The Changing Face of the Diagnosis of Chronic and Malignant Liver Diseases: Potential New Biomarkers.

The early diagnosis of primary sclerosing cholangitis, hepatocellular carcinoma, and cholangiocarcinoma is often challenging. In a recent study in 134 patients (Arbelaiz, Hepatology 2017; 66:1125-1143), it was reported that specific proteins found in serum extracellular vesicles of patients with primary sclerosing cholangitis, hepatocellular carcinoma,orcholangiocarcinomamay be useful as noninvasive diagnostic and prognostic tools. This current article critically appraises this study.

More Evidence for the Genetic Susceptibility of Mexican Population to Nonalcoholic Fatty Liver Disease through PNPLA3.

BACKGROUND: The gene for patatin-like phospholipase domain containing 3 (PNPLA3) is associated with nonalcoholic fatty liver disease (NAFLD) development. We previously found that Mexican indigenous population had the highest frequency reported of the PNPLA3 148M risk allele. Further, we observed a relationship between M148M genotype with elevated ALT levels in individuals with normal weight, overweight and obese. We sought to investigate whether PNPLA3 polymorphism is associated with NAFLD development in Mexicans. MATERIAL AND METHODS: We enrolled 189 Mexican patients with NAFLD and 201 healthy controls. Anthropometric, metabolic, and biochemical variables were measured, and rs738409 (Ile148Met substitution) polymorphism was genotyped by sequencing. RESULTS: Logistic regression analysis, using a recessive model, suggested that PNPLA3 polymorphism in Mexican population is significantly associated (OR = 1.711, 95% CI: 1.014-2.886; P = 0.044) with NAFLD. CONCLUSIONS: The PNPLA3 gene is associated with NAFLD in Mexican population. More studies are required to explain the high prevalence of PNPLA3 polymorphism in Mexican-Americans, Mexican-Indians, and Mexican-Mestizos.

Thrombosis of the Portal Venous System in Cirrhotic vs. Non-Cirrhotic Patients.

INTRODUCTION AND AIM: Thrombosis is a vascular disorder of the liver often associated with significant morbidity and mortality. Cirrhosis is a predisposing factor for portal venous system thrombosis. The aim of this study is to determine differences between cirrhotics and non-cirrhotics that develop thrombosis in portal venous system and to evaluate if cirrhosis severity is related to the development of portal venous system thrombosis. MATERIAL AND METHODS: We studied patients diagnosed with portal venous system thrombosis using contrast-enhanced computed tomography scan and doppler ultrasound at Medica Sur Hospital from 2012 to 2017. They were categorized into two groups; cirrhotics and non-cirrhotics. We assessed the hepatic function by Child-Pugh score and model for end-stage liver disease. RESULTS: 67 patients with portal venous system thrombosis (25 with non-cirrhotic liver and 42 with cirrhosis) were included. The mean age (± SD) was 65 ± 9.5 years in cirrhotic group and 57 ± 13.2 years (p = 0.009) in non-cirrhotic group. Comparing non-cirrhotics and cirrhotics, 8 non-cirrhotic patients showed evidence of extra-hepatic inflammatory conditions, while in the cirrhotic group no inflammatory conditions were found (p < 0.001). 27 (64.29%) cirrhotic patients had thrombosis in the portal vein, while only 9 cases (36%) were found in non-cirrhotics (p = 0.02). CONCLUSIONS: In cirrhotic patients, hepatocellular carcinoma and cirrhosis were the strongest risk factors to develop portal venous system thrombosis. In contrast, extrahepatic inflammatory conditions were main risk factors associated in non-cirrhotics. Moreover, the portal vein was the most frequent site of thrombosis in both groups.

New Aspects of Lipotoxicity in Nonalcoholic Steatohepatitis.

