Improved survival in liver transplant recipients receiving prolonged-release tacrolimus in the European Liver Transplant Registry.

This study was a retrospective analysis of the European Liver Transplant Registry (ELTR) performed to compare long-term outcomes with prolonged-release tacrolimus versus tacrolimus BD in liver transplantation (January 2008-December 2012). Clinical efficacy measures included univariate and multivariate analyses of risk factors influencing graft and patient survival at 3 years posttransplant. Efficacy measures were repeated using propensity score-matching for baseline demographics. Patients with <1 month of follow-up were excluded from the analyses. In total, 4367 patients (prolonged-release tacrolimus: n = 528; BD: n = 3839) from 21 European centers were included. Tacrolimus BD treatment was significantly associated with inferior graft (risk ratio: 1.81; p = 0.001) and patient survival (risk ratio: 1.72; p = 0.004) in multivariate analyses. Similar analyses performed on the propensity score-matched patients confirmed the significant survival advantages observed in the prolonged-release tacrolimus- versus tacrolimus BD-treated group. This large retrospective analysis from the ELTR identified significant improvements in long-term graft and patient survival in patients treated with prolonged-release tacrolimus versus tacrolimus BD in primary liver transplant recipients over 3 years of treatment. However, as with any retrospective registry evaluation, there are a number of limitations that should be considered when interpreting these data.

Compared efficacy of preservation solutions in liver transplantation: a long-term graft outcome study from the European Liver Transplant Registry.

Between 2003 and 2012, 42 869 first liver transplantations performed in Europe with the use of either University of Wisconsin solution (UW; N = 24 562), histidine-tryptophan-ketoglutarate(HTK; N = 8696), Celsior solution (CE; N = 7756) or Institute Georges Lopez preservation solution (IGL-1; N = 1855) preserved grafts. Alternative solutions to the UW were increasingly used during the last decade. Overall, 3-year graft survival was higher with UW, IGL-1 and CE (75%, 75% and 73%, respectively), compared to the HTK (69%) (p < 0.0001). The same trend was observed with a total ischemia time (TIT) >12 h or grafts used for patients with cancer (p < 0.0001). For partial grafts, 3-year graft survival was 89% for IGL-1, 67% for UW, 68% for CE and 64% for HTK (p = 0.009). Multivariate analysis identified HTK as an independent factor of graft loss, with recipient HIV (+), donor age ≥65 years, recipient HCV (+), main disease acute hepatic failure, use of a partial liver graft, recipient age ≥60 years, no identical ABO compatibility, recipient hepatitis B surface antigen (-), TIT ≥ 12 h, male recipient and main disease other than cirrhosis. HTK appears to be an independent risk factor of graft loss. Both UW and IGL-1, and CE to a lesser extent, provides similar results for full size grafts. For partial deceased donor liver grafts, IGL-1 tends to offer the best graft outcome.

A proposed new method for assessing the pathological response to chemotherapy in resected colorectal liver metastases.

BACKGROUND: Pathological response (PR) to preoperative chemotherapy for colorectal liver metastases (CLM) is recognised as a prognostic factor of outcome. However, the optimal system to assess this parameter is still debated. This study focuses on current methods and proposes a possibly better method for assessing PR. METHODS: Among 223 patients resected for CLM between 2004 and 2011, after more than three cycles of chemotherapy, the percentage of tumour cells, necrosis and fibrosis, and the tumour regression grade were assessed for each of 802 nodules. Pathological response was evaluated according to validated methods and their combinations. A new method combined the percentage of tumour cells and the size of all nodules as follows: , where n is each separate nodule, % is the percentage of remaining tumour cells within nodule n (%) and s is the size of nodule n (cm).The prognostic value of each method was calculated. RESULTS: After a median follow-up of 47 months (3-106), the cumulative 5-year overall survival rate after liver resection was 59%. The proposed method categorised as follows: 0 residual tumour; 0.1-6-cm residual tumour; >6-cm residual tumour, and necrosis rate >50% stratified prognosis (P=0.0027; P=0.02), while the other methods did not. At multivariate analysis, our method remained an independent predictor of outcome (P=0.001). CONCLUSIONS: Combining the percentage of tumour cells multiplied by the size of each separate tumour seems to be a better method for assessing PR. External validation is required.

Liver transplantation for alcoholic liver disease in Europe: a study from the ELTR (European Liver Transplant Registry).

Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988-2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10,943 VIR, 1478 ALD+VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p=0.04, p=0.05). By multivariate analysis, ALD+VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results.

Major hepatectomy for hilar cholangiocarcinoma type 3 and 4: prognostic factors and longterm outcomes.

