Personalized medicine and nutrition in hepatology for preventing chronic liver disease in Mexico.

Chronic liver disease is a global health issue. Patients with chronic liver disease require a fresh approach that focuses on the genetic and environmental factors that contribute to disease initiation and progression. Emerging knowledge in the fields of Genomic Medicine and Genomic Nutrition demonstrates differences between countries in terms of genetics and lifestyle risk factors such as diet, physical activity, and mental health in chronic liver disease, which serves as the foundation for the implementation of Personalized Medicine and Nutrition (PerMed-Nut) strategies. Most of the world's populations have descended from various ethnic groupings. Mexico's population has a tripartite ancestral background, consisting of Amerindian, European, and African lineages, which is common across Latin America's regional countries. The purpose of this review is to discuss the genetic and environmental components that could be incorporated into a PerMed-Nut model for metabolic-associated liver disease, viral hepatitis B and C, and hepatocellular carcinoma in Mexico. Additionally, the implementation of the PerMed-Nut approach will require updated medicine and nutrition education curricula. Training and equipping future health professionals and researchers with new clinical and investigative abilities focused on preventing liver illnesses in the field of genomic hepatology globally is a vision that clinicians and nutritionists should be concerned about.

Epidemiology of Hepatitis C Virus in HIV Patients from West Mexico: Implications for Controlling and Preventing Viral Hepatitis.

The complex epidemiology of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV) patients in West Mexico remains poorly understood. Thus, this study aimed to investigate the HCV prevalence, HCV-associated risk factors, and HCV genotypes/subtypes and assess their impacts on liver fibrosis in 294 HIV patients (median age: 38 years; 88.1% male). HCV RNA was extracted and amplified by PCR. Hepatic fibrosis was assessed using three noninvasive methods: transient elastography (TE), the aspartate aminotransferase (AST)-to-platelets ratio index score (APRI), and the fibrosis-4 score (FIB4). Patients with liver stiffness of ≥9.3 Kpa were considered to have advanced liver fibrosis. HCV genotypes/subtypes were determined by line probe assay (LiPA) or Sanger sequencing. The prevalence of HIV/HCV infection was 36.4% and was associated with injection drug use (odds ratio (OR) = 13.2; 95% confidence interval (CI) = 5.9-33.6; p < 0.001), imprisonment (OR = 3.0; 95% CI = 1.7-5.4; p < 0.001), the onset of sexual life (OR = 2.6; 95% CI = 1.5-4.5; p < 0.001), blood transfusion (OR = 2.5; 95% CI = 1.5-4.2; p = 0.001), tattooing (OR = 2.4; 95% CI = 1.4-3.9; p = 0.001), being a sex worker (OR = 2.3; 95% CI = 1.0-5.4; p = 0.046), and surgery (OR = 1.7; 95% CI = 1.0-2.7; p = 0.042). The HCV subtype distribution was 68.2% for 1a, 15.2% for 3a, 10.6% for 1b, 3.0% for 2b, 1.5% for 2a, and 1.5% for 4a. The advanced liver fibrosis prevalence was highest in patients with HIV/HCV co-infection (47.7%), especially in those with HCV subtype 1a. CD4+ counts, albumin, direct bilirubin, and indirect bilirubin were associated with liver fibrosis. In conclusion, HCV infection had a significant impact on the liver health of Mexican HIV patients, highlighting the need for targeted preventive strategies in this population.

Hepatitis B Virus Genotype H: Epidemiological, Molecular, and Clinical Characteristics in Mexico.

The hepatitis B virus (HBV), comprising of ten genotypes (A-J), has been a silent threat against humanity, constituting a public health problem worldwide. In 2016, the World Health Organization set forth an impressive initiative for the global elimination of viral hepatitis by 2030. As the target date approaches, many nations, particularly in the Latin American region, face challenges in designing and implementing their respective elimination plan. This review aimed to portray the state of knowledge about the epidemiological, molecular, and clinical characteristics of HBV genotype H (HBV/H), endemic to Mexico. PubMed, Scopus, Web of Science, and Google Scholar were searched to compile scientific literature over 50 years (1970-2022). A total of 91 articles were organized into thematic categories, addressing essential aspects such as epidemiological data, risk factors, HBV genotype distribution, HBV mixed infections, clinical characteristics, and vaccination. The prevalence and its associated 95% confidence interval (95% CI) were estimated using the Metafor package in R programming language (version 4.1.2). We provide insights into the strengths and weaknesses in diagnostics and prevention measures that explain the current epidemiological profile of HBV/H. Training, research, and awareness actions are required to control HBV infections in Mexico. These actions should contribute to creating more specific clinical practice guides according to the region's characteristics. Mexico's elimination plan for HBV will require teamwork among the government health administration, researchers, physicians, specialists, and civil society advocates to overcome this task jointly.

Host and HBV Interactions and Their Potential Impact on Clinical Outcomes.

