Patients with hepatitis who received treatment to reduce hepatic inflammation experienced decreased fibrosis progression and fewer clinical outcomes than controls in a recent study.
Researchers evaluated 834 patients with hepatitis C and advanced fibrosis or cirrhosis who were participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis (HALT-C) trial. Patients randomly received either a maintenance dose of 90 mcg/week of peginterferon (n=420) or served as controls (n=414) for 3.5 years. Among these participants, 657 had received full-dose peginterferon/ribavirin lead-in therapy before randomization. Biopsies were conducted at baseline and at 1.5 and 3.5 years after randomization. Inflammation was measured according to the Ishak hepatic activity index (HAI).
At 1.5 years, the mean change in HAI was –0.87 (95% CI, –1.10 to –0.64) in the treated group compared with 0.12 (95% CI, –0.12 to 0.35) in controls. Virological suppression through prior therapy was associated with improved HAI at 3.5 years in both groups (P=.001 for treated patients; P=.01 for controls). Maximal suppression was associated with fewer clinical outcomes to 8.5 years in both the treated (HR=0.37; 95% CI, 0.18-.073) and control groups (HR=0.50; 95% CI, 0.27-0.92).
After a median of 6 years of follow-up, investigators found that patients with an improvement in HAI at biopsy, regardless of whether they were in the treated or control groups, were prone to fewer clinical outcomes compared with treated patients without HAI improvement (HR=0.63; 95% CI, 0.41-0.95) and controls (HR=0.60; 95% CI, 0.36-0.99). Fibrosis progression was reduced among patients with Ishak 3-4 fibrosis at baseline whose HAI had improved at biopsy (P=.0003 compared with treated patients without HAI improvement and P=.02 compared with controls). Cox regression analysis indicated that HAI improvement was a significant predictor for clinical outcomes (HR=0.64; 95% CI, 0.46-0.89).
“Decreased hepatic inflammation … appeared to be a critical factor that was associated with reduced fibrosis progression and, to a lesser extent, fewer clinical outcomes,” the researchers wrote. “We conclude that reduction of hepatic inflammation appears to be an important target for future therapeutic interventions to retard the progression of hepatitis C-related liver disease.”
Disclosure: See the study for a full list of relevant disclosures.