Prevalence of non alcoholic fatty liver disease in premenopausal, posmenopausal and polycystic ovary syndrome women. The role of estrogens.

BACKGROUND & AIM: Non alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. Population studies have demonstrated that men and posmenopausal women have higher prevalence of NAFLD. The aim was to investigate the prevalence of NAFLD in premenopausal, posmenopausal and polycystic ovary syndrome (PCOS) women. METHODS: A cross sectional study carried out at University Hospital in Mexico City from January 2009 to November 2009. One hundred ninety seven women who agreed to participate were divided into groups, comprising 93 with NAFLD and without NAFLD. Anthropometric, metabolic and biochemical variables were measured. Serum estradiol and cortisol concentrations were determined and compared between the groups. RESULTS: Of the 197 patients, 93(47.2%) had NAFLD and 104 (52.8%) did not have NAFLD. The prevalence of NAFLD in premenopausal, postmenopausal and PCOS patients was 32.2, 57.9, and 62%, respectively. Age, BMI, hip to waist ratio, fasting glucose, HOMA -IR, and insulin were significantly higher in NAFLD patients. Women without NAFLD had significantly higher levels of serum estradiol (100 ± 95.4) compared with NAFLD patients (55.5 ± 66.6) p = 0.001. By group with and without NAFLD: premenopausal (55.44±93.3 vs. 128.56 ± 109.22), posmenopausal (44.98 ± 51.41 vs. 42.72 ± 51.48) and PCOS women (64.9 ± 53.3 vs. 101.36 ± 80.89) had significantly different hormone profile. CONCLUSION: These results suggest that NAFLD is more prevalent in postmenopausal and women with PCOS than those premenopausal ones. The estrogens may have a protective effect of against NAFLD in women.

High ghrelin and obestatin levels and low risk of developing fatty liver.

AIM: Obesity and insulin resistance are associated with nonalcoholic fatty liver disease (NAFLD). It was recently reported that the ratio between levels of ghrelin and obestatin is also associated with obesity and insulin resistance. We investigated the association between the ghrelin/obestatin ratio and NAFLD. METHODS: This cross-sectional study included 98 subjects (51 NAFLD patients and 47 controls). Anthropometric, metabolic and biochemical variables were measured and serum concentrations of ghrelin and obestatin were determined. Logistic regression analyses (univariate and multivariate) were conducted to determine whether NAFLD was associated with ghrelin and obestatin levels and the ghrelin/obestatin ratio. RESULTS: We studied 51 NAFLD cases and 47 controls. Men comprised 82% of cases and 61% of controls. The mean ages of the groups differed significantly. Body mass index (P < 0.001), waist circumference (P < 0.001) and WHR (P < 0.001) were significantly greater in the NAFLD group than in the control group. The NAFLD group had higher mean fasting glucose level (P = 0.001), HOMA-IR index (P < 0.001) and triglyceride level (P < 0.001) than the controls. Ghrelin and obestatin concentrations were classed according to tertiles. Multivariate analysis revealed a negative correlation between ghrelin and obestatin levels and an overweight status, obesity and metabolic syndrome. Ghrelin and obestatin were evaluated in multivariate logistic regression analysis, they had a protective effect against hepatic steatosis after controlling for potential confounders. CONCLUSION: Serum ghrelin and obestatin concentrations are correlated with a low risk of developing NAFLD. However, ghrelin/obestatin ratio was not correlated with NAFLD.

Metabolic syndrome and estimates of cardiovascular disease in cirrhotic patients.

OBJECTIVE: The expected survival rate in patients with liver cirrhosis has increased in recent years, putting them into a clinical scenario in which cardiovascular disease and metabolic syndrome could be common causes of morbidity and mortality. This study aimed to analyze the prevalence of metabolic syndrome and other risk factors and estimate the risk of cardiovascular disease in patients with liver cirrhosis. METHODS: We conducted a cross-sectional study assessing the patients' lifestyle, and their anthropometric and biochemical data. Their metabolic syndrome and estimates of their risk of cardiovascular disease were calculated, comparing patients with and without liver cirrhosis. RESULTS: The study included 355 patients (99 cirrhotic and 256 non-cirrhotic patients). There were no differences between them in the prevalence of metabolic syndrome (39.4% vs. 45.7%, P = 0.340). In patients with liver cirrhosis, the mean values of criteria for metabolic syndrome increased as the model end-stage liver disease (MELD) score increased (P = 0.01). The mean value of a 10-year risk for cardiovascular disease was lower in the cirrhotic patients (3.4 +/- 3.5% vs. 5.8 +/- 6.8%, P = 0.001). CONCLUSION: Metabolic syndrome is prevalent in patients with liver cirrhosis, but their estimated risk for cardiovascular disease is lower than in non-cirrhotics. The MELD score is a good marker for assessing the severity of the metabolic syndrome in this group.

