Long-Term (≥25 Years) Kidney Allograft Survivors: Retrospective Analysis at a Single Center.

INTRODUCTION: Despite great improvements in the short-term patient and kidney graft survival, the long-term morbidity and mortality in kidney transplant recipients still remains a significant problem. The aim of the study was to evaluate the impact of both donor and transplant recipient factors, as well as renal function indices on the very long-term (>25 years) kidney allograft survival. MATERIAL AND METHODS: Retrospective analysis was performed on the data of 41 kidney transplant recipients (KTR), group A: follow-up = 25 years, 20 KTR, 10 male, mean age (mean [M] ± standard deviation [SD]): 34.6 ± 12.6 years, 14 living donors (LD), 6 cadaveric donors (CD); group B: follow-up > 25 years, 21 KTR, 16 male, mean age (M ± SD): 30.86 ± 12.37 years, 14 LD, 7 CD). Kidney graft origin, post-kidney transplantation diabetes mellitus, HLA compatibility, delayed graft function, and acute rejection episodes were also analyzed retrospectively. Statistical analysis with Mann-Whitney test and Kaplan-Meier survival analysis was performed (SPSS 20.0 for Windows). RESULTS: The mean age of CDs was lower than that of LDs: CD mean age (M ± SD): 23.84 ± 16.26 years vs LD mean age: 52.75 ± 12.42 years (P < .001). Cadaveric kidney graft was associated with better renal allograft function 10, 15, and 25 years post kidney transplant. None of the other factors analyzed reached statistical significance between the 2 groups. CONCLUSION: The age of the donor and the kidney graft origin are important co-factors of the very long-term kidney allograft survival.

Solid Organ Transplantation After Retrieval From Deceased Donors With Abdominal Aortic Grafts.

INTRODUCTION: Organ procurement from deceased donors has been steadily augmented over the last 20 years. With a more aged donor population, a higher incidence of intraabdominal pathologies, including abdominal aortic aneurysms and atherosclerotic aortic disease, is commonly being encountered. The objective of our study was to report our institutional experience with abdominal aortic grafts during solid organ harvesting. PATIENTS AND METHODS: Data concerning the presence of aortic grafts in deceased solid organ donors during a 36-month period were retrospectively reviewed. RESULTS: During the study period, the organ retrieval team of our institution performed 246 multiorgan retrievals from deceased donors. More specifically, we harvested 6 livers and 12 kidneys from 6 donors with abdominal aortic grafts, which were not known/diagnosed to the organ retrieving team prior to the harvesting procedure. Severe atherosclerosis was present in all these donors. All 18 harvested organs were successfully transplanted. Apart of the absence of the aortic patch in 5 kidney grafts, no further special technical difficulties have been reported by the transplant teams. Data analysis of the recipient and graft outcome was performed through the Eurotransplant database. CONCLUSION: There are so far no literature data on the outcome of recipients and grafts from deceased donors with abdominal aortic grafts. Although retrieval of such organs is very challenging and requires a very experienced team, the transplantation of the corresponding organs can be performed without special technical problems.

Kidney Transplantation in Old Recipients From Old Donors: A Single-Center Experience.

PURPOSE: The program Old for Old or European Senior Program (ESP), allocates donors aged ≥65 years to recipients of ≥65, within a narrow geographic area in order to minimize cold ischemia time, decrease the waiting time for elderly patients listed for kidney transplantation and expand the transplant resource in this group. The ESP is not officially applied in Greece. In our center, the Old for Old criteria have been used since 2003 for elderly patients who are candidates for kidney transplantation. METHODS: We aimed to retrospectively evaluate the results of kidney transplantation from donors ≥65 years to recipients ≥65 years (Old for Old group), by examining a 5-year actual survival of the recipient and the graft. Ten Old for Old transplantations were performed at our center and the graft and patient survival was estimated during a 5-year follow-up. This group was compared to a control group of 10 recipients under the age of 65, who received grafts from deceased donors aged ≥65 years; it was found that graft and patient survival was significantly lower in the Old for Old group (50% and 58% respectively), compared to the control group, with graft and patient survival 72% and 80%, respectively (P < .05). The main cause of death was cardiovascular disease. CONCLUSIONS: More studies with higher number of patients are needed for the assessment of survival outcome between the elderly transplanted patient and those on dialysis listed for renal allografts to conclude whether Old for Old transplantation is beneficial. It is also important to consider a better pre-transplant medical evaluation with attention to cardiovascular status of the candidates and modification of the immunosuppression protocol in order to avoid serious infections and long hospital stays.

Association of Double-J Stenting in Renal Transplant Patients With Urinary Tract Colonization and Infections in a Multidrug-resistant Microbe Endemic Nosocomial Environment.

PURPOSE: We investigated the association of ureteral stenting after kidney transplantation with the development of urinary tract infections (UTIs) and/or urinary tract colonization, in a hospital environment considered endemic for multidrug resistant (MDR) Gram-negative Enterobacteriaceae. METHODS: Seventy-five recipients of deceased donor grafts were divided in groups A and B. Group A (with subgroups A1 and A2) included 45 transplanted patients without urinary stenting, and group B 30 patients with stenting. Subgroup A1 consisted of 30 patients transplanted before 2006, and A2 of 15 patients transplanted after 2006, when MDR, mainly carbapenem-resistant, Enterobacteriaceae, frequency has risen in our hospital. RESULTS: The incidence and the number of UTIs per patient were significantly higher in patients without stenting compared to those with stenting. (Group A: 32/45 vs group B: 9/30, P < .001, and group A: 2.86 ± 0.43 vs group B: 0.6 ± 0.19, P < .01 respectively). Patients without stenting tended to have a higher frequency of recurrent UTIs compared to those with stenting (group A: 16/45 vs group B: 4/30, P < .05). Asymptomatic bacteriuria was more frequent in the patients with stent (group A: 8/45 vs group B: 14/30, P < .05). Further sub-comparison of the A1 and A2 subgroups with group B did not change the statistical results. CONCLUSIONS: There is no clinically significant association of ureteral stenting after kidney transplantation with the high frequency of MDR Gram-negative bacteria in our hospital.

Human Leukocyte Antigen Compatibility and De Novo Donor-Specific Antibodies in Long-term Renal Transplant Patients With Stable Graft Function.

PURPOSE: De novo donor-specific antibodies (DSA) are associated with antibody-mediated rejection leading to late renal transplant failure. The aim of this study was to evaluate whether HLA compatibility is associated with sensitization along with other risk factors. METHODS: Eighty-nine stable renal transplant recipients (47 men) were studied. Patients were classified into 2 groups according to HLA compatibility between donor and recipient, group A (1-4/8 matches) and group B (5-8/8 matches). Cold ischemia time (CIT) and delayed graft function (DGF) were recorded along with time with a functional graft. Anti-HLA antibodies were detected using a Luminex single-antigen bead assay and were further classified into DSA and non-DSA. RESULTS: HLA group A consisted of 49 (56%) transplant recipients while 38 (44%) were classified to group B, with functional grafts for 10.9 ± 6.7 and 14.8 ± 8.5 years, respectively (P = .019). Group A patients had more anti-HLA antibodies than group Β (P = .001) and this correlation was retained for DSA patients. De novo anti-HLA were detected in 40 patients; DSA were detected in 19 (21.8%). DSA (+) patients had recorded with functional renal grafts for 11 ± 5 years, compared to 14.4 ± 8.6 years (P = .048) for anti-HLA negative patients. Increased CIT and DGF were associated with anti-HLA antibodies detection but no with DSA. CONCLUSION: HLA compatibility is probably correlated with DSA in a context of a more general anti-HLA sensitization, and both have a negative effect on long-term renal graft outcome.

