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Sample records for include alcoholic liver

  1. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy.

    Science.gov (United States)

    Yang, Lili; Rozenfeld, Raphael; Wu, Defeng; Devi, Lakshmi A; Zhang, Zhenfeng; Cederbaum, Arthur

    2014-03-01

    Acute alcohol drinking induces steatosis, and effective prevention of steatosis can protect liver from progressive damage caused by alcohol. Increased oxidative stress has been reported as one mechanism underlying alcohol-induced steatosis. We evaluated whether cannabidiol, which has been reported to function as an antioxidant, can protect the liver from alcohol-generated oxidative stress-induced steatosis. Cannabidiol can prevent acute alcohol-induced liver steatosis in mice, possibly by preventing the increase in oxidative stress and the activation of the JNK MAPK pathway. Cannabidiol per se can increase autophagy both in CYP2E1-expressing HepG2 cells and in mouse liver. Importantly, cannabidiol can prevent the decrease in autophagy induced by alcohol. In conclusion, these results show that cannabidiol protects mouse liver from acute alcohol-induced steatosis through multiple mechanisms including attenuation of alcohol-mediated oxidative stress, prevention of JNK MAPK activation, and increasing autophagy. Published by Elsevier Inc.

  2. Liver Transplants for Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    RJ Fingerote

    1991-01-01

    Full Text Available Alcohol related end-stage liver disease is a principal cause of liver failure. The scarcity of donor livers and the predominance of alcohol related end-stage liver disease has raised the issue of including alcoholics as candidates for liver transplantation. In rationalizing the arguments for and against the treatment of alcoholic end-stage liver disease with transplantation, factors such as recidivism, resource allocation and principles of medical practice must be considered. Public confidence in organ transplantation depends on the scientific validity and moral integrity of the policies adopted. Sound policies will prove defensible while policies based on perceptions or prejudices will, in the long run, harm the process.

  3. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Fede, Giuseppe; Germani, Giacomo; Gluud, Christian

    2011-01-01

    Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease.......Randomised clinical trials have addressed the question whether propylthiouracil has any beneficial effects in patients with alcoholic liver disease....

  4. Propylthiouracil for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2002-01-01

    Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease.......Alcohol is the most common cause of liver disease in the Western world today. Randomised clinical trials have addressed the question whether propylthiouracil has any efficacy in patients with alcoholic liver disease....

  5. Pharmacological interventions for alcoholic liver disease (alcohol-related liver disease)

    DEFF Research Database (Denmark)

    Buzzetti, Elena; Kalafateli, Maria; Thorburn, Douglas

    2017-01-01

    Background: Alcohol-related liver disease is due to excessive alcohol consumption. It includes a spectrum of liver diseases such as alcohol-related fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. Mortality associated with alcoholic hepatitis is high. The optimal pharmacological treatment...... of alcoholic hepatitis and other alcohol-related liver disease remains controversial. Objectives: To assess the comparative benefits and harms of different pharmacological interventions in the management of alcohol-related liver disease through a network meta-analysis and to generate rankings of the available...... Citation Index Expanded, World Health Organization International Clinical Trials Registry Platform and randomised controlled trials registers until February 2017 to identify randomised clinical trials on pharmacological treatments for alcohol-related liver diseases. Selection criteria: Randomised clinical...

  6. Folate, alcohol, and liver disease.

    Science.gov (United States)

    Medici, Valentina; Halsted, Charles H

    2013-04-01

    Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of ALD with particular focus on ethanol-induced alterations in methionine metabolism, which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of ALD based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    countries - covering the period 1970-2006 - where both alcohol consumption and liver cirrhosis seem best described as trend-stationary variables. Therefore a fixed effects model including individual trends is applied in the analysis but also a more flexible non-linear functional form with fewer restrictions...... on the relationship between liver cirrhosis mortality and alcohol consumption is included. The conclusion is that the total level of alcohol consumption as well as the specific beverages - beer, wine and spirits - contributes to liver cirrhosis mortality, but the present study also reveals that directly addressing...... the question of panel unit roots and in this case subsequently applying a trend-stationary modeling methodology reduces the estimates of the impacts from alcohol consumption to liver cirrhosis. Finally, more restrictive alcohol policies seem to have positively influenced the country-specific development...

  8. Alcoholic hepatitis: appropriate indication for liver transplantation?

    Science.gov (United States)

    Schneekloth, Terry D; Niazi, Shehzad K; Simonetto, Douglas A

    2017-12-01

    The majority of liver transplantation centers have required patients with alcohol-induced liver disease to demonstrate a period of abstinence (generally 6 months' duration) to qualify for transplant listing. This requirement has excluded patients with alcoholic hepatitis from transplant consideration. Since 2011, several studies have examined the outcomes of patients undergoing liver transplantation with brief abstinence as a lifesaving intervention for alcoholic hepatitis. This review includes each of the recent studies and discusses their implications for general transplant practice. A Medical Literature Analysis and Retrieval System search revealed five published studies - three prospective and two retrospective - pertaining to liver transplantation for alcoholic hepatitis. Among patients with medication-nonresponsive alcoholic hepatitis, those who underwent transplantation had superior survival. Liver recipients with alcoholic hepatitis had comparable survival to those with 6 or more months of abstinence. Their relapse rates were not statistically different in the short term over those transplanted with longer abstinence, although some patients in each prospective cohort relapsed to drinking despite narrow inclusion criteria and extensive pretransplant staff reviews and posttransplant surveillance. Liver transplantation is a reasonable treatment consideration for highly selective cases of alcoholic hepatitis. Further research is needed to refine inclusion criteria, address posttransplant relapse prevention interventions, and monitor long-term outcomes.

  9. Acetaldehyde Adducts in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Mashiko Setshedi

    2010-01-01

    Full Text Available Chronic alcohol abuse causes liver disease that progresses from simple steatosis through stages of steatohepatitis, fibrosis, cirrhosis, and eventually hepatic failure. In addition, chronic alcoholic liver disease (ALD, with or without cirrhosis, increases risk for hepatocellular carcinoma (HCC. Acetaldehyde, a major toxic metabolite, is one of the principal culprits mediating fibrogenic and mutagenic effects of alcohol in the liver. Mechanistically, acetaldehyde promotes adduct formation, leading to functional impairments of key proteins, including enzymes, as well as DNA damage, which promotes mutagenesis. Why certain individuals who heavily abuse alcohol, develop HCC (7.2–15% versus cirrhosis (15–20% is not known, but genetics and co-existing viral infection are considered pathogenic factors. Moreover, adverse effects of acetaldehyde on the cardiovascular and hematologic systems leading to ischemia, heart failure, and coagulation disorders, can exacerbate hepatic injury and increase risk for liver failure. Herein, we review the role of acetaldehyde adducts in the pathogenesis of chronic ALD and HCC.

  10. COMPLICATIONS OF ALCOHOLIC LIVER DISEASE AND DIAGNOSTIC MARKERS

    Directory of Open Access Journals (Sweden)

    Milena Ilić

    2011-12-01

    Full Text Available Alcoholism is one of the leading diseases affecting people’s health and immunity worldwide. Nearly 30 thousand people in the USA die from chronic liver damage. The liver is the central organ in the metabolism of alcohol. Alcohol is primarily a hepatotoxic agent. Hepatotoxicity of alcohol is clinically manifested by the development of alcoholic fatty liver, alcoholic hepatitis and alcoholic cirrhosis. It is characterized by appropriate symptomatology, depending on the degree of liver damage. Excessive use of alcohol for a long period of time, along with malnutrition, genetic and ethnic predisposition, leads to alcoholic cirrhosis and the development of its complications. Portal hypertension damages other organs and organ systems, causing hepatopulmonary syndrome, hepatorenal syndrome, hepatic encephalopathy, spontaneous bacterial peritonitis, etc. For these reasons, alcoholism reduction is given priority, as well as reduction of morbidity and mortality of people with alcoholic chronic liver damage. Therefore, early diagnosis of alcohol abuse is necessary, as well as timely diagnosis of different degrees of alcoholic liver damage. The diagnosis of chronic alcoholic liver damage is set on the basis of confirmed data of alcohol consumption; liver function test (serum markers aminotransferase, gammaglutamyl transferase, prothrombin time, serum bilirubin and albumin level; serum markers of liver fibrosis. Fibrosis markers are directly involved in sedimentation and dissolution of extracellular matrix, i.e. in the process of fibrogenesis and fibrinolysis of liver tissues. They include markers and enzymes of metabolism, as well as cytokines and chemokines.

  11. Alcoholic Liver Disease and Malnutrition

    OpenAIRE

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2011-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepat...

  12. Acute alcohol-induced liver injury

    Directory of Open Access Journals (Sweden)

    Gavin Edward Arteel

    2012-06-01

    Full Text Available Alcohol consumption is customary in most cultures and alcohol abuse is common worldwide. For example, more than 50% of Americans consume alcohol, with an estimated 23.1% of Americans participating in heavy and/or binge drinking at least once a month. A safe and effective therapy for alcoholic liver disease (ALD in humans is still elusive, despite significant advances in our understanding of how the disease is initiated and progresses. It is now clear that acute alcohol binges not only can be acutely toxic to the liver, but also can contribute to the chronicity of ALD. Potential mechanisms by which acute alcohol causes damage include steatosis, dysregulated immunity and inflammation and altered gut permeability. Recent interest in modeling acute alcohol exposure has yielded new insights into potential mechanisms of acute injury, that also may well be relevant for chronic ALD. Recent work by this group on the role of PAI-1 and fibrin metabolism in mediating acute alcohol-induced liver damage serve as an example of possible new targets that may be useful for alcohol abuse, be it acute or chronic.

  13. Diagnosis of alcohol misuse and alcoholic liver disease among ...

    African Journals Online (AJOL)

    Introduction: Uganda is among the top ten consumers of alcohol worldwide though there is little data on alcohol related liver disease. We describe alcohol use, alcohol misuse, and alcoholic liver disease among adults at the emergency admission service of a large urban hospital in Uganda. Methods: All adults who ...

  14. Pediatric Non-alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Uppal, Vikas; Mansoor, Sana; Furuya, Katryn N

    2016-05-01

    Childhood obesity has reached epidemic proportions, and by 2012, more than one third of American children were overweight or obese. As a result, increasingly, children are developing complications of obesity including liver disease. In fact, non-alcoholic fatty liver disease is the most common form of chronic liver disease seen in children today. Recently, there has been a burgeoning literature examining the pathogenesis, genetic markers, and role of the microbiome in this disease. On the clinical front, new modalities of diagnosing hepatic steatosis and hepatic fibrosis are being developed to provide non-invasive methods of surveillance in children. Lastly, the mainstay of treatment of pediatric non-alcoholic fatty liver disease (NAFLD) has been largely through lifestyle interventions, namely, dieting and exercise. Currently, there are a number of clinical trials examining novel lifestyle and drug therapies for NAFLD that are registered with the US National Institutes of Health ClinicalTrials.gov website.

  15. Health and economic benefits of reducing sugar intake in the USA, including effects via non-alcoholic fatty liver disease: a microsimulation model

    Science.gov (United States)

    Vreman, Rick A; Goodell, Alex J; Rodriguez, Luis A; Porco, Travis C; Lustig, Robert H; Kahn, James G

    2017-01-01

    Objectives Excessive consumption of added sugars in the human diet has been associated with obesity, type 2 diabetes (T2D), coronary heart disease (CHD) and other elements of the metabolic syndrome. Recent studies have shown that non-alcoholic fatty liver disease (NAFLD) is a critical pathway to metabolic syndrome. This model assesses the health and economic benefits of interventions aimed at reducing intake of added sugars. Methods Using data from US National Health Surveys and current literature, we simulated an open cohort, for the period 2015–2035. We constructed a microsimulation model with Markov chains for NAFLD (including steatosis, non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC)), body mass index, T2D and CHD. We assessed reductions in population disease prevalence, disease-attributable disability-adjusted life years (DALYs) and costs, with interventions that reduce added sugars consumption by either 20% or 50%. Findings The model estimated that a 20% reduction in added sugars intake will reduce prevalence of hepatic steatosis, NASH, cirrhosis, HCC, obesity, T2D and CHD. Incidence of T2D and CHD would be expected to decrease by 19.9 (95% CI 12.8 to 27.0) and 9.4 (95% CI 3.1 to 15.8) cases per 100 000 people after 20 years, respectively. A 20% reduction in consumption is also projected to annually avert 0.767 million (M) DALYs (95% CI 0.757M to 0.777M) and a total of US$10.3 billion (B) (95% CI 10.2B to 10.4B) in discounted direct medical costs by 2035. These effects increased proportionally when added sugars intake were reduced by 50%. Conclusions The decrease in incidence and prevalence of disease is similar to results in other models, but averted costs and DALYs were higher, mainly due to inclusion of NAFLD and CHD. The model suggests that efforts to reduce consumption of added sugars may result in significant public health and economic benefits. PMID:28775179

  16. Alcoholic Liver Disease and Malnutrition

    Science.gov (United States)

    McClain, Craig J.; Barve, Shirish S.; Barve, Ashutosh; Marsano, Luis

    2013-01-01

    Malnutrition, both protein energy malnutrition (PEM) and deficiencies in individual nutrients, is a frequent complication of alcoholic liver disease (ALD). Severity of malnutrition correlates with severity of ALD. Malnutrition also occurs in patients with cirrhosis due to etiologies other than alcohol. The mechanisms for malnutrition are multifactorial, and malnutrition frequently worsens in the hospital due to fasting for procedures and metabolic complications of liver disease, such as hepatic encephalopathy. Aggressive nutritional support is indicated in inpatients with ALD, and patients often need to be fed through an enteral feeding tube to achieve protein and calorie goals. Enteral nutritional support clearly improves nutrition status and may improve clinical outcome. Moreover, late-night snacks in outpatient cirrhotics improve nutritional status and lean body mass. Thus, with no FDA-approved therapy for ALD, careful nutritional intervention should be considered as frontline therapy. PMID:21284673

  17. Influence of unrecorded alcohol consumption on liver cirrhosis mortality

    OpenAIRE

    Lachenmeier, Dirk W; Monakhova, Yulia B; Rehm, Jürgen

    2014-01-01

    Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unre...

  18. Influence of unrecorded alcohol consumption on liver cirrhosis mortality.

    Science.gov (United States)

    Lachenmeier, Dirk W; Monakhova, Yulia B; Rehm, Jürgen

    2014-06-21

    Unrecorded alcohol includes illegally distributed alcohol as well as homemade or surrogate alcohol which is unintended for consumption by humans (e.g., cosmetics containing alcohol). The highest unrecorded alcohol consumption occurs in Eastern Europe and some of these countries have an over proportional liver cirrhosis mortality. Compounds besides ethanol have been hypothesized as being responsible for this observation. On the other hand, chemical investigations were unable to prove that unrecorded alcohol regularly contains contaminants above toxicological thresholds. However, illegally produced spirits regularly contain higher percentages of alcohol (above 45% by volume), but for considerably less costs compared with licit beverages, potentially causing more problematic patterns of drinking. In this review, it is investigated whether patterns of drinking rather than product composition can explain the liver cirrhosis mortality rates. Statistical examination of World Health Organization country data shows that the originally detected correlation of the percentage of unrecorded alcohol consumption and liver cirrhosis mortality rates disappears when the data is adjusted for the prevalence of heavy episodic drinking. It may be concluded that there is currently a lack of data to demonstrate causality between the composition of illicit spirits (e.g., higher levels of certain contaminants in home-produced products) and liver toxicity on a population scale. Exceptions may be cases of poisoning with antiseptic liquids containing compounds such as polyhexamethyleneguanidine, which were reported to be consumed as surrogate alcohol in Russia, leading to an outbreak of acute cholestatic liver injury, histologically different from conventional alcoholic liver disease.

  19. Alcohol consumption and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    regarding per capita consumption of wine among the European countries. Also for the total consumption of alcohol, i.e. the per capita consumption of beer, wine and spirits, the hypothesis of convergence seems to hold. In the same time span the number of alcohol related diseases as e.g. liver diseases, have...... changed significantly in the same direction as the developments in alcohol consumption. The changes in the consumption levels of alcohol in general -- and wine in particular -- are influenced by many factors of which health arguments may have played a crucial role. The alcohol policies of the European...... countries have become more restrictive during the last decades. Using data on alcohol consumption, alcohol related diseases and alcohol policies of 16 European countries we discuss the questions of whether the intake of alcohol is associated with (liver) diseases. Our empirical analysis provides us...

  20. Liver scintigraphic features associated with alcoholism

    International Nuclear Information System (INIS)

    Drum, D.E.; Beard, J.O.

    1978-01-01

    The relationships between scintigraphic features and clinical alcoholism were studied by review of 2406 liver scintiphotos. Two distinct patterns were significantly associated with alcoholism: heterogeneous distribution of radiocolloid in the liver, and jointly increased uptake of tracer by the spleen and vertebral bone marrow. A total of 13 overall patterns were found to distinguish, with considerable reliability, alcoholics from all other patients. This finding reflects the frequency with which alcohol abuse is associated with hepatic dysfunction in hospital patients. These observations indicate an important role for the nuclear medicine physician in detection of alcoholism among patients referred for liver-spleen imaging, and they form a basis for comparison with the diagnostic efficacy of other methods of evaluating diffuse liver diseases

  1. Correlation between liver morphology and haemodynamics in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1985-01-01

    was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance.......In 32 alcoholic patients the degree of hepatic architectural destruction was graded (preserved architecture, nodules alternating with preserved architecture, totally destroyed architecture) and related to portal pressure. A significant positive correlation was found between degree of architectural...... destruction and wedged-to-free hepatic vein pressure (W-FHVP) (p less than 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W-FHVP (p less than 0...

  2. Alcoholic liver disease: pathologic, pathogenetic and clinical aspects.

    Science.gov (United States)

    Ishak, K G; Zimmerman, H J; Ray, M B

    1991-02-01

    Alcoholic liver disease includes steatosis, alcoholic hepatitis and cirrhosis. Other liver diseases of genetic origin, but with a curious association with alcohol intake, are hemochromatosis and porphyria cutanea tarda. The attribution of chronic hepatitis to alcohol intake remains speculative, and the association may reflect hepatitis C infection. Hepatic injury attributed to alcohol includes the changes reported in the fetal alcohol syndrome. Steatosis, the characteristic consequence of excess alcohol intake, is usually macrovesicular and rarely microvesicular. Acute intrahepatic cholestasis, which in rare instances accompanies steatosis, must be distinguished from other causes of intrahepatic cholestasis (e.g., drug-induced) and from mechanical obstruction of the intrahepatic bile ducts (e.g., pancreatitis, choledocholithiasis) before being accepted. Alcoholic hepatitis (steatonecrosis) is characterized by a constellation of lesions: steatosis, Mallory bodies (with or without a neutrophilic inflammatory response), megamitochondria, occlusive lesions of terminal hepatic venules, and a lattice-like pattern of pericellular fibrosis. All these lesions mainly affect zone 3 of the hepatic acinus. Other changes, observed at the ultrastructural level, are of importance in progression of the disease. They include widespread cytoplasmic shedding, and capillarization and defenestration of sinusoids. Progressive fibrosis complicating alcoholic hepatitis eventually leads to cirrhosis that is typically micronodular but can evolve to a mixed or macronodular pattern. Hepatocellular carcinoma occurs in 5 to 15% of patients with alcoholic liver disease. The clinical syndrome of alcoholic liver disease is the result of three factors--parenchymal insufficiency, portal hypertension and the clinical consequences of extrahepatic damage produced by alcohol. At the several phases of the life history of alcoholic liver disease, the individual factors play a different role. The clinical

  3. Treatment of Alcohol Use Disorder in Patients with Alcoholic Liver Disease

    Science.gov (United States)

    Leggio, Lorenzo; Lee, Mary R.

    2016-01-01

    Alcohol is a leading cause of liver disease worldwide. Although alcohol abstinence is the crucial therapeutic goal for patients with alcoholic liver disease, these patients have less access to psychosocial, behavioral and/or pharmacological treatments for alcohol use disorder. Psychosocial and behavioral therapies include 12-step facilitation, brief interventions, cognitive behavioral therapy, and motivational enhancement therapy. In addition to medications approved by the Food and Drug Administration (FDA) for alcohol use disorder (disulfiram, naltrexone and acamprosate), recent efforts to identify potential new treatments have yielded promising candidate pharmacotherapies. Finally, more efforts are needed to integrate treatments across disciplines toward patient-centered approaches in the management of patients with alcohol use disorder and alcoholic liver disease. PMID:27984008

  4. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  5. Transferrin metabolism in alcoholic liver disease

    International Nuclear Information System (INIS)

    Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

    1985-01-01

    The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

  6. Correlation between liver morphology and haemodynamics in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1985-01-01

    destruction and wedged-to-free hepatic vein pressure (W-FHVP) (p less than 0.001). The degree of necrosis, fatty change and inflammation showed no correlation with portal pressure, whereas a significant positive correlation was found between the occurrence of Mallory bodies and W-FHVP (p less than 0......, hepatic architectural destruction (p less than 0.01) was positively correlated to hepatic resistance. Necrosis, fatty change, occurrence of Mallory bodies or inflammation showed no significant correlation with hepatic resistance. Mean hepatocyte volume was calculated in 29 patients, but no correlation...... was found with haemodynamic variables. The present data substantiate the concept that established portal hypertension in alcoholic liver disease is mainly accomplished by a derangement in hepatic architecture, whereas parenchymal changes, including hepatocyte size, are of less importance....

  7. Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease.

    Science.gov (United States)

    Pavlov, Chavdar S; Casazza, Giovanni; Semenistaia, Marianna; Nikolova, Dimitrinka; Tsochatzis, Emmanuel; Liusina, Ekaterina; Ivashkin, Vladimir T; Gluud, Christian

    2016-03-02

    Heavy alcohol consumption causes alcoholic liver disease and is a causal factor of many types of liver injuries and concomitant diseases. It is a true systemic disease that may damage the digestive tract, the nervous system, the heart and vascular system, the bone and skeletal muscle system, and the endocrine and immune system, and can lead to cancer. Liver damage in turn, can present as multiple alcoholic liver diseases, including fatty liver, steatohepatitis, fibrosis, alcoholic cirrhosis, and hepatocellular carcinoma, with presence or absence of hepatitis B or C virus infection. There are three scarring types (fibrosis) that are most commonly found in alcoholic liver disease: centrilobular scarring, pericellular fibrosis, and periportal fibrosis. When liver fibrosis progresses, alcoholic cirrhosis occurs. Hepatocellular carcinoma occurs in 5% to 15% of people with alcoholic cirrhosis, but people in whom hepatocellular carcinoma has developed are often co-infected with hepatitis B or C virus.Abstinence from alcohol may help people with alcoholic disease in improving their prognosis of survival at any stage of their disease; however, the more advanced the stage, the higher the risk of complications, co-morbidities, and mortality, and lesser the effect of abstinence. Being abstinent one month after diagnosis of early cirrhosis will improve the chance of a seven-year life expectancy by 1.6 times. Liver transplantation is the only radical method that may change the prognosis of a person with alcoholic liver disease; however, besides the difficulties of finding a suitable liver transplant organ, there are many other factors that may influence a person's survival.Ultrasound is an inexpensive method that has been used for years in clinical practice to diagnose alcoholic cirrhosis. Ultrasound parameters for assessing cirrhosis in people with alcoholic liver disease encompass among others liver size, bluntness of the liver edge, coarseness of the liver parenchyma

  8. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    OpenAIRE

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is k...

  9. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, Andrea; Iaquinto, Gaetano; Gluud, Christian

    2002-01-01

    The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease.......The objectives were to assess the beneficial and harmful effects of anabolic-androgenic steroids for alcoholic liver disease....

  10. Genetics Home Reference: non-alcoholic fatty liver disease

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions NAFLD Non-alcoholic fatty liver disease Printable PDF Open All Close All Enable ... view the expand/collapse boxes. Description Non-alcoholic fatty liver disease ( NAFLD ) is a buildup of excessive fat ...

  11. Association of restriction fragment length polymorphism in alcohol dehydrogenase 2 gene with alcohol induced liver damage.

    OpenAIRE

    Sherman, D I; Ward, R J; Warren-Perry, M; Williams, R; Peters, T J

    1993-01-01

    OBJECTIVE--To investigate the role of genetically determined differences in the enzymes of alcohol metabolism in susceptibility to liver damage from misusing alcohol. DESIGN--Use of pADH36 probe to study PVU II restriction length fragment polymorphism in alcohol dehydrogenase 2 gene in white alcohol misusers and controls. SETTING--Teaching hospital referral centres for liver disease and alcohol misuse. SUBJECTS--45 white alcohol misusers (38 with alcoholic liver disease) and 23 healthy contro...

  12. Anabolic-androgenic steroids for alcoholic liver disease

    DEFF Research Database (Denmark)

    Rambaldi, A; Iaquinto, G; Gluud, C

    2003-01-01

    Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease.......Alcohol is one of the most common causes of liver disease in the Western World today. Randomised clinical trials have examined the effects of anabolic-androgenic steroids for alcoholic liver disease....

  13. Non-alcoholic steatohepatitis and liver transplantation.

    Science.gov (United States)

    Gitto, Stefano; Vukotic, Ranka; Vitale, Giovanni; Pirillo, Martina; Villa, Erica; Andreone, Pietro

    2016-06-01

    Non-alcoholic steatohepatitis is a growing liver-related health problem. In Europe, non-alcoholic fatty liver disease is the most usual reason of chronic liver illness while steatohepatitis, its progressive form, affects 1% of Europeans and North Americans. In the United States steatohepatitis-related cirrhosis is one of the main indications for liver transplant. A targeted stratification for patients waiting for transplant and affected by this disease is mandatory especially because of their increased cardiovascular and cancer risk. The adequate treatment of NAFLD is crucial for the reduction of the disease related morbidity and mortality. In post-transplant setting, the recurrent or de novo steatosis might seriously affect the allograft short- and long-term outcome. Many conditions can represent the basis of the post-transplant steatohepatitis: obesity, hyperlipidaemia, diabetes mellitus, arterial hypertension, immunosuppressant treatment, alcoholic habit and liver graft steatosis. Today, the only consolidated therapy is represented by a deep life-style intervention since the use of drug-based alternative strategies is still limited and a very few data are available for the post-transplant period. Targeted and personalized behaviour and pharmacological interventions have to be developed for both the pre- and post-transplant phase. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  14. Multicausality in fatty liver disease: is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    Science.gov (United States)

    Völzke, Henry

    2012-07-21

    Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term "non-alcoholic" fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and "non-alcoholic" fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and "non-alcoholic" fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and "non-alcoholic" fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level.

  15. Links of gut microbiota composition with alcohol dependence syndrome and alcoholic liver disease.

    Science.gov (United States)

    Dubinkina, Veronika B; Tyakht, Alexander V; Odintsova, Vera Y; Yarygin, Konstantin S; Kovarsky, Boris A; Pavlenko, Alexander V; Ischenko, Dmitry S; Popenko, Anna S; Alexeev, Dmitry G; Taraskina, Anastasiya Y; Nasyrova, Regina F; Krupitsky, Evgeny M; Shalikiani, Nino V; Bakulin, Igor G; Shcherbakov, Petr L; Skorodumova, Lyubov O; Larin, Andrei K; Kostryukova, Elena S; Abdulkhakov, Rustam A; Abdulkhakov, Sayar R; Malanin, Sergey Y; Ismagilova, Ruzilya K; Grigoryeva, Tatiana V; Ilina, Elena N; Govorun, Vadim M

    2017-10-17

    Alcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems. Gut microbiota has been implicated in the pathogenesis of alcohol-related liver diseases, with its composition manifesting expressed dysbiosis in patients suffering from alcoholic dependence. Due to its inherent plasticity, gut microbiota is an important target for prevention and treatment of these diseases. Identification of the impact of alcohol abuse with associated psychiatric symptoms on the gut community structure is confounded by the liver dysfunction. In order to differentiate the effects of these two factors, we conducted a comparative "shotgun" metagenomic survey of 99 patients with the alcohol dependence syndrome represented by two cohorts-with and without liver cirrhosis. The taxonomic and functional composition of the gut microbiota was subjected to a multifactor analysis including comparison with the external control group. Alcoholic dependence and liver cirrhosis were associated with profound shifts in gut community structures and metabolic potential across the patients. The specific effects on species-level community composition were remarkably different between cohorts with and without liver cirrhosis. In both cases, the commensal microbiota was found to be depleted. Alcoholic dependence was inversely associated with the levels of butyrate-producing species from the Clostridiales order, while the cirrhosis-with multiple members of the Bacteroidales order. The opportunist pathogens linked to alcoholic dependence included pro-inflammatory Enterobacteriaceae, while the hallmarks of cirrhosis included an increase of oral microbes in the gut and more frequent occurrence of abnormal community structures. Interestingly, each of the two factors was associated with the expressed enrichment in many Bifidobacterium and Lactobacillus-but the exact set of the species was different between alcoholic dependence and liver cirrhosis. At the level of

  16. Colchicine for alcoholic and non-alcoholic liver fibrosis or cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    Colchicine is an anti-inflammatory and anti-fibrotic drug. Several randomized clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic as well as non-alcoholic fibrosis and cirrhosis. The objectives were to assess the efficacy of colchicine...... evaluated in randomized trials on mortality, liver related mortality, liver related complications, liver fibrosis markers, liver histology, alcohol consumption, quality of life, and health economics in patients with alcoholic and non-alcoholic fibrosis or cirrhosis....

  17. Non-alcoholic fatty liver disease: A poorly known pandemic.

    Science.gov (United States)

    Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

    2017-12-20

    Non-alcoholic fatty liver disease (NAFLD) consists of an excessive depositing of fat in the liver, which can end up by causing inflammation, fibrosis and also cirrhosis with the corresponding complications including liver cancer. NAFLD has become the most common liver disease worldwide. The incidence has increased in parallel with the obesity, diabetes and metabolic syndrome epidemic, thus resulting in becoming one of the main indications for liver transplant. The diagnosis has principally been through histology but with the development of non-invasive methods, these have helped in simplifying the management of these patients in clinical practice. The only therapeutic strategies currently available are focused on weight loss (lifestyle changes or bariatric surgery). There is still no approved pharmacological option for the treatment of NAFLD, however there are a number of molecular studies in advanced stages of development. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  18. Liver proteomics in progressive alcoholic steatosis

    Energy Technology Data Exchange (ETDEWEB)

    Fernando, Harshica [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Wiktorowicz, John E.; Soman, Kizhake V. [Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Kaphalia, Bhupendra S.; Khan, M. Firoze [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States); Shakeel Ansari, G.A., E-mail: sansari@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-02-01

    Fatty liver is an early stage of alcoholic and nonalcoholic liver disease (ALD and NALD) that progresses to steatohepatitis and other irreversible conditions. In this study, we identified proteins that were differentially expressed in the livers of rats fed 5% ethanol in a Lieber–DeCarli diet daily for 1 and 3 months by discovery proteomics (two-dimensional gel electrophoresis and mass spectrometry) and non-parametric modeling (Multivariate Adaptive Regression Splines). Hepatic fatty infiltration was significantly higher in ethanol-fed animals as compared to controls, and more pronounced at 3 months of ethanol feeding. Discovery proteomics identified changes in the expression of proteins involved in alcohol, lipid, and amino acid metabolism after ethanol feeding. At 1 and 3 months, 12 and 15 different proteins were differentially expressed. Of the identified proteins, down regulation of alcohol dehydrogenase (− 1.6) at 1 month and up regulation of aldehyde dehydrogenase (2.1) at 3 months could be a protective/adaptive mechanism against ethanol toxicity. In addition, betaine-homocysteine S-methyltransferase 2 a protein responsible for methionine metabolism and previously implicated in fatty liver development was significantly up regulated (1.4) at ethanol-induced fatty liver stage (1 month) while peroxiredoxin-1 was down regulated (− 1.5) at late fatty liver stage (3 months). Nonparametric analysis of the protein spots yielded fewer proteins and narrowed the list of possible markers and identified D-dopachrome tautomerase (− 1.7, at 3 months) as a possible marker for ethanol-induced early steatohepatitis. The observed differential regulation of proteins have potential to serve as biomarker signature for the detection of steatosis and its progression to steatohepatitis once validated in plasma/serum. -- Graphical abstract: The figure shows the Hierarchial cluster analysis of differentially expressed protein spots obtained after ethanol feeding for 1 (1–3

  19. Managing non-alcoholic fatty liver disease.

    Science.gov (United States)

    Ngu, Jing Hieng; Goh, George Boon Bee; Poh, Zhongxian; Soetikno, Roy

    2016-07-01

    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. Copyright: © Singapore Medical Association.

  20. Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Engin, Atilla

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) is in parallel with the obesity epidemic and it is the most common cause of liver diseases. The development of hepatic steatosis in majority of patients is linked to dietary fat ingestion. NAFLD is characterized by excess accumulation of triglyceride in the hepatocyte due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Insulin resistance with the deficiency of insulin receptor substrate-2 (IRS-2)-associated phosphatidylinositol 3-kinase (PI3K) activity causes an increase in intracellular fatty acid-derived metabolites such as diacylglycerol, fatty acyl CoA or ceramides. Lipotoxicity-related mechanism of NAFLD could be explained still best by the "double-hit" hypothesis. Insulin resistance is the major mechanism in the development and progression of NAFLD/Non-alcoholic steatohepatitis (NASH). Metabolic oxidative stress, autophagy, and inflammation induce NASH progression. In the "first hit" the hepatic concentrations of diacylglycerol increase with rising saturated liver fat content in human NAFLD. Activities of mitochondrial respiratory chain complexes are decreased in liver tissue of patients with NASH. Furthermore, hepatocyte lipoapoptosis is a critical feature of NASH. In "second hit" reduced glutathione levels due to oxidative stress lead to overactivation of c-Jun N-terminal kinase (JNK)/c-Jun signaling that induces cell death in the steatotic liver. Accumulation of toxic levels of reactive oxygen species (ROS) is caused by the ineffectual cycling of the endoplasmic reticulum (ER) oxidoreductin (Ero1)-protein disulfide isomerase oxidation cycle through the downstream of the inner membrane mitochondrial oxidative metabolism and Kelch like-ECH-associated protein 1 (Keap1)- Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.

  1. Non-Alcoholic Fatty Liver Disease in HIV Infection.

    Science.gov (United States)

    Macías, Juan; Pineda, Juan A; Real, Luis M

    2017-01-01

    Non-alcoholic fatty liver disease is one of the most frequent chronic hepatic conditions worldwide. The spectrum of non-alcoholic fatty liver disease goes from hepatic steatosis to steatohepatitis, cirrhosis, and hepatocellular carcinoma. Risk factors for non-alcoholic fatty liver disease are metabolic, mainly obesity and the accompanying consequences. Treatment and prevention of non-alcoholic fatty liver disease should target those metabolic abnormalities. The frequency of and the factors associated with hepatic steatosis in HIV infection seem to be similar to those reported in the general population, though direct comparisons are lacking. Hepatic steatosis in HIV infection may also be secondary to antiretroviral drugs or HCV-related factors in HCV-coinfected subjects. However, more recent data suggest that hepatic steatosis in HIV infection represents true non-alcoholic fatty liver disease. As such, management of non-alcoholic fatty liver disease in HIV infection should follow the same principles as in the general population.

  2. Liver fibrosis in non-alcoholic fatty liver disease - diagnostic challenge with prognostic significance.

    Science.gov (United States)

    Stål, Per

    2015-10-21

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the Western world, with a prevalence of 20%. In a subgroup of patients, inflammation, ballooning degeneration of hepatocytes and a varying degree of fibrosis may develop, a condition named non-alcoholic steatohepatitis. Advanced liver fibrosis (stage F3) and cirrhosis (stage F4) are histologic features that most accurately predict increased mortality in both liver-related and cardiovascular diseases. Patients with advanced fibrosis or cirrhosis are at risk for complications such as hepatocellular carcinoma and esophageal varices and should therefore be included in surveillance programs. However, liver disease and fibrosis are often unrecognized in patients with NAFLD, possibly leading to a delayed diagnosis of complications. The early diagnosis of advanced fibrosis in NAFLD is therefore crucial, and it can be accomplished using serum biomarkers (e.g., the NAFLD Fibrosis Score, Fib-4 Index or BARD) or non-invasive imaging techniques (transient elastography or acoustic radiation force impulse imaging). The screening of risk groups, such as patients with obesity and/or type 2 diabetes mellitus, for NAFLD development with these non-invasive methods may detect advanced fibrosis at an early stage. Additionally, patients with a low risk for advanced fibrosis can be identified, and the need for liver biopsies can be minimized. This review focuses on the diagnostic challenge and prognostic impact of advanced liver fibrosis in NAFLD.

  3. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells

    OpenAIRE

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has...

  4. Alcohol modulates autophagy and apoptosis in pig liver tissue.

    Science.gov (United States)

    Potz, Brittany A; Lawandy, Isabella J; Clements, Richard T; Sellke, Frank W

    2016-06-01

    Autophagy serves as a cellular protective mechanism against alcohol-induced tissue injury but excessive autophagy can also be detrimental leading to apoptosis. Our laboratory has previously shown that moderate alcohol consumption alters expression of proteins in the insulin signaling pathway and worsens glucose metabolism in the liver in a swine model of metabolic syndrome. We examined the effect of alcohol consumption on apoptosis and autophagy signaling in the liver in our clinically relevant animal model of chronic hypercholesterolemia. Twenty-six Yorkshire swine were fed a high-fat diet for 4 wks and were then split into three groups: hypercholesterolemic diet alone (HCC, n = 9), hypercholesterolemic diet with vodka (hypercholesterolemic vodka [HCV], n = 9), and hypercholesterolemic diet with wine (hypercholesterolemic wine [HCW], n = 8) for 7 wks. Animals underwent euthanasia, and liver tissue samples were harvested for analysis. Liver tissue was analyzed via Western blot analysis. Protein density data were normalized to GAPDH and is reported as fold-change values ± standard error of the mean compared to the high-cholesterol diet control group. A Kruskal-Wallis test with a Dunn's multiple comparison test was used to compare the means among groups. The HCV group showed significant increases in several proapoptotic proteins (including caspase 3, caspase 8, caspase 9, and cleaved caspase 9) compared with the HCC group. There was a decrease in the proapoptotic protein (BAD) and an increase in anti-apoptotic signal (B-cell lymphoma-2) in the HCW group compared with HCC control. There were increases in pro-survival proteins (AKT, p-AKT, mTOR, p-mTOR) in the HCW and the HCV group compared with control (HCC). There were decreases in autophagy protein LCB-3 in the HCW and HCV compared with the control. We found that moderate alcohol consumption altered protein expression related to apoptosis and autophagy signaling in pig liver in the setting of

  5. A disease-specific quality of life instrument for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis: CLDQ-NAFLD.

    Science.gov (United States)

    Younossi, Zobair M; Stepanova, Maria; Henry, Linda; Racila, Andrei; Lam, Brian; Pham, Huong T; Hunt, Sharon

    2017-08-01

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P.15, intraclass correlations .76-.88). The Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version is a disease-specific health-related quality of life instrument developed and validated using an established methodology and useful for clinical trials of non-alcoholic

  6. Non-alcoholic fatty liver disease: The diagnosis and management

    Science.gov (United States)

    Abd El-Kader, Shehab M; El-Den Ashmawy, Eman M Salah

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) is now the most frequent chronic liver disease that occurs across all age groups and is recognized to occur in 14%-30% of the general population, representing a serious and growing clinical problem due to the growing prevalence of obesity and overweight. Histologically, it resembles alcoholic liver injury but occurs in patients who deny significant alcohol consumption. NAFLD encompasses a spectrum of conditions, ranging from benign hepatocellular steatosis to inflammatory nonalcoholic steatohepatitis, fibrosis, and cirrhosis. The majority of hepatocellular lipids are stored as triglycerides, but other lipid metabolites, such as free fatty acids, cholesterol, and phospholipids, may also be present and play a role in disease progression. NAFLD is associated with obesity and insulin resistance and is considered the hepatic manifestation of the metabolic syndrome, a combination of medical conditions including type 2 diabetes mellitus, hypertension, hyperlipidemia, and visceral adiposity. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies; however, staging the disease requires a liver biopsy. Current treatment relies on weight loss and exercise, although various insulin-sensitizing agents, antioxidants and medications appear promising. The aim of this review is to highlight the current information regarding epidemiology, diagnosis, and management of NAFLD as well as new information about pathogenesis, diagnosis and management of this disease. PMID:25937862

  7. Tc-99 m-GSA liver scintigraphy in alcoholic liver cirrhosis

    International Nuclear Information System (INIS)

    Itano, Satoshi; Harada, Masaru; Nagamatsu, Hiroaki

    2003-01-01

    We compared 15 alcoholic liver cirrhosis patients with 10 viral liver cirrhosis patients using technetium-99 m-galactosyl human serum albumin (Tc-99 m-GSA) liver scintigraphy and could clinically reveal the disorder of metabolism of asialoglycoprotein in alcoholic liver cirrhosis. Receptor index (LHL 15 = liver count divided by the sum of liver and heart counts at 15 minutes) was significantly (p <0.01) lower in patients with alcoholic cirrhosis (median: 0.821), compared with patients with viral cirrhosis (0.915). Grading score, which was an index showed by the difference in the isotope uptake patterns between liver and heart, was significantly (p <0.01) worse in patients with alcoholic cirrhosis, compared with patients with viral cirrhosis. These results suggested that alcoholic liver cirrhosis had a specific disorder of a metabolic function for asialoglycoprotein. (author)

  8. Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    Science.gov (United States)

    Völzke, Henry

    2012-01-01

    Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic and “non-alcoholic” fatty liver disease. The MEDLINE database was searched using the PubMed search engine, and a review of reference lists from original research and review articles was conducted. The concept to distinguish between alcoholic and “non-alcoholic” fatty liver disease is mainly based on specific pathomechanisms. This concept has, however, several limitations including the common overlap between alcohol misuse and obesity-related metabolic disorders and the non-consideration of additional causal factors. Both entities share similar histopathological patterns. Studies demonstrating differences in clinical presentation and outcome are often biased by selection. Risk factor reduction is the main principle of prevention and treatment of both disease forms. In conclusion, alcoholic and “non-alcoholic” fatty liver diseases are one and the same disease caused by different risk factors. A shift from artificial categories to a more general approach to fatty liver disease as a multicausal disorder may optimize preventive strategies and help clinicians more effectively treat patients at the individual level. PMID:22826613

  9. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research.

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Crespo Yanguas, Sara; Colle, Isabelle; Van Den Bossche, Bert; Da Silva, Tereza Cristina; de Oliveira, Cláudia Pinto Marques Souza; Andraus, Wellington; Alves, Venâncio Avancini; Cogliati, Bruno; Vinken, Mathieu

    2015-07-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and '-omics'-based read-outs are still in their infancy, but show great promise. In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  10. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research

    Science.gov (United States)

    Willebrords, Joost; Pereira, Isabel Veloso Alves; Maes, Michaël; Yanguas, Sara Crespo; Colle, Isabelle; Van Den Bossche, Bert; Da silva, Tereza Cristina; Oliveira, Cláudia P; Andraus, Wellington; Alves, Venâncio Avancini Ferreira; Cogliati, Bruno; Vinken, Mathieu

    2015-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of liver diseases, including simple steatosis, steatohepatitis, liver fibrosis and cirrhosis and hepatocellular carcinoma. Non-alcoholic fatty liver disease is currently the most dominant chronic liver disease in Western countries due to the fact that hepatic steatosis is associated with insulin resistance, type 2 diabetes mellitus, obesity, metabolic syndrome and drug-induced injury. A variety of chemicals, mainly drugs, and diets is known to cause hepatic steatosis in humans and rodents. Experimental non-alcoholic fatty liver disease models rely on the application of a diet or the administration of drugs to laboratory animals or the exposure of hepatic cell lines to these drugs. More recently, genetically modified rodents or zebrafish have been introduced as non-alcoholic fatty liver disease models. Considerable interest now lies in the discovery and development of novel non-invasive biomarkers of non-alcoholic fatty liver disease, with specific focus on hepatic steatosis. Experimental diagnostic biomarkers of non-alcoholic fatty liver disease, such as (epi)genetic parameters and ‘-omics’-based read-outs are still in their infancy, but show great promise. . In this paper, the array of tools and models for the study of liver steatosis is discussed. Furthermore, the current state-of-art regarding experimental biomarkers such as epigenetic, genetic, transcriptomic, proteomic and metabonomic biomarkers will be reviewed. PMID:26073454

  11. Probiotics and Alcoholic Liver Disease: Treatment and Potential Mechanisms

    Directory of Open Access Journals (Sweden)

    Fengyuan Li

    2016-01-01

    Full Text Available Despite extensive research, alcohol remains one of the most common causes of liver disease in the United States. Alcoholic liver disease (ALD encompasses a broad spectrum of disorders, including steatosis, steatohepatitis, and cirrhosis. Although many agents and approaches have been tested in patients with ALD and in animals with experimental ALD in the past, there is still no FDA (Food and Drug Administration approved therapy for any stage of ALD. With the increasing recognition of the importance of gut microbiota in the onset and development of a variety of diseases, the potential use of probiotics in ALD is receiving increasing investigative and clinical attention. In this review, we summarize recent studies on probiotic intervention in the prevention and treatment of ALD in experimental animal models and patients. Potential mechanisms underlying the probiotic function are also discussed.

  12. [The catalase inhibitor aminotriazole alleviates acute alcoholic liver injury].

    Science.gov (United States)

    Ai, Qing; Ge, Pu; Dai, Jie; Liang, Tian-Cai; Yang, Qing; Lin, Ling; Zhang, Li

    2015-02-25

    In this study, the effects of catalase (CAT) inhibitor aminotriazole (ATZ) on alcohol-induced acute liver injury were investigated to explore the potential roles of CAT in alcoholic liver injury. Acute liver injury was induced by intraperitoneal injection of alcohol in Sprague Dawley (SD) rats, and various doses of ATZ (100-400 mg/kg) or vehicle were administered intraperitoneally at 30 min before alcohol exposure. After 24 h of alcohol exposure, the levels of aspartate transaminase (AST), alanine transaminase (ALT) and lactate dehydrogenase (LDH) in plasma were determined. The degree of hepatic histopathological abnormality was observed by HE staining. The activity of hepatic CAT, hydrogen peroxide (H₂O₂) level and malondialdehyde (MDA) content in liver tissue were measured by corresponding kits. The levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in plasma were determined by ELISA method. The results showed that treatment with ATZ dose-dependently suppressed the elevation of ALT, AST and LDH levels induced by alcohol exposure, and that ATZ alleviated alcohol-induced histopathological alterations. Furthermore, ATZ inhibited the activity of CAT, reduced hepatic levels of H₂O₂and MDA in alcohol exposed rats. ATZ also decreased the levels of plasma TNF-α and IL-6 in rats with alcohol exposure. These results indicated that ATZ attenuated alcohol-induced acute liver injury in rats, suggesting that CAT might play important pathological roles in the pathogenesis of alcoholic liver injury.

  13. [Non-alcoholic fatty liver disease--new view].

    Science.gov (United States)

    Raszeja-Wyszomirska, Joanna; Lawniczak, Małgorzata; Marlicz, Wojciech; Miezyńska-Kurtycz, Joanna; Milkiewicz, Piotr

    2008-06-01

    Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others

  14. Models of alcoholic liver disease in rodents: a critical evaluation

    DEFF Research Database (Denmark)

    de la M. Hall, P.; Lieber, C.S.; De Carli, L.M.

    2001-01-01

    ) Lieber-DeCarli liquid diet for alcohol-induced liver injury in rats, by C. S. Lieber and L. M. DeCarli; (3) Tsukamoto-French model of alcoholic liver injury, by S. W. French; (4) Animal models to study endotoxin-ethanol interactions, by K. O. Lindros and H. Järveläinen; and (5) Jejunoileal bypass...

  15. Alcohol and the Liver | Awosusi | Journal of the Obafemi Awolowo ...

    African Journals Online (AJOL)

    Alcohol and the Liver. ... Journal of the Obafemi Awolowo University Medical Student's Association (IFEMED) ... Sustained excessive alcohol consumption is a brain-centred behavioural disorder; it might lead to liver disease but also predisposes to development of cardiovascular, renal, neurological and endocrine disorders ...

  16. S-adenosyl-L-methionine for alcoholic liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2006-01-01

    Alcohol is a major cause of liver disease and disrupts methionine and oxidative balances. S-adenosyl-L-methionine (SAMe) acts as a methyl donor for methylation reactions and participates in the synthesis of glutathione, the main cellular antioxidant. Randomised clinical trials have addressed...... the question whether SAMe may benefit patients with alcoholic liver diseases....

  17. Autophagy and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Vanessa J. Lavallard

    2014-01-01

    Full Text Available Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD, have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH, steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  18. Autophagy and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lavallard, Vanessa J; Gual, Philippe

    2014-01-01

    Autophagy, or cellular self-digestion, is a catabolic process that targets cell constituents including damaged organelles, unfolded proteins, and intracellular pathogens to lysosomes for degradation. Autophagy is crucial for development, differentiation, survival, and homeostasis. Important links between the regulation of autophagy and liver complications associated with obesity, non-alcoholic fatty liver disease (NAFLD), have been reported. The spectrum of these hepatic abnormalities extends from isolated steatosis to non-alcoholic steatohepatitis (NASH), steatofibrosis, which sometimes leads to cirrhosis, and hepatocellular carcinoma. NAFLD is one of the three main causes of cirrhosis and increases the risk of liver-related death and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to steatosis and then more severe disease are complex and still unclear. The regulation of the autophagic flux, a dynamic response, and the knowledge of the role of autophagy in specific cells including hepatocytes, hepatic stellate cells, immune cells, and hepatic cancer cells have been extensively studied these last years. This review will provide insight into the current understanding of autophagy and its role in the evolution of the hepatic complications associated with obesity, from steatosis to hepatocellular carcinoma.

  19. Intestinal fungi contribute to development of alcoholic liver disease

    Science.gov (United States)

    Yang, An-Ming; Inamine, Tatsuo; Hochrath, Katrin; Chen, Peng; Wang, Lirui; Llorente, Cristina; Bluemel, Sena; Hartmann, Phillipp; Koyama, Yukinori; Kisseleva, Tatiana; Torralba, Manolito G.; Moncera, Kelvin; Beeri, Karen; Chen, Chien-Sheng; Freese, Kim; Hellerbrand, Claus; Lee, Serene M.L.; Hoffman, Hal M.; Mehal, Wajahat Z.; Garcia-Tsao, Guadalupe; Mutlu, Ece A.; Keshavarzian, Ali; Brown, Gordon D.; Bataller, Ramon; Stärkel, Peter; Fouts, Derrick E.

    2017-01-01

    Chronic liver disease with cirrhosis is the 12th leading cause of death in the United States, and alcoholic liver disease accounts for approximately half of all cirrhosis deaths. Chronic alcohol consumption is associated with intestinal bacterial dysbiosis, yet we understand little about the contribution of intestinal fungi, or mycobiota, to alcoholic liver disease. Here we have demonstrated that chronic alcohol administration increases mycobiota populations and translocation of fungal β-glucan into systemic circulation in mice. Treating mice with antifungal agents reduced intestinal fungal overgrowth, decreased β-glucan translocation, and ameliorated ethanol-induced liver disease. Using bone marrow chimeric mice, we found that β-glucan induces liver inflammation via the C-type lectin–like receptor CLEC7A on Kupffer cells and possibly other bone marrow–derived cells. Subsequent increases in IL-1β expression and secretion contributed to hepatocyte damage and promoted development of ethanol-induced liver disease. We observed that alcohol-dependent patients displayed reduced intestinal fungal diversity and Candida overgrowth. Compared with healthy individuals and patients with non–alcohol-related cirrhosis, alcoholic cirrhosis patients had increased systemic exposure and immune response to mycobiota. Moreover, the levels of extraintestinal exposure and immune response correlated with mortality. Thus, chronic alcohol consumption is associated with an altered mycobiota and translocation of fungal products. Manipulating the intestinal mycobiome might be an effective strategy for attenuating alcohol-related liver disease. PMID:28530644

  20. To Study the Activity of Paraoxonase-1 and High Density Lipoprotein-Cholesterol in Alcoholic Liver Cirrhosis

    Directory of Open Access Journals (Sweden)

    Pooja Nemagoudar

    2017-01-01

    Full Text Available Background: Alcoholic liver cirrhosis is the most common complication of ethanol abuse. Alcoholic fatty liver progresses to alcoholic hepatitis, cirrhosis and liver failure. Lipoproteins are synthesized by the liver and secreted into the circulation. Alcoholic liver cirrhosis causes alteration in lipoprotein metabolism producing liver steatosis and necrosis. Paraoxonase-1 (PON-1 is an enzyme synthesized in liver and has an esterase activity towards lipid peroxides and circulates in plasma bound to High-Density Lipoproteins-cholesterol (HDL-c. Aim and Objectives: To determine the activity of PON-1 and levels of HDL-c in alcoholic liver disease and to correlate PON-1 activity with HDL-c. Materials and Methods: A Cross sectional study done in Department of Biochemistry and Department of Medicine, Belagavi Institute of Medical Sciences, Belagavi, Karnataka, India, from 1st December 2014 to 31st January 2016 Study included 50 males (age range 25-55 years with alcoholic liver cirrhosis and 50 healthy male participants (age range 25-55 years. PON-1 activity was estimated using spectrophotometric method by the hydrolysis of phenylacetate. HDL-c level was measured by cholesterol oxidase-peroxidase method. Results: The serum PON-1 activity and levels of HDL-c in patients with alcoholic liver cirrhosis were significantly reduced (p<0.001 compared with controls. Conclusion: A significant decrease in PON-1 and HDL-c in alcoholic liver cirrhosis may contribute to the risk of atherosclerosis in alcoholic liver cirrhosis patients.

  1. Pharmacological promotion of autophagy alleviates steatosis and injury in alcoholic and non-alcoholic fatty liver conditions in mice.

