Background: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel diseases (IBD). ... more Background: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel diseases (IBD). Evidence suggests an association between the gut microbiome and PSC. However, the putative relationship between exposure to antibiotics and onset of PSC has never been reported. We observed 3 cases in which patients without antecedent liver or bowel issues developed symptoms leading to diagnosis of IBD and subsequently PSC after being exposed to doxycycline. We aimed to identify, through the PSC Partners national patient registry, additional cases of PSC in which there is a temporal relationship between exposure to doxycycline and onset of PSC or PSC-IBD. Areas of Uncertainty: The etiopathogenesis of PSC remains an enigma. Data Sources: We collected data from patients with PSC and PSC-IBD in which there seemed to be a temporal relationship between exposure to doxycycline and PSC. Time from doxycycline exposure to: (1) onset of PSC or PSC-IBD symptoms and (2) diagnosis of PSC were documen...
Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflamma... more Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large, international cohort of patients with PSC. We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Of the 7121 patients in the cohort, 2616 met the primary endpoin...
Although highly sensitive and specific, the revised International Autoimmune Hepatitis Group (IAI... more Although highly sensitive and specific, the revised International Autoimmune Hepatitis Group (IAIHG) diagnostic criteria for autoimmune hepatitis (AIH) are cumbersome to use in clinical practice and rely upon a number of autoantibodies that are costly and are not widely available. The simplified scoring system for AIH attempts to rectify the complexity of the IAIHG criteria. To date, there have been few studies assessing the specificity of the simplified score for AIH when applied to patients with cholestatic liver diseases. The purpose of this study was to examine the specificity of the simplified scoring system for AIH as compared to the revised IAIHG criteria in a large cohort of patients with primary sclerosing cholangitis (PSC). The patient population consisted of 147 patients enrolled in two prospective trials at the Mayo Clinic examining the use of ursodeoxycholic acid in PSC. All of the patients underwent baseline blood work (including standard serologic testing to exclude o...
Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been sugge... more Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.
Background: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel diseases (IBD). ... more Background: Primary sclerosing cholangitis (PSC) is linked to inflammatory bowel diseases (IBD). Evidence suggests an association between the gut microbiome and PSC. However, the putative relationship between exposure to antibiotics and onset of PSC has never been reported. We observed 3 cases in which patients without antecedent liver or bowel issues developed symptoms leading to diagnosis of IBD and subsequently PSC after being exposed to doxycycline. We aimed to identify, through the PSC Partners national patient registry, additional cases of PSC in which there is a temporal relationship between exposure to doxycycline and onset of PSC or PSC-IBD. Areas of Uncertainty: The etiopathogenesis of PSC remains an enigma. Data Sources: We collected data from patients with PSC and PSC-IBD in which there seemed to be a temporal relationship between exposure to doxycycline and PSC. Time from doxycycline exposure to: (1) onset of PSC or PSC-IBD symptoms and (2) diagnosis of PSC were documen...
Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflamma... more Primary sclerosing cholangitis (PSC) is an orphan hepatobiliary disorder associated with inflammatory bowel disease (IBD). We aimed to estimate the risk of disease progression based on distinct clinical phenotypes in a large, international cohort of patients with PSC. We performed a retrospective outcome analysis of patients diagnosed with PSC from 1980 through 2010 at 37 centers in Europe, North America, and Australia. For each patient, we collected data on sex, clinician-reported age at and date of PSC and IBD diagnoses, phenotypes of IBD and PSC, and date and indication of IBD-related surgeries. The primary and secondary endpoints were liver transplantation or death (LTD) and hepatopancreatobiliary malignancy, respectively. Cox proportional hazards models were applied to determine the effects of individual covariates on rates of clinical events, with time-to-event analysis ascertained through Kaplan-Meier estimates. Of the 7121 patients in the cohort, 2616 met the primary endpoin...
Although highly sensitive and specific, the revised International Autoimmune Hepatitis Group (IAI... more Although highly sensitive and specific, the revised International Autoimmune Hepatitis Group (IAIHG) diagnostic criteria for autoimmune hepatitis (AIH) are cumbersome to use in clinical practice and rely upon a number of autoantibodies that are costly and are not widely available. The simplified scoring system for AIH attempts to rectify the complexity of the IAIHG criteria. To date, there have been few studies assessing the specificity of the simplified score for AIH when applied to patients with cholestatic liver diseases. The purpose of this study was to examine the specificity of the simplified scoring system for AIH as compared to the revised IAIHG criteria in a large cohort of patients with primary sclerosing cholangitis (PSC). The patient population consisted of 147 patients enrolled in two prospective trials at the Mayo Clinic examining the use of ursodeoxycholic acid in PSC. All of the patients underwent baseline blood work (including standard serologic testing to exclude o...
Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been sugge... more Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.
Uploads
Papers by Keith Lindor