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PubMed2005

Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis.

OBJECTIVE: Animal studies show that small intestinal bacterial overgrowth and infusion of bacterial antigens into portal blood cause hepatic histological changes similar to those seen in primary sclerosing cholangitis in man. It has been suggested that aa similar mechanism involving bacterial overgrowth with increased small-bowel permeability may play a pathogenic role in patients with primary sclerosing cholangitis (13 M, 9 F, median age 37 years, range 21-74 years), 19 of whom (83%) had quiescent inflammatory bowel disease, were included in the study along with 18 healthy volunteers (9 F, ( M, median age 36 years, range 23-80 years). Small-bowel bacterial overgrowth was defined as the presence of colonic flora>10(5) colony-forming units (cfu)/ml from duodenal aspirations. Small-bowel intestinal permeability was assessed as the differential urinary excretion of lactulose/L-rhamnose. RESULTS: Bacterial overgrowth was evident in one patient with primary sclerosing cholangitis (4.5%) (Enterobacter) and in none of the controls. Intestinal permeability in patients with primary sclerosing cholangitis (0.034 (0.026-0.041) (median, interquartile range (IQR)) did not differ significantly from that of the controls (0.033 (0.025-0.041). CONCLUSIONS: Small intestinal bacterial overgrowth and increased intestinal permeability does not seem to play an important pathogenic role in patients with primary sclerosing cholangitis.

3-O-Methylglucose↗
PubMed2002

MR characteristics of acute cholangitis.

PURPOSE: To describe the MR appearance of acute cholangitis and discuss the role of MR imaging as a diagnostic method in this disease. MATERIAL AND METHODS: Of 60 patients with clinical acute cholangitis, 12 were examined with MR before endoscopic retrograde pancreatography (ERCP). A retrospective review was performed of MR and ERCP findings. The MR findings registered were presence of biliary duct dilatation, intraluminal filling defects due to stones or sludge, bands of mucosal oedema of the biliary ducts, intra- and retroperitoneal oedema/fluid, and definition of the cause of obstruction, e.g. stones, stenosis or tumour was made. RESULTS: Acute cholangitis was related to obstruction from choledocholithiasis (n=8), pancreatic cancer (n=1), benign biliary duct stricture (n=1), papillary stenosis (n=1) and without evidence of an obstructing cause (n=1). One patient had an acute obstructive suppurative (toxic) cholangitis. CONCLUSION: MR imaging has a role in the non-invasive radiographic arsenal of techniques to confirm or exclude the diagnosis of acute cholangitis, especially in older patients where the clinical symptoms may be vague.

Acute Disease↗
PubMed1994

Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis.

Cholangitis is usually the consequence of a combination of factors: impairment of the flow of bile and bacterial colonization of the biliary tract. Although reestablishing biliary drainage is the mainstay of treatment, antibiotics play an important role in the management of cholangitis. In this review, the use of antibiotics for treatment, prophylaxis, and maintenance therapy is discussed. Antibiotics for the treatment of acute cholangitis should be given for 7-10 days in therapeutic dosages and may allow a more selective timing of further interventions. Antibiotic prophylaxis for cholangitis ought to be given as a single (high) dose shortly before surgical or nonsurgical manipulations of the biliary system. Patients with a compromised biliary system (e.g., on account of an endoprosthesis in situ or hepaticojejunostomy) who are prone to develop recurrent bouts of cholangitis may benefit from antibiotic maintenance therapy, given daily in lower-than-therapeutic dosages.

Acute Disease↗
PubMed1995

Sclerosing cholangitis following human orthotopic liver transplantation.

