Differential Effect of HCV Eradication and Fibrosis Grade on Hepatocellular Carcinoma and All-cause Mortality

Yun Bin Lee,Dong Ho Lee,Eun Ju Cho,Young Chang,Jeong Min Lee,Joon Yeul Nam,Seong Gyu Hwang,Hyeki Cho,Su Jong Yu,Hwi Young Kim,Jeong-Hoon Lee,Jung-Hwan Yoon,Yoon Jun Kim,Young Youn Cho

doi:10.1038/s41598-018-31839-y

Abstract

Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. We investigated the differential effect of SVR on the risk of outcomes according to hepatic fibrosis grade. Fibrosis grade was categorised using FIB-4: <1.45, low-probability of significant fibrosis; 1.45–3.25, intermediate-probability; and ≥3.25, high-probability. Primary and secondary endpoints were hepatocellular carcinoma (HCC) occurrence and death, respectively. Among 1,373 included chronic hepatitis C patients, 744 patients were treated with interferon-based or –free regimens and 622 (83.6%) achieved SVR. SVR was independently associated with lower risk of HCC (vs. untreated: adjusted hazard ratio [aHR], 0.165; 95% confidence interval [CI], 0.077–0.350; P < 0.001) and overall death (vs. untreated; aHR, 0.146; 95% CI, 0.050–0.424; P < 0.001) during the median observation of 3.5 (interquartile range, 1.9–6.6) years. The SVR group had significantly lower risk of HCC than the untreated group among patients with intermediate-probability (n = 492: aHR, 0.171; 95% CI, 0.051–0.578; P = 0.004) and high-probability (n = 446: aHR, 0.243; 95% CI, 0.107–0.551; P < 0.001) of significant fibrosis. HRs were maintained after balancing with inverse probability weighting. SVR was associated with reduced risk of HCC development and all-cause mortality in patients with chronic hepatitis C.

Highlights

Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established
Patients treated with direct-acting antivirals (DAAs) received daclatasvir/asunaprevir (n = 198) or elbasvir/grazoprevir (n = 4) for patients infected by genotype 1B hepatitis C virus (HCV), sofosbuvir/ledipasvir (n = 39) or daclatasvir/sofosbuvir (n = 9) for patients infected by genotype 1 A HCV and genotype 1B HCV with resistance-associated variants (i.e., L31W/V/F/N/I/S/P/R and Y93N/H/C/P/D variants), or sofosbuvir plus ribavirin (n = 76) for patients infected by genotype 2 HCV
SVR achieved with antiviral treatment including IFN-based therapy and DAAs was associated with a reduced risk of developing hepatocellular carcinoma (HCC)

Summary

Introduction

Whether a sustained virological response (SVR) improves long-term outcomes in chronic hepatitis C patients with earlier-stage fibrosis has not been established. SVR was associated with reduced risk of HCC development and all-cause mortality in patients with chronic hepatitis C. The introduction of new direct-acting antivirals (DAAs) for the treatment of CHC has derived excellent sustained virological response (SVR) rates in most HCV-infected patients, including patients with advanced fibrosis and extrahepatic comorbidities. While the risk of developing hepatic decompensation, HCC, or death has been reported to be significantly lower in patients with METAVIR fibrosis grades F0–F213,14, higher SVR rates are achievable and liver disease progression can be halted after SVR achievement in patients with lower-stage fibrosis, augmenting treatment benefits[2]. We aimed to analyse the association between eradication of HCV and the risk of HCC development and all-cause mortality in HCV-infected patients according to fibrosis stage of liver

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