Treatment Of Primary Sclerosing Cholangitis Research Articles

The safety and efficacy of oral docosahexaenoic acid supplementation for the treatment of primary sclerosing cholangitis – a pilot study

Primary sclerosing cholangitis (PSC) is characterised by progressive inflammatory and fibrotic destruction of the biliary ducts. There are no effective medical therapies and presently high dose ursodeoxycholic acid is no longer recommended due to significant adverse events in a recent clinical trial. Cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction is associated with PSC in both children and adults. Since CFTR dysfunction leads to altered fatty acid metabolism, specifically reduced docosahexaenoic acid (DHA), we hypothesised that DHA supplementation might be an effective therapy for patients with PSC. To determine the safety and efficacy of oral DHA supplementation for the treatment of PSC. We conducted a 12 month open-label pilot study to evaluate safety of oral DHA and its effects on serum alkaline phosphatase as a primary outcome measure in 23 patients with PSC. DHA was administered orally at 800 mg twice per day. Secondary outcomes included changes in other liver function tests and fibrosis biomarkers. A 1.7-fold increase in serum DHA levels was observed with supplementation. The mean alkaline phosphatase level (±S.E.) at baseline was 357.8 ± 37.1 IU compared to 297.1 ± 23.7 IU (P < 0.05) after 12 months of treatment. There were no changes in other liver function tests and fibrosis biomarkers. No adverse events were reported. Oral DHA supplementation is associated with an increase in serum DHA levels and a significant decline in alkaline phosphatase levels in patients with PSC. These data support the need for a rigorous trial of DHA therapy in PSC.

Primary Sclerosing Cholangitis: Is Any Treatment Worthwhile?

While many therapeutic agents have been evaluated in Primary Sclerosing Cholangitis (PSC), none have been shown in controlled trials to modify the course of disease. The bile acid ursodeoxycholic acid (UDCA) has been widely used in the treatment of PSC but its use remains controversial. It may have a role in providing chemoprotection against the development of colonic dysplasia/cancer in patients with associated inflammatory bowel disease. The exclusion of IgG4-associated cholangitis, which generally responds to immunosuppressant agents, is essential prior to deciding on an appropriate therapeutic strategy in PSC. In the absence of proven therapeutic agents, treatment strategies are usually aimed at minimizing the complications of the biliary disease. Endoscopic management of dominant strictures may improve long-term outcomes. Orthotopic liver transplantation has a good outcome in patients with end stage PSC.

Medical and endoscopic therapy of primary sclerosing cholangitis

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease mainly affecting young male patients. PSC is characterised by chronic inflammation and fibrotic strictures of the intra- and extrahepatic biliary system, which eventually lead to cholestasis and biliary cirrhosis. However, the clinical course remains very variable. As the aetiology remains unknown, the development of a causative treatment is challenging and today no specific medical therapy is available. Ursodeoxycholic acid has been widely used for the treatment of PSC, but improved only biochemistry and/or symptoms in low- or medium dosages and is probably harmful in higher dosages. Other drugs such as immunosuppressive, antifibrotic or antibiotic agents have not been proven to be effective in large clinical trials. The endoscopic therapy encompasses balloon-dilatation and/or stenting of strictures, relieves clinical symptoms and improves a cholestatic enzyme profile. However, endoscopic therapy is limited to patients in advanced stages of PSC with biliary obstruction.

Hepatobiliary Complications of Inflammatory Bowel Disease

Several hepatobiliary abnormalities have been described in association with inflammatory bowel disease (IBD), including primary sclerosing cholangitis (PSC), small duct PSC, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma, and cholelithiasis. PSC is the most common biliary condition in patients with IBD, with an incidence ranging from 2.5% to 7.5%. PSC usually progresses insidiously and eventually leads to cirrhosis independent of inflammatory bowel disease activity. There is a very high incidence of cholangiocarcinoma and an elevated risk for developing colon cancer in patients with PSC. Medical therapy has not proven successful in slowing disease progression or prolonging survival. Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins, such as cholestyramine or colestipol. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been conclusively demonstrated to improve survival or decrease the need for liver transplantation. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.

