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Roger W. Chapman - One of the best experts on this subject based on the ideXlab platform.
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An update on Primary Sclerosing Cholangitis.
Current opinion in gastroenterology, 2008Co-Authors: James R. L. Maggs, Roger W. ChapmanAbstract:PURPOSE OF REVIEW: Primary Sclerosing Cholangitis is a chronic cholestatic liver disease characterized by strictures of the biliary tree complicated by cirrhosis and cholangiocarcinoma. It is immune mediated, although the precise aetiology remains unknown. RECENT FINDINGS: The research into aetiology, genetic associations, pathogenesis, epidemiology, diagnosis of cholangiocarcinoma and medical treatments are discussed. SUMMARY: Multiple gene polymorphisms and human leucocyte antigen haplotype associations with Primary Sclerosing Cholangitis have been investigated. Common inflammatory bowel disease associated polymorphisms and ulcerative colitis associated human leucocyte antigen haplotypes are not associated with Primary Sclerosing Cholangitis. Biliary epithelial cells may mediate their own destruction by exaggerating innate and adaptive immune responses to bacterial products in the liver. The natural history of large and small duct Primary Sclerosing Cholangitis has been reviewed. Positron emission tomography may be a useful adjunct to current imaging modalities in the pretransplant assessment of patients to exclude cholangiocarcinoma. Ursodeoxycholic acid remains the most studied medical treatment for Primary Sclerosing Cholangitis; pilot studies suggest a possible role for tacrolimus and silymarin, however further studies are required.
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The management of Primary Sclerosing Cholangitis.
Clinics in liver disease, 1998Co-Authors: S A Mitchell, Roger W. ChapmanAbstract:Primary Sclerosing Cholangitis is a chronic cholestatic liver disease characterized by a progressive, obliterating fibrosis of the intrahepatic and extrahepatic bile ducts. The pathogenesis of PSC is unknown, but it is thought to be an immune-mediated disease. Although the role of cupruretics, immunosuppressants (corticosteroids, azathioprine, tacrolimus, methotrexate), antifibrogenic agents, and ursodeoxycholic acid in the treatment of Primary Sclerosing Cholangitis is reviewed, none of these agents has been shown to retard or reverse the rate of disease progression. Of these therapies, ursodeoxycholic acid at high doses looks the most promising, but large trials are needed to establish whether treatment with high-dose ursodeoxycholic acid influences the morbidity and mortality associated with Primary Sclerosing Cholangitis.
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Superficial thrombophlebitis, dysplasia, and cholangiocarcinoma in Primary Sclerosing Cholangitis
Gastroenterology, 1994Co-Authors: Eduardo B. Martins, Kenneth A. Fleming, Maria C. Garrido, Keith R. Hine, Roger W. ChapmanAbstract:Cholangiocarcinoma occurs in approximately 10% of patients with Primary Sclerosing Cholangitis. Usually, liver failure, rapidly progressing jaundice, and an increase in alkaline phosphatase levels are suggestive diagnostic features. We report two cases of patients with Primary Sclerosing Cholangitis who developed cholangiocarcinoma without jaundice and with no changes in their serum biochemistry. Both patients were taking ursodeoxycholic acid at the time of tumor diagnosis. Initial suspicion of malignancy was based on the development of superficial thrombophlebitis. Liver histology showed evidence of bile duct epithelial dysplasia in areas free from tumor in one patient, and in the other, bile duct epithelial dysplasia preceded the appearance of cholangiocarcinoma by at least 18 months. In one of the cases, the dysplastic epithelium stained positively for carcinoembryonic antigen. The histological finding of bile duct epithelial dysplasia in patients with Primary Sclerosing Cholangitis may suggest either imminent or actual development of cholangiocarcinoma and may thus affect consideration of orthotopic liver transplantation. In addition, the development of superficial thrombophlebitis in patients with Primary Sclerosing Cholangitis should arouse suspicion of the presence of cholangiocarcinoma even if there is no evidence of deterioration of the liver function or a dominant stricture on endoscopic retrograde cholangiography.
