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Hepatocellular carcinoma (HCC) risk declined but remained high enough for screening in the first 7 years for some patients cured of their hepatitis C virus infections with direct-acting antivirals, an observational study showed.

For patients with cirrhosis or high fibrosis-4 (FIB-4) scores who achieved sustained virologic response, the risk for HCC persisted and justified continued screening, reported George Ioannou, MD, MS, of the Veterans Affairs Puget Sound Health Care System in Seattle, and colleagues.

While annual HCC incidence declined from 3.8% in the first year to 1.4% in the seventh year after patients with a FIB-4 score of ≥3.25 achieved sustained virologic response, it still substantially exceeded the 1% per year threshold that could be considered cost-effective (P<0.001 for test of trends), the group wrote in a research letter.

Subgroup analyses showed a higher incidence of HCC in patients with cirrhosis (1.0-4.5 per 100 patient-years), regardless of any change in their FIB-4 score, than in those without cirrhosis (0.3-2.2 per 100 patient-years), they added.

Over roughly 5 years of average follow-up, more patients who had cirrhosis before treatment developed HCC over time versus those without pre-treatment cirrhosis (12.6% vs 2.5%). For patients with cirrhosis and a FIB-4 score <3.25, the annual HCC incidence ranged from 0.7% to 1.3%, with no significant change over time.

"We are still not sure to what extent the risk of liver cancer declines after hepatitis C eradication as more and more time accrues," Ioannou told MedPage Today. "The most important take-home message is that patients who had already developed cirrhosis or had a FIB-4 greater than 3.25 before their hepatitis C was eradicated, need to continue screening for liver cancer 'indefinitely' for the time being."

Direct-acting antivirals can cure hepatitis C and reduce the risk for HCC, but there remains a significant risk for cirrhosis or advanced fibrosis in these patients, the authors noted.

Prior work from Ioannou's group found that the annual incidence of HCC within the first 4 years of achieving sustained virologic response stayed above 2% for those with and over 1% for those without cirrhosis but with a FIB-4 score ≥3.25. While that study showed a declining annual HCC risk, it could not confirm whether continuing HCC screening was warranted because of its short follow-up.

"This is an interesting piece for two main reasons. Firstly, it shows that the likelihood of HCC development decreases but still remains elevated up to 7 years after achieving an HCV [hepatitis C virus] cure," Andrew Talal, MD, of the University at Buffalo in New York, told MedPage Today. "Secondly, even in those without cirrhosis, the risk of HCV development remains."

"Both of these points argue for ongoing HCC screening in those with advanced liver disease and most importantly cirrhosis," said Talal, who was not involved in this study.

The current study provided a 7-year extended follow-up of the prior cohort. It assessed electronic health record data on 29,033 VA patients with hepatitis C virus infections who achieved sustained virologic response (with or without ribavirin) from January 2013 to December 2015. Of these, 7,533 patients had pre-treatment cirrhosis and 21,500 did not. Follow-up occurred until December 2021.

Nearly all patients were men, and 52% were white. Mean age was 61, and mean BMI was 27-29. Common comorbidities included alcohol use disorder (44%), substance use disorder (38%), and diabetes (29%).

In the group with pre-treatment cirrhosis, those with a FIB-4 score ≥3.25 experienced their lowest HCC incidence at their 7-year follow-up and in 2020, which could be caused by the impact of COVID-19, the researchers said.

Among the group without pre-treatment cirrhosis, 4,682 had a FIB-4 score ≥3.25 at baseline. HCC incidence was significantly higher for those who had this higher FIB-4 score versus those with a lower score (1.2 vs 0.2 per 100 patients-years). Notably, patients who lowered their FIB-4 score from ≥3.25 pre-treatment to under that cutoff after treatment had lower HCC incidence than those with a continuously high score (1.0 vs 2.2 per 100 patient-years).

Study limitations included the fact that all participants were veterans and follow-up extended into the pandemic.

"These early results require validation in non-veteran cohorts and with follow-up that extends beyond the COVID-19 pandemic, when, hopefully, HCC screening and diagnosis practices return to normal," the authors stated.

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