Antibiotics for the Treatment of Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease that is associated with considerable morbidity and mortality. The disease etiopathogenesis has not been well defined. Several observations suggest that portal bacteremia or chronic bile duct infection may be factors that could play a role in the pathogenesis of the disease. Clinical trials have tested different treatments for PSC but without convincing evidence of benefit. Liver transplantation is the only available therapeutic option that is thought to be beneficial for PSC. Antibiotics have been used in several case series over the years to treat PSC and have had, in some cases, impressive benefits when compared with other drugs used for treating the disease. We gathered the available data for different antibiotics used in PSC in this review. Further studies are needed to support the efficacy of using antibiotics for PSC patients.

Systematic review: management options for primary sclerosing cholangitis and its variant forms - IgG4-associated cholangitis and overlap with autoimmune hepatitis

Primary sclerosing cholangitis (PSC) remains a challenging disease to manage. The main goals are prevention of disease progression and reduction of the increased cancer risk. To review the management strategies for PSC and its variant forms based on published studies. Publications were identified using Pubmed, Medline and Ovid search engines. Distinguishing PSC from variants, such as IgG4-associated cholangitis, and overlap with autoimmune hepatitis is essential to guide treatment decisions. There is no proven efficacious medical treatment for PSC. Ursodeoxycholic acid has been disappointing in low and moderate doses, and potentially dangerous in higher doses, although its role and optimal dose in chemoprevention requires investigation. The novel bile acid, 24-norursodeoxycholic acid, has shown promise in mouse models; human trials are in progress. Dominant strictures are optimally managed by dilatation and stenting to relieve obstructive complications, although exclusion of biliary malignancy is essential. Liver transplantation is the only proven therapy for those with advanced disease. Cholangiocarcinoma remains the most unpredictable and feared complication. In highly selected groups, neo-adjuvant chemoradiation with liver transplantation seems promising, but requires further validation. Screening for inflammatory bowel disease and surveillance for colorectal carcinoma should not be overlooked. The effective management of PSC and its variants is hindered by uncertainties regarding pathogenesis of disease and factors responsible for its progression. Genome studies may help to identify further targets for drug therapy and factors leading to malignant transformation.

Current Management of Primary Sclerosing Cholangitis in Pediatric Patients

Primary sclerosing cholangitis (PSC) is a chronic cholestatic condition affecting the extrahepatic and intrahepatic biliary tree. The incidence is seemingly increasing in children as a result of increased use of cholangiographic screening techniques in children with inflammatory bowel disease. The clinical presentation of PSC in childhood is variable and frequently without obvious cholestatic features, and cholangiography is essential for the diagnosis of this disorder. Histologic findings may help to exclude autoimmune sclerosing cholangitis. The underlying pathogenesis remains poorly understood and, as a result, therapeutic agents that halt disease progression and improve prognosis are lacking. PSC treatment is mainly supportive and directed at controlling cholestatic symptoms and preventing complications. Ursodeoxycholic acid is helpful in inducing biochemical improvement; long-term pediatric studies to determine a benefit of this agent in young patients are lacking, although results from adult studies have not been promising. Some agents such as antibiotics are under investigation with some promising results. Liver transplantation is required for children who progress to end-stage liver disease. Prospective multicenter trials in children with PSC are needed.

β-Adrenoceptor blockade in sclerosing cholangitis of Mdr2 knockout mice: antifibrotic effects in a model of nonsinusoidal fibrosis

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease with high propensity to develop into cholangiocarcinoma. The hepatobiliary disorder of PSC is due to progressive fibrosis surrounding the intra- and extrahepatic bile ducts. Until now, no effective medical therapy exists. To study the progression of sclerosing cholangitis after inhibition of the sympathetic nervous system by blockade of the β-adrenoceptors, we used the Mdr2−/− mouse model, which develops periportal fibrosis similar to human PSC. Liver tissues of Mdr2−/− mice untreated or treated with the β-adrenoceptor antagonist propranolol were analyzed for inflammation and fibrosis progression at different time points by histological scoring and immunostaining for α-smooth muscle actin (α-SMA), CD45 and S100A4. Transaminases and hydroxyproline contents were determined. Expression of angiotensinogen, endothelin-1, TGF-β, TNF-α, CTGF and procollagen 1A1 was studied by real-time PCR on laser-microdissected areas of acinar zones I and II–III. After 3 months, periportal fibrosis had developed in Mdr2−/− mice, but immunostaining revealed no sinusoidal and only minor periportal contribution of myofibroblasts with prominent fibroblasts. Propranolol treatment of Mdr2−/− mice improved liver architecture. Additionally, inflammation and fibrosis were significantly reduced. After 3 months of treatment, the antifibrotic effect of the β-blockade was most obvious. The transcript levels of procollagen 1A1, TNF-α, TGF-β, CTGF and endothelin-1 were markedly repressed in the portal areas of treated mice. Taken together, these data show that propranolol efficiently delays progression of sclerosing cholangitis. Therefore, the blockade of β-adrenoceptors is a promising option to support future therapeutic strategies in the treatment of human PSC.

