What do we know about nutrient-based strategies targeting molecular mechanisms associated with obesity-related fatty liver disease?

Obesity is a risk factor for developing nonalcoholic fatty liver disease (NAFLD), and the associated molecular mechanisms could be targeted with nutrient-based strategies. Therefore, it is necessary to review the current mechanisms to propose further treatments. Obesity facilitates the onset of insulin resistance, lipidic abnormalities, hepatic fat accumulation, lipid peroxidation, mitochondrial dysfunction, excessive reactive oxygen species (ROS) production, and inflammation, all related to further steatosis progression and fibrosis. Microbiota alterations can also influence liver disease by the translocation of pathogenic bacteria, energy extraction from short chain fatty acids (SCFAs), intestinal suppression of the expression of fasting-induced adipose factor (FIAF), reduction of bile acids, and altered choline metabolism. There are also genetic polymorphisms in metabolic proteins that predispose to a higher risk of liver diseases, such as those found in the patatin-like phospholipase domain-containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), membrane-bound O-acyltransferase domain-containing 7 (MBOAT7) or also known as lysophosphatidylinositol acyltransferase 1 (LPIAT1), transmembrane channel-like 4 genes (TMC4), fat mass and obesity-associated protein (FTO), the b Klotho (KLB) and carboxylesterase (CES1). No clear dietary guidelines target all mechanisms related to NAFLD development and progression. However, energy and carbohydrate intake restriction, regular physical exercise, supplementation of antioxidants, and restoration of gut microbiota seem to have beneficial effects on the new proposed features of NAFLD.

A hospital-based study of the prevalence of HBV, HCV, HIV, and liver disease among a low-income population in West Mexico.

INTRODUCTION AND OBJECTIVES: Viral hepatitis is a global health problem with unequal distribution of disease burden in which low-income people are at higher risk for acquisition and underlying liver diseases. This study aimed to seek the prevalence of hepatitis B and C viruses, HIV, and liver damage among low-income patients attending a public tertiary care hospital in West Mexico. METHODS: A retrospective/cross-sectional study at the Department of Genomic Medicine in Hepatology was conducted between March 1, 2016 to March 30, 2017. A total of 10,352 patients tested for anti-HCV, HBsAg, or anti-HIV (n=23,074) were included. Age, gender, and hospital service were registered. Liver fibrosis was assessed using APRI and FIB-4 scores. RESULTS: Overall, 3.9% were anti-HCV+ (305/7848), 1.0% were HBsAg+ (80/7894), and 2.9% were anti-HIV+ (210/7332). A 43.8% (750/1959) of patients negative for all viruses had either abnormal AST, ALT, or GGT (≥40 UI/L). Also, significant liver fibrosis (APRI ≥ 0.7) was prevalent in 10.6% (191/1804). In patients who tested positive for viral infections, liver fibrosis was detected in 20.4% (11/54) of HBsAg+, 34.2% (53/155) in anti-HCV+ and 15.5% (16/103) in anti-HIV+. Anti-HCV+ was highest in Geriatrics (11.1%), HBsAg+ in HIV patients (3.0%) and anti-HIV+ in Emergency room attendees (33.3%). CONCLUSION: High seroprevalence of HCV, HBV, and HIV infections was found among the studied population. Significant liver fibrosis was detected in negative and positive patients for viral infections. Medical services need to continuously test for viral infections, promote early detection of chronic liver damage and identify target patients for elimination strategies to decrease disease burden.

Analysis of the complete genome of HBV genotypes F and H found in Brazil and Mexico using the next generation sequencing method.

