Donor BMI >30 Is Not a Contraindication for Live Liver Donation.

The increased prevalence of obesity worldwide threatens the pool of living liver donors. Although the negative effects of graft steatosis on liver donation and transplantation are well known, the impact of obesity in the absence of hepatic steatosis on outcome of living donor liver transplantation (LDLT) is unknown. Consequently, we compared the outcome of LDLT using donors with BMI <30 versus donors with BMI ≥30. Between April 2000 and May 2014, 105 patients received a right-lobe liver graft from donors with BMI ≥30, whereas 364 recipients were transplanted with grafts from donors with BMI <30. Liver steatosis >10% was excluded in all donors with BMI >30 by imaging and liver biopsies. None of the donors had any other comorbidity. Donors with BMI <30 versus ≥30 had similar postoperative complication rates (Dindo-Clavien ≥3b: 2% vs. 3%; p = 0.71) and lengths of hospital stay (6 vs. 6 days; p = 0.13). Recipient graft function, assessed by posttransplant peak serum bilirubin and international normalized ratio was identical. Furthermore, no difference was observed in recipient complication rates (Dindo-Clavien ≥3b: 25% vs. 20%; p = 0.3) or lengths of hospital stay between groups. We concluded that donors with BMI ≥30, in the absence of graft steatosis, are not contraindicated for LDLT.

First-Degree Living-Related Donor Liver Transplantation in Autoimmune Liver Diseases.

Liver transplantation (LT) is the treatment of choice for end-stage autoimmune liver diseases. However, the underlying disease may recur in the graft in some 20% of cases. The aim of this study is to determine whether LT using living donor grafts from first-degree relatives results in higher rates of recurrence than grafts from more distant/unrelated donors. Two hundred sixty-three patients, who underwent a first LT in the Toronto liver transplant program between January 2000 and March 2015 for autoimmune liver diseases, and had at least 6 months of post-LT follow-up, were included in this study. Of these, 72 (27%) received a graft from a first-degree living-related donor, 56 (21%) from a distant/unrelated living donor, and 135 (51%) from a deceased donor for primary sclerosing cholangitis (PSC) (n = 138, 52%), primary biliary cholangitis (PBC) (n = 69, 26%), autoimmune hepatitis (AIH) (n = 44, 17%), and overlap syndromes (n = 12, 5%). Recurrence occurred in 52 (20%) patients. Recurrence rates for each autoimmune liver disease were not significantly different after first-degree living-related, living-unrelated, or deceased-donor LT. Similarly, time to recurrence, recurrence-related graft failure, graft survival, and patient survival were not significantly different between groups. In conclusion, first-degree living-related donor LT for PSC, PBC, or AIH is not associated with an increased risk of disease recurrence.

Live donor liver transplantation: a valid alternative for critically ill patients suffering from acute liver failure.

We report the outcome of live donor liver transplantation (LDLT) for patients suffering from acute liver failure (ALF). From 2006 to 2013, all patients with ALF who received a LDLT (n = 7) at our institution were compared to all ALF patients receiving a deceased donor liver transplantation (DDLT = 26). Groups were comparable regarding pretransplant ICU stay (DDLT: 1 [0-7] vs. LDLT: 1 days [0-10]; p = 0.38), mechanical ventilation support (DDLT: 69% vs. LDLT: 57%; p = 0.66), inotropic drug requirement (DDLT: 27% vs. LDLT: 43%; p = 0.64) and dialysis (DDLT: 2 vs. LDLT: 0 patients; p = 1). Median evaluation time for live donors was 24 h (18-72 h). LDLT versus DDLT had similar incidence of overall postoperative complications (31% vs. 43%; p = 0.66). No difference was detected between LDLT and DDLT patients regarding 1- (DDLT: 92% vs. LDLT: 86%), 3- (DDLT: 92% vs. LDLT: 86%), and 5- (DDLT: 92% vs. LDLT: 86%) year graft and patient survival (p = 0.63). No severe donor complication (Dindo-Clavien ≥3 b) occurred after live liver donation. ALF is a severe disease with high mortality on liver transplant waiting lists worldwide. Therefore, LDLT is an attractive option since live donor work-up can be expedited and liver transplantation can be performed within 24 h with excellent short- and long-term outcomes.