Hepatitis B virus (HBV) is a challenge for global health services, affecting millions and leading thousands to end-stage liver disease each year. This comprehensive review explores the interactions between HBV and the host, examining their impact on clinical outcomes. HBV infection encompasses a spectrum of severity, ranging from acute hepatitis B to chronic hepatitis B, which can potentially progress to cirrhosis and hepatocellular carcinoma (HCC). Occult hepatitis B infection (OBI), characterized by low HBV DNA levels in hepatitis B surface antigen-negative individuals, can reactivate and cause acute hepatitis B. HBV genotyping has revealed unique geographical patterns and relationships with clinical outcomes. Moreover, single nucleotide polymorphisms (SNPs) within the human host genome have been linked to several clinical outcomes, including cirrhosis, HCC, OBI, hepatitis B reactivation, and spontaneous clearance. The immune response plays a key role in controlling HBV infection by eliminating infected cells and neutralizing HBV in the bloodstream. Furthermore, HBV can modulate host metabolic pathways involved in glucose and lipid metabolism and bile acid absorption, influencing disease progression. HBV clinical outcomes correlate with three levels of viral adaptation. In conclusion, the clinical outcomes of HBV infection could result from complex immune and metabolic interactions between the host and HBV. These outcomes can vary among populations and are influenced by HBV genotypes, host genetics, environmental factors, and lifestyle. Understanding the degrees of HBV adaptation is essential for developing region-specific control and prevention measures.

High Frequency of Antiviral Resistance Mutations in HBV Genotypes A2 and H: Multidrug Resistance Strains in Mexico.

Background and Aims: Lamivudine (3TC), telbivudine (LdT), entecavir (ETV), adefovir (ADF), and tenofovir (TFV) are drugs used to treat hepatitis B virus (HBV) infection, but specific mutations allow some viruses to become resistant to antiviral drugs or to acquire immune escape capacities. These mutations have not been thoroughly investigated in Mexico. This study aimed to estimate the prevalence of HBV antiviral resistance and escape mutations. Methods: This cross-sectional study analyzed 158 samples. HBV DNA was extracted, amplified, and sequenced in serum samples using the spin column method, PCR assay, and Sanger's sequencing, respectively. HBV genotypes were determined, and HBV mutations were tested using the Geno2pheno tool. Results: Overall, 68.4% (108/158) of HBV patients were infected with genotype H, followed by G (11.4%, 18/158), A2 (10.8%, 17/158), F1b (6.9.0%, 11/158), D (1.9%, 3/158), and E (0.6%, 1/158), and 5.1% (8/158) had evidence of recombination. The prevalence of resistance mutations was 8.2% (13/158) and the most common combined mutation was rt180M+rt204V. Notably, we found the combinations rt180M+rt204V+rt173L (n=2) and rt180M+rt204V+rt202G (n=1) that confer multidrug resistance to 3TC, LdT, and ETV. Resistance mutations were found in genotypes A2 (11.8%, 2/17), and H (10.2%, 11/108), and escape mutations were detected in HBV genotypes A2 (11.8%, 2/17), H (10.2%, 11/108), F1b (9.1%, 1/11) and G (5.6%, 1/18). Conclusions: The highest prevalence of antiviral resistance mutations or escape mutations was detected in HBV genotypes A2 and H. The earliest cases of HBV multidrug resistance were detected in Mexico.

Tracing the evolutionary history of hepatitis B virus genotype H endemic to Mexico.

Hepatitis B virus (HBV) spreads efficiently among all human populations worldwide. HBV is classified into ten genotypes (A to J) with their geographic distribution and clinical features. In Mexico, HBV genotype H is the leading cause of hepatitis B and has been detected in indigenous populations, suggesting that HBV genotype H may be native to Mexico. However, little is known about the evolutionary history of HBV genotype H. Thus, we aimed to determine the age of HBV genotype H in Mexico using molecular dating techniques. Ninety-two HBV sequences of the reverse transcriptase (RT) domain of the polymerase gene (~1,251 bp) were analyzed; 48 were genotype H, 43 were genotype F, and the oldest HBV sequence from America was included as the root. All sequences were aligned, and the most recent common ancestor (TMRCA) time was calculated using the Bayesian Skyline Evolutionary Analysis. Our results estimate a TMRCA for the genotype H in Mexico of 2070.9 (667.5-4489.2) years before the present (YBP). We identified four major diversification events in genotype H, named H1, H2, H3, and H4. The TMRCA of H1 was 1213.0 (253.3-2638.3) YBP, followed by H2 1175.5 (557.5-2424.2) YBP, H3 949.6 (279.3-2105.0) YBP, and H4 1230.5 (336.3, 2756.7) YBP. We estimated that genotype H diverged from its sister genotype F around 8140.8 (1867.5-18012.8) YBP. In conclusion, this study found that genotype H in Mexico has an estimated age of 2070.9 (667.5-4489.2) YBP and has experienced at least four major diversification events since then.

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.

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.