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Tissue distribution of autoantigen specific for Primary Sclerosing Cholangitis
Journal of clinical pathology, 1993Co-Authors: Roger W. Chapman, Kenneth A. FlemingAbstract:AIM: To investigate the tissue distribution of the autoantigen specific for Primary Sclerosing Cholangitis. METHODS: A range of normal frozen tissues including nervous system, muscle, uterus, ovary, prostate, pancreas, thyroid, salivary gland, adrenal gland, colon, gall bladder, stomach, jejunum, aorta, skin, kidney, liver, spleen and thymus was sectioned, fixed with acetone, and air-dried. Normal bone marrow and HL60, K562, and U937 cells were cytocentrifuged on to slides, air-dried, and alcohol fixed. Four sera from Primary Sclerosing Cholangitis with high titre antibody (> 1/100) were used to screen the tissues using either two-step or APAAP immunohistochemistry. Normal sera were used as controls. RESULTS: Positive signal was detected in neutrophils in spleen with three out of four Primary Sclerosing Cholangitis sera while one out of four Primary Sclerosing Cholangitis sera stained spindle cells in the liver. All four sera stained mature neutrophils of the normal bone marrow. Some bone marrow neutrophil precursors (metamyelocytes and myelocytes) were also positive. All other tissues, including HL60, K562, and U937 cells, were negative. Normal sera were negative on all tissues. CONCLUSION: Antigen specific for Primary Sclerosing Cholangitis seems to be unique to neutrophil polymorphs and is present only after myeloblast differentiation of the myeloid cell line. The antigen may be within the secondary granule of the neutrophil polymorph.
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Antineutrophil antibody: a test for autoimmune Primary Sclerosing Cholangitis in childhood?
Gut, 1993Co-Authors: Roger W. Chapman, Giorgina Mieli-vergani, P. Cheeseman, C. P. J. Charlton, J. A. Walker-smith, Kenneth A. FlemingAbstract:The detection of an antineutrophil antibody which is highly sensitive and specific for adult Primary Sclerosing Cholangitis using indirect immunoalkaline phosphatase has been previously described. In this study, the diagnostic potential of this method in childhood Primary Sclerosing Cholangitis is described. A range of 72 blinded children's sera (36 boys), aged six months to 21 years (10 Primary Sclerosing Cholangitis, eight autoimmune chronic active hepatitis, 10 alpha-1 antitrypsin deficiency, 12 extrahepatic bile duct atresia, 11 ulcerative colitis and 21 normal subjects) was assayed. Eight of the 10 Primary Sclerosing Cholangitis patients were correctly identified. Three patients with chronic active hepatitis also showed the characteristic Primary Sclerosing Cholangitis pattern of staining. No ulcerative colitis patients or any other patients showed this pattern of staining. All normal subjects were negative. As in adult Primary Sclerosing Cholangitis, there is a specific antineutrophil antibody in childhood Primary Sclerosing Cholangitis and this provides further evidence towards an autoimmune aetiology of this condition. The test may have diagnostic potential.
Keith D. Lindor - One of the best experts on this subject based on the ideXlab platform.
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Advances in Primary Sclerosing Cholangitis.
The lancet. Gastroenterology & hepatology, 2016Co-Authors: Jennifer L. Horsley-silva, Elizabeth J Carey, Keith D. LindorAbstract:Primary Sclerosing Cholangitis is a chronic, progressive cholangiopathy that frequently affects men and is associated with inflammatory bowel disease. Although the cause of the disease is still debated, a genetic association and link to immune-mediated disease triggered by environmental factors are thought to contribute. The disease can present as isolated imaging abnormalities, biochemical changes, cholangiocarcinoma, or end-stage complications such as cirrhosis. Symptoms of Primary Sclerosing Cholangitis include fatigue, jaundice, pruritus, or steatorrhoea. Differentiation of Primary Sclerosing Cholangitis can be challenging because other chronic cholangiopathies can present similarly; however, the distinction is necessary to optimise disease surveillance. Management involves assessment for comorbid inflammatory bowel disease and exclusion of other associated cholangiopathic disorders. Patients with Primary Sclerosing Cholangitis have a poor prognosis; progression to liver cirrhosis is common, and an increased risk of hepatobiliary and colorectal cancers is present in those with inflammatory bowel disease. Although much research involves locating an active therapy that can alter the disease course, the only available treatment is liver transplantation, and risk for disease recurrence remains. Use of ursodeoxycholic acid can improve alkaline phosphatase and bilirubin concentrations but does not alter the disease course. In this Review, we summarise aetiological theories, provide an update on hepatobiliary malignancies that require surveillance, and discuss exciting areas of investigation for potential treatment.
