Hello everybody, my son has recently been diagnosed with this disease and I have been really nervous about it. He is only 15 and a really good kid. What should I expect from this disease?
Patients with small duct primary sclerosing cholangitis have a favourable long term prognosis. Background: Patients with cholestatic liver function tests and histological features of primary sclerosing cholangitis (PSC) but a normal cholangiogram are considered to have small duct PSC. The natural history of this condition is unknown.
Methods: Thirty three patients with small duct PSC were identified among patients admitted for diagnostic workup of cholestatic liver function tests in one centre in the UK (Oxford) and one centre in Norway (Oslo). A total of 260 patients with large duct PSC were compared, and prognosis in terms of death, cholangiocarcinoma, biochemical features, histological features, and symptoms analysed.
Results: Mean age at diagnosis was 38 years and 39 years in small duct and large duct PSC, respectively. Mean follow up was 106 months in small duct and 105 months in large duct patients. Four patients originally considered to have small duct developed large duct PSC. Two of these underwent liver transplantation during follow up. Of the remainder who did not develop large duct PSC, two patients died during follow up: one of liver failure and the other of cardiac death unrelated to her liver disease. A total of 122 (47%) large duct patients either required liver transplantation (34 patients) or died (88 patients). Small duct patients had a significantly better survival compared with large duct patients. Among small duct patients, none developed cholangiocarcinoma compared with 28 of 260 (11%) large duct patients.
Conclusions: Patients with small duct PSC seem to have a good prognosis in terms of survival and development of cholangiocarcinoma. Small duct PSC progresses to large duct PSC in a small proportion of patients.
Keywords: primary sclerosing cholangitis, cholangiocarcinoma, liver transplantation, inflammatory bowel disease
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder with fibrosis of the intrahepatic and/or extrahepatic bile ducts. PSC is characterised by periductal concentric obliterative fibrosis and bile duct strictures. Its course is very variable and can in individual cases follow a benign course, but for the most part PSC is a progressive disease which leads eventually to cirrhosis and is strongly associated with the development of cholangiocarcinoma. It is associated with inflammatory bowel disease (IBD) in the majority of cases. No specific disease marker has however been observed and the diagnosis is based on typical cholangiographic and histological findings, with exclusion of secondary sclerosing cholangitis.1
The clinical course of PSC is highly variable. Patients with IBD may be found to have abnormal liver function tests on routine follow up or patients may present with symptoms of PSC such as fatigue, pruritus, abdominal pain, or fever.2–6 The natural history of PSC is quite well characterised. Median survival to death or liver transplantation has been estimated to be 12 years in studies from Sweden,3 as well as from the USA4 and England.5 In the largest study,3 66% of patients were symptomatic at diagnosis and 26% died of cholangiocarcinoma which was diagnosed after a median time of 32 months after diagnosis. Some patients have cholestatic liver function tests and typical histological features of PSC but a normal cholangiogram. These patients with a clinical diagnosis of PSC but without the typical intra- and/or extrahepatic cholangiographic changes have been identified as having small duct PSC.7–9 Only a small number of patients with small duct PSC have so far been reported10–11 and the natural history of patients fulfilling the criteria for small duct PSC has been largely unexplored.11 It has been proposed that patients with small duct PSC would eventually develop large duct PSC.8 However, to date there is only anecdotal evidence for this suggestion and no systematic evaluation has been reported on this condition.9 The aim of the current study was to assess the clinical features at presentation and disease course in patients with small duct PSC compared with a large cohort of patients with large duct PSC.
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METHODS
Patients
Patients with small duct PSC were identified among those admitted for a diagnostic workup of cholestatic liver function tests (LFTs) in one centre in the UK (Oxford) and one in Norway (Oslo). Both are tertiary referral centres with a longstanding interest in PSC.2,6,11 This was a retrospective analysis of patients, covering the past 20 years. Among patients with a diagnosis of PSC, 22 patients were identified in Oxford and 11 in Oslo who fulfilled the diagnostic criteria for small duct PSC. The diagnosis of small duct PSC was based on cholestatic LFTs not explained by other cholestatic liver disorders other than PSC, typical histological changes identified in PSC, assessed by pathologists with a longstanding experience in this field (KF and OPC), and a normal cholangiogram. Age at diagnosis is the age at which the first endoscopic retrograde cholangiopancreatography (ERCP) was performed with a normal cholangiogram. All patients were investigated with ERCP and only patients with good quality imaging were included. Good filling of the intrahepatic biliary system and no intra- and/or extrahepatic changes were present in all patients, as evaluated by two experienced endoscopists (RWC and OF). All patients, symptomatic as well as asymptomatic, were investigated by colonoscopy for evidence for IBD. For comparison, we used 100 patients with large duct PSC from Oxford and 160 from Oslo. These patients had been hospitalised previously or were followed up at these two centres and were already on a database in both hospitals.
Diagnostic approach
In patients with large duct PSC, the radiological diagnosis was based on typical cholangiographic findings, with bile duct irregularities, strictures, or local narrowing of bile ducts.12 Standard histological techniques were applied to prepare the liver biopsy specimens obtained in every patient included in the study. Specimens were stained with haematoxylin, eosin, Goermoris and Sweet’s silver method for reticulin, Van Gieson or Sirius red for fibrosis, Pearl stain for iron, and orcein for copper associated protein. Biopsies were classified using Ishak inflammation and fibrosis scores as well as Ludwig’s score of fibrosis.
