Predictors of hepatitis C treatment response: what's new?

Abstract

Hepatitis C virus infection is a growing, global health problem, with mortality expected to reach a peak in the next ten years in many western countries. A number of host and viral factors have been established as useful predictors of treatment response in the context of interferon and ribavirin. Several new markers have recently been identified that improve our understanding of treatment response. The addition of protease inhibitors to treatment regimens has highlighted the importance of viral kinetics on-treatment in predicting response to treatment. Many new classes of direct acting anti-virals are currently being developed and expected to be clinically available in the near future. Current predictors of treatment response will be redefined in the context of interferon free regimens.

Keywords::

• direct-acting antivirals
• hepatitis C virus
• IL-28B
• interferon
• predictors
• ribavirin
• sustained virological response

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Numerous host and viral factors have been identified as predictors of response to treatment for HCV. Important pre-treatment viral factors include: genotype, subtype and baseline viral load. Host factors include: IL-28B genotype, race, age, BMI, fibrosis, coinfection and adherence.

• Viral genotype and host IL-28B genotype are the strongest pre-treatment predictors of response in treatment-naïve patients.

• Viral genotype, IL-28B genotype and cirrhosis remain relevant for many of the new direct-acting antivirals (DAAs).

• Other immune markers have been identified that may increase the predictive value of IL-28B genotype, for example, HLA-C, IP-10 levels and anti-E1E2 antibody titers. IFNL4 may succeed IL-28B as a more powerful predictor of response.

• For treatment-experienced patients, previous response to interferon/ribavirin is one of the strongest predictors.

• Rapid virological response is the strongest on-treatment predictor of sustained virological response (SVR) and forms the basis of response-guided treatment.

• Further work needs to be done to clarify the role of vitamin D supplementation in response to treatment.

• Larger trials are required to understand how current predictors of response are relevant to newer DAAs.