Evolution of hepatology practice in Mexico and Latin America: From biochemical markers to genomic medicine

Abstract

Genomic medicine has evolved significantly, merging centuries of scientific progress with modern molecular biology and clinical care. It utilizes knowledge of the human genome to enhance disease prevention, diagnosis, treatment, and potential reversal. Genomic medicine in hepatology is particularly promising due to the crucial role of the liver in several metabolic processes and its association with diseases such as metabolic dysfunction-associated steatotic liver disease, type 2 diabetes mellitus, liver cirrhosis, and cardiovascular conditions. The mid-20^th century witnessed a paradigm shift in medicine, marked by the emergence of molecular biology, which enabled a deeper understanding of gene expression and regulation. This connection between basic science and clinical practice has enhanced our knowledge of the role of gene-environment interactions in the onset and progression of liver diseases. In Latin America, including Mexico, with its genetically diverse and admixed populations, genomic medicine provides a foundation for personalized and culturally relevant health strategies. This review highlights the need for genomic medicine, examining its historical evolution, integration into hepatology in Mexico, and its potential applications in the prevention of chronic diseases. It emphasizes the importance of training in genomic literacy and interdisciplinary education in medical training, particularly in the field of hepatology, with a focus on genomic medicine expertise.

Key Words: Genomic medicine; Hepatology; Liver disease; Gene and environmental interactions; Exposome; Personalized medicine; Training; Latin America; Mexico

Core Tip: Genomic medicine in hepatology studies the gene-environment interactions that lead to the development of liver diseases. The liver expresses numerous genes involved in the physiology and pathophysiology of several comorbidities, such as diabetes, chronic liver disease, and cardiovascular disease. This work aimed to provide an overview of the study of the liver from its early days to genomic medicine, emphasizing its role in chronic diseases and its use in diagnosing and preventing them at early stages. It also highlighted the need to train healthcare professionals in genomic medicine, creating a new approach to medicine in Mexico and other Latin American countries.

INTRODUCTION

Genomic medicine aims to prevent and reverse chronic diseases by understanding the structure and function of the human genome. Analyzing genetic variations that predispose individuals to disease provides a foundation for personalized interventions and predictive care[1]. This approach is particularly relevant in addressing non-communicable diseases, which are increasingly prevalent in Latin America[2].

Hepatology, which focuses on liver function and disease, is relevant to genomic medicine due to the significant role of the liver in metabolic regulation and gene expression. Liver dysfunction contributes to diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD), type 2 diabetes mellitus (T2DM), liver cirrhosis, and cardiovascular and renal disorders, the leading causes of death and disability in Latin America with Mexico being one of the most affected countries[2,3].

Genomic medicine bridges the gap between basic science and clinical practice by identifying genetic susceptibility to chronic diseases and enabling early medical and nutritional interventions[4]. This progress stems from a historical trajectory of scientific discovery from ancient theories to molecular biology and the Human Genome Project, which laid the foundation for the current genomic era.

Humans share 99.9% of their DNA, yet the remaining 0.1%, comprising key genetic polymorphisms, is crucial in determining disease susceptibility and treatment response[5]. This genetic diversity is particularly significant in Latin America where admixed populations have been shaped by unique gene-environment interactions stemming from Amerindian, European, and African ancestries[6]. In this context, genomic medicine offers an opportunity to deliver culturally and genetically tailored healthcare that meets the diverse needs of these populations.

This article outlines the historical development of genomic medicine and its integration into hepatology. We describe the emergence of genomic medicine in hepatology in Mexico and highlight its role in preventing chronic diseases. Furthermore, we emphasize the importance of training future healthcare professionals in genomic literacy and promoting integrative approaches to disease prevention.

HISTORICAL MILESTONES OF SCIENTIFIC MEDICINE

The early days

Ancient Greek medicine focused on balancing the bodily humors (phlegm, blood, black bile, and yellow bile) linking the patient’s temperament with their environment. Hippocrates of Cos (c. 460-c. 375 BC), often referred to as the father of medicine, introduced this theory of the Four Humors[7,8] that prevailed to the mid-19^th century.

