Management of biliary tract complications following liver transplantation.

BACKGROUND: A review of biliary tract complications was performed in 32 patients who underwent liver transplantation by the Western Australian Liver Transplantation Service during a 2-year period. METHODS: A review was made of patient data collected prospectively, and confirmed by retrospective casenote review. RESULTS: A total of 30 patients (31 grafts) survived more than 2 days after transplantation, and of these 28 had an end-to-end biliary anastomosis. Analysis of these 28 patients found that eight of 17 patients with T-tubes had complications: three leaks at T-tube removal; two strictures and leaks; and three strictures. Six of 11 patients without a T-tube had complications: one leak; three strictures and leaks; and two strictures. Predisposing factors were present in eight of the 14 patients with biliary tract complications: hepatic artery stenosis in three; and one each with hepatic artery thrombosis; biliary calculi; donor-recipient bile duct mismatch; severe cellular rejection: and prolonged postoperative hypotension. Acute rejection, steroid-resistant rejection and cytomegalovirus infection were all significantly more common in those patients with biliary tract complications compared with those without. There was no difference in cold ischaemic time or donor age. Twelve of the 14 patients with biliary complications required endoscopic stenting with or without balloon dilation, and eight patients required radiological percutaneous drainage of bile collections. Only one patient required biliary reconstruction and two patients required re-transplantation. One patient died of uncontrolled infection. Of three patients who underwent choledochojejunostomy, biliary leak developed in two patients, both of whom required operative biliary and hepatic repair. One of the three patients died from disseminated Aspergillus infection. The median total hospital stay of patients with biliary complications was 61 days (range: 30-180 days) compared with 33.5 days (range: 22-70 days) for patients without. Of patients with end-to-end biliary anastomosis, 50% had biliary tract complications and more than half of these had predisposing factors. The majority of biliary complications were managed without the need for surgery. CONCLUSION: A total of 50% of patients with end-to-end biliary anastomosis had biliary tract complications. Biliary strictures presented later than leaks, and the majority of these complications were managed without the need for surgery.

Banff schema for grading liver allograft rejection: utility in clinical practice.

An accurate and functional system for grading acute liver allograft rejection is important for patient management, research, and communication. The Banff schema is a consensus document designed to provide an internationally accepted standard for this purpose. The aim of this study is to determine if application of the Banff schema would significantly alter the grading of acute liver allograft rejection compared with the Birmingham system. One hundred twenty-four post-liver transplantation biopsies performed by the Western Australian Liver Transplantation Service between 1992 and 1997 were retrospectively analyzed by a pathologist and a hepatologist. Each was supplied with a brief clinical history before applying the Banff and Birmingham criteria. Results were compared with each other and to the diagnosis made at the time of the biopsy, which was based on the European grading system. Rejection was diagnosed by the reviewers in 61 of 124 biopsy specimens according to the criteria of Snover. The Banff schema and Birmingham system agreed on the grade of rejection in 22 of the 61 biopsy specimens. The Banff schema elevated the grade of rejection in 39 specimens by an increment of one. In no instance did the Banff schema reduce the grade. Comparison between the Banff schema and diagnosis made at the time of biopsy showed agreement in 39 specimens, whereas the Banff schema elevated the grade in 15 specimens and reduced the grade in 23 specimens. In comparison to the Birmingham system, the Banff schema elevated the grade of liver allograft rejection in the majority of biopsy specimens, and this has the potential to alter clinical management with the adoption of the Banff schema or if the systems are used interchangeably.

Genotyping as a diagnostic aid in genetic haemochromatosis.

BACKGROUND: Two mutations in a newly described gene, HFE, have been proposed as genetic markers for the inherited iron overload disease, genetic haemochromatosis. METHODS: We assessed the frequency of both mutations in a cohort of genetic haemochromatosis patients and compared these with a control population. The patients were genetic haemochromatosis patients from Western Australia whose diagnosis met strict criteria for phenotypic expression. Control patients had other liver disease where iron overload was excluded. RESULTS: Genomic DNA of 72 genetic haemochromatosis patients and 69 controls was examined for the C282Y and H63D mutations of the HFE gene using polymerase chain reaction amplification and restriction enzyme digestion. In genetic haemochromatosis patients, the C282Y mutation was homozygous in 64 of 72, giving a sensitivity of 89% (95% confidence interval 82-96%), heterozygous in five (7%) and absent in another three (4%), whereas none of the control subjects were homozygous. The H63D mutation was present in one genetic haemochromatosis patient and was not useful as a diagnostic marker. In this cohort of Western Australian patients with phenotypic expression of genetic haemochromatosis, the specificity of a homozygous C282Y mutation for genetic haemochromatosis was 100%. CONCLUSIONS: The results indicate that genotyping for the C282Y mutation is a useful test for the diagnosis of genetic haemochromatosis in clinical practice.