    Science.gov (United States)

    Lin, Chih-Wen; Zhang, Hao; Li, Min; Xiong, Xiwen; Chen, Xi; Chen, Xiaoyun; Dong, Xiaocheng C; Yin, Xiao-Ming

    2013-05-01

    Pharmacological approaches can potentially improve fatty liver condition in alcoholic and non-alcoholic fatty liver diseases. The salutary effects of reducing lipid synthesis or promoting lipid oxidation have been well reported, but the benefits of increasing lipid degradation have yet to be well explored. Macroautophagy is a cellular degradation process that can remove subcellular organelles including lipid droplets. We thus investigated whether pharmacological modulation of macroautophagy could be an effective approach to alleviate fatty liver condition and liver injury. C57BL/6 mice were given ethanol via intraperitoneal injection (acute) or by a 4-week oral feeding regime (chronic), or high fat diet for 12 weeks. An autophagy enhancer, carbamazepine or rapamycin, or an autophagy inhibitor, chloroquine, was given before sacrifice. Activation of autophagy, level of hepatic steatosis, and blood levels of triglycerides, liver enzyme, glucose and insulin were measured. In both acute and chronic ethanol condition, macroautophagy was activated. Carbamazepine, as well as rapamycin, enhanced ethanol-induced macroautophagy in hepatocytes in vitro and in vivo. Hepatic steatosis and liver injury were exacerbated by chloroquine, but alleviated by carbamazepine. The protective effects of carbamazepine and rapamycin in reducing steatosis and in improving insulin sensitivity were also demonstrated in high fat diet-induced non-alcoholic fatty liver condition. These findings indicate that pharmacological modulation of macroautophagy in the liver can be an effective strategy for reducing fatty liver condition and liver injury. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  2. Radiologic evaluation of the liver in the alcoholic patient

    International Nuclear Information System (INIS)

    Peng, J.J.; Hirsch, G.; Posteraro, R.H.; Leo, J.S.; Blackwell, D.E.

    1985-01-01

    It has been well documented that long-term abuse of alcohol leads to dysfunction of multiple organ systems of the body. The liver, which is the primary organ responsible for alcohol metabolism, is also a major target for damage. Cirrhosis of the liver is the seventh leading cause of death in the United States. The radiologist plays an important role in the evaluation and possibly in the treatment of the conditions which result from alcohol abuse. The advantages and limitations of various radiologic diagnostic modalities in the evaluation of alcoholic liver disease are presented and discussed. 47 references

  3. Caput medusae in alcoholic liver disease | Hari Kumar | Nigerian ...

    African Journals Online (AJOL)

    Caput medusae and palmar erythema are cardinal signs in cirrhosis of liver with portal hypertension. Palmar erythema is described more often as a marker for alcoholic etiology of chronic liver disease. The peripheral stigmata of chronic liver disease are not routinely seen now a days due to early diagnosis and better ...

  4. A meta-analysis of HLA-antigen prevalences in alcoholics and alcoholic liver disease

    DEFF Research Database (Denmark)

    List, S; Gluud, C

    1994-01-01

    In the search for genetic factors influencing susceptibility to the development of alcoholism and alcoholic liver disease, 28 studies have been published analysing the distribution of human leucocyte antigens (HLA) in alcoholics compared to healthy controls. A number of HLA-phenotypes has been...... suspected of being associated with both alcoholism and alcoholic liver disease. In the present study a meta-analysis is carried out on the data from these studies, subdivided according to race and degree of liver injury. The conclusion is that none of the HLA-phenotypes so far investigated in Caucasians can...

  5. Homocysteine, Liver Function Derangement and Brain Atrophy in Alcoholics.

    Science.gov (United States)

    Fernández-Rodríguez, Camino; González-Reimers, Emilio; Quintero-Platt, Geraldine; de la Vega-Prieto, María José; Pérez-Hernández, Onán; Martín-González, Candelaria; Espelosín-Ortega, Elisa; Romero-Acevedo, Lucía; Santolaria-Fernández, Francisco

    2016-11-01

    Hyperhomocysteinemia may be involved in the development of brain atrophy in alcoholics. Its pathogenesis is multifactorial. In the present study, we analyse the relationship between homocysteine levels and brain atrophy, and the relative weight of co-existing factors such as liver function impairment, the amount of ethanol consumed, serum vitamin B12, B6, and folic acid levels on homocysteine levels and brain alterations in alcoholic patients. We included 59 patients admitted to this hospital for major withdrawal symptoms and 24 controls. The mini-mental state examination test and a brain computed tomography (CT) scan were performed and several indices were calculated. Serum levels of homocysteine, folic acid, vitamin B6 and vitamin B12 were determined. Liver function was assessed by Child-Pugh score. The daily consumption of ethanol in grams per day and years of addiction were recorded. A total of 83.6% and 80% of the patients showed cerebellar or frontal atrophy, respectively. Patients showed altered values of brain indices, higher levels of homocysteine and vitamin B12, but lower levels of folic acid, compared with controls. Homocysteine, B12 and liver function variables showed significant correlations with brain CT indices. Multivariate analyses disclosed that Pugh's score, albumin and bilirubin were independently related to cerebellar atrophy, frontal atrophy, cella index or ventricular index. Serum vitamin B12 was the only factor independently related to Evans index. It was also related to cella index, but after bilirubin. Homocysteine levels were independently related to ventricular index, but after bilirubin. Vitamin B12 and homocysteine levels are higher among alcoholics. Liver function derangement, vitamin B12 and homocysteine are all independently related to brain atrophy, although not to cognitive alterations. Hyperhomocysteinemia has been described in alcoholics and may be related to brain atrophy, a reversible condition with an obscure pathogenesis

  6. Role of IRAK-M in alcohol induced liver injury.

    Directory of Open Access Journals (Sweden)

    Yipeng Wang

    Full Text Available Increasing evidence suggests that innate immunity plays an important role in alcohol-induced liver injury and most studies have focused on positive regulation of innate immunity. The main objective of this study was to investigate the negative regulator of innate immunity, IL-1/Toll-like receptor (TLR signaling pathways and interleukin receptor-associated kinase-M (IRAK-M in alcoholic liver injury. We established an alcohol-induced liver injury model using wild type and IRAK-M deficient B6 mice and investigated the possible mechanisms. We found that in the absence of IRAK-M, liver damage by alcohol was worse with higher alanine transaminase (ALT, more immune cell infiltration and increased numbers of IFNγ producing cells. We also found enhanced phagocytic activity in CD68(+ cells. Moreover, our results revealed altered gut bacteria after alcohol consumption and this was more striking in the absence of IRAK-M. Our study provides evidence that IRAK-M plays an important role in alcohol-induced liver injury and IRAK-M negatively regulates the innate and possibly the adaptive immune response in the liver reacting to acute insult by alcohol. In the absence of IRAK-M, the hosts developed worse liver injury, enhanced gut permeability and altered gut microbiota.

  7. Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

    2009-01-01

    cirrhosis were 1.7 (0.6-4.7), 2.0 (0.8-7.1), 6.5 (2.0-21), and 13 (4.6-37) (P for trendeffect of alcohol on biochemical tests or risk of liver disease. CONCLUSIONS: Increasing alcohol intake from none to low (1-6 drinks per...... week) through to moderate (7-20 drinks per week) and excessive intake (> or = 21 drinks per week) leads to stepwise increases in signs of liver damage with no threshold effect, and to an increased risk of liver disease. The minor changes in biochemical tests for low alcohol intake may not account......OBJECTIVES: We tested the hypothesis that alcohol, alone and in combination with alcohol dehydrogenase (ADH) 1B and ADH1C genotypes, affects liver damage and disease in the general population. METHODS: Information on alcohol intake and on liver disease was obtained from 9,080 men and women from...

  8. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    Science.gov (United States)

    Meikle, Peter J; Mundra, Piyushkumar A; Wong, Gerard; Rahman, Khairunnessa; Huynh, Kevin; Barlow, Christopher K; Duly, Alastair M P; Haber, Paul S; Whitfield, John B; Seth, Devanshi

    2015-01-01

    Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  9. Circulating Lipids Are Associated with Alcoholic Liver Cirrhosis and Represent Potential Biomarkers for Risk Assessment.

    Directory of Open Access Journals (Sweden)

    Peter J Meikle

    Full Text Available Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

  10. Alcohol intake, alcohol dehydrogenase genotypes, and liver damage and disease in the Danish general population

    DEFF Research Database (Denmark)

    Tolstrup, J.S.; Gronbaek, M.; Tybjaerg-Hansen, A.

    2009-01-01

    OBJECTIVES: We tested the hypothesis that alcohol, alone and in combination with alcohol dehydrogenase (ADH) 1B and ADH1C genotypes, affects liver damage and disease in the general population. METHODS: Information on alcohol intake and on liver disease was obtained from 9,080 men and women from...... volume. RESULTS: Increasing alcohol intake was associated with increasing erythrocyte volume, AST/ALT, and levels of ALT, gamma-GT, albumin, bilirubin, coagulation factors, and with decreasing levels of alkaline phosphatase. Multifactorially adjusted hazard ratios for alcoholic liver disease overall were...... 0.9 (95% confidence interval (CI), 0.6-1.4), 1.4 (0.8-2.5), 1.8 (0.9-3.5), and 4.1 (2.5-7.0) for an alcohol intake of 1-13, 14-20, 21-27, and > or = 28 drinks per week, respectively, compared with drinking alcoholic liver...

  11. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P

    1983-01-01

    in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.......The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

  12. Alcohol Increases Liver Progenitor Populations and Induces Disease Phenotypes in Human IPSC-Derived Mature Stage Hepatic Cells.

    Science.gov (United States)

    Tian, Lipeng; Deshmukh, Abhijeet; Prasad, Neha; Jang, Yoon-Young

    2016-01-01

    Alcohol consumption has long been a global problem affecting human health, and has been found to influence both fetal and adult liver functions. However, how alcohol affects human liver development and liver progenitor cells remains largely unknown. Here, we used human induced pluripotent stem cells (iPSCs) as a model to examine the effects of alcohol, on multi-stage hepatic cells including hepatic progenitors, early and mature hepatocyte-like cells derived from human iPSCs. While alcohol has little effect on endoderm development from iPSCs, it reduces formation of hepatic progenitor cells during early hepatic specification. The proliferative activities of early and mature hepatocyte-like cells are significantly decreased after alcohol exposure. Importantly, at a mature stage of hepatocyte-like cells, alcohol treatment increases two liver progenitor subsets, causes oxidative mitochondrial injury and results in liver disease phenotypes (i.e., steatosis and hepatocellular carcinoma associated markers) in a dose dependent manner. Some of the phenotypes were significantly improved by antioxidant treatment. This report suggests that fetal alcohol exposure may impair generation of hepatic progenitors at early stage of hepatic specification and decrease proliferation of fetal hepatocytes; meanwhile alcohol injury in post-natal or mature stage human liver may contribute to disease phenotypes. This human iPSC model of alcohol-induced liver injury can be highly valuable for investigating alcoholic injury in the fetus as well as understanding the pathogenesis and ultimately developing effective treatment for alcoholic liver disease in adults.

  13. SIRT3 as a Regulator of Non-alcoholic Fatty Liver Disease

    OpenAIRE

    Cho, Eun-Hee

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a hepatic presentation of obesity and metabolic syndrome. NAFLD includes a large spectrum of hepatic pathologies that range from simple steatosis and non-alcoholic steatohepatitis (NASH), to liver cirrhosis without an all-encompassing approved therapeutic strategy. Mitochondrial dysfunction is a key component of many metabolic diseases, such as obesity, type 2 diabetes, cancer, NAFLD, and aging. Sirtuin 3 (SIRT3) is a NAD+-dependent deacetylase tha...

  14. Paediatric non-alcoholic fatty liver disease: an overview.

    Science.gov (United States)

    AlKhater, S A

    2015-05-01

    Non-alcoholic fatty liver disease (NAFLD) is a progressive disease that encompasses a spectrum of liver diseases, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Data related to survival in children are scarce, but these data firmly associate NAFLD with higher risks of hepatic and non-hepatic morbidities and mortalities compared with the general population. More recently, the association between NAFLD and cardiovascular disease among children has increasingly been recognized. Given that obesity is a major risk factor for the disease, paediatric NAFLD is becoming a global issue, paralleling the dramatic rise in obesity worldwide. NASH, which is more common in obese children, has the potential to advance to liver fibrosis and failure. It is unclear why certain patients undergo such transformation but this susceptibility is likely related to an interaction between a genetically susceptible host and the surrounding environment. Currently, treatment is largely conservative and includes lifestyle modification, attainable through healthy weight reduction via diet and exercise. In this review, current knowledge about NAFLD in children is summarized. This review aims to increase the awareness of the medical community about a hidden public health issue and to identify current gaps in the literature while providing directions for future research. © 2015 World Obesity.

  15. Clinico-Biochemical Correlation to Histological Findings in Alcoholic Liver Disease: A Single Centre Study from Eastern India

    Science.gov (United States)

    Khanra, Dibbendhu; Sonthalia, Nikhil; Kundu, Supratip; Biswas, Kaushik; Talukdar, Arunansu; Saha, Manjari; Bera, Himel

    2014-01-01

    Background: Alcoholism is a health problem not only in developed countries but also in developing countries. Cirrhosis due to alcohol is a common cause of death among individuals abusing alcohol. A better knowledge of the spectrum of alcoholic liver diseases, its clinical, biochemical and histopathological features could result in early detection and prevention of alcoholic liver diseases before it’s catastrophic and life threatening effects. Materials and Methods: A total of 200 patients with alcoholic liver diseases were studied with respect to alcohol consumption, clinical features, biochemical and histopathological changes. The clinical features, biochemical parameters, and histopathology of liver including Ishak’s modified histological activity index (HAI) were correlated with the amount and duration of alcohol consumed. Result: Majority of the patients were in the age group of 40-49 years and all the cases were males. Majority consumed alcohol of about 75-90 grams per day for a duration of 10–12 years. Anorexia and jaundice were the most common symptom and clinical finding respectively. Hyperbilirubinemia and hypoalbuminemia were the most common abnormalities observed in liver function tests. Advanced HAI stages with features of cirrhosis were most frequent histo-pathological finding noted in this study. Clinico-biochemical profile was significantly correlated with degree of alcohol ingestion as well as with liver histopathology. Conclusion: The wide prevalence of alcoholic liver disease including cirrhosis among Indian males was noted with significantly lower quantity and duration of alcohol ingestion. The severity of liver damage is directly proportional to the quantity and duration of alcohol consumed. Clinical features and biochemical changes may forecast the liver histopathology among the patients of alcoholic liver disease. PMID:25478382

  16. Hypertrophic osteoarthropathy associated with alcoholic liver disease without cirrhosis.

    Science.gov (United States)

    Varju, T; Lesch, M; Adorján, A

    1986-01-01

    Two cases of secondary hypertrophic osteoarthropathy associated with alcoholic liver disease without cirrhosis are reported. Conditions which can be associated with hypertrophic osteoarthropathy and theoretical factors which can play a role in its pathomechanism are briefly discussed.

  17. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions.

    Science.gov (United States)

    Adolph, Timon E; Grander, Christoph; Grabherr, Felix; Tilg, Herbert

    2017-07-29

    Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD). Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC) also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  18. Adipokines and Non-Alcoholic Fatty Liver Disease: Multiple Interactions

    Directory of Open Access Journals (Sweden)

    Timon E. Adolph

    2017-07-01

    Full Text Available Accumulating evidence links obesity with low-grade inflammation which may originate from adipose tissue that secretes a plethora of pro- and anti-inflammatory cytokines termed adipokines. Adiponectin and leptin have evolved as crucial signals in many obesity-related pathologies including non-alcoholic fatty liver disease (NAFLD. Whereas adiponectin deficiency might be critically involved in the pro-inflammatory state associated with obesity and related disorders, overproduction of leptin, a rather pro-inflammatory mediator, is considered of equal relevance. An imbalanced adipokine profile in obesity consecutively contributes to metabolic inflammation in NAFLD, which is associated with a substantial risk for developing hepatocellular carcinoma (HCC also in the non-cirrhotic stage of disease. Both adiponectin and leptin have been related to liver tumorigenesis especially in preclinical models. This review covers recent advances in our understanding of some adipokines in NAFLD and associated HCC.

  19. Alcoholism and liver disease in Mexico: Genetic and environmental factors

    Science.gov (United States)

    Roman, Sonia; Zepeda-Carrillo, Eloy Alfonso; Moreno-Luna, Laura Eugenia; Panduro, Arturo

    2013-01-01

    Alcoholism and cirrhosis, which are two of the most serious health problems worldwide, have a broad spectrum of clinical outcomes. Both diseases are influenced by genetic susceptibility and cultural traits that differ globally but are specific for each population. In contrast to other regions around the world, Mexicans present the highest drinking score and a high mortality rate for alcoholic liver disease with an intermediate category level of per capita alcohol consumption. Mexico has a unique history of alcohol consumption that is linked to profound anthropological and social aspects. The Mexican population has an admixture genome inherited from different races, Caucasian, Amerindian and African, with a heterogeneous distribution within the country. Thus, genes related to alcohol addiction, such as dopamine receptor D2 in the brain, or liver alcohol-metabolizing enzymes, such as alcohol dehydrogenase class I polypeptide B, cytochrome P450 2E1 and aldehyde dehydrogenase class 2, may vary from one individual to another. Furthermore, they may be inherited as risk or non-risk haplogroups that confer susceptibility or resistance either to alcohol addiction or abusive alcohol consumption and possibly liver disease. Thus, in this era of genomics, personalized medicine will benefit patients if it is directed according to individual or population-based data. Additional association studies will be required to establish novel strategies for the prevention, care and treatment of liver disease in Mexico and worldwide. PMID:24307790

  20. Hospital contacts with alcohol problems prior to liver cirrhosis or pancreatitis diagnosis

    DEFF Research Database (Denmark)

    Askgaard, Gro; Neermark, Søren; Leon, David A.

    2017-01-01

    AIM To evaluate prior hospital contacts with alcohol problems in patients with alcoholic liver cirrhosis and pancreatitis. METHODS This was a register-based study of all patients diagnosed with alcoholic liver cirrhosis or pancreatitis during 2008-2012 in Denmark. Hospital contacts with alcohol p...... alcoholic liver cirrhosis or pancreatitis with preventive interventions in the hospital setting....

  1. Bermuda Triangle for the liver: alcohol, obesity, and viral hepatitis.

    Science.gov (United States)

    Zakhari, Samir

    2013-08-01

    Despite major progress in understanding and managing liver disease in the past 30 years, it is now among the top 10 most common causes of death globally. Several risk factors, such as genetics, diabetes, obesity, excessive alcohol consumption, viral infection, gender, immune dysfunction, and medications, acting individually or in concert, are known to precipitate liver damage. Viral hepatitis, excessive alcohol consumption, and obesity are the major factors causing liver injury. Estimated numbers of hepatitis B virus (HBV) and hepatitis C virus (HCV)-infected subjects worldwide are staggering (370 and 175 million, respectively), and of the 40 million known human immunodeficiency virus positive subjects, 4 and 5 million are coinfected with HBV and HCV, respectively. Alcohol and HCV are the leading causes of end-stage liver disease worldwide and the most common indication for liver transplantation in the United States and Europe. In addition, the global obesity epidemic that affects up to 40 million Americans, and 396 million worldwide, is accompanied by an alarming incidence of end-stage liver disease, a condition exacerbated by alcohol. This article focuses on the interactions between alcohol, viral hepatitis, and obesity (euphemistically described here as the Bermuda Triangle of liver disease), and discusses common mechanisms and synergy. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  2. Non-Alcoholic Fatty Liver Disease: From patient to population

    NARCIS (Netherlands)

    E.M. Koehler (Edith)

    2013-01-01

    textabstractNon-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in Western countries, in parallel with epidemics in obesity and type 2 diabetes mellitus. NAFLD comprises a wide range of histological findings, extending from simple steatosis to

  3. The Molecular Circadian Clock and Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Uduak S. Udoh

    2015-10-01

    Full Text Available Emerging evidence from both experimental animal studies and clinical human investigations demonstrates strong connections among circadian processes, alcohol use, and alcohol-induced tissue injury. Components of the circadian clock have been shown to influence the pathophysiological effects of alcohol. Conversely, alcohol may alter the expression of circadian clock genes and the rhythmic behavioral and metabolic processes they regulate. Therefore, we propose that alcohol-mediated disruption in circadian rhythms likely underpins many adverse health effects of alcohol that cut across multiple organ systems. In this review, we provide an overview of the circadian clock mechanism and showcase results from new studies in the alcohol field implicating the circadian clock as a key target of alcohol action and toxicity in the liver. We discuss various molecular events through which alcohol may work to negatively impact circadian clock-mediated processes in the liver, and contribute to tissue pathology. Illuminating the mechanistic connections between the circadian clock and alcohol will be critical to the development of new preventative and pharmacological treatments for alcohol use disorders and alcohol-mediated organ diseases.

  4. Risk for alcoholic liver cirrhosis after an initial hospital contact with alcohol problems

    DEFF Research Database (Denmark)

    Askgaard, Gro; Leon, David A; Kjaer, Mette S

    2017-01-01

    Alcoholic liver cirrhosis is usually preceded by many years of heavy drinking, in which cessation in drinking could prevent the disease. Alcohol problems are not consistently managed in hospital patients. We followed all Danish patients with an initial hospital contact with alcohol problems (into...

  5. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2005-01-01

    Alcohol and hepatotropic viruses cause the majority of liver cirrhosis cases in the Western World. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients with alcoholic or non-alcoholic...

  6. Molecular pathways in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD.

  7. Molecular pathways in non-alcoholic fatty liver disease

    Science.gov (United States)

    Berlanga, Alba; Guiu-Jurado, Esther; Porras, José Antonio; Auguet, Teresa

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the “double-hit” hypothesis. The primary insult or the “first hit” includes lipid accumulation in the liver, followed by a “second hit” in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs) and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA synthesis is increased, but FAs are also taken up from the serum. Furthermore, a decrease in mitochondrial FA oxidation and secretion of very-low-density lipoproteins has been reported. This review discusses the molecular mechanisms that underlie the pathophysiological changes of hepatic lipid metabolism that contribute to NAFLD. PMID:25045276

  8. ORIGINAL ARTICLE Non-Alcoholic Fatty Liver Disease and ...

    African Journals Online (AJOL)

    2018-01-01

    Jan 1, 2018 ... ABSTRACT. BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic ...

  9. [Non-alcoholic fatty liver disease and steatohepatitis].

    Science.gov (United States)

    Pár, Gabriella; Horváth, Gábor; Pár, Alajos

    2013-07-21

    Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, the hepatic manifestations of metabolic syndrome with close association with inzulin resistance and obesity, are the most common liver diseases, affecting up to a third of the population worldwide. They confer increased risk for hepatocellular carcinoma as well as cardiovascular diseases. The review aims to summarize advances in epidemiology, pathogenesis and clinical management of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Besides liver biopsy and biomarkers, a novel non-invasive diagnostic tool the called "controlled attenuation parameter" measuring the attenuation of ultrasound generated by the transient elastography transducer, can quantitatively assess the hepatic fat content and differentiate between steatosis grades. At the same time, liver stiffness (fibrosis) can also be evaluated. The authors present their own results obtained with the latter procedure. In non-alcoholic fatty liver disease, the lifestyle intervention, weight loss, diet and exercise supported by cognitive behavioural therapy represent the basis of management. Components of metabolic syndrome (obesity, dyslipidaemia, diabetes and arterial hypertension) have to be treated. Although there is no approved pharmacological therapy for NASH, it seems that long lasting administration of vitamin E in association with high dose ursodeoxycholic acid may be beneficial. In addition, omega-3 polyunsaturated fatty acid substitution can also decrease liver fat, however, the optimal dose is not known yet. Further controlled clinical studies are warranted to establish the real value of any suggested treatment modalities for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, although these are in experimental phase yet.

  10. Alcohol drinking pattern and risk of alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette Skalshøi

    2015-01-01

    BACKGROUND & AIMS: Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. METHODS: We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993......-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. RESULTS......: We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50...

  11. Molecular pathways in non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Berlanga A

    2014-07-01

    Full Text Available Alba Berlanga,1,* Esther Guiu-Jurado,1,* José Antonio Porras,1,2 Teresa Auguet1,21Group GEMMAIR (AGAUR and Applied Medicine Research Group, Department of Medicine and Surgery, Universitat Rovira i Virgili (URV, IISPV, Hospital Universitari Joan XXIII, Tarragona, Spain; 2Department of Internal Medicine, Hospital Universitari Joan XXIII Tarragona, Tarragona, Spain *These authors contributed equally to this workAbstract: Non-alcoholic fatty liver disease (NAFLD is a clinicopathological change characterized by the accumulation of triglycerides in hepatocytes and has frequently been associated with obesity, type 2 diabetes mellitus, hyperlipidemia, and insulin resistance. It is an increasingly recognized condition that has become the most common liver disorder in developed countries, affecting over one-third of the population and is associated with increased cardiovascular- and liver-related mortality. NAFLD is a spectrum of disorders, beginning as simple steatosis. In about 15% of all NAFLD cases, simple steatosis can evolve into non-alcoholic steatohepatitis, a medley of inflammation, hepatocellular injury, and fibrosis, often resulting in cirrhosis and even hepatocellular cancer. However, the molecular mechanism underlying NAFLD progression is not completely understood. Its pathogenesis has often been interpreted by the "double-hit" hypothesis. The primary insult or the "first hit" includes lipid accumulation in the liver, followed by a "second hit" in which proinflammatory mediators induce inflammation, hepatocellular injury, and fibrosis. Nowadays, a more complex model suggests that fatty acids (FAs and their metabolites may be the true lipotoxic agents that contribute to NAFLD progression; a multiple parallel hits hypothesis has also been suggested. In NAFLD patients, insulin resistance leads to hepatic steatosis via multiple mechanisms. Despite the excess hepatic accumulation of FAs in NAFLD, it has been described that not only de novo FA

  12. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Prasad, Vikram; Chirra, Shivani; Kohli, Rohit; Shull, Gary E.

    2014-01-01

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na + /H + exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors

  13. NHE1 deficiency in liver: Implications for non-alcoholic fatty liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Vikram, E-mail: prasadvm@ucmail.uc.edu [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Chirra, Shivani [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States); Kohli, Rohit [Department of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital, University of Cincinnati, Cincinnati, OH 45267 (United States); Shull, Gary E. [Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine (United States)

    2014-07-25

    Highlights: • FXR, PGC1α and PPARγ levels are upregulated in NHE1 deficient livers. • NHE1 deficiency downregulates expression of pro-lipogenic genes in liver. • Chronic exposure to high-fat diet upregulates hepatic NHE1 expression. • Loss of NHE1 better preserves hepatic insulin signaling in high-fat diet-fed mice. - Abstract: Non-alcoholic fatty liver disease NAFLD is closely associated with the dysregulation of lipid homeostasis. Diet-induced hepatic steatosis, which can initiate NAFLD progression, has been shown to be dramatically reduced in mice lacking the electroneutral Na{sup +}/H{sup +} exchanger NHE1 (Slc9a1). In this study, we investigated if NHE1 deficiency had effects in liver that could contribute to the apparent protection against aberrant lipid accumulation. RT-PCR and immunoblot analyses of wild-type and NHE1-null livers revealed an expression profile that strongly suggested attenuation of both de novo lipogenesis and hepatic stellate cell activation, which is implicated in liver fibrosis. This included upregulation of the farnesoid X receptor FXR, peroxisome proliferator-activated receptor PPARγ, its co-activator PGC1α, and sestrin 2, an antioxidant protein involved in hepatic metabolic homeostasis. Furthermore, expression levels of the pro-lipogenic liver X receptor LXRα, and acetyl CoA carboxylases 1 and 2 were downregulated. These changes were associated with evidence of reduced cellular stress, which persisted even upon exposure to a high-fat diet, and the better preservation of insulin signaling, as evidenced by protein kinase B/Akt phosphorylation (Ser473). These results indicate that NHE1 deficiency may protect against NAFLD pathogenesis, which is significant given the availability of highly specific NHE1 inhibitors.

  14. P-31 MR spectroscopy of alcoholic liver diseases

    International Nuclear Information System (INIS)

    Meyerhoff, D.J.; Boska, M.D.; Thomas, A.; Twieg, D.B.; Rockey, D.; Weiner, M.W.

    1988-01-01

    The goal of the experiments was to measure absolute molar metabolite concentrations of phosphorus metabolites in livers of healthy humans and patients with acute alcoholic hepatitis and hepatitis cirrhosis. Quantitative P-31 MR spectroscopy was performed at 2.0 T with a surface coil and the ISIS technique. Absolute hepatic P-31 metabolite concentrations in patients with alcoholic hepatitis and cirrhosis were decreased by 20% - 40% compared with levels in controls. Therefore, these experiments demonstrate that alcoholic liver disease is associated with decreased concentrations of adenosine triphosphate and other phosphorylated metabolites

  15. Recidivism in Liver Transplant Recipients With Alcoholic Liver Disease: Analysis of Demographic, Psychosocial, and Histology Features.

    Science.gov (United States)

    Satapathy, Sanjaya K; Eason, James D; Nair, Satheesh; Dryn, Oleksandra; Sylvestre, Pamela B; Kocak, Mehmet; Vanatta, Jason M

    2015-10-01

    Liver transplant for alcoholic liver disease requires identifying potential recipients at risk for recidivism. We sought to identify risk factors for recidivism and survival in recipients of liver transplant with alcoholic liver disease. Demographic, psychosocial, and histology features were evaluated as risk factors toward harmful recidivism in 148 recipients of liver transplant with alcoholic liver disease. Based on the univariate analysis using Cox proportional hazards model, duration of alcohol abstinence 6 months (HR 3.74; P = .011, 95% CI: 1.36-10.3), non-alcohol related criminal history (HR 3.18; P = .032, 95% CI: 1.1-9.15), support from immediate family (HR 0.24; P = .0061, 95% CI: 0.09-0.67), and active smoking at the time of liver transplant (HR 2.74; P = .041, 95% CI: 1-7.53) were identified as significant predictors for recidivism. Older patients had less likelihood of alcohol relapse (HR 0.91; P = .0014, 95% CI: 0.87-0.97) on univariate model. In multivariate model older patients (HR 0.91; P = .004, 95% CI: 0.86-0.97) and patients who have immediate family support (HR 0.27; P = .012, 95% CI: 0.10-0.76) predicated against recidivism. Suggestive features of alcoholic hepatitis on liver explant did not predict recidivism or long-term survival. One-, three-, and five-year patient survival rates estimated by Kaplan-Meier survival model in the recipients that remained abstinent were 95%, 87%, and 80%, compared with 87%, 49%, and 49% for the recipients with recidivism (P = .001). Recidivism is associated with earlier death after liver transplant. Older recipients and patients with immediate family support are less likely to have alcohol relapse, and have better long-term survival.

  16. [Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2016-06-19

    In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

  17. Alcoholic Liver Disease | Badenhorst | South African ...

    African Journals Online (AJOL)

    % of men and 30% of women consuming alcohol on a regular basis, alcohol related disease accounted for up to 7% of the total disease burden in South Africa. Nearly 20% of unintentional and 40.9% of intentional injuries is related to alcohol ...

  18. Curcumin improves alcoholic fatty liver by inhibiting fatty acid biosynthesis.

    Science.gov (United States)

    Guo, Chang; Ma, Jingfan; Zhong, Qionghong; Zhao, Mengyuan; Hu, Tianxing; Chen, Tong; Qiu, Longxin; Wen, Longping

    2017-08-01

    Alcoholic fatty liver is a threat to human health. It has been long known that abstinence from alcohol is the most effective therapy, other effective therapies are not available for the treatment in humans. Curcumin has a great potential for anti-oxidation and anti-inflammation, but the effect on metabolic reconstruction remains little known. Here we performed metabolomic analysis by gas chromatography/mass spectrometry and explored ethanol pathogenic insight as well as curcumin action pattern. We identified seventy-one metabolites in mouse liver. Carbohydrates and lipids were characteristic categories. Pathway analysis results revealed that ethanol-induced pathways including biosynthesis of unsaturated fatty acids, fatty acid biosynthesis and pentose and glucuronate interconversions were suppressed by curcumin. Additionally, ethanol enhanced galactose metabolism and pentose phosphate pathway. Glyoxylate and dicarboxylate metabolism and pyruvate metabolism were inhibited in mice fed ethanol diet plus curcumin. Stearic acid, oleic acid and linoleic acid were disease biomarkers and therapical biomarkers. These results reflect the landscape of hepatic metabolism regulation. Our findings illustrate ethanol pathological pathway and metabolic mechanism of curcumin therapy. Copyright © 2017. Published by Elsevier Inc.

  19. Prevalence of psoriasis in patients with alcoholic liver disease.

    LENUS (Irish Health Repository)

    Tobin, A M

    2012-02-01

    BACKGROUND: Excessive alcohol use has been implicated as a risk factor in the development of psoriasis, particularly in men. Despite this, little is known of the incidence or prevalence of psoriasis in patients who misuse alcohol. OBJECTIVE: To assess the prevalence of psoriasis in patients with alcoholic liver disease. METHODS: In total, 100 patients with proven alcoholic liver disease were surveyed for a history of psoriasis and a full skin examination was performed if relevant. RESULTS: Of the 100 patients, 15 reported a history of psoriasis and another 8 had evidence of current activity, suggesting a prevalence (past or present) of 15% in this group of patients. CONCLUSION: It would appear that the prevalence of psoriasis in patients who misuse alcohol is much higher than the 1-3% variously quoted in the general population.

  20. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues

    OpenAIRE

    Ursic-Bedoya, José; Faure, Stéphanie; Donnadieu-Rigole, Hélène; Pageaux, Georges-Philippe

    2015-01-01

    The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a “self-inflicted” condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common in...

  1. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ter Horst, Kasper W; Serlie, Mireille J

    2017-09-06

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be used for gluconeogenesis and de novo lipogenesis (DNL). Fructose-derived precursors also act as nutritional regulators of the transcription factors, including ChREBP and SREBP1c, that regulate the expression of hepatic gluconeogenesis and DNL genes. In support of these mechanisms, fructose intake increases hepatic gluconeogenesis and DNL and raises plasma glucose and triglyceride levels in humans. However, epidemiological and fructose-intervention studies have had inconclusive results with respect to liver fat, and there is currently no good human evidence that fructose, when consumed in isocaloric amounts, causes more liver fat accumulation than other energy-dense nutrients. In this review, we aim to provide an overview of the seemingly contradicting literature on fructose and NAFLD. We outline fructose physiology, the mechanisms that link fructose to NAFLD, and the available evidence from human studies. From this framework, we conclude that the cellular mechanisms underlying hepatic fructose metabolism will likely reveal novel targets for the treatment of NAFLD, dyslipidemia, and hepatic insulin resistance. Finally, fructose-containing sugars are a major source of excess calories, suggesting that a reduction of their intake has potential for the prevention of NAFLD and other obesity-related diseases.

  2. Inorganic arsenic causes fatty liver and interacts with ethanol to cause alcoholic liver disease in zebrafish

    Directory of Open Access Journals (Sweden)

    Kathryn Bambino

    2018-02-01

    Full Text Available The rapid increase in fatty liver disease (FLD incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD. We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf, including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR caused by endoplasmic reticulum (ER stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin, suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease. This article has an associated First Person interview with the first author of the paper.

  3. Therapeutic Potential of Chinese Herbal Medicines in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Kuan-Hung Lu

    2012-04-01

    Full Text Available Alcoholic liver disease (ALD is a complex chronic disease and is associated with a spectrum of liver injury ranging from steatosis and steatohepatitis to fibrosis and cirrhosis. Since effective therapies for ALD are still limited, Chinese herbal medicine is thought to be an important and alternative approach. This review focuses on the current scientific evidence of ALD by ten Chinese Materia Medica (中藥 zhōng yào, including Salviae Miltiorrhizae Radix (丹參 dān shēn, Notoginseng Radix (三七 sān qī, Lycii Fructus (枸杞子 gǒu qǐ zǐ, Cnidii Fructus (蛇床子 shé chuáng zǐ, Gentianae Radix (龍膽 lóng dǎn, Puerariae Radix (葛根 gé gēn, Puerariae Flos (葛花 gé huā, Magnoliae Officinalis Cortex (厚朴 hòu pò, Platycodonis Radix (桔梗 jié gěng, and Trigonellae Semen (胡蘆巴 hú lú bā. Potential mechanisms of these herbal medicines in ALD are involved in amelioration of enhanced inflammation, reduction of hepatic oxidative stress and lipogenesis, and enhancement of intestinal permeability in alcohol-induced liver injury models in vitro and in vivo. Accordingly, the evidenced therapeutic potential suggests that these herbs are promising candidates for prevention and development of new drugs for ALD in the future.

  4. NON-ALCOHOLIC FATTY LIVER DISEASE IN CHILDREN

    Directory of Open Access Journals (Sweden)

    L.V. Chistova

    2010-01-01

    Full Text Available Metabolic syndrome that represents a totality of interrelated carbohydrate metabolism and lipid disorders, as well as a mechanism regulating arterial tension and endothelium function is one of the critical issues in pediatrics. In recent years, children with metabolic syndrome are increasingly diagnosed with liver injuries symptoms that are associated with a fatty transformation of the liver [1–3]. In this case, non-alcoholic fatty liver disease (NAFLD, a liver manifestation of metabolic syndrome is diagnosed. The diagnosis is confirmed in the absence of alcohol abuse in the past medical history, virus and autoimmune liver disease markers, elimination of toxic and drug influence, as wells as disorders of copper and iron exchange in the patient’s system. One of the key risk factors for developing NAFLD in children is overeating and reduced physical activities. It was believed in the past that NAFLD is relatively benign, however, there is evidence in current literature that this is a pathological condition that may develop and result in extreme fibrotic alterations in the liver parenchymatous tissue all the way to cirrhosis and hepatocellular carcinoma [4]. Early-stage identification and timely launch of therapy for NAFLD in children represents one of the most important objectives in modern healthcare. Key words: metabolic syndrome, non-alcoholic fatty liver disease, children, steatohepatosis. (Pediatric Pharmacology. – 2010; 7(6:68-72

  5. Clinical utility of red cell distribution width in alcoholic and non-alcoholic liver cirrhosis.

    Science.gov (United States)

    Milić, Sandra; Mikolasević, Ivana; Radić, Mladen; Hauser, Goran; Stimac, Davor

    2011-09-01

    Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as apart of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We retrospectively analyzed 241 patients (176 men and 65 women) with liver cirrhosis and anemia, defined as a hemoglobin value reference range is 11-15%. Alcoholic liver cirrhosis had 204 patients (85%) while non-alcoholic cirrhosis had 37 patients (15%). In group of alcoholic cirrhosis the average RDW was 16.8%. In relation to severity of disease the average RDW for Child-Pugh A was 16.80%, for Child-Pugh B was 16.92%, for Child-Pugh C was 17.10%. In the group of non-alcoholic cirrhosis the average RDW was 16.73% and in relation to severity of disease for Child-Pugh A was 16.25%, for Child-Pugh B 17.01% and for Child-Pugh C was 16.87%. We didn't find statistically significant difference of RDW between alcoholic and non alcoholic cirrhosis (p > 0.05) and we didn't proved any statistically significant increase of RDW in relation to severity of disease in group of alcoholic cirrhosis (p = 0.915) nor in group of patients with non-alcoholic cirrhosis (p = 0.697). Our study showed that RDW had not any clinical value in differentiation of anemia neither in alcoholic and non-alcoholic liver cirrhosis nor in severity of liver disease.

  6. Hepatocyte oxidant stress and alcoholic liver disease

    NARCIS (Netherlands)

    Conde de la Rosa, L.; Moshage, H.; Nieto, N.

    Acute and chronic alcohol consumption increases the production of reactive oxygen species (ROS), and enhances lipid peroxidation of lipids, proteins, and DNA. The mechanism by which alcohol causes cell injury is still not clear but a major role for ROS and lipid peroxidation-end products is

  7. Nuclear Receptor-Mediated Alleviation of Alcoholic Fatty Liver by Polyphenols Contained in Alcoholic Beverages

    OpenAIRE

    Yao, Ruiqing; Yasuoka, Akihito; Kamei, Asuka; Ushiama, Shota; Kitagawa, Yoshinori; Rogi, Tomohiro; Shibata, Hiroshi; Abe, Keiko; Misaka, Takumi

    2014-01-01

    To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppre...

  8. Non-alcoholic fatty liver disease in 2016.

    Science.gov (United States)

    Townsend, S A; Newsome, Philip N

    2016-09-01

    Non-alcoholic fatty liver disease is the commonest cause of liver disease worldwide, and is rapidly becoming the leading indication for liver transplantation. Original articles, reviews and meta-analyses, guidelines. NAFLD strongly correlates with obesity and insulin resistance; currently, the best management strategy is weight loss and treatment of the metabolic syndrome. Recent data suggest that the presence of fibrosis and not non-alcoholic steatohepatitis (NASH) is the predictor of clinical outcome. Many phase 2 and 3 trials are underway. Drugs hoped to be effective are obeticholic acid, elafibranor, glucagon-like peptide-1 analogues and CCR2/5 inhibitors. Improved understanding of the pathophysiology of NAFLD should help us identify which patients progress to significant liver disease and to develop therapies to target this population. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. The Natural Course of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Calzadilla Bertot, Luis; Adams, Leon Anton

    2016-05-20

    Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, paralleling the epidemic of obesity and Type 2 diabetes mellitus (T2DM). NAFLD exhibits a histological spectrum, ranging from "bland steatosis" to the more aggressive necro-inflammatory form, non-alcoholic steatohepatitis (NASH) which may accumulate fibrosis to result in cirrhosis. Emerging data suggests fibrosis, rather than NASH per se, to be the most important histological predictor of liver and non-liver related death. Nevertheless, only a small proportion of individuals develop cirrhosis, however the large proportion of the population affected by NAFLD has led to predictions that NAFLD will become a leading cause of end stage liver disease, hepatocellular carcinoma (HCC), and indication for liver transplantation. HCC may arise in non-cirrhotic liver in the setting of NAFLD and is associated with the presence of the metabolic syndrome (MetS) and male gender. The MetS and its components also play a key role in the histological progression of NAFLD, however other genetic and environmental factors may also influence the natural history. The importance of NAFLD in terms of overall survival extends beyond the liver where cardiovascular disease and malignancy represents additional important causes of death.

  10. Pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    Dowman, J. K.; Tomlinson, J.W.; Newsome, P.N.

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of disease ranging from hepatocellular steatosis through steatohepatitis to fibrosis and irreversible cirrhosis. The prevalence of NAFLD has risen rapidly in parallel with the dramatic rise in obesity and diabetes, and is rapidly becoming the most common cause of liver disease in Western countries. Indeed, NAFLD is now recognized to be the aetiology in many cases previously labelled as cryptogenic cirrhosis.

  11. Colchicine for alcoholic and non-alcoholic liver fibrosis and cirrhosis. Protocol for a Cochrane Review

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2000-01-01

    The majority of liver fibrosis and liver cirrhosis cases in the Western World is caused by alcohol and hepatotoxic viruses. Colchicine is an anti-inflammatory and anti-fibrotic medication. Several randomised clinical trials have addressed the question whether colchicine has any efficacy in patients...

  12. Modern approach to the clinical management of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Del Ben, Maria; Polimeni, Licia; Baratta, Francesco; Pastori, Daniele; Loffredo, Lorenzo; Angelico, Francesco

    2014-07-14

    Non-alcoholic fatty liver disease (NAFLD) is the most common and emerging form of chronic liver disease worldwide. It includes a wide spectrum of liver diseases ranging from simple fatty liver to steatohepatitis, which may progress to cirrhosis, liver cancer, and liver mortality. Common metabolic diseases, which are well established cardiovascular risk factors, have been associated to NAFLD and cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. The pathogenesis of NAFLD appears multifactorial and many mechanisms have been proposed as possible causes of fatty liver infiltration. Management of fatty liver has become a major challenge to healthcare systems as the consequence of the increasing rates of obesity worldwide. First-line management focuses on lifestyle modifications. Moderate weight reduction either by dietary restriction or by increased habitual physical activity is safe and highly recommended. Several therapeutic interventions have been proposed. These include insulin sensitizer agents, lipid lowering drugs, antioxidants such as vitamin E and supplementation of vitamin D3. However, therapeutic strategies have been largely empirical so far, and experimental trials have mostly been carried out in uncontrolled settings with small sample sizes. Metabolic conditions such as diabetes mellitus, obesity, hypertension and hyperlipidemia, should be strongly considered and a multidisciplinary approach should be personalized for individual patients. Treatment of co-morbidities should be regarded as of paramount importance in the management of these patients. The purpose of this review is to examine different approaches for the clinical management of non-alcoholic fatty liver disease.

  13. Hypogonadism and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Mintziori, Gesthimani; Poulakos, Pavlos; Tsametis, Christos; Goulis, Dimitrios G

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is more common in men than in women. Thus, it has been suggested that sex steroids do have a role in the development of NAFLD. The aim of the current paper is to illustrate the association between NAFLD and hypogonadism, by reviewing data derived from both human and animal studies. The prevalence of NAFLD is high in men with hypogonadism, including those with idiopathic hypogonadotropic hypogonadism (IHH), as well as in women in post-menopause, those under estrogen receptor antagonist treatment or women with Turner syndrome. Estrogens seem to play a pivotal role in hepatic lipid homeostasis, as demonstrated in animal models with diminished ovarian estrogens (i.e., ovariectomized mice) and low serum testosterone (T) concentration is independently associated with NAFLD. The elucidation of the exact role of sex steroids in NAFLD pathogenesis would create a unique opportunity to develop novel therapies to tackle NAFLD disease.

  14. Chronic alcohol drinking: Liver and pancreatic cancer?

    Science.gov (United States)

    Zakhari, Samir

    2015-09-01

    Cancer is a multifactorial disease that results from complex interactions of numerous risk factors - genetic and environmental - over time, eventually leading to the diseased phenotypes. Thus, while epidemiological studies can point to risk factors, they cannot determine cause and effect relationships, and are unable to give biological and clinical insights into carcinogenesis. The link between any risk factor and carcinogenesis needs to be validated in experimental models. This is particularly true in epidemiological studies on alcohol consumption and its consequences. While there is no doubt that heavy alcohol consumption has devastating health effects, the inconsistencies in alcohol-related epidemiological studies and cancer suffer from possible sources of the variability in outcomes, ranging from inaccuracy of self-report of consumption to the problem of correlating cancer that started decades earlier to current or recent alcohol consumption. To further study the interactions between alcohol and cancer, the use of "Molecular Pathological Epidemiology" (MPE) advocated by Ogino et al. for dissecting the interplay between etiological factors, cellular and molecular characteristics, and disease progression in cancer is appropriate. MPE does not consider cancer as a single entity, rather it integrates analyses of epidemiological studies with the macroenvironment and molecular and microenvironment. This approach allows investigating the relationships between potential etiological agents and cancer based on molecular signatures. More research is needed to fully elucidate the link between heavy alcohol consumption and pancreatic cancer, and to further investigate the roles of acetaldehyde and FAEEs in pancreatic carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. A clinical and biochemical profile of biopsy-proven non-alcoholic fatty liver disease subjects

    International Nuclear Information System (INIS)

    Khurram, M.; Mushraf, M.

    2007-01-01

    To describe clinical and biochemical features of patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). Fifty patients of either and of all ages were included, who had ultrasound evidence of fatty liver, deranged liver enzymes, and negative history of alcohol uptake. Serological/biochemical tests/markers of other liver diseases were negative. Each subject underwent liver biopsy reported by a single histopathologist. Clinical (symptoms, hypertension, hepatomegaly, and obesity) and biochemical evaluation (for diabetes, lipid abnormalities, and aspartate to alanine aminotransferase ratio (AST/ALT)) of each subject was done. Chi-square and t-tests were used for p-value calculation for finding significant difference between fatty liver and non-alcoholic steato-hepatitis groups. Thirty three (66%) patients were female and 34% were male. Mean age was 45.50+-11.50 years. Histopathologically, 62% subjects had fatty liver alone, while 38% had nonalcoholic steatohepatitis (NASH). Fatigue (100%), hypertriglyceridemia (80%), hepatomegaly (72%), AST/ALT ratio <1 (72%), and obesity/overweight (54%) were common NAFLD-related features. Except for hypertriglycedemia (p-value 0.008), no statistically significant association was noted between these features and histopathological subtypes of NAFLD. NAFLD-related clinical and biochemical features included fatigue, obesity, hepatomegaly, AST/ALT ratio <1, and hypertriglycedemia. Significant relationship existed between hypertriglyceridemia and NASH. (author)

  16. Multicausality in fatty liver disease: Is there a rationale to distinguish between alcoholic and non-alcoholic origin?

    OpenAIRE

    Völzke, Henry

    2012-01-01

    Apart from alcohol, there are other factors that may induce complications, which resemble alcohol-related liver disorders. In particular, obesity has been brought into focus as a risk factor for fatty liver disease. The term “non-alcoholic” fatty liver disease is commonly used to distinguish between obesity-related and alcohol-related hepatic steatosis. This review uses the epidemiological perspective to critically assess whether it is necessary and useful to differentiate between alcoholic a...

  17. Liver damage caused by hepatitis C viral infection and ethyl alcohol consumption

    Directory of Open Access Journals (Sweden)

    Kostić Velimir

    2006-01-01

    Full Text Available Background/Aim. Hepatitis C virus infection (HCV is a complex disease, most commonly chronicle (80-85%. The aim of this research was to determinate the level of the liver damage in the patients cansed by HCV in conjunction with consuming ethyl alcohol. Methods. The research included 15 patients with chronic HCV infection supported by the misuse of ethyl alcohol, as well. The diagnosis of C infection hepatitis was proved using the ELISA test and PCR method. Results. The results of the study showed the liver damage by both HCV infection and ethyl alcohol, which was verified by the presence of biochemical changes and patohystological processing of the patients (liver biopsy and prosection. Patohystological changes were at the level of liver cirrhosis and carcinoma (2 patients. There was a signficant difference between the two subgroups (p < 0.001 regarding the examined values γ-GT, PLT and PTV. The basic therapeutic procedure was to introduce this category of patients into alcohol abstinence, and, in a few patients, to apply the antivirus therapy, as well. Conclusion. Based on the number of the examined patients (n = 15, we could conclude that a prolonged ethyl alcohol misuse with the presence of HCV infection was in a correlation with the liver disease progression.

  18. The short-term psychological health of alcoholic and non-alcoholic liver transplant recipients.

    Science.gov (United States)

    Beresford, T P; Schwartz, J; Wilson, D; Merion, R; Lucey, M R

    1992-10-01

    In response to limited resources and overwhelming clinical need, we previously developed an approach to alcoholic patient selection for liver transplant based on factors reported to predict short- and long-term sobriety in prospective studies of alcoholics. The present study reports follow-up data comparing alcohol dependent (n = 22, DSM-3-R criteria) and non-dependent (n = 39) subjects followed from 6 months to 3 years post-transplant. Nine percent of the alcoholics had returned to symptomatic drinking with 14% reporting some exposure to ethyl alcohol. Nearly half (46%) of the non-alcoholic group reported occasional social alcohol use. The alcoholic patients were less likely to be in their first marriage and more likely to be asked about alcohol use at follow-up clinic visits. In most other respects the two groups resembled each other more often than they differed. The alcoholic group reported continued high rates of prognostic factors associated with long-term abstinence although the content of these shifted noticeably between pre- and postoperative assessment. Members of both groups reported high frequencies of medication side effects, of missed doses of medications, and of depressive symptoms. Most felt the transplant had improved their lives but had brought on significant financial burden. There were no differences in subjective appraisals of either psychological or physical health between the two groups. These follow-up data suggest that carefully selected alcohol dependent patients will do as well as non-dependent patients after liver transplant.

  19. Gut-liver axis and probiotics: Their role in non-alcoholic fatty liver disease

    Science.gov (United States)

    Paolella, Giulia; Mandato, Claudia; Pierri, Luca; Poeta, Marco; Di Stasi, Martina; Vajro, Pietro

    2014-01-01

    The incidence of obesity and its related conditions, including non-alcoholic fatty liver disease (NAFLD), has dramatically increased in all age groups worldwide. Given the health consequences of these conditions, and the subsequent economic burden on healthcare systems, their prevention and treatment have become major priorities. Because standard dietary and lifestyle changes and pathogenically-oriented therapies (e.g., antioxidants, oral hypoglycemic agents, and lipid-lowering agents) often fail due to poor compliance and/or lack of efficacy, novel approaches directed toward other pathomechanisms are needed. Here we present several lines of evidence indicating that, by increasing energy extraction in some dysbiosis conditions or small intestinal bacterial overgrowth, specific gut microbiota and/or a “low bacterial richness” may play a role in obesity, metabolic syndrome, and fatty liver. Under conditions involving a damaged intestinal barrier (“leaky gut”), the gut-liver axis may enhance the natural interactions between intestinal bacteria/bacterial products and hepatic receptors (e.g., toll-like receptors), thus promoting the following cascade of events: oxidative stress, insulin-resistance, hepatic inflammation, and fibrosis. We also discuss the possible modulation of gut microbiota by probiotics, as attempted in NAFLD animal model studies and in several pilot pediatric and adult human studies. Globally, this approach appears to be a promising and innovative add-on therapeutic tool for NAFLD in the context of multi-target therapy. PMID:25400436

  20. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Iaquinto, G

    2005-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases.......Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  1. Plasmatic higher levels of homocysteine in Non-alcoholic fatty liver disease (NAFLD)

    OpenAIRE

    Carvalho, Sylene Coutinho Rampche de; Muniz, Maria Tereza Cartaxo; Siqueira, Maria Deozete Vieira; Siqueira, Erika Rabelo Forte; Gomes, Adriana Vieira; Silva, Karina Alves; Bezerra, Lais Carvalho Luma; D'Almeida, Vania [UNIFESP; Oliveira, Claudia Pinto Marques Souza de; Pereira, Leila Maria M. Beltrao

    2013-01-01

    Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between ...