Sclerosing cholangitis defined by cholangiographic criteria may occur after orthotopic liver transplantation. In this retrospective study, we analyzed failed grafts and antecedent serial biopsies of 24 patients who developed this type of nonanastomotic biliary strictures. Sclerosing cholangitis was histologically diagnosed if there was a combination of periductal fibrosis and features of large bile duct obstruction. The condition was observed in all but one available failed allografts. This later showed ischemic-type lesions without periductal fibrosis. Liver biopsy specimens were nondiagnostic relative to sclerosing cholangitis, although 85% of the patients had evidence of large bile duct obstruction. Numerous associated factors may explain the pathogenesis of secondary sclerosing cholangitis: an immunologically related etiologic factor (10 recipients of ABO-incompatible allografts) and compromised arterial blood flow that likely resulted from hepatic artery thrombosis (12 patients), focal arterial fibrointimal hyperplasia (three patients), chronic ductopenic arteriopathic rejection (three patients) and/or preservation-related ischemia (four patients). Sclerosing cholangitis may be a significant cause of graft failure that often has misleading biopsy manifestations. From a practical standpoint, cholestasis with evidence of large bile duct obstruction warrants cholangiographic assessment of the biliary tree.

Adolescent↗
PubMed1982

The clinical and pathologic correlations in mechanical biliary obstruction and acute cholangitis.

Recently reported series of patients with cholangitis have shown no consistently recognizable differences in clinical presentation between patients with and patients without purulence in the biliary tree, in spite of a clearly higher mortality associated with suppurative cholangitis. To determine whether microscopic changes in the liver ductular system more accurately correspond to clinical status than does the gross finding of suppuration in the common bile duct, a retrospective study was made of 70 patients operated upon for mechanical biliary obstruction and in whom liver biopsy was obtained. Forty patients had benign obstruction, and 30 had malignant disease. The severity of morphologic cholangitis in liver biopsies was graded in a semiquantitative fashion based on inflammatory changes within the portal triads. No significant correlation (chi-square analysis) was found between liver histology and clinical presentation, laboratory data, or mechanism of biliary obstruction. In fact, three patients exhibiting clinical cholangitis had but mild histologic changes; conversely, four patients with minimal symptoms had multiple hepatic microabscesses. The clinical presentations of patients with mechanical biliary obstruction fail to correspond uniformly to either gross or microscopic pathologic findings in the biliary tree. Symptoms and signs of cholangitis may be attributed to some other as yet undefined factors.

Acute Disease↗
PubMed1987

A scientific evaluation of operative choledochoscopy in acute cholangitis.

A prospective study to determine the safety and effectiveness of choledochoscopy in acute cholangitis and acute suppurative cholangitis due to common bile duct stones was conducted on 70 patients. Common bile duct pressures determined on the first 20 patients showed that choledochoscopy was unlikely to cause cholangiovenous reflux. Laboratory and clinical parameters revealed that choledochoscopy did not cause septicemia, worsen cholangitis, or provoke acute pancreatitis. There was no iatrogenic injury during choledochoscopy, and the choledochoscopic views were minimally affected by cholangitis. Choledochoscopy detected overlooked stones after conventional methods of exploration of common bile ducts in 14.3% of patients and it helped to remove impacted stones in 2.9% of patients. As a result, the incidence of retained stones after choledochoscopy was 1.4%. Time spent in choledochoscopy was short, and the total postoperative septic complication rate was only 10%. There was no operative mortality. It is concluded that choledochoscopy is safe and effective in cholangitis.

Acute Disease↗
PubMed1989

Cholescintigraphy in AIDS-related cholangitis: a case report.

Acalculous inflammatory biliary disease has been reported in patients with acquired immune deficiency syndrome (AIDS). AIDS-related cholangitis manifests the intrahepatic and extrahepatic biliary changes seen in sclerosing cholangitis, including strictures, dilatation, and decreased arborization. Biliary scanning was used to evaluate a patient with suspected AIDS-related cholangitis. The hepatobiliary images showed prompt hepatic uptake, with nonvisualization of the gallbladder, common bile duct, and bowel at two hours. Thus, the overall hepatic clearance time approached infinity. There was also a central photopenic region at the porta hepatis. ERCP confirmed the diagnosis of AIDS-related cholangitis. Infection with cytomegalovirus is the proposed etiology. AIDS-related cholangitis should be included in the differential diagnosis of an obstructive cholescintigraphic pattern.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Predictors for emergency biliary decompression in acute cholangitis.

