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374 The Risk of Colonic Dysplasia After Liver Transplantation for Primary Sclerosing Cholangitis
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Long-Term Outcome of Gallbladder Polyps in Patients With Primary Sclerosing Cholangitis Sombat Treeprasertsuk, Emmanouil Sinakos, Jill C. Keach, Keith D. Lindor
Outcomes and Response to Therapy in Patients With Primary Biliary Cirrhosis Assessed by Patient Gender Paul J. Gaglio, Stuart Akerman
Background and Aims: Gallbladder (GB) polyps in PSC patients have a risk of malignancy. Recently, European Association for the study of the liver (EASL) guideline recommends cholecystectomy for GB polyp at any size in patients with PSC without strong evidences of back-up studies. We aimed to evaluate the predictors and long-term outcomes of PSC patients with GB polyps for developing malignancy. Methods: We identified 86 patients with PSC and GB polyp using HICDA codes (05756-21 with 05760-31) and radiological diagnosis codes of GB polyp/mass (760.3104) at the Mayo Clinic, Rochester, MN between January 1, 2000 and August 31, 2009. Twenty-six patients were excluded due to the indefinite diagnosis of PSC or GB polyp (n=22), known cases of cholangiocarcinoma (n=2) and no follow up data (n=2). Clinical information and pathological findings of GB polyps were reviewed. GB polyp was defined by at least two serial reports of radiological diagnosis. The estimated size of small GB polyp was 0.2 cm. Results: Of the 2281 patients with PSC, 60 patients (2.6%) were diagnosed as GB polyp with median age (interquartile range; IQR) of 49.8 years (39.3, 58.6) and 67% of them were male. Median (IQR) Mayo risk score at baseline were 0.33 (-0.11, 1.36). At baseline, 35.7% of patients had GB polyps of at least 2 polyps and 70% of patients had GB polyp with size of less than 0.6 cm. Thirty-one patients (52%) were subsequent received cholecystectomy. Eight of 60 patients (13.3%) develop GB cancer (n=8) while 2 patients had GB dysplasia. No patients without cholecystectomy develop malignant GB lesion during the median (IQR) duration of follow up of 44 (17.5, 84.3) months. By univariate analysis, patients with malignant GB lesions had significantly less frequent number of GB polyp of less than 0.6 cm at first diagnosis and at the last follow up, larger size of GB polyps at first diagnosis and at the last follow up than those with benign GB lesions. By a multivariable logistic analysis, the size of GB polyps at the last follow up was associated with malignant GB lesions (OR= 8.9; 95%CI 2.6-30.3). By using the ROC curve, the GB polyp' size ≥ 1.0 cm had a sensitivity of 99%, specificity of 94%, a negative predictive value of 99% and a positive predictive value of 77%, with an area under the curve of 98% for predicting malignant GB lesion. At the end of follow up, 6 patients (10%) died and 9 patients (15%) received liver transplantation. Conclusions: Thirteen percent of GB polyps in patients with PSC develop GB cancer. The size of GB polyps of at least 1.0 cm at the last follow up was a good predictor for malignant GB lesion.
Introduction: Primary Biliary Cirrhosis (PBC) is a disease with a significantly higher prevalence in women. At present, the vast majority of data related to outcomes and response to therapy has been evaluated in a ”gender neutral” manner, without an analysis of various aspects of PBC when comparing women to men. Methods: We performed a Pubmed/ MESH Database internet search utilizing the topic headings “Liver Cirrhosis, Biliary”, “Mortality”, “Prognosis”, “Survival”; and a secondary search linked to the topic heading “Ursodeoxycholic Acid”. Studies were then evaluated and considered if they contained outcome data relating to liverrelated death and/or liver transplantation in patients with PBC, as well as response to treatment for the secondary search. Published data was reviewed, and for studies without explicit mention of outcomes displayed by gender, the corresponding author was contacted via email to request the unpublished data. A total of 5 studies for the primary search