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1.
Rev Gastroenterol Mex (Engl Ed) ; 87(3): 362-379, 2022.
Article in English | MEDLINE | ID: mdl-35778341

ABSTRACT

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this second part of the document, the topics related to the treatment of HCC are presented.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Consensus , Humans , Liver Cirrhosis/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Non-alcoholic Fatty Liver Disease/epidemiology
2.
Rev Gastroenterol Mex (Engl Ed) ; 87(2): 216-234, 2022.
Article in English | MEDLINE | ID: mdl-35431142

ABSTRACT

Hepatocellular carcinoma (HCC) is more frequently manifesting as one of the main complications of cirrhosis of the liver, its principal risk factor. There have been modifications in its incidence over the past decade, related to an epidemiologic transition in the etiology of cirrhosis, with a decrease in the prevalence of hepatitis C and an increase in nonalcoholic fatty liver disease (NAFLD) as a cause, as well as the development of HCC in the non-cirrhotic liver due to NAFLD. Genetic markers associated with the disease have been identified, and surveillance and diagnosis have improved. Regarding treatment, surgical techniques, in both resection and transplantation, have advanced and radiologic techniques, at the curative stage of the disease, have enhanced survival in those patients. And finally, there have been radical changes in the systemic approach, with much more optimistic expectations, when compared with the options available a decade ago. Therefore, the Asociación Mexicana de Hepatología decided to carry out the Second Mexican Consensus on Hepatocellular Carcinoma, which is an updated review of the available national and international evidence on the epidemiology, risk factors, surveillance, diagnosis, and treatment of the disease, to offer the Mexican physician current information on the different topics regarding hepatocellular carcinoma. In this first part of the document, the topics related to epidemiology and diagnosis are presented.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Non-alcoholic Fatty Liver Disease , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/epidemiology , Carcinoma, Hepatocellular/etiology , Consensus , Humans , Liver Cirrhosis/complications , Liver Neoplasms/diagnosis , Liver Neoplasms/epidemiology , Liver Neoplasms/etiology , Non-alcoholic Fatty Liver Disease/epidemiology
3.
Rev Gastroenterol Mex (Engl Ed) ; 85(1): 56-68, 2020.
Article in English, Spanish | MEDLINE | ID: mdl-31836274

ABSTRACT

Hepatic encephalopathy is a frequent complication in patients with cirrhosis of the liver and is associated with a high mortality rate. Costs attributed to the management of patients with cirrhosis are especially high due to complications, such as hepatic encephalopathy, given that they increase the number of days of hospital stay. Different drugs are currently used to treat hepatic encephalopathy, and the main ones are lactulose, L-ornithine L-aspartate (LOLA), and certain antibiotics, especially rifaximin-α (RFX). Even though many of them have been shown to be effective to greater or lesser degrees, it is important to understand the differences between them, so that every patient receives individualized treatment and the best option is chosen, in accordance with the different clinical scenarios. Thus, the aim of the present study was to analyze the evidence on the advantages and disadvantages of the individual or combined use of the 3 main treatments for hepatic encephalopathy, specifically taking into consideration their different degrees of efficacy, their impact on quality of life, prophylaxis, and cost reduction.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Hepatic Encephalopathy/drug therapy , Rifaximin/therapeutic use , Aspartic Acid/therapeutic use , Drug Therapy, Combination , Gastrointestinal Agents/therapeutic use , Hepatic Encephalopathy/diagnosis , Humans , Lactulose/therapeutic use , Quality of Life , Severity of Illness Index , Treatment Outcome
4.
Rev Gastroenterol Mex (Engl Ed) ; 84(1): 69-99, 2019.
Article in English, Spanish | MEDLINE | ID: mdl-30711302

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.


Subject(s)
Non-alcoholic Fatty Liver Disease/therapy , Consensus , Disease Progression , Humans , Mexico , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/physiopathology , Prevalence , Risk Factors
5.
Rev. colomb. gastroenterol ; 81(3): 149-167, July­Sept. 2018.
Article in Spanish | BIGG - GRADE guidelines, LILACS | ID: biblio-987533

ABSTRACT

El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario.


The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.