OBJECTIVE: Medical treatment is the first-line management in patients with acute cholangitis but those who fail to respond to antibiotic treatment need urgent biliary decompression. Early prediction of patients with acute cholangitis who require urgent biliary drainage is important because this group of patients has a higher morbidity and mortality from this pathology. This study was undertaken to identify early predictors for emergency biliary decompression in patients with acute cholangitis. METHODS: This is a retrospective analysis of a prospective database of 171 consecutive patients with acute cholangitis managed in a regional hospital in Hong Kong. Emergency biliary drainage was performed when conservative treatment failed. Twenty-four variables that could be assessed upon admission were analyzed for the prediction of the need for emergency biliary decompression. RESULTS: Thirty-one (18.1%) patients needed emergency biliary drainage. Older age (P=0.001), habit of chronic smoking (P=0.04), prolonged prothrombin time (P=0.025), higher blood glucose level (P=0.002), and dilated common bile duct diameter on ultrasonography (P=0.047) predicted the need for urgent biliary drainage. Patients aged older than 75 years had a significantly higher chance of failure of conservative treatment than those aged 75 years or less (26.5% versus 10.2%, P=0.005). CONCLUSIONS: Biliary drainage should be considered early in cholangitic patients aged older than 75 years and/or chronic smoking because they are less likely to respond to conservative treatment. Further studies are required to confirm that the outcome of patients with acute cholangitis can be improved by this selective approach.

Acute Disease↗
PubMed2004

A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis.

BACKGROUND: Ursodeoxycholic acid has been ineffective in the treatment of primary sclerosing cholangitis. Because the pathogenesis of primary sclerosing cholangitis is related to immune destruction of bile duct epithelium, several immune suppressive agents have been evaluated. Mycophenolate mofetil is a potent immunosuppressant that is now widely used in organ transplantation. AIM: In this pilot study to determine if mycophenolate mofetil when combined with ursodeoxycholic acid could prevent evidence of clinical progression and improve the biochemical, histological and/or cholangiographic features of primary sclerosing cholangitis compared with patients treated with ursodeoxycholic acid alone. METHODS: Twenty-five patients with well-defined primary sclerosing cholangitis were randomized to ursodeoxycholic acid (13-15 mg/kg/day) with or without mycophenolate mofetil (1000 mg b.d.). Cholangiography and liver biopsy were performed at study entry and after 2 years of treatment. Symptoms, clinical features of liver disease and biochemical tests were monitored at 3-month intervals. RESULTS: The mean age 44 years, 58% male, 84% Caucasian and 64% had ulcerative colitis. After 2 years, there were no differences in laboratory values, histological stage or cholangiograms between patients treated with ursodeoxycholic acid alone and those treated with mycophenolate mofetil + ursodeoxycholic acid. CONCLUSIONS: Mycophenolate mofetil combined with ursodeoxycholic acid does not appear to provide additional benefit compared with standard doses of ursodeoxycholic acid alone in the treatment of primary sclerosing cholangitis.

Adult↗
PubMed2004

Autoimmune cholangitis in a patient with thymoma.

Autoimmune cholangitis is characterized biochemically by chronic cholestasis and histopathologically by chronic non-suppurative destructive cholangitis. It is associated with positive antinuclear antibody test and negative antimitochondrial antibody test results. Recently, we experienced a case of a 35-year-old woman with autoimmune cholangitis associated with thymoma who presented with pruritus, jaundice, chronic fatigue and anterior chest discomfort. Her laboratory examinations revealed marked increases in levels of serum alkaline phosphatase and gamma-glutamyl transpeptidase. In serological tests, antinuclear antibody was found, but antimitochondrial antibody was not. Liver biopsy findings were compatible with chronic non-suppurative destructive cholangitis. On computed tomography (CT) of the chest, a large anterior mediastinal mass was found. The mass was totally resected and the patient was treated with ursodeoxy cholic acid. Thereafter, her clinical symptoms improved and liver functions completely returned to the normal range. We describe here an uncommon association of autoimmune cholangitis with thymoma, which has not been reported previously in the English-written literature.