  2. Alcoholic liver disease and hepatitis C virus infection.

    Science.gov (United States)

    Novo-Veleiro, Ignacio; Alvela-Suárez, Lucía; Chamorro, Antonio-Javier; González-Sarmiento, Rogelio; Laso, Francisco-Javier; Marcos, Miguel

    2016-01-28

    Alcohol consumption and hepatitis C virus (HCV) infection have a synergic hepatotoxic effect, and the coexistence of these factors increases the risk of advanced liver disease. The main mechanisms of this effect are increased viral replication and altered immune response, although genetic predisposition may also play an important role. Traditionally, HCV prevalence has been considered to be higher (up to 50%) in alcoholic patients than in the general population. However, the presence of advanced alcoholic liver disease (ALD) or intravenous drug use (IDU) may have confounded the results of previous studies, and the real prevalence of HCV infection in alcoholic patients without ALD or prior IDU has been shown to be lower. Due to the toxic combined effect of HCV and alcohol, patients with HCV infection should be screened for excessive ethanol intake. Patients starting treatment for HCV infection should be specifically advised to stop or reduce alcohol consumption because of its potential impact on treatment efficacy and adherence and may benefit from additional support during antiviral therapy. This recommendation might be extended to all currently recommended drugs for HCV treatment. Patients with alcohol dependence and HCV infection, can be treated with acamprosate, nalmefene, topiramate, and disulfiram, although baclofen is the only drug specifically tested for this purpose in patients with ALD and/or HCV infection.

  3. Non-Alcoholic Fatty Liver Disease (NAFLD) in Obesity

    OpenAIRE

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal; Sheth, Smit; Shah, Purav; Jasdanwala, Sarfaraz

    2014-01-01

    Background and Objectives: Limited studies have been undertaken to characterize Non-Alcoholic Fatty Liver Disease (NAFLD) in the Indian population. The main objective of our study was to document the prevalence of NAFLD amongst a cohort of obese Indian patients and demonstrate its relationship with other components of the metabolic syndrome.

  4. Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease

    NARCIS (Netherlands)

    ter Horst, Kasper W.; Serlie, Mireille J.

    2017-01-01

    Increased fructose consumption has been suggested to contribute to non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and insulin resistance, but a causal role of fructose in these metabolic diseases remains debated. Mechanistically, hepatic fructose metabolism yields precursors that can be

  5. Alcohol Consumption and Viral Hepatitis in Chronic Liver Disease in ...

    African Journals Online (AJOL)

    Background: Precise assessment of the risks and interactions of alcohol consumption and viral hepatitis in the aetiology of chronic liver disease [CLD] are not locally available. Methodology: 74 patients with CLD and 74 controls were evaluated for Hepatitis B and C infection [anti-HCV, HBsAg]. The type and amount of ...

  6. Adipose tissue, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Polyzos, Stergios A; Kountouras, Jannis; Mantzoros, Christos S

    2017-06-01

    The association of obesity with non-alcoholic fatty liver disease (NAFLD) has been established. Obesity has been linked not only to initial stages of the disease, i.e., simple steatosis (SS), but also to its severity. From an epidemiologic point of view, both diseases has an increasing prevalence worldwide. From a pathogenetic point of view, obesity and its associate IR contribute to the initial fat accumulation in the hepatocyte (SS), but also to the progression of SS to nonalcoholic steatohepatitis (NASH), NASH-related cirrhosis and hepatocellular carcinoma (HCC). From a clinical point of view, obesity has increased morbidity and mortality when combined with NAFLD, owing to cardiovascular and liver-specific mortality, including higher HCC risk. From a therapeutic point of view, weight loss is regarded as the cornerstone for the disease prevention and treatment. Although diet and exercise are the first choice to this aim, they are both difficult to achieve and sustain. Thus, the need for pharmacological treatment is considered of high importance. To treat obesity through pharmacologic weight loss, orlistat has been investigated, though with limited efficacy. Currently, liraglutide appears to be more efficacious, but it has not been officially approved for specifically NASH patients. Bariatric surgery is another alternative for severely obese patients showing histological improvement in NASH patients. However, since relative data from randomized trials are very limited, morbid obesity-related NASH patients may be subjected to bariatric surgery only after a careful individualized risk-benefit assessment.

  7. Alcoholic Liver Disease and Hepatitis C Chronic Infection.

    Science.gov (United States)

    Federico, Alessandro; Dallio, Marcello; Ormando, Vittorio M; Abenavoli, Ludovico; Masarone, Mario; Persico, Marcello; Loguercio, Carmela

    2016-01-01

    Alcoholic and virus C hepatitis currently represent the main causes of chronic liver disease worldwide. Every year many people die and are subjected to complex hospitalization and medical assistance due to these pathologies. Alcoholic liver disease and hepatitis C virus chronic infection are often present in the same patient. These two pathologies sinergically act in determining the onset and progression of liver damage that, from the chronic hepatitis staging, may rapidly progress to fibrosis, cirrhosis and hepatocellular carcinoma. In this review we analysed physiopathological aspects and biomolecular interactions that relate ethanol and hepatitis C virus in determining liver damage; moreover we took into account the effect on the natural history of liver disease deriving from the co-presence of these pathologies. Therefore we paid particular attention to the ability of ethanol and hepatitis C virus to in inducing oxidative stress or lipid accumulation, and analyzed the basic mechanisms of fibrogenesis that both diseases have got, amplified by their co-presence in the same patient. Finally we paid attention to the oncogenetic mechanisms inducing hepatocellular carcinoma and variability of response to antiviral therapy that derives from alcohol abuse in a subject affected by C hepatitis.

  8. [Advances in the pathogenesis of non alcoholic fatty liver disease].

    Science.gov (United States)

    Pár, Alajos; Pár, Gabriella

    2017-06-01

    Non alcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, and the most common liver disease. Its more aggressive form is the non alcoholic steatohepatitis. Multiple genetic and environmental factors lead to the accumulation of triglicerides and the inflammatory cascade. High fat diet, obesity, adipocyte dysfunction with cytokine production, insulin resistance and increased lipolysis with free fatty acid flux into the liver - all are the drivers of liver cell injury. Activation of inflammasome by damage- or pathogen-associated molecular patterns results in "steril inflammation" and immune response, while the hepatic stellate cells and progenitor cells lead to fibrogenesis. Small intestinal bacterial overgrowth and gut dysbiosis are also of pivotal importance in the inflammation. Among the susceptible genetic factors, mutations of patatin-like phospholipase domain containing 3 and the transmembrane 6 superfamily 2 genes play a role in the development and progression of the disease, similarly as do epigenetic regulators such as microRNAs and extracellular vesicles. Better understanding of the pathogenesis of non alcoholic fatty liver disease may identify novel therapeutic agents that improve the outcome of the disease. Orv Hetil. 2017; 158(23): 882-894.

  9. Hepatic venous oxygen content in alcoholic cirrhosis and non-cirrhotic alcoholic liver disease

    DEFF Research Database (Denmark)

    Bendtsen, F; Henriksen, Jens Henrik Sahl; Widding, A

    1987-01-01

    Blood gas analyses and hepatic blood flow were determined during hepatic vein catheterization in order to establish a possible hypoxic component in alcoholic liver disease. Fifty-six patients (9 non-cirrhotic liver disease, 14 cirrhosis Child-Turcotte class A, 23 class B, 10 class C) and 10 control...... venous difference of base excess was small and of the same size in all groups, indicating no enhanced production of lactic acid in the liver. Our results do not support the concept that hepatic venous oxygen content is low in alcoholic liver disease and thereby contributes to hypoxic liver damage....... subjects were studied. Mean hepatic venous oxygen saturation and tension were almost the same in all groups, and hepatic blood flow was inversely correlated to the arteriohepatic venous oxygen difference (r = -0.53, P less than 0.01). Splanchnic oxygen uptake was similar in all groups studied. The arterio-hepatic...

  10. Insulin resistance in clinical and experimental alcoholic liver disease.

    Science.gov (United States)

    Carr, Rotonya M; Correnti, Jason

    2015-09-01

    Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of healthcare dollars annually. Since the advent of the obesity epidemic, insulin resistance (IR) and diabetes have become common clinical findings in patients with ALD; and the development of IR predicts the progression from simple steatosis to cirrhosis in ALD patients. Both clinical and experimental data implicate the impairment of several mediators of insulin signaling in ALD, and experimental data suggest that insulin-sensitizing therapies improve liver histology. This review explores the contribution of impaired insulin signaling in ALD and summarizes the current understanding of the synergistic relationship between alcohol and nutrient excess in promoting hepatic inflammation and disease. © 2015 New York Academy of Sciences.

  11. An update on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in Asia.

    Science.gov (United States)

    Hsu, Ching-Sheng; Kao, Jia-Horng

    2017-08-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most overwhelming liver disease in Asia. In consideration of its increasing medical and economic impact on Asian people, it is time for us to review the update data in Asian countries and formulate strategies to cope with this emerging health problem in Asia. Moreover, growing data indicates that NAFLD may be a systemic disease, not just confined to liver-specific morbidity and mortality, but also associated with several extra-hepatic manifestations, such as cardiovascular diseases, chronic renal diseases, and malignancy. As the co-occurrence of NAFLD and viral hepatitis is common in Asia, issues related to the impact of NAFLD on the clinical outcomes and management of viral hepatitis remain to be elucidated. Areas covered: In this article, a narrative review was conducted, searching for literature from PubMed, Ovid MEDLINE, and the Cochrane Library database till August 2016. Studies relevant to the emerging data of NAFLD in Asia, including the diagnosis, risk factors, the assessment and management of Asian NAFLD patients were examined and discussed. Expert commentary: Collaboration in Asian countries to develop an effective and practical measurement to assess the severity of NAFLD is urgently required.

  12. The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Pietrobattista Andrea

    2009-05-01

    Full Text Available Abstract Background Liver fibrosis is a stage of non-alcoholic fatty liver disease (NAFLD which is responsible for liver-related morbidity and mortality in adults. Accordingly, the search for non-invasive markers of liver fibrosis has been the subject of intensive efforts in adults with NAFLD. Here, we developed a simple algorithm for the prediction of liver fibrosis in children with NAFLD followed at a tertiary care center. Methods The study included 136 male and 67 female children with NAFLD aged 3.3 to 18.0 years; 141 (69% of them had fibrosis at liver biopsy. On the basis of biological plausibility, readily availability and evidence from adult studies, we evaluated the following potential predictors of liver fibrosis at bootstrapped stepwise logistic regression: gender, age, body mass index, waist circumference, alanine transaminase, aspartate transaminase, gamma-glutamyl-transferase, albumin, prothrombin time, glucose, insulin, triglycerides and cholesterol. A final model was developed using bootstrapped logistic regression with bias-correction. We used this model to develop the 'pediatric NAFLD fibrosis index' (PNFI, which varies between 0 and 10. Results The final model was based on age, waist circumference and triglycerides and had a area under the receiver operating characteristic curve of 0.85 (95% bootstrapped confidence interval (CI with bias correction 0.80 to 0.90 for the prediction of liver fibrosis. A PNFI ≥ 9 (positive likelihood ratio = 28.6, 95% CI 4.0 to 201.0; positive predictive value = 98.5, 95% CI 91.8 to 100.0 could be used to rule in liver fibrosis without performing liver biopsy. Conclusion PNFI may help clinicians to predict liver fibrosis in children with NAFLD, but external validation is needed before it can be employed for this purpose.

  13. Reduced impact of renal failure on the outcome of patients with alcoholic liver disease undergoing liver transplantation.

    Science.gov (United States)

    Cheong, Jaeyoun; Galanko, Joseph A; Arora, Sumant; Cabezas, Joaquin; Ndugga, Nambi J; Lucey, Michael R; Hayashi, Paul H; Barritt, Alfred Sidney; Bataller, Ramon

    2017-02-01

    Pretransplant renal failure is commonly reported to be a poor prognostic indicator affecting survival after liver transplantation (LT). However, whether the impact of renal failure on patient outcome varies according to the aetiology of the underlying liver disease is largely unknown. We investigated the association between renal failure at the time of LT and patient outcome in patients with alcoholic liver disease (ALD) (n = 6920), non-alcoholic steatohepatitis (NASH) (n = 2956) and hepatitis C (HCV) (n = 14 922) using the United Network for Organ Sharing (UNOS) database between February 2002 and December 2013. A total of 24 798 transplant recipients were included. The presence of renal failure was more frequently seen in patients with ALD (23.95%) and NASH (23.27%) compared to patients with HCV (19.38%) (P renal failure was an independent predictor of poor survival. Renal failure showed detrimental effect on patient survival in the overall series (HR = 1.466, P renal failure was less marked in patients with ALD (HR = 1.31, P renal failure had better long-term prognosis than non-ALD patients. Renal failure at the time of LT conferred a lower patient and graft survival post-LT. However, renal failure has less impact on the outcome of patients with ALD than that of patients with non-alcoholic liver disease after LT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Efficacy of Qianggan capsule in treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia

    Directory of Open Access Journals (Sweden)

    Zhi-Jun He

    2016-07-01

    Full Text Available Objective: To observe the clinical effects of Qianggan capsule and silibinin capsule in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia. Methods: A total of 112 patients with non-alcoholic fatty liver disease were included in the study and divided into the control group (n=50 and the observation group (n=62. The patients in the control group were given silibinin capsule, while the patients in the observation group were given Qianggan capsule. The patients in the two groups were treated for 24 weeks. The liver/ spleen CT was performed before and after treatment. BMI was measured. The liver function, serum lipid, and leptin were detected. Results: TG, LDL-C, BMI, and liver/spleen CT ratio in the observation group were significantly reduced when compared with the control group. The levels of HDL-C and adiponectin in the observation group were significantly elevated when compared with the control group. The differences of ALT, GGT, and AST after treatment between the two groups were not statistically significant. Conclusions: Qianggan capsule and silibinin capsule has an accurate efficacy and high safety in the treatment of non-alcoholic fatty liver disease complicated with hyperlipidemia.

  15. Heme oxygenase-1 alleviates alcoholic liver steatosis: histopathological study

    Science.gov (United States)

    Palipoch, Sarawoot; Koomhin, Phanit; Punsawad, Chuchard; Na-Ek, Prasit; Sattayakhom, Apsorn; Suwannalert, Prasit

    2015-01-01

    Excessive alcohol consumption is one of the most important causes of hepatic steatosis, which involves oxidative stress. In particular, increased oxidative stress has been strongly linked to stimulation of the expression of heme oxygenase-1 (HO-1). This study aimed to investigate whether HO-1 could alleviates alcoholic steatosis in rats. Male Wistar rats were randomly divided into 4 groups: 1) the control group, 2) the EtOH group, 3) the EtOH + ZnPP-IX group and 4) the EtOH + Hemin group. Liver histopathology was investigated in weeks 1 and 4 after the start of the treatment period. Alcohol treatment significantly increased the hepatic malondialdehyde (MDA) levels, an oxidative stress marker. In addition, it increased the triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in both weeks. Gross examination demonstrated a yellowish and slightly enlarged liver in the alcohol-treated rats. Hematoxylin and eosin (H&E) and Oil Red O staining indicated hepatic steatosis, which was characterized by diffuse, extensive fatty accumulation and discrete lipid droplets of variable size in hepatocytes of the alcohol-treated rats. Administration of the HO-1 inducer hemin resulted in upregulation of hepatic HO-1 gene expression, reduced the MDA, triglyceride, ALT and AST levels and alleviated alcoholic hepatic steatosis, whereas administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX) resulted in downregulation of hepatic HO-1 gene expression and could not alleviate alcoholic hepatic steatosis either week. In conclusion, HO-1 could alleviate alcoholic hepatic steatosis in male Wistar rats and may be useful in development of a new therapeutic approach. PMID:26989297

  16. Liver fat content, non-alcoholic fatty liver disease, and ischaemic heart disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Kristensen, Thomas Skårup

    2018-01-01

    Aims: In observational studies, non-alcoholic fatty liver disease (NAFLD) is associated with high risk of ischaemic heart disease (IHD). We tested the hypothesis that a high liver fat content or a diagnosis of NAFLD is a causal risk factor for IHD. Methods and results: In a cohort study...... of the Danish general population (n = 94 708/IHD = 10 897), we first tested whether a high liver fat content or a diagnosis of NAFLD was associated observationally with IHD. Subsequently, using Mendelian randomization, we tested whether a genetic variant in the gene encoding the protein patatin......-like phospholipase domain containing 3 protein (PNPLA3), I148M (rs738409), a strong and specific cause of high liver fat content and NAFLD, was causally associated with the risk of IHD. We found that the risk of IHD increased stepwise with increasing liver fat content (in quartiles) up to an odds ratio (OR) of 2...

  17. Non-alcoholic fatty liver disease and colorectal cancer.

    Science.gov (United States)

    Mikolasevic, I; Orlic, L; Stimac, D; Hrstic, I; Jakopcic, I; Milic, S

    2017-03-01

    As a significant cause of cancer death worldwide, colorectal cancer (CRC) is still one of the most common cancers in the world. The most efficient strategies to reduce CRC incidence include identifying risk factors for CRC and performing a preventive colonoscopy in high-risk populations. Some well-established risk factors for CRC development include hereditary syndromes and inflammatory bowel disease. Of note, in recent years, attention has been given to new evidence indicating that more than 75%-95% of CRC occurs in individuals with little or no genetic risk. For these individuals, the risk for CRC is associated with their lifestyle and dietary factors, including central obesity, overweight and physical inactivity. Recently, evidence demonstrated a connection between non-alcoholic fatty liver disease (NAFLD) and CRC. Insulin resistance and metabolic syndrome (MetS) are common risks that NAFLD and colorectal neoplasms share. The incidence of NAFLD is increasing in parallel with an increasing prevalence of MetS and obesity. Consequently, the question arises: will the incidence of CRC increase together with this dramatic increase in obesity, MetS and ultimately NAFLD prevalence? Recent studies of adenomatous polyps, CRC and NAFLD are discussed in this manuscript. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. A meta-analysis of HLA-antigen prevalences in alcoholics and alcoholic liver disease

    DEFF Research Database (Denmark)

    List, S; Gluud, C

    1994-01-01

    suspected of being associated with both alcoholism and alcoholic liver disease. In the present study a meta-analysis is carried out on the data from these studies, subdivided according to race and degree of liver injury. The conclusion is that none of the HLA-phenotypes so far investigated in Caucasians can...... be shown to be significantly more common in any of the studied patient categories than in controls, whereas the results of Japanese studies are less clear. The limitations of the data material and the design of the studies are discussed, as well as the strength and limitations of the method of meta-analysis....

  19. NON-ALCOHOLIC FATTY LIVER DISEASE AT OUR INSTITUTE

    Directory of Open Access Journals (Sweden)

    Madhavi

    2015-12-01

    Full Text Available INTRODUCTION A Correlation clinical observational hospital based clinical study with 50 patients were undertaken to study the Clinical Profile of incidentally detected Non Alcoholic Fatty Liver Disease. The cases for the study were selected retrospectively who were diagnosed as fatty liver by ultrasound imaging who attended the Department of General Medicine, Government General Hospital Kakinada Rangaraya Medical College. Data has been enumerated for those who fulfilled the inclusion criteria. This study was conducted between January 2013-January 2015. The study has limitations of observer variant dependent diagnostic ultrasound for inclusion in to study. A BMI of>25 kg/m2 taken as definition for obesity for analysis.

  20. Impact of bariatric surgery on non-alcoholic fatty liver disease.

    Science.gov (United States)

    Major, Piotr; Pędziwiatr, Michał; Rubinkiewicz, Mateusz; Stanek, Maciej; Głuszewska, Anna; Pisarska, Magdalena; Małczak, Piotr; Budzyński, Andrzej; Budzyński, Piotr

    2017-04-30

    Introduction; p to 300 million people have the body mass index (BMI) greater than 30 kg/m2. Obesity is the cause of many serious diseases, such as type 2 diabetes, hypertension, and non-alcoholic fatty liver disease (NAFLD). Bariatric surgery is the only effective method of achieving weight loss in patients with morbid obesity. The aim of the study was to assess the impact of bariatric surgery on non-alcoholic fatty liver disease in patients operated on due to morbid obesity. We included 20 patients who were qualified for bariatric procedures based on BMI > 40 kg/ m2 or BMI > 35kg/m2 with the presence of comorbidities. The average body weight in the group was 143.85kg, with an average BMI of 49.16kg/m2. Before the procedure, we evaluated the severity of non-alcoholic fatty liver disease in each patient using the Sheriff-Saadeh ultrasound scale. We also evaluated the levels of liver enzymes. Follow-up evaluation was performed twelve months after surgery. Twelve months after surgery, the average weight was 102.34 kg. The mean %WL was 33.01%, %EWL was 58.8%, and %EBMIL was 61.37%. All patients showed remission of fatty liver disease. Liver damage, evaluated with ultrasound imaging, decreased from an average of 1.85 on the Sheriff-Saadeh scale, before surgery, to 0.15 twelve months after surgery (p < 0.001). As regards liver enzymes, the level of alanine aminotransferase decreased from 64.5 (U/l) to 27.95 (U/l) (p < 0.001), and the level of aspartate aminotransferase decreased from 54.4 (U/l) to 27.2 (U/l). Bariatric procedures not only lead to a significant and lasting weight loss, but they also contribute to the reduction of fatty liver disease and improve liver function.

  1. Predictors of heavy drinking after liver transplantation for alcoholic liver disease in Denmark (1990-2013)

    DEFF Research Database (Denmark)

    Askgaard, Gro; Tolstrup, Janne S.; Gerds, Thomas A.

    2016-01-01

    incidence of heavy drinking among patients transplanted for alcoholic liver disease in Denmark 1990-2013. We then analyzed pre-transplant demographic and psychiatric characteristics as predictors of post-transplant heavy drinking. Information was obtained from medical records, from nationwide registries...

  2. An in vitro method of alcoholic liver injury using precision-cut liver slices from rats

    NARCIS (Netherlands)

    Klassen, Lynell W.; Thiele, Geoffrey M.; Duryee, Michael J.; Schaffert, Courtney S.; DeVeney, Amy L.; Hunter, Carlos D.; Olinga, Peter; Tuma, Dean J.

    2008-01-01

    Alcohol abuse results in liver injury, but investigations into the mechanism(s) for this injury have been hampered by the lack of appropriate in vitro culture models in which to conduct in depth and specific studies. In order to overcome these shortcomings, we have developed the use of precision-cut

  3. Drinking patterns and biochemical signs of alcoholic liver disease in Danish and Greenlandic patients with alcohol addiction

    DEFF Research Database (Denmark)

    Lavik, Berit; Holmegaard, Claes; Becker, Ulrik

    2006-01-01

    . This study was designed to document the prevalence of alcoholic liver diseases in Greenlanders with a high alcohol intake, and to describe and compare the populations of patients with alcohol addiction in Greenland and Denmark. STUDY DESIGN: Clinical cross-sectional study of patients attending alcohol...

  4. Pathogenesis of hepatic steatosis: The link between hypercortisolism and non-alcoholic fatty liver disease

    OpenAIRE

    Tarantino, Giovanni; Finelli, Carmine

    2013-01-01

    Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of p...

  5. Epidemiological modifiers of non-alcoholic fatty liver disease: focus on high-risk groups

    OpenAIRE

    Lonardo, A.; Bellentani, S.; Argo, C.K.; Ballestri, S.; Byrne, Christopher D.; Caldwell, S.H.; Cortez-Pinto, H.; Grieco, A.; Machado, M.V.; Miele, L.; Targher, G.

    2015-01-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups.We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to r...

  6. EXPERIENCE OF ORNITHINE ASPARTATE (HEPA-MERZ AND PROBIOTICS BIOFLORUM FORTE IN THE TREATMENT OF NON-SEVERE FORMS OF ALCOHOLIC AND NON-ALCOHOLIC FATTY LIVER DISEASE

    Directory of Open Access Journals (Sweden)

    L. Yu. Ilchenko

    2016-01-01

    Full Text Available Aim: to evaluate the efficacy and tolerability of ornithine aspartate, probiotic Bioflorum Forte and their combination with steatosis and steatohepatitis in patients  with alcohol and non-alcoholic  fatty  liver disease. Materials and methods.  An open, randomized,  comparative  clinical study, which included 30 outpatients and inpatients with a diagnosis of steatosis, steatohepatitis. We analyzed the clinical symptoms, functional state of the liver. With the help of questionnaires  (Grids LeGo and post intoxication alcohol syndrome have established the presence of chronic alcohol intoxication. Test transmissions of numbers used to characterize the cognitive function, as well as detection  of minimal hepatic encephalopathy. Quality of life was assessed by questionnaire for patients with chronic liver disease — CLDQ (The chronic liver disease questionnaire. The duration of treatment was4 weeks. Results: all three treatment regimens have demonstrated therapeutic  efficacy: clinical improvement, recovery of liver function and results in cognitive function. When combined therapy also produced a significant improvement  in patients’ quality of life. It is shown that  the safety and tolerability of the means employed, adverse events were not reported. Conclusion: the results obtained allow us to recommend the use of ornithine aspartate (Hepa-Merz, both as monotherapy and as part of complex therapy of steatosis,  steatohepatitis with probiotic Bioflorum Forte in patients with alcoholic and non-alcoholic fatty liver disease.

  7. Obstructive Sleep Apnea and Non-alcoholic Fatty Liver Disease: Is the Liver Another Target?

    Directory of Open Access Journals (Sweden)

    Aibek eMirrakhimov

    2012-10-01

    Full Text Available Obstructive sleep apnea (OSA is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH. OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD. NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohepatitis (NASH, liver fibrosis and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure (CPAP treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1 IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA flux into the liver; (2 IH up-regulates lipid biosynthetic pathways in the liver; (3 IH induces oxidative stress in the liver; (4 IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.

  8. Prevalence of non alcoholic fatty liver disease in patients with metabolic syndrome

    International Nuclear Information System (INIS)

    Iftikhar, R.; Kamran, S.M.

    2015-01-01

    To determine frequency of Non Alcoholic fatty liver disease in patients with Metabolic Syndrome (MetS). Study Design: Cross sectional study. Place and Duration of Study: Department of medicine, CMH Okara, Jan 2013 to July 2013. Patients and Methods: We included 491 adult males, diagnosed with metabolic syndrome (MetS), presenting in outpatient department for routine review. MetS was diagnosed as per the International Diabetes Federation (IDF) proposed criteria of 2004. Detailed history and examination of each individual was done and data entered in pre designed performa. Brightness and posterior attenuation on ultrasound abdomen were considered indices for fatty liver disease in presence of elevated ALT, negative hepatitis serology and absence of alcohol intake. All the data was analyzed using SPSS version 16. p value of less than 0.05 was considered statistically significant. Results: Out of 491 participants with MetS, 222 (45.2%) had fatty liver disease. Mean BMI in patients with metabolic syndrome was 26.1 (± .89) and mean BMI in fatty liver patients was 27.3 (± 0.67). Out of total 5 components of Mets, patients with fatty liver disease had 3.24 (± 0.25) components, as compared to 2.1 (± 0.34) in whole of study group. Conclusion: A large number of patients with metabolic syndrome have fatty liver disease. Fatty liver disease is more frequent in patients who are overweight and those having multiple risk factors of metabolic syndrome. (author)

  9. Alcoholic liver disease in Nepal: identifying homemade alcohol as a culprit.

    Science.gov (United States)

    Pradhan, Bickram; Hadengue, Antoine; Chappuis, François; Chaudhary, Shatdal; Baral, Dharanidhar; Gache, Pascal; Karki, Prahlad; Rijal, Suman

    2015-01-01

    Though the type of alcohol consumed is not thought to be associated with alcoholic liver disease (ALD), some studies have shown a beverage-specific effect. In the present study, we aim to study the effects of locally brewed alcoholic beverages on the development of liver disease. This cross-sectional study was conducted at the internal medicine department of a university hospital in Nepal. All patients classified as having either alcohol abuse or alcohol dependence by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition were evaluated for the presence of ALD. A total of 1,500 patients were screened, of which, 447 patients had ALD. Chronic liver disease (CLD) was detected in 144 patients (9.6%). Most of the patients consumed homemade locally brewed alcohol. On multivariate analysis, the following variables were found to be significantly associated with CLD: male sex (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.12-2.94; P=0.02): rakshi consumption ≥30 units (OR: 2.53; 95% CI: 1.07-6.01; P=0.04); and tongba consumption (OR: 3.02; 95% CI: 1.22-7.50; P=0.02). There was a significant increase in the risk of developing ALD with the consumption of rakshi and tongba after adjusting for total units consumed. The absence of striking differences between our patients with CLD and non-CLD patients with regards to the amount of alcohol consumed demonstrates that, although alcohol consumption is a prerequisite for the development of ALD, other factors like type of alcoholic beverage consumed may be involved.

  10. Alcoholic liver disease in Nepal: identifying homemade alcohol as a culprit

    Directory of Open Access Journals (Sweden)

    Pradhan B

    2015-07-01

    Full Text Available Bickram Pradhan,1 Antoine Hadengue,2 François Chappuis,3 Shatdal Chaudhary,1 Dharanidhar Baral,4 Pascal Gache,5 Prahlad Karki,6 Suman Rijal6 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, B P Koirala Institute of Health Sciences, Dharan, Nepal; 2Department of Gastroenterology and Hepatology, 3Division of Tropical and Humanitarian Medicine, Geneva University Hospital, Geneva, Switzerland; 4Department of Community Medicine and School of Public Health, B P Koirala Institute of Health Sciences, Dharan, Nepal; 5Department of Health and Community Medicine. Geneva University Hospital, Geneva, Switzerland; 6Department of Internal Medicine, B P Koirala Institute of Health Sciences, Dharan, Nepal Background: Though the type of alcohol consumed is not thought to be associated with alcoholic liver disease (ALD, some studies have shown a beverage-specific effect. In the present study, we aim to study the effects of locally brewed alcoholic beverages on the development of liver disease.Patients and methods: This cross-sectional study was conducted at the internal medicine department of a university hospital in Nepal. All patients classified as having either alcohol abuse or alcohol dependence by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition were evaluated for the presence of ALD.Results: A total of 1,500 patients were screened, of which, 447 patients had ALD. Chronic liver disease (CLD was detected in 144 patients (9.6%. Most of the patients consumed homemade locally brewed alcohol. On multivariate analysis, the following variables were found to be significantly associated with CLD: male sex (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.12–2.94; P=0.02: rakshi consumption ≥30 units (OR: 2.53; 95% CI: 1.07–6.01; P=0.04; and tongba consumption (OR: 3.02; 95% CI: 1.22–7.50; P=0.02.Conclusion: There was a significant increase in the risk of developing ALD with the consumption of rakshi

  11. Alcohol intake and colorectal cancer: a comparison of approaches for including repeated measures of alcohol consumption

    DEFF Research Database (Denmark)

    Thygesen, Lau Caspar; Wu, Kana; Grønbaek, Morten

    2008-01-01

    BACKGROUND: In numerous studies, alcohol intake has been found to be positively associated with colorectal cancer risk. However, the majority of studies included only one exposure measurement, which may bias the results if long-term intake is relevant.METHODS: We compared different approaches...... for including repeated measures of alcohol intake among 47,432 US men enrolled in the Health Professionals Follow-up Study. Questionnaires including questions on alcohol intake had been completed in 1986, 1990, 1994, and 1998. The outcome was incident colorectal cancer during follow-up from 1986 to 2002.RESULTS......: During follow-up, 868 members of the cohort experienced colorectal cancer. Baseline, updated, and cumulative average alcohol intakes were positively associated with colorectal cancer, with only minor differences among the approaches. These results support moderately increased risk for intake >30 g...

  12. Perceptions of post-transplant recidivism in liver transplantation for alcoholic liver disease

    Science.gov (United States)

    Kawaguchi, Yoshikuni; Sugawara, Yasuhiko; Akamatsu, Nobuhisa; Kaneko, Junichi; Tanaka, Tomohiro; Tamura, Sumihito; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2014-01-01

    Although alcoholic liver disease (ALD) is regarded as a common indication for liver transplantation (LT), debatable issues exist on the requirement for preceding alcoholic abstinence, appropriate indication criteria, predictive factors for alcoholic recidivism, and outcomes following living-donor LT. In most institutions, an abstinence period of six months before LT has been adopted as a mandatory selection criterion. Data indicating that pre-transplant abstinence is an associated predictive factor for alcoholic recidivism supports the reasoning behind this. However, conclusive evidence about the benefit of adopting an abstinence period is yet to be established. On the other hand, a limited number of reports available on living-donor LT experiences for ALD patients suggest that organ donations from relatives have no suppressive effect on alcoholic recidivism. Prevention of alcoholic recidivism has proved to be the most important treatment after LT based on the resultant inferior long-term outcome of patients. Further evaluations are still needed to establish strategies before and after LT for ALD. PMID:25429319

  13. Non-alcoholic Fatty Liver Disease: East Versus West

    Science.gov (United States)

    Agrawal, Swastik; Duseja, Ajay K

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease worldwide with prevalence ranging from 10% to 30% in various countries. It has become an important cause of unexplained rise in transaminases, cryptogenic cirrhosis, and cryptogenic hepatocellular carcinoma. Pathogenesis is related to obesity, insulin resistance, oxidative stress, lipotoxicity, and resultant inflammation in the liver progressing to fibrosis. Pharmacological treatment in patients with NAFLD is still evolving and the treatment of these patients rests upon lifestyle modification with diet and exercise being the cornerstones of therapy. While there are many similarities between patients with NAFLD from Asia and the West, there are certain features which make the patients with NAFLD from Asia stand apart. This review highlights the data on NAFLD from Asia comparing it with the data from the West. PMID:25755421

  14. Case report : tuberculosis liver abscess in male alcoholism patient

    Science.gov (United States)

    Siahaan, W. P.; Ginting, F.

    2018-03-01

    A liver abscess often occurs in low-middle income countries such as Indonesia. Two most common liver abscesses are amoebic and pyogenic liver abscess. Data that reported tuberculosis liver abscess (TLA) is extremely rare. A diagnostic criterion for tuberculosis liver abscess is rare and remains unclear. A 52-year-old man developed a TLA which was not associated with any pulmonary or gastrointestinal tract foci of tuberculosis. An ultrasonogram and abdominal scan showed an abscess in the right lobe. We performed paracentesis, and the pus from the lesion was positive tubercular bacilli on acid-fast bacilli staining. The patient was started on systemic antitubercular therapy to which he responded favorably. This report emphasizes the fact that, although a TLA is a very rare entity, it should be included in the differential diagnosis of liver abscess especially in Indonesia where the prevalence of tuberculosis is extremely high.

  15. Iron homeostasis and H63D mutations in alcoholics with and without liver disease

    Science.gov (United States)

    Machado, Mariana Verdelho; Ravasco, Paula; Martins, Alexandra; Almeida, Maria Rosário; Camilo, Maria Ermelinda; Cortez-Pinto, Helena

    2009-01-01

    AIM: To evaluate the prevalence of HFE gene mutation and indices of disturbed iron homeostasis in alcoholics with and without liver disease. METHODS: One hundred and fifty-three heavy drinkers (defined as alcohol consumption > 80 g/d for at least 5 years) were included in the study. These comprised 78 patients with liver disease [liver disease alcoholics (LDA)] in whom the presence of liver disease was confirmed by liver biopsy or clinical evidence of hepatic decompensation, and 75 subjects with no evidence of liver disease, determined by normal liver tests on two occasions [non-liver disease alcoholics (NLDA)], were consecutively enrolled. Serum markers of iron status and HFE C282Y and H63D mutations were determined. HFE genotyping was compared with data obtained in healthy blood donors from the same geographical area. RESULTS: Gender ratio was similar in both study groups. LDA patients were older than NLDA patients (52 ± 10 years vs 48 ± 11 years, P = 0.03). One third and one fifth of the study population had serum transferrin saturation (TS) greater than 45% and 60% respectively. Serum iron levels were similar in both groups. However, LDA patients had higher TS (51 ± 27 vs 36 ± 13, P < 0.001) and ferritin levels (559 ± 607 ng/mL vs 159 ± 122 ng/mL, P < 0.001), and lower total iron binding capacity (TIBC) (241 ± 88 μg/dL vs 279 ± 40 μg/dL, P = 0.001). The odds ratio for having liver disease with TS greater than 45% was 2.20 (95% confidence interval (CI): 1.37-3.54). There was no difference in C282Y allelic frequency between the two groups. However, H63D was more frequent in LDA patients (0.25 vs 0.16, P = 0.03). LDA patients had a greater probability of carrying at least one HFE mutation than NLDA patients (49.5% vs 31.6%, P = 0.02). The odds ratio for LDA in patients with H63D mutation was 1.57 (95% CI: 1.02-2.40). CONCLUSION: The present study confirms the presence of iron overload in alcoholics, which was more severe in the subset of subjects with

  16. An empirical analysis of the relationship between the consumption of alcohol and liver cirrhosis mortality

    DEFF Research Database (Denmark)

    Bentzen, Jan Børsen; Smith, Valdemar

    The question whether intake of alcohol is associated with liver cirrhosis mortality is analyzed using aggregate data for alcohol consumption, alcohol related diseases and alcohol policies of 16 European countries. The empirical analysis gives support to a close association between cirrhosis...... mortality and intake of alcohol - and the latter also concerns each of the specific beverages, i.e. spirits, wine and beer, where other studies usually only find evidence of spirits and wine related to liver cirrhosis mortality.  ...

  17. Hepatoprotective effect of kaempferol against alcoholic liver injury in mice.

    Science.gov (United States)

    Wang, Meng; Sun, Jianguo; Jiang, Zhihui; Xie, Wenyan; Zhang, Xiaoying

    2015-01-01

    Kaempferol is a biologically active component present in various plants. The hepatoprotective effect of kaempferol in drug-induced liver injury has been proven, while its effect against alcoholic liver injury (ALI) remains unclear. Hence, the present study aimed to evaluate the effect of kaempferol against ALI in mice. The experimental ALI mice model was developed and the mice were treated with different doses of kaempferol for 4 weeks. The liver functions were observed by monitoring the following parameters: Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) levels in serum; histopathological studies of liver tissue; oxidative stress by hydrogen peroxide (H2O2), superoxide dismutase (SOD) and glutathione (GSH); the lipid peroxidation status by malondialdehyde (MDA) and lipid accumulation by triglyceride (TG) level in serum; and the expression levels and activities of a key microsomal enzyme cytochrome 2E1 (CYP2E1), by both in vitro and in vivo methods. The ALI mice (untreated) showed clear symptoms of liver injury, such as significantly increased levels of oxidative stress, lipid peroxidation and excessive CYP2E1 expression and activity. The mice treated with different kaempferol dosages exhibited a significant decrease in the oxidative stress as well as lipid peroxidation, and increased anti-oxidative defense activity. The kaempferol treatment has significantly reduced the expression level and activity of hepatic CYP2E1, thus indicating that kaempferol could down regulate CYP2E1. These findings show the hepatoprotective properties of kaempferol against alcohol-induced liver injury by attenuating the activity and expression of CYP2E1 and by enhancing the protective role of anti-oxidative defense system.

  18. Alcohol drinking pattern and risk of alcoholic liver cirrhosis: a prospective cohort study.

    Science.gov (United States)

    Askgaard, Gro; Grønbæk, Morten; Kjær, Mette S; Tjønneland, Anne; Tolstrup, Janne S

    2015-05-01

    Alcohol is the main contributing factor of alcoholic cirrhosis, but less is known about the significance of drinking pattern. We investigated the risk of alcoholic cirrhosis among 55,917 participants (aged 50-64 years) in the Danish Cancer, Diet, and Health study (1993-2011). Baseline information on alcohol intake, drinking pattern, and confounders was obtained from a questionnaire. Follow-up information came from national registers. We calculated hazard ratios (HRs) for alcoholic cirrhosis in relation to drinking frequency, lifetime alcohol amount, and beverage type. We observed 257 and 85 incident cases of alcoholic cirrhosis among men and women, respectively, none among lifetime abstainers. In men, HR for alcoholic cirrhosis among daily drinkers was 3.65 (95% CI: 2.39; 5.55) compared to drinking 2-4 days/week. Alcohol amount in recent age periods (40-49 and 50-59 years) was associated with an increased risk, whereas the amount in 20-29 and 30-39 years was not. In men drinking 14-28 drinks/week, HR was 7.47 (95% CI: 1.68; 33.12), 3.12 (95% CI: 1.53; 6.39), and 1.69 (95% CI: 0.79; 3.65) in drinkers of little (drinking drinks/week. In general, results were similar for women. In men, daily drinking was associated with an increased risk of alcoholic cirrhosis. Recent alcohol consumption rather than earlier in life was associated with risk of alcoholic cirrhosis. Compared to beer and liquor, wine might be associated with a lower risk of alcoholic cirrhosis. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  19. Alcohol

    Science.gov (United States)

    If you are like many Americans, you drink alcohol at least occasionally. For many people, moderate drinking ... risky. Heavy drinking can lead to alcoholism and alcohol abuse, as well as injuries, liver disease, heart ...

  20. Serum adipokines might predict liver histology findings in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Jamali, Raika; Razavizade, Mohsen; Arj, Abbas; Aarabi, Mohammad Hossein

    2016-06-07

    To assess significance of serum adipokines to determine the histological severity of non-alcoholic fatty liver disease. Patients with persistent elevation in serum aminotransferase levels and well-defined characteristics of fatty liver at ultrasound were enrolled. Individuals with a history of alcohol consumption, hepatotoxic medication, viral hepatitis or known liver disease were excluded. Liver biopsy was performed to confirm non-alcoholic liver disease (NAFLD). The degrees of liver steatosis, lobular inflammation and fibrosis were determined based on the non-alcoholic fatty liver activity score (NAS) by a single expert pathologist. Patients with a NAS of five or higher were considered to have steatohepatitis. Those with a NAS of two or lower were defined as simple fatty liver. Binary logistic regression was used to determine the independent association of adipokines with histological findings. Receiver operating characteristic (ROC) analysis was employed to determine cut-off values of serum adipokines to discriminate the grades of liver steatosis, lobular inflammation and fibrosis. Fifty-four participants aged 37.02 ± 9.82 were enrolled in the study. Higher serum levels of visfatin, IL-8, TNF-α levels were associated independently with steatosis grade of more than 33% [β = 1.08 (95%CI: 1.03-1.14), 1.04 (95%CI: 1.008-1.07), 1.04 (95%CI: 1.004-1.08), P < 0.05]. Elevated serum IL-6 and IL-8 levels were associated independently with advanced lobular inflammation [β = 1.4 (95%CI: 1.09-1.8), 1.07 (95%CI: 1.003-1.15), P < 0.05]. Similarly, higher TNF-α, resistin, and hepcidin levels were associated independently with advanced fibrosis stage [β = 1.06 (95%CI: 1.002-1.12), 19.86 (95%CI: 2.79-141.19), 560.72 (95%CI: 5.98-5255.33), P < 0.05]. Serum IL-8 and TNF-α values were associated independently with the NAS score, considering a NAS score of 5 as the reference value [β = 1.05 (95%CI: 1.01-1.1), 1.13 (95%CI: 1.04-1.22), P < 0.05]. Certain adipokines may

  1. Non-alcoholic Fatty Liver Disease: Beneficial Effects of Flavonoids.

    Science.gov (United States)

    Akhlaghi, Masoumeh

    2016-10-01

    Non-alcoholic fatty liver disease (NAFLD) has been known as the hepatic feature of metabolic syndrome. Extra fat depots, especially in visceral areas, develop insulin resistance as a result of mild oxidation and inflammation. Insulin resistance induces lipolysis and releases free fatty acids into the circulation, where they are transported to the liver. In the liver, free fatty acids are converted to triglycerides and accumulate, causing simple steatosis that, if left untreated, can lead to steatohepatitis, and subsequently liver necrosis and cirrhosis.Flavonoids, a group of plant compounds with incredible biological characteristics, have shown advantages in pathological conditions. Beneficial effects of flavonoids against NAFLD and its related disorders have been observed in both animal and human studies. Various mechanisms have been found for their protection. Flavonoids prevent hepatosteatosis by increasing fatty acid oxidation in the liver. They can also reduce caloric intake and decrease body weight and fat deposition in visceral tissues. Flavonoids are unique antioxidants that exert their beneficial effects through inhibition of nuclear factor κB, thereby attenuating release of inflammatory cytokines, which are triggers of insulin resistance. Finally, flavonoids have shown to increase adiponectin, improve insulin sensitivity and glucose tolerance, correct dyslipidemia, and reduce blood pressure in patients with NAFLD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Non-alcoholic fatty liver disease: An expanded review

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients. PMID:28652891

  3. Clinical approaches to non-alcoholic fatty liver disease

    Science.gov (United States)

    Schwenger, Katherine JP; Allard, Johane P

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) ranges from simple steatosis to nonalcoholic steatohepatitis (NASH), leading to fibrosis and potentially cirrhosis, and it is one of the most common causes of liver disease worldwide. NAFLD is associated with other medical conditions such as metabolic syndrome, obesity, cardiovascular disease and diabetes. NASH can only be diagnosed through liver biopsy, but noninvasive techniques have been developed to identify patients who are most likely to have NASH or fibrosis, reducing the need for liver biopsy and risk to patients. Disease progression varies between individuals and is linked to a number of risk factors. Mechanisms involved in the pathogenesis are associated with diet and lifestyle, influx of free fatty acids to the liver from adipose tissue due to insulin resistance, hepatic oxidative stress, cytokines production, reduced very low-density lipoprotein secretion and intestinal microbiome. Weight loss through improved diet and increased physical activity has been the cornerstone therapy of NAFLD. Recent therapies such as pioglitazone and vitamin E have been shown to be beneficial. Omega 3 polyunsaturated fatty acids and statins may offer additional benefits. Bariatric surgery should be considered in morbidly obese patients. More research is needed to assess the impact of these treatments on a long-term basis. The objective of this article is to briefly review the diagnosis, management and treatment of this disease in order to aid clinicians in managing these patients. PMID:24587650

  4. Non-alcoholic fatty liver disease: An expanded review.

    Science.gov (United States)

    Benedict, Mark; Zhang, Xuchen

    2017-06-08

    Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the "magic bullet" in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients.

  5. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-04-01

    Full Text Available Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  6. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant.

    Science.gov (United States)

    Gitto, Stefano; Villa, Erica

    2016-04-02

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent significant causes of morbidity and mortality. This is especially true for metabolic syndrome. Non-alcoholic steatosis and steatohepatitis are hepatic manifestations of metabolic syndrome and after liver transplant both recurrent and de novo steatosis can be found. Usually, post-transplant steatosis shows an indolent outcome with few cases of fibrosis progression. However, in the post-transplant setting, both metabolic syndrome and steatosis might play a key role in the stratification of morbidity and mortality risk, being commonly associated with cardiovascular disease. The single components of metabolic syndrome can be treated with targeted drugs while lifestyle intervention is the only reasonable therapeutic approach for transplant patients with non-alcoholic steatosis or steatohepatitis.

  7. Novel Action of Carotenoids on Non-Alcoholic Fatty Liver Disease: Macrophage Polarization and Liver Homeostasis.

    Science.gov (United States)

    Ni, Yinhua; Zhuge, Fen; Nagashimada, Mayumi; Ota, Tsuguhito

    2016-06-24

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is characterized by a wide spectrum of hepatic changes, which may progress to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is considered a hepatic manifestation of metabolic syndrome; however, mechanisms underlying the onset and progression of NAFLD are still unclear. Resident and recruited macrophages are key players in the homeostatic function of the liver and in the progression of NAFLD to NASH. Progress has been made in understanding the molecular mechanisms underlying the polarized activation of macrophages. New NAFLD therapies will likely involve modification of macrophage polarization by restraining M1 activation or driving M2 activation. Carotenoids are potent antioxidants and anti-inflammatory micronutrients that have been used to prevent and treat NAFLD. In addition to their antioxidative action, carotenoids can regulate macrophage polarization and thereby halt the progression of NASH. In this review, we summarize the molecular mechanisms of macrophage polarization and the function of liver macrophages/Kupffer cells in NAFLD. From our review, we propose that dietary carotenoids, such as β-cryptoxanthin and astaxanthin, be used to prevent or treat NAFLD through the regulation of macrophage polarization and liver homeostasis.

  8. Correlation between liver morphology and portal pressure in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1984-01-01

    evaluation of liver biopsies, no significant correlation was found between mean hepatocyte volume or relative sinusoidal vascular volume and portal pressure. To test whether an increase in hepatocyte volume compresses the vascular structures and causes portal hypertension, the ratio of relative sinusoidal...... volume. The present findings are in accordance with the hypothesis that elevated hepatic vascular resistance and portal pressure in alcoholic liver disease are in part determined by the severity of the hepatic architectural destruction and subsequent distorsion and compression of the efferent vein system...

  9. Th17 involvement in nonalcoholic fatty liver disease progression to non-alcoholic steatohepatitis.

    Science.gov (United States)

    Chackelevicius, Carla Melisa; Gambaro, Sabrina Eliana; Tiribelli, Claudio; Rosso, Natalia

    2016-11-07

    The nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a wide histological spectrum ranging from benign simple steatosis to non-alcoholic steatohepatitis (NASH). Sustained inflammation in the liver is critical in this process. Hepatic macrophages, including liver resident macropaghes (Kupffer cells), monocytes infiltrating the injured liver, as well as specific lymphocytes subsets play a pivotal role in the initiation and perpetuation of the inflammatory response, with a major deleterious impact on the progression of fatty liver to fibrosis. During the last years, Th17 cells have been involved in the development of inflammation not only in liver but also in other organs, such as adipose tissue or lung. Differentiation of a naïve T cell into a Th17 cell leads to pro-inflammatory cytokine and chemokine production with subsequent myeloid cell recruitment to the inflamed tissue. Th17 response can be mitigated by T regulatory cells that secrete anti-inflammatory cytokines. Both T cell subsets need TGF-β for their differentiation and a characteristic plasticity in their phenotype may render them new therapeutic targets. In this review, we discuss the role of the Th17 pathway in NAFLD progression to NASH and to liver fibrosis analyzing different animal models of liver injury and human studies.

  10. CLINICAL PROFILE OF PATIENTS WITH ALCOHOLIC LIVER DISEASE IN UPPER ASSAM OF NORTH EAST INDIA

    Directory of Open Access Journals (Sweden)

    Ardhendu Kumar Sen

    2017-05-01

    Full Text Available BACKGROUND Alcohol is the most commonly abused drug worldwide causing liver injury with respect to dose, duration, type of alcohol consumption and drinking patterns and gender with diverse ethnicity and social customs. There is high prevalence of alcohol use in the society without much social taboo in the North Eastern States of India and also there is a high prevalence of different ethnic tribes with the custom of taking country made alcohol casually as a part of their tradition. The aim of this study is to study the clinical profile of patients with alcoholic liver disease in upper Assam of north east India. MATERIALS AND METHODS The study was a hospital-based observational study in which patients of 18 years and older and diagnosed to have alcoholic liver disease were included. Cases excluded were patients of NASH, viral hepatitis, drug-induced hepatitis, haemochromatosis, alcoholic liver disease with diabetes and kidney disease. Informed written consent was taken from the patients or their attendants. Ethical clearance was taken from the Institutional Ethical Committee. A total of 138 cases were selected for the study. A detailed evaluation of clinical history, examination and investigations and the results were recorded in a predesigned proforma. RESULTS Out of 138 patients, 113 were males and 25 were females with male:female ratio of 4.5:1. Majority of cases (34.78% were in the age group of (41-50 years. It was observed that 98 patients (71.01% belonged to the lower socioeconomic status group. The average duration of alcohol intake was 18.39 ± 6.24 years for males and 16.76 ± 6.59 years for females. The overall average duration of alcohol intake was 18.09 ± 6.29 years. The majority of the patients (104 cases, 75.36% took both foreign and country-made liquors. The most common clinical presentation was abdominal distension and swelling of feet (71 cases, 51.45% followed by jaundice (68 cases, 49.28% and anorexia (56 cases, 40.58%. The

  11. Gastrointestinal complications of obesity: non-alcoholic fatty liver disease (NAFLD) and its sequelae.

    Science.gov (United States)

    Karlas, Thomas; Wiegand, Johannes; Berg, Thomas

    2013-04-01

    Obesity is a major risk factor for malign and non-malign diseases of the gastrointestinal tract. Non-alcoholic fatty liver disease (NAFLD) is an outstanding example for the complex pathophysiology of the metabolic system and represents both source and consequence of the metabolic syndrome. NAFLD has a growing prevalence and will become the leading cause of advanced liver disease and cirrhosis. Obesity has a negative impact on NAFLD at all aspects and stages of the disease. The growing epidemic will strain health care resources and demands new concepts for prevention, screening and therapeutic approaches. A better understanding of the interplay of liver, gut and hormonal system is necessary for new insights in the underlying mechanisms of NAFLD and the metabolic syndrome including obesity. Identification of patients at risk for progressive liver disease will allow a better adaption of treatment strategies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Role of Adaptive Immunity in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Emanuele Albano

    2012-01-01

    Full Text Available Stimulation of innate immunity is increasingly recognized to play an important role in the pathogenesis of alcoholic liver disease (ALD, while the contribution of adaptive immunity has received less attention. Clinical and experimental data show the involvement of Th-1 and Th-17 T-lymphocytes in alcoholic hepatitis. Nonetheless, the mechanisms by which alcohol triggers adaptive immunity are still incompletely characterized. Patients with advanced ALD have circulating IgG and T-lymphocytes recognizing epitopes derived from protein modification by hydroxyethyl free radicals and end products of lipid-peroxidation. High titers of IgG against lipid peroxidation-derived antigens are associated with an increased hepatic production of proinflammatory cytokines/chemokines. Moreover, the same antigens favor the breaking of self-tolerance towards liver constituents. In particular, autoantibodies against cytochrome P4502E1 (CYP2E1 are evident in a subset of ALD patients. Altogether these results suggest that allo- and autoimmune reactions triggered by oxidative stress might contribute to hepatic inflammation during the progression of ALD.

  13. Nuclear Receptor-Mediated Alleviation of Alcoholic Fatty Liver by Polyphenols Contained in Alcoholic Beverages

    Science.gov (United States)

    Yao, Ruiqing; Yasuoka, Akihito; Kamei, Asuka; Ushiama, Shota; Kitagawa, Yoshinori; Rogi, Tomohiro; Shibata, Hiroshi; Abe, Keiko; Misaka, Takumi

    2014-01-01

    To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages. PMID:24498295

  14. Nuclear receptor-mediated alleviation of alcoholic fatty liver by polyphenols contained in alcoholic beverages.

    Directory of Open Access Journals (Sweden)

    Ruiqing Yao

    Full Text Available To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR, we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages.

  15. Alteration in substrate specificity of horse liver alcohol dehydrogenase by an acyclic nicotinamide analog of NAD(+).

    Science.gov (United States)

    Malver, Olaf; Sebastian, Mina J; Oppenheimer, Norman J

    2014-11-01

    A new, acyclic NAD-analog, acycloNAD(+) has been synthesized where the nicotinamide ribosyl moiety has been replaced by the nicotinamide (2-hydroxyethoxy)methyl moiety. The chemical properties of this analog are comparable to those of β-NAD(+) with a redox potential of -324mV and a 341nm λmax for the reduced form. Both yeast alcohol dehydrogenase (YADH) and horse liver alcohol dehydrogenase (HLADH) catalyze the reduction of acycloNAD(+) by primary alcohols. With HLADH 1-butanol has the highest Vmax at 49% that of β-NAD(+). The primary deuterium kinetic isotope effect is greater than 3 indicating a significant contribution to the rate limiting step from cleavage of the carbon-hydrogen bond. The stereochemistry of the hydride transfer in the oxidation of stereospecifically deuterium labeled n-butanol is identical to that for the reaction with β-NAD(+). In contrast to the activity toward primary alcohols there is no detectable reduction of acycloNAD(+) by secondary alcohols with HLADH although these alcohols serve as competitive inhibitors. The net effect is that acycloNAD(+) has converted horse liver ADH from a broad spectrum alcohol dehydrogenase, capable of utilizing either primary or secondary alcohols, into an exclusively primary alcohol dehydrogenase. This is the first example of an NAD analog that alters the substrate specificity of a dehydrogenase and, like site-directed mutagenesis of proteins, establishes that modifications of the coenzyme distance from the active site can be used to alter enzyme function and substrate specificity. These and other results, including the activity with α-NADH, clearly demonstrate the promiscuity of the binding interactions between dehydrogenases and the riboside phosphate of the nicotinamide moiety, thus greatly expanding the possibilities for the design of analogs and inhibitors of specific dehydrogenases. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Multiparametric magnetic resonance imaging for the assessment of non-alcoholic fatty liver disease severity.

    Science.gov (United States)

    Pavlides, Michael; Banerjee, Rajarshi; Tunnicliffe, Elizabeth M; Kelly, Catherine; Collier, Jane; Wang, Lai Mun; Fleming, Kenneth A; Cobbold, Jeremy F; Robson, Matthew D; Neubauer, Stefan; Barnes, Eleanor

    2017-07-01

    The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (Pliver inflammation and fibrosis (r s =.51, Pliver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (Pliver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (PLiver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (Pliver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0.89. Multiparametric magnetic resonance is a promising technique with good diagnostic accuracy for non-alcoholic fatty liver disease histological parameters, and can potentially identify patients with non-alcoholic steatohepatitis and cirrhosis. © 2017 The Authors Liver International Published by John Wiley & Sons Ltd.

  17. Association of water softness and heavy alcohol consumption with higher hospital admission rates for alcoholic liver disease.

    Science.gov (United States)

    Howarth, Mark; Riva, Antonio; Marks, Peter; Williams, Roger

    2012-01-01

    To test the hypothesis that regional variations in the prevalence of alcoholic liver disease are contributed to by regional variations in 'softness' of drinking water, i.e. its mineral content. Annual hospital admission rates for alcoholic liver disease per 100,000 population in the 28 Strategic Health Authorities (SHAs) existing in England over the period 2003-2006 were compared with regional measures of water hardness, alcohol consumption and social deprivation. As corroborative evidence, the same relations were examined for hospital admission rates for osteoporosis, a disorder with an already established link with calcium deficiency in drinking water (as well as with heavy drinking). Hospital admissions rates for alcoholic liver disease were higher in predominant-soft-water SHAs than with hard water SHAs. These areas, with one exception, were also associated with high alcohol consumption, but not with greater social deprivation. Hospital admission rates for osteoporosis were found to vary in a way similar to that for alcoholic liver disease, with significant correlations with soft water and alcohol consumption. Given experimental evidence that magnesium deficiency can aggravate liver damage from alcohol, soft water with its low magnesium concentration may be a factor additional to alcohol consumption in the development of liver damage. The parallel findings with osteoporosis admissions, explainable by low calcium and magnesium levels present in soft water, along with the known effect of heavy drinking on bone metabolism, provide corollary support for the hypothesis linking soft water with the pathogenesis of these two diseases.

  18. Liver transplantation for alcoholic liver disease: Lessons learned and unresolved issues

    Science.gov (United States)

    Ursic-Bedoya, José; Faure, Stéphanie; Donnadieu-Rigole, Hélène; Pageaux, Georges-Philippe

    2015-01-01

    The use of liver transplantation (LT) as a treatment for alcoholic liver disease (ALD) has been highly controversial since the beginning. The ever increasing shortage of organs has accentuated the low priority given to patients suffering from ALD, which is considered a “self-inflicted” condition. However, by improving the long-term survival rates, making them similar to those from other indications, and recognizing that alcoholism is a primary disease, ALD has become one of the most common indications for LT in Europe and North America, a situation thought unfathomable thirty years ago. Unfortunately, there are still many issues with the use of this procedure for ALD. There are significant relapse rates, and the consequences of excessive drinking after LT range from asymptomatic biochemical and histological abnormalities to graft failure and death. A minimum three-month period of sobriety is required for an improvement in liver function, thus making LT unnecessary, and to demonstrate the patient’s commitment to the project, even though a longer abstinence period does not guarantee lower relapse rates after LT. Recent data have shown that LT is also effective for severe alcoholic hepatitis when the patient is unresponsive to corticosteroids therapy, with low relapse rates in highly selected patients, although these results must be confirmed before LT becomes a standard procedure in this setting. Finally, LT for ALD is accompanied by an increased risk of de novo solid organ cancer, skin cancer, and lymphoproliferative disorders, which has a large impact on the survival rates. PMID:26494956

  19. Epidemiological modifiers of non-alcoholic fatty liver disease: Focus on high-risk groups.

    Science.gov (United States)

    Lonardo, Amedeo; Bellentani, Stefano; Argo, Curtis K; Ballestri, Stefano; Byrne, Christopher D; Caldwell, Stephen H; Cortez-Pinto, Helena; Grieco, Antonio; Machado, Mariana V; Miele, Luca; Targher, Giovanni

    2015-12-01

    An improved understanding of non-alcoholic fatty liver disease epidemiology would lead to identification of individuals at high risk of developing chronic liver disease and extra-hepatic complications, thus contributing to more effective case finding of non-alcoholic fatty liver disease among selected groups. We aimed to illustrate the epidemiology of non-alcoholic fatty liver disease in high-risk groups, which were identified based on existing literature. To this end, PubMed was searched to retrieve original articles published until May 2015 using relevant and pertinent keywords "nonalcoholic fatty liver disease" and "diabetes", "obesity", "hyperlipidaemia", "familial heterozygous hypobetalipoproteinaemia", "hypertension", "metabolic syndrome", "ethnicity", "family history" or "genetic polymorphisms". We found that age, sex and ethnicity are major physiological modifiers of the risk of non-alcoholic fatty liver disease, along with belonging to "non-alcoholic fatty liver disease families" and carrying risk alleles for selected genetic polymorphisms. Metabolic syndrome, diabetes, obesity, mixed hyperlipidaemia and hypocholesterolaemia due to familial hypobetalipoproteinaemia are the major metabolic modifiers of non-alcoholic fatty liver disease risk. Compared with these metabolic conditions, however, arterial hypertension appears to carry a relatively more modest risk of non-alcoholic fatty liver disease. A better understanding of the epidemiology of non-alcoholic fatty liver disease may result in a more liberal policy of case finding among high-risk groups. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  20. Glycosyltransferases and non-alcoholic fatty liver disease

    Science.gov (United States)

    Zhan, Yu-Tao; Su, Hai-Ying; An, Wei

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease and its incidence is increasing worldwide. However, the underlying mechanisms leading to the development of NAFLD are still not fully understood. Glycosyltransferases (GTs) are a diverse class of enzymes involved in catalyzing the transfer of one or multiple sugar residues to a wide range of acceptor molecules. GTs mediate a wide range of functions from structure and storage to signaling, and play a key role in many fundamental biological processes. Therefore, it is anticipated that GTs have a role in the pathogenesis of NAFLD. In this article, we present an overview of the basic information on NAFLD, particularly GTs and glycosylation modification of certain molecules and their association with NAFLD pathogenesis. In addition, the effects and mechanisms of some GTs in the development of NAFLD are summarized. PMID:26937136

  1. Dramatic increase in alcoholic liver cirrhosis mortality in Estonia in 1992-2008.

    Science.gov (United States)

    Pärna, Kersti; Rahu, Kaja

    2010-01-01

    The aim of the study was to describe trends in alcoholic liver cirrhosis mortality rates in 1992-2008 and to examine socio-demographic differences in alcoholic liver cirrhosis mortality. Individual records of deaths from alcoholic liver cirrhosis among 25-64-year olds in 1992-2008 in Estonia were analysed. Age-standardized mortality rates for men and women aged 25-44 and 45-64 were calculated. Association between alcoholic liver cirrhosis mortality and socio-demographic variables (age, education and ethnicity) for the data of the years around the census in 2000 was measured by mortality rate ratios using Poisson regression models. In 1992-2008, alcoholic liver cirrhosis mortality rates were higher among men than that in women and that in the older than in the younger age group. Over the whole study period, mortality from alcoholic liver cirrhosis increased steeply. The increase was sharper among men and women in the older age group. In 1998-2001, higher alcoholic liver cirrhosis mortality rates occurred in non-Estonians and those with lower levels of education. Alcoholic liver cirrhosis mortality has increased steadily in Estonia, and is reflected in an increase in heavy drinking. National alcohol policies should address all strata of society. However, in order to reduce alcohol-related damage in the population most effectively, special attention should be paid to non-Estonians and people with low levels of education.

  2. Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, P

    1983-01-01

    The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

  3. Clinical Utility of Red Cell Distribution Width in Alcoholic and Non-alcoholic Liver Cirrhosis

    OpenAIRE

    Milić, Sandra; Mikolašević, Ivana; Radić, Mladen; Hauser, Goran; Štimac, Davor

    2011-01-01

    Red blood cell distribution width (RDW) is a measure of the variation of red blood cell width that is reported as a part of standard complete blood count. Red blood cell distribution width results are often used together with mean corpuscular volume (MCV) results to figure out mixed anemia. The aim of our study was to compare the values of RDW in alcoholic and non-alcoholic liver cirrhosis and to determine if RDW follows the severity of disease according to Child-Pugh score. We re...

  4. Epidemiology of alcoholic liver disease in Denmark 2006-2011

    DEFF Research Database (Denmark)

    Deleuran, Thomas; Vilstrup, Hendrik; Becker, Ulrik

    2015-01-01

    AIMS: To describe incidence, prevalence, hospitalization rates and survival for alcoholic liver disease (ALD) in Denmark 2006-2011. METHODS: Using nationwide healthcare registries we identified all Danish residents with a hospital diagnosis of ALD and computed standardized incidence, prevalence....... CONCLUSION: In Denmark, persons born in 1950-1959 have had the highest age-specific incidence. The overall ALD incidence has been decreasing (along with per capita consumption). Despite increases in affordability during the study period, Denmark did not experience the increase in ALD seen, for example......, in the UK. It is possible that this is due to the greater impact of government recommendations on safer drinking in Denmark than the UK....

  5. Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

    Directory of Open Access Journals (Sweden)

    Shubha Ghosh Dastidar

    2018-01-01

    Full Text Available Both chronic and acute (binge alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD. There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH feeding (Lieber–DeCarli liquid diet model, chronic intragastric EtOH administration (Tsukamoto–French model, and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA model. This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.

  6. Enhanced expression of BMP6 inhibits hepatic fibrosis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Arndt, Stephanie; Wacker, Eva; Dorn, Christoph; Koch, Andreas; Saugspier, Michael; Thasler, Wolfgang E; Hartmann, Arndt; Bosserhoff, Anja Katrin; Hellerbrand, Claus

    2015-06-01

    Bone morphogenetic protein 6 (BMP6) has been identified as crucial regulator of iron homeostasis. However, its further role in liver pathology including non-alcoholic fatty liver disease (NAFLD) and its advanced form non-alcoholic steatohepatitis (NASH) is elusive. The aim of this study was to investigate the expression and function of BMP6 in chronic liver disease. BMP6 was analysed in hepatic samples from murine models of chronic liver injury and patients with chronic liver diseases. Furthermore, a tissue microarray comprising 110 human liver tissues with different degree of steatosis and inflammation was assessed. BMP6-deficient (BMP6(-/-)) and wild-type mice were compared in two dietary NASH-models, that is, methionine choline-deficient (MCD) and high-fat (HF) diets. BMP6 was solely upregulated in NAFLD but not in other murine liver injury models or diseased human livers. In NAFLD, BMP6 expression correlated with hepatic steatosis but not with inflammation or hepatocellular damage. Also, in vitro cellular lipid accumulation in primary human hepatocytes induced increased BMP6 expression. MCD and HF diets caused more hepatic inflammation and fibrosis in BMP6(-/-) compared with wild-type mice. However, only in the MCD and not in the HF diet model BMP6(-/-) mice developed marked hepatic iron overload, suggesting that further mechanisms are responsible for protective BMP6 effect. In vitro analysis revealed that recombinant BMP6 inhibited the activation of hepatic stellate cells (HSCs) and reduced proinflammatory and profibrogenic gene expression in already activated HSCs. Steatosis-induced upregulation of BMP6 in NAFLD is hepatoprotective. Induction of BMP6-signalling may be a promising antifibrogenic strategy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  7. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-01-01

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and ...

  8. Probiotics as a novel treatment for non-alcoholic Fatty liver disease; a systematic review on the current evidences.

    Science.gov (United States)

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: "non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver". Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.

  9. Focus on emerging drugs for the treatment of patients with non-alcoholic fatty liver disease

    Science.gov (United States)

    Federico, Alessandro; Zulli, Claudio; de Sio, Ilario; Del Prete, Anna; Dallio, Marcello; Masarone, Mario; Loguercio, Carmela

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become the most common liver disorder in Western countries and is increasingly being recognized in developing nations. Fatty liver disease encompasses a spectrum of hepatic pathology, ranging from simple steatosis to non-alcoholic steatohepatitis, cirrhosis, hepatocellular carcinoma and end-stage liver disease. Moreover, NAFLD is often associated with other metabolic conditions, such as diabetes mellitus type 2, dyslipidemia and visceral obesity. The most recent guidelines suggest the management and treatment of patients with NAFLD considering both the liver disease and the associated metabolic co-morbidities. Diet and physical exercise are considered the first line of treatment for patients with NAFLD, but their results on therapeutic efficacy are often contrasting. Behavior therapy is necessary most of the time to achieve a sufficient result. Pharmacological therapy includes a wide variety of classes of molecules with different therapeutic targets and, often, little evidence supporting the real efficacy. Despite the abundance of clinical trials, NAFLD therapy remains a challenge for the scientific community, and there are no licensed therapies for NAFLD. Urgently, new pharmacological approaches are needed. Here, we will focus on the challenges facing actual therapeutic strategies and the most recent investigated molecules. PMID:25492998

  10. Non-alcoholic fatty liver disease in obese adults: clinical aspects and current management strategies.

    Science.gov (United States)

    Pallayova, M; Taheri, S

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder whose prevalence is strongly linked to the current epidemic of obesity in many western countries. The prevalence of NAFLD is two to four times higher in populations with pre-existing metabolic comorbidities than in the general population. The diagnosis of primary NAFLD involves establishing the presence of hepatic steatosis or steatohepatitis by imaging or histology, along with establishing the non-alcoholic nature of the disease process and excluding competing aetiologies for hepatic steatosis. Among the indirect serum biomarkers, the NAFLD fibrosis score can help to identify patients with NAFLD and with higher likelihood of having fibrosis or cirrhosis. A liver biopsy should be considered in NAFLD patients at increased risk for steatohepatitis/advanced fibrosis and in cases where a liver biopsy is necessary to exclude co-existing chronic liver diseases and other aetiologies for hepatic steatosis. The treatment and management recommendations for obesity-associated NAFLD are aimed towards weight reduction. The currently available interventions employed to promote weight loss and improve the metabolic responses in NAFLD include lifestyle modification, pharmacotherapy and bariatric surgery. © 2014 The Authors. Clinical Obesity © 2014 World Obesity.

  11. [Cinnamon rolls are not associated with admission for toxic or alcoholic hepatitis in a Danish liver referral centre].

    Science.gov (United States)

    Gr Ønbæk, Henning; Borre, Mette

    2014-12-08

    Cinnamon contains cumarin, which may be toxic to the liver. EU-regulations standardardize the amount of cinnamon in pastry including cinnamon rolls. The aim of the study was to investigate if cinnamon intake from pastry was associated with toxic or alcoholic hepatitis. We registered 58 patients with toxic hepatitis, 38 (66%) women and 20 (34%) men with a median age of 51 (range: 32-80) and 53 (range: 18-78) years, respectively. A total of 22 patients had primarily cholestasis and 36 had hepatitis biochemically. The duration of toxic liver disease from admission to normalization of liver enzymes was similar in the two groups (3.5 ± 3.5 vs 3.6 ± 3.5 months). Toxic hepatitis was most often caused by drugs e.g. NSAID (n = 15; 26%), antibiotics (n = 9; 16%), alternative medicine (n = 7; 12%) and Antabuse (n = 5; 9%). We registered eight patients admitted with severe alcoholic hepatitis, five men and three women, median age of 60 (range: 34-67) years. Alcoholic hepatitis was associated with high alcohol intake. None of the patients with toxic or alcoholic hepatitis reported of excessive intake of cinnamon rolls and there was no evidence of cinnamon added to alcohol of alternative medicine products. Intake of cinnamon from cinnamon rolls is not associated with admission for toxic or alcoholic hepatitis. However, for the diagnosis of toxic liver diseases including alcohol it is very important to have patient information regarding any new drugs, alternative medicine and alcohol intake. Further, other causes of liver diseases should be excluded. not relevant. not relevant.

  12. Etiology of liver cirrhosis in Brazil: chronic alcoholism and hepatitis viruses in liver cirrhosis diagnosed in the state of Espírito Santo.

    Science.gov (United States)

    Gonçalves, Patricia Lofego; Zago-Gomes, Maria da Penha; Marques, Carla Couzi; Mendonça, Ana Tereza; Gonçalves, Carlos Sandoval; Pereira, Fausto Edmundo Lima

    2013-01-01

    To report the etiology of liver cirrhosis cases diagnosed at the University Hospital in Vitoria, Espirito Santo, Brazil. The medical charts of patients with liver cirrhosis who presented to the University Hospital in Vitoria were reviewed. Chronic alcoholism and the presence of hepatitis B or C infections (HBV and HCV, respectively) were pursued in all cases. The sample consisted of 1,516 cases (male:female ratio 3.5:1, aged 53.2 ± 12.6 years). The following main etiological factors were observed: chronic alcoholism alone (39.7%), chronic alcoholism in association with HBV or HCV (16.1 %), HCV alone (14.5%) and in association with alcoholism (8.6%) (total, 23.1 %), and HBV alone (13.1%) and in association with alcoholism (7.5%, total 20.6%). The remaining etiologies included cryptogenic cases (9.8%) and other causes (6.0%). The mean patient age was lower and the male-to-female ratio was higher in the cirrhosis cases that were associated with alcoholism or HBV compared with other causes. Intravenous drug abuse and a history of surgery or blood transfusion were significantly associated with HCV infection. Hepatocellular carcinoma was present at the time of diagnosis in 15.4% of cases. Chronic alcoholism associated with HCV infection was significantly associated (pAlcoholism, HCV and HBV are the main factors associated with liver cirrhosis in the state of Espirito Santo. Chronic alcoholism associated with HCV infection reduced the age of patients at the time of liver cirrhosis diagnosis.

  13. Relationships among alcoholic liver disease, antioxidants, and antioxidant enzymes.

    Science.gov (United States)

    Han, Kyu-Ho; Hashimoto, Naoto; Fukushima, Michihiro

    2016-01-07

    Excessive consumption of alcoholic beverages is a serious cause of liver disease worldwide. The metabolism of ethanol generates reactive oxygen species, which play a significant role in the deterioration of alcoholic liver disease (ALD). Antioxidant phytochemicals, such as polyphenols, regulate the expression of ALD-associated proteins and peptides, namely, catalase, superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase. These plant antioxidants have electrophilic activity and may induce antioxidant enzymes via the Kelch-like ECH-associated protein 1-NF-E2-related factor-2 pathway and antioxidant responsive elements. Furthermore, these antioxidants are reported to alleviate cell injury caused by oxidants or inflammatory cytokines. These phenomena are likely induced via the regulation of mitogen-activating protein kinase (MAPK) pathways by plant antioxidants, similar to preconditioning in ischemia-reperfusion models. Although the relationship between plant antioxidants and ALD has not been adequately investigated, plant antioxidants may be preventive for ALD because of their electrophilic and regulatory activities in the MAPK pathway.

  14. Multipotent mesenchymal stromal cells: A promising strategy to manage alcoholic liver disease.

    Science.gov (United States)

    Ezquer, Fernando; Bruna, Flavia; Calligaris, Sebastián; Conget, Paulette; Ezquer, Marcelo

    2016-01-07

    Chronic alcohol consumption is a major cause of liver disease. The term alcoholic liver disease (ALD) refers to a spectrum of mild to severe disorders including steatosis, steatohepatitis, cirrhosis, and hepatocellular carcinoma. With limited therapeutic options, stem cell therapy offers significant potential for these patients. In this article, we review the pathophysiologic features of ALD and the therapeutic mechanisms of multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSCs), based on their potential to differentiate into hepatocytes, their immunomodulatory properties, their potential to promote residual hepatocyte regeneration, and their capacity to inhibit hepatic stellate cells. The perfect match between ALD pathogenesis and MSC therapeutic mechanisms, together with encouraging, available preclinical data, allow us to support the notion that MSC transplantation is a promising therapeutic strategy to manage ALD onset and progression.

  15. Iron and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Britton, Laurence J; Subramaniam, V Nathan; Crawford, Darrell Hg

    2016-09-28

    The mechanisms that promote liver injury in non-alcoholic fatty liver disease (NAFLD) are yet to be thoroughly elucidated. As such, effective treatment strategies are lacking and novel therapeutic targets are required. Iron has been widely implicated in the pathogenesis of NAFLD and represents a potential target for treatment. Relationships between serum ferritin concentration and NAFLD are noted in a majority of studies, although serum ferritin is an imprecise measure of iron loading. Numerous mechanisms for a pathogenic role of hepatic iron in NAFLD have been demonstrated in animal and cell culture models. However, the human data linking hepatic iron to liver injury in NAFLD is less clear, with seemingly conflicting evidence, supporting either an effect of iron in hepatocytes or within reticulo-endothelial cells. Adipose tissue has emerged as a key site at which iron may have a pathogenic role in NAFLD. Evidence for this comes indirectly from studies that have evaluated the role of adipose tissue iron with respect to insulin resistance. Adding further complexity, multiple strands of evidence support an effect of NAFLD itself on iron metabolism. In this review, we summarise the human and basic science data that has evaluated the role of iron in NAFLD pathogenesis.

  16. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    OpenAIRE

    Temple, J. L.; Cordero, P.; Li, J.; Vi, N.; Oben, J. A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation ...

  17. Non-alcoholic fatty liver disease and obesity: biochemical, metabolic and clinical presentations.

    Science.gov (United States)

    Milić, Sandra; Lulić, Davorka; Štimac, Davor

    2014-07-28

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Presentation of the disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH). NAFLD is a hepatic manifestation of metabolic syndrome that includes central abdominal obesity along with other components. Up to 80% of patients with NAFLD are obese, defined as a body mass index (BMI) > 30 kg/m(2). However, the distribution of fat tissue plays a greater role in insulin resistance than the BMI. The large amount of visceral adipose tissue (VAT) in morbidly obese (BMI > 40 kg/m(2)) individuals contributes to a high prevalence of NAFLD. Free fatty acids derived from VAT tissue, as well as from dietary sources and de novo lipogenesis, are released to the portal venous system. Excess free fatty acids and chronic low-grade inflammation from VAT are considered to be two of the most important factors contributing to liver injury progression in NAFLD. In addition, secretion of adipokines from VAT as well as lipid accumulation in the liver further promotes inflammation through nuclear factor kappa B signaling pathways, which are also activated by free fatty acids, and contribute to insulin resistance. Most NAFLD patients are asymptomatic on clinical presentation, even though some may present with fatigue, dyspepsia, dull pain in the liver and hepatosplenomegaly. Treatment for NAFLD and NASH involves weight reduction through lifestyle modifications, anti-obesity medication and bariatric surgery. This article reviews the available information on the biochemical and metabolic phenotypes associated with obesity and fatty liver disease. The relative contribution of visceral and liver fat to insulin resistance is discussed, and recommendations for clinical evaluation of affected individuals is provided.

  18. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions.

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-09-28

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A "multiple-hit" pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the "imperfect" gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended lifestyle

  19. Pediatric non-alcoholic fatty liver disease: Recent solutions, unresolved issues, and future research directions

    Science.gov (United States)

    Clemente, Maria Grazia; Mandato, Claudia; Poeta, Marco; Vajro, Pietro

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) in children is becoming a major health concern. A “multiple-hit” pathogenetic model has been suggested to explain the progressive liver damage that occurs among children with NAFLD. In addition to the accumulation of fat in the liver, insulin resistance (IR) and oxidative stress due to genetic/epigenetic background, unfavorable lifestyles, gut microbiota and gut-liver axis dysfunction, and perturbations of trace element homeostasis have been shown to be critical for disease progression and the development of more severe inflammatory and fibrotic stages [non-alcoholic steatohepatitis (NASH)]. Simple clinical and laboratory parameters, such as age, history, anthropometrical data (BMI and waist circumference percentiles), blood pressure, surrogate clinical markers of IR (acanthosis nigricans), abdominal ultrasounds, and serum transaminases, lipids and glucose/insulin profiles, allow a clinician to identify children with obesity and obesity-related conditions, including NAFLD and cardiovascular and metabolic risks. A liver biopsy (the “imperfect” gold standard) is required for a definitive NAFLD/NASH diagnosis, particularly to exclude other treatable conditions or when advanced liver disease is expected on clinical and laboratory grounds and preferably prior to any controlled trial of pharmacological/surgical treatments. However, a biopsy clearly cannot represent a screening procedure. Advancements in diagnostic serum and imaging tools, especially for the non-invasive differentiation between NAFLD and NASH, have shown promising results, e.g., magnetic resonance elastography. Weight loss and physical activity should be the first option of intervention. Effective pharmacological treatments are still under development; however, drugs targeting IR, oxidative stress, proinflammatory pathways, dyslipidemia, gut microbiota and gut liver axis dysfunction are an option for patients who are unable to comply with the recommended

  20. Manifestation of Non-Alcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Different Dietary Mouse Models

    Directory of Open Access Journals (Sweden)

    Vera HI Fengler

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD and non-alcoholic steatohepatitis (NASH, which are usually associated with obesity and metabolic syndrome, are considerable health and economic issues due to the rapid increase of their prevalence in Western society. Histologically, the diseases are characterised by steatosis, hepatic inflammation, and if further progressed, fibrosis. Dietary-induced mouse models are widely used in investigations of the development and progression of NAFLD and NASH; these models attempt to mimic the histological and metabolic features of the human diseases. However, the majority of dietary mouse models fail to reflect the whole pathophysiological spectrum of NAFLD and NASH. Some models exhibit histological features similar to those seen in humans while lacking the metabolic context, while others resemble the metabolic conditions leading to NAFLD in humans but fail to mimic the whole histological spectrum, including progression from steatosis to liver fibrosis, and thus fail to mimic NASH. This review summarises the advantages and disadvantages of the different dietary-induced mouse models of NAFLD and NASH, with a focus on the genetic background of several commonly used wild-type mouse strains as well as gender and age, which influence the development and progression of these liver diseases.

  1. Non-alcoholic fatty liver disease and associated factors among type ...

    African Journals Online (AJOL)

    Background: Non-alcoholic Fatty Liver Disease (NAFLD) among type 2 diabetic patients is completely ignored in developing regions like Africa paving the way for public health and economic burden in the region. Therefore, the main objective of this research was to evaluate non-alcoholic fatty liver disease and associated

  2. Milk thistle for alcoholic and/or hepatitis B or C virus liver diseases

    DEFF Research Database (Denmark)

    Rambaldi, A; Jacobs, B P; Gluud, C

    2007-01-01

    Alcohol and hepatotoxic viruses cause the majority of liver diseases. Randomised clinical trials have assessed whether extracts of milk thistle, Silybum marianum (L) Gaertneri, have any effect in patients with alcoholic and/or hepatitis B or C virus liver diseases....

  3. Knowing What's Out There: Awareness of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ghevariya, Vishal; Sandar, Nan; Patel, Kishor; Ghevariya, Nehal; Shah, Ruchit; Aron, Joshua; Anand, Sury

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic disorder, which poses a significant health burden in the western countries. As the epidemic of obesity slides health downward, the incidence of NAFLD is evidently increasing. We aimed to ascertain the awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection, and treatment of this disorder. A survey of 5000 non-institutionalized residents of Brooklyn, NY, USA was conducted. Sixteen items were included in the survey questionnaire including awareness of fatty liver, predisposing factors of NAFLD, awareness of cirrhosis, and conditions that advance to cirrhosis. The questionnaire also addressed awareness of prevention, diagnostic methods and treatment of NAFLD, and education of physicians to their patients about NAFLD. Overwhelming majority of the subjects was not aware of NAFLD and stated that their physicians did not have a discussion about NAFLD. Non-alcoholic fatty liver disease is a preventable liver disorder with limited treatment options. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. We should target our teenage population in an era of obesity epidemics of all times.

  4. Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

    Science.gov (United States)

    Wang, Zhiguo; Su, Bo; Fan, Sumei; Fei, Haixia; Zhao, Wei

    2015-03-20

    The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Relative effects of heavy alcohol use and hepatitis C in decompensated chronic liver disease in a hospital inpatient population.

    Science.gov (United States)

    Mankal, Pavan Kumar; Abed, Jean; Aristy, Jose David; Munot, Khushboo; Suneja, Upma; Engelson, Ellen S; Kotler, Donald P

    2015-03-01

    Heavy alcohol use has been hypothesized to accelerate disease progression to end-stage liver disease in patients with hepatitis C virus (HCV) infection. In this study, we estimated the relative influences of heavy alcohol use and HCV in decompensated chronic liver disease (CLD). Retrospectively, 904 patients with cirrhotic disease admitted to our hospitals during January 2010-December 2012 were identified based on ICD9 codes. A thorough chart review captured information on demographics, viral hepatitis status, alcohol use and progression of liver disease (i.e. decompensation). Decompensation was defined as the presence of ascites due to portal hypertension, bleeding esophageal varices, hepatic encephalopathy or hepatorenal syndrome. Heavy alcohol use was defined as a chart entry of greater than six daily units of alcohol or its equivalent. 347 patients were included based on our selection criteria of documented heavy alcohol use (n = 215; 62.0%), hepatitis titers (HCV: n = 182; 52.5%) and radiological evidence of CLD with or without decompensation (decompensation: n = 225; 64.8%). Independent of HCV infection, heavy alcohol use significantly increased the risk of decompensation (OR = 1.75, 95% CI 1.11-2.75, p < 0.02) relative to no heavy alcohol use. No significance was seen with age, sex, race, HIV, viral hepatitis and moderate alcohol use for risk for decompensation. Additionally, dose-relationship regression analysis revealed that heavy, but not moderate alcohol use, resulted in a three-fold increase (p = 0.013) in the risk of decompensation relative to abstinence. While both heavy alcohol use and HCV infection are associated with risk of developing CLD, our data suggest that heavy, but not moderate, alcohol consumption is associated with a greater risk for hepatic decompensation in patients with cirrhosis than does HCV infection.

  6. Prediction of non-alcoholic fatty-liver disease and liver fat content by serum molecular lipids

    DEFF Research Database (Denmark)

    Orešic, Matej; Hyötyläinen, Tuulia; Kotronen, Anna

    2013-01-01

    We examined whether analysis of lipids by ultra-performance liquid chromatography (UPLC) coupled to MS allows the development of a laboratory test for non-alcoholic fatty-liver disease (NAFLD), and how a lipid-profile biomarker compares with the prediction of NAFLD and liver-fat content based...

  7. Serum Concentrations of Selected Heavy Metals in Patients with Alcoholic Liver Cirrhosis from the Lublin Region in Eastern Poland

    Directory of Open Access Journals (Sweden)

    Andrzej Prystupa

    2016-06-01

    Full Text Available According to the WHO report, alcohol is the third most significant health risk factor for the global population. There are contrary reports about heavy metals concentrations in patients with alcoholic liver cirrhosis. The aim of this study was to investigate serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis living in the eastern part of Poland according to cirrhosis stage. The participants came from various hospitals of the Lublin region were enrolled. The study group included 46 male and 16 female patients. The control group consisted of 18 healthy individuals without liver disease. High Performance Ion Chromatography was used to determine the concentrations of metal ions (Cd, Zn, Cu, Ni, Co, Mn, and Pb in serum samples. The concentrations of copper, zinc, nickel, and cobalt were found to be significantly lower in patients with alcoholic liver cirrhosis compared to the control group. The serum concentration of cadmium was significantly higher in patients with advanced alcoholic liver cirrhosis compared to the control group. We hypothesize that disorders of metabolism of heavy metals seem to be the outcome of impaired digestion and absorption, which are common in cirrhosis, improper diet, environmental and occupational exposure.

  8. Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

    Science.gov (United States)

    Kelishadi, Roya; Farajian, Sanam; Mirlohi, Maryam

    2013-01-01

    Context Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics. Evidence Acquisition We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”. Results Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD. Conclusions Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up. PMID:23885277

  9. Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace.

    Science.gov (United States)

    Baffy, György; Brunt, Elizabeth M; Caldwell, Stephen H

    2012-06-01

    Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC. Published by Elsevier B.V.

  10. Epigenetic Mechanisms Underlying the Link between Non-Alcoholic Fatty Liver Diseases and Nutrition

    Directory of Open Access Journals (Sweden)

    Joo Ho Lee

    2014-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is defined as a pathologic accumulation of fat in the form of triglycerides (TG in the liver (steatosis that is not caused by alcohol. A subgroup of NAFLD patients shows liver cell injury and inflammation coupled with the excessive fat accumulation (steatohepatitis, which is referred to as non-alcoholic steatohepatitis (NASH. Patients with NASH may develop cirrhosis and hepatocellular carcinoma (HCC. NAFLD shares the key features of metabolic syndrome including obesity, hyperlipidemia, hypertension, and insulin resistance. The pathogenesis of NAFLD is multi-factorial, however the oxidative stress seems to plays a major role in the development and progression of the disease. The emerging field of epigenetics provides a new perspective on the pathogenesis of NAFLD. Epigenetics is an inheritable but reversible phenomenon that affects gene expression without altering the DNA sequence and refers to DNA methylation, histone modifications and microRNAs. Epigenetic manipulation through metabolic pathways such as one-carbon metabolism has been proposed as a promising approach to retard the progression of NAFLD. Investigating the epigenetic modifiers in NAFLD may also lead to the development of preventive or therapeutic strategies for NASH-associated complications.

  11. When a liver transplant recipient goes back to alcohol abuse: Should we be more selective?

    Science.gov (United States)

    Leon, Monica; Varon, Joseph; Surani, Salim

    2016-05-28

    Alcoholic liver disease (ALD) is one of the most common indications for liver transplantation (LT). However, it has always remained as a complicated topic from both medical and ethical grounds, as it is seen for many a "self-inflicted disease". Over the years, the survival rate of transplanted patients has significantly improved. The allocation system and the inclusion criteria for LT has also undergone some modifications. Early LT for acute alcoholic hepatitis has been subject to recent clinical studies with encouraging results in highly selected patients. We have learned from studies the importance of a multidisciplinary evaluation of candidates for LT. Complete abstinence should be attempted to overcome addiction issues and to allow spontaneous liver recovery. Risk factors for relapse include the presence of anxiety or depressive disorder, short duration of sobriety pre-LT and lack of social support. The identification of risk factors and the strengthen of social support system may decrease relapse among these patients. Family counseling of candidates is highly encouraged to prevent relapse to alcohol. Relapse has been associated with different histopathological changes, graft damage, graft loss and even decrease in survival among some studies. Therefore, each patient should be carefully selected and priority is to continue to lean on patients with high probability of success. The ethical issue remains as to the patient returning to drinking after the LT, hindering the way for other patients who could have received the same organ.

  12. Correlation between liver morphology and portal pressure in alcoholic liver disease

    DEFF Research Database (Denmark)

    Krogsgaard, K; Gluud, C; Henriksen, Jens Henrik Sahl

    1984-01-01

    volume. The present findings are in accordance with the hypothesis that elevated hepatic vascular resistance and portal pressure in alcoholic liver disease are in part determined by the severity of the hepatic architectural destruction and subsequent distorsion and compression of the efferent vein system......In 14 alcoholic patients, the degree of hepatic architectural destruction was graded (preserved architecture; nodules alternating with preserved architecture; totally destroyed architecture) and related to portal pressure. A positive correlation was found between the degree of architectural...... destruction and both wedged hepatic vein pressure (r = 0.72, p less than 0.01) and wedged-to-free hepatic vein pressure (r = 0.67, p less than 0.02). Degree of fatty change, fibrosis, inflammation, necrosis and occurrence of Mallory bodies showed no correlation with portal pressure. After morphometrical...

  13. Editor’s Pick: Non-Alcoholic Fatty Liver Disease – Changing the Prevalence of Liver Cancer?

    OpenAIRE

    Benedetta Campana; David Semela; Markus Heim; Christine Bernsmeier

    2015-01-01

    Due to its increasing prevalence, exceeding 25% of the Western population, non-alcoholic fatty liver disease (NAFLD) merits recognition as one of the most frequent chronic liver diseases (CLD) and requires consideration of the associated disease-related complications and their consequences for the surveillance and treatment of patients and the socio-economy worldwide. Along with the increasing incidence of NAFLD-related cirrhosis and end-stage liver disease, the frequency of NAFLD-related he...

  14. Mediterranean diet and non-alcoholic fatty liver disease: the need of extended and comprehensive interventions.

    Science.gov (United States)

    Trovato, Francesca M; Catalano, Daniela; Martines, G Fabio; Pace, Patrizia; Trovato, Guglielmo M

    2015-02-01

    Non-alcoholic fatty liver disease (NAFLD) is mostly related to increased BMI and sedentary life, even if it not directly attributable only to these or to single specific factors. Unhealthy lifestyle and obesity are the most probable causes, also in non-diabetic and without alcohol abuse patients, even if lean individuals can be involved. NAFLD treatment is currently warranted and driven by comprehensive lifestyle intervention, a valuable objective that is more often wished for than actually achieved. The aim is to re-assess the effectiveness of an intervention focused to increase the Adherence to Mediterranean Diet Score (AMDS) and the level of physical exercise, investigating the factors associated with failure and reporting the time that must elapse before such intervention becomes effective. The study included 90 (F 46, M 44) non-alcoholic non-diabetic patients, aged 50.13 ± 13.68 years, BMI 31.01 ± 5.18 with evidence of fatty liver by ultrasound. A significant decrease of Bright Liver Score (BLS) was observed only after 6 months of intervention: differently, at the first and third month of monitoring fatty liver changes were still not significant. By a multiple linear regression model Adherence to Mediterranean Diet change (p:0.015) and body mass index changes (p:Diet is a significant predictor of changes in the fat content of the liver in overweight patients with NAFLD. The effect of the diet is gradual and favorable and it is independent of other lifestyle changes. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  15. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    OpenAIRE

    LU Ran; HONG Tianpei

    2015-01-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disea...

  16. Low incidence of non-alcoholic steatohepatitis in a Danish liver unit

    DEFF Research Database (Denmark)

    Semb, Synne; Dam-Larsen, Sanne; Mogensen, Anne Mellon

    2012-01-01

    Non-alcoholic fatty liver disease encompasses a spectrum of histological lesions ranging from steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. Simple steatosis is generally benign, while NASH can progress to severe liver disease. The aim of the present study was to quantify the nu...... the number of patients with NASH and assess the prognosis associated with the condition in a large Danish referral centre for liver disease....

  17. The contribution of metabolic and adipose tissue inflammation to non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Mulder, P.C.A.

    2017-01-01

    Non-alcoholic fatty liver disease (NAFLD) has rapidly become the most common cause of chronic liver disease, and its worldwide prevalence continues to increase in parallel of the obesity epidemic. NAFLD comprises a wide spectrum of liver damage ranging fat accumulation (steatosis) to steatosis with

  18. 'Non-alcoholic fatty liver disease' bij kinderen : een nieuwe complicatie van obesitas

    NARCIS (Netherlands)

    Bocca, Gianni; Stolk, R.P.; Scheenstra, R.; Sauer, P.J.

    2008-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a range of chronic liver diseases from simple steatosis to steatohepatitis and cirrhosis with liver failure. In children, NAFLD is mainly associated with obesity and metabolic syndrome, the results of an unhealthy lifestyle. Insulin resistance and

  19. Practical approach to non-alcoholic fatty liver disease in patients with diabetes.

    Science.gov (United States)

    Tai, F W D; Syn, W-K; Alazawi, W

    2015-09-01

    The prevalence of Type 2 diabetes is expected to increase in parallel with obesity rates and the ageing population. Recent studies show that Type 2 diabetes is associated with a twofold increase in the risk of non-alcoholic fatty liver disease, a leading cause of chronic liver disease. Individuals with non-alcoholic steatohepatitis, a more advanced stage of non-alcoholic fatty liver disease, are specifically at risk of developing fibrosis/cirrhosis (end-stage liver disease) and hepatocellular carcinoma; therefore, identifying individuals (with Type 2 diabetes) who are likely to develop hepatic complications is paramount. In the present clinical review, we discuss the potential impact of non-alcoholic fatty liver disease diagnosis on Type 2 diabetes, and the putative risk factors for developing non-alcoholic steatohepatitis and non-alcoholic steatohepatitis fibrosis. We highlight the limitations of currently used tools in non-alcoholic fatty liver disease diagnosis and staging, and provide an insight into future developments in the field. We present an example of a non-alcoholic fatty liver disease screening protocol and discuss the therapeutic options currently available to our patients. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

  20. Trends in European liver death rates: implications for alcohol policy.

    Science.gov (United States)

    Jewell, Jo; Sheron, Nick

    2010-06-01

    Changing alcohol consumption has led to a three- to fivefold increase in liver deaths in the UK and Finland, and a three- to fivefold decrease in France and Italy. Increasing consumption from a low baseline has been driven by fiscal, marketing and commercial factors--some of which have occurred as a result of countries joining the EU. In contrast consumption has fallen from previously very high levels as a result of shifting social and cultural factors; a move from rural to urban lifestyles and increased health consciousness. The marketing drive in these countries has had to shift from a model based on quantity to one based on quality, which means that health gains have occurred alongside a steady improvement in the overall value of the wine industry. Fiscal incentives--minimum pricing, restricting cross border trade and more volumetric taxation could aid this shift. A healthier population and a healthy drinks industry are not incompatible.

  1. Disturbed Vitamin A Metabolism in Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Ali Saeed

    2017-12-01

    Full Text Available Vitamin A is required for important physiological processes, including embryogenesis, vision, cell proliferation and differentiation, immune regulation, and glucose and lipid metabolism. Many of vitamin A’s functions are executed through retinoic acids that activate transcriptional networks controlled by retinoic acid receptors (RARs and retinoid X receptors (RXRs.The liver plays a central role in vitamin A metabolism: (1 it produces bile supporting efficient intestinal absorption of fat-soluble nutrients like vitamin A; (2 it produces retinol binding protein 4 (RBP4 that distributes vitamin A, as retinol, to peripheral tissues; and (3 it harbors the largest body supply of vitamin A, mostly as retinyl esters, in hepatic stellate cells (HSCs. In times of inadequate dietary intake, the liver maintains stable circulating retinol levels of approximately 2 μmol/L, sufficient to provide the body with this vitamin for months. Liver diseases, in particular those leading to fibrosis and cirrhosis, are associated with impaired vitamin A homeostasis and may lead to vitamin A deficiency. Liver injury triggers HSCs to transdifferentiate to myofibroblasts that produce excessive amounts of extracellular matrix, leading to fibrosis. HSCs lose the retinyl ester stores in this process, ultimately leading to vitamin A deficiency. Non-alcoholic fatty liver disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a spectrum of conditions ranging from benign hepatic steatosis to non-alcoholic steatohepatitis (NASH; it may progress to cirrhosis and liver cancer. NASH is projected to be the main cause of liver failure in the near future. Retinoic acids are key regulators of glucose and lipid metabolism in the liver and adipose tissue, but it is unknown whether impaired vitamin A homeostasis contributes to or suppresses the development of NAFLD. A genetic variant of patatin-like phospholipase domain-containing 3 (PNPLA3-I148M is the most prominent

  2. Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in Japanese patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kato, Ken-Ichiro; Takeshita, Yumie; Misu, Hirofumi; Zen, Yoh; Kaneko, Shuichi; Takamura, Toshinari

    2015-03-01

    To examine the association between liver histological features and organ-specific insulin resistance indices calculated from 75-g oral glucose tolerance test data in patients with non-alcoholic fatty liver disease. Liver biopsy specimens were obtained from 72 patients with non-alcoholic fatty liver disease, and were scored for steatosis, grade and stage. Hepatic and skeletal muscle insulin resistance indices (hepatic insulin resistance index and Matsuda index, respectively) were calculated from 75-g oral glucose tolerance test data, and metabolic clearance rate was measured using the euglycemic hyperinsulinemic clamp method. The degree of hepatic steatosis, and grade and stage of non-alcoholic steatohepatitis were significantly correlated with Matsuda index (steatosis r = -0.45, P hepatic insulin resistance index. Multiple regression analyses adjusted for age, sex, body mass index and each histological score showed that the degree of hepatic steatosis (coefficient = -0.22, P steatosis and metabolic clearance rate (coefficient = -0.62, P = 0.059). Liver steatosis is associated with insulin resistance in skeletal muscle rather than in the liver in patients with non-alcoholic fatty liver disease, suggesting a central role of fatty liver in the development of peripheral insulin resistance and the existence of a network between the liver and skeletal muscle.

  3. Implications for the pathogenesis of non-alcoholic fatty liver disease

    African Journals Online (AJOL)

    Aim. Explore the possibility that increased gastrointestinal alcohol production may play a role in the pathogenesis of non-alcoholic fatty liver disease in patients with the metabolic syndrome. Methods. Blood, urine and breath levels of alcohol measured in 20 patients with the metabolic syndrome were compared with those of ...

  4. Alcohol, liver disease, and transplantation: shifting attitudes and new understanding leads to changes in practice.

    Science.gov (United States)

    Mathurin, Philippe; Lucey, Michael R

    2018-04-01

    Review the current status of liver transplantation for patients with alcohol use disorder (AUD). Alcohol-related liver disease (ALD) will increase as a source of patients requiring liver transplantation. Attitudes to use of liver transplantation as rescue therapy for patients with severe alcohol-related hepatitis are changing. The long-term health of ALD liver transplantation recipients requires continued assistance to patients with AUD. Liver transplantation of patients with ALD increased during the last decade and we predict that this trend will continue because of the decline in the number of hepatitis C virus-infected candidates. Concomitantly, a shift in the selection for liver transplantation has occurred of patients with severe alcohol-related hepatitis not responding to medical therapy. Although rescue liver transplantation is a valuable option for patients with severe alcohol-related hepatitis, worldwide practice regarding rescue liver transplantation remains very heterogeneous. There is increasing recognition that excessive consumption of alcohol after liver transplantation is harmful to graft function and patient survival. Factors associated with relapse are younger age at liver transplantation and shorter duration of sobriety prior to liver transplantation. The long-term health of the ALD liver transplant recipient requires continued assistance regarding AUD, a lifelong disorder of craving, relapse, and remission. However, there have been very few studies evaluating best practices for long-term addiction care in transplant recipients. After liver transplantation, the prevalence of cardiovascular disease, infections, and cancer increases over time. Addiction to tobacco constitutes an important issue that must be considered as tobacco cessation may decrease the incidence of tobacco-related cardiovascular and lung disease and aerodigestive cancers.

  5. Autologous bone marrow mononuclear cell transplantation in patients with decompensated alcoholic liver disease: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Laurent Spahr

    Full Text Available OBJECTIVE: Impaired liver regeneration is associated with a poor outcome in patients with decompensated alcoholic liver disease (ALD. We assessed whether autologous bone marrow mononuclear cell transplantation (BMMCT improved liver function in decompensated ALD. DESIGN: 58 patients (mean age 54 yrs; mean MELD score 19, all with cirrhosis, 81% with alcoholic steatohepatitis at baseline liver biopsy were randomized early after hospital admission to standard medical therapy (SMT alone (n = 30, including steroids in patients with a Maddrey's score ≥32, or combined with G-CSF injections and autologous BMMCT into the hepatic artery (n = 28. Bone marrow cells were harvested, isolated and reinfused the same day. The primary endpoint was a ≥3 points decrease in the MELD score at 3 months, corresponding to a clinically relevant improvement in liver function. Liver biopsy was repeated at week 4 to assess changes in Ki67+/CK7+ hepatic progenitor cells (HPC compartment. RESULTS: Both study groups were comparable at baseline. After 3 months, 2 and 4 patients died in the BMMCT and SMT groups, respectively. Adverse events were equally distributed between groups. Moderate alcohol relapse occurred in 31% of patients. The MELD score improved in parallel in both groups during follow-up with 18 patients (64% from the BMMCT group and 18 patients (53% from the SMT group reaching the primary endpoint (p = 0.43 (OR 1.6, CI 0.49-5.4 in an intention to treat analysis. Comparing liver biopsy at 4 weeks to baseline, steatosis improved (p<0.001, and proliferating HPC tended to decrease in both groups (-35 and -33%, respectively. CONCLUSION: Autologous BMMCT, compared to SMT is a safe procedure but did not result in an expanded HPC compartment or improved liver function. These data suggest either insufficient regenerative stimulation after BMMCT or resistance to liver regenerative drive in patients with decompensated alcoholic cirrhosis. TRIAL REGISTRATION

  6. Serum uric acid and non-alcoholic fatty liver disease in non-obesity Chinese adults.

    Science.gov (United States)

    Zheng, Xiaoya; Gong, Lilin; Luo, Rong; Chen, Hua; Peng, Bin; Ren, Wei; Wang, Yonghong

    2017-10-16

    Previous studies found elevated serum uric acid (SUA) was associated with the development or progression of non-alcoholic fatty liver disease (NAFLD) in general population; in this study we aim to investigate the association of SUA and the severity of NAFLD based on grade of fatty liver on ultrasonography in non-obese subjects. Data were obtained from subjects via routine physical examinations in the Public Health Center of our hospital between 2011 and 2014. The data included completed anthropometry and blood biochemical indicators and the results of abdominal ultrasound. The diagnosis of NAFLD was according to the clinical diagnosis of the Guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease in 2008. In total, 95,924 subjects were analyzed in this study. The prevalence rate of lean-NAFLD was 8.16%, among which 7.58% had mild steatosis, and 0.58% had moderate and severe steatosis. The prevalence of fatty liver was increased progressively with SUA. Among which the prevalence of mild fatty liver from Q1 to Q4 were 10.33%, 18.39%, 23.11% and 25.93%; the prevalence of moderate and severe fatty liver from Q1 to Q4 were 1.06%, 2.82%, 5.05% and 7.27%. Lean-subjects with hyperuricemia had an OR of 1.718 (95% CI 1.622-1.820) to have NAFLD, after adjusted for other metabolic disorders. The area under curve (AUC) for detecting mild fatty liver based on SUA was 0.70; and the AUC for detecting moderate and severe fatty liver based on SUA was 0.78. Our data showed positive associations between elevated SUA levels and lean-NAFLD risk in the inland Chinese adults, independent of other metabolic factors. Our study also suggests that SUA could be considered as a simple and non-invasive method to follow up patients with lean-NAFLD.

  7. Adrenal disorders and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Papanastasiou, Labrini; Fountoulakis, Stelios; Vatalas, Ioannis-Anastasios

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the developed world and its pathogenesis is complex and multifactorial. It is considered the hepatic manifestation of the metabolic syndrome and is the leading cause of hepatic cirrhosis. This review aims to present current knowledge on the involvement of the adrenal glands in the development of NAFLD. Clinical and animal studies have shown that excess glucocorticoids (GC) have been implicated in the pathogenesis of NAFLD. Patients with NAFLD seem to have a subtle chronic activation of the hypothalamic pituitary adrenal axis leading to a state of subclinical hypercortisolism. Regulators of GC such as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), an enzyme that regenerates cortisol from inactive cortisone, and 5α/5β-reductases, enzymes that increase cortisol clearance, are implicated in the development of NAFLD by amplifying local GC action. Adrenal androgen (dehydroepiandrosterone) abnormalities and increased aldosterone levels may also have a role in the development of NAFLD whereas the contribution of adrenergic signaling in NAFLD pathogenesis remains unclear.

