Search

Background/Aims Mucosal addressin cellular adhesion molecule-1 ( MAdCAM-1 ) has been implicated in the aberrant homing of intestinal lymphocytes to the liver in primary sclerosing cholangitis (PSC). Intercellular adhesion molecule-1 ( ICAM-1 ) has also been implicated in the pathogenesis of PSC and the E/E genotype of the K469E polymorphism has been reported to be associated with PSC susceptibility. The aims of this study were to determine if MAdCAM-1 polymorphisms or the K469E polymorphism of ICAM-1 are associated with PSC in Scandinavia. Methods Seven single nucleotide polymorphisms (SNPs) in MAdCAM-1 and the G421R and K469E ICAM-1 SNPs were genotyped in 365 PSC patients from Norway and Sweden. 327 Norwegian ulcerative colitis (UC) patients and 368 Norwegian bone marrow donors served as controls. Results No significant association with PSC was found for any of the MAdCAM-1 or ICAM-1 SNPs. Allele frequencies for these polymorphisms were not significantly different between PSC patients with UC, UC patients and healthy controls. Conclusions Polymorphisms in MAdCAM-1 are not likely to significantly affect PSC susceptibility. In addition, the E/E genotype of the K469E in ICAM-1 does not influence PSC susceptibility in Scandinavia.

Background/Aims The aim of the present study was to determine whether PSC can present with acute liver failure (ALF) and to determine its frequency. Methods Medical records from all patients with a well-defined PSC ( n =246), treated at Karolinska University Hospital, Huddinge between 1984 and 2004 were scrutinized. Information on PSC and inflammatory bowel disease (IBD) characteristics including mode of presentation of PSC was evaluated. A group of patients with ALF of indeterminate cause at our hospital diagnosed (1993–2003) was identified as a reference group ( n =46). Results Two patients with PSC presented with ALF (1%) and are described in detail. Both of them had an underlying IBD. Nobody in the reference group had IBD. Conclusions In conclusion, PSC patients can present with ALF in approximately 1% of all patients. PSC should be considered as a differential diagnosis in patients with ALF of indeterminate cause, especially in patients with IBD.

Patients with primary sclerosing cholangitis (PSC) have an increased risk of developing cholangiocarcinoma (CC), which is notoriously difficult to diagnose since these patients may have increased levels of bilirubin due to benign strictures. To evaluate the validity of different tumor markers as an aid to diagnosing CC, we have carried out serial serum tumor marker analyses in patients with PSC who have been followed for several years.Seventy-five patients with PSC, without any clinical signs of CC were included in the study. They were investigated every 6th months for 3 years, with extensive liver function tests and four tumor serum markers CEA, CA 19-9, CA 50 and CA 242. The patients were then followed for 5 years to exclude the possibility that CC remained unrecognized.Of the 75 patients, two (3%) developed CC during the 3-year period. One of these had normal levels, and one had significantly increased levels of the tumor markers. In the follow-up part of the study two further patients died from CC and one from hepatocellular carcinoma, 3 and 4 years after the 3-year study, respectively. Twenty-one patients had an increase of one of the markers on at least one occasion. Five patients had a transient increase of more than double the upper normal limit of the tumor markers on more than one occasion. There was a good correlation between CA 19-9, CA 50 and CA 242, but not with CEA. Fourteen of the 75 patients had periods of increased bilirubin levels, but none of these showed increased tumor markers.The serum tumor markers CEA, CA 19-9, CA 50 and CA 242 are of limited value for the detection of CC in patients with PSC because of low specificity. However, we found no falsely increased values in patients with hyperbilirubinemia.

Recently three large studies have been presented in which the prognostic significance of clinical, laboratory and histological parameters measured early in the course of the disease was determined in primary sclerosing cholangitis patients. A different prognostic index was presented in each study. The aim of the present study was to evaluate these prognostic indices in a group of 37 patients with primary sclerosing cholangitis, assessed for liver transplantation. The results are compared to the outcome in the patients. At first referral, 12 patients were considered too healthy for transplantation and 17 were accepted for transplantation, six of whom died during the waiting time. Ten patients had cholangiocarcinoma or hepatocellular cancer. Albumin and bilirubin differed significantly between the patients accepted for transplantation and those considered too healthy. Only one prognostic index, presented by Dickson et al., could discriminate between "too healthy" and "in need of transplantation". However, the overlap between the groups was large, suggesting that this index may be of little or no help in the clinical situation with individual patients. Moreover, neither the prognostic index, nor any of the laboratory values could identify the patients with cancer. It is concluded that prognostic indicators have been found that may help to characterise primary sclerosing cholangitis patients. However, primary sclerosing cholangitis patients with an accompanying cholangiocarcinoma still cannot be identified.

Background/Aims The aim of the present study was to investigate the familial occurrence of autoimmune diseases in a large group of patients with primary sclerosing cholangitis (PSC). Methods All patients with PSC treated at Huddinge University Hospital between 1984 and 1999 were included ( n =145). For every patient with PSC and inflammatory bowel disease (IBD) ( n =126) we randomly selected a control patient with IBD ( n =126), matched for age, sex and type of IBD. A questionnaire comprising information about autoimmune diseases among first-degree relatives was answered by all patients and controls. Results We identified 22 index cases with PSC from 21 families with a first-degree relative with either chronic liver disease and/or IBD. Five patients with PSC had a first-degree relative with PSC (3.4%). The prevalence of PSC among first-degree relatives was 0.7% (5/717). In siblings the prevalence was 1.5% (4/269). The prevalence of first-degree relatives with autoimmune diseases outside the liver was similar in PSC patients and controls. Conclusions First-degree relatives of patients with PSC have a PSC prevalence of 0.7%. This represents a nearly 100-fold increased risk of developing PSC compared with the general population, supporting the hypothesis that genetic factors are of importance for development of PSC.

