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Review
. 2015 Nov 7;21(41):11552-66.
doi: 10.3748/wjg.v21.i41.11552.

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

Omar Ramos-Lopez  1 , Erika Martinez-Lopez  1 , Sonia Roman  1 , Nora A Fierro  1 , Arturo Panduro  1
Affiliations
Review

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

Omar Ramos-Lopez et al. World J Gastroenterol. .

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.

Keywords: Genomic medicine; Nonalcoholic steatohepatitis; Obesity; Polymorphisms; Risk factors; Viral hepatitis.

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Figures

Figure 1
Figure 1
Stages of liver fibrosis. Liver fibrosis may be evaluated by liver biopsy and non-invasive methods. Regardless of etiological factors, liver fibrosis encompasses 3 stages until the development of cirrhosis. NAFLD: Nonalcoholic fatty liver disease.
Figure 2
Figure 2
Hepatic fibrogenesis. Different etiological factors induce production of several stimuli to HSCs activation. Activated HSCs promote fibrosis and necrosis of hepatocytes. These pathogenic processes can be modulated by genetic polymorphisms involved in each stage of the pathophysiological process. HSC: Hepatic stellate cells; DRD2: Dopamine receptor D2; TAS2R38: Bitter taste receptor; CYP2E1: Cytochrome P450, family 2, subfamily E, polypeptide 1; ALDH2: Aldehyde dehydrogenase 2 family; ADH1B: Alcohol dehydrogenase class I, beta polypeptide; PNPLA3: Patatin-like phospholipase 3; MTTP: Microsome triglyceride transfer protein; PPAR-γ2: Peroxisome proliferator-activated receptors; IL-28B: Interleukin-28B; APOE: Apolipoprotein E; LDLr: Low-density lipoprotein receptor; TGF-β1: transforming growth factor beta 1; COL: Collagenases; MMP: Matrix metalloproteinase; TNF-α: Tumor necrosis factor alpha; NF-κB: Nuclear factor kappa B; ROS: Reactive oxygen species.
Figure 3
Figure 3
Nonalcoholic fatty liver disease pathogenesis. The spectrum of NAFLD includes simple steatosis, NASH, LC and even HCC. Risk factors such as obesity, hepatopathogenic diet, insulin resistance and adipose tissue lipolysis lead to accumulation of triglycerides. This abnormality can stimulate lipotoxicity, ER stress, mitochondria dysfunction and inflammation, promoting fibrosis. Chronic fibrogenesis causes histological changes in the liver that lead to LC, which in turn may evolve to HCC. NAFLD: Nonalcoholic fatty liver disease; NASH: Nonalcoholic steatohepatitis; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; FA: Fatty acids; VLDL: Very low-density lipoprotein; ER: Endoplasmic reticulum.
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