Karolina M. Wronka

Negative outcomes after liver transplantation in patients with alcoholic liver disease beyond the fifth post‐transplant year

Although up to 50% of patients with alcoholic liver disease (ALD) resume alcohol consumption after liver transplantation (LT), numerous studies indicate that long‐term results are not compromised. This study focused on evaluating the impact of ALD on outcomes up to and beyond the fifth year after LT. Among the 432 primary LT recipients included in this study, 97 underwent transplantation for ALD. Alcohol relapse rate at 10 yr was 33.5%, with younger recipient age being the only independent predictor (p = 0.019). Survival of patients with ALD (77.0%) was similar to those without (79.0%) up to the fifth post‐transplant year (p = 0.655) but worse during the five subsequent years among the five‐yr survivors (70.6% vs. 92.9%; p = 0.002). ALD was an independent risk factor for poorer survival beyond the fifth post‐transplant year (p = 0.049), but not earlier (p = 0.717). Conversely, alcohol relapse increased the risk of death only during the first five post‐transplant years (p = 0.039). There were no significant differences regarding graft failure incidence between ALD and non‐ALD recipients up to the fifth post‐transplant year (7.3% vs. 11.6%; p = 0.255) and beyond (12.9% vs. 5.0%; p = 0.126). In conclusion, pre‐transplant diagnosis of ALD yields negative effects on post‐transplant outcomes beyond the fifth post‐transplant year, not attributable to recidivism.

Relevance of Pre-Transplant α-fetoprotein Dynamics in Liver Transplantation for Hepatocellular Cancer.

BACKGROUND The magnitude of pre-transplant a-fetoprotein (AFP) changes has been advocated to be a superior predictor of hepatocellular cancer (HCC) recurrence following liver transplantation. The aim of this study was to compare AFP dynamics and last pre-transplant AFP as risk factors for post-transplant HCC recurrence. MATERIAL AND METHODS Data of 146 patients after liver transplantation for HCC were analyzed retrospectively. RESULTS While last pre-transplant AFP was a significant predictor of microvascular invasion (p=0.006) and poor tumor differentiation (p=0.020), AFP slope was associated only with microvascular invasion (p=0.029). Notably, last pre-transplant AFP (p<0.001), but not AFP slope (p=0.279), was an independent risk factor for recurrence. No significant effects of AFP slope were also found following division of patients into those with pre-transplant AFP <100 (p=0.260) and those with AFP >100 (p=0.178) ng/mL. Moreover, prediction of recurrence based on last pre-transplant AFP was superior (p=0.018) to those based on AFP slope. Recurrence-free survival at 5 years was superior in patients with pre-transplant AFP persistently at (97.3%) or dropping to <100 ng/mL (100.0%) as compared to patients with AFP rising to (75.0%) or persistently at >100 ng/mL (38.4%; p<0.001). CONCLUSIONS The risk of post-transplant HCC recurrence is dependent on the last pre-transplant AFP regardless of its previous dynamics.

Post-transplant outcomes of patients with and without hepatitis C virus infection according to donor age and gender matching

BACKGROUND The purpose of this study was to evaluate the impact of donor age and donor-recipient gender matching on liver transplantation outcomes, focusing on differences between patients with and without hepatitis C virus (HCV) infection. MATERIAL AND METHODS This retrospective cohort study evaluated 622 liver transplantation recipients. HCV (n=164) and non-HCV (n=458) patients were subdivided by donor age (≤ 30, 31-50, and >50 years) and donor-recipient gender configurations. Five-year patient survival (PS) and graft survival (GS) were set as outcome measures. RESULTS Five-year PS was 83.1% for HCV-positive and 81.6% for HCV-negative patients (p=0.614), with the corresponding GS rates of 81.2% and 79.3% (p=0.538), respectively. In HCV patients, transplantations from donors older than 50 years were associated with lower PS (p=0.035) and GS (p=0.006) than those from donors aged 31-50 years. This difference was not observed among non-HCV recipients (PS, p=0.994; GS, p=0.878). Regarding donor-recipient gender configurations, outcomes were similar in HCV (PS, p=0.751; GS, p=0.592) and non-HCV patients (PS, p=0.217; GS, p=0.249), except for a tendency toward lower PS for male-to-female transplantations than female-to-female transplantations in non-HCV patients (p=0.064). Outcomes of HCV patients were superior to those of non-HCV patients after transplantation from donors aged 31-50 years (PS, p=0.080; GS, p=0.026). CONCLUSIONS Avoiding the transplantation of grafts from donors aged over 50 years to patients with HCV infection might improve the general outcomes of liver transplantation programs. There is no specific rationale for gender matching with respect to HCV status.