Xanthogranulomatous cholecystitis complicated with primary sclerosing cholangitis: Report of a case

Patients with primary sclerosing cholangitis (PSC) are at an increased risk for biliary tract carcinoma. The preoperative diagnosis of a biliary tract tumor as a malignancy is difficult, even using new modalities such as multidetector computed tomography (MD-CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiography (ERC), and (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). Surgery is considered to be first line of treatment when these examinations suggest the presence of malignancy in the biliary tract, depending on both the curability of the cancer and the impaired liver function due to PSC. The management of gallbladder masses in patients with PSC remains problematic due to difficulties with the precise diagnosis and adequate surgery. Xanthogranulomatous cholecystitis (XGC) is a type of chronic cholecystitis, and sometimes coexists with gallbladder cancer. It is very difficult to make a preoperative diagnosis differentiating these two diseases. This report presents the case of a patient with XGC, who had been suspected of having gallbladder cancer before surgery, because the tumorous lesion emerged within a year and showed a focally increased uptake by FDG-PET during the follow up for PSC for years. This is the first case of XGC discovered during treatment for PSC.

Update on primary sclerosing cholangitis

Early studies in primary sclerosing cholangitis (PSC) were concerned with disease characterization, and were followed by epidemiological studies of PSC and clinical subsets of PSC as well as a large number of treatment trials. Recently, the molecular pathogenesis and the practical handling of the patients have received increasing attention. In the present review we aim to give an update on the pathogenesis of PSC and cholangiocarcinoma in PSC, as well as to discuss the current opinion on diagnosis and treatment of PSC in light of the recent European Association for the Study of the Liver and the American Association for the Study of Liver Diseases practice guidelines.

The urgent need for evaluating recurrent primary sclerosing cholangitis in living donor liver transplantation

In an earlier issue this year, Alabraba and colleagues1 evaluated the risk factors for recurring primary sclerosing cholangitis (PSC); we read with great interest their article entitled “A Re-Evaluation of the Risk Factors for the Recurrence of Primary Sclerosing Cholangitis in Liver Allografts.” Analyzing prospectively collected data for 230 consecutive deceased donor liver transplantation (DDLT) procedures for PSC over a 20-year period with an 83-month follow-up, the authors reported that 54 (24%) of the DDLT recipients presented with recurrent PSC at a median of 4.6 years after transplantation. An analysis of the risk factors indicated that colectomy offered a protective effect against PSC recurrence, whereas the use of grafts recovered under extended donor criteria (EDC) was associated with a higher rate of recurrence. Indeed, although liver transplantation has become an accepted treatment for PSC with liver failure with excellent overall survival, recurrent disease continues to be a threat with a higher rate of retransplantation.2 Identification of the factors affecting recurrence is therefore important. In this context, we were disappointed that some of the recently reported disturbing aspects of living donor liver transplantation (LDLT) are not discussed in the article.1 In contrast to Western countries, liver transplantation from a living donor remains the most realistic option in the Far East. Following the successful results with DDLT reported from the West, LDLT has been applied for PSC with liver failure in Japan. One concern in applying LDLT for PSC has been the unknown effect of a shared genetic disposition in a blood-related recipient and donor pair, which may affect the recurrence of PSC and hence graft survival over the long term. Until recently, however, only sporadic case reports have been published with short follow-up periods, and little information on this aspect has been available. To fill the void, we conducted a retrospective study on the clinical course of PSC after LDLT at our institution. The results of our analysis indicated that PSC not only recurred as in the DDLT series but also recurred at a much higher rate.3 When the analysis was restricted to cases with biologically related live donors, recurrent PSC occurred in 50% of the recipients with a mean time to diagnosis from LDLT of 3.3 years. An observation supporting this finding was reported by another high-volume center.4 Among the 22 patients who survived for more than a year in the series, 13 (59%) presented with PSC recurrence with a mean follow-up period of 2.6 years, 5 of whom died or required retransplantation for graft failure. These preliminary reports have raised considerable concerns, and currently, a nationwide survey, supported by the Ministry of Health, Labor, and Welfare, is ongoing in Japan. The first study by the authors analyzing the risk factors for recurrent PSC in the allograft was published in 2002,5 and since then, LDLT has evolved and spread worldwide, becoming a realistic option in the West and in the East because of the universal organ shortage. Findings regarding the mid-term to long-term outcomes of LDLT for PSC from European or North American series, however, have not been reported despite the rapid accumulation of adult-to-adult LDLT cases. In their analysis, Alabraba and colleagues1 reported that the use of EDC grafts resulted in a 5-fold increase of recurrent PSC, with a 5-year recurrence-free survival of 71% versus 91% for non-EDC grafts. Preliminary studies in LDLT, however, have suggested a further significant impact when a graft donated by a blood-related living donor is used for PSC. In this era of severe graft shortage, the interpretation of these outcomes requires caution, but the implications are nonetheless alarming. Further validation is urgently needed. Currently, however, PSC accounts for less than 3% of all LDLT procedures performed in Japan because of its rarity in comparison with the higher prevalence in Nordic countries and the United States. Studies focusing on the outcomes of LDLT for PSC in a Western series are greatly anticipated. Sumihito Tamura*, Yasuhiko Sugawara*, Noriyo Yamashiki*, Junichi Kaneko*, Norihiro Kokudo*, * Artificial Organ and Transplantation Division, Department of Surgery, Graduate School of Medicine, University of Tokyo Tokyo, Japan.

