A randomized clinical trial of ursodeoxycholic acid as adjuvant treatment to prevent liver transplant rejection.

Acute rejection following orthotopic liver transplantation is a common problem despite current immunosuppressive regimens. Ursodeoxycholic acid (UDCA) has been shown in small, open-labeled studies to prevent rejection episodes, although its effects on complications such as infections, length of hospital stay, and survival have not been evaluated. We conducted a randomized, placebo-controlled, double-blind trial to determine if UDCA (10-15 mg/kg/d) added to a cyclosporine-based immunosuppressive regimen was associated with a decrease in the incidence of at least one episode of acute cellular rejection. Secondary end-points included determining differences in the total number of rejection episodes, the use of muromonab-CD3, the incidence of infections, length of hospital stay, and survival at 90 days and 1 year. Fifty-two patients were randomized, 28 to the treatment group and 24 to the placebo group. During the 3 months of the trial, there was no difference between the placebo and UDCA groups in the number of patients who were rejection-free; however, there were significantly fewer patients in the treatment group who had multiple episodes of acute rejection (0 vs. 6; P = .007). Patients in the treatment group experienced a significantly lower incidence of bacterial infections (4% vs. 29%; P = .02), shorter hospital stay (25 days vs. 34 days; P = .03), and better 90-day survival (100% vs. 83%; P = .04) and 1-year survival (93% vs. 79%). The addition of UDCA to a cyclosporine-based immunosuppressive regimen results in significantly fewer patients experiencing multiple episodes of rejection and improved survival at 90 days and at 1 year. The use of UDCA as adjuvant therapy for patients undergoing liver transplantation who are treated with a cyclosporine-based immunosuppressive regimen should be considered.

Prevalence and reversibility of the hepatopulmonary syndrome after liver transplantation. The Cleveland Clinic experience.

To ascertain the prevalence and reversibility of the hepatopulmonary syndrome, we reviewed the cases of 98 patients undergoing liver transplantation at the Cleveland (Ohio) Clinic Foundation from June 1988 through July 1992 and identified 4 patients with clinically recognized hepatopulmonary syndrome (prevalence 4%). All 4 patients ultimately had complete reversal of their disorder. As reviewed herein, the prevalence of the hepatopulmonary syndrome in the current series is lower than in previous reports, possibly reflecting a dependence on its clinical recognition in this series rather than the use of routine screening tests. This report confirms previous experience that the hepatopulmonary syndrome may be reversible after transplantation.

The prevalence of coronary artery disease in liver transplant candidates over age 50.

The prevalence of angiographically proven coronary artery disease (CAD) in adults with end-stage liver disease who undergo evaluation for liver transplantation is unknown; also it is unclear if cholestatic liver disease represents an independent risk factor. Patients with end-stage liver disease over age 50 having liver transplantation were studied using coronary angiography. Arterial stenosis was graded as normal, mild (< 30%), moderate (30 to 70%), or severe (> 70%). Risk factors for CAD were also assessed (male sex, smoking, hypertension, diabetes, family history of premature heart disease). Complications related to the angiography and decision making based on the findings were recorded. Thirty seven patients (23 females) with a median age of 61 years (range 50 to 71) underwent angiography. Thirteen patients (35.1%) had cholestatic liver disease. Thirty patients had no history of heart disease. The overall prevalence of severe coronary artery disease was 16.2% (95% confidence interval [CI] = 6.2% to 32.0%). No association was detected between CAD and cholestatic liver disease (P = 0.72). After eliminating seven patients with a prior history of angina (n = 1), myocardial infarction (n = 1), or coronary revascularization (n = 5), the frequency of moderate or severe CAD was 13.3% (95% CI = 3.8% to 30.7%). No association was detected between unsuspected CAD and cholestatic liver disease (P = 0.61). Diabetes was the most important risk factor for moderate or severe disease (P = 0.01). Patients without risk factors had significantly less CAD than the group as a whole regardless of the liver disease type (P = 0.02). Two patients experienced transient renal insufficiency after the angiography. Three patients with severe CAD were denied transplantation. We conclude that CAD represents a significant problem in patients over age 50 undergoing liver transplant evaluation. Cholestatic liver disease was not associated with a significantly higher prevalence of moderate or severe CAD in our population. Diabetes was the most predictive risk factor, and those without risk factors do not require extensive preoperative cardiac evaluation.

Selective bowel decontamination with quinolones and nystatin reduces gram-negative and fungal infections in orthotopic liver transplant recipients.

Gram-negative and fungal infections are the most important cause of morbidity and mortality after liver transplantation, especially in the first postoperative month. From February 1989 to February 1990, all liver transplant recipients at The Cleveland Clinic Foundation, Cleveland, Ohio, were placed on a selective bowel decontamination regimen employing oral quinolones and nystatin beginning at the time they were put on the active waiting list for transplantation and continuing until the fourth postoperative week. The incidence of gram-negative and fungal infections for these patients was compared against a historical control group. Selective bowel decontamination was well tolerated and highly effective in reducing early serious gram-negative and fungal infections. This regimen may also reduce mortality.

Failure of hepatitis B immunization in liver transplant recipients: results of a prospective trial.

Twenty patients with advanced liver disease, in need of transplantation, were given three injections of 20 micrograms and three injections of 40 micrograms hepatitis B vaccine to see if an antibody response could be obtained. Only 20% of patients developed measurable anti-HBs. One who failed to develop anti-HBs developed chronic hepatitis B after exposure to her infected sexual partner. Type of liver disease in the native liver, age, sex, sexual preference, timing of immunization (before or after transplantation), and dosage of hepatitis B vaccine did not seem to explain the lack of immunologic response to hepatitis B vaccine. It is presumed that immunosuppression, both from the underlying disease and from immunosuppressive medications, best explains our findings. Liver transplantation patients infrequently benefit from hepatitis B vaccine. It is possible that other vaccines given to prevent viral and bacterial illness may also fail to elicit immunologic response in such patients.