Primär sklerosierende Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic progressive cholestatic disease leading to multiple strictures of the extra- and intrahepatic bile ducts and to biliary cirrhosis. The majority of patients are young men who also suffer from inflammatory bowel disease. The risk of cholangiocarcinoma and of colorectal cancer is significantly increased. PSC is diagnosed based on characteristic cholangiographic patterns with multifocal strictures and intervening segments of normal or dilated ducts, when secondary causes of sclerosing cholangitis have been excluded. The pathogenesis of PSC is elusive, and there is currently no causal therapeutic strategy. Ursodeoxycholic acid may be beneficial for a subgroup of PSC patients, and new innovative therapeutics are currently under evaluation in clinical trials. Endoscopic interventions are used and effective to dilate dominant bile duct strictures and useful to diagnose biliary malignancy. The only definitive therapy is liver transplantation. It offers excellent long-term outcome, when timing is right. However, in a subset of patients biliary strictures and also recurrent PSC can limit the posttransplant prognosis.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic bile duct disease leading to fibrotic biliary strictures and liver cirrhosis. The patient population is heterogeneous with regard to disease progression and the presence of co-morbidities, complicating the practical handling of patients as well as studies of pathogenetic mechanisms. The aetiology of PSC is unknown, but the recent findings of several robust susceptibility genes emphasise the importance of genetic risk factors. There is no effective medical treatment available to delay the disease progression, but endoscopic therapy of biliary stenoses may be indicated. Follow-up of patients includes management of the inflammatory bowel disease that is found in the majority of cases along with investigations aimed at the early detection of cholangiocarcinoma and colorectal cancer, which also occur at increased frequencies. In the present review, we aim to summarise the present knowledge of PSC with a particular emphasis on the possible basis of disease variability.     

Immunogenetic Aspects of Primary Sclerosing Cholangitis: Implications for Therapeutic Strategies

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by fibro-obliterative inflammation of the intra- and extrahepatic bile ducts; in 70% of cases, it is associated with inflammatory bowel disease. The disease usually runs a progressive course, ultimately leading to biliary cirrhosis, hepatic failure, and sometimes cholangiocarcinoma, with a median survival of 12 yr after diagnosis. As yet, the etiology of primary sclerosing cholangitis remains unknown, although several recent studies have implicated immunogenetic factors as important pathogenic mechanisms.
Besides liver transplantation for patients with end-stage cirrhotic liver disease and endoscopic therapy for patients with dominant extrahepatic bile duct strictures, recent studies have also shown promising results of drug therapy with ursodeoxycholic acid in the treatment of PSC. The purpose of this article is to summarize our current knowledge of the immunogenetic factors in the pathogenesis of PSC and to present support for drug therapy with ursodeoxycbolic acid in the treatment of PSC. The genetic and immunological factors in the pathogenesis of PSC are outlined first, followed by a rationale of drug therapy with ursodeoxycholic acid in the treatment of PSC.     

Diagnosis and management of primary sclerosing cholangitis-perspectives from a therapeutic endoscopist

Primary sclerosing cholangitis(PSC) is a chronic,cholestatic liver condition characterized by inflammation,fibrosis,and destruction of the intra-and extrahepatic bile ducts.The therapeutic endoscopist plays a key role in the diagnosis and management of PSC.In patients presenting with a cholestatic profile,endoscopic retrograde cholangiopancreatography(ERCP) is warranted for a definite diagnosis of PSC.Dominant strictures of the bile duct occur in 36%-57% of PSC patients.Endoscopic balloon dilatation with or without stenting have been employed in the management of dominant strictures.In addition,PSC patients are at increased risk of developing cholangiocarcinoma with a 20% lifetime risk.Brush cytology obtained during ERCP and use of fluorescence in situ hybridization forms the initial diagnostic step in the investigation of patients with dominant biliary strictures.Our review aims to summarize the current evidence supporting the role of a therapeutic endoscopist in the management of PSC patients.     