and 3 studies for the secondary search met these criteria and were included in the final analysis. Results: For the primary outcomes, a total of 244 Men and 2213 Women with PBC were included in the analysis representing a 9:1 Female:Male ratio. For the combined outcome of Liver-related death or Liver Transplant, there were 37/244 (15.2%) outcomes in the male cohort compared to 400/2213 (18.1%) outcomes in the female cohort. This difference was not statistically significant when comparing the two groups (p = 0.29). For the secondary outcome of response to treatment (UCDA therapy) defined as improvement in serum Alkaline phosphatase an/or total bilirubin, a total of 41 Men and 513 Women were included in the analysis. 15/41 Men (36.6%) responded to treatment, whereas 300/513 Women (58.5%) responded (p< 0.01) Conclusions: 1) Current literature regarding PBC does not clearly differentiate outcomes in men versus women 2) In this meta-analysis of 5 large PBC studies, we found no statistically significant difference when comparing outcome of PBC in men versus women related to progression to liver transplant or liver-related death, however, a greater percentage of women displayed improvement in biochemical testing with therapy when compared to men. 3) Further studies that evaluate response to therapy of PBC based on gender are warranted. Acknowledgements:. We thank these investigators for contributing their data: Fusao Ikeda, Okayama University Hospital, Okayama Japan Christophe Corpechot, Universite Pierre et Marie Curie, Paris, France Martin I Prince, Manchester Biomedical Research Center, Manchester, UK
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The Risk of Colonic Dysplasia After Liver Transplantation for Primary Sclerosing Cholangitis Ibrahim Hanouneh, Carole Macaron, Rocio Lopez, Nizar N. Zein, Bret Lashner
Health-Related Quality of Life in Patients With Primary Sclerosing Cholangitis: An International Study in Two Population-Based Patient Cohorts Maria Benito de Valle, Monira Rahman, Björn Lindkvist, Einar Bjornsson, Roger W. Chapman, Evangelos Kalaitzakis
Primary sclerosing cholangitis (PSC) carries an increased risk of colon cancer in patients with inflammatory bowel disease (IBD). However, there is scarcity of data to determine whether the rate of colon cancer increased after liver transplantation (LT) in IBD patients with PSC. The Aims of this study are 1) to estimate the risk of colonic dysplasia after LT in IBD patients with PSC, and 2) to identify the factors associated with colonic dysplasia after LT in IBD patients with PSC. Methods: we identified all adult patients with IBD/PSC who underwent LT between 1998-2005 (n=43). Two control groups were identified during same time period. Control 1 were patients with IBD/PSC who did not undergo LT and matched 1:1 for age, gender and type of IBD. Control 2 patients were those with chronic liver disease other than PSC who underwent LT, who were matched 1:1 for age, gender and duration since LT. To assess for development of colon dysplasia, all patients were monitored by serial colonoscopy. Univariable and multivariable Cox regression analysis were used to assess associations between colon dysplasia and factors of interest. Results: During median follow up of 5.9 (P25, P75: 2.6, 9.9) yrs, patients with IBD/PSC who underwent LT had similar rate of colonic dysplasia compared to those who did not have LT (32% vs. 29%,p=0.24). The rate of colonic dysplasia in LT recipients was higher in PSC patients compared to those with other forms of chronic liver disease (32% vs. 0%,p=0.018) Figure. Post-LT cytomegalovirus infection was associated with higher likelihood of colonic dysplasia post-LT in IBD/PSC patients (HR=4.4,p=0.024). The use of ursodeoxycholic acid had no impact on colonic dysplasia in IBD/PSC patients before or after LT (p=0.49). There was no significant difference in survival outcome between the three study groups. Conclusion: IBD/ PSC patients remain at an increased risk of colonic dysplasia after LT. Cytomegalovirus infection increases the risk of post-LT colonic dysplasia in IBD/PSC patients.
