Small-Duct Primary Sclerosing Cholangitis. A Single-Center Seven-Year Experience

Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but without the typical cholangiographic changes are considered to have small-duct PSC. The incidence of small-duct PSC and the natural history still is not known. We performed a retrospective search for patients diagnosed with small-duct PSC between January 1997 and December 2003. The diagnosis of small-duct PSC was based on biochemical features of chronic cholestasis, liver biopsy findings consistent with PSC, and a normal cholangiogram on endoscopic retrograde cholangiography. Six patients fulfilled the diagnostic criteria for small-duct PSC. All patients received medical therapy. After a mean follow-up time of 26.0 ± 29.8 months (range, 7–84 months), all patients are alive. Repeated liver biopsy was performed in one patient, 58 months after the initial one, and disclosed amelioration of histological findings (reduction in the Ludwig fibrosis score from 4 to 2). During follow-up symptoms disappeared in all patients who were symptomatic at diagnosis; none of those who were asymptomatic at diagnosis developed symptoms. At the time of last follow-up all patients showed significant improvement of their biochemical variables compared to baseline. Administration of aminosalicylates seemed to be of benefit irrespective of the presence of inflammatory bowel disease. No patients underwent liver transplantation or developed cholangiocarcinoma. Even though our study included a low number of patients and the follow-up time was relatively short, we can suggest that small-duct PSC rarely progresses to large-duct PSC and does not seem to be associated with development of cholangiocarcinoma. It thus seems to represent a separate entity with a favorable prognosis.     

Primary Sclerosing Cholangitis: A Clinical Review

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by fibro-obliterative inflammation of the entire biliary tree. It is a slowly progressive disease with an undulating course, resulting in terminal biliary cirrhosis after a median period of about 12 years after diagnosis. The etiology of the disease is unknown and there is no effective therapy that can halt disease progression. Around 8% of PSC patients develop cholangiocarcinoma, which, by the time it is diagnosed, cannot be treated curatively. The purpose of this article is to review the current knowledge about primary sclerosing cholangitis and to speculate on future strategies to address the issues of etiology and therapy.     

Primary Sclerosing Cholangitis and Inflammatory Bowel Disease: A Review

Primary sclerosing cholangitis is a disease affecting around 0.006–0.016% of the population. Of these, around 75% have concomitant inflammatory bowel disease (IBD) according to the most recent epidemiological studies. Several theories have been proposed regarding the pathogenesis of primary sclerosing cholangitis (PSC). These include changes in the function of cholangiocytes, effects of the gut microbiome, association with specific human leukocyte antigen haplotypes and dysregulation of the immune system. However, these do not explain the observed association with IBD. Moreover, there are considerable differences in the frequency and outcomes between patients with PSC and ulcerative colitis compared with PSC and Crohn’s disease. The aim of this review is to appraise the most recent studies that have contributed to the epidemiology, advances in the pathophysiology, and characterization of important clinical aspects of the association of PSC and IBD.     

Cholangiocarcinoma Secondary to Primary Sclerosing Cholangitis in Explanted Livers: A Single-Center Study in the South of Iran

Background:

Primary sclerosing cholangitis (PSC) is a chronic disease, characterized by chronic inflammation and fibrosis of bile duct epithelial cells. This is a significant contributory factor to the development of malignancy, most commonly cholangiocarcinoma (CCA), which is the second most common malignant liver tumor.

Objectives:

For the first time in Iran, we intend to describe our experience with cases of PSC, with and without CCA, in explanted livers, and compare our results with those found in other areas of the world.

Patients and Methods:

The study population comprised 181 individuals with a diagnosis of PSC who had undergone liver transplantation in the main liver transplant center of Iran, the largest center of hepatobiliary surgery in the south of that country, over a 3-year period between 2012 and 2014. All explanted livers, with and without CCA, were evaluated.

Results:

Of the 181 patients, 16 were found to have CCA, two of whom had been diagnosed after pathologic study of the explanted livers. Therefore it appeared that 8.8% of the patients with PSC in our center had developed CCA before liver transplantation.

Conclusions:

A comparison of our results with those obtained from other centers in both Western and Asian countries (which reported CCA in 3.6% - 36.5% of patients with PSC), shows that the incidence of CCA in the patients we studied is intermediate.     

