Association between Liver Fluke Infection and Hepatobiliary Pathological Changes: A Systematic Review and Meta-Analysis

Objective
To provide information about the role of liver fluke infection as a risk factor for hepatobiliary pathological changes and promote awareness among the people living in endemic areas, a systematic review and meta-analysis based on published studies was conducted to examine the association between liver fluke infection and hepatobiliary pathological changes.
Methods
Relevant original literature was searched in multiple literature databases, including PubMed, Cochrane, Clinical Evidence, Trip Database, Clinical Trials, Current Controlled Trials, Web of Science, the China National Knowledge Infrastructure (CNKI) database, and the Wanfang academic journal full-text database. Studies were selected based on strict screening with inclusion and exclusion criteria. Tests of heterogeneity, sensitivity and publication bias were performed with the Review Manager software, version 5.3, and meta-regression analyses were performed with the Stata software, version 11.0 (Stata Corporation, College Station, TX, USA). Pooled risk ratios (RRs) and odds ratios (ORs) with their 95% confidence intervals (95% CIs) were calculated and used to evaluate the risk of hepatobiliary pathological changes resulting from liver fluke infection. Linear trend analyses were conducted to determine the dose-response relationship using IBM SPSS Statistics 20.0.
Result
A total of 36 studies were included in the meta-analysis. Significant associations were found between liver fluke infection and cholangitis or cholecystitis (RR: 7.80, P<0.001; OR: 15.98, P<0.001), cholelithiasis (RR: 2.42, P = 0.03; OR: 4.96, P = 0.03), hepatocellular carcinoma (OR: 4.69, P<0.001) and cholangiocarcinoma (RR: 10.43, P<0.001; OR: 4.37, P<0.001). In addition, heavier infection was significantly associated with higher incidence of hepatobiliary pathological changes (P<0.05). However, cirrhosis was not significantly associated with liver fluke infection (RR: 3.50, P = 0.06; OR: 5.79, P = 0.08). The statistical heterogeneity was significant, no significant difference was observed in the sensitivity analysis, and no publication bias was found.
Conclusion
The meta-analysis found that liver fluke infection was significantly associated with cholangitis, cholecystitis, cholelithiasis, hepatocellular carcinoma and cholangiocarcinoma and that more severe infection was associated with higher incidence. However, the association between liver fluke infection and cirrhosis was not significant.

研究目的：为明确肝吸虫感染作为肝胆病理改变危险因素的作用，并提升流行区人群的防控认知，本研究基于已发表文献开展系统评价与荟萃分析，以探讨肝吸虫感染与肝胆病理改变之间的关联。
研究方法：在PubMed、Cochrane图书馆、Clinical Evidence、Trip Database、Clinical Trials、Current Controlled Trials、Web of Science、中国知网（China National Knowledge Infrastructure, CNKI）及万方学术期刊全文数据库等多个文献数据库中检索相关原始文献；依据严格的纳入与排除标准对文献进行筛选。采用Review Manager 5.3版软件进行异质性检验、敏感性分析及发表偏倚检验，采用Stata 11.0版软件（美国德克萨斯州大学站Stata公司）进行Meta回归分析。计算合并风险比（risk ratios, RRs）、比值比（odds ratios, ORs）及其95%置信区间（95% confidence intervals, 95% CIs），以评估肝吸虫感染所致肝胆病理改变的风险；采用IBM SPSS Statistics 20.0软件进行线性趋势分析，以明确剂量-反应关系。
研究结果：本荟萃分析共纳入36项研究。结果显示，肝吸虫感染与胆管炎或胆囊炎（RR=7.80，P<0.001；OR=15.98，P<0.001）、胆石症（RR=2.42，P=0.03；OR=4.96，P=0.03）、肝细胞癌（OR=4.69，P<0.001）及胆管癌（RR=10.43，P<0.001；OR=4.37，P<0.001）均存在显著关联。此外，感染负荷较重与肝胆病理改变发生率升高显著相关（P<0.05）。但肝硬化与肝吸虫感染未发现显著关联（RR=3.50，P=0.06；OR=5.79，P=0.08）。本研究存在显著的统计学异质性，敏感性分析未发现显著差异，且未检出发表偏倚。
研究结论：本荟萃分析表明，肝吸虫感染与胆管炎、胆囊炎、胆石症、肝细胞癌及胆管癌均存在显著关联，且感染程度越重，肝胆病理改变发生率越高；但肝吸虫感染与肝硬化的关联并不显著。