The Impact of Ulcerative Colitis on Patients With PSC
The Impact of Ulcerative Colitis on Patients With PSC
This historical cohort study was approved by the Cleveland Clinic Institutional Review Board. A prospectively maintained EDIT (Electronic Data Interface for Transplantation) database has accrued information for all patients who underwent OLT at the Cleveland Clinic. We collected this information from 1985 to 2011. Patients with PSC with and without UC who required OLT were identified from the database. Patients with PSC and UC who did not require OLT and patients with PSC alone were identified from the PSC database. The PSC database was accrued retrospectively over the time period from 1985 to 2011, using the International Classification of Diseases 9th revision (ICD 9 CM) codes for sclerosing cholangitis and chart review were done by the investigators (U.N, B.S) to confirm the diagnosis of PSC. In addition, we reviewed our IBD database which was also accrued retrospectively using the ICD codes for UC and CD from 1998 to 2011, and chart review was done by the investigators (U.N, B.S) to confirm the diagnosis of PSC. A total of 55 PSC patients without UC (PSC alone group) and 167 patients with PSC-UC were finally included in the study (PSC-UC group) (Figure 1).
(Enlarge Image)
Figure 1.
Patient selection algorithm for the study.
Inclusion criteria were defined by the presence of PSC with or without UC. Patients with CD, indeterminate colitis and patients with UC who did not have follow-up at the Cleveland Clinic were excluded. UC patients who underwent OLT for liver disease other than PSC were excluded.
Primary sclerosing cholangitis was defined as the presence of intra- and/or extra- hepatic bile duct abnormalities in the form of beading, duct ectasia and stricturing of the intra- or extra-hepatic bile ducts documented in the medical record from endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography. Small duct PSC was defined when there was histological features consistent with PSC on liver biopsy in the absence of characteristic radiological features, and clinical cholestasis with persistently elevated serum alkaline phosphatase levels for greater than 6 months.
The diagnosis of UC was made by the typical clinical, endoscopical and histological criteria.
Demographic and clinical variables were studied from patient medical records including age, gender, smoking and alcohol history, and family history of IBD, PSC or liver/colon cancer in first degree relatives. The clinical variables were defined as follows- 'duration of UC' defined as the time from the diagnosis of UC to the time of last clinical follow-up, 'family history of IBD'-CD or UC in first degree relatives, 'smoking'-smoking more than seven cigarettes a week, 'Alcohol use' defined as more than two drinks a day, extent of UC 'Extensive colitis' -endoscopic, macroscopic or microscopic evidence of disease proximal to the splenic flexure.
The following variables with regard to UC were obtained; UC activity in the last 5 years of the follow-up period; type of UC treatment used during the whole follow-up period [steroids, azathioprine, biologics (infliximab and adalimumab) and surgery]; severity of disease at last colonoscopy (before last follow-up or before OLT), assessed macroscopically and histologically and information on UC flares during the last 5 years of follow-up. We had earlier described the collection of these data into the database.
PSC duration from diagnosis; the calendar year of diagnosis of PSC, severity of PSC at last follow-up or before OLT (serum albumin, bilirubin values and presence of ascites); prevalence of cholangiocarcinoma and hepatocellular carcinoma during the whole follow-up period; outcome (patient alive at last follow-up, dead or had OLT). The use of ursodeoxycholic acid (UDCA) and its dose was obtained from the EDIT and PSC/IBD databases. UDCA was defined by the use of this medication for at least 50% of the follow-up period. The follow-up period was obtained from the date of diagnosis and the time of the last clinical visit or death.
The Mayo Risk Score was calculated at entry using the revised PSC Mayo Risk Score. This score was developed to assess 1-year to 4-year probability of survival of patients with PSC and its advantage is that there is no requirement for liver histology.
It is our practise that PSC patients get a screening colonoscopy at diagnosis of PSC and if negative every 5 years. However, colonoscopy is done if these patients have any new diarrhoea or new symptoms.
The primary outcome of interest was an evaluation of the phenotype and prognosis of PSC in patient cohorts with and without concurrent UC defined by the development of cholangiocarcinoma, requirement for OLT and mortality.
Descriptive statistics were computed for all factors. These include medians, 25th and 75th percentiles, range or mean and standard deviation for continuous factors and frequencies and percentages for categorical factors. Wilcoxon's rank sum tests for continuous factors and Pearson's chi-square or Fisher's exact tests for categorical factors were used.
Survival rates were estimated using a Kaplan–Meier approach from the date of diagnosis of liver disease to the date of death or OLT. Patients who were alive at the time of last follow-up were censored. Kaplan–Meier curve for patient's survival in patients with PSC-UC and PSC alone was compared using the log-rank test.
We sought to evaluate the influence of UC on the outcome of PSC. Cox proportional hazards analysis was constructed by including variables that had significant univariable associations with OLT or death, then performing backward stepwise selection with a removal criterion of P > 0.05 adjusting for age, gender, year of PSC diagnosis and Mayo PSC risk score. A significance level of 0.05 was used for all analyses. R 2.10.1 software (The R Foundation for Statistical Computing, Vienna, Austria) was used to perform all analyses.