  8. Alcohol consumption and risk of fatty liver disease: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Guoli Cao

    2016-10-01

    Full Text Available Background Observational studies have shown inconsistent results regarding alcohol consumption and risk of fatty liver. We performed a meta-analysis of published literature to investigate the association between alcohol consumption and fatty liver disease (FLD. Methods We searched Medline, Embase, Web of Science, and several Chinese databases, identifying studies that reported an association between alcohol consumption and the risk of FLD. Results A total of 16 studies with 76,608 participants including 13 cross-sectional studies, two cross-sectional following longitudinal studies, and one cohort study met the inclusion criteria. For light to moderate alcohol consumption (LMAC, there was a 22.6% reduction in risk of FLD (odds ratio [OR] = 0.774, 95% confidence interval CI [0.695–0.862], P <0.001, and subgroup analysis showed that a greater reduction in risk of FLD was found in the female drinkers (30.2% and the drinkers with BMI ≥25 kg/m2(31.3% compared with the male drinkers (22.6% and the drinkers with BMI <25 kg/m2(21.3%, respectively. For heavy alcohol consumption, there was no significant influence on risk of FLD (OR = 0.869, 95% CI [0.553–1.364], P = 0.541 in Japanese women, but there was a 33.7% reduction in risk of FLD (OR = 0.663, 95% CI [0.574–0.765], P < 0.001 in Japanese men and a significant increased risk of FLD (OR = 1.785, 95% CI [1.064–2.996], P = 0.028 in Germans. Conclusion LMAC is associated with a significant protective effect on FLD in the studied population, especially in the women and obese population. However, the effect of heavy alcohol consumption on FLD remains unclear due to limited studies and small sample sizes.

  9. Increased Nitroxidative Stress Promotes Mitochondrial Dysfunction in Alcoholic and Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Byoung-Joon Song

    2013-01-01

    Full Text Available Increased nitroxidative stress causes mitochondrial dysfunctions through oxidative modifications of mitochondrial DNA, lipids, and proteins. Persistent mitochondrial dysfunction sensitizes the target cells/organs to other pathological risk factors and thus ultimately contributes to the development of more severe disease states in alcoholic and nonalcoholic fatty liver disease. The incidences of nonalcoholic fatty liver disease continuously increase due to high prevalence of metabolic syndrome including hyperlipidemia, hypercholesterolemia, obesity, insulin resistance, and diabetes. Many mitochondrial proteins including the enzymes involved in fat oxidation and energy supply could be oxidatively modified (including S-nitrosylation/nitration under increased nitroxidative stress and thus inactivated, leading to increased fat accumulation and ATP depletion. To demonstrate the underlying mechanism(s of mitochondrial dysfunction, we employed a redox proteomics approach using biotin-N-maleimide (biotin-NM as a sensitive biotin-switch probe to identify oxidized Cys residues of mitochondrial proteins in the experimental models of alcoholic and acute liver disease. The aims of this paper are to briefly describe the mechanisms, functional consequences, and detection methods of mitochondrial dysfunction. We also describe advantages and limitations of the Cys-targeted redox proteomics method with alternative approaches. Finally, we discuss various applications of this method in studying oxidatively modified mitochondrial proteins in extrahepatic tissues or different subcellular organelles and translational research.

  10. Neutrophil depletion improves diet-induced non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Ou, Rongying; Liu, Jia; Lv, Mingfen; Wang, Jingying; Wang, Jinmeng; Zhu, Li; Zhao, Liang; Xu, Yunsheng

    2017-07-01

    Non-alcoholic fatty liver disease is highly associated with morbidity and mortality in population. Although studies have already demonstrated that the immune response plays a pivotal role in the development of non-alcoholic fatty liver disease, the comprehensive regulation is unclear. Therefore, present study was carried out to investigate the non-alcoholic fatty liver disease development under neutrophil depletion. To achieve the aim of the study, C57BL/6 J mice were fed with high fat diet for 6 weeks before treated with neutrophil deplete antibody 1A8 or isotype control (200 μg/ mouse every week) for another 4 weeks. Treated with 1A8 antibody, obese mice exhibited better whole body metabolic parameters, including reduction of body weight gain and fasting blood glucose levels. Neutrophil depletion also effectively reduced hepatic structural disorders, dysfunction and lipid accumulation. Lipid β-oxidative markers, phosphorylated-AMP-activated protein kinase α and phosphorylated-acetyl-CoA carboxylase levels were increased in 1A8 antibody-treated obese mouse group. The mitochondrial number and function were also reversed after 1A8 antibody treatment, including increased mitochondrial number, reduced lipid oxidative damage and enhanced mitochondrial activity. Furthermore, the expression of inflammatory cytokines, tumor necrosis factor-α, interleukin-6, and monocyte chemoattractant protein-1 were obviously reduced after neutrophil depletion, accompanied with decreased F4/80 mRNA level and macrophage percentage in liver. The decreased NF-κB signaling activity was also involved in the beneficial effect of neutrophil depletion. Taken together, neutrophil depletion could attenuate metabolic syndromes and hepatic dysfunction.

  11. Ethanol Extract of Pinus koraiensis Leaf Ameliorates Alcoholic Fatty Liver via the Activation of LKB1-AMPK Signaling In Vitro and In Vivo.

    Science.gov (United States)

    Hong, Sang-Hyuk; Lee, Hyemin; Lee, Hyo-Jung; Kim, Bonglee; Nam, Min-Ho; Shim, Bum-Sang; Kim, Sung-Hoon

    2017-05-01

    Although Pinus koraiensis leaf (PKL) was reported for its anti-diabetes, anti-obesity and anticancer effects as a folk remedy, the inhibitory effect of PKL on alcoholic fatty liver has never been elucidated yet. This study investigated the molecular mechanisms of PKL on alcoholic fatty liver in HepG2 cells, Sprague Dawley (SD) rats and Imprinting Control Region (ICR) mice. Pinus koraiensis leaf increased phosphorylation of liver kinase B1 (LKB1)/AMP-activated protein kinase signaling, low-density lipoprotein receptor and decreased fatty acid biosynthesis-related proteins such as sterol regulatory element-binding protein 1c, fatty acid synthase, 3-hydroxy-3-methylglutaryl-CoA reductase in HepG2 cells. In SD rats with 25% alcohol-induced fatty liver, PKL suppressed the levels of aspartate aminotransferase and triglyceride and also enhanced the activities of antioxidant enzymes including superoxide dismutase, glutathione peroxidase and glutathione s-transferase compared with untreated control. Furthermore, PKL increased serum alcohol dehydrogenase and serum aldehyde dehydrogenase, but decreased serum alcohol concentration in ICR mice after alcohol administration. Consistently, histochemical analysis revealed that PKL attenuated alcohol-induced fatty liver in SD rats. Overall, these findings suggest that PKL ameliorates alcohol-induced fatty liver via activation of LKB1-AMP-activated protein kinase and modulation of proteins related to lipogenesis synthesis, cholesterol synthesis and fatty acid oxidation. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  12. Expression of resistin in the liver of patients with non-alcoholic fatty liver disease

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    Piotr Gierej

    2017-11-01

    Full Text Available Adipokines are cytokines that presumably connect the pathologies of metabolic syndrome. One of the adipokines is resistin, the role of which in insulin resistance, obesity, and non-alcoholic fatty liver disease (NAFLD needs to be determined. Liver biopsy specimens were obtained intraoperatively from 214 obese patients. Histological assessment was based on NAFLD activity score according to Kleiner. Statistical analysis involved semi-quantitive immunohistochemistry assessment of resistin staining and: NAFLD status in obese patients compared with a non-obese control group, selected clinical data (age, sex, body mass index – BMI, selected biochemical data, comorbidities (hypertension, type 2 diabetes mellitus, dyslipidaemia, and metformin treatment in patients with type 2 diabetes mellitus. Resistin expression was observed in the histiocytes of inflammatory infiltrate, Kupffer cells, and histiocytes surrounding the hepatocytes with steatosis. There was a positive correlation between the total expression of resistin and: (1 NAFLD advancement (NAFLD Activity Score- NAS, (2 AST, ALT, BMI, glucose, insulin, Homeostasis Model Assessment (HOMA, LDH, GGT, triglycerides (TG, and glycated haemoglobin (HbA1c. Resistin expression was more intense in patients with type 2 diabetes mellitus and dyslipidaemia and less intense in the control group. Resistin probably plays a role in the pathogenesis of hepatic insulin resistance and aggravates pathologic changes in the liver of patients with NAFLD.

  13. Interobserver Variability in Scoring Liver Biopsies with a Diagnosis of Alcoholic Hepatitis.

    Science.gov (United States)

    Horvath, Bela; Allende, Daniela; Xie, Hao; Guirguis, John; Jeung, Jennifer; Lapinski, James; Patil, Deepa; McCullough, Arthur J; Dasarathy, Srinivasan; Liu, Xiuli

    2017-09-01

    Alcoholic hepatitis (AH) is one of the most severe forms of alcoholic liver disease. Recently, a histologic scoring system for predicting prognosis in this patient cohort was proposed as Alcoholic Hepatitis Histologic Score (AHHS). We aimed to assess interobserver variability in recognizing histologic features of AH and the effect of this variability on the proposed AHHS categories. Hematoxylin-eosin- and trichrome-stained slides from 32 patients diagnosed with AH with liver biopsies within 1 month of presentation (2000 to 2015) were reviewed by 5 pathologists including 3 liver pathologists and 2 gastrointestinal (GI) pathologists masked to the clinical findings or outcome. Histologic features of AH were assessed, the AHHS was calculated, and an AHHS category (mild, moderate, severe) was assigned. The Fleiss' kappa coefficient (κ) analysis was performed to determine the interobserver agreement. A slight-to-moderate level of interobserver agreement existed among 5 reviewers on histopathologic features of AH with κ value ranging from 0.20 (95% confidence interval (CI): 0.03 to 0.46, megamitochondria) to 0.52 [95% CI: 0.40 to 0.68, polymorphonuclear leukocyte (PMN) infiltration]. There was only a fair level of agreement in assigning AHHS category (κ = 0.33, 95% CI: 0.20 to 0.51). While overall fibrosis and neutrophilic inflammation were comparably evaluated by 3 liver pathologists and 2 GI pathologists, bilirubinostasis and megamitochondria were more consistently diagnosed by liver pathologists. Overall, 18 of 32 (56%) were uniformly assigned to an AHHS category by all liver pathologists with a κ value of 0.40 (95% CI: 0.22 to 0.60). In general, features of AH can be recognized with a slight-to-moderate level of interobserver agreement and there was fair interobserver agreement on assigning an AHHS category. Significant interobserver variability among pathologists revealed by the current study can limit its usefulness in everyday clinical practice. Copyright

  14. The let-7/Lin28 axis regulates activation of hepatic stellate cells in alcoholic liver injury.

    Science.gov (United States)

    McDaniel, Kelly; Huang, Li; Sato, Keisaku; Wu, Nan; Annable, Tami; Zhou, Tianhao; Ramos-Lorenzo, Sugeily; Wan, Ying; Huang, Qiaobing; Francis, Heather; Glaser, Shannon; Tsukamoto, Hidekazu; Alpini, Gianfranco; Meng, Fanyin

    2017-07-07

    The let-7/Lin28 axis is associated with the regulation of key cellular regulatory genes known as microRNAs in various human disorders and cancer development. This study evaluated the role of the let-7/Lin28 axis in regulating a mesenchymal phenotype of hepatic stellate cells in alcoholic liver injury. We identified that ethanol feeding significantly down-regulated several members of the let-7 family in mouse liver, including let-7a and let-7b. Similarly, the treatment of human hepatic stellate cells (HSCs) with lipopolysaccharide (LPS) and transforming growth factor-β (TGF-β) significantly decreased the expressions of let-7a and let-7b. Conversely, overexpression of let-7a and let-7b suppressed the myofibroblastic activation of cultured human HSCs induced by LPS and TGF-β, as evidenced by repressed ACTA2 (α-actin 2), COL1A1 (collagen 1A1), TIMP1 (TIMP metallopeptidase inhibitor 1), and FN1 (fibronectin 1); this supports the notion that HSC activation is controlled by let-7. A combination of bioinformatics, dual-luciferase reporter assay, and Western blot analysis revealed that Lin28B and high-mobility group AT-hook (HMGA2) were the direct targets of let-7a and let-7b. Furthermore, Lin28B deficiency increased the expression of let-7a/let-7b as well as reduced HSC activation and liver fibrosis in mice with alcoholic liver injury. This feedback regulation of let-7 by Lin28B is verified in hepatic stellate cells isolated by laser capture microdissection from the model. The identification of the let-7/Lin28 axis as an important regulator of HSC activation as well as its upstream modulators and down-stream targets will provide insights into the involvement of altered microRNA expression in contributing to the pathogenesis of alcoholic liver fibrosis and novel therapeutic approaches for human alcoholic liver diseases. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Vyberg, M

    1991-01-01

    . No relationship was found between TTHV and PSF. The results were compared to similar data obtained in liver biopsies from 117 non-alcoholics with normal morphology or slight non-specific changes. No significant difference concerning TTHV and THV diameter was found between alcoholic and non-alcoholic patients......The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less....... The results suggest that the initial liver fibrosis in alcoholics is slightly asymmetrical distributed in each acinar zone 3 area. With progression, the fibrosis tends to be more uniformly distributed and septa appear, eventually linking THV with portal tracts. Apparently, thickening of the THV walls does...

  16. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    Directory of Open Access Journals (Sweden)

    Jonathan L. Temple

    2016-06-01

    Full Text Available Non-Alcoholic Fatty Liver Disease (NAFLD is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention.

  17. A Guide to Non-Alcoholic Fatty Liver Disease in Childhood and Adolescence

    Science.gov (United States)

    Temple, Jonathan L.; Cordero, Paul; Li, Jiawei; Nguyen, Vi; Oben, Jude A.

    2016-01-01

    Non-Alcoholic Fatty Liver Disease (NAFLD) is now the most prevalent form of chronic liver disease, affecting 10%–20% of the general paediatric population. Within the next 10 years it is expected to become the leading cause of liver pathology, liver failure and indication for liver transplantation in childhood and adolescence in the Western world. While our understanding of the pathophysiological mechanisms underlying this disease remains limited, it is thought to be the hepatic manifestation of more widespread metabolic dysfunction and is strongly associated with a number of metabolic risk factors, including insulin resistance, dyslipidaemia, cardiovascular disease and, most significantly, obesity. Despite this, ”paediatric” NAFLD remains under-studied, under-recognised and, potentially, undermanaged. This article will explore and evaluate our current understanding of NAFLD in childhood and adolescence and how it differs from adult NAFLD, in terms of its epidemiology, pathophysiology, natural history, diagnosis and clinical management. Given the current absence of definitive radiological and histopathological diagnostic tests, maintenance of a high clinical suspicion by all members of the multidisciplinary team in primary and specialist care settings remains the most potent of diagnostic tools, enabling early diagnosis and appropriate therapeutic intervention. PMID:27314342

  18. Antifibrotic and molecular aspects of rifaximin in alcoholic liver disease: study protocol for a randomized controlled trial

    DEFF Research Database (Denmark)

    Madsen, Bjørn Stæhr; Trebicka, Jonel; Thiele, Maja

    2018-01-01

    BACKGROUND: Alcoholic liver disease is the leading cause of cirrhosis worldwide. Due to an increase in alcohol overuse, alcoholic liver disease has become an increased burden on health care systems. Abstinence from alcohol remains the cornerstone of alcoholic liver disease treatment; however......, this approach is hampered by frequent relapse and lack of specific therapy for treating advanced cases of liver disease. In the present study, we hypothesized that gut microbiota drive the development of liver fibrosis and that modulation of gut microbiota with the gut-selective, nonabsorbable antibiotic...

  19. Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project.

    Science.gov (United States)

    Petrick, Jessica L; Campbell, Peter T; Koshiol, Jill; Thistle, Jake E; Andreotti, Gabriella; Beane-Freeman, Laura E; Buring, Julie E; Chan, Andrew T; Chong, Dawn Q; Doody, Michele M; Gapstur, Susan M; Gaziano, John Michael; Giovannucci, Edward; Graubard, Barry I; Lee, I-Min; Liao, Linda M; Linet, Martha S; Palmer, Julie R; Poynter, Jenny N; Purdue, Mark P; Robien, Kim; Rosenberg, Lynn; Schairer, Catherine; Sesso, Howard D; Sinha, Rashmi; Stampfer, Meir J; Stefanick, Marcia; Wactawski-Wende, Jean; Zhang, Xuehong; Zeleniuch-Jacquotte, Anne; Freedman, Neal D; McGlynn, Katherine A

    2018-03-09

    While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type. The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR ≥7 drinks/day  = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR ≥5 drinks/day  = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of 0-0.5-<1 drinks/day  = 0.57, 95% CI: 0.44-0.73; HR 1-<3 drinks/day  = 0.71, 95% CI: 0.58-0.87), but not ICC. These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

  20. Comparing Effects of Medication Therapy and Exercise Training with Diet on Liver enzyme Levels and Liver Sonography in Patients with Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Azadeh Nabizadeh Haghighi

    2016-03-01

    Full Text Available Background & Objectives: Non-alcoholic fatty liver disease, characterized by the deposition of fat in liver cells, can cause fibrosis, cirrhosis, and liver cell damage if not controlled. The aim of this study is to compare the effects of medication therapy and exercise training with diet on liver enzyme levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD. Materials & Methods :In this quasi-experimental study, female patients with non-alcoholic fatty liver were randomly divided into two groups: medication therapy (n = 10 and exercise therapy (n = 10 for 8 weeks. During this period, the exercise group performed exercise training three days a week for 90 minutes per session. The drug was given to the medication group. In both groups, the diet was 500 calories less than their daily energy. Before and after intervention, blood tests and liver sonography were executed. All statistical analyses were done using SPSS for Windows version 20. Comparisons between and within groups were performed by Student's t-test and Wilcoxon test on paired and unpaired data. P < 0.05 was considered statistically significant. Results :In both groups, liver enzyme levels and disease severity in sonography reduced significantly (p<0.05. Conclusion: The findings of the present research showed that both methods of therapy have the same effect on reducing the severity of NAFLD.

  1. Benefits of exenatide on obesity and non-alcoholic fatty liver disease with elevated liver enzymes in patients with type 2 diabetes.

    Science.gov (United States)

    Shao, Ning; Kuang, Hong Yu; Hao, Ming; Gao, Xin Yuan; Lin, Wen Jian; Zou, Wei

    2014-09-01

    The purpose of this study was to evaluate the advantages of exenatide treatment on obesity and non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes in patients with type 2 diabetes (T2D). A total of 60 newly diagnosed patients with obesity, NAFLD with elevated liver enzymes and T2D were included in the study. The patients were randomly divided into two groups. The exenatide treatment group (n = 30) were treated with exenatide and insulin glargine, and the intensive insulin therapy group (n = 30) were treated with insulin aspart and insulin glargine for 12 weeks. Selected clinical characteristics were determined, and ultrasonography was performed at both baseline and 12 weeks following treatment. At baseline, the clinical characteristics were matched between the two groups. After 12 weeks, fasting blood glucose (FBG), postprandial blood glucose (PBG), glycosylated haemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and total bilirubin levels were significantly decreased in the two groups (p fatty liver was significantly higher in the exenatide group (93.3%) than the intensive insulin group (66.7%) (p obesity, non-alcoholic fatty liver disease with elevated liver enzymes and T2D. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Circulating lipocalin 2 is neither related to liver steatosis in patients with non-alcoholic fatty liver disease nor to residual liver function in cirrhosis.

    Science.gov (United States)

    Meier, Elisabeth M; Pohl, Rebekka; Rein-Fischboeck, Lisa; Schacherer, Doris; Eisinger, Kristina; Wiest, Reiner; Krautbauer, Sabrina; Buechler, Christa

    2016-09-01

    Lipocalin 2 (LCN2) is induced in the injured liver and associated with inflammation. Aim of the present study was to evaluate whether serum LCN2 is a non-invasive marker to assess hepatic steatosis in patients with non-alcoholic fatty liver disease (NAFLD) or residual liver function in patients with liver cirrhosis. Therefore, LCN2 was measured by ELISA in serum of 32 randomly selected patients without fatty liver (controls), 24 patients with ultrasound diagnosed NAFLD and 42 patients with liver cirrhosis mainly due to alcohol. Systemic LCN2 was comparable in patients with liver steatosis, those with liver cirrhosis and controls. LCN2 negatively correlated with bilirubin in both cohorts. In cirrhosis, LCN2 was not associated with more advanced liver injury defined by the CHILD-PUGH score and model for end-stage liver disease score. Resistin but not C-reactive protein or chemerin positively correlated with LCN2. LCN2 levels were not increased in patients with ascites or patients with esophageal varices. Consequently, reduction of portal pressure by transjugular intrahepatic portosystemic shunt did not affect LCN2 levels. Hepatic venous blood (HVS), portal venous blood and systemic venous blood levels of LCN2 were similar. HVS LCN2 was unchanged in patients with end-stage liver cirrhosis compared to those with well-compensated disease arguing against increased hepatic release. Current data exclude that serum LCN2 is of any value as steatosis marker in patients with NAFLD and indicator of liver function in patients with alcoholic liver cirrhosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Handgrip dynamometry: a surrogate marker of malnutrition to predict the prognosis in alcoholic liver disease.

    Science.gov (United States)

    Gaikwad, Nitin Rangrao; Gupta, Sudhir Jagdishprasad; Samarth, Amol Rajendra; Sankalecha, Tushar Hiralal

    2016-01-01

    The aim of the study was to determine the utility of handgrip dynamometry (HGD) in predicting short term mortality and complications in alcoholic liver disease. Patients with alcoholic liver disease were included and nutritional assessment was done using the Subjective Global Assessment (SGA), HGD and other conventional parameters. Mortality rates and complications were compared to nutritional status. 80 patients were included in the study. Mean age of patients was 43.06±10.03 years. 69 patients survived and 11 patients died within the 3 month study duration. Handgrip strength (HGS) was higher in SGA A (28.76±5.48 kg) than SGA B (22.43±4.95 kg) and SGA C (16.78±3.83 kg) (P=<0.001). Number of complications including spontaneous bacterial Peritonitis, gastrointestinal bleeding and encephalopathy in SGA C group were 66.66%, in SGA B 20.75% and SGA A 10%. Mean HGS was significantly higher in the survivors (24.23±5.86) compared to non-survivors (18.04±4.82) (P=0.0011). There was a strong negative correlation between the HGS and Child-Pugh score (P=<0.0012). Multivariate logistic regression analysis to assess the risk factors for death showed handgrip to be in the suggestive significance range (P=0.072). The sensitivity of HGS was 88.41% in predicting short term mortality. HGS correlates with Child-Pugh score in predicting short term mortality. HGD is a simple, inexpensive and sensitive tool for assessing the nutritional status in alcoholic liver disease and can reliably predict its complications and survival.

  4. [Dietetary recommendation for non-alcoholic fatty liver disease].

    Science.gov (United States)

    Jeznach-Steinhagen, Anna; Ostrowska, Joanna; Czerwonogrodzka-Senczyna, Aneta; Boniecka, Iwona; Gronostajska, Wioletta

    2017-12-22

    Non-alcoholic Fatty Liver Disease (NAFLD) is currently the most common chronic liver disease in the developed world. Nowadays, in the adult population of Europe it is estimated at 14% to 21%. Its most important risk factors are obesity and metabolic syndrome. Introducing lifestyle changes such as: dietary intervention and increased physical activity are the first-line treatment and are intended to support not only NAFLD but also associated diseases such as obesity, insulin resistance, diabetes and dyslipidemia. Dietary management focuses on weight reduction of overweight or obese people by decreasing energy in diet. It is recommended to limit the intake of saturated fats and trans fatty acids as well as cholesterol. Instead, it is important to increase the proportion of polyunsaturated fatty acid diets, mainly from the n-3 family, which exhibit anti-inflammatory activity. It is also beneficial to eat nuts, despite their high energy value, as a source of alpha linolenic acid, which lowers LDL cholesterol. It is important to increase the share of vegetable protein (eg. soya) and limit the intake of fat meat, milk and the dairy products. A key role in the treatment and prevention of NAFLD is also a reduction of simple sugars and total exclusion of added sugar in the diet. The rise of NAFLD in developed countries is analogous to the increase of fructose consumption, which high intake is directly indicated as the main cause of the disease. Choosing foods with high fiber content, low glycemic index and meals composed with low glycemic load, is conducive to weight reduction. An important role in supporting NAFLD treatment is also attributed to vitamin D, C and E supplementation and some probiotic bacteria, as well as cinnamon and turmeric, which improve insulin sensitivity. Daily physical activity is strongly recommended as the supplement of healthy lifestyle.

  5. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Mouzaki, Marialena; Wang, Alice Y; Bandsma, Robert; Comelli, Elena M; Arendt, Bianca M; Zhang, Ling; Fung, Scott; Fischer, Sandra E; McGilvray, Ian G; Allard, Johane P

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM) and bile acids (BA) suggest that dysbiosis may be accompanied by an altered bile acid (BA) homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data. This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH) and healthy controls (HC). Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4) and intestinal BA signalling, as well as IM composition were assessed. 53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA), chenodeoxycholic acid (CDCA) and BA synthesis were higher in patients with NASH compared to HC (pLCA) (r = 0.526, p = 0.003) and inversely with unconjugated CA (r = -0.669, pinjury.

  6. Horse Liver Alcohol Dehydrogenase: Zinc Coordination and Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Plapp, Bryce V.; Savarimuthu, Baskar Raj; Ferraro, Daniel J.; Rubach, Jon K.; Brown, Eric N.; Ramaswamy, S. (Iowa)

    2017-07-07

    During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism might involve a pentacoordinated zinc or a double-displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1, and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. The apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174, and a water molecule. The bidentate chelators 2,2'-bipyridine and 1,10-phenanthroline displace the water and form a pentacoordinated zinc. The enzyme–NADH complex has a closed conformation similar to that of ternary complexes with coenzyme and substrate analogues; the coordination of the catalytic zinc is similar to that found in the apoenzyme, except that a minor, alternative position for the catalytic zinc is ~1.3 Å from the major position and closer to Glu-68, which could form the alternative coordination to the catalytic zinc. Complexes with NADH and N-1-methylhexylformamide or N-benzylformamide (or with NAD+ and fluoro alcohols) have the classical tetracoordinated zinc, and no water is bound to the zinc or the nicotinamide rings. The major forms of the enzyme in the mechanism have a tetracoordinated zinc, where the carboxylate group of Glu-68 could participate in the exchange of water and substrates on the zinc. Hydride transfer in the Michaelis complexes does not involve a nearby water.

  7. Diagnostic and pathogenetic significance of apolipoprotein disorders in patients with alcoholic fatty liver

    Directory of Open Access Journals (Sweden)

    Mladenović Bojan

    2017-01-01

    Full Text Available Background/Aim. Alcohol is the most common cause of fatty liver. Alcohol metabolism takes place in the liver by alcohol dehydrogenase, to toxic acetaldehyde, with fatty acids accumulation in the liver as a consequence. By daily intake of the amount greater than 80 g/day for men and 20 g for women, there is the risk for developing the alcoholic fatty liver (AFLD. The aim of this study was to determine the profile of atherogenic factors in plasma of patients with AFLD compared to patients with non-alcoholic fatty liver (NAFLD and determine its diagnostic significance. Methods. The study included 74 patients with AFLD who consumed alcoholic beverages daily in large quantities and over 80 g [for men: 3–4 units (U of alcohol and for women 2–3 U]; the control group consisted of 70 patients with NAFLD verified with ultrasound. A total holesterol (TC, triglycerides (TG, high-density lipoprotein cholesterol (HDL-C, low-density lipoprotein cholesterol (LDL-C and apoliporoteins (ApoA1 and ApoB were determined and the ratios TC/HDL-C, ApoB/ApoA1 and LDL-C/HDL-C were calculated. Results. The study included two group: 74 AFLD patients (21% of women and 79% of men, mean age 42.65 ± 9.73 years, who consumed alcoholic beverages daily in the amounts of 80 g, or greter, during the average 2.31 ± 0.96 years and 70 patients with NAFLD (37.5% of women and 63.5% of men with the average 41.3 ± 4.1 years. There was no significant difference in gender distribution and the average age between the examined groups. Higher values of TG – 9.94 ± 2.94 mmol/L, TC 14.53 ± 2.81 mmol/L, LDL-C 8.57 ± 2.15 mmol/L and ApoB 3.97 ± 0.28 g/L and lower values of HDL-C 0.43 ± 0.11 mmol/L, Apo A1 0.49 ± 0.09 g/L and ApoB/ApoA1 ratio 2.43 ± 1.27 were registered in the AFLD group compared to those registered in the NAFLD group, (TG 8.74 ± 2.54 mmol/L TC 9.87 ± 2.36, LDL-C 6.72 ± 1.98 mmol/L, Apo B 2.38 ± 0.16 g/L, HDL-C 0.78 ± 0.09 mmol/L, Apo A1 0.98 ± 0.04 g/L and Apo

  8. No effect of long-term oral testosterone treatment on liver morphology in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Christoffersen, Pernille Yde; Eriksen, J

    1987-01-01

    The effect of oral testosterone treatment (200 mg tid) on liver morphology was examined in a double-blind, placebo controlled study including men with alcoholic cirrhosis (n = 126). Liver biopsies obtained before randomization showed micronodular cirrhosis in 119 patients (94%), alcoholic hepatitis...... influence the prevalence of these changes. Further, testosterone treatment had no significant effect on the prevalence of other morphological changes, including vascular and malignant changes. However, in the testosterone-treated group one patient developed diffuse sinusoidal dilation and one patient showed...... not establish any indication or any contraindication in terms of hepatic histopathology with the possible exception of hepatic venous thrombosis for the use of oral testosterone treatment in men with alcoholic cirrhosis....

  9. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease

    Directory of Open Access Journals (Sweden)

    Stefano Gitto

    2016-01-01

    Full Text Available Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption.

  10. Multidisciplinary View of Alcohol Use Disorder: From a Psychiatric Illness to a Major Liver Disease

    Science.gov (United States)

    Gitto, Stefano; Golfieri, Lucia; Caputo, Fabio; Grandi, Silvana; Andreone, Pietro

    2016-01-01

    Alcohol use disorder is a significant health problem being a cause of increased morbidity and mortality worldwide. Alcohol-related illness has a relevant economic impact on the society and a negative influence on the life of patients and their family members. Psychosocial support might be useful in the management of people affected by alcohol use disorder since psychiatric and pharmaceutical approaches show some limits. In fact, many drugs are accessible for the treatment of alcohol disorder, but only Baclofen is functional as an anti-craving drug in patients with advanced liver disease. The alcohol-related liver damage represents the most frequent cause of advanced liver disease in Europe, and it is the main cause of death among adults with high alcohol consumption. The multidisciplinary action of clinical-psychologists, psychiatrics and hepatologists, is essential in the management of patients with alcohol liver disease especially in the case of liver transplantation. In general, the multidisciplinary approach is necessary in prevention, in framing patients and in the treatment. More resources should be used in prevention and research with the main aim of decreasing the harmful alcohol consumption. PMID:26784248

  11. Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

    Science.gov (United States)

    Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

    2016-03-01

    Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

  12. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice

    OpenAIRE

    Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2017-01-01

    Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apo...

  13. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Gemma Aragonès

    2016-04-01

    Full Text Available Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3 in the pathology of non-alcoholic fatty liver disease (NAFLD. Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18, simple steatosis (SS, n = 20, and non-alcoholic steatohepatitis (NASH, n = 17. Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  14. PNPLA3 Expression Is Related to Liver Steatosis in Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Aragonès, Gemma; Auguet, Teresa; Armengol, Sandra; Berlanga, Alba; Guiu-Jurado, Esther; Aguilar, Carmen; Martínez, Salomé; Sabench, Fátima; Porras, José Antonio; Ruiz, Maikel Daniel; Hernández, Mercé; Sirvent, Joan Josep; Del Castillo, Daniel; Richart, Cristóbal

    2016-04-27

    Recent reports suggest a role for the Patatin-like phospholipase domain-containing protein 3 (PNPLA3) in the pathology of non-alcoholic fatty liver disease (NAFLD). Lipid deposition in the liver seems to be a critical process in the pathogenesis of NAFLD. The aim of the present work was to evaluate the association between the liver PNPLA3 expression, key genes of lipid metabolism, and the presence of NAFLD in morbidly obese women. We used real-time polymerase chain reaction (PCR) analysis to analyze the hepatic expression of PNPLA3 and lipid metabolism-related genes in 55 morbidly obese subjects with normal liver histology (NL, n = 18), simple steatosis (SS, n = 20), and non-alcoholic steatohepatitis (NASH, n = 17). Liver biopsies were collected during bariatric surgery. We observed that liver PNPLA3 expression was increased in NAFLD than in NL. It was also upregulated in SS than in NL. Interestingly, we found that the expression of PNPLA3 was significantly higher in severe than mild SS group. In addition, the expression of the transcription factors LXRα, PPARα, and SREBP2 was positively correlated with PNPLA3 liver expression. Regarding rs738409 polymorphism, GG genotype was positive correlated with the presence of NASH. In conclusion, our results show that PNPLA3 could be related to lipid accumulation in liver, mainly in the development and progression of simple steatosis.

  15. [Retinal and carotid changes in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Baloşeanu, Cristina; Rogoveanu, I; Mocanu, Carmen

    2013-01-01

    This article presents the results of a study on 85 patients with non-alcoholic fatty liver disease (NAFLD). We evaluate the retinal vascular changes using retinal photography and carotid vascular changes, by ultrasounds, occured in this group of patients.

  16. Imaging of non alcoholic fatty liver disease: A road less travelled

    Directory of Open Access Journals (Sweden)

    Divya Singh

    2013-01-01

    Full Text Available Non alcoholic fatty liver disease (NAFLD is a spectrum that includes simple steatosis, nonalcoholic steatohepatitis and cirrhosis. It is increasingly emerging as a cause of elevated liver enzymes, cryptogenic cirrhosis and hepatocellular carcinoma. The morbidity and mortality related to NAFLD is expected to rise with the upsurge of obesity and type 2 diabetes mellitus. The need of the hour is to devise techniques to estimate and then accurately follow-up hepatic fat content in patients with NAFLD. There are lots of imaging modalities in the radiological armamentarium, namely, ultrasonography with the extra edge of elastography, computed tomography, and magnetic resonance imaging with chemical shift imaging and spectroscopy to provide an estimation of hepatic fat content.

  17. Alimentary regimen in non-alcoholic fatty liver disease: Mediterranean diet

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Peta, Valentina; Alfieri, Francesco; De Lorenzo, Antonino; Bellentani, Stefano

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. The mechanisms of the underlying disease development and progression are awaiting clarification. Insulin resistance and obesity-related inflammation status, among other possible genetic, dietary, and lifestyle factors, are thought to play the key role. There is no consensus concerning the pharmacological treatment. However, the dietary nutritional management to achieve weight loss is an essential component of any treatment strategy. On the basis of its components, the literature reports on the effectiveness of the Mediterranean diet in reducing cardiovascular risk and in preventing major chronic diseases, including obesity and diabetes. New evidence supports the idea that the Mediterranean diet, associated with physical activity and cognitive behaviour therapy, may have an important role in the prevention and the treatment of NAFLD. PMID:25492997

  18. Luteolin alleviates alcoholic liver disease induced by chronic and binge ethanol feeding in mice.

    Science.gov (United States)

    Liu, Gaigai; Zhang, Yuxue; Liu, Chunchun; Xu, Daqian; Zhang, Rui; Cheng, Yuan; Pan, Yi; Huang, Cheng; Chen, Yan

    2014-07-01

    Ethanol consumption can lead to hepatic steatosis that contributes to late-stage liver diseases such as cirrhosis and hepatocellular carcinoma. In this study, we investigated the potential protective effect of a flavonoid, luteolin, on ethanol-induced fatty liver development and liver injury. Six-wk-old male C57BL/6 mice were divided into 3 groups: a control group; a group exposed to alcohol by using a chronic and binge ethanol feeding protocol (EtOH); and a group that was administered daily 50 mg/kg of luteolin in addition to ethanol exposure (EtOH + Lut). A chronic and binge ethanol feeding protocol was used, including chronic ethanol consumption (1%, 2%, and 4% for 3 d, and 5% for 9 d) and a binge (30% ethanol) on the last day. Compared with the control group, the EtOH group had a significant elevation in serum concentrations of alanine aminotransferase (ALT) (561%), triglyceride (TG) (47%), and LDL cholesterol (95%), together with lipid accumulation in the liver. Compared with the EtOH group, the EtOH + Lut group had significant reductions in serum concentrations of ALT (43%), TG (22%), LDL cholesterol (52%), and lipid accumulation in the liver. Ethanol elevated liver expression of lipogenic genes including sterol regulatory element-binding protein 1c (Srebp1c) (560%), fatty acid synthase (Fasn) (190%), acetyl-CoA carboxylase (Acc) (48%), and stearoyl-CoA desaturase 1 (Scd1) (286%). Luteolin reduced ethanol-induced expression of these genes in the liver: Srebp1c (79%), Fasn (80%), Acc (60%), and Scd1 (89%). In cultured hepatocytes, luteolin prevented alcohol-induced lipid accumulation and increase in the expression of lipogenic genes. The transcriptional activity of the master regulator of lipid synthesis, sterol regulatory element-binding protein (SREBP), was enhanced by ethanol treatment (160%) and reduced by luteolin administration (67%). In addition, ethanol-induced reduction of AMP-activated protein kinase and SREBP-1c phosphorylation was abrogated by

  19. Global Epidemiology of Non-Alcoholic Fatty Liver Disease and Perspectives on US Minority Populations

    Science.gov (United States)

    Sherif, Zaki A.; Saeed, Armana; Ghavimi, Shima; Nouraie, Seyed-Mehdi; Laiyemo, Adeyinka O.; Brim, Hassan; Ashktorab, Hassan

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), a clinical syndrome that is predicted to affect millions of people worldwide, will become the next global epidemic. The natural course of this disease, including its subtype, non-alcoholic steatohepatitis (NASH), is not clearly defined, especially in the US minority populations. The aim of this review is to report the global epidemiology of NAFLD, with emphasis on US minority populations on the basis of database searches using using Pubmed and other online databases. The US Hispanic population is the most disproportionately affected ethnic group with hepatic steatosis whereas African-Americans are the least affected. Genetic disparities involved in lipid metabolism seem to be the leading explanation for the lowest incidence and prevalence of both NAFLD and NASH in African-Americans. PMID:27038448

  20. Inaccessibility of alcohol-induced cirrhosis of the liver to radiopharmaceutical methods of investigation

    International Nuclear Information System (INIS)

    Roh, T.G.

    1983-01-01

    Three cases of chronic alcohol abuse are described where the scintigrams recorded completely failed to visualise the hepatic structures. The female patients included in the study abused alcohol over a period of several years and the quantities consumed were far above the dose generally believed to cause cirrhosis in women. All of them displayed signs of advanced cirrhosis of the liver like portal hypertension, icterus, coagulation disorders, hepatic encephalopathy, etc. and the disease eventually led to the death of the patients. Hepatic scintiscanning was performed using Au198, Hg197, Tc99m sulfur colloid, Tc99m antimonial colloid as well as rose bengal iodine 131 tagged isotope; one patient was additionally subjected to radionuclide examination of the abdominal cavity. The causes of the described phenomenon still remain obscure. Damage to the reticuloendothelial system appears to be one of the predominant factors in the etiology of the disease. (TRV) [de

  1. When a liver transplant recipient goes back to alcohol abuse: Should we be more selective?

    OpenAIRE

    Leon, Monica; Varon, Joseph; Surani, Salim

    2016-01-01

    Alcoholic liver disease (ALD) is one of the most common indications for liver transplantation (LT). However, it has always remained as a complicated topic from both medical and ethical grounds, as it is seen for many a “self-inflicted disease”. Over the years, the survival rate of transplanted patients has significantly improved. The allocation system and the inclusion criteria for LT has also undergone some modifications. Early LT for acute alcoholic hepatitis has been subject to recent clin...

  2. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence......A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...

  3. [Electron microscopic study of cytoplasmic crystals in liver damages caused by alcoholism].

    Science.gov (United States)

    Schaff, Z; Lapis, K

    1975-01-01

    Liver biopsy of 50 patients with liver disease of alcoholic etiology was examined electronmicroscopically. In every stage of the disease presence of intramitochondrial paracrystalloids was revealed. Hyalin of alcoholic origin of fibrillar structure was seen in cases of alcoholic hepatitis. By the electronmicroscopic examination of three cases of alcoholic fatty liver a special form of cytoplasmatic paracristalloid inclusion could be seen. This inclusion consists of membranless parallely lying fibrills. Changing the plain of the preparats containing inclusions by the aid of a goniometer the structure of the inclusions appeared in a form of "honey-comb". Inclusion in the question can not be regarded identical neither with intramitochondrial inclusions nor with the fibrills of the so called alcoholic hyalin. Formation and function of these inclusions are as yet unknown.

  4. Circulating immune complexes and complement concentrations in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Gluud, C; Jans, H

    1982-01-01

    A prospective evaluation of circulating immune complexes (CIC) and the activity of the complement system was undertaken in 53 alcoholic patients just before diagnostic liver biopsy. Circulating immune complexes were detected in 39% of patients with alcoholic steatosis (n = 26), 58% of patients...... with alcoholic hepatitis (n = 12), and 60% of patients with alcoholic cirrhosis (n = 15). No significant difference was found between the three group of patients. The activity of the complement system was within reference limits in the majority of patients and only slight differences were detected between...... the three groups. No significant differences were observed in liver biochemistry and complement concentrations in CIC-positive and CIC-negative patients. Detection of CIC in patients with alcoholic liver disease does not seem to be of any diagnostic value or play any pathogenic role. The high prevalence...

  5. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    OpenAIRE

    Betzel, Bark; Drenth, Joost PH

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but its sensitivity is limited and liver biopsy is still considered to be the gold standard. Less invasive techniques that accurately quantify liver steatosis are warranted. Jimenez-Aguero and colleagues...

  6. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  7. Contemporary Policies Regarding Alcohol and Marijuana Use Among Liver Transplant Programs in the United States.

    Science.gov (United States)

    Zhu, Jiaming; Chen, Ping-Yu; Frankel, Marla; Selby, Robert Rick; Fong, Tse-Ling

    2018-03-01

    Alcoholic liver disease is a common indication for orthotopic liver transplantation (OLT). Although OLT has been shown to confer survival benefit to patients with acute alcoholic hepatitis (AAH), historically most programs require a 6-month abstinence period before OLT which excludes patients with AAH. Marijuana has become legal in more than half the states in the United States. This survey of liver transplant programs was conducted to evaluate current policies regarding alcohol, marijuana and methadone use. A questionnaire was distributed to 100 United Network for Organ Sharing-approved liver transplant programs in North America that have performed at least 30 liver transplants/year in the last 5 years. Forty-nine programs responded. Only 43% of the programs required a specific period of abstinence before transplant for alcoholic liver disease and only 26% enforced 6-month abstinence policy. For patients with AAH, 71% programs waived the 6-month abstinence requirement and considered psychosocial factors, such as family support, patient's motivation, or commitment to rehabilitate. Few programs used validated instruments to assess risk of relapse in AAH patients. Fourteen percent of programs transplant patients actively using marijuana and an additional 28% of programs listed patients using marijuana provided they discontinue by the time of OLT. Active methadone users were accepted in 45% of the programs. Policies regarding alcohol use have become more flexible particularly toward patients with AAH. Marijuana use is also more accepted. Although policies regarding alcohol and marijuana have changed significantly in the last decade, they remain highly variable among programs.

  8. IL-17 Axis Driven Inflammation in Non-Alcoholic Fatty Liver Disease Progression

    Science.gov (United States)

    Giles, Daniel A.; Moreno-Fernandez, Maria E; Divanovic, Senad

    2016-01-01

    Obesity is a primary risk factor for the development of non-alcoholic fatty liver disease (NAFLD). NAFLD, the most common chronic liver disease in the world, represents a spectrum of disorders that range from steatosis (NAFL) to steatohepatitis (NASH) to cirrhosis. It is anticipated that NAFLD will soon surpass chronic hepatitis C infection as the leading cause for needing liver transplantation. Despite its clinical and public health significance no specific therapies are available. Although the etiology of NAFLD is multifactorial and remains largely enigmatic, it is well accepted that inflammation is a central component of NAFLD pathogenesis. Despite the significance, critical immune mediators, loci of immune activation, the immune signaling pathways and the mechanism(s) underlying disease progression remain incompletely understood. Recent findings have focused on the role of Interleukin 17 (IL-17) family of proinflammatory cytokines in obesity and pathogenesis of obesity-associated sequelae. Notably, obesity favors a Th17 bias and is associated with increased IL-17A expression in both humans and mice. Further, in mice, IL-17 axis has been implicated in regulation of both obesity and NAFLD pathogenesis. However, despite these recent advances several important questions require further evaluation including: the relevant cellular source of IL-17A production; the critical IL-17RA-expressing cell type; the critical liver infiltrating immune cells; and the underlying cellular effector mechanisms. Addressing these questions may aid in the identification and development of novel therapeutic targets for prevention of inflammation-driven NAFLD progression. PMID:26028039

  9. Discrimination of individuals in a general population at high-risk for alcoholic and non-alcoholic fatty liver disease based on liver stiffness: a cross section study

    Directory of Open Access Journals (Sweden)

    Kasai Kenji

    2011-06-01

    Full Text Available Abstract Background Factors associated with liver stiffness (LS are unknown and normal reference values for LS have not been established. Individuals at high risk for alcoholic (ALD and non-alcoholic fatty (NAFLD liver disease need to be non-invasively discriminated during routine health checks. Factors related to LS measured using a FibroScan and normal reference values for LS are presented in this report. Methods We measured LS using a FibroScan in 416 consecutive individuals who presented for routine medical checks. We also investigated the relationship between LS and age, body mass index (BMI, liver function (LF, alcohol consumption, and fatty liver determined by ultrasonography. We identified individuals at high-risk for ALD and NAFLD as having a higher LS value than the normal upper limit detected in 171 healthy controls. Results The LS value for all individuals was 4.7 +/- 1.5 kPa (mean +/- SD and LS significantly and positively correlated with BMI and LF test results. The LS was significantly higher among individuals with, than without fatty liver. Liver stiffness in the 171 healthy controls was 4.3 +/- 0.81 kPa and the upper limit of LS in the normal controls was 5.9 kPa. We found that 60 (14.3% of 416 study participants had abnormal LS. The proportion of individuals whose LS values exceeded the normal upper limit was over five-fold higher among those with, than without fatty liver accompanied by abnormal LF test results. Conclusions Liver stiffness could be used to non-invasively monitor the progression of chronic liver diseases and to discriminate individuals at high risk for ALD and NAFLD during routine health assessments.

  10. Effectiveness of exercise in hepatic fat mobilization in non-alcoholic fatty liver disease: Systematic review.

    Science.gov (United States)

    Golabi, Pegah; Locklear, Cameron T; Austin, Patrick; Afdhal, Sophie; Byrns, Melinda; Gerber, Lynn; Younossi, Zobair M

    2016-07-21

    To investigate the efficacy of exercise interventions on hepatic fat mobilization in non-alcoholic fatty liver disease (NAFLD) patients. Ovid-Medline, PubMed, EMBASE and Cochrane database were searched for randomized trials and prospective cohort studies in adults aged ≥ 18 which investigated the effects of at least 8 wk of exercise only or combination with diet on NAFLD from 2010 to 2016. The search terms used to identify articles, in which exercise was clearly described by type, duration, intensity and frequency were: "NASH", "NAFLD", "non-alcoholic steatohepatitis", "non-alcoholic fatty liver disease", "fat", "steatosis", "diet", "exercise", "MR spectroscopy" and "liver biopsy". NAFLD diagnosis, as well as the outcome measures, was confirmed by either hydrogen-magnetic resonance spectroscopy (H-MRS) or biopsy. Trials that included dietary interventions along with exercise were accepted if they met all criteria. Eight studies met selection criteria (6 with exercise only, 2 with diet and exercise with a total of 433 adult participants). Training interventions ranged between 8 and 48 wk in duration with a prescribed exercise frequency of 3 to 7 d per week, at intensities between 45% and 75% of VO2 peak. The most commonly used imaging modality was H-MRS and one study utilized biopsy. The effect of intervention on fat mobilization was 30.2% in the exercise only group and 49.8% in diet and exercise group. There was no difference between aerobic and resistance exercise intervention, although only one study compared the two interventions. The beneficial effects of exercise on intrahepatic triglyceride (IHTG) were seen even in the absence of significant weight loss. Although combining an exercise program with dietary interventions augmented the reduction in IHTG, as well as improved measures of glucose control and/or insulin sensitivity, exercise only significantly decreased hepatic lipid contents. Prescribed exercise in subjects with NAFLD reduces IHTG independent of

  11. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment.

    Science.gov (United States)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina; Haldrup, David; Pedersen, Steen Bønløkke; Jessen, Niels; Christensen, Lars Porskjaer; Grønbaek, Henning

    2016-03-01

    Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. Resveratrol (RSV) prevents the development of steatosis in a number of experimental fatty liver (non-alcoholic fatty liver [NAFL]) models, but the preventive or therapeutic effects on experimental NASH are not yet clarified, and clinical results on non-alcoholic fatty liver disease are ambiguous. Thus, we aimed to compare the RSV-mediated preventive and therapeutic effects on experimental NAFL and NASH. We used a high-fat (HF) diet to generate a rat NAFL model and a high-fat, high-cholesterol (HFC) diet to generate a rat NASH model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after 1 week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites. Resveratrol reduced the development of histological steatosis (P = 0.03) and partly triglyceride accumulation (fold change reduced from 3.6 to 2.4, P = 0.08) in the male NAFL model, although effects were moderate. In NASH prevention, RSV reduced the accumulation of triglyceride in hepatic tissue (P hepatic benefit of RSV treatment is seen in prevention of steatosis only. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  12. Relationship between hepatocellular carcinoma, metabolic syndrome and non-alcoholic fatty liver disease: which clinical arguments?

    Science.gov (United States)

    Rosmorduc, Olivier

    2013-05-01

    Obesity and the metabolic syndrome are growing epidemics associated with an increased risk for many types of cancer. In the liver, inflammatory and angiogenic changes due to insulin resistance and fatty liver disease are associated with an increased incidence of liver cancer. Regardless of underlying liver disease, cirrhosis remains the most important risk factor for hepatocellular carcinoma (HCC) although are cases of HCC arising without cirrhosis raise the possibility of a direct carcinogenesis secondary to Non-alcoholic Fatty Liver Disease (NAFLD). Moreover, metabolic syndrome and its different features may also increase the risk of HCC in the setting of chronic liver diseases of other causes such as viral hepatitis or alcohol abuse. Taking into account all these data, it is necessary to better determine the risk of developing HCC in patients with metabolic syndrome to improve the screening guidelines and develop prophylactic treatments in this setting. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  13. Novel protocol including liver biopsy to identify and treat CD8+ T-cell predominant acute hepatitis and liver failure.

    Science.gov (United States)

    McKenzie, Rebecca B; Berquist, William E; Nadeau, Kari C; Louie, Christine Y; Chen, Sharon F; Sibley, Richard K; Glader, Bertil E; Wong, Wendy B; Hofmann, Lawrence V; Esquivel, Carlos O; Cox, Kenneth L

    2014-08-01

    In the majority of children with ALF, the etiology is unknown and liver transplantation is often needed for survival. A patient case prompted us to consider that immune dysregulation may be the cause of indeterminate acute hepatitis and liver failure in children. Our study includes nine pediatric patients treated under a multidisciplinary clinical protocol to identify and treat immune-mediated acute liver injury. Patients with evidence of inflammation and no active infection on biopsy received treatment with intravenous immune globulin and methylprednisolone. Seven patients had at least one positive immune marker before or after treatment. All patients had a CD8+ T-cell predominant liver injury that completely or partially responded to immune therapy. Five of the nine patients recovered liver function and did not require liver transplantation. Three of these patients subsequently developed bone marrow failure and were treated with either immunosuppression or stem cell transplant. This series highlights the importance of this tissue-based approach to diagnosis and treatment that may improve transplant-free survival. Further research is necessary to better characterize the immune injury and to predict the subset of patients at risk for bone marrow failure who may benefit from earlier and stronger immunosuppressive therapy. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Screening for non-alcoholic fatty liver disease in children: do guidelines provide enough guidance?

    NARCIS (Netherlands)

    Koot, B. G. P.; Nobili, V.

    2017-01-01

    Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the industrialized world in children. Its high prevalence and important health risks make NAFLD highly suitable for screening. In practice, screening is widely, albeit not consistently, performed. Aim:

  15. Non alcoholic fatty liver disease in a Nigerian population with type II ...

    African Journals Online (AJOL)

    Introduction: Worldwide, Non-alcoholic fatty liver disease (NAFLD) has become an important cause of chronic liver disease and cardiovascular morbidity, even more so in subjects with Type II Diabetes Mellitus (T2DM). The aim of this study was to determine the prevalence and risk factors of NAFLD in an African population ...

  16. New insights in the pathogenesis of non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Gaemers, Ingrid C.; Groen, Albert K.

    2006-01-01

    PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent

  17. Fatty liver disease in Sudan is not alcohol related | Nail | Sudan ...

    African Journals Online (AJOL)

    Background: The finding of fatty liver disease (FLD) has generally been assumed to be a consequence of ethanol ingestion. However, non- alcoholic fatty liver disease (NAFLD) was identified as a specific entity. Although FLD is generally nonprogressive or only slowly progressive, cirrhosis and HCC can develop.