Subject(s)
Humans , Hepatitis C , Hepatitis C/therapy , Ribavirin/therapeutic use , Hepatitis C/drug therapy , Antimetabolites/therapeutic use
6.
Rev Gastroenterol Mex (Engl Ed) ; 83(3): 275-324, 2018.
Article in English, Spanish | MEDLINE | ID: mdl-29803325

ABSTRACT

The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.


Subject(s)
Hepatitis C/therapy , Antiviral Agents/therapeutic use , Consensus , Evidence-Based Medicine , Hepatitis C/drug therapy , Humans , Mexico
7.
J Viral Hepat ; 22 Suppl 1: 46-73, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25560841

ABSTRACT

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries, and the relative impact of two scenarios was considered: (i) increased treatment efficacy while holding the treated population constant and (ii) increased treatment efficacy and increased annual treated population. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. In most countries, the annual treated population had to increase several fold to achieve the largest reductions in HCV-related morbidity and mortality. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. In most of the studied countries, the majority of patients were born between 1945 and 1985.


Subject(s)
Antiviral Agents/therapeutic use , Cost of Illness , Hepatitis C, Chronic/drug therapy , Mass Screening , Models, Biological , Disease Progression , Global Health , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/epidemiology , Humans , Prevalence , Treatment Outcome
8.
J Viral Hepat ; 22 Suppl 1: 26-45, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25560840

ABSTRACT

Morbidity and mortality attributable to chronic hepatitis C virus (HCV) infection are increasing in many countries as the infected population ages. Models were developed for 15 countries to quantify and characterize the viremic population, as well as estimate the number of new infections and HCV related deaths from 2013 to 2030. Expert consensus was used to determine current treatment levels and outcomes in each country. In most countries, viremic prevalence has already peaked. In every country studied, prevalence begins to decline before 2030, when current treatment levels were held constant. In contrast, cases of advanced liver disease and liver related deaths will continue to increase through 2030 in most countries. The current treatment paradigm is inadequate if large reductions in HCV related morbidity and mortality are to be achieved.


Subject(s)
Antiviral Agents/therapeutic use , Cost of Illness , Hepatitis C, Chronic/epidemiology , Models, Biological , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Disease Progression , Female , Global Health , Hepatitis C, Chronic/drug therapy , Humans , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Young Adult
9.
J Eur Acad Dermatol Venereol ; 29(4): 656-62, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25418531

ABSTRACT

BACKGROUND: Psoriasis has been linked to an increased risk of metabolic syndrome (MetS). Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of MetS, is now the commonest liver disease worldwide and can evolve into cirrhosis in a subgroup of patients. Psoriasis has been reported to be associated to NAFLD. AIM: The aim of this study was to evaluate the strength of the association between psoriasis and NAFLD. METHODS: A systematic review of the literature was conducted in six databases (Medline, CINAHL, Scopus, LILACS, Cochrane Library and EMBASE). Data from studies assessing frequency of NAFLD in psoriatic and non-psoriatic patients were extracted and meta-analysed using the Mantel-Haenszel method. Subgroups analysis of patients with psoriatic arthritis and moderate to severe psoriasis was also performed. RESULTS: Seven case-control studies were included, all of them of low or moderate quality. Psoriatic patients exhibited an increased risk of NAFLD compared to non-psoriatic controls (six studies; n = 267,761 patients; odds ratio (OR): 2.15, 95% CI: 1.57-2.94). The association remained significant (OR: 2.07, 95% CI: 1.62-2.64) when only high/moderate quality studies were analysed (three studies; n = 3345 patients). The risk of NAFLD was significantly greater in patients with psoriatic arthritis (three studies; n = 505 patients; OR: 2.25, 95% IC: 1.37-3.71) and in patients with moderate to severe psoriasis compared to those with mild psoriasis (two studies; 51,930 patients, OR: 2.07, 95% CI: 1.59-2.71). LIMITATIONS: Data quality and heterogeneity may restrict the interpretation of the pooled risk estimates. CONCLUSION: Case-control studies support an association between psoriasis and NAFLD. Screening of NAFLD in this group of patients may be warranted.


