Evolution of hepatic steatosis in patients with advanced hepatitis C: results from the hepatitis C antiviral long-term treatment against cirrhosis (HALT-C) trial

Abstract

Hepatic steatosis is a common histologic feature in patients with chronic hepatitis C (CHC) but there are no large longitudinal studies describing the progression of steatosis in CHC. We examined changes in steatosis on serial biopsies among CHC patients participating in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial. All 1050 patients in the trial had advanced fibrosis at baseline biopsy and were documented not to have had a sustained virological response to peginterferon and ribavirin. Most (94%) patients had genotype 1 infection. At least one protocol follow-up biopsy was read on 892 patients, and 699 had the last biopsy performed 3.5 years after randomization. At enrollment, 39% had cirrhosis and 61% had bridging fibrosis; 18%, 41%, 31%, and 10% had steatosis scores of 0, 1, 2, and 3 or 4, respectively. The mean steatosis score decreased in the follow-up biopsies in both the interferon-treated patients and controls with no effect of treatment assignment (P = 0.66). A decrease in steatosis score by > or =1 point was observed in 30% of patients and was associated with both progression to cirrhosis and continued presence of cirrhosis (P = 0.02). Compared to patients without a decrease in steatosis, those with a decrease in steatosis had worse metabolic parameters at enrollment, and were more likely to have a decrease in alcohol intake, improvement in metabolic parameters, and worsening liver disease (cirrhosis, esophageal varices, and deterioration in liver function).

Conclusion: Serial biopsies demonstrated that in patients with CHC, steatosis recedes during progression from advanced fibrosis to cirrhosis. Decreased alcohol intake and improved metabolic parameters are associated with a decline in steatosis and may modulate hepatitis C progression.

Trial registration: ClinicalTrials.gov NCT00006164.

Figure 1

Changes in Steatosis Scores in Patients with Fibrosis vs. Cirrhosis – Stacked columns show percent of patients with decrease in steatosis score by ≥1 points, no change, and increase in steatosis score by ≥1 points among all 892 patients (ALL), 256 patients who had bridging fibrosis on baseline and last biopsies (F → F), 89 patients who had cirrhosis on baseline biopsy and bridging fibrosis on last biopsy (C → F), 398 patients who had cirrhosis on both biopsies (C → C), and 187 patients who had bridging fibrosis on baseline biopsy and cirrhosis on last biopsy (F → C). Decrease in steatosis score by >1 points was observed in 30.4% of ALL patients, being most common in those who progressed from fibrosis to cirrhosis: 41.6% of F → C vs. 25.1% of F → F patients, 29.2% of C → F patients, 32.4% of C → C patients.

Figure 2

Correlation between change in steatosis score and progression to cirrhosis on follow-up biopsy – 38.3% of patients with decrease in steatosis score by ≥1 point progressed to cirrhosis compared to 23.1% of those with no change and 21.4% of those with increase in steatosis score (p=0.0008).

Figure 3

Serial biopsies of a patient obtained at baseline, Year 1.5 and Year 3.5 showing progression from Ishak fibrosis score of 3 to 6 with concomitant decrease in steatosis score from 3 to 2.