Drug disposition in patients with HBsAg-positive chronic liver disease

Chronic infection with hepatitis B virus (HBV) results in a spectrum of hepatic abnormalities ranging from minimal liver dysfunction to severe liver failure. These patients provide an opportunity to examine the relationship between the evolution of the liver disease and the ability to metabolize drugs. We have examined hepatic drug disposition in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis due to HBV infection. Four model drugs were used: two low-extraction capacity-limited drugs (antipyrine and aminopyrine) and two high-extraction flow-limited drugs (ICG and lidocaine). The disposition of the four drugs tested was comparable to that of healthy controls in patients with chronic persistent hepatitis, chronic active hepatitis, and mild cirrhosis. In patients with severe cirrhosis (as defined by the presence of ascites, encephalopathy, or large esophageal varices), there was a significant impairment in the aminopyrine breath test (–31%) and in the clearance of antipyrine (–53%), lidocaine (–49%), and ICG (–54%). These results indicate that impairment of drug clearance occurs only late in the evolution of HBV-related chronic liver disease. This is in keeping with the known slow and insidious progression of the disease.Supported by grants from the Medical Research Council of Canada, The Canadian Liver Foundation and the Fonds de Recherche en Santé du Québec