IL28B-Gene Polymorphisms (rs12979860) in HCV Liver Parenchymal changes legitimize Screening for SNPs before DAAs Therapy

Background and objective: IL28B-gene polymorphisms show inconclusive relationships with CHCV DAAs-treatment outcomes on evaluation by serum-PCR. Solitary intra-PBMCs HCV-RNA antisense-strands are independently found in naïve and experienced cases regardless to viremia or hepatic-parenchymal changes. We correlated frequencies of IL28B-gene SNPs and alleles with HCV induced liver-changes during SVR evaluation by PBMCs-PCR after DAAs-therapy. Methods: Twelve weeks after completing DAAs-therapy, the impacts of IL28B-gene-SNPs were evaluated in three groups of patients: group-I (n=25) with negative serum and PBMCs HCV-PCR, group-II (n=52) had solitary intra-PBMCs HCV-RNA, and group-III (n=25) had positive serum HCV-RNA. All cases were subjected to IL28B-gene-SNP analyses and correlated with their ultrasonographic liver changes.Results: IL28B-genotyping in post-DAAs-treatment HCV-SVR and viral relapse revealed: a) dominant CC-genotype and C allele in normal hepatic parenchyma in group-I compared to group-II (P=0.0047, 0.0007) and group-III (P=0.0564, 0.000003) b) frequent CT-SNP and T-allele in bright hepatic parenchyma in group-II when compared with group-I (P=0.0077, 0.002 ) and group-III (P=0.0363, 0.0005) c) increased TT-SNP and T-allele frequencies in coarse liver in group-III compared to group-I (P=0.02256, 0.000130) and group-II (P=0.08647, 0.004308). Conclusions: Outcomes of HCV treatment with DAAs are dependent on host IL28B-gene polymorphisms and HCV induced liver changes. SVR is achieved when wild type-CC-genotype and C-allele are dominant in normal hepatic parenchyma; solitary intra-PBMCs-relapse occurs in increased frequency of CT-genotype when liver tissues are fibrotic; serologic-relapse is dominant when TT-genotype and T-allele are frequent in cirrhotic liver. IL28B-gene SNP analyses in relation to hepatic parenchymal changes are recommended before treating CHCV-infection with DAAs.

Differential Effects of ‘Vaping’ on Lipid and Glucose Profiles and Liver Metabolic Markers in Obese Versus Non-obese Mice

Tobacco smoking increases the risk of metabolic disorders due to the combination of harmful chemicals, whereas pure nicotine can improve glucose tolerance. E-cigarette vapour contains nicotine and some of the harmful chemicals found in cigarette smoke at lower levels. To investigate how e-vapour affects metabolic profiles, male Balb/c mice were exposed to a high-fat diet (HFD, 43% fat, 20kJ/g) for 16weeks, and e-vapour in the last 6weeks. HFD alone doubled fat mass and caused dyslipidaemia and glucose intolerance. E-vapour reduced fat mass in HFD-fed mice; only nicotine-containing e-vapour improved glucose tolerance. In chow-fed mice, e-vapour increased lipid content in both blood and liver. Changes in liver metabolic markers may be adaptive responses rather than causal. Future studies can investigate how e-vapour differentially affects metabolic profiles with different diets.

Exercise Intervention Mitigates Pathological Liver Changes in NAFLD Zebrafish by Activating SIRT1/AMPK/NRF2 Signaling

