How useful is the machine perfusion in liver transplantation? An answer from a national survey.

Machine perfusion (MP) has been shown worldwide to offer many advantages in liver transplantation, but it still has some gray areas. The purpose of the study is to evaluate the donor risk factors of grafts, perfused with any MP, that might predict an ineffective MP setting and those would trigger post-transplant early allograft dysfunction (EAD). Data from donors of all MP-perfused grafts at six liver transplant centers have been analyzed, whether implanted or discarded after perfusion. The first endpoint was the negative events after perfusion (NegE), which is the number of grafts discarded plus those that were implanted but lost after the transplant. A risk factor analysis for NegE was performed and marginal grafts for MP were identified. Finally, the risk of EAD was analyzed, considering only implanted grafts. From 2015 to September 2019, 158 grafts were perfused with MP: 151 grafts were implanted and 7 were discarded after the MP phase because they did not reach viability criteria. Of 151, 15 grafts were lost after transplant, so the NegE group consisted of 22 donors. In univariate analysis, the donor risk index >1.7, the presence of hypertension in the medical history, static cold ischemia time, and the moderate or severe macrovesicular steatosis were the significant factors for NegE. Multivariate analysis confirmed that macrosteatosis >30% was an independent risk factor for NegE (odd ratio 5.643, p = 0.023, 95% confidence interval, 1.27-24.98). Of 151 transplanted patients, 34% experienced EAD and had worse 1- and 3-year-survival, compared with those who did not face EAD (NoEAD), 96% and 96% for EAD vs. 89% and 71% for NoEAD, respectively (p = 0.03). None of the donor/graft characteristics was associated with EAD even if the graft was moderately steatotic or fibrotic or from an aged donor. For the first time, this study shows that macrovesicular steatosis >30% might be a warning factor involved in the risk of graft loss or a cause of graft discard after the MP treatment. On the other hand, the MP seems to be useful in reducing the donor and graft weight in the development of EAD.

Graft factors as determinants of postoperative delirium after liver transplantation.

Post-operative delirium (POD) is a frequent complication after surgery, occurring in 15-20% of patients. POD is associated with a higher complications rate and mortality. Literature on POD after liver transplantation (LT) is limited, with the few available studies reporting an incidence of 10-47%. The aim of this study was analyzing pattern, risk factors and clinical impact of POD after LT. Data on donor and recipient characteristics, postoperative course and POD of consecutive adult LT recipients from March 2016 to May 2018 were prospectively collected and retrospectively analyzed. Risk factors for POD were analyzed using univariable logistic regression and Lasso regression. Kaplan-Meier method was used for survival analysis. 309 patients underwent LT during study period; 3 were excluded due to perioperative death. Incidence of POD was 13.4% (n = 41). The median day of onset was 5th (IQR [4-7]) with a median duration of 4 days (IQR [3-7]). Several risk factors, related to the severity of liver disease and graft characteristics, were identified. Graft macrovesicular steatosis was the only factor independently associated with POD at multivariable analysis (OR 1.27, CI 1.09-1.51, p = 0.003). POD was associated with a higher rate of severe postoperative complications and longer intensive care unit and hospital stay, but did not significantly impact on patient and graft survival. Incidence of POD after LT is comparable to that observed after general surgery and graft factors are strongly associated with its onset. These results help identifying a subset of patients to be considered for preventive interventions.

A simplified regimen of targeted antifungal prophylaxis in liver transplant recipients: A single-center experience.

BACKGROUND: Invasive fungal infection (IFI) is a severe complication of liver transplantation burdened by high mortality. Guidelines recommend targeted rather than universal antifungal prophylaxis based on tiers of risk. METHODS: We aimed to evaluate IFI incidence, risk factors, and outcome after implementation of a simplified two-tiered targeted prophylaxis regimen based on a single broad-spectrum antifungal drug (amphotericin B). Patients presenting 1 or more risk factors according to literature were administered prophylaxis. Prospectively collected data on all adult patients transplanted in Turin from January 2011 to December 2015 were reviewed. RESULTS: Patients re-transplanted before postoperative day 7 were considered once, yielding a study cohort of 581 cases. Prophylaxis was administered to 299 (51.4%) patients; adherence to protocol was 94.1%. Sixteen patients developed 18 IFIs for an overall rate of 2.8%. All IFI cases were in targeted prophylaxis group; none of the non-prophylaxis group developed IFI. Most cases (81.3%) presented within 30 days after transplantation during prophylaxis; predominant pathogens were molds (94.4%). Only 1 case of candidemia was observed. One-year mortality in IFI patients was 33.3% vs 6.4% in patients without IFI (P = .001); IFI attributable mortality was 6.3%. At multivariate analysis, significant risk factors for IFI were renal replacement therapy (OR = 8.1) and re-operation (OR = 5.2). CONCLUSIONS: The implementation of a simplified targeted prophylaxis regimen appeared to be safe and applicable and was associated with low IFI incidence and mortality. Association of IFI with re-operation and renal replacement therapy calls for further studies to identify optimal prophylaxis in this subset of patients.

