Safety and Efficacy of Citrate Anticoagulation for Continuous Renal Replacement Therapy for Acute Kidney Injury After Liver Transplantation: A Single-Center Experience.

BACKGROUND: Acute kidney injury (AKI) after liver transplantation (LT) is a frequent and serious complication. The incidence of AKI requiring continuous renal replacement therapy (CRRT) ranges from 10% to 30%. Kidney Disease: Improving Global Outcomes guidelines indicate the use of citrate as a locoregional anticoagulant drug for CRRT regardless of the patient's hemorrhagic risk. Despite this indication, however, the use of citrate is still under debate in patients with liver failure and/or LT owing to the potential risk of plasmatic citrate accumulation due to reduced liver clearance. The aim of this study was to evaluate the safety and efficacy of citrate as a locoregional anticoagulation drug in CRRT for AKI after LT. METHODS: A retrospective analysis was performed in patients with AKI after liver transplantation who were treated with CRRT using citrate as local anticoagulant. Five patients were enrolled from January to December 2015. RESULTS: No patients showed complications related to citrate (metabolic acidosis, hyperlactatemia, hypercalcemia, or hypernatremia). All treatments with heparin were stopped owing to circuit clotting. Treatments with citrate was interrupted where it was no longer needed or when other examinations had to be made. None were stopped because of circuit coagulation. CONCLUSIONS: At our center, 5 patients have been successfully treated with the use of CRRT with citrate for AKI during the post-LT course. Our results, though on a small series of patients, provide evidence that CRRT with citrate can be a safe and promising treatment for AKI after LT.

Validation of the BCLC prognostic system in surgical hepatocellular cancer patients.

BACKGROUND/AIM: Prognosis assessment in surgical patients with hepatocellular carcinoma (HCC) remains controversial. The most widely used HCC prognostic tool is the Barcelona Clinic Liver Cancer (BCLC) classification, but its prognostic ability in surgical patients has not been yet validated. The aim of this study was to investigate the value of known prognostic systems in 400 Italian HCC patients treated with radical surgical therapies. METHODS: We analyzed a prospective database collection (400 surgical, 315 nonsurgical patients) observed at a single institution from 2000 and 2007. By using survival times as the only outcome measure (Kaplan-Meier method and Cox regression), the performance of the BCLC classification was compared with that of Okuda, Cancer of the Liver Italian Program, United Network for Organ sharing TNM, and Japan Integrated Staging Score staging systems. RESULTS: Two hundred twenty-five patients underwent laparotomy resection; 55, laparoscopic procedures (ablation and/or resection); and 120, liver transplantations. In the surgical group, BCLC proved the best HCC prognostic system. Three-year survival rates of patients in BCLC Stages A, B, and C were 81%, 56%, and 44% respectively, (P < .01); whereas all other tested staging systems did not show significant stratification ability. When all 715 HCC patients were considered, surgery proved to be a significant survival predictor in each BCLC stage (A, B, and C). CONCLUSIONS: BCLC staging showed the best interpretation of the survival distribution in a surgical HCC population. The BCLC treatment algorithm should consider the role of surgery also for intermediate-advanced stages of liver disease.

Hepatitis C virus-related cirrhosis as a significant mortality factor in intention-to-treat analysis in liver transplantation.

INTRODUCTION: Liver transplantation represents the gold standard for the treatment of chronic liver disease. The whole transplantation process was assessed using an intention-to-treat analysis and considering patients from the time of their inclusion on the list and throughout lengthy follow-up. MATERIALS AND METHODS: From January 1, 1999 to June 1, 2004, 373 adults joined the waiting list for liver transplantation at our institution. The main variables analyzed were: age, gender, etiology, Model for End-stage Liver Disease score, Child-Pugh class, United Network for Organ Sharing (UNOS) status. Global survival was evaluated using intention-to-treat analysis from the time of patient inclusion in the list to the end of their late follow-up. RESULTS: The median waiting time was 20 months (range 0.1 to 70.2). By univariate analysis, the variables significantly influencing survival when patients joined the waiting list were: encephalopathy; ascites, poor nutritional status, Child-Pugh class C, UNOS 2, hepatitis C virus (HCV) and bilirubin > 2 mg/dL. By multivariate analysis, only HCV-related cirrhosis emerged as having an independent prognostic value. By intention-to-treat analysis, the 5-year survival rate was 67% and 79% for HCV-positive and HCV-negative patients, respectively (P = .0003). CONCLUSIONS: HCV-related cirrhosis is an independent prognostic factor for survival according to an intention-to-treat analysis. Different inclusion criteria or treatments while on the waiting list and after transplantation need to be considered in the future for HCV-positive patients.

Combined liver and kidney transplantation: analysis of Padova experience.

BACKGROUND/AIM: The main indications for combined liver and kidney transplantation (CLKT) are as follows: (1) cirrhosis with renal damage dependent or not upon liver disease, (2) renal failure with dialysis and concomitant liver end-stage disease, (3) congenital diseases, and (4) enzymatic liver deficiency with concomitant renal failure. The aim of this study was to evaluate our results with CLKT both in adult and pediatric patients. METHODS: From September 1995 to September 2006, 15 CLKT (2.8%) among 541 liver transplantations included 4 pediatric patients (27%). The main indications for CLKT were hepatitis C virus (HCV) and polycystic diseases in adult patients, and primary hyperoxaluria in pediatric patients. RESULTS: The double transplantation was performed from the same donor in all cases. All adult patients received whole liver grafts, whereas 3 split transplants and 1 whole liver graft were transplanted in the pediatric patients. Median liver and kidney cold ischemia times were 468 and 675 minutes, respectively. After a median follow-up of 36 months (range, 1-125), the overall survival rate was 80%. Five-year patient and graft survival rates were 100% for adult CLKT, whereas they were 50% for pediatric patients. We observed only 2 cases (18%) of delayed renal function, requiring temporary hemodialysis with progressive graft improvement. There was only 1 case of kidney retransplantation due to early graft nonfunction in a pediatric patient. CONCLUSION: Although CLKT is related to major surgical risks, results after transplantation are satisfactory with an evident immunological advantage.

