There has been uncertainty about the risk of HCC in AIH patients between different gender and among various regions. To address the issues, in this systematic review, we assembled data from 39 observational studies reporting the HCC incidence rate in AIH patients. The incidence rate varied strikingly, from 0.75 to 10.02 per 1,000 person years according to the geographical location of the population under study. After analysis, we found that an overall HCC incidence rate of 3.54 per 1,000 person-years (95%CI = 2.76–4.55) among patients with AIH.
Our study confirmed the risk of HCC in male patients with AIH was over 2-fold higher than in female ones. Moreover, globally, we revealed a higher incidence rate of HCC in AIH patients among Asian populations, compared to those from Europe, Oceania or North America. The regional disparities were consistent when we combined the incidence rate in different gender by continent. When it came to AIH patients accompanied with cirrhosis, we found that cirrhosis status at AIH diagnosis was significantly associated with an increased incidence rate for HCC, which was much more pronounced among Asian populations.
To further explore the factors related to the disparities, we estimate the association between three covariates (percentage of female in AIH patients, percentage of AIH patients with cirrhosis at index, mean age of patients at AIH diagnosis) and HCC incidence respectively. Consequently, we found that the proportion of AIH patients with cirrhosis at index was positively associated with HCC incidence. However, surprisingly, the studies in Asia had relatively lower proportion of AIH-cirrhosis patients, which implied the regional disparities might not result from the initial cirrhotic condition of the cohorts.
We made a combination of the HCC incidence in AIH patients and AIH prevalence to estimate every single country. After analysis, we deduced there might exist more HCC patients evolved from AIH in Japan and New Zealand. Unfortunately, the risk value could not be calculated in all countries owing to lack of statistics on AIH prevalence. The HCC incidence rate among AIH patients in India and China ranked in the top two places. As we all know, India and China are the two most populous countries in the world, which are bound to possess a large population of AIH patients no matter the AIH prevalence. Thus, even though we failed to confirm the exact risk value, we recommended that clinical workers should pay more attention to the AIH patients in India and China. Previous meta-analysis reported the overall pooled incidence of patients with AIH cirrhosis was 1.007% per year (10.07 per 1,000 person-years).14 According to the latest cost-benefit analysis, an HCC incidence > 0.4% per year was necessary for ultrasound with serum AFP level to be cost-effective compared with no surveillance in patients with compensated cirrhosis.15 The annual incidence rates of HCC in AIH related cirrhosis no matter in Asian, European and North American populations all exceeded 0.4%. (Asia: 1.7%; North America: 1.1%; Europe: 0.6%) Thus we recommended routine HCC surveillance for patients with AIH cirrhosis, especially for those in Asia.
Several limitations in our study should be mentioned. Of 39 studies involved in our analysis, there were 11 studies published as abstract, which provided limited information for us to estimate the validity of the methodology and the credibility of the result. Furthermore, the majority of the data were derived from single center and multicenter and only 3 of them reported the data on general populations, which might cause inaccuracy when we simply treated these data as representative for some countries. The inaccuracy could be exacerbated if there was merely one study involved and no combined analysis to reduce the bias. For example, such happens in the comparison among continents (Oceania). Almost all the studies involved, except for Ohira 2013, reported a small number of HCC cases that ranged from 0 to 15 during the follow-up period. Therefore, the estimates of incidence rate might not be precise. What’s more, we found that there existed gender differences and global disparities but we failed to figure out the exact reason on account that the information from original studies was not sufficient for us to further explore the risk factors.
In summary, this systematic review and meta-analysis provides a comprehensive summary of the current literatures on the HCC incidence rate of AIH patients. A higher incidence was observed among male patients and patients in the Asian population. Further study should be committed to the cause of the disparities.