Subject(s)
Non-alcoholic Fatty Liver Disease/epidemiology , Psoriasis/epidemiology , Arthritis, Psoriatic/epidemiology , Humans , Risk Factors , Severity of Illness Index
10.
Curr Med Chem ; 19(28): 4850-60, 2012.
Article in English | MEDLINE | ID: mdl-22709007

ABSTRACT

Liver fibrosis represents a health problem with significant morbidity and mortality that affects 100 million people worldwide. It is a final pathway to several chronic liver diseases and is characterized by excess collagen and accumulation of extracellular matrix in response to chronic hepatocellular damage. Clinical and experimental data suggest that oxidative stress (OS) mediates the progression of fibrosis, and that OS-related molecules may act as mediators of molecular and cellular events implicated in liver fibrosis. The generation of reactive oxygen species (ROS) plays an important role in producing liver damage and initiating hepatic fibrogenesis. OS disrupts lipids, proteins and DNA, induces necrosis and apoptosis of hepatocytes and amplifies the inflammatory response. ROS also stimulate the production of profibrogenic mediators from Kupffer cells and circulating inflammatory cells and directly activate hepatic stellate cells, resulting in the initiation of fibrosis. Advances in understanding the mechanisms involved in fibrosis have identified new molecular targets with therapeutic potential for more targeted and personalized control of this disease. This review will highlight recent concepts in OS, antioxidants and the molecular pathways involved in hepatic fibrosis.


Subject(s)
Liver Cirrhosis/metabolism , Oxidative Stress , Antioxidants/metabolism , Hepatic Stellate Cells/metabolism , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/therapy , Liver Transplantation , RNA, Small Interfering/therapeutic use , Reactive Nitrogen Species/metabolism , Reactive Oxygen Species/metabolism
11.
Curr Med Chem ; 19(18): 2918-23, 2012.
Article in English | MEDLINE | ID: mdl-22519397

ABSTRACT

Metformin is an antidiabetic drug used widely in clinical practice. Its main clinical effect is to reduce blood glucose levels by improving insulin resistance. Nonalcoholic fatty liver disease is characterized by chronic liver damage and can develop into liver cirrhosis. Nonalcoholic fatty liver disease is associated with obesity and contributes to insulin resistance, and metformin is used to treat individuals with these conditions. The mechanisms underlying the clinical effects of metformin in treating nonalcoholic fatty liver disease are unclear. This article summarizes the literature on the mechanisms associated with liver glucose metabolism and the beneficial effects of metformin on this common liver disease.


Subject(s)
Fatty Liver/metabolism , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Animals , Fatty Liver/drug therapy , Humans , Hypoglycemic Agents/therapeutic use , Liver/metabolism , Metformin/therapeutic use , Non-alcoholic Fatty Liver Disease
12.
Nutr. hosp ; 26(4): 677-684, jul.-ago. 2011. ilus, tab
Article in Spanish | IBECS | ID: ibc-111138

ABSTRACT

Introducción: Se estima que dos terceras partes de los pacientes con cáncer sufren de anorexia o pérdida significativa de apetito, lo que conduce a la disminución acentuada de peso y desnutrición, con repercusiones significativas en la calidad de vida y morbimortalidad de los afectados. Aún se desconocen los mecanismos precisos que originan la pérdida de apetito; diversas hipótesis proponen que la patogénesis es multifactorial, destacándose las características biológicas del tumor, del huésped y las relacionadas al tratamiento. Existen nuevas teorías que señalan diversas substancias con efectos antimetabólicos en el sistema nervioso central y que parecen asociarse con resistencia a señales periféricas que informan al hipotálamo sobre el estado de consumo y gasto energético corporal. El objetivo de la revisión es describir conceptos actuales sobre la patogénesis de la anorexia asociada al cáncer, con particular interés en alteraciones del sistema nervioso central. Conclusiones: Es necesario continuar investigando los mecanismos participantes a nivel neural involucrados en la regulación alimentaria, con la finalidad de implementar mejores medidas de alimentación y tratamiento de los pacientes oncológicos con pérdida de apetito, mejorar su estado nutricio, su calidad de vida y sobre todo, reducir la morbimortalidad asociada a desnutrición (AU)


