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.

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.

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.

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.

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 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.

Etiology and outcome of acute pancreatitis in children in Kashmir (India). An endemic area of hepatobiliary ascariasis.

BACKGROUND: The purpose of the present study was to determine the etiology, management, and outcome of acute pancreatitis (AP) in children in an endemic area of hepatobiliary ascariasis (HBA). METHODS: This was a prospective, hospital-based study over a 9-year period that included 156 children younger than 12 years of age who had a diagnosis of AP. RESULTS: Of the 156 patients, 71 were boys and 85 were girls with a mean age of 8.4 ± 1.5 years (range 3-12 years). The various factors contributing to AP were biliary ascariasis in 93 cases (60 %), gallstones 16 (10 %), trauma 5 (3 %), choledochal cyst 4 (3 %), impacted bile duct stone 3 (2 %), and gallbladder sludge 2 (1 %). Idiopathic group 33 cases (21 %). Diagnosis was based on clinical picture, abdominal ultrasonography, and elevated serum amylase level. Pancreatitis was mild in 113 (72 %) patients and severe in 43 (28 %). With conservative therapy, 123 patients (79 %) improved, whereas the remaining 33, who had intractable abdominal pain, cholangitis, or worsening cholecystitis, underwent emergency endoscopic retrograde cholangiopancreatography for removal of worms (26 patients) and stones in the bile duct (7 patients). Bile duct stones were extracted in all 7 patients with that condition, and worms were extracted from 23 of the 26 patients with ascariasis. Emergency surgery was performed in five patients. Three patients died. Pancreatitis recurred in 16 patients due to HBA. CONCLUSIONS: Pancreatitis is not uncommon in children. Ascariasis is a leading cause of AP in endemic areas. Patients usually respond to conservative management, but endoscopic treatment is effective. Surgery is rarely required.

Ruptured hydatid cyst in biliary tract.

A lady aged 26 years reported with a 2 months history of fever, upper abdominal pain and weight loss. Her abdominal ultrasonographic scan revealed a complex cystic mass in left lobe of liver suggestive of hydatid cyst that was confirmed on magnetic resonance imaging of abdomen and magnetic resonance cholangiopancreatogram. With strong suspicion of a hydatid cyst, endoscopic retrograde cholangiogram was performed which confirmed the diagnosis. During the procedure, hydatid membranes protruding from the papilla were removed after sphincterotomy. She was put on albendazole 400 mg twice daily after the procedure and showed a remarkable clinical improvement.

Characteristic MR and CT imaging findings of hepatobiliary paragonimiasis and their pathologic correlations.

BACKGROUND: Hepatobiliary paragonimiasis (HP) is not commonly encountered and may be confused with hepatobiliary tumors; however, computed tomography (CT) and magnetic resonance imaging (MRI) features of HP allow this entity to be distinguished from other diseases. PURPOSE: To present the CT and MRI findings in patients with HP and to describe some specific imaging findings along with their pathological correlations. MATERIAL AND METHODS: Imaging and clinical findings of 21 patients (9 boys/men and 12 girls/women; age range 3-67 years; mean age 40 years) who were diagnosed with HP were retrospectively evaluated. Among these patients, 16 underwent CT examination only, two had MR examination only, and three underwent both CT and MR. All patients underwent surgery, and the HP diagnosis was confirmed by the surgical and histopathologic results. RESULTS: Chronic abdominal pain or back pain was reported by 14 patients, severe abdominal pain with acute onset was reported by one patient, and six patients were asymptomatic and were discovered incidentally. Peripheral eosinophilia was present in 14 patients (14/21, 66.7%), and abnormal liver function tests were found in 16 patients (16/21, 76.2%). Of the 19 patients who underwent CT imaging, 17 patients showed multiple mixed hypodense lesions or multiple cysts with inlaying septation with separate irregular rims or circular enhancement on post-contrast CT images. Tunnel-shaped microabscesses and necrotic cavities were found in the lesions of 12 of those 17 patients. The other two patients showed smaller cystic masses. MRI showed faveolate T1 hypointense and T2 hyperintense areas in the liver parenchyma with rim or peripheral enhancement. Nodular or circular hyperintense materials were found scattered in the lesions on T1-weighted imaging. CONCLUSION: CT and MRI can reveal the radiological-pathological features of HP. Together with laboratory findings, MRI and CT findings may provide diagnostic clues, especially in endemic areas, that are very important for the selection of treatment methods.

Morphological and genetic analysis of three new species of Ceratomyxa Thélohan, 1892 (Myxozoa: Myxosporea) from carcharhinid sharks off Australia.

Three new species of Ceratomyxa Thélohan, 1892 are described from the gall-bladders of two species of carcharhinid sharks collected off Heron and Lizard Islands on the Great Barrier Reef, Australia. Ceratomyxa carcharhini n. sp. and C. melanopteri n. sp. are described from Carcharhinus melanopterus (Quoy & Gaimard), and Ceratomyxa negaprioni n. sp. is described from Negaprion acutidens (Rüppell). These species are the first ceratomyxids reported from Australian elasmobranchs, and this is the first paper to formally characterise a novel Ceratomyxa species from an elasmobranch using both morphology and small subunit ribosomal DNA sequence data. Maximum parsimony and Bayesian inference analyses of the SSU rDNA dataset revealed that ceratomyxids from elasmobranchs form a sister clade to that of species infecting marine teleosts and Palliatus indecorus Schulman, Kovaleva & Dubina, 1979. Furthermore, the only sequenced freshwater ceratomyxid, Ceratomyxa shasta Noble, 1950, fell outside the overall marine ceratomyxid clade. These data show that Ceratomyxa, as currently recognised, is polyphyletic and ignites discussion on whether Ceratomyxa should be split. However, further taxon sampling, particularly in freshwater systems, is required to establish relevant biological divisions within the genus.

