Should Surveillance for Liver Cancer be Modified in Hepatitis C Patients After Treatment-related Cirrhosis Regression?

Roberta D'Ambrosio; Massimo Colombo

Disclosures

Liver International. 2016;36(6):783-790. 

In This Article

Abstract and Introduction

Abstract

Surveillance of hepatocellular carcinoma (HCC) with abdominal ultrasound (US) is recommended for patients with advanced liver fibrosis because of hepatitis C virus (HCV) infections who achieve a sustained virological response (SVR) to antiviral therapy. HCC, in fact, may still develop following SVR as a consequence of long-standing carcinogenic activity of either HCV or hepatic fibrosis, whereas HCC risk in non-viraemic patients may also be driven by cofactors like alcohol abuse or diabetes. This explains the debate on whether surveillance for HCC should be continued in patients with documented cirrhosis regression following a SVR too. While regression of cirrhosis was documented to occur in a majority of patients with compensated cirrhosis 5 years after an SVR to interferon, it should be noted that this clinical benefit could be the consequence of treating a selected population with well-compensated liver disease who in fact were interferon able. This may not be the case for most real-life patients with advanced cirrhosis receiving direct antivirals, in whom liver fibrosis may have reached a point of no-return thus potentially preventing the recovery of a normal liver architecture following SVR. Both invasive and non-invasive tools have suboptimal diagnostic accuracy for fibrosis regression in non-viraemic patients, and this prompts to follow international societies' recommendation to perform surveillance in patients with advanced liver fibrosis achieving a SVR, independently on liver histology outcome.

Introduction

Chronic infection with the hepatitis C virus (HCV) is a leading cause of anticipated liver-related death and a major indication to liver transplantation, worldwide.[1–7] Clearance of serum HCV (sustained virological response, SVR) by means of interferon (IFN) therapy has long remained the only curative option that results in a reduction in all cause and liver-related mortality rates, the survival benefits being the consequence of a reduction in both extrahepatic complications like myocardial infarction, stroke, end-stage renal disease and lymphoma,[8–11] and of end-stage liver complications, including hepatocellular carcinoma (HCC).[12–17] This notwithstanding, HCC may still develop in SVR patients with advanced liver fibrosis at the start of therapy,[8,13–30] a finding that challenges in terms of cost benefits ratio current strategies of treatment prioritization of patients with advanced liver disease. At the same time, evidence has emerged that in a proportion of patients with a SVR survival, benefits were strictly the consequence of a treatment-induced reversal of cirrhosis documented by sequential liver histology examination.[15] The fact that such a favourable clinical event does not occur in all SVR patients has suggested the existence of a point of no-return in the course of hepatitis C beyond which most clinical benefits of HCV eradication are lost. While the mechanisms beyond reversal of cirrhosis remain elusive, the universal access of patients with advanced HCV to the newer, potent and safe direct antiviral agents (DAAs) will cause a substantial accumulation of SVR patients who need surveillance for the residual risk of HCC.[31–34] While this raises the question whether surveillance is still needed in patients with a cirrhosis reversal, a breakthrough in the management of HCV would be developing non-invasive, user-friendly tools for the identification of reversal of cirrhosis to avoid invasive procedures like liver biopsy and optimize surveillance algorithms of SVR patients.

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