Genetic, metabolic and environmental factors involved in the development of liver cirrhosis in Mexico

Abstract

Liver cirrhosis (LC) is a chronic illness caused by inflammatory responses and progressive fibrosis. Globally, the most common causes of chronic liver disease include persistent alcohol abuse, followed by viral hepatitis infections and nonalcoholic fatty liver disease. However, regardless of the etiological factors, the susceptibility and degree of liver damage may be influenced by genetic polymorphisms that are associated with distinct ethnic and cultural backgrounds. Consequently, metabolic genes are influenced by variable environmental lifestyle factors, such as diet, physical inactivity, and emotional stress, which are associated with regional differences among populations. This Topic Highlight will focus on the genetic and environmental factors that may influence the metabolism of alcohol and nutrients in the setting of distinct etiologies of liver disease. The interaction between genes and environment in the current-day admixed population, Mestizo and Native Mexican, will be described. Additionally, genes involved in immune regulation, insulin sensitivity, oxidative stress and extracellular matrix deposition may modulate the degree of severity. In conclusion, LC is a complex disease. The onset, progression, and clinical outcome of LC among the Mexican population are influenced by specific genetic and environmental factors. Among these are an admixed genome with a heterogenic distribution of European, Amerindian and African ancestry; a high score of alcohol consumption; viral infections; a hepatopathogenic diet; and a high prevalence of obesity. The variance in risk factors among populations suggests that intervention strategies directed towards the prevention and management of LC should be tailored according to such population-based features.

Early detection of liver damage in Mexican patients with chronic liver disease

“…[3,4,25] In contrast, among the developing countries, LC is stable or has risen, and the diagnosis is mainly performed in the advanced stages of disease when clinical complications are present. [9,10] Notably, in this study, the early detection of liver fibrosis (F1-F3) using TE was possible in one-third of the total cases. Likewise, the diagnosis of LC, both clinically and by TE, was confirmed in one third of the cases and the etiologies were ALD, followed by HCV and NASH.…”

“…[4,7] This pattern of drinking may explain why the prevalence and mortality rate of cirrhosis due to ALD in Mexico have not significantly declined, remaining as the highest in Latin America. [2,10] Furthermore, these individuals commonly do not seek medical advice until the disease has reached advanced stages of clinical complications.…”

“…Besides, in health institutions, LC is often diagnosed at end stages when clinical complications are already present, such as variceal bleeding, encephalopathy, and ascites. [9] Since the course of disease may be influenced by genetic and environmental risk factors, [10] it is important that the causes and degree of liver damage be detected at early stages.…”

The Significance of Vitamin D Receptor Gene Polymorphisms for Susceptibility to Hepatocellular Carcinoma in Subjects Infected with Hepatitis C Virus

“…The pathogenic mechanisms of genetic factors [gene polymorphisms of cytokines, growth factors, and receptors] relating chronic HCV to HCC development are not entirely well established [20]. VDR gene polymorphisms have been described in several chronic liver diseases such as liver cirrhosis [21], autoimmune hepatitis [22], primary sclerosing cholangitis [23] and primary biliary cirrhosis [24]. Moreover, it has been reported that there is a significant association between polymorphisms of VDR gene and the occurrence of HCC in alcoholic liver cirrhosis in Caucasian subjects [25], in HBV-infected patients [26] and even in patients with chronic HCV [27].…”

Association of Lactase Persistence Genotypes with High Intake of Dairy Saturated Fat and High Prevalence of Lactase Non-Persistence among the Mexican Population

“…This association was later confirmed when we evaluated the influence of the frequency of dairy intake on several parameters, since subjects consuming milk and dairy products daily or frequently had a significantly higher intake of SFAs than those who consumed these products occasionally or never. This diet high in SFAs has been associated with pathophysiological processes involved in hepatic steatosis and insulin resistance [42] that can eventually lead to inflammation, dyslipidemia and fibrosis [43]. …”