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Background: Alcohol-related chronic liver disease (ALD) and its complications are major causes of morbidity and mortality. Predisposing factors for ALD include the amount, type, duration of alcohol consumption, patient’s genetic predisposition, race, sex, and other comorbid conditions. Aims: To study the dose, duration, and type of alcohol consumption in ALD and the effect of these parameters on severity and outcome Methods: This was a prospective study conducted at the Department of Gastroenterology, SMS hospital, Jaipur, between December 2017 to December 2018. All patients with alcoholic liver disease admitted in the department were consecutively enrolled. Data relating to dose, duration, type, alcohol intake pattern, biochemical, ultrasonographic, and clinical parameters were analysed. Results: One hundred ten patients (age 43.5±9.9, all-male) were studied. Mean alcohol consumption was 130.47±35.37gm/day. Sixty-three (57.3%) patients consumed <120gm, 25(22.7%) between 120-239gm, while 22(20%) patients consumed =240gm of alcohol per day. The mean duration of alcohol consumption was 15.89±6.57 years. Fifty-nine (53.63%) patients consumed country-made spirit, 25 (22.72%) branded spirit, 23 (20.91%) mixed or variable type, while three (2.73%) patients consumed only wine. The occurrence of hepatic encephalopathy (HE) was significantly associated with dose (p <0.001) and type (p <0.001) of alcohol consumption. MELD Na score significantly correlated (r=0.48, p <0.001) with dose of alcohol. Conclusion: Our study found a dose-dependent relationship of alcohol intake with hepatic encephalopathy and MELD-Na score. The incidence of ALD did not change with the type of alcohol consumed. Low lymphocyte counts were significantly associated with dose and duration of alcohol intake.
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Alcoholic fatty liver disease (AFLD) is the first step to wards alcoholic liver disease (ALD). A beffer knowledge of AFLD will contribute to the prevention and therapy of ALD. It has been found that the occurrence and development of AFLD mainly involve the pathways of cytochrome P450 (CYP2E1),peroxisome proliferator-activated receptor α(PPARα),sterol regulatory element-binding proteins (SREBPs),AMP-activated protein kinase(AMPK),sirtuin 1(SIRT1),adiponectin and insulin.This review focuses on the importance of PPARα,SREBPs and AMPK pathway in alcoholic steatosis.It's reported that alcohol and its metabolite acetaldehyde inhibit PPARα and AMPK,and activate SREBP protein directly or indirectly,leading to liver lipid metabolic disorders,reducing the ability of fatty acid oxidation,causing lipid accumulation, and eventually inducing AFLD. Additionally, this review outlines the prospect of a therapeutics of AFLD targetting PPARα,SREBPs and AMPK.
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Chronic alcohol consumption is a leading cause of chronic liver diseases worldwide, resulting in cirrhosis and hepa-tocellular carcinoma. Almost all heavy drinkers develop fatty liv-er, but only 20% ~40% of them develop more severe forms of alcoholic liver diseases such as alcoholic hepatitis and alcoholic fibrosis, and the underlying mechanisms that contribute to the disease progression remain largely unknown. The animal models which can mimic human alcoholic liver diseases are very neces-sary tools for better understanding and exploring the therapy strat-egy of the disease. Currently, the most widely used models for alcoholic liver injury are Lieber-DeCarli model, Tsukamoto-French model, Gao-binge model and others. Here we summarize the recent advances in animal models recapitulating different fea-tures and etiologies of human alcoholic liver diseases. These ani-mal models will be very useful for the mechanism study of alco-holic liver diseases and further new therapeutic drug screening.
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Objective To discuss the clinical value of aspartate aminotransferase mitochondrial isoenzyme(m‐AST ) in serum to alcoholic liver diseases .Methods 61 cases of patients with alcoholic liver diseases and 60 cases of patients with nonalcoholic fatty liver disease in our hospital from Jan 2015 to Dec 2015 were selected as research subjects ,and 60 cases healthy volunteers in the same period were selected as control group ,and then their venous blood samples were collected .ELISA was used to detect the levels of aspartate aminotransferase mitochondrial isoenzyme (m‐AST ) ,aspartate amino transferase (AST ) ,alanine aminotransferase (ALT) and gamma glutamyltransferase (GGT) in serum ,the differences between patients and volunteers were compared .Results The levels of m‐AST ,AST ,ALT and GGT in group A and group B were significantly higher than those in healthy control group (P<0 .05);After 3 months treatment ,the difference of m‐AST ,AST ,ALT and GGT in patients with fatty liver ,viral hepatitis and liver cirrhosis was significant(P<0 .05);The positive rate of m‐AST were significantly higher than other index(P<0 .05) .Conclu‐sion The detection of m‐AST is significance to diagnosis and treatment for alcoholic liver diseases .
