Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial

The impact of virologic response on hepatic function has not been previously defined. To determine the relationships of quantitative liver function tests (QLFTs) with virological responses to peginterferon (PEG) +/- ribavirin (RBV) in patients with chronic hepatitis C and to use serial QLFTs to define the spectrum of hepatic improvement after sustained virological response (SVR). Participants (n = 232) were enrolled in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial, had failed prior therapy, had bridging fibrosis or cirrhosis and were retreated with PEG/RBV. All 232 patients had baseline QLFTs; 24 patients with SVR and 68 nonresponders had serial QLFTs. Lidocaine, [24-C-13]cholate, galactose and Tc-99m-sulfur colloid were administered intravenously; [2,2,4,2-H-2]cholate, [1-C-13]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath (CO2)-C-13, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Rates of SVR were 18-26% in patients with good function by QLFTs, but <= 6% in patients with poor function. Hepatic metabolism, measured by caffeine k(elim) (P = 0.02), antipyrine k(elim) (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cl-oral (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM.