Morbidity in patients with posttransplant diabetes mellitus following orthotopic liver transplantation.

It is not well understood whether posttransplant diabetes mellitus (PTDM) following orthotopic liver transplantation (OLTx) alters postoperative morbidity. This study was designed to evaluate this question. All adult patients who received an OLTx between July 1985 and March 1993 (n = 497) were evaluated by retrospective chart review for evidence of PTDM after OLTx. The patients identified with PTDM (n = 26) were case matched with nondiabetic OLTx recipients based on primary liver disease diagnosis, age, gender, date of first OLTx, and survival. Liver synthetic function, number and severity of rejection episodes, graft survival, total number of hospital days within the first year post-OLTx, renal function, and number and type of infection episodes were analyzed to assess differences in morbidity between the PTDM and control patients after OLTx. Of the 497 adult patients who underwent OLTx, 26 (5.2%) were identified as having PTDM within 1 month of discharge. Factors which identified individuals at higher risk for DM after OLTx included higher pre-OLTx fasting blood glucose (P = .04); lower body mass index after OLTx (P = .02); and cyclosporine rather than OKT3 induction (P = .009). Graft survival, synthetic function, and the total number of rejection episodes during the first year were not different between the two groups. The morbidity variables of total number of days in the hospital during the first 12 months, renal function, and type and number of infections were also similar between the two groups. In summary, 5.2% of adult patients developed DM within 1 month of OLTx. Pre-existing insulin resistance, postoperative stress, and immunosuppression medications all likely contribute to the development of overt hyperglycemia after OLTx. Although PTDM can be a consequence of OLTx, it does not have a significant impact on patient outcome in the first year after OLTx.

Results of liver transplantation in diabetic recipients.

BACKGROUND: The results of orthotopic liver transplantation (OLTx) in patients with diabetes mellitus (DM) are not well defined. METHODS: Between 1985 and 1991, 45 adult patients with pretransplantation DM (5 type I, 40 type II) underwent OLTx at our center as identified by retrospective chart review. We compared this diabetic recipient group to a case-control nondiabetic group matched for age, gender, primary liver disease, weight, and timing of OLTx. A total of 30 variables were collected and analyzed with McNemar's test for categorical data, paired t tests for continuous data, and survival and repeated measures analysis for longitudinal data. RESULTS: No differences between diabetic and nondiabetic recipients were noted in patient or graft survival, the incidence or severity of rejection, blood transfusions, operative complications, readmissions, major infections, or number of hospital days after OLTx. However, the incidence of minor bacterial (p = 0.046) and minor fungal (p = 0.035) infections were higher in the DM group. Serum blood urea nitrogen (p = 0.02) and creatinine (p = 0.03) levels were also higher in patients with diabetes versus control patients during the first year after OLTx. CONCLUSIONS: In carefully selected patients with pretransplantation DM, OLTx can be accomplished with results similar to nondiabetic recipients in spite of a higher incidence of minor infections and renal dysfunction.

Liver transplantation at the University of Nebraska Medical Center from 1985 to 1992.

Based on our 7 and one-half-year experience with liver transplantation at the University of Nebraska Medical Center: 1. Success and growth of the program has been, in part, the result of close interaction and support of the various specialists involved. 2. We have demonstrated that outstanding patient and graft survival rates can be obtained with cyclosporine/prednisone immunosuppression. 3. Few, if any, technical contraindications exist to liver transplantation. 4. Surgical advances have allowed allografts to be salvaged which would otherwise require replacement. 5. Routine donor-liver biopsy prior to implantation has reduced the rate of primary nonfunction. 6. New strategies to improve survival for patients with hepatitis-B-related liver disease and hepatic malignancies undergoing liver transplantation need to be developed. 7. The management of patients with fulminant hepatic failure is evolving and now includes innovative approaches such as the use of ECLS and auxiliary transplants.

A randomized prospective trial of acyclovir and immune globulin prophylaxis in liver transplant recipients receiving OKT3 therapy.

