Huynh T, Huynh K, Zhou J, Hu KQ. Persistent alpha-fetoprotein elevation in patients without viral hepatitis, cirrhosis, hepatocellular carcinoma: A report of six cases and literature review. World J Clin Cases 2026; 14(28): 126184 [DOI: 10.12998/wjcc.126184]
Corresponding Author of This Article
Ke-Qin Hu, FAASLD, MD, Professor, Director, Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, 101 The City Drive, Building 22C, Room 1503, Orange, CA 92868, United States. kqhu@uci.edu
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Infectious Diseases
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case-report
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Huynh T, Huynh K, Zhou J, Hu KQ. Persistent alpha-fetoprotein elevation in patients without viral hepatitis, cirrhosis, hepatocellular carcinoma: A report of six cases and literature review. World J Clin Cases 2026; 14(28): 126184 [DOI: 10.12998/wjcc.126184]
World J Clin Cases. Oct 26, 2026; 14(28): 126184 Published online Oct 26, 2026. doi: 10.12998/wjcc.126184
Persistent alpha-fetoprotein elevation in patients without viral hepatitis, cirrhosis, hepatocellular carcinoma: A report of six cases and literature review
Tung Huynh, Kim Huynh, Joey Zhou, Ke-Qin Hu
Tung Huynh, Department of Pharmacy, University of California Irvine Medical Center, Orange, CA 92868, United States
Tung Huynh, School of Pharmacy and Pharmaceutical Sciences, University of California Irvine, Irvine, CA 92697, United States
Kim Huynh, Fairmont Preparatory Academy, Anaheim, CA 92801, United States
Joey Zhou, Orange County School of the Arts, Santa Ana, CA 92701, United States
Ke-Qin Hu, Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, Orange, CA 92868, United States
Author contributions: Hu KQ developed study proposal; Huynh T and Hu KQ contributed to data collection and analysis; Huynh T, Hu KQ, Huynh K and Zhou J contributed in manuscript preparation and revision; Hu KQ and Huynh T were responsible for final writing and editing of the manuscript; and all authors have reviewed and approved the final version of the manuscript.
AI contribution statement: The authors declare that no AI tools were used in the development or writing of this manuscript and take full responsibility for its integrity, accuracy, and originality.
Informed consent statement: Informed consent was waived per approved Institutional Review Board of University of California Irvine.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
CARE Checklist (2016) statement: The authors have read the CARE Checklist (2016), and the manuscript was prepared and revised according to the CARE Checklist (2016).
Corresponding author: Ke-Qin Hu, FAASLD, MD, Professor, Director, Division of Gastroenterology and Hepatology, University of California Irvine, School of Medicine, 101 The City Drive, Building 22C, Room 1503, Orange, CA 92868, United States. kqhu@uci.edu
Received: July 31, 2026 Revised: October 2, 2026 Accepted: October 22, 2026 Published online: October 26, 2026 Processing time: 88 Days and 7.5 Hours
Abstract
BACKGROUND
Alpha-fetoprotein (AFP) is an oncofetal protein present at high concentrations during fetal life and subsequently replaced by albumin. Serum AFP levels remain very low throughout adulthood life without malignancy, but may become elevated in individuals with pregnancy, viral hepatitis, active liver injury, cirrhosis, germ cell tumors, or hepatocellular carcinoma (HCC).
CASE SUMMARY
In this descriptive case series, we present 6 patients with mild, persistent, and stable AFP elevation in the absence of active liver injury, advanced fibrosis (or cirrhosis), or neoplasms, with a mean follow-up of 48 months in our liver clinic. None of the 6 cases had identifiable causes or a diagnosis of viral hepatitis, cirrhosis, or HCC. AFP elevation was relatively mild and stable throughout follow-up, liver function tests remained normal, and no patient developed active liver injury or malignancy, including HCC. We summarize their presentations and prognoses and review the related literature.
CONCLUSION
These six cases represent an uncommon clinical presentation of AFP elevation characterized by mild, persistent, and stable elevation in the absence of active liver injury, advanced hepatic fibrosis (or cirrhosis), and neoplasms. The prognosis in this case series was excellent: No patient had a doubling of AFP from baseline, and none developed malignancy. This descriptive case series suggests that comprehensive evaluation and regular follow-up remain necessary in this clinical scenario until larger cohort studies confirm its benign course and outcome.
Core Tip: This case series presents 6 cases of mild, persistent, and stable alpha-fetoprotein elevation in the absence of active liver injury, advanced hepatic fibrosis (or cirrhosis), or neoplasms, with a mean follow-up of 48 months. This is a unique and benign clinical presentation that has not been thoroughly described or previously reported.