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Commentary: Primary Sclerosing Cholangitis
Management of Benign Biliary Stenosis and Injury, 2015Co-Authors: Keith D. LindorAbstract:This chapter provides a nice overview of Primary Sclerosing Cholangitis (PSC). It brings the reader up to date on current state of knowledge; however it also points out a number of areas in which further work is necessary to answer currently unresolved questions.
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Primary Sclerosing Cholangitis
The Lancet, 2013Co-Authors: Gideon M Hirschfield, Keith D. Lindor, Tom H Karlsen, David H AdamsAbstract:Summary Primary Sclerosing Cholangitis is the classic hepatobiliary manifestation of inflammatory bowel disease and is generally chronic and progressive. Patients frequently present with asymptomatic, anicteric cholestasis, but many develop progressive biliary strictures with time, leading to recurrent Cholangitis, biliary cirrhosis, and end-stage liver disease. Medical treatment does not slow the progression of disease, and many patients need liver transplantation, after which recurrent disease is a risk. The increased incidence of hepatobiliary cancer, which is not related to the underlying severity of biliary fibrosis, is of particular concern. Risk of colorectal cancer is also increased in patients with coexistent inflammatory bowel disease. Mechanistic insights have arisen from studies of secondary Sclerosing Cholangitis, in which a similar clinical profile is associated with a specific cause, and genomic studies have elucidated potential disease-initiating pathways in the Primary form. The close association between inflammatory bowel disease and Primary Sclerosing Cholangitis underscores the need to further understand the role of environmental factors in generation of lymphocytes that are postulated to be retargeted, deleteriously, to the biliary tree. Treatment of Primary Sclerosing Cholangitis is confined to supportive measures, but advances in pathobiology suggest that new stratified approaches will soon be available.
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Serum lipids in Primary Sclerosing Cholangitis.
Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver, 2011Co-Authors: Emmanouil Sinakos, Ghulam Abbas, Roberta A. Jorgensen, Keith D. LindorAbstract:Abstract Background Limited data are available regarding the serum lipids in Primary Sclerosing Cholangitis. Aims To determine the lipid levels in patients with Primary Sclerosing Cholangitis. Methods We monitored the serum lipid levels annually for up to 6 years in 157 patients included in three previous trials of ursodeoxycholic acid. Results The baseline lipid values were: total cholesterol = 207 mg/dL (127–433); high-density lipoprotein = 56 mg/dL (26–132); low-density lipoprotein = 129 mg/dL (48–334); triglycerides = 102 mg/dL (41–698). Cirrhotic stage was associated with lower levels of total cholesterol (186 mg/dL vs. 217 mg/dL, p = .02). A significant correlation between the liver biochemistries and total and low-density lipoprotein cholesterol levels was observed. Ursodeoxycholic acid, as compared to placebo, significantly decreased total (−27 mg/dL vs. 22 mg/dL, p = .0004) and low-density lipoprotein cholesterol (−24 mg/dL vs. 17 mg/dL, p = .0001). After extended follow-up, small changes in the lipid levels were noticed. The incidence of coronary artery disease was 4%. Conclusions Our findings suggest that the lipid levels in Primary Sclerosing Cholangitis are often above levels where treatment with lipid-lowering agents is recommended. However, Primary Sclerosing Cholangitis patients seem to have no elevated risk for cardiovascular events. The correlation of total and low-density lipoprotein cholesterol with liver biochemistries implies that mechanisms linked to cholestasis may regulate cholesterol metabolism.
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Clinical features and management of Primary Sclerosing Cholangitis.
World journal of gastroenterology, 2008Co-Authors: Marina G. Silveira, Keith D. LindorAbstract:Primary Sclerosing Cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in cirrhosis and need for liver transplantation and reduced life expectancy. The majority of cases occur in young and middle-aged men, often in association with inflammatory bowel disease. The etiology of Primary Sclerosing Cholangitis includes immune-mediated components and elements of undefined nature. No effective medical therapy has been identified. The multiple complications of Primary Sclerosing Cholangitis include metabolic bone disease, dominant strictures, bacterial Cholangitis, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of Primary Sclerosing Cholangitis. Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease, although recurrence in the allografted liver has been described. A PSC-like variant attracting attention is Cholangitis marked by raised levels of the immunoglobulin G4 subclass, prominence of plasma cells within the lesions, and steroid responsiveness.
