Psychological distress in patients listed for liver transplantation.

PURPOSE: To assess the level of depression in patients listed for liver transplantation. METHODS: Sixty-four adult patients, listed for liver transplantation, were submitted to psychological evaluation, including assessment of depression by means of the Beck Depression Inventory. RESULTS: Twenty-two percent of the patients had mild/major depression. The group consisted mainly of male patients aged 47 on average, with a history of alcohol abuse and a Meld (Model for End-Liver Disease) value of 14.5. Patients that had been awaiting liver transplant longer presented less severe liver disease according to the Child-Pugh criteria. CONCLUSION: It is extremely important to assess psychological distress in patients listed for liver transplantation. An interdisciplinary approach is essential to improve the patients' quality of life both in the pre- and post-transplant periods.

Nonalcoholic fatty liver disease and obesity.

PURPOSE: The aim of this review is to update concepts of the nonalcoholic fatty liver disease (NAFLD) and to establish a relationship between this condition and obesity. METHODS: By means of a comprehensive literature review where special attention was devoted to articles published in the last 5 years, NAFLD is discussed in view of new concepts, diagnosis, staging, and treatment. RESULTS: NAFLD is emerging as one of the main causes of chronic liver disease and it is believed to be the hepatic component of the metabolic syndrome, whose central features include obesity, hyperinsulinemia, peripheral insulin resistance, diabetes, dyslipidemia, and hypertension. The surgical treatment of morbid obesity is one of the options available for the treatment of NAFLD. CONCLUSION: Nonalcoholic fatty liver disease is strongly related with obesity.

Liver transplantation: expectation with MELD score for liver allocation in Brazil.

Liver transplantation represents the most effective therapy for patients suffering from chronic end-stage liver disease. Until very recently, in Brazil, liver allocation was based on the Child-Turcotte-Pugh score and the waiting list followed a chronological criterion. In February 2002 the Model for End-stage Liver Disease (MELD) score was adopted for the allocation of donor livers in the US. After that change, an increased number of patients with more severe liver disease was observed, although there was no difference in 1-year patient and graft survival. A reduction in waiting-list mortality was also observed. In Brazil, the MELD score was adopted on May 31st, 2006. Good results are expected regarding the new criterion for allocation.

Hepatitis C: a challenge to hepatologists and to the liver transplantation team.

Hepatitis C is the main cause of cirrhosis and hepatocellular carcinoma and the leading indication of liver transplantation. The aim of this article was to review specific epidemiological, clinical and therapeutic aspects of hepatitis C and their implication for the hepatologists belonging to liver transplantation services. These specific aspects were reviewed in the literature mainly using Medline. Data regarding the epidemiological, clinical and therapeutic aspects of hepatitis C are discussed, with emphasis on their consequences for the liver transplantation team. Hepatitis C is a challenge for hepatologists and for the liver transplantation team. The burden we observe today is the late consequence of infection that occurred in the past. Measures for early recognition of complications of liver disease are recommended. HCV treatment should always be performed before liver transplantation if possible, but if not, HCV recurrence should be recognized and treated early after transplantation.

Pyruvate kinase activation and lipoperoxidation after selective hepatic ischemia in Wistar rats.

PURPOSE: Hepatic ischemia and reperfusion can cause several problems in hepatic surgery. The aim of this study was to determine pyruvate kinase activation and lipid peroxidation after hepatic ischemia. METHODS: Twenty-four Wistar rats were submitted to 90 minutes of selective liver ischemia and 15 minutes of reperfusion. Twelve animals were submitted to selective liver ischemia and reperfusion (Group A) and the other 12 were submitted to sham operation (Group B). After 15 minutes of reperfusion, the following parameters were measured: mean arterial pressure (MAP), alanine aminotransferase (ALT), glycemia (GLY), hepatic glycogen (GH), pyruvate kinase (PK) activation, hepatic glutathione (GSH) and malondialdehyde (MDA). Analysis of the results were made by the Student t-test and has been considered significant difference for p<0.05. RESULTS: A and B were differents for all parameters analized. CONCLUSION: The animals of group A showed reperfusion syndrome with a fall in MAP, activation of glycid metabolism through the glycolitic pathway and presence of lipid peroxidation compared to group B.

Effect of liver ischemic preconditioning in cirrhotic rats submitted to hepatic ischemia/reperfusion injury.

PURPOSE: The main aim of this study was to determine the influence of ischemic preconditioning (IPC) on rat liver cirrhosis. METHODS: Cirrhosis was induced in Wistar rats by occlusion of the hepatic duct. The animals were divided into four groups of six animals each: non-cirrhotic group (simulated operation only), cirrhotic control group (simulated operation in cirrhotic rats), I/R group (40-minute ischemia without IPC), and IPC group (cirrhotic rats with ischemia, previously submitted to IPC). The IPC procedure consisted of partial hepatic ischemia for five minutes, followed by 10 minutes of reperfusion. In the case of the IPC group, the animals were submitted to liver ischemia for 40 minutes after the preconditioning procedure, followed by 2 hours of reperfusion. Blood samples were collected for measurement of serum aminotransferases (ALT and AST). The respiratory control ratio (RCR), the mitochondrial membrane potential (MMP), and malondialdehyde (MDA) values in the hepatic tissue were analyzed. Nonparametric statistical analysis was used and a value of p<0.05 was considered statistically significant. RESULTS: Ischemia did not induce significant increase in ALT and AST levels. MDA values were significantly higher in cirrhotic animals. MMP did not significantly change in cirrhosis and liver ischemia. Mitochondrial RCR decreased in liver cirrhosis, accentuated upon liver ischemia, and did not significantly change with IPC. CONCLUSION: Ischemic preconditioning does not protect the liver from hepatic injury induced by the ischemia/reperfusion process.

The effect of laser on remanescent liver tissue after 90% hepatectomy in rats.

PURPOSE: To evaluate the effect of laser beam on reminiscent liver after partial hepatectomy 90%. METHODS: Wistar rats, (N=42), were divided into six groups with seven specimens each. The partial hepatectomy (HP) was performed in all animals through exeresis of approximately 90% of the liver parenchyma. The animals from groups HP and Laser application, HPL24, HPL48 and HPL72 undertook laser irradiation carried out through application (dose of 22.5 J/cm2) in five different sites in the reminiscent liver. The rats were then sacrificed 24, 48 and 72 hours after HP procedure, for the liver regeneration analysis,using the Proliferating Cell Nuclear Antigen (PCNA),and for dosage of serum aminotransferases. RESULTS: Were demonstrated an increase of the serum levels of alanine aminotransferase for the group of 24 hours and a decrease for the group of 72 hours exposed to laser. The index of marked cells had a considerable more improvement for the group of 72 hours exposed in laser compared to other groups. CONCLUSION: Laser did not cause hepatic injuries additional to the partial hepatectomy and perhaps led to a benefit by stimulating the proliferative activity.

Liver cirrhosis and hepatic stellate cells.

The cirrhosis represents the final stage of several chronic hepatic diseases and it is characterized by the presence of fibrosis and morphologic conversion from the normal hepatic architecture into structurally abnormal nodules. In the evolution of the disease there is loss of the normal vascular relationship and portal hypertension. There are also regenerative hepatocellular alterations that become more prominent with the progression of the disease. The liver transplantation continues to be the only therapeutic option in cases of disease in terminal phase. The hepatic stellate cells (HSC) are perisinusoidal cells that store vitamin A and produce growth factors, citocins, prostaglandins and other bioactive substances. They can suffer an activation process that convert them to cells with a phenotype similar to myofibroblasts. When activated, they present increased capacity of proliferation, mobility, contractility and synthesis of collagen and other components of extracellular matrix. They possess cytoplasmic processes adhered to sinusoids and can affect the sinusoidal blood flow. HSC are important in pathogenesis of fibrosis and portal hypertension.

A molecular view of liver regeneration.

