Gender Differences and Regional Disparities of Incidence of Hepatocellular Carcinoma in Autoimmune Hepatitis Patients: A Systematic Review and Meta-Analysis

Background: Recent studies have identified an increased risk of hepatocellular carcinoma (HCC) among individuals diagnosed with autoimmune hepatis (AIH). Nevertheless, the gender differences and global disparities in HCC risk among AIH patients have not been studied yet. Method: We did a systematic review and meta-analysis of HCC incidence in AIH patients and further explored the gender differences and regional disparities. We searched several databases including PubMed, Embase, Web of Science, Cochrane Library, Wangfang Data, CNKI and Sinomed from the inception of the databases through December 23, 2020. Observational studies which reported incidence rates of HCC in AIH patients or provided sufficient raw data to calculate incidence rates were included in our analysis. Incidence rates of HCC in AIH patients were combined and analyzed following the Ebayes method. Incidence rate ratios were pooled to assess the gender differences. The impact of population difference, gender, age, cirrhotic condition was further analyzed with subgroup analysis and liner regression. Our study protocol was registered in the PROSPERO database (CRD42020157000). Findings: We found 1,350 studies from the literature search, of which 39 studies meeting our eligibility criteria were chosen for the analysis, including a total of 14,597 AIH patients. The pooled incidence rate of HCC in AIH patients was 3.54 per 1,000 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 patients according to continents was as follows: Europe 2.37 per 1,000 person-years (95%CI = 1.45-3.88), Asia 6.18 per 1,000 person-years (95%CI = 5.51-6.93), North America 2.97 per 1,000 person-years (95%CI = 2.40-3.68), Oceania 2.60 (95%CI 0.54-7.58). The pooled HCC incidence rate in AIH-cirrhosis patients by continent was as follows: Europe 6.35 per 1,000 person-years (95%CI = 3.94-10.22), Asia 17.02 per 1,000 person-years (95%CI = 11.18-25.91), North America 10.89 per 1,000 person-years (95%CI = 6.69-17.74). Interpretation: It is more risky for male AIH patients to develop HCC. AIH patients in Asia were at an increased risk for HCC. Routine HCC surveillance is cost effective for patients with AIH cirrhosis, especially for those in Asia. Registration : Our study protocol was registered in the PROSPERO database (CRD42020157000). Funding Statement: This work was supported by the grants from the Taishan Scholars Program for Young Expert of Shandong Province (Grant No. tsqn20161064) and National Natural Science Foundation of China (Grant No. 82073200 & 81874178). Declaration of Interests: There are no conflicts of interest to declare.