Historically, life was attributed to mystical forces. During the Middle Ages (5^th-16^th century), vitalism dominated, positing a “vital force” in all living beings[9]. Although later challenged by mechanistic explanations, the concept has had a lasting influence on medical terminology as evident in phrases such as “vital signs” and “resuscitation.”

Alchemy, blending early chemistry and philosophy, prevailed until the Enlightenment. Paracelsus (1493-1541) integrated alchemical practices into medicine, paving the way for the development of pharmacology[10,11]. René Descartes’ (1596-1650) mechanistic view of the body promoted systematic reasoning, known as Cartesian reasoning, which is crucial for modern clinical methods[12,13].

Pregenomic era: From cell theory to molecular biology

The 19^th century brought scientific rigor to the field of biology. Matthias Schleiden (1804-1881) and Theodor Schwann (1810-1882) proposed the cell theory[14,15]; Ernst Haeckel (1834-1919) linked heredity to the nucleus[16,17]. Gregor Mendel’s (1822-1884) experiments with pea plants in 1865 established the principles of inheritance patterns[18-20]. In the early 1900s, DE Vries[21] expanded on this concept by proposing the theory of mutation, suggesting that new species arise from sudden genetic changes. Garrod’s (1857-1936) work[22] on alkaptonuria linked genes to metabolism while Bateson[23] (1861-1926) coined the term genetics.

By 1920, chemists had synthesized numerous organic compounds[24], helping to consolidate a new scientific area: Physical chemistry[25], in which outstanding chemists and physicists began studying the structural-function relationships of organic polymers. By the 1930s and 1940s, biochemistry had become a recognized discipline[26], focusing on the structure and properties of proteins, driven by the hypothesis that they were the “secret of life,” i.e., the primary carriers of genetic information.

Among the scientists of this stage were Hermann Emil Fischer (1852-1919), who described peptide bonds[27,28], and Phoebus Levene (1869-1940), who distinguished DNA from RNA by their specific nucleotides[29,30]. Gilbert Newton Lewis (1875-1946) introduced the concept of covalent bonds[31] while Linus Pauling and others identified hydrogen bonds and secondary protein structures[32,33].

In 1938, Warren Weaver (1894-1978), director of the Division of Natural Sciences at the Rockefeller Foundation, coined the term molecular biology to describe the study of biological processes at the molecular level, thereby uniting an interdisciplinary team of mathematicians, physicists, chemists, and biologists[34,35]. This field gained momentum with studies of the fruit fly Drosophila melanogaster, which led to the chromosomal theory of inheritance by Thomas Hunt Morgan (1866-1945)[36]. George Beadle’s (1903-1989) and Edward Tatum’s (1909-1975) work on the yeast Neurospora crassa linked genes and enzymatic functions, establishing the concept of one gene-one enzyme[37].

Rosalind Franklin’s (1920-1958) X-ray diffraction images, notably Photo 51, were pivotal in revealing the double-helix structure of DNA, which was later modeled by James Watson (b. 1928- ) and Francis Crick (1916-2004) in 1953[38]. Crick, Brenner (1927-2019), and others later cracked the genetic code[39].

By the 1970s and 1980s, tools like the plasmid vector pBR322 cloned by Bolivar et al[40] and Soberon et al[41], complemented by Southern and northern blotting techniques to identify sequences[42,43], and the polymerase chain reaction by Kary Bank Mullis (1944-2019) transformed gene analysis and molecular diagnostics[44], opening the gate to genetic engineering and recombinant DNA. Finally, DNA sequencing techniques have undergone several stages of improvement, ultimately achieving greater speed and higher data output through automation and massive sequencing. As shown in Figure 1, scientific advances paved the way for the emergence of molecular biology and its integration into genomic medicine.

Figure 1 Timeline of the evolution of the development in science and its impact on medicine. From philosophy and alchemy as fundamental precursors of chemistry and chemical physics, through the transition of these disciplines into molecular biology, culminating in the emergence of genomic medicine.