Adult↗
PubMed1990

Endoscopic decompression for acute cholangitis due to stones.

The prognosis in patients with acute cholangitis is poor, particularly when the cholangitis is 'severe' as defined by the presence of hypotension and/or confusion. This prospective study evaluates 16 elderly patients with acute cholangitis ('severe' in 11) due to stones in whom endoscopic biliary decompression was attempted. It was technically successful on 13 (81%) of the 16 occasions and the cholangitis rapidly resolved in these patients. In seven of 13, this was the definitive treatment while six underwent subsequent surgery consisting of: cholecystectomy or cholecystostomy (five) and secondary bile duct exploration (one). Two patients died following laparotomy for stones that were not amendable to endoscopic removal. Urgent endoscopic retrograde choledochography is recommended in elderly patients with acute cholangitis, because it confirms the diagnosis and allows decompression of the biliary tract by sphincterotomy. This stabilizes the patient's general condition and facilitates subsequent open surgery when required.

Aged↗
PubMed1998

Gallstone pancreatitis: a prospective study on the incidence of cholangitis and clinical predictors of retained common bile duct stones.

OBJECTIVE: The aim of this study was to define the incidence of cholangitis in gallstone pancreatitis, in the absence of cholangitis, to identify the clinical predictors of persistent common bile duct (CBD) stones at endoscopic retrograde cholangiography (ERCP) or at intraoperative cholangiography (IOC). METHODS: A total of 122 consecutive patients with acute gallstone pancreatitis were prospectively evaluated for the presence of CBD stones as determined by elective ERCP or IOC. Urgent ERCP was restricted to patients with concomitant cholangitis. APACHE II scores and serial laboratory data were obtained. RESULTS: Four (3%) patients had cholangitis and all underwent urgent ERCP successfully. Eighteen (15%) patients without cholangiogram were excluded. The remaining 100 patients underwent elective ERCP or IOC on a mean of hospital day 6.8. Twenty-one (21%) patients had persistent CBD stones. Univariate analysis detected significant differences in serum total bilirubin, ALT, and alkaline phosphatase levels between patients with and without persistent CBD stones. On multivariate analysis, serum total bilirubin on hospital day 2 was the best predictor of CBD stones. A serum total bilirubin level > 1.35 mg/dl had a sensitivity of 90.5% and specificity of 63%. Age, gender, mean APACHE II score, amylase, and presence of CBD dilation on ultrasound were not predictive of CBD stones. CONCLUSION: In patients with gallstone pancreatitis, 1) cholangitis is uncommon, and 2) the best clinical predictor of persistent CBD stones is serum total bilirubin on hospital day 2.

APACHE↗
PubMed1995

Granulomas in primary sclerosing cholangitis.

Granulomas in liver biopsy specimens from adult patients with chronic ductopenic cholestatic liver disease are a characteristic feature of primary biliary cirrhosis. However, we found a similar combination of abnormalities in 7 out of 100 native livers (7%) from patients who had orthotopic liver transplantation for primary sclerosing cholangitis. In a control group of native livers from 100 patients with primary biliary cirrhosis, the prevalence of granulomas was exactly the same, 7%. In the primary sclerosing cholangitis group, 13 addition livers showed a granulomatous epithelioid cell response, with or without foreign body type giant cells, to extravasated bile. All granulomas were noncaseating and non-necrotizing; they consisted of epithelioid cells and often contained giant cells. Perigranulomatous lymphocytic infiltrates were generally mild to moderate. The granulomas involved portal tracts, scars, and hepatic parenchyma. Biopsy experience revealed that granulomas can be found in all stages of the disease. In contradistinction to the granulomas in primary biliary cirrhosis, the granulomas in primary sclerosing cholangitis did not represent granulomatous cholangitis--that is, they were not a feature of the duct destruction. The etiology of these lesions is not clear, but in some cases we found strong morphologic evidence that granulomas may form as a response to the leakage of bile or bile components. No evidence of infection or of sarcoidosis was found. Although adverse drug responses cannot be ruled out with certainty, review of the clinical histories made that mechanism unlikely. Thus, the presence of granulomas in chronic ductopenic cholestatic liver disease is not pathognomonic for primary biliary cirrhosis and, in rare instances (on average, in 3-4% of the biopsy samples), may be a feature of primary sclerosing cholangitis.

