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

Abstract

Backgroud: The impact of virologic response on hepatic function has not been previously defined. Aim: 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). Methods: 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, [24-13C]cholate, galactose and 99mTc-sulfur colloid were administered intravenously; [2,2,4,2-2H]cholate, [1-13C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath 13CO2, monoethylglycylxylidide (MEGX), perfused hepatic mass (PHM) and liver volume were measured. Results: 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 kelim (P = 0.02), antipyrine kelim (P = 0.05) and antipyrine Cl (P = 0.02) and the portal circulation, measured by cholate Cloral (P = 0.0002) and cholate shunt (P = 0.0003) and PHM (P = 0.03) improved after SVR. Conclusion: Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM. © 2009 The Authors.