EASL Clinical Practice Guidelines: Management of cholestatic liver diseases

EASL Clinical Practice Guidelines (CPG) on the management of cholestatic liver diseases define the use of diagnostic, therapeutic and preventive modalities, including non-invasive and invasive procedures, in the management of patients with cholestatic liver diseases. They are intended to assist physicians and other healthcare providers as well as patients and interested individuals in the clinical decision-making process by describing a range of generally accepted approaches for the diagnosis, treatment and prevention of specific cholestatic liver diseases. The clinical care for patients with cholestatic liver diseases has advanced considerably during recent decades thanks to growing insight into pathophysiological mechanisms and remarkable methodological and technical developments in diagnostic procedures as well as therapeutic and preventive approaches. Still, various aspects in the care of patients with cholestatic disorders remain incompletely resolved. The EASL CPG on the management of cholestatic liver diseases aim to provide current recommendations on the following issues:

Minocycline in the Treatment of Patients With Primary Sclerosing Cholangitis: Results of a Pilot Study

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of young adults that is associated with significant morbidity and mortality. No effective medical therapy is available. Minocycline has been found to exert biological effects independent of its antimicrobial properties, including anti-inflammatory activities such as inhibition of inducible nitric oxide synthase, upregulation of interleukin 10, and direct suppressive effect on B- and T-cell function. Minocycline may also inhibit cell death pathways by reducing both proapoptotic and proinflammatory enzyme activation. We sought to investigate the safety and efficacy of minocycline among patients with PSC. We evaluated the efficacy of minocycline in patients with PSC in a pilot study. Sixteen patients with PSC were enrolled. Minocycline, 100 mg orally twice daily, was given for 1 year. A statistically significant improvement in serum alkaline phosphatase activity (330 U/l vs. 265 U/l, P=0.04) and Mayo risk score (0.55 vs. 0.02, P=0.05) occurred with treatment. Serum bilirubin and albumin remained essentially unchanged while on treatment. The results of this pilot study indicate that minocycline is reasonably well tolerated and potentially effective in patients with PSC. These findings might be explained by the anti-inflammatory and antiapoptotic properties of minocycline. Though the data presented are too preliminary to support the clinical use of minocycline in the treatment of PSC at this time, its use should be further investigated.

Medical Treatment of Primary Sclerosing Cholangitis: A Role for Novel Bile Acids and other (post-)Transcriptional Modulators?

