Synergistic effects of cagA+ Helicobacter pylori co-infected with Opisthorchis viverrini on hepatobiliary pathology in hamsters.

Human liver fluke infection caused by Opisthorchis viverrini is associated with several biliary diseases including cholangiocarcinoma (CCA). Recently, it was discovered that the liver fluke is a reservoir of Helicobacter pylori, particularly the cagA-positive strain (cytotoxin-associated gene A) in its gut. Given that two carcinogenic pathogens are associated with CCA development, however, the role of cagA-positive H. pylori in opisthorchiasis has not been clarified. The present study was therefore aimed to investigate histopathological changes of the biliary system in hamsters co-infected with O. viverrini and cagA-positive H. pylori or O. viverrini and cagA-negative H. pylori, with controls of O. viverrini, cagA-positive H. pylori, or cagA-negative H. pylori alone, over time. Major histopathological changes were systematically investigated. All pathological features were quantified/semi-quantified and compared among the experimental groups. The results showed that O. viverrini infection groups (O. viverrini, cagA-positive H. pylori and cagA-negative H. pylori) showed a high degree of eosinophil and mononuclear cell infiltration, lymphoid aggregation and granuloma. Specifically, O. viverrini co-infected with cagA-positive H. pylori presented significantly higher inflammatory scores than O. viverrini and O. viverrini with cagA-positive H. pylori. Proliferation and adaptive lesions such as hyperplasia, goblet cell metaplasia and dysplasia were detected only in O. viverrini infection groups. Dysplasia, the precancerous lesion of CCA, was observed in the first-order bile ducts, especially where the inflammation existed and was found earlier and more severely in O. viverrini with cagA-positive H. pylori than other groups. Similarly, the BrdU (bromodeoxyuridine) proliferation index was significantly higher in O. viverrini co-infected with cagA-positive H. pylori than O. viverrini and O. viverrini with cagA-negative H. pylori groups. Periductal fibrosis was a prominent histopathologic feature in chronic infection in O. viverrini infection groups. Multiple logistic regression showed that O. viverrini co-infected with cagA-positive H. pylori and the duration of infection were the most important factors associated with periductal fibrosis (OR 3.02, 95% CI 1.02-9.29, p = 0.04 and OR 3.82, 95% CI 2.61-5.97, p<0.001). This study demonstrates that the liver fluke co-infected with cagA-positive H. pylori induces severe biliary pathology that may predispose to cholangiocarcinogenesis.

Complications of Cryptosporidium infection after pediatric liver transplantation: Diarrhea, rejection, and biliary disease.

BACKGROUND: Cryptosporidium enteritis can be devastating in the immunocompromised host. In pediatric liver transplant recipients, infection may be complicated by prolonged carriage of the parasite, rejection, and biliary tree damage and fibrosis. Herein, we report on six patients and their long-term outcomes following cryptosporidiosis. METHODS: We reviewed all cases of cryptosporidiosis in a pediatric liver transplant population over a 17-year period at a single center. Six patients with infection were identified, and their outcomes were analyzed. RESULTS: Infection was associated with significant diarrhea and dehydration in all cases, and led to hospitalization in one-half of patients. Four of the six patients developed biopsy-proven rejection following infection, with three of those patients developing rejection that was recalcitrant to intravenous steroid treatment. Additionally, three patients developed biliary tree abnormalities with similarity to sclerosing cholangitis. In one patient, those biliary changes led to repeated need for biliary drain placement and advancing fibrotic liver allograft changes. CONCLUSIONS: Cryptosporidiosis in pediatric liver transplant recipients may lead to significant complications, including recalcitrant episodes of rejection and detrimental biliary tree changes. We advocate for increased awareness of this cause of diarrheal disease and the allograft injuries that may accompany infection.

Biliary ascariasis and severe bacterial outcomes: Report of three cases from a paediatric hospital in Brazil.