A new experimental model of isolated perfused pig liver to support acute hepatic failure.

Liver transplantation still represents the only effective treatment for patients with liver failure, but many patients die while awaiting transplantation, even though many attempts have been made to increase the organ procurement rates and to partially support hepatic function in recent years. Our aim was to design an "open" ex vivo perfused liver model to simplify liver support using an isolated porcine liver perfused with arterial and portal blood from the recipient pig, while monitoring the metabolic capacity of the supporting graft. It was possible to perfuse the isolated liver for 6 hours as a bridging procedure with satisfactory hemodynamic homeostasis controlled by software biofeedbacks.

Posttransplant diabetes mellitus after kidney transplantation with different immunosuppressive agents.

Posttransplant diabetes mellitus (PTDM) is a disturbing side effect of immunosuppression. The aim of this study was to evaluate the effect of different immunosuppressive agents on the development of PTDM in renal transplant recipients (KTx). The incidence of PTDM was evaluated in 538 consecutive KTx. Baseline immunosuppression was azathioprine (AZA), cyclosporine (CSA), or tacrolimus (TAC), or sirolimus in combination with calcineurin inhibitors (SIR). All patients received steroids for both induction and maintenance therapy during the first 6 months posttransplantation. Mean follow-up after KTx was 73 +/- 53.5 months (range 6 months to 16 years). PTDM was defined as two consecutive blood glucose determinations above 126 mg/dL. Thirty-six of 538 (6.7%) recipients experienced PTDM, 31 of whom required insulin treatment and five oral antidiabetic medications. PTDM occurred at 25.3 +/- 38 months posttransplantation in 4.8% of KTx treated with AZA, 4.8% of CSA, 6.5% of KTx treated with TAC and 12.5% of KTx treated with SIR. The time of onset of PTDM was significantly shorter (P =.003) among TAC (2.1 +/- 1.7 months posttransplantation) versus CSA (27.8 +/- 34 months). PTDM disappeared in 6 of 36 patients. We conclude that with current levels of immunosuppression, there is no difference in the incidence of PTDM between TAC- and CSA-treated KTx.

Liver transplantation for the management of hepatoblastoma.

INTRODUCTION: Hepatoblastoma (HEP) is the most frequent liver malignancy occurring in childhood. Surgical resection currently represents the gold standard for treatment. In patients with initially unresectable tumors, chemotherapy may induce remarkable reductions in size. In nonresponder patients, liver transplantation (OLTx) may offer a chance of cure. MATERIALS AND METHODS: From 1990 to 2003, a total of 400 OLTx (31 pediatric transplants) have been performed at Padua University. Seven patients (4 males and 3 females) underwent OLTx for hepatoblastoma. All patients presented with bilobar liver involvement and had received chemotherapy according to the SIOPEL-1. In all patients preoperative staging was negative for extrahepatic involvement. RESULTS: The mean age of the pts was 8.2 years (range 6.4 months to 34 years). Mean follow-up after OLTx was 41.4 months (median 36, range 3 to 108 months). Actuarial patient survival rates after OLTx for hepatoblastoma are 83.3%, 83.3%, and 56% at 1, 3, and 5 years, respectively. Five of seven subjects with HEP are alive after transplant at 3, 12, 36, 65, and 108 months. Two patients died owing to recurrent disease after 6 and 60 months, respectively, from transplantation. Another subject, primarily treated with surgical resection, shows HEP recurrence at 40 months after OLTx. The remaining 4 patients are alive and well at a mean follow-up of 28 months (median 24, range 3 to 65 months). CONCLUSIONS: Liver transplantation may represent a valid therapeutic option for patients with unresectable HEP, but it is contraindicated in cases of recurrence following previous resection surgery. Neo-adjuvant chemotherapy is of paramount importance to obtain good long-term results.

Rapid conversion to sirolimus for chronic progressive deterioration of the renal function in kidney allograft recipients.

The aim of this study was to evaluate the safety of conversion to sirolimus (SRL) immunosuppression among 19 renal transplant recipients (KTX) with progressive chronic renal allograft dysfunction (CRAD). Conversion to SRL was performed with concomitant sharp withdrawal of the calcineurin inhibitor (CI). SRL was added at a starting dose of 3 mg, then adjusted to obtain SRL target trough blood levels of 8 to 10 ng/mL. CI were stopped the evening before starting SRL. All patients enrolled in the study have now completed 6 months of follow-up: all are alive without acute rejection or major infection following rapid conversion to SRL. No significant change in the 6 months postconversion hematologic and hepatic profile was observed compared with the preconversion values, while significant dyslipidemia was induced. After conversion to SRL, significant amelioration of the renal function was found in 36% of patients, stabilization in 21%, and continuous deterioration in 43%. Patients whose renal function improved were found to have been converted at a significantly lower creatinine: (pre 2.6 +/- 0.9 vs post 1.9 +/- 0.2; P =.038) with respect to those patients who had continuous renal deterioration. In KTX with CRAD, sharp withdrawal of CI with concomitant conversion to SRL is safe, avoiding major infections, acute rejections, and significant side effects. Short-term amelioration of the renal function is best obtained when early conversion is performed. Long-term follow-up will be necessary to confirm these preliminary data.