA lowers the incidence of major complications of PBC and results in lower medical care costs. (Pasha T, et al. Hepatology 1999; 29: 21-26)

Significance of serum bilirubin levels in PBC. Anne-Marie Bonnand et al retrospectively analyzed data from three clinical trials (548 patients) that assessed UDCA therapy in PBC to investigate if normalization of the serum bilirubin induced by 6 months of UDCA treatment confers an improved clinical outcome. Survival free of liver transplantation was longer in patients who had normalization of the serum bilirubin versus those who had not normalized (P<0.0001). In addition, the prognosis of UDCA patients with normalized bilirubin was similar to that of placebo patients with normal bilirubin at baseline. These results indicate that the serum bilirubin is a prognostic factor in PBC and normalization of the bilirubin is associated with clinical benefit. (Bonnand A-M, et al. Hepatology 1999; 29: 39-43)

Elevated levels of bile acids in patients with intrahepatic cholestasis of pregnancy (ICP). Dora Brites and Cecilia Rodrigues investigated bile acid excretion in the colostrum of 16 lactating women with ICP compared to 5 normal pregnancies. Seven ICP patients received UDCA beginning < 21 days prior to term. Bile acid levels were higher in the colostrum of ICP patients than in normals (P<0.01) and cholic acid was the major bile acid detected. UDCA decreased bile acid levels in the serum and colostrum of ICP patients and was detected in colostrum at concentrations much lower than that measured in serum (P<0.05). These data show that bile acid concentrations are elevated in ICP and UDCA lowers endogenous bile acid levels in the colostrum of ICP patients. (Brites D and Rodriques CMP. J Hepatol 1998; 29: 743-751)

IRON AND HFE MUTATIONS IN HCV
Hemochromatosis gene mutations in chronic hepatitis C virus (HCV) patients. Lili Kazemi-Shirazi and coworkers studied the role of HFE gene mutations (C282Y and H63D) in hepatic iron accumulation in 184 chronic HCV patients. The chronic HCV patients had a similar frequency of HFE gene mutations to that of 487 healthy control subjects. Biochemical evidence of iron overload was more common in patients with HFE mutations compared to those without HFE mutations (P=0.0045). However, there was an overlap among patients with and without HFE gene mutations in hepatic iron content and histological iron grading. The authors conclude that HFE gene mutations contribute to hepatic iron overload in chronic HCV patients. (Kazemi-Shirazi L, et al. Gastroenterology 1999; 116: 127-134)

HFE gene mutations in chronic viral hepatitis patients. Alberto Piperno and colleagues investigated the role of HFE gene mutations (C282Y and H63D) in the development of iron overload in 110 chronic B or C viral hepatitis (CH) patients. The frequency of HFE gene mutations was similar in the CH patients compared to 139 control subjects and in female CH patients with or without hepatic iron overload. However, in men all C282Y heterozygotes had iron overload and the H63D mutation was associated with an increased frequency of marked hepatic siderosis (P=0.0039). These data show that HFE gene mutations may have a role in the development of hepatic iron overload in male CH patients. (Piperno A, et al. Hepatology 1998; 28: 1105-1109)

HEPATITIS C
Chronic hepatitis C prognosis. Claus Niederau and colleagues assessed the prognosis of 838 chronic hepatitis C virus (HCV) patients in a prospective study with a mean follow-up of 50.2 months (range, 6-122 months). Cirrhosis, long disease duration (> 15 years), intravenous drug abuse, and excessive alcohol consumption were found to adversely effect survival while interferon therapy improved survival. The development of hepatocellular carcinoma was predominantly associated with cirrhosis. These data indicate that chronic HCV infection results in considerable morbidity and mortality, especially when cirrhosis is present. (Niederau C, et al. Hepatology 1998; 28: 1687-1695)