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BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered the most common chronic liver disease worldwide. NAFLD is related to changes in lipid metabolism and is characterized by the increase or accumulation of fat in hepatocytes that may progress to nonalcoholic steatohepatitis (NASH), which leads to the appearance of inflammatory processes. Treatment consists of changes in diet, physical activity, and weight control; however, these disorders represent a health problem and require the development of novel alternatives to treatment and prevention. NAFLD/NASH are strongly associated with other disorders, such as metabolic syndrome (MetS); in fact, NAFLD is considered the hepatic manifestation of MetS. These disorders are related to other components of MetS, including dyslipidemia, which is characterized by an imbalance in blood cholesterol and triglyceride levels. Prebiotics and probiotics benefit from treating and preventing several ailments, including liver diseases. Specifically, in dyslipidemia, NAFLD, and NASH, probiotics play a fundamental role in conducting the biotransformation of primary bile acids into secondary bile acids, which generally have important activity as immunomodulators and metabolism regulators. The mechanisms of action of pre and probiotics involve the activity of bile acid receptors, such as FXR and TGR-5, and the events resulting from their activation. Therefore, prebiotics and probiotics may be reasonable options to prevent and treat metabolic- related liver diseases.

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Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). In the present study, we demonstrate that the combination of IUGR and fructose treatment during adulthood also results in increased hepatic myeloperoxidase (MPO) activity, AKT phosphorylation and serum aspartate transaminase. Growth-restricted rats also presented reduced hepatic TRIB3 and GADD45a after fructose treatment. Other markers of cell proliferation, such as Cyclin D, PCNA, Hgf and Hspa4/Hsp70 expression and the number of Ki-67 positive cells, were all increased in the liver of growth- restricted rats treated with fructose. On the other hand, the combination of IUGR and fructose treatment during adult life reduced the levels of IGF-1. In conclusion, our data indicate that after exposure to fructose, adult rats subjected to dexamethasone-induced IUGR display exacerbated molecular changes in markers of NASH and HCC.

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Non-alcoholic fatty liver disease (NAFLD) is a complex and heterogeneous disorder considered a liver-damaging manifestation of metabolic syndrome. Its prevalence has increased in the last decades due to modern-day lifestyle factors associated with overweight and obesity, making it a relevant public health problem worldwide. The clinical progression of NAFLD is associated with advanced forms of liver injury such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). As such, diverse pharmacological strategies have been implemented over the last few years, principally focused on metabolic pathways involved in NAFLD progression. However, a variable response rate has been observed in NAFLD patients, which is explained by the interindividual heterogeneity of susceptibility to liver damage. In this scenario, it is necessary to search for different therapeutic approaches. It is worth noting that chronic low-grade inflammation constitutes a central mechanism in the pathogenesis and progression of NAFLD, associated with abnormal composition of the intestinal microbiota, increased lymphocyte activation in the intestine and immune effector mechanisms in liver. This review aims to discuss the current knowledge about the role of the immune response in NAFLD development. We have focused mainly on the impact of altered gut-liver-microbiota axis communication on immune cell activation in the intestinal mucosa and the role of subsequent lymphocyte homing to the liver in NAFLD development. We further discuss novel clinical trials that addressed the control of the liver and intestinal immune response to complement current NAFLD therapies.

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Modifications in the microbiota caused by environmental and genetic reasons can unbalance the intestinal homeostasis, deregulating the host's metabolism and immune system, intensifying the risk factors for the development and aggravation of non-alcoholic fat liver disease (NAFLD). The use of probiotics, prebiotics and synbiotics have been considered a potential and promising strategy to regulate the gut microbiota and produce beneficial effects in patients with liver conditions. For this reason, this review aimed to evaluate the effectiveness of probiotics, prebiotics, and symbiotics in patients with NAFLD and NASH. Pubmed, Embase, and Cochrane databases were consulted, and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines were followed. The clinical trials used in this study demonstrated that gut microbiota interventions could improve a wide range of markers of inflammation, glycemia, insulin resistance, dyslipidemia, obesity, liver injury (decrease of hepatic enzymes and steatosis and fibrosis). Although microbiota modulators do not play a healing role, they can work as an important adjunct therapy in pathological processes involving NAFLD and its spectrums, either by improving the intestinal barrier or by preventing the formation of toxic metabolites for the liver or by acting on the immune system.