Benefit of Treating Hepatocellular Carcinoma Recurrence after Liver Transplantation and Analysis of Prognostic Factors for Survival in a Large Euro-American Series.

PURPOSE: To identify prognostic factors after hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). METHODS: We retrospectively reviewed the combined experience at Toronto General Hospital and Hospital Vall d'Hebron managing HCC recurrence after LT (n = 121) between 2000 and 2012. We analyzed prognostic factors by uni- and multi-variate analysis. Median follow-up from LT was 29.5 (range 2-129.4) months. Median follow-up from HCC recurrence was 12.2 (range 0.1-112.5) months. RESULTS: At recurrence, 31.4 % were treated with curative-intent treatments (surgery or ablation), 42.1 % received palliative treatment, and 26.4 % received best supportive care. The 1-, 3-, and 5-year survivals, respectively, after HCC recurrence were 75, 60, and 31 %, vs. 60, 19, and 12 %, vs. 52, 4, and 5 % (p < 0.001). By multivariate analysis, not being amenable to a curative-intent treatment [hazard ratio (HR) 4.7, 95 % confidence interval (CI) 2.7-8.3, p < 0.001], α-fetoprotein of ≥100 ng/mL at the time of HCC recurrence (HR 2.1, 95 % CI 1.3-2.3, p = 0.002) and early recurrence (<12 months) after LT (HR 1.6, 95 % CI 1.1-2.5, p = 0.03) were found to be poor prognosis factors. A prognostic score was devised on the basis of these three independent variables. Patients were divided into three groups, as follows: good prognosis, 0 points (n = 22); moderate prognosis, 1 or 2 points (n = 84); and poor prognosis, 3 points (n = 15). The 1-, 3-, and 5-year actuarial survival for each group was 91, 50, and 50 %, vs. 52, 7, and 2 %, vs. 13, 0, and 0 %, respectively (p < 0.001). CONCLUSIONS: Patients with HCC recurrence after transplant amenable to curative-intent treatments can experience significant long-term survival (~50 % at 5 years), so aggressive management should be offered. Poor prognosis factors after recurrence are not being amenable to a curative-intent treatment, α-fetoprotein of ≥100 ng/mL, and early (<1 year) recurrence after LT.

Living vs. deceased donor liver transplantation provides comparable recovery of renal function in patients with hepatorenal syndrome: a matched case-control study.

Outcomes of living versus deceased donor liver transplantation in patients with chronic liver disease and hepatorenal syndrome (HRS) was compared using a matched pair study design. Thirty patients with HRS receiving a live donor liver transplantation (LDLT) and 90 HRS patients receiving a full graft deceased donor liver transplantation (DDLT) were compared. LDLT versus DDLT of patients with HRS was associated with decreased peak aspartate aminotransferase levels (339 ± 214 vs. 935 ± 1253 U/L; p = 0.0001), and similar 7-day bilirubin (8.42 ± 7.89 vs. 6.95 ± 7.13 mg/dL; p = 0.35), and international normalized ratio levels (1.93 ± 0.62 vs. 1.78 ± 0.78; p = 0.314). LDLT vs. DDLT had a decreased intensive care unit (2 [1-39] vs. 4 [0-93] days; p = 0.004), and hospital stay (17 [4-313] vs. 26 [0-126] days; p = 0.016) and a similar incidence of overall postoperative complications (20% vs. 27%; p = 0.62). No difference was detected between LDLT and DDLT patients regarding graft survival at 1 (80% vs. 82%), at 3 (69% vs. 76%) and 5 years (65% vs. 76%) (p = 0.63), as well as patient survival at 1 (83% vs. 82%), 3 (72% vs. 77%) and 5 years (72% vs. 77%) (p = 0.93). The incidence of chronic kidney disease post-LT (10% vs. 6%; p = 0.4) was similar between both groups. LDLT results in identical long-term outcome when compared with DDLT in patients with HRS.

