Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy

Brandsæter, Bjørn; Isoniemi, Helena; Broomé, Ulrika; Olausson, Michael; Bäckman, Lars; Hansen, Bent Adel; Schrumpf, E.; Oksanen, Antti; Ericzon, Bo‐Göran; Höckerstedt, K; Mäkisalo, Heikki; Kirkegaard, Preben; Friman, Styrbjörn; Bjøro, Kristian

doi:10.1016/j.jhep.2004.01.002

Cited by 191 publications

(122 citation statements)

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“…A recent Scandinavian study demonstrated that patients with PSC who were treated with UDCA while on a waiting list for liver transplantation had significantly fewer cholangiocarcinomas than patients who did not receive UDCA therapy, suggesting that even a standard dose of UDCA may have a positive effect on the clinical outcome of the disease. 40 Very few studies have actually evaluated the effect of UDCA on ERCP changes, 3,14,41 one of them demonstrating that it does not prevent major bile duct occlusion even during therapy lasting up to 13 years, 41 making it questionable that a higher dose can really improve cholangiographic appearance within 2 years. 14 In the present study, we excluded patients with end-stage liver disease, and half of the patients were actually asymptomatic and had intrahepatic disease of only 3.4 years' mean duration (range, 0-18 years).…”

Section: Discussionmentioning

confidence: 99%

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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No effective medical therapy is currently available for primary sclerosing cholangitis (PSC). Ursodeoxycholic acid (UDCA) improves liver enzymes, but its effect on liver histology is controversial. Metronidazole (MTZ) prevents PSC-like liver damage in animal models and reduces intestinal permeability. We recruited 80 patients with PSC into a randomized placebo-controlled study to evaluate the effect of UDCA and MTZ (UDCA/MTZ) compared with UDCA/placebo on the progression of PSC. Patients (41 UDCA/placebo and 39 UDCA/ MTZ) were followed every third month. Assessment of liver function test, histological stage and grade, and cholangiography (via ERCP) at baseline showed no differences between the groups. After 36 months, serum aminotransferases ␥-glutamyltransferase, and alkaline phosphatase (ALP) decreased markedly in both groups, serum ALP more significantly in the UDCA/MTZ group (؊337 ؎ 54 U/L, P < .05) compared with the UDCA/placebo group. The New Mayo Risk Score decreased markedly only in the UDCA/MTZ group (؊0.50 ؎ 0.13, P < .01). The number of patients with improvement of stage (P < .05) and grade (P < .05) was higher in the combination group. ERCP findings showed no progression or improvement in 77% and 68% of patients on UDCA/MTZ and UDCA/placebo, respectively. In conclusion, combining MTZ with UDCA in PSC improved serum ALP levels and New Mayo Risk Score, but no statistically significant effect on disease progression as assessed via liver histology or ERCP was seen. Long-term studies using a higher dose of UDCA combined with MTZ in larger patient populations are indicated. (HEPATOLOGY 2004;40:1379 -1386

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Section: Discussionmentioning

confidence: 99%

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

et al. 2004

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“…Liver transplantation is the only therapy that can reverse or correct end-stage liver disease from PSC. [150][151][152] In the United States, approximately 250 liver transplants are done yearly in adults for PSC, representing 5% of all liver transplants (Scientific Registry of Transplant Recipients, 2005). Males account for 70% of candidates, and the median age is 50 years.…”

Section: Session Six Liver Transplantation For Pscmentioning

confidence: 99%

“…31,[150][151][152][153] At any time, 800 to 900 adult patients with PSC are on the national waiting list, representing 5% to 6% of candidates.In 2004, there were only 10 deaths per 100 patient-years among PSC transplant candidates compared to 17 per 100 among non-PSC candidates. PSC candidates had the lowest death rate of any diagnostic subgroup.…”