Russell H. Wiesner - One of the best experts on this subject based on the ideXlab platform.
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Primary Sclerosing Cholangitis and Celiac Disease
Annals of Internal Medicine, 2020Co-Authors: J. Eileen Hay, Russell H. Wiesner, Nicholas F. Larusso, Roy G. Shorter, William P. BaldusAbstract:Abstract The association of Primary Sclerosing Cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with ...
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Etiology and natural history of Primary Sclerosing Cholangitis
Journal of hepato-biliary-pancreatic surgery, 1999Co-Authors: K. V. Narayanan Menon, Russell H. WiesnerAbstract:The etiology of Primary Sclerosing Cholangitis remains unknown. Bacteria, toxins, viral infections, and immunological and genetic factors have all been proposed as etiological agents. Portal bacteremia, toxins absorbed from the diseased colon in inflammatory bowel disease, and cytomegalovirus and reovirus infections have been implicated by various investigators but there is little evidence to support these hypotheses. The close association between Primary Sclerosing Cholangitis and various human leukocyte antigen haplotypes is now well established and lends support to the theory that immunologic and genetic mechanisms may be involved in its pathogenesis. Patients with Primary Sclerosing Cholangitis may have elevated levels of circulating immune complexes, immunoglobulins, and non-organ specific autoantibodies. The association between ulcerative colitis and Primary Sclerosing Cholangitis remains unexplained and both groups of patients have a high prevalence of antibodies to the perinuclear cytoplasmic antigen. The long-term prognosis in Primary Sclerosing Cholangitis is tempered by the development of cholangiocarcinoma in 6%–30% of patients when followed over long periods of time. Detecting cholangiocarcinoma early in a patient with Primary Sclerosing Cholangitis is one of the most frustrating problems faced by a clinician while caring for these patients. The long-term outlook for patients with Primary Sclerosing Cholangitis and cholangiocarcinoma remains dismal, whatever the treatment modality employed. However, the development of a multivariate statistical survival model from long-term survival data from the Mayo Clinic and other centers has been a major step in identifying individual Primary Sclerosing Cholangitis patients at low, moderate, and high risk of dying. Such models have been useful for stratifying patients in therapeutic trials, for in patient counseling, and in patient selection and timing of liver transplantation.
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Are patients with cirrhotic stage Primary Sclerosing Cholangitis at risk for the development of hepatocellular cancer
Journal of hepatology, 1997Co-Authors: Denise M. Harnois, Nicholas F. Larusso, Jurgen Ludwig, Gregory J. Gores, Jeffery L. Steers, Russell H. WiesnerAbstract:Abstract Background/Aims: The risk of cholangiocarcinoma in Primary Sclerosing Cholangitis is widely recognized to be 8–30%, whereas the risk of acquiring hepatocellular carcinoma in Primary Sclerosing Cholangitis is unknown. As in other chronic liver diseases, the presence of hepatocellular carcinoma in a patient with Primary Sclerosing Cholangitis undergoing evaluation for orthotopic liver transplantation would clearly impact on the candidacy, diagnostic evaluation, and alternative treatment options. Thus, the aim of our study was to determine the prevalence of hepatocellular carcinoma in patient undergoing liver transplantation for Primary Sclerosing Cholangitis. Methods: The records of the 520 patients undergoing orthotopic liver transplantation our institution between 1985 and May 1995 were reviewed. Of the 134 patients with Primary Sclerosing Cholangitis, three (2%) had hepatocellular carcinoma. In the 386 patients without Primary Sclerosing Cholangitis under-going orthotopic liver transplantation, 22 (6%) had hepatocellular carcinoma. Results: Neither the duration of Primary Sclerosing Cholangitis (range 7–23 years) nor the presence of ulcerative colitis (two of three patients) distinguished those patients with Primary Sclerosing Cholangitis plus hepatocellular carcinoma from those with Primary Sclerosing Cholangitis alone. None of the three patients with Primary Sclerosing Cholangitis plus hepatocellular carcinoma had evidence for hepatitis B or C, alpha-1-antitrypsin deficiency, or hemochromatosis. None of the tumors was of the fibrolamellar variety of hepatocellular carcinoma. Conclusions: The prevalence of hepatocellular carcinoma in patients with Primary Sclerosing Cholangitis undergoing orthotopic liver transplantation is 2%. These data suggest that patients with advanced cirrhotic-stage Primary Sclerosing Cholangitis are at increased risk for developing hepatocellular carcinoma and should be screened for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation.