The relevance of intestinal dysbiosis in liver transplant candidates

The gut microbial ecosystem plays an important role in the pathogenesis of liver diseases. However, the association of microbial community structure with the severity of liver dysfunction is not completely understood.

Relevance of male-to-female sex mismatch in liver transplantation for primary biliary cirrhosis.

BACKGROUND Because male-to-female transplantations are related to exposure to H-Y antigen, sex matching may influence the outcomes after liver transplantation for autoimmune diseases. The purpose of this retrospective study was to evaluate the relevance of male-to-female mismatch in liver transplantation for primary biliary cirrhosis (PBC). MATERIAL AND METHODS This retrospective study was based on the data of 82 female liver transplant recipients with PBC from a single institution. The primary outcome measure was graft survival at 10 years. The negative effects of well-known risk factors for poor outcomes were evaluated separately and compared between the female-to-female and male-to-female transplantations. RESULTS Graft survival was similar after female-to-female and male-to-female transplantations (74.7% versus 73.1% at 10 years, respectively, p=0.676). Regarding the differential impact of other risk factors, prolonged cold ischemia and increased amount of blood transfusions adversely influenced outcomes after male-to-female transplantation (p=0.039 and p=0.039, respectively) but not after female-to-female transplantation (p=0.843 and p=0.110, respectively). Sex mismatched transplantations were associated with lower 10-year graft survival in subgroups of patients with blood transfusions >4 units (61.4% versus 100.0%, p=0.063) and >8 hours of cold ischemia (54.7% versus 75.8%, p=0.418). CONCLUSIONS Although male-to-female sex mismatch does not seem to yield a direct negative impact on outcomes following liver transplantation for PBC, it can aggravate the negative effects of prolonged cold ischemia and blood transfusions.

Outcomes Following Liver Transplantation for Metastatic Neuroendocrine Tumors

INTRODUCTION Metastatic disease is generally considered as an absolute contraindication for liver transplantation. However, due to relatively low aggressiveness and slow progression rates, liver metastases from neuroendocrine tumors (NETs) form an exception to this rule. Given the scarcity of available data, the purpose of this study was to evaluate long-term outcomes following liver transplantation for NET metastases. MATERIAL AND METHODS There were 12 primary liver transplantations in patients with NET metastases out of 1334 liver transplantations performed in the Department of General, Transplant and Liver Surgery (Medical University of Warsaw) in the period between December 1989 and October 2013. Overall survival (OS) and disease-free survival (DFS) were set as primary and secondary outcome measures, respectively. RESULTS Median follow-up was 7.9 years. For all patients, OS rate was 78.6% at 10 years and DFS rate was 15.5% at 9 years. Intraoperative transfusions of packed red blood cells (P = .021), Ki-67 proliferative index more than 2% (P = .048), and grade 2 tumors (P = .037) were identified as factors significantly associated with worse DFS. Notably, loss of E-cadherin expression (P = .444), mitotic rate (P = .771), extent of liver involvement (P = .548), primary tumor site (P = .983), and recipient age (P = .425) were not significantly associated with DFS. CONCLUSIONS Excellent long-term OS rates support liver transplantation for unresectable NET metastases despite almost universal post-transplantation tumor recurrence. Selection of patients with G1 tumors with Ki-67 index not exceeding 2% and reducing the requirement for intraoperative blood transfusions might improve DFS rates.

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.

Risk Factors of Acute Renal Failure After Orthotopic Liver Transplantation: Single-center Experience