Non-alcoholic fatty liver disease (NAFLD) is a common disease that causes serious liver damage. Exercise is recognized as a non-pharmacological tool to improve the pathology of NAFLD. However, the antioxidative effects and mechanisms by which exercise ameliorates NAFLD remain unclear. The present study conducted exercise training on zebrafish during a 12-week high-fat feeding period to study the antioxidant effect of exercise on the liver. We found that swimming exercise decreased lipid accumulation and improved pathological changes in the liver of high-fat diet-fed zebrafish. Moreover, swimming alleviated NOX4-derived reactive oxygen species (ROS) overproduction and reduced methanedicarboxylic aldehyde (MDA) levels. We also examined the anti-apoptotic effects of swimming and found that it increased the expression of antiapoptotic factor bcl2 and decreased the expression of genes associated with apoptosis (caspase3, bax). Mechanistically, swimming intervention activated SIRT1/AMPK signaling-mediated lipid metabolism and inflammation as well as enhanced AKT and NRF2 activation and upregulated downstream antioxidant genes. In summary, exercise attenuates pathological changes in the liver induced by high-fat diets. The underlying mechanisms might be related to NRF2 and mediated by SIRT1/AMPK signaling.

Effects of dietary aflatoxin on biochemical parameters and histopathology of liver in Matrinxã (Brycon cephalus) and Pacu (Piaractus mesopotamicus) fish

The objective of this study was to evaluate biochemical parameters and histopathology of liver in Matrinxã (Brycon cephalus) and Pacu (Piaractus mesopotamicus) fish chronically exposed to dietary aflatoxins. Fish feed was artificially contaminated with aflatoxins and the treatments were: Control – feed without toxin; Treatment A – feed + 10 μg aflatoxin B1 (AFB1)/kg; Treatment B – feed + 20 μg AFB1/kg; and Treatment C – feed + 50 μg AFB1/kg. Matrinxã and Pacu juvenile fish were placed in tanks for 180 days. Five experimental units per treatment were monthly sampled and submitted to blood collection and removal of hepatic tissue. Thus, twenty blood and liver samples for each species were collected monthly, adding up to 240 samples analysed. To verify biochemical changes, analyses included total proteins, albumin, globulins, aspartate aminotransferase (AST) and alkaline phosphatase (ALP). The hepatic tissue was examined microscopically and the slides presenting histopathological changes were photo-documented. There was effect of treatment (P<0.05) for AST and ALP in Matrinxã, while no effect (P>0.05) was observed in Pacu. A reduction (P<0.05) in AST and ALP values during the time of exposure was observed in all treatments for both species. Fatty degeneration and liver damage were observed for both species in treatments exposed to aflatoxins. Fatty degeneration in Pacu was noticed after 30 days of exposure, while in Matrinxã it was observed after 60 days. Disorganisation of the hepatocyte cord arrangement was also observed in those treatments exposed to aflatoxin, following 90 days of exposure in Matrinxã, and after 60 days in Pacu. Therefore, aflatoxins have little influence on biochemical parameters in the species evaluated. However, exposure to aflatoxins caused liver changes, such as cell death, fatty and hydropic degeneration, thus it could be concluded that both species are susceptible to the toxic effects of long-term exposure to dietary AFB1.

Protective Effects of Rheum Turkestanicum Janischagainst Diethylnitrosamine-Induced Hepatocellular Carcinoma in Rats

Aim of the study Hepatocellular carcinoma (HCC) is common cancer that causes many deaths worldwide. Recent studies have reported anti-cancer effects of R. turkestanicum against various cell lines including leukemia cervical tumor, and breast cancer. In this study, we aimed to identify the effect of R. turkestanicum against diethylnitrosamine (DEN)-induced HCC. Methods Wistar rats were divided into four groups of control, DEN, DEN + 100 mg/kg or 400 mg/kg of hydroethanolic extract of the plant roots. Results After four months, the animals in the DEN group showed HCC foci in the liver, an increase of hepatic lipid peroxidation, attenuation of hepatic antioxidant capacity, an increase of blood liver enzymes (ALT, AST, and ALP), bilirubin, albumin, creatinine, glucose, and reduction of the body weight. The plant extract could decrease the levels of liver enzymes, total bilirubin, direct bilirubin, albumin, urea, and creatinine in the blood. Also, the extract attenuated oxidative stress and improved pathological changes in the liver. Quantitative real-time PCR revealed a decrease in gene expression of Wnt/β-catenin and Akt and an increase in PTEN as the tumor suppressor gene. Conclusion The extract of R. turkestanicum reduced DEN-induced liver changes through inhibiting oxidative stress and attenuating the expression of Wnt/β-catenin and Akt and elevating PTEN expression.