Cierre de bolsillo subpectoral para la reconstrucción mamaria: descripción de una nueva técnica quirúrgica mediante el uso de celulosa oxidada regenerada NU-KNIT® / Closure of the sub pectoral pocket for breast reconstruction: description of a new surgical technique using oxidized regenerated cellulose NU-KNIT TM

Introducción: El uso de expansor mamario, previo a la reconstrucción definitiva con prótesis, no está exento de complicaciones. Las mismas no solo tienen relación con la presencia de radioterapia perioperatoria, o factores propios de las pacientes, sino que también guardan relación con la cobertura muscular íntegra del expansor mamario. Material y métodos: Revisión retrospectiva de pacientes sometidas a reconstrucción mamaria diferida utilizando una modificación de la técnica del cierre de bolsillo submuscular con celulosa oxidada regenerada NU-KNIT® de expansor mamario. Entre el 1 de enero de 2014 y el 31 de diciembre de 2015 un solo cirujano plástico (J.V.) de la Unidad de Patología Mamaria de la Clínica Alemana de Santiago realizó reconstrucción con dicha técnica en 31 pacientes. Se describe la modificación de la técnica, así como los datos demográficos, histológicos y complicaciones de la fase de expansión de las mismas. Resultados: Se realizaron 40 reconstrucciones mamarias en 31 pacientes. Se presentaron 11 seromas (27,5% del total de los expansores), 2 sufrimientos de colgajo cutáneo con dehiscencia de la herida (5% de los expansores) y una infección de la herida operatoria (2,5% de los expansores). Dos pacientes requirieron aseo quirúrgico por dehiscencia e infección. Una paciente requirió explantación del expansor (2,5% del total de los expansores). Discusión: La modificación de la técnica quirúrgica representa una alternativa segura y reproducible para lograr un cierre total del bolsillo muscular y con ello la cobertura completa del expansor, evitando así algunas de las complicaciones descritas secundarias a una cobertura insuficiente del mismo.

Introduction: The use of breast expander, prior to the final prosthetic reconstruction, is not exempt from complications. They not only relate to the presence of peri-operative radiation therapy, or patient-related issues; but also related to the muscle integrate coverage of the breast expander. Material and methods: Retrospective review of patients undergoing deferred breast reconstruction using a modification of the technique of sub muscular pocket closing with oxidized regenerated cellulose NU-KNIT TM for the breast expander. Between January 1, 2014 and December 31, 2015 one plastic surgeon (J.V.), from the Breast Pathology Unit at Clínica Alemana de Santiago, performed reconstruction surgeries with this technique in 31 patients. In the present article, the technique modification, demographic data, histological data and the complications which arose during the expansion phase of the same, will be described. Results: 40 breast reconstructions were performed in 31 patients. 11 seromas (27.5% of total expanders), 2 sufferings of skin flap wound dehiscence (5% expanders) and 1 wound infection (2.5% of expanders) were presented. Two patients required surgical debridement due to surgical dehiscence and infection. One patient required explantation of the expander (2.5% of total expanders). Discussion: The modification of the surgical technique represents a safe and reproducible alternative to achieve a complete closure of the muscular pocket and thus a complete coverage of the expander, consequently; avoiding some of the secondary complications drawn from an insufficient coverage of the expander.

First Evidence of Cardiac Stem Cells From the Left Ventricular Apical Tip in Patients With Left Ventricular Assist Device Implantation.