Biliary guidewire facilitates bile duct biopsy and endoscopic drainage

BACKGROUND: The introduction of a guidewire through bile duct strictures may facilitate transpapillary bile duct biopsy and subsequent biliary drainage. METHODS: Endoscopic bile duct biopsy was attempted in 61 patients with bile duct strictures. After the introduction of a guidewire into the bile duct, biopsy forceps were inserted via the papilla. Both devices were inserted through the working channel (3.2 mm in diameter) of a conventional duodenoscope. After the procedure, an endoscopic naso-biliary drainage catheter was advanced along the guidewire. The success rate of inserting the biopsy forceps, the sensitivity of the biopsy, and the success rate of endoscopic biliary drainage after the biopsy were analyzed prospectively. RESULTS: The final diagnosis was malignant strictures in 50 patients and benign strictures in 11. The success rate of inserting biopsy forceps without performing endoscopic papillary balloon dilation was 85%. The sensitivity of the biopsy for primary bile duct cancer (83%) was significantly higher (P < 0.05) than that of pancreatic cancer (47%). All patients had successful endoscopic biliary drainage after the procedure. CONCLUSION: A previously placed guidewire facilitates insertion of biopsy forceps and endoscopic biliary drainage. The histological diagnosis of cancer is more likely with bile duct cancer than with pancreatic cancer.     

Hepatobiliary Complications of Inflammatory Bowel Disease

Several hepatobiliary abnormalities have been described in association with inflammatory bowel disease (IBD), including primary sclerosing cholangitis (PSC), small duct PSC, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma, and cholelithiasis. PSC is the most common biliary condition in patients with IBD, with an incidence ranging from 2.5% to 7.5%. PSC usually progresses insidiously and eventually leads to cirrhosis independent of inflammatory bowel disease activity. There is a very high incidence of cholangiocarcinoma and an elevated risk for developing colon cancer in patients with PSC. Medical therapy has not proven successful in slowing disease progression or prolonging survival. Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins, such as cholestyramine or colestipol. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been conclusively demonstrated to improve survival or decrease the need for liver transplantation. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.     

Primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disease of uncertain etiopathogenesis commonly associated with inflammatory bowel disease (IBD) and is characterized by patchy inflammation of the biliary tree progressing to fibrosis and strictures. The natural history of PSC is highly variable but characteristically follows a progressive clinical course leading to biliary tree strictures, cholestasis, and choledocholithiasis. The course of the disease may be complicated by cholangitis, secondary biliary cirrhosis, liver failure, and cholangiocarcinoma. The diagnosis of PSC is based on typical cholangiographic findings, supported by nonspecific clinical signs and symptoms, cholestatic liver biochemical tests, and liver biopsy. Uncommon and usually clinically obvious secondary causes of sclerosing cholangitis are excluded before establishing the diagnosis of PSC. Therapeutic approaches that show promise include endoscopic therapy and ursodeoxycholic acid. The only accepted therapy for end-stage PSC that can improve long-term outcome is liver transplantation. The diagnosis of cholangiocarcinoma--often difficult and elusive--usually precludes liver transplantation because its prognosis is very poor.     

Endoscopy in the management of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver condition characterized by progressive fibrosis and destruction of the intra-and extrahepatic biliary tree. PSC has a clear association with inflammatory bowel disease and is often progressive, leading to cirrhosis and end-stage liver failure. For many patients, liver transplantation offers the only hope of long-term survival. No effective medical treatment exists, and therapy is often aimed at treating complications of the disorder, including dominant biliary strictures, which may cause symptomatic jaundice, cholangitis, and pruritus. Studies on endoscopic therapy (eg, biliary dilation and/or stent insertion) have shown favorable results, although most studies have been small, retrospective, and uncontrolled. Up to 20% of patients with PSC develop cholangiocarcinoma; however, distinguishing between cholangiocarcinoma and benign strictures can be difficult. Ideally, randomized trials are required to determine the safest and most effective endoscopic management for symptomatic dominant strictures.     

