Association between Helicobacter spp. infections and hepatobiliary malignancies: a review

Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma, the bile ducts intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, the gallbladder and the ampulla of Vater (collectively known as biliary tract cancers). These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies. Cholangiocarcinoma (CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available. Population genetics, geographical and environmental factors, cholelithiasis, obesity, parity, and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors. Other important factors affecting the carcinogenesis of these tumors include chronic inflammation, obstruction of the bile ducts, and impaired bile flow. It has been suggested that CCA is caused by infection with Helicobacter species, such as Helicobacter bilis and Helicobacter hepaticus, in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer. Due to the difficulty in culturing these Helicobacter species, molecular methods, such as polymerase chain reaction and sequencing, or immunologic assays have become the methods of choice for diagnosis. However, clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings, and the use of uniform and validated techniques is needed.