Benefits of Hepatocellular Carcinoma Screening Continue After HCV Cure, Study Finds

Catherine Mezzacappa, MD, MPH

Credit: Yale School of Medicine

Findings from a recent study are calling attention to a protective association of hepatocellular carcinoma (HCC) screening with overall survival after HCC in patients with hepatitis C virus (HCV)-associated cirrhosis.¹

Results of the retrospective cohort study showed greater time spent up to date with screening was associated with an increased likelihood of early-stage HCC diagnosis and subsequent receipt of curative treatment, highlighting the benefit of identifying cirrhosis among persons with cured HCV and maintaining recommended HCC screening in these individuals.¹

“Individuals with HCV-associated cirrhosis who have achieved viral cure may be particularly susceptible to lapses in HCC screening due to treatment-induced stabilization of their liver disease,” Catherine Mezzacappa, MD, MPH, a fellow in the division of digestive diseases at Yale School of Medicine, and colleagues wrote.¹ “However, data on clinical HCC screening practices and outcomes in these patients are sparse.”

According to the World Health Organization, an estimated 50 million people have chronic HCV, with about 1 million new infections occurring each year. In 2022, approximately 242,000 people died from hepatitis C, mostly due to cirrhosis and HCC.²

To evaluate the association of HCC screening after HCV cure with overall survival, investigators conducted a retrospective cohort study of older patients with HCV-related cirrhosis who achieved DAA-induced HCV cure in the Veterans Affairs health care system between January 2014 and December 2022. They identified 16,902 individuals with HCV-associated cirrhosis prescribed a DAA between 2014 and 2021 with a subsequent confirmatory negative HCV RNA polymerase chain reaction test. Among the cohort, the median age was 64.0 (Interquartile range [IQR], 60.5-67.4) years, 97% of patients were male, and 49.4% were White.¹

Individuals were considered eligible for HCC screening until development of HCC, other metastatic cancer, CTP class C cirrhosis, death, or end of follow-up. Individuals were considered up to date with screening for up to 180 days after a qualifying imaging study or until their next study if it occurred within less than 180 days.¹

In order to assess the association between HCC screening and survival after HCC diagnosis, investigators calculated the percentage of time participants were up to date with screening during the 4 years preceding HCC diagnosis. Individuals who remained up to date with screening for at least 50% of each year during up to 4 years preceding HCC diagnosis were classified as consistently up to date with screening.¹

Of the 16,902 individuals included in the study, 1622 developed HCC. Of these patients, 856 (52.8%) had cirrhosis due to HCV alone, and CirCom scores at HCC diagnosis reflected a range of comorbid disease.¹

In the total sample, the mean percentage of time up to date with screening after HCV cure declined from 53.9% (Standard deviation [SD], 36.8%) in year 1 to 40.5% (SD, 40.5%) in year 4, then increased to a maximum of 64.2% (SD, 48.0%) among individuals who remained screening eligible in year 8. The annual cumulative incidence of HCC among individuals who remained eligible for screening after HCV cure gradually declined from 2.4% during the first year of follow-up to 1.0% during year 8.¹

Investigators noted being up to date with screening for at least 50% of the time during the 4 years preceding HCC diagnosis was associated with improved overall survival (log-rank test of equality over strata P = .002). In multivariate analysis, each 10% increase in follow-up spent up to date with screening during the 4 years before HCC diagnosis was associated with a 3.2% decrease in the hazard of death after HCC diagnosis (hazard ratio [HR], 0.97; 95% CI, 0.95-0.99).¹

There was a statistically significant interaction between the number of years since HCV cure and percentage of time up to date with screening (χ2 = 13.6; P = .03). Stratified by year since HCV cure, each 10% increase in the percentage of eligible follow-up spent up to date with screening was associated with an 8.0% reduction in the hazard of death after HCC diagnosis in individuals who received a diagnosis of HCC 3 to less than 4 years after HCV cure (adjusted HR, 0.92; 95% CI, 0.87-0.98) and 13.0% in those who received a diagnosis 4 to less than 5 years after HCV cure (adjusted HR, 0.87; 95% CI, 0.79-0.95). Of note, no association was observed for those who received a diagnosis of HCC more than 5 years after HCV cure.¹

Investigators pointed out greater time spent up to date with screening during the 4 years preceding HCC diagnosis was associated with an increased likelihood of diagnosis with early-stage HCC and receipt of potentially curative treatment. For every 10% increase in the percentage of time spent up to date with screening, individuals with HCC were 10.1% (95% CI, 6.3%-14.0%) more likely to receive a diagnosis of early-stage disease and 6.8% (95% CI, 2.8%-11.0%) more likely to receive curative treatment.¹

Investigators outlined several potential limitations to these findings, including the retrospective, observational nature of the study; the potential for residual confounding; and the underrepresentation of female patients.¹

“In this cohort study of older adults with cirrhosis and cured HCV, HCC screening was associated with a survival benefit. As the population most impacted by HCV ages, the role of HCC screening after HCV cure requires ongoing evaluation to balance its potential harms and benefits," investigators concluded.¹ "Our findings suggest that individuals with cirrhosis should be maintained in HCC screening after HCV cure.”

References

1. ^{Mezzacappa C, Kim NJ, Vutien P, et al. Screening for Hepatocellular Carcinoma and Survival in Patients With Cirrhosis After Hepatitis C Virus Cure. JAMA Netw Open. 2024;7(7):e2420963. doi:10.1001/jamanetworkopen.2024.20963}
2. ^{World Health Organization. Hepatitis C. Newsroom. April 9, 2024. Accessed July 10, 2024. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}