Treatment of primary sclerosing cholangitis in children

Primary sclerosing cholangitis(PSC) is a rare disease of stricturing and destruction of the biliary tree with a complex genetic and environmental etiology.Most patients have co-occurring inflammatory bowel disease. Children generally present with uncomplicated disease, but undergo a variable progression to endstage liver disease. Within ten years of diagnosis, 50% of children will develop clinical complications including 30% requiring liver transplantation.Cholangiocarcinoma is a rare but serious complication affecting 1% of children.Ursodeoxycholic acid and oral vancomycin therapy used widely in children as medical therapy, and may be effective in a subset of patients. Gamma glutamyltransferase is a potential surrogate endpoint for disease activity, with improved survival in patients who achieve a normal value. Endoscopic retrograde cholangiopancreatography is a necessary adjunct to medical therapy to evaluate mass lesions or dominant strictures for malignancy, and also to relieve biliary obstruction. Liver transplantation remains the only option for patients who progress to end-stage liver disease. We review special considerations for patients before and after transplant, and in patients with inflammatory bowel disease. There is presently no published treatment algorithm or guideline for the management of children with PSC. We review the evidence for drug efficacy, dosing, duration of therapy, and treatment targets in PSC, and provide a framework for endoscopic and medical management of this complex problem.     

Pathogenesis of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) represents a chronic cholestatic liver disease with fibroobliterative sclerosis of intra- and/or extrahepatic bile ducts, eventually leading to biliary cirrhosis. The association with human leukocyte antigen (HLA) and non-HLA haplotypes and the presence of autoantibodies in sera of PSC patients support a crucial role for immune-mediated mechanisms in the initiation and progression of PSC. The strong clinical association between PSC and inflammatory bowel diseases led to intriguing pathogenetic concepts, in which the inflamed gut with translocation of bacterial products and homing of gut-primed memory T lymphocytes via aberrantly expressed adhesion molecules plays a fundamental role. Genetically or chemically modified bile composition was shown to induce sclerosing cholangitis and liver fibrosis in a number of animal models ("toxic bile concept"). The potential role of vascular injury with ischemia of bile duct epithelium cells in the development of sclerosing cholangitis is supported by animal models of endothelial cell injury showing close morphological similarities with human PSC.     

A case of sclerosing cholangitis without pancreatic involvement thought to be associated with autoimmunity

Sclerosing cholangitis (SC) is one of the lesions frequently seen in IgG4-related systemic diseases, causing biliary stricture and mimicking bile duct carcinoma and primary sclerosing cholangitis (PSC). Although it often accompanies autoimmune pancreatitis (AIP), autoimmune-related SC without a pancreatic lesion is very rare. A 79-year-old woman was referred to our institution with suspected diagnosis of bile duct carcinoma in the previous hospital. The patient was not icteric and fever free, but with an elevated level of serum biliary enzyme, which lead us to detect this disease. Clinical images including computed tomography (CT), endoscopic retrograde cholangiopancreatography (ERCP) and intraductal ultrasonography (IDUS) demonstrated multiple strictures at the intrahepatic bile duct and enhanced wall thickness at the upper common bile duct, however her pancreas was normal. Repeated endoscopic procedures with multiple biopsies from the biliary strictures demonstrated fibrous ductal tissues with lymph-plasma cell infiltration (>10 IgG4(+) cells/HPF). By positron emission tomography using (18)F-fluorodeoxyglucose (FDG-PET), the uptake of FDG was not remarkable in areas other than the biliary lesions. Additional laboratory tests showed elevated levels of serum IgG (2,571 mg/dL), and γ-globulin (29%), and positive autoantibodies, but normal IgG4 (53.2 mg/dL). Together with clinical images, laboratory and histological findings, we diagnosed this patient as sclerosing cholangitis which was thought to be associated with autoimmunity. After one year of follow-up without steroid therapy, idiopathic thrombocytopenic purpura (ITP) developed with an increased level of serological markers. We encountered a rare case of sclerosing cholangitis expected to be associated with autoimmunity, which showed biliary strictures mimicking bile duct carcinoma and needed careful diagnosis. Unlike the typical AIP, the current case demonstrated distinct serological findings and no other organ involvement. Further study is needed to clarify the characteristics of sclerosing cholangitis associated with autoimmunity with a large number of cases.     

Primary Sclerosing Cholangitis: Is Any Treatment Worthwhile?

While many therapeutic agents have been evaluated in Primary Sclerosing Cholangitis (PSC), none have been shown in controlled trials to modify the course of disease. The bile acid ursodeoxycholic acid (UDCA) has been widely used in the treatment of PSC but its use remains controversial. It may have a role in providing chemoprotection against the development of colonic dysplasia/cancer in patients with associated inflammatory bowel disease. The exclusion of IgG4-associated cholangitis, which generally responds to immunosuppressant agents, is essential prior to deciding on an appropriate therapeutic strategy in PSC. In the absence of proven therapeutic agents, treatment strategies are usually aimed at minimizing the complications of the biliary disease. Endoscopic management of dominant strictures may improve long-term outcomes. Orthotopic liver transplantation has a good outcome in patients with end stage PSC.     

