U. Ołdakowska-Jedynak

Biliary tract complications following liver transplantation

INTRODUCTION Biliary tract complications, which occur in 5.8% to 24.5% of adult liver transplant recipients, remain one of the most common problems following transplantation. The aim of this study was to evaluate these problems and analyze methods of treatment. MATERIAL AND METHODS From 1989 to 2003, 36 (18.7%) among 193 patients who underwent orthotopic liver transplantations in our center developed biliary complications. Biliary strictures that developed in 18 cases (9.3%) were the most common complications. Clinical manifestations of strictures developed at 2 to 24 months after transplantation. Bile leaks occurred in 10 patients (5.2%), and were diagnosed in along the T-tube 4 cases and was not accompanied by any clinical manifestation. Bile leak to the peritoneum after T-tube removal occurred in 2 patients (1.1%). Solitary gallstone formation in one case (0.5%) was removed with the use of ECPW. One patient required retransplantation within 3 months after transplantation, because of the most severe complication-ischemic necrosis of biliary tract. RESULTS Uneventful recovery was achieved in 34 patients in the analyzed group (94.4%). There was no case of recurrence during outpatient follow up. Two patients died in late follow-up of unrelated causes: namely, gastrointestinal bleeding due to a duodenal ulcer and multi-organ failure (MOF) due to a third severe episode of acute liver transplant rejection. CONCLUSIONS Biliary complications remain an important problem in liver transplantation. Endoscopic and radiologic management are effective in the majority of cases. Surgical intervention is obligatory in selected cases.

Renal function after liver transplantation: calcineurin inhibitor nephrotoxicity

Renal failure, mainly due to calcineurin inhibitor (CNI) nephrotoxicity, is the most common complication following orthotopic liver transplantation (ltx). The aim of this study was to evaluate the incidence and course of renal failure in adult ltx patients. Severe acute renal failure in early postoperative period due to impaired hemodynamics and CNI nephrotoxicity, occurred in 14 patients, 3 of whom required dialysis. The creatinine clearance after ltx showed a tendency to decrease, but there was no statistically significant difference (P >.05) in the change in serum creatinine clearance levels between patients treated with tacrolimus (TAC) versus Cyclosporine (CsA) during the first 2 years of follow-up. Fourteen patients required conversion of their regimen because of CNI nephrotoxicity namely, dose reduction (n = 7) or discontinuation of CNI therapy with the replacement by mycophenolate mofetil (MMF) (n = 5) or SRL (n = 5). Dose reduction or CNI withdrawal significantly improved the creatinine clearance (P <.05) without affecting lives graft function. No episode of acute rejection was observed after conversion. Neither conversion of CsA to TAC nor the reverse maneuver significantly influenced the serum creatinine level (P >.05). Reduction of the CNI dose or CNI discontinuation or replacement with MMF or SRL in patients with stable liver but impaired renal function is safe, resulting in a significant improvement in renal function.

1000 liver transplantations at the Department of General, Transplant and Liver Surgery, Medical University of Warsaw--analysis of indications and results.

THE AIM OF THE STUDY was to analyze indications and results of the first one thousand liver transplantations at Chair and Clinic of General, Transplantation and Liver Surgery, Medical University of Warsaw. MATERIAL AND METHODS Data from 1000 transplantations (944 patients) performed at Chair and Clinic of General, Transplantation and Liver Surgery between 1994 and 2011 were analyzed retrospectively. These included 943 first transplantations and 55 retransplantations and 2 re-retransplantations. Frequency of particular indications for first transplantation and retransplantations was established. Perioperative mortality was defined as death within 30 days after the transplantation. Kaplan-Meier survival analysis was used to estimate 5-year patient and graft survival. RESULTS The most common indications for first transplantation included: liver failure caused by hepatitis C infection (27.8%) and hepatitis B infection (18%) and alcoholic liver disease (17.7%). Early (< 6 months) and late (> 6 months) retransplantations were dominated by hepatic artery thrombosis (54.3%) and recurrence of the underlying disease (45%). Perioperative mortality rate was 8.9% for first transplantations and 34.5% for retransplantations. Five-year patient and graft survival rate was 74.3% and 71%, respectively, after first transplantations and 54.7% and 52.9%, respectively, after retransplantations. CONCLUSIONS Development of liver transplantation program provided more than 1000 transplantations and excellent long-term results. Liver failure caused by hepatitis C and B infections remains the most common cause of liver transplantation and structure of other indications is consistent with European data.