  18. Antioxidant Activity and Protective Effects of Enzyme-Extracted Oudemansiella radiata Polysaccharides on Alcohol-Induced Liver Injury

    Directory of Open Access Journals (Sweden)

    Xiuxiu Wang

    2018-02-01

    Full Text Available This work was to examine the antioxidation in vitro and hepatoprotective effects of enzyme-extracted Oudemansiella radiata polysaccharides (En-OPS on alcohol-induced liver damage in mice. The antioxidant activities were determined according to the scavenging effects of En-OPS on hydroxyl, superoxide, and 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals, and the level of reducing power. En-OPS showed hepatoprotective activities on decreasing the serum levels of aspertate aminotransferase (AST, alamine aminotransferase (ALT, and alkaline phosphatase (ALP, as well as hepatic lipid levels of total cholesterol (TC and triacylglycerols (TG. En-OPS treatment reversed the acute impairment induced by alcohol consumption, including reactive oxygen species (ROS generation, malondialdehyde (MAD, and lipid peroxide (LPO elevation; and superoxide dismutase (SOD, GSH peroxide (GSH-Px, catalase (CAT, and total antioxidant capacity (T-AOC impairment. The En-OPS effectively ameliorated alcohol metabolism by activating alcohol dehydrogenase (ADH and aldehyde dehydrogenase (ALDH, and reducing cytochrome P450 2E1 (CYP2E1 levels. Furthermore, the histopathological observations also displayed that En-OPS could alleviate liver damage. These results indicated that En-OPS could be suitable to be an ingredient of preventing alcoholic liver diseases (ALD. In addition, the preliminary structure characteristics of En-OPS were also analyzed by Fourier transform infrared (FT-IR spectroscopy and a gas chromatography-flame ionization detector (GC-FID.

  19. Inflammation-adapted liver stiffness values for improved fibrosis staging in patients with hepatitis C virus and alcoholic liver disease.

    Science.gov (United States)

    Mueller, Sebastian; Englert, Stefan; Seitz, Helmut K; Badea, Radu I; Erhardt, Andreas; Bozaari, Bita; Beaugrand, Michel; Lupșor-Platon, Monica

    2015-12-01

    It is well known that inflammation increases liver stiffness (LS) in patients with chronic hepatitis C (HCV) and alcoholic liver disease (ALD) independent of fibrosis stage, but no inflammation-adapted cut-off values have been settled so far. An early identification of rapid fibrosers, however, is essential to decide whom to treat first with the novel but expensive antiviral drugs. Liver stiffness, biopsy-proven fibrosis stages F0-F4 (METAVIR or Kleiner score) and routine laboratory parameters were studied in 2068 patients with HCV (n = 1391) and ALD (n = 677). Among the routine parameters for liver damage, AST correlated best with LS (HCV: r = 0.54, P liver diseases. Especially in HCV, they could help to decide whom to treat first with the novel but expensive antiviral drugs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Lipotoxicity and steatohepatitis in an overfed mouse model for non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Gaemers, Ingrid C.; Stallen, Jan M.; Kunne, Cindy; Wallner, Christian; van Werven, Jochem; Nederveen, Aart; Lamers, Wouter H.

    2011-01-01

    The major risk factors for non-alcoholic fatty liver disease (NAFLD) are obesity, insulin resistance and dyslipidemia. The cause for progression from the steatosis stage to the inflammatory condition (non-alcoholic steatohepatitis (NASH)) remains elusive at present. Aim of this study was to test

  1. The contribution of alcohol to chronic liver disease in patients from ...

    African Journals Online (AJOL)

    Objective: This study aimed at determining the level and type of alcohol consumed by patients diagnosed with chronic liver disease (CLD) and, hence, the extent to which alcohol may have contributed to the development of the condition. Study Design: Patients with diagnosis ofCLDwere consecutively recruited and a ...

  2. Status quo of chronic liver diseases, including hepatocellular carcinoma, in Mongolia.

    Science.gov (United States)

    Jazag, Amarsanaa; Puntsagdulam, Natsagnyam; Chinburen, Jigjidsuren

    2012-06-01

    Because Mongolia has much higher liver disease burden than any other regions of the world, it is necessary to provide information on real-time situation of chronic liver disease in Mongolia. In this article, we reviewed studies performed in Mongolia from 2000 to 2011 on seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) among healthy individuals and patients with chronic liver diseases, and on the practice patterns for the management of liver cirrhosis and hepatocellular carcinoma (HCC). According to previous reports, the seroprevalence of HBV and HCV in general population in Mongolia is very high (11.8% and 15% for HBV and HCV, respectively). Liver cirrhosis is also highly prevalent, and mortality from liver cirrhosis remained high for the past decade (about 30 deaths per 100,000 populations per year). Among patients with cirrhosis, 40% and 39% are positive for HBsAg and anti-HCV, respectively, and 20% are positive for both. The seroprevalence is similar for HCC and more than 90% of HCC patients are positive for either HBV or HCV. The incidence of HCC in Mongolia is currently among the highest in the world. The mortality from HCC is also very high (52.2 deaths per 100,000 persons per year in 2010). Partly due to the lack of established surveillance systems, most cases of HCC are diagnosed at an advanced stage. The mortality from liver cirrhosis and HCC in Mongolia may be reduced by implementation of antiviral therapy program and control of alcohol consumption.

  3. Sexual dysfunction in men with alcoholic liver cirrhosis. A comparative study

    DEFF Research Database (Denmark)

    Jensen, S B; Gluud, C

    1985-01-01

    not significantly different comparing alcoholic cirrhotic men to chronic alcoholic men without overt liver disease (matched for duration of alcoholism, age and duration of partnership) and to insulin-dependent diabetic men (matched for age and duration of partnership). However, all groups had a significantly (p...... less than 0.025) raised prevalence of sexual dysfunction when compared to men without chronic disease (matched for age and duration of partnership)....

  4. Advanced non-alcoholic fatty liver disease and adipose tissue fibrosis in patients with Alström syndrome.

    Science.gov (United States)

    Gathercole, Laura L; Hazlehurst, Jonathan M; Armstrong, Matthew J; Crowley, Rachel; Boocock, Sarah; O'Reilly, Michael W; Round, Maria; Brown, Rachel; Bolton, Shaun; Cramb, Robert; Newsome, Phillip N; Semple, Robert K; Paisey, Richard; Tomlinson, Jeremy W; Geberhiwot, Tarekegn

    2016-11-01

    Alström syndrome (AS) is a recessive monogenic syndrome characterized by obesity, extreme insulin resistance and multi-organ fibrosis. Despite phenotypically being high risk of non-alcoholic fatty liver disease (NAFLD), there is a lack of data on the extent of fibrosis in the liver and its close links to adipose in patients with AS. Our aim was to characterize the hepatic and adipose phenotype in patients with AS. Observational cohort study with comprehensive assessment of metabolic liver phenotype including liver elastography (Fibroscan ® ), serum Enhanced Liver Fibrosis (ELF) Panel and liver histology. In addition, abdominal adipose histology and gene expression was assessed. We recruited 30 patients from the UK national AS clinic. A subset of six patients underwent adipose biopsies which was compared with control tissue from nine healthy participants. Patients were overweight/obese (BMI 29.3 (25.95-34.05) kg/m 2 ). A total of 80% (24/30) were diabetic; 74% (20/27) had liver ultrasound scanning suggestive of NAFLD. As judged by the ELF panel, 96% (24/25) were categorized as having fibrosis and 10/21 (48%) had liver elastography consistent with advanced liver fibrosis/cirrhosis. In 7/8 selected cases, there was evidence of advanced NAFLD on liver histology. Adipose tissue histology showed marked fibrosis as well as disordered pro-inflammatory and fibrotic gene expression profiles. NAFLD and adipose dysfunction are common in patients with AS. The severity of liver disease in our cohort supports the need for screening of liver fibrosis in AS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China.

    Science.gov (United States)

    Yi, M; Chen, R-P; Yang, R; Chen, H

    2017-04-01

    To investigate the prevalence of and risk factors for non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes mellitus. We recruited patients with Type 2 diabetes with a BMI ≥ 24 kg/m 2 , who visited the diabetes clinics of 60 hospitals in 21 cities in Guangdong Province, China from August 2011 to March 2012. Anthropometric measurements, biochemical tests and abdominal ultrasonography were performed for all the patients. The study included 3861 patients (1860 men) with a mean ± sd (range) age of 58.91 ± 13.06 (18-90) years. Non-alcoholic fatty liver disease was found in 1751 patients (45.4%), with a significantly higher prevalence among men than women (48.0 vs 42.9%). The peak of non-alcoholic fatty liver disease prevalence was in patients with a BMI of 34-35 kg/m 2 , those with a triglyceride/HDL cholesterol ratio of 5.5-6.0, men aged non-alcoholic fatty liver disease, while heart rate and female gender were protective factors. The prevalence of non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes in South China is high. Multiple metabolic disorders were significantly associated with non-alcoholic fatty liver disease in overweight and obese patients with Type 2 diabetes. © 2016 Diabetes UK.

  6. Tissue Inhibitors of Metalloproteinase-1 and 2 and Obesity Related Non-Alcoholic Fatty Liver Disease: Is There a Relationship.

    Science.gov (United States)

    Abdelaziz, Rokaya; Elbasel, Mohamed; Esmat, Serag; Essam, Kareem; Abdelaaty, Sahar

    2015-01-01

    Non-alcoholic fatty liver disease is a spectrum of clinical conditions, including simple steatosis and non-alcoholic steatohepatitis (NASH). The aim of the study is to evaluate the tissue inhibitors of metalloproteinase-1 and 2 (TIMPs) as noninvasive predictors of NASH. Three groups were included in the study. Obese patients (n = 30) with normal liver enzymes were included in group I and obese patients (n = 30) with elevated liver enzymes with liver biopsy-based diagnosis of NASH were included in group II. Age-matched subjects (n = 30) formed the control as group III. The lipid profile, liver enzyme levels and levels of TIMPs were compared among all the patients and subjects. Comparison of groups I and II showed significantly elevated levels of TIMP-1 and TIMP-2 in group II as compared to group I (p < 0.05). Similarly, comparison between groups II and III showed significantly increased levels of TIMP-1 and TIMP-2 in group II as compared to group III (p < 0.05). TIMP-1 (sensitivity 96.7%, specificity 100%) and TIMP-2 (sensitivity 93.3%, specificity 100%) showed high accuracy in NASH diagnosis. TIMP-1 and TIMP-2 may be considered noninvasive markers for the diagnosis of NASH. © 2015 S. Karger AG, Basel.

  7. Diagnostical significance of dimethylarginine in the development of hepatorenal syndrome in patients with alcoholic liver cirrhosis

    Directory of Open Access Journals (Sweden)

    Ničković Vanja

    2012-01-01

    Full Text Available Background/Aim. Chronic consumption of alcohol during a longer period of time leads to the development of cirrhosis with the reduction in metabolic liver function and disorders in arginine metabolism. Hepatorenal syndrome (HRS is the most severe complication of alcoholic liver cirrhosis. The aim of the study was to analyze disorders in arginine metabolism by monitoring concentrations of asymmetric dimethylarginine (ADMA and symmetric dimethylarginine (SDMA in patients with liver cirrhosis and HRS. Methods. The study included three groups of subjects: a group of patients with cirrhosis and HRS (24 patients, a group of patients with cirrhosis without HRS (18 patients and a control group composed of 42 healthy voluntary blood donors. Concentrations of ADMA, SDMA and L-arginine in plasma were measured in all groups using the high pressure liquid chromatography (HPLC method. Results. The concentration of SDMA was significantly higher in the patients with HRS compared to the patients without HRS and it was also higher than the values obtained from the healthy participants (1.76 ± 0.3 μmol/L; 1.01 ± 0.32 and 0.520 ± 0.18 μmol/L, respectively; p < 0.01. The concentrations of ADMA were higher in the cirrhotic patients with HRS than in those without this serious complication of cirrhosis. The concentration of ADMA in all the examined cirrhotic patients was higher than those obtained from healthy volunteers (1.35 ± 0.27 μmol/L, 1.05 ± 0.35 μmol/L and 0.76 ± 0.21 μmol/L, respectively. In the patients with terminal alcoholic liver cirrhosis, the concentrations of ADMA and SDMA correlated with the progress of cirrhosis as well as with the development of cirrhosis complications. In the patients with HRS there was a positive correlation between creatinine and SDMA in plasma (r2 = 0.0756, p < 0.001 which was not found between creatinine and ADMA. Conclusion. The obtained results demonstrate that the increase in SDMA concentration is proportionate to

  8. Increased risk of non-alcoholic fatty liver disease after diagnosis of celiac disease.

    Science.gov (United States)

    Reilly, Norelle R; Lebwohl, Benjamin; Hultcrantz, Rolf; Green, Peter H R; Ludvigsson, Jonas F

    2015-06-01

    Non-alcoholic fatty liver disease is a common cause of chronic liver disease. Celiac disease alters intestinal permeability and treatment with a gluten-free diet often causes weight gain, but so far there are few reports of non-alcoholic fatty liver disease in patients with celiac disease. Population-based cohort study. We compared the risk of non-alcoholic fatty liver disease diagnosed from 1997 to 2009 in individuals with celiac disease (n = 26,816) to matched reference individuals (n = 130,051). Patients with any liver disease prior to celiac disease were excluded, as were individuals with a lifetime diagnosis of alcohol-related disorder to minimize misclassification of non-alcoholic fatty liver disease. Cox regression estimated hazard ratios for non-alcoholic fatty liver disease were determined. During 246,559 person-years of follow-up, 53 individuals with celiac disease had a diagnosis of non-alcoholic fatty liver disease (21/100,000 person-years). In comparison, we identified 85 reference individuals diagnosed with non-alcoholic fatty liver disease during 1,488,413 person-years (6/100,000 person-years). This corresponded to a hazard ratio of 2.8 (95% CI 2.0-3.8), with the highest risk estimates seen in children (HR = 4.6; 95% CI 2.3-9.1). The risk increase in the first year after celiac disease diagnosis was 13.3 (95% CI 3.5-50.3) but remained significantly elevated even beyond 15 years after the diagnosis of celiac disease (HR = 2.5; 95% CI 1.0-5.9). Individuals with celiac disease are at increased risk of non-alcoholic fatty liver disease compared to the general population. Excess risks were highest in the first year after celiac disease diagnosis, but persisted through 15 years after diagnosis with celiac disease. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  9. Effect of resveratrol on experimental non-alcoholic fatty liver disease depends on severity of pathology and timing of treatment

    DEFF Research Database (Denmark)

    Heebøll, Sara; El-Houri, Rime Bahij; Hellberg, Ylva Erika Kristina

    2016-01-01

    BACKGROUND AND AIM: Non-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease with few therapeutic options. RSV prevents the development of steatosis in a number of experimental fatty liver (NAFL) models but the preventive or therapeutic effects on experimental NASH...... model. The preventive and therapeutic potential of RSV was tested by adding RSV to the HF and HFC diet from study start or after one week of the diets. Animals were sacrificed after 8 weeks with appropriate controls. Blood and liver were harvested for analysis, including measurement of RSV metabolites.......01), while there was no effect on biochemical, histopathological, or transcriptional NASH changes. Further, RSV had no therapeutic effect on established NASH. We found RSV metabolites but no parent RSV in serum or liver tissue, confirming low bioavailability. CONCLUSIONS: These experimental findings suggest...

  10. Knowing what’s out there: awareness of Non Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Vishal eGhevariya

    2014-03-01

    Full Text Available Background: Non Alcoholic Fatty Liver Disease (NAFLD is the most common hepatic disorder, which poses a significant health burden in the western countries. As the epidemic of obesity slides health downward, the incidence of NAFLD is evidently increasing. Aims: We aimed to ascertain the awareness of NAFLD and its risk factors in the general population, which may be helpful in designing educational tools to promote prevention, early detection and treatment of this disorder. Methods: A survey of 5000 non-institutionalized residents of Brooklyn, NY was conducted. Sixteen items were included in the survey questionnaire including awareness of fatty liver, predisposing factors of NAFLD, awareness of cirrhosis, and conditions that advance to cirrhosis. The questionnaire also addressed awareness of prevention, diagnostic methods and treatment of NAFLD and education of physicians to their patients about NAFLD. Results: Overwhelming majority of the subjects was not aware of NAFLD and stated that their physicians did not have a discussion about NAFLD. Conclusion: NAFLD is a preventable liver disorder with limited treatment options. Thorough counseling by primary care physicians can be of paramount importance in preventive strategy for NAFLD. We should target our teen-age population in an era of obesity epidemics of all times.

  11. Susceptibility of L-FABP−/− mice to oxidative stress in early-stage alcoholic liver[S

    Science.gov (United States)

    Smathers, Rebecca L.; Galligan, James J.; Shearn, Colin T.; Fritz, Kristofer S.; Mercer, Kelly; Ronis, Martin; Orlicky, David J.; Davidson, Nicholas O.; Petersen, Dennis R.

    2013-01-01

    Chronic ethanol consumption is a prominent cause of liver disease worldwide. Dysregulation of an important lipid uptake and trafficking gene, liver-fatty acid binding protein (L-FABP), may contribute to alterations in lipid homeostasis during early-stage alcoholic liver. We have reported the detrimental effects of ethanol on the expression of L-FABP and hypothesize this may deleteriously impact metabolic networks regulating fatty acids. Male wild-type (WT) and L-FABP−/− mice were fed a modified Lieber-DeCarli liquid diet for six weeks. To assess the response to chronic ethanol ingestion, standard biochemical indicators for alcoholic liver disease (ALD) and oxidative stress were measured. Ethanol ingestion resulted in attenuation of hepatic triglyceride accumulation and elevation of cholesterol in L-FABP−/− mice. Lipidomics analysis validated multiple alterations in hepatic lipids resulting from ethanol treatment. Increased immunohistochemical staining for the reactive aldehydes 4-hydroxynonenal and malondialdehyde were observed in WT mice ingesting ethanol; however, L-FABP−/− mice displayed prominent protein adducts in liver sections evaluated from pair-fed and ethanol-fed mice. Likewise, alterations in glutathione, thiobarbituric acid reactive substances (TBARS), 8-isoprostanes, and protein carbonyl content all indicated L-FABP−/− mice exhibit high sustained oxidative stress in the liver. These data establish that L-FABP is an indirect antioxidant protein essential for sequestering FFA and that its impairment could contribute to in the pathogenesis of ALD. PMID:23359610

  12. Change in size, shape and radiocolloid uptake of the alcoholic liver during alcohol withdrawal, as demonstrated by single photon emission computed tomography

    International Nuclear Information System (INIS)

    Blomquist, L.; Yansen Wang; Jacobsson, H.; Kimiaei, S.

    1994-01-01

    The volume of the total liver and separate right and left lobes was studied before and after 1 week of alcohol withdrawal in 16 consecutive alcoholics by means of single photon emission computed tomography after intravenous injection of 99 Tc m -human albumin colloid; the relative tissue distribution of radioactivity was also followed. The left liver lobe increased in volume more than the right lobe during drinking and decreased more rapidly after alcohol withdrawal. Median volume reductions during 1 week of alcohol withdrawal were: total liver 12%, left lob 26%, and right lobe 8%, indicating that half of the reduction to values of a control group was achieved during this first week. The volume of the right but not of the left lobe was significantly correlated to body size in alcoholics and in controls. The left lobe had a lower capacity to concentrate the radiocolloid than the right lobe in alcoholics and in controls. The liver/spleen, liver/bone marrow and liver/background radioactivity concentration ratios in the alcoholics increased during alcohol withdrawal We conclude that heavy drinking causes both an increased total liver volume and a change in liver shape, with a relatively more enlarged left right lobe, as well as a decreased capacity to concentrate radiocolloid. These changes are rapidly reversible during abstinence from alcohol. (au) (26 refs.)

  13. Non-alcoholic fatty liver disease is not associated with a lower health perception.

    Science.gov (United States)

    Mlynarsky, Liat; Schlesinger, Dalit; Lotan, Roni; Webb, Muriel; Halpern, Zamir; Santo, Erwin; Shibolet, Oren; Zelber-Sagi, Shira

    2016-05-07

    To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1

  14. A new noninvasive technique for estimating hepatic triglyceride: will liver biopsy become redundant in diagnosing non-alcoholic fatty liver disease?

    NARCIS (Netherlands)

    Betzel, B.; Drenth, J.P.H.

    2014-01-01

    Obesity and metabolic syndrome are healthcare problems that continue to rise in frequency worldwide. Both phenotypes are a strong predictor for development of liver steatosis in the context of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis. Ultrasound may detect steatosis, but

  15. Diabetes mellitus and non-alcoholic fatty liver disease: the thread of Ariadne.

    Science.gov (United States)

    Kosmidou, Maria; Milionis, Haralampos

    2017-06-01

    Non alcoholic fatty liver disease (NAFLD, the hepatic fat accumulation) and non alcoholic steatohepatitis (NASH, the aggressive form of liver steatosis plus inflammation and hepatocyte necrosis) are reaching epidemic dimensions in subjects with diabetes mellitus (DM). Taking into account that the incidence of DM increases worldwide, these entities represent major health problems. There is accumulating evidence that diabetic subjects with NASH are at increased risk not only for cardiovascular disease compications but also for cirrhosis and hepatocellular cancer. On the other hand, the presence of NAFLD correlates with an increased risk for the development of DM. The most-widely accepted pathophysiological mechanisms relating DM and NAFLD include central obesity and insulin resistanc, but new insights are under scrutiny. Therapeutic modalities used for the management of diabetes have been studied for their impact on NAFLD/NASH and both neutral and beneficial effects have been reported. In this review, we discuss issues regarding the epidemiology, the pathophysiological pathways relating NAFLD with DM and consider strategies that may be useful in the management of NAFLD in the diabetic population.

  16. Osteoporosis and bone fractures in alcoholic liver disease: a meta-analysis.

    Science.gov (United States)

    Bang, Chang Seok; Shin, In Soo; Lee, Sung Wha; Kim, Jin Bong; Baik, Gwang Ho; Suk, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

    2015-04-07

    To evaluate the association between alcoholic liver disease (ALD) and bone fractures or osteoporosis. Non-randomized studies were identified from databases (PubMed, EMBASE, and the Cochrane Library). The search was conducted using Boolean operators and keywords, which included "alcoholic liver diseases", "osteoporosis", or "bone fractures". The prevalence of any fractures or osteoporosis, and bone mineral density (BMD) were extracted and analyzed using risk ratios and standardized mean difference (SMD). A random effects model was applied. In total, 15 studies were identified and analyzed. Overall, ALD demonstrated a RR of 1.944 (95%CI: 1.354-2.791) for the development of bone fractures. However, ALD showed a RR of 0.849 (95%CI: 0.523-1.380) for the development of osteoporosis. BMD was not significantly different between the ALD and control groups, although there was a trend toward lower BMD in patients with ALD (SMD in femur-BMD: -0.172, 95%CI: -0.453-0.110; SMD in spine-BMD: -0.169, 95%CI: -0.476-0.138). Sensitivity analyses showed consistent results. Current publications indicate significant associations between bone fractures and ALD, independent of BMD or the presence of osteoporosis.

  17. The absence of obstructive sleep apnea may protect against non-alcoholic fatty liver in patients undergoing bariatric surgery.

    Directory of Open Access Journals (Sweden)

    Kathleen E Corey

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development.This study sought to identify factors predictive of normal liver histology in a bariatric cohort.Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded.One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR of 6.8, 95% confidence interval (CI 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9. In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83. Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1. In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85.Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD.

  18. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men

    OpenAIRE

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-01-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of ab...

  19. Liver haemodynamics and function in alcoholic cirrhosis. Relation to testosterone treatment and ethanol consumption

    DEFF Research Database (Denmark)

    Gluud, C; Henriksen, Jens Henrik Sahl

    1987-01-01

    Liver haemodynamics and liver function were measured in 34 alcoholic cirrhotic men before entry and after 12 months (median) in a double-blind, placebo-controlled study on the effect of oral testosterone treatment (200 mg t.i.d.). Comparing data at entry with those at follow-up in the total patient......, testosterone-treated patients did not differ significantly from placebo-treated patients regarding any of the measured variables. No significant relationships could be demonstrated between ethanol consumption and liver haemodynamics and liver function, but the number of patients consuming more than 100 g...... ethanol per day decreased significantly (P less than 0.001) from 22 (65%) before entry to one (3%) during follow-up. In conclusion, oral testosterone treatment of men with alcoholic cirrhosis does not explain the significant improvement of liver haemodynamics and function observed in this study. However...

  20. Text Messaging to Reduce Alcohol Relapse in Prelisting Liver Transplant Candidates: A Pilot Feasibility Study.

    Science.gov (United States)

    DeMartini, Kelly S; Schilsky, Michael L; Palmer, Amanda; Fehon, Dwain C; Zimbrean, Paula; O'Malley, Stephanie S; Lee, Hochang B; Toll, Benjamin A

    2018-03-02

    Many liver transplantation programs require documented alcohol sobriety prior to United Network for Organ Sharing (UNOS) listing. This pilot study examined the feasibility of the first mobile, alcohol relapse prevention intervention for liver transplant patients with alcoholic liver disease (ALD). This was a randomized 8-week pilot feasibility trial of a text message-based alcohol intervention. In-treatment assessment was conducted at 4 weeks (4W), and immediate posttreatment assessment was conducted at 8W. Participants were liver transplant candidates (N = 15) diagnosed with ALD who reported at least 1 drinking episode in the past year. Primary feasibility outcomes were percent of messages responded to and posttreatment intervention satisfaction ratings. Preliminary clinical efficacy outcomes were any biologically confirmed alcohol consumption, stress, abstinence self-efficacy, and alcohol craving. On feasibility outcomes, participants responded to 81% of messages received and reported high rates of intervention satisfaction, looked forward to receiving the messages, and found it easy to complete the intervention. On preliminary efficacy outcomes, zero participants in the text message (TM) had positive urine alcohol tests at 8W. Two of the 6 participants in standard care (SC) tested positive at 8W. No effects were seen on craving. For stress, a condition × time interaction emerged. TM participants had less stress at 4W and 8W compared with SC at baseline. They maintained their stress level during the intervention. For self-efficacy, a trend for condition effect emerged. TM participants had higher self-efficacy than SC participants. Participants reported high satisfaction with the intervention, looked forward to the messages, and found it easy to complete. Participants who received the intervention had better treatment outcomes than those who received standard care. They maintained higher levels of self-efficacy and lower stress. Mobile alcohol interventions

  1. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort.

    Directory of Open Access Journals (Sweden)

    Eline H van den Berg

    Full Text Available Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the largest population-based cohort to date.Biochemical characteristics, type 2 diabetes mellitus and metabolic syndrome were determined in the Lifelines Cohort Study (N = 167,729, a population-based cohort in the North of the Netherlands. Non-alcoholic fatty liver disease was defined as Fatty Liver Index (FLI≥60. Exclusion criteria were age <18 years, immigrants, missing data to assess FLI and metabolic syndrome, excessive alcohol use, previous-diagnosed hepatitis or cirrhosis and non-fasting blood sampling.Out of 37,496 included participants (median age 44 years, 62.1% female, 8,259 (22.0% had a FLI≥60. Individuals with a FLI≥60 were more often male, older, obese, had higher levels of hemoglobinA1c, fasting glucose, liver enzymes, total cholesterol, low-density lipoprotein cholesterol, triglycerides, c-reactive protein and leucocytes and lower high-density lipoprotein cholesterol (all P<0.0001. Participants with a FLI≥60 showed higher prevalence of type 2 diabetes mellitus (9.3% vs. 1.4%, metabolic syndrome (54.2% vs. 6.2%, impaired renal function (20.1% vs. 8.7% and cardiovascular disease (4.6% vs. 1.6% (all P<0.0001. Multivariable logistic analysis showed that smoking, hemoglobin, leucocytes, c-reactive protein, platelets, alanine aminotransferase, alkaline phosphatase, albumin, impaired renal function (OR 1.27, 95%CI 1.15-1.41, metabolic syndrome (OR 11.89, 95%CI 11.03-12.82 and its individual components hyperglycemia (OR 2.53, 95%CI 2.34-2.72, hypertension (OR 1.89, 95%CI 1.77-2.01 and reduced high-density lipoprotein cholesterol (OR 3.44, 95%CI 3.22-3.68 were independently associated with suspected non-alcoholic fatty liver disease (all P<0.0001.Twenty

  2. Association between non-alcoholic fatty liver disease, insulin resistance and Helicobacter pylori.

    Science.gov (United States)

    Abenavoli, Ludovico; Milic, Natasa; Masarone, Mario; Persico, Marcello

    2013-11-01

    Here we report a case of a 55-year Caucasian man, who improved the metabolic profile after the treatment for Helicobacter pylori eradication. In particular, we report the changes in homeostatic model assessment of insulin resistance, fatty liver index and echographic liver pattern. We hypothesize the co-factorial role of H. pylori in the mechanisms involved in non-alcoholic fatty liver disease pathogenesis and insulin resistance, by the cytokine serum changes. If this correlation is confirmed, the H. pylori treatment may represent an option in the clinical management of liver steatosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Determination of Ethyl Glucuronide in Hair for Detection of Alcohol Consumption in Patients After Liver Transplantation.

    Science.gov (United States)

    Andresen-Streichert, Hilke; von Rothkirch, Gregor; Vettorazzi, Eik; Mueller, Alexander; Lohse, Ansgar W; Frederking, Dorothea; Seegers, Barbara; Nashan, Bjoern; Sterneck, Martina

    2015-08-01

    Early detection of alcohol misuse in orthotopic liver transplantation recipients is essential to offer patients support and prevent organ damage. Here, ethyl glucuronide, a metabolite of ethanol found in hair (hEtG), was evaluated for detection of alcohol consumption. In 104 transplant recipients, 31 with underlying alcoholic liver disease (ALD) and 73 with non-ALD, hEtG was determined in addition to the alcohol markers urine EtG, blood ethanol, methanol, and carbohydrate-deficient transferrin. Results were compared with patients' self-reports in a questionnaire and with physicians' assessments. By physicians' assessments, 22% of the patients were suspected of consuming alcohol regularly, although only 6% of the patients acknowledged consumption of a moderate or high amount of alcohol. By testing all markers except for hEtG, alcohol consumption was detected in 7% of the patients. When hEtG testing was added to the assessment, consumption was detected in 17% of the patients. Hair-EtG determination alone revealed chronic alcohol consumption of >10 g/d in 15% of the patients. ALD patients had a positive hEtG result significantly more often than non-ALD patients did (32% versus 8%; P = 0.003). Also, the concentration of hEtG was higher in ALD patients (P = 0.049) and revealed alcohol abuse with consumption of >60 g ethanol per day in 23% of ALD and 3% of non-ALD patients. Patients' self-reports and physicians' assessments had a low sensitivity of 27% and 67%, respectively, for detecting regular alcohol intake as indicated by hEtG. Hair-EtG determination improved the detection of liver transplant patients who used alcohol, and revealed regular alcohol consumption in 32% of ALD and 8% of non-ALD patients.

  4. Multiple hypervascular FNH-like lesions in a patient with no history of alcohol abuse or chronic liver disease.

    Science.gov (United States)

    Tani, Joji; Miyoshi, Hisaaki; Sasaki, Motoko; Nakanuma, Yasuni; Nomura, Takako; Yoneyama, Hirohito; Morishita, Asahiro; Kobara, Hideki; Hirohito, Mori; Himoto, Takashi; Masaki, Tsutomu

    2013-01-01

    A 64-year-old Japanese woman with a history of bronchiectasis presented with multiple hypervascular nodules in both lobes of the liver without hepatitis B or C virus infection. Imaging studies, including ultrasound, contrast-enhanced computed tomography and magnetic resonance imaging, showed hypervascularity in the early phase. Histologically, no lipid degeneration was observed; however, there was a mild increase in cell density, miniaturization of nuclei, increased chromatin content, partial sinusoidal dilatation and congestion. No unpaired arteries were evident. The diagnosis based on the pathology and diagnostic radiology findings was multiple hypervascular focal nodular hyperplasia (FNH)-like lesions with no history of alcohol abuse or chronic liver disease.

  5. Relationships between serum selenium and zinc concentrations versus profibrotic and proangiogenic cytokines (FGF-19 and endoglin) in patients with alcoholic liver cirrhosis.

    Science.gov (United States)

    Prystupa, Andrzej; Kiciński, Paweł; Luchowska-Kocot, Dorota; Błażewicz, Anna; Kurys-Denis, Ewa; Niedziałek, Jarosław; Sak, Jarosław; Panasiuk, Lech

    2017-09-21

    Liver cirrhosis is a disease involving the liver parenchyma, which is characterised by fibrosis and impaired architectonics of the parenchyma with regenerative nodules. The aim of the study was to determine the relationship between stage of alcoholic liver cirrhosis, concentrations of selenium, zinc and profibrotic and proangiogenic cytokines (FGF-19, ENG). The study included 99 patients with alcoholic cirrhosis and 20 healthy subjects. Ion chromatography with UV/VIS detection was used for determination of zinc ions in the previously mineralized serum samples. The measurements of selenium were performed with the ContrAA700 high-resolution continuum source graphite tube atomic absorption spectrometer. ELISA was used to determine concentration of FGF-19 and ENG in serum samples. Concentrations of zinc and selenium were significantly decreased in cirrhotic patients (pzinc and selenium in serum of patients with alcoholic liver cirrhosis are not independently related to concentrations of FGF-19 and ENG.

  6. Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo.

    Science.gov (United States)

    Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten; Mayer, Dirk; Collins, Amy M; Luong, Richard; Pfefferbaum, Adolf

    2016-07-01

    Serious neurological concomitants of alcoholism include Wernicke's encephalopathy (WE), Korsakoff's syndrome (KS), and hepatic encephalopathy (HE). This study was conducted in animal models to determine neuroradiological signatures associated with liver damage caused by carbon tetrachloride (CCl4), thiamine deficiency caused by pyrithiamine treatment, and nonspecific nutritional deficiency caused by food deprivation. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) were used to evaluate brains of wild-type Wistar rats at baseline and following treatment. Similar to observations in ethanol (EtOH) exposure models, thiamine deficiency caused enlargement of the lateral ventricles. Liver damage was not associated with effects on cerebrospinal fluid volumes, whereas food deprivation caused modest enlargement of the cisterns. In contrast to what has repeatedly been shown in EtOH exposure models, in which levels of choline-containing compounds (Cho) measured by MRS are elevated, Cho levels in treated animals in all three experiments (i.e., liver damage, thiamine deficiency, and food deprivation) were lower than those in baseline or controls. These results add to the growing body of literature suggesting that MRS-detectable Cho is labile and can depend on a number of variables that are not often considered in human experiments. These results also suggest that reductions in Cho observed in humans with alcohol use disorder (AUD) may well be due to mild manifestations of concomitants of AUD such as liver damage or nutritional deficiencies and not necessarily to alcohol consumption per se.

  7. Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

    Science.gov (United States)

    Manti, Sara; Romano, Claudio; Chirico, Valeria; Filippelli, Martina; Cuppari, Caterina; Loddo, Italia; Salpietro, Carmelo; Arrigo, Teresa

    2014-01-01

    Context: Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased. Evidence Acquisition: A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver". Results: NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown. Conclusions: Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH. PMID:24829591

  8. PATHOGENESIS OF HEPATOCELLULAR CARCINOMA DEVELOPMENT IN NON ALCOHOLIC FATTY LIVER DISEASE.

    Science.gov (United States)

    Shetty, Kirti; Chen, Jian; Shin, Ji-Hyun; Jogunoori, Wilma; Mishra, Lopa

    2015-06-01

    Non-alcoholic fatty liver disease (NAFLD) is being recognized as an increasingly important contributor to the burden of hepatocellular carcinoma (HCC) worldwide. It is often accompanied by obesity and diabetes mellitus and is believed to be the hepatic representation of the metabolic syndrome. HCC development in NAFLD is multifactorial and complex. It is dependent on not only the well-described mechanisms noted in chronic liver injury, but also on the molecular derangements associated with obesity and dysmetabolism. These include adipocyte remodeling, adipokine secretion, lipotoxicity and insulin resistance. Recent advances focus on the importance of the gut-liver axis in accelerating the process of oncogenesis in NAFLD. The farnesoid X nuclear receptor (FXR) has been demonstrated to have important metabolic effects and its pharmacological activation by obeticholic acid has been recently reported to produce histological improvement in NASH. It is hoped that delineating the mechanisms of hepatic fibrosis and oncogenesis in NASH will lead to enhanced strategies for cancer prevention, surveillance and therapy in this population.

  9. [Efficacy of probiotics on the treatment of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Wang, W; Shi, L P; Shi, L; Xu, L

    2018-02-01

    Objective: To study the clinical effect of probiotics in the treatment of non-alcoholic fatty liver disease (NAFLD). Methods: A total of 200 patients with NAFLD were randomly divided into 4 groups: control group (routine treatment group) and combined treatment group A, B and C. Each group had equal patients. The control group received orally polyene phosphatidylcholine capsules; whereas combined group A, B and C were given orally the live "combined Bifidobacterium Lactobacillus and Enterococcus powder" , "two live combined Bacillus subtilis and Enterococcus " , and the both probiotics respectively. The duration of treatment was 1 month. Laboratory parameters were evaluated before treatment and thirtieth day after treatment, including cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol(LDL-C), alanine aminotransferase(ALT), aspartate aminotransferase (AST), fasting blood glucose (FPG), serum high molecular weight adiponectin (HMW-APN) and serum TNFα. Meanwhile the faece sample was collected for routine test and bacterial culture. Liver ultrasound scan was done in all patients. Results: In terms of blood lipids and blood glucose, each group improved after treatment with significant differences ( PProbiotics improve intestinal microecological system in NAFLD patients via inhibiting TNFα and enhancing adiponectin, possibly resulting in regulating blood glucose, lipid metabolism, and protecting liver injury from NAFLD.

  10. Hepatic energy metabolism in human diabetes mellitus, obesity and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Koliaki, Chrysi; Roden, Michael

    2013-10-15

    Alterations of hepatic mitochondrial function have been observed in states of insulin resistance and non-alcoholic fatty liver disease (NAFLD). Patients with overt type 2 diabetes mellitus (T2DM) can exhibit reduction in hepatic adenosine triphosphate (ATP) synthesis and impaired repletion of their hepatic ATP stores upon ATP depletion by fructose. Obesity and NAFLD may also associate with impaired ATP recovery after ATP-depleting challenges and augmented oxidative stress in the liver. On the other hand, patients with obesity or NAFLD can present with upregulated hepatic anaplerotic and oxidative fluxes, including β-oxidation and tricarboxylic cycle activity. The present review focuses on the methods and data on hepatic energy metabolism in various states of human insulin resistance. We propose that the liver can adapt to increased lipid exposition by greater lipid storing and oxidative capacity, resulting in increased oxidative stress, which in turn could deteriorate hepatic mitochondrial function in chronic insulin resistance and NAFLD. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. Protective Effects of Korean Red Ginseng against Alcohol-Induced Fatty Liver in Rats

    Directory of Open Access Journals (Sweden)

    Hyo Jin Lee

    2015-06-01

    Full Text Available The present study tested the hypothesis that Korean red ginseng (KRG provides a protective effect against alcoholic fatty liver. Male Sprague-Dawley rats were divided into four groups and fed a modified Lieber-DeCarli diet containing 5% (w/v alcohol or an isocaloric amount of dextrin-maltose for the controls for 6 weeks: normal control (CON, alcohol control (ET, and ET treated with 125 or 250 mg/kg body weight/day of KRG (RGL or RGH, respectively. Compared with the CON group, the ET group exhibited a significant increase in triglycerides, total cholesterol and the presence of lipid droplets in the liver, and a decrease in fat mass, which were all attenuated by KRG supplementation in adose-dependent manner. The mitigation was accompanied by AMP-activated protein kinase (AMPK signaling pathways in the liver and adipose tissue. In addition, suppression in the alcohol-induced changes of adipose adipokine mRNA expression was also observed in KRG supplementation group. These findings suggest that KRG may have the potential to ameliorate alcoholic fatty liver by suppressing inappropriate lysis of adipose tissue and preventing unnecessary de novo lipogenesis in the liver, which are mediated by AMPK signaling pathways. A mechanism for an interplay between the two organs is still needed to be examined with further assays.

  12. Pathogenesis of hepatic steatosis: the link between hypercortisolism and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tarantino, Giovanni; Finelli, Carmine

    2013-10-28

    Based on the available literature, non alcoholic fatty liver disease or generally speaking, hepatic steatosis, is more frequent among people with diabetes and obesity, and is almost universally present amongst morbidly obese diabetic patients. Non alcoholic fatty liver disease is being increasingly recognized as a common liver condition in the developed world, with non alcoholic steatohepatitis projected to be the leading cause of liver transplantation. Previous data report that only 20% of patients with Cushing's syndrome have hepatic steatosis. Aiming at clarifying the reasons whereby patients suffering from Cushing's syndrome - a condition characterized by profound metabolic changes - present low prevalence of hepatic steatosis, the Authors reviewed the current concepts on the link between hypercortisolism and obesity/metabolic syndrome. They hypothesize that this low prevalence of fat accumulation in the liver of patients with Cushing's syndrome could result from the inhibition of the so-called low-grade chronic-inflammation, mainly mediated by Interleukin 6, due to an excess of cortisol, a hormone characterized by an anti-inflammatory effect. The Cushing's syndrome, speculatively considered as an in vivo model of the hepatic steatosis, could also help clarify the mechanisms of non alcoholic fatty liver disease.

  13. The expanding role of fish models in understanding non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Yoichi Asaoka

    2013-07-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH, a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC. NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio and medaka (Oryzias latipes. Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.

  14. Bile Acids and Dysbiosis in Non-Alcoholic Fatty Liver Disease.

    Directory of Open Access Journals (Sweden)

    Marialena Mouzaki

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is characterized by dysbiosis. The bidirectional effects between intestinal microbiota (IM and bile acids (BA suggest that dysbiosis may be accompanied by an altered bile acid (BA homeostasis, which in turn can contribute to the metabolic dysregulation seen in NAFLD. This study sought to examine BA homeostasis in patients with NAFLD and to relate that with IM data.This was a prospective, cross-sectional study of adults with biopsy-confirmed NAFLD (non-alcoholic fatty liver: NAFL or non-alcoholic steatohepatitis: NASH and healthy controls (HC. Clinical and laboratory data, stool samples and 7-day food records were collected. Fecal BA profiles, serum markers of BA synthesis 7-alpha-hydroxy-4-cholesten-3-one (C4 and intestinal BA signalling, as well as IM composition were assessed.53 subjects were included: 25 HC, 12 NAFL and 16 NASH. Levels of total fecal BA, cholic acid (CA, chenodeoxycholic acid (CDCA and BA synthesis were higher in patients with NASH compared to HC (p<0.05 for all comparisons. The primary to secondary BA ratio was higher in NASH compared to HC (p = 0.004, but ratio of conjugated to unconjugated BAs was not different between the groups. Bacteroidetes and Clostridium leptum counts were decreased in in a subset of 16 patients with NASH compared to 25 HC, after adjusting for body mass index and weight-adjusted calorie intake (p = 0.028 and p = 0.030, respectively. C. leptum was positively correlated with fecal unconjugated lithocholic acid (LCA (r = 0.526, p = 0.003 and inversely with unconjugated CA (r = -0.669, p<0.0001 and unconjugated CDCA (r = - 0.630, p<0.0001. FGF19 levels were not different between the groups (p = 0.114.In adults with NAFLD, dysbiosis is associated with altered BA homeostasis, which renders them at increased risk of hepatic injury.

  15. Coping and rehabilitation in alcoholic liver disease patients after hepatic encephalopathy

    DEFF Research Database (Denmark)

    Rudkjær Mikkelsen, Maria; Hendriksen, Carsten; Schiødt, Frank Vinholt

    2015-01-01

    AIMS AND OBJECTIVES: To identify and describe conditions that limit or support patients, with alcoholic liver disease after surviving alcohol-induced hepatic encephalopathy, ability to cope with current and potential physical and psychosocial problems--in interaction with professionals and relati......AIMS AND OBJECTIVES: To identify and describe conditions that limit or support patients, with alcoholic liver disease after surviving alcohol-induced hepatic encephalopathy, ability to cope with current and potential physical and psychosocial problems--in interaction with professionals......' coping and rehabilitation. DESIGN: A grounded theory study. METHODS: Semi-structured interviews, conducted with 11 alcoholic liver disease patients who were diagnosed with hepatic encephalopathy. The interview guide was inspired by Richard S. Lazarus's theory of stress and coping. RESULTS: The elements...... that support or limit alcoholic liver disease patients' ability to cope with physical and psychosocial problems in interaction with professionals and relatives were represented by the core category 'Struggle for preservation of identity as a significant individual'. It was characterised by three categories...

  16. Nontargeted nuclear magnetic resonance (NMR) analysis to detect hazardous substances including methanol in unrecorded alcohol from Novosibirsk, Russia

    OpenAIRE

    Hausler, Thomas; Okaru,  Alex O.; Neufeld, Maria; Rehm, Jürgen; Kuballa, Thomas; Luy, Burkhard; Lachenmeier, Dirk W.

    2016-01-01

    Nuclear magnetic resonance (NMR) spectroscopy was applied to the analysis of alcoholic products in the context of health and safety control. A total of 86 samples of unrecorded alcohol were collected in Novosibirsk and nearby cities in Russia. Sampling was based on interviews with alcohol dependent patients, and unrecorded alcohol thus defined included illegally or informally produced alcoholic products (e.g., counterfeit or home-made alcoholic beverages) or surrogate alcohol in the form of c...

  17. Quality of Life of Patients with Stable Coronary Artery Disease Combined with Non-Alcoholic Fatty Liver Disease

    OpenAIRE

    Vakalyuk, Iryna; Virstyuk, Nataliya; Petryna, Vitaliy

    2016-01-01

    Quality of life assessment is an integral part of a comprehensive treatment in modern medical practice. Analysis of quality of life of patients with comorbidities is an interesting and poorly understood issue.  The objective of the research was to evaluate the quality of life of patients with postinfarction cardiosclerosis depending on the presence and progression of non-alcoholic fatty liver disease (NAFLD). Material and methods. The research included 300 patients with stable coronary ...

  18. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Eslamparast, Tannaz; Tandon, Puneeta; Raman, Maitreyi

    2017-07-26

    Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD). The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a "high quality healthy diet" to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

  19. Plasmatic higher levels of homocysteine in non-alcoholic fatty liver disease (NAFLD).

    Science.gov (United States)

    de Carvalho, Sylene Coutinho Rampche; Muniz, Maria Tereza Cartaxo; Siqueira, Maria Deozete Vieira; Siqueira, Erika Rabelo Forte; Gomes, Adriana Vieira; Silva, Karina Alves; Bezerra, Laís Carvalho Luma; D'Almeida, Vânia; de Oliveira, Claudia Pinto Marques Souza; Pereira, Leila Maria M Beltrão

    2013-04-02

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, which includes a spectrum of hepatic pathology such as simple steatosis, steatohepatitis, fibrosis and cirrhosis. The increased serum levels of homocysteine (Hcy) may be associated with hepatic fat accumulation. Genetic mutations in the folate route may only mildly impair Hcy metabolism. The aim of this study was to investigate the relation between liver steatosis with plasma homocysteine level and MTHFR C677T and A1298C polymorphisms in Brazilian patients with NAFLD. Thirty-five patients diagnosed with NAFLD by liver biopsy and forty-five healthy controls neither age nor sex matched were genotyped for C677T and A1298C MTHFR polymorphisms using PCR-RFLP and PCR-ASA, respectively, and Hcy was determined by HPLC. All patients were negative for markers of Wilson's, hemochromatosis and autoimmune diseases. Their daily alcohol intake was less than 100 g/week. A set of metabolic and serum lipid markers were also measured at the time of liver biopsies. The plasma Hcy level was higher in NAFLD patients compared to the control group (p = 0.0341). No statistical difference for genotypes 677C/T (p = 0.110) and 1298A/C (p = 0.343) in patients with NAFLD and control subjects was observed. The genotypes distribution was in Hardy-Weinberg equilibrium (677C/T p = 0.694 and 1298 A/C p = 0.188). The group of patients and controls showed a statistically significant difference (p MTHFR C677T and A1298C polymorphisms did not differ significantly between groups, despite the 677TT homozygous frequency was higher in patients (17.14%) than in controls (677TT = 4.44%) (p > 0.05). The suggested genetic susceptibility to the MTHFR C677T and A1298C should be confirmed in large population based studies.

  20. Alcohol

    International Nuclear Information System (INIS)

    Navarro Junior, L.

    1988-01-01

    The alcohol production as a secondary energy source, the participation of the alcohol in Brazilian national economic and social aspects are presented. Statistical data of alcohol demand compared with petroleum by-products and electricity are also included. (author)

  1. Transient and 2-Dimensional Shear-Wave Elastography Provide Comparable Assessment of Alcoholic Liver Fibrosis and Cirrhosis

    DEFF Research Database (Denmark)

    Thiele, Maja; Detlefsen, Sönke; Møller, Linda Maria Sevelsted

    2016-01-01

    predictive value for cirrhosis was >66% in the high-risk group vs approximately 50% in the low-risk group. Evidence of alcohol-induced damage to cholangiocytes, but not ongoing alcohol abuse, affected liver stiffness. The collagen-proportionate area correlated with Ishak grades and accurately identified......BACKGROUND & AIMS: Alcohol abuse causes half of all deaths from cirrhosis in the West, but few tools are available for noninvasive diagnosis of alcoholic liver disease. We evaluated 2 elastography techniques for diagnosis of alcoholic fibrosis and cirrhosis; liver biopsy with Ishak score...... and collagen-proportionate area were used as reference. METHODS: We performed a prospective study of 199 consecutive patients with ongoing or prior alcohol abuse, but without known liver disease. One group of patients had a high pretest probability of cirrhosis because they were identified at hospital liver...

  2. Fatty liver index vs waist circumference for predicting non-alcoholic fatty liver disease.

    Science.gov (United States)

    Motamed, Nima; Sohrabi, Masoudreza; Ajdarkosh, Hossein; Hemmasi, Gholamreza; Maadi, Mansooreh; Sayeedian, Fatemeh Sima; Pirzad, Reza; Abedi, Khadijeh; Aghapour, Sivil; Fallahnezhad, Mojtaba; Zamani, Farhad

    2016-03-14

    To determine the discriminatory performance of fatty liver index (FLI) for non-alcoholic fatty liver disease (NAFLD). The data of 5052 subjects aged over 18 years were analyzed. FLI was calculated from body mass index, waist circumference (WC), triglyceride, and gamma glutamyl transferase data. Logistic regression analysis was conducted to determine the association between FLI and NAFLD. The discriminatory performance of FLI in the diagnosis of NAFLD was evaluated by receiver operating characteristic analysis. Area under the curves (AUCs) and related confidence intervals were estimated. Optimal cutoff points of FLI in the diagnosis of NAFLD were determined based on the maximum values of Youden's index. The mean age of men and women in the study population were 44.8 ± 16.8 and 43.78 ± 15.43, respectively (P = 0.0216). The prevalence of NAFLD was 40.1% in men and 44.2% in women (P < 0.0017). FLI was strongly associated with NAFLD, so that even a one unit increase in FLI increased the chance of developing NAFLD by 5.8% (OR = 1.058, 95%CI: 1.054-1.063, P < 0.0001). Although FLI showed good performance in the diagnosis of NAFLD (AUC = 0.8656 (95%CI: 0.8548-0.8764), there was no significant difference with regards to WC (AUC = 0.8533, 95%CI: 0.8419-0.8646). The performance of FLI was not significantly different between men (AUC = 0.8648, 95%CI: 0.8505-0.8791) and women (AUC = 0.8682, 95%CI: 0.8513-0.8851). The highest performance with regards to age was related to the 18-39 age group (AUC = 0.8930, 95%CI: 0.8766-0.9093). The optimal cutoff points of FLI were 46.9 in men (sensitivity = 0.8242, specificity = 0.7687, Youden's index = 0.5929) and 53.8 in women (sensitivity = 0.8233, specificity = 0.7655, Youden's index = 0.5888). Although FLI had acceptable discriminatory power in the diagnosis of NAFLD, WC was a simpler and more accessible index with a similar performance.

  3. High AST/ALT ratio may indicate advanced alcoholic liver disease rather than heavy drinking.

    Science.gov (United States)

    Nyblom, H; Berggren, U; Balldin, J; Olsson, R

    2004-01-01

    To assess the place of AST/ALT ratio (the ratio of serum aspartate aminotransferase to serum alanine aminotransferase) as a diagnostic marker in medical populations. Laboratory tests were viewed retrospectively in three groups of patients: 313 patients with alcohol dependence, consecutively admitted to an alcohol and drug treatment unit for treatment of withdrawal (W) symptoms, 78 patients with alcohol abuse or dependence consecutively admitted to surgical or medical wards with various primary somatic (S) diagnoses (e.g. respiratory, gastrointestinal and metabolic), and 48 consecutive patients with alcohol abuse or dependence admitted to surgical or medical wards for treatment of alcohol-related liver cirrhosis and its complications (C). Comparison between groups was made of the pattern of patients' AST/ALT ratios using, for Groups S and C, laboratory data from patients' first admission for their condition. There was a significant rise in the AST/ALT ratio from the W to the S patients, and from the S to the C patients. In the W group, the ratio was or = 2. In the C group, 69% had a ratio > or = 2, and 8% a ratio < or = 1.0. The mean ratio was midway in the S group. In the C group, there was a progressive decline in aspartate (AST/ALT) ratios after admission. Most patients with high alcohol consumption but without severe liver disease do not have an AST/ALT ratio above 1. High AST/ALT ratio suggests advanced alcoholic liver disease.

  4. Bacterial infections in alcoholic and nonalcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Sargenti, Konstantina; Prytz, Hanne; Bertilsson, Sara

    2015-01-01

    .001), this relationship was not significant after adjustment for confounders in Cox regression analysis (P=0.056). Resistance to piperacilin-tazobactam and carbapenems was more common in infections occurring in alcoholic versus nonalcoholic cirrhosis (13 vs. 5%, P=0.057 and 12 vs. 2%, P=0.009). Alcoholic etiology...

  5. Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome after Liver Transplant

    OpenAIRE

    Gitto, Stefano; Villa, Erica

    2016-01-01

    Liver transplant is the unique curative therapy for patients with acute liver failure or end-stage liver disease, with or without hepatocellular carcinoma. Increase of body weight, onset of insulin resistance and drug-induced alterations of metabolism are reported in liver transplant recipients. In this context, post-transplant diabetes mellitus, hyperlipidemia, and arterial hypertension can be often diagnosed. Multifactorial illnesses occurring in the post-transplant period represent signifi...

