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Occult liver disease refers to the presence of unrecognized chronic liver disease and cirrhosis. Liver disease is currently the eleventh cause of death globally, representing 4% of all deaths in the world. Alcohol consumption is the leading cause of cirrhosis globally, accounting for approximately 60% of cases. The estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 32.4% and has been steadily increasing over the last years. Viral hepatitis B and C accounted for 1.3 million deaths in 2020.Several studies in populations at high risk of chronic liver disease (elevated liver enzymes, type 2 diabetes, excessive alcohol consumption) have found an elevated prevalence of occult liver disease. Attempts should be made to assess the prevalence of occult liver disease in Latin America, a region with one of the highest rates of metabolic diseases and excessive alcohol consumption.Screening for NAFLD in high-risk subjects and screening for excessive drinking and alcohol use disorders at every level of medical care is relevant. Efforts should also focus on the early treatment of occult liver disease to try to reduce liver disease burden and, in the case of occult viral hepatitis infection, prevent further spreading.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a term that entails a broad spectrum of conditions that vary in severity. Its development is influenced by multiple factors such as environment, microbiome, comorbidities, and genetic factors. MASLD is closely related to metabolic syndrome as it is caused by an alteration in the metabolism of fatty acids due to the accumulation of lipids because of an imbalance between its absorption and elimination in the liver. Its progression to fibrosis is due to a constant flow of fatty acids through the mitochondria and the inability of the liver to slow down this metabolic load, which generates oxidative stress and lipid peroxidation, triggering cell death. The development and progression of MASLD are closely related to unhealthy lifestyle habits, and nutritional epigenetic and genetic mechanisms have also been implicated. Currently, lifestyle modification is the first-line treatment for MASLD and nonalcoholic steatohepatitis; weight loss of ≥10% produces resolution of steatohepatitis and fibrosis regression. In many patients, body weight reduction cannot be achieved; therefore, pharmacological treatment should be offered in particular populations.

The prevalence of hypothyroidism in patients with nonalcoholic fatty liver disease (NAFLD) is high (22.4%). Thyroid hormones (THs) regulate many metabolic activities in the liver by promoting the export and oxidation of lipids, as well as de novo lipogenesis. They also control hepatic insulin sensitivity and suppress hepatic gluconeogenesis. Because of its importance in lipid and carbohydrate metabolism, the involvement of thyroid dysfunction in the pathogenesis of NAFLD seems plausible. The mechanisms implicated in this relationship include high thyroid-stimulating hormone (TSH) levels, low TH levels, and chronic inflammation. The activity of the TH receptor (THR)-β in response to THs is essential in the pathogenesis of hypothyroidism-induced NAFLD. Therefore, an orally active selective liver THR-β agonist, Resmetirom (MGL-3196), was developed, and has been shown to reduce liver fat content, and as a secondary end point, to improve nonalcoholic steatohepatitis. The treatment of NAFLD with THR-β agonists seems quite promising, and other agonists are currently under development and investigation. This review aims to shine a light on the pathophysiological and epidemiological evidence regarding this relationship and the effect that treatment with THs and selective liver THR-β agonists have on hepatic lipid metabolism.

Hepatic encephalopathy (HE) is a brain dysfunction caused by liver insufficiency and/or portosystemic shunts. Between 30%–40% of patients with cirrhosis will present overt HE during their lifetime. While the pathophysiology of HE is not entirely understood, three critical factors have been identified: hyperammonaemia, systemic inflammation and oxidative stress by glutaminase gene alterations. Minimal HE is defined by the presence of signs of cognitive abnormalities in a patient without asterixis or disorientation; it can only be diagnosed with neuropsychological or psychometric tests. The diagnosis of overt HE is based on clinical examination with clinical scales. Currently, only overt HE should be routinely treated. The aims of treatment in an acute episode should be to improve the mental status, identify and treat the precipitating factor, reduce duration and limit consequences. Treatment strategies are targeted at reducing ammonia production and/or increasing its elimination. Even though minimal HE has negative effects on the patient's quality of life and effects on prognosis, indications for treatment are still controversial. There are still many unanswered questions regarding the pathophysiology and management of HE. We should also endeavor to develop more accurate and objective diagnostic methods for overt HE that would permit early detection and help improve outcomes on quality of life and economic burden.

Introduction and objectives: Metabolic-associated fatty liver disease (MAFLD) is defined by steatosis in more than 5% of hepatocytes without other liver diseases. Patients with this disease can progress to multiple stages like liver fibrosis, cirrhosis, and hepatocellular carcinoma. miRNAs are single-stranded molecules that regulate metabolic homeostasis; their differential expression postulates them as potential circulating biomarkers for MAFLD. Previous research reported that hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p have a differential expression in patients with MAFLD. This study aimed to investigate the correlation between liver hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p and serum biomarkers CK-18, APOB, IL-6, IL-32, and TNF-α in patients with MAFLD compared with control patients. Materials and methods: A cross-sectional study was carried out with 16 patients of both sexes, aged between 18-60 years, to determine the association between the levels of hsa-miR-140-5p, hsa-miR-148-5p, and hsa-miR-122-3p with MAFLD in liver biopsies of patients who underwent laparoscopic cholecystectomy. Results: Twelve patients presented MAFLD, four without hepatic steatosis. Circulating levels of CK-18 showed a significant difference in patients with MAFLD, and a strong correlation was found between hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-5p versus the CAP value. Conclusion: There is a correlation between elevated tissue expression of hsa-miR-122-3p, hsa-miR-140-5p, and hsa-miR-148b-3p with plasma levels of CK-18 in patients with simple steatosis compared with patients without the disease.

