Michał Grąt

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.

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.

Incidence, pattern and clinical relevance of microbial contamination of preservation fluid in liver transplantation

BACKGROUND Transmission of pathogens via preservation fluid (PF) is a potential cause of infection among liver transplant recipients. Here, we evaluated the incidence and pattern of microbial contamination of PF and its impact on postoperative graft function after liver transplantation. MATERIAL/METHODS This longitudinal study included data from 41 primary liver transplantations and 5 re-transplantations performed between December 2010 and September 2011. Results of microbiological analyses of 92 PF samples collected before and after the back-table procedure were evaluated in order to establish the incidence and pattern of contamination. The impact of positive PF cultures on early graft function and rate of pathogen transmission was assessed. Post-transplant antibiotic protocol was based on piperacillin/tazobactam administration for a minimum of 10 days. RESULTS The incidence of contamination was 84.8% (39/46), both for samples collected before and after the back-table procedure. Gram-positive low-virulence organisms typical for superficial saprophytic flora, mainly coagulase-negative staphylococci, were predominant. There were no cases of pathogen transmission from PF to the recipient. Positive cultures of PF samples obtained after the back-table procedure were associated with significant elevation of aspartate (p=0.034) and alanine aminotransferase (p=0.048) on the first 5 postoperative days. No significant differences were found regarding serum bilirubin concentration (p=0.335) and international normalized ratio (p=0.137). CONCLUSIONS Despite high incidence of PF contamination, infections caused by pathogens isolated from PF were not observed. However, presence of pathogens in PF might lead to temporary impairment of graft function.

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.

Early post-operative prediction of morbidity and mortality after a major liver resection for colorectal metastases

BACKGROUND An early prediction of poor outcomes is essential in the management of patients after a liver resection. The aim of this study was to evaluate the role of selected biochemical parameters on post-operative day 1 (POD 1) in the prediction of morbidity and mortality after a liver resection for colorectal metastases. METHOD This retrospective study was based on 236 major liver resections for colorectal metastases performed between 2006 and 2011. Results of biochemical tests of blood samples obtained on POD 1 were assessed as predictors of primary outcome measures (hepatic and overall morbidity, 90-day mortality) using multiple regression and receiver-operating characteristics (ROC). RESULTS Hepatic morbidity, overall morbidity and 90-day mortality rates were 18.6%, 28.0% and 4.7%, respectively. On the basis of multiple regression analysis and comparisons of the prediction models, serum bilirubin was selected for the prediction of hepatic (>2.05 mg/dl, sensitivity 69.2%, specificity 71.2%) and overall (>2.05 mg/dl, sensitivity 61.1% and specificity 71.2%) morbidity, and aspartate aminotransferase (AST) was selected for the prediction of 90-day mortality (>798 U/l, sensitivity 62.5% and specificity 90.4%). DISCUSSION Biochemical analyses of blood on POD1 enables stratification of patients into low- and high-risk groups for negative outcomes, with serum bilirubin associated with overall and hepatic morbidity and AST associated with mortality.

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 impact of surgical technique on the results of liver transplantation in patients with hepatocellular carcinoma

BACKGROUND Although piggyback technique has gained widespread acceptance for liver transplantation in general, there is an exceptional lack of data on the choice of appropriate surgical technique for patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the impact of surgical technique on outcomes after liver transplantation for HCC. MATERIAL AND METHODS We conducted a retrospective cohort study on 90 HCC patients who underwent liver transplantation with the conventional (n=19) or piggyback (n=71) technique. Both techniques were compared with respect to intraoperative variables and long-term outcomes, determined by 3-year overall (OS) and recurrence-free (RFS) survival. The potential role of confounding factors was excluded in a series of Cox proportional regression models. RESULTS The piggyback technique was associated with shorter procedure duration (p=0.0005), shorter anatomical anhepatic phase (p<0.0001), shorter duration of total (p=0.018) and warm ischemia (p<0.0001), and fewer blood transfusions (p=0.006). Three-year OS was 89.1% after piggyback and 49.9% after conventional transplantation (p=0.0008), with 3-year RFS of 89.4% and 56.0% (p=0.0006), respectively. Piggyback transplantations provided outcomes superior to conventional procedures both in patients within (p=0.019 for OS; p=0.003 for RFS) and beyond (p=0.023 for OS; p=0.031 for RFS) Milan criteria. Multivariate analysis of the risks of death and recurrence confirmed the benefits of piggyback technique. CONCLUSIONS Given its superior long-term outcome, piggyback transplantation might be considered primarily for HCC patients.

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.