Cellular expression and regulation of iron transport and storage proteins in genetic haemochromatosis.

Genetic haemochromatosis is a common iron overload disorder of unknown aetiology. To characterize the defect of iron metabolism responsible for this disease, this study localized and semi-quantified the mRNA and protein expression of transferrin, transferrin receptor and ferritin in the liver and duodenum of patients with genetic haemochromatosis. Biopsies were obtained from iron-loaded non-cirrhotic patients with genetic haemochromatotic and control patients with normal iron stores. Additional duodenal biopsies were obtained from patients with iron deficiency. Immunohistochemical and in situ hybridization analysis for transferrin, transferrin receptor and ferritin was performed. Hepatic transferrin, transferrin receptor and ferritin protein expression was localized predominantly to hepatocytes and was increased in patients with genetic haemochromatosis when compared with normal controls. Interestingly, hepatic ferritin mRNA expression was not increased in these same patients. In the genetic haemochromatotic duodenum, ferritin mRNA and protein was localized mainly to crypt and villus epithelial cells and the level of expression was decreased compared with normal controls, but similar to iron deficiency. Duodenal transferrin receptor mRNA and protein levels colocalized to epithelial cells of the crypt and villus were similar to normal controls. Early in the course of genetic haemochromatosis and before the onset of hepatic fibrosis, transferrin receptor-mediated iron uptake by hepatocytes contributes to hepatic iron overload. Increased hepatic ferritin expression suggests this is the major iron storage protein. While persisting duodenal transferrin receptor expression may be a normal response to increased body iron stores in patients with genetic haemochromatosis, decreased duodenal ferritin levels suggest that duodenal mucosa is regulated as if the patient were iron deficient.

Liver transplantation in Western Australia: improved services to an isolated population.

OBJECTIVE: To assess performance of the Western Australian Liver Transplantation Service in the light of debate about whether small transplant centres can produce optimal outcomes. DESIGN: Review of patient data collected prospectively and confirmed by retrospective casenote review. SUBJECTS: All patients referred to the Western Australian Liver Transplantation Assessment Panel. Those who underwent transplantation at the Western Australian Liver Transplantation Service (to June 1996) were compared with those referred to other transplant centres before the elective service was established in July 1994. OUTCOME MEASURES: Numbers of referrals and transplants; characteristics of the transplantation procedure; and patient outcomes. RESULTS: Annual referrals for liver transplant in Western Australia (WA) increased from 12 (1985-1993) to 41 (July 1994-June 1996), with five deaths on the "activated" list before July 1994, but none after. To June 1996, 30 patients had received 31 transplants by the Western Australian Liver Transplantation Service (two emergency transplants in 1992 and 1993, respectively, and 28 elective transplants and one retransplant after June 1994), with median operation time of 5.5 hours (range, 3-10.5), median red cell transfusion of 4 units (range, 0-55) and median hospital stay of 24 days (range, 12-128). There was no severe primary graft dysfunction. Major complications included hepatic artery thrombosis or stenosis (5 patients, one requiring retransplant), biliary stricture not associated with hepatic artery pathology, bile leak and perihepatic abscess (4 each), and cytomegalovirus infection (3). Patient survival was 83% and graft survival 81% at a mean follow-up of 13 months, compared with 86% and 83%, respectively, at one year for WA patients who received transplants elsewhere before July 1994. CONCLUSIONS: Performance of the Western Australian Liver Transplantation Service compares favourably with national and international standards, and WA patients receiving liver transplants have increased dramatically since the service was established. This supports the viability of committed liver transplantation centres with only 10-15 patients a year and argues the need for nationally decentralised services.

Intra-abdominal fluid collections after liver transplantation.