Efforts were made to exclude all other causes of liver disease. Apart from routine LFTs, autoantibodies (antimitochondrial antibody, smooth muscle antibody, and antinuclear antibody) were measured in all patients as well as electrophoresis and serology for hepatitis A, B, and C. Thus evidence of other liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, as well as viral aetiology and drug induced liver disease were excluded by appropriate serological tests and clinical evaluation. The following variables were available in both groups: sex, follow up in months, age at diagnosis and at follow up, symptoms at diagnosis and follow up, occurrence and type of IBD, and information on colectomy, cholangiocarcinoma, liver transplantation, and survival. The specific symptoms recorded in both groups were jaundice (defined as bilirubin levels above 40 μmol/l), abdominal pain, fever, itching, fatigue, and weight loss. The following biochemical test were measured and compared between groups: haemoglobin, bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), albumin, prothrombin complex in the early part of the study and later international normalised ratio (INR). Information on the use of ursodeoxycholic acid (Ursofalk) was available only for patients from Oxford and was compared between the respective groups.
Patients were followed until 1 June 2001 and end points were liver transplantation and death. Findings from both centres were entered into a new database.
Statistical methods
The Student’s t test was used for continuous variables to compare duration of follow up, age at diagnosis and follow up, as well as results of LFTs. Fisher’s exact test was applied for comparison between symptoms at diagnosis and at follow up, and occurrence of cholangiocarcinoma, liver transplantation, and death. The χ2 test was used for comparison of the prevalence of subtypes of IBD. The correlation between biochemical parameters and symptoms between groups was calculated using the permutation test.13 Results are expressed as mean (SEM). The level of significance was 5%.
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RESULTS
General features
Patients with small duct PSC represented 33 of 293 patients with PSC (11%). Among the 33 patients with small duct PSC, 19 were male (58%) and 14 were female (42%). In the large duct group, 188 (72%) were male and 72 (28%) were female (NS). Mean age at diagnosis was 38 (3) years in patients with small duct PSC which was similar to the mean age in the large duct group (39 (1) years) (p>0.3). Mean age at follow up was also similar (47 (3) and 48 (1) years in small duct and large duct PSC patients, respectively). Mean follow up time was 106 (12) months in small duct and 105 (5) months in large duct patients (p>0.3). Among those who were originally considered to have small duct PSC, four (12%) developed large duct PSC. The first ERCP was normal but because of clinical worsening of the liver disorder, another ERCP was performed which showed cholangiographic changes intra- and/or extrahepatically. Among the 33 patients with small duct PSC, 29 (88%) had concomitant IBD; 20 (61%) were found to have ulcerative colitis (UC), seven (21%) had Crohn’s disease, all with colitis and one also with small bowel involvement, and two (6%) had indeterminate colitis. Two patients did not have IBD at diagnosis but developed IBD during follow up. IBD was detected among 218 (83%) of 260 large duct patients; 172 patients had UC (66%), 25 (9.6%) had Crohn’s disease, and 21 (8%) indeterminate colitis. No statistically significant differences were observed in the prevalence of IBD among the small and large duct PSC patients, and the proportion of UC and indeterminate colitis, respectively, was similar in both groups. However, Crohn’s disease was more common in small duct (21%) than in large duct (9.6%) patients (p<0.05). Among the British patients with small duct PSC, 31% were treated with ursodeoxycholic acid for more than three years of follow up whereas 47% of large duct patients received ursodeoxycholic acid (Ursofalk) for more than three years of follow up (NS).
Biochemical and histological findings
Biochemical results in patients with small duct and large duct PSC are compared in table 1 
. At diagnosis, serum levels of albumin were significantly higher in patients with small duct PSC. There was also a clear trend towards a lower INR in small duct patients (p=0.05) and lower ALP values compared with large duct patients (p=0.08). Serum bilirubin, ALT, and AST were not significantly different between the groups at diagnosis (table 1 ). No significant differences were observed between the groups for any of the measured biochemical variables at follow up, except for serum albumin which was higher in the small duct group (table 2 ). In four patients, original liver biopsies were not available for reevaluation (one in Oxford and three in Oslo). However, experienced pathologists had made the histological diagnosis of PSC previously and they were therefore included in the study. At diagnosis, none of the small duct patients had cirrhosis, 69% of small duct patients were classified as stage I on Ludwig’s fibrosis score, and 31% were stages II–III (table 4 ). Ishak inflammation and fibrosis scores as well as Ludwig’s fibrosis score are shown in tables 3 and 4 .
READ MORE @ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1773443/
I hope this helps. I will keep your son in my Prayers.
Pam
Everyone with PSC is different. I was diagnosed at age 51. My doctors said I had it from infancy. I did not know it, so I did not think about it and I grew up enjoying my childhood, youth and manhood. Yes, there were digestive and intestinal issues I had that other boys did not. They turned out to be a forerunner to Ulcerative Colitis in my 20’s that did not get bad until I was 49.
Your son can live a close to normal life. I certainly did. And, when PSC got too bad at age 65, I got a liver transplant. Six years later, I am healthy and enjoying life. Each year PSC treatment and transplantation get better and better. That bodes well for your son’s future.