BACKGROUND: Recent studies have challenged the dogma that the adult heart is a postmitotic organ and raise the possibility of the existence of resident cardiac stem cells (CSCs). Our study aimed to explore if these CSCs are present in the "ventricular tip" obtained during left ventricular assist device (LVAD) implantation from patients with end-stage heart failure (HF) and the relationship with LV dysfunctional area extent. METHODS: Four consecutive patients with ischemic cardiomyopathy and end-stage HF submitted to LVAD implantation were studied. The explanted "ventricular tip" was used as a sample of apical myocardial tissue for the pathological examination. Patients underwent clinical and echocardiographic examination, both standard transthoracic echocardiography (TTE) and speckle tracking echocardiography (STE), before LVAD implantation. RESULTS: All patients presented severe apical dysfunction, with apical akinesis/diskinesis and very low levels of apical longitudinal strain (-3.5 ± 2.9%). Despite this, the presence of CSCs was demonstrated in pathological myocardial samples of "ventricular tip" in all 4 of the patients. It was found to be a mean of 6 c-kit cells in 10 fields magnification 40×. CONCLUSIONS: Cardiac stem cells can be identified in the LV apical segment of patients who have undergone LVAD implantation despite LV apical fibrosis.

Simultaneous Liver-Kidney Transplantation in Adults: A Single-center Experience Comparing Results With Isolated Liver Transplantation.

BACKGROUND: After introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, a worldwide increasing number of simultaneous liver-kidney transplantations (SLKTx) has been observed. However, organ shortage puts into question the allocation of 2 grafts to 1 recipient. This retrospective, single-center study compared SLKTx results with isolated liver transplantation (LTx). METHODS: Between 1995 and 2013, 37 SLKTx were performed in adult recipients. Every SLKTx was matched by donor age (±5 years) and transplantation date with 2 LTx (n = 74). Pretransplant, intraoperative, and post-transplant variables were collected; liver graft and patient survivals were calculated. RESULTS: As expected, donor age was similar in the 2 groups (median, 39.7 years), whereas serum creatinine level, glomerular filtration rate, and MELD and D-MELD (donor age*MELD) scores were significantly higher in the SLKTx group. SLKTx had longer waiting list time (P = .0034) as well as higher surgical difficulty, testified by more blood transfusions (P = .0083), increased use of classic caval reconstruction (P = .0024), and more frequent need of abdominal packing for bleeding control (P = .0003). In addition, duration of hospital stay (P < .0001), second-look surgery (P = .0082), post-transplant dialysis (P < .0001), and post-transplant infections (P = .04) were significantly greater in SLKTx group. Acute rejection episodes involving the liver were significantly less in SLKTx than in LTx (14% vs 41%; P = .0045). Liver graft and patient survival at 10 years after transplantation was similar in the 2 groups (liver graft: SLKTx, 80% vs LTx, 77% [P = .85]; patient: SLKTx, 86% vs LTx, 79% [P = .56]). CONCLUSIONS: Despite being technically challenging, SLKTx provided excellent long-term results and was shown to be an effective use of liver grafts.

Minimization of anti-hepatitis B surface antigen immunoglobulins for prophylaxis of hepatitis B viral recurrence in the first month after liver transplantation: the meaning of HBsAg quantitative level at the time of transplant.

BACKGROUND: Hepatitis B virus recurrence after liver transplantation (LT) has practically disappeared with a prophylaxis combining anti-hepatitis B surface antigen Immunoglobulins (HBIg) and antiviral drugs. Recently, cost-saving requirements pushed us to move from a fixed schedule of 50,000 IU intravenous HBIg in the first month after LT to an "on demand" administration guided by close monitoring of HBV surface antigen (HBsAg) and anti-HBV surface Antigen antibody (HBsAb) with a serological target of HBsAg negative and HBsAb>300 mIU/mL. In this context, we investigated the meaning of HBsAg quantitative determination at LT in predicting the need of HBIg in the first month after LT. METHODS: From February 2012 to July 2013, we performed 35 LTs in HBsAg-positive patients, 18 of whom had hepatitis Delta virus coinfection (Delta-positive). Anti-HBV prophylaxis was based on nucleos(t)ide analogues from day 1 post-LT and intravenous HBIg (10,000 IU intraoperatively and, in the following days, 5,000 IU and 2,500 IU pulses to reach and maintain the serological target). RESULTS: The HBsAg quantitative level at LT was significantly higher in Delta-positive recipients. Complete negativization of HBsAg and HBsAb serum level>300 mIU/mL was achieved on day 3 in Delta-positive and on day 2 in Delta-negative. A positive linear correlation between HBsAg quantitative level at LT and HBIg administered in the first month after LT was observed (RHO=.788), with a total of 32,500 IU HBIg used in HDV-positive and 22,000 IU in HDV-negative recipients (P=.0016). Compared to the old schedule, we saved a median of 14,750 IU in HDV-positive and 28,000 IU in Delta-negative. No HBV recurrence was observed in a median follow-up of 10.5 months. CONCLUSIONS: Delta-positive patients need higher doses of HBIg to reach the serological target after LT because they have greater HBsAg quantitative levels at LT. In future studies, pre-LT HBsAg quantitative determination will be helpful to predict the actual need of HBIg early after LT.