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Nonalcoholic fatty liver disease (NAFLD) pathogenesis is explained by the complex relationship among diet and lifestyle-predisposing factors, the genetic variance of the nuclear and mitochondrial genome, associated phenotypic traits, and the yet not fully explored interactions with epigenetic and other environmental factors, including the microbiome. Despite the wealth of knowledge gained from molecular and genome-wide investigations in patients with NAFLD, the precise mechanisms that explain the variability of the histological phenotypes are not fully understood. Earlier studies of the gut microbiota in patients with NAFLD and nonalcoholic steatohepatitis (NASH) provided clues on the role of the fecal microbiome in the disease pathogenesis. Nevertheless, the composition of the gut microbiota does not fully explain tissue-specific mechanisms associated with the degree of disease severity, including liver inflammation, ballooning of hepatocytes, and fibrosis. The liver acts as a key filtration system of the whole body by receiving blood from the hepatic artery and the portal vein. Therefore, not only microbes would become entrapped in the complex liver anatomy but, more importantly, bacterial derived products that are likely to be potentially powerful stimuli for initiating the inflammatory response. Hence, the study of liver tissue microbiota offers the opportunity of changing the paradigm of host-NAFLD-microbial interactions from a "gut-centric" to a "liver-centric" approach. Here, we highlight the evidence on the role of liver tissue bacterial DNA in the biology of NAFLD and NASH. Besides, we provide evidence of metagenomic findings that can serve as the seed of further hypothesis-raising studies as well as can be leveraged to discover novel therapeutic targets.

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INTRODUCTION: Laparoscopic bariatric surgery (LBS) in liver end-stage organ disease has been proven to improve organ function and patients' symptoms. A series of LBS in patients with cirrhosis have shown good results in weight loss, but increased risk of complications. Current literature is based on clinical series. This paper aims to compare LBS (69% gastric bypass) between patients with cirrhosis and without cirrhosis. METHODS: We conducted a retrospective 1:3 matched case-control study including bariatric patients with cirrhosis and without cirrhosis. Demographics, operative variables, postoperative complications, long-term weight loss, and comorbidity resolution were compared between groups. RESULTS: Sixteen Child A patients were included in the patients with cirrhosis (PC) group and 48 in patients without cirrhosis (control) group. Mean age was 50 years; preoperative BMI was 39 ± 6.8 kg/m2. Laparoscopic gastric bypass and laparoscopic sleeve gastrectomy were performed in 69% and 31%, respectively. Follow-up was 81% at 2 years for both groups. PC group had a higher rate of overall (31% vs. 6%; p < 0.05) and severe (Clavien-Dindo ≥ III; 13% vs. 0%; p = 0.013) complications than that of the control group. Mean %EWL of PC at 2 years of follow-up was 84.9%, without differences compared with that of the control group (83.1%). Comorbidity remission in PC was 14%, 50%, and 85% for hypertension, type 2 diabetes, and dyslipidemia, respectively. Patients without cirrhosis had a higher resolution rate of hypertension (65% vs. 14%, p = 0.03). CONCLUSION: LBS is effective for weight loss and comorbidity resolution in patients with obesity and Child A liver cirrhosis. However, these results are accompanied by significantly increased risk of complications.

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Non-alcoholic steatohepatitis (NASH) is considered the advanced stage of non-alcoholic fatty liver disease (NAFLD). It is characterized by liver steatosis, inflammation and different degrees of fibrosis. Although the exact mechanisms by which fatty liver progresses to NASH are still not well understood, innate and adaptive immune responses seem to be essential key regulators in the establishment, progression, and chronicity of these disease. Diet-induced lipid overload of parenchymal and non-parenchymal liver cells is considered the first step for the development of fatty liver with the consequent organelle dysfunction, cellular stress and liver injury. These will generate the production of pro-inflammatory cytokines, chemokines and damage-associated molecular patterns (DAMPs) that will upregulate the activation of Kupffer cells (KCs) and monocyte-derived macrophages (MMs) favoring the polarization of the tolerogenic environment of the liver to an immunogenic phenotype with the resulting transdifferentiation of hepatic stellate cells (HSCs) into myofibroblasts developing fibrosis. In the long run, dendritic cells (DCs) will activate CD4+ T cells polarizing into the pro-inflammatory lymphocytes Th1 and Th17 worsening the liver damage and inflammation. Therefore, the objective of this review is to discuss in a systematic way the mechanisms known so far of the immune and non-proper immune liver cells in the development and progression of NASH.

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The post antiretroviral therapy (ART) era for human immunodeficiency virus (HIV) infection resulted in a dramatically increased proportion of deaths attributed to liver-related causes in patients with HIV treated with ART. Additionally, as patients become older as a result of effective ART, liver-related conditions and application of safe therapies are now major concerns in the setting of HIV infection.

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La obesidad es el factor que más se asocia a la esteatohepatitis no alcohólica (EHNA). La cirugía bariátrica ha demostrado ser eficaz en la EHNA y junto con el tratamiento de la diabetes mellitus tipo 2 (DMT2) y la dislipidemia, logran una mejoría en las alteraciones de las enzimas hepáticas y de los cambios ecográficos hepáticos. Objetivo: Analizar el efecto de la cirugía bariátrica en pacientes con índice de masa corporal (IMC) ≥ 35 kg/m2 y EHNA. Método: se hizo una investigación retrospectiva de 20 pacientes sometidos a cirugía bariátrica: bypass gástrico en Y de Roux (BPGYR) y gastrectomía vertical (GV) entre 2014 y 2015. Resultados: De los 20 pacientes, 14 fueron intervenidas de BPGYR y 6 de GV; 95% fueron del sexo femenino, con edad promedio de 35,95 ± 8,54 años. Los valores preoperatorios de aspartato aminotransferasa (AST) y alanino aminotransferasa (ALT) de todos los pacientes fue > 30 U/L. Los valores postoperatorios de AST y ALT al año de la cirugía fueron normales en 85% y 80% de los casos respectivamente. No se observaron alteraciones en los niveles pre y postoperatorios de lactato deshidrogenasa (LDH). Todos los pacientes presentaron infiltración grasa hepática moderada la cual se redujo a leve o sin infiltración grasa al año de la cirugía de acuerdo a la evaluación ecográfica. Conclusiones: La cirugía bariátrica demostró tener un impacto favorable en EHNA dado por la mejoría en los niveles de AST, ALT y de la esteatosis hepática corroborada por controles ecográficos(AU)

