Evaluation of abnormal liver function tests.

Interpretation of abnormalities in liver function tests is a common problem faced by clinicians. This has become more common with the introduction of automated routine laboratory testing. Not all persons with one or more abnormalities in these tests actually have liver disease. The various biochemical tests, their pathophysiology, and an approach to the interpretation of abnormal liver function tests are discussed in this review.

Histological changes associated with the use of intravenous cyclosporin in the treatment of severe ulcerative colitis may mimic dysplasia.

BACKGROUND: During six years experience of intravenous cyclosporin (i.v. Cy) for severe ulcerative colitis we have noted that changes of villous architecture and epithelial regeneration occur even when the disease fails to enter clinical remission and colectomy is required. OBJECTIVE: To describe the histological changes in patients who received i.v. Cy and steroids compared with those treated with i.v. steroids alone. PATIENTS AND METHODS: Two groups of histological sections were reviewed. The first group was of 23 colectomy specimens from patients who had been treated with i.v. Cy and steroids. For 11 patients pre-Cy histological sections were available. The second group was of 10 colectomy specimens from patients who had received i.v. steroids alone. Biopsies were scored for their histological disease activity (HDAI), villous architecture and epithelial regeneration. The HDAI assesses the degree of acute and chronic inflammation. RESULTS: The post-Cy group had higher median scores for villous architecture and epithelial regeneration compared to the pre-Cy and poststeroid groups. For the patients where both pre- and post-Cy histological sections were available 63% increased their villous score post-Cy and 82% increased their epithelial regeneration score post-Cy. CONCLUSION: Although villous transformation and epithelial regeneration may be seen in UC they are more frequent and more severe in those patients who received i.v. Cy and i.v. steroids, compared to controls who received i.v. steroids alone. These histological changes may mimic dysplasia. Increased awareness of this potential mimic of dysplasia is crucial for patient management.

Cyclosporin for severe ulcerative colitis does not increase the rate of perioperative complications.

PURPOSE: Cyclosporin is used in severe ulcerative colitis that is refractory to intravenous steroids. Cyclosporin is a potent immunosuppressant and can cause side effects such as opportunistic infections. This study aimed to investigate the incidence of perioperative complications in patients treated with intravenous cyclosporin and steroids compared with patients treated with intravenous steroids alone. METHODS: We retrospectively reviewed the case notes of 44 patients with severe ulcerative colitis who underwent total abdominal colectomy and ileostomy. Twenty-five patients were treated with intravenous steroids and 19 patients were treated with intravenous cyclosporin and steroids. Details were recorded with respect to age, length of illness, extent of disease, Truelove and Witt's criteria, hemoglobin and albumin at surgery, surgical procedure, and perioperative morbidity. RESULTS: Twenty-four percent of patients treated with intravenous steroids alone and 15.8 percent of patients treated with intravenous cyclosporin and steroids had major surgical complications. Sixteen percent of patients treated with intravenous steroids alone and 5.2 percent of patients treated with intravenous cyclosporin and steroids had minor surgical complications. Eight percent of patients treated with intravenous steroids alone and 10.5 percent of patients treated with intravenous cyclosporin and steroids had major medical complications. There was no mortality in either group. CONCLUSIONS: There is no increased incidence of perioperative complications associated with the use of intravenous cyclosporin in addition to steroids in acute severe ulcerative colitis provided cyclosporin treatment is for a defined period and surgery is not delayed.

Intravenous cyclosporin as rescue therapy in severe ulcerative colitis: time for a reappraisal?

BACKGROUND: Intravenous cyclosporin is the only new therapy in recent years to have made a significant impact on the management of acute severe ulcerative colitis (UC). It is increasingly recommended for use in patients who prove refractory to the standard regimen of intravenous (i.v.) and rectal hydrocortisone but do not warrant immediate surgery. This practice is based on uncontrolled and controlled studies which suggest a short-term efficacy of 80% and long-term efficacy of 60% in avoiding colectomy. AIM: The aim of this study was to assess the short- and long-term efficacy of i.v. cyclosporin in patients admitted to our hospital with acute severe ulcerative colitis refractory to i.v. steroids, over a 6-year period. METHOD: A retrospective survey of patients admitted to the John Radcliffe Hospital, Oxford, with acute severe UC over a 6-year period (1991-97) was performed. Truelove and Witts criteria for acute severe UC were satisfied by 216 patients. RESULTS: The standard regimen achieved remission in 132 patients (61%). Of the 84 patients who failed to respond, 34 (40%) proceeded directly to colectomy whilst 50 received cyclosporin (4 mg/kg by continuous slow infusion). Remission was achieved by i.v. cyclosporin in 28/50 (56%) patients who were subsequently transferred to oral cyclosporin (5 mg/kg). However, 8/28 (29%) who initially responded later relapsed after discharge from hospital and underwent colectomy. The short-term efficacy of 56% therefore falls to 40% in the longer term (mean follow-up of 19 months). CONCLUSION: This is the largest survey to date of patients with refractory severe UC treated with i.v. cyclosporin. The findings confirm the potential value of i.v. cyclosporin in severe UC but its effectiveness in clinical practice is less dramatic than previously reported.

Review article: the management of severe ulcerative colitis.

Severe ulcerative colitis is a potentially life-threatening condition but the mortality has fallen dramatically over the past 30-40 years. It is now less than 2%, including surgical mortality, and should only be seen in patients with significant co-existing disease. Early recognition of the severity of the colitis, intensive medical therapy, close liaison between physician and surgeon, and prompt surgery when necessary have all contributed to this improved outcome. Despite the use of high-dose intravenous corticosteroids, 20-30% of patients will make a poor response and will require urgent surgery. The use of intravenous cyclosporin has proved effective at reducing the immediate surgical rate in this group of unresponsive patients and appears safe. Whether cyclosporin reduces the need for surgery in the longer term is much less certain. Clinical, radiological, endoscopic and laboratory parameters can now be used to predict the course of a severe attack. These help in the timing of urgent surgery and are potentially helpful in determining when to begin other therapies such as cyclosporin.

HIV associated cytomegalovirus colitis as a mimic of inflammatory bowel disease.

Cytomegalovirus (CMV) colitis may cause symptoms and signs identical to those of idiopathic inflammatory bowel disease. Although difficult to diagnose with certainty, the histological finding of cytomegalovirus inclusions in tissue from a case of suspected inflammatory bowel disease is strongly suggestive. CMV colitis is an entity almost entirely confined to cases of severe immunosuppression. The case of a 79 year old widower who was admitted to hospital with symptoms suggestive of inflammatory bowel disease is presented. Despite medical treatment his condition worsened and he developed toxic dilatation of the colon requiring colectomy. Histological examination showed a mild superficial pancolitis, with focal severe inflammation, deep fissuring ulceration, and pseudopolyposis. Abundant CMV inclusions were seen in cells associated with the ulcerating inflammatory tissue. A diagnosis of indeterminate colitis with CMV was made. The patient's condition worsened after surgery and he died a few days later despite intensive treatment, including antiviral chemotherapy directed against CMV. After death HIV serology was found to be positive. Regardless of the age and perceived lifestyle of the patient, a diagnosis of CMV colitis in someone not known to be immunosuppressed raises the possibility of HIV infection.