Portal venous versus systemic venous drainage of pancreas grafts: impact on long-term results.

Portal venous (PV) and systemic venous (SV) drainage methods are used in pancreas transplantation. The impact of the reconstruction technique on long-term outcome remains unclear. We compared the efficacy and side effects of both methods in 192 recipients who received synchronous pancreas kidney transplants between November 1995 and November 2007. SV and PV drainage were used in 147 and 45 cases, respectively. Pancreas function was determined by hemoglobin A1c levels and annual oral glucose tolerance test. Serum creatinine assessed kidney function. Serum lipid (low-density lipoprotein, high-density lipoprotein and cholesterol) levels and body mass index were measured annually. Patient and graft survival were calculated by log-rank analysis. Pancreas survival for SV versus PV patients was similar after 5 years (81.8% vs. 75.5%) and 10 years (65.1% vs. 60%; p = NS). Similarly, no difference was detected between the groups regarding kidney survival after 5 years (92.9% vs. 84.4%) and 10 years (81.6% vs. 75.5%; p = NS). Patient survival did not differ at 5 years (94.3% vs. 88.8%) and 10 years (85.1% vs. 84.4%; p = NS). Pancreas and kidney function and the lipid profiles were similar in both groups. SV and PV drainage of pancreas grafts offer similar long-term graft survival and function and choice of method should remain the preference of the surgeon.

Adult living liver donors have excellent long-term medical outcomes: the University of Toronto liver transplant experience.

Right lobe living donor liver transplantation is an effective treatment for selected individuals with end-stage liver disease. Although 1 year donor morbidity and mortality have been reported, little is known about outcomes beyond 1 year. Our objective was to analyze the outcomes of the first 202 consecutive donors performed at our center with a minimum follow-up of 12 months (range 12-96 months). All physical complications were prospectively recorded and categorized according to the modified Clavien classification system. Donors were seen by a dedicated family physician at 2 weeks, 1, 3 and 12 months postoperatively and yearly thereafter. The cohort included 108 males and 94 females (mean age 37.3 +/- 11.5 years). Donor survival was 100%. A total of 39.6% of donors experienced a medical complication during the first year after surgery (21 Grade 1, 27 Grade 2, 32 Grade 3). After 1 year, three donors experienced a medical complication (1 Grade 1, 1 Grade 2, 1 Grade 3). All donors returned to predonation employment or studies although four donors (2%) experienced a psychiatric complication. This prospective study suggests that living liver donation can be performed safely without any serious late medical complications and suggests that long-term follow-up may contribute to favorable donor outcomes.

Combined lung-liver-pancreas transplantation in a recipient with cystic fibrosis.

Cystic fibrosis (CF) affects multiple organs including the lung, liver, and pancreas. Lung transplant, liver transplant, and combined lung-liver transplant have become well-established therapies for CF patients with end-stage organ failure. Thus far, however, there has been limited experience with pancreas transplantation in CF. In this report, we detail the clinical history, transplant procedure, and post-operative recovery of a patient who underwent combined lung-liver-pancreas transplant for advanced CF.

The effect of systemic versus portal insulin delivery in pancreas transplantation on insulin action and VLDL metabolism.

