The risk of hepatobiliary complications in Clonorchis and Opisthorchis infection: a systematic review and meta-analysis

Clonorchis sinensis, Opisthorchis viverrini, and Opisthorchis felineus are the three important liver flukes, infecting approximately 25 million people worldwide. Despite the reporting of the carcinogenesis of these liver flukes, the comprehensive and systematic analysis of the pathogenicity of these parasites in hepatobiliary system is still not sufficient. We conducted a thorough systematic review and search for published articles in MEDLINE, Embase, Cochrane Library, China National Knowledge Infrastructure databases until early 2024. Cohort studies, case-control studies, and cross-sectional studies associated with C. sinensis, O. viverrini, or O. felineus infection were selected. Pooled risk ratio (RR), odds ratio (OR) and their 95% confidence intervals (95% CIs) were calculated to assess the risk of hepatobiliary complications due to these liver fluke infections. From a total of 6488 articles, 22 eligible studies and 34367 participants were included for review. Our results showed C. sinensis, O. viverrini, and O. felineus infections were significantly associated with cholangiocarcinoma, with an overall OR of 4.24 (95% CI: 3.33-5.39, P<0.00001) and an overall RR of 10.43 (95% CI: 2.90-37.47, P=0.0003). The ORs for the association between cholangiocarcinoma and C. sinensis and O. viverrini infection were 4.49 (95% CI:3.43-5.87, P<0.00001) and 3.69 (95% CI: 2.07-6.55, P<0.00001) respectively. For the association between cholelithiasis and C. sinensis infection, the OR was 6.46 (95% CI: 5.15-8.11, P<0.00001). C. sinensis infection increased the risk of cholecystitis and cirrhosis, with the RR of 21.02 (95% CI: 17.27-25.58) and an overall RR of 8.77 (95% CI: 6.79-11.33, P<0.00001) respectively. C. sinensis infection was also significantly associated with fatty liver, with an overall OR of 2.46 (95% CI: 1.79-3.37, P<0.00001). This comprehensive study, reviewing the largest dataset to date, provided an overall risk of hepatobiliary complications due to Clonorchis and Opisthorchis infections, and aids more systematic understanding for the pathogenicity of Opisthorchiidae family parasites.