The use of OKT3 therapy is a major risk factor for opportunistic infections in liver transplant recipients. In the last 2 years, we prospectively randomized 100 patients receiving OKT3 therapy into either a control group (n = 50) or a prophylaxis group (n = 50). Prophylaxis consisted of six doses of intravenous immune globulin over 4 weeks and oral acyclovir for 3 months after OKT3 therapy. The two groups were comparable with respect to demographic, immunologic, and clinical characteristics. The regimen of prophylaxis resulted in (1) a significant reduction in the incidence of herpetic and Epstein-Barr viral infections; (2) no change in the incidence of cytomegalovirus infections; (3) a significant decrease in the incidence of fungal infections; and (4) fewer deaths due to sepsis. The incidence of viral and fungal infections was higher after OKT3 induction than after rescue therapy. Our conclusion is that opportunistic infections are frequent after OKT3 therapy in hepatic allograft recipients. Treatment with intravenous immune globulin and oral acyclovir is safe and effective in preventing non-cytomegaloviral and fungal infections in this setting, thus conferring a survival advantage with fewer deaths due to sepsis.

Clinical spectrum of fungal infections after orthotopic liver transplantation.

During a 50-month period, we identified 91 episodes of fungal infection in 72 liver transplant recipients (23.8%). Candida species accounted for 83.5% of cases. Clinical patterns of fungal infections included disseminated infection (19), peritonitis (17), pneumonitis (15), multiple sites of colonization (13), fungemia (11), and other sites (16). The diagnosis of fungal infection was usually made in the first 2 months (84.7% of cases), at a mean time of 16 days after transplantation. Risk factors for fungal infections included retransplantation, Risk score, intraoperative transfusion requirement, urgent status, Roux limb biliary reconstruction (in adults), steroid dose, bacterial infections and antibiotic therapy, and vascular complications. Fungal infections were successfully treated with amphotericin B in 63 cases (74.1%) but were associated with diminished patient survival (50% vs 83.5%). Fungal infection is a frequent source of early morbidity and can be related to well-defined risk factors, suggesting the need for effective prophylaxis.

Predictive value of intraoperative liver biopsies of donor organs in patients undergoing orthotopic liver transplantation.

The evaluation of prerevascularization and postrevascularization biopsies in comparison with clinical and laboratory data has revealed a direct correlation between elevated PT and AST levels and pericentral and panlobular individual hepatocyte necrosis. No other significant correlations were determined when comparing selected histologic features to selected clinical laboratory values. In conclusion, these biopsies are of limited use in predicting subsequent allograft function in the absence of prominent individual hepatocyte or pericentral necrosis.

Optimal therapy for patients with biliary atresia: portoenterostomy ("Kasai" procedures) versus primary transplantation.

As the results with liver transplantation have improved, a controversy has arisen regarding the precise role of a portoenterostomy in the treatment of infants with biliary atresia. The controversy centers around three issues: (1) the short- and long-term survival rates achieved with both procedures, (2) the influence of a portoenterostomy on a subsequent transplant, and (3) the shortage of suitable liver donors for very small infants. To address these questions, we retrospectively reviewed the charts of 48 children with biliary atresia who underwent liver transplantation and compared these results with 35 children transplanted for other liver diseases. As a group, the biliary atresia patients had significantly lower mean body weights and ages and spent a significantly longer time on the waiting list. In addition, significantly more of the biliary atresia patients had undergone prior abdominal surgery when compared with the non-biliary atresia group. There was no difference in the intraoperative variables of mean anesthesia time, mean operative time, mean anesthesia preparation time, nor the mean amount of blood transfused intraoperatively between the two groups. However, when the biliary atresia patients who had undergone a portoenterostomy with a stoma were compared with either the biliary atresia patients who did not have a stoma created as part of their portoenterostomy or the non-biliary atresia patients, significant differences were noted in mean total anesthesia time, mean operative time, and the mean amount of blood transfused intraoperatively. The survival rate of the biliary atresia patients was significantly greater than the non-biliary atresia patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical patterns of cytomegalovirus disease after liver transplantation.