INTRODUCTION: Biliary ascariasis, although uncommon, can lead to infectious complications and severe outcomes. This study reported three patients with biliary ascariasis and who were admitted to a paediatric hospital in Salvador, Brazil. CASE REPORTS: Case 1: A 1-year-old boy, with HIV, hospitalised with diarrhoea, fever, pain, and abdominal distension. He underwent an exploratory laparotomy, which showed peritonitis secondary to a perforation of the hepatic duct by ascaris. Case 2: A 3-year-old boy admitted with fever, abdominal pain and jaundice. Imaging examination was suggestive of ascaris in the intrahepatic biliary tract and a hepatic abscess. Case 3: A 7-year-old boy who was hospitalised with a history of abdominal colic, jaundice and fever, with a suggestive image of ascaris in the biliary tract and evolution to sepsis. DISCUSSION: Three cases of biliary ascariasis were reported with severe infectious complications involving peritonitis, hepatic abscess and sepsis. CONCLUSION: In endemic regions, biliary ascariasis should be considered in cases with jaundice, abdominal pain and fever, due to its morbidity and risk of complications.

[A Rare Complication of Acute Diarrhae Caused by Cryptosporidium: Possible Hepatobiliary System Involvement in a Child without Immunodeficiency]. / Akut Cryptosporidium Ishalinin Nadir Bir Komplikasyonu: Immün Yetmezlik Bulunmayan Çocuk Olguda Olasi Hepatobiliyer Tutulum.

Cryptosporidium spp. is one of the leading causes of parasitic diarrhea. It is the most common parasite in humans all over the world with Giardia. Cryptosporidium is an important cause of chronic diarrhea in Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) patients. Patients with normal immune system may have an asymptomatic course or clinical presentation such as acute watery diarrhea without blood and persistent diarrhea. The severity and duration of the disease may be a reflection of the immune deficiency. Children under two years of age and children with malnutrition may have a risk of prolonged Cryptosporidium spp. infection, even if immunodeficiency work-up is normal, as they may have defects in the natural immune system and lymphocyte functions. Cryptosporidium spp. oocysts contaminate water sources, swimming pools, vegetables and fruits because oocysts are partially resistant to chlorination. So it may be problem for public health. Pets, livestock and humans can be carriers of Cryptosporidium spp. Factors such as developmental level of the countries, immune system, nutritional status, living in crowded environments, contact with contaminated water, close contact with animals, working at a hospital and hot and humid climate affect the incidence of Cryptosporidiosis. Cryptosporidium spp. may cause asymptomatic infection, mild diarrheal disease or severe diarrhea with high volume, which may be accompanied by nausea, vomiting, abdominal pain and fever, following a 1-7 day incubation period. Diarrhea may be acute or chronic, transient, intermittent, or continuous; loss of fluid can be up to 25 L/day in severe diarrhea. Cryptosporidium spp. are mainly located in intestines, but non-intestinal (bile ducts, pancreas, stomach, respiratory system, kidney) involvement may occur in immunocompromised patients. Hepatobiliary system involvement occurs in 10-30% of patients with AIDS; stone-free cholecystitis can lead to sclerosing cholangitis and pancreatitis. Hepatobiliary involvement is not expected in patients without immunodeficiency. In this article, we present a case of Cryptosporodiosis with hepatobiliary system involvement who were admitted to the pediatric emergency clinic with the complaints of severe diarrhea and Cryptosporidium spp. oocysts were detected in parasitological examination of the stool specimen. Immunodeficiency was not considered with her resume and laboratuary examinations. We would like to emphasize that Cryptosporodium spp. may be the cause of severe acute diarrhea in non-immunocompromised patients and may also involve hepatobiliary system involvement.

Evaluation of a short term effect of praziquantel treatment in opisthorchiasis-induced hepatobiliary inflammation by urinary 8-oxodG.

Inflammation of the hepatobiliary system in chronic opisthorchiasis is associated with an elevated level of urinary 8-oxo-7,8 dihydro-2'deoxyguanosine (8-oxodG) during active as well as past exposure to Opisthorchis viverrini infection. In this study, we evaluated the short-term effect of praziquantel treatment on hepatobiliary disease (HBD) using urinary 8-oxodG as an inflammatory marker in a cohort of residents in endemic areas of opisthorchiasis in Khon Kaen, Thailand. The HBD status in terms of periductal fibrosis (PDF) was determined by abdominal ultrasonography and O. viverrini infection was monitored at baseline and 2-4 weeks after curative treatment by praziquantel. Analysis of O. viverrini-infected participants who were PDF-ve revealed that there was a significant reduction of urinary 8-oxodG after treatment compared with the baseline levels (p < 0.001). By contrast, in PDF+ve individuals, the levels of urinary 8-oxodG were similar between baseline and those post-treatment. Although confirmation by using a larger sample size is needed, the positive association between HBD and urinary 8-oxodG level after worm clearance suggests that chronic hepatobiliary inflammation is neither affected nor interrupted by short-term praziquantel treatment. Individuals with persistent PDF at pre- and post-treatment who have a high risk of cholangiocarcinoma, could be identified within 2-4 weeks after parasite removal by drug treatment. Thus, urinary 8-oxodG is a useful biomarker for predicting persistent PDF in individuals with a recent drug treatment history who require further clinical investigation, management and treatment.

