Sorting Out Cirrhosis: Mechanisms of Non-response to Hepatitis C Therapy

Saeed H. Al Marzooqi; Jordan J. Feld


Liver International. 2015;35(8):1923-1933. 

In This Article

Abstract and Introduction


Although cirrhosis has long been recognized as an important negative predictor of treatment response for hepatitis C virus (HCV) therapy, the mechanisms underlying this association remain relatively poorly understood. Treatment has progressed rapidly with the introduction of highly effective all-oral therapies, with promising outcomes even in patients with advanced cirrhosis. However, even with the new therapies, it is clear that patients with cirrhosis require special attention. Efficacy continues to be somewhat reduced compared to non-cirrhotic patients and safety is an important concern. In this review, we explore the reasons for treatment non-response in patients with cirrhosis. We focus on how cirrhosis impacts on four important areas including drug delivery, drug uptake and metabolism, immune responses and drug toxicity with examples from the clinical and basic literature. Fortunately, as treatment continues to progress, many of the challenges of treating patients with cirrhosis will become less and less problematic.


Since the introduction of interferon-based therapy for hepatitis C virus (HCV) infection, predictors of response have been carefully evaluated to determine which patients are more likely to respond and why. While many of these factors were identified and explained, the presence of cirrhosis remains one of the well established yet least understood conditions that complicate HCV therapy.[1] In this review, we aim to shed light on the various and likely multifactorial mechanisms responsible for impaired responses in patients with cirrhosis.