The purpose of this review was to carry out an analysis of the liver regenerative process focusing on the molecular interactions involved in this process. The authors undertook a review of scientific publications with a focus on the liver regeneration. The cellular processes involved in liver regeneration require multiple systematic actions related to cytokines and growth factors. These interactions result in the initiation of mitogenic potential of the hepatocytes. The action of these modulators in the regenerative process require a processing in the extra-cellular matrix. Serines and metal proteins are responsible for the bio availability of cytokines and growth factors so that they can interact as receptors in the cellular membrane generating signaling events for the beginning and end of the liver regenerative process. The exact mechanism of interaction between cells, cytokines and growth factors is not well established yet. A series of ordered events that result in the hepatic tissue regeneration has been described. The better understanding of these interactions should provide a new approach of the treatment for liver diseases, aiming at inducing the regenerative process.

Cellular aspects of liver regeneration.

This paper has the objective to analyze the cellular aspects of liver regeneration (LR). Upon damage in this organ, the regenerative capacity of hepatocyte is sufficiently able to reestablish the parenchyma as a whole. Taking into account the regenerative capacity of hepatocyte, the need of a progenitor or a liver trunk cell was not obvious. Nowadays it is well-established that precursor cells take part in the liver regenerative process. The liver trunk cell, oval cell, acts as a by-potential precursor, contributing for the liver restoration, mainly when the hepatocytes are unable to proliferate. Another precursor, trunk cell of hematopoetic origin (HSC), takes part in the regenerative process, originating cells of the hepatocytic lineage and colangiocytes, as well as the oval cell. The way the trans-differentiation takes place is not established yet. A number of studies must be undertaken in order to clarify questions, such as the possible occurrence of cellular fusion process between the HSC and the hepatic cells and the possibility of application as a new therapeutic procedure in the treatment of diseases associated with insufficiency of this noble organ.

Liver disease associated with intestinal failure in the small bowel syndrome.

The introduction of the Total Parenteral Nutrition (TPN) has given rise to a new hope in the treatment of intestinal failure (LF) associated with the Short Bowel Syndrome (SBS). However, together with the TPN and the increase of survival of these patients, new problems and questions have emerged, as well as new therapeutical procedures. Taking into consideration this emerging reality, this paper has the purpose to undertake a review of current concepts and available treatments for patients with IF associated-liver disease. Although TPN provides an increase of survival of patients with intestinal failure, it is a potential source of complication such as: septicemia, hyperglycemia, venous thrombosis and liver disease. There are several hypothesis conceived to explain the liver disease associated to intestinal failure, however the only definite treatment as a potential to reverse the non-cirrhotic liver disease is the small intestine transplantation. Despite indications for intestine transplantation are not entirely defined in literature, the trend is its early indication in high-risk patients, preserving the liver integrity and preventing the eventual need of both liver and intestine transplantations altogether.

Chronic liver disease prevention strategies and liver transplantation.

Chronic liver disease is a considerable burden on society, being one of the three main causes of death in certain regions of Africa and Asia. Liver transplant is the only treatment option for cirrhosis, which is the end stage of many chronic liver diseases. This article reviews the preventable causes of cirrhosis and the preventive strategies which could be implemented in order to avoid the catastrophic consequences of cirrhosis. With small variations around the world, 70 to 80% of the end stage liver diseases are caused by excessive alcohol consumption and by viral hepatitis, both of which are potentially preventable. Excessive alcohol consumption has important public health consequences because of its involvement not only with cirrhosis, but also with motor vehicle accidents, unemployment, domestic violence etc. Among the viral causes, Hepatitis Virus B and C have the greatest impact on public health. Effective vaccine is available for Hepatitis Virus B and must be put in use. While a vaccine for Hepatitis Virus C is awaited, effective preventive strategies should be undertaken to avoid the preventable cases of end stage liver disease.

Proliferative effect of the aqueous extract of Hyptis pectinata on liver regeneration after partial hepatectomy in rats.

PURPOSE: This study was carried out to assess the effects of the aqueous extract of Hyptis pectinata leaves on liver regeneration and on serum enzymes (AST, ALT and gamma-GT) after 67% partial hepatectomy in rats. METHODS: AST, ALT and gamma-GT, were determined by conventional procedures using a spectrophotometer (Model E2250-CELM). Liver regeneration was evaluated by immunohistochemical staining for proliferating cell nuclear antigen (PCNA). RESULTS: Oral pretreatment during 4 days at 100 mg/kg increased liver regeneration index. At 200 mg/kg, AST level was statistically decreased in comparison to the group submitted to distilled water administration. The other enzymes assessed disclosed no difference when all groups were compared. CONCLUSION: The present study shows that the aqueous extract of Hyptis pectinata leaves contains some biological active principles that stimulate liver regeneration at 100 mg/kg and cause slight hepatic protection at 200 mg/kg.