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Primary Sclerosing Cholangitis: refinement and validation of survival models.
Gastroenterology, 1992Co-Authors: E. Rolland Dickson, Roger W. Chapman, Russell H. Wiesner, Nicholas F. Larusso, Jurgen Ludwig, Paul A. Murtaugh, Patricia Grambsch, Thomas R. Fleming, Michael Malinchoc, Marshall M. KaplanAbstract:The natural history of Primary Sclerosing Cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with Primary Sclerosing Cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with Primary Sclerosing Cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for Primary Sclerosing Cholangitis, including transplantation.
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Cholangiocarcinoma complicating Primary Sclerosing Cholangitis.
Annals of surgery, 1991Co-Authors: Charles B. Rosen, David M. Nagorney, Russell H. Wiesner, Robert J. Coffey, Nicholas F. LarussoAbstract:Cholangiocarcinoma is more likely to develop in patients with Primary Sclerosing Cholangitis. Our aims were to describe the clinical presentation, course, and management of patients afflicted with both cholangiocarcinoma and Primary Sclerosing Cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with Primary Sclerosing Cholangitis. A retrospective analysis was conducted of 30 patients with both Primary Sclerosing Cholangitis and cholangiocarcinoma managed at our institution during an 8-year period. Development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice, weight loss, and abdominal discomfort. Cholangiocarcinoma complicating Primary Sclerosing Cholangitis often was detected at an advanced tumor stage, which precluded effective therapy, and overall median survival was 5 months. Earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates. Seventy patients with Primary Sclerosing Cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months. Twelve patients died and five were found at autopsy to have cholangiocarcinoma. The potential for cholangiocarcinoma to develop in patients with Primary Sclerosing Cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease.
Hiroshi Shimada - One of the best experts on this subject based on the ideXlab platform.
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Liver transplantation for Primary Sclerosing Cholangitis.
Journal of hepato-biliary-pancreatic surgery, 1999Co-Authors: Hitoshi Sekido, Kazuhisa Takeda, Daisuke Morioka, Toru Kubota, Kuniya Tanaka, Itaru Endo, Kaoru Nagahori, Shinji Togo, Hiroshi ShimadaAbstract:Although the development of interventional radiology and biliary surgical techniques has prolonged the survival time of patients with Primary Sclerosing Cholangitis, liver transplantation remains the only effective treatment for patients with Primary Sclerosing Cholangitis with liver cirrhosis. Several prognostic survival models have been establised for this disease, and the efficacy of actual liver transplantations has been reported in comparison with these survival models. One- and 5-year actuarial patient survivals after liver transplantation for Primary Sclerosing Cholangitis were shown to be greater than and approximately equal to 90%, respectively. An association with cholangiocarcinoma is the most adverse factor affecting survival after liver transplantation for Primary Sclerosing Cholangitis, while the association of inflammatory bowel disease or previous bili-ary surgery does not adversely affect the outcome of the liver transplantation. Recurrent Sclerosing Cholangitis is an important issue for posttransplant patients with Primary Sclerosing Cholangitis, and occurs in 10%–20% of such patients. Although our understanding of recurrent Sclerosing Cholangitis is still in the early stages, its potential occurrence indicates the need for a longer follow-up period after liver transplantation.
Nicholas F. Larusso - One of the best experts on this subject based on the ideXlab platform.
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Primary Sclerosing Cholangitis and Celiac Disease
Annals of Internal Medicine, 2020Co-Authors: J. Eileen Hay, Russell H. Wiesner, Nicholas F. Larusso, Roy G. Shorter, William P. BaldusAbstract:Abstract The association of Primary Sclerosing Cholangitis and celiac disease was observed in three patients, an association not previously reported. All three patients were men who presented with ...
