Nahum Méndez-Sánchez

Role of Oxidative Stress and Molecular Changes in Liver Fibrosis: A Review

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.

Current concepts in the pathogenesis of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause of chronic liver disease, representing the leading cause of hepatology referral in some centres. However, its pathophysiology is not completely understood. Insulin resistance is one of the major mechanisms involved in disease prevalence and progression. Owing to the lack of an effective pharmacological therapy, recommendations on treatment are scarce and are based mainly on lifestyle changes, including diet and exercise. A review of the current literature on pathogenesis of NAFLD is presented in this article.

Effect of Ezetimibe on the Prevention and Dissolution of Cholesterol Gallstones

BACKGROUND & AIMS Cholesterol cholelithiasis is one of the most prevalent and most costly digestive diseases in developed countries and its incidence has increased markedly in Asian countries owing to the adoption of Western-type dietary habits. Because animal experiments showed that high efficiency of intestinal cholesterol absorption contributes to gallstone formation, we explored whether the potent cholesterol absorption inhibitor ezetimibe could prevent gallstones and promote gallstone dissolution in mice and reduce biliary cholesterol content in human beings. METHODS Male gallstone-susceptible C57L mice were fed a lithogenic diet and concomitantly administered with ezetimibe at 0, 0.8, 4, or 8 mg/kg/day for 8 or 12 weeks. Gallbladder biles and gallstones were examined by microscopy. Gallbladder emptying in response to cholecystokinin octapeptide was measured gravimetrically. Biliary lipid outputs were analyzed by physical-chemical methods. Cholesterol absorption efficiency was determined by fecal dual-isotope ratio and mass balance methods. Lipid changes in gallbladder biles of gallstone patients vs overweight subjects without gallstones were examined before (day 0) and at 30 days after ezetimibe treatment (20 mg/day). RESULTS Ezetimibe prevented gallstones by effectively reducing intestinal cholesterol absorption and biliary cholesterol secretion, and protected gallbladder motility function by desaturating bile in mice. Treatment with ezetimibe promoted the dissolution of gallstones by forming an abundance of unsaturated micelles. Furthermore, ezetimibe significantly reduced biliary cholesterol saturation and retarded cholesterol crystallization in biles of patients with gallstones. CONCLUSIONS Ezetimibe is a novel approach to reduce biliary cholesterol content and a promising strategy for preventing or treating cholesterol gallstones by inhibiting intestinal cholesterol absorption.

Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease

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.

Strong Association between Gallstones and Cardiovascular Disease

BACKGROUND AND AIM:Obesity is closely associated with the increased morbidity and mortality of many common diseases in the Western world, including coronary heart disease (CHD) and gallstone diseases (GD). We have investigated the association between GD and CHD in a cross-sectional study.METHODS AND RESULTS:Subjects who had gallstones visible by ultrasound were considered as cases and subjects negative for gallstones were classified as controls. Positive CHD was defined when the stress test was positive. Body mass index (BMI), waist circumference, blood pressure, serum lipid concentrations, and insulin resistance were measured. The association was estimated by odds ratios using logistic regression models adjusted for confounders. Four hundred and seventy-three subjects (292 males and 181 females) were included, comprising 354 controls and 119 cases. Subjects with GD had higher prevalence of CHD (15.96%) than controls (4.52%) (p < 0.0001). In univariate unconditional logistic regression analysis CHD, BMI ≥ 30 kg/m2, waist circumference, high blood pressure, and HOMA-IR > 2.5 were the most important risk factors for GD. In multivariate analysis (adjusted for age and gender, and BMI) the risk for GD in subjects with CHD was higher (OR 2.84, 95% CI: 1.33–6.07, p < 0.007).CONCLUSIONS:Subjects with CHD have an increased risk to have GD, both diseases are strongly associated and the main characteristics of these subjects are those frequently involved as part of the metabolic syndrome.

In vivo 3T spectroscopic quantification of liver fat content in nonalcoholic fatty liver disease: Correlation with biochemical method and morphometry