BACKGROUND: Radical operation for hilar cholangiocarcinoma, including major hepatectomy with vascular resection, seems to improve longterm survival. This study retrospectively evaluates several prognostic risk factors that can influence survival after resection of types 3 to 4 Klatskin tumors. STUDY DESIGN: Between 1984 and 2003, 59 patients (36 men and 23 women) with types 3 to 4 hilar cholangiocarcinoma underwent liver resection with curative intent. Medical records and pathologic findings were reviewed to assess prognostic risk factors and survival. Disease-free and overall survival were analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Survival rates at 1, 3, and 5 years were 82%, 45%, and 20% respectively. In-hospital mortality was 5% and morbidity was 42%. In multivariable analysis, male gender (relative risk [RR] = 5.4; 95% CI, 2.2 to 13.5), absence of preoperative chemotherapy (RR = 4; 95% CI, 1.5 to 10.7), R1 biliary tract margin (RR = 2.6; 95% CI, 1.1 to 4.4), and metastatic celiac lymph nodes (RR = 19.9; 95% CI, 4 to 71.4) were found to be independent factors for overall survival. Pedicular metastatic lymph nodes were not associated with poorer overall survival. If biliary positive-margin is the only risk factor, the 5-year estimated overall survival is 70%. CONCLUSIONS: Major hepatectomy can improve outcomes of hilar cholangiocarcinoma. Compared with nonoperative treatment or R0 hepatectomy, R1 resection in patients with no other risk factor can offer longterm survival.

Hepatic resection for metastatic renal tumors: is it worthwhile?

BACKGROUND: Liver metastases of malignant renal tumors are regarded as having an ominous prognosis because they are infrequently amenable to radical surgery and respond poorly to chemotherapy. Little is known of the outcome of isolated metastases to the liver for which resection is potentially curative. METHODS: Data on 14 patients with liver metastases from renal tumors who underwent a liver resection in a single center between 1982 and 2001 were analyzed retrospectively. RESULTS: There was no operative or postoperative mortality. The median survival was 26 months, with a survival rate of 69% at 1 year and 26% at 3 years. The curative pattern of hepatectomy (2-year survival, 69% vs. 0%; P =.001), an interval between the nephrectomy and the diagnosis of liver metastases in excess of 24 months (2-year survival, 71% vs. 25%; P =.05), tumor size <50 mm (2-year survival, 83% vs. 17%; P =.006), and the possibility of achieving a repeat hepatectomy in the case of recurrence (2-year survival, 100% vs. 21%; P =.02) were associated with a better outcome after the liver resection. Four patients were alive without evidence of disease at 6, 12, 26, and 96 months after the first hepatic resection, and one was alive with hepatic recurrence 18 months after resection. CONCLUSIONS: In patients with liver metastases of malignant renal tumors, an aggressive policy for achieving tumor eradication seems to offer a chance for long-term survival, especially after a long disease-free interval from the nephrectomy. However, despite an aggressive policy for achieving tumor eradication, recurrence frequently occurs after liver resection.

Auxiliary partial orthotopic versus standard orthotopic whole liver transplantation for acute liver failure: a reappraisal from a single center by a case-control study.

OBJECTIVE: To reappraise the results of auxiliary partial orthotopic liver transplantation (APOLT) compared with those of standard whole-liver transplantation (OLT) in terms of postoperative death and complications, including neurologic sequelae. SUMMARY BACKGROUND DATA: Compared with OLT, APOLT preserves the possibility for the native liver to recover, and to stop immunosuppression. METHODS: In a consecutive series of 49 patients transplanted for fulminant or subfulminant hepatitis, 37 received OLT and 12 received APOLT. APOLT was done when logistics allowed simultaneous performance of graft preparation and the native liver partial hepatectomy to revascularize the graft as soon as possible. Each patient undergoing APOLT (12 patients) was matched to two patients undergoing OLT (24 patients) according to age, grade of coma, etiology, and fulminant or subfulminant type of hepatitis. All grafts in the study population were retrieved from optimal donors. RESULTS: Before surgery, both groups were comparable in all aspects. In-hospital death occurred in 4 of 12 patients undergoing APOLT compared with 6 of 24 patients undergoing OLT. Patients receiving APOLT had 1 +/- 1.3 technical complications compared with 0.3 +/- 0.5 for OLT patients. Bacteriemia was significantly more frequent after APOLT than after OLT. The need for retransplantation was significantly higher in the APOLT patients (3/12 vs. 0/24). Brain death from brain edema or neurologic sequelae was significantly more frequent after APOLT (4/12 vs. 2/24). One-year patient survival was comparable in both groups (66% vs. 66%), and there was a trend toward lower 1-year retransplantation-free survival rates in the APOLT group (39% vs. 66%). Only 2 of 12 (17%) patients had full success with APOLT (i.e., patient survival, liver regeneration, withdrawal of immunosuppression, and graft removal). One of these two patients had neurologic sequelae. CONCLUSIONS: Using optimal grafts, APOLT and OLT have similar patient survival rates. However, the complication rate is higher with APOLT. On an intent-to-treat basis, the efficacy of the APOLT procedure is low. This analysis suggests that the indications for an APOLT procedure should be reconsidered in the light of the risks of technical complications and neurologic sequelae.

Salvage transjugular intrahepatic portosystemic shunt for uncontrolled variceal bleeding in patients with decompensated cirrhosis.