Gallstones are associated with carotid atherosclerosis.

BACKGROUND/AIMS: Gallstone disease (GD) and cardiovascular disease (CD) are common diseases worldwide with considerable economical impact and they are strongly associated. Carotid atherosclerosis is an excellent marker of risk for CD like stroke and myocardial infarction. The aim of this study was to assess the association between gallstones and carotid atherosclerosis. METHODS: A cross-sectional study was conducted. We evaluated subjects with ultrasonographical evidence of GD and asymptomatic subjects without such evidence. Anthropometric, clinical and biochemical variables were collected. The Metabolic syndrome was evaluated using adult treatment panel III criteria. Carotid artery intima-media thickness (CIMT) was determined by a standard ultrasound protocol. Insulin-like growth factor-1 (IGF-1) serum levels were measured in all subjects. RESULTS: We studied 191 subjects: 62 subjects with GD (53.2% males) and 129 asymptomatic subjects without GD (65.9% males). Subjects with GD exhibited a higher body mass index, body fat percent, insulin serum levels and CIMT (P<0.05 for all). The prevalence of GD was higher in subjects with a CIMT>0.75 independently of other factors [odds ratio (OR) 2.12, 95% confidence interval (CI) 1.04-4.34; P=0.039], and for every 0.1 mm increase in CIMT the independent probability to be a case of GD increased by a factor of 1.25 (95% CI 1.02-1.53; P=0.027). IGF-1 levels did not differ among groups. CONCLUSIONS: Subjects with GD exhibit greater carotid atherosclerosis, and therefore have a higher risk for stroke and myocardial infarction.

Association among C-reactive protein, Fatty liver disease, and cardiovascular risk.

Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a marker of coronary heart disease and other chronic diseases, has not been investigated in NAFLD. We tested the relationship between uCRP and NAFLD in middle-aged asymptomatic subjects, independently of other metabolic disturbances associated with metabolic syndrome and cardiovascular risk. We compared 310 subjects with steatosis visible on ultrasound (cases) with 630 and without (controls). Body mass index (BMI), blood pressure and serum levels of uCRP, glucose, lipids, and lipoproteins were measured in all subjects. Differences between groups and the impact of serum uCRP levels were tested by univariate and multivariate logistic regression analysis. Cases were statistically different from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P < 0.001). Cases were significantly older (P < 0.001), and had significantly higher values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis, variables significantly associated with cases were glucose (OR, 4.09; 95% CI, 2.98-5.61), BMI (OR 5.54; 95% CI, 4.09-7.49), and uCRP (OR 7.06; 95% CI, 4.51-11.02). By multivariate analysis, uCRP levels were associated with hepatic steatosis (OR 5.83; 95% CI, 3.07-11.06). Cardiovascular risk was also higher in subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an increased concentration of uCRP independently of other metabolic disturbances; this suggests an increased risk of cardiovascular diseases and could be used as a marker of chronic inflammation.

Risk factors and prevalence of hepatitis virus B and C serum markers among nurses at a tertiary-care hospital in Mexico City, Mexico: a descriptive study.