Primary sclerosing cholangitis (PSC) is a rare chronic cholestatic disease of the liver and bile ducts that is associated with inflammatory bowel disease, generally leads to end-stage liver disease, and is complicated by malignancies of the biliary tree and the large intestine. The pathogenesis of PSC remains enigmatic, making the development of targeted therapeutic strategies difficult. Immunosuppressive and antifibrotic therapeutic agents were ineffective or accompanied by major side effects. Ursodeoxycholic acid (UDCA) has consistently been shown to improve serum liver tests and might lower the risk of colon carcinoma and cholangiocarcinoma by yet unknown mechanisms. Whether "high dose" UDCA improves the long-term prognosis in PSC as suggested by small pilot trials remains to be demonstrated. The present overview discusses potential therapeutic options aside of targeted immunological therapies and UDCA. The C23 bile acid norUDCA has been shown to markedly improve biochemical and histological features in a mouse model of sclerosing cholangitis without any toxic effects. Studies in humans are eagerly being awaited. Nuclear receptors like the farnesoid-X receptor (FXR), pregnane-X receptor (PXR), vitamin D receptor (VDR), and peroxisome-proliferator-activator receptors (PPARs) have been shown to induce expression of diverse carriers and biotransformation enzymes of the intestinal and hepatic detoxification machinery and/or to modulate fibrogenesis. Pros and cons of respective receptor agonists for the future treatment of PSC are discussed in detail. In our view, the novel bile acid norUDCA and agonists of PPARs, VDR, and PXR appear particularly attractive for further studies in PSC.

Current Treatments of Primary Sclerosing Cholangitis

Primary Sclerosing Cholangitis (PSC) is a chronic cholestatic disease characterized by hepatic inflammation and obliterative fibrosis, resulting in both intra- and extra-hepatic bile duct strictures. End-stage liver disease and bile duct carcinoma represent frequent complications. Incidence and prevalence of PSC in USA have been recently estimated as 0.9 per 100,000 person-years, and 1-6 per 100,000 person-years, respectively. Major diagnostic criteria include the presence of multifocal strictures, beadings of bile ducts, and compatible biochemical profile, once excluded secondary causes of cholangitis. Since the aetiology of PSC remains poorly defined, medical therapy is currently limited to symptom improvement and prolonged survival. Ursodeoxycholic acid (UDCA), corticosteroids and immunosuppressants have been proposed alone or in combination to improve the clinical outcome. In selected cases, surgical or endoscopic procedures need to be considered. Orthotopic liver transplantation (OLT) is at the moment the only definitive approach although disease relapse has been reported. In this article the state of the art in PSC treatment and future promises in this field are reviewed.

Multidisciplinary approach to benign biliary strictures

The various approaches used for the management of patients with benign biliary strictures are justified by the diverse nature, clinical presentation, and severity of these strictures. Benign biliary strictures are most commonly postoperative, a consequence of injury during laparoscopic cholecystectomy or fibrosis after biliary duct-to-duct or bilioenteric anastomoses (ie, liver transplantation). Less frequently, benign strictures are due to chronic pancreatitis or other nonmalignant diseases, including external compression, parasites, stone perforation, and infections. Because of their peculiar pathogenesis, localization, and short extension into the bile duct, the majority of these strictures can be approached by operative treatments such as surgical bypass and endoscopic--or radiological--dilation. In contrast, primary sclerosing cholangitis (PSC) is a systemic disease with immune-mediated inflammation and subsequent fibrosis of the bile ducts with the development of multiple strictures due to an "intrinsic" liver disease; thus, medical therapy and pharmacologic research are mainly focused on the treatment of PSC rather than other benign biliary strictures. However, none of the previously mentioned benign strictures has a univocal and sole treatment. Any attempt to identify a standard treatment for all the strictures is questionable, inconclusive, and most likely useless due to the diversity of patients and diseases. Gastroenterologists, radiologists, and surgeons work in tight collaboration, not in competition, to individualize the patients' treatment. The morphology and extension of the stricture, its location, the theoretical pathogenesis (eg, intrinsic strictures, strictures due to inflammation and fibrosis after bile leak, ischemic lesions), the patients' specific characteristics (comorbidity and history of prior surgery, including enterobiliary anastomoses and gastric resection), and preferences should indicate the treatment that may offer the patient major benefits with a lower complication rate. Unfortunately, in most of the cases, choosing between different treatments is more likely based on local availability than their actual effectiveness and indication.