Primary sclerosing cholangitis (PSC) is a chronic liver disease with a major impact on morbidity and mortality. However, data on health-related quality of life (QoL) in patients with PSC are scarce and limited to patients from tertiary referral centers. We aimed to evaluate QoL in two European population-based PSC patient cohorts and to identify relevant determinants of QoL in these patients. Methods All PSC patients within Vastragotaland, Sweden (n=232) (population 1.5 million) and Oxfordshire, England, UK (n=60) (population 640000) were identified and asked to fill in three validated questionnaires: the Chronic Liver Disease Questionnaire (CLDQ,liver-specific QoL instrument), the Short-Form 36 (SF36,generic QoL instrument), and the Hospital Anxiety and Depression(HAD) scale. SF-36 results were compared to those obtained from age- and gender-matched controls from the general population. Any symptom on CLDQ occurring more often than “some of the time” was considered significant. Clinical and biochemical data were also analyzed. Results A total of 182/292 (62%) patients agreed to participate (mean age 50 (SD 16), 70% male, 82% with inflammatory bowel disease (IBD), 7% with cirrhosis, 12% post-transplant). Compared with controls, PSC patients demonstrated significantly lower scores (reduced QoL) in 6/8 SF-36 domains: role-physical, general health, vitality, social functioning, roleemotional, mental health (p<0.05 for all). Compared to controls, PSC patients had lower mental component summary (MCS, 50.4(10) vs. 45.3(12), p<0.001) and tended to have lower physical component summary (PCS, 49(10) vs. 47(11), p=0.08). Transplanted patients showed lower scores in 2/8 SF-36 domains compared to controls (role-physical, general health; p<0.05 for both) but not in PCS or MCS (p>0.05 for both). According to CLDQ, 15% of patients had significant pruritus, 11% fatigue, 11% body pain and 10% mouth dryness. According to HAD, 9% had significant depression and 9% significant anxiety. In multivariate analysis the SF-36 physical component summary was independently related to significant body pain (b=-11.6), age (b=-0.28), and significant fatigue (b=-10.5, p<0.05 for all); the mental component summary was independently related to depression (b=-1.6) and anxiety scores (b=-0.8), older age (b=0.2), and significant mouth dryness (b=-7.8, p<0.05 for all). Small-duct PSC, the Mayo PSC risk score or IBD were not related to any QoL domain. Conclusion PSC is associated with reduced health-related QoL. Non life-threatening symptoms such as psychological distress and fatigue, rather than associated IBD or severity of PSC, seem to be major determinants of poor QoL in these patients. 470 HBV Suppresses TLR Signaling and the Crosstalk to the Adaptive Immune System in Murine and Human Cells Min Jiang, Martin Trippler, Ruth Broering, Lena Poggenpohl, Jun Wu, Guido Gerken, Mengji Lu, Joerg F. Schlaak Background: We have previously shown that the hepatitis B virus (HBV) can suppress TLR3 and -4 signaling in murine parenchymal and non-parenchymal (NPC) liver cells. It is not clear, however, whether this immunosuppressive effect may also affect adaptive immune responses and is also relevant for the human system. Methods: To address these questions, murine hepatocytes and NPC (Kupffer cells, KC and sinusoidal endothelial cells, LSEC) were stimulated by TLR3 and TLR4 ligands in the presence or absence of HBsAg. Total
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AASLD Abstracts
AASLD Abstracts
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Long-Term Outcome of Gallbladder Polyps in Patients With Primary Sclerosing Cholangitis Sombat Treeprasertsuk, Emmanouil Sinakos, Jill C. Keach, Keith D. Lindor
Outcomes and Response to Therapy in Patients With Primary Biliary Cirrhosis Assessed by Patient Gender Paul J. Gaglio, Stuart Akerman
Background and Aims: Gallbladder (GB) polyps in PSC patients have a risk of malignancy. Recently, European Association for the study of the liver (EASL) guideline recommends cholecystectomy for GB polyp at any size in patients with PSC without strong evidences of back-up studies. We aimed to evaluate the predictors and long-term outcomes of PSC patients with GB polyps for developing malignancy. Methods: We identified 86 patients with PSC and GB polyp using HICDA codes (05756-21 with 05760-31) and radiological diagnosis codes of GB polyp/mass (760.3104) at the Mayo Clinic, Rochester, MN between January 1, 2000 and August 31, 2009. Twenty-six patients were excluded due to the indefinite diagnosis of PSC or GB polyp (n=22), known cases of cholangiocarcinoma (n=2) and no follow up data (n=2). Clinical information and pathological findings of GB polyps were reviewed. GB polyp was defined by at least two serial reports of radiological diagnosis. The estimated size of small GB polyp was 0.2 cm. Results: Of the 2281 patients with PSC, 60 patients (2.6%) were diagnosed as GB polyp with median age (interquartile range; IQR) of 49.8 years (39.3, 58.6) and 67% of them were male. Median (IQR) Mayo risk score at baseline were 0.33 (-0.11, 1.36). At baseline, 35.7% of patients had GB polyps of at least 2 polyps and 70% of patients had GB polyp with size of less than 0.6 cm. Thirty-one patients (52%) were subsequent received cholecystectomy. Eight of 60 patients (13.3%) develop GB cancer (n=8) while 2 patients had GB dysplasia. No patients without cholecystectomy develop malignant GB lesion during the median (IQR) duration of follow up of 44 (17.5, 84.3) months. By univariate analysis, patients with malignant GB lesions had significantly less frequent number of GB polyp of less than 0.6 cm at first diagnosis and at the last follow up, larger size of GB polyps at first diagnosis and at the last follow up than those with benign GB lesions. By a multivariable logistic analysis, the size of GB polyps at the last follow up was associated with malignant GB lesions (OR= 8.9; 95%CI 2.6-30.3). By using the ROC curve, the GB polyp' size ≥ 1.0 cm had a sensitivity of 99%, specificity of 94%, a negative predictive value of 99% and a positive predictive value of 77%, with an area under the curve of 98% for predicting malignant GB lesion. At the end of follow up, 6 patients (10%) died and 9 patients (15%) received liver transplantation. Conclusions: Thirteen percent of GB polyps in patients with PSC develop GB cancer. The size of GB polyps of at least 1.0 cm at the last follow up was a good predictor for malignant GB lesion.
