Older hep C patients may remain at risk for HCC even after viral clearance

Last Updated: 2020-07-06

By Marilynn Larkin

NEW YORK (Reuters Health) - Chronic hepatitis C patients ages 75-84 remained at high risk of liver cancer even after direct-acting antivirals (DAAs) cleared the virus, according to an observational study in Japan.

"In this era in which therapy with DAAs has replaced interferon-based therapies, HCV cure rates between 90% and 100% have been reported, regardless of age or liver fibrosis status," Dr. Elichi Ogawa of Kyushu University Hospital in Fukuoka told Reuters Health by email. "As a result, the number of patients requiring a liver transplant has fallen sharply, as have deaths associated with HCV."

"However, whether or not DAA treatment and HCV cure decreases the risk for the development of hepatocellular cancer (HCC) such that HCC surveillance is no longer necessary remained unclear," he said. "Our study focused on patients 75-84, an age that has been under-represented in clinical trials, in an attempt to clarify this problem."

"Our findings showed that regular monitoring of patients in this age group is necessary," he said, "even after HCV elimination and improvement of hepatic fibrosis markers."

As reported in the Journal of Infectious Diseases, the multicenter cohort study included 2,405 chronic hepatitis C patients without a history of liver cancer in whom HCV elimination was achieved by DAAs.

Five hundred (20.8%) were ages 75-84 and 1,101 (45.8%) were 60-74 at the time of DAA initiation.

In the 75-84 group, 34.8% were men, 27.2% had a diagnosis of cirrhosis, and 71.6% were treatment-na ve. At baseline, two-thirds had a fibrosis biomarker (FIB-4) index of 3.25 or greater. They also had a higher FIB-4 index and lower serum albumin level than those ages 60-74, and were more likely to have undergone HCV treatment.

Overall, 64 patients (2.7%) developed HCC during the median 3.5 years of follow-up.

The researchers analyzed the incidence of HCC according to the transition of the FIB-4 index from baseline to week 12 after the end of treatment. Among patients ages 75-84 with high FIB-4 at baseline (at least 3.25), there was no significant difference in the annual incidence of HCC between those with a week-12 FIB-4 index of at least 3.25 (2.75%/year) or <3.25 (2.16%/year). By contrast, annual incidence did differ significantly among those ages 60-74, at 3.61% and 1.51%/year, respectively (adjusted hazard ratio, 2.20).

After adjustment, a higher risk of developing HCC was conferred by, among other factors: age 60-74 (HR 4.95); age 75-84 (HR 6.93); being male (HR 2.29); and having cirrhosis (HR 2.41).

Further, in 495 propensity-matched pairs, the cumulative HCC incidence in the 75-84 group without cirrhosis was significantly higher compared to the 60-74/non-cirrhosis group.

The authors conclude, "Older patients aged 75-84 remained at high risk for the development of HCC, even after HCV elimination and the improvement of FIB-4 index to <3.25."

Dr. Nadeem Anwar, Director of Hepatology at the University of Cincinnati Medical Center said the finding "seems to be compatible with what is seen in clinical experience."

"The incidence of HCC is dependent on various risk factors, like age, gender, family history of HCC and absence or presence of cirrhosis. Twenty percent of HCC is seen in non-cirrhotic patients. Hence, despite the treatment of hepatitis C, the risk for cancer remains, especially in the older populations."

"Liver biopsy is still considered the gold standard for determination of the degree of fibrosis," he noted. "Among the currently available non-invasive tools for measuring fibrosis, FIB-4 fares quite well, but still there is room for error."

"Since it uses transaminases (AST and ALT) as markers of fibrosis," he said, "any fluctuation in these enzymes would affect the FIB-4 score and may under- or over-report the degree of fibrosis. Hence, any study where it is used to distinguish cirrhotic from non-cirrhotic patients could be prone to introducing error."

SOURCE: https://bit.ly/2VU1yzg Journal of Infectious Diseases, online June 25, 2020.