Hepatic Artery Anatomic Variations and Reconstruction in Liver Grafts Procured in Greece: The Effect on Hepatic Artery Thrombosis.

AIMS: Variations of the anatomy of donor hepatic arteries increase the number of arterial anastomoses during liver transplantation and, possibly, the incidence of hepatic artery thrombosis (HAT). In this study, we describe the arterial anatomic variations in liver grafts procured and transplanted by a single center in Greece, the techniques of arterial anastomosis, and their effect on the incidence of early HAT. MATERIALS AND METHODS: From January 2013 to December 2017, the arterial anatomy of 116 grafts procured for liver transplantation were recorded, as well as the technique of arterial anastomosis and the incidence of early hepatic artery thrombosis (HAT <30 days). RESULTS: A single hepatic artery was recorded in 72.41% of the procured grafts, an aberrant left hepatic artery (accessory or replaced) in 18 grafts (15.52%), and an aberrant right hepatic artery (accessory or replaced) in 17 grafts (14.66%), while other variations were observed in less than 1% of the procured livers. Of the 116 primary liver transplantations, 6 patients (5.17%) developed early HAT <30 days. Two of these patients (1.72%) had 1 anastomosis of the hepatic artery and 4 (3.45%) had 2 anastomoses due to anatomic variations. CONCLUSIONS: Anatomic variations of the hepatic artery in liver grafts is a common finding and increase the incidence of early HAT but not to a degree to make these grafts unusable.

Prediction of Microvascular Tumor Invasion in Liver Transplant Candidates With Hepatocellular Carcinoma: A Feasible Concept or a Misleading Illusion?

INTRODUCTION: Hepatocellular carcinoma (HCC) in cirrhosis is a widely accepted indication for liver transplantation (LT). Many scoring systems have been proposed intending to an extension of the established Milan criteria. Bridging treatments are systematically applied in order to maintain or to downstage such patients to the listing criteria. The objective of our study was to estimate the feasibility of the prediction of microvascular tumor invasion in transplant candidates. PATIENTS AND METHODS: Data corresponding to transplanted HCC patients were reviewed for the purposes of this study. All tumor slices were blindly re-evaluated by a single pathologist in order to score for tumor necrosis and microvascular invasion. Recipients of pediatric or split LT were excluded. RESULTS: Eighty patients (30 women and 50 men) were included in the study. Tumor necrosis was absent in 29 of 80 liver explants (36.25%). In the majority of instances (63.75%) tumor necrosis was evident in proportions between 5% and 100%. In 58 liver explants showing 0%-60% tumor necrosis and 22 liver explants showing > 60% tumor necrosis, microvascular tumor invasion was detectable in 11 and 0 cases, respectively (P = .0385). CONCLUSION: In about one-fourth of the cases (27.5%) microvascular tumor invasion could not be detected due to extended areas of tumor necrosis. Preoperative detection of microvascular invasion is misleading.

Prevalence and Impact of Reformed and De Novo Anti-HLA Donor-Specific Antibodies in Liver Transplantation.

INTRODUCTION: The prevalence and impact of pre-existing and de novo anti-HLA donor-specific antibodies (DSAs) after orthotopic liver transplantation (OLT) is still controversial. We investigated the prevalence of DSAs and their implication in the development of allograft dysfunction after OLT. PATIENTS AND METHODS: A total of 65 liver transplant patients were tested for anti-HLA antibodies, with single antigen bead technology, before, 1, 3, 6, and 12 months after transplantation, and thereafter annually, along with other risk factors. Sixteen out of 65 patients (24.6%) had circulating pre-existing anti-HLA antibodies, and 4 of them (25%) had DSAs. All patients positive for anti-HLA antibodies (100%) presented allograft dysfunction. Fourteen out of 65 patients (21.5%) had circulating de novo DSAs, and 12 out of 14 (85.7%) presented allograft dysfunction. The investigated risk factors for allograft dysfunction were: recipient and donor age, time on the waiting list, cold ischemia time, cytomegalovirus infection, immunosuppression regimen, de novo DSAs, Model for End-Stage Liver Disease, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase (GGT), direct bilirubin and total bilirubin peak post-transplant, and alkaline phosphatase. The multivariate analysis showed that de novo DSAs and time on the waiting list were independent risk factors for allograft dysfunction. CONCLUSION: Our results show that de novo DSAs are an independent risk factor for allograft dysfunction, along with time on the waiting list.

Comparison Between Salvage Liver Transplantation and Repeat Liver Resection for Recurrent Hepatocellular Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: Repeat liver resection (RLR) has been adopted by surgeons as the first-line treatment in the case of intrahepatic recurrence of hepatocellular carcinoma (HCC), whereas salvage liver transplantation (SLT) is considered a second-line option. The aim of our study was to evaluate the results of SLT and RLR for HCC. METHODS: We searched for articles published up to December 1, 2017, in the PubMed database that compared SLT with RLR for HCC. We extracted data about patient and tumor characteristics, operative and postoperative outcomes, and survival and performed a meta-analysis. RESULTS: Patients who underwent SLT had somewhat larger liver lesions (mean difference: 0.73 cm, 95% confidence interval [CI]: 0.29-1.18, P = .001; I2: 0%, P = .82). Moreover, salvage liver transplantation resulted in higher blood loss, longer operating time, longer hospital stay, and higher postoperative morbidity (risk ratio [RR]: 2.45, 95% CI: 1.6-3.75, P < .0001; I2: 0%, P = .58) than RLR, whereas there was no significant difference in terms of postoperative mortality (RR: 6.48, 95% CI: 0.51-82.54, P = .15; I2: 61%, P = .08). On the other hand, SLT led to longer disease-free survival (DFS) than RLR (HR: 0.42, 95% CI: 0.25-0.7, P = .0009; I2: 63%, P = .03), but there was no significant difference in regard to overall survival (OS) (HR: 0.82, 95% CI: 0.55-1.23, P = .34; I2: 0%, P = .62). CONCLUSIONS: SLT seems to be inferior to RLR regarding operative and postoperative results but presents a significant advantage in terms of DFS over RLR.

Liver Transplantation for Wilson's Disease in Non-adult Patients: A Systematic Review.

INTRODUCTION: Wilson's disease (WD) is a rare autosomal recessive disorder transmitted through a gene located on chromosome 13. Liver transplantation (LT) provides a therapeutic option for patients with WD presenting fulminant liver failure or drug resistance. LT in patients with WD has a twofold aim: to save the patient's life when the disorder has progressed to hepatic (or other organ) failure and to cure the underlying metabolic defect. The aim of our study was to investigate the indications, aspects and post-operative outcomes in pediatric patients (< 18 years old) with WD who underwent LT. METHODS: A meticulous search of the literature since 1971 was performed. A retrospective analysis of all the studies, presenting cases of LT in children due to WD, was conducted. Studies that did not report patients' characteristics, transplantation indications, post-operative outcomes, and complications, as well as those with small study populations (< 10 patients), were excluded. RESULTS: Six studies were included in the present review, which involved 290 children. The main indications for LT included chronic liver failure and fulminant liver failure. The average 1-year survival rate was 91.9%, while the average 5-year survival rate was 88.2%. Retransplantation was performed in 16 patients due to transplant rejection. In general, patients transplanted for WD displayed an excellent quality of life after LT. CONCLUSION: LT is a safe and efficient procedure in selected pediatric patients with WD, demonstrating excellent long-term outcomes and quality of life.

Colonization and Infection With Extensively Drug Resistant Gram-Negative Bacteria in Liver Transplant Recipients.