An Unwanted Guest in the Biliary Tract: A Case Report.

Ascariasis is a frequent human gastrointestinal tract helminthic disease caused by Ascaris lumbricoide. It usually stays in the intestinal lumen and occasionally migrates into the biliary tract through ampulla of Vater .Biliary ascariasis is a critical complication of intestinal ascariasis with life-threatening manifestations .We report a case of a-38 year-old lady who presented with colicky type epigastric pain radiating to back with diffuse tenderness over abdomen on examination. Ultrasonography abdomen showed linear echogenic structure in common bile duct .Biliary ascariasis was noted on Endoscopic Retrograde CholangioPancreaticography following which extraction was done .Our report highlights the varied clinical features of biliary ascariasis. Keywords: ascariasis; ascaris lumbricoides; cholangiopancreatography endoscopic retrograde; common bile duct.

Biliary ascariasis presenting with gangrenous perforation of the gall bladder: report of a case and brief review of literature.

The most common cause of gallbladder perforation is calculous cholecystitis. Rarer causes include trauma, iatrogenic injuries, biliary stasis and gall bladder ischemia. We report a case of gall bladder gangrene with perforation, secondary to extensive ascariasis. A 45-year-old woman presented with acute intestinal obstruction and jaundice. She had abdominal distension and right hypochondrial tenderness. Abdominal radiography showed dilated bowel loops and ultrasonogram showed worms in the small intestine and biliary tree. On exploration, a bolus of worms 2 feet proximal to the ileocaecal junction was found causing obstruction. Worms were also present in the bile duct and gallbladder causing gangrene and perforation. She underwent cholecystectomy, bile-duct exploration and enterotomy. However, she died on the third postoperative day of overwhelming sepsis. Enteric complications of ascaris leading to bowel obstruction are well-known. Hepatobiliary complications such as cholangitis and obstructive jaundice are rare. However, such an extreme degree of infestation leading to gangrene and perforation of the gall bladder is extremely rare.

Biliary Tract-Infecting Myxosporeans from Estuarine and Reef Stonefish (Scorpaeniformes: Synanceiidae) Off Eastern Australia, with Descriptions of Sphaeromyxa horrida n. sp. and Myxidium lapipiscis n. sp. (Myxosporea: Bivalvulida).

Two new species of myxosporeans are described from the gallbladders of estuarine stonefish, Synanceia horrida, and reef stonefish, Synanceia verrucosa, from localities off Cairns, in tropical north Queensland and in Moreton Bay in southern Queensland, Australia. Sphaeromyxa horrida n. sp. can be distinguished from congeners in the morphologically distinct "balbianii" species group within Sphaeromyxa on the basis of morphometric differences in length and width of mature spores, length and width of polar capsules, and unique small-subunit (SSU) ribosomal (rDNA) sequence composition relative to other taxa. Replicate SSU rDNA sequences generated from Sph. horrida n. sp. collected from Sy. horrida and Sy. verrucosa in tropical north Queensland and from Sy. horrida in Moreton Bay were identical, suggesting that this species is widely distributed along the east coast of Australia. Myxidium lapipiscis n. sp. can be distinguished from the majority of described Myxidium species on the basis of its relatively small mature spore size (6.1-7.9 µm long × 3.1-3.9 µm wide), and its unique SSU rDNA sequence. Specimens putatively identified as M. lapipiscis n. sp. were found in Sy. horrida from both tropical north Queensland and Moreton Bay, suggesting that this taxon is also widely distributed along the east coast of Australia. However, no molecular data were available for the specimens from tropical north Queensland for comparative genetic analyses. Bayesian inference and maximum likelihood analysis of the SSU rDNA sequences for these 2 new species revealed that Sph. horrida n. sp. formed a strongly supported clade with Sphaeromyxa zaharoni Diamant, Whipps, and Kent, 2004, which was described from the scorpaeniform, Pterois miles, from the Red Sea. This is the first report of myxozoans infecting stonefish (Synanceiidae).

