Normalization of serum alpha fetoprotein after direct acting antivirals in hepatitis C patients lowers hepatocellular carcinoma risk.

The elevation of serum alpha-fetoprotein (AFP) is frequently observed in patients with chronic hepatitis C (CHC). In most cases, the level decreased after antiviral treatment. This study investigated the relationship between post-treatment AFP normalization and the risk of hepatocellular carcinoma (HCC) in CHC patients without baseline HCC. A total of 483 patients treated with sofosbuvir-based direct-acting antivirals (DAAs) were enrolled and followed for a mean duration of 38.8 months. The mean age was 59.6 years, and 27.1% of patients had liver cirrhosis. The sustained virological response (SVR) rate was 98.6%. The pre-treatment AFP levels > 7 ng/mL, > 10 ng/mL, and > 15 ng/mL were observed in 25.4%, 18.8%, and 9.7% of patients, respectively. By 12 weeks post-treatment, 86.2% of patients had AFP levels < 7 ng/mL. During follow-up, 5.4% of patients developed HCC. The independent risk factors for HCC included age ≥ 65 years, liver cirrhosis, and post-treatment AFP > 7 ng/mL. The hazard ratio of HCC was 0.03 (95% CI: 0.01-0.3, P < 0.01) in the "Normalization" group, compared to the "Persistent elevation" group. The hazard ratio was 0.28 (95% CI: 0.1-0.73, P = 0.01) in the "Stable normal" group, compared to the "Elevation" group. The findings suggest that normalization of AFP levels or stable normal levels after treatment are associated with a reduced risk of HCC.