Combined kidney-pancreas transplantation (KPT) with anastomosis of the pancreatic vein to the systemic circulation (KPT-S) or to the portal circulation (KPT-P) provides a human model in which the chronic effects of portal versus systemic insulin delivery on glucose and VLDL metabolism can be examined. Despite similar plasma glucose and C-peptide levels, KPT-S (n = 9) had an approximate twofold elevation of fasting and intravenous glucose-stimulated plasma insulin levels compared with both KPT-P (n = 7) and healthy control subjects (n = 15). The plasma free fatty acid (FFA) levels were elevated in both transplant groups versus control subjects, but the plasma insulin elevation necessary to lower plasma FFA by 50% was approximately two times higher in KPT-S versus KPT-P and control subjects. Endogenous glucose production was similar in KPT-S and KPT-P, despite approximately 35% higher hepatic insulin levels in the latter, and was suppressed to a greater extent during a euglycemic-hyperinsulinemic clamp in KPT-S versus KPT-P. Total-body glucose utilization during the euglycemic-hyperinsulinemic clamp was approximately 40% lower in KPT-S versus KPT-P, indicating peripheral tissue but not hepatic insulin resistance in KPT-S versus KPT-P. Both transplant groups had an approximate twofold elevation of triglyceride (TG)-rich lipoprotein apolipoprotein B (apoB) and lipids versus control subjects. Elevation of VLDL-apoB and VLDL-TG in both transplant groups was entirely explained by an approximately 50% reduction in clearance of VLDL compared with healthy control subjects. In the presence of increased FFA load but in the absence of hepatic overinsulinization and marked hepatic insulin resistance, there was no elevation of VLDL secretion in KPT-S versus KPT-P and control subjects. These findings suggest that chronic systemic hyperinsulinemia and peripheral tissue insulin resistance with the consequent elevation of plasma FFA flux are insufficient per se to cause VLDL overproduction and that additional factors, such as hepatic hyperinsulinemia and/or gross insulin resistance, may be an essential prerequisite in the pathogenesis of VLDL overproduction in the common form of the insulin resistance syndrome.

Toxic effects of intravenous and oral prostaglandin E therapy in patients with liver disease.

BACKGROUND: Prostaglandins are cytoprotective agents that have been shown to benefit patients with a variety of acute and chronic liver diseases. Few data exist on the frequency of adverse effects of prostaglandins in these patients. METHODS: We retrospectively studied 105 patients with liver disease who were treated with either intravenous (i.v.) or oral prostaglandin E (PGE). Forty-four patients with primary nonfunction after liver transplantation and 36 patients with fulminant hepatic failure received i.v. PGE1 for 4.5 +/- 2.6 and 12.6 +/- 10.9 days, respectively. Twenty-five patients with recurrent hepatitis B viral infection after liver transplantation received oral PGE1 for 105 +/- 94 days or PGE2 for 464 +/- 399 days. RESULTS: Twenty-six of 80 patients (33%) receiving i.v. PGE1 developed gastrointestinal and/or cardiovascular side effects and 8% developed arthritis. Twenty-three of 25 patients (92%) who received high-dose oral PGE1 or PGE2 incurred arthritis and/or gastrointestinal adverse effects. Twenty-five patients received prolonged PGE therapy (oral > 60 days; i.v. > 28 days). Of this group, 23 (92%) developed clubbing and cortical hyperostosis resembling hypertrophic osteoarthropathy. All adverse effects were dose related and resolved with reduction or cessation of therapy. CONCLUSION: PGE therapy resulted in a wide spectrum of multisystem adverse effects which were reversible with reduction or cessation of therapy. Although the administration of PGE was safe and generally well tolerated, close medical supervision is necessary to avoid serious side effects.

Reconstruction of middle hepatic vein of a living-donor right lobe liver graft with recipient left portal vein.

Venous outflow problems in right lobe, living-donor liver transplantation are uncommon, but devastating when they occur. We describe the successful use of the recipient's left portal vein as an interposition graft to drain a dominant middle hepatic vein in a right lobe liver transplant. Two weeks after transplantation, the vein graft accounted for 56% of the total venous outflow of the liver.

The effect of cryopreservation on the survival and MHC antigen expression of murine islet allografts.

Cryopreservation is an effective method of islet storage that can facilitate clinical trials of islet transplantation. In the present study we examined the effect of cryopreservation on the survival of islet allografts and the quantity of islet MHC antigen expression. Islets isolated from CBA/J (H-2k) mice were transplanted into streptozotocin-induced diabetic BALB/c (H-2d) mice treated with or without antilymphocyte serum (ALS). Frozen/thawed (F/T) grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. Fresh and F/T isograft controls reversed diabetes promptly and maintained normoglycemia > 100 days. Allografts of fresh and F/T islets induced normoglycemia initially, but graft failure ensued at 18.2 +/- 1.5 and 16.4 +/- 1.9 days, respectively. ALS treatment prolonged allograft survival significantly to 35.3 +/- 3.9 and 37.5 +/- 6.3 days for fresh and F/T islets, respectively. Following cryopreservation, the quantity of class I antigen expression was reduced by 40%, while the quantity of class II expression was variable. These data indicate that murine islet MHC class I expression is reduced after cryopreservation. This decrease was not associated with altered survival of allogeneic grafts.