The challenges in primary sclerosing cholangitis--aetiopathogenesis, autoimmunity, management and malignancy

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease, characterized by progressive inflammation and fibrosis of the bile ducts, resulting in biliary cirrhosis and is associated with a high risk of cholangiocarcinoma. The majority of patients are young, male and have coexisting inflammatory bowel disease. PSC is found with a prevalence of 10/100,000 in Northern European populations. The pathophysiology of PSC is a complex multistep process including immunological mechanisms, immunogenetic susceptibility and disorders of the biliary epithelia. The diagnosis is primarily based on endoscopic cholangiography although magnetic resonance imaging is increasingly used; biochemistry and immunoserology as well as histology play only a minor role. Due to the high risk of developing cholangiocarcinoma and also other tumours of the GI tract, surveillance strategies are essential, however they have yet to be established and evaluated. Biochemical parameters, clinical risk factors, endoscopic procedures and imaging techniques contribute to the early identification of patients at risk. Since medical therapy of PSC with ursodeoxycholic acid does not improve survival, to date, liver transplantation is the only option with a cure potential; if transplantation is accurately timed, transplanted PSC patients have an excellent rate of survival. However if cholangiocarcinoma is detected, a curative treatment is not possible in the majority of cases. The present review critically summarizes the current knowledge on the aetiopathogenesis of PSC and gives an overview of the diagnostic approaches, surveillance strategies and therapeutic options. Primary sclerosing cholangitis is a disease of unknown aetiology and without any further curative treatment options apart from liver transplantation. Therefore it may be regarded as the greatest challenge in hepatology today.     

Risk factors for proximal migration of biliary tube stents

AIM: To analyze the risk factors for biliary stent migration in patients with benign and malignant strictures. METHODS: Endoscopic stent placement was performed in 396 patients with bile duct stenosis, at our institution, between June 2003 and March 2009. The indications for bile duct stent implantation included common bile duct stone in 190 patients, malignant lesions in 112, chronic pancreatitis in 62, autoimmune pancreatitis in 14, trauma in eight, surgical complications in six, and primary sclerosing cholangitis(PSC) in four. We retrospectively examined the frequency of stent migration, and analyzed the patient factors(disease, whether endoscopic sphincterotomy was performed, location of bile duct stenosis and diameter of the bile duct) and stent characteristics(duration of stent placement, stent type, diameter and length). Moreover, we investigated retrieval methods for migrated stents and their associated success rates. RESULTS: The frequency of tube stent migration inthe total patient population was 3.5%. The cases in which tube stent migration occurred included those with common bile duct stones(3/190; 1.6%), malignant lesions(2/112; 1.8%), chronic pancreatitis(4/62; 6.5%), autoimmune pancreatitis(2/14; 14.3%), trauma(1/8; 12.5%), surgical complications(2/6; 33.3%), and PSC(0/4; 0%). The potential risk factors for migration included bile duct stenosis secondary to benign disease such as chronic pancreatitis and autoimmune pancreatitis(P = 0.030); stenosis of the lower bile duct(P = 0.031); bile duct diameter > 10 mm(P = 0.023); duration of stent placement > 1 mo(P = 0.007); use of straight-type stents(P < 0.001); and 10-Fr sized stents(P < 0.001). Retrieval of the migrated stents was successful in all cases. The grasping technique, using a basket or snare, was effective for pig-tailed or thin and straight stents, whereas the guidewire cannulation technique was effective for thick and straight stents. CONCLUSION: Migration of tube stents within the bile duct is rare but possible, and it is important to determine the risk factors involved in stent migration.     