BACKGROUND: Infections due to extensively drug resistant Gram-negative bacteria (GNB) after solid organ transplantation are increasing in prevalence and are associated with high morbidity and mortality. Surveillance culture (SC) seems to be an important tool for extensively drug resistant GNB control. The aim of this study was to evaluate colonization rates and subsequent infections by XDR-GNB in liver transplant recipients. MATERIAL AND METHODS: This was a prospective cohort study in patients who underwent liver transplantation (LT) between January 2016 and January 2018. Data on demographics, extensively drug resistant colonization, and 3-month clinical outcomes were obtained. Colonization was defined as a positive surveillance culture (SC-perirectal) immediately before transplantation, once weekly after LT, and after intensive care unit discharge, with emphasis to carbapenem-resistant Gram-negative bacteria (CR-GNB). RESULTS: Forty-four patients who underwent LT were included in the study. Ten patients (22.72%) were colonized with CR-GNB prior to transplantation, and 7/10 (70%) developed infection due to the same pathogen (5 patients bloodstream infections, 2 patients pneumonia) during the study period. Intensive care unit length of stay was significantly longer in colonized with CR-GNB patients (P < .05). Mortality rate was higher in colonized patients (30%) than in noncolonized (11.76%) (P = .2). CONCLUSION: Our study results suggest an overall 70% risk of CR-GNB infection among colonized patients. Given the high mortality rate and the difficulty in treating these infections, further research to investigate and develop strategies to eliminate the colonization is needed.

Trough Levels of Everolimus Are Associated With Recurrence Rates of Hepatocellular Carcinoma After Liver Transplantation.

PURPOSE: Everolimus, a mammalian target of rapamycin inhibitor, may have a protective role on hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT), but data regarding the impact of its trough serum levels on HCC recurrence are missing. METHODS: Fifty-five patients (43 men, age 55 ± 8 years) who underwent LT for HCC were evaluated. Several demographic and clinical variables were recorded, including radiological and histological characteristics of HCC as well as dosages and trough levels of immunosuppressive regimens. RESULTS: HCC recurrence occurred in 11 (20%) patients: 5 (25%) of 20 patients under calcineurin inhibitors and 6 (17%) of the 35 patients under everolimus (P = .48). The patients with HCC recurrence (n = 11, group 1), compared to those without recurrence (n = 44, group 2), had significantly more frequent HCC in the explant: outside Milan criteria (P = .001), microvascular invasion (P < .001), and higher number of nodules (P = .001). In multivariate analysis, microvascular invasion was the only independent factor significantly associated with HCC recurrence (OR: 2.3, 95% CI: 1.4-10.5, P = .03). Among the patients who received everolimus-based immunosuppression, the recipients with HCC recurrence, compared to those without HCC recurrence, had significantly lower mean trough levels of everolimus at 7-12 months post-LT (3.9 vs 5.9 ng/mL, P = .001), while the patients with mean trough levels of everolimus >6 ng/mL had decreased HCC recurrence rates (log rank: 2.3, P = .007). CONCLUSIONS: We found for the first time mean concentrations of everolimus between 7-12 months post-LT as the only modifiable variable related with HCC recurrence in LT recipients. However, larger studies are needed for final conclusions.

Perioperative Chemoprophylaxis οr Treatment for Extensively Drug Resistant Gram-Negative Bacteria in Patients Undergoing Liver Transplantation Based on Preoperative Donor/Recipient Surveillance Cultures: A Prospective Study.

