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Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis

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Abstract

Background

Among liver injury causes, few result in marked elevation of liver enzymes to a level > 1,000 international units per liter (IU/L). This review summarizes common etiologies of marked transaminase elevation and associated prognostic factors.

Methods

We performed a comprehensive search on PubMed, EMBASE, Cochrane Library, and Google Scholar from inception through December 2022 using MOOSE guidelines for studies reporting frequency of etiologies of marked transaminase elevation. We used a proportion meta-analysis to pool frequencies with corresponding 95% confidence interval (CI). I2 was used to adjudicate heterogeneity. We used CMA software for statistical analysis.

Results

Seven relevant studies (n = 1608 patients) were included. The pooled frequency of ischemic hepatitis was 51% (95% CI 42–60%, I2 = 91%), viral hepatitis was 13.1% (95% CI 9.7–17.6%, I2 = 80%), toxins or drug-induced liver injury (DILI) was 13% (95% CI 8–18%, I2 = 85%), and pancreaticobiliary-related injury was 7.8% (95% CI 4.4–13.6%, I2 = 89%). Mortality was significantly higher in ischemic hepatitis versus other causes of marked transaminase elevation, with an odds ratio of 21 (95% CI 9.9–44.8, P value < 0.0001, I2 = 64% Q 11.1).

Discussion

This is the first meta-analysis to examine etiologies of marked transaminase elevation > 1000 IU/L. Liver ischemia is the most common cause, while other causes include DILI or toxins, viral hepatitis, and biliary pathologies. We found biliary pathologies to be the fourth most common cause. This is clinically relevant as it has been traditionally linked to a cholestatic pattern of liver injury. Being aware of this presentation may help prevent delayed or missed diagnoses and unnecessary testing.

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Author notes

  1. Mouhand F. Mohamed and Neha Wadhavkar Designated as co-first authors.

Authors and Affiliations

  1. Division of Medicine, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Mouhand F. Mohamed, Neha Wadhavkar & Daniel Marino

  2. Division of Gastroenterology, The Warren Alpert Medical School of Brown University, Providence, RI, USA

    Yousef Elfanagely & Kittichai Promrat

  3. Gastroenterology and Hepatology Department, Indiana University, Indianapolis, IN, USA

    Azizullah Beran

  4. Division of Gastroenterology, University of Minnesota, Minneapolis, MN, USA

    Mohamed Abdallah

  5. Providence Veterans Affairs Medical Center, Providence, RI, USA

    Kittichai Promrat

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  1. Mouhand F. Mohamed
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  4. Daniel Marino
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Contributions

MFM and NW contributed equally to this manuscript and are shared first authors. Conception, design: MFM. Writing the initial draft: MFM and NW. Study search, review, and selection: MFM, NW, and MA. Data collection and synthesis: MFM, NW. Statistical analysis and generation of figures: MFM. Interpretation of data, drafting, and critical revision of the article: All authors. Approval of the final version for publication: All authors.

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Correspondence to Mouhand F. Mohamed.

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Mohamed, M.F., Wadhavkar, N., Elfanagely, Y. et al. Etiologies and Outcomes of Transaminase Elevation > 1000 IU/L: A Systematic Review and Meta-Analysis. Dig Dis Sci 68, 2843–2852 (2023). https://doi.org/10.1007/s10620-023-07962-w

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