DAA, Interferon HCV Treatments Result in Similar Hepatocellular Carcinoma Risk

Jennifer Rosenthal Kramer, PhD, MPH

Credit: Baylor College of Medicine

Patients with chronic hepatitis C virus (HCV)-related cirrhosis treated with direct-acting antiviral (DAA) therapy have a lower risk of de novo hepatocellular carcinoma (HCC) than patients who received no treatment, according to findings from a recent study.¹

Leveraging data from the US Department of Veterans Affairs healthcare system, the study found a lower risk of HCC with DAA treatment than no treatment. However, compared with a historical cohort of patients treated with interferon (IFN) therapy, the risk of HCC was similar in DAA-treated patients.¹

“Based on the evidence of a reduced risk of HCC following SVR with IFN-containing therapy, the high SVR rates associated with DAAs and the ability to treat populations at the highest risk of HCC, it has been postulated that treatment with DAAs will lead to further reductions in HCC incidence among HCV-infected populations,” Jennifer Rosenthal Kramer, PhD, MPH, an associate professor at Baylor College of Medicine and a health science specialist at the Michael E. DeBakey VA Medical Center, and colleagues wrote.¹

According to the World Health Organization, globally, an estimated 50 million people have chronic HCV infection, with about 1 million new infections occurring per year. In 2022, approximately 242,000 people died from hepatitis C, mostly from cirrhosis and HCC. Although the advent of DAAs has increased HCV cure rates to more than 95%, HCV patients remain at an increased risk of de novo HCC after achieving SVR.²

To estimate the risk of de novo HCC with DAA treatment in cirrhotic HCV patients compared to no anti-HCV treatment and those treated with IFN-based therapy, investigators conducted a retrospective cohort study of patients ≥ 18 years of age with chronic HCV infection and compensated cirrhosis in the US Department of Veterans Affairs healthcare system who sought care at any of the medical centers and ambulatory care and community-based outpatient clinics.¹

The study population included 2 groups of patients: those who initiated treatment with an IFN-free DAA regimen between January 2014 and December 2017, and those who initiated treatment with an IFN-containing regimen between January 2005 and December 2013. Follow-up for IFN-treated patients ended in December 2013 and for untreated and DAA-treated patients in December 2018.¹

Investigators identified de novo HCC based on the primary site of liver with histology/cancer type of HCC in VA Central Cancer Registry. For the remaining patients, HCC was defined by > 1 instance of recorded ICD9/10 codes.¹

In total, 53,847 patients contributed to untreated time, 27,147 patients contributed to DAA-treated time, and 6809 patients contributed to IFN-treated time. Of note, 15,641 patients contributed to both untreated and DAA-treated times.¹

Among the DAA-treated patients, 24,267 (89.39%) achieved SVR, 964 (3.55%) failed to achieve SVR, and 1916 (7.06%) had missing SVR status. Among the IFN-treated patients, 2489 (36.55%) achieved SVR, 3331 (48.92%) failed to achieve SVR, and 989 (14.53%) had missing SVR status.¹

Investigators noted the crude incidence rate (IR) of HCC per 1000 person-years was higher for patients' untreated time (IR, 28.09; 95% CI, 27.34–28.87) compared with patients' DAA treatment time (IR, 22.26; 95% CI, 21.16–23.41).¹

Upon analysis, HCC risk associated with DAA treatment was significantly lower than no treatment in both the unadjusted Cox model (hazard ratio [HR], 0.79; 95% CI, 0.74–0.84) and the multivariable Cox model (HR, 0.70; 95% CI, 0.65–0.74).¹

The crude incidence rate of HCC per 1000 person-years was greater in IFN-treated patients (IR, 24.84; 95% CI, 23.02–26.80) compared with DAA-treated patients (IR, 22.26; 95% CI, 21.16–23.42). However, the risk of HCC was not significantly different across the two groups in the unadjusted Cox model (HR, 1.08; 95% CI, 0.97–1.20) or the multivariable analysis (HR, 0.98; 95% CI, 0.87–1.10).¹

“These findings strongly support the practice of offering DAA treatment to chronic HCV patients with cirrhosis and illustrate a favorable risk-benefit for DAA treatment in this vulnerable high-risk population as well as affirm the chemopreventive effect of DAA on de novo HCC risk,” investigators concluded.¹

References

1. ^{El-Serag HB, Duong H, Luster M, et al. Risk of Hepatocellular Cancer in U.S. Patients With Compensated Cirrhosis Treated With Direct-Acting Antivirals Versus Interferon. Alimentary Pharmacology & Therapeutics. https://doi.org/10.1111/apt.18525}

2. ^{World Health Organization. Hepatitis C. April 9, 2024. Accessed February 14, 2025. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c}