Impact of blood salvage during liver transplantation on reduction in transfusion requirements.

PURPOSE: The aim of this study was to analyse the changes in transfusion requirements, in patients submitted to orthotopic liver transplantation from cadaveric donors, with the use of intraoperative red blood cell salvage (Cell Saver). METHODS: Data from 41 transplants were analysed. Intraoperative blood loss was calculated from the cell salvage, suction and the swabs. The autologous and heterologous transfusions were recorded The red blood salvage was performed using the Cell Saver 5 System (Haemonetics). For analysis the patients were divided in two groups: one that used the Cell Saver and another that didn't. RESULTS: The median age of the patients was 50 years and the main indication for liver transplantation was cirrhosis (35 cases-85.3%). The median blood loss was 8362+3994 ml (with the Cell Saver) and 10824+7002 ml (without the Cell Saver) and the median transfusion of heterologous packed red blood cells was 9.6+8 units (with the Cell Saver) compared to 22.3+21 units (without the Cell Saver). CONCLUSIONS: The Cells Saver has the potential to reduce the need for heterologous blood transfusion reducing the risks of transmissible diseases.

Effect of the aqueous extract of Sida cordifolia on liver regeneration after partial hepatectomy.

PURPOSE: The use of medicinal plants for the treatment of human diseases has increased worldwide. Many of them are used by oral administration and, after absorption, may affect many organs. Therefore, this study aimed at assessing the effects of the aqueous extract of Sida cordifolia leaves, popularly known in Brazil as "malva-branca", on liver regeneration. METHODS: Twenty rats were divided into four groups: control, Sida100, Sida200 and Sida400 groups. All animals were submitted to oral administration of distilled water, 100, 200 and 400 mg/kg of the aqueous extract of Sida cordifolia, respectively. Immediately after this, they underwent 67% partial hepatectomy. Twenty four hours later, their livers were removed. Hepatic regeneration was assessed by immunohistochemical staining for proliferating cell nuclear antigen (PCNA) using the PC-10 monoclonal antibody. RESULTS: Sida100 and Sida200 groups disclosed higher liver regeneration indices than control group (p<0.001 and p<0.05, respectively). CONCLUSION: The aqueous extract of Sida cordifolia stimulates liver regeneration after 67% partial hepatectomy in rats.

Effect of irradiation with different laser wavelengths on oxidative stress of non-hepatectomized rats.

PURPOSE: To assess the effect of two laser wavelengths, either separate or combined, on intact rat livers. METHOD: Nineteen male Wistar rats (200-300 g) were submitted to laser irradiation at 5 different sites on the liver surface.Wavelengths 660 and 780 nm were used, with a dose of irradiation of 60 J/cm2/site.The animals were divided into the groups:control (C) and animals irradiated with 660 nm laser (L1), with 780 nm laser (L2) or withboth wavelengths (L3).Mitochondrial function, mitochondrial swelling, and hepatocellular malondialdehyde (MDA) levels were determined.Data were analyzed by the Mann-Whitney test, with the level of significance set at 5%. RESULTS: There was a reduction of ADP-activated respiration (state 3) in group L1 compared to group C (p=0.0016), whereas the values of group L2 were similar to control.Group L3 also showed a reduction of state 3 (p=0.0159).There was a reduction of RCR in group L1 compared to control (p=0.0001) and to group L2 (p=0.0040).Mitochondrial swelling only differed between group L3 and control (p=0.0286).There was a increase in MDA levels in group L3 compared to control (p=0.0476) and to group L2 (p=0.0286) and in group L1 compared to group L2 (p=0.0132). CONCLUSION: Although laser irradiation reduced mitochondrial function,it did not interfere with the hepatocellular energy status.