BACKGROUND & AIM: Alcohol consumption and viral infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the first causes of chronic hepatopathy in Mexico. Medical personnel are at high risk of developing HBV and HCV infection because both viruses are transmitted parenteraly. The aim of this study was to determine the prevalence of HCV and HBV infection as well as risk factors in nurses working at Medica Sur Clinic and Foundation. METHODS: The complete nurse staff personal from our hospital was included; a questionnaire of risk factors for HCV and HBV infection was assessed. HBV and HCV infection (anti-HCV anti-HBc, and HBsAg) was determined to all of them. In anti-HCV positive persons HCV genotype and viral load was assessed. RESULTS: Three hundred seventy six nurses where studied, Anti-HBc was positive in 1.6% of all participants, none were positive for HBsAg. 0.8% of all studied population was positive for anti- HCV. Major risk factors for HBV infection where tattooing and having more than 4 sexual partners previously, and for HCV infection transfusions before 1992 and age. Only one person was anti-HCV positive with a viral charge of 5 X 106 copies, genotype 2b. CONCLUSIONS: HCV seropositivity in people with high risk was lower than general population. None was positive for HBV infection.

Obesity-related leptin receptor polymorphisms and gallstones disease.

OBJECTIVE: Investigate the association between polymorphisms in the leptin receptor gene associated with obesity and gallstone disease. DESIGN: We conducted a cross-sectional study, carried out at a tertiary setting. SUBJECTS: We enrolled 97 subjects, comprising 54 subjects with gallstones (cases) and 43 controls (without gallstones). MEASUREMENTS: Diet was assessed using a validated questionnaire for the Mexican population. Body mass index, waist circumference, serum glucose,insulin, leptin, lipids and lipoproteins levels were measured. Insulin resistance was calculated by HOMA-IR. Genomic DNA was isolated from lymphoblastoid cells, and Q223R and K656N polymorphisms in the leptin receptor gene were typed using polymerase chain reaction. Unconditional univariate logistic regression analysis was conducted to estimate the probability of gallstone disease associated with the polymorphisms as main effect. RESULTS: Cases were different in gender(40.74% males in cases vs 74.41% in controls; p < 0.001), older (49.74 vs 44.83 years; p < 0.05), and had more body fat (32.34% vs 28.14%; p = 0.01). Individuals carrying the polymorphism Q223R exhibited a higher BMI (28.44 +/- 6.6 kg/m2 vs 25.94 +/- 3.67 kg/m2, p < 0.05) and waist circumference (96.7 +/- 16.39 cm vs 89.2 +/- 11.05 cm, p < 0.05). In univariate analysis, we did not observe a relation between the presence of a R223 or N656 genotype and gallstone disease in our population (OR = 0.78, 95% CI 0.35-1.73). CONCLUSION: Obesity-related leptin receptor polymorphisms are not associated with gallstones disease.

Low serum levels of ghrelin are associated with gallstone disease.

AIM: To explore the role of ghrelin in gallstone disease. METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA. CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.

The efficacy of adipokines and indices of metabolic syndrome as predictors of severe obesity-related hepatic steatosis.

The aim of this study was to investigate adiponectin, leptin, and metabolic syndrome as predictors of the severity of obesity-related steatosis. By ultrasonography steatosis-positive (cases) subjects (n = 141) were compared with controls (n = 111). Demographic and anthropometric data and serum concentrations of adiponectin, leptin, and insulin were measured. The impact of several criteria of metabolic syndrome, serum adiponectin concentrations, and serum leptin concentrations were tested using a multivariate logistic regression analysis. The frequency of metabolic syndrome was higher in cases (44.0% versus 9.2%; P < .0001). Cases were older and had higher insulin resistance, waist circumference, and lower concentrations of adiponectin (all P < .001). The upper adiponectin quartile was associated with a lesser grade of steatosis. Metabolic syndrome and adiponectin concentrations were independently associated with the probability of steatosis. In conclusion, adipokines and metabolic syndrome are useful indices for the prediction of the severity of obesity-related steatosis.

[Therapeuric aspects of NAFLD. A literature review]. / Aspectos terapéuticos en la esteatohepatitis no alcohólica. Revisión de la literatura.

The prevalence of non-alcoholic steatohepatitis has increased in the last years, paralleling the increasing incidence of overweight and obesity in the general population and related comorbidities. It is expected that in near future, non-alcoholic steatohepatitis will be responsible for a large number of subjects with chronic liver disease due to fatty liver Because of this, treatment options for fatty liver are necessary. To date, the cornerstone of treatment is based in weight reduction, with diet and increased physical activity, although reports indicating that insulin sensitizers and medications that reduce oxidative stress may hold promise for the treatment of this condition. This article reviews the most important aspects of treatment of non-alcoholic steatohepatitis.

