Hepatitis C virus genotype 1b increases cumulative lifetime risk of hepatocellular carcinoma

Abstract

The association between subtypes of hepatitis C virus (HCV) and risk of hepatocellular carcinoma (HCC) remained inconclusive and evaluated in both case-control and cohort studies. In the case-control study, 397 HCC cases from medical centers were compared with 410 community-based non-HCC controls. All of them were anti-HCV-seropositive, HBsAg-seronegative with serum HCV RNA levels 1,000 IU/mL. Logistic regression models were used to estimate the odds ratio (OR) with 95% confidence interval (95% CI) of HCV subtype after controlling for other HCC risk factors. In the cohort study, 866 anti-HCVseropositive individuals were followed from 1991 to 2008 to assess the long-term HCC predictability of HCV subtypes. Newly developed HCC cases were ascertained by follow-up health examinations and computerized linkage with national databases. The percentage of HCV 1b subtype was higher among HCC cases than controls (64 vs. 55%, p < 0.001). Participant infected with HCV 1b had a higher mean serum HCV RNA level (2.0 3 10 6 IU/mL) than those infected with HCV non-1b (1.2 3 10 6 IU/mL, p < 0.001). The multivariate-adjusted OR (95% CI) of developing HCC for HCV 1b comparing to non-1b was 1.43 (1.02-2.02). After the long-term follow-up, the cumulative lifetime (30-80 years old) HCC risk was 19.2 and 29.7% for patients infected with HCV non-1b and 1b, respectively (p < 0.001). The multivariate-adjusted hazard ratio (95% CI) was 1.85 (1.06-3.22) for HCV 1b compared to non-1b. HCV subtype 1b, the most prevalent subtype in Taiwan, was associated with an increased HCC risk and a proactive clinical management is suggested for patients with HCV 1b.Hepatitis C virus (HCV) infection affected 180 million people worldwide with 3-4 millions were newly infected each year. 1,2 In patients chronically infected with HCV for more than 20 years, the risk of developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related mortality was reported to be 10-50, 1-23 and 4-15%, respectively 3-5 ; the

A review of the burden of hepatitis C virus infection in China, Japan, South Korea and Taiwan

“…Second, HCV prevalence in all countries examined increased with advancing age, and HCV genotypes 1b and 2 were the most common genotypes among the general populations, although no recent data (2011-2014) were available for Japan or South Korea. A cohort study from Taiwan that examined the association of HCV genotypes and the risk for HCC found that HCV 1b was an independent risk factor for HCC and that genotype 1b carried a higher risk for HCC than genotype 1a [38]. In addition, it was estimated that the cumulative lifetime risk for HCC is 6.5, 19.2 and 29.7 % for those with HCV RNA levels \1000 IU/ml, HCV non-1b and HCV 1b, respectively (p \ 0.001) [38,47].…”

“…Five studies, four [7,[35][36][37] from China and one [38] from Taiwan, reported the prevalence of HCV by HCV genotype. No studies were identified that reported the prevalence of HCV by HCV genotype in Japan and South Korea.…”

Hepatitis C Virus (HCV) genotypes distribution among hepatocellular carcinoma patients in Southern Italy: a three year retrospective study

“…The role of genotypes 1b and 3 in increasing the risk of HCC development has been widely questioned recently and even though numerous studies have often suggested their association with the HCC carcinogenetic progression [68][69][70][71][72][73][74], especially in patients with underlying cirrhosis, [38][39][40][41][75][76][77], probably for the strict correlation existing between these subtypes and liver damage, no consensus has emerged yet. Whether HCV 1b genotype contains specific nucleotide sequences that may be associated with direct pathogenesis or may trigger a stronger inflammatory response still needs to be extensively investigated.…”

“…Despite several published studies showing that patients infected with HCV genotype 1b may have a higher risk of developing HCC than those infected with other genotypes [39][40][41], other authors did not confirm this result [42,43]. As a consequence, no consensus has yet emerged and the role of HCV genotypes in both accelerating the progression of the disease and as a risk factor for HCC remains to be established.…”

Hepatocellular Carcinoma Risk Scores: Ready to Use in 2015?

“…In the community-based REVEAL-HBV/HCV study, HCC risk predictors for chronic hepatitis B patients include male gender, increasing age, family history of HCC, habitual alcohol consumption, HBeAg serostatus, genotype C (versus genotype B) and basal core promoter A1762T/G1764A mutant of HBV, co-infection with HCV, and elevated serum levels of HBV DNA, HBsAg and ALT [4,[7][8][9][10]. The long-term HCC risk predictors for chronic hepatitis C patients include increasing age, cirrhosis status, HCV genotype 1, elevated serum levels of HCV RNA and ALT, increased ratio between serum AST and ALT level (AST/ALT ratio), and co-infection with HBV [5,[11][12].…”