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Current Issue

July - September, 2008

Vol. 7 Issue 3

On the cover: Official Journal of the Mexican Association of Hepatology and the Latin-American Association for the Study of the Liver

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • PTEN at the crossroad of metabolic diseases and cancer in the liver Manlio Vinciguerra, Michelangelo Foti Page 192-199

    The tumor suppressor PTEN is a phosphoinositide phosphatase regulating the PI3K/Akt signaling pathways and mutated or deleted in a variety of human cancers. Recent evidence indicates that dysregulated PTEN expression and activity in the liver critically affect hepatic insulin sensitivity and trigger the development of non-alcoholic fatty liver diseases. As well, PTEN expression/activity is also affected with HBV and HCV infection, or following alcohol-related injury. Finally, PTEN mutations/deletions or low PTEN expression are associated with diverse liver malignancies thus suggesting a critical role for PTEN in hepatic cancers. This review will focus on our current knowledge of the regulation of PTEN expression/activity and the role of this phosphatase in liver diseases.

  • Cavoportal hemitransposition for the simultaneous thrombosis of the caval and portal systems - A review of the literature Dietmar H. Borchert Page 200-211

    Portal venous thrombosis was originally considered to be a contraindication for liver transplantation. Currently, several methods exist to re-establish blood flow to the hepatic portal system. Cavoportal hemitransposition is a surgical procedure that can be used in liver transplantation when the portal venous system is thrombosed and portal flow cannot be re-established from the mesenteric venous system. In cavoportal hemitransposition the blood flow from the inferior vena cava of the recipient is directed to the portal vein of the donor liver to compensate for the lost portal venous supply. This can either be done by end-to-end or endto- side anastomosis. Seventy-one cases of cavoportal hemitransposition have been reported worldwide. All patients reported had been in a critical and life-threatening condition, presenting with either end–stage–liver disease or acute hepatic failure combined with severe vascular pathology. Of the cases reported, 32 patients died for reasons non-related to the surgical procedure. Seven of the 71 patients had Budd-Chiari syndrome complicated by thrombosis of the portal–venous system. This means thrombosis in two different venous systems at the same time, the mesenteric and main venous system. To date this «two-system» venous thrombosis of both the caval and portal system has only been reviewed together with the possible medical, radiological and non-transplant treatment options. This article evaluates the available literature and reviews the evolution of the surgical procedure of cavoportal hemitransposition emphasising its role in combined thrombosis of the hepatic veins and portal venous systems.

  • Imaging techniques for assessing hepatic fat content in nonalcoholic fatty liver disease Ernesto Roldán Valadez, Rafael Favila, Manuel Martínez-López, Misael Uribe, Nahum Méndez-Sánchez Page 212-220

    Nonalcoholic fatty liver disease (NAFLD), an emerging clinical entity with worldwide recognition, is today the most common cause of abnormal liver function tests among adults in the United States. In Mexico City, its prevalence has been reported by our group to be around 14%, but its incidence is higher in the hispanic population in the United States (hispanic population 45%, white population 33%, black population 24%). The main issues in the diagnosis, follow-up, and management of NAFLD are our limited understanding of its pathophysiology and the difficulties involved in developing a noninvasive diagnostic method. Several imaging techniques can detect fatty infiltration of the liver, each with its own advantages and disadvantages. Ultrasound is still in the first option for diagnosis, but its accuracy depends on the operator and the patient's features. Computed tomography can detect hepatic fat content, but only at a threshold of 30%, and it involves ionizing radiation. Magnetic resonance (MR) spectroscopy is probably the most accurate and fastest method of detecting fat, but it is expensive and the necessary software is still not easily available in most MRI units. MR elastography, a new technique to detect liver stiffness, has not been demonstrated to detect NAFLD, and is still undergoing research in patients with hepatitis and cirrhosis. In conclusion, all these imaging tools are limited in their ability to detect coexisting inflammation and fibrosis. In this review, we discuss the radiological techniques currently used to detect hepatic fat content.

ORIGINAL ARTICLES

  • Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis Vijaya D. Boyella, Anthony D. Nicastri, Nora V. Bergasa Page 221-225

    Endogenous opioids participate in growth regulation. Liver regeneration relates to growth. Thus, we explored the expression of methionine enkephalin and of the delta opioid receptor 1 immunoreactivities with a polyclonal rabbit antibody in deparaffinized liver of patients with chronic liver disease. Fifteen of a total of fifty-eight samples expressed both opioid receptor and methionine enkephalin immunoreactivities, one sample expressed receptor but not methionine enkephalin immunoreactivity, and two samples expressed methionine enkephalin but not receptor immunoreactivity. Ten of the 45 (22%) samples from patients with chronic hepatitis C, four of the eight (50%) samples from patients with chronic hepatitis B, one of the five (20%) samples from patients with autoimmune hepatitis expressed both met-enkephalin and delta opioid receptor 1 immunoreactivities. The expression of methionine enkephalin and delta opioid receptor 1 immunoreactivities suggests that methionine enkephalin exerts an effect in situ, which may include regulation of liver regeneration. However, another possibility that concerns an effect of methionine enkephalin in the liver arises. As morphine, which acts via opioid receptors, has been reported to increase hepatitis C virus replication in vitro and to interfere with the antiviral effect of interferon, methionine enkephalin, analogous to morphine, may enhance the replication of the hepatitis C virus in the liver of patients with this type of viral hepatitis, and interfere with the therapeutic effect of interferon. These results may explain at least in part, why some patients with chronic hepatitis C infection do not respond to interferon therapy.