Serum leptin levels and insulin resistance are associated with gallstone disease in overweight subjects.

AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD). METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate) stratified by BMI was used to calculate the risk of GD. RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI <30. The selected variables in the model were HOMA-IR index with OR = 1.31, P = 0.02 and leptin higher than median with OR = 2.11, P = 0.05. In the stratum of BMI >=30, we did not find a useful model. CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.

Prevalence of hepatitis C infection in a population of asymptomatic people in a checkup unit in Mexico city.

Hepatitis C virus (HCV) infection has an estimated prevalence of 3% around the world. Unfortunately, many persons with HCV infection are asymptomatic. The aim of this study was to determine the prevalence of hepatitis C Virus infection in asymptomatic persons. This study was carried out in a population-based cross-sectional study in the Checkup Unit of University Hospital in Mexico City. Patients with two or more HCV risk factors were studied. Serum specimens from all patients were screened for HCV RNA by qualitative polymerase chain reaction (PCR). HCV RNA-positive serum was also screened by quantitative PCR and for HCV genotype. Three hundred asymptomatic people were included, 194 men and 106 women, with a mean age of 46.8+/-11.9. Six (2%) of the 300 people were positive and viremic. The most common risk factors in positive patients were manicures or pedicures with a nonpersonal instrument and more than three sexual partners. We concluded that hepatitis C is frequent in asymptomatic people, and those people are often viremic. In addition, this study suggests that the spectrum of liver disease in asymptomatic and newly diagnosed HCV-positive persons is broad.

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/m(2), 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.

Adiponectin as a protective factor in hepatic steatosis.

AIM: Obesity and insulin resistance (IR) are closely related to hepatic steatosis (HS), and adiponectin is a hepatic insulin sensitizer that has important effects in liver function. This study aims at investigating the relationship between serum adiponectin concentration and the presence of HS. METHODS: We carried out a cross-sectional study in a check-up unit of a University Hospital in Mexico City. We enrolled 196 subjects, comprising 98 subjects with HS (27 women, 71 men) and 98 controls (37 women and 61 men). Anthropometric, metabolic and biochemical variables were measured in the two groups. Serum adiponectin and leptin concentrations were determined, their association with grade of HS tested, and concentrations, according to quartiles, compared between cases and controls. chi(2) analysis for linear trends was used to test for a dose-response relationship and logistic regression analysis was conducted to test for a protective effect of adiponectin. RESULTS: The HS subjects were older and more obese than controls, with a central obesity pattern. In the fourth quartile of adiponectin concentrations, HS was less common and severe. In a multivariate model of the fourth quartile of the adiponectin concentrations, we observed a protective effect (OR = 0.17, 95%CI: 0.04-0.67, P = 0.01). In subjects with more severe HS, we observed higher leptin concentrations, and caloric intakes, total fat and iron consumption were higher than in controls. CONCLUSION: The results of the present study suggest that a high serum concentration of adiponectin is associated with a protective effect against HS.

Metabolic syndrome as a risk factor for gallstone disease.

AIM: To establish an association between the presence of metabolic syndrome and the development of gallstone disease. METHODS: We carried out a cross-sectional study in a check-up unit in a university hospital in Mexico City. We enrolled 245 subjects, comprising 65 subjects with gallstones (36 women, 29 men) and 180 controls (79 women and 101 men without gallstones). Body mass index, waist circumference, blood pressure, plasma insulin, and serum lipids and lipoproteins levels were measured. Insulin resistance was calculated by homeostasis model assessment. Unconditional logistic regression analysis (univariate and multivariate) was used to calculate the risk of gallstone disease associated with the presence of at least three of the criteria (Adult Treatment Panel III). Analyses were adjusted for age and sex. RESULTS: Among 245 subjects, metabolic syndrome was present in 40% of gallstone disease subjects, compared with 17.2% of the controls, adjusted by age and gender (odds ratio (OR) = 2.79; 95%CI, 1.46-5.33; P = 0.002), a dose-dependent effect was observed with each component of metabolic syndrome (OR = 2.36, 95%CI, 0.72-7.71; P = 0.16 with one component and OR = 5.54, 95%CI, 1.35-22.74; P = 0.02 with four components of metabolic syndrome). Homeostasis model assessment was significantly associated with gallstone disease (adjusted OR = 2.25; 95%CI, 1.08-4.69; P = 0.03). CONCLUSION: We conclude that as for cardiovascular disease and diabetes mellitus, gallstone disease appears to be strongly associated with metabolic syndrome.