Introduction: Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia. Defined as the loss of the desire to eat, anorexia lower the energy intake which further exacerbates a progressive deterioration of the patient nutritional status. Malnutrition has a large impact on morbidity and mortality affecting the quality of life. Cancer anorexia etiologyis multifactorial including complex interactions among the tumor, host metabolism and antineoplastic treatment. New related theories include peripheral and brain mechanisms affecting hypothalamic pathways; inducing behavioral and metabolic failure of responses to energy balance. The aim of this review is to describe actual concepts involved in the pathogenesis of cancer anorexia with special interest in brain mechanisms. Conclusions: Anorexia and reduced food in take are important issues in the management of cancer patients, more knowledge about pathogenic mechanism is needed to improve therapeutic options, prognosis and quality of life in cancer patients (AU)


Subject(s)
Humans , Anorexia/etiology , Neoplasms/complications , Central Nervous System/physiology , Appetite Regulation/physiology , Malnutrition/prevention & control , Risk Factors
13.
Aliment Pharmacol Ther ; 34(5): 509-18, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21707680

ABSTRACT

BACKGROUND: Antibiotic prophylaxis seems to decrease the incidence of bacterial infections in patients with cirrhosis and upper gastrointestinal bleeding and is considered standard of care. However, there is no updated information regarding the effects of this intervention. AIM: To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding by performing a systematic review of randomised trials. METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index EXPANDED until June 2010. We statistically combined data calculating relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. RESULTS: Twelve trials (1241 patients) evaluating antibiotic prophylaxis against placebo or no antibiotic prophylaxis were included. Antibiotic prophylaxis was associated with reduced mortality (RR 0.79, 95% CI 0.63-0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19-0.97), bacterial infections (RR 0.35, 95% CI 0.26-0.47), rebleeding (RR 0.53, 95% CI 0.38-0.74) and days of hospitalisation (MD -1.91, 95% CI -3.80-0.02). Trials analysing rebleeding rate and hospitalisation length are still scarce, thus, caution should be exerted when interpreting the results. CONCLUSIONS: Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and reduce all-cause mortality, bacterial infection mortality, rebleeding events and hospitalisation length. Novel clinically significant outcomes were included in this meta-analysis. Some benefits are biased and the risks are not yet properly assessed, this encourages future research in this field.


Subject(s)
Antibiotic Prophylaxis , Bacterial Infections/prevention & control , Gastrointestinal Hemorrhage/drug therapy , Liver Cirrhosis/drug therapy , Gastrointestinal Hemorrhage/complications , Gastrointestinal Hemorrhage/mortality , Humans , Liver Cirrhosis/complications , Liver Cirrhosis/mortality , Randomized Controlled Trials as Topic , Treatment Outcome
14.
Nutr Hosp ; 26(4): 677-84, 2011.
Article in Spanish | MEDLINE | ID: mdl-22470010

ABSTRACT

INTRODUCTION: Approximately two thirds of cancer patients at advanced stages of the disease suffer from anorexia. Defined as the loss of the desire to eat, anorexia lower the energy intake which further exacerbates a progressive deterioration of the patient nutritional status. Malnutrition has a large impact on morbidity and mortality affecting the quality of life. Cancer anorexia etiology is multifactorial including complex interactions among the tumor, host metabolism and antineoplastic treatment. New related theories include peripheral and brain mechanisms affecting hypothalamic pathways; inducing behavioral and metabolic failure of responses to energy balance. The aim of this review is to describe actual concepts involved in the pathogenesis of cancer anorexia with special interest in brain mechanisms. CONCLUSIONS: Anorexia and reduced food intake are important issues in the management of cancer patients, more knowledge about pathogenic mechanism is needed to improve therapeutic options, prognosis and quality of life in cancer patients.