Endoscopic removal of a spontaneously fractured biliary uncovered self-expandable metal stent

Self-expandable metal stents (SEMS) are widely used for the palliative treatment of unresectable malignant biliary obstruction. However, the long-term durability of SEMSs in biliary strictures is not clear. We describe a case of endoscopic removal of spontaneously fractured uncovered biliary SEMS. A 59-year-old woman presented to our institution with a 1-year history of recurrent cholangitis. Her medical history included a proctectomy for rectal cancer and right hemihepatectomy for liver metastasis 10 years earlier. Five years after these operations, she developed a benign hilar stricture and had an uncovered SEMS placed in another hospital. Endoscopic retrograde cholangiopancreatography demonstrated that the SEMS was torn in half and the distal part of the stent was floating in the dilated common bile duct. The papillary orifice was dilated by endoscopic papillary large balloon dilation (EPLBD) using a 15-mm wire-guided balloon catheter. Subsequently, we inserted biopsy forceps into the bile duct and grasped the distal end of the broken SEMS under fluoroscopy. We successfully removed the fragment of the SEMS from the bile duct, along with the endoscope. The patient was discharged without complications. Placement of an uncovered biliary SEMS is not the preferred treatment for benign biliary strictures. Spontaneous fracture of an uncovered biliary SEMS is an extremely rare complication. We should be aware that stent fracture can occur when placing uncovered biliary SEMSs in patients with a long life expectancy. EPLBD is very useful for retrieving the fractured fragment of SEMS.     

Treatment of biliary problems in inflammatory bowel disease

Opinion statement The most common biliary problem in patients with inflammatory bowel disease is primary sclerosing cholangitis (PSC). The treatment of this disease is multifaceted and frequently requires a multidisciplinary approach involving internists, nutritionists, gastroenterologists, and surgeons. Unfortunately, other than liver transplantation, no therapy that is currently available has been proven to alter the natural history of PSC or prolong survival. Ursodeoxycholic acid is currently the most promising pharmacologic treatment option for slowing disease progression and should be used in higher than usual doses (20 to 30 mg/kg/d). Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins such as cholestyramine or colestipol (which is generally better tolerated than cholestyramine). Endoscopic therapy should be reserved for patients with obstructive jaundice, cholangitis, or symptomatic dominant biliary strictures. We recommend dilation of dominant strictures with graduated or balloon dilators followed by temporary stenting if the postdilation cholangiographic appearance is not improved or adequate biliary drainage cannot be assured. There is indirect evidence that the combination of ursodeoxycholic acid and endoscopic therapy to maintain biliary patency may improve transplant-free survival in patients with PSC, although this remains to be proven. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.     

Small bile duct involvement in IgG4-related sclerosing cholangitis: liver biopsy and cholangiography correlation

Background

IgG4-related sclerosing cholangitis (IgG4-SC) needs to be differentiated from primary sclerosing cholangitis (PSC). In this study, we performed a retrospective study to reveal cases in which liver needle biopsy was useful for differential diagnosis.

Methods

Nineteen patients with IgG4-SC and 22 patients with PSC were studied. All patients underwent endoscopic retrograde cholangiography and liver needle biopsy. We defined small bile duct involvement of IgG4-SC histologically as damage to the small bile duct associated with infiltration of ??10 IgG4+ plasma cells per high power field (HPF). Clinicopathological characteristics were compared between IgG4-SC patients with and without small bile duct involvement.

Results

Small bile duct involvement was observed in 5 (26%) of the patients with IgG4-SC. Patients with small bile duct involvement showed a higher incidence of intrahepatic biliary strictures on cholangiography (80 vs. 21%, p?=?0.038). Conversely, 4 of 7 (57%) patients with intrahepatic biliary strictures on cholangiography had histologically evident small duct involvement. The number of IgG4+ plasma cells was significantly correlated with the site of the most proximal stricture on cholangiograms (p?=?0.021). The number of IgG4+ plasma cells per HPF was significantly higher in IgG4-SC patients with intrahepatic biliary strictures than in those with PSC (13.4 vs. 0.4?cells/HPF, p?<?0.001).

Conclusions

Involvement of small bile ducts is more frequent in patients with intrahepatic biliary strictures on cholangiography, and liver needle biopsy is especially useful for these patients.     