Posthepatectomy liver failure after simultaneous versus staged resection of colorectal cancer and synchronous hepatic metastases.

BACKGROUND: Posthepatectomy liver failure (PHLF) is the third most frequent complication and the major cause of postoperative mortality after resection of colorectal cancer liver metastases (CRLM). In case of synchronous resectable CRLM, it is still unclear if surgical strategy (simultaneous versus staged resection of colorectal cancer and hepatic metastases) influences the incidence and severity of PHLF. The aim of this study was to evaluate the impact of surgical strategy on PHLF and on the early and long-term outcome. PATIENTS AND METHODS: Retrospective study on 106 consecutive patients undergoing hepatectomy for synchronous CRLM between 1997 and 2012. RESULTS: Of 106 patients, 46 underwent simultaneous resection and 60 had staged hepatectomy. The rate of PHLF was similar between groups (16.7% vs 15.2%; p=1) and subgroup analysis restricted to patients undergoing major hepatectomy confirmed this observation (31.8% vs 23.8%; p=0.56). Propensity-score analysis showed that preoperative total bilirubin level and the amount of intra-operative blood transfusion were independently associated with an increased risk of PHLF. Nevertheless, the risk of severe PHLF (grade B - C) was increased in patients who underwent simultaneous resection and major hepatectomy (OR: 4.82; p=0.035). No significant differences were observed in severe (Dindo - Clavien 3 - 4) postoperative morbidity (23.9% vs 20.0%; p=0.64) and survival (3 and 5-year survival: 55% and 34% vs 56% and 33%; p=0.83). CONCLUSIONS: The risk of PHLF is not associated with surgical strategy in the treatment of synchronous CRLM. Nevertheless, the risk of severe PHLF is increased in patients undergoing simultaneous resection and major hepatectomy.

Bisphenol A alters ß-hCG and MIF release by human placenta: an in vitro study to understand the role of endometrial cells.

A proper fetomaternal immune-endocrine cross-talk in pregnancy is fundamental for reproductive success. This might be unbalanced by exposure to environmental chemicals, such as bisphenol A (BPA). As fetoplacental contamination with BPA originates from the maternal compartment, this study investigated the role of the endometrium in BPA effects on the placenta. To this end, in vitro decidualized stromal cells were exposed to BPA 1 nM, and their conditioned medium (diluted 1 : 2) was used on chorionic villous explants from human placenta. Parallel cultures of placental explants were directly exposed to 0.5 nM BPA while, control cultures were exposed to the vehicle (EtOH 0.1%). After 24-48 h, culture medium from BPA-treated and control cultures was assayed for concentration of hormone human Chorionic Gonadotropin ( ß -hCG) and cytokine Macrophage Migration Inhibitory Factor (MIF). The results showed that direct exposure to BPA stimulated the release of both MIF and ß -hCG. These effects were abolished/diminished in placental cultures exposed to endometrial cell-conditioned medium. GM-MS analysis revealed that endometrial cells retain BPA, thus reducing the availability of this chemical for the placenta. The data obtained highlight the importance of in vitro models including the maternal component in reproducing the effects of environmental chemicals on human fetus/placenta.

Liver transplantation in defects of cholesterol biosynthesis: the case of lathosterolosis.