  • Mortality trends for liver cancer in Mexico from 2000 to 2006 Nahum Méndez-Sánchez, Antonio R. Villa, Genaro Vazquez-Elizondo, Guadalupe Ponciano-Rodríguez, Misael Uribe Page 226-229

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with an estimated incidence of half a million new cases per year around the world. Furthermore, HCC is the third greatest cause of cancer- related death in the world, and most of these deaths are registered in developing countries. Recently it has been suggested that Hispanics in the United States have high rates of HCC, but no information regarding this is available in Mexico. The aim of this study was to investigate recent trends (2000–2006) in HCC mortality rates in Mexico. Methods. Data on national mortality (death certificates) reported for the years 2000–2006 by the Health Ministry of Mexico were analyzed (www.salud.gob.mx). HCC as a cause of death was analyzed. Mortality rates were calculated for all population ages. Causes of death related to HCC were selected in accordance with the International Classification of Diseases, 10th Revision, Liver Cancer (C22.0, C22.7, C22.9). Results. We found that age-adjusted mortality rates were remarkably higher in men than in women in the period 2000–2006. In addition, we found an increase in the general mortality rates of HCC from 4.1 per 100,000 in 2000 to 4.7 per 100,000 in 2006. Conclusions. The results of this study suggest an increase in the mortality rate for HCC in the period 2000–2006. HCC will become a significant cause of morbidity and mortality in the near future.

  • Model for end stage of liver disease (MELD) is better than the Child-Pugh score for predicting in-hospital mortality related to esophageal variceal bleeding Ángel Ricardo Flores-Rendón, José Alberto González-González, Diego García Compean, Héctor Jesús Maldonado-Garza, Aldo Azael Garza-Galindo Page 230-234

    Aim: The Child Pugh and MELD are good methods for predicting mortality in patients with chronic liver disease. We investigated their performance as risk factors for failure to control bleeding, in-hospital overall mortality and death related to esophageal variceal bleeding episodes. Methods: From a previous collected database, 212 cirrhotic patients with variceal bleeding admitted to our hospital were studied. The predictive capability of Child Pugh and MELD scores were compared using c statistics. Results: The Child-Pugh and MELD scores showed marginal capability for predicting failure to control bleeding (the area under receiver operating characteristics curve (AUROC) values were < 0.70 for both). The AUROC values for predicting inhospital overall mortality of Child-Pugh and MELD score were similar: 0.809 (CI 95%, 0.710 - 0.907) and 0.88 (CI 95% 0.77- 0.99,) respectively. There was no significant difference between them (p > 0.05). The AUROC value of MELD for predicting mortality related to variceal bleeding was higher than the Child-Pugh score: 0.905 (CI 95% 0.801-1.00) vs 0.794 (CI 95% 0.676 – 0.913) respectively (p < 0.05). Conclusions: MELD and Child-Pugh were not efficacious scores for predicting failure to control bleeding. The Child-Pugh and MELD scores had similar capability for predicting in-hospital overall mortality. Nevertheless, MELD was significantly better than Child-Pugh score for predicting in-hospital mortality related to variceal bleeding.

  • Thrombopoietin level in patients with chronic liver diseases Laila A Eissa, Lamees S. Gad, Ahmed M Rabie, Amal M. El-Gayar Page 235-244

    Thrombocytopenia and oxidative stress are the most frequent problems in patients with chronic liver diseases as viral cirrhosis and schistosomiasis. So, this study aimed to evaluate the role of thrombopoietin (TPO) on the occurrence of thrombocytopenia and in differentiation between these diseases. It also aimed to investigate the relation between TPO, oxidative stress and antioxidant status in these two types of chronic liver disease. So, We measured serum TPO level, lipid peroxide (MDA) and serum total antioxidant activity (TAO) in 40 patients with cirrhosis caused by hepatitis C virus and 37 patients with schistosomiasis from The Specialized Medical Hospital, Mansoura University. Results: Both serum TPO level and serum TAO activity were significantly lower (p < 0.05) in thrombocytopenic patients with viral cirrhosis when compared to both non thrombocytopenic and control groups. In contrast, TPO level was within the normal range in the patients with scistosomiasis either thrombocytopenic or not. while serum TAO activity was significantly lower (p < 0.05) in both thrombocytopenic and non thrombocytopenic patients with schistosomiasis in comparison to control subjects with no significant difference between these two subgroups. Serum MDA concentration was increased significantly (p < 0.05) in all diseased groups when compared to controls with significant increase in thrombocytopenic patients as compared to non thrombocytopenic. Conclusion: TPO hypoproduction played a role in the pathogenesis and treatment of viral cirrhosis associated with thrombocytopenia. Also, total antioxidant activity and MDA are useful markers for monitoring patients with these chronic liver diseases.

