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Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis

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Abstract

Background

Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) in autoimmune hepatitis (AIH). Sex and regional disparities in incidence of HCC in AIH continue to be reported worldwide. Nevertheless, the magnitude of this gap remains unknown.

Method

We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wanfang Data, CNKI and SinoMed. Incidence rates of HCC in AIH were combined and analyzed following the EBayes method. Incidence rate ratios were pooled to assess the sex differences. The impact of population difference, sex, age, cirrhotic condition was further analyzed with subgroup analysis and linear regression analysis.

Result

39 studies meeting our eligibility criteria were chosen for the analysis. The pooled incidence rate of HCC in AIH was 3.54 per 1000 person years (95% CI 2.76–4.55). Pooled IRR for the risk of HCC in male AIH patients compared to female was 2.16 (95% CI 1.25–3.75), with mild heterogeneity among studies. The pooled HCC incidence rate in AIH by continents was as follows: Europe 2.37 per 1000 person-years (95% CI 1.45–3.88), Asia 6.18 per 1000 person-years (95%CI 5.51–6.93), North America 2.97 per 1000 person-years (95%CI 2.40–3.68), Oceania 2.60 (95%CI 0.54–7.58). The pooled HCC incidence rate in AIH-related cirrhosis by continent was as follows: Europe 6.35 per 1000 person-years (95%CI 3.94–10.22), Asia 17.02 per 1000 person-years (95%CI 11.18–25.91), North America 10.89 per 1000 person-years (95%CI 6.69–17.74).

Conclusion

A higher HCC incidence in AIH was observed among male and in Asian populations. Cirrhosis status at AIH diagnosis is significantly associated with an increased incidence rate for HCC, and routine HCC surveillance is recommended for patients with AIH cirrhosis, especially for those in Asia.

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Data transparency

The manuscript's guarantors (L.-J.Y. and T.L.) affirm that the manuscript shows an honest, accurate, and transparent study; that no important aspects of the study have been omitted and that any discrepancies from the study have been explained.v

Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

AIH:

Autoimmune hepatitis

SIR:

Standardized incidence rate

SMR:

Standardized mortality rate

NOS:

Newcastle–Ottawa scale

CI:

Confidential interval

IRR:

Incidence rate ratio

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Funding

This work was supported by the grants from the Taishan Scholars Program for Young Expert of Shandong Province (Grant No. tsqn20161064), National Natural Science Foundation of China (Grant Nos. 82073200 & 81874178), and founds for Independent Cultivation of Innovative Team from Universities in Jinan (Grant No.2020GXRC023).

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Authors and Affiliations

  1. Department of General Surgery, Qilu Hospital, Shandong University, 107 West Wen Hua Road, Jinan, 250012, People’s Republic of China

    Lun-Jie Yan, Sheng-Yu Yao, Guang-Xiao Meng, Kai-Xuan Liu, Hai-Chao Li, Zi-Niu Ding, Zhao-Ru Dong, Jian-Guo Hong, Zhi-Qiang Chen & Tao Li

  2. Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan, 250012, People’s Republic of China

    Tao Li

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  1. Lun-Jie Yan
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Contributions

All authors had full access to the data in the study and take responsibility for the integrity and authenticity of the data. L-JY formulated the study objective, conceptualized the study, performed the statistical analysis, and interpreted the results; K-XL and G-XM designed the protocol of the systematic reviews; Z-RD, J-GH, Z-QC provided important guidance to the protocols and modified them; L-JY and S-YY assessed the availability of each study retrieved from online databases respectively and disagreements were identified and discussed with K-XL; H-CL, and Z-ND performed the methodology, data collection, and data validation; L-JY guided the task of formal statistical analysis and analysis of the data; L-JY and TL contributed to outlining the manuscript and drafting the manuscript; L-JY and TL verified the underlying data. TL supervised and coordinated the study. All authors have read and approved the final version.

Corresponding author

Correspondence to Tao Li.

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Lun-Jie Yan, Sheng-Yu Yao, Guang-Xiao Meng, Kai-Xuan Liu, Hai-Chao Li, Zi-Niu Ding, Zhao-Ru Dong, Jian-Guo Hong, Zhi-Qiang Chen and Tao Li declare no conflict of interests for this article.

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Yan, LJ., Yao, SY., Meng, GX. et al. Sex and regional disparities in incidence of hepatocellular carcinoma in autoimmune hepatitis: a systematic review and meta-analysis. Hepatol Int 15, 1413–1420 (2021). https://doi.org/10.1007/s12072-021-10249-9

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