Six (26%) of the 23 patients had quiescent ulcerative colitis prior to liver transplantation and had not required treatment for their ulcerative colitis. Colonoscopy with multiple colonic biopsies documented pancolitis to be present in all. The indication for OLTx in these six patients was primary sclerosing cholangitis. This clinically quiescent ulcerative colitis subgroup of four males and two females was 34.7 ± 6.2 years of age at time of OLTx, and the duration of their follow-up post OLTx was 109.9 ± 5.9 weeks (range: 104–136 weeks). The daily immunosuppressive regimen in this group was 400.0 ± 44.7 mg of cyclosporine and 10.8 ± 0.5 mg of prednisone. At time of follow-up, five patients (83.3%) were working full-time and one was not working but able to care for herself at home. All six patients reported themselves to be free of ulcerative colitis symptoms following transplantation.
Seventeen patients, 11 males and six females, had had symptomatic ulcerative colitis prior to transplantation. Seven of these patients (40%) had mild clinical ulcerative colitis, eight had moderate colitis (47%), and two (13%) had severe clinical colitis. The duration of ulcerative colitis prior to OLTx was 15.4 ± 1.9 years. (The initial onset had been mild in 29.4%, moderate in 47.1%, and severe in 23.5%). The course of the ulcerative colitis had been continuous in 35.3% and intermittent in 64.7%. Among the 11 patients with an intermittent course, the intervening attacks had been severe in two, moderate in seven, and mild in two. Prior to transplant, 66.7% of these patients had been treated for their ulcerative colitis with sulfasalazine, 46.7% with steroid enemas, 40.0% with Lomotil, 26.7% with prednisone, and 18.8% with azathioprine. Colonoscopy performed during evaluation for liver transplantation demonstrated pancolitis to be present in all 17 patients. Histologically, prior to transplantation, 80% of the subjects had minimal disease based upon a histologic examination of multiple colonic biopsies obtained at the time of the preoperative colonoscopy. Ten percent of the subjects had moderate and 10% had severe colitis histologically.
At time of transplant, the mean range was 39.8 ± 1.6 years; the indication for OLTx was primary sclerosing cholangitis in 16 and congenital hepatic fibrosis in one. In this subgroup of 17 patients with symptomatic ulcerative colitis prior to OLTx, the duration of follow-up was 82.7 ± 9.6 weeks, (range: 31–175 weeks). At time of follow-up, the daily immunosuppressive regimen was 383.8 ± 27.2 mg of cyclosporine and 13.8 ± 0.8 mg of prednisone; in addition, 23.5% were taking sulfasalazine, and 5.9% were using diphenoxylate hydrochloride with atropine sulfate (Lomotil).
In the symptomatic group, in response to the question, “overall, since your liver transplant, are the symptoms of your ulcerative colitis better, worse or the same?”, 82.4% indicated improvement, none reported a worsening, and 17.6% indicated no change (P < 0.001 compared to pre-OLTx). Of the three patients reporting no change, however, two reported that the overall severity of colitis symptoms continued to be moderate following OLTx and one reported a shift from severe to moderate overall colitis severity.
A separate question was asked about overall symptom severity. During the year prior to transplant, the overall severity of colitis symptoms was rated as having been severe by 35.3%, moderate by 52.9%, and mild by 11.8% of these patients. In contrast, at follow-up, 88.2% patients reported improvement, with 52.9% reporting no colitis symptoms, 29.4% mild symptoms, 17.6% moderate symptoms, and none indicating severe colitis symptoms (P < 0.001, pre- versus post-OLTx, mild versus moderate plus severe symptom categories combined).
The frequencies of various ulcerative colitis symptoms before and after transplantation are shown in . The percentages of patients who indicated improvement in symptom severity or frequency were calculated and tested using the binomial test; the results are summarized in . In assessing improvement, all stated levels of severity or frequency were used, and a shift from a more severe to a less severe category was considered to be improvement. Further, those patients reporting no abnormality prior to OLTx (eg, 1 to 2) bowel movements per day or a frequency of “never”) were not considered to be “at risk” for improvement and thus were not included in the denominator for these calculations. As may be seen in , compared to the year prior to OLTx, there was significant improvement at time of follow-up in overall colitis symptom severity, and the frequency of occurrence of daily bowel movements, crampy abdominal pain, bowel urgency, the presence of pus or mucus in the stool, and the occurrence of flares. There was no significant improvement in either rectal pain or rectal bleeding. Among the eight patients experiencing a flare, the mean interval between OLTx and the first flare was 37.0 ± 9.1 weeks; the earliest flare reported occurred at 12 weeks, while one patient indicated the first flare to have occurred as late as 85 weeks. Nine patients reported that colonoscopy (N = 7) or barium enema (N = 2) had been performed during the follow-up period (No patient reported the occurrence of colon surgery following transplantation.) The histological appearance in 16 of the 17 patients with symptomatic colitis during the follow-up period revealed mild colitis in six (46%), moderate colitis in six (47%), and severe colitis in three (18%). This distribution in terms of disease severity graded histologically did not differ significantly from that observed prior to transplantation.
Frequency of Ulcerative Colitis Symptoms in 17 Symptomatic Patients Before and After Transplantation
Ulcerative Colitis Symptom Improvement in 17 Patients following Orthotopic Liver Transplantation
Two aspects of quality of life were assessed: the first involved the impact of ulcerative colitis symptoms on the ability to function normally in daily activities, and the second assessed the overall impact of liver transplantation with immunosuppression as estimated by changes in the ability to work or carry out normal activities. As may be seen in , the impact of ulcerative colitis symptomatology on the ability to function normally was substantially less, but not eliminated, during the follow-up period. Of the 17 with symptomatic disease, 11 patients reported improvement and six reported no change; of these six, three reported that there had been no days during which their ulcerative colitis symptoms had prevented them from functioning normally during the year prior to transplant. Thus, there was overall improvement in 11 of the 14 patients (78.6%) who had been unable to function normally at least once a month pretransplant (P < 0.006). None of these patients had been able to function normally, as measured by the ability to work or participate in usual activities, at time of transplantation because of the severity of their liver disease. Thus, the responses to the question “which category best describes your present activity?” primarily reflect the effect of transplantation, which reversed the end-stage liver disease. As may be seen in , altogether 13 of the 17 patients reported an improvement in their overall ability to pursue normal activities following liver transplantation (P < 0.006). This finding suggests that ability to work or feeling well enough to work following transplantation may have reflected factors other than ulcerative colitis disease activity per se.
Number of Days Unable to Function Normally in Daily Activities because of Ulcerative Colitis Symptoms or Complications—Responses of 17 Symptomatic Patients
Overall Ability to Function following Liver Transplantation—Responses of 17 Symptomatic Patients