Abstract The registered incidence of nonalcoholic fatty liver disease (NAFLD) in primary healthcare centers is lower than expected, suggesting a lack of awareness by primary care healthcare professionals. The implementation of educational tools for healthcare workers has been found to increase timely referral and treatment of patients. We aimed to determine healthcare workers’ knowledge of NAFLD to identify their educational needs in one marginalized region. We performed a cross-sectional survey of 261 healthcare professionals in Tlapa de Comonfort, Guerrero, Mexico from October 2019 to December 2019. We created a questionnaire that assessed domains most relevant to NAFLD knowledge. Two hundred and forty-six questionnaires were completed. Of the respondents, 38.3% were nurses and 63.4% were women. Most nurses identified NAFLD as a prevalent (89%) and preventable (93%) disease. Hypertension (33%) and obesity (84%) were recognized as risk factors. The associations between NAFLD and cancer, cirrhosis and cardiovascular disease were identified by 53%, 67% and 72% of respondents, respectively. The largest gaps were found in diagnostic workup, therapeutic approach and the current treatments. We identify modifiable knowledge gaps in NAFLD. Educational strategies for primary care workers could enhance the identification of patients with NAFLD and prevent complications.

Introduction: Metabolic (dysfunction) associated fatty liver disease (MAFLD) and cholelithiasis are highly prevalent and are associated with common risk factors such as obesity, hypertriglyceridemia, and fasting glucose levels; however, it is not clear whether cholelithiasis is associated with MAFLD or fibrosis. Objective: To determine MAFLD severity and associated risk factors in patients diagnosed with cholelithiasis. Materials and methods: Observational, cross-sectional and prolective study (from October 2018 to March 2020) of patients undergoing elective laparoscopic cholecystectomy with liver biopsy, excluding other causes of hepatic disease or significant alcohol consumption. MAFLD detection was based on histology using the Kleiner score and one of the following criteria: overweight/obesity, T2DM, or evidence of metabolic dysregulation. The AST to Platelet Ratio Index, the NAFLD Fibrosis Score, the fibrosis-4 index and the hepatic steatosis index were performed to assess the relationship of non-invasive hepatic scores with histopathology. Results: 80 patients median age (interquartile range) was 42 (18) years, with a BMI of 27.9 (6.11) Kg/m2. Of all patients, 58.8% had MAFLD, 78.7% were women, and 13.8% had the severe form (formerly named NASH). No substantial correlation between biochemical parameters and histopathological analysis of MAFLD and fibrosis was observed. Conclusion: Because cholelithiasis and MAFLD are highly prevalent diseases, it is essential to conduct studies on the relationship between both pathologies. Currently, liver biopsy is the best diagnostic method since the predictive biochemical models did not show a substantial correlation to classify MAFLD. Its early detection is relevant since a considerable percentage of advanced fibrosis (8.7%) was found.

Introduction and objectives: Hepatitis B virus (HBV) infection can lead to cirrhosis, hepatocellular carcinoma, and death if untreated. In Mexico, HBV vaccination for all children and adolescents was implemented in 1999. In 2000 the estimated HBV was 0.21% in the population aged 20 years and older. We estimated the national prevalence for hepatitis B surface antigen (HBsAg) and its association with sociodemographic characteristics, including sexual behavior information for those aged 20 to 49 years. Materials and methods: From the 2018 National Health and Nutrition Survey, blood samples were collected from a subsample of 2,280 adults to determine HBsAg. We estimated the national prevalence for HBsAg and evaluated its association with sociodemographic characteristics, adding sexual behavior information for those aged 20 to 49 years. We performed a multiple logistic regression to estimate the association of HBsAg and relevant variables. Results: The 2018 estimated prevalence of HBsAg in the Mexican adult population was 0.51% (95%CI 0.19, 2.33), which represents 411,000 cases. This prevalence was higher than previously estimated and it was higher in women than in men (0.54% versus 0.46%, respectively). We did not find an association between HBsAg and sociodemographic characteristics or sexual behaviors. Conclusions: Vaccination and screening strategies towards the elimination of viral hepatitis should be reinforced to further reduce the prevalence over the next years.