Transplantation of purified frozen/thawed canine pancreatic islet allografts with cyclosporine.

We studied the survival of defined volumes of highly purified frozen/thawed islets transplanted into the spleen of 4 groups of apancreatic mongrel dogs (total, 21), with or without cyclosporine from day -4 to day 30: group 1 (controls), without CsA, autograft of mean (+/- SE) islet volume 5 +/- 1 microliters/kg body weight; group 2, single-donor allograft, and group 3, multiple-donor allograft (both, 6 +/- 1 microliters/kg), both with CsA; and group 4, large-volume multiple-donor allograft (24 +/- 1 microliters/kg) with CsA. Grafts were cooled slowly to -40 degrees C, stored at -196 degrees C, and thawed rapidly. The CsA dose was adjusted to maintain whole-blood trough values of 600-800 micrograms/L, and allograft recipients manifesting early hyperglycemia were given insulin to maintain plasma glucose concentration below 150 mg/dl. In group 1, two dogs died early (graft failure in 1, intussusception in 1), but the remaining five were normoglycemic at 30 days. In groups 2 and 3, hyperglycemia ensued from about day 2.5, but 4 of 5 grafts in group 2 and all grafts in group 3 secreted insulin into the splenic vein at 30 days. In group 4, normoglycemia ensued within 24 hr of transplantation and was maintained in all 6 dogs for 30 days; the grafts failed 15 +/- 2 days after CsA was stopped. The data demonstrate prolonged function of purified frozen/thawed islets after transplantation into these outbred dogs but indicate a need for a greater volume of allogeneic islets from multiple donors than of autologous islets to achieve normoglycemia.

Transplantation of purified single-donor canine islet allografts with cyclosporine.

We evaluated the survival of highly purified freshly isolated pancreatic islets transplanted from single canine donors into 20 outbred mongrel dogs immunosuppressed with cyclosporine or untreated. The grafts (mean weight +/- SE, 0.5 +/- 0.1 g, containing 122 +/- 8 X 10(3) islets; purity 91% by electron microscopy) were transplanted into 3 groups of dogs: group 1, autograft without CsA (5444 +/- 688 islets/kg body weight, n = 6); group 2, allograft without CsA (6669 +/- 1744, n = 4); and group 3, allograft with CsA (8645 +/- 1149, n = 10). The CsA was injected i.m. daily for 4 days before and 30 days after transplantation. Fasting plasma glucose (PG, mg/dl) and serum CsA trough values were determined daily. Intravenous glucose tolerance tests were done before and after transplantation, for calculation of K values (decline in glucose, %/min; preoperatively, mean K = 3.9 +/- 0.2). In group 1 all 6 dogs were normoglycemic (PG = 98 +/- 2 and K = 1.8 +/- 0.2) at 1 month; in group 2 the graft failed in all 4 dogs, at 4 +/- 1.2 days; in group 3 all 10 dogs were normoglycemic initially. Of the group 3 dogs, 4 died (intussusception developed in 2, and the graft failed at 3 and 9 days in 2 the CsA values of which were less than 300 micrograms/L preoperatively), but the other 6 were still normoglycemic when the CsA was stopped at 30 days (mean PG = 132 +/- 16 and K = 0.9 +/- 0.2; P less than 0.05 vs. group 1). Their CsA values were 708 +/- 197 before and 359 +/- 41 micrograms/L during the third week after transplantation; their grafts failed 12.3 +/- 3.4 days after the cessation of CsA. This data is unique in demonstrating prolonged function of purified allogeneic islets transplanted from individual outbred canine donors, but glucose tolerance was impaired. CsA at serum levels greater than 300 micrograms/L induced prolonged survival of purified canine islets and rejection was prompt when it was stopped.

