Risk factors for recurrence of primary sclerosing cholangitis of liver allograft

doi:10.1016/S0140-6736(02)11861-7

The Lancet

Volume 360, Issue 9349, 14 December 2002, Pages 1943-1944

https://doi.org/10.1016/S0140-6736(02)11861-7 Get rights and content

Summary

Primary sclerosing cholangitis (PSC) is a disease of unknown cause that effects the biliary tree and is closely associated with inflammatory bowel disease. We did a retrospective analysis of the risk factors associated with recurrence of PSC in an allograft after liver transplantation. Recurrence of disease, assessed by liver histology or imaging the biliary tree, occurred in 56 of 152 patients (37%) at a median of 36 months (range 1·4–120 months). Multivariate analysis showed that being male (relative risk 1·2, 95% Cl 0·73–2·15) and an intact colon before transplantation (8·7, 1·19–64·48) were associated with recurrence. These observations could help elucidate the pathogenesis of the disease.

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Autoimmune liver diseases (AILDs) are a group of conditions where immune-mediated liver damage can lead to the need for transplantation. Collectively, they account for almost a quarter of all liver transplants. Outcomes in terms of graft and patient survival for all liver transplants have improved markedly over decades with improvements in patient selection, surgical techniques and longer-term care and this is also seen in patients with AILDs. The current five- and ten-year survival rates post-transplant in autoimmune disease are excellent, at 88% and 78%, respectively. A key factor in maintaining good outcomes post liver transplant for these autoimmune conditions is the immunosuppression strategy. These patients have increased the rates of rejection, and autoimmune conditions can all recur in the graft ranging from 12 to 60% depending on the population studied. Immunosuppressive regimens are centred on calcineurin inhibitors, often combined with low dose corticosteroids, with or without the addition of antimetabolite therapy. There is no clear evidence-based immunosuppressive regimen for these conditions, and a tailored approach balancing the individuals’ immunological profile against the risks of immunosuppression is often used. There are disease-specific considerations to optimised graft function including the role of ursodeoxycholic acid in both primary biliary cholangitis and primary sclerosing cholangitis and the role and timing of colectomy in primary sclerosing cholangitis in inflammatory bowel disease patients. However, unmet needs still exist in the management of AILDs post liver transplantation particularly in building the evidence base for optimal immunosuppression as well as mitigating the risk of recurrent disease.
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Inflammatory conditions play a role in recurrence of PSC after liver transplantation: An international multicentre study
2022, JHEP Reports
Liver transplantation (LT) for primary sclerosing cholangitis (PSC) is complicated by recurrence of PSC (rPSC) in up to 25% of recipients. Recurrence has been shown to be detrimental for both graft and patient survival. For both PSC and rPSC, a medical cure is not available. To predict and ideally to prevent rPSC, it is imperative to find risk factors for rPSC that can be potentially modified. Therefore, we aimed to identify such factors for rPSC in a large international multicentre study including 6 centres in PSC-prevalent countries.
In this international multicentre, retrospective cohort study, 531 patients who underwent transplantation for PSC were included. In 25% of cases (n = 131), rPSC was diagnosed after a median follow-up of 6.72 (3.29–10.11) years post-LT.
In the multivariable competing risk model with time-dependent covariates, we found that factors representing an increased inflammatory state increase the risk for rPSC. Recurrent cholangitis before LT as indication for LT (hazard ratio [HR] 3.6, 95% CI 2.5–5.2), increased activity of inflammatory bowel disease after LT (HR 1.7, 95% CI 1.08–2.75), and multiple acute cellular rejections (HR: non-linear) were significantly and independently associated with an increased risk of rPSC. In contrast to the findings of previous studies, pretransplant colectomy was not found to be independently protective against the development of rPSC.
An increased inflammatory state before and after LT may play a causal and modifiable role in the development of rPSC. Pretransplant colectomy did not reduce the risk of rPSC per se. Recurrent cholangitis as indication for LT was associated with an increased risk of rPSC.
Recurrence of PSC (rPSC) negatively affects survival after liver transplant (LT). Modifiable risk factors could guide clinical management and prevention of rPSC. We demonstrate that an increased inflammatory state both before and after LT increases the incidence of rPSC. As these are modifiable factors, they could serve as targets for future studies and therapies. We also added further evidence to the ongoing debate regarding preventive colectomy for rPSC by reporting that in our multicenter study, we could not find an independent association between colectomy and risk of rPSC.
De novo and recurrent liver disease
2020, Best Practice and Research: Clinical Gastroenterology
Citation Excerpt :
Some studies have shown colectomy pre-LT reduces the incidence of rPSC [56], but this observation was not confirmed in a larger, multicenter study [55]. Multiple risk factors for rPSC have been identified including extremes of age at the time of LT, male gender, presence of cholangiocarcinoma, gender mismatch, cytomegalovirus (CMV) mismatch, or living-related donors (especially from parents) [57–62] (Table 1). Because numerous post-LT complications can cause biliary strictures, the diagnosis of rPSC can be challenging.
Decompensated cirrhosis due to nonalcoholic steatohepatitis (NASH), and autoimmune liver diseases (AILD) are the most common indications for liver transplantation (LT). AILD include autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). NASH and AILD share some peculiarities as they can recur in the new graft, compromising the quality of life, and graft and patient survival. De novo NASH or AIH connotes the development of these liver diseases in patients transplanted for other indications. The diagnosis of recurrent or de novo liver disease usually requires a liver biopsy aside from recurrent PSC, which can be diagnosed with compatible imaging studies and exclusion of other causes of biliary strictures. The treatment of recurrent NASH is lifestyle modifications aiming for weight loss. Recurrent and de novo AIH is usually treated with corticosteroids with or without azathioprine. Recurrent PBC should be treated with ursodeoxycholic acid. There are no proven treatment options for recurrent PSC. Patients with graft failure should be considered for repeat LT. Future investigations should use standardized diagnostic criteria for each disease, seek diagnostic biomarkers, and evaluate treatments that improve outcomes.

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Research LettersRisk factors for recurrence of primary sclerosing cholangitis of liver allograft

Summary

Lancet

Primary sclerosing cholangitis. Semin Gastrointestin

Dis

Research Letters
Risk factors for recurrence of primary sclerosing cholangitis of liver allograft