We report the outcome of liver transplantation (LT) in the only surviving patient with lathosterolosis, a defect of cholesterol biosynthesis characterized by high lathosterol levels associated with progressive cholestasis, multiple congenital anomalies and mental retardation. From her diagnosis at age 2 she had shown autistic behavior, was unable to walk unaided and her sight was impaired by cataracts. By age 7 she developed end-stage liver disease. After a soul-searching discussion within the transplantation team, she was treated with LT as this represented her only lifesaving option. At 1-year follow-up, her lathosterol levels had returned to normal (0.61 mg/dL from 13.04 ± 2.65) and her nutrition improved. She began exploring her environment and walking by holding onto an adult's hand and then independently. Her brain magnetic resonance imaging (MRI) had shown a normal picture at age 1, whereas a volume reduction of white matter with ex vacuo ventricular dilatation and defective myelinization were observed before transplant. At 5-year follow-up, a complete biochemical recovery, an arrest of mental deterioration and a stable MRI picture were achieved, with a return to her every day life albeit with limitations. Timely liver transplant in defects of cholesterol biosynthesis might arrest the progression of neurological damage.

Susceptibility to Toxoplasma gondii proliferation in BeWo human trophoblast cells is dose-dependent of macrophage migration inhibitory factor (MIF), via ERK1/2 phosphorylation and prostaglandin E2 production.

INTRODUCTION: Macrophage migration inhibitory factor (MIF) participates in the immune response to Toxoplasma gondii, triggers ERK1/2 and prostaglandin E2 (PGE2) activation, but there is limited information on these mechanisms in human trophoblast. The present study aimed to verify the role of MIF in the ERK1/2 phosphorylation and PGE2 production, as well as its effect on the susceptibility to T. gondii in BeWo cells. METHODS: BeWo cells were treated with increasing concentrations of recombinant MIF (rMIF) and/or T. gondii-soluble tachyzoite antigen (STAg) and analyzed for ERK1/2 phosphorylation and PGE2 production by Western blotting and ELISA, respectively. Cells were also treated with increasing concentrations of rMIF, rPGE2, or ERK1/2 inhibitor and tested for T. gondii proliferation. The supernatants of cells treated with rPGE2 were assayed for cytokine production by ELISA or CBA. RESULTS: ERK1/2 phosphorylation and PGE2 production increased when the cells were treated with low MIF concentrations while the parasitism control occurred only at high MIF concentrations. STAg was unable to change ERK1/2 phosphorylation or PGE2 release. BeWo cells demonstrated increased T. gondii proliferation and reduced production of pro-inflammatory cytokines when treated with PGE2, while PD98059 diminished the parasite proliferation. DISCUSSION: The intracellular mechanisms triggered by MIF are dose-dependent in BeWo cells, and PGE2 is an important factor for the persistence of T. gondii at the maternal fetal interface. CONCLUSION: MIF was unable to control T. gondii infection in BeWo cells at low concentrations since ERK1/2 and PGE2 expression were activated, demonstrating a critical effect of these mediators favoring parasite proliferation.

2-Aminothiophene-3-carboxylic acid ester derivatives as novel highly selective cytostatic agents.

Cytostatic agents often do not discriminate in their cytostatic potential between different tumor cell types in vitro. In this study, several 2-aminothiophene-3-carboxylic acid ester derivatives were discovered that show an unusual cytostatic selectivity for several T-cell (but not B-cell) lymphoma, prostate cancer, kidney carcinoma and hepatoma cell lines. Their 50 % cytostatic concentrations were generally in the higher nanomolar range and were approximately 20- to 50-fold lower for these tumor cell types than for any other tumor cell line or non-tumorigenic cells. The tumor-selective compounds caused a more preferential suppression of protein synthesis than DNA or RNA synthesis and the prototype compound 3 resulted in an accumulation of prostate cancer cells in the G1 phase of their cell cycle. Compound 3 was also shown to induce apoptosis in prostate cancer cells. The 2-aminothiophene-3-carboxylic acid ester derivatives represent novel candidate cytostatic agents to be further explored for their tumor-selective potential.

Liver transplantation for hepatocellular carcinoma within Milan Criteria in patients with Model for End-Stage Liver Disease score below 15: the impact of the etiology of cirrhosis on long-term survival.