Differential distribution of gene polymorphisms associated with hypercholesterolemia, hypertriglyceridemia, and hypoalphalipoproteinemia among Native American and Mestizo Mexicans.

BACKGROUND: Dyslipidemias are metabolic abnormalities associated with chronic diseases caused by genetic and environmental factors. The Mexican population displays regional differences according to ethnicity with an impact on the type of dyslipidemia. AIM: To define the main dyslipidemias, the frequency of lipid-related risk alleles, and their association with hyperlipidemic states among different ethnic groups in West Mexico. METHODS: In a retrospective study, 1324 adults were selected to compare dyslipidemias and lipid-related gene polymorphisms. Demographic, clinical, and laboratory data were collected. A subgroup of 196 normal weight subjects without impaired glucose was selected for the association analyses. Genotyping was determined by allelic discrimination assay. RESULTS: Hypercholesterolemia was the most prevalent dyslipidemia (42.3%). The frequency of the risk alleles associated with hypoalphalipoproteinemia (ABCA1) and hypercholesterolemia (APOE, LDLR) was higher in the Native Americans (P = 0.047). In contrast, the Mestizos with European ancestry showed a higher frequency of the risk alleles for hypertriglyceridemia (APOE2, MTTP) (P = 0.045). In normal weight Mestizo subjects, the APOB TT and LDLR GG genotypes were associated risk factors for hypercholesterolemia (OR = 5.33, 95%CI: 1.537-18.502, P = 0.008 and OR = 3.90, 95%CI: 1.042-14.583, P = 0.043, respectively), and displayed an increase in low-density lipoprotein cholesterol levels (APOB: ß = 40.39, 95%CI: 14.415-66.366, P = 0.004; LDLR: ß = 20.77, 95%CI: 5.763-35.784, P = 0.007). CONCLUSION: Gene polymorphisms and dyslipidemias showed a differential distribution. Regional primary health care strategies are required to mitigate their prevalence considering the genetic and environmental features which could have important implications for personalized medicine within the new era of precision medicine.

Evaluating Dietary Patterns in Women from Southern Italy and Western Mexico.

Traditional diets are known to be beneficial; however, both Italian and Mexican populations are gradually moving away from the Mediterranean and traditional Mexican diets. Since women play a key role in safeguarding dietary traditions and may reflect population dietary changes, we aimed to identify Italian and Mexican women's current dietary patterns (DPs) and characterize their nutrient content. Cross-sectional analyses were separately conducted on two convenience samples of 811 women from Southern Italy and 215 women from Western Mexico. Food frequency questionnaires, 24 h recalls, and a principal component analysis (PCA) approach were used to derive a posteriori DPs. In Italian women, the first DP was characterized by the consumption of legumes, vegetables, and fish (8.8% of the total variance), while the second DP was characterized by snack foods, processed meats, and non-olive oils. In Mexican women, the first DP was characterized by the consumption of meats and processed foods (12.6% of the total variance), while the second DP by fruits, vegetables, and whole grains. In both populations, adhering to the DPs rich in healthy foods (i.e., fruits, vegetables, legumes, and fish) was associated with a higher quality of diet in terms on nutrient content. However, adherence to the Western-type DPs was more common among women of younger age (p < 0.035). Thus, more extraordinary efforts are needed in promoting each country's traditional healthy diet, especially among the new generations.

Viral Kinetics of an Acute Hepatitis B Virus Subgenotype F1b Infection in a Mexican Subject.

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Influence of a Nutrigenetic Intervention on Self-Efficacy, Emotions, and Rewarding Behaviors in Unhealthy Eating among Mexicans: An Exploratory Pilot Study.

The Genome-based Mexican (GENOMEX) diet is a strategy for preventing and managing obesity. Emotion and eating behavior in the context of a nutrigenetic intervention have not been thoroughly studied. We aimed to explore the influence of the GENOMEX diet on emotions, self-efficacy, and rewarding behaviors in unhealthy eating among subjects with risk factors for obesity-related chronic diseases. Twenty-eight subjects included in the six-month GENOMEX intervention answered questions regarding emotions that influence food consumption. Additionally, the Patient Health Questionnaire (PHQ-9) and the Reward-based eating drive scale (RED) were applied. In the study, minimal, mild, moderate, and severe depression were present in 46.4%, 39.3%, 10.7%, and 3.6%, respectively. RED did not change, but it correlated with a higher intake of fats (r2 = 0.684, ß = 2.066, p = 0.003). Mood influenced unhealthy eating in 71.7% of subjects, and 76.9% experienced binge episodes triggered by anxiety. Sugars were the most consumed foods during binge episodes (42.2%). Both low self-efficacy levels and binge episodes were associated with high consumption of unhealthy foods. After the intervention, 10.7% of subjects reported a high level of self-efficacy. In conclusion, a culturally acceptable and genetically compatible regional Mexican food diet reduced negative emotions and unhealthy eating while increasing self-efficacy.

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.