Duration and Cost-Effectiveness of HCC Surveillance in Patients Cured of Hepatitis C

The majority of patients with hepatitis C virus (HCV) infection have now been treated and cured in the US. Although these patients generally do well from a liver standpoint after HCV cure, they require ongoing hepatocellular carcinoma (HCC) surveillance if they had pretreatment cirrhosis. The American Association for the Study of Liver Diseases (AASLD) does not currently recommend HCC surveillance in patients with pretreatment advanced fibrosis. Mueller and Chen et al evaluated the cost-effectiveness of biannual HCC surveillance with an ultrasound and serum alpha-fetoprotein test to determine the age at which surveillance may be stopped in patients who achieved HCV cure after direct-acting antiviral therapy. They reported that biannual HCC surveillance, if started at the age of 40 years or later, is cost-effective until the age of 70 years for patients with cirrhosis and until the age of 60 years for patients with advanced fibrosis, using a willingness-to-pay threshold of $150,000 or less per quality-adjusted life year (QALY) gained. This would result in an additional 130 and 24 liver cancers detected at an early stage for every 1000 patients with cirrhosis and advanced fibrosis, respectively.

This is an interesting study as we currently advise biannual HCC surveillance “indefinitely” after treatment for patients with cirrhosis, which can place a burden on patients and healthcare systems. However, caution should be exercised before deciding to discontinue HCC surveillance for patients based on these results alone. A very large proportion of patients with cirrhosis who have been cured of HCV are “baby boomers” in their sixties and seventies whose HCV was eradicated only in the past 4 to 5 years. These patients have a very high risk of HCC and may have near-normal life expectancy otherwise if their liver function is preserved and their comorbidity profile is favorable. It is unclear why it would make sense for such patients to stop screening at the age of 70 years. A more nuanced approach might be to consider time since sustained virological response (HCC risk likely declines as time accrues after HCV cure^1,2), liver function (CTP and MELD score), and comorbidities to determine when to consider screening cessation, rather than a simple age cut-off. In addition, for patients who received treatment when younger than 40 years or older than 70 years, this model does not apply. Finally, other limitations of this model include the assumption that patients with advanced fibrosis do not develop cirrhosis after HCV cure and that comorbidities are assumed to be stable over time. It is also unclear why the incremental cost-effectiveness ratio increases dramatically after the age of 70 years in patients with cirrhosis and after the age of 60 years in patients with advanced fibrosis. Further evaluation is therefore needed before these findings are used in patient care.

References

1. Kim NJ, Vutien P, Berry K, et al. Hepatocellular carcinoma risk declines but remains high enough for screening in the first 7 years after HCV cure with DAAs in patients with cirrhosis or high FIB-4. Gastroenterology. 2022;S00165085(22):00681-3. https://www.gastrojournal.org/article/S0016-5085(22)00681-3/pdf?referrer=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F#relatedArticles
2. Kim NJ, Vutien P, Cleveland E, et al. Fibrosis-stage Specific Incidence of Hepatocellular Cancer after Hepatitis C Cure with Direct-Acting Antivirals: A Systematic Review & Meta-analysis. Clin Gastroenterol Hepatol. 2022;S-1542365(22):00438-4. https://www.cghjournal.org/article/S1542-3565(22)00438-4/fulltext