Introduction: Primary Biliary Cirrhosis (PBC) is a disease with a significantly higher prevalence in women. At present, the vast majority of data related to outcomes and response to therapy has been evaluated in a ”gender neutral” manner, without an analysis of various aspects of PBC when comparing women to men. Methods: We performed a Pubmed/ MESH Database internet search utilizing the topic headings “Liver Cirrhosis, Biliary”, “Mortality”, “Prognosis”, “Survival”; and a secondary search linked to the topic heading “Ursodeoxycholic Acid”. Studies were then evaluated and considered if they contained outcome data relating to liverrelated death and/or liver transplantation in patients with PBC, as well as response to treatment for the secondary search. Published data was reviewed, and for studies without explicit mention of outcomes displayed by gender, the corresponding author was contacted via email to request the unpublished data. A total of 5 studies for the primary search and 3 studies for the secondary search met these criteria and were included in the final analysis. Results: For the primary outcomes, a total of 244 Men and 2213 Women with PBC were included in the analysis representing a 9:1 Female:Male ratio. For the combined outcome of Liver-related death or Liver Transplant, there were 37/244 (15.2%) outcomes in the male cohort compared to 400/2213 (18.1%) outcomes in the female cohort. This difference was not statistically significant when comparing the two groups (p = 0.29). For the secondary outcome of response to treatment (UCDA therapy) defined as improvement in serum Alkaline phosphatase an/or total bilirubin, a total of 41 Men and 513 Women were included in the analysis. 15/41 Men (36.6%) responded to treatment, whereas 300/513 Women (58.5%) responded (p< 0.01) Conclusions: 1) Current literature regarding PBC does not clearly differentiate outcomes in men versus women 2) In this meta-analysis of 5 large PBC studies, we found no statistically significant difference when comparing outcome of PBC in men versus women related to progression to liver transplant or liver-related death, however, a greater percentage of women displayed improvement in biochemical testing with therapy when compared to men. 3) Further studies that evaluate response to therapy of PBC based on gender are warranted. Acknowledgements:. We thank these investigators for contributing their data: Fusao Ikeda, Okayama University Hospital, Okayama Japan Christophe Corpechot, Universite Pierre et Marie Curie, Paris, France Martin I Prince, Manchester Biomedical Research Center, Manchester, UK
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The Risk of Colonic Dysplasia After Liver Transplantation for Primary Sclerosing Cholangitis Ibrahim Hanouneh, Carole Macaron, Rocio Lopez, Nizar N. Zein, Bret Lashner
Health-Related Quality of Life in Patients With Primary Sclerosing Cholangitis: An International Study in Two Population-Based Patient Cohorts Maria Benito de Valle, Monira Rahman, Björn Lindkvist, Einar Bjornsson, Roger W. Chapman, Evangelos Kalaitzakis
Primary sclerosing cholangitis (PSC) carries an increased risk of colon cancer in patients with inflammatory bowel disease (IBD). However, there is scarcity of data to determine whether the rate of colon cancer increased after liver transplantation (LT) in IBD patients with PSC. The Aims of this study are 1) to estimate the risk of colonic dysplasia after LT in IBD patients with PSC, and 2) to identify the factors associated with colonic dysplasia after LT in IBD patients with PSC. Methods: we identified all adult patients with IBD/PSC who underwent LT between 1998-2005 (n=43). Two control groups were identified during same time period. Control 1 were patients with IBD/PSC who did not undergo LT and matched 1:1 for age, gender and type of IBD. Control 2 patients were those with chronic liver disease other than PSC who underwent LT, who were matched 1:1 for age, gender and duration since LT. To assess for development of colon dysplasia, all patients were monitored by serial colonoscopy. Univariable and multivariable Cox regression analysis were used to assess associations between colon dysplasia and factors of interest. Results: During median follow up of 5.9 (P25, P75: 2.6, 9.9) yrs, patients with IBD/PSC who underwent LT had similar rate of colonic dysplasia compared to those who did not have LT (32% vs. 29%,p=0.24). The rate of colonic dysplasia in LT recipients was higher in PSC patients compared to those with other forms of chronic liver disease (32% vs. 0%,p=0.018) Figure. Post-LT cytomegalovirus infection was associated with higher likelihood of colonic dysplasia post-LT in IBD/PSC patients (HR=4.4,p=0.024). The use of ursodeoxycholic acid had no impact on colonic dysplasia in IBD/PSC patients before or after LT (p=0.49). There was no significant difference in survival outcome between the three study groups. Conclusion: IBD/ PSC patients remain at an increased risk of colonic dysplasia after LT. Cytomegalovirus infection increases the risk of post-LT colonic dysplasia in IBD/PSC patients.