Adult↗
PubMedDate not supplied

HLA antigens in ulcerative colitis and primary sclerosing cholangitis.

The aims of this study were to find out whether the alleles of the HLA class I or II region are associated with susceptibility to ulcerative colitis, and to show whether there is a difference or similarity in HLA associations between primary sclerosing cholangitis and ulcerative colitis. HLA-A, B, C and DR antigens were studied using the standard lymphocyte microcytotoxicity test in 24 Finnish patients with primary sclerosing cholangitis, 77 patients with ulcerative colitis, and 106 controls. HLA-B8 (54%) and DR3 (60%) were associated with primary sclerosing cholangitis. HLA-DR1 (46%) and DR6 (20%) seemed more common in ulcerative colitis than in controls. A positive association with Cw7 was common to both ulcerative colitis (25%) and primary sclerosing cholangitis (33%). Our results indicate that ulcerative colitis is more heterogeneous than primary sclerosing cholangitis in its HLA-DR associations.

Adolescent↗
PubMed1983

Association of primary sclerosing cholangitis with HLA-B8.

The frequency of HLA antigens was studied in 25 patients with primary sclerosing cholangitis and compared with a control group of 562 kidney donors. Fourteen patients also had ulcerative colitis. A significant increase in the frequency of HLA-B8 (60%) was found in the primary sclerosing cholangitis patients compared with controls (25%) (p less than 0.001). HLA-B8 was found in eight patients with ulcerative colitis. The frequency of HLA-B12 was significantly decreased (8%) compared with controls (30%) (p less than 0.02). Piecemeal necrosis was observed on liver histology in 66% of HLA-B8 positive and 50% of HLA-B8 negative patients. Low titres of serum autoantibodies were frequently found in the primary sclerosing cholangitis group but did not correspond to the presence of HLA-B8. Raised serum concentrations of IgM and IgG were not related to HLA-B8. This study has shown that in patients with primary sclerosing cholangitis there exists a disease susceptibility gene closely associated with the B locus of the major histocompatibility complex which may be modified by other factors such as ulcerative colitis. Patients with ulcerative colitis and HLA-B8 may be particularly liable to develop primary sclerosing cholangitis.

Autoantibodies↗
PubMed2002

A randomised controlled trial of endoscopic sphincterotomy in acute cholangitis without common bile duct stones.

BACKGROUND: Biliary decompression with endoscopic sphincterotomy (EPT) is beneficial in patients with biliary obstruction due to common bile duct (CBD) stones. However, it is not known whether EPT with decompression of the bile duct is beneficial in patients with acute cholangitis and gall bladder stones but without evidence of CBD stones. AIM: A randomised controlled study to assess the effect of EPT on the outcome of patients suffering from acute cholangitis with gall bladder stones but with no CBD stones on initial endoscopic retrograde cholangiopancreatography. PATIENTS: A total of 111 patients were recruited into the study. METHODS AND RESULTS: Fifty patients were randomised to receive EPT while 61 patients received no endoscopic intervention. There was a significant difference in the duration of fever in the EPT and non-EPT groups (mean (SD): 3.2 (2.2) days v 4.3 (2.1) days; p<0.001). Duration of hospital stay was also shorter in the EPT group than in the non-EPT group (mean (SD): 8.1 (3.0) v 9.1 (3.2) days; p=0.04). Patients were followed up for a mean (SD) of 42.4 (11.1) months. Twenty three patients (20.3%) developed recurrent acute cholangitis (RAC): 14 patients (12.6%) in the EPT group and nine patients (8.1%) in the non-EPT group (p=0.09). CONCLUSION: EPT in patients with acute cholangitis without CBD stones decreased the duration of acute cholangitis and reduced hospital stay but it did not decrease the incidence of RAC.