Genomic era

The publication of the DNA sequence blueprint of the human genome, the ultimate goal of the Human Genome Project, by the private sector and the United States National Institutes of Health marked the inception of the genomic era[44,45]. Genomics involves studying the structure and regulation of gene expression, encompassing transcription (RNA synthesis, editing, and translocation) and translation (protein synthesis) whether structural or functional and ultimately resulting in proteins that perform intracellular or extracellular functions[45]. More importantly, genomics unified the diverse biomedical sciences, which had conventionally studied cellular processes in isolation. Genomics integrates the knowledge of molecular biology (genes), biochemistry, immunology (intracellular and extracellular molecules), and cell biology (cell organization) to form the foundation for physiology (normal cell function) and pathophysiology (altered cell function), providing the basis for genomic medicine (Figure 2). It provides us with a comprehensive vision of health and disease by understanding the stages involved in gene expression under physiological conditions and interpreting what occurs when disruptions arise at any stage due to changes in protein function.

Figure 2 Integration of biomedical disciplines into genomics. Genomics unifies the diverse biomedical sciences that conventionally studied cellular processes in isolation. Genomics enables a comprehensive and holistic approach to health and disease by analyzing gene expression and regulation at multiple biological levels, bridging fragmented views into a symbiotic biological model.

From this integration emerges the broader concept of “omics”. Genomics aligns closely with molecular biology; metabolomics pertains to the study of molecules involved in various metabolic pathways while proteomics focuses on the structure and function of proteins, particularly their biochemical and immunological properties. In the following sections, we describe how genomic medicine has evolved the study of the liver.

EVOLVING PRACTICE OF HEPATOLOGY

Historical roots

In ancient Greek medicine, the liver was regarded as the organ through which the gods communicated with humans, symbolizing life, intelligence, and the soul’s indestructibility due to its regenerative capacity[8]. Hippocrates emphasized two key humors, yellow and black bile (produced by the liver), which influence temperament. This belief endured, reaching colonial Latin America where the Spanish term bilioso (meaning bilious, quick-tempered) and herbal remedies to restore liver health reflected its lasting cultural and medical significance.

Early stage of modern hepatology

A turning point in hepatology came after World War II when doctors began to focus on liver research, particularly on conditions like alcoholic liver disease (ALD), viral hepatitis, and Laennec’s cirrhosis, which was then believed to be caused by malnutrition. Since World War II, our understanding of liver function and disease has undergone significant advancements. Early histopathological studies laid the groundwork for identifying and classifying viral hepatitis. Research on alcohol metabolism clarified the pathogenesis of alcoholic cirrhosis. As knowledge grew, several liver conditions were redefined: Laennec’s cirrhosis became obsolete[46,47]; non-A, non-B hepatitis was identified as hepatitis C; and cryptogenic cirrhosis was then recognized as part of nonalcoholic fatty liver disease, recently renamed MASLD, highlighting progress in metabolic and genomic research[48,49].

Modern hepatology has advanced significantly with the development of liver function tests, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin as well as protein-based assays such as albumin and prothrombin. These biochemical markers remain the primary laboratory studies used by physicians to differentiate between acute and chronic liver damage and assess overall liver function recovery[50]. Nonetheless, as we will comment further, powerful molecular diagnostic tools will soon complement these tests.

In the mid-20^th century, pathologists, clinicians, and biochemists launched further investigations into chronic liver diseases. Key figures in this movement included Hans Popper (United States) (1903-1988), Dame Sheila Sherlock (United Kingdom) (1918-2001), Ruy Pérez-Tamayo (1924-2022), and his student Marcos Rojkind-Matluk (Mexico) (1935-2011). Dr. Popper’s three-dimensional studies of cirrhosis provided critical insights into liver pathology[51]. Dr. Sherlock transformed clinical practice by introducing the needle liver biopsy, defining autoimmune liver diseases, and authoring a seminal textbook that guided generations of hepatologists[52]. In Mexico, Dr. Pérez-Tamayo, a distinguished pathologist, contributed to the experimental pathology of liver diseases[53]. Dr. Rojkind explored the molecular mechanisms of fibrosis, focusing on cell-matrix interactions and the dynamics of the extracellular matrix[54,55]. Together, their work bridged pathology, clinical insight, and the emerging field of molecular biology, establishing the multidisciplinary framework of modern hepatology.

Molecular hepatology

In the 1980s during the pregenomic era, the study of molecular biology in liver diseases expanded rapidly, leading to the emergence of the field of molecular hepatology. At the Liver Research Center of the Albert Einstein College of Medicine in the Bronx, David Shafritz (b. 1940- ) led one of the first studies on hepatocellular carcinoma, demonstrating the integration of the hepatitis B virus (HBV) genome into the human genome as an etiological factor[56,57]. Around the same time James E. Darnell Jr (b. 1930- ) developed the “run-off transcription assay”[58], a technique that enabled the study of transcriptional and post-transcriptional regulation of liver genes during normal function, regeneration, and cirrhosis[59].

Initially, molecular hepatology and gastroenterology received little attention at academic meetings. However, by the 1980s-1990s, advances in molecular biology transformed these fields by integrating biochemistry with molecular methods, revealing mechanisms of liver gene expression from induction to protein function[60]. During this stage, advances in molecular biology, as mentioned in the previous section, with their clinical applications, led to the integration of molecular biology in medicine, enriching conventional diagnostics, which are based on biochemical markers and immunological assays, with molecular techniques.

Molecular hepatology in Mexico

As a result of the global scientific transition from classical pathology to molecular hepatology, Mexico embraced molecular biology in the 1990s under the leadership of Secretary of Health Jesús Kumate Rodríguez (1924-2018), who supported specialized training and research in genomic medicine. He left for posterity the famous phrase, “Whoever does not enter molecular biology is like not getting into the major leagues”[61]. Postdoctoral researchers with experience in molecular biology in medicine, who had returned to Mexico, created new laboratories in reproductive biology, psychiatry, gastroenterology, hepatology, infectology, and rheumatology.

At the then-called National Institute of Nutrition, the first Molecular Gastroenterology and Hepatology laboratory was established (1989). Shortly thereafter, the first Doctorate in Molecular Biology in Medicine was created at the University of Guadalajara (1994), along with the first Department of Genomic Medicine in Hepatology at the Civil Hospital of Guadalajara (1996) in Guadalajara, Mexico[62], focusing on the study of genetic and environmental factors involved in the onset and progression of liver diseases and related conditions among the Mexicans (Figure 3).

Figure 3 Evolution of science and its impact on the study of hepatology in Mexico. Scientific transition from classical pathology in hepatology to the current genomic medicine era.

GENOMIC MEDICINE IN HEPATOLOGY

When medical specialties were formalized in the mid-20^th century, hepatology was initially grouped under the umbrella of gastroenterology and internal medicine. However, the liver, as a central and integrative organ in human physiology, has been of interest in several medical specialties. Liver diseases garnered interest across various disciplines: Pathologists led early descriptions of fibrosis and cirrhosis; geneticists studied inherited disorders; neurologists and psychiatrists examined links to hunger, satiety, and addiction; infectious disease specialists focused on hepatitis; endocrinologists addressed obesity and diabetes; oncologists investigated hepatocellular carcinoma; and transplant surgeons managed end-stage liver failure (Figure 4).

Figure 4 Liver as a central and integrative organ in human physiology. A focal point of interest for medical training, specialties, and other health sciences disciplines. A key point for preventing, detecting, and reversing chronic degenerative diseases.

However, genomic medicine marks a new era in hepatology, driven by technological advancements in the late 20^th and early 21^st centuries. The paradigm shift from viewing fibrosis/cirrhosis as irreversible to potentially reversible in early stages[63] mirrors similar changes in the understanding of other chronic conditions, such as T2DM, cardiovascular, and kidney diseases[64-66]. As genomics uncovered the complex interplay between genes and the exposome (the sum of environmental exposures across the lifespan, including diet, physical activity, toxins, infections, and emotional stressors)[67-69], it has become clear that enabling targeted prevention strategies could reduce chronic disease progression (Figure 5).

Figure 5 Gene-environment interaction and the progression of chronic degenerative disease. The interaction between the genome and a harmful exposome (including obesogenic surroundings, hepatopathogenic diets, obesogens, toxins, and environmental pollution) promotes the progression of chronic disease. Personalized and precision medicine, as well as nutrition, may prevent, halt, or reverse the early development of disease. BMI: Body mass index.

Unlike conventional medicine, which often targets advanced diseases, genomic medicine focuses on the genetic and exposomic factors unique to each population (Figure 6). These gene-environmental interactions influence the various stages of gene expression from induction to protein function, affecting the onset and progression of chronic diseases. Thus, the populations’ phenotypes and genotypes reflect these environmental adaptations. Genomic medicine in hepatology aims to identify allelic and genotypic variations linked to ancestry influenced by the exposome, particularly those modifying lifestyle factors such as diet and avoiding detrimental environmental exposures[70].

Figure 6 Therapeutic targets in genomic medicine. Genomic-exposomic interactions occur in distinct organs, including the liver, affecting gene expression, which may cause chronic disease. SNP: Single-nucleotide polymorphism.

The role of the liver in metabolizing proteins, carbohydrates, and lipids is crucial for health. Genes are essential for expressing enzymes, receptors, and transporters, and gene expression is regulated by genetic variation and dietary (nutritional) factors, which influence the progression of chronic diseases. Specific genetic variants influence taste preferences, such as those for sweet, bitter, salty, or fatty flavors, which can impact dietary behavior. Other genes regulate lipid absorption and transportation (chylomicron formation and lipoprotein metabolism) with dysregulation contributing to atherosclerosis and steatosis in different organs[71]. Identifying these genetic variations enables earlier diagnosis and targeted lifestyle interventions as part of the genomic medicine approach in hepatology.

This framework is especially relevant in Latin America where admixed populations shaped by Amerindian, European, and African ancestries require culturally and genetically tailored healthcare approaches[70]. Studying the evolutionary gene-environment interactions in these populations can uncover unique susceptibility to liver disease. Furthermore, given the diversity of regional food cultures, medical and nutritional interventions need to be tailored accordingly. The following section explains how genomic medicine in hepatology can be effectively applied in Latin American contexts, such as Mexico.

Genomic medicine in hepatology in Mexico

Prevention of obesity and associated comorbidities: From a genomic perspective, the Mexican genome reflects the evolutionary gene-environment interactions that shaped the survival of First Nation (Native Amerindian) peoples in the ancestral regions of Arid America and Mesoamerica[70]. Anthropometric traits, such as skin tone, height, weight, and diet-related gene polymorphisms, have been linked to these biogeographic conditions, thereby defining the population’s phenotypic, genetic, metabolic, and sociocultural profile[72]. Colonization by Europeans and the arrival of enslaved Africans led to genetic and cultural admixture, introducing new foods and culinary traditions that eventually transformed into Mexican cuisine[73].

Until the 1970s, metabolic chronic diseases such as T2DM, MASLD, and cardiovascular disease were rare in Mexico[74]. Instead, infectious diseases and malnutrition predominated, and the diet was primarily traditional and plant-based, centered on beans, corn, squash, nopales, tomatoes, and chili with low sugar intake and small portions due to economic hardship. However, globalization has shifted dietary patterns in which festive foods have become everyday snacks; ultra-processed foods and sugary drinks have proliferated; and physical activity has declined[75,76]. These lifestyle changes, intensified after the Free Trade Agreement, led to a rise in obesity and T2DM, first observed among Amerindian migrants in the United States and later across Mexico[74,76].