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Are patients with cirrhotic stage Primary Sclerosing Cholangitis at risk for the development of hepatocellular cancer
Journal of hepatology, 1997Co-Authors: Denise M. Harnois, Nicholas F. Larusso, Jurgen Ludwig, Gregory J. Gores, Jeffery L. Steers, Russell H. WiesnerAbstract:Abstract Background/Aims: The risk of cholangiocarcinoma in Primary Sclerosing Cholangitis is widely recognized to be 8–30%, whereas the risk of acquiring hepatocellular carcinoma in Primary Sclerosing Cholangitis is unknown. As in other chronic liver diseases, the presence of hepatocellular carcinoma in a patient with Primary Sclerosing Cholangitis undergoing evaluation for orthotopic liver transplantation would clearly impact on the candidacy, diagnostic evaluation, and alternative treatment options. Thus, the aim of our study was to determine the prevalence of hepatocellular carcinoma in patient undergoing liver transplantation for Primary Sclerosing Cholangitis. Methods: The records of the 520 patients undergoing orthotopic liver transplantation our institution between 1985 and May 1995 were reviewed. Of the 134 patients with Primary Sclerosing Cholangitis, three (2%) had hepatocellular carcinoma. In the 386 patients without Primary Sclerosing Cholangitis under-going orthotopic liver transplantation, 22 (6%) had hepatocellular carcinoma. Results: Neither the duration of Primary Sclerosing Cholangitis (range 7–23 years) nor the presence of ulcerative colitis (two of three patients) distinguished those patients with Primary Sclerosing Cholangitis plus hepatocellular carcinoma from those with Primary Sclerosing Cholangitis alone. None of the three patients with Primary Sclerosing Cholangitis plus hepatocellular carcinoma had evidence for hepatitis B or C, alpha-1-antitrypsin deficiency, or hemochromatosis. None of the tumors was of the fibrolamellar variety of hepatocellular carcinoma. Conclusions: The prevalence of hepatocellular carcinoma in patients with Primary Sclerosing Cholangitis undergoing orthotopic liver transplantation is 2%. These data suggest that patients with advanced cirrhotic-stage Primary Sclerosing Cholangitis are at increased risk for developing hepatocellular carcinoma and should be screened for hepatocellular carcinoma as well as for cholangiocarcinoma prior to orthotopic liver transplantation.
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Primary Sclerosing Cholangitis: refinement and validation of survival models.
Gastroenterology, 1992Co-Authors: E. Rolland Dickson, Roger W. Chapman, Russell H. Wiesner, Nicholas F. Larusso, Jurgen Ludwig, Paul A. Murtaugh, Patricia Grambsch, Thomas R. Fleming, Michael Malinchoc, Marshall M. KaplanAbstract:The natural history of Primary Sclerosing Cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with Primary Sclerosing Cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with Primary Sclerosing Cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for Primary Sclerosing Cholangitis, including transplantation.
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Cholangiocarcinoma complicating Primary Sclerosing Cholangitis.
Annals of surgery, 1991Co-Authors: Charles B. Rosen, David M. Nagorney, Russell H. Wiesner, Robert J. Coffey, Nicholas F. LarussoAbstract:Cholangiocarcinoma is more likely to develop in patients with Primary Sclerosing Cholangitis. Our aims were to describe the clinical presentation, course, and management of patients afflicted with both cholangiocarcinoma and Primary Sclerosing Cholangitis and to estimate the prevalence of cholangiocarcinoma in patients with Primary Sclerosing Cholangitis. A retrospective analysis was conducted of 30 patients with both Primary Sclerosing Cholangitis and cholangiocarcinoma managed at our institution during an 8-year period. Development of cholangiocarcinoma was heralded by rapid clinical deterioration with jaundice, weight loss, and abdominal discomfort. Cholangiocarcinoma complicating Primary Sclerosing Cholangitis often was detected at an advanced tumor stage, which precluded effective therapy, and overall median survival was 5 months. Earlier recognition and treatment of cholangiocarcinoma in such patients will be necessary to increase survival rates. Seventy patients with Primary Sclerosing Cholangitis were followed prospectively in a clinical trial of medical therapy for an average of 30 months. Twelve patients died and five were found at autopsy to have cholangiocarcinoma. The potential for cholangiocarcinoma to develop in patients with Primary Sclerosing Cholangitis may indicate that liver transplantation should be considered earlier in the course of the disease.