A study conducted 15-year ago showed that only 13.5% of chronic alcoholics developed alcohol-induced liver damage, which misled some people to believe a lack of relationship between the amount of alcohol and the occurrence of liver disease. However, it is true that a significant correlation exists between per capita consumption and the prevalence of cirrhosis. Alcoholic fatty liver is observed in most of chronic alcoholics even though the severity is not uniform. Abstinence remains the cornerstone of therapy for alcoholic liver disease (ALD). There is also consensus for the use of corticosteroids and pentoxifylline in severe alcoholic hepatitis maintaining good nutritional status to treat comorbidities in all forms of ALD, and liver transplantation in the end-stage ALD patients who can stop drinking for 6 months pre-transplantation period. Several clinical trials targeting tumor necrosis factor (TNF-alpha) and reducing oxidative stress have not been successful at this time. There is still a large field of alcohol research to explore in order to go farther in the area of pathophysiology. We need to understand a role of various cytokines and immune cells in the development of ALD to have more treatment tools to cope with ALD.
Alcohols/metabolism ; Cytochrome P-450 CYP2E1/metabolism ; Fatty Liver, Alcoholic/pathology/therapy ; Humans ; Liver Cirrhosis, Alcoholic/pathology/therapy ; Liver Diseases, Alcoholic/*etiology/pathology/therapy ; Oxidative Stress

Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Hypoglycemic Agents/therapeutic use* ; Liver Cirrhosis/pathology* ; Biopsy ; Patients ; Liver/pathology* ; Fibrosis

Along with the aging process, the spectrum of liver disease changes greatly. Nonalcoholic fatty liver disease (NAFLD) in elderly people lead to low liver function and is also the major cause of extrahepatic diseases, such as cardiovascular disease and malignant tumor. This review provides an overview of the morphological structure and function of the liver in aged people, and discusses the characteristics of weakness, malnutrition and limited movement in the elderly, as well as the current status of multiple diseases and multiple drug use. Finally, this article puts forward some appropriate regimens for the diagnosis and treatment of NAFLD in elderly people to provide a reference for clinical practice.
Aged ; Cardiovascular Diseases ; Humans ; Liver ; pathology ; Malnutrition ; Neoplasms ; Non-alcoholic Fatty Liver Disease ; diagnosis ; pathology ; therapy ; Risk Factors

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the "mucus layer-soil" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between "mucus layer-soil" and "gut bacteria-seed" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the "gut bacteria-seed". However, a lack of effective repair and management of the "mucus layer-soil" may be a reason why "seeds" cannot be well colonized and grow in the host gut, as the thinning and destruction of the "mucus layer-soil" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that "mucus layer-soil" restoration combined with "gut bacteria-seed" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.
Humans ; Non-alcoholic Fatty Liver Disease/therapy* ; Gastrointestinal Microbiome ; Probiotics ; Prebiotics ; Fecal Microbiota Transplantation ; Bacteria ; Liver/pathology*

OBJECTIVETo investigate the fat decreasing effects of fenofibrate on alcoholic fatty liver and drug-induced fatty liver in rats.

METHODSAlcoholic fatty liver and drug-induced fatty liver rats models were established. The two kinds of rats with fatty liver were seperatedly divided into fenofibrate treatment group (80 mg/kg daily) and control group without treatment. Rats were killed after four weeks, then the levels of serum triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and malondialdehyde (MDA), hepatic lipase (HL), lipoprotein lipase (LPL) both in serum and liver tissue were measured according to the Test Kits. Histopathological changes in liver was dyed with HE and observed under light microscope.