Fluid collections are commonly seen following orthotopic liver transplantation. The majority of these collections are not infected and resolve spontaneously. However, infected collections are associated with significant morbidity and mortality and usually require drainage. Clinical signs of infection are frequently masked following transplantation due to immunosuppression. Intrahepatic collections usually represent abscesses or bilomas and invariably require intervention. Altered anatomical relationships result in signs that frequently help to differentiate these from loculated fluid within hepatic fissures. Other imaging features indicating infection include the presence of gas where none was seen previously, the development of a discrete wall and changes in the surrounding liver.

[Placement of stent for bile drainage by using combined percutaneous and endoscopic technique].

44 patients with malignant biliary obstruction underwent attempted placement of stent for bile drainage by using a combined percutaneous transhepatic and endoscopic transpapillary approach (combined procedure). In all the patients endoscopic procedures had failed and there were contraindications for surgery. The initial procedure was percutaneous transhepatic access to the biliary tree. The bile duct was drained externally for three days before the combined procedure. Combined procedure was performed in these 44 cases and successful in 37 (84.1%). The procedure-related morbidity and 30-day mortality were 46.7% and 16.7% respectively for lower common bile duct obstruction and 50.0% and 21.4% for hepatic hilus obstruction. The total morbidity and 30-day mortality were 47.7% and 18.2% respectively. The combined procedure extends the use of endoscopy and offers nonsurgical therapy for patients with malignant biliary obstruction.

Carbamazepine hepatotoxicity: another cause of the vanishing bile duct syndrome.

Serious carbamazepine hepatotoxicity is being recognized more frequently and is usually manifest as an acute granulomatous hepatitis that is self-limiting if the drug is withdrawn. The case of a 59-year-old man who developed the vanishing bile duct syndrome after 2 months of treatment with carbamazepine for glossopharyngeal neuralgia is reported. The characteristic histological features of this syndrome may also be seen in primary biliary cirrhosis, primary sclerosing cholangitis, graft-vs.-host disease after allogeneic bone marrow transplantation, chronic liver allograft rejection, and other drug reactions. The progress of this patient to date suggests that irreversible liver injury resulting in chronic liver disease is likely, in keeping with the clinical course of the vanishing bile duct syndrome in most cases.

Mouse cytomegalovirus infection induces antibodies which cross-react with virus and cardiac myosin: a model for the study of molecular mimicry in the pathogenesis of viral myocarditis.

Mouse cytomegalovirus (MCMV) infection induces persisting myocarditis in the susceptible BALB/c strain. Autoantibodies to cardiac myosin are produced in both susceptible BALB/c and resistant C57BL/6 mice following MCMV infection. These affinity-purified anti-cardiac myosin antibodies cross-react with MCMV protein(s). The polypeptides of CMV which share immunological cross-reactivity with the 200,000 MW polypeptide, the heavy chain of myosin, were viral polypeptides of 83,000, 94,000 and 116,000 MW recognized by BALB/c post-infection sera and polypeptides of 66,000 and 94,000 MW recognized by C57BL/6 post-infection sera. Passive transfer of anti-cardiac myosin antibodies from Day 56 post-infection sera of the BALB/c strain induced inflammation and necrosis of the myocardium of uninfected BALB/c recipients. This late immune sera contains autoantibodies specific for the cardiac isoform of myosin. Furthermore, immunization with cardiac myosin induced myocarditis and high titres of cardiac myosin antibodies in uninfected mice of the susceptible BALB/c strain only. However, antibodies to myosin elicited in cardiac myosin-immunized BALB/c mice did not cross-react with MCMV by ELISA. We suggest that virus infection may modulate the immune recognition of the common-epitope(s) shared between MCMV protein(s) and the heavy chain of myosin. Of particular interest is the possibility that molecular mimicry of CMV with cardiac myosin may contribute to the pathogenesis of autoimmune myocarditis following virus infection.

Histological and immunohistochemical study of the gall bladder lesion in primary sclerosing cholangitis.

