Hepatitis C Virus Cure Before Hepatocellular Carcinoma Diagnosis Is Associated With Improved Survival

Ian Lockart; Behzad Hajarizadeh; Maryam Alavi; Scott Davison; Emilia Prakoso; Miriam T. Levy; Jacob George; Gregory J. Dore; Mark Danta

Disclosures

J Viral Hepat. 2021;28(5):710-718. 

In This Article

Abstract and Introduction

Abstract

The impact of hepatitis C virus (HCV) cure on survival in patients with HCV-related hepatocellular carcinoma (HCC) has been examined, although many studies have been subject to survivor treatment selection bias. We assessed the impact of HCV cure before HCC diagnosis on overall survival. Patients with HCV-related HCC at three referral hospitals in Australia were included retrospectively (January 2008 to December 2019). The risk of death following HCC diagnosis among patients who achieved HCV cure before HCC diagnosis was compared to patients who were viraemic at diagnosis. Among 422 patients with HCV-related HCC, 101 (24%) achieved HCV cure before HCC diagnosis, 37 with interferon (IFN) and 64 with direct-acting antiviral (DAA) therapy. Patients with HCV cure were more likely to have no cirrhosis or Child-Pugh A liver disease (83% vs. 66%, p = .002), surveillance detection (71% vs. 48%, p < .001), HCC stage O or A (64% vs. 45%, p < .001) and receive curative initial HCC management (51% vs. 28%, p < .001), compared with patients who were viraemic at diagnosis. The 5-year overall survival was 51% in the HCV cure group and 22% in the viraemic group. In adjusted analysis, risk of death was lower in patients with HCV cure before HCC diagnosis compared with patients who were viraemic at diagnosis (adjusted hazard ratio: 0.63; 95% CI: 0.44–0.91; p = .013). Patients with HCV-related HCC who have achieved HCV cure before HCC diagnosis have improved overall survival compared with patients who were viraemic at diagnosis.

Introduction

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in many parts of the world and is the fastest growing cause of cancer-related death in Australia.[1,2] Typically occurring in patients with underlying chronic liver disease, HCC is often detected at an advanced stage and has a high mortality-to-incidence ratio.[2–4] Chronic hepatitis C virus (HCV) infection is the most common cause of chronic liver disease and HCC in the majority of developed countries, including Australia.[5] Despite advances in HCC therapeutics in recent decades, HCC survival remains poor with a 5-year survival of 20%.[2]

The recent advent of direct-acting antiviral (DAA) therapy has revolutionized HCV treatment. Rates of HCV cure, defined by sustained virologic response (SVR), exceed 95%.[6] For patients with a history of HCC, DAAs remain well-tolerated and effective, although HCV cure rates are reduced.[7,8] With increasing numbers of patients achieving HCV cure, both before and after HCC diagnosis, it is important to understand the impact on HCC outcomes. It has been shown that HCV cure following interferon (IFN)-based therapy is associated with improved outcomes, including reduced HCC recurrence and mortality.[9–13] The impact of DAA therapy on HCC outcomes is less clear. After initial controversy, it has been shown that DAA therapy does not increase HCC recurrence.[14–16] More recently, studies have suggested that DAA therapy, specifically HCV cure, improves HCC survival, although many studies have been subject to survivor treatment selection bias and further studies are required.[17–20] This study aimed to assess the impact of HCV cure before HCC diagnosis, following IFN or DAA therapy, on overall survival.

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