INTRODUCTION: The importance of preoperative donor/recipient colonization or donor infection by extensively drug-resistant Gram-negative bacteria (XDR-GNB) and its relation to serious post-transplantation infection pathogenicity in liver transplantation (LT) patients has not been clarified. AIM: Prevention of postoperative infection due to XDR-GNB with the appropriate perioperative chemoprophylaxis or treatment based on preoperative donor/recipient surveillance cultures in LT patients, as well as their outcome. MATERIALS AND METHOD: Twenty-six patients (20 male, 6 female) were studied (average preoperative Model for End-Stage Liver Disease score ≈15, range: 8-29) from January 2017 to January 2018. In all patients, blood, urine, and bronchial secretions culture samples as well as a rectal colonization culture were taken pre- and postoperatively, once weekly after LT, and after intensive care unit discharge. Recipients with positive XDR-GNB colonization and patients receiving a transplant from a donor with an XDR-GNB positive culture or colonization received the appropriate chemoprophylaxis one half hour preoperatively according to culture results. De-escalation of the antibiotic regimen was done in 2 to 5 days based on the colonization/culture results of the donor and recipient and their clinical condition. Evaluation for serious infection was done at 1 week and at 28 days for outcome results. RESULTS: Fourteen out of 26 recipients (53.8%) were positive for XDR-GNB colonization preoperative, with 2/14 (14.28%) presenting serious infection due to the same pathogen. Intensive care unit length of stay was significantly longer in colonized with XDR-GNB patients (P < .0001). The outcome of colonized patients was 6/14 (42.8%) expired, but only in 2/14 (14.2%) was mortality attributable to infection. CONCLUSION: Administering appropriate perioperative chemoprophylaxis and treatment may limit the frequency of XDR-GNB infections and intensive care unit length of stay and may improve the outcome in LT recipients.

New-Onset Diabetes After Transplantation: Comparison Between a Cyclosporine-Based and a Tacrolimus-Based Immunosuppressive Regimen.

INTRODUCTION: New-onset diabetes after transplantation (NODAT) is a complication of renal transplantation (RT) with an adverse effect on graft survival. OBJECTIVES: The purpose of the present study was to compare modifiable or non-modifiable clinical and laboratory parameters as well as the course of patients and transplants between 2 groups of RT recipients with NODAT in relation to the use of either a cyclosporine-based (group A) or a tacrolimus-based immunosuppressive regimen (group B). MATERIALS AND METHODS: Retrospectively comparing 66 renal transplant recipients with NODAT, multiple clinical, and laboratory parameters were investigated. For statistical analysis, the χ2 test, the Student t test, and the patient and graft survival or the Kaplan-Meier analysis from the statistical software SPSS 22.0 for Windows were used. RESULTS: There was no statistically significant difference in association with the majority of the investigated parameters. In group B (tacrolimus [Tac]), more patients had HbA1c >7.2% at 3 years after RT. The mean value of systolic blood pressure was higher in group A (cyclosporine [CsA]) at 6 months and at 1 year after RT. More patients in group A (CsA) experienced at least one acute rejection episode. Finally, greater levels of cold ischemia time were recorded in group B (Tac) and statistically significant difference was found in connection with the patient and graft survival in the fourth year after RT. CONCLUSIONS: NODAT in patients on tacrolimus requires the adjustment of modifiable clinical and metabolic parameters and possible change of the immunosuppressive regimen to a cyclosporine-based one.

Prevalence of hepatitis E in liver transplant recipients in Greece.

Hepatitis E virus (HEV) is a well-known cause of acute hepatitis. Immunocompromised subjects, including liver transplant recipients, are considered to be at risk for HEV infection, which occasionally follows a chronic course. The diagnosis of HEV infection in these patients must be based on HEV RNA testing, as serology has variable performance. The aim of this study was to assess the prevalence of HEV infection in liver transplant recipients in Greece by means of HEV RNA testing. Liver transplant recipients followed in the sole transplant centre in Greece were prospectively included. HEV RNA was detected by real-time RT-PCR. Positive samples were further analysed using a nested reverse transcription RT-PCR kit, which amplifies a 137-nucleotide sequence within the ORF2/ORF3 overlapping region to detect the HEV genotype and perform phylogenetic analysis. The mean age of the included patients (n = 76) was 54 years. The most common indication for liver transplantation was viral hepatitis (57%). The majority of the patients (75%) received a calcineurin inhibitor as part of their immunosuppressive regimen and had normal liver enzymes. HEV RNA was found positive in only 1/76 (1.3%) patient. Phylogenetic analysis showed that the sequence clustered into the HEV genotype 3 clade. This patient experienced an acute hepatitis flare, which nonetheless did not become chronic. The prevalence of HEV infection in liver transplant recipients in Greece is similar (1.3%) to that reported previously in other countries. Transplant physicians should be aware of this condition and its associated consequences.