The histological features and type of mononuclear cell infiltrate in gall bladders from six patients with primary sclerosing cholangitis were studied using routine staining techniques and immunohistochemistry. Control studies were performed using the gall bladders from six patients (age and sex matched) with chronic cholecystitis and four with primary biliary cirrhosis. A range of histological abnormalities was present in gall bladders from patients with primary sclerosing cholangitis including a mild to moderate degree of epithelial hyperplasia, pseudogland formation, and mononuclear cell infiltrate of the epithelium; moderate to severe chronic inflammatory cell infiltrate and fibrosis affecting the superficial and deep layers of the gall bladder wall; and minimal smooth muscle hypertrophy. These abnormalities were non-specific and were also present in gall bladders from patients with chronic cholecystitis and primary biliary cirrhosis. Vasculitis and granulomas were not present in the patients with primary sclerosing cholangitis. Immunohistochemistry showed that the superficial and deep mononuclear cell infiltrate in primary sclerosing cholangitis gall bladders was composed predominantly of lymphocytes, in contrast to chronic cholecystitis where macrophages were found in similar or greater numbers. Moreover, T lymphocytes (activated and resting) were present throughout the lymphocytic infiltrate and were apposed to the base and interdigitated between the biliary epithelial cells in significantly greater numbers than in chronic cholecystitis gall bladders. B lymphocytes were present only in lymphoid follicles. Comparative studies using liver biopsy specimens from three of the primary sclerosing cholangitis patients showed a similar T lymphocyte portal tract infiltrate. We conclude that a number of non-specific chronic inflammatory histological abnormalities were present in primary sclerosing cholangitis gall bladders. Immunohistochemistry found other features that were present in this disease - a predominantly lymphocytic mononuclear cell infiltrate of the superficial and deep layers of the gall bladder wall and the presence of T lymphocytes that infiltrated the biliary epithelial cells. These findings support the hypothesis that aberrant cell mediated immune mechanisms may play a role in the pathogenesis of both the intrahepatic and extrahepatic lesions in primary sclerosing cholangitis.

Diclofenac hepatitis.

We report five cases of biopsy-proven hepatitis developing between six and 20 weeks after administration of diclofenac. In one patient jaundice had previously developed following use of ibuprofen. In another the clinical, biochemical and histopathological features were those of chronic active hepatitis and treatment with corticosteroids was required. All patients recovered from their liver injury without sequelae. Resolution of symptoms occurred between three and 12 weeks following cessation of the drug, while liver function tests returned to normal between seven and 16 weeks after drug withdrawal, except in the patient with chronic active hepatitis who remained biochemically abnormal for eight months. Three of the five patients developed transient circulating autoantibodies, suggesting immune mechanisms may be important in the pathogenesis of this injury. The incidence of severe hepatic dysfunction related to the use of diclofenac appears low and is probably in the order of one case per 50-100,000 prescriptions.

Nodular regenerative hyperplasia of the liver: the importance of combined macroscopic and microscopic findings.

A 40-year-old man with rheumatoid arthritis, splenomegaly and mild thrombocytopenia presented with gross ascites and a history of excess alcohol consumption. Oesophageal varices were documented endoscopically. Alcoholic cirrhosis was suspected and laparoscopy revealed a macronodular liver surface. Liver biopsy disclosed subtle microscopic structural variations which together with the laparoscopic findings were consistent with the diagnosis of nodular regenerative hyperplasia. The importance in diagnosis of macroscopic appearance combined with histological findings is emphasised. Clinically significant portal hypertension may be present at a histologically early stage of this condition.

Murine anti-cytomegalovirus monoclonal antibodies with autoreactivity.

Certain murine monoclonal antibodies (mAb) raised against structural proteins of mouse cytomegalovirus (MCMV) display distinct patterns of multiple organ-autoreactivity in addition to their viral specificities. We analysed the autoreactivity of five such mAb by immunoperoxidase histochemistry, western immunoblot and enzyme-linked immunosorbent assay (ELISA). Four mAb recognized cellular autoantigens in the salivary gland, lung, heart, liver, kidney, ileum, striated muscle and brain, as detected by immunoperoxidase histochemistry. However, the mAb showed different specificities for nuclear, cytoplasmic and surface membrane antigens on various cell types in addition to common autoreactivities. Immunoblot analyses showed that some of the mAb recognized polypeptides of various molecular weights obtained from 100,000 g supernatants of normal BALB/c liver, brain, striated and cardiac muscle homogenates. Reactivity of the mAb with a 200,000 molecular weight (MW) polypeptide was similar to our previous finding of the reaction of late immune polyclonal sera with a 200,000 MW polypeptide, the heavy chain of myosin. The mAb reacted to the cardiac isoform of myosin as determined by ELISA and immunoblot. Reactivity of mAb with cardiac myosin, as detected by immunoblot, was removed by absorption with cardiac myosin and recovered in the eluate. However, cardiac myosin used in a competitive inhibition ELISA did not abrogate the reactivity of the mAb with MCMV antigens. These anti-MCMV mAb appear to be multispecific for both virus and self-antigens, including cardiac myosin, and possibly recognize these different antigens through partly similar or distinct antigen-binding sites.

