The Impact of Ulcerative Colitis on Patients With PSC
The Impact of Ulcerative Colitis on Patients With PSC
The basic demographic and clinical information including age, gender, race, age at PSC diagnosis and colonoscopic extent of UC are summarised in Table 1. Patients with PSC were divided into two groups: 167 with PSC-UC (PSC-UC) and 55 with PSC alone (PSC). The median age at presentation for the subgroup of PSC alone patients was 48 (range 12–72) years. These patients were significantly older than the group of PSC-UC patients whose median age at diagnosis was 37 (range 11–62) years. (P < 0.001) The male to female ratio was slightly lower in patients in PSC alone group, although the difference was not statistically significant. (Table 1) There was no significant difference in the age of the patients at the time of last follow-up in the two groups: mean age was 53.4 ± 13.1 years in the PSC alone group vs. 51.5 ± 12.8 years in the PSC-UC group. (P = 0.24)
Among the PSC-UC patients, 11 patients were diagnosed with PSC first and later UC, whereas in the remaining patients UC was diagnosed concurrently or earlier than PSC. Patients diagnosed with PSC first and later UC were considered in the PSC-UC group as the outcomes of OLT happened after the diagnosis of UC. Fewer patients with PSC-UC had extrahepatic strictures (7.2% vs. 23.6%, P < 0.001) than those with PSC alone. (Table 1)
Patients in the PSC alone group had much higher serum bilirubin and aspartate aminotransferase at the time of PSC diagnosis/earliest available at our centre than patients in the PSC-UC group. (Table 1) The median initial Mayo PSC risk score at the time of PSC diagnosis/earliest available at our centre was also much higher in patients with PSC alone than in patients with PSC-UC. [1.69 (™2.0–5.03) vs. 0.95 (™2.33–5.19), P < 0.001] Patients with PSC/UC had a total of 2321 person years follow-up, whereas patients with PSC alone had a total of 412 person years follow-up. In patients with PSC alone, the median time to OLT from PSC diagnosis was 6 (range 3–10) years, whereas in patients with PSC-UC, the median time to OLT from PSC diagnosis was 13 (range 11–15) years.
At the end of the follow-up period or just before OLT, the PSC alone group had significantly higher serum bilirubin (median 6.3 mg/dL vs. 5 mg/dL; P < 0.001) compared with the PSC-UC group.
Among the 167 patients with concomitant UC, 153 (91.6%) had extensive colitis. UC activity (in the last 5 years of follow-up) was quiescent endoscopically and histologically in 71/167 (42.5%) of patients. A total of 46 of 167 (27.5%) patients had greater than three flares of UC requiring corticosteroids during the last 5 years of follow-up.
The use of azathioprine/mercaptopurine was required in 15/167 (9%), whereas biologics were required in 8/167 (4.8%). 5-Aminosalicylates were used in 131/167 (78.4%) of patients. A total of 92 of 167 (55.1%) patients required colectomy during follow-up. Twenty seven patients required colectomy for steroid refractory disease, 15 patients for steroid dependent disease, whereas 50 patients underwent colectomy for colon dysplasia/colon cancer. Among the patients who required colectomy suggesting severe disease, concomitant PSC was less severe (requirement for OLT). Requirement for OLT was less frequent in the group requiring colectomy [30 (32.6%) vs. 56 (74.7%), P < 0.001].
Among the 30 patients who requiring colectomy in the OLT group, 12 patients had colectomy performed for medically refractory or steroid dependent disease. In PSC patients who did not require OLT, but required colectomy, 30/62 patients had colectomy for medically refractory or steroid dependent disease. (P < 0.001) In addition, the use of azathioprine/mercaptopurine was significantly more frequent in PSC patients who did not require OLT (17.3% vs. 1.2%, P = 0.006). However, there was no difference in the use of biologics between the two groups. (3.7% vs. 5.8%, P = 0.72).
One patient (1.8%) in the PSC alone group developed cholangiocarcinoma vs. seven patients (4.2%) in the PSC-UC group. (P = 0.68) (Table 2). Only 1 of the 55 (1.8%) patients with PSC alone developed colon neoplasia as compared with 55/167 (32.9%) patients with PSC-UC. (P < 0.001) In the group of patients with PSC alone, one patient was diagnosed with colon carcinoma when colonoscopy was performed for abdominal pain and anaemia. In the PSC-UC group, 16 patients had low grade dysplasia, 25 patients had high grade dysplasia and 14 patients had colorectal cancer. (P < 0.001) The patients in the PSC-UC group have more colonoscopies as a part of surveillance, a mean of 1.3 ± 1.2 vs. 0.9 ± 0.3 in the group with PSC alone. The PSC alone patients had colonoscopies to rule out associated IBD. In addition, screening colonoscopies were performed in patients above 50 years of age or as a part of OLT work up.