RESULTSAfter treatment by fenofibrate, in the serum of rats with alcoholic fatty liver, the level of TG decreased significantly (1.07 mmol/L 0.06 mmol/L vs 1.56 mmol/L 0.29 mmol/L, t=5.115, p<0.001), while the level of TC had no alteration. The levels of MDA both in serum and liver tissue decreased (1.10 nmol/L 0.22 nmol/L vs 1.26 nmol/L 0.21 nmol/L, t=0.592, p<0.05; 5.92 nmol/g 1.24 nmol/g vs 7.42 nmol/g 1.22 nmol/g, t=3.477, p<0.05, respectively), while the levels of HL, LPL in serum and liver tissue increased significantly (Serum: 0.053muEq/ml/h 0.006muEq/ml/h vs 0.037 muEq/ml/h 0.006muEq/ml/h, t=-5.086, p<0.001; 0.018 muEq/ml/h 0.004 muEq/ml/h vs 0.014muEq/ml/h 0.004muEq/ml/h, t=-2.485, p<0.05. Liver tissue: 0.075muEq/ml/h 0.010muEq/ml/h vs 0.065muEq/ml/h 0.007muEq/ml/h, t=-2.437, p<0.05; 0.022 muEq/ml/h 0.014 muEq/ml/h vs 0.008 muEq/ml/h 0.002 muEq/ml/h, t=-2.876, p<0.05). Fat content in liver decreased (26.01 mg/g 1.69 mg/g vs 71.45 mg/g 2.66 mg/g, t=-43.224, p<0.001). The pathological changes of liver in fenofibrate-treated rats with alcoholic fatty liver were improved. For the drug-induced fatty liver rats, fenofibrate treatment group had no difference from the untreated control group.

CONCLUSIONFenofibrate can significantly decrease the fat content in liver tissue of rats with alcoholic fatty liver, as well as ameliorating liver pathological changes. But fenofibrate has no effect on drug-induced fatty liver.

Animals ; Carbon Tetrachloride ; toxicity ; Fatty Liver ; chemically induced ; drug therapy ; pathology ; Fatty Liver, Alcoholic ; blood ; drug therapy ; pathology ; Fenofibrate ; therapeutic use ; Hypolipidemic Agents ; therapeutic use ; Lipids ; blood ; Liver ; pathology ; Male ; Rats ; Rats, Wistar

OBJECTIVETo observe the effects of curcumin derivative on non-alcoholic steatohepatitis (NASH).

METHODS60 SD male rats were randomly divided into 5 groups. The NASH model was induced by high fat diet combined with carbon tetrachloride. These rats were then treated with curcumin and curcumin derivative, saline treating group as control. The serum biochemical parameters and liver histological examinations were observed. The TNF alpha, NF-kappa B and HMG-CoA reductase mRNA transcriptions of liver tissue were detected with RT-PCR. The protein expressions of TNF alpha and NF-kappa B were detected by western blot.

RESULTSCompared with the saline group, A remarkable reduction was observed in serum ALT (U/L), AST (U/L) and TC (mmol/L) in rats treated with curcumin derivatives [(69.20 +/- 27.58) vs (102.43 +/- 47.29), (158.00 +/- 39.15) vs (229.50 +/- 105.20) and (2.08 +/- 0.30) vs (2.58 +/- 1.02), P < 0.05]. The degrees of fibrosis were significantly alleviated; Compared with curcumin group, liver index and serum ALT, AST of curcumin derivative group were also significantly decreased [(4.88 +/- 0.62) vs (5.16 +/- 0.61); (69.20 +/- 27.58) vs (82.5 +/- 33.23); (158.00 +/- 39.15) vs (211.75 +/- 106.30), P < 0.05]; The liver steatosis and inflammation grade were also significantly improved .The gene transcriptions of TNF alpha, NF-kappa B and HMG-CoA reductase in curcumin derivative group were significantly lower than those in curcumin and saline group (P < 0.05).

CONCLUSIONThese results indicate that the water-soluble curcumin derivative displays superior bioavailability to the parent curcumin, which can effectively improve the lipid metabolism and delay the progression of hepatic fibrosis in rats with steatohepatitis.

