Maciej Krasnodębski

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.

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.

Poor Outcomes After Liver Transplantation in Patients With Incidental Cholangiocarcinoma Irrespective of Tumor Localization

INTRODUCTION After liver transplantation for cholangiocarcinoma (CCC), patients have a poor prognosis without use of specific therapeutic strategies. Accordingly, recipients with incidental CCC might have the highest risk of recurrent disease; however, sparse data on the long-term outcome of unselected patients with incidental CCC have been published. The aim of this study was to evaluate the post-transplantation outcomes of patients with incidental CCC with special focus on tumor localization. MATERIAL AND METHODS There were 11 primary liver transplantations in patients with incidental CCC of 1310 liver transplantation procedures performed between December 1994 and August 2013. All patients with incidental CCC received a chemotherapy regiment including gemcitabine/5 fluorouracil, doxorubicin, and mitomycin. The patients were switched from calcineurin inhibitors to mammalian target of rapamycin inhibitor-based immunosuppression shortly after CCC diagnosis. RESULTS Intra- and extrahepatic tumors were found in 6 and 5 patients, respectively. At median follow-up examination of 26.3 months there were 8 CCC recurrences and 7 patient deaths. Overall survival after liver transplantation for incidental CCC was 88.9% at 1 year, 44.4% at 2 years, and 14.8% at 3 years. The corresponding rates of recurrence-free survival were 45.7%, 45.7%, and 0.0%, respectively. Post-transplantation CCC recurrences were universal with 0% 3-year recurrence-free survival both in patients with intra- and extrahepatic tumors (P = .475). CONCLUSIONS Incidental CCC in liver transplantation is associated with poor outcomes irrespective of tumor localization. Introduction of new adjuvant multimodal treatment concepts is necessary to improve the prognosis for this subgroup of patients.

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.

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.

Differential Impact of Risk Factors for Tumor Recurrence in Hepatitis B and Hepatitis C Virus-Infected Patients Undergoing Liver Transplantation for Hepatocellular Carcinoma

BACKGROUND Hepatitis B (HBV) and C (HCV) virus infection are the 2 most important risk factors for the development of the hepatocellular carcinoma (HCC). The aim of this study was to assess the importance of the type of viral infection in evaluation of HCC recurrence risk after liver transplantation (LT). MATERIAL AND METHODS This retrospective study was based on 130 HCC patients undergoing LT. Patients were subdivided by HBV or HCV infection only or HBV and HCV co-infection (HBV-HCV). The primary outcome measure was recurrence-free survival (RFS) 5 years after transplantation. RESULTS The 5-year RFS did not differ significantly according to HBV infection, HCV infection, or HBV-HCV co-infection in the entire study cohort (p=0.902) or among patients who fulfilled (p=0.454) or did not fulfill (p=0.999) the Milan criteria. Neither HCV (p=0.869) nor HBV (p=0.968) infection significantly affected 5-year RFS following adjustment for covariates. Higher lesion number (p=0.004), increased alpha-fetoprotein (p=0.017), microvascular invasion (p=0.004), and female donor sex (p=0.025) were significant risk factors for poor RFS in HBV patients; older recipient age (p=0.010) and increased total tumor volume (p=0.028) were significant risk factors in HCV patients. CONCLUSIONS Although the viral infection type does not affect post-LT outcomes in HCC patients, the influence of other risk factors is markedly different in HBV- and HCV-related HCC.

Robotic stereotactic body radiation therapy for liver-limited malignant tumors

Introduction Stereotactic body radiotherapy (SBRT) is rapidly gaining favor as a new treatment modality for malignant liver tumors. Most of the studies have recruited patients with disseminated disease originating from the liver. This study focuses on disease limited to the liver. Aim To perform a retrospective analysis of all patients with liver tumors treated by robotic stereotactic body radiation therapy in a single center. Material and methods The study included 13 patients with 22 lesions. The inclusion criteria were: patients with 1–4 inoperable liver lesions and absence of any extrahepatic disease. All but 3 patients received 3 fractions delivered by the Cyberknife system of a total of 45 grey (Gy). The other 3 patients received 30 Gy. Results The median follow-up time was 10.8 months (range: 7–16). The median dose was 41.5 Gy (range: 30–45). One lesion regressed (8%). In 5 patients, the disease was locally stabilized (38%), and in 7 other patients progression occurred (54%). Twelve patients (92%) are still alive, and 1 patient (8%) died. In 1 patient a new cancer (leukemia) was diagnosed. Conclusions The SBRT is well tolerated and effective for local control of most liver malignant tumors. It appears that SBRT is best suited for those patients in whom systemic recurrence can be controlled by chemotherapy. Further studies are mandatory to elucidate these effects on tumors of varying histology and to elaborate upon criteria used to select patients who can benefit most from this treatment.

Liver Transplantation Outcomes in Recipients with High Model for End-Stage Liver Disease (MELD) Scores: The Relevance of MELD Scores

BACKGROUND The aim of this study was to assess risk factors for postoperative mortality after liver transplantation among patients with Model for End-Stage Liver Disease (MELD) scores ≥35, with special focus on the MELD scores. MATERIAL AND METHODS Data from 68 primary liver transplantations in patients with MELD scores ≥35 among 1376 liver transplantations performed in the Department of General, Transplant, and Liver Surgery (Medical University of Warsaw) between January 2002 and October 2014 were analyzed retrospectively. Postoperative (90-day) mortality was set as the primary outcome measure. RESULTS Postoperative mortality was 29.4% (20 of 68). The overall survival rates after 1, 5, and 10 years were 61.9%, 59.7%, and 59.7%, respectively. According to univariate analyses, MELD (p=0.014), conventional technique of liver transplantation (p=0.049), intraoperative fresh frozen plasma (p=0.040), and red blood cells (p=0.026) transfusions were risk factors for postoperative mortality. MELD score was the only independent risk factor for postoperative mortality (p=0.023) in multivariate analysis. According to receiver operating characteristics analysis, the optimal cut-off for MELD score in prediction of postoperative mortality was ≥43 (Area Under Curve=0.703, 95% Confidence Interval 0.575-0.831). Postoperative mortality was 21.4% and 42.3% among patients with MELD score <43 and ≥43, respectively (p=0.066). CONCLUSIONS MELD score is an important predictor of early mortality after liver transplantation, even among recipients with high MELD scores. In particular, patients with MELD score ≥43 should be considered as very high-risk candidates for liver transplantation.