Fasciola hepatica-a "Diver" in the Biliary Tree.

Fasciola hepatica is an endemic trematode that affects millions of people worldwide. The human being can be an accidental host through consumption of contaminated food or water. The authors present a case of hepatic fascioliasis in a 69-year-old Portuguese woman who recently traveled from Egypt, Brazil, and India.

Elevated prevalence of Helicobacter species and virulence factors in opisthorchiasis and associated hepatobiliary disease.

Recent reports suggest that Opisthorchis viverrini serves as a reservoir of Helicobacter and implicate Helicobacter in pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA). Here, 553 age-sex matched cases and controls, 293 and 260 positive and negative for liver fluke O. viverrini eggs, of residents in Northeastern Thailand were investigated for associations among infection with liver fluke, Helicobacter and hepatobiliary fibrosis. The prevalence of H. pylori infection was higher in O. viverrini-infected than uninfected participants. H. pylori bacterial load correlated positively with intensity of O. viverrini infection, and participants with opisthorchiasis exhibited higher frequency of virulent cagA-positive H. pylori than those free of fluke infection. Genotyping of cagA from feces of both infected and uninfected participants revealed that the AB genotype accounted for 78% and Western type 22%. Participants infected with O. viverrini exhibited higher prevalence of typical Western type (EPIYA ABC) and variant AB'C type (EPIYT B) CagA. Multivariate analyses among H. pylori virulence genes and severity of hepatobiliary disease revealed positive correlations between biliary periductal fibrosis during opisthorchiasis and CagA and CagA with CagA multimerization (CM) sequence-positive H. pylori. These findings support the hypothesis that H. pylori contributes to the pathogenesis of chronic opisthorchiasis and specifically to opisthorchiasis-associated CCA.

Emergence of the Zoonotic Biliary Trematode Pseudamphistomum truncatum in Grey Seals (Halichoerus grypus) in the Baltic Sea.

The biliary trematode Pseudamphistomum truncatum parasitizes a wide range of fish-eating mammals, including humans. Here we report the emergence of this parasite in grey seals (Halichoerus grypus) in the Baltic Sea. One hundred eighty-three of 1 554 grey seals (11.9%) examined from 2002-2013 had detectable hepatobiliary trematode infection. Parasite identification was confirmed as P. truncatum by sequencing the ITS2 region of a pool of five to 10 trematodes from each of ten seals collected off the coast of seven different Swedish counties. The proportion of seals parasitized by P. truncatum increased significantly over time and with increasing age of seals. Males were 3.1 times more likely to be parasitized than females and animals killed in fishery interactions were less likely to be parasitized than animals found dead or hunted. There was no significant difference in parasitism of seals examined from the Gulf of Bothnia versus those examined from the Baltic Proper. Although the majority of infections were mild, P. truncatum can cause severe hepatobiliary disease and resulted in liver failure in at least one seal. Because cyprinid fish are the second intermediate host for opisthorchiid trematodes, diets of grey seals from the Baltic Sea were analysed regarding presence of cyprinids. The proportion of gastrointestinal tracts containing cyprinid remains was ten times higher in seals examined from 2008 to 2013 (12.2%) than those examined from 2002 to 2007 (1.2%) and coincided with a general increase of trematode parasitism in the host population. The emergence and relatively common occurrence of P. truncatum in grey seals signals the presence of this parasite in the Baltic Sea ecosystem and demonstrates how aquatic mammals can serve as excellent sentinels of marine ecosystem change. Investigation of drivers behind P. truncatum emergence and infection risk for other mammals, including humans, is highly warranted.

Hepatobiliary complications of alveolar echinococcosis: A long-term follow-up study.