Section: Session Six Liver Transplantation For Pscmentioning

confidence: 99%

“…Transplantation for PSC generally involves resection of the extra-hepatic biliary tree and use of a Roux-en-Y loop. 150 Recurrence of PSC in the transplanted graft bile ducts has been reported, but its frequency, natural history, and optimal management are not well defined. The diagnosis of recurrent PSC is a challenge, in that many features can be mimicked by liver injury caused by ischemia, infection, chronic rejection, biliary obstruction, and medications.…”

Section: Session Six Liver Transplantation For Pscmentioning

confidence: 99%

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Primary sclerosing cholangitis: Summary of a workshop

et al. 2006

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Primary sclerosing cholangitis (PSC) is a rare but important liver disease that leads to cirrhosis and need for liver transplantation in a high proportion of cases. The disease occurs in approximately 1 per 100,000 population per year, usually presents in adulthood, and affects men more often than women. Typical serum biochemical results, autoantibodies and liver biopsy are suggestive but not diagnostic of PSC, the diagnosis requiring cholangiographic demonstration of stricturing and dilatation of the intra-and/or extra-hepatic bile ducts. The natural history of PSC is variable, the average survival being 12 to 17 years. The cause of PSC is still unknown. Although considered an autoimmune disease, PSC has several atypical features and a strong genetic component. The therapy of PSC is unsatisfactory. Standard doses of ursodeoxycholic acid (UDCA) lead to improvements in biochemical abnormalities but not in histology, cholangiographic appearance or survival. Several innovative therapies have been tried in PSC, but with scant evidence of benefit. For patients with high grade strictures, endoscopic dilatation is beneficial. Liver transplantation is successful for end-stage liver disease due to PSC and improves survival. PSC may recur after transplantation but is rarely progressive. The most dreaded complication of PSC is cholangiocarcinoma. Diagnosis of this highly malignant tumor is difficult, and there are no biomarkers for its early detection. Liver transplantation for cholangiocarcinoma has an exceedingly poor outcome, although transplantation with neoadjuvant chemoirradiation holds promise in selected patients. Thus, significant opportunities remain for basic and clinical research into the cause, natural history, and therapy of PSC. 44:746-764.)

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“…The clinical course of the disease is heterogeneous and PSC may be asymptomatic for years in some patients. PSC may also lead to liver cirrhosis and chronic liver failure or eventually cholangiocarcinoma [1][2][3]. In PSC, human leukocyte antigen (HLA) class II expression has been found in liver tissue (bile ducts, Kuppfer cells, arterial and venous endothelium) [4] and genetic factors have been proposed to contribute to the pathogenesis of PSC [5].…”

Section: Introductionmentioning

confidence: 99%

Human leukocyte antigen associations in Finnish liver transplantations due to primary sclerosing cholangitis and primary biliary cirrhosis

et al. 2007

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AbstractA genetic predisposition has been suggested in primary sclerosing cholangitis (PSC) and primary biliary cirrhosis (PBC). The aim of the study was to evaluate human leukocyte antigen (HLA) frequencies and HLA associations in Finnish PSC and PBC patients. The relative frequencies of HLA-A,-B, and-DR antigens were compared between patients with PSC (n=50), or PBC (n=89), transplanted due to end-stage liver disease, and healthy members in the Finnish bone marrow donor registry (n=10000). Prevalence differences, prevalence ratios and the associated large-sample significance probabilities (2-sided P-values) and 95% confidence intervals were calculated.We found a strong positive association between PSC and HLA-B8 and-DR3, and a weak positive association between HLA-A1 and PSC. HLA-DR3 also had a weak positive association with PBC, and a weak negative association between HLA-DR5 and PBC was found. In conclusion, HLA-B8, and-DR3 are susceptible for progressive liver disease in PSC, and HLA-DR3 may also be susceptible for disease progression in PBC. HLA-DR5 may be protective against severe PBC.

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Liver transplantation for primary sclerosing cholangitis; predictors and consequences of hepatobiliary malignancy

Cited by 191 publications

References 31 publications

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: A randomized placebo-controlled trial

Primary sclerosing cholangitis: Summary of a workshop

Human leukocyte antigen associations in Finnish liver transplantations due to primary sclerosing cholangitis and primary biliary cirrhosis

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