Advanced therapeutic endoscopist and inflammatory bowel disease: Dawn of a new role

Endoscopy plays a key role in the diagnosis and treatment of patients with inflammatory bowel disease(IBD).Colonoscopy has been traditionally used in the diagnosis of IBD and helps in determination of an important end point in patient management,"mucosal healing".However,the involvement of an advanced endoscopist has expanded with innovations in therapeutic and newer imaging techniques.Endoscopists are increasingly being involved in the management of anastomotic and small bowel strictures in these patients.The advent of balloon enteroscopy has helped us access areas not deemed possible in the past for dilations.An advanced endoscopist also plays an integral part in managing ileal pouchanal anastomosis complications including management of pouch strictures and sinuses.The use of rectal endoscopic ultrasound has been expanded for imaging of perianal fistulae in patients with Crohn’s disease and appears much more sensitive than magnetic resonance imaging and exam under anesthesia.Advanced endoscopists also play an integral part in detection of dyspla-sia by employing advanced imaging techniques.In fact the paradigm for neoplasia surveillance in IBD is rapidly evolving with advancements in endoscopic imaging technology with pancolonic chromoendoscopy becoming the main imaging modality for neoplasia surveillance in IBD patients in most institutions.Advanced endoscopists are also called upon to diagnose primary sclerosing cholangitis(PSC)and also offer options for endoscopic management of strictures through endoscopic retrograde cholangiopancreatography(ERCP).In addition,PSC patients are at increased risk of developing cholangiocarcinoma with a 20%lifetime risk.Brush cytology obtained during ERCP and use of fluorescence in situ hybridization which assesses the presence of chromosomal aneuploidy(abnormality in chromosome number)are established initial diagnostic techniques in the investigation of patients with biliary strictures.Thus advanced endoscopists play an integral part in the management of IBD patients and our article aims to summarize the current evidence which supports this role and calls for developing and training a new breed of interventionalists who specialize in the management of IBD patients and complications specific to those patients.     

Cutting edge issues in juvenile sclerosing cholangitis

Sclerosing cholangitis (SC) is a rare chronic disorder characterised by inflammation and progressive obliterative fibrosis of the intrahepatic and/or extrahepatic bile ducts.Diagnosis is based on cholangiogram showing bile duct dilatation, narrowing and obliteration of the biliary tree, and histologically, on the presence of inflammatory bile duct damage leading to periductal fibrosis.In children the most common SC is associated with strong autoimmune features, overlapping with those of autoimmune hepatitis (AIH); this form is known as autoimmune sclerosing cholangitis, ASC.Conversely, primary SC (PSC), a condition in which the term “primary” indicates that aetiology and pathogenesis are unknown, is rare in paediatrics. Secondary SC (SSC) defines a cholangiopathy associated with an identifiable aetiology such as immunodeficiencies, infections or haematological disorders. ASC and PSC are strongly associated with inflammatory bowel disease (IBD).ASC responds biochemically well to immunosuppressive drugs and ursodeoxycholic acid (UDCA). Primary forms are exclusively managed with oral UDCA, while in the secondary forms the medical treatment depends on the underlying aetiology.Despite treatment, SC often progresses to biliary cirrhosis and end-stage liver disease requiring liver transplantation. The disease can recur after transplant.Better understanding of pathogenic mechanisms and better treatment modalities are needed to improve the prognosis of this invalidating hepatic disorder.     

Immunopathogenesis of primary sclerosing cholangitis: possible role of a shared colonic and biliary epithelial antigen

Abstract   Primary sclerosing cholangitis (PSC) is a chronic fibrosing disease of both extrahepatic as well as intrahepatic bile ducts that is strongly associated with inflammatory bowel disease, particularly ulcerative colitis. It is characterized by progressive destruction of the bile ducts leading to widespread biliary obstructions and biliary cirrhosis. PSC is currently one of the more common indications for liver transplantation. It is an immune mediated disorder associated with autoantibodies against both colon epithelium as well as biliary epithelium, infiltration of the portal tract with functional T cells, abnormal expression of HLA molecules on biliary epithelial cells and a restricted T-cell receptor repertoire. Activation of the complement system, following the deposition of antigen-specific autoantibody with biliary epithelial cells, may also contribute to the pathogenesis of PSC. Four different HLA haplotypes have been associated with PSC: three with increased risk of disease and one with reduced risk. Bacterial products entering the biliary epithelium from colon may be a triggering factor strongly associated with ulcerative colitis; however, a further immune mediated chronic inflammation may be associated with cellular antigen(s) which is shown to be shared by human colon and biliary epithelium by molecular mimicry.