Introduction and objectives: Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. Some dietary fatty acids have showed different bioactive functions in metabolic syndrome. The aim of this study is to determine the dietary consumption patterns and serum percentage of bioactive fatty acids in NAFLD patients. Patients and methods: Cross-sectional study with NAFLD patients and non-NAFLD patients. Dietary consumption of bioactive fatty acids was assessed by a food frequency questionnaire. NAFLD and liver fibrosis were diagnosed by transient elastography. The identification of serum bioactive fatty acids was achieved by gas chromatography–mass spectrometry (%). Bioactive fatty acids consumption was correlated with NAFLD clinical characteristics with the Spearman correlation analysis. Results: A total of 299 patients were included, whose mean of age and body mass index were 44.2 ± 9.9 years and 25.9 ± 3.8 kg/m2, respectively. The consumption of bioactive fatty acids was no different regarding the presence of NAFLD; however, the consumption of stearic and linoleic fatty acids was higher in relation with NAFLD severity (p ≤ 0.05). The consumption of myristic acid was higher in patients with fibrosis (p = 0.02). Serum percentage and dietary consumption did not show correlations. Conclusion: Dietary consumption of bioactive fatty acids is different according to NAFLD severity. Individualized diets according to NAFLD severity could be successful in order to prevent liver injury-related outcomes.

Introduction and Objectives: As of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. Materials & Methods: We performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. Results: A total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27−9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35−9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40−6.55; p = 0.005) were associated with higher odds for in-hospital death. Conclusions: Our results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.

Hepatic steatosis is characterized by triglyceride accumulation within hepatocytes in response to a high calorie intake, and it may be related to intestinal microbiota disturbances. The prebiotic inulin is a naturally occurring polysaccharide with a high dietary fiber content. Here, we evaluate the effect of inulin on the intestinal microbiota in a non-alcoholic fatty liver disease model. Mice exposed to a standard rodent diet or a fat-enriched diet, were supplemented or not, with inulin. Liver histology was evaluated with oil red O and H&E staining and the intestinal microbiota was determined in mice fecal samples by 16S rRNA sequencing. Inulin treatment effectively prevents liver steatosis in the fat-enriched diet group. We also observed that inulin re-shaped the intestinal microbiota at the phylum level, were Verrucomicrobia genus significantly increased in the fat-diet group; specifically, we observed that Akkermansia muciniphila increased by 5-fold with inulin supplementation. The family Prevotellaceae was also significantly increased in the fat-diet group. Overall, we propose that inulin supplementation in liver steatosis-affected animals, promotes a remodeling in the intestinal microbiota composition, which might regulate lipid metabolism, thus contributing to tackling liver steatosis.

Introduction and aim. Nonalcoholic fatty liver disease (NAFLD) is closely associated with overweight and obesity, becoming one of the most prevalent hepatic diseases nowadays. Circulating hemoglobin (Hb) concentration is significantly higher in people with NAFLD, compared to healthy patients. While liver biopsy remains the gold standard for NAFLD diagnosis, it is not the best technique due to adverse events that may occur. Therefore it is important to find less invasive and more sensitive markers. This study aimed to determine the association of serum Hb levels in patients with steatosis and fibrosis as a noninvasive marker.Material and methods. A 1,186 patient cross-sectional study nested in a randomized clinical trial (NCT01874249) was conducted. Patients were diagnosed by ultrasound for hepatic steatosis and fibroscan for fibrosis; blood test and anthropometric measurements were also assessed.Results. Serum Hb increased proportionally related to the steatosis level, being significantly higher in patients with severe steatosis than in patients with moderate and mild steatosis.Conclusion. Patients with non-alcoholic fatty liver disease showed elevated levels of circulating Hb, evidence that suggests that Hb exerts a protective role, as it may act as an antioxidant and may counteract the adverse effects of this disease.

Background. The Rockall, Glasgow-Blatchford, and AIMS65 are useful and validated scoring systems for predicting the outcomes of patients with nonvariceal gastrointestinal bleeding. However, there are no validated evidence for using them to predict outcomes on variceal bleeding. The aim of this study was to evaluate and compare the prognostic accuracy of different nonvariceal bleeding scores with other liver-specific scoring systems in cirrhotic patients. Material and methods. A retrospective multicenter study that included 160 cirrhotic patients with acute variceal bleeding. The AUROC’s to predict in-hospital mortality, and rebleeding, were analyzed for each scoring system.Results. Overall in-hospital mortality occurred in 13% and in-hospital rebleeding in 12% of patients. The systems with the best AUROC value for predicting mortality were MELD (0.828; 95% CI 0.748-0.909), and AIMS65 (0.817; 95% CI 0.724-0.909). The best score systems for predicting rebleeding were Glasgow-Blatchford (0.756; 95% CI 0.640-0.827), and Rockall (0.691; 95% CI 0.580-0.802).Conclusions. In addition to liver-specific scores, the AIMS65 score is accurate for predicting in-hospital mortality in cirrhotic patients with acute variceal bleeding. Other scoring systems might be useful for predicting significant clinical outcomes in these patients.