Indications for non‐transplant surgery in primary sclerosing cholangitis

Primary sclerosing cholangitis (PCS) is a progressive disease leading to secondary biliary cirrhosis. Patients are at increased risk of developing cholangiocarcinoma, which is usually diagnosed at an advanced stage. Treatment of PCS includes medical therapy, endoscopic biliary dilation, percutaneous transhepatic stenting, extrahepatic biliary resection and liver transplantation. The most effective management of primary sclerosing cholangitis before the onset of cirrhosis remains unclear. Non‐transplant surgical procedures have a limited but defined role in patients with PCS. Resection of the extrahepatic biliary tree in symptomatic non‐cirrhotic patients improves hyperbilirubinaemia and prolongs both transplant‐free and overall survival when compared with non‐operative dilation and/or stenting. Surgical resection may also definitively establish or exclude a diagnosis of cholangiocarcinoma in patients with dominant extrahepatic or perihilar strictures. Extrahepatic bile duct resection may also reduce the risk of cholangiocarcinoma. Extrahepatic biliary resection should be considered in selected non‐cirrhotic patients with symptomatic biliary obstruction and dominant extrahepatic and/or perihilar strictures. Those patients in whom cholangiocarcinoma is suspected should also undergo resection.

This Month in Gastroenterology

This Month in Gastroenterology

Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Author's reply

1 Bambha K, Kim WR, Talwalkar J, et al. Incidence, clinical spectrum, and outcomes of primary sclerosing cholangitis in a United States community. Gastroenterology 2003; 125: 1364–9. 2 Van Milligen de Wit, AW, van Deventer, SJ, Tytgat, GN. Immunogenetic aspects of primary sclerosing cholangitis: Implications for therapeutic strategies. Am J Gastroenterol 1995; 90: 893–900. 3 Chapman RW. The management of primary sclerosing cholangitis. Curr Gastroenterol Rep 2003; 5: 9–18. 4 Ponsioen CY, Vrouenraets SM, Prawirodirdjo W, et al. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population. Gut 2002; 51: 562–6. 5 Lipsky JJ. Mycophenolate mofetil. Lancet 1996; 348: 1357–9. 6 Sterling RK, Salvatori JJ, Luketic VA, et al. A prospective, randomized-controlled pilot study of ursodeoxycholic acid combined with mycophenolate mofetil in the treatment of primary sclerosing cholangitis. Aliment Pharmacol Ther 2004; 20: 943–9. 7 Talwalkar JA, Angulo P, Keach JC, Petz JL, Jorgensen RA, Lindor KD. Mycophenolate mofetil for the treatment of primary sclerosing cholangitis. Am J Gastroenterol 2005; 100: 308–12. 8 Schramm C, Schirmacher P, Helmreich-Becker I, Gerker G, Meyer zum Buschenfelde KH, Lohse AW. Combined therapy with azathioprine, prednisolone, and ursodiol in patients with primary sclerosing cholangitis. A case series. Ann Intern Med 1999; 131: 943–6. 9 Corpechot C, Carrat F, Bahr A, Chretien Y, Poupon RE, Poupon R. The effect of ursodeoxycholic acid therapy on the natural course of primary biliary cirrhosis. Gastroenterology 2005; 128: 297–303. 10 Lankarani KB. Use of mycophenolate mofetil in the treatment of primary sclerosing cholangitis. J Clin Gastroenterol 2003; 36: 86. doi: 10.1111/j.1365-2036.2005.02495.x

Restorative Proctocolectomy and Ileal Pouch–Anal Anastomosis for Ulcerative Colitis after Liver Transplant for Primary Sclerosing Cholangitis: Case Report and Review of Literature

Primary sclerosing cholangitis (PSC) is present in 5 per cent of patients with ulcerative colitis (UC). Conversely, as many as 90 per cent of patients with PSC have been found to have UC. The accepted treatment for advanced PSC is orthotopic liver transplant, and the treatment of ulcerative colitis with concomitant PSC is restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). A small number of studies have shown that there is an increased risk of pouchitis in UC patients with PSC after ileal pouch-anal anastomosis. We report a case of a 45-year-old male who underwent a two-stage restorative proctocolectomy with IPAA after previous orthotopic liver transplant for PSC. We have reviewed the available literature concerning restorative proctocolectomy after liver transplantation, giving special attention to postoperative complications and subsequent development of pouchitis. It is important to be aware of the possibility of increased risk for development of pouchitis and to follow these patients closely to prevent complications.