Nucleos(t)ide analog(s) prophylaxis after hepatitis B immunoglobulin withdrawal against hepatitis B and D recurrence after liver transplantation.

BACKGROUND/AIMS: Nucleos(t)ide analogs (NAs) have made a hepatitis B immunoglobulin (HBIG)-sparing protocol an attractive approach against hepatitis B virus (HBV) recurrence after liver transplantation (LT). However, this approach is considered controversial in patients transplanted for HBV and hepatitis D (HDV) co-infection. MATERIAL/METHODS: All patients transplanted for HBV/HDV cirrhosis were evaluated. After LT, each patient received HBIG + NAs and then continued with NAs prophylaxis. All patients were followed up with HBV serum markers and HBV DNA, while anti-HDV/HDV RNA was performed in those with HBV recurrence. RESULTS: A total of 34 recipients were included (22 men, age: 46.7 ± 16 years). After HBIG discontinuation, NAs were received as monoprophylaxis (lamivudine [LAM]: 2, adefovir [AFV]: 1, entecavir: 9, tenofovir [TDF]: 12) or dual prophylaxis (LAM + AFV [or TDF]: 10 patients). Two (5.8%) of the 34 patients had HBV/HDV recurrence after HBIG withdrawal (median follow-up: 28 [range, 12-58] months). These 2 patients had undetectable HBV DNA at LT. Statistical analysis revealed that those with recurrence had received HBIG for shorter period, compared to those without recurrence (median: 9 vs. 28 months, P = 0.008). CONCLUSIONS: We showed for the first time, to our knowledge, that maintenance therapy with NAs prophylaxis after HBIG discontinuation was effective against HBV/HDV recurrence, but it seems that a longer period of HBIG administration might be needed before it is withdrawn after LT.

The effect of sorafenib on liver regeneration and angiogenesis after partial hepatectomy in rats.

BACKGROUND: Liver regeneration is vital for the survival of patients submitted to extensive liver resection as a treatment of hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor of angiogenesis and cell division, both of which are integral components of liver regeneration. We investigated the effect of preoperative treatment with sorafenib, a drug used for the treatment of HCC, on liver regeneration and angiogenesis in healthy rats, after two-thirds partial hepatectomy (PH2/3). METHODS: In total 48 Wistar rats received intragastric injections of sorafenib (30 mg/kg/d) or vehicle, underwent PH2/3, and were sacrificed at 48, 96 or 168 hours after that. The regenerative index of the liver remnant was studied, as well as the mitotic index. DNA synthesis and angiogenesis were estimated by immunohistochemistry for the Ki-67 and CD34 antigens, respectively. RESULTS: Sorafenib reduced significantly the regenerative index at all time points but not the mitotic index at 48, 96 or 168 hours. Deoxyribonucleic acid (DNA) synthesis and angiogenesis were not affected significantly either. CONCLUSIONS: Sorafenib, when administered preoperatively, reduces incompletely and transiently the regeneration of the liver after PH2/3 in rats. This could mean that sorafenib can be used as neoadjuvant treatment of patients with HCC prior to liver resection, but further experimental and clinical studies are needed to establish the safety of this treatment. Hippokratia 2015; 19 (3): 249-255.

Telbivudine is associated with improvement of renal function in patients transplanted for HBV liver disease.

