Chronic hepatitis C (CHC) infection is a major risk factor for hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP), an oncofetal protein, is widely used in HCC surveillance but is non-specific, as levels may rise in conditions such as hepatic inflammation, fibrosis, or regeneration. Previous studies have shown that AFP levels often decline following antiviral therapy, yet the prognostic role of post-treatment AFP dynamics remains under investigation.
This retrospective observational study assessed 483 CHC patients without baseline HCC who received a 12-week course of sofosbuvir-based direct-acting antiviral (DAA) therapy. Researchers examined the relationship between AFP changes after treatment and subsequent HCC development. Over a mean follow-up of 38.8 months, three independent risk factors for HCC were identified: age ≥65 years, liver cirrhosis, and serum AFP>7 ng/mL at 12 weeks post-treatment.
Importantly, patients with normalised or persistently normal AFP after therapy had a lower risk of developing HCC. Among those with elevated AFP prior to treatment, 86.2% achieved normalisation by 12 weeks, and these individuals showed reduced cancer risk compared with patients whose AFP remained elevated. This finding highlights AFP dynamics as a practical, time-dependent biomarker for risk stratification following DAA therapy.
The study also revealed that some HCC cases occurred within 3–6 months of treatment, suggesting that occult tumours may have been present but undetected at baseline. Conversely, around one-quarter of cases emerged after more than three years, indicating a subgroup prone to late-onset HCC despite viral clearance.
While DAA therapy substantially lowers overall HCC risk, it does not eliminate it. Dynamic AFP monitoring, particularly at 12 weeks post-treatment, offers a simple, clinically relevant tool to identify patients who remain at elevated risk. Such patients may benefit from intensified surveillance, especially those who are older or have cirrhosis.
These findings reinforce the importance of personalised post-treatment monitoring in CHC, ensuring timely detection of HCC and better long-term outcomes.
Reference
Lin CK et al. Normalization of serum alpha fetoprotein after direct acting antivirals in hepatitis C patients lowers hepatocellular carcinoma risk. Sci Rep. 2025;15(1):32312.