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The consumption of alcohol causes several liver-associated diseases all over the world. Alcoholic liver diseases (ALD) include hepatic inflammation, fatty liver, hepatitis, liver cirrhosis and fibrosis and finally hepatocellular carcinoma. Although the cellular, metabolic and biochemical mechanisms for these diseases are quite explicable, the roles of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are still under investigation. The present review describes the roles and regulation of MMPs and TIMPs in different ALDs along with the involvement of other pathways. This review also summarizes the present knowledge on clinical and experimental trials with different antioxidants that help against alcohol associated liver diseases.
Subject(s)
Antioxidants/pharmacology , Cytoprotection/drug effects , Inflammation/complications , Liver Diseases, Alcoholic/complications , Liver Diseases, Alcoholic/enzymology , Liver Diseases, Alcoholic/pathology , Liver Diseases, Alcoholic/prevention & control , Matrix Metalloproteinases/metabolismABSTRACT
Objective To characterize the effects of Sanchi on the alcoholic hepatopathy rats.Methods 70 SD male rats were randomly divided into five groups:normal group(n=10),control group(n=15),high-dose Sanchi group(n=15),low-dose Sanchi group(n=15),and Tiopronin group(n=15).In order to induce alcoholic hepatopathy,animals in the control,high-dose and low dose Sanchi,and Tiopronin groups were orally dosed with HongXing ErGuoTou(56% ethanol;5g/kg),corn oil(2ml/kg),and pyrazole(27.2 mg/kg)every morning for 14 weeks.Rats in high-dose Sanchi,low dose Sanchi,and Tiopronin groups,were treated every afternoon during the 14-week induction of hepatopathy,with 1.2g/kg Sanchi,0.6g/kg,and 100mg/kg Tiopronin,respectively.All rats were sacrificed 12 hours following the last injection.Blood samples were obtained prior to euthanization.Blood-fat and serum lipoidase activity were measured using an automatic blood biochemical analyzer.Blood haluronic acid(HA),laminin(LN)were determined by ELISA.Histopathological changes of hepatic tissues(i.e.steatosiss,inflammation,and fibrosis)were assessed by microscopic examination of HE and Masson staining of the right lobe of livers.Results Compared with rats from the normal group(treated with ddH2O),rats in the control group have significantly higher steatosis,inflammation,liver fibrosis,and increased level of serum cholesterol,HDL-C,LDL-C,haluronic acid,laminin and AST/ALT activity,(P0.05).More importantly,treatment with high-dose,low-dose Sanchi,or Tiopronin resulted in less severe steatosis,inflammation,fibrosis in the liver,and reduced the levels of serum haluronic acid,laminin(P0.05).Conclusions(1)Daily dosing of alcohol,corn oil,and pyrozole for 14 weeks faithfully replicated the alcoholic hepatopathy symptoms observed in the ALD model,such as hepatic steatosis,immune cell infiltration,blood-fat disturbance,increase in serum AST/ALT activity,and liver fibrosis.(2)Sanchi can significantly alleviate the symptoms in the alcoholic hepatopathy rats including steatosis,improve hepatic function and fibrosis.
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BACKGROUND/AIMS: Increased intestinal permeability has been possible contributing factors to the pathogenesis of alcoholic liver disease. Moreover, it can contribute to the development of bacterial infection and intestinal endotoxemia in patients with liver cirrhosis. This study aimed to examine the difference of intestinal barrier dysfunction between alcoholic and viral liver disease patients through the comparison of the intestinal permeabilities of patients with clinical characteristics. METHODS: Intestinal permeabilities were measured in 18 healthy controls, 41 patients with alcoholic liver disease (17 cases of alcoholic liver disease without cirrhosis and 24 cases of alcoholic liver cirrhosis) and 46 patients with viral liver disease (14 cases of chronic viral hepatitis and 32 cases of viral liver cirrhosis) by measuring 24 hour urine excretion of 51Cr-EDTA. RESULTS: The intestinal permeability was significantly increased in the patients with alcoholic liver disease without cirrhosis (5.62 +/- 2.80%), alcoholic liver cirrhosis (5.29 +/- 2.48%) and viral liver cirrhosis (3.15 +/- 1.39%) compared with that in control subjects (1.99 +/- 0.53%). On the contrary, it was not increased in the patients with chronic viral hepatitis (2.05 +/- 0.57%) versus controls. The significant correlation was not found between intestinal permeability and clinical and laboratory findings. CONCLUSIONS: The intestinal permeability was elevated in patients with alcoholic liver disease compared to those with viral liver cirrhosis. The pathophysiology of liver injury secondary to intestinal epithelial damage may be different between alcoholic and viral liver diseases.