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

Abstract

ObjectiveTo 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.MethodsRelevant 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.ResultA 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.ConclusionThe 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.

Human liver flukes

“…Chronic symptoms may mirror acute symptoms, and may be due to chronic irritation of bile ducts or physical obstruction by liver flukes. Cholangitis, cholecystitis, obstructive jaundice, periportal fibrosis, cholelithiasis, and cholangiocarcinoma are all recognised consequences of clonorchiasis and opisthorchiasis (27) . Pancreatitis, as a result of pancreatic duct obstruction, has been described but is rare and usually mild (5) .…”

“…H. bilis and H. pylori infection is associated with cholangiocarcinoma in patients in both areas endemic for human liver fluke infection and in areas where human liver fluke infection is rarely seen (73)(74)(75) . In 2009, the IARC found no evidence of an association between liver fluke infection and hepatocellular carcinoma (6) , however a recent meta-analysis of seven studies did demonstrate a positive association (27) . Severin, an excretory/secretory product of Clonorchis sinensis inhibits apoptosis of HCC cell lines in vitro (48) .…”

Fraction and incidence of liver cancer attributable to hepatitis B and C viruses worldwide

“…4,5 As part of an ongoing project to estimate the global burden of cancer attributable to infections, we estimated the number of incident liver cancers attributable to HBV and HCV worldwide. The United Nations recently set a goal of eliminating viral hepatitis as a major public health threat by 2030.…”

“…4,5 As part of an ongoing project to estimate the global burden of cancer attributable to infections, we estimated the number of incident liver cancers attributable to HBV and HCV worldwide. 1 Most primary liver tumors are hepatocellular carcinoma (HCC) with the exception of some areas of South-Eastern Asia where intrahepatic bile duct cancer is also common due to the endemic presence of liver flukes.…”

Fasciola Hepatica in Explanted Cirrhotic Liver of a Patient with Chronic Hepatitis B Virus Infection: An Accidental Finding

“…Furthermore, the liver fluke may secrete some metabolites that can play an immunogenic stimulatory role leading to strong humoral immune responses (9). In fact, the presence of parasite antigens in various hepatobiliary portions such as biliary epithelium and its surrounding tissue can facilitate inflammatory cell infiltration and also activate host immune responses (10).…”