Posttransplantation diabetus mellitus under calcineurin inhibitor

BACKGROUND The development of postransplantation diabetes mellitus (PTDM) is a serious complication of kidney transplantation. PTDM has a major impact on quality of life decreasing rates of patient and graft survival. It is well known that some currently used immunosuppressants are diabetogenic. Greater diabetogenicity of FK-506 has been reported in multicenter trials. We initiated a study of conversion from tacrolimus (FK-506) to cyclosporine (CsA) among kidney allograft recipients presenting with PTDM to evaluate whether this maneuver would ameliorate a diabetic state. METHODS This analysis of 20 adult, renal allograft recipients presenting with PTDM assumed the need for insulin therapy or oral hypoglycemics before and after conversion of the immunosuppressive regimen. The criteria for evaluating the outcome were as follows: dose reduction of insulin or oral hypoglycemic agents, adequacy of glucose control, C-peptide levels, and insulin concentration. RESULTS During the follow-up, we observed an improvement in the control of blood glucose in the converted group. In 13 patients, satisfactory glucose control was obtained without insulin or any other agent. In 3 patients a significant dose reduction of required insulin was possible. In another 2 patients who were insulin-dependent, the switch to oral hypoglycemic treatment was clinically possible after conversion. After conversion we observed significantly lowered fasting blood glucose levels and increased C-peptide levels. CONCLUSIONS The conversion from a tacrolimus to a CsA-based immunosuppressive regimen resulted in better glucose metabolism. We demonstrated a positive effect of conversion on the diabetic state of patients with PTDM.

Cytomegalovirus infection as a common complication following liver transplantation

The aim of our study was to assess the incidence course, influence on liver function, diagnostic methods, prophylaxis of, and cost treatment effectiveness of CMV infection among 123 consecutive liver transplant recipients. All patients received immunoglobulin and parenterall gancyclovir as prophylaxis. CMV IgM and IgG antibodies were determined using an ELISA method. Thirty seven patients (30.0%) developed CMV infection. Main indications for primary LTX were: immune liver disease (n = 22), viral hepatitis (n = 5), and other (n = 10). CMV infection occurred between the days 5 and 416. Ten patients (27.0%) developed more than one infection (52 infections in total). Asymptomatic CMV infection was diagnosed in six cases (16.2%), CMV syndrome in 11 cases (29.7%), and hepatitis in 35 cases. All patients were treated with gancyclovir and immunoglobulin (18 cases). The intensity of infection was mild or moderate. There was no case of pneumonia or neurological disease, nor the need to use foscarnet. The correlations between the incidence of CMV infection and acute rejection, tacrolimus versus cyclosporine regimens, dual versus triple immunosupressive schemes were not statistically significant, whereas anti-IL-2R-ab antibodies markedly reduced the incidence of CMV infection (P <.05). The values of CMV IgM significantly differred before/during infection (P <.001) and before/after infection (P <.05). In conclusion, prophylaxis and antiviral treatment result in a mild or moderate intensity of CMV infection with acceptable costs. Among immunosuppressive drugs, only anti-IL-2Rab was proved to significantly reduce the incidence of CMV.

Comparison of the results of liver transplantation for elective versus urgent indications.

The authors present an analysis of early and remote liver transplantation outcomes related to the presence of emergent indications among 196 of the 209 operations performed from 1989 to April 2003; namely 178 elective and 18 emergent transplantations. Perioperative mortality was 15%. The survival rate during the first 12 months was 79.8% and within 3 years 73.5% among patients operated on an elective basis (UNOS 3 and 2B). In contrast, patients with acute liver failure (UNOS 1 and 2A) showed rates of 45%, 50%, and 47%, respectively. Liver transplant outcomes depend primarily on the urgency of an operation. Longterm results are much better among patients operated on electively. Liver transplantation in patients with acute hepatic insufficiency is burdened with a high 45% mortality.

Myeloproliferative neoplasms and recurrent thrombotic events in patients undergoing liver transplantation for Budd-Chiari syndrome: a single-center experience.