BACKGROUND/AIMS: The place of transjugular intrahepatic porto-systemic shunt (TIPS) for variceal haemorrhage uncontrolled by sclerotherapy and medical treatment is still undefined. To investigate the outcome of early salvage TIPS for active uncontrolled variceal haemorrhage, and to identify the factors associated with mortality. METHODS: Salvage TIPS was performed in 58 patients as soon as possible after the diagnosis of variceal bleeding refractory to the combination of sclerotherapy and of pharmacological therapy. Twenty-three variables were assessed prospectively to identify predictors of mortality within 60 days of the procedure. RESULTS: The haemorrhage was controlled in 52 of 58 patients (90%). Bleeding persisted in six of 58 patients (10%), and recurred in four patients (7%). Overall, 17 (29%) and 20 (35%) patients died within respectively 30 days and 60 days of TIPS: five patients died of persistent bleeding, two patients died of recurrent bleeding, and 13 patients died of terminal liver failure. The actuarial survival following salvage TIPS was 51.7% at 1 year. On multivariate analysis, independent predictors of early mortality were: the presence of sepsis (P=0.001), the use of catecholamines for systemic hemodynamic impairment (P=0.009), and the use of balloon tamponade (P=0.04). Neither a single factor, nor a combination of factors before TIPS allowed to predict mortality confidently in a given patient. CONCLUSIONS: Early salvage TIPS is an effective treatment to stop active variceal bleeding refractory to sclerotherapy and pharmacological treatment. Pre-treatment prognostic determinants that correlate to mortality can not be used to predict the outcome in individual cases.

Primary non-Hodgkin's lymphomas of the liver with nodular and diffuse infiltration patterns have different prognoses.

BACKGROUND: Primary liver non-Hodgkin's lymphomas have peculiar clinical and biological patterns. This study correlates these patterns with pathology and outcome. PATIENTS AND METHODS: Clinical records and histology of patients with primary liver non-Hodgkin's lymphoma, treated at our institution over a 20-year period, were reviewed. Lymphoproliferations occurring after liver transplantation were excluded. Survival analyses were performed with patients from the other published series (62 patients). RESULTS: Our series included eight patients. Three patients had a nodular liver infiltration, corresponding to a large B-cell lymphoma. Five patients had a diffuse liver infiltration, of whom three had a T-cell lymphoma with predominant sinusoid infiltration, and two had a large B-cell lymphoma. Patients with diffuse liver infiltration presented with hepatomegaly, and two of these also had acute liver failure. Diffuse infiltration had a worse prognosis than nodular infiltration (P = 0.0033). Among these latter patients, those treated with an anthracycline-based chemotherapy had a better outcome (P < 0.0001). CONCLUSIONS: Patients with primary liver lymphomas can be classified in two groups, depending on the type of infiltration. Those with nodular infiltration may benefit from anthracycline-based chemotherapy. Diffuse infiltration has a bad prognosis, and should be suspected in patients presenting with altered liver functions and hepatomegaly.

Split-liver transplantation for two adult recipients: feasibility and long-term outcomes.

OBJECTIVE: To identify the outcomes and risks of split-liver transplantation (SLT) for two adult recipients to determine the feasibility of more widespread use of this procedure to increase the graft pool for adults. SUMMARY BACKGROUND DATA: The shortage of cadaver liver grafts for adults is increasing. Using livers from donors defined as optimal, the authors have been developing techniques for SLT for two adult recipients at their center. METHODS: From July 1993 to December 1999, 34 adults have undergone SLT with grafts from optimal donors prepared by ex situ split (n = 30) or in situ split (n = 4), and 88 adults received optimal whole-liver grafts that were not split. Four split-grafts were transplanted at other centers. The outcomes of transplantation with right and left split-liver grafts were compared with those of whole-liver transplants. The main end points were patient and graft survival at 1 and 2 years and the incidence and types of complications. RESULTS: For whole-liver, right and left split-liver grafts, respectively, patient survival rates were 88%, 74%, and 88% at 1 year and 85%, 74%, and 64% at 2 years. Graft survival rates were 88%, 74%, and 75% at 1 year and 85%, 74%, and 43% at 2 years. Patient survival was adversely affected by graft steatosis and recipients inpatient status before transplantation. Graft survival was adversely affected by steatosis and a graft-to-recipient body weight ratio of less than 1%. Primary nonfunction occurred in three left split-liver grafts. The rates of arterial (6%) and biliary (22%) complications were similar to published data from conventional transplantation for an adult and a child. SLT for two adults increased the number of recipients by 62% compared with whole-liver transplantation and was logistically possible in 16 of the 104 (15%) optimal cadaver donors. CONCLUSIONS: Split-liver transplantation for two adults is technically feasible. Outcomes and complication rates can be improved by rigid selection criteria for donors and recipients, particularly for the smaller left graft, and possibly also by in situ splitting in cadaver donors. Wider use will require changes in the procedures for graft allocation and coordination between centers experienced in the techniques.