BACKGROUND & AIMS The clinical application of liver fat quantification has increased in recent years, paralleling the epidemic increase in nonalcoholic fatty liver disease. The aim of this study was to perform a diagnostic evaluation of spectroscopy by comparing its measurement of total lipid content with that from liver biopsies and morphometry in normal subjects and patients with nonalcoholic fatty liver disease. METHODS Patients with symptomatic cholelithiasis underwent 3T MR cholangiography with spectroscopic quantification of TLC. A laparoscopic cholecystectomy was performed on the day of admission, with liver samples taken during surgery. Microcolorimetric assessment quantified lipid content in liver samples and morphometric evaluation in stained slides. Statistical analysis included bivariate correlation, regression, and ROC analysis. RESULTS The study was conducted in 18 patients, 5 men (mean age, 35.2+/-11.03 years; range, 27-54 years) and 13 women (mean age, 46.77+/-11.77 years; range, 21-61 years). Using a cut-off value >5% for fat content, 8 patients presented with steatosis and 10 patients presented with normal liver fat content. A significant correlation was observed between fat spectroscopy and lipid content (r=0.876, p<0.001). A lower and non-significant correlation was observed between lipid content and morphometry (r=0.190, p>0.05). CONCLUSIONS The accuracy of spectroscopy in assessing fat concentration with a cut-off level of 7.48% was 100%. Spectroscopy showed a strong and significant correlation with lipid content. It may reliably replace liver biopsy for the assessment of liver fat content.

Eosinophilic Gastroenteritis: A Review

Eosinophilic gastroenteritis is a rare benign disease characterized by tissue eosinophilic infiltration that may involve several digestive tract layers. Also known as allergic, or eosinophilic allergic, gastroenteropathy, it usually involves the stomach and small intestine: rarely the colon. It may or may not be accompanied by higher counts of eosinophils in the peripheral blood. The main clinical manifestations depend on the site affected. It has been classified according to clinical and pathological features, and the symptoms depend on the patient’s immunological response to several cytokines released by eosinophils. Because of lack of understanding of the etiology and triggering factors, treatment is based mainly on corticosteroids; although other drugs acting on the immune system have been tested, the results are not always satisfactory. This review focuses on the epidemiology, pathophysiology, clinical features, and treatment of this hitherto under-diagnosed disease.

Prevalence of Hepatitis C Virus Infection among Hemodialysis Patients at a Tertiary-Care Hospital in Mexico City, Mexico

ABSTRACT We determined the prevalence of hepatitis C virus (HCV) in hemodialysis patients by antibody testing and HCV RNA determination by PCR. A total of 149 patients with kidney failure with replacement therapy were tested. The prevalence of anti-HCV was 6.7% (10 of 149 patients), and viremia was detectable in 8 of 149 (5%) patients. Three of 149 patients (2%) were anti-HCV negative with detectable HCV RNA.

Lack of association between Helicobacter sp colonization and gallstone disease.

Recently, Helicobacter sp has been identified in resected gallbladder tissue and in collected bile from Chilean patients with chronic cholecystitis. Therefore, it an association between bile Helicobacter sp and gallbladder cancer has been proposed. Interestingly, both Helicobacter colonization and gallstone disease (GD) happen very frequently in Chile. However, whether there is an association between Helicobacter colonization and GD has not been completely studied. The aim of this study was to determine the incidence of Helicobacter in human gallbladder tissues with GD. The study included 95 Mexican patients undergoing cholecystectomy. Collected gallbladder specimens were assessed to identify Helicobacter sp using histology, immunohistochemistry, and polymerase chain reaction (PCR) analysis using Helicobacter-specific 16-S ribosomal RNA primers. Of the 95 specimens examined in detail, all had stones as follows: 56 (59%) had chronic cholecystitis; 7 (7.4%), acute cholecystitis; 15 (16%), both chronic and acute cholecystitis, 10 (9.5%), cholesterolosis, and 7 (7.4%), lymphoid hyperplasia. Specimens were considered positive for Helicobacter when histology was positive. Only 1 of the 95 specimens was positive for Helicobacter by immunohistochemistry analysis; 1 of 32 cases, by PCR. These results suggest a low incidence of Helicobacter in the gallbladder epithelium of Mexican patients with GD. However, we can not discard the existence of uncommon Helicobacter sp in gallbladder epithelium and its association with gallstone pathogenesis. Additionally, this study suggests no apparent association between GD and Helicobacter colonization in a Mexican population.

Prevalence of gallstone disease in Mexico : a necropsy study

The prevalence of gallstone disease in Mexico was investigated by studying a sample of 21,446 necropsies performed at the Department of Pathology of the General Hospital of Mexico City during a 35-year period (1953–1988). For each decade, 1000 necropsy cases were randomly selected. The crude prevalence of gallstone disease was 14.3%, 8.5% for males and 20.4% for females. The age groups ranged from 20 to more than 80 years old; the age-standardized prevalence for males was 5.6% and for females 16.2%. These rates are intermediate between those found in Chile and some African countries, comparable to some European studies, and less than those found in Mexican-Americans. No significant trend in the prevalence of gallstone disease was found when the different decades were compared.