Today, the Mexican population faces an evolutionary mismatch. Genes adapted for survival in resource-scarce environments now increase disease risk in an obesogenic environment[78]. Risk alleles, combined with a hepatopathogenic diet, increase the risk of chronic conditions like obesity, T2DM, and MASLD[79]. Preventing or reversing these pathogenic conditions using a genomic medicine approach has been achieved by recommending the genome-based Mexican (GENOMEX) diet, a nutrigenetic clinical trial designed by our research group to normalize anthropometric, metabolic, and behavioral traits[80]. The rationale behind the GENOMEX diet is based on the genetic landscape of the Mexican population and its food culture[73,78,79,81], incorporating traditional Mexican foods rich in nutrients that activate nutrigenomic signaling pathways[71,82]. The GENOMEX diet is also compatible with a sustainable food culture, designed to strengthen local economies and provide a foundation for national dietary guidelines[83] that align with Mexico’s genetic and cultural background, rather than relying on foreign standards, such as the Mediterranean diet[79]. Other nutrigenetic clinical trials have been conducted among the Mexican population, aiming to reduce blood lipids and low-grade inflammation[84].

Prevention of hepatitis viruses: Molecular biology-based laboratory techniques have significantly enhanced diagnostics for infectious diseases, offering greater sensitivity and specificity compared to traditional biochemical and immunological methods[85]. In the case of hepatitis viruses, these advancements were pivotal. Interestingly, the discovery of HBV relied heavily on immunological assays, which facilitated the identification of viral antigens and later supported the development of recombinant DNA vaccines for prevention[86,87]. Unlike HBV, the hepatitis C virus (HCV) was discovered using molecular cloning techniques without prior viral visualization or cultivation. Scientists extracted RNA from the plasma of infected individuals, created complementary DNA libraries, and screened for sequences that triggered immune reactions in patients with non-A, non-B hepatitis[88].

Another key contribution of molecular biology was sequencing the genomes of viral hepatitis A through E, revealing their genetic diversity and differential global distribution. HBV and HCV exhibit high genetic diversity and are classified into genotypes (A-J for HBV, 1-7 for HCV)[89,90]. HBV genotype information is particularly relevant because it enables molecular epidemiology, tracking mutations, understanding resistance mechanisms, and evaluating their impact on liver disease progression. In Latin America, for example, genotype H is predominant in Mexico while genotype F (F1-F4) is distributed across Central and South America. Notably, genotype F1 has been associated with a higher risk of hepatocellular carcinoma than genotype H[91].

Conversely, HCV treatment has improved dramatically due to antiviral drugs targeting specific stages of the viral replication cycle. These therapies have significantly increased cure rates and raised hopes for the eventual eradication of the virus[92,93]. However, due to the high mutation rates of hepatitis viruses, ongoing molecular surveillance remains essential[94]. This feature is key in global migration as it facilitates the spread of non-endemic viral strains[95].

Genomic medicine has significantly deepened our understanding of hepatitis viruses by providing valuable insights into viral evolution, host-pathogen interactions, disease progression, and treatment responses. Together, these genomic approaches provide a robust framework for precision prevention, diagnosis, and treatment, cornerstones of personalized medicine in hepatology.

Prevention of ALD: Unique environmental and genetic factors shape alcohol consumption and related liver disease in Mexico. Alcohol addiction (heavy drinking) has been a public health issue since colonial times and remains so today[96], involving mainly the consumption of beer, fermented beverages, and distilled beverages(spirits)[97]. The country has one of the highest “drinking scores” and mortality rates from ALD globally despite only intermediate per-capita alcohol intake[98]. Various sociobehavioral determinants shape the pattern of consumption, which has been identified in at least three stages: (1) Stage 1, incremental weekend beer consumption; (2) Stage 2, the addition of midweek spirit drinks; and (3) Stage 3, the eventual switch to heavy intake of spirits[99].

Due to the admixture, key alcohol-metabolizing genes (ADH1B, CYP2E1, ALDH2) exhibit significant variation among individuals. These genes can form “risk” or “non-risk” haplotypes that influence alcohol dependence and liver injury. For example, protective alleles like ADH1B*2 or ALDH2*2 are virtually absent in Mexico. In contrast, the CYP2E1c2 risk allele is highly prevalent among certain native groups, likely due to historical exposure to fermented beverages such as “tejuino” and “pulque”[99]. Alongside, the TAS2R38 alanine-valine-valine (AVV) non-taster haplotype and the DRD2/ANKK1 Taq1A polymorphisms associated with brain reward and addiction are considered risk factors for alcohol abuse and ALD[99]. Thus, personalized prevention and treatment will require understanding of the relative distribution of these variants and the specific pattern of alcohol consumption, helping to identify individuals at risk for alcohol-related liver disease and addiction.