BACKGROUND: Liver transplantation (OLT) is the gold standard therapy for patients with cirrhosis complicated by hepatocellular carcinoma (HCC) within Milan Criteria (MC). We evaluated the impact of the etiology of the underlying liver disease on long-term outcomes of patients undergoing OLT for HCC within MC having a Model for End-stage Liver Disease (MELD) score < 15. METHODS: From November 2002 to December 2009, we performed 203 primary OLTs from brain-dead donors in recipients with HCC and cirrhosis with biochemical MELD scores below 15. We excluded 31 patients outside MC on the explant pathology of the native liver. The remaining 172 were divided into 3 groups according to the etiology of the underlying cirrhosis: hepatitis C virus-positive (HCV+; n = 78; 45%), hepatitis B virus-positive (HBV+; n = 65; 38%) and other indications (n = 29; 17%). The groups were compared for donor and recipient features, donor-recipient match, and transplant variables. The study endpoint was long-term patient survival. RESULTS: The groups were similar, except for a greater prevalence of hepatitis B core antibody-positive grafts in the HBV+ group and less frequent HCC bridging procedures in the other indications group. After a median follow-up of 72 months, HCC recurrence was observed in 8 (4.7%) patients (6 HCV+, 2 other indications), 5 of whom died. Overall 5-year patient survival of 82%, revealed significant differences among groups: 98.3% in HBV+, 67.1% in HCV+, and 85.8% in other indications (HBV+ vs other indications: P = .01; HBV+ vs HCV+: P = .0001; HCV+ vs other indications: P = NS). In the HCV+ group, recurrent HCV hepatitis was the most frequent cause of death. Upon multivariate analysis, HBV positivity in the recipient was an independent predictor of better patient survival (hazard ratio = 0.10, 95% confidence interval 0.02-0.64, P = .013). CONCLUSIONS: Etiology of the underlying cirrhosis significantly influenced the long-term survival after OLT of patients with HCC within MC and MELD < 15. It should be taken into account in estimation of survival benefit.

The application of bioactive compounds from the food industry to control mold growth in indoor waterborne coatings.

Microbial growth in indoor environments creates health problems, especially in people with asthma; approximately 80% of these patients are allergic to mold. Antimicrobial coatings are formulated to generate surfaces that are easy to clean and may also incorporate active agents, commonly called biocides, which inhibit microbial colonization, subsequent growth and bio-deterioration of the substrates. Some research lines seek to replace traditional organometallic and organochlorines biocides with environmentally acceptable ones. The aim of this research was, primarily, to explore the possible application of different compounds used in food industry like preservatives to be used as antimicrobial additives for antimicrobial coatings. Four biocides were tested against two different ambient molds isolated from an interior painted wall (Chaetomium globosum and Alternaria alternate). The selected biocides were zinc salicylate, zinc benzoate, calcium benzoate and potassium sorbate. The resulting paints were subjected to biological and physical tests (viscosity, hiding power, humidity absorption and biocides leaching rate). Bioassays revealed that zinc benzoate and zinc salicylate resulted active against both fungi.

Outcomes of liver transplantation in simultaneously hepatitis B surface antigen and hepatitis C virus RNA positive recipients: the deleterious effect of donor hepatitis B core antibody positivity.

BACKGROUND: Recent data from Italian studies have shown excellent results of liver transplantation (LT) in hepatitis B virus (HBV)-infected patients with grafts from hepatitis B core antibody (HBcAb)-positive donors, whereas such grafts in hepatitis C virus (HCV)-infected recipients have displayed poorer outcomes. We investigated the results of LT with HBcAb-positive grafts in patients with ongoing HBV and HCV coinfections. METHODS: From August 1999 to December 2009, we performed 27 adult primary LTs from deceased heart-beating donors into recipients showing hepatitis B surface antigen (HBsAg)- and HCV-RNA-positivity simultaneously: 12 patients received a graft from an HBsAg-negative HBcAb-positive donor (core+D group) and 15 from an HBcAb-negative donor (core-D group). Immunosuppression included a calcineurin inhibitor, antimetabolite and steroids which were suspended at 6 months. Anti-HBV prophylaxis was always perfomed with anti-HBs immunoglobulins and nucleos(t)idic analogues. RESULTS: The groups were similar regarding variables of donor, recipient, donor-recipient match, LT procedure, and acute rejection treatment. Median follow-up for surviving grafts was 67 months (range, 16-141). Among all patients, HCV-RNA remained positive after LT. The prevalence of histologically proven recurrent HCV hepatitis was similar in the 2 groups: 83% core+D vs 73% core-D. No recurrent HBV hepatitis occurred during the follow-up. Graft survival at 5 years was significantly lower in the core+D group (core+D 48% vs core-D 87%; P = .018), in which a significantly higher prevalence of graft loss was caused by HCV recurrence (core+D 5/12, 42% vs core-D 1/15, 7%; P = .03). All of the 5 core+D patients who lost their grafts due to HCV recurrence did not receive anti-HCV therapy (4 owing to an aggressive disease and 1 because of patient refusal). CONCLUSIONS: Outcomes of LT in patients with ongoing HBV and HCV coinfection are adversely affected by donor HBcAb positivity, an effect that is mainly mediated by the dismal course of HCV recurrence after LT.

Outcomes of liver transplantation from hepatitis B core antibody-positive donors in viral cirrhosis patients: the prevailing negative effect of recipient hepatitis C virus infection.

BACKGROUND: Liver transplantation (LT) with grafts from hepatitis B core antibody (HBcAb)-positive donors has been the object of recent studies, suggesting different outcomes depending on the etiology of viral cirrhosis in the recipient. METHODS: From November 2002 to December 2009, we transplanted 124 livers from hepatitis B surface antigen (HBsAg)-negative HBcAb-positive deceased heart-beating donors to adult recipients with viral cirrhosis, classified as: HBsAg positive (group 1; n = 63); hepatitis C virus (HCV) RNA positive (group 2; n = 52); and simultaneously HBsAg and HCV-RNA positive (group 3; n = 9). Immunosuppression included a calcineurin inhibitor, mycophenolate, and steroids (tapered to suspension in 6 months). In all groups, anti-HBV prophylaxis was performed with anti-HBs immunoglobulins and nucleos(t)idic analogues. RESULTS: The groups were similar regarding donor, recipient, donor-recipient match, transplant procedure, variables, and treatment of acute rejection, except for younger recipient age in group 1 (P = .009), lower recipient body mass index in group 3 (P = .03), and longer cold ischemia time in group 2 (P = .003). Median follow-up for surviving grafts was 63 (range, 16-102) months. No case of recurrent or de novo hepatitis B occurred. The prevalence of histologically proven recurrent HCV hepatitis was similar in groups 2 and 3 (65% vs 78%). Graft survival at 5 years was 86% in group 1, 35% in group 2, and 31% in group 3 (P < .0001 for group 1 vs 2; P < .01 for group 1 vs 3). On multivariate analysis, independent predictors of worse graft survival were HCV infection in the recipient (HR 8.08, 95% CI 3.36-17.97; P < .0001) and MELD at LT ≥25 (HR 3.72, 95% CI 1.12-12.37; P = .032). CONCLUSIONS: The presence of HCV infection in the recipient is the factor which most negatively influenced the outcome of LT using grafts from HBcAb-positive donors. Allocation of such grafts should consider the type of viral cirrhosis among LT candidates.

Variation in macrophage migration inhibitory factor [MIF] immunoreactivity during bovine gestation.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in several aspects of the immune response. MIF appears to play important roles in materno-fetal immuno-tolerance during placental establishment, modulation and growth as studied in epitheliochorial porcine and hemochorial human and mouse placentae. Here we studied the bovine placenta being multiplex, villous and synepitheliochorial with a low degree of invasion, to see if MIF could be involved. Placental tissues sampled from 12 cows at 9 stages of gestation (days 18-250), and endometrial tissues from two non-pregnant animals were processed for immunohistochemistry. Bovine MIF was detected by Western blot using anti-human MIF monoclonal antibodies. An immunoreactive band of approximately 12kDa confirmed similarities between bovine and human MIFs. Compared to the non-pregnant stage with very faint staining, the caruncular epithelium during pregnancy showed stronger staining for MIF. The intercaruncular epithelium in non-pregnant endometrium showed some reaction apically with increasing intensity at uterine gland openings; in contrast, at day 18 of gestation this staining was markedly increased. During gestation both caruncular and trophoblast epithelium of the placentomes were positive with different intensity in relation to the gestational stage. In the uterine glands, some strongly stained cells were present. The mature binucleated trophoblast giant cells were negative throughout pregnancy. During reestablishment of vascularisation, the vasculature in the caruncular area showed MIF reactivity. While supporting involvement of MIF in different placental types, the spatio-temporal variation in the bovine placenta suggests a regulatory role for MIF mainly in the interhemal barrier and during vascular development.