HCV-6 infection ups risk of HCC in Asian patients with liver cirrhosis
In Asian patients with hepatitis C virus (HCV) infection, the genotype 6 infection contributes to an increased risk of hepatocellular carcinoma (HCC), particularly among those with liver cirrhosis, reports a multinational team of investigators.
“Once patients develop cirrhosis, HCV 6 genotype accelerates disease progression,” said lead investigator Dr Mindie Nguyen from the Stanford University Medical Center in Palo Alto, California, US. “Since HCC rarely occurs in patients without cirrhosis, this study suggested that early antiviral therapy should be advocated for patients with HCV genotype 6 to prevent development of cirrhosis and subsequent HCC risk.”
In a cohort of 851 Asian HCV-infected patients (mean age 53.3 years; 57.8 percent male), comprising 222 with genotype 6 and 629 with other genotypes, Nguyen and colleagues identified 96 patients who developed HCC after 4,072 person-years of follow-up, yielding an incidence rate of 23.6 per 1,000 person-years. The cumulative HCC risk was 21.0 percent in the HCV genotype 6 group vs 14.8 percent in the HCV non-6 group (p=0.07) during a mean follow-up of 5.3 and 5.5 years, respectively. [Am J Gastroenterol 2017;112:1111–1119]
When patients were stratified by cirrhosis status, HCC incidence was found to be especially higher among those with cirrhosis (n=313) vs those without the condition (n=538; 44.0 vs 4.1 per 1,000 person-years; p<0.05). There was no difference in the cumulative HCC risk by various HCV genotypes among patients without liver cirrhosis (2.2 percent for HCV genotype 6 vs 2.9 percent for HCV non-6; p=0.45).
However, among those with liver cirrhosis, HCV genotype 6 patients had significantly greater cumulative HCC risk compared with those who had the non-6 genotypes (76.2 vs 36.2 percent; p<0.05). On Cox analysis, HCV genotype 6 was particularly associated with a more than twofold increased risk of developing HCC (adjusted hazard ratio [HR], 2.12; 95 percent CI, 1.33 to 3.39; p<0.05).
In a model evaluating HCV genotypes 6 and 1 against other genotypes, genotype 6 remained significantly associated with an increased risk of HCC (adjusted HR, 2.34; 1.12 to 4.86) among cirrhotic patients. The adjusted HR for HCC for HCV genotype 1 was 1.13 (0.56 to 2.27).
“HCV genotype 6 is dominant in East and Southeast Asia. Most of these regions are also very populous with high HCV seroprevalence and a very large HCV disease burden,” Nguyen pointed out. [Hepatology 2015;61:77–87; Aliment Pharmacol Ther 2014;39:137–47]
Moreover, among patients with chronic hepatitis C and cirrhosis, Asians have been shown to be four times as likely as Caucasians to develop HCC. [Clin Gastroenterol Hepatol 2004;2:820–24]
Dr Desmond Wai, a gastroenterologist in private practice at the a gastroenterologist at Mount Elizabeth Novena Hospital in Singapore and who was not involved in the current study, told
MIMS that the present data have important clinical implications, such that
genotype 6 patients should be treated with priority mainly to prevent progression of disease to cirrhosis.
In the past, specifically in the peginterferon alfa and ribavirin era of HCV treatment, side effects are rampant, and more so among cirrhotic patient, Wai said.
“Nowadays, treatment is highly effective with little side effects. Besides, cost of generic DAA [direct-acting antiviral], which is widely available in Southeast Asia, is cheap and very affordable. So I feel all patients with viral hepatitis C in Southeast Asia should receive treatment once diagnosis is made,” he continued.
“And once they are cirrhotic, maybe they need more aggressive follow-up, like once every 3 months, instead of the standard 6 months follow-up for surveillance of HCC,” he pointed out.
However, Wai highlighted the usual biases inherent to the study's retrospective design, particularly specifying lack of information regarding the duration of cirrhosis in the 313 cirrhotic patients who were followed up.
Determining cirrhosis duration is especially important, because the longer the duration of cirrhosis in untreated HCV, the greater the degree of severity of cirrhosis is, which in turn contributes to a higher risk of HCC, he said.