  6. Length of Variable Numbers of Tandem Repeats in the Carboxyl Ester Lipase (CEL) Gene May Confer Susceptibility to Alcoholic Liver Cirrhosis but Not Alcoholic Chronic Pancreatitis.

    Science.gov (United States)

    Fjeld, Karianne; Beer, Sebastian; Johnstone, Marianne; Zimmer, Constantin; Mössner, Joachim; Ruffert, Claudia; Krehan, Mario; Zapf, Christian; Njølstad, Pål Rasmus; Johansson, Stefan; Bugert, Peter; Miyajima, Fabio; Liloglou, Triantafillos; Brown, Laura J; Winn, Simon A; Davies, Kelly; Latawiec, Diane; Gunson, Bridget K; Criddle, David N; Pirmohamed, Munir; Grützmann, Robert; Michl, Patrick; Greenhalf, William; Molven, Anders; Sutton, Robert; Rosendahl, Jonas

    2016-01-01

    Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP. Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups. Twelve repeats were overrepresented in UK ACP patients (P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls (P = 0.03 and 0.008, respectively). However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16-16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients (P = 0.034 and 0.02, respectively). In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC. We did not obtain evidence that CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.

  7. Non-Alcoholic Fatty Liver Disease: Lipids and Insulin Resistance

    Science.gov (United States)

    Berk, Paul D; Verna, Elizabeth C

    2016-01-01

    Abstract/Synopsis Obesity and its major co-morbidities, including type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD), obesity cardiomyopathy, and certain cancers, are major public health problems worldwide. They are responsible for substantial morbidity and mortality, to a degree that life expectancy in the United States has actually declined in recent years because of it. Obesity is the increased accumulation of fat, i.e. triglycerides (TG), which are synthesized from glycerol and long chain fatty acids (LCFA), throughout the body. Although long believed to enter cells solely by passive diffusion, it has been established over the past 30 years that LCFA enter adipocytes, hepatocytes and cardiomyocytes via specific, facilitated transport processes, and that these processes are hormonally up-regulated in obesity. Metabolism of increased cellular TG content in obesity may lead to cell-specific lipotoxicity, contributing to co-morbidities such as NAFLD and cardiomyopathy. In contrast to the popular perception, dietary control and bariatric surgery can each achieve major initial weight loss in many patients. However several mechanisms, including persistent up-regulation of LCFA transport, contribute to weight regain in the large majority of patients. Better understanding of these transport processes and their regulation may be a key to successful future strategies to treat obesity and NAFLD. PMID:27063267

  8. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD) and European Association for the Study of Obesity (EASO) clinical practice recommendations for the management of non-alcoholic fatty liver disease: evaluation of their application in people with Type 2 diabetes.

    Science.gov (United States)

    Sberna, A L; Bouillet, B; Rouland, A; Brindisi, M C; Nguyen, A; Mouillot, T; Duvillard, L; Denimal, D; Loffroy, R; Vergès, B; Hillon, P; Petit, J M

    2018-03-01

    To evaluate the application of the recently proposed recommendations by the European Association for the Study of the Liver, European Association for the Study of Diabetes and European Association for the Study of Obesity for the diagnosis, treatment and follow-up of non-alcoholic fatty liver disease in people with Type 2 diabetes. A total of 179 people with Type 2 diabetes were included in this study. Liver fat content (assessed using proton magnetic resonance spectroscopy), fatty liver index score, non-alcoholic fatty liver disease fibrosis score, and SteatoTest and FibroTest scores were determined. According to proton magnetic resonance spectroscopy, 68.7% of participants had steatosis (liver fat content >5.5%). The application of the guidelines using several combinations (fatty liver index + non-alcoholic fatty liver disease fibrosis scores, Steatotest + FibroTest scores, proton magnetic resonance spectroscopy + non-alcoholic fatty liver disease fibrosis score, proton magnetic resonance spectroscopy + FibroTest) resulted in a referral to a liver clinic for 33.5-84.9% people with Type 2 diabetes. The application of these new algorithms for the diagnosis, and follow-up of non-alcoholic fatty liver disease would lead to an excessive number of people with Type 2 diabetes being referred to a liver clinic. We suggest that new clinical and/or biological biomarkers of steatosis and fibrosis be specifically validated in people with Type 2 diabetes. © 2017 Diabetes UK.

  9. Roles of abnormal lipid metabolism in pathogenesis of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    LU Ran

    2015-07-01

    Full Text Available The prevalence of non-alcoholic fatty liver disease (NAFLD keeps rising worldwide along with the increasing prevalence of metabolic diseases such as obesity, type 2 diabetes, and dyslipidemia. Although most NAFLD patients present with simple steatosis of hepatocytes, some patients progress to non-alcoholic steatohepatitis, liver cirrhosis, and even cancer. In the Western world, NAFLD is the most common cause of elevated liver enzymes, and hence there has been a growing interest in this disease. Given that fat deposition in the liver is the hallmark of NAFLD, we review the roles and the underlying mechanism of disturbed lipid metabolism in the development of NAFLD and suggest that more insights into the pathogenesis of NAFLD will help develop targeted strategies for the prevention and treatment of this disease.

  10. Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Johansen, Julia S; Christensen, Erik

    2003-01-01

    patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS: Serum YKL-40 and PIIINP were elevated...... with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (Plevels of YKL-40 and PIIINP are elevated......BACKGROUND/AIMS: YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS: Three hundred and seventy...

  11. ADH1B and ADH1C Genotype, Alcohol Consumption and Biomarkers of Liver Function

    DEFF Research Database (Denmark)

    Lawlor, Debbie A; Benn, Marianne; Zuccolo, Luisa

    2014-01-01

    BACKGROUND: The effect of alcohol consumption on liver function is difficult to determine because of reporting bias and potential residual confounding. Our aim was to determine this effect using genetic variants to proxy for the unbiased effect of alcohol. METHODS: We used variants in ADH1B and ADH......1C genes as instrumental variables (IV) to estimate the causal effect of long-term alcohol consumption on alanine aminotransferase (ALT), γ-glutamyl-transferase (γ-GT), alkaline phosphatase (ALP), bilirubin and prothrombin action. Analyses were undertaken on 58,313 Danes (mean age 56). RESULTS......: In both confounder adjusted multivariable and genetic-IV analyses greater alcohol consumption, amongst those who drank any alcohol, was associated with higher ALT [mean difference per doubling of alcohol consumption: 3.4% (95% CI: 3.1, 3.7) from multivariable analyses and 3.7% (-4.5, 11.9) from genetic...

  12. The role of oxidative stress in the development of alcoholic liver disease.

    Science.gov (United States)

    Galicia-Moreno, M; Gutiérrez-Reyes, G

    2014-01-01

    Alcohol is the most accepted addictive substance worldwide and its consumption is related to multiple health, economic, and social problems. The liver is the organ in charge of ethanol metabolism and it is susceptible to alcohol's toxic effects. To provide a detailed review of the role of oxidative stress in alcoholic liver disease and the mechanisms of damage involved, along with current information on the hepatoprotective effectiveness of the molecules that have been studied. A search of the PubMed database was conducted using the following keywords oxidative stress, alcoholic liver damage, alcoholic cirrhosis, and antioxidants. There was no time limit for gathering all available information on the subject at hand. According to the literature reviewed, oxidative stress plays an important role in the pathogenesis of alcoholic liver damage. Molecules such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), formed during ethanol metabolism, structurally and functionally modify organic molecules. Consequently, biologic processes are altered and hepatocytes are sensitized to the action of cytokines like tumor necrosis factor-α, as well as to the action of endotoxins, activating signaling pathways such as those controlled by nuclear factor kappa B, extracellular signal regulated kinases, and mitogen activated protein kinase. Oxidative stress plays an important role in the development of liver damage resulting from alcohol consumption. The molecules that have currently displayed a hepatoprotective effect in preclinical and clinical trials must be studied further so that their effectiveness can be confirmed and they can possibly be used as adjuvant treatments for this disease. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

  13. Ubiquitin: an immunohistochemical marker of Mallory bodies and alcoholic liver disease

    DEFF Research Database (Denmark)

    Vyberg, Mogens; Leth, Peter Mygind

    1991-01-01

    One hundred forty eight liver needle biopsies, comprising 88 consecutive biopsies from patients with clinically diagnosed or suspected alcoholic liver disease and 60 selected biopsies from non-alcoholics, were immunostained for the cell stress protein ubiquitin (Ub). Ub + cells were detected in all...... of 33 biopsies with alcoholic hepatitis (AH). Practically all Mallory bodies (MBs) showed intense Ub-staining. In addition, many cells revealed Ub + granules lying aggregated (pre-MBs) or dispersed in the cytoplasm of ballooned cells. The mean number of Ub + cells in 10 biopsies with AH was more than 30...... times the number of MBs and more than 6 times the number of MBs + pre-MBs found in adjacent Haematoxylin-Eosin (HE) stained sections. Among 55 biopsies from alcoholic patients without AH (i.e. without MBs or pre-MBs in HE stained sections), Ub + cells occurred in eight (14.5%). Among the 60 selected...

  14. The benefits of exercise for patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Keating, Shelley E; George, Jacob; Johnson, Nathan A

    2015-01-01

    As exercise is now an established therapy for the management of non-alcoholic fatty liver disease (NAFLD), recent investigations have sought to identify the optimal dose (type, intensity and amount) of exercise for hepatic benefit. Here, the authors discuss the following: the role of aerobic exercise for the modulation of hepatic steatosis; the limited evidence for the role of resistance training in reducing liver fat; the lack of evidence from clinical trials on the role of exercise in non-alcoholic steatohepatitis; and the benefits of exercise for patients with NAFLD, beyond steatosis. Based on current evidence, the authors provide recommendations for exercise prescription for patients with NAFLD.

  15. Aerobic vs. resistance exercise in non-alcoholic fatty liver disease: A systematic review.

    Science.gov (United States)

    Hashida, Ryuki; Kawaguchi, Takumi; Bekki, Masafumi; Omoto, Masayuki; Matsuse, Hiroo; Nago, Takeshi; Takano, Yoshio; Ueno, Takato; Koga, Hironori; George, Jacob; Shiba, Naoto; Torimura, Takuji

    2017-01-01

    Exercise is a first-line therapy for patients with non-alcoholic fatty liver disease (NAFLD). We sought to: 1) summarize effective aerobic and resistance exercise protocols for NAFLD; and 2) compare the effects and energy consumption of aerobic and resistance exercises. A literature search was performed using PubMed, Web of Science, and Scopas to January 28, 2016. From a total of 95 articles, 23 studies including 24 aerobic and 7 resistance exercise protocols were selected for the summary of exercise protocols. Twelve articles including 13 aerobic and 4 resistance exercise protocols were selected for the comparative analysis. For aerobic exercise, the median effective protocol was 4.8 metabolic equivalents (METs) for 40min/session, 3times/week for 12weeks. For resistance exercise, the median effective protocol was 3.5 METs for 45min/session, 3times/week for 12weeks. Aerobic and resistance exercise improved hepatic steatosis. No significant difference was seen in the duration, frequency, or period of exercise between the two exercise groups; however, %VO 2 max and energy consumption were significantly lower in the resistance than in the aerobic group (50% [45-98] vs. 28% [28-28], p=0.0034; 11,064 [6394-21,087] vs. 6470 [4104-12,310] kcal/total period, p=0.0475). Resistance exercise improves NAFLD with less energy consumption. Thus, resistance exercise may be more feasible than aerobic exercise for NAFLD patients with poor cardiorespiratory fitness or for those who cannot tolerate or participate in aerobic exercise. These data may indicate a possible link between resistance exercise and lipid metabolism in the liver. Both aerobic and resistance exercise reduce hepatic steatosis in non-alcoholic fatty liver disease (NAFLD) with similar frequency, duration, and period of exercise (40-45min/session 3times/week for 12weeks); however, the two forms of exercise have different characteristics. Intensity and energy consumption were significantly lower for resistance than for

  16. The Possible Role of Helicobacter pylori Infection in Non-alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Dan-dan Cheng

    2017-05-01

    Full Text Available Helicobacter pylori (H. pylori which colonizes the stomach can cause a wide array of gastric disorders, including chronic gastritis, peptic ulcer, and gastric cancer. Recently, accumulating evidence has implicated H. pylori infection in extragastrointestinal diseases such as cardiovascular diseases, neurological disorders, and metabolic diseases. At the same time, many scholars have noted the relationship between H. pylori infection and non-alcoholic fatty liver disease (NAFLD. Despite the positive association between H. pylori and NAFLD reported in some researches, there are opposite perspectives denying their relationship. Due to high prevalence, unclear etiology and difficult treatment of NAFLD, confirming the pathogenicity of H. pylori infection in NAFLD will undoubtedly provide insights for novel treatment strategies for NAFLD. This paper will review the relationship between H. pylori infection and NAFLD and the possible pathogenic mechanisms.

  17. PROTECTIVE EFFECTS OF HYPOTHALAMIC BETA-ENDORPHIN NEURONS AGAINST ALCOHOL-INDUCED LIVER INJURIES AND LIVER CANCERS IN RAT ANIMAL MODELS

    Science.gov (United States)

    Murugan, Sengottuvelan; Boyadjieva, Nadka; Sarkar, Dipak K.

    2014-01-01

    Background Recently, retrograde tracing has provided evidence for an influence of hypothalamic β-endorphin (BEP) neurons on the liver, but functions of these neurons are not known. We evaluated the effect of BEP neuronal activation on alcohol-induced liver injury and hepatocellular cancer. Methods Male rats received either BEP neuron transplants or control transplants in the hypothalamus and randomly assigned to feeding alcohol-containing liquid diet or control liquid diet for 8 weeks or to treatment of a carcinogen diethylnitrosamine (DEN). Liver tissues of these animals were analyzed histochemically and biochemically for tissue injuries or cancer. Results Alcohol-feeding increased liver weight and induced several histopathological changes such as prominent microvesicular steatosis and hepatic fibrosis. Alcohol feeding also increased protein levels of triglyceride, hepatic stellate cell activation factors and catecholamines in the liver and endotoxin levels in the plasma. However, these effects of alcohol on the liver were reduced in animals with BEP neuron transplants. BEP neuron transplants also suppressed carcinogen-induced liver histopathologies such as extensive fibrosis, large focus of inflammatory infiltration, hepatocelluar carcinoma, collagen deposition, numbers of preneoplastic foci, levels of hepatic stellate cell activation factors and catecholamines, as well as inflammatory milieu and the levels of NK cell cytotoxic factors in the liver. Conclusion These findings are the first evidence for a role of hypothalamic BEP neurons in influencing liver functions. Additionally, the data identify that BEP neuron transplantation prevents hepatocellular injury and hepatocellular carcinoma formation possibly via influencing the immune function. PMID:25581653

  18. Prediction of prevalent but not incident non-alcoholic fatty liver disease by levels of serum testosterone.

    Science.gov (United States)

    Seo, Nam Kyoung; Koo, Hyung Suk; Haam, Ji-Hee; Kim, Hyung Yuk; Kim, Moon Jong; Park, Kyung-Chae; Park, Kye-Seon; Kim, Young-Sang

    2015-07-01

    The association between testosterone level and development of non-alcoholic fatty liver disease (NAFLD) is not well known. We examined the relationship of total testosterone level with development and regression of NAFLD. Among the men who had undergone repeated liver ultrasonography in 2 years or more at a health promotion center, subjects with available serum testosterone level at baseline were included in the study. Alcohol consumers (> 20 g/day) were excluded from the study. Among the 1944 men, 44.3% of subjects were diagnosed with NAFLD. Higher level of testosterone significantly lowered the prevalence of fatty liver (odds ratios per SD increase, 0.686 and 0.795 at baseline and follow-up, respectively). During the median 4.2 years follow-up, 22.4% of subjects in the normal group developed fatty liver, and 21.0% of subjects in the NAFLD group recovered at the follow-up. In longitudinal analyses, higher level of testosterone was significantly associated with the development or regression of fatty liver, before adjustment for obesity and metabolic parameters. However, in the full-adjusted model, testosterone level did not influence the development or regression of fatty liver. Although testosterone level was significantly low in the subjects with NAFLD in cross-sectional analyses, baseline testosterone level did not independently influence the development or regression of fatty liver at the median 4.2 years follow-up. Obesity and metabolic parameters may play key roles in the link between testosterone level and NAFLD. © 2015 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  19. Serum acid sphingomyelinase is upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease.

    Science.gov (United States)

    Grammatikos, Georgios; Mühle, Christiane; Ferreiros, Nerea; Schroeter, Sirkka; Bogdanou, Dimitra; Schwalm, Stephanie; Hintereder, Gudrun; Kornhuber, Johannes; Zeuzem, Stefan; Sarrazin, Christoph; Pfeilschifter, Josef

    2014-07-01

    Sphingolipids constitute bioactive molecules with functional implications in homeostasis and pathogenesis of various diseases. However, the role of sphingolipids as possible disease biomarkers in chronic liver disease remains largely unexplored. In the present study we used mass spectrometry and spectrofluorometry methods in order to quantify various sphingolipid metabolites and also assess the activity of an important corresponding regulating enzyme in the serum of 72 healthy volunteers as compared to 69 patients with non-alcoholic fatty liver disease and 69 patients with chronic hepatitis C virus infection. Our results reveal a significant upregulation of acid sphingomyelinase in the serum of patients with chronic liver disease as compared to healthy individuals (phepatitis C infection acid sphingomyelinase activity correlated significantly with markers of hepatic injury (r=0.312, p=0.009) and showed a high discriminative power. Accumulation of various (dihydro-) ceramide species was identified in the serum of patients with non-alcoholic fatty liver disease (pliver disease (phepatic injury was identified. Chronic hepatitis C virus infection and non-alcoholic fatty liver disease induce a significant upregulation of serum acid sphingomyelinase which appears as a novel biomarker in chronic hepatopathies. Further studies are required to elucidate the potential of the sphingolipid signaling pathway as putative therapeutic target in chronic liver disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Modest alcohol consumption reduces the incidence of fatty liver in men: a population-based large-scale cohort study.

    Science.gov (United States)

    Hashimoto, Yoshitaka; Hamaguchi, Masahide; Kojima, Takao; Ohshima, Yasuhiro; Ohbora, Akihiro; Kato, Takahiro; Nakamura, Naoto; Fukui, Michiaki

    2015-03-01

    Recent cross-sectional studies have been reported the possibility that light to moderate alcohol consumption might be negatively associated with fatty liver. However, there has been no large-scale longitudinal study addressing an impact of alcohol consumption on a development of fatty liver diagnosed by ultrasonography. Thus, we investigated the impact of alcohol consumption on a natural history of fatty liver. We analyzed 5437 apparently healthy Japanese who received the health checkup programs repeatedly over 10 years. In this study, we used a standardized questionnaire for addressing the medical history and lifestyle and used a standardized ultrasonographic diagnosis for fatty liver. The total amount of alcohol consumed per week was calculated and classified into four grades; none or minimal, light, moderate, or heavy alcohol consumption ( 280 g/week, respectively). The hazard risks of alcohol consumption for the development of fatty liver were calculated by Cox hazard model after adjusting age, BMI, and parameters for lifestyle. During 10 years of follow-up, fatty liver was continuously diagnosed just in 10% of men and 20% of women with fatty liver at the baseline. In men, the adjusted hazard risks of light and moderate alcohol consumption for the development of fatty liver were 0.72 (95% confidence interval 0.60-0.86, P alcohol. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  1. The Risk of Abdominal Obesity according to the Degree of Non-Alcoholic Fatty Liver Disease in Korean Men.

    Science.gov (United States)

    Park, Sung Keun; Ryoo, Jae-Hong; Choi, Joong-Myung; Seo, Min Woo; Park, Chung Min

    2016-03-01

    Although non-alcoholic fatty liver disease has been reported as a cardiometabolic risk factor, the effect of non-alcoholic fatty liver is yet to be clarified on abdominal obesity. Therefore, this study was conducted to investigate the longitudinal relationship of non-alcoholic fatty liver on the development of abdominal obesity. The study participants were composed of 11,212 Korean men without abdominal obesity. They were followed up from 2005 to 2010 to be monitored for the development of abdominal obesity according to their degree of non-alcoholic fatty liver disease (normal, mild, and moderate to severe). Cox-proportional hazard model was used to calculate the hazard ratios for abdominal obesity according to the degree of non-alcoholic fatty liver disease. While the average incidence was 15.5%, the incidence of abdominal obesity increased according to the degree of non-alcoholic fatty liver (normal: 11.6%, mild: 25.2%, moderate to severe: 41.0%, P obesity independently increased proportionally to the degree of NAFLD (mild [1.07; 0.94-1.23], moderate to severe [1.58; 1.11-2.26], P for trend obesity increased proportionally to the degree of non-alcoholic fatty liver disease. This finding guarantees further studies to reveal the incidental relationship of abdominal obesity with non-alcoholic fatty liver disease.

  2. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines : A large Dutch population cohort

    NARCIS (Netherlands)

    van den Berg, Eline H.; Amini, Marzyeh; Dullaart, Robin P. F.; Faber, Klaas Nico; Alizadeh, Behrooz Z.; Blokzijl, Hans

    2017-01-01

    Background & aims Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the

  3. Meta-analysis of propylthiouracil for alcoholic liver disease--a Cochrane Hepato-Biliary Group Review

    DEFF Research Database (Denmark)

    Rambaldi, A; Gluud, C

    2001-01-01

    The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease.......The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease....

  4. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-07-21

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.

  5. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

    Science.gov (United States)

    Firneisz, Gábor

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

  6. Alcohol-Attributable Fraction in Liver Disease: Does GDP Per Capita Matter?

    Science.gov (United States)

    Kröner, Paul T; Mankal, Pavan Kumar; Dalapathi, Vijay; Shroff, Kavin; Abed, Jean; Kotler, Donald P

    2015-01-01

    The alcohol-attributable fraction (AAF) quantifies alcohol's disease burden. Alcoholic liver disease (ALD) is influenced by alcohol consumption per capita, duration, gender, ethnicity, and other comorbidities. In this study, we investigated the association between AAF/alcohol-related liver mortality and alcohol consumption per capita, while stratifying to per-capita gross domestic product (GDP). Data obtained from the World Health Organization and World Bank for both genders on AAF on liver disease, per-capita alcohol consumption (L/y), and per-capita GDP (USD/y) were used to conduct a cross-sectional study. Countries were classified as "high-income" and "very low income" if their respective per-capita GDP was greater than $30,000 or less than $1,000. Differences in total alcohol consumption per capita and AAF were calculated using a 2-sample t test. Scatterplots were generated to supplement the Pearson correlation coefficients, and F test was conducted to assess for differences in variance of ALD between high-income and very low income countries. Twenty-six and 27 countries met the criteria for high-income and very low income countries, respectively. Alcohol consumption per capita was higher in high-income countries. AAF and alcohol consumption per capita for both genders in high-income and very low income countries had a positive correlation. The F test yielded an F value of 1.44 with P = .357. No statistically significant correlation was found among alcohol types and AAF. Significantly higher mortality from ALD was found in very low income countries relative to high-income countries. Previous studies had noted a decreased AAF in low-income countries as compared to higher-income countries. However, the non-statistically significant difference between AAF variances of low-income and high-income countries was found by this study. A possible explanation is that both high-income and low-income populations will consume sufficient amount of alcohol, irrespective of its

  7. Aerobic exercise training in the treatment of non‐alcoholic fatty liver disease related fibrosis

    Science.gov (United States)

    Linden, Melissa A.; Sheldon, Ryan D.; Meers, Grace M.; Ortinau, Laura C.; Morris, E. Matthew; Booth, Frank W.; Kanaley, Jill A.; Vieira‐Potter, Victoria J.; Sowers, James R.; Ibdah, Jamal A.; Thyfault, John P.; Laughlin, M. Harold

    2016-01-01

    Key points Physiologically relevant rodent models of non‐alcoholic steatohepatitis (NASH) that resemble the human condition are limited.Exercise training and energy restriction are first‐line recommendations for the treatment of NASH.Hyperphagic Otsuka Long–Evans Tokushima fatty rats fed a western diet high in fat, sucrose and cholesterol for 24 weeks developed a severe NASH with fibrosis phenotype.Moderate intensity exercise training and modest energy restriction provided some improvement in the histological features of NASH that coincided with alterations in markers of hepatic stellate cell activation and extracellular matrix remodelling.The present study highlights the importance of lifestyle modification, including exercise training and energy restriction, in the regulation of advanced liver disease. Abstract The incidence of non‐alcoholic steatohepatitis (NASH) is rising but the efficacy of lifestyle modifications to improve NASH‐related outcomes remain unclear. We hypothesized that a western diet (WD) would induce NASH in the Otsuka Long–Evans Tokushima Fatty (OLETF) rat and that lifestyle modification would improve this condition. Eight‐week‐old Long–Evans Tokushima Otsuka (L) and OLETF (O) rats consumed a control diet (10% kcal fat, 3.5% sucrose) or a WD (45% kcal fat, 17% sucrose, 1% cholesterol) for 24 weeks. At 20 weeks of age, additional WD‐fed OLETFs were randomized to sedentary (O‐SED), food restriction (O‐FR; ∼25% kcal reduction vs. O‐SED) or exercise training (O‐EX; treadmill running 20 m min–1 with a 15% incline, 60 min day–1, 5 days week–1) conditions for 12 weeks. WD induced a NASH phenotype in OLETFs characterized by hepatic fibrosis (collagen 1α1 mRNA and hydroxyproline content), as well as elevated inflammation and non‐alcoholic fatty liver disease activity scores, and hepatic stellate cell activation (α‐smooth muscle actin) compared to Long–Evans Tokushima Otsuka rats. FR and EX modestly

  8. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, S; Poulsen, M K; Ornstrup, M J

    2017-01-01

    BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD).We explored this association further by investigating correlations between sCD36 levels....... An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty acid load to the liver.Clinical Trials.gov (NCT01464801, NCT01412645, NCT01446276).International Journal of Obesity accepted article preview online, 05 December 2016. doi:10.1038/ijo.2016.223....... resonance imaging (n=94, subcutaneous and visceral adipose tissue) and liver biopsy (n=28 NAFLD patients) performed. Plasma sCD36 was assessed by ELISA. RESULTS: NAFLD patients had elevated sCD36 levels compared to controls (0.68 (0.12-2.27) versus 0.43 (0.10-1.18), P

  9. Quercetin prevents alcohol-induced liver injury through targeting of PI3K/Akt/nuclear factor-κB and STAT3 signaling pathway

    Science.gov (United States)

    Zhu, Minglin; Zhou, Xuefeng; Zhao, Jinping

    2017-01-01

    Quercetin is a type of flavonoid compound, which has potent antioxidant and anti-inflammatory activities, capable of treating a variety of diseases including neurodegenerative diseases, tumors, diabetes and obesity. The present study selected alcohol-induced liver injury model mice and aimed at studying the protective role of quercetin in preventing alcohol-induced liver injury. In alcohol-induced liver injury mice treated with quercetin, it was demonstrated that levels of aspartate transaminase, alanine transaminase, total bilirubin and triglyceride were reduced. In addition to this, the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were increased, malondialdehyde was inhibited, and interleukin (IL)-1β, IL-6, IL-10 and inducible nitric oxide synthase were suppressed. Quercetin additionally suppressed the protein expression levels of B-cell lymphoma (Bcl)-2, Bcl-2 associated X apoptosis regulator, Caspase-3, poly ADP-ribose polymerase, and signal transducer and activator of transcription (STAT) 3 phosphorylation, nuclear factor (NF)-κB and protein kinase B (Akt) phosphorylation levels in alcohol-induced liver injured mice. These results suggested that the protective role of quercetin prevents alcohol-induced liver injury through the phosphoinositide 3-kinase/Akt/NF-κB and STAT3 pathway. PMID:29285175

  10. Changes in the Prevalence of Hepatitis C Virus Infection, Nonalcoholic Steatohepatitis, and Alcoholic Liver Disease Among Patients With Cirrhosis or Liver Failure on the Waitlist for Liver Transplantation.

    Science.gov (United States)

    Goldberg, David; Ditah, Ivo C; Saeian, Kia; Lalehzari, Mona; Aronsohn, Andrew; Gorospe, Emmanuel C; Charlton, Michael

    2017-04-01

    Concurrent to development of more effective drugs for treatment of hepatitis C virus (HCV) infection, there has been an increase in the incidence of nonalcoholic fatty liver disease. Data indicate that liver transplantation prolongs survival times of patient with acute hepatitis associated with alcoholic liver disease (ALD). We compared data on disease prevalence in the population with data from liver transplantation waitlists to evaluate changes in the burden of liver disease in the United States. We collected data on the prevalence of HCV from the 2010 and 2013-2014 cycles of the National Health and Nutrition Examination Survey. We also collected data from the HealthCore Integrated Research Database on patients with cirrhosis and chronic liver failure (CLF) from 2006 through 2014, and data on patients who received transplants from the United Network for Organ Sharing from 2003 through 2015. We determined percentages of new waitlist members and transplant recipients with HCV infection, stratified by indication for transplantation, modeling each calendar year as a continuous variable using the Spearman rank correlation, nonparametric test of trends, and linear regression models. In an analysis of data from the National Health and Nutrition Examination Survey (2013-2014), we found that the proportion of patients with a positive HCV antibody who had a positive HCV RNA was 0.5 (95% confidence interval, 0.42-0.55); this value was significantly lower than in 2010 (0.64; 95% confidence interval, 0.59-0.73) (P = .03). Data from the HealthCore database revealed significant changes (P liver transplant waitlist, or undergoing liver transplantation, for CLF, there was a significant decrease in the percentage with HCV infection and increases in percentages of patients with nonalcoholic fatty liver disease or ALD. Among patients new to the liver transplant waitlist or undergoing liver transplantation for HCC, proportions of those with HCV infection, nonalcoholic fatty liver

  11. A mouse model of alcoholic liver fibrosis-associated acute kidney injury identifies key molecular pathways

    International Nuclear Information System (INIS)

    Furuya, Shinji; Chappell, Grace A.; Iwata, Yasuhiro; Uehara, Takeki; Kato, Yuki; Kono, Hiroshi; Bataller, Ramon; Rusyn, Ivan

    2016-01-01

    Clinical data strongly indicate that acute kidney injury (AKI) is a critical complication in alcoholic hepatitis, an acute-on-chronic form of liver failure in patients with advanced alcoholic fibrosis. Development of targeted therapies for AKI in this setting is hampered by the lack of an animal model. To enable research into molecular drivers and novel therapies for fibrosis- and alcohol-associated AKI, we aimed to combine carbon tetrachloride (CCl 4 )-induced fibrosis with chronic intra-gastric alcohol feeding. Male C57BL/6J mice were administered a low dose of CCl 4 (0.2 ml/kg 2 × week/6 weeks) followed by alcohol intragastrically (up to 25 g/kg/day for 3 weeks) and with continued CCl 4 . We observed that combined treatment with CCl 4 and alcohol resulted in severe liver injury, more pronounced than using each treatment alone. Importantly, severe kidney injury was evident only in the combined treatment group. This mouse model reproduced distinct pathological features consistent with AKI in human alcoholic hepatitis. Transcriptomic analysis of kidneys revealed profound effects in the combined treatment group, with enrichment for damage-associated pathways, such as apoptosis, inflammation, immune-response and hypoxia. Interestingly, Havcr1 and Lcn2, biomarkers of AKI, were markedly up-regulated. Overall, this study established a novel mouse model of fibrosis- and alcohol-associated AKI and identified key mechanistic pathways. - Highlights: • Acute kidney injury (AKI) is a critical complication in alcoholic hepatitis • We developed a novel mouse model of fibrosis- and alcohol-associated AKI • This model reproduces key molecular and pathological features of human AKI • This animal model can help identify new targeted therapies for alcoholic hepatitis

  12. Peran Antioksidan pada Non Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Yusri Diane Jurnalis

    2014-01-01

    Full Text Available AbstrakNonalcoholic Fatty Liver Disease (NAFLD merupakan penyebab tersering penyakit hati kronik pada anak dan remaja diseluruh dunia. NAFLD berhubungan dengan obesitas, diabetes melitus tipe 2 dan sindrom metabolik. Resistensi insulin memegang peranan penting dalam patogenesis molecular terjadinya NAFLD. Ketidakseimbangan prooksidan dan antioksidan pada sel hepatosis menentukan progresifitas penyakit ini. Sebagai antioksidan telah dilakukan penelitian mengenai efek antioksidan vitamin E, vitamin C, betaine, N-asetil sistein, probucol dan silymarin. Antioksidan tersebut memperlihatkan perbaikan fungsi hepar dan gambaran histopatologis.Kata kunci: Arial 9 NAFLD, resistensi insulin, antioksidanAbstractNonalcoholic fatty liver disease (NAFLD is the most common cause of liver disease in pediatric and adolescent population. NAFLD related with obesity, type 2 diabetes mellitus and metabolic syndrome. Insulin resistance and oxidative stress have important role in molecular pathogenesis of NAFLD. Prooxidant and antioxidant factor in hepatosit can determine progressivity of liver disease. As antioxidant agent for treatment NAFLD have been studied effect of vitamin E, vitamin C, betaine, N-acetyl cystein, probucol and sylimarin. They have been shown improvement of liver function test and histopathologycal feature.Keywords:NAFLD, insulin resistance, antioxidant

  13. Light alcohol consumption plays a protective role against non-alcoholic fatty liver disease in Japanese men with metabolic syndrome.

    Science.gov (United States)

    Sogabe, Masahiro; Okahisa, Toshiya; Taniguchi, Tatsuya; Tomonari, Tetsu; Tanaka, Takahiro; Tanaka, Hironori; Nakasono, Masahiko; Takayama, Tetsuji

    2015-06-01

    Although excess alcohol consumption has been believed to cause liver injury, light alcohol consumption (LAC) has been reported to play a protective role against fatty liver in recent studies. However, the association between non-alcoholic fatty liver disease (NAFLD) and LAC in men with metabolic syndrome (MS) is unclear. The aim of this study was to examine the association between NAFLD and LAC in men with MS. Subjects were 1055 men with MS who underwent a regular health check-up and drank less 20 g/day of alcohol. A distinction was made between non-drinkers and light drinkers and the association between NAFLD and LAC in men with MS was elucidated. NAFLD was referred as fatty liver with alanine aminotransferase (ALT) levels ≧31 IU/L in this study. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and the prevalence of NAFLD were significantly lower in light drinkers than in non-drinkers. Logistic regression analysis showed body mass index (BMI), waist circumference (WC), uric acid (UA), haemoglobin A1c (HbA1c), visceral fat type MS and LAC (odds ratios: 0.654; 95% confidence intervals: 0.473-0.906; <0.05) were significant predictors of the prevalence of NAFLD. The prevalence of NAFLD in light drinkers was significantly lower than in non-drinkers, and supporting previous reports studying the general population, LAC is one of the significant predictors of a decreased prevalence of NAFLD in men with MS. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Role of stellate cells in alcoholic liver fibrosis

    Directory of Open Access Journals (Sweden)

    Krzysztof Plewka

    2009-07-01

    Full Text Available Many different diseases and toxins can cause liver damage, which is diffi cult to treat and often leads to the development of liver fi brosis or even cirrhosis. The key event in this process is the activation of hepatic stellate cells (HSCs. During such activation, HSCs undergo a dramatic transformation in morphology and behavior, changing from a neuronal-like to a fi broblast-like morphology. After activation, HSCs increase their proliferation rate and extracellular matrix (ECM production. Overproduction of ECM, which contains mainly collagen type I, is a direct cause of liver disruption. HSCs also produce substances which inhibit protease activities, such as TIMPs, which enhance ECM deposition in the liver. On the molecular level, HSCs are activated by cytokines, growth factors, and oxidative stress, which are abundant in affl icted liver. These factors induce intracellular signals transmitted by many kinases, the most important of which are JNK, ERK1/2, p38, TAK-1, PKC, FAK, and P3IK. Signals transmitted via these pathways change the activities of transcription factors such as Smad, AP-1, and NF-κβ. This in turn causes changes In gene transcription and ultimately alters the whole cell’s behavior and morphology. The cell begins the production collagen type I, TIMP-1, and aSMA. Activated HSCs can sustain their own activation by producing growth factors such as PDGF and TGF-β. Despite the vast knowledge about the mechanisms causing liver fi brosis and cirrhosis, there is still no effective cure. Further studies are therefore needed to solve this problem.

  15. Transient elastography for diagnosis of stages of hepatic fibrosis and cirrhosis in people with alcoholic liver disease

    DEFF Research Database (Denmark)

    Pavlov, Chavdar S; Casazza, Giovanni; Nikolova, Dimitrinka

    2015-01-01

    of the diagnosis of alcoholic liver disease was not provided in one study and was not clearly defined in two studies, but it was clear in the remaining 11 studies. The study authors used different liver stiffness cut-off values of transient elastography for the hepatic fibrosis stages.There was only one study (103......BACKGROUND: The presence and progression of hepatic (liver) fibrosis into cirrhosis is a prognostic variable having impact on survival in people with alcoholic liver disease. Liver biopsy, although an invasive method, is the recommended 'reference standard' for diagnosis and staging of hepatic...... fibrosis in people with liver diseases. Transient elastography is a non-invasive method for assessing and staging hepatic fibrosis. OBJECTIVES: To determine the diagnostic accuracy of transient elastography for diagnosis and staging hepatic fibrosis in people with alcoholic liver disease when compared...

  16. Human leucocyte antigens in patients with alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Aldershvile, J; Dietrichson, O

    1980-01-01

    No significant differences in the frequencies of HLA-B8, -B40, and other HLA-A, -B, and -C phenotypes were found among patients with histologically verified alcoholic cirrhosis compared with normal controls when the p values were multiplied by the number of comparisons. This was found both...... in the present study of 45 patients and in the combined data of this and three other similar studies. However, these findings do not rule out that alcoholic cirrhosis might be associated with HLA factors (for example. HLA-D/DR antigens) controlling immune responses....

  17. Alcoholic liver cirrhosis increases the risk of left ventricular diastolic dysfunction

    Czech Academy of Sciences Publication Activity Database

    Brotánek, J.; Ort, Michael; Kubánek, M.; Stiborová, M.

    2013-01-01

    Roč. 34, Suppl.2 (2013), s. 64-70 ISSN 0172-780X R&D Projects: GA MŠk(CZ) 1M0517 Institutional research plan: CEZ:AV0Z50110509 Keywords : left ventricular diastolic dysfunction * cirrhosis * liver * alcohol Subject RIV: FH - Neurology Impact factor: 0.935, year: 2013

  18. Phenotyping the effect of diet on non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Wit, de N.J.W.; Afman, L.A.; Mensink, M.R.; Muller, M.R.

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with the growing incidence of metabolic syndrome. Diet is an important contributor to the pathogenesis of NAFLD. In this review, we focused on recent publications reporting on the effect of macro- and micronutrients on development and

  19. Preserved hemostatic status in patients with non-alcoholic fatty liver disease

    NARCIS (Netherlands)

    Potze, Wilma; Siddiqui, Mohammad S.; Boyett, Sherry L.; Adelmeijer, Jelle; Daita, Kalyani; Sanyal, Arun J.; Lisman, Ton

    2016-01-01

    Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of thrombosis. However, it remains unclear if hypercoagulability contributes to this risk. We, therefore, determined an in-depth hemostatic profile in a cohort of well-defined patients with NAFLD.

  20. Maternal western diet primes non-alcoholic fatty liver disease in adult mouse offspring

    NARCIS (Netherlands)

    Pruis, M. G. M.; Lendvai, A.; Bloks, V. W.; Zwier, M. V.; Baller, J. F. W.; de Bruin, A.; Groen, A. K.; Plosch, T.

    AimMetabolic programming via components of the maternal diet during gestation may play a role in the development of different aspects of the metabolic syndrome. Using a mouse model, we aimed to characterize the role of maternal western-type diet in the development of non-alcoholic fatty liver

  1. In Vitro and in Vivo Models of Non-Alcoholic Fatty Liver Disease (NAFLD

    Directory of Open Access Journals (Sweden)

    Ina Bergheim

    2013-06-01

    Full Text Available By now, non-alcoholic fatty liver disease (NAFLD is considered to be among the most common liver diseases world-wide. NAFLD encompasses a broad spectrum of pathological conditions ranging from simple steatosis to steatohepatitis, fibrosis and finally even cirrhosis; however, only a minority of patients progress to end-stages of the disease, and the course of the disease progression to the later stages seems to be slow, developing progressively over several years. Key risk factors including overweight, insulin resistance, a sedentary life-style and an altered dietary pattern, as well as genetic factors and disturbances of the intestinal barrier function have been identified in recent years. Despite intense research efforts that lead to the identification of these risk factors, knowledge about disease initiation and molecular mechanisms involved in progression is still limited. This review summarizes diet-induced and genetic animal models, as well as cell culture models commonly used in recent years to add to the understanding of the mechanisms involved in NAFLD, also referring to their advantages and disadvantages.

  2. Pathogenesis, diagnosis and treatment of non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Verónica Martín-Domínguez

    2013-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD includes a broad spectrum of alterations that go from simple steatosis to steatohepatitis and cirrhosis. Type 2 diabetes mellitus (DM-2 and obesity are the principle factors associated to NAFLD. A 20-30 % prevalence in general population has been described. The survival of this type of patient is lower than the general population's, showing a higher incidence of hepatic and cardiovascular complications. The aetiopathogenesis is still unclear, but we know the intervention of different factors that produce fatty-acid accumulation in hepatic parenchyma, causing oxidative stress, oxygen-free radicals and the synthesis of an inflammatory cascade, that determine the progression of this disease from steatosis up to advanced fibrosis. The diagnostic gold-standard is still the liver biopsy, even though the development of newer non-invasive techniques, like serological and imaging (radiology, have opened a new field for research that allows bloodless testing of these patients and better study of the natural history of this disease. Nowadays, there is still no specific treatment for NAFLD. The development of healthy life habits and moderate exercise continue to be the pillars of treatment. Different pharmacological approaches have been studied and applied, such as the control of insulin resistance, lowering cholesterol levels, antioxidants, and other alternatives in experimental trials.

  3. Associations of Fatty Liver Disease with Hypertension, Diabetes, and Dyslipidemia: Comparison between Alcoholic and Nonalcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Nobuyuki Toshikuni

    2017-01-01

    Full Text Available Alcoholic steatohepatitis (ASH and nonalcoholic steatohepatitis (NASH are representative types of fatty liver disease (FLD and have similar histologic features. In this study, we aimed to compare the associations of the two FLD types with hypertension (HT, diabetes mellitus (DM, and dyslipidemia (DL. A nationwide survey investigating FLD status included 753 Japanese subjects (median age 55 years; male 440, female 313 with biopsy-proven ASH (n=172 or NASH (n=581. We performed a multiple logistic regression analysis to identify the factors associated with HT, DM, or DL. Older age and a higher body mass index were significant factors associated with HT. Older age, female sex, a higher body mass index, advanced liver fibrosis, and the NASH type of FLD (odds ratio 2.77; 95% confidence interval 1.78–4.31; P<0.0001 were significant factors associated with DM. Finally, the NASH type of FLD (odds ratio 4.05; 95% confidence interval 2.63–6.24; P<0.0001 was the only significant factor associated with DL. Thus, the associations of NASH with DM and DL were stronger than those of ASH with DM and DL. In the management of FLD subjects, controlling DM and DL is particularly important for NASH subjects.

  4. Bioinformatics-driven identification and examination of candidate genes for non-alcoholic fatty liver disease.

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    Karina Banasik

    2011-01-01

    Full Text Available Candidate genes for non-alcoholic fatty liver disease (NAFLD identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes.By integrating public database text mining, trans-organism protein-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs which captured all common variation in these genes were genotyped in 10,196 Danes, and analyzed for association with NAFLD-related quantitative traits, type 2 diabetes (T2D, central obesity, and WHO-defined metabolic syndrome (MetS.273 genes were included in the protein-protein interaction analysis and EHHADH, ECHS1, HADHA, HADHB, and ACADL were selected for further examination. A total of 10 nominal statistical significant associations (P<0.05 to quantitative metabolic traits were identified. Also, the case-control study showed associations between variation in the five genes and T2D, central obesity, and MetS, respectively. Bonferroni adjustments for multiple testing negated all associations.Using a bioinformatics approach we identified five candidate genes for NAFLD. However, we failed to provide evidence of associations with major effects between SNPs in these five genes and NAFLD-related quantitative traits, T2D, central obesity, and MetS.

  5. Healthy dietary pattern is inversely associated with non-alcoholic fatty liver disease in elderly.

    Science.gov (United States)

    Adriano, Lia Silveira; Sampaio, Helena Alves de Carvalho; Arruda, Soraia Pinheiro Machado; Portela, Clarissa Lima de Melo; de Melo, Maria Luisa Pereira; Carioca, Antônio Augusto Ferreira; Soares, Nadia Tavares

    2016-06-01

    The prevalence of non-alcoholic fatty liver disease (NAFLD) is rising, an increase that may be associated with changes in lifestyle such as unhealthy dietary patterns. Although advanced age is a risk factor for NAFLD, no studies reporting this association in the elderly population were found. In the present study, the association between dietary patterns and NAFLD in the elderly was assessed. A study including 229 older adults was conducted. NAFLD diagnosis was defined as individuals whose ultrasound examination disclosed hepatic steatosis at any stage, in the absence of excess intake of alcoholic beverages. Dietary patterns were obtained by principal components analysis. Mean scores and standard errors of each dietary pattern were calculated for the groups with and without NAFLD, and mean scores of the two groups were compared using the Mann-Whitney U test. The prevalence ratios and 95 % CI were estimated for each tertile of the dietary pattern adherence scores using Poisson multiple regression models with robust variance. A total of 103 (45 %) elderly with NAFLD and four dietary patterns were identified: traditional, regional snacks, energy dense and healthy. Mean scores for adherence to the healthy pattern in the groups with and without NAFLD differed. NAFLD was inversely associated with greater adherence to the healthy pattern and directly associated with the regional snacks, after adjustment for confounders. In conclusion, healthy dietary pattern is inversely associated with NAFLD in elderly.

  6. A Preclinical Model of Chronic Alcohol Consumption Reveals Increased Metastatic Seeding of Colon Cancer Cells in the Liver.

    Science.gov (United States)

    Im, Hwi-Jin; Kim, Hyeong-Geug; Lee, Jin-Seok; Kim, Hyo-Seon; Cho, Jung-Hyo; Jo, Il-Joo; Park, Sung-Joo; Son, Chang-Gue

    2016-04-01

    Liver metastasis is the main cause of death from colorectal cancer. Alcohol consumption impacts liver function and is suggested to be an independent risk factor for liver metastasis of colorectal cancer, but no experimental evidence supporting this hypothesis has been demonstrated to date. In this study, we investigated the effect of alcohol intake on liver metastasis. We examined colon cancer cell spread from the spleen in mice provided with water (control group), alcohol for 4 weeks before tumor injection (prealcohol), alcohol for 3 weeks after tumor injection (postalcohol), or alcohol throughout the 7-week study (alcohol). Alcohol intake significantly increased hepatic metastatic burden in the prealcohol (2.4-fold, P < 0.001), postalcohol (2.0-fold, P < 0.01), and alcohol groups (2.2-fold, P < 0.001). A fluorescence-based metastasis tracking assay also confirmed an alcohol-induced increase in the abundance of tumor cells in the liver (2.5-fold, P < 0.001). Investigation of the host microenvironment revealed an alcohol-induced inflammatory response marked by elevated TNFα, IL1β, IL6, and IFNγ protein levels, as well as increased expression of intercellular molecule-1 (ICAM1) in hepatic tissues after 4 weeks of alcohol consumption. Moreover, the peripheral blood of mice provided with alcohol for 4 weeks exhibited reduced natural killer and CD8(+) T-cell counts. Collectively, our findings suggest that chronic alcohol consumption accelerates liver metastasis of colorectal cancer cells through alterations to the liver microenvironment and inactivation of immune surveillance. Cancer Res; 76(7); 1698-704. ©2016 AACR. ©2016 American Association for Cancer Research.

  7. Liver glycerol permeability and aquaporin-9 are dysregulated in a murine model of Non-Alcoholic Fatty Liver Disease.

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    Patrizia Gena

    Full Text Available One form of liver steatosis, namely Non-Alcoholic Fatty Liver Disease (NAFLD, is a worrisome health problem worldwide characterized by intrahepatic triacylglycerol (TG overaccumulation. NAFLD is a common feature of metabolic syndrome being often associated with obesity, dyslipidemia and diabetes and mostly closely linked to insulin resistance. The mechanism of NAFLD pathogenesis is object of intense investigation especially regarding complex systems ultimately resulting in excessive TG deposition in hepatocytes. However, scarce is the attention about the relevance of hepatic import of glycerol, the other primary source (as glycerol-3-phosphate of increased TG in hepatocytes. Obese leptin-deficient (ob/ob mice, an animal model of NAFLD, were used to evaluate the functional involvement of Aquaporin-9 (AQP9, the major pathway of liver glycerol entry, in hepatosteatosis. By RT-PCR and qPCR, the level of Aqp9 mRNA in the liver of starved obese mice was comparable with the corresponding control lean littermates. By immunoblotting, the AQP9 protein at the hepatocyte sinusoidal plasma membrane of obese mice was markedly lower (33% than lean mice, a finding fully confirmed by immunohistochemistry. By stopped-flow light scattering, the liver glycerol permeability of ob/ob mice was significantly lower (53% than lean mice, a finding consistent with both the observed down-regulation of AQP9 protein and increased level of plasma glycerol characterizing obese mice. In summary, our results suggest implication of AQP9 in liver steatosis. The reduction of hepatocyte AQP9 and, consequently, glycerol permeability might be a defensive mechanism to counteract further fat infiltration in liver parenchyma.

  8. Protective Effects of Lemon Juice on Alcohol-Induced Liver Injury in Mice

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    Tong Zhou

    2017-01-01

    Full Text Available Chronic excessive alcohol consumption (more than 40–80 g/day for males and more than 20–40 g/day for females could induce serious liver injury. In this study, effects of lemon juice on chronic alcohol-induced liver injury in mice were evaluated. The serum biochemical profiles and hepatic lipid peroxidation levels, triacylglycerol (TG contents, antioxidant enzyme activities, and histopathological changes were examined for evaluating the hepatoprotective effects of lemon juice in mice. In addition, the in vitro antioxidant capacities of lemon juice were determined. The results showed that lemon juice significantly inhibited alcohol-induced increase of alanine transaminase (ALT, aspartate transaminase (AST, hepatic TG, and lipid peroxidation levels in a dose-dependent manner. Histopathological changes induced by alcohol were also remarkably improved by lemon juice treatment. These findings suggest that lemon juice has protective effects on alcohol-induced liver injury in mice. The protective effects might be related to the antioxidant capacity of lemon juice because lemon juice showed in vitro antioxidant capacity.

  9. A randomised controlled trial of a Mediterranean Dietary Intervention for Adults with Non Alcoholic Fatty Liver Disease (MEDINA): study protocol.

    Science.gov (United States)

    Papamiltiadous, Elena S; Roberts, Stuart K; Nicoll, Amanda J; Ryan, Marno C; Itsiopoulos, Catherine; Salim, Agus; Tierney, Audrey C

    2016-02-02

    Non-alcoholic fatty liver disease, the most prevalent liver disease in developed countries, remains difficult to manage with no proven safe and effective pharmacotherapy available. While weight reduction is the most commonly practiced treatment strategy, this is difficult to both achieve and/or maintain in the majority. Furthermore evidence-based dietary recommendations to guide the nutritional management of these patients are lacking. Using a randomised controlled trial design, this study compares the effectiveness of the Mediterranean diet to a standard low fat diet in terms of differences in insulin sensitivity, hepatic steatosis and metabolic outcomes in participants with non-alcoholic fatty liver disease. Ninety four eligible patients who have non-alcoholic fatty liver disease and who are insulin resistant, will be randomised into either a Mediterranean or low fat diet group for a 3 month intervention period. Insulin sensitivity will be measured on peripheral blood using Homeostatic Model Assessment and liver fat content quantified using Magnetic Resonance Spectroscopy. Both arms will consist of three face to face and three telephone call follow up consultations delivered by an Accredited Practicing Dietitian. The intervention arm focuses on recommendations from the traditional Mediterranean diet which have been tailored for use in the Australian population The standard arm uses the Australian Guide to Healthy Eating and the Australian National Heart Foundation dietary guidelines. Study recruitment will take place at four major metropolitan hospitals in Melbourne, Australia. Data collection will occur at all face to face reviews including baseline, 6, and 12 weeks. A follow up assessment to measure sustainability will take place at 6 and 12 months. The primary end point is improved insulin sensitivity scores at the 12 week time point. This trial aims to demonstrate in a large cohort of participants with NALFD that a Mediterranean diet independent of weight

  10. Anti-apoptotic effects of phyllanthin against alcohol- induced liver ...

    African Journals Online (AJOL)

    HepG2 cells alone and in co-culture with human monocytic (THP-1) differentiated macrophage cells. Methods: Cell viability was ... Results: Alcohol exposure significantly increased intracellular ROS generation (p < 0.001), decreased. MMP changes (p .... both cell types were cultured at a density of 3 x. 104 cells/well. Before ...

