Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

Fosby, Bjarte; Karlsen, Tom H.; Melum, Espen

doi:10.3748/wjg.v18.i1.1

Cited by 136 publications

(103 citation statements)

References 167 publications

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“…However, organ rejection is a thorny problem after transplantation, especially acute rejection which is the main cause of early dysfunction and retransplantation [21]. Therefore, it is very important to search new and effective methods to prevent and inhibit the organ rejection response in organ transplantation.…”

Section: Discussionmentioning

confidence: 99%

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

Shi

Song

et al. 2013

BioMed Research International

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The 4-1BB signal pathway plays a key role in organ transplantation tolerance. In this study, we have investigated the effect of gene silencing of 4-1BB by RNA interference (RNAi) on the acute rejection in rats with liver transplantation. The recombination vector of lentivirus that contains shRNA targeting the 4-1BB gene (LV-sh4-1BB) was constructed. The liver transplantation was performed using the two-cuff technique. Brown-Norway (BN) recipient rats were infected by the recombinant LVs. The results showed that gene silencing of 4-1BB by RNAi downregulated the 4-1BB gene expression of the splenic lymphocytes in vitro, and the splenic lymphocytes isolated from the rats with liver transplantation. LV-sh4-1BB decreased the plasma levels of liver injury markers including AST, ALT, and BIL and also decreased the level of plasma IL-2 and IFN-γ in recipient rats with liver transplantation. Lentivirus-mediated delivery of shRNA targeting 4-1BB gene prolonged the survival time of recipient and alleviated the injury of liver morphology in recipient rats with liver transplantation. In conclusion, our results demonstrate that gene silencing of 4-1BB by RNA interference inhibits the acute rejection in rats with liver transplantation.

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Section: Discussionmentioning

confidence: 99%

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

Shi

Song

et al. 2013

BioMed Research International

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“…22 It is hypothesized that bacterial products can translocate through an inflamed gut while gut-derived memory T-lymphocytes target the liver via aberrantly expressed adhesion molecules and contribute to cholangiocyte damage. 23 This concept is also supported by the fact that pre-liver transplant colectomy may afford protection against recurrent PSC in the transplanted liver, 24 as well as the presence of common peripheral anti-neutrophil cytoplasmic antibodies (pANCA) in both these disease. 25 Nonetheless, this concept does not explain the pathogenesis of PSC in patients without IBD.…”

Section: Pathogenesismentioning

confidence: 99%

Primary Sclerosing Cholangitis: Diagnosis, Prognosis, and Management

Singh

Talwalkar

2013

Clinical Gastroenterology and Hepatology

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Primary sclerosing cholangitis (PSC) is a chronic immune-mediated disease of the liver of unclear etiology, characterized by chronic inflammation and fibrosis of bile ducts. It primarily affects middle aged men, and is associated with 4-fold increased mortality as compared to ageand gender-matched population. Progressive biliary and hepatic damage results in portal hypertension and hepatic failure in a significant majority of patients over a 10–15 year period from initial diagnosis. In addition, PSC confers a markedly increased risk of hepatobiliary cancer, including cholangiocarcinoma and gallbladder cancer as compared to the general population, and cancer is the leading cause of mortality in patients with PSC. It is associated with inflammatory bowel disease in 70% patients, and increases the risk of colorectal cancer almost 10-fold. Despite significant research efforts in this field, the pathogenic mechanisms of PSC are still incompletely understood, although growing evidence supports the role of genetic and immunologic factors. There are no proven medical therapies that alter the natural course of the disease. Thus, liver transplantation is the only available treatment for patients with advanced PSC, with excellent outcomes in this population.

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“…2 However, the disease may reappear in approximately 25% of patients after transplant. 53 Diagnosis of recurrence is made when there is no evidence of long-term rejection or vascular insults in the liver. Colectomy before or during the first liver transplant in patients with associated inflammatory bowel disease may reduce the rate of post-transplant recurrence.…”

Section: Primary Sclerosing Cholangitismentioning

confidence: 99%

The Cholangiopathies

Lazaridis

LaRusso

2015

Mayo Clinic Proceedings

178

170

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Cholangiocytes (ie, the epithelial cells that line the bile ducts) are an important subset of liver cells. They are actively involved in the modification of bile volume and composition, are activated by interactions with endogenous and exogenous stimuli (eg, microorganisms, drugs), and participate in liver injury and repair. The term cholangiopathies refers to a category of chronic liver diseases that share a central target: the cholangiocyte. The cholangiopathies account for substantial morbidity and mortality given their progressive nature, the challenges associated with clinical management, and the lack of effective medical therapies. Thus, cholangiopathies usually result in end-stage liver disease requiring liver transplant to extend survival. Approximately 16% of all liver transplants performed in the United States between 1988 and 2014 were for cholangiopathies. For all these reasons, cholangiopathies are an economic burden on patients, their families, and society. This review offers a concise summary of the biology of cholangiocytes and describes a conceptual framework for development of the cholangiopathies. We also present the recent progress made in understanding the pathogenesis of and how this knowledge has influenced therapies for the 6 common cholangiopathies—primary biliary cirrhosis, primary sclerosing cholangitis, cystic fibrosis involving the liver, biliary atresia, polycystic liver disease, and cholangiocarcinoma—because the latest scientific progress in the field concerns these conditions. We performed a search of the literature in PubMed for published papers using the following terms: cholangiocytes, biliary epithelia, cholestasis, cholangiopathy, and biliary disease. Studies had to be published in the past 5 years (from June 1, 2009, through May 31, 2014), and non-English studies were excluded.

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Recurrence and rejection in liver transplantation for primary sclerosing cholangitis

Cited by 136 publications

References 167 publications

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

Gene Silencing of 4-1BB by RNA Interference Inhibits Acute Rejection in Rats with Liver Transplantation

Primary Sclerosing Cholangitis: Diagnosis, Prognosis, and Management

The Cholangiopathies

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