BACKGROUND Acute renal failure (ARF) is one of the most significant complications of orthotopic liver transplantation (OLT), associated with increased mortality rate and the development of chronic renal dysfunction. The aim of the study was to determine the perioperative risk factors for ARF in patients without previous history of renal disease who are undergoing OLT. MATERIALS AND METHODS Forty-six patients who developed ARF after OLT performed in 1 transplant center were included in the study, and 52 consecutive patients without that complication served as a control group. Renal dysfunction was defined as a glomerular filtration rate <60 mL/min/1.73 m(2). The data concerning preoperative diseases, perioperative renal function, first-line immunosuppressive therapy, and blood transfusion requirement were retrospectively analyzed and compared among groups. Logistic regression modeling was used to determine risk factors for ARF. RESULTS Patients who developed ARF were significantly older (mean age 53.3 vs 46.3 years, P = .057), had higher level of preoperative (0.79 vs 0.71 mg/dL, P = .0062) and intraoperative (0.85 vs 0.74 mg/dL, P = .0045) creatinine. The risk factors for ARF were intraoperative and 24-hour post-transplant creatinine level >0.9 mg/dL and high-dose tacrolimus-based immunosuppression. Transfusion of ≤6 units of red blood cells diminished the risk of ARF. Sex and preoperative diseases were not predictive to ARF in our regression models. CONCLUSION Careful operative technique with low blood loss and immunosuppressive therapy of low nephrotoxic potential should be recommended in older patients to diminish the risk of renal dysfunction after orthotopic liver transplantation. Patients with higher levels of perioperative creatinine should be considered to have first-line immunosuppression without calcineurin inhibitors or with low-dose immunosuppressants of known nephrotoxic potential.

Short and Long-Term Outcomes After Primary Liver Transplantation in Elderly Patients

UNLABELLED The number of elderly patients undergoing liver transplantation (LT) is increasing worldwide. The aim of the study was to evaluate the impact of recipient age exceeding 60 years on early and long-term outcomes after LT. MATERIAL AND METHODS This study comprised data of 786 patients after primary LT performed at a single center between January 2005 and October 2012. Patients over and under 60 years of age were compared with respect to baseline characteristics and outcomes: postoperative mortality (90-day) and 5-year patient (PS) and graft (GS) survival. Associations between recipient age exceeding 60 years and LT results were assessed in multiple Cox regression models. RESULTS Recipients older than 60 years (n=107; 13.6%) were characterized by more frequent hepatitis C virus infections (p<0.001), malignancies (p<0.001), and cardiovascular comorbidities (p<0.001); less frequent primary sclerosing cholangitis (p=0.002) and Roux-en-Y hepaticojejunostomy (p<0.001); lower Model for End-stage Liver Disease (MELD; p=0.043); and increased donor age (p=0.012). Fiveyear PS of older and younger recipients was 72.7% and 80.6% (p=0.538), while the corresponding rates of GS were 70.3% and 77.5% (p=0.548), respectively. Recipient age exceeding 60 years was not significantly associated with postoperative mortality (p=0.215), PS (p=0.525) and GS (p=0.572) in multivariate analyses. The list of independent predictors comprised MELD (p<0.001) for postoperative mortality; malignancies (p=0.003) and MELD (p<0.001) for PS; and malignancies (p=0.003), MELD (p<0.001) and donor age (p=0.017) for GS. CONCLUSIONS Despite major differences between elderly and young patients, chronological age exceeding 60 years alone should not be considered as a contraindication for LT.

Limitations of predicting microvascular invasion in patients with hepatocellular cancer prior to liver transplantation

Microvascular invasion (MVI) is well known to negatively influence outcomes following surgical treatment of hepatocellular cancer (HCC) patients. The aim of this study was to evaluate the rationale for prediction of MVI before liver transplantation (LT). Data of 200 HCC patients after LT were subject to retrospective analysis. MVI was present in 57 patients (28.5%). Tumor number (p = 0.001) and size (p = 0.009), and alpha-fetoprotein (p = 0.049) were independent predictors of MVI used to create a prediction model, defined as: 0.293x(tumor number) + 0.283x(tumor size in cm) + 0.164xloge(alpha-fetoprotein in ng/ml) (c statistic  =  0.743). The established cut-off (≥2.24) was associated with sensitivity and specificity of 72%. MVI was not an independent risk factor for recurrence (p = 0.307), in contrast to tumor number (p = 0.047) and size (p < 0.001), alpha-fetoprotein (p < 0.001) and poor differentiation (p = 0.039). Recurrence-free survival at 5 years for patients without MVI was 85.9% as compared to 83.3% (p = 0.546) and 55.3% (p = 0.001) for patients with false negative and true positive prediction of MVI, respectively. The use of both morphological and biological tumor features enables effective pre-transplant prediction of high-risk MVI. Provided that these parameters are combined in selection of HCC patients for LT, pre-transplant identification of all patients with MVI does not appear necessary.