Comparative study on presentation of biliary ascariasis with dead and living worms.

BACKGROUND/AIM: Ascariasis is a common parasitic infestation in Asia and Latin America. The most serious presentation is biliary and pancreatic ascariasis (BPA). The aim of the present study was to compare the clinical presentation of BPA with dead worms with that with living worms. MATERIALS AND METHODS: We included 138 consecutive cases of BPA that occured during the period January 2005 to July 2009. All the patients had endoscopically proven BPA consisting of living or dead worms. Comparison was done by chi-square and independent t tests. RESULTS: The age (mean +/- SD) of the patients was 36.8 +/- 16.1 years. Prevalence ratio between male and female patients was 1:5. Ninety eight patients contained living worms and 40 had dead worms. Males were more prone to develop dead worm BPA. The commonest presentation was biliary colic (131; 94.9%); others were acute cholangitis (30; 21.7%), obstructive jaundice (19; 13.8%), choledocholithiasis (20; 14.5%), acute pancreatitis (10; 7.2%), acute cholecystitis (6; 4.3%), liver abscess (2; 1.4%), hepatolithiasis (3; 2.2%), stricture of common bile duct (2; 1.4%), pancreatic abscess (1; 0.7%) and cirrhosis of liver (1; 0.7%). Choledocholithiasis, hepatolithiasis, liver abscess and cirrhosis were associated only with dead worms. We could successfully remove all the worms with endoscopic interventions, but 5 patients required surgical intervention as there were strictures and stones within the biliary tree or Ascaris were in gallbladder. Recurrences of stone and cholangitis occurred only in those with dead worms. CONCLUSION: Biliary ascariasis with dead worms is more dangerous than that with living worms. Endoscopic or surgical intervention may be required repeatedly in those with dead worms.

Endoscopic retrograde cholangiography for intrabiliary rupture of hydatid cyst.

The most common complication of hydatid cysts of the liver is cholestasis due to rupture of hepatic cysts into the biliary tree. Such a complicated cyst is usually managed by surgical cyst resection. Endoscopic retrograde cholangiogram with sphincterotomy is a well-established method for preoperative and postoperative extraction of cyst material from the biliary tree. Successful nonsurgical treatments of complicated hydatid cyst are reported with a combination of pharmaceutical therapy and endoscopic techniques consisting of endoscopic sphincterotomy and instillation of hypertonic saline solutions. We report feasibility and outcome of the endoscopic method for treatment of ruptured hepatic hydatid cyst into the biliary tract that also benefited from drainage of the whole cyst and membranes into the major biliary duct.

[Intrabiliary rupture of hepatic hydatid cysts: results of 17 years' experience]. / Chisturile hidatice hepatice rupte în arborele biliar: experienta a 17 ani.

UNLABELLED: Between 1990 and 2006 in the III-rd Surgical Clinic Cluj-Napoca, 366 pacients with hepatic hydatid cyst were admitted and underwent surgery; 81 (22.13%) of them, who had a cyst-biliary comunication, were retrospectively reviewed: 52 (64.2%) had an occult communications and 29 (35.8%) had a frank intrabiliary rupture. The sex ratio was M/F=46/35 with a mean age of 44.5 years and with ages between 17 and 73 years. Choledochotomy, evacuation of parasitic material and lavage of the CBP were performed in all patients with frank intrabiliary rupture. In 25 patients, partial pericystectomy and choledochoduodenostomy/T-tube drainage of CBP was performed. Internal drainage by a Roux-en-Y pericystectojejunostomy and biliodigestive anastomosis was carried out in 2 patients, while other two patients underwent external drainage of cystic cavity and T-tube drainage of CBP. 15 patients (51.7%) had postoperative external bile leaks (fistulas). Occult communications were managed by partial pericystectomy +/- narrowing of the residual cavity (capitonage with an omentum flap or invagination of the fibrosis capsule margins into the cavity) in 35 patients (67.3%) while in 10 patients (19.2%) internal drainage by a Roux-en-Y pericystectojejunostomy was carried out. Regional resection of the liver was performed in 4 cases (7.7%) and external drainage of residual cavity in 3 patients (5.7%). 13 patients (25%) had postoperative external bile leaks (fistulas). The mean postoperative hospitalisation was 20 days with the range 5-85 days. The mortality rate was 2.4% (2 patients): one died due to septicemia and MOFS and the other due to pulmonary thromboembolism. CONCLUSION: Postoperative bile leaks (fistulas) fallowing conservative surgery of ruptured hydatid hepatic cyst into the biliary tract are not rare regardless of the type of rupture (frank or occult). Although the opening of the biliary duct is sutured, the risk of biliary fistulas is not clearly corelated with this approach; in such cases internal drainage provides a good alternative with low morbidity.