Hepatitis C Virus Genotype 3 Was Associated With the Development of Hepatocellular Carcinoma in Korea

Sang Soo Lee; Cha Young Kim; Bo Ra Kim; Ra Ri Cha; Wan Soo Kim; Jin Joo Kim; Jae Min Lee; Hong Jun Kim; Chang Yoon Ha; Hyun Jin Kim; Tae Hyo Kim; Woon Tae Jung; Ok-Jae Lee

Disclosures

J Viral Hepat. 2019;26(4):459-465. 

In This Article

Abstract and Introduction

Abstract

Although hepatitis C virus (HCV) genotype 3 infection is thought to be an important risk factor for hepatocellular carcinoma (HCC), current evidence is limited because only a few Western studies have evaluated the occurrence of HCC in patients with HCV genotype 3 infection. We evaluated the impact of genotype 3 and non-3 on HCC incidence and on disease progression in chronic HCV patients; this is the first study reporting such findings in an Asian population. We performed a retrospective cohort study using the data of 1448 consecutive chronic HCV patients evaluated at three centres in Korea between January 2005 and December 2016. Of these, 604, 675 and 169 had genotype 1, genotype 2 and genotype 3 HCV infections, respectively. Over a mean follow-up period of 53.2 months, 75 and 143 patients of all the patients developed HCC and experienced disease progression, respectively. The incidences of HCC were 1.10, 0.92 and 2.50 per 100 person-years, and those of disease progression were 1.95, 1.62 and 6.72 per 100 person-years for HCV genotypes 1, 2 and 3, respectively. In multivariate Cox regression analysis, genotype 3 was associated with an increased risk of HCC (hazard ratio [HR] = 4.26, 95% confidence interval [CI] = 2.02-8.97) and an increased risk of disease progression (HR = 4.88, 95%; CI = 2.94-8.08). Our study proposes that HCV genotype 3 is an independent risk factor for HCC and disease progression in chronic HCV patients.

Introduction

Hepatitis C virus (HCV) affects more than 185 million individuals worldwide,[1] representing a major cause of liver-related morbidity, including liver cirrhosis, hepatocellular carcinoma (HCC) and death.[2,3] HCC is the most serious complication in patients with chronic hepatitis C infection. The incidence rate of HCC has been shown to vary geographically. For example, the yearly incidence of HCC in patients with HCV-related cirrhosis may be higher in Asian populations (5%-8%) than in Western populations (1%-4%).[4,5] Several factors increase the risk of HCC development in patients with chronic hepatitis C: older age; the male gender; a more advanced fibrosis status; heavy alcohol intake; diabetes; and hepatitis B virus (HBV) co-infection.[5–8] In addition, HCV genotypes may influence the risk of the development of HCC.[9,10]

Hepatitis C virus strains are classified into seven genotypes on the basis of phylogenetic and sequence analyses.[11] The distribution of HCV genotypes shows varied geographic patterns.[12] HCV genotype 1 is the most prevalent worldwide (46.2%), approximately one-third of its occurrence is in East Asia. Genotype 2 is responsible for a total of 9.1% of HCV infections, and East Asia accounts for the majority of its occurrences. Genotype 3 is the second most prevalent globally (30.1%), approximately three-quarters of all infections with the virus occur in South Asian countries such as India and Pakistan. In addition, HCV genotype 3 is especially prevalent among people who inject drugs (PWID) in European countries.[13]

Hepatitis C virus genotype 1 infection might also play an important role in HCC development, although it was argued that the association between HCC development and genotype 1 could largely be explained by a birth cohort effect.[9] However, the recent challenge in treating HCV genotype 3 infection has raised new concerns regarding the possible association between genotype 3 infection status and HCC development in patients with chronic hepatitis C infection. HCV genotype 3 has become the most difficult HCV genotype to treat using current direct-acting agents (DAA).[14] With a large global distribution, HCV genotype 3 has become an important healthcare problem, with a specific transmission route in PWID and a unique pathophysiology. Moreover, it has the highest rate of steatosis among the HCV genotypes.[15] In a recent meta-analysis of cross-sectional single-biopsy studies, HCV genotype 3 was associated with a more accelerated progression of liver fibrosis than the other genotypes.[16] However, only a few Western studies have evaluated the rate of HCC development among patients with HCV genotype 3 infection.[17–19] Although HCV genotype 3 infection is thought to be an important risk factor for HCC, current evidence is limited. Moreover, there has been no report of genotype 3 infection as a risk factor for HCC development in an Asian population.

We established a retrospective, multicenter HCV cohort study in Korea to investigate the outcomes of patients with chronic hepatitis C infection. The aims of the current study were to compare the rate of HCC development and disease progression among patients with chronic hepatitis C who have genotype 3 HCV compared to those of patients with chronic hepatitis C who have the other HCV genotypes (non-3) infection.

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