  • Liver overload in Brazilian triathletes after half-ironman competition is related muscle fatigue Marcos Bürger-Mendonça, Monica Bielavsky, Fernanda C.R. Barbosa Page 245-248

    Triathlon competition is dependent on the athletes' ability to perform each discipline at optimal time, without excessive fatigue influencing the next one. Objectives: Determine the effects of a long distance triathlon on biochemistry parameters related to liver function. Design and methods: Blood samples from six athletes were collected before (T = 0) and immediately after the triathlon competition (T = 1). AST, ALT and alkaline phosphatase (ALP) values were assessed. Results: Significant changes after triathlon competition were found for AST and ALP and no significant changes were found for ALT over time. Conclusions: A series of metabolically alterations, mainly related to energy production and also to muscle and skeletal adaptations occurs during and after strenuous exercise. The altered status of those metabolical changes cannot directly reflect the intensity of any possible muscular or hepatic damage or overload and elevated AST/ALT ratio is better associated to skeletal muscle lesion during competition.

  • Leptin in nonalcoholic fatty liver disease Billur Canbakan, Veysel Tahan, Huriye Balci, Ibrahim Hatemi, Burak Erer, Gulsen Ozbay, Necdet Sut, Munire Hacibekiroglu, Nese Imeryuz, Hakan Senturk Page 249-254

    Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. Methods: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. Results: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). Conclusion: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.

EDITORIAL

IMAGES IN HEPATOLOGY

CASE REPORTS

  • Gallstone ileus one quarter of a century post cholecystectomy Mahmud Saedon, Stavros Gourgiotis, Nikolaos S. Salemis, Ali W. Majeed, Apostolos Zavos Page 258-259

    Gallstone ileus is a rare but potentially serious complication of cholelithiasis. It is usually preceded by history of biliary symptoms. It usually occurs as a result of a large gallstone creating and passing through a cholecysto- enteric fistula. Most of the time, the stone will pass the GI tract without any problems, but large enough stones can cause obstruction. The two most common locations of impaction are the terminal ileum and the ileocaecal valve because of the anatomical small diameter and less active peristalsis. We present an unusual case of small bowel obstruction secondary to gallstone ileus 24 years after an open cholecystectomy.

  • Salmonella sp Group A: A rare cause of bacterascites. A case report Gustavo López-Arce, Aldo Torre-Delgadillo, Félix I. Téllez-Ávila Page 260-261

    Bacterascites (BA) is a minimally studied and defined entity. Its prognosis and clinical course are not well defined, and currently there are no management guidelines. We present a rare cause of BA in which Salmonella sp group A was isolated in a 44 year old man with cirrhosis who had diarrhea and fever three days earlier. Treatment with intravenous ceftriaxone was effective.

LIVER NEWS ELSEWHERE

  • Hepatic insulin resistance ties cholesterol gallstone formation and the metabolic syndrome Peter Kovacs, Ulrike Kurtz, Henning Wittenburg Page 262-264

    Biddinger SB, Haas JT, Yu BB, Bezy O, Jing E, Zhang W, Unterman TG, Carey MC, Kahn CR. Hepatic insulin resistance directly promotes formation of cholesterol gallstones. Nature Medicine 2008; 14: 778–782. Despite the well-documented association between gallstones and the metabolic syndrome,1,2 the mechanistic links between these two disorders remain unknown. Here we show that mice solely with hepatic insulin resistance, created by liver-specific disruption of the insulin receptor (LIRKO mice)3 are markedly predisposed toward cholesterol gallstone formation due to at least two distinct mechanisms. Disinhibition of the forkhead transcription factor FoxO1, increases expression of the biliary cholesterol transporters Abcg5 and Abcg8, resulting in an increase in biliary cholesterol secretion. Hepatic insulin resistance also decreases expression of the bile acid synthetic enzymes, particularly Cyp7b1, and produces partial resistance to the farnesoid X receptor, leading to a lithogenic bile salt profile. As a result, after twelve weeks on a lithogenic diet, all of the LIRKO mice develop gallstones. Thus, hepatic insulin resistance provides a crucial link between the metabolic syndrome and increased cholesterol gallstone susceptibility. Abstract published under permission of the Nature Publishing Group.

The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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