  11. Prevalence and risk factors for non-alcoholic fatty liver in children and youth with obesity.

    Science.gov (United States)

    Jimenez-Rivera, Carolina; Hadjiyannakis, Stasia; Davila, Jorge; Hurteau, Julie; Aglipay, Mary; Barrowman, Nick; Adamo, Kristi B

    2017-04-26

    Non- Alcoholic Fatty Liver (NAFL) is a spectrum of liver diseases (LD) that ranges from benign fatty infiltration of the liver to cirrhosis and hepatic failure. Hepatic ultrasound (US) and serum alanine aminotransferase (ALT) are often used as markers of NAFL. Our aim is to describe prevalence of NAFL and associated findings on ultrasound (US) and biochemical parameters in a population of children and adolescents with obesity at the Children's Hospital of Eastern Ontario. Children with Obesity (BMI >95th percentile) ages 8-17 years presenting to the Endocrinology and Gastroenterology clinics, without underlying LD were prospectively recruited from 2009 to 2012. Fasting lipid profile, HOMA IR) and serum adiponectin levels were measured. NAFL was defined as ALT > 25 and >22 IU/mL (males and females respectively) and/or evidence of fatty infiltration by US. Logistic regression was performed to assess associations. 97 children with obesity included in the study (Male 43%). Mean age was 12.9 ± 3.2 years (84% were older than 10 y). Mean BMI-Z score was 3.8 ± 1.4. NAFL was identified in 85%(82/97) of participants. ALT was elevated in 61% of patients. Median triglyceride (TG) level was higher in children with NAFL(1.5 ± 0.9 vs. 1.1 ± 0.5 mmol/L, p = 0.01). Total cholesterol, HDL, LDL and Non HDL cholesterol were similar in both groups(p = 0.63, p = 0.98, p = 0.72 and p = 0.37 respectively). HOMA IR was ≥3.16 in 53% of children(55% in those with NAFL and 40% in those without NAFL). Median serum adiponectin was 11.2 μg/ml(IQR 7.3-18.3) in children with NAFL vs. 16.1 μg/ml(IQR 9.0-21.9) in those without NAFL(p = 0.23). Liver US was reported as normal in 30%, mild fatty infiltration in 38%, moderate in 20% and severe in 12%. TG were significantly higher(1.5 mmol/L vs. 1.0 mmol/L, p obese children and youth. Elevated TG levels are associated with NAFL; these findings may serve as a noninvasive screening tool to help clinicians identify

  12. Role of Hedgehog signaling pathway in progression of non-alcoholic fatty liver fibrosis

    Directory of Open Access Journals (Sweden)

    AN Baiquan

    2015-03-01

    Full Text Available Obesity and related metabolic syndromes are prevalent on the global scale. Thus far, non-alcoholic fatty liver (NAFL disease has caused wide attention from domestic and overseas scholars. NAFL cirrhosis is considered to be the central part and inevitable stage of liver cirrhosis developed from simple fatty liver and non-alcoholic steatohepatitis. The effect of Hedgehog signaling pathway on hepatocytes in the progression of NAFL fibrosis was elucidated and investigated by a population study. Results showed that abnormal activation of the Hedgehog signaling pathway promoted the progression of NAFL fibrosis. In-depth study on the Hedgehog signaling pathway may provide a new approach for the treatment of NAFL fibrosis.

  13. Pituitary-testicular function in patients with alcoholic cirrhosis of the liver

    DEFF Research Database (Denmark)

    Bahnsen, M; Gluud, C; Johnsen, S G

    1981-01-01

    %) and reduced axillary hair (71%) was without significant relation to raised levels of sex-hormone binding globulin or progressively reduced liver function. In the presence of clinical or hormonal hypo-gonadism we found evidence of a state of primary hypogonadism together with an inadequate secretion......In forty-two patients with alcoholic liver cirrhosis and without recent alcohol ingestion the pituitary-testicular function was studied in an effort to relate the endocrine abnormalities with the degree of liver cell dysfunction, evaluated on a quantitative basis. Compared with values in twenty......-one healthy controls, we found significantly elevated serum oestrone, oestradiol, follicle-stimulating hormone, luteinizing hormone and prolactin (P less than 0.01). Serum dehydro-epiandrosterone and dehydroepiandrosterone sulphate were significantly reduced in the cirrhotics (P less than 0.01), whereas serum...

  14. Non-alcoholic fatty liver disease: the role of nuclear receptors and circadian rhythmicity.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Vinciguerra, Manlio; Oben, Jude; Tarquini, Roberto; De Cosmo, Salvatore

    2014-09-01

    Non-alcoholic fatty liver disease (NAFLD) is the accumulation of triglycerides in the hepatocytes in the absence of excess alcohol intake, and is caused by an imbalance between hepatic synthesis and breakdown of fats, as well as fatty acid storage and disposal. Liver metabolic pathways are driven by circadian biological clocks, and hepatic health is maintained by proper timing of circadian patterns of metabolic gene expression with the alternation of anabolic processes corresponding to feeding/activity during wake times, and catabolic processes characterizing fasting/resting during sleep. A number of nuclear receptors in the liver are expressed rhythmically, bind hormones and metabolites, sense energy flux and expenditure, and connect the metabolic pathways to the molecular clockwork throughout the 24-h day. In this review, we describe the role played by the nuclear receptors in the genesis of NAFLD in relationship with the circadian clock circuitry. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome.

    Science.gov (United States)

    Qureshi, K; Abrams, G A

    2016-04-01

    Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD). NAFLD encompasses simple fatty liver (FL) and non-alcoholic steatohepatitis (NASH) in its spectrum. NASH can progress to liver cirrhosis and is associated with liver cancer. Not all obese subjects have insulin resistance (IR) or develop metabolic syndrome (MS). This study evaluates the prevalence of NAFLD in severely obese subjects without MS. We retrospectively reviewed 445 charts from our database of severely obese subjects with clinical suspicion of NAFLD and who were selected for laparoscopic Roux-en-Y gastric bypass surgery. One hundred five subjects who did not have MS, as defined by the International Diabetes Foundation, based on comprehensive pre-operative metabolic evaluation were included. Liver biopsy specimens were evaluated for NAFLD. 24% of morbidly obese (mean body mass index [BMI] 48 kg m(-2) ) adult subjects (mean age 38 years) who underwent bariatric surgery did not have MS. NAFLD was identified in 77 (73%) on liver biopsy, out of which 59 (56%) were labelled as FL and 18 (17%) had histological diagnosis of NASH. Age, gender, race and BMI were the same among all groups. Among NAFLD subjects, 22% did not have any additional metabolic component of MS, while 36% had low high-density lipoprotein, 27% had hypertension, 8% had high triglycerides and 6% had hyperglycaemia. IR calculated by HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and diagnosis of hyperglycaemia was statistically higher in NASH group compared to those who did not have NASH. NAFLD is highly prevalent in morbidly obese individuals who undergo bariatric surgery despite the absence of MS. Diagnosis of hyperglycaemia in such subjects suggests the presence of IR and may have underlying NASH, which is a progressive form of NAFLD. © 2016 World Obesity.

  16. Hepatic lipase activity is increased in non-alcoholic fatty liver disease beyond insulin resistance.

    Science.gov (United States)

    Miksztowicz, V; Lucero, D; Zago, V; Cacciagiú, L; Lopez, G; Gonzalez Ballerga, E; Sordá, J; Fassio, E; Schreier, L; Berg, G

    2012-09-01

    Hepatic lipase is a lipolytic enzyme mostly synthesized and localized at the surface of liver sinusoidal capillaries, which hydrolyses triglycerides and phospholipids of intermediate density, large low density (LDL) and high density lipoproteins. Hepatic lipase activity is increased in insulin resistant states. Non-alcoholic fatty liver disease (NAFLD) is characterized by insulin resistance. However, at present, no data are available regarding the behaviour of hepatic lipase with regard to the degree of hepatic steatosis. Our aim was to evaluate hepatic lipase activity in NAFLD patients and its relationship to the severity of hepatic steatosis. We studied 48 patients with NAFLD (diagnosed by ultrasonography and confirmed by liver biopsy) and 30 controls. Steatosis was semi-quantitatively assessed and considered as mild or grade 1, moderate or grade 2 and severe or grade 3. hepatic lipase activity, lipid and lipoprotein profile (including intermediate density lipoproteins and dense LDL), adiponectin, insulin, glucose and high sensitivity C-reactive protein were measured. Homeostasis model assessment for insulin resistance (HOMA) index was calculated. Patients with hepatic steatosis presented with higher hepatic lipase activity, HOMA and dense LDL and lower levels of adiponectin, high density lipoproteins, cholesterol and apoA-I. Hepatic lipase activity positively correlated significantly with the severity of hepatic steatosis. Hepatic lipase correlated with a more atherogenic profile and persisted higher in patients even after corrected for age, gender, body mass index, HOMA and adiponectin. The higher hepatic lipase activity in NAFLD patients contributes to a more atherogenic profile linked to increased cardiovascular risk, beyond the insulin resistance and the reduction in adiponectin. Copyright © 2012 John Wiley & Sons, Ltd.

  17. Hepatic NAD(+) deficiency as a therapeutic target for non-alcoholic fatty liver disease in ageing.

    Science.gov (United States)

    Zhou, Can-Can; Yang, Xi; Hua, Xia; Liu, Jian; Fan, Mao-Bing; Li, Guo-Qiang; Song, Jie; Xu, Tian-Ying; Li, Zhi-Yong; Guan, Yun-Feng; Wang, Pei; Miao, Chao-Yu

    2016-08-01

    Ageing is an important risk factor of non-alcoholic fatty liver disease (NAFLD). Here, we investigated whether the deficiency of nicotinamide adenine dinucleotide (NAD(+) ), a ubiquitous coenzyme, links ageing with NAFLD. Hepatic concentrations of NAD(+) , protein levels of nicotinamide phosphoribosyltransferase (NAMPT) and several other critical enzymes regulating NAD(+) biosynthesis, were compared in middle-aged and aged mice or patients. The influences of NAD(+) decline on the steatosis and steatohepatitis were evaluated in wild-type and H247A dominant-negative, enzymically-inactive NAMPT transgenic mice (DN-NAMPT) given normal or high-fat diet (HFD). Hepatic NAD(+) level decreased in aged mice and humans. NAMPT-controlled NAD(+) salvage, but not de novo biosynthesis pathway, was compromised in liver of elderly mice and humans. Given normal chow, middle-age DN-NAMPT mice displayed systemic NAD(+) reduction and had moderate NAFLD phenotypes, including lipid accumulation, enhanced oxidative stress, triggered inflammation and impaired insulin sensitivity in liver. All these NAFLD phenotypes, especially release of pro-inflammatory factors, Kupffer cell accumulation, monocytes infiltration, NLRP3 inflammasome pathway and hepatic fibrosis (Masson's staining and α-SMA staining), deteriorated further under HFD challenge. Oral administration of nicotinamide riboside, a natural NAD(+) precursor, completely corrected these NAFLD phenotypes induced by NAD(+) deficiency alone or HFD, whereas adenovirus-mediated SIRT1 overexpression only partially rescued these phenotypes. These results provide the first evidence that ageing-associated NAD(+) deficiency is a critical risk factor for NAFLD, and suggest that supplementation with NAD(+) substrates may be a promising therapeutic strategy to prevent and treat NAFLD. © 2016 The British Pharmacological Society.

  18. HFE MUTATIONS AND IRON OVERLOAD IN PATIENTS WITH ALCOHOLIC LIVER DISEASE

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    Luis COSTA-MATOS

    2013-03-01

    Full Text Available Context Alcoholic liver disease (ALD is generally associated with iron overload, which may contribute to its pathogenesis, through increased oxidative stress and cellular damage. There are conflicting reports in literature about hemochromatosis (HFE gene mutations and the severity of liver disease in alcoholic patients. Objectives To compare the prevalence of mutations in the hemochromatosis (HFE gene between patients with ALD and healthy controls; to assess the relation of HFE mutations with liver iron stores and liver disease severity. Methods Liver biopsy specimens were obtained from 63 ALD patients (during routine treatment and 52 healthy controls (during elective cholecystectomy. All individuals underwent routine liver function tests and HFE genotyping (to detect wild-type sequences and C282Y, H63D, S65C, E168Q, E168X, V59M, H63H, P160delC, Q127H, Q283P, V53M and W164X mutations. Associations between HFE mutations and risk of excessive liver iron stores, abnormal serum ferritin, liver fibrosis, or necroinflammatory activity were assessed by multivariate logistic regression analysis. Results ALD patients had significantly higher serum ferritin and transferrin saturation than controls (both P<0.05, but the distribution of HFE mutations was similar between the two groups. For ALD patients, the odds ratio for having at least one HFE mutation and excessive liver iron stores was 17.23 (95% confidence interval (CI: 2.09-142.34, P = 0.008. However, the presence of at least one HFE mutation was not associated with an increased risk of liver fibrosis or necroinflammatory activity. Active alcohol ingestion showed the strongest association to increased serum ferritin (OR = 8.87, 95% CI: 2.11-34.78, P = 0.003. Conclusions ALD patients do not present with a differential profile of HFE mutations from healthy controls. In ALD patients, however, the presence of at least one HFE mutation increases the risk of having excessive liver iron stores but has no

  19. [Role of the endocrine system in the pathogenesis of non-alcoholic fatty liver disease].

    Science.gov (United States)

    Hagymási, Krisztina; Reismann, Péter; Rácz, Károly; Tulassay, Zsolt

    2009-11-29

    The most frequent liver disorder in metabolic syndrome is the nonalcoholic fatty liver disease. Its pathogenesis is a complex, multifactorial process, characterized by insulin resistance and involvement of the endocrine system. Hypothyroidism may lead to nonalcoholic steatohepatitis via hyperlipidemia and obesity. Adult patients with growth hormone deficiency have a metabolic syndrome-like phenotype with obesity and many characteristic metabolic alterations. The chronic activation of the hypothalamic-pituitary-adrenal axis results in metabolic syndrome as well. Cushing's syndrome has also features of metabolic syndrome. Mild elevation of transaminase activities is commonly seen in patients with adrenal failure. Non-alcoholic steatosis is twice as common in postmenopusal as in premenopausal women and hormonal replacement therapy decreases the risk of steatosis. Insulin resistance, diabetes mellitus type 2, sleeping apnoe syndrome, cardiovascular disorders and non-alcoholic fatty liver disease are more frequent in polycystic ovary syndrome. Hypoandrogenism in males and hyperandrogenism in females may lead to fatty liver via obesity and insulin resistance. Adipokines (leptin, acylation stimulating protein, adiponectin) have a potential role in the pathogenesis of nonalcoholic fatty liver. The alterations of endocrine system must be considered in the background of cryptogenic liver diseases. The endocrine perspective may help the therapeutic approaches in the future.

  20. Frequency of non alcoholic fatty liver disease (NAFLD) and its biochemical derangements in Type-2 diabetic patients

    International Nuclear Information System (INIS)

    Taseer, I.H.; Hussain, L.; Safdar, S.; Mirbahar, A.M.; Ahmad, I.

    2010-01-01

    Objective: To see the frequency of non-alcoholic fatty liver disease in Type-2 diabetic patients and to see iochemical derangements in NAFLD patients. Methodology: It is a cross-sectional study, conducted at Diabetic Research Centre and outpatient department Nishtar Hospital and PMRC Research Centre Nishtar Medical College, Multan. One hundred patients of either sex having type 2 diabetes mellitus attending diabetic out-patient department Nishtar Hospital Multan were included in the study. A pre-designed study proforma was filled with relevant investigations and clinical assessments were carried out in all cases. All the patients underwent abdominal ultrasonography. Data were entered in SPSS-11 and analyzed. Results: Out of one hundred patients, 51 (51%) were female and 49 (49%) were male. Mean age of the patients was 47.93 +- 8.57 years. Fifty one (51%) of the diabetic patients had fatty liver. Out of these 32 (62.75%) were female and 19 (37.25%) were male. Fatigue was present in 49 (53.26%), generalized weakness in 48 (52.18%), heaviness right upper abdomen in 22 (64.70%) and pain right upper abdomen in 20 (58.82%) of fatty liver patients. Corresponding figure in Non Fatty Liver Patients were 43 (46.74%), 44 (47.82%), 12 (35.30%) and 14(41.18%), respectively. Itching was noted in 19 (44.18%) patients of fatty liver while it was 24(55.82%) in non-fatty liver patients. Serum triglyceride level more than 160 mg/dl in 47 (92.15%) patients of fatty liver while serum cholesterol level more than 200 mg/dl was seen in 24(47.05%). Aspartate amino transferase (AST) more than 35 u/l was noted in seven (13.72%), alanine amino-transferase (ALT) more than 40u/l was noted in 6(11.76%) fatty liver patients while serum albumin and serum bilirubin were within normal range in all fatty liver and non-fatty liver patients. Conclusion: Nonalcoholic fatty liver disease (NAFLD) is more commonly seen in Type-2 diabetic patients. Serum triglyceride and serum cholesterol are significantly

  1. A Comparative Study Between Alcoholics of Koraga Community, Alcoholics of General Population and Healthy Controls for Antioxidant Markers and Liver Function Parameters

    Directory of Open Access Journals (Sweden)

    Virupaksha Devaramane

    2010-04-01

    Full Text Available Objectives: It is well established that long-term alcohol consumption leads to liver cirrhosis and other related disorders. Sufficient work has been done on biochemical markers of liver damage and antioxidant status of chronic alcoholics in general population. In the current study chronic alcoholics from a community called Koraga are analysed for the same parameters in a view to assess the extent of liver damage as compared to healthy controls and other alcoholics. Methods: Serum and urine samples from Koraga alcoholics (n=28, general alcoholics (n=30 and healthy controls (n=31 were analysed for liver function parameters and antioxidant markers. Liver function parameters were determined by automated analyzer. Markers of antioxidant status were estimated spectrophotometrically. The data was analysed using SPSS version 16.0. Results: There was significant increase in serum AST, serum ALT, serum GST and urine GST in both general and Koraga alcoholics when compared to healthy controls (p<0.0001. Serum ALT, serum GST and urine GST activity was significantly higher in general alcoholics when compared to Koraga alcoholics (p<0.001. Serum and urine total thiol levels were significantly lower in general alcoholics when compared to healthy controls and Koraga alcoholics (p<0.0001. We have observed no difference in total thiols level between healthy controls and Koraga alcoholics, in fact, there was significant increase in urine total thiols level in Koraga alcoholics compared to healthy controls (p<0.001. On Pearson’s correlation serum AST, serum ALT correlated positively with serum and urine GST (p<0.0001 and negatively with serum total thiols (p<0.0001. Serum GST correlated negatively with serum total thiols (p<0.0001. Conclusion: Results of our study possibly indicate that the extent of alcohol induced liver damage in Koraga subjects is comparatively lower than general alcoholics, even though the alcohol consumption is found to be higher in them

  2. The outcome of critical illness in decompensated alcoholic liver cirrhosis

    DEFF Research Database (Denmark)

    Kavli, M; Strøm, T; Carlsson, M

    2012-01-01

    BACKGROUND: The mortality of patients suffering from acute decompensated liver disease treated in the intensive care unit (ICU) varies between 50% and 100%. Previously published data suggest that liver-specific score systems are less accurate compared with the ICU-specific scoring systems acute...... physiology and chronic health evaluation II (APACHE II) and simplified organ failure assessment (SOFA) in predicting outcome. We hypothesized that in a Scandinavian cohort of ICU patients, APACHE II, SOFA, and simplified acute physiology score (SAPS II) were superior to predict outcome compared......%. If respiratory failure was further complicated by shock treated with vasopressor agents, the 90-day mortality increased to 89%. Ninety-day mortality for patients in need of mechanical ventilation, vasoactive medication, and renal replacement therapy because of acute kidney injury was 93%. CONCLUSION: APACHE II...

  3. FGF21, a liver hormone that inhibits alcohol intake in mice, increases in human circulation after acute alcohol ingestion and sustained binge drinking at Oktoberfest

    DEFF Research Database (Denmark)

    Søberg, Susanna; Andersen, Emilie S; Dalgaard, Niels B

    2018-01-01

    OBJECTIVE: Excessive alcohol consumption is a leading cause of global morbidity and mortality. However, knowledge of the biological factors that influence ad libitum alcohol intake may be incomplete. Two large studies recently linked variants in the KLB locus with levels of alcohol intake in humans....... KLB encodes β-klotho, co-receptor for the liver-derived hormone fibroblast growth factor 21 (FGF21). In mice, FGF21 reduces alcohol intake, and human Fgf21 variants are enriched among heavy drinkers. Thus, the liver may limit alcohol consumption by secreting FGF21. However, whether full-length, active...... plasma FGF21 (FGF21 (1-181)) levels in humans increase acutely or sub-chronically in response to alcohol ingestion is uncertain. METHODS: We recruited 10 healthy, fasted male subjects to receive an oral water or alcohol bolus with concurrent blood sampling for FGF21 (1-181) measurement in plasma...

  4. Lifestyle Modification through Dietary Intervention: Health Promotion of Patients with Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Manoochehr Khoshbaten

    2011-12-01

    Full Text Available Background: Prevalence of non-alcoholic fatty liver disease (NAFLD is more common worldwide and no certain treatment apart from lifestyle modification has been established yet. Available data consistently show that energy intake is significantly higher in patients with NAFLD than in individuals with no evidence of fatty liver. Changing nutritional behaviors seems to be the primary approach for treatment, simultaneously addressing all the clinical and biochemical defects. This study was aimed to examine the effects of two different composition of low energy diet (diet I vs. diet II on non-alcoholic fatty liver disease patients.Methods: In this double-blind randomized controlled trial, 44 ultrasonography-proven overweight non-alcoholic fatty liver disease patients were divided into two groups and received two low-energy diets (-500 kcal less than energy requirement individually inc. diet I (Carbohydrate: Fat: Protein: 55:25:20 and diet II (Carbohydrate: Fat: Protein: 40:40:20 for six weeks. Anthropometric and biochemical measures as well as liver enzymes were assessed after 12 hours fasting.Results: After diet I and diet II, weight decreased significantly (%1.82 and %2.45, respectively. Liver enzymes and echogenicity decreased significantly by both diet I and diet II. Mean of triglyceride concentration decreased (%18.09 after diet II (P=0.023, while there was no significant change after diet I. Significant correlations were found between changes in aspartate aminotransferase with triglyceride and LDL-C diet I.Conclusion: Low energy diets can decrease liver enzymes regardless of their composition, while diet II seems to be more effective than diet I in reduction of weight and triglyceride level.

  5. Transplanting Patients with Alcohol-related Liver Disease in the National Health System: New Rules and Decisions.

    Science.gov (United States)

    Parker, Richard; Holt, Andrew

    2018-01-23

    The UK has a socialized healthcare system that provides treatment that is free at the point of care for acute and chronic health disorders (the National Health Service-NHS), which is currently experiencing a period of unprecedented challenge. A narrative review that discusses present and future arrangements for transplantation of alcohol-related liver disease (ArLD) in the UK. Liver disease in the UK is reaching epidemic proportions due to obesity and metabolic disease compounding alcohol-mediated liver damage. Unfortunately, hepatology services in the UK are geographically disparate and subject to significant variations in liver morbidity and mortality, prompting concerns that this may negatively impair access to transplantation. In an attempt to improve referrals to tertiary liver services, the UK listing criteria for alcohol-associated liver disease were revised in 2016 by a working party under the aegis of the UK-Liver Advisory Group with the ambition of increasing opportunities for disease evaluation and improving the condition of candidates referred for assessment. Liver transplantation for ArLD is well established in the UK. Recent organizational changes seek to reduce inequities in access to transplant services. Liver disease in the UK is reaching epidemic proportions. Concerns over equity of access to liver transplantation prompted revision of the UK listing criteria for alcohol-associated liver disease in 2016, to improve to the availability of tertiary hepatology services. Transplanting patients with alcohol-related liver disease in the National Health System: New Rules and Decisions '…The second property of your excellent sherris is, the warming of the blood; which, before cold and settled, hath left the liver white and pale…'Falstaff; Henry IV Part 2: Act 4, Scene 3. © The Author 2018. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  6. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection--Liver: The "Musketeer" in the Spotlight.

    Science.gov (United States)

    Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

    2016-03-09

    The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a "vicious circle", eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved.

  7. Type 2 Diabetes in Non-Alcoholic Fatty Liver Disease and Hepatitis C Virus Infection—Liver: The “Musketeer” in the Spotlight

    Science.gov (United States)

    Ballestri, Stefano; Nascimbeni, Fabio; Romagnoli, Dante; Baldelli, Enrica; Targher, Giovanni; Lonardo, Amedeo

    2016-01-01

    The pathogenesis of type 2 diabetes (T2D) involves chronic hyperinsulinemia due to systemic and hepatic insulin resistance (IR), which if uncorrected, will lead to progressive pancreatic beta cell failure in predisposed individuals. Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of fatty (simple steatosis and steatohepatitis) and non-fatty liver changes (NASH-cirrhosis with or without hepatocellular carcinoma (HCC)) that are commonly observed among individuals with multiple metabolic derangements, notably including visceral obesity, IR and T2D. Hepatitis C virus (HCV) infection is also often associated with both hepatic steatosis and features of a specific HCV-associated dysmetabolic syndrome. In recent years, the key role of the steatotic liver in the development of IR and T2D has been increasingly recognized. Thus, in this comprehensive review we summarize the rapidly expanding body of evidence that links T2D with NAFLD and HCV infection. For each of these two liver diseases with systemic manifestations, we discuss the epidemiological burden, the pathophysiologic mechanisms and the clinical implications. To date, substantial evidence suggests that NAFLD and HCV play a key role in T2D development and that the interaction of T2D with liver disease may result in a “vicious circle”, eventually leading to an increased risk of all-cause mortality and liver-related and cardiovascular complications. Preliminary evidence also suggests that improvement of NAFLD is associated with a decreased incidence of T2D. Similarly, the prevention of T2D following HCV eradication in the era of direct-acting antiviral agents is a biologically plausible result. However, additional studies are required for further clarification of mechanisms involved. PMID:27005620

  8. Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects: the Lifelines Cohort Study.

    Science.gov (United States)

    van den Berg, Eline H; van Tienhoven-Wind, Lynnda J N; Amini, Marzyeh; Schreuder, Tim C M A; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P F

    2017-02-01

    Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a number of health issues, including atherosclerosis development and biochemical markers of increased cardiovascular risk. However, the association of thyroid hormones with NAFLD in euthyroid subjects has not been unequivocally established. We therefore determined associations of thyroid hormone parameters with NAFLD among euthyroid subjects. The study was conducted in the Lifelines Cohort Study, a population-based cohort study of participants living in the North of the Netherlands. Only euthyroid subjects (thyroid-stimulating hormone (TSH) 0.5-4.0mU/L, free thyroxine (FT4) 11-19.5pmol/L and free triiodothyronine (FT3) 4.4-6.7pmol/L) older than 18years were included. Exclusion criteria were participants with excessive alcohol use, known hepatitis or cirrhosis, liver functions ≥ three times the upper limit, current cancer, non-white ancestry, previous or current use of thyroid medication and current use of lipid or glucose lowering medication. A priori defined liver biochemistry, thyroid function parameters and metabolic syndrome (MetS) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI≥60 was categorized as NAFLD. A PNAFLD are characterized by higher FT3, lower FT4 and higher FT3/FT4 ratio, probably consequent to central obesity. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Reduction of obesity-associated white adipose tissue inflammation by rosiglitazone is associated with reduced non-alcoholic fatty liver disease in LDLr-deficient mice

    NARCIS (Netherlands)

    Mulder, P.; Morrison, M.C.; Verschuren, L.; Liang, W.; Bockel, J.H. van; Kooistra, T.; Wielinga, P.Y.; Kleemann, R.

    2016-01-01

    Obesity is associated with chronic low-grade inflammation that drives the development of metabolic diseases, including non-alcoholic fatty liver disease (NAFLD). We recently showed that white adipose tissue (WAT) constitutes an important source of inflammatory factors. Hence, interventions that

  10. Non-Alcoholic Fatty Liver Disease: The Bile Acid-Activated Farnesoid X Receptor as an Emerging Treatment Target

    Directory of Open Access Journals (Sweden)

    Michael Fuchs

    2012-01-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is currently evolving as the most common liver disease worldwide. It may progress to liver cirrhosis and liver cancer and is poised to represent the most common indication for liver transplantation in the near future. The pathogenesis of NAFLD is multifactorial and not fully understood, but it represents an insulin resistance state characterized by a cluster of cardiovascular risk factors including obesity, dyslipidemia, hyperglycemia, and hypertension. Importantly, NAFLD also has evolved as independent risk factor for cardiovascular disease. Unfortunately thus far no established treatment does exist for NAFLD. The bile acid-activated nuclear farnesoid X receptor (FXR has been shown to play a role not only in bile acid but also in lipid and glucose homeostasis. Specific targeting of FXR may be an elegant and very effective way to readjust dysregulated nuclear receptor-mediated metabolic pathways. This review discusses the body's complex response to the activation of FXR with its beneficial actions but also potential undesirable side effects.

  11. The Potential of Non-Provitamin A Carotenoids for the Prevention and Treatment of Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Ana Gabriela Murillo

    2016-11-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is an obesity-associated spectrum of comorbidities defined by the presence of metabolic dysfunction, oxidative stress, inflammation, and fibrosis in the liver. If left untreated, NAFLD can progress to cirrhosis, liver failure, or hepatocellular carcinoma. NAFLD is recognized as the most common liver disease in the United States, affecting around 30% of the population. Identification of dietary components capable of reducing or preventing NAFLD is therefore essential to battle this condition. Dietary carotenoids including astaxanthin, lycopene, lutein, and zeaxanthin have been demonstrated to be potent antioxidants as well as to exhibit anti-inflammatory effects. Many studies report the protective effect(s of these carotenoids against different conditions such as atherosclerosis, diabetic complications, age-related macular degeneration, and liver diseases. In this review, we will focus on the effects of these carotenoids in the prevention or reduction of NAFLD as seen in epidemiological observations and clinical trials, as well as the suggested mechanism of action derived from animal and cell studies.

  12. Rapid Recovery from Acute Liver Failure Secondary to Pancreatoduodenectomy-Related Non-Alcoholic Steatohepatitis

    Directory of Open Access Journals (Sweden)

    Kazushige Nirei

    2013-01-01

    Full Text Available This report describes a case of liver failure secondary to pancreatoduodenectomy and rapid recovery following treatment. A 68-year-old woman with cancer on the ampulla of Vater underwent surgery for pancreatoduodenectomy. The patient developed liver failure 3 months postsurgically. She was hospitalized after presenting with jaundice, hypoalbuminemia and decreased serum zinc. Computed tomography (CT of the abdomen showed a reduction in CT attenuation values postoperatively. We suspected fatty liver due to impaired absorption caused by pancreatoduodenectomy. We initiated treatment with branched-chain amino acids and a zinc formulation orally. Trace elements were administered intravenously. Two months after treatment, there was a noticeable improvement in CT findings. The patient’s jaundice and hypoalbuminemia prompted a liver biopsy, which led to a diagnosis of non-alcoholic steatohepatitis.

  13. [Psychosocial indication of liver transplantation for alcohol-related liver failure: current controversies and imminent issues in Japanese society].

    Science.gov (United States)

    Kiuchi, Tetsuya

    2012-10-01

    Organ transplant therapy is becoming a usual practice also in Japan, which dramatically improves the length and quality of life in patients with end-stage organ disease. Liver transplantation was resumed in Japan much later than that in the West and is continued now under unique circumstances where more than 90% of grafts come from living donors. Nevertheless the number of liver transplantation for alcohol-related liver failure shows a sharp rise to the level comparable to the West, and not a few physical and/or psychosocial problems caused by recidivism after transplantation are coming up. To find appropriate solutions to how to predict recidivism and define psychosocial indication of liver transplantation in our society, and to how to monitor and support sobriety after transplantation, there is an urgent need for multidisciplinary management by hepatologist, transplant surgeon, psychiatrist, and dependence specialist. Life-saving therapy and dependence management are expected to work closely together from the viewpoints of transparency, equity, utility, and autonomy requested in transplant therapy, protection of living donors, and consideration for donor family and public emotion.

  14. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Schütz, Tanja

    2000-01-01

    BACKGROUND/AIMS: No information is yet available about the influence of alcohol abuse on the translocation of larger molecules (Mr>1200) through the intestinal mucosa in man. The present study aimed to determine the intestinal permeability to macromolecules in patients with chronic alcohol abuse...... and mild to more advanced stages of liver disease, and to measure the concentration of endotoxins in the plasma, as these compounds derive from the intestinal flora and are suspected to contribute to the development of alcoholic liver disease (ALD). METHODS: The permeability to polyethylene glycol Mr 400......, Mr 1500, Mr 4000, and Mr 10,000 and endotoxin plasma concentrations were measured in 54 patients with alcoholic liver disease, 19 of them with cirrhosis, and in 30 non-alcoholic healthy controls. RESULTS: Permeability to polyethylene glycol Mr 400 was found to be unchanged in patients with ALD...

  15. Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease.

    Science.gov (United States)

    Rotman, Yaron; Sanyal, Arun J

    2017-01-01

    Given the high prevalence and rising incidence of non-alcoholic fatty liver disease (NAFLD), the absence of approved therapies is striking. Although the mainstay of treatment of NAFLD is weight loss, it is hard to maintain, prompting the need for pharmacotherapy as well. A greater understanding of disease pathogenesis in recent years was followed by development of new classes of medications, as well as potential repurposing of currently available agents. NAFLD therapies target four main pathways. The dominant approach is targeting hepatic fat accumulation and the resultant metabolic stress. Medications in this group include peroxisome proliferator-activator receptor agonists (eg, pioglitazone, elafibranor, saroglitazar), medications targeting the bile acid-farnesoid X receptor axis (obeticholic acid), inhibitors of de novo lipogenesis (aramchol, NDI-010976), incretins (liraglutide) and fibroblast growth factor (FGF)-21 or FGF-19 analogues. A second approach is targeting the oxidative stress, inflammation and injury that follow the metabolic stress. Medications from this group include antioxidants (vitamin E), medications with a target in the tumour necrosis factor α pathway (emricasan, pentoxifylline) and immune modulators (amlexanox, cenicriviroc). A third group has a target in the gut, including antiobesity agents such as orlistat or gut microbiome modulators (IMM-124e, faecal microbial transplant, solithromycin). Finally, as the ongoing injury leads to fibrosis, the harbinger of liver-related morbidity and mortality, antifibrotics (simtuzumab and GR-MD-02) will be an important element of therapy. It is very likely that in the next few years several medications will be available to clinicians treating patients with NAFLD across the entire spectrum of disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  16. An Animal Model for the Juvenile Non-Alcoholic Fatty Liver Disease and Non-Alcoholic Steatohepatitis.

    Science.gov (United States)

    Marin, Veronica; Rosso, Natalia; Dal Ben, Matteo; Raseni, Alan; Boschelle, Manuela; Degrassi, Cristina; Nemeckova, Ivana; Nachtigal, Petr; Avellini, Claudio; Tiribelli, Claudio; Gazzin, Silvia

    2016-01-01

    Non Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are the hepatic manifestations of the metabolic syndrome; worrisome is the booming increase in pediatric age. To recreate the full spectrum of juvenile liver pathology and investigate the gender impact, male and female C57Bl/6 mice were fed with high fat diet plus fructose in the drinking water (HFHC) immediately after weaning (equal to 3-years old human), and disease progression followed for 16 weeks, until adults (equal to 30-years old human). 100% of subjects of both genders on HFHC diet developed steatosis in 4weeks, and some degree of fibrosis in 8weeks, with the 86% of males and 15% of females presenting a stage 2 fibrosis at 16weeks. Despite a similar final liver damage both groups, a sex difference in the pathology progression was observed. Alterations in glucose homeostasis, dyslipidemia, hepatomegaly and obese phenotype were evident from the very beginning in males with an increased hepatic inflammatory activity. Conversely, such alterations were present in females only at the end of the HFHC diet (with the exception of insulin resistance and the hepatic inflammatory state). Interestingly, only females showed an altered hepatic redox state. This juvenile model appears a good platform to unravel the underlying gender dependent mechanisms in the progression from NAFLD to NASH, and to characterize novel therapeutic approaches.

  17. Liver enzymes: interaction analysis of smoking with alcohol consumption or BMI, comparing AST and ALT to γ-GT.

    Directory of Open Access Journals (Sweden)

    Lutz P Breitling

    Full Text Available BACKGROUND: A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT, routine liver markers less prone to enzyme induction. METHODOLOGY/PRINCIPAL FINDINGS: The present cross-sectional analysis was based on records from routine occupational health examinations of 15,281 male employees predominantly of the construction industry, conducted from 1986 to 1992 in Southern Germany. Associations of smoking intensity with log-transformed activities of γ-GT, AST, and ALT were examined in regression models adjusted for potential confounders and including an interaction of smoking with alcohol consumption or body mass index (BMI. Statistically significant interactions of smoking were observed with both alcohol consumption (AST and ALT, each with P<0.0001 and BMI (AST only, P<0.0001. The interactions all were in the same directions as for γ-GT, i.e. synergistic with alcohol and opposite with BMI. CONCLUSION: The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for γ-GT. This renders enzyme induction a less probable mechanism for these associations, whereas it might implicate exacerbated hepatocellular vulnerability and injury.

  18. Liver enzymes: interaction analysis of smoking with alcohol consumption or BMI, comparing AST and ALT to γ-GT.

    Science.gov (United States)

    Breitling, Lutz P; Arndt, Volker; Drath, Christoph; Brenner, Hermann

    2011-01-01

    A detrimental interaction between smoking and alcohol consumption with respect serum γ-glutamyltransferase (γ-GT) has recently been described. The underlying mechanisms remain unknown. The present work aimed to provide further insights by examining similar interactions pertaining to aspartate and alanine transaminase (AST, ALT), routine liver markers less prone to enzyme induction. The present cross-sectional analysis was based on records from routine occupational health examinations of 15,281 male employees predominantly of the construction industry, conducted from 1986 to 1992 in Southern Germany. Associations of smoking intensity with log-transformed activities of γ-GT, AST, and ALT were examined in regression models adjusted for potential confounders and including an interaction of smoking with alcohol consumption or body mass index (BMI). Statistically significant interactions of smoking were observed with both alcohol consumption (AST and ALT, each with P<0.0001) and BMI (AST only, P<0.0001). The interactions all were in the same directions as for γ-GT, i.e. synergistic with alcohol and opposite with BMI. The patterns of interaction between smoking and alcohol consumption or BMI with respect to AST and ALT resembled those observed for γ-GT. This renders enzyme induction a less probable mechanism for these associations, whereas it might implicate exacerbated hepatocellular vulnerability and injury.

  19. [Combination of NAFLD Fibrosis Score and liver stiffness measurement for identification of moderate fibrosis stages (II & III) in non-alcoholic fatty liver disease].

    Science.gov (United States)

    Drolz, Andreas; Wehmeyer, Malte; Diedrich, Tom; Piecha, Felix; Schulze Zur Wiesch, Julian; Kluwe, Johannes

    2018-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become one of the most frequent causes of chronic liver disease. Currently, therapeutic options for NAFLD patients are limited, but new pharmacologic agents are being investigated in the course of clinical trials. Because most of these studies are focusing on patients with fibrosis stages II and III (according to Kleiner), non-invasive identification of patients with intermediate fibrosis stages (II and III) is of increasing interest. Evaluation of NAFLD Fibrosis Score (NFS) and liver stiffness measurement (LSM) for prediction of fibrosis stages II/III. Patients with histologically confirmed NAFLD diagnosis were included in the study. All patients underwent a clinical and laboratory examination as well as a LSM prior to liver biopsy. Predictive value of NFS and LSM with respect to identification of fibrosis stages II/III was assessed. 134 NAFLD patients were included and analyzed. Median age was 53 (IQR 36 - 60) years, 55 patients (41 %) were female. 82 % of our patients were overweight/obese with typical aspects of metabolic syndrome. 84 patients (66 %) had liver fibrosis, 42 (50 %) advanced fibrosis. LSM and NFS correlated with fibrosis stage (r = 0.696 and r = 0.685, respectively; p stages II/III. If both criteria were met, probability of fibrosis stage II/III was 61 %. If none of the two criteria was met, chance for fibrosis stage II/III was only 6 % (negative predictive value 94 %). Combination of LSM and NFS enables identification of patients with significant probability of fibrosis stage II/III. Accordingly, these tests, especially in combination, may be a suitable screening tool for fibrosis stages II/III in NAFLD. The use of these non-invasive methods might also help to avoid unnecessary biopsies. © Georg Thieme Verlag KG Stuttgart · New York.

  20. A Nutrigenomic Approach to Non-Alcoholic Fatty Liver Disease.

    Science.gov (United States)

    Dongiovanni, Paola; Valenti, Luca

    2017-07-16

    Following the epidemics of obesity due to the consumption of high-calorie diet and sedentary lifestyle, nonalcoholic fatty liver disease (NAFLD) is now the leading cause of liver disease in Western countries. NAFLD is epidemiologically associated with metabolic syndrome and insulin resistance, and in susceptible individuals it may progress to cirrhosis and hepatocellular carcinoma. Genetic factors play a key role in NAFLD predisposition by interacting with nutritional and other environmental factors. To date, there is no drug therapy for the treatment of NAFLD, and the main clinical recommendation is lifestyle modification. In the last years, nutrigenomics is promoting an increased understanding of how nutrition affects the switch from health to disease by altering the expression of an individual's genetic makeup. The present review tries to summarize the most recent data evidencing how the interactions between nutrients and genetic factors can influence NAFLD development. The final goal should be to develop tools to quantify these complex interactions. The definition of a "nutrigenomic risk score" for each individual may represent a novel therapeutic approach for the management of NAFLD patients.

  1. Hepatic steatosis and non-alcoholic fatty liver disease are not associated with decline in renal function in people with Type 2 diabetes.

    Science.gov (United States)

    Jenks, S J; Conway, B R; Hor, T J; Williamson, R M; McLachlan, S; Robertson, C; Morling, J R; Strachan, M W J; Price, J F

    2014-09-01

    We aimed to determine whether the presence of hepatic steatosis and/or non-alcoholic fatty liver disease was associated with decline in renal function or onset of microalbuminuria in a cohort of people with Type 2 diabetes, including those managed in both primary and secondary care. Nine hundred and thirty-three patients from the Edinburgh Type 2 Diabetes Study, a cohort of Scottish men and women aged 60-74 years with Type 2 diabetes, underwent assessment for hepatic steatosis by liver ultrasonography 1 year after recruitment. Non-alcoholic fatty liver disease was defined as the presence of steatosis following exclusion of secondary causes of liver disease. Patients were followed for 4 years and decline in renal function was assessed by the change in estimated glomerular filtration rate over time. Of the 933 subjects, 530 had hepatic steatosis and, of those with hepatic steatosis, 388 had non-alcoholic fatty liver disease. Neither hepatic steatosis nor non-alcoholic fatty liver disease were significantly associated with rate of decline in renal function, with the mean rate of decline in estimated glomerular filtration rate being -1.55 ml min(-1) 1.73 m(-2) per year for participants with hepatic steatosis compared with -1.84 ml min(-1) 1.73 m(-2) for those without steatosis (P = 0.19). Similar results were obtained when the analysis was restricted to participants with and without non-alcoholic fatty liver disease (-1.44 vs. -1.64 ml min(-1) 1.73 m(-2) per year, respectively; P = 0.44). Additionally, neither hepatic steatosis nor non-alcoholic fatty liver disease were associated with the onset or regression of albuminuria during follow-up (all P ≥ 0.05). The presence of hepatic steatosis/non-alcoholic fatty liver disease was not associated with decline in renal function during a 4-year follow-up in our cohort of older people with Type 2 diabetes. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  2. Non-alcoholic fatty liver disease: What the clinician needs to know

    Science.gov (United States)

    Machado, Mariana Verdelho; Cortez-Pinto, Helena

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691

  3. CORRECTION OF MICROCIRCULATORY DISORDERS IN NON-ALCOHOLIC FATTY LIVER DISEASE IN PATIENTS WITH CHRONIC HEART FAILURE PATIENTS

    Directory of Open Access Journals (Sweden)

    M. E. Statsenko

    2016-01-01

    Full Text Available Combined liver damage in patients with chronic heart failure and non-alcoholic fatty liver disease leads to the formation of pathological hemodynamic types of microcirculation with prevalence of shunt blood flow, nutritional deficiency, that correlated with changes in the functional state of the liver. Using cytoprotector mexicor for 16 weeks as part of the basic treatment of patients with chronic heart failure and non-alcoholic fatty liver disease can correct these microcirculatory disorders, has a beneficial effect on endothelial function, autonomic tone of microvessels, which is accompanied by the positive dynamics of indicators of cytolysis and cholestasis.

  4. The Association between Non-Alcoholic Fatty Liver Disease and Cardiovascular Risk in Children

    Directory of Open Access Journals (Sweden)

    Anna Di Sessa

    2017-07-01

    Full Text Available The rising prevalence of childhood obesity in the past decades has made Non-Alcoholic Fatty Liver Disease (NAFLD the most common cause of pediatric chronic liver disease worldwide. Currently, a growing body of evidence links NAFLD with cardiovascular disease (CVD even at an early age. Data on the pediatric population have shown that NAFLD could represent an independent risk factor not only for cardiovascular events but also for early subclinical abnormalities in myocardial structure and function. Briefly, we review the current knowledge regarding the relationship between pediatric NAFLD and cardiovascular risk in an attempt to clarify our understanding of NAFLD as a possible cardiovascular risk factor in childhood.

  5. GLP-1 Receptor Agonist and Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Jinmi Lee

    2012-08-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD, one of the most common liver diseases, is caused by the disruption of hepatic lipid homeostasis. It is associated with insulin resistance as seen in type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1 is an incretin that increases insulin sensitivity and aids glucose metabolism. In recent in vivo and in vitro studies, GLP-1 presents a novel therapeutic approach against NAFLD by increasing fatty acid oxidation, decreasing lipogenesis, and improving hepatic glucose metabolism. In this report, we provide an overview of the role and mechanism of GLP-1 in relieving NAFLD.

  6. Noninvasive assessment of alcoholic liver disease using unidimensional transient elastography (Fibroscan®)

    Science.gov (United States)

    Lupsor-Platon, Monica; Badea, Radu

    2015-01-01

    Unidimensional transient elastography (TE) is a noninvasive technique, which has been increasingly used in the assessment of diffuse liver diseases. This paper focuses on reviewing the existing data on the use of TE in the diagnosis of fibrosis and in monitoring disease progression in alcoholic liver disease, on the factors that may influence the result of fibrosis prediction, and last but not least, on its potential use in assessing the steatosis degree. Therefore, this field is far from being exhausted and deserves more attention. Further studies are required, on large groups of biopsied patients, in order to find answers to all the remaining questions in this field. PMID:26576080

  7. Bioinformatics-Driven Identification and Examination of Candidate Genes for Non-Alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Banasik, Karina; Justesen, Johanne M.; Hornbak, Malene

    2011-01-01

    Objective: Candidate genes for non-alcoholic fatty liver disease (NAFLD) identified by a bioinformatics approach were examined for variant associations to quantitative traits of NAFLD-related phenotypes. Research Design and Methods: By integrating public database text mining, trans-organism protein......-protein interaction transferal, and information on liver protein expression a protein-protein interaction network was constructed and from this a smaller isolated interactome was identified. Five genes from this interactome were selected for genetic analysis. Twenty-one tag single-nucleotide polymorphisms (SNPs...

  8. Non-Alcoholic Fatty Liver Disease (NAFLD): new challenge for general practitioners and important burden for health authorities?

    Science.gov (United States)

    Ahmed, Mohamed H; Abu, Emmanuel O; Byrne, Christopher D

    2010-10-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of hepatic dysfunction encountered in general practice. A large proportion of individuals with type 2 diabetes and the metabolic syndrome develop NAFLD. NAFLD is associated with severe insulin resistance and increased risk of cardiovascular disease and can progress to non-alcoholic steato-hepatitis, liver cirrhosis and cancer. Currently the only known effective treatments for NAFLD are lifestyle changes including stable weight loss and a diet low in calories. General practitioners will increasingly play a key role in dealing with this evolving but serious epidemic of NAFLD and associated metabolic complications. However, success will depend on the appropriate systems and mechanisms being in place in primary care and the proper motivation, support and education of the patient. This review provides the primary care physician with: (a) a step-by step guide of how to identify NAFLD, (b) information to exclude common other causes of liver fat accumulation and (c) additional insight into relationships between NAFLD and other conditions such as obesity, cardiovascular disease and type 2 diabetes. Copyright © 2010 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  9. Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease.

    Science.gov (United States)

    Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

    2016-03-01

    The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). A total of 186 patients were included 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, psteatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥ 90%, CAP cutoffs for the detection of ≥ S2 and ≥ S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.

  10. Protective effect of Zhuyeqing liquor, a Chinese traditional health liquor, on acute alcohol-induced liver injury in mice.

    Science.gov (United States)

    Gao, Hong-Ying; Huang, Jian; Wang, Hang-Yu; Du, Xiao-Wei; Cheng, Suo-Ming; Han, Ying; Wang, Li-Fei; Li, Guo-Yu; Wang, Jin-Hui

    2013-10-03

    The study first evaluated the hepatoprotective effect of Zhuyeqing Liquor (ZYQL) against acute alcohol-induced liver injury in mice. Animals were administered orally with 50% alcohol 12 ml/kg at 4 h after the doses of ZYQL everyday for fourteen consecutive days except mice in normal group. The protective effect was evaluated by biochemical parameters including serum aspartate transaminase (AST), alanine transferase (ALT), total-bilirubin (TBIL) and reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD) in liver tissue. The result were confirmed histopathologically and the expression of TNF-α in mice liver was determined by immunohistochemistry analysis. HPLC-PDA was used for phytochemical analysis of ZYQL, and the plant source of each compound was claritied by UPLC-TOF-MS. The result showed that pretreatment with ZYQL exhibited a significant protective effect by reversing the biochemical parameters and histopathological changes in a dose depended manner. HPLC analysis indicated that ZYQL contained flavonoids, iridoids, terpenoids and phenolic acids, which might be the active chemicals. This study demonstrated the hepatoprotective activity of ZYQL, thus scientifically supported the function of its health care.

  11. Interaction of occupational manganese exposure and alcohol drinking aggravates the increase of liver enzyme concentrations from a cross-sectional study in China.

    Science.gov (United States)

    Deng, Qi; Liu, Jing; Li, Qing; Chen, Kangcheng; Liu, Zhenfang; Shen, Yuefei; Niu, Piye; Yang, Yiping; Zou, Yunfeng; Yang, Xiaobo

    2013-04-15

    Over exposure to manganese (Mn) can damage the human central nervous system and potentially cause liver toxicity. Alcohol drinking is also one of the well-known harmful factors to hepatic organism. The interaction between Mn exposure and alcohol consumption to liver function was investigated in this study. A total of 1112 on-the-spot workers were included in the cross-sectional survey from a large scale of manganese exposed workers healthy cohort (MEWHC) in a ferro-manganese refinery company. A questionnaire was used to collect the demographic information, occupational history, and alcohol drinking habits. Occupational health examination was carried out for each worker. The five key serum indices, including total bilirubin (TBILI), direct bilirubin (DBILI), indirect bilirubin (IBILI), alanine transaminase (ALT), and aspartate transaminase (AST), were determined to evaluate the liver function of each subject. Workers exposed to high levels of Mn had significantly elevated serum concentrations of liver enzymes (DBILI: 3.84±1.20 μmol/L, ALT: 27.04±19.12 IU/L, and AST: 29.96±16.68 IU/L), when compared to those in the low-exposure group (DBIL: 3.54±0.85 μmol/L, ALT: 20.38±10.97 IU/L, and AST: 26.39±8.07 IU/L), all Palcohol drinking also showed higher concentrations of liver enzymes than those non-drinkers, especially, and there was significant interaction between Mn exposure and alcohol consumption in terms of these three indices (Palcohol drinking to potentially aggravate the liver damage. It will be important for Mn exposed workers to control drinking and also assess liver function in the occupational health examination.

  12. Where should the safe limits of alcohol consumption stand in light of liver enzyme abnormalities in alcohol consumers?

    Directory of Open Access Journals (Sweden)

    Onni Niemelä

    Full Text Available To estimate the prevalence and risk factors for abnormal liver enzymes in a large age- and gender stratified population-based sample of apparently healthy individuals with or without alcohol consumption and other health-related risk factors (adiposity, physical inactivity, smoking.Data on alcohol use, smoking, diet and physical activity were recorded using structured questionnaires from 13,976 subjects (6513 men, 7463 women, aged 25-74 years in the national FINRISK studies. Alcohol data was used to categorize the participants into abstainers, light drinkers, moderate drinkers and heavy drinkers. Serum gamma-glutamyltransferase (GGT and alanine aminotransferase (ALT activities were measured using standard kinetic methods.Male light drinkers, moderate drinkers and heavy drinkers showed significantly higher relative risks of abnormal GGT than abstainers: 1.37 (95% confidence interval 1.11 to 1.71, p < 0.01, 2.72 (2.08 to 3.56, p < 0.0005, and 6.10 (4.55 to 7.17, p < 0.0005, respectively. Corresponding values for women were 1.22 (0.99 to 1.51, p = 0.065, 1.90 (1.44 to 2.51, p < 0.0005, and 5.91 (3.80 to 9.17, p < 0.0005. Estimated threshold doses for a significant GGT elevation was 14 standard weekly alcohol doses for men and 7 for women. Excess body weight and age over 40 years modulated the thresholds towards smaller quantities of alcohol. The risk of abnormal GGT was also significantly influenced by physical inactivity and smoking. The relative risks of abnormal ALT activities were increased in male heavy drinkers, especially in those presenting with adiposity and sedentary lifestyle.Alcohol use markedly increases the risk for abnormal liver enzyme activities in those presenting with age over 40 years, obesity, smoking or sedentary lifestyle. The data should be considered in public health recommendations and in the definitions of safe limits of alcohol use.

  13. Analysis of the relationship between interleukin polymorphisms within miRNA-binding regions and alcoholic liver disease.

    Science.gov (United States)

    Novo-Veleiro, I; Cieza-Borrella, C; Pastor, I; González-Sarmiento, Rogelio; Laso, F-J; Marcos, M

    2018-03-19

    Alcohol consumption promotes inflammation through the Toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, leading to organic damage. Some micro-RNA (miRNA) molecules modulate this inflammatory response by downregulating TLR4/NF-κB pathway mediators, like interleukins (ILs). Thus, polymorphisms within IL genes located near miRNA binding sites could modify the risk of ethanol-induced damage. The present study analyzed potential relationships between alcoholism or alcoholic liver disease (ALD) and IL12B 2124 G>T (rs1368439), IL16 5000 C>T (rs1131445), IL1R1 3114 C>T (rs3917