During a 43-month period, we performed 248 liver transplantations in 211 patients (127 adults and 84 children). Cytomegalovirus (CMV) disease was documented in 73 recipients (34.6%). Risk factors for CMV disease included donor CMV seropositivity, antilymphocyte therapy, and retransplantation. The mean time of occurrence of CMV disease was 38.3 days after transplantation, and the most frequent site of disease was the hepatic allograft. A total of 69 patients were treated with intravenous ganciclovir, with a prompt and lasting response documented in 51 (73.9%). The remaining 18 (26.1%) developed recurrent CMV disease, which was more common after primary CMV exposure. Cytomegalovirus disease was ultimately controlled by ganciclovir in 94.2% of cases. This disease occurs early after transplantation and can be related to well-defined risk factors. Although ganciclovir therapy is effective, preliminary experience with prophylaxis shows promise in reducing the incidence of CMV disease.

Diagnosis and treatment of biliary tract complications after orthotopic liver transplantation.

Biliary tract complications are a continuing source of morbidity after liver transplantation. In a 3.5-year period we performed 264 liver transplants in 226 patients (132 adults, 94 children). Biliary tract reconstruction was via Roux limb choledochojejunostomy (n = 144) or choledochocholedochostomy (n = 118). Fifty (19.1%) biliary complications occurred, and 35 (13.4%) necessitated operative repair. The incidence was similar in adults and children and after each method of reconstruction. Risk factors were vascular thrombosis and reduced-sized transplants. Diagnosis was based on the algorithmic use of multiple modalities with early biliary visualization. Roux limb complications usually occurred in the first month after transplant and necessitated operative intervention, whereas duct-to-duct problems appeared later and were more accessible to percutaneous or endoscopic manipulations. Eight (6.8%) patients required conversion to a Roux limb, whereas 8/15 (53.3%) cases of biliary stricture were successfully managed nonoperatively. Three (1.3%) patients and four (1.5%) grafts were lost as a result of biliary complications. One-year actuarial patient survival is 76.4% with a mean follow-up of 13.2 months. Early recognition of biliary complications and prompt interventional therapy can effectively prevent long-term sequelae. Although choledochocholedochostomy is more physiologic and expeditious, Roux-en-Y choledochojejunostomy remains a safe and versatile alternative and is the preferred method of reconstruction in select cases.

Stratifying the causes of death in liver transplant recipients. An approach to improving survival.

The causes of death in 21 adults and 23 children in a consecutive series of 180 liver transplantations were reviewed and classified into four categories. A previously described preoperative risk score was applied prospectively to estimate the relative risk of mortality following liver transplantation in adults. Categorization of the causes of death allowed for a systematic search for errors in management and technique. Comparison of the preoperative risk score with the cause of death category revealed that higher-risk adults were most likely to die of causes related to preoperative morbidity. They also accrued higher hospital costs, regardless of outcome. The data are useful for designing strategies to reduce mortality. However, the inexorable role that preoperative morbidity has on outcome was also emphasized. This has important implications in developing strategies to reduce the costs of liver transplantation and to provide optimal distribution of scarce donor organs.

Complications requiring operative intervention after orthotopic liver transplantation.

Survival rates after liver transplantation continue to improve, but the postoperative morbidity in these patients remains significant. The clinical courses of 96 consecutive patients who received transplants were reviewed retrospectively. Forty-two patients experienced complications requiring surgical intervention. These complications were primarily related to biliary tract reconstruction, bowel complications, and septic complications. None of the factors examined, except a second transplant procedure, proved helpful in identifying those patients most likely to experience surgical complications; however, a risk factor scoring system was found to accurately identify that group of patients at highest risk of dying in the postoperative period. Only 2 of 21 deaths could be attributed directly to the surgical complication. We believe that a policy of prompt, aggressive surgical intervention, coupled with careful tailoring of immunosuppression to both the patient and the clinical situation, can lead to a low mortality rate in patients who require reoperation.