Diarrhoea--an unrecognised hazard of coeliac plexus block.

Coeliac plexus block is a safe procedure with relatively few side-effects. We report two cases of persistent severe diarrhoea following coeliac plexus block and explore the possible reasons for this previously unrecognised side-effect. We postulate that somatostatin analogue may be useful as treatment for diarrhoea following neurolytic coeliac plexus block that is unresponsive to conventional anti-diarrhoeal agents.

Confirmation of the efficacy of hepatic tissue iron index in differentiating genetic haemochromatosis from alcoholic liver disease complicated by alcoholic haemosiderosis.

The hepatic tissue iron index proposed by Bassett et al was evaluated in 35 patients with homozygous genetic haemochromatosis, 67 patients with alcoholic liver disease, and 18 patients with other forms of chronic liver disease with and without cirrhosis. In patients with cirrhosis hepatic tissue iron concentration reliably differentiated alcoholic liver disease from genetic haemochromatosis. Although mean iron concentration was greater in patients with prefibrotic haemochromatosis than in those with prefibrotic alcoholic liver disease, some overlap occurred and complete differentiation of the two conditions was not possible. This overlap was particularly evident in some young patients with haemochromatosis in whom the tissue iron concentration grade fell in the range commonly seen in alcoholic haemosiderosis. Inability to differentiate early genetic haemochromatosis from alcoholic liver disease complicated by haemosiderosis was also a problem with standard Perls's staining. When the hepatic tissue iron index was calculated (hepatic tissue iron concentration/patient's age in years), clear differentiation of genetic haemochromatosis from both alcoholic liver disease and other forms of chronic liver disease was obtained in both cirrhotic and precirrhotic patients. This study confirms that the hepatic tissue iron index is a useful means of differentiating patients with genetic haemochromatosis from those with alcoholic liver disease. We suggest that biochemical estimation of tissue iron concentration and calculation of the tissue iron index in all patients in whom genetic haemochromatosis is a possible diagnosis will reduce the likelihood of misdiagnosing this as alcoholic liver disease.

Primary biliary cirrhosis: clinicopathological characteristics and outcome.

Thirty-five patients with primary biliary cirrhosis were seen between 1974 and 1989. The median mean age at presentation was 53 years (range: 30-77) and the female to male ratio was 7.8:1. Thirteen (37%) were asymptomatic and nine (26%) had associated auto-immune disorders. Pruritus and hepatomegaly were present in half of the patients. Advanced histological stages of disease (Stages 3 and 4) were present in 57% of patients. The median period of follow-up was 5 years (range: 0.1-20). Twelve patients died, nine from hepatic causes and three from non-hepatic causes. One has undergone liver transplantation. A Kaplan-Meier curve estimated the median survival to be 11 years. Asymptomatic patients developed progressive disease and survival was similar to that of symptomatic patients. Using Cox's proportional hazards model, age, serum bilirubin and serum albumin were found to be independent prognostic variables correlating with reduced survival.

Familial hypocalciuric hypercalcaemia and pancreatitis: no causal link proven.

A case of a patient with pancreatitis and familial hypocalciuric hypercalcaemia is presented and the literature linking FHH and pancreatitis is reviewed. The case for a causal link between the two conditions is not proven and seems unlikely. In view of this we strongly challenge the recommendation of total parathyroidectomy in such cases.

Autoantibodies to cardiac myosin in mouse cytomegalovirus myocarditis.

