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World J Hepatol. Aug 27, 2026; 18(8): 124108
Published online Aug 27, 2026. doi: 10.4254/wjh.124108
Acute hepatitis B in the vaccination era: Predictors of functional cure and chronicity
David Yardeni, Julianna Gershbaum Tobin, Bryan Itkowitz, Inna Lipnizkiy, Ali Abu Juma’a, Naim Abu-Freha, Ayelet Keren-Naus, May Turgeman, Anat Nevo-Shor, Robert Gareth Gish, Ohad Etzion
David Yardeni, Inna Lipnizkiy, Ali Abu Juma’a, Naim Abu-Freha, Anat Nevo-Shor, Ohad Etzion, Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, Beersheba 84101, Southern, Israel
Julianna Gershbaum Tobin, Medical School for International Health, Soroka University Medical Center, Beersheba 84101, Southern, Israel
Bryan Itkowitz, Clinical Research Center, Soroka University Medical Center, Beersheba 84101, Southern, Israel
Ayelet Keren-Naus, Laboratory of Virology Services, Soroka University Medical Center, Beer Sheva 84101, Israel
May Turgeman, Department of Internal Medicine E, Soroka University Medical Center, Beersheba 84101, Southern, Israel
Robert Gareth Gish, Hepatitis B Foundation, Doylestown, PA 18902, United States
Author contributions: Yardeni D and Etzion O contributed to the conception and design of the study as well as writing of manuscript and approval of final draft; Gershbaum Tobin J and Itkowitz B contributed to the data analysis as well as editing, writing and review of the manuscript and performed the formal statistical analysis; Lipnizkiy I, Abu Juma’a A, Abu-Freha N, Keren-Naus A, Turgeman M and Nevo-Shor A provided resources and performed a review and editing of the manuscript; Gish RG performed a revision of the manuscript and approved the final draft.
AI contribution statement: AI tools were not used during the preparation of this study.
Institutional review board statement: The study was approved by the Institutional Review Board of Soroka University Medical Center and was conducted in compliance with the Declaration of Helsinki, Good Clinical Practice guidelines, and local regulatory requirements.
Informed consent statement: For this study of existing patient data, the Institutional Review Board of Soroka University Medical Center granted a full waiver of informed consent (Approval No. 0138-23-SOR) on September 26, 2023, under study protocol SCRC23018.
Conflict-of-interest statement: All authors declare no conflict-of-interest in this study.
Data sharing statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Corresponding author: David Yardeni, MD, Department of Gastroenterology and Liver Diseases, Soroka University Medical Center, 151 Rager Blvd., Beersheba 84101, Southern, Israel.
yardeda@post.bgu.ac.il
Received: June 8, 2026
Revised: June 30, 2026
Accepted: July 31, 2026
Published online: August 27, 2026
Processing time: 73 Days and 12.8 Hours
BACKGROUND
Despite the existence of an effective vaccine and treatment for the hepatitis B virus (HBV) more than 880000 people die each year from complications of cirrhosis and hepatocellular carcinoma associated with chronic HBV (CHB) infection. Limited information exists regarding the effect of antiviral treatment or the effect of patient background and viral factors on acute HBV outcome in a population with wide vaccine availability. Previous studies have demonstrated that widespread availability of the vaccine in developed countries has shifted the epidemiology of acute HBV infection to vulnerable subpopulations.
AIM
To evaluate the hypothesis that this epidemiologic shift in susceptibility of populations to acute HBV infection may alter the immune responses during acute infection and affect the rates of functional cure (FC) and viral persistence.
METHODS
We performed a retrospective evaluation of all patients above the age of 18 with acute HBV infection in Southern Israel between the years 2004-2022. Evaluated outcomes were FC, defined as hepatitis B surface antigen (HBsAg) clearance, or CHB infection defined as positive HBsAg at 6 months past the acute event. Clinical, biochemical, metabolic, and socioeconomic variables were analyzed.
RESULTS
Among 78 patients with acute HBV infection, 51 (65.3%) achieved FC, while 27 (34.6%) progressed to CHB infection. Patients who achieved FC had significantly higher peak alanine aminotransferase levels at presentation than those who developed CHB infection (2117 ± 1509 IU/mL vs 1103 ± 1540 IU/mL; P = 0.01). No differences in early initiation of nucleos(t)ide analogue therapy were found between patients who achieved FC and patients who developed CHB. Progression to CHB infection was significantly more common among patients with a background of low socioeconomic status (SES; 70% vs 41%; P = 0.04) and diabetes mellitus (DM; 26% vs 3.9%; P = 0.007). In univariable analysis, DM presence and a high SES were associated with a significant effect on HBsAg persistence (odds ratio = 8.57 and 0.46, respectively).
CONCLUSION
In the vaccination era, we postulate that acute HBV carries a higher-than-expected risk of chronicity, particularly among patients with metabolic disease and those from socioeconomic disadvantage backgrounds. Early risk stratification, targeted follow-up for high-risk cases, and further study of metabolic and social factors in FC are warranted.
Core Tip: The widespread availability of the universal hepatitis B virus (HBV) vaccination reduced acute HBV incidence in developed countries. Acute HBV usually resolves with functional cure in > 95% of adults. In our study we evaluated all acute HBV cases in southern Israel between 2004-2022 and found a striking 34% chronicity rate. Further analysis revealed that a background of diabetes and low socioeconomic status were found to strongly predict chronic infection. These findings highlight the need for risk stratification in acute HBV patients from vulnerable populations.