Recent studies showed that telbivudine in patients with hepatitis B virus (HBV) infection improved their glomerular filtration rate (GFR), but data regarding its impact on renal function in liver transplant (LT) recipients are very limited. We evaluated 17 consecutive recipients who received at baseline nucleos(t)ide analogue(s) (NAs) other than telbivudine for 12 months, and then they were switched to telbivudine prophylaxis for another 12 months. In each patient, laboratory data including evaluation of GFR (using MDRD and CKD-EPI) were prospectively recorded. The changes in GFR (ΔGFR) between baseline and after 12 months (1st period) and between telbivudine initiation and 24 months (2nd period) were evaluated. All patients remained serum HBsAg and HBV-DNA negative. GFR-MDRD at baseline, 12 months and 24 months were 72 ± 18, 67.8 ± 16 and 70.3 ± 12 mL/min, respectively, (P = 0.025 for comparison between 12 months and 24 months). ΔGFR at the 1st period was significantly lower, compared with ΔGFR at the 2nd period [mean ΔGFR-MDRD: -4.2 (range: -24-9) vs 2.5 (range: -7-22) mL/min, P = 0.013; mean ΔGFR-CKD-EPI: -4.2 (range: -19-10) vs 4.0 (range: -7-23) mL/min, P = 0.004], although the serum levels of calcineurin inhibitors were similar between the two periods. A second group of recipients (n = 17) who remained under the same nontelbivudine NA(s) for 24 months had a decline in the mean eGFR during the total follow-up period. In conclusion, we showed that telbivudine administration in LT recipients for HBV cirrhosis was effective and it was associated with significant improvement in renal function, but this remains to be confirmed in larger well-designed studies.

Single-center experience of transplantation for polycystic liver disease.

BACKGROUND: Polycystic liver disease (PLD) may lead to massive hepatomegaly, abdominal distension, pain, and various degrees of dyspnea. The surgical treatment of this entity remains controversial. METHODS: We report our experience from a retrospective analysis of 23 patients suffering from PLD who were treated with liver transplantation (LT) in our institution. RESULTS: Liver transplantation for PLD patients with extensive hepatic involvement offers excellent symptoms relief. The actuarial 1-, 3-, and 5-year survival rate after transplantation was 86%. CONCLUSIONS: Our experience demonstrates that PLD patients with extensive hepatic involvement and who are treated with LT have good long-term prognosis and excellent symptoms relief. LT might be considered in severe PLD cases where conventional surgery is not a curative option, and it must be balanced against the risks of LT and lifelong commitment to immunosuppression.

Bloodstream infections caused by carbapenemase-producing Klebsiella pneumoniae among intensive care unit patients after orthotopic liver transplantation: risk factors for infection and impact of resistance on outcomes.

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged as an important cause of bloodstream infections in intensive care units (ICUs). The aim of this study was to determine risk factors for bloodstream infections caused by CRKP as well as risk factors for CRKP-associated mortality among ICU patients after orthotopic liver transplantation (LT). METHODS: The study cohort of this observational study comprised 17 ICU patients after LT with CRKP bloodstream infections. The data from these patients were matched with 34 ICU patients (1:2) after LT without CRKP infections. The 2 groups were compared to identify risk factors for development of CRKP infection and risk factors for mortality. RESULTS: Seventeen CRKP bloodstream infections occurred in ICU patients after LT from January 1, 2008, to December 31, 2011. In univariate analysis, primary liver disease and especially hepatitis C virus infection or hepatocellular cancer were significant factors for development of CRKP. Acute Physiology and Chronic Health Evaluation (APACHE II) score and Sequential Organ Failure Assessment (SOFA) score as well as CRKP bloodstream infection were predictors for ICU death (P < .05) in univariate analysis. CONCLUSIONS: CRKP bloodstream infections affect immunocompromised post-transplantation patients more. Bloodstream infections with CRKP along with APACHE and SOFA scores were predictors of death in ICU patients after LT.