NASH is becoming increasingly common worldwide because of the growing global prevalence of obesity and consequently NAFLD. Unfortunately, the mechanism of progression of NAFLD to NASH and then cirrhosis is not completely understood. Several factors, including insulin resistance, inflammation, oxidative stress, lipotoxicity, and bile acid (BA) toxicity, have been reported to be associated with NASH progression. The release of fatty acids from dysfunctional and insulin-resistant adipocytes results in lipotoxicity, which is caused by the ectopic accumulation of triglyceride-derived toxic metabolites and the subsequent activation of inflammatory pathways, cellular dysfunction, and lipoapoptosis. Adipose tissue (AT), especially visceral AT, comprises multiple cell populations that produce adipokines and insulin-like growth factor, plus macrophages and other immune cells that stimulate the development of lipotoxic liver disease. These biomolecules have been recently linked with many digestive diseases and gastrointestinal malignancies such as hepatocellular carcinoma. This made us question what role lipotoxicity has in the natural history of liver fibrosis. Therefore, this review focuses on the close relationship between AT and NASH. A good comprehension of the pathways that are related to dysregulated AT, metabolic dysfunction, and hepatic lipotoxicity will result in the development of prevention strategies and promising therapeutics for patients with NASH.

The Role of the Gut Microbiota in Bile Acid Metabolism.

The gut microbiota has been considered a cornerstone of maintaining the health status of its human host because it not only facilitates harvesting of nutrients and energy from ingested food, but also produces numerous metabolites that can regulate host metabolism. One such class of metabolites, the bile acids, are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. These bioconversions modulate the signaling properties of bile acids through the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate diverse metabolic pathways in the host. In addition, bile acids can regulate gut microbial composition both directly and indirectly by activation of innate immune response genes in the small intestine. Therefore, host metabolism can be affected by both microbial modifications of bile acids, which leads to altered signaling via bile acid receptors, and by alterations in the composition of the microbiota. In this review, we mainly describe the interactions between bile acids and intestinal microbiota and their roles in regulating host metabolism, but we also examine the impact of bile acid composition in the gut on the intestinal microbiome and on host physiology.

Bile Acids in Nonalcoholic Fatty Liver Disease: New Concepts and therapeutic advances.

Nonalcoholic liver disease (NAFLD) is a major emerging health burden that is a common cause of illness and death worldwide. NAFLD can progress into nonalcoholic steatohepatitis (NASH) which is a severe form of liver disease characterized by inflammation and fibrosis. Further progression leads to cirrhosis, which predisposes patients to hepatocellular carcinoma or liver failure. The mechanism of the progression from simple steatosis to NASH is unclear. However, there are theories and hypothesis which support the link between disruption of the bile acids homeostasis and the progression of this disorder. Previous studies have been demonstrated that alterations to these pathways can lead to dysregulation of energy balance and increased liver inflammation and fibrosis. In this review, we summarized the current knowledge of the interaction between BA and the process related to the development of NAFLD, besides, the potential targets for novel therapies.

The Role of the Gut Microbiota in Bile Acid Metabolism.

The gut microbiota has been considered a cornerstone of maintaining the health status of its human host because it not only facilitates harvesting of nutrients and energy from ingested food, but also produces numerous metabolites that can regulate host metabolism. One such class of metabolites, the bile acids, are synthesized from cholesterol in the liver and further metabolized by the gut microbiota into secondary bile acids. These bioconversions modulate the signaling properties of bile acids through the nuclear farnesoid X receptor and the G protein-coupled membrane receptor 5, which regulate diverse metabolic pathways in the host. In addition, bile acids can regulate gut microbial composition both directly and indirectly by activation of innate immune response genes in the small intestine. Therefore, host metabolism can be affected by both microbial modifications of bile acids, which leads to altered signaling via bile acid receptors, and by alterations in the composition of the microbiota. In this review, we mainly describe the interactions between bile acids and intestinal microbiota and their roles in regulating host metabolism, but we also examine the impact of bile acid composition in the gut on the intestinal microbiome and on host physiology.

Dyslipidemia as a risk factor for liver fibrosis progression in a multicentric population with non-alcoholic steatohepatitis.