Subject(s)
Anorexia/etiology , Anorexia/physiopathology , Neoplasms/complications , Neoplasms/physiopathology , Nervous System/physiopathology , Anorexia/diagnosis , Anorexia/therapy , Brain/physiopathology , Cytokines/blood , Eating/physiology , Hormones/blood , Humans , Malnutrition/etiology , Neoplasms/therapy , Neurotransmitter Agents/blood , Nutritional Status
15.
Rev Gastroenterol Mex ; 75(3): 360-2, 2010.
Article in English | MEDLINE | ID: mdl-20959193

ABSTRACT

Pyloric gland adenoma (PGA), also called adenoma with gastric differentiation, is a rare neoplasm of the gastric mucosa that can appear as gastric heterotopia in several organs. A 49-year-old woman presented with gastric reflux and chronic elevation of liver enzymes. She had a history of type 2 diabetes mellitus, hypothyroidism and an unspecified allergy treated with deflazacor, and a family history of autoimmune diseases. A liver biopsy showed macro- and microvesicular steatohepatitis. Hepatitis B and virus serum tests were negative. Autoimmune hepatitis was suspected and investigated. As an evaluation for dyspeptic symptoms an upper gastrointestinal endoscopy was performed, showing diffuse gastroduodenitis. A few polyps were found and resected from the gastric fundus; histopathology revealed a pyloric gland adenoma. There is very few clinical data on this tumor type because it is frequently underdiagnosed and reported as dysplasia. Further research is needed on the pathophysiology of this disease.


Subject(s)
Adenoma/pathology , Gastric Mucosa/pathology , Stomach Neoplasms/pathology , Female , Gastroesophageal Reflux , Humans , Immunohistochemistry , Middle Aged , Mucin 5AC/metabolism , Mucin-6/metabolism
16.
Rev Gastroenterol Mex ; 74(3): 246-8, 2009.
Article in English | MEDLINE | ID: mdl-19858016

ABSTRACT

The prevalence of inflammatory bowel disease in Mexico is low. The occurrence in familial cases has been attributed to genetic influences. We described the first report of inflammatory bowel diseases in one pairs of husband-wife in Mexico. According with characteristics of this case, we can speculate that the environmental and infectious etiology might play some role in the development of IBD.


Subject(s)
Colitis, Ulcerative/pathology , Adult , Biopsy , Colonoscopy , Crohn Disease/complications , Crohn Disease/therapy , Female , Gastroesophageal Reflux/complications , Gastroesophageal Reflux/therapy , Humans , Male , Marriage , Mexico
17.
Liver Int ; 27(2): 215-9, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17311616

ABSTRACT

BACKGROUND AND AIM: Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes. AIM: To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver. METHODS: We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/beta-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann-Whitney U-test. We considered as significant differences those with a P-value <0.05. RESULTS: Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/beta-actin ratio of 0.001+/-0.01, steatosis 6.52+/-17.3 (P=0.05 vs normal) and NASH 6.49+/-12.2 (P=0.06 vs normal and P=0.6 vs steatosis). CONCLUSION: CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver.


Subject(s)
Fatty Liver/metabolism , Receptor, Cannabinoid, CB2/metabolism , Fatty Liver/pathology , Hepatitis/metabolism , Hepatitis/pathology , Humans , Immunohistochemistry , Liver/metabolism , Liver/pathology , Prospective Studies , RNA, Messenger/metabolism , Receptor, Cannabinoid, CB2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Tissue Distribution
18.
Mini Rev Med Chem ; 6(6): 651-6, 2006 Jun.
Article in English | MEDLINE | ID: mdl-16787375

ABSTRACT

Obesity is a major risk factor for the development of the metabolic syndrome, a cluster of diseases including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, microalbuminuria, atherosclerosis, and non-alcoholic steatohepatitis. On the other hand, it is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered hormone produced exclusively by adipocytes. In fact, adiponectin is considered currently as a major factor in obesity-related insulin resistance and atherosclerosis. This new hormone differs from other adipocytokines in that its production and concentrations are actually decreased in insulin resistant subjects. The aim of this review is to summarize the current knowledge about the chemistry and physiology of adiponectin and to discuss its implications in the pathophysiology and potential treatment of insulin resistance and non-alcoholic fatty liver disease.


