Biliary Migration, Colonization, and Pathogenesis of O. viverrini Co-Infected with CagA+ Helicobacter pylori

Abstract

Co-infection with the cagA strain of Helicobacter pylori exacerbates the pathology of human liver fluke Opisthorchis viverrini (OV) infection leading to cholangiocarcinoma. However, underlying mechanisms remain unclear. We report a significant increase in cagA-positive and cagA-negative H. pylori in the stomach, blood, bile, and in the OV worms of co-infected Syrian golden hamsters at one hour, three hours, and one month, post-infection, compared to hamsters infected with either OV or H. pylori alone. Except in the worms, H. pylori numbers declined at three months post-infection, particularly in the bile fluid of co-infected animals. Both strains of H. pylori were immunohistochemically detected in the tegument of the worm, as well as in the bile duct epithelium when co-infected with O. viverrine, but not in H. pylori infection alone. Interestingly, only the cagA-positive strain was detected in the gut of the worm. Co-infection between cagA-positive H. pylori and O. viverrini resulted in a more severe biliary pathology and decreased E-cadherin expression in vivo and in vitro than those of the cagA-negative strain. These data suggest that O. viverrini acts as a carrier of cagA-positive H. pylori and co-migrates to the bile ducts, whereas O. viverrini facilitates H. pylori colonization and enhances the biliary pathogenesis and carcinogenesis.

Persistent advanced periductal fibrosis is associated with cagA‐positive Helicobacter pylori infection in post‐praziquantel treatment of opisthorchiasis

“…Second, persistent APF may be driven The association between O. viverrini and Helicobacter infection has been reported in animal and human studies. 14,[18][19][20][21][22] The majority of O. viverrini-infected residents in liver fluke endemic areas in northeastern Thailand are co-infected with H. pylori. 15 Moreover, APF, which is the major pathologic characteristic of chronic opisthorchiasis, is associated with cagA-positive H. pylori.…”

“…pylori and co-migrates to the bile ducts, and that O. viverrini facilitates H. pylori colonization and enhances biliary pathogenesis in a hamster model. 22 This evidence suggests that H. pylori depends on the liver fluke to be able to survive and colonize the bile ducts.…”

“…17 During the past decade, there has been increasing evidence from both animal and human studies that H. pylori, particularly cagA-positive strains, may be involved in the pathogenesis of APF and CCA in opisthorchiasis. 14,[18][19][20][21][22] Interestingly, O. viverrini has been demonstrated as a reservoir of Helicobacter spp., especially cagA-positive H. pylori. 15,18 The H. pylori co-migrates with the liver fluke, colonizes in the biliary epithelium and induces inflammation and APF in chronic opisthorchiasis in animals 22 and humans.…”

“…14,[18][19][20][21][22] Interestingly, O. viverrini has been demonstrated as a reservoir of Helicobacter spp., especially cagA-positive H. pylori. 15,18 The H. pylori co-migrates with the liver fluke, colonizes in the biliary epithelium and induces inflammation and APF in chronic opisthorchiasis in animals 22 and humans. 15 We propose that O. viverrini may act as a carrier for cagA-positive H. pylori which is the key driver of APF and eventually CCA development.…”

Meta-analysis and systematic review of liver transplantation as an ultimate treatment option for secondary sclerosing cholangitis

“…Arterial hypotension of the peribiliary vascular plexus causes ischaemic injury of the bile duct epithelium [ 1 ]. The available clinical data indicate that ischaemic injury to the intrahepatic biliary tree followed by bacterial colonization leading to destructive biliary changes may be one of the earliest events in the development of this severe form of SSC-CIP [ 3 ]. These patients usually have no prior history of biliary disease or liver disease and no evidence of a pathological process or injury that has obviously caused obstruction of the bile duct [ 4 – 10 ].…”