Obesity is the factor that is most associated with non-alcoholic steatohepatitis (NASH). Bariatric surgery has been shown to be effective in NASH and, along with treatment of type 2 diabetes (T2D) and dyslipidemia, they achieve a significant improvement in liver enzymes and liver ultrasound changes. Objective: To analyze the effect of bariatric surgery in patients with a body mass index (BMI) > 35 kg/m2 and NASH. Method: It was performed a retrospective investigation of 20 patients who underwent bariatric surgery: Roux-en-Y gastric bypass (RYGBP) or sleeve gastrectomy (SG) between 2014 and 2015. Results: Of the 20 patients, 14 underwent BPGYR and 6 GV; 95% were female, with a mean age of 35.95 ± 8.54 years. The preoperative levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) for all patients were >30 U/L. Postoperative levels of AST and ALT one year after surgery were normal in 85% and 80% of cases, respectively. No alterations were observed in pre and postoperative levels of lactate dehydrogenase (LDH). All patients presented moderate hepatic fat infiltration which was reduced to mild or without fat infiltration one year after surgery according to the ultrasonographic evaluation. Conclusions: Bariatric surgery was shown to have a favorable impact on NASH due to the improvement observed in AST and ALT levels, and hepatic steatosis corroborated by ultrasound scans(AU)

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Introducción: la cirrosis es la condición médica final de diversas enfermedades hepáticas de carácter progresivo, con una prevalencia variable de un país a otro; en la actualidad, el abuso de alcohol, el hígado graso no alcohólico y las hepatitis crónicas virales son mencionados como sus principales causas. En nuestros centros no se dispone de estudios clínicos en relación con esta enfermedad. Materiales y métodos: estudio retrospectivo y descriptivo de pacientes con diagnóstico de cirrosis hepática entre el 1 de enero del 2010 al 31 de marzo del 2014. Se realizó revisión de historias clínicas. Resultados: la serie incluyó 419 pacientes, 50,1% mujeres y 49,9% hombres, con una edad promedio de diagnóstico de cirrosis de 63 años; el 73% de los pacientes presentaban hallazgos de hepatopatía crónica en el examen físico y el 27% tenía un examen físico normal. Las principales etiologías en esta serie fueron: esteatohepatitis no alcohólica (25,5%), alcohólica (14,8%), infección por virus C (14,6%), autoinmunidad (10%), esteatohepatitis no alcohólica más alcohol (6,7%), y otras (14,6%). La clasificación de Child-Pugh se pudo calcular en 394 pacientes y de estos, el 59,1%, 32,4% y 8,3% eran A, B y C, respectivamente. En relación con las descompensaciones, las principales fueron ascitis (36,1%), sangrado variceal (28,4%) y hepatocarcinoma (15,3%). Conclusiones: el comportamiento epidemiológico local no difiere en relación con el mundial. Llama la atención su detección en fases tempranas y la NASH como factor etiológico principal.

Introduction: Cirrhosis is the final medical condition of various progressive liver disease. Its prevalence varies from one country to another. Currently alcohol abuse, non-alcoholic fatty liver disease and chronic viral hepatitis are mentioned as the main causes. In our centers we have no clinical studies regarding this disease. Materials and Methods: This is a retrospective, descriptive study of the clinical histories of patients who were diagnosed with liver cirrhosis between January 1, 2010 to March 31, 2014. Results: The study included 419 patients, 50.1% of whom were women and 49.9% of whom were men. The average age at diagnosis of cirrhosis 63 years. 73% of patients had physical findings of chronic liver disease and 27% had normal physical examinations. The main etiologies in this series were nonalcoholic steatohepatitis (25.5%), alcoholic cirrhosis (14.8%), hepatitis C infection (14.6%), autoimmune cirrhosis (10%), nonalcoholic steatohepatitis plus alcohol (6.7%), and others (14.6%). The Child-Pugh classification could be calculated in 394 patients. Of these 59.1% were classified A, 32.4% were classified B, and 8.3% were classified C. The primary reasons for decompensation ascites (36.1%), bleeding varices (28.4%) and hepatocellular carcinoma (15.3%). Conclusions: Local epidemiological behavior does not differ from those found elsewhere in the world. Attention needs to be paid to detection in early stages and NASH as the main etiological factor.

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