Subject(s)
Adiponectin/chemistry , Adiponectin/physiology , Drug Design , Fatty Liver/drug therapy , Obesity/drug therapy , Adiponectin/agonists , Fatty Liver/metabolism , Humans , Insulin Resistance , Obesity/metabolism , Receptors, Adiponectin , Receptors, Cell Surface/physiology
19.
Eur J Clin Invest ; 31(9): 773-80, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11589719

ABSTRACT

BACKGROUND: We have evidence for enterohepatic cycling of bilirubin experimentally and in vivo in humans. This study was designed to investigate whether Zn salts might inhibit such cycling of bilirubin. MATERIALS AND METHODS: Micellar bile salt solutions with unconjugated bilirubin were prepared, appropriate concentrations of Zn salts were added, and unconjugated bilirubin precipitation was measured. Hamsters and Wistar rats were fed a chow diet or a chow diet enriched with 1% ZnSO4, and bilirubin secretion rates were monitored. RESULTS: Unconjugated bilirubin was precipitated maximally (90%) after a 10-min incubation with 5 mM Zn salts in the pH range of 6.8-9.0. In control hamsters, total bilirubin secretion rates into bile were 36.0 +/- 2.8 nmol h(-1) 100g(-1) body weight, whereas they were 25.0 +/- 3.3 nmol h-1 100(-1) g in the ZnSO4 group (P < 0.05). CONCLUSIONS: Zn salts that flocculate at physiological pH adsorb unconjugated bilirubin almost completely from unsaturated micellar BS solutions. In addition, Zn salts administered orally suppress biliary bilirubin secretion rates in hamsters. These findings suggest that the administration of Zn salts may inhibit the enterohepatic cycling of unconjugated bilirubin in humans who are predisposed to pigment gallstone formation due to diet, disease or drugs.


Subject(s)
Bilirubin/metabolism , Liver/metabolism , Zinc Sulfate/pharmacokinetics , Animals , Bile Acids and Salts/chemistry , Bile Acids and Salts/pharmacology , Biliary Fistula/metabolism , Bilirubin/chemistry , Carbonates/chemistry , Carbonates/pharmacology , Chemical Precipitation , Cholelithiasis/metabolism , Cricetinae , Hydrogen-Ion Concentration , In Vitro Techniques , Male , Mesocricetus , Rats , Rats, Wistar , Zinc Acetate/chemistry , Zinc Acetate/pharmacology , Zinc Compounds/chemistry , Zinc Compounds/pharmacology , Zinc Sulfate/chemistry
20.
J Nutr ; 131(9): 2300-3, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11533270

ABSTRACT

It has been reported that intake of (n-3) polyunsaturated fatty acids (PUFA) reduces the risk of coronary heart disease and decreases biliary cholesterol saturation in the bile of gallstone patients. We investigated the effect of n-3 PUFA on cholesterol saturation index (CSI) and nucleation time (NT) in obese subjects who were losing weight. This was a double-blind, placebo-controlled clinical trial. Obese women (n = 35) with a body mass index (BMI) > or = 30 kg/m(2), with no prior history of gallstones or cholecystectomy by ultrasound were first studied to ensure absence of stones or biliary sludge. The women were then assigned to a hypocaloric regimen [5.02 MJ (1200 kcal)/d] and to receive 1200 mg/d of ursodeoxycholic acid (UDCA), 11.3 g/d of (n-3) PUFA or a placebo for 6 wk. BMI, CSI and NT were recorded at baseline and at the end of the experimental period. BMI decreased 5.75 +/- 2.7%/mo (range, 1.5-12.42%/mo) during the experiment. The CSI did not change in any of the groups. Cholesterol NT decreased significantly in the UDCA and placebo groups, but not in the (n-3) PUFA group. None of the women had developed gallstones at 6 wk. These results suggest that (n-3) PUFA maintain the CSI and NT in obese women during rapid weight loss, which probably results in the prevention of cholesterol gallstone formation.


Subject(s)
Bile/metabolism , Cholelithiasis/prevention & control , Cholesterol/physiology , Fatty Acids, Omega-3/pharmacology , Fish Oils/pharmacology , Obesity/metabolism , Weight Loss , Adult , Diet, Reducing , Double-Blind Method , Female , Humans , Middle Aged , Obesity/diet therapy , Obesity/pathology , Time Factors
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