INTRODUCTION AND OBJECTIVES: Hepatitis B Virus is classified into ten different genotypes (A- J). Genotypes F and H cluster apart from others in phylogenetic trees and is particularly frequent in the Americas. The aim of this study was to sequence complete genomes of samples of HBV genotypes F and H from Brazil and Mexico using next generation sequencing (NGS) and to study relevant characteristics for the disease associated with this virus. MATERIALS AND METHODS: Ninety plasma samples with detectable HBV DNA belonging to the F (n=59) and H (n=31) genotypes were submitted to amplification of the complete HBV genome by three different methologies. Data analysis was developed using bioinformatics tools for quality assurance and comprehensive coverage of the genome. Sequences were aligned with reference sequences for subgenotyping and detecting variants in relevant positions. A phylogenetical tree was constructed using Bayesian methods. RESULTS: HBV genome of 31 samples were amplified and 18 of them were sequenced (HBV/F=16 and HBV/H=2). One genotype F sample was co-infected with the F1b and F3 subgenotypes, while the other samples were all F2a subgenotype. Two genotype H samples clustered with other Mexican sequences. The main variants observed were found in preS and S genes (7/18) and mutations in the precore/core region (11/18). CONCLUSIONS: A NGS methodology was applied to F and H genotypes samples from Mexico and Brazil to fully characterize their sequences. This methodology will be relevant for clinical and epidemiological studies of hepatitis B in Latin America.

CD36 polymorphism, sugary drinks, and sedentarism are associated with hypertriglyceridemic waist phenotype.

Background: The hypertriglyceridemic waist (HTGW) phenotype is characterized by concomitant increases in waist circumference (WC) and blood triglyceride levels (TG), which has been identified as a predictor of metabolic disorders. This study aimed to analyze associations between food consumption, exercise, and the CD36 gene rs1761667 G>A polymorphism with the HTGW phenotype in adult Mexicans. Methods: This cross-sectional study included a total of 255 participants (both genders, between 18-64 years of age). The HTGW phenotype was defined as WC >88 cm in women, WC >102 cm in men, and TG >150 mg/dL. Body composition was analyzed by electrical bioimpedance. Dietary intakes (macro and micronutrients) were evaluated through a validated 64-item food frequency questionnaire and a 24-h recall. Physical exercise was subjectively recorded asking the participants if they regularly performed some systematic exercise or sport of moderate intensity at least 150-300 minutes a week. Biochemical tests were determined by an automated system. A Taqman real-time assay was used to detect the rs1761667 (G>A) polymorphism of the CD36 gene. A multivariate logistic regression model was performed to analyze the variables potentially associated with the HTGW phenotype (adjusted for age, energy intake, and total fat mass). Results: Overall, 21.6% of the population presented the HTGW phenotype; compared to the HTGW-, also, they were older, had more body fat, higher glucose, cholesterol and insulin levels, and high blood pressure. Female sex (OR=2.92, 95% CI: 1.12-7.60, p=0.028), body mass index (OR=1.19, 95% CI: 1.07-1.32, p=0.001), total cholesterol (OR=1.01, 95% CI:1.00-1.02, p=0.039), daily consumption of sugary drinks (OR=6.94, 95% CI: 1.80-26.8, p=0.005), and the CD36 AG genotype (OR=3.81, 95% CI: 1.08-13.4, p=0.037) were positively associated with the HTGW phenotype, while performing exercise played a protective role (OR=0.23, 95% CI: 0.08-0.62, p=0.004). Overall, the model predicted HTGW phenotype in 47% (R2=0.47, p≤0.001). Conclusion: The CD36 AG genotype, daily consumption of sugary drinks and sedentarism are risk factors for HTGW phenotype in Mexicans.

A comprehensive update of the status of hepatitis C virus (HCV) infection in Mexico-A systematic review and meta-analysis (2008-2019).

INTRODUCTION AND OBJECTIVES: HCV infection is targeted by the WHO's Global Health Sector Strategy on Viral Hepatitis to be reduced notably by 2030. However, renovated epidemiological data is needed to line up with such goals. Herein, we provide an updated review of incidence, prevalence, genotypes (GTs), and risk factors (RFs) of HCV infection in Mexico to build elimination strategies. MATERIAL AND METHODS: HCV incidence was charted using the cumulative new cases/year at week 52. Prevalence, GTs, and RFs data from low-risk (LR-G) and high-risk (HR-Gs) groups were searched in PubMed/MEDLINE/Medigraphic/Scielo databases from January 2008 to December 2019 as per PRISMA guidelines. Weighted mean prevalence (WMP) was estimated; GTs and RFs were registered. RESULTS: In this study, 25,247 new cases were reported. Ten states accumulated 76.32% of HCV incidence that peaked in men at 50-59 years and women at 60-64 years. Thirty-four studies revealed a WMP between 0.774%-2.5% in LR-Gs and 11.8%-39.6% in HR-Gs that included mainly prison inmates, drug users, and dialyzed patients. GT1 and GT2 were predominant; GT3a emerged. Subtypes 1a and 1b circulate differentially, whereas novel GT2 subtypes appeared. Unsafe blood transfusion was infrequent in younger groups, but parenteral/intravenous transmission through drug-related risk behaviors has arisen. CONCLUSIONS: HCV transmission increased notably among LR-Gs and HR-Gs in Mexico. Novel genotypes/subtypes emerged as well as risky behavioral routes of transmission. A national elimination strategy will require pro-active screening in designated risk groups, research in molecular epidemiology, medical training, robust epidemiological databases, and antiviral treatment available to all eligible HCV-infected patients.

How far is Mexico from Viral Hepatitis Global Health Sector Strategy 2030 targets.

In 2016 WHO member states endorsed the 69th World Health Assembly's Global Health Sector Strategies (GHSS) towards eliminating Hepatitis B (HBV) infections by 2030. Substantial progress has been made in Mexico regarding HBV vaccination, blood safety and health-care setting injection safety but minor progress has been identified regarding timely HBV birth-dose coverage, access to diagnostic testing and treatment. Most importantly, Mexico's lack of a national plan for the fight against viral hepatitis was identified as a major obstacle for the development and implementation of actions and procuring funding. Insight of these deficiencies, we propose six actions that are in line with GHSS strategic directions to better allow Mexico to reach the goal of eliminating viral hepatitis by 2030. 1) the creation of a National Viral Hepatitis Task Group capable of providing direction, recommendations as well as innovative solutions in the fight against viral hepatitis in Mexico; 2) the drafting of a National Plan for viral hepatitis; 3) establishing a national viral hepatitis information database; 4) development of Clinical Practice Guidelines; 5) appeal for governmental responsibility and accountability; 6) promote basic, applied science projects as well as clinical research to determine the viral, epidemiological, genomic, ethnic and cultural peculiarities of viral hepatitis infections in Mexico. These basic actions will better equip Mexico to meet GHSS targets, lead to high-impact health interventions and ultimately enhance the cascade of care, from diagnosis to chronic care. Political commitment is a requirement to the implementation of these actions but civil society involvement is also seen to be crucial.

Latin American Association for the study of the liver (ALEH) practice guidance for the diagnosis and treatment of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) currently represents an epidemic worldwide. NAFLD is the most frequently diagnosed chronic liver disease, affecting 20-30% of the general population. Furthermore, its prevalence is predicted to increase exponentially in the next decades, concomitantly with the global epidemic of obesity, type 2 diabetes mellitus (T2DM), and sedentary lifestyle. NAFLD is a clinical syndrome that encompasses a wide spectrum of associated diseases and hepatic complications such as hepatocellular carcinoma (HCC). Moreover, this disease is believed to become the main indication for liver transplantation in the near future. Since NAFLD management represents a growing challenge for primary care physicians, the Asociación Latinoamericana para el Estudio del Hígado (ALEH) has decided to organize this Practice Guidance for the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease, written by Latin-American specialists in different clinical areas, and destined to general practitioners, internal medicine specialists, endocrinologists, diabetologists, gastroenterologists, and hepatologists. The main purpose of this document is to improve patient care and awareness of NAFLD. The information provided in this guidance may also be useful in assisting stakeholders in the decision-making process related to NAFLD. Since new evidence is constantly emerging on different aspects of the disease, updates to this guideline will be required in future.

First detection of hepatitis E virus genotype 3 as a common infectious agent in patients with chronic liver damage in Mexico.

INTRODUCTION AND OBJECTIVES: To characterize the virological features of hepatitis E virus (HEV) in serum from patients exhibiting chronic liver damage. METHODS: A data-base of 513 unrelated individuals from West-Mexico with liver-disease determined by clinical and biochemical tests and transient elastography between 2011 and 2016 were retrospectively analyzed. According to infectious etiologies, patients were classified as hepatitis B virus (HBV)-, hepatitis C virus (HCV)-infected patients, and patients exhibiting chronic liver damage with non-identified infectious etiological agent (NIIEA). Available serum samples from NIIEA-patients were tested by RT-nPCR for the presence of HEV-RNA and partially sequenced for genotyping. RESULTS: Out of the 513 cases, 5.85% were patients infected with HBV, 67.64% with HCV, and 26.51% were NIIEA-patients. Among 76 available samples from NIIEA-cases, 30.26% tested positive for HEV-RNA. Twelve (15.79%) partial HEV sequences allowed phylogenetic analysis, revealing the classification of HEV as HEV-Gt3. Advanced fibrosis (F3-F4 stage) was found in a 26.1% of patients with HEV-active infection. CONCLUSION: Although HCV is the main infectious agent related to chronic liver disease in Mexico, liver damage without an infectious etiology is common. Our findings reveal that an elevated rate of chronic liver disease might be represented by autochthonous infection of HEV-Gt3, whose detection makes Mexico unique in Latin-America with the circulation of HEV strains belonging to three genotypes (Gt1, Gt2, and Gt3). Thus, HEV infection should be a matter of health concern, and mandates for HEV screening to properly handle this commonly undiagnosed disease.

DRD2/ANKK1 TaqI A1 polymorphism associates with overconsumption of unhealthy foods and biochemical abnormalities in a Mexican population.

PURPOSE: The dopamine receptor 2/ankyrin repeat domain and content kinase 1 (DRD2/ANKK1) TaqIA polymorphism (rs1800497) has been associated with rewarding behaviors. This study aimed to investigate the association of DRD2/ANKK1 TaqIA polymorphism with the dietary intake, the intake frequency of food groups and biochemical profile in Mexican mestizo subjects. METHODS: A cross-sectional/analytical study with 276 Mexican subjects was performed. Dietary intake was assessed with a 24-h recall and a food frequency questionnaire (FFQ). An allelic discrimination assay evaluated DRD2/ANKK1 TaqIA genotypes. Anthropometric and biochemical data were evaluated. RESULTS: Genotype frequencies were A1A1 (18.48%), A1A2 (45.29%) and A2A2 (36.23%). TaqI A1 allele carriers had a higher intake of carbohydrates (p = 0.038), meats (p = 0.005), fried dishes (p = 0.039), and sugars (p = 0.009). Male TaqI A1 carriers consumed more carbohydrates (p = 0.009) and meats (p = 0.018) while females consumed fewer legumes (p = 0.005). TaqI A1 carriers had glucose (p = 0.037) and triglycerides (p = 0.011) abnormalities. TaqI A1 was associated with higher risk of consumption of unhealthy foods such as fried dishes (OR 3.79, 95% CI 1.53-9.35, p = 0.002) and meats (OR 2.31, 95% CI 1.32-4.05, p = 0.003), and lower healthy foods (OR 1.89, 95% CI 1.04-3.29, p = 0.038). TaqI A1 allele was associated with risk of abnormal glucose, triglycerides, and VLDL levels (OR 2.148, 95% CI 1.068-4.322, p = 0.036; OR 1.999, 95% CI 1.194-3.348, p = 0.011; OR 2.021, 95% CI 1.203-3.392, p = 0.007), respectively. CONCLUSIONS: The presence of the TaqI A1 allele in Mexicans is a genetic risk factor for detrimental dietary quality that may predispose to metabolic disturbances. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Hepatitis E Virus Genotype 1 and Hepatitis A Virus Dual Infection in Pediatric Patients with a Low Socioeconomic Status from Mexico.

OBJECTIVE: We aimed to detect and characterize hepatitis E virus (HEV) RNA in sera samples from a pediatric population infected with the hepatitis A virus (HAV) exhibiting acute hepatitis and to correlate the infection status with the clinical outcome. METHODS: Seventy-five ELISA-positive samples from children containing anti-HAV and anti-HEV IgM were used to amplify and characterize partial regions within HEV ORF2. A statistical comparison of clinical data between HEV IgM-positive/HEV RNA-positive patients and HEV IgM-positive/HEV RNA-negative patients was performed. RESULTS: Thirteen out of 75 IgM-positive samples provided amplification of discrete regions of the HEV genome. Nested RT-PCR-based detection and subsequent sequencing of 5 samples confirmed the identity of HEV genotype 1 (G1), which had not been previously reported in Mexico. Though not significant, a trend towards exacerbated clinical manifestations was found in HEV RNA-positive patients relative to HEV RNA-negative patients. CONCLUSIONS: An elevated rate of G1 RNA was detected. Hepatitis E seems to be a neglected disease in Mexico and epidemic strains of HEV are likely to play a role as causative agents of acute hepatitis in highly exposed children. Although HAV is endemic in Mexico, an HEV-RNA detection rate of 17% in co-infected samples shows the need for screening for HEV as a part of future vaccination strategies.

The Editorial Challenges Faced by International Medical Journals in Latin America.

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Challenges in research and management of hepatitis E virus infection in Cuba, Mexico, and Uruguay.

The symposium "Epidemiology of Hepatitis E virus (HEV) Infection and Associated Immune Response" was held at the Universidad de Guadalajara, Mexico, on 14 June 2017, to define the status of research on HEV infection in three countries in Latin America and the Caribbean (LAC)-Cuba, Mexico, and Uruguay-compared to the situation in Germany. Scientists identified specific research gaps in understanding HEV transmission and the resulting impact on development of disease in the three abovementioned LAC countries. Specific recommendations for implementing standardized serologic and molecular diagnostic methods and epidemiologic, basic, and applied research aimed to develop prevention and handling strategies for this infection, along with the associated comorbidities in the three LAC countries, were also discussed. Given similar demographic, sanitary, and economic conditions in other LAC countries that could predispose them to be at high risk for HEV transmission and infection, these research gaps and recommendations might apply to the entire LAC region. This report was -prepared by meeting participants based on 1) symposium presentations, 2) literature reviews, and 3) group discussions.

El 14 de junio del 2017 se realizó en la Universidad de Guadalajara (México) un simposio sobre las características epidemiológicas de la infección por el virus de la hepatitis E (VHE) y la respuesta inmunitaria asociada. El objetivo fue definir el estado de las investigaciones sobre la infección por el VHE en tres países de América Latina y el Caribe ­Cuba, México y Uruguay­ en comparación con la situación en Alemania. Los científicos señalaron que para comprender la transmisión del VHE y la consiguiente repercusión en el avance de la infección en estos tres países latinoamericanos aún faltan investigaciones sobre ciertos temas específicos. También analizaron recomendaciones concretas para poner en práctica métodos estandarizados de diagnóstico serológico y molecular, y realizar investigaciones epidemiológicas, básicas y aplicadas a fin de elaborar estrategias de prevención y tratamiento de esta infección y las comorbilidades asociadas en los tres países antes mencionados. Considerando que otros países de América Latina y el Caribe presentan condiciones demográficas, sanitarias y económicas similares que podrían implicar una predisposición a un riesgo alto de transmisión del VHE y de infección por este virus, este análisis sobre las brechas y recomendaciones en el ámbito de la investigación podría aplicarse en toda la subregión. El presente informe fue elaborado por los participantes del simposio sobre la base de: 1) presentaciones del simposio; 2) revisiones bibliográficas; y 3) debates en grupos.