Hyperbaric oxygen therapy and ischemia and reperfusion: a valuable association to attenuate ischemic lesion and hepatic reperfusion.

PURPOSE: To investigate the consequences of the association between hyperbaric oxygen therapy and hepatic ischemia / reperfusion. METHODS: Wistar rats were divided into three groups: SHAM, rats submitted to surgical stress and anesthetic but not hepatic ischemia or reperfusion, I / R, rats submitted to total hepatic pedicle ischemia for 30 min, followed by 5 min of reperfusion; HBO120, rats submitted to 120 min of hyperbaric oxygen therapy at two absolute atmospheres and immediately after submitted to the experimental protocol of ischemia and reperfusion. The preservation of the hepatic function was evaluated by determining mitochondrial swelling and malondialdehyde tissue level, as well as alanine aminotransferase and aspartate aminotranferase serum levels. The results were analyzed using the Mann-Whitney test and differences were considered significant for p<0.05. RESULTS: There were significant differences in values: mitochondrial swelling of the I / R group compared to SHAM and HBO120; malondialdehyde between SHAM vs. I / R, SHAM vs HBO120, and I / R vs HBO120, alanine aminotransferase between SHAM vs. I / R . There was no significant difference between groups in aspartate aminotransferase serum levels. CONCLUSION: The association between hyperbaric oxygen therapy and hepatic ischemia and reperfusion process was positive.

The use of perioperative serial blood lactate levels, the APACHE II and the postoperative MELD as predictors of early mortality after liver transplantation.

PURPOSE: To evaluate the accuracy of different parameters in predicting early (one-month) mortality of patients submitted to orthotopic liver transplantation (OLT). METHODS: This is a retrospective study of forty-four patients (38 males and 10 females, mean age of 52.2 ± 8.9 years) admitted to the Intensive Care Unit of a tertiary hospital. Serial lactate blood levels, APACHE II, MELD post-OLT, creatinine, bilirubin and INR parameters were analyzed by receiver-operator characteristic (ROC) curves as evidenced by the area under the curve (AUC). The level of significance was set at 0.05. RESULTS: The mortality of OLT patients within one month was 17.3%. Differences in blood lactate levels became statistically significant between survivors and nonsurvivors at the end of the surgery (p<0.05). The AUC was 0.726 (95%CI = 0.593-0.835) for APACHE II (p = 0.02); 0.770 (95%CI = 0.596-0.849) for blood lactate levels (L7-L8) (p = 0.03); 0.814 (95%CI = 0.690-0.904) for MELD post-OLT (p < 0.01); 0.550 (95%CI = 0.414-0.651) for creatinine (p = 0.64); 0.705 (95%CI = 0.571-0.818) for bilirubin (p = 0.05) and 0.774 (95%CI = 0.654-0.873) for INR (p = 0.02). CONCLUSION: Among the studied parameters, MELD post-OLT was more effective in predicting early mortality after OLT.

Effect of laser on the remnant liver after the first 24 hours following 70% hepatectomy in rats.

PURPOSE: To evaluate the mitochondrial function of the remnant liver (RL) in the early phase of liver regeneration in rats after 70% partial hepatectomy (PH). METHODS: Sixty male Wistar rats (200-250g) submitted to 70% PH were divided into five groups according to the time of euthanasia and application or not of laser light: C = Control, time zero; 2 minutes, 4, 6 and 24 hours after PH. The dose of laser radiation was 22.5 J/cm(2), wavelength of 660 nm (visible/red), in the remnant liver. We studied the respiration activated by ADP (state 3), basal mitochondrial respiration (state 4), respiratory control ratio (RCR) and mitochondrial membrane potential (MMP). RESULTS: The mitochondrial function of RL changed at 4 and 6 hours after PH, with a significant increase in state 3 and a concomitant increase in state 4 and with maintenance of RCR. MMP differed significantly between the groups biostimulated with laser radiation and the control group 4 hours after HP, with a substantial reduction in the non-laser groups. CONCLUSION: The laser light at the dose used in this study did not induce additional damage to the RL and seems to have delayed the hepatocellular metabolic overload of the remnant liver.