Innominate artery interposition graft simplifies the portal venous drainage method of pancreas transplantation.

Pancreas transplantation utilizing portal venous and enteric exocrine drainage has potential benefits over the standard systemic venous and bladder exocrine drainage method. Unfortunately, technical difficulties are often experienced with the arterial anastomosis after the portal venous anastomosis is completed. We have found that the addition of an innominate artery interposition graft has greatly simplified the procedure.

Improved survival of in vitro cultured canine islet allografts.

Pure islets transplanted from single donors survive in outbred dogs when CsA is administered at high doses (15-20 mg/kg/day), but not report has documented prolonged function with less CsA. In this study, we investigated survival of canine islets that were immunomodulated with in vitro culture and transplanted with minimal CsA. Highly purified islets from single donors (n = 17) were cultured in vitro at 22 degrees C for 7 days. Four groups of apancreatic, outbred mongrel dogs received islets into the spleen: group 1 (n = 4), fresh islet controls; group 2 (n = 5), cultured islet controls; group 3 (9033 +/- 994 islets/kg, n = 12), culture and CsA; group 4 (9050 +/- 1091 islets/kg, n = 8), fresh islet and CsA. CsA was administered in doses of 5-8 mg/kg/day to maintain whole blood trough levels of 300-500 ng/ml. At 30 days after implant, the CsA was stopped. After 7-day culture, 80% of the endocrine mass was recovered. All grafts restored plasma glucose to < 150 mg/dl. Group 1 and 2 dogs became hyperglycemic at 5 +/- 1 (+/- SE) and 6 +/- 1 days. Three grafts in group 3 failed when CsA did not reach target blood levels. Of the 9 dogs with CsA levels of 300-500 ng/ml, 1 died at 9 days while normoglycemic, and the remainder were normoglycemic for 35.5 +/- 8.3 days (median 38 days). Seven group 4 dogs with these CsA levels achieved normoglycemia for 7.7 +/- 1.9 days (median 9 days, survival vs. group 3, P = 0.03, by Mann-Whitney test). In vitro tissue culture of mass quantities of single-donor allogeneic islets enhances their survival with low dose immunosuppression in outbred diabetic dogs.

A pilot study of ribavirin therapy for recurrent hepatitis C virus infection after liver transplantation.

Ribavirin is a guanosine analogue that normalizes serum liver enzymes in most nontransplant patients with chronic hepatitis C virus (HCV) infection. We conducted an uncontrolled pilot study of ribavirin in 9 liver transplantation recipients that had persistently elevated liver enzymes, active hepatitis by liver biopsy, and HCV RNA in serum by polymerase chain reaction. Ribavirin was given orally at dosages of 800-1200 mg per day for 3 mo. All 9 patients promptly responded to ribavirin: mean (+/- SD) ALT decreased from 392 +/- 377 IU/L immediately before treatment to 199 +/- 185 and 68 +/- 37 IU/L after 1 and 12 weeks of treatment, respectively, complete normalization of enzymes occurred in 4 patients. None of the patients cleared the virus from their serum during therapy, and biochemical relapse occurred in all patients 4 +/- 4.2 weeks after cessation of therapy. The hepatitis activity index of liver biopsy specimens obtained before and at the cessation of therapy was similar. Ribavirin treatment was resumed in 4 patients because of increasing fatigue (2 patients), rising bilirubin (3), or increasing necroinflammation on liver biopsy (2); the biochemical response to the second course of therapy was similar to the first course in all 4 patients. Ribavirin caused reversible hemolysis in all patients, including symptomatic anemia in 3 patients that resolved after reduction of drug dosage. These results suggest that ribavirin may be of benefit in the treatment of HCV infection after liver transplantation. Further studies are needed to determine the optimal dosage and duration of therapy.

Transfusion-induced graft-versus-host disease after liver transplantation. Documentation using polymerase chain reaction with HLA-DR sequence-specific primers.