Animals ; Curcumin ; therapeutic use ; Fatty Liver ; drug therapy ; metabolism ; pathology ; Hydroxymethylglutaryl CoA Reductases ; metabolism ; Liver ; metabolism ; pathology ; Male ; NF-kappa B ; metabolism ; Non-alcoholic Fatty Liver Disease ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Objective To explore the potential targets of triclosan in the treatment of nonalcoholic fatty liver disease(NAFLD) and to provide new clues for the future research on the application of triclosan. Methods The targets of triclosan and NAFLD were obtained via network pharmacology.The protein-protein interaction network was constructed with the common targets shared by triclosan and NAFLD.The affinity of triclosan to targets was verified through molecular docking.Gene ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were carried out to analyze the key targets and the potential mechanism of action.NAFLD model was established by feeding male C57BL/6J mice with high-fat diet for 12 weeks.The mice were randomly assigned into a model group and a triclosan group [400 mg/(kg·d),gavage once a day for 8 weeks].The hematoxylin-eosin(HE) staining was used for observation of the pathological changes and oil red O staining for observation of fat deposition in mouse liver.Western blotting was employed to detect the protein level of peroxisome proliferator-activated receptor alpha(PPARα) in the liver tissue. Results Triclosan and NAFLD had 34 common targets,19 of which may be the potential targets for the treatment,including albumin(ALB),PPARα,mitogen-activated protein kinase 8(MAPK8),and fatty acid synthase.Molecular docking predicted that ALB,PPARα,and MAPK8 had good binding ability to triclosan.KEGG pathway enrichment showcased that the targets were mainly enriched in peroxisome proliferator-activated receptor signaling pathway,in which ALB and MAPK8 were not involved.Triclosan alleviated the balloon-like change and lipid droplet vacuole,decreased the lipid droplet area,and up-regulated the expression level of PPARα in mouse liver tissue. Conclusion PPARα is a key target of triclosan in the treatment of NAFLD,which may be involved in fatty acid oxidation through the peroxisome proliferator activated receptor signaling pathway.
Animals ; Liver/pathology* ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Network Pharmacology ; Non-alcoholic Fatty Liver Disease/drug therapy* ; PPAR alpha/therapeutic use* ; Triclosan/therapeutic use*

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing rapidly with the obesity and diabetes mellitus epidemics. It is rapidly becoming the most common cause of liver disease worldwide. NAFLD can progress to serious complications such as cirrhosis, hepatocellular carcinoma and death. Therefore, it is important to recognise this condition so that early intervention can be implemented. Lifestyle modifications and strict control of metabolic risk factors are the mainstay of treatment. As disease progression is slow in the majority of NAFLD patients, most can be managed well by primary care physicians. NAFLD patients with advanced liver fibrosis should be referred to specialist care for further assessment.
Carcinoma, Hepatocellular ; pathology ; Diet ; Disease Progression ; Humans ; Life Style ; Liver ; pathology ; Liver Cirrhosis ; pathology ; Liver Neoplasms ; pathology ; Metabolic Syndrome ; complications ; Non-alcoholic Fatty Liver Disease ; diagnosis ; therapy ; Obesity ; complications ; Prevalence ; Risk Factors ; Treatment Outcome

The prevalence of non-alcoholic fatty liver disease (NAFLD) is estimated to be 25-30% of the population, and is the most common cause of elevated liver enzymes in Korea. NAFLD is a "hot potato" for pharmaceutical companies. Many clinical trials are underway to develop a first-in-class drug to treat NAFLD. However, there are several challenging issues regarding the diagnosis of NAFLD. Currently, liver biopsy is the gold standard method for the diagnosis of NAFLD and steatohepatitis. Ideally, globally recognized standards for histological diagnosis and methods to optimize observer agreement on biopsy interpretation should be developed. Liver biopsy is the best method rather than a perfect one. Recently, multi-parametric magnetic resonance imagery can estimate the amount of intrahepatic fat successfully and is widely used in clinical trials. But no diagnostic method can discriminate between steatohepatitis and simple steatosis. The other unresolved issue in regard to NAFLD is the absence of satisfactory treatment options. Vitamin E and obeticholic acid have shown protective effects in randomized controlled trials, but this drug has not been approved for use in Korea. This study will provide a description of diagnostic methods and treatments that are currently recommended for NAFLD.
Biomarkers/analysis ; Chenodeoxycholic Acid/analogs & derivatives/therapeutic use ; Clinical Trials as Topic ; Fatty Liver/diagnosis ; Fibrosis ; Humans ; Liver/diagnostic imaging/pathology ; Magnetic Resonance Imaging ; Non-alcoholic Fatty Liver Disease/*diagnosis/drug therapy ; Tomography, X-Ray Computed ; Ultrasonography ; Vitamin E/therapeutic use

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome