The 14bp-deletion allele in the HLA-G gene confers susceptibility to the development of hepatocellular carcinoma in the Brazilian population.

Human leukocyte antigen-G (HLA-G) is a nonclassical HLA class I molecule involved in tumor escape mechanisms. Considering that the HLA-G 14bp insertion/deletion polymorphism is located at the 3' untranslated region (3'UTR) in exon 8, and since it has been associated with the magnitude of HLA-G production, we studied the association of 14bp insertion/deletion polymorphism with the risk of developing hepatocellular carcinoma (HCC). A total of 109 HCC patients followed at the University Hospital, Faculty of Medicine of Ribeirão Preto, São Paulo, Brazil, and 202 healthy controls from the same geographic area were genotyped for the 14bp insertion/deletion polymorphism using polymerase chain reaction (PCR) and polyacrylamide gel electrophoresis. Compared to controls, the frequency of the 14bp deletion allele was overrepresented in HCC patients (65% versus 56%, respectively, P = 0.0326). The 14bp deletion conferred an odds ratio (OR) of 1.46 [95% confidence interval (CI): 1.04-2.05]. Similarly, the deletion/deletion genotype was marginally overrepresented in HCC patients (45% versus 35% in controls, P = 0.0871), conferring an OR of 1.54 (95% CI: 0.96-2.48). The frequencies of the deletion/insertion or insertion/insertion genotypes observed in patients were not statistically different from those observed in controls (P > 0.05). Our results suggest that the 14bp-deletion allele in HLA-G gene is associated with HCC susceptibility in a Brazilian population.

Prophylactic Use of Laser Light and Methylene Blue on Ischemia and Liver Reperfusion Injury.

OBJECTIVE: This study aimed to evaluate the effect of hepatic preconditioning with laser light in the presence of methylene blue (MB) in the liver ischemia-reperfusion injury process. METHOD: Forty male Wistar rats were divided into 8 experimental groups (n = 5). Saline (.5 mL) or MB (15 mg/kg) was injected intravenously (inferior vena cava). After 2 minutes, 660 nm laser light was applied at a dose of 112.5 DE. Fifteen minutes after the application of saline or MB, 1 hour partial ischemia followed by 15 minutes of reperfusion was applied when the rats were sacrificed. The mitochondrial function parameters (O2 consumption rates in states 3 and 4 and the respiratory control ratio), osmotic swelling, and determination of malondialdehyde were evaluated. Hepatic function was studied using the serum determination of the alanine aminotransferase and aspartate aminotransferase enzymes. RESULTS AND CONCLUSIONS: MB therapy alone showed the capacity of preserving the rate of oxygen consumption in the mitochondrial respiratory state of the group submitted to ischemia compared to the sham group. However, when combined with low-intensity laser therapy, it failed to replicate the relevant protective effects in relation to oxidative phosphorylation or the mitochondrial membrane ischemia/reperfusion injury. Whether or not MB was combined with laser treatment, it was shown to be efficient in reducing oxidative stress. In relation to alanine aminotransferase enzymes, whether or not laser treatment was combined with MB had a protective effect on the hepatic lesion, whereas in relation to aspartate aminotransferase enzymes only laser treatment was able to provide this protection.

Liver mitochondrial function in familial amyloidotic polyneuropathy.

The objective of the present study was to analyze hepatic mitochondrial function in patients with familial amyloidotic polyneuropathy (FAP) undergoing cadaveric donor orthotopic liver transplantation. From February 2005 to May 2007, eight patients with FAP, ranging in age from 34 to 41 years and with Model for End-Stage Liver Disease scores ranging from 24 to 29. Underwent orthotopic transplantation using a liver from a deceased donor by the piggyback method. Immediately before beginning the recipient hepatectomy in a patient with FAP, a biopsy was obtained for analysis of mitochondrial function (FAP group). The control group consisted of 15 patients undergoing hepatic surgery to treat small tumors of the liver. Mitochondrial respiration was determined on the basis of oxygen consumption by energized mitochondria using a polarographic method. The membrane potential of the mitochondria was determined spectrofluorometrically. Data were analyzed statistically by the Mann-Whitney test, with the level of significance set at 5%. State 3 and 4 values, respiratory control ratio, and membrane potential were 47 +/- 8 versus 28 +/- 10 natoms O/min/mg protein (P < .05); 14 +/- 3 vs 17 +/- 7 nat.O/min/mg.prot.mit. (P > .05); 3.6 +/- .5 vs 1.7 +/- 0.7 (P < .05); and 135 +/- 5.2 vs 135 +/- 6 mV (P > .05) for control versus FAP patients, respectively, demonstrating a decreased energy status of the liver in FAP.

Liver transplantation at a university hospital, faculty of the medicine of Ribeirão Preto, University of São Paulo: results for the first 60 recipients.

The purpose of the present article was to present the series operated by a Liver Transplant Group of the interior of the State of Sao Paulo, Brazil. Sixty patients were transplanted from May 2001 to May 2007. Thirty percent of the patients had alcoholic cirrhosis. 18.3% had C virus-induced cirrhosis, 10% had C virus- and alcohol-induced cirrhosis, 6% had B virus-induced cirrhosis, 13.3% had cryptogenic cirrhosis, 8.3% autoimmune cirrhosis, 13.3% had familial amyloidotic polyneuropathy (FAP), and 13.3% had hepatocellular carcinomas. The series was divided by a chronological criterion into two periods: A (n = 42) and B (n = 18) with the latter group operated based upon the Model for End-stage Liver Disease (MELD) criterion. Sixty-nine percent were men. Age ranged from 14 to 66 years. Period A included 12% Child A: 59.2%, Child B; 24%, Child C; and 4.8%, FAP. Period B comprises 22.2% Child A: 11.1%, Child B: 33.3%, Child C: and 33.3%, FAP. MELD scores ranged from 8 to 35 for period A and from 14 to 31 for period B. Intraoperative mortality was 2/42 patients for period A and 0/18 for period B, overall postoperative mortality was 40% including for period A, 35% among Child B and C patients, and 5% among FAP and Child A patients (P < .05) and 16.6% for period B among 11.1% Child B patients and 5.5% FAP patients; 3.3% of patients required retransplantation due to hepatic artery thrombosis. Real postoperative survival was 60% during period A and 83.3% during period B, with an overall survival rate of 67% for the two periods. The present results show levels of postoperative mortality, (especially during period B), and survival rates similar to those reported by several other centers in Brazil.

Evaluation of Lung Function in Liver Transplant Candidates.

INTRODUCTION: A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. OBJECTIVE: To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. PATIENTS AND METHODS: Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. RESULTS: Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. CONCLUSION: In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted.

Effects of ischemic liver preconditioning on hepatic ischemia/reperfusion injury in the rat.

To minimize bleeding during major liver resections or liver transplantation, surgical measures have been adopted that induce ischemia-reperfusion injury (I/R) which may significantly contribute to morbidity and mortality of partial liver resections. Several methods have sought to minimize I/R hepatic lesions. The present project assessed the protective role of ischemic preconditioning (IPC) in rat livers. The IPC was accomplished by clamping the hepatic pedicle for 5 minutes, followed by a 5-minute reperfusion (R) period before a 2-hour ischemia. Thereafter, reperfusions of 1, 3, and 24 hours were compared among IPC and control groups without IPC. Liver biopsy and blood samples were measured for mitochondrial respiratory control ratio (RCR), serum aspartate aminotransferase (AST), and alanine aminotransferase (ALT). IPC protected liver mitochondrial function. Serum aminotransferase levels were significantly lower among animals undergoing IPC compared with groups without IPC. Thus, we verified the effects of IPC for hepatocellular protection against I/R lesions.

Therapeutic effect of hyperbaric oxygen in hepatic artery thrombosis and functional cholestasis after orthotopic liver transplantation.

Among the postoperative complications, hepatic artery thrombosis can occur in up to 10% of adult orthotopic liver transplants and intervention is indicated when this occurs within 30 days by retransplantation. Primary graft dysfunction, which can occur in up to 30% of the cases and is another potential complication, although reversible, has a relatively high mortality rate. Hyperbaric therapy, an efficient mode of tissue oxygenation, is being used in an increasing number of clinical situations. We report here two cases where hyperbaric oxygen therapy greatly benefited patients with complications after orthotopic liver transplantation: one with hepatic artery thrombosis and the other with primary graft dysfunction. Both patients showed rapid clinical recovery with gradual reduction of liver and canalicular enzymes soon after commencing hyperbaric oxygen therapy.

Sleep Quality Assessment and Daytime Sleepiness of Liver Transplantation Candidates.

OBJECTIVE: The goal of this study was to evaluate the sleep quality and daytime sleepiness of patients eligible for liver transplants. METHODS: A cross-sectional prospective study was conducted on liver transplant candidates from a transplant center in the interior of São Paulo State. The Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale questionnaires were applied to obtain demographic and clinical characteristics and to assess sleep quality and daytime sleepiness. RESULTS: The mean (±SD) score on the Epworth Sleepiness Scale of the 45 liver transplantation candidates was 7.00 ± 2.83 points, with 28.89% having scores >10 points, indicating excessive daytime sleepiness. The mean score on the Pittsburgh Sleep Quality Index was 6.64 ± 4.95 points, with 60% of the subjects showing impaired sleep quality, with scores >5 points. The average sleep duration was 07:16 h. Regarding sleep quality self-classification, 31.11% reported poor or very poor quality. It is noteworthy that 73.33% of patients had to go to the bathroom, 53.33% woke up in the middle of the night, and 40.00% reported pain related to sleeping difficulties. Comparison of subjects with good and poor sleep quality revealed a significant difference in time to sleep (P = .0002), sleep hours (P = .0003), and sleep quality self-classification (P = .000072). CONCLUSION: Liver transplant candidates have a compromised quality of sleep and excessive daytime sleepiness. In clinical practice, we recommend the evaluation and implementation of interventions aimed at improving the sleep and wakefulness cycle, contributing to a better quality of life.

A new formula as a predictive score of post-liver transplantation outcome: postoperative MELD-lactate.

INTRODUCTION: Liver transplantation (OLT) involves a 5% to 10% 30-day mortality rate. Multiple scores have been used as predictors of early postoperative mortality, such as the original Model for End-stage Liver Disease (MELD) and MELD sodium. Investigations have been conducted over the last 5 years to find new predictors of early post-OLT mortality. OBJECTIVE: The aim of this study was to develop a new mathematical model to predict the individual chance of 30-day mortality after OLT. METHODS: The study was conducted on 58 patients submitted to OLT at the University Hospital, between October 2008 and March 2012. The 29 latest survivor and 29 latest nonsurvivor cases were selected. Arterial blood sodium, lactate, international normalized ratio, total bilirubin, and creatinine values were determined 1 hour after the end of surgery. The MELD original equation, MELD sodium, and new MELD lactate were also elaborated. The results were analyzed by the Mann-Whitney and Wilcoxon tests. The level of significance was set at .05. RESULTS: The new formula elaborated was as follows: MELD lactate = 5.68 × loge (lactate) + 0.64 × (Original MELD) + 2.68. The MELD lactate values were significantly higher than the MELD sodium and original MELD values (P < .05). The area under the receiver operating characteristic curve of MELD lactate in predicting the outcome of patients submitted to OLT was 0.80, as opposed to 0.71 for the original MELD and 0.72 for MELD sodium (P < .05). CONCLUSION: The postoperative MELD lactate score proved to be more specific and sensitive than the original MELD and MELD sodium as a predictive model of the outcome of patients submitted to OLT.

Evaluation of oxidative stress in the late postoperative stage of liver transplantation.

INTRODUCTION: Liver transplant recipients are at an increased oxidative stress risk due to pre-existing hepatic impairment, ischemia-reperfusion injury, immunosuppression, and functional graft rejection. This study compared the oxidative status of healthy control subjects, patients with liver cirrhosis on the list for transplantation, and subjects already transplanted for at least 12 months. PATIENTS AND METHODS: Sixty adult male patients, aged between 27 and 67 years, were subdivided into 3 groups: a control group (15 healthy volunteers), a cirrhosis group (15 volunteers), and a transplant group (30 volunteers). Oxidative stress was evaluated by activity of reduced glutathione, malondialdehyde, and vitamin E. RESULTS: There was a significant difference (P < .01) in the plasma concentration of reduced glutathione in the 3 groups, with the lowest values observed in the transplanted group. The malondialdehyde values differed significantly (P < .01) among the 3 groups, with the transplanted group again having the lowest concentrations. The lowest concentrations of vitamin E were observed in patients with cirrhosis compared with control subjects, and there was a significant correlation (P < .05) among the 3 groups. No correlations were found between reduced glutathione and vitamin E or between vitamin E and malondialdehyde. However, there were strong correlations between plasma malondialdehyde and reduced glutathione in the 3 groups: control group, r = 0.9972 and P < .0001; cirrhotic group, r = 0.9765 and P < .0001; and transplanted group, r = 0.8981 and P < .0001. CONCLUSIONS: In the late postoperative stage of liver transplantation, oxidative stress persists but in attenuated form.

Treatment of hepatocellular carcinoma with liver transplantation: a single-center experience from Brazil.

INTRODUCTION: Orthotopic liver transplantation (OLT) is the treatment of choice of hepatocellular carcinoma (HCC) for patients with cirrhosis, mainly those with early HCC. Herein we have present the clinical characteristics and outcomes of cirrhotic patients with HCC who underwent OLT from cadaveric donors in our institution. METHODS: From May 2001 to May 2009, we performed 121 OLT including 24 patients (19.8%) with cirrhosis and HCC within the Milan criteria. In 4 cases, HCC was an incidental finding in the explants. RESULTS: The patients' average age was 55 +/- 10 years, including 82% men. Fifty percent of patients were Child class B or C. The average Model for End Stage Liver Disease for Child A, B, and C categories were 11, 15, and 18, respectively. The HCC diagnosis was made by 2 dynamic images in 16 cases; 1 dynamic image plus alphafetoprotein >400 ng/mL in 4; and 4 by histologic confirmation. Twenty patients received a locoregional treatment before OLT: 6 percutaneous ethanol injection, 9 transarterial chemoembolization, 1 transarterial embolization, and 4 a combination of these modalities. The median follow-up after OLT was 19.7 months (range, 1-51). A vascular invasion was observed in the explant of 1 patient, who developed an HCC recurrence and succumbed at 8 months after OLT. Two further patients, without vascular invasion or satellite tumor displayed tumor recurrences at 7 and 3 months after OLT, and death at 2 and 1 month after the diagnosis. The remaining 25 patients have not shown a tumor recurrence. CONCLUSION: In the present evaluation, OLT patients with early HCC and no vascular invasion showed satisfactory results and good disease-free survival. Strictly following the Milan criteria for liver transplantation in patients with HCC greatly reduces but does not completely avoid, the chances of tumor recurrence.

Transplante de ilhotas pancreáticas em dispositivos de imunoisolamento celular: resultados iniciais / pancreatic islet transplantation in capsules of cellular immunoisolation: preliminary results

O transplante de pâncreas e de ilhotas pancreáticas vem apresentando grande desenvolvimento nos últimos anos. O isolamento das ilhotas em cápsulas com membrana semi-permeáveis pode ser tratamento de escolha para o diabetes, pois dispensa o uso de imunossupressores. O material ideal para a confecçäo de uma cápsula para o isolamento celular ainda permanece um sonho. Um novo material a base de látex natural foi implantado no subcutâneo de ratos normais e diabéticos para estudar a biocompatibilidade e a neoformaçäo vascular. A análise após 21 dias de implante mostrou intensa formaçäo capilar na interface membrana-tecido e pouco tecido fibrótico. Estes achados iniciais mostram que o material pode ter algum potencial para a confecçäo de dispositivos de isolamento celular.

Duodenoplastia associada à vagotomia gástrica proximal no tratamento das úlceras duodenais estenosantes / Duodenoplasty associated the gastric vagotomy in the treatment of stenosing duodenal ulcers

A vagotomia gástrica proximal firmou-se como o procedimento de escolha no tratamento cirúrgico eletivo das úlceras duodenais crônicas, por ser a operaçäo mais segura quanto à morbidade e mortalidade. Sua aplicaçäo tem sido estendida às complicaçöes da úlcera duodenal, mediante operaçäo complementar que visa solucionar a complicaçäo. Com o objetivo de avaliar a vagotomia gástrica proximal no tratamento das úlceras duodenais estenosantes os resultados clínicos de uma série consecutiva de 80 pacientes submetidos à vagotomia gástrica proximal e duodenoplastia (VGP + Dp) foram comparativos aos de uma série de 106 pacientes submetidos à vagotomia gástrica seletiva e antrectomia (VGS + A); os pacientes foram avaliados 2 a 16 anos após a cirurgia. As séries foram homogêneas quanto ao sexo e à idade. Cinco diferentes tipos de duodenoplastia foram realizados, de acordo com as características anatômicas do duodeno estenosado No grupo da VGS + A a reconstruçäo do trânsito alimentar foi gastroduodenal em 46 pacientes e gastrojejunal nos 60 pacientes restantes. O índice de mortalidade operatória foi de 1,2 por cento com VGP + Dp e de 1,9 por cento com VGS + A. Controle endoscópico pós-operatório demonstrou patência da luz duodenal e piloro conservado nos pacientes submetidos à duodenoplastia. A recorrência ulcerosa ocorreu em 5 por cento após VGP + Dp e em 1,9 por cento após VGS + A. Conclui-se que: 1. a duodenoplastia resolve a estenose duodenal sem dano do esfíncter pilórico, mantendo as vantagens da vagotomia gástrica proximal sem operaçäo complementar de drenagem do estômago. 2 Na avaliaçäo clínica global os melhores resultados foram obtidos com a vagotomia gástrica proximal. 3. A vagotomia gástrica proximal associada à duodenoplastia é uma boa opçäo de tratamento da úlcera duodenal estenosante.

Aspecto funcional do remanescente hepático em condiçöes de isquemia e reperfusäo após hepatectomia parcial / Functional aspects of hepatic remmanescent in ischemia and reperfusion condiction after parcial hepatectomy

O efeito da hipotermia, precondicionamento isquêmico e drogas protetoras das lesöes de isquemia e reperfusäo têm sido amplamente estudado. O objetivo do presente estudo é avaliar os efeitos da deferoxamina na isquemia e reperfusäo sobre o fígado remanescente após ressecçäo hepática parcial a 70 por cento, avaliando-se a funçäo mitocondrial hepática. Estudou-se 34 ratos divididos em grupos: Grupo HP (n = 8) - submetidos a hepatectomia parcial (HP) a 70 por cento; Grupo HPD (n = 4) - submetidos a administraçäo de deferoxamina (40 mg/kg) e HP a 70 por cento; Grupo HPI (n = 7) - hepatectomizados (HP a 70 por cento) e submetidos a isquemia (40 minutos); Grupo HPID (n = 7) - semelhante ao anterior, porém recebendo previamente deferoxamina; Grupo C (n = 8) - controle, submetido a operaçäo simulada para HP a 70 por cento. A análise estatística entre os diversos grupos foi feita pelos testes de Kruskal - Wallis e de Mann - Whitney, com nível de significância de 5 por cento. Dessa maneira, o estado III foi semelhante em todos os procedimentos; o estado IV: C