Hepatitis C infection is a worldwide problem. The global prevalence of the hepatitis C virus (HCV) averages 3%. Moreover, its prevalence among patients undergoing haemodialysis (HD) varies worldwide, ranging from as low as 1% to up to 70%. There are few data on its prevalence in developing countries, and even less information is available on HD patients. A literature review revealed that the prevalence of HCV infection among patients undergoing HD in Latin America ranges from 4.2 to 83.9%, with most data stemming from Argentina, Brazil, Mexico, Peru, Chile, Venezuela and Cuba. The most common genotype was genotype 1, and subtype 1b was the most frequent. The risk factors associated with this condition were the duration of the HD treatment and blood transfusion before hepatitis C screening. In addition, HCV RNA detection by polymerase chain reaction is crucial for the diagnosis of HCV infection in HD patients. Trials using combinations of new oral antiviral drugs, such as sofosbuvir and combo (ombitasvir, paritaprevir, ritonavir and dasabuvir), should be the next step in the improvement of care among HD patients with HCV, because these therapeutic agents apparently do not require dose adjustment according to renal function. Finally, information on this subgroup of patients remains unavailable in some countries; therefore, additional studies are needed to determine the prevalence trend of HCV infection in these populations.

The human gastrointestinal tract contains bacterial species that, among other functions, maintain a microbial barrier against potential pathogens and help regulate the immune response in the human body. The composition of gut microbiota and its variations hold an important role in the development of liver diseases. Under pathological conditions, bacterial components are released into the liver–gut axis and cause proinflammatory and autoimmune responses in the liver; these responses can initiate direct damage to liver cells. Probiotics have been shown to have favorable effects when used to treat several liver diseases by reducing the production of bacterial toxins and by modulating autoimmune responses, intestinal permeability, and the inflammatory response. This review discusses current data concerning the role of gut microbiota and its relationship with the immune system and the progression of liver diseases, as well as the use of different strains of bacteria for treatments of such diseases.

Background. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. Patients with non-alcoholic steatohepatitis (NASH) have increased plasmatic and hepatic concentrations of bile acids (BA), suggesting that they can be associated with the progression of the disease. Hepatic nuclear receptors are known to modulate genes controlling BA metabolism; thus, in this work we aimed to compare the expression of liver nuclear receptors -farnesoid X (FXR), small heterodimer partner (SHP) and liver X alpha (LXRα) receptors- and BA transporters -sodium+/taurocholate cotransporting polypeptide (NTCP) and bile salt export pump (BSEP)- in liver biopsy samples of patients with simple steatosis (SS) and NASH.Material and methods. Forty patients with biopsy-proven NALFD were enrolled between 2009 and 2012; liver biopsies were classified as SS (N = 20) or NASH (N = 20) according to the NAFLD activity score. Gene expression of nuclear FXR, LXRa, SHP, NTCP and BSEP was analyzed by real-time reverse transcription polymerase chain reaction and protein level was quantified by western blot.Results. Gene expression of FXR, SHP, NTCP and BSEP was significantly up-regulated in the NASH group in comparison with SS patients (P < 0.05). In contrast, protein level for FXR, SHP and NTCP was decreased in the NASH patients vs. the SS group (P < 0.05). Gene and protein profile of LXRa did not show differences between groups.Conclusions. The results suggest that liver nuclear receptors (FXR and SHP) and BA transporters (NTCP and BSEP) are associated with the progression of NAFLD.

Background. Treatment of hepatitis C virus (HCV) infection with newer direct-acting antivirals is unrealistic in some countries because of the lack of availability.Aim. Assess benefits and harms of boceprevir (BOC) and telaprevir (TLV) in treatment of genotype 1 HCV infection, and identifying subgroups with most benefit.Material and methods. Search from 2009-2013 in PubMed, EMBASE, and “gray literature” of published and unpublished randomized trials reporting sustained viral response (SVR) or adverse events (AE) with BOC or TLV + pegylated interferon and ribavirin (PR) in HCV-infected patients; cohorts or case reports for comparison protease inhibitors (PI), evaluation of predictors of SVR, and resistant variants. Cochrane guidelines were applied. Comparisons between PI + PR vs. PR were performed. Main outcomes were expressed as risk-ratios with 95% CIs. Meta-regression and trial sequential analysis were performed.Results. 33 studies (10,525 patients) were analyzed. SVR was higher for PI + PR (RR, 2.05; 95% CI 1.70-2.48). In meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47; 95% CI, 2.78-4.33). AE were higher with PI + PR (RR, 1.01; 95% CI, 1-1.03; NNH 77.59), also the discontinuation rate (RR, 1.69; 95% CI, 1.36-2.10, NNH, 18). Predictors of SVR were IL-28 TT, nonblack race, low viral load, age, no cirrhosis, statin use, undetectable viral load at the first anemia episode and at week 2 of treatment, and low IL-6 levels. In conclusion SVR was higher in patients treated with PIs, patients previously exposed to PR showed superior response rates. Specific predictors will determine the best candidates for treatments that will offer real-life therapeutic alternatives.

