Real-world Impact Following Initiation of Interferon-free Hepatitis C Regimens on Liver-related Outcomes and All-cause Mortality Among Patients With Compensated Cirrhosis

Scott A. McDonald; Kevin G. Pollock; Stephen T. Barclay; David J. Goldberg; Andrew Bathgate; Peter Bramley; John F. Dillon; Andrew Fraser; Hamish A. Innes; Nicholas Kennedy; Judith Morris; April Went; Peter C. Hayes; Sharon J. Hutchinson

Disclosures

J Viral Hepat. 2020;27(3):270-280. 

In This Article

Abstract and Introduction

Abstract

Few studies have investigated clinical outcomes among patients with cirrhosis who were treated with interferon (IFN)-free direct-acting antiviral (DAA). We aimed to quantify treatment impact on first decompensated cirrhosis hospital admission, first hepatocellular carcinoma (HCC) admission, liver-related mortality and all-cause mortality among a national cohort of cirrhotic patients. Through record linkage between Scotland's HCV Clinical Database and inpatient/day-case hospitalization and deaths records, a study population comprising chronic HCV-infected patients with compensated cirrhosis and initiated on IFN-free DAA between 1 March 2013 and 31 March 2018 was analysed. Cox regression evaluated the association of each clinical outcome with time-dependent treatment status (on treatment, responder, nonresponder or noncompliant), adjusting for patient factors including Child-Pugh class. Among the study population (n = 1073) involving 1809 years of follow-up, 75 (7.0%) died (39 from liver-related causes), 47 progressed to decompensated cirrhosis, and 28 developed HCC. Compared with nonresponders, treatment response (96% among those attending their 12 weeks post-treatment SVR test) was associated with a reduced relative risk of decompensated cirrhosis (hazard ratio [HR] = 0.14; 95% CI: 0.05–0.39), HCC (HR = 0.17; 95% CI: 0.04–0.79), liver-related death (HR = 0.13; 95% CI: 0.05–0.34) and all-cause mortality (HR = 0.30; 95% CI: 0.12–0.76). Compared with responders, noncompliant patients had an increased risk of liver-related (HR = 6.73; 95% CI: 2.99–15.1) and all-cause (HR = 5.45; 95% CI: 3.07–9.68) mortality. For HCV patients with cirrhosis, a treatment response was associated with a lower risk of severe liver complications and improved survival. Our findings suggest additional effort is warranted to address the higher mortality among the minority of cirrhotic patients who do not comply with DAA treatment or associated RNA testing.

Introduction

Direct-acting antiviral (DAA) drugs for chronic hepatitis C virus (HCV) infection have prompted considerable optimism that the escalating HCV-related liver disease burden in countries may be reduced through treatment.[1,2] DAA regimens have produced sustained virological response (SVR) rates in excess of 90% for patients with compensated cirrhosis, more than twice the rate achieved by interferon-based regimens.[3] Given initial clinical guidelines and practice involving treatment prioritization for those with advanced fibrosis,[4,5] an appreciable proportion of the 5 million people treated with DAAs globally to date will have had compensated cirrhosis.[6] Despite this, there remains relatively little evidence regarding the impact of IFN-free therapy for patients with compensated cirrhosis on important clinical outcomes, such as progression to decompensated cirrhosis (DC), development of HCC and mortality

There is robust and compelling evidence from the interferon treatment era that patients achieving SVR have significantly reduced risk of severe liver complications and all-cause mortality compared with non-SVR.[7,8] More recently, well-conducted clinical trials and real-world studies have demonstrated the ability of DAAs to effectively clear HCV from the host.[9–11] Yet the clinical utility of a DAA-induced SVR has been disputed by authors of a Cochrane review, who advocated that the impact of DAA therapy on HCV-related liver morbidity remains unproven;[12] an aim of our study was to provide real-world observational evidence to address this issue.

The main objective of our study was to evaluate the clinical benefit of IFN-free regimens through examination of the development of severe outcomes (including first DC admission, first hepatocellular cancer (HCC) admission, and liver-related and all-cause mortality) from the point of initiation on treatment for an entire national cohort of chronically HCV-infected patients diagnosed with compensated cirrhosis. In a real-world patient cohort, a significant minority of patients fail to complete treatment or do not return for RNA testing;[13] as a secondary objective, we examined the same clinical outcomes in these patients. Although we would anticipate high rates of viral clearance among those compensated cirrhosis patients who do not return for HCV RNA testing upon completion of DAA therapy, the same behavioural factors associated with noncompliance may also lead to a heightened risk of liver disease progression and mortality.

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