BACKGROUND Budd-Chiari syndrome is a heterogeneous disease. The role of liver transplantation as a treatment option has been discussed since 1976. Many cases are related to underlying myeloproliferative neoplasms associated with prothrombotic propensity. The aim of this study was to evaluate the long-term clinical outcome after liver transplantation for Budd-Chiari syndrome at our center, with special emphasis on recurrent thrombosis and underlying myeloproliferative disorders. MATERIAL/METHODS A medical records search revealed 25 patients transplanted at our center for Budd-Chiari syndrome between 2000 and 2009. Indications for transplantation were complications of end-stage liver disease or acute liver failure. RESULTS Ten patients were men (40.0%). Median age of recipients at transplantation was 29.0 (17-51) years. Eighteen patients (72%) had evidence of myeloproliferation, 1 had paroxysmal nocturnal hemoglobinuria, and 6 had idiopathic disease. In 55.5% of cases eventually diagnosed with myeloproliferative neoplasms, Budd-Chiari syndrome was their initial presentation. All patients were maintained on long-term post-transplant anticoagulation protocol. The median follow-up time was 58.8 months. Four patients (16%) died during follow-up. Acute graft rejection occurred in 16% of cases. During the observation period, 5 patients had recurrent thrombotic events. The 5-year patient and graft survival rate was 84%. No case of transformation to acute leukemia was seen. CONCLUSIONS Our data show satisfactory long-term survival of patients and grafts in the study group. Occult course of myeloproliferative neoplasms is frequent in this population and exceeds 50%. We observed recurrent thrombosis in 20% of recipients.

Treatment of pruritus with Prometheus dialysis and absorption system in a patient with benign recurrent intrahepatic cholestasis.

Benign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive liver disorder characterized by recurrent episodes of jaundice and itching. Episodes of cholestasis last variously from 1 week to several months, may start at any age and usually resolve spontaneously. No effective treatment has been found as yet. We report a case of genetically proven BRIC in a male patient who developed three episodes of pruritus and jaundice at the age of 14, 16 and 19 years. During the third episode, he did not respond to pharmacological medical therapy, and fractionated plasma separation and absorption (FPSA, Prometheus) was performed to manage intractable pruritus. The treatment immediately alleviated pruritus, lowered serum bilirubin concentration and induced sustained remission in the 5‐year follow up. FPSA seems to be a safe and effective way of treatment for BRIC in patients with severe pruritus and prolonged jaundice.

High-resolution 1H nuclear magnetic resonance spectroscopy analysis of bile samples obtained from a patient after orthotopic liver transplantation: new perspectives

The liver is involved in many synthetic and metabolic functions. It takes part in the regulation of circulation, thermoregulation, and digestion. All liver functions are disturbed during harvesting, preservation, and transplantation. The assessment of graft function is still a matter of concern. Many methods including analysis of hepatic enzymes, ketone body ratio, and level of drug metabolites do not give complete and reliable information on graft function. Liver biopsy is still the best diagnostic tool, however, it is invasive, carrying the risk of complications. High-resolution proton spectroscopy of nuclear magnetic resonance was used for analysis of the bile sample obtained from a patient after orthotopic liver transplantation.

Evolution Of The Results Of 1500 Liver Transplantations Performed In The Department Of General, Transplant And Liver Surgery Medical University Of Warsaw.

UNLABELLED Liver transplantation is a well-established treatment of patients with end-stage liver disease and selected liver tumors. Remarkable progress has been made over the last years concerning nearly all of its aspects. The aim of this study was to evaluate the evolution of long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw). MATERIAL AND METHODS Data of 1500 liver transplantations performed between 1989 and 2014 were retrospectively analyzed. Transplantations were divided into 3 groups: group 1 including first 500 operations, group 2 including subsequent 500, and group 3 comprising the most recent 500. Five year overall and graft survival were set as outcome measures. RESULTS Increased number of transplantations performed at the site was associated with increased age of the recipients (p<0.001) and donors (p<0.001), increased rate of male recipients (p<0.001), and increased rate of piggyback operations (p<0.001), and decreased MELD (p<0.001), as well as decreased blood (p=0.006) and plasma (p<0.001) transfusions. Overall survival was 71.6% at 5 years in group 1, 74.5% at 5 years in group 2, and 85% at 2.9 years in group 3 (p=0.008). Improvement of overall survival was particularly observed for primary transplantations (p=0.004). Increased graft survival rates did not reach the level of significance (p=0.136). CONCLUSIONS Long-term outcomes after liver transplantations performed in the Department of General, Transplant and Liver Surgery are comparable to those achieved in the largest transplant centers worldwide and are continuously improving despite increasing recipient age and wider utilization of organs procured from older donors.