Background and Aims. Acute-on-chronic liver failure has been recognized as a sudden deterioration of cirrhosis, with a high short-term mortality. Prognostic scores are used to assess liver dysfunction. However, there is not enough information on a score to predict short term mortality in those patients. We aimed to investigate the prognostic value of bilirubin concentration in predicting the 1-week outcome of patients with acute-on-chronic liver failure.Material and methods. We performed a retrospective analysis with a cohort of 65 patients (33 women/32 men), age average of 64 years, diagnosed with acute-on-chronic liver failure with at least 1 week follow-up. Demographics, clinical and biochemical variables were analyzed. Most patients died (59 %) within 1 week of follow-up.Results. In univariate logistic regression analysis, admission to the intensive care unit, use of vasoactive drugs, need for parenteral nutrition, and levels of conjugated, unconjugated, and total bilirubin at the time of hospital admission were significantly associated with 1-week mortality; in a multivariate logistic regression, conjugated (p = 0.01), unconjugated (p = 0.01), and total bilirubin (p = 0.009) were independently associated with 1-week mortality. In ROC curve analysis, conjugated (0.751, p < 0.05) and total bilirubin (0.746, p < 0.05) levels were significantly the best short-term mortality predictors.Conclusions. High levels of bilirubin are able to predict short-term mortality in these patients. Also, we suggest that bilirubin can be used as a biochemical marker to improve triage of patients with acute-on-chronic liver failure especially with emerging interventions such as extracorporeal liver assist devices and possibly improved early phase pharmacological therapies.

Background. The information available on time and dose effects of the exposure of hepatocytes to free fatty acids (FFA) in vitro is controversial, and very few studies have assessed the hepatocyte inflammatory response in an in vitro model.Aim. To analyze the effect of treatment with FFA on cell viability and on the kinetics of cytokine expression using hepatic cell lines.Material and methods. Hepatic cell lines, IHH and HuH7, were cultured for 3 h, 6 h, 12 h and 24 h in an enriched medium with palmitic and oleic acids. The cytotoxicity of the FFA was assessed by the MTT test and the intracellular fat content determined cytofluorimetrically and by fluorescence microscopy using Nile Red staining. The expression of mRNA for interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF)-α was assessed by real time reverse transcription-polymerase chain reaction (RT-PCR).Results. Treatment with 600 μM FFA did not affect the viability of either cell line despite a significant increase in the intracellular content of lipid droplets already evident after 3 h of treatment. A time- and dose-dependent upregulation of the expression of IL-6 and IL-8 mRNA was observed during the treatment at 3 and 24 h. In contrast, TNF-α mRNA expression was highly upregulated at 3 h after FFA exposure but returned to control values at 24 h. In conclusion, hepatocytes exposed in vitro for a short time to low FFA concentrations showed a significant upregulation of IL-6 and IL-8 to, and a rapid but transitory elevation of TNF-α.

Background. Endothelial dysfunction has been previously described in metabolic syndrome patients. The levels of circulating endothelial progenitor cells (EPCs) inversely correlates with the incidence of cardiovascular disease. The aim of this study was to investigate the association between NAFLD, metabolic syndrome and EPC levels.Material and methods. A cross-sectional pilot study was performed at a university hospital in Mexico. Two groups of patients without previously known chronic diseases were studied and classified according to the presence of NAFLD. Anthropometric, dietary, and biochemical variables, and circulating EPC number were measured and compared between the groups.Results. Forty subjects were included and classified into two groups: patients with NAFLD (n = 20) and a control group (n = 20). The overall prevalence of insulin resistance and metabolic syndrome was 25% and 17.5%, respectively. EPC levels were found to be higher in the NAFLD group (p < 0.05) as in the patients with insulin resistance (p < 0.01) and metabolic syndrome (p < 0.01). These levels showed correlation with the severity of steatosis.Conclusions. Patients with NAFLD have increased levels of EPC, such levels are associated with the severity of NAFLD. These findings may suggest that these cells may play a role in the early natural history of NAFLD. EPC might be increased in an attempt to repair the endothelial damage resulting from metabolic alterations accompanying NAFLD. Further studies are needed to establish the dynamics of these cells in NAFLD.

