The challenges in primary sclerosing cholangitis – Aetiopathogenesis, autoimmunity, management and malignancy

Abstract

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.

Multisystem Langerhans cell histiocytosis with liver dysfunction as the first presentation: A case report

“…Bile duct involvement is capable of progressing to a SC-type image, fibrosis and eventually to liver failure. Although SC patients typically present with a cholestatic biochemical profile with 3-10 times the upper limit of serum ALP, this finding is neither specific nor mandatory (6). The serum levels increase with fluctuations due to choledocholithiasis or dominant stenoses with progression of the disease.…”

Survival Without Biliary Complications After Liver Transplant for Primary Sclerosing Cholangitis

“…The frequency of recurrent primary sclerosing cholangitis varies because of differences in duration of follow-up and protocols to detect biliary strictures between different studies. 2,7,30,31 The definition of recurrent primary sclerosing cholangitis usually is based on published criteria 3 including biopsy and cholangiographic findings. 4,5 In selected cases, partial resection of liver graft tissue that has limited biliary injury may be possible to prevent complete loss of the transplanted liver and revision transplant.…”

A combined bile and urine proteomic test for cholangiocarcinoma diagnosis in patients with biliary strictures of unknown origin

“…In the last decade, invasive methods such as endoscopic retrograde cholangiopancreatography (ERCP) with or without cholangioscopy, intraductal ultrasound, brush cytology or forceps biopsies have found their way into clinical practice without having demonstrated a significant impact on the differentiation between malignant and benign biliary lesions. 2 Magnetic resonance imaging/magnetic resonance cholangiopancreatography (MRI/MRCP) and computed tomography (CT) are valuable tools for the assessment of unclear bile duct lesions. However, the differentiation of malignant bile duct strictures solely through imaging studies is difficult and not feasible.…”

“…However, the differentiation of malignant bile duct strictures solely through imaging studies is difficult and not feasible. 1,2 Furthermore, tumor markers like carbohydrate antigen (CA) 19-9 demonstrated a low sensitivity and specificity in different studies and are therefore not useful to detect CC or for surveillance of patients with risk factors for CC. 3 We recently demonstrated that bile and urine proteome analysis (BPA and UPA) have a good diagnostic accuracy to detect CC in patients with PSC.…”