Rate of progression of hepatic fibrosis in patients with chronic hepatitis C: results from the HALT-C Trial

Abstract

Background & aims: The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies.

Methods: The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years.

Results: The RFSP as average fibrosis score vs average time in intervals (0-3 and >3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 ± 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 ± 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope ≥ 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P <.0001) with clinical outcomes in multivariate analysis.

Conclusions: Rapid RFSP (>0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes.

Trial registration: ClinicalTrials.gov NCT00006164.

Figure 1

Flow diagram of prestudy serial histology patients. Of 1,050 patients enrolled, 545 had a pre-study biopsy, but in only 457 of these patients was a biopsy available longer than >10 mm, and in only 344 was the interval between the first and the HALT-C Trial screening liver biopsy (LBx) at least 4 years. The analysis performed in each group of biopsies is listed on the left side of the figure and described in the text..

Figure 2

Figure 2a. The rate of clinical outcomes excluding HCC (± SEM) by rate of Ishak score progression. Log rank test of equality of distributions, P <0.0001. Figure 2b. Distribution of cumulative HCC incidence rates (± SEM) by rate of Ishak score progression. Log rank test of equality of distributions P = 0.04.