Quantitative tests of liver function measure hepatic improvement after sustained virological response: results from the HALT-C trial.
BACKGROUND
The impact of virologic response on hepatic function has not been previously defined.


OBJECTIVE
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-(13)C]cholate, galactose and (99m)Tc-sulfur colloid were administered intravenously; [2,2,4,2-(2)H]cholate, [1-(13)C]methionine, caffeine and antipyrine were administered orally. Clearances (Cl), breath (13)CO(2), 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 < or =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.


CONCLUSIONS
Hepatic dysfunction impairs the virological response to PEG/RBV. SVR improves hepatic metabolism, the portal circulation and PHM.
Everson
G T
GT
Section of Hepatology, Division of Gastroenterology and Hepatology, University of Colorado School of Medicine, Aurora, CO 80045, USA. greg.everson@uchsc.edu
Shiffman
M L
ML
Hoefs
J C
JC
Morgan
T R
TR
Sterling
R K
RK
Wagner
D A
DA
Desanto
J L
JL
Curto
T M
TM
Wright
E C
EC
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000503:physiopathology / Q000821:virology; D006801:Humans; D007372:Interferons / Q000627:therapeutic use*; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D008875:Middle Aged; D012254:Ribavirin; D013223:Statistics as Topic
D000998:Antiviral Agents; D012254:Ribavirin; D007372:Interferons