Acute Disease↗
PubMed2003

Progressive sclerosing cholangitis after septic shock: a new variant of vanishing bile duct disorders.

BACKGROUND: We present nine patients with progressive sclerosing cholangitis after septic shock. PATIENTS: All nine patients had previously required long term treatment in an intensive care unit for septic shock: two patients with polytrauma, five with burn injury, and two with extensive surgery. They were admitted to our hospital because of cholangitis. Endoscopic retrograde cholangiography revealed severe intrahepatic stenoses in all patients and liver biopsies showed typical signs of sclerosing cholangitis. No patient had pre-existing liver disease. RESULTS: Mean follow up time was 35 months. In patients with major bile duct stenoses (3/9), 12 endoscopic dilations were performed in total. In one patient, concrements were extracted and intermittent stenting was necessary. To date, 4/9 patients have rapidly developed liver cirrhosis. During follow up, 5/9 patients died: two after fulminant cholangitis, one after liver failure, one due to liver transplantation associated problems, and one after cerebral ischaemia. One patient has been registered for transplantation and the remaining three patients show no acute signs of liver failure. CONCLUSIONS: Patients with sclerosing cholangitis, following septic shock, represent a new variant of vanishing bile duct disorders. In such patients liver disease rapidly progresses to cirrhosis. Endoscopic treatment may only transiently improve the course of the disease. Orthotopic liver transplantation is indicated in end stage disease.

Adolescent↗
PubMed2003

Glucocorticoid receptors are downregulated in hepatic T lymphocytes in rats with experimental cholangitis.

BACKGROUND: and aims: Primary sclerosing cholangitis is a Th1 cytokine driven disease with a poor clinical responsiveness to glucocorticoid therapy. We have previously documented elevated circulating glucocorticoid levels in cholestatic rats and in addition have noted increased hepatic expression of the Th1 cytokine interferon gamma (IFN-gamma) in a rat model of cholangitis. Therefore, we examined the relationship between circulating glucocorticoid levels, hepatic IFN-gamma expression, and hepatic T cell glucocorticoid receptor (GR) expression in a rat model of cholangitis to provide insight into the possible mechanism underlying hepatic T cell glucocorticoid resistance in cholangitic diseases. METHODS: Cholangitis was induced in male Sprague-Dawley rats by oral administration of low dose alpha-naphthylisothiocyanate (ANIT). On day 14, ANIT fed and control rats were sacrificed, serum collected, and hepatic, splenic, and peripheral blood T lymphocytes isolated for GR expression, as determined by reverse transcription-polymerase chain reaction and western blotting. RESULTS: Circulating glucocorticoid levels were markedly elevated in ANIT fed rats. Hepatic T lymphocyte GR mRNA and protein levels were significantly reduced in ANIT treated rats compared with controls. In contrast, GR mRNA and protein expression in splenic and circulating T lymphocytes was similar in both groups. Furthermore, reduced hepatic T cell GR expression in ANIT fed rats was associated with reduced hepatic CD4(+) T cell sensitivity to dexamethasone inhibitory effects (that is, inhibition of interleukin 2 receptor expression). CONCLUSION: We conclude that hepatic T lymphocyte resistance to elevated endogenous glucocorticoid levels in rats with experimental cholangitis appears, in part, to be mediated by decreased GR expression.

1-Naphthylisothiocyanate↗