Myocarditis accompanies sublethal mouse cytomegalovirus (MCMV) infection in susceptible BALB/c mice and persists beyond the acute phase of infection, in the absence of demonstrable virus antigen but in the continuing presence of autoantibodies to cardiac muscle. Heart tissue autoantibodies of the IgG class were first detected by ELISA in sera at Days 3-5 post-infection (PI) and persisted to Day 100, in two strains of MCMV-infected mice which are susceptible (BALB/c) and resistant (C57BL/10) to MCMV-induced myocarditis. Analysis by immunoblot showed that autoantibodies in early immune sera (Day 10) from both mouse strains reacted with the contractile proteins troponin, tropomyosin and myosin, as well as with other unidentified polypeptides within normal mouse organ homogenates. However, the dominant reactivity of late immune sera (Day 100) was to a 200,000 molecular weight (MW) polypeptide in muscle homogenates identified as the heavy chain of myosin. Autoantibodies reacting with the cardiac or striated muscle isoforms of myosin were assessed by ELISA in BALB/c and C57BL/10 mice. At Days 28, 56 and 100 PI only the susceptible BALB/c strain had high titres of autoantibodies reacting with the cardiac isoform of myosin. Increasing the virus dose given to C57BL/10 mice resulted in slight increases in titres of anti-myosin antibody; however, the peak antibody titres did not approach those of BALB/c mice and persisting myocarditis did not develop. Absorption experiments showed that cardiac myosin-specific antibodies were present in immune sera from susceptible BALB/c mice at Day 100 but not in resistant C57BL/10 mice by ELISA and immunoblot. These results demonstrate that autoimmunity to myosin is a prominent feature of the humoral autoimmune response following MCMV infection, and that there are differences both in fine isoform specificity and titre of anti-myosin antibodies between strains of mice that develop persisting myocarditis and strains that do not. Cardiac myosin-specific autoantibodies may play an immunopathogenic role in CMV-induced myocarditis.

Does hepatitis C virus play a role in "non-viral" chronic liver disease?

It has recently been suggested that the hepatitis C virus may play a significant role in chronic liver diseases, such as autoimmune chronic active hepatitis, which are usually attributed to non-viral causes. We tested for antibodies to hepatitis C virus (anti-HCV) in sera from 140 patients with well characterised "non-viral" chronic liver diseases as well as sera from 51 patients thought to have chronic non-A, non-B (NANB) hepatitis (acting as positive controls) and 25 patients with non-hepatic autoimmune disorders. As expected, 45 of 51 patients (88%) diagnosed as having chronic NANB hepatitis were anti-HCV seropositive. Among 26 patients with cryptogenic cirrhosis, 8 were anti-HCV seropositive; in 5 patients (22%) there was no apparent risk factor for parenteral transmission. In the remaining 114 patients with chronic liver disease, 10 patients (9%) were seropositive for anti-HCV. However, 5 of these patients had a significant risk factor for parenteral transmission of hepatitis C virus, leaving only 5 of 106 (4.7%) with unexplained positive anti-HCV test results. Among patients with high titres of circulating autoantibodies but no liver disease, no positive results occurred. It is concluded that hepatitis C virus infection may account for some cases of cryptogenic cirrhosis. Although anti-HCV occurs more commonly in patients with other "non-viral" chronic liver diseases than has been reported in the community (0.5%-1.2%), the low prevalence of the antibodies indicates that hepatitis C virus infection is unlikely to be important in the aetiology or pathogenesis of autoimmune chronic active hepatitis and other poorly understood chronic liver diseases.

Bile duct antibodies crossreacting with blood group antigens in primary sclerosing cholangitis.

Indirect immunoperoxidase histochemistry was used to localise and determine the disease, species, and tissue specificity of bile duct antibodies in primary sclerosing cholangitis. Serum was collected from: 29 patients with primary sclerosing cholangitis, 18 patients with ulcerative colitis alone, 19 patients with extrahepatic biliary obstruction of other causes, and 42 healthy control subjects. Bile duct antibodies reacted with an antigen localised to the small and large intrahepatic bile ducts. When blood group A human liver was used they were detected in 34% of patients with primary sclerosing cholangitis. They were not detected when blood group O human liver was used. Bile duct antibodies that reacted with obstructed and normal rabbit liver were detected in 34% and 17% respectively of patients with primary sclerosing cholangitis but were also present in similar proportions of control subjects. Colon antibodies that reacted with human and rabbit colon were found in 52% and 24% respectively of patients with primary sclerosing cholangitis. Absorption studies using blood group substances A and B abolished the reactivity of bile duct antibodies with human and rabbit liver and that of colon antibodies' with rabbit colon. Colon antibodies that reacted with human colon were not absorbed. Absorption studies using isolated peripheral white blood cells did not affect reactivity of bile duct or colon antibodies. We conclude that bile duct antibodies are disease, species, and tissue non-specific and react with blood group A/B antigens present in human and rabbit bile ducts and rabbit colon. This suggests that they do not play a role in the pathogenesis of primary sclerosing cholangitis.