Histologic Outcomes in Hepatitis C–Infected Patients with Varying Degrees of Virologic Response to Interferon-Based Treatments

Abstract

Patients with chronic hepatitis C with partial virologic response or nonresponse to interferon‐based therapies can experience treatment‐related improvements in liver histology. This retrospective analysis assessed the histologic response to treatment in patients with varying degrees of virologic response (sustained virologic response [SVR], breakthrough, relapse, or nonresponse), time to hepatitis C virus (HCV) RNA undetectability, and duration of viral suppression. Patients (HCV genotypes 1‐6) with baseline and follow‐up liver biopsies from eight phase 2 to phase 4 interferon‐based trials were analyzed. Blinded biopsies were evaluated by a single pathologist. Improvements or worsening of METAVIR necroinflammatory activity and fibrosis were defined as increase or decrease of ≥1 grading category from baseline to 24 weeks after end of treatment. A majority of the 1571 patients with paired biopsy data were white, male, with HCV genotype 1/4, baseline HCV RNA levels >800,000 IU/mL, and baseline alanine aminotransferase levels ≤3 × upper limit of the normal range; mean baseline activity and fibrosis scores were 1.8 and 1.7, respectively. Overall, 80% of patients received peginterferon alfa‐2a monotherapy or peginterferon alfa‐2a/ribavirin combination therapy. Mean treatment duration was 46 weeks. There was a positive correlation between the degree of virologic response and improvements in METAVIR activity and fibrosis, and an inverse correlation with worsening activity and fibrosis (all comparisons, P < 0.0001). Patients with SVR had the greatest histologic benefit. As a combined group, relapsers and patients with breakthrough had significantly greater benefits than nonresponders (activity, P = 0.0001; fibrosis, P = 0.003). Consistent with these results, a better histologic response was correlated with a shorter time to undetectable HCV RNA and a longer duration of viral suppression (all comparisons, P < 0.0001). Conclusion: In patients with chronic hepatitis C who were treated with interferon‐based therapies, histologic benefits may be observed even in the absence of an SVR. (HEPATOLOGY 2010;)

Predictors of Early Virological Response of Viral Hepatitis C to Combination Therapy with Pegylated Interferon Plus Ribavirin

“…This finding is in agreement with the finding of [34] who demonstrated that serum AST levels < 40 U/l is correlated independently with complete response. Pockros et al [35] demonstrated that there is no significant difference in ALT level between responders and non-responders.…”

Serum Biomarkers Indicate Long-term Reduction in Liver Fibrosis in Patients With Sustained Virological Response to Treatment for HCV Infection

“…1–4 A significant regression of fibrosis has been observed previously among hepatitis B patients after long-term virologic suppression with tenofovir disoproxil fumate. 23 Although the exact mechanism is unclear, suppression of viral replication may reduce hepatic inflammation and consequent fibrosis, allowing regeneration of healthy tissue.…”

Randomized clinical trial

“…However, even in the absence of SVR treatment, benefits have been observed. Both reduction in portal pressure [20] and significant histological improvement with antiviral therapy have been observed in the absence of achievement of SVR [21]. This observation is supported by studies in animal models where type 1 interferons have been shown to have a direct antifibrotic effect [22,23].…”