O simpósio Epidemiologia da infecção pelo vírus da hepatite E (HEV) e ­resposta imune associada foi realizado na Universidade de Guadalajara, no México, em 14 de junho de 2017, para determinar a situação da pesquisa em HEV em três países da América Latina e Caribe (ALC) ­ Cuba, México e Uruguai ­ em comparação à Alemanha. Os especialistas identificaram lacunas específicas nas pesquisas no que se refere ao entendimento da transmissão do HEV e ao impacto resultante do surgimento da doença nos três países da ALC mencionados. Também foram debatidas recomendações aos três países da ALC, especificamente implementar métodos sorológicos e moleculares padronizados de diagnóstico e realizar pesquisa epidemiológica, básica e aplicada visando elaborar estratégias de prevenção e de enfrentamento da infecção e das comorbidades associadas. Diante da semelhança das condições demográficas, econômicas e de saúde que poderia predispor outros países da ALC a um maior risco de transmissão e infecção de HEV, as lacunas em pesquisa e recomendações provavelmente se aplicam à toda a Região da ALC. Este relatório foi preparado pelos participantes do encontro embasado nas apresentações do simpósio, revisão da literatura científica e discussões em grupo.

High prevalence of HBV infection, detection of subgenotypes F1b, A2, and D4, and differential risk factors among Mexican risk populations with low socioeconomic status.

Hepatitis B virus (HBV) infection may be underestimated among high-risk individuals in regions of low HBs antigenemia. This study aimed to assess HBV serological markers, genotypes, and risk factors in Mexican patients with risk of HBV infection and low socioeconomic status. Demographics, clinical, and risk factor data were collected in patients with HIV (n = 289), HCV (n = 243), deferred blood donors (D-BD) (n = 83), and two native populations, Mixtecos (n = 57) and Purepechas (n = 44). HBV infection was assessed by HBsAg, anti-HBc, and HBV-DNA testing. Overall, patients had low education and very-low income. Totally, HBsAg prevalence was 16.5% (113/684) ranging from 0.7% (HCV) to 37.3% (D-BD), while anti-HBc was 30.2% (207/684). Among 52 sequences, genotypes H (n = 34, 65.4%), G (n = 4, 7.7%), subgenotypes F1b (n = 7, 13.5%), A2 (n = 6, 11.5%), and D4 (n = 1, 1.9%) were detected. Surgeries, sexual promiscuity, and blood transfusions had a differential pattern of distribution. In HCV patients, single (OR = 5.84, 95%Cl 1.91-17.80, P = 0.002), MSM (OR = 4.80, 95%Cl 0.75-30.56, P = 0.097), and IDU (OR = 2.93, 95%CI 1.058-8.09, P = 0.039) were predictors for HBV infection. While IDU (OR = 2.68, 95%CI 1.08-6.61, P = 0.033) and MSM (OR = 2.64, 95%CI 1.39-5.04, P = 0.003) were predictors in HIV patients. In this group, MSM was associated with HBsAg positivity (OR = 3.45, 95%CI 1.48-8.07, P = 0.004) and IDU with anti-HBc positivity (OR = 5.12, 95%CI 2.05-12.77, P < 0.001). In conclusion, testing with a combined approach of three different HBV markers, a high prevalence of HBV infection, a differential distribution of HBV genotypes, including subgenotypes F1b, A2, and D4, as well as risk factors in low-income Mexican risk groups were detected.

High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population.

BACKGROUND: The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. MATERIAL AND METHODS: In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. RESULTS: The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p &lt; 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p &gt; 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p &lt; 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. CONCLUSION: A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.