The Amerindian's genes in the Mexican population are associated with development of gallstone disease.

BACKGROUND: It has been suggested that genes related to Amerindian ancestry account for the high prevalence of gallstone disease (GD) observed in Mexican-Americans. The HLA-B39 is an allele found in higher frequency in Amerindians whereas HLA-B15 is rarely found. The aim of this study was to test the hypothesis that gallstone susceptibility genes are more prevalent in Mexicans with recent Amerindian ancestry. METHODS: We carried out a prospective case-controlled study. Subjects were divided into those who had stones visible on gallbladder ultrasound (cases), and those whose ultrasounds were negative for gallstones (controls). Body mass index (BMI) was calculated, and serum lipids and lipoprotein, and glucose levels were measured. Class I HLA (HLA-B) typing was performed by PCR amplification of genomic DNA. RESULTS: Of the 1,101 subjects, 146 were classified as subjects with GD (cases) and 955 as subjects without GD (controls). Mean age of the cases was 53.5 +/- 12.5 yr versus 44.78 +/- 12.0 yr for the controls, p= 0.001. A family history of GD was observed in 48% of the cases versus 28.4% of the controls, p= 0.001. HLA-B39 was more frequently increased in GD subjects (0.162), compared with controls (0.063), p= 0.008. The odds ratio of having HLA-B39 was 2.8 and 95% (CI 95%= 1.3-6.3) for GD; HLA-B15 was more frequently increased in controls than in cases. CONCLUSIONS: The most prevalent HLA alleles detected in these GD cases are characteristic of Amerindian populations, supporting the role of genetics in the high prevalence of the development of GD in Mexican mestizos.

Weight reduction and ursodeoxycholic acid in subjects with nonalcoholic fatty liver disease. A double-blind, placebo-controlled trial.

OBJECTIVE: Nonalcoholic fatty liver disease is an increasingly recognized condition that may progress to end-stage liver disease. We investigated the effects of weight reduction and ursodeoxycholic acid administration in patients with this disease. RESEARCH METHODS AND PROCEDURES: A double-blind, placebo-controlled trial. Twenty-seven women with a body mass index of >30 kg/m2 and willing to participate in the diet plan for six weeks were studied were assigned to one of two treatment groups (ursodeoxycholic acid, n = 14: placebo n = 13). Both groups received a normal diet (1,200 kcal/d) plus 1200 mg/d of ursodeoxycholic acid or placebo. Hepatic steatosis, was assessed by abdominal ultrasound. Fasting glucose, cholesterol, triglycerides, and aminotransferases levels were determined before and after treatment. RESULTS: Body mass index decreases significantly from 34.2 +/- 4.2 kg/m2 and 33.3 +/- 1.6 kg/m2 to 31.8 +/- 4.5 kg/m2 and 30.6 +/- 2.6 kg/m2 in the ursodeoxycholic acid and placebo groups, p < 0.001. The hepatic steatosis index decreased from 2.3 +/- 0.7 to 1.0 +/- 0.6 and 2.2 +/- 0.7 to 1.1 +/- 0.7 in the ursodeoxycholic acid and placebo groups, p<0.003. Serum AST decreased significantly from 41.2 +/- 5.6 to 34.5 +/- 3.4 in the ursodeoxycholic acid group, p <0.001, and from 43.6 +/- 4.2 to 35.3 +/- 2.9 in the placebo group, p <0.001. Serum ALT decreased from 62.9 +/- 6.5 to 44.0 +/- 3.5 in the ursodeoxycholic acid group, p <0.001, and from 63.5 +/- 4.5 to 44.0 +/- 3.5 in the placebo group. We did not find any differences in all variables studied between groups. CONCLUSIONS: The present study shows beneficial effect of weight reduction, producing improvements in biochemical and imaging markers of liver disease.