Patients and Methods
Patients
This historical cohort study was approved by the Cleveland Clinic Institutional Review Board. A prospectively maintained EDIT (Electronic Data Interface for Transplantation) database has accrued information for all patients who underwent OLT at the Cleveland Clinic. We collected this information from 1985 to 2011. Patients with PSC with and without UC who required OLT were identified from the database. Patients with PSC and UC who did not require OLT and patients with PSC alone were identified from the PSC database. The PSC database was accrued retrospectively over the time period from 1985 to 2011, using the International Classification of Diseases 9th revision (ICD 9 CM) codes for sclerosing cholangitis and chart review were done by the investigators (U.N, B.S) to confirm the diagnosis of PSC. In addition, we reviewed our IBD database which was also accrued retrospectively using the ICD codes for UC and CD from 1998 to 2011, and chart review was done by the investigators (U.N, B.S) to confirm the diagnosis of PSC. A total of 55 PSC patients without UC (PSC alone group) and 167 patients with PSC-UC were finally included in the study (PSC-UC group) (Figure 1).
(Enlarge Image)
Figure 1.
Patient selection algorithm for the study.
Inclusion and Exclusion Criteria
Inclusion criteria were defined by the presence of PSC with or without UC. Patients with CD, indeterminate colitis and patients with UC who did not have follow-up at the Cleveland Clinic were excluded. UC patients who underwent OLT for liver disease other than PSC were excluded.
Diagnostic Criteria
Primary sclerosing cholangitis was defined as the presence of intra- and/or extra- hepatic bile duct abnormalities in the form of beading, duct ectasia and stricturing of the intra- or extra-hepatic bile ducts documented in the medical record from endoscopic retrograde cholangiopancreatography, and/or magnetic resonance cholangiopancreatography. Small duct PSC was defined when there was histological features consistent with PSC on liver biopsy in the absence of characteristic radiological features, and clinical cholestasis with persistently elevated serum alkaline phosphatase levels for greater than 6 months.
The diagnosis of UC was made by the typical clinical, endoscopical and histological criteria.
Demographic and Clinical Variables
Demographic and clinical variables were studied from patient medical records including age, gender, smoking and alcohol history, and family history of IBD, PSC or liver/colon cancer in first degree relatives. The clinical variables were defined as follows- 'duration of UC' defined as the time from the diagnosis of UC to the time of last clinical follow-up, 'family history of IBD'-CD or UC in first degree relatives, 'smoking'-smoking more than seven cigarettes a week, 'Alcohol use' defined as more than two drinks a day, extent of UC 'Extensive colitis' -endoscopic, macroscopic or microscopic evidence of disease proximal to the splenic flexure.
The following variables with regard to UC were obtained; UC activity in the last 5 years of the follow-up period; type of UC treatment used during the whole follow-up period [steroids, azathioprine, biologics (infliximab and adalimumab) and surgery]; severity of disease at last colonoscopy (before last follow-up or before OLT), assessed macroscopically and histologically and information on UC flares during the last 5 years of follow-up. We had earlier described the collection of these data into the database.
PSC duration from diagnosis; the calendar year of diagnosis of PSC, severity of PSC at last follow-up or before OLT (serum albumin, bilirubin values and presence of ascites); prevalence of cholangiocarcinoma and hepatocellular carcinoma during the whole follow-up period; outcome (patient alive at last follow-up, dead or had OLT). The use of ursodeoxycholic acid (UDCA) and its dose was obtained from the EDIT and PSC/IBD databases. UDCA was defined by the use of this medication for at least 50% of the follow-up period. The follow-up period was obtained from the date of diagnosis and the time of the last clinical visit or death.
The Mayo Risk Score was calculated at entry using the revised PSC Mayo Risk Score. This score was developed to assess 1-year to 4-year probability of survival of patients with PSC and its advantage is that there is no requirement for liver histology.
It is our practise that PSC patients get a screening colonoscopy at diagnosis of PSC and if negative every 5 years. However, colonoscopy is done if these patients have any new diarrhoea or new symptoms.
Outcome Measurement
The primary outcome of interest was an evaluation of the phenotype and prognosis of PSC in patient cohorts with and without concurrent UC defined by the development of cholangiocarcinoma, requirement for OLT and mortality.
Statistical Analysis
Descriptive statistics were computed for all factors. These include medians, 25th and 75th percentiles, range or mean and standard deviation for continuous factors and frequencies and percentages for categorical factors. Wilcoxon's rank sum tests for continuous factors and Pearson's chi-square or Fisher's exact tests for categorical factors were used.
Survival rates were estimated using a Kaplan–Meier approach from the date of diagnosis of liver disease to the date of death or OLT. Patients who were alive at the time of last follow-up were censored. Kaplan–Meier curve for patient's survival in patients with PSC-UC and PSC alone was compared using the log-rank test.
We sought to evaluate the influence of UC on the outcome of PSC. Cox proportional hazards analysis was constructed by including variables that had significant univariable associations with OLT or death, then performing backward stepwise selection with a removal criterion of P > 0.05 adjusting for age, gender, year of PSC diagnosis and Mayo PSC risk score. A significance level of 0.05 was used for all analyses. R 2.10.1 software (The R Foundation for Statistical Computing, Vienna, Austria) was used to perform all analyses.