Background/Aims Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation. Methods Data from all Nordic PSC patients listed for liver transplantation during 1990–2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed. Results Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively. Conclusions Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.

This study aims at describing the natural history and outcome of small duct primary sclerosing cholangitis (PSC).Thirty-two patients with small duct PSC were studied. The average time taken for diagnosis was 69 (1-168) months. The median follow-up time was 63 (1-194) months.All patients including one who underwent liver transplantation because of end-stage liver disease and hepatocellular carcinoma were alive at follow-up. None developed cholangiocarcinoma. In 27 patients repeated cholangiographic examinations were done after a median time of 72 (12-192) months from first ERCP. Four developed features of large duct PSC.Small duct PSC rarely progresses to large bile duct PSC and it seems to have a benign course in most patients and no development of cholangiocarcinoma was found.

Backround/Aims : Hepatobiliary carcinoma (HBC) has been considered to be a late complication of end-stage primary sclerosing cholangitis (PSC). The incidence of HBC is approximately 20% in PSC patients evaluated for liver transplantation. The diagnosis of HBC is difficult, at least at an early stage and the prognosis is poor even after liver transplantation. The aim of the study was to look for signs and risk factors for developing hepatobiliary carcinoma in patients with PSC. Methods : Thirty-six consecutive patients with PSC and HBC (32 with bile duct carcinoma, BDC, and four with hepatocellular carcinoma, HCC) were pair-matched to control patients referred for liver transplantation because of PSC but who did not have HBC. Gender and age at referral were used as matching factors. Clinical and biochemical data were registered. Results : PSC patients with BDC had a shorter median duration of PSC (1 year) compared with the controls (7 years) and PSC patients with HCC (8 years). There were no statistically significant differences in the liver biochemistry between the patient groups. Varices were more common in patients with PSC and HCC (100%) than in controls (56%) or patients with PSC and HBC (12%) ( P Conclusions : The relatively short duration of PSC and the absence of varices in patients with BDC suggest that BDC, unlike HCC, is not necessarily a late complication of end-stage PSC, as was previously assumed.

The significance of DNA ploidy determinations for diagnosing cholangiocarcinoma (CC) in primary sclerosing cholangitis (PSC) has not previously been evaluated. Knowledge of tumour cell ploidy by DNA cytometry may facilitate the evaluation of malignant and premalignant lesions in PSC.Twenty-eight patients with CC were studied; 10 of the patients had PSC. Seventeen samples from 15 patients with PSC but without CC were used as controls for benign strictures. Gallbladder tissue from 100 patients with chronic cholecystitis was also analysed. DNA was measured using flow cytometry on cells from paraffin-embedded tissues.Tumours from patients with PSC displayed non-tetraploid DNA aneuploidy significantly more often (80%) than tumours from patients without PSC (39%) (p0.05). CC from patients with PSC significantly more often displayed DNA aneuploidy: 80% (8/10) compared with 12% (2/17) in bile ducts in PSC without CC (p=0.0007). The frequency of DNA aneuploidy in gallbladder tissue from patients with chronic cholecystasis was 1% (1/100).The high prevalence of DNA aneuploidy in PSC-related CC and the low prevalence in benign PSC strictures point to DNA cytometry as a possible future method for detecting malignant and premalignant changes in bile duct strictures in patients with PSC. This method may be useful in selecting PSC patients for liver transplantation.

Background/Aim: Cholangiocarcinoma is a feared complication of primary sclerosing cholangitis (PSC). Neoplastic bile duct strictures may be difficult to differentiate cholangiographically from the non-neoplastic bile duct irregularities characteristic of this disorder, and the diagnosis of cholangiocarcinoma may be difficult to establish with certainty, even in tissue samples. Thus, new methods which can improve the diagnostic accuracy of cholangiocarcinoma in PSC are needed. Methods: We investigated the occurrence of K- ras codon 12 and 13 mutations, p53 protein accumulation, and Ki-67 expression in tumor tissue from PSC patients ( n =33) who had developed cholangiocarcinoma, using bile duct specimens exised at liver transplantation of PSC patients without cholangiocarcinoma ( n =15) as controls. Results: K- ras mutations were present in 11 (33%) of the cholangiocarcinoma samples and significantly more frequent in females. Nine tumors carried a codon 12 mutation, and 2 had a codon 13 mutation. The most frequent substitutions in codon 12 were GGT→GAT ( n =5) and GGT→TGT ( n =3). None of the control bile ducts had K- ras mutations. p53 protein was accumulated in 10 (31%) of the tumors, as opposed to negative findings in all the control samples. Sixteen (48%) tumors revealed either K- ras mutation or p53 accumulation. Ki-67 positivity was significantly higher in cholangiocarcinomas than in the non-neoplastic bile ducts (median 29% vs 12%, respectively; p =0.011). Conclusion: We conclude that K- ras mutations and p53 dysfunction are implicated in tumorigenesis of cholangiocarcinomas arising in PSC patients and that these abnormalities together with increased Ki-67 index may indicate neoplastic progression of bile ducts in these patients.