Persistent Elevation of Alpha-fetoprotein in a Healthy Man Without Evidence of Malignancy: A Case Report and Focused Narrative Review

Alpha-fetoprotein (AFP) is widely used as a serum biomarker in the evaluation of hepatocellular carcinoma and nonseminomatous germ cell tumors, but persistent AFP elevation may occasionally occur without demonstrable malignancy or active liver disease. We report a 54-year-old asymptomatic man in whom routine health screening showed persistently elevated AFP values in the 200-400 ng/mL range. Liver biochemistry was normal; viral hepatitis and human immunodeficiency virus (HIV) testing were negative; AFP-L3, protein induced by vitamin K absence or antagonist II (PIVKA-II), carcinoembryonic antigen, and carbohydrate antigen 19-9 (CA 19-9) were not elevated; and targeted imaging, including abdominal ultrasonography, triple-phase contrast-enhanced computed tomography, testicular ultrasonography, and whole-body positron emission tomography/computed tomography, revealed no evidence of malignancy. Incidental simple hepatic cysts were identified, but they lacked suspicious imaging features; cyst-fluid cytology was negative, and cyst-fluid AFP was not elevated. Over 6 years of serial follow-up, AFP remained elevated. After exclusion of hepatocellular carcinoma, germ-cell tumor, active hepatic injury, and other occult malignancy, hereditary persistence of AFP or idiopathic persistent AFP elevation was considered the most plausible explanation. This case highlights the importance of confirming persistence, excluding common malignant and hepatic causes in a stepwise manner, and avoiding repeated invasive or high-burden investigations when the patient remains clinically stable.