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

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.

Keywords: Autoimmune hepatitis; Autoimmune liver disease; Cirrhosis; Hepatocellular carcinoma; Incidence; Liver; Meta-analysis; Prevalence; Regional disparities; Risk; Sex differences.