The spectrum of hepatic functional impairment in compensated chronic hepatitis C: results from the hepatitis C anti-viral long-term treatment against cirrhosis trial

Background The spectrum of functional impairment in patients with compensated chronic hepatitis C is incompletely defined. Aim To define hepatic impairment by quantitative tests (quantitative liver function tests) and correlate results with disease severity in patients with chronic hepatitis C. Methods We studied 285 adult patients with chronic hepatitis C prior to treatment in the Hepatitis C Anti-viral Long-term Treatment against Cirrhosis Trial; 171 had Ishak fibrosis stages 2-4 (fibrosis) and 114 had stage 5 or 6 (cirrhosis). None had had clinical decompensation. A battery of 12 quantitative liver function test assessed the spectrum of hepatic microsomal, mitochondrial and cytosolic functions, and hepatic and portal blood flow. Results Twenty-six to 63% of patients with fibrosis and 45-89% with cirrhosis had hepatic impairment by quantitative liver function test; patients with cirrhosis had the greatest impairment (P-value ranging from 0.15 to < 0.0001). Cholate Cl-oral, cholate shunt and perfused hepatic mass correlated with cirrhosis, stage of fibrosis (r = -0.51, +0.49, -0.51), varices and variceal size (r = -0.39, +0.36, -0.41). PHM < 95 and cholate shunt > 35% identified 91% of patients with medium- or large-sized varices. Conclusions Hepatic impairment is common in compensated patients with fibrosis or cirrhosis because of chronic hepatitis C. Cholate shunt, and cholate Cl-oral and perfused hepatic mass, identify patients at risk for cirrhosis or varices.