AIM: To determine the long-term hepatobiliary complications of alveolar echinococcosis (AE) and treatment options using interventional methods. METHODS: Included in the study were 35 patients with AE enrolled in the Echinococcus Multilocularis Data Bank of the University Hospital of Ulm. Patients underwent endoscopic intervention for treatment of hepatobiliary complications between 1979 and 2012. Patients' epidemiologic data, clinical symptoms, and indications for the intervention, the type of intervention and any additional procedures, hepatic laboratory parameters (pre- and post-intervention), medication and surgical treatment (pre- and post-intervention), as well as complications associated with the intervention and patients' subsequent clinical courses were analyzed. In order to compare patients with AE with and without history of intervention, data from an additional 322 patients with AE who had not experienced hepatobiliary complications and had not undergone endoscopic intervention were retrieved and analyzed. RESULTS: Included in the study were 22 male and 13 female patients whose average age at first diagnosis was 48.1 years and 52.7 years at the time of intervention. The average time elapsed between first diagnosis and onset of hepatobiliary complications was 3.7 years. The most common symptoms were jaundice, abdominal pains, and weight loss. The number of interventions per patient ranged from one to ten. Endoscopic retrograde cholangiopancreatography (ERCP) was most frequently performed in combination with stent placement (82.9%), followed by percutaneous transhepatic cholangiodrainage (31.4%) and ERCP without stent placement (22.9%). In 14.3% of cases, magnetic resonance cholangiopancreatography was performed. A total of eight patients received a biliary stent. A comparison of biochemical hepatic function parameters at first diagnosis between patients who had or had not undergone intervention revealed that these were significantly elevated in six patients who had undergone intervention. Complications (cholangitis, pancreatitis) occurred in six patients during and in 12 patients following the intervention. The average survival following onset of hepatobiliary complications was 8.8 years. CONCLUSION: Hepatobiliary complications occur in about 10% of patients. A significant increase in hepatic transaminase concentrations facilitates the diagnosis. Interventional methods represent viable management options.

Biliary ascariasis: an uncommon cause for recurrent biliary colic after biliary sphincterotomy and common bile duct stone removal.

Endoscopic retrograde cholangiography is the most commonly used technique for removal of common bile duct stones. Biliary sphincterotomy during the procedure facilitates stone retrieval from the common bile duct. However, sphincterotomy ablates the normal biliary sphincter mechanism. This facilitates duodeno-biliary reflex and can result in inward migration of luminal parasite into the biliary system. In areas where ascariasis is endemic there is an increased risk of biliary ascariasis in postbiliary sphincterotomy patients. We report an unusual case where a patient presented with recurrent biliary colic after cholecystectomy and common bile duct stone extraction and was diagnosed to have biliary ascariasis with the help of endoscopic ultrasound examination of the biliary system.

Biliary ascariasis in a bile duct stones-removed female patient.

Biliary ascariasis is a common problem in rural areas in China. The common presentations include biliary colic, acute cholangitis, obstructive jaundice, choledocholithiasis and acute cholecystitis. Here, we describe a case with biliary ascariasis two days after endoscopic sphincterotomy for choledocholithiasis. A living ascaris was successfully removed by endoscopic retrograde cholangiopancreatography. This case indicated that biliary ascariasis is not an uncommon complication of endoscopic sphincterotomy in some regions where ascariasis is epidemic.

Hepatolithiasis after Hepaticojejunostomy: Ascaris lumbricoides in the biliary tract.

BACKGROUND: Biliary ascariasis is a common problem in Third World countries and other underdeveloped areas of the world. Ascaris lumbricoides migrates into the biliary tree, where it is apparent commonly on diagnostic imaging. We present a unique case of a patient with chronic right upper quadrant abdominal pain, massive hepatolithiasis, and stricture of a previous hepaticojejunostomy in whom ascariasis was found. METHODS: A 28-year-old female presented to the emergency department with right upper quadrant abdominal pain, syncope, and seizure-like activity. She was found by magnetic resonance cholangiopancreatography to have cholangitis, choledocholithiasis, and bile duct stricture. After multiple radiographic studies, she was taken to the operating room for revision of a hepaticojejunostomy performed 10 years previously. RESULTS: Ascaris lumbricoides was found in the right intrahepatic bile duct, that had not been identified by multiple radiologic modalities. The worm was sent to the pathology department for identification. A Fogarty catheter was passed into the hepatic ducts for successful stone extraction. The hepaticojejunostomy was revised, with catheter placement in the Roux limb to accommodate radiologic stone extraction as necessary. Post-operatively, she was given a single dose of albendazole and discharged on hospital day 19. CONCLUSION: The worm was likely the nidus for the stricture and stone formation. Surgical exploration of the biliary tree was required to diagnose and treat her condition accurately. This case is unique in that typical means of diagnosis failed to identify the causative agent of hepatolithiasis because of the prior Roux-en-Y hepaticojejunostomy.