TRAINING IN GENOMIC MEDICINE IN HEPATOLOGY

Scientific advances in the early 20^th century, led by European and American researchers were disrupted by World War II. After the war, foundational disciplines such as organic and inorganic chemistry matured, and new fields, including biochemistry, pharmacology, cell biology, and immunology, emerged (Figure 2). These developments led to the creation of new postgraduate programs and the revision of medical curricula, which integrated basic sciences into clinical education. Consequently, medicine heavily emphasized pharmacology and pathophysiology while biochemistry and molecular biology remained underutilized in clinical practice. Furthermore, during that stage, medical genetics focused primarily on single genes and their inheritance, including monogenic disorders, mutations, and Mendelian traits, which appear at early stages of life. However, the turning point was the advent of molecular biology in medicine and the emergence of genomic medicine, fields linking molecular mechanisms to clinical outcomes. Unlike genetics, genomics encompasses the holistic and integrative analysis of the genome, including the regulation of gene expression, epigenetic modifications, and gene-gene and gene-exposome interactions that influence complex diseases (Figure 7). This shift highlights the need to update educational programs at all levels, encouraging health sciences students to adopt a preventative, genomic-informed approach to healthcare.

Figure 7 From medical genetics to genomics. Transition from conventional medical genetics, primarily focused on rare, monogenic disorders manifesting in childhood, toward genomics, which addresses complex, polygenic conditions prevalent in adulthood.

The renovation of hepatology training is essential to align with the paradigm shift toward prevention and precision medicine. Historically, hepatology has been integrated into gastroenterology training with an emphasis on the management of cirrhosis, liver failure, and liver transplantation[100,101]. However, the increasing understanding of the molecular and genetic underpinnings of liver diseases demands a broader, more forward-looking educational approach. Reorienting hepatology towards early detection and prevention strategies, integrating genomic medicine to address chronic liver diseases before they progress to irreversible stages is warranted[102]. Future hepatologists will require competencies in genomics, molecular diagnostics, and personalized therapeutic interventions. Training pathways should begin at the undergraduate level, incorporating genomic literacy into medical curricula and extending through specialty and doctoral programs that foster research skills in liver pathophysiology and public health[103]. Moreover, due to workforce shortages in hepatology, there is a necessity for expanded and diversified training models[104,105].

Developing a new generation of hepatologists who are proficient in genomics, exposomics, and preventive care is imperative for addressing the global rise in liver-related morbidity and mortality. In particular, the liver should be a primary focus in medical specialties, given its crucial role in the development and management of chronic diseases. A dedicated specialty in Hepatology with a genomic medicine perspective is urgently needed[106], especially considering the growing burden of obesity-related morbidities, such as MASLD, T2DM, liver cirrhosis, cardiovascular, and renal diseases. Finally, new postgraduate programs in Genomic Medicine are essential for generating national evidence, supporting preventive strategies, and developing clinical guidelines tailored to the unique genetic and cultural characteristics of Latin American populations[70].

PERSPECTIVES

Scientific advancements over the centuries have continually propelled the progress of medicine, and with the emergence of genomic medicine, this trajectory has entered a transformative phase. Genomic medicine applies genetic insights in clinical settings to enhance disease prevention, facilitate early diagnosis, and enable more effective and personalized treatments. Unlike conventional medicine, which often focuses on managing complications or late-stage conditions, genomic medicine emphasizes proactive, personalized care.

A fundamental component of this approach is the necessity for each society to analyze its population’s unique genetic makeup and cultural context. However, genomic research continues to be disproportionately concentrated on populations of European descent, limiting the global applicability of findings and perpetuating health disparities. This concern is particularly acute in underrepresented regions, such as Latin America, Asia, and Africa, which collectively face significant health burdens and remain excluded from much of global genomic research[107,108].