MORPHOLOGICAL CHANGES IN THE LIVER AT DIFFERENT INVASIVE DOSES OF OPHISTORCHIS FELINEUS (RIVOLTA, 1884) IN RODENTS (ORYCTOLAGUS CUNICULUS)

A morphometric study of liver changes at different invasive doses was conducted in rodents (Oryctolagus cuniculus). In a comparative aspect, the thickness of connective tissue formed around the portal tracts and the thickness of cellular infiltrates in the same area were studied at an invasive dose of 100, 50 and 10 metacercariae of Ophistorchis felineus (Rivolta, 1884). The experiment was conducted on sexually mature male rabbits at the age of 6 months, in each observation group of 10 individuals. Clinically healthy animals were infested with Ophistorchis felineus per os metacercariae once. The intermediate stage of the parasite was isolated from a dead fish (ide, Leuciscus idus (Linnaeus, 1758) and dace fish, Leuciscus leuciscus) obtained from the Tom River in Tomsk. The invasion that took place after 1 month was confirmed by a positive analysis of feces for parasite eggs by the Ragaser and KatoMiura methods. The animals were sacrificed after 5 weeks from the period of infestation. Histological preparations of the liver were made, stained with hematoxylin and eosin, according to Van Gieson. Histological preparations were studied by light microscopy with morphometry. The results obtained characterize a twofold change in the morphometric parameters of connective tissue thickness and cellular infiltration around the portal tracts of the liver lobes with an increase in the invasive dose.

Detectability of Liver Steatosis and Fibrosis with Transient Elastography and Controlled Attenuation Parameter in Residents of St. Petersburg

Aim. Estimation of the liver steatosis and fibrosis incidence with transient elastography and the controlled attenuation parameter in residents of St. Petersburg.Materials and methods. A prospective open single-centre population study included history, anthropometric and laboratory data on 318 outpatients aged 24—89 years (mean age 52.6 ± 14.6 years). The degrees of steatosis (assessed with the controlled attenuation parameter as ultrasound amplitude dropdown quantification in liver) and fibrosis were determined with a Fibroscan 502 Touch unit (Echosens, France).Results. Hepatic steatosis of predominantly high degree was revealed in 44.7%, combined fibrosis and steatosis — in 28%; isolated fibrosis of various stage — in 2.5%, no structural changes — in 24.8% individuals. The growth of body mass index and waist circumference significantly correlated in women with pronounced liver changes. Serum transaminase activity increased with more severe liver changes, being statistically significant for aspartic transaminase only.Conclusion. A high incidence of primary liver steatosis and fibrosis in residents of St. Petersburg warrants improved diagnostic algorithms and routine preventive measures. Transient elastography with the controlled attenuation parameter estimation provides a convenient non-invasive screening for hepatic fibrosis and steatosis.

Gut–Liver Axis in Nonalcoholic Fatty Liver Disease: the Impact of the Metagenome, End Products, and the Epithelial and Vascular Barriers

Nonalcoholic fatty liver disease (NAFLD) is a systemic, dynamic, heterogeneous, and multiaxis entity, the pathogenesis of which is still uncertain. The gut–liver axis is regulated and stabilized by a complex network encompassing a metabolic, immune, and neuroendocrine cross-talk between the gut, the microbiota, and the liver. Changes in the gut–liver axis affect the metabolism of lipids and carbohydrates in the hepatocytes, and they impact the balance of inflammatory mediators and cause metabolic deregulation, promoting NAFLD and its progression to nonalcoholic steatohepatitis. Moreover, the microbiota and its metabolites can play direct and indirect roles in gut barrier function and fibrosis development. In this review, we will highlight findings from the recent literature focusing on the gut–liver axis and its relation to NAFLD. Finally, we will discuss the impact of technical issues, design bias, and other limitations on current knowledge of the gut microbiota in the context of NAFLD.