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

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Findings underscore the importance of HCC screening adherence in patients with HCV-related cirrhosis who achieve HCV cure for improving overall survival.

Catherine Mezzacappa, MD, MPH | Credit: Yale School of Medicine

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
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