Latin America, despite its rich human genetic diversity, is markedly underrepresented in global genomic studies. Although the region accounts for over 8% of the world’s population and bears a significant burden of chronic diseases, it contributes only about 1.3% to global genomic datasets[107,109]. This underrepresentation poses a threat to the development of accurate and effective prevention and treatment strategies tailored to the genetic and environmental profiles of these populations.

To address this gap, several initiatives have emerged throughout the region, including the Mexican Biobank Project, the GLAD Project, and the Latin American Genomics Consortium, which aim to collect regional genetic data and establish biobanks[110-113]. Nevertheless, further efforts are necessary to build more inclusive genomic databases, promote ethical community engagement, and enhance local research capacities.

In Mexico, despite taking steps forward[114], genomic medicine knowledge remains largely derived from candidate gene associations with disease. Large-scale clinical or interventional trials in genomic medicine in hepatology, incorporating genetic findings into healthcare practice, are virtually nonexistent or in their early stages[70]. This situation must be urgently reversed through sustained investment, strategic policy support, and interdisciplinary collaboration to ensure the equitable realization of genomic medicine’s promise in improving public health[61,115].

Likewise, African countries face underrepresentation in global genomic studies despite their rich genetic diversity and the challenges their populations face in addressing health issues that can be mitigated by incorporating genomic data into clinical practice[116,117]. For example, it is well known that individuals of African ancestry have a higher risk of developing nephrotic conditions. Therefore, applying this approach could lead to more effective public health policies tailored to African populations as well as to Mexican subpopulations with a higher proportion of African genetic ancestry. Interest in genomic medicine in Africa is advancing through a combination of local initiatives, international collaborations, and strategic investments[118-120].

Expanding genomic research globally is not only a scientific imperative but also a matter of health equity. Ensuring that diverse populations are adequately represented in genomic studies is crucial for developing precision medicine strategies that are effective, inclusive, and culturally sensitive[121]. Achieving this goal requires stronger international collaboration, investment in local research capacity, and the implementation of policies that respect both genetic diversity and cultural contexts.

Nonetheless, critical barriers, such as limited funding, restricted access to genomic technologies, ethical and regulatory complexities, and fragmented research infrastructure in low-income and middle-income countries, continue to impede progress. Without deliberate efforts to address these issues, genomic medicine may risk widening health disparities instead of reducing them[122,123].

CONCLUSION

Understanding how genomic traits and the exposome contribute to the development of prevalent chronic conditions is crucial for creating region-based biobanks, establishing national biochemical reference values, and developing national clinical practice guidelines, rather than relying on data extrapolated from unrelated populations. This framework lays the foundation for personalized and precision medicine in the Mexican context. In this landscape the liver stands out as a central organ due to its role in regulating numerous genes essential for maintaining metabolic balance and overall health.

Genomic medicine in hepatology aims to understand liver function and prevent chronic liver dysfunctions associated with metabolic disorders, such as dyslipidemia, hyperglycemia, and hyperinsulinemia, which are linked to T2DM, cardiovascular diseases, and renal diseases, by integrating genetic and environmental information. Updating and redesigning educational curricula across health sciences, including medicine and nutrition, is essential to support this paradigm shift. These changes will modernize academic training and provide the basis for innovative programs in genomic medicine, equipping future professionals with the skills needed to implement this transformative approach. Such educational reforms are crucial to reducing the incidence and complications of chronic diseases while lowering regional healthcare costs and improving patient outcomes.

Finally, addressing the genomic data gap is critical for Latin America, Africa, Southeast Asia, and Native territories where distinct genome-exposome architectures and interplay may influence disease susceptibility. We advocate for greater international collaboration and investment in inclusive genomic research to mitigate disparities and promote equity in precision medicine.

ACKNOWLEDGEMENTS

Leonardo Leal-Mercado, Juan P Cardenas-Benitez, Irene M Mariscal-Martinez are recipients of CONAHCYT (Mexico) scholarships as doctoral students of the PhD Program of Molecular Biology in Medicine, Health Sciences Center, University of Guadalajara.