Background. The incidence of liver cirrhosis is significantly high in Latin population. The high prevalence of nonalcoholic fatty liver disease NAFLD is likely partially responsible for these figures. Liver biopsy is not a practical diagnostic option in this scenario. The validation of noninvasive markers of fibrosis is important in populations with a high prevalence of NAFLD.Aim. To compare the diagnostic value of noninvasive assessment systems to detect fibrosis in a cohort of Latin patients with biopsy-proven NAFLD.Material and methods. Patients with biopsy-proven NAFLD were included. Noninvasive evaluations included calculations of NAFLD fibrosis, FIB–4, BARD scores, APRI, and AST/ALT ratio. The sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver-operating characteristic curve (AUROC) were calculated.Results. A total of 228 patients (mean age, 48.6 ± 12.7 years) were included. Fifty-one percent were women; 48% were overweight and 23% were obese. The severity of fibrosis was classified as G0, 56.6%; G1, 25%; G2, 6.6%; G3, 7%; and G4, 4.8%. The AUROC values for advanced fibrosis were 0.72 for the NAFLD fibrosis score, 0.74 for FIB–4 score, 0.67 for AST/ALT ratio, 0.66 for APRI score, and 0.65 for BARD score. In 54% of patients with undetermined FIB–4 score and in 60% of patients with undetermined NAFLD fibrosis score, fibrosis was observed in the liver biopsy.Conclusions. The NAFLD fibrosis, FIB–4, and APRI scores can be used for the noninvasive diagnosis of fibrosis. However, 25% of patients evaluated by these methods have an indeterminate degree of fibrosis.

Introduction. The treatment of hepatitis C virus (HCV) genotype 1 with ribavirin (RBV) and pegylated-interferon alpha (peg-IFNα) provides a low-level sustained virological response (SVR). Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene have been identified as SVR predictors. Our aim was to establish an association between three IL28B SNPs (rs8099917, rs12979860, and rs8103142) and the peg-IFNα/RBV treatment response in a Mexican population cohort with chronic HCV.Material and methods. A cohort study was performed with 83 chronic HCV patients at the Fundación Clínica Médica Sur in Mexico City. All patients were treated with peg-IFNα and RBV. The data were analyzed by logistic regression, with adjustments for age, gender, and viral genotype, to determine any associations between the SNPs and the treatment response.Results. In the study group of 83 HCV patients, the main genotype was genotype 1 (70%, n = 58) and the overall SVR was 32.53% (n = 27). In the HCV-1 group, SVR was 27%, whereas SVR was 44% in the HCV-2 group. We found an association between rs12979860 CC and SVR in a codominant model (OR = 4.83, 95% CI = 1.12-20.8, P = 0.033). There was no statistically significant association between SVR and rs8099917 or rs8103142. rs12979860 polymorphisms of CC, CT, and TT, were present in 24%, 41%, and 35% of patients, respectively.Conclusion. A Mexican HCV-1-infected population treated with peg-IFNα and RVB had a low SVR rate, which was associated with the SNP rs12979860 (CC). SVR was not associated with the SNPs rs8099917 or rs8103142.

Background and aim. Bacterial peritonitis (SBP) is the most frequent infection in patients with cirrhosis causing significant mortality. Delay in SBP diagnosis is a serious problem. The aim of this study was to evaluate the diagnostic yield of Uri-Quick Clini-10SGR vs. Multistix 10SGR reagent strips in an Emergency Department.Material and methods. A prospective study of consecutive patients with ascites and paracentesis attending to Emergency Department from March 2005 to February 2007 was made. SBP was defined by 250 neutrophiles /mm3. The ascites obtained at bedside was immediately tested in a dry test tube with both the Uri-Quick Clini 10SGR and MultistixSG10R. The Uri-Quick Clini 10SGR and Multistix SG10R. Strips were considered positive at grade. 3 (.125 leukocytes/mL).Results. A total of 223 ascitic fluid samples were obtained. There were 49 episodes of SBP. Median age was 54 (range 18-87 year) years; 62.3% were female. The sensitivity, specificity, PPV, NPV, and 95% CI for Uri-Quick Clini 10SGR were 79.6 (64-87), 98.2 (94-99), 90.5 (78-96) and 93.9 (89-96), respectively. For MultistixSG10R the values were 77.5 (64-88), 97.7 (93-98), 90 (77.9-96.2), and 94 (89.4-96.6), respectively.Conclusion. The use of reagent strip is useful for SBP diagnosis in an emergency setting. The high PPV allow start antibiotic treatment. In areas without the resources to perform conventional ascites fluid analyses, these strips could be presentlyused.

Introduction. There is significant geographic variation in the etiology and prognosis of acute liver failure (ALF). Since, little information is available for Latin America. We analyzed ALF mortality trends in Mexico.Material and methods. The rates of mortality attributable to ALF were obtained for 1998 to 2009 from the National System of Health Information in Mexico and analyzed according to date, etiology, sex, age and geographic characteristics through graphical assessment and joinpoint regression.Results. From 1998 to 2009, 2,193 ALF-related deaths were reported. A threefold increase in ALF mortality was observed during the period from 1998 to 2009 (the global mortality rate increased from 13.1 to 40.2 deaths per 10,000,000 inhabitants). The most significant increase was observed for viral etiologies after 2006, affecting people 45 years old and over.Conclusion. ALF-related deaths have increased since 2006. Although we cannot speculate on the specific causes of this increase, it may reflect improvements in the access of vulnerable populations to health care.

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.

