SynthesisFrontiers in cellular and infection microbiology2023
The incidence of hepatocellular carcinoma and clearance of hepatitis B surface for CHB patients in the indeterminate phase: a systematic review and meta-analysis.
Synthesis in Frontiers in cellular and infection microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 13 citations in OpenAlex.
- Comparison of Peg-INF plus TDF versus TDF Monotherapy in Indeterminate-phase Chronic Hepatitis B Patients with High HBsAg levels, HBeAg-negative status, and Normal ALT Levels.Journal of clinical and translational hepatology · 2026Article
- Indeterminate Phase/Grey Zone of Chronic Hepatitis B: Clinical Features, Outcomes and Molecular Insights.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Global strategies and actions to eliminate hepatitis B virus infection.Clinical and molecular hepatology · 2025Review
- [Application value of an aMAP score in predicting the occurrence of hepatocellular carcinoma in patients with chronic hepatitis B receiving antiviral therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2025Article
- The interactive role of microRNA and other non-coding RNA in hepatitis B (HBV) associated fibrogenesis.Functional & integrative genomics · 2025Review
- Factors Associated with Progressive Liver Disease in Untreated HBV Patients in Tunisia.F1000Research · 2025Article
- [Analysis of the clinical characteristics of HBeAg-negative chronic HBV infection in indeterminate phase with a low viral load].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- [Analysis of the incidence of low viral load/low-level viremia and its associated factors in patients with HBV-related primary liver cancer].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Factors Positively Correlated with Hepatitis B Surface Antigen Seroconversion in Chronic Hepatitis B.Journal of personalized medicine · 2024Article
- IFN-treated macrophage-derived exosomes prevents HBV-HCC migration and invasion via regulating miR-106b-3p/PCGF3/PI3K/AKT signaling axis.Frontiers in cellular and infection microbiology · 2024Article
- Should we expand treatment initiation criteria for chronic HBV infection: Pros.Clinical liver diseaseReview
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Nearly 30%-40% of patients with chronic hepatitis B do not fall into any of the traditional natural history classification and thus are classified as indeterminate. However, it is unclear whether patients in the indeterminate phase (IP) are at a higher risk for hepatocellular carcinoma (HCC) than those in the defined phases (DP) and would benefit from antiviral therapy. We performed a systematic review and meta-analysis of HCC incidence and HBsAg clearance among patients in the IP versus DP. Methods: We defined the clinical phases as per the AASLD 2018 hepatitis B guidance. We searched PubMed, Embase, Medline, and Web of Science for relevant studies that reported HCC incidence or HBsAg clearance in IP versus DP patients published between January 2007 and March 2023. Annual HCC incidence and HBsAg clearance rates were pooled using a random/common-effects model. Results: We analyzed data from 14 studies, comprising 7798 IP patients (222 patients developed HCC and 239 achieved HBsAg clearance) and 10,725 DP patients. The pooled annual HCC incidence was 2.54 cases per 1,000 person-years (95% CI, 1.14-4.39) and HBsAg clearance rate was 12.36 cases per 1,000 person-years (95% CI, 10.70-14.13) for the IP patients. IP patients were associated with significantly higher HCC incidence risk (RR = 1.64, 95% CI, 1.34-2.00) and slightly lower annual HBsAg clearance rate (RR = 0.83, 95% CI, 0.70-0.99) than the DP patients. In addition, HBeAg-negative IP patients (2.31%; 95% CI, 0.87-4.45) showed a significantly higher HCC incidence than those who were HBeAg positive (0.00%; 95% CI, 0.00-0.99) ( Conclusion: The systematic review and meta-analysis showed a high HCC incidence and low HBsAg clearance among patients in the IP, especially for HBeAg-negative patients and the Asian population. We emphasize that future multicenter prospective cohort studies or randomized trials are needed to verify if expanding antiviral therapy for patients in the IP is associated with reduced HCC risk or good treatment outcomes.
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