Infection with the hepatitis C virus (HCV) can lead to a chronic hepatitis C infection (CHC) and subsequent liver complications such as fibrosis, cirrhosis, end-stage liver disease, and hepatocellular carcinoma (HCC).¹Mukherjee R et al. J Lab Autom. 2015;20(5):519-538. HCV infections are historically treated with pegylated interferon-α and ribavirin, but the advent of direct-acting antiviral agents (DAAs) over the past recent years has remarkably improved the sustained virological response (SVR) rates, defined as undetectable viral RNA for six months after treatment completion.^2,32. Preciado MV et al. World J Gastroenterol WJG. 2014;20(43):15992-16013.
3. Jhaveri MA et al. Drugs Aging. 2018;35(2):117-122. Older patients are beginning to represent majority of outpatient cases for hepatitis C, due to the progressive aging of the HCV-infected population and fewer new cases.⁴Vespasiani-Gentilucci U et al. World J Gastroenterol WJG. 2015;21(24):7412-7426. Real world cohorts now show that almost all older patients are able to obtain similar virological outcomes with younger patients.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359.

The results of a multicentre cohort study in Japan assessing the risk for HCC development in patients aged 75-84 years with CHC and without a history of HCC and who had achieved HCV elimination with DAAs were recently published in The Journal of Infectious Diseases.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. Data of 2,405 Japanese patients who received treatment with interferon-free DAA regimens for CHC between September 2014 and December 2019 were analysed. The primary endpoint was de novo incidence of HCC after achieving an SVR with DAA treatment.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. At the time of DAA initiation, 45.8% of patients were aged 60-74 and 20.8% of patients were aged 75-84.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. In the older group of 75-84, 34.8% were men, 27.2% had a diagnosis of cirrhosis, and 71.6% were treatment-naïve.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. Compared with patients aged 60-74, the older patients had lower serum albumin levels and were more likely to have experienced HCV treatment.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359.

Overall, 64 patients developed HCC during the follow-up period from 1 year after initiation of DAAs.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. Multivariable analysis adjusting for background characteristics showed certain factors conferred a higher risk of HCC.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. Patients aged 60-74 years had over a quadruple risk of HCC development (HR=4.95; 95% CI: 1.57-15.6; p=0.006), and patients aged 75-84 even higher (HR=6.93; 95% CI: 2.00-24.0; p=0.002). Other predictive factors included male sex (HR=2.29; 95% CI: 1.25-4.18; p=0.007) and cirrhosis (HR=2.41; 95% CI: 1.40-4.15; p=0.002).⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359.

After propensity score matching between the 60-74 and 75-84 age groups, significant variables predicting HCC incidence were male sex (adjusted HR=2.62; 95% CI: 1.39-4.93; p=0.003), cirrhosis (adjusted HR=2.22; 95% CI: 1.03-4.75; p=0.04), and AFP level 12 weeks after treatment completion (>7ng/mL) (adjusted HR=2.80; 95% CI: 1.33-5.91; p=0.007).⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. The Kaplan-Meier curve for age and cirrhosis status for the propensity-score matched cohort indicated that the 5-year cumulative incidence for HCC was significantly higher in the 75-84 age group than 60-74 (5.2% vs 1.3%, respectively; p=0.048).⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359.

The findings from this study suggest that patients aged ≥75 may remain at high risk for HCC, even after HCV clearance with DAAs.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359. Regular monitoring of this patient population should be necessary for early detection of HCC.⁵Ogawa E et al. J Infect Dis. DOI: 10.1093/infdis/jiaa359.