Graft-versus-host disease (GVHD) occurring after liver transplantation can pose a difficult diagnostic dilemma. Similar clinical and pathologic skin and gastrointestinal manifestations can result from other causes (i.e., drugs, infections). Treatment for each of these entities differs, and the high mortality associated with GVHD makes this distinction critical. GVHD has been assumed to result from the cotransplantation of donor lymphoid tissue along with the allograft. In most instances, the patient also receives blood products during the operation, and occasionally during the postoperative period, and the lymphoid cells in these products are also a potential source of concern. In this report, we describe a patient who developed GVHD after liver transplantation. Using molecular diagnostic techniques, we determined that the source for this GVHD was not the organ donor, but was most likely nonirradiated blood products received during the hospital course. Our results suggest that transplant recipients with concomitant hematopoietic dysfunction would benefit from irradiated blood products to reduce the likelihood of this complication.

Viral prophylaxis in combined pancreas-kidney transplant recipients.

The purpose of this study was to analyze different regimens of viral prophylaxis after combined pancreas-kidney transplantation (PKT). Over a 4-year period, we performed 82 PKTs with quadruple immunosuppression with OKT3 induction. Four regimens of prophylaxis were studied. The first 30 patients received standard intravenous immunoglobulin (IVIG; 0.5 g/kg) for 6 doses and oral acyclovir for 3 months. The next 34 recipients received intravenous ganciclovir (2.5 mg/kg) twice daily for 2 weeks followed by oral acyclovir for 3 months. In the third group, patients were randomized to 5 doses over 2 months of either standard IVIG (n = 9) or CMV hyperimmune globulin (Cytogam; n = 9; 100-150 mg/kg) plus 2 weeks of i.v. ganciclovir followed by 3 months of oral acyclovir. The 4 groups were similar with respect to clinical, demographic, and immunologic variables, including donor and recipient CMV serologic status and blood transfusions. All patients were monitored for viral infections in the first 6 months after PKT. The regimens of prophylaxis resulted in (1) no major non-CMV (including no EBV) viral infections; (2) 3 cases of minor non-CMV viral infections (shingles); and (3) no differences in the incidence, timing, or severity of symptomatic CMV infections in the 4 groups. No death or graft loss was due to viral infection. Prophylaxis is effective in reducing the incidence of non-CMV viral infections and may reduce the severity of symptomatic CMV infection. However, we could not show any added benefit of either Cytogam or standard IVIG when used in combination with other antiviral agents. For economic as well as efficacy reasons, we recommended that IVIG preparations not be used routinely with antilymphocyte therapy but only in high-risk situations such as primary CMV exposure.

A microemulsion of cyclosporine without intravenous cyclosporine in liver transplantation.

A microemulsion formulation of cyclosporine (CsA) has improved absorption compared with the original form. The purpose of this case control study was to assess the safety and efficacy of the microemulsion without intravenous CsA for induction immunosuppression in adult liver transplantation. Twenty-one consecutive patients receiving induction immunosuppression with the microemulsion 15 mg/kg/day were compared with 20 patients receiving intravenous CsA and the original oral form. Both groups received the same dose of methylprednisilone. Twenty of 21 patients receiving the microemulsion required no intravenous CsA to achieve target CsA levels. All patients receiving the original form received initial intravenous CsA. There was no difference in trough CsA levels between the two groups at 24 and 48 hours. The microemulsion group had 24 hr and 48 hr trough CsA levels of 227+/-15 and 520+/-300 ng/ml by monoclonal RIA while the intravenous CsA group had 24 and 48 hr trough levels of 293+/-18 and 405+/-91 ng/ml. CsA levels analyzed by HPLC were 20% lower than by RIA. The frequency of adverse events resulting in reduction of drug dosage was similar for the microemulsion and the original form: neurotoxicity (23 vs. 40%, P=.30); nephrotoxicity (25 vs. 45%, P=.32), and no patients required dialysis. There was no difference in septic complications. One patient required discontinuation of the microemulsion in an attempt to reverse severe neurotoxicity. A total of 75% of microemulsion patients were rejection free at 3 months while only 35% of CsA patients remained rejection free (P=0.02). These data suggest that the use of the microemulsion without intravenous CsA in liver transplantation is safe and efficacious, and may result in decreased episodes of acute rejection.