Background: Nonalcoholic fatty liver disease (NAFLD) is a serious worldwide health problem, with an estimated global prevalence of 24%; it has a notable relationship with other metabolic disorders, like obesity and type 2 diabetes mellitus (T2DM). Nonalcoholic steatohepatitis (NASH) is one of the most important clinical entities of NAFLD, which is associated with an increased risk of progression to liver cirrhosis and hepatocellular carcinoma (HCC). Mexico is one of the countries with the highest prevalence of metabolic diseases; therefore, we sought to investigate the impact that these clinical entities have in the progression to advanced fibrosis in Mexican patients with NASH. Methods: We performed a multicenter retrospective cross-sectional study, from January 2012 to December 2017. A total of 215 patients with biopsy-proven NASH and fibrosis were enrolled. NASH was diagnosed according NAS score and liver fibrosis was staged by the Kleiner scoring system. For comparing the risk of liver fibrosis progression, we divided our sample into two groups. Those patients with stage F0-F2 liver fibrosis were included in the group with non-significant liver fibrosis (n=178) and those individuals with F3-F4 fibrosis were included in the significant fibrosis group (n=37). We carried out a multivariate analysis to find risk factors associated with liver fibrosis progression. Results: From the 215 patients included, 37 had significant liver fibrosis (F3-4). After logistic regression analysis T2DM (p=0.044), systemic arterial hypertension (p=0.014), cholesterol (p=0.041) and triglycerides (p=0.015) were the main predictor of advanced liver fibrosis. Conclusions: In a Mexican population, dyslipidemia was the most important risk factor associated with advanced liver fibrosis and cirrhosis.

Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis in HIV infection: a metabolic approach of an infectious disease.

INTRODUCTION: With the successes of antiretroviral therapy, patients infected with human immunodeficiency virus (HIV) living longer. Regarding this, the common diseases of HIV population (i.e., opportunistic infections) are now losing ground in front of metabolic alterations. This phenomenon is related to the delay in progression to acquired immune deficiency syndrome (AIDS), making it so that patients live in a chronic inflammatory state which, combined with other mechanisms such infectious ones, cause metabolic diseases. Areas covered: Considering a high prevalence of metabolic alterations, the relationship between metabolic syndrome (MetS) with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and liver diseases as a major cause of death in the HIV-infected population, this paper aims to overview the mechanisms and prevalence of NAFLD and NASH as they relate to the developed metabolic diseases of HIV patients. Expert opinion: The pathways underlying MetS include the effects of HIV and ART on the liver, adipose tissue, and muscle. These mechanisms result in liver damage, consequently leading to NAFLD and its more severe form NASH. These conditions have increased in HIV-infected population in recent years and since their life expectancy is improving it is important to be ready to attend their new emerging diseases.

Gastroenteritis in an adult female revealing hemolytic uremic syndrome: Case report.

Nowadays acute gastroenteritis infection caused by Escherichia coli (E. coli) O157:H7 is frequently associated with hemolytic uremic syndrome (HUS), which usually developed after prodromal diarrhea that is often bloody. The abdominal pain accompanied by failure kidney is a suspicious symptom to develop this disorder. Their pathological characteristic is vascular damage which manifested as arteriolar and capillary thrombosis with abnormalities in the endothelium and vessel walls. The major etiological agent of HUS is enterohemorragic (E coli) strain belonging to serotype O157:H7. The lack of papers about HUS associated to gastroenteritis lead us to report this case for explain the symptoms that are uncommon. Furthermore, this report provides some strategies to suspect and make an early diagnosis, besides treatment approach to improving outcomes and prognosis for patients with this disorder.

Current trends of liver cirrhosis in Mexico: Similitudes and differences with other world regions.

AIM: To investigate the main current etiologies of cirrhosis in Mexico. METHODS: We performed a cross-sectional retrospective multicenter study that included eight hospitals in different areas of Mexico. These hospitals provide health care to people of diverse social classes. The inclusion criteria were a histological, clinical, biochemical, endoscopic, or imaging diagnosis of liver cirrhosis. Data were obtained during a 5-year period (January 2012-December 2017). RESULTS: A total of 1210 patients were included. The mean age was 62.5 years (SD = 12.1), and the percentages of men and women were similar (52.0% vs 48.0%). The most frequent causes of liver cirrhosis were hepatitis C virus (HCV) (36.2%), alcoholic liver disease (ALD) (31.2%), and nonalcoholic steatohepatitis (23.2%), and the least frequent were hepatitis B virus (1.1%), autoimmune disorders (7.3%), and other conditions (1.0%). CONCLUSION: HCV and ALD are the most frequent causes of cirrhosis in Mexico. However, we note that non-alcoholic fatty liver disease (NAFLD) as an etiology of cirrhosis increased by 100% compared with the rate noted previously. We conclude that NAFLD will soon become one of the most frequent etiologies of liver cirrhosis in Mexico.