Laparoscopic Findings in Primary Sclerosing Cholangitis

Abstract: The laparoscopic appearance of the liver surface in patients with primary sclerosing cholangitis (PSC) has not been fully delineated. We examined 5 patients with PSC and reviewed 35 previously reported cases. Intense white markings in a mesh-like pattern were characteristic of PSC. The findings varied depending on the histologic stage and affected site. Red patches which have also been seen in primary biliary cirrhosis (PBC), green patches indicating cholestasis, and dilatation of the terminal bile ducts were also observed. The red patches were wider than those in PBC. The white markings were less well defined in the red patches than in other areas. The severity of the fibrosis and histologic damage was judged to be mild at the red sites. The green patches were caused by localized cholestasis. This indicated that PSC unevenly affects the liver. Severe obstruction may be present between the interlobular bile ducts and the septal bile ducts in anicteric stages. (Dig Endosc 1999; 10: 37–41)     

Endoscopic Management of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) remains a rare but potentially devastating chronic, cholestatic liver disease. PSC causes obstruction of intra- and/or extra-hepatic bile ducts by inflammation and fibrosis, leading to biliary obstruction, cirrhosis and portal hypertension with all associated sequelae. The most dreaded consequence of PSC is cholangiocarcinoma, occurring in 10-20% of patients with PSC, and with population-based estimates of a 398-fold increased risk of cholangiocarcinoma in patients with PSC compared to the general population. We use the 4-D approach to endoscopic evaluation and management of PSC based on currently available evidence. After laboratory testing with liver chemistries and high-quality cross-sectional imaging with MRCP, the first D is Dominant stricture diagnosis and evaluation. Second, Dilation of strictures found during ERCP is performed using balloon dilation to as many segments as possible. Third, Dysplasia and cholangiocarcinoma diagnosis is performed by separated brushings for conventional cytology and fluorescence in situ hybridization (FISH), and consideration for direct cholangioscopy with SpyGlass™. Fourth and finally, Dosing of antibiotics is critical to prevent peri-procedural cholangitis. The aim of this review article is to explore endo-scopic tools and techniques for the diagnosis and management of PSC and provide a practical approach for clinicians.     

Pirfenidone in the Treatment of Primary Sclerosing Cholangitis

Our aim was to evaluate the safety and assess the efficacy of pirfenidone, an antifibrotic drug, in patients with primary sclerosing cholangitis (PSC). Twenty-four patients with PSC were enrolled in this pilot study. Oral pirfenidone, 2400 mg daily, was given for one year. Liver biochemistries were determined at three-month intervals. The Mayo risk score was calculated, and liver biopsy and endoscopic cholangiography were performed at entry and at one year of treatment. No significant changes in liver biochemistries were noted at the end of the treatment period or at any of the three-month intervals. The Mayo risk score did not change significantly, and no significant changes were noted in the degree of inflammation, fibrosis, histologic stage of disease, or cholangiographic findings at the end of the treatment period. Adverse events occurred in 20/24 (83%) patients, but disappeared shortly after pirfenidone was discontinued. Pirfenidone did not benefit patients with PSC, and it was frequently associated with adverse events. The results of this pilot study discourage further trials of pirfenidone in patients with PSC.     

Current Status of Primary Sclerosing Cholangitis in China

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Immunological Similarities Between Primary Sclerosing Cholangitis and Chronic Sclerosing Sialadenitis

Primary sclerosing cholangitis (PSC) is characterized by destructive inflammation and fibrosis affecting the bile ducts. The etiology of PSC is still unknown, although lymphocytic infiltration in the portal areas suggests an immune-mediated destruction of the bile ducts. Patients with one autoimmune disease often suffer from one or more other autoimmune diseases. It is well known that there is a close relationship between PSC and inflammatory bowel disease, particularly ulcerative colitis(UC). However, the pathological findings in UC and other overlap diseases do not resemble those of PSC. In the present study, we report a patient with chronic sclerosing sialadenitis (Kuttner's tumor) and PSC. It is compared the sclerosing changes in both salivary glands and bile ducts histologically. In addition, the expression pattern of mast cell tryptase, b-FGF, and HLA-DR were examined in both tissues immunohistochemically. Histological features of sclerosing change in both salivary and bile ducts were quite similar. Marked mast cell infiltration and b-FGF expression were seen in the sclerosing areas in both tissues. In active inflammatory areas of the salivary glands, HLA-DR expression was also seen. We hypothesized that similar immune reactions occur in both the salivary gland and bile ducts and are responsible for the fibrosis that follows.     

A Review of the Challenges Associated with the Diagnosis and Therapy of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic and progressive cholestatic liver disease that often leads to the development of cirrhosis. Complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, dominant biliary strictures, gallstones, and hepatobiliary malignancies, most commonly cholangiocarcinoma (CCA). Despite the presumed autoimmune etiology of PSC, a clear benefit from immunosuppressive agents has not yet been established, and their use is limited by their side effects. Endoscopy is required in evaluation of biliary strictures in PSC to rule out the possibility of CCA. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease. However, disease recurrence can be a source of morbidity and mortality as transplanted patients survive longer. Further studies are needed to develop an optimal therapeutic strategy for patients with PSC to decrease the incidence of complications of the disease, to decrease the need for transplantation, and to extend life expectancy.