Primary sclerosing cholangitis (PSC) is a chronic liver disease with a major impact on morbidity and mortality. However, data on health-related quality of life (QoL) in patients with PSC are scarce and limited to patients from tertiary referral centers. We aimed to evaluate QoL in two European population-based PSC patient cohorts and to identify relevant determinants of QoL in these patients. Methods All PSC patients within Vastragotaland, Sweden (n=232) (population 1.5 million) and Oxfordshire, England, UK (n=60) (population 640000) were identified and asked to fill in three validated questionnaires: the Chronic Liver Disease Questionnaire (CLDQ,liver-specific QoL instrument), the Short-Form 36 (SF36,generic QoL instrument), and the Hospital Anxiety and Depression(HAD) scale. SF-36 results were compared to those obtained from age- and gender-matched controls from the general population. Any symptom on CLDQ occurring more often than “some of the time” was considered significant. Clinical and biochemical data were also analyzed. Results A total of 182/292 (62%) patients agreed to participate (mean age 50 (SD 16), 70% male, 82% with inflammatory bowel disease (IBD), 7% with cirrhosis, 12% post-transplant). Compared with controls, PSC patients demonstrated significantly lower scores (reduced QoL) in 6/8 SF-36 domains: role-physical, general health, vitality, social functioning, roleemotional, mental health (p<0.05 for all). Compared to controls, PSC patients had lower mental component summary (MCS, 50.4(10) vs. 45.3(12), p<0.001) and tended to have lower physical component summary (PCS, 49(10) vs. 47(11), p=0.08). Transplanted patients showed lower scores in 2/8 SF-36 domains compared to controls (role-physical, general health; p<0.05 for both) but not in PCS or MCS (p>0.05 for both). According to CLDQ, 15% of patients had significant pruritus, 11% fatigue, 11% body pain and 10% mouth dryness. According to HAD, 9% had significant depression and 9% significant anxiety. In multivariate analysis the SF-36 physical component summary was independently related to significant body pain (b=-11.6), age (b=-0.28), and significant fatigue (b=-10.5, p<0.05 for all); the mental component summary was independently related to depression (b=-1.6) and anxiety scores (b=-0.8), older age (b=0.2), and significant mouth dryness (b=-7.8, p<0.05 for all). Small-duct PSC, the Mayo PSC risk score or IBD were not related to any QoL domain. Conclusion PSC is associated with reduced health-related QoL. Non life-threatening symptoms such as psychological distress and fatigue, rather than associated IBD or severity of PSC, seem to be major determinants of poor QoL in these patients. 470 HBV Suppresses TLR Signaling and the Crosstalk to the Adaptive Immune System in Murine and Human Cells Min Jiang, Martin Trippler, Ruth Broering, Lena Poggenpohl, Jun Wu, Guido Gerken, Mengji Lu, Joerg F. Schlaak Background: We have previously shown that the hepatitis B virus (HBV) can suppress TLR3 and -4 signaling in murine parenchymal and non-parenchymal (NPC) liver cells. It is not clear, however, whether this immunosuppressive effect may also affect adaptive immune responses and is also relevant for the human system. Methods: To address these questions, murine hepatocytes and NPC (Kupffer cells, KC and sinusoidal endothelial cells, LSEC) were stimulated by TLR3 and TLR4 ligands in the presence or absence of HBsAg. Total
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AASLD Abstracts
AASLD Abstracts
373