Despite the public concern about the controversial use and abuse of marijuana, the scientific community has focused on the therapeutic potentials of cannabinoid compounds and had highlighted the importance of endocannabinoids and their receptors in physiology and disease. Endocannabinoids have been shown to be important mediators in neuroendocrine and psychiatric processes such as food intake, drug reward and energy metabolism. Cannabinoid receptors are expressed by several cell lines in the liver, such as hepatocytes, myofibroblastic cells, endothelial cells and probably cholangiocytes. A perpetuating role in liver damage for the endocannabinoid system has been proposed in several steps of chronic liver disease progression. Being a major cause of death worldwide, chronic liver disease is an important problem. New therapies are needed in order to stop or slow damage progression. This review summarizes the results of experimental studies involving the endocannabinoid system in liver disease and their clinical and therapeutical implications in hepatology.

Little information exists in the international scientific or medical literature about the hepatic manifestations and complications of Epstein-Barr virus (EBV). The aim of this study was to describe a series of patients with hepatic manifestations of EBV infection. Our sample population was a series of patients whose hepatic dysfunction was correlated with a documented EBV infection. Serum concentrations of IgG and IgM antibodies against the EBV viral capsid antigen (anti-EBV VCA IgG), EBV early antigen, and EBV nuclear antigen (EBV-EBNA), and heterophilic antibodies were determined. The expression of latent membrane protein (LMP 1) was also evaluated in each patient. RESULTS. The study included nine patients (six men, three women) with a mean age of 43.5 years. Five patients presented with recent clinical pictures suggestive of acute EBV infection. Five patients began with a cholestatic pattern. Two patients required liver biopsies. Those liver biopsies showed positive immunohistochemical staining for LPM 1. No fatalities were attributed to EBV infection. In conclusion, the bilirubin levels of patients with acute EBV infection differed from those reported in the medical literature. EBV infection should be considered in the differential diagnosis of patients with liver abnormalities or diverse hepatic manifestations, increased levels of aminotransferases, or a transitory cholestatic pattern with a favorable outcome.

Background and Aims. The epidemiology of liver cirrhosis differs across sex, ethnic groups, and geographic regions. In 2000, chronic liver disease was the fifth leading cause of death in Mexico. Accurate knowledge of the demographics of liver disease is essential in formulating health-care policies. Our main aim was to project the trends in liver disease prevalence in Mexico from 2005 to 2050 based on mortality data. Methods. Data on national mortality reported for the year 2002 in Mexico were analyzed. Specific-cause mortality rates were calculated for a selected age population (≥25 years old) and classified by sex and projected year (2005–2050). The following codes of the International Classification of Diseases for liver diseases were included: non-alcoholic chronic liver disease and cirrhosis, alcoholic liver disease, liver cancer, and acute and chronic hepatitis B and C infection. The projected prevalence of a chronic liver disease was estimated using the following equation: P = (ID × T) / [(ID × T) + 1], where P = prevalence, ID = incidence density (mortality rate multiplied by 2), T = median survival with the disease (= 20 years). Results: Nearly two million cases of chronic liver disease are expected. Alcohol-related liver diseases remain the most important causes of chronic liver disease, accounting for 996,255 cases in 2050. An emergent syndrome is non-alcoholic liver disease, which will be more important that infectious liver diseases (823,366 vs 46,992 expected cases, respectively). Hepatocellular carcinoma will be the third leading cause of liver disease. Conclusions: Chronic liver disease will be an important cause of morbidity and mortality in the future. Preventive strategies are necessary, particularly those related to obesity and alcohol consumption, to avoid catastrophic consequences.

Introduction: There are risk factors associated with mortality in patients older than 70 years with hip fracture, including kidney function. However, indirect formulas to calculate glomerular filtration rate are not validated in patients older than 70 years. We analyzed whether the formula hematocrit, urea, and gender (HUGE) can be used as a prognostic factor. Material and Methods: A retrospective cohort study of 88 patients older than 70 years with a diagnosis of hip fracture. At admission, clinical and biochemical parameters were measured and glomerular filtration rate by Cockcroft-Gault, Modification Of Diet In Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and HUGE value. Accuracy to assess long-term mortality was analyzed with receiver–operating curve analysis. Cox regression analysis was performed to identify risk factor for mortality. Results: Sample included 88 patients; overall mortality was 13.63%, 17.85%, 28.57%, and 75.85% at 6 months, 1, 2, and 3 years, respectively. There was no significant difference in glomerular filtration rate by different formulas, contrary to HUGE, with higher values in the mortality group (1.83 ± 6.38 vs −2.61 ± 2.70, P = .0001). Survival was lower in patients with higher HUGE values (22.7 months, 95% confidence interval [CI] 16.1-29.5 vs 32.9 months, 95% CI 30.2-35.7; P ≤ .001). In the Cox regression analysis, a negative HUGE value is associated with lower mortality (hazards ratio = 0.238; 95% CI 0.568-0.099). Conclusion: The HUGE formula is an independent risk factor for mortality in elderly patients with hip fracture, but not the glomerular filtration rate determined by Cockcroft-Gault, MDRD, and CKD-EPI.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer death, and accounts for 5.6% of all cancers. Nearly 82% of the approximately 550,000 liver cancer deaths each year occur in Asia. In some regions, cancer-related death from HCC is second only to lung cancer. The incidence and mortality of HCC are increasing in America countries as a result of an ageing cohort infected with chronic hepatitis C, and are expected to continue to rise as a consequence of the obesity epidemic. Clinical care and survival for patients with HCC has advanced considerably during the last two decades, thanks to improvements in patient stratification, an enhanced understanding of the pa-thophysiology of the disease, and because of developments in diagnostic procedures and the introduction of novel therapies and strategies in prevention. Nevertheless, HCC remains the third most common cause of cancer-related deaths worldwide. These LAASL recommendations on treatment of hepatocellular carcinoma are intended to assist physicians and other healthcare providers, as well as patients and other interested individuals, in the clinical decision-making process by describing the optimal management of patients with liver cancer.

Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition that can progress to nonalcoholic steatohepatitis, cirrhosis and cancer. It is considered an emerging health problem due to malnourishment or a high-fat diet (HFD) intake, which is observed worldwide. It is well known that the hepatocytes’ apoptosis phenomenon is one of the most important features of NAFLD. Thus, this review focuses on revealing, through a proteomics approach, the complex network of protein interactions that promote fibrosis, liver cell stress, and apoptosis. According to different types of in vitro and murine models, it has been found that oxidative/nitrative protein stress leads to mitochondrial dysfunction, which plays a major role in stimulating NAFLD damage. Human studies have revealed the importance of novel biomarkers, such as retinol-binding protein 4, lumican, transgelin 2 and hemoglobin, which have a significant role in the disease. The post-genome era has brought proteomics technology, which allows the determination of molecular pathogenesis in NAFLD. This has led to the search for biomarkers which improve early diagnosis and optimal treatment and which may effectively prevent fatal consequences such as cirrhosis or cancer.

Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease.

The consequences of pathologic adipose tissue accumulation have been described for almost all organs. Nonalcoholic fatty liver disease (NAFLD) is considered the most relevant hepatic manifestation of obesity. There is great interest in the study of NAFLD, and new insights into its pathogenic process have been described. Currently, in addition to insulin resistance, which was considered the hallmark of this disease, endocrine, immu-nologic, and central nervous system factors are attracting interest as explanatory variables. In this review, new factors associated with the main theories on the pathophysiology of NAFLD are analyzed.

Obesity and related disorders are a common cause of morbidity worldwide. Nonalcoholic fatty liver disease is the most important hepatic consequence of adipose accumulation. There is strong evidence of obesity-related disorders as risk factors for hepatocellular carcinoma and of nonalcoholic fatty liver disease as a cause of hepatocellular carcinoma, but it is apparently less important than other chronic liver diseases. Unfortunately, preventive measures are not well validated in the population of patients with NAFLD. In this review, we analyze the available information supporting the increased risk of hepatocellular carcinoma in obese patients and patients with nonalcoholic fatty liver disease, considering the epidemiological and basic research-derived evidence.

The aim was to evaluate the initial success, rebleeding rate, need for emergent surgery, and mortality rates of patients with Dieulafoy's lesion (DL) and endoscopic treatment (ET). Patients with DL from a tertiary center were included. We included 20 patients with follow-up of 90 (60—550) days. The lesser curvature was the most common localization. Initial success, rebleeding, and emergent surgery requirement were observed in 90%, 10%, and 15%, respectively. No objective variables were related with response to ET. In conclusion, ET is secure and useful in patients with DL and it must be considered as the first-line treatment modality.

Original abstract: Background & Aims. Several outbreaks of hepatitis A affecting homosexual men have been reported in Europe. However, the prevalence of HIV infection in patients affected by hepatitis A has not been extensively studied and hepatitis A is not considered as an indicator disease for routine HIV testing.Methods. We retrospectively analyzed all adult cases of acute hepatitis A, reported by the National Institute of Infectious Disease “L. Spallanzani”, Rome-Italy, in 2002-2008. Data on HIV infection were obtained by chart review and cross-linkage with laboratory. Information on exposure to risk factors were collected from the standard questionnaire of the Local Health Unit.Results. We analyzed a total of 473 cases of hepatitis A, 368 (77.2%) males that accounted for 75% of all reported cases in Rome, aged 25-64 years (same gender distribution). During the study period, we diagnosed a high proportion of cases among male individuals (78%). Among the male patients, HIV serology was available for 203/368 (55.2%). The overall HIV prevalence was 15.2% (56/368); it was significantly associated with same gender sex and was significantly higher than that observed among patients with hepatitis B (4.0%).Conclusions. We found a high HIV prevalence, associated with same gender sex, among adult male patients diagnosed with hepatitis A in the period 2002-2008, except for 2006. Our data suggest that in a low incidence area for hepatitis A, with a constant high proportion of cases among male individuals, all individuals with acute hepatitis A should be routinely offered an HIV test.