More patients underwent OLT in the PSC alone group in comparison to the PSC-UC group (P = 0.001). Among the PSC-UC patients, 86 underwent OLT. The predominant indication for OLT in this group was end-stage liver disease/cirrhosis in 66 (76.7%) patients, recurrent cholangitis in 19 (22.1%) patients and cholangiocarcinoma in 1 (1.1%) patient. Among patients with PSC alone, 29 patients underwent OLT and cirrhosis was responsible in 15 (51.7%) patients and recurrent cholangitis in 14 (48.3%) patients (P = 0.02). We observed more episodes of cholangitis in patients with PSC alone. Figure 2 shows the Kaplan–Meier curve for proportion of patients free of orthotopic liver transplantation (OLT). PSC alone patients were less likely to be OLT-free than PSC patients with UC (Log rank P = 0.004). Figures 3 and 4 shows the unadjusted Kaplan–Meier curve of the OLT-free survival and the overall survival in patients with PSC with and without UC. PSC alone patients had worse overall survival and OLT-free survival than patients with PSC-UC (Log Rank P < 0.001).
(Enlarge Image)
Figure 2.
Kaplan–Meier curve for proportion of patients free of orthotopic liver transplantation (OLT). PSC alone patients were less likely to be OLT-free than PSC patients with UC (P = 0.004, Log-rank test).
(Enlarge Image)
Figure 3.
Kaplan–Meier survival curve for orthotopic liver transplant (OLT) free survival of PSC patients with and without UC. PSC alone patients have a reduced OLT-free survival than PSC patients with UC (P < 0.001, Log-rank test).
(Enlarge Image)
Figure 4.
Kaplan–Meier survival curve for overall survival of PSC patients with and without UC. PSC alone patients had a reduced overall survival than PSC patients with UC (P < 0.001, Log-rank test).
Ninety-two patients in the PSC-UC group underwent colectomy in contrast to one in the PSC alone group (Table 2). Among the patients who underwent colectomy, 7/92 (7.6%) patients underwent total proctocolectomy with end ileostomy, 1/92 (1.1%) patient underwent total proctocolectomy with Brooke's ileostomy, whereas the remaining 84 (91.3%) patients underwent total proctocolectomy with ileal-pouch anal anastomosis. (IPAA) In the PSC alone group, one patient underwent total proctocolectomy with end ileostomy for colon carcinoma.
On Cox proportional hazards analysis, presence of UC [hazard ratio (HR) = 0.90 (95% confidence interval (CI) 0.60–1.34, P = 0.60] was not associated with death or OLT, after adjusting for gender, Mayo PSC risk score and calendar year of PSC diagnosis. As expected, the revised Mayo risk score for PSC [HR = 5.08, 95% CI: (2.62–9.86), P < 0.001] was associated with a greater risk for OLT or death (Table 3).
Results
Demographic and Clinical Characteristics
The basic demographic and clinical information including age, gender, race, age at PSC diagnosis and colonoscopic extent of UC are summarised in Table 1. Patients with PSC were divided into two groups: 167 with PSC-UC (PSC-UC) and 55 with PSC alone (PSC). The median age at presentation for the subgroup of PSC alone patients was 48 (range 12–72) years. These patients were significantly older than the group of PSC-UC patients whose median age at diagnosis was 37 (range 11–62) years. (P < 0.001) The male to female ratio was slightly lower in patients in PSC alone group, although the difference was not statistically significant. (Table 1) There was no significant difference in the age of the patients at the time of last follow-up in the two groups: mean age was 53.4 ± 13.1 years in the PSC alone group vs. 51.5 ± 12.8 years in the PSC-UC group. (P = 0.24)
Among the PSC-UC patients, 11 patients were diagnosed with PSC first and later UC, whereas in the remaining patients UC was diagnosed concurrently or earlier than PSC. Patients diagnosed with PSC first and later UC were considered in the PSC-UC group as the outcomes of OLT happened after the diagnosis of UC. Fewer patients with PSC-UC had extrahepatic strictures (7.2% vs. 23.6%, P < 0.001) than those with PSC alone. (Table 1)
Patients in the PSC alone group had much higher serum bilirubin and aspartate aminotransferase at the time of PSC diagnosis/earliest available at our centre than patients in the PSC-UC group. (Table 1) The median initial Mayo PSC risk score at the time of PSC diagnosis/earliest available at our centre was also much higher in patients with PSC alone than in patients with PSC-UC. [1.69 (™2.0–5.03) vs. 0.95 (™2.33–5.19), P < 0.001] Patients with PSC/UC had a total of 2321 person years follow-up, whereas patients with PSC alone had a total of 412 person years follow-up. In patients with PSC alone, the median time to OLT from PSC diagnosis was 6 (range 3–10) years, whereas in patients with PSC-UC, the median time to OLT from PSC diagnosis was 13 (range 11–15) years.
At the end of the follow-up period or just before OLT, the PSC alone group had significantly higher serum bilirubin (median 6.3 mg/dL vs. 5 mg/dL; P < 0.001) compared with the PSC-UC group.
Clinical Activity of UC
Among the 167 patients with concomitant UC, 153 (91.6%) had extensive colitis. UC activity (in the last 5 years of follow-up) was quiescent endoscopically and histologically in 71/167 (42.5%) of patients. A total of 46 of 167 (27.5%) patients had greater than three flares of UC requiring corticosteroids during the last 5 years of follow-up.
The use of azathioprine/mercaptopurine was required in 15/167 (9%), whereas biologics were required in 8/167 (4.8%). 5-Aminosalicylates were used in 131/167 (78.4%) of patients. A total of 92 of 167 (55.1%) patients required colectomy during follow-up. Twenty seven patients required colectomy for steroid refractory disease, 15 patients for steroid dependent disease, whereas 50 patients underwent colectomy for colon dysplasia/colon cancer. Among the patients who required colectomy suggesting severe disease, concomitant PSC was less severe (requirement for OLT). Requirement for OLT was less frequent in the group requiring colectomy [30 (32.6%) vs. 56 (74.7%), P < 0.001].
Among the 30 patients who requiring colectomy in the OLT group, 12 patients had colectomy performed for medically refractory or steroid dependent disease. In PSC patients who did not require OLT, but required colectomy, 30/62 patients had colectomy for medically refractory or steroid dependent disease. (P < 0.001) In addition, the use of azathioprine/mercaptopurine was significantly more frequent in PSC patients who did not require OLT (17.3% vs. 1.2%, P = 0.006). However, there was no difference in the use of biologics between the two groups. (3.7% vs. 5.8%, P = 0.72).
Colon Cancer and Cholangiocarcinoma
One patient (1.8%) in the PSC alone group developed cholangiocarcinoma vs. seven patients (4.2%) in the PSC-UC group. (P = 0.68) (Table 2). Only 1 of the 55 (1.8%) patients with PSC alone developed colon neoplasia as compared with 55/167 (32.9%) patients with PSC-UC. (P < 0.001) In the group of patients with PSC alone, one patient was diagnosed with colon carcinoma when colonoscopy was performed for abdominal pain and anaemia. In the PSC-UC group, 16 patients had low grade dysplasia, 25 patients had high grade dysplasia and 14 patients had colorectal cancer. (P < 0.001) The patients in the PSC-UC group have more colonoscopies as a part of surveillance, a mean of 1.3 ± 1.2 vs. 0.9 ± 0.3 in the group with PSC alone. The PSC alone patients had colonoscopies to rule out associated IBD. In addition, screening colonoscopies were performed in patients above 50 years of age or as a part of OLT work up.
Orthotopic Liver Transplantation and Death
More patients underwent OLT in the PSC alone group in comparison to the PSC-UC group (P = 0.001). Among the PSC-UC patients, 86 underwent OLT. The predominant indication for OLT in this group was end-stage liver disease/cirrhosis in 66 (76.7%) patients, recurrent cholangitis in 19 (22.1%) patients and cholangiocarcinoma in 1 (1.1%) patient. Among patients with PSC alone, 29 patients underwent OLT and cirrhosis was responsible in 15 (51.7%) patients and recurrent cholangitis in 14 (48.3%) patients (P = 0.02). We observed more episodes of cholangitis in patients with PSC alone. Figure 2 shows the Kaplan–Meier curve for proportion of patients free of orthotopic liver transplantation (OLT). PSC alone patients were less likely to be OLT-free than PSC patients with UC (Log rank P = 0.004). Figures 3 and 4 shows the unadjusted Kaplan–Meier curve of the OLT-free survival and the overall survival in patients with PSC with and without UC. PSC alone patients had worse overall survival and OLT-free survival than patients with PSC-UC (Log Rank P < 0.001).
(Enlarge Image)
Figure 2.
Kaplan–Meier curve for proportion of patients free of orthotopic liver transplantation (OLT). PSC alone patients were less likely to be OLT-free than PSC patients with UC (P = 0.004, Log-rank test).
(Enlarge Image)
Figure 3.
Kaplan–Meier survival curve for orthotopic liver transplant (OLT) free survival of PSC patients with and without UC. PSC alone patients have a reduced OLT-free survival than PSC patients with UC (P < 0.001, Log-rank test).
(Enlarge Image)
Figure 4.
Kaplan–Meier survival curve for overall survival of PSC patients with and without UC. PSC alone patients had a reduced overall survival than PSC patients with UC (P < 0.001, Log-rank test).
Surgery for UC
Ninety-two patients in the PSC-UC group underwent colectomy in contrast to one in the PSC alone group (Table 2). Among the patients who underwent colectomy, 7/92 (7.6%) patients underwent total proctocolectomy with end ileostomy, 1/92 (1.1%) patient underwent total proctocolectomy with Brooke's ileostomy, whereas the remaining 84 (91.3%) patients underwent total proctocolectomy with ileal-pouch anal anastomosis. (IPAA) In the PSC alone group, one patient underwent total proctocolectomy with end ileostomy for colon carcinoma.
Multi-variable Analysis of Risk Factors for Adverse Liver Outcome
On Cox proportional hazards analysis, presence of UC [hazard ratio (HR) = 0.90 (95% confidence interval (CI) 0.60–1.34, P = 0.60] was not associated with death or OLT, after adjusting for gender, Mayo PSC risk score and calendar year of PSC diagnosis. As expected, the revised Mayo risk score for PSC [HR = 5.08, 95% CI: (2.62–9.86), P < 0.001] was associated with a greater risk for OLT or death (Table 3).
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