Elevated alpha-fetoprotein in asymptomatic adults: Clinical features, outcome, and association with body composition

Abstract

Background and aim: Apparently healthy individuals with elevated serum alpha-fetoprotein (AFP) levels (>7 ng/mL) for unknown causes visit clinics. We investigated their clinical characteristics, outcomes, and relationship with body fat deposition and muscle mass.

Methods: The case group included asymptomatic 137 individuals with "elevated AFP level" (R772) diagnostic code from 2009 to 2018 in a tertiary hospital. The control group enrolled 274 age- and sex-matched patients with <5 cm hepatic hemangiomas. Hepatic, visceral, and psoas muscle adiposity and psoas muscle index (PMI) were measured in the subgroups of 45 cases and 90 controls with pre-contrast computed tomography (CT) images.

Results: The case group (mean age 47.5 years, male 35.8%) showed higher AFP levels (10.3 vs 2.5 ng/mL, p<0.001) and total bilirubin (0.8 vs 0.7 mg/dL, p<0.001), but a lower body mass index (22.2 vs 23.3 kg/m2, p = 0.011) and alanine aminotransferase levels (17.0 vs 19.0 IU/L, p = 0.047) than the controls. During 13 months of median follow-up, there was no cancer or liver disease development. The AFP levels were stable. In the subgroups with CT images, cases showed a lower proportion of hepatic steatosis (4.4% vs 18.9%, p = 0.023), higher psoas muscle attenuation (48.2 vs 43.8 Hounsfield units, p<0.001) and higher PMI (5.7 vs 4.2 cm2/m2, p<0.001) than the controls.

Conclusion: Elevated AFP levels in asymptomatic individuals may play a role in expressing a protective phenotype against hepatic steatosis, myosteatosis, and sarcopenia. AFP levels in patients with elevated AFP were stable during follow-up without liver injury or cancer development. Interaction between AFP expression and steatosis warrants further study.

Fig 1. Patient selection flow gram.

A total of 137 patients with an elevated AFP level without any malignancy, ovarian teratoma, liver cirrhosis, chronic hepatitis, or elevated serum aspartate aminotransferase or alanine aminotransferase level above the upper normal limit of 40 IU/mL were compared with the hemangioma control group who had normal serum AFP levels. To analyze adiposity, 45 patients with non-enhanced CT images in the elevated AFP level group were compared to 90 patients with non-enhanced CT images in the hemangioma control group.

Fig 2. Longitudinal follow-up of AFP in the case group.

The Median follow-up period was 12.9 months. No patients had newly developed malignancy or liver cirrhosis. AFP level stayed stable and there was no significant change over time among patients during follow-up.