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Long-term surveillance of liver histological changes in chronic hepatitis C patients completing pegylated interferon-α plus ribavirin therapy: an observational cohort study.

ABSTRACT:

Background

For chronic hepatitis C (CHC) patients completing pegylated interferon (PegIFN)-α/ribavirin therapy, long-term liver histological changes remain largely unexplored.

Methods

This observational cohort study included 85 CHC patients completing PegIFN-α/ribavirin therapy with liver biopsies performed at baseline and the end of surveillance (EOS). Median years between paired biopsies were 6.75 (interquartile range: 5.63-7.54).

Results

In patients with baseline METAVIR fibrosis stages (F) <4 (able to undergo fibrosis progression; n = 77), cases achieving sustained virological response (SVR) (n = 52) had a significantly lower rate of fibrosis progression than non-SVR cases (n = 25) (3.8% versus 24.0%, p = 0.012). Among the entire cohort (n = 85), the rate of activity response [METAVIR activity grades (A) decreasing or maintaining at A0] in SVR cases (n = 59) was significantly higher than that in non-SVR cases (n = 26) (94.9% versus 65.4%, p = 0.001). For SVR cases among the entire cohort, independent predictors of fibrosis clearance included baseline F <2 [odds ratio (OR) = 7.877, p = 0.042] and aspartate transaminase (AST) levels declining by >70% at EOS compared with baseline (OR = 9.013, p = 0.038). For non-SVR cases among the entire cohort, baseline AST levels >80 U/l and glucose levels ⩽ 105 mg/dl independently predicted significant fibrosis (F2/F3/F4) at EOS (OR = 12.558, p = 0.049) and activity response (OR = 17.741, p = 0.047), respectively.

Conclusions

Among CHC patients completing PegIFN-α/ribavirin therapy, SVR lowers the risk of liver histological progression but does not guarantee fibrosis clearance. For SVR cases, those with baseline F ⩾ 2 or without significantly declined follow-up AST levels should be specifically monitored. As for non-SVR cases, those with a higher baseline AST or glucose level should preferentially receive retreatment.

SUBMITTER: Hsieh MH

PROVIDER: S-EPMC8771741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:UNLABELLED:Combination treatment with pegylated-interferon-alpha (PEG IFN-alpha) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-alpha2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2-2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders (P = 0.006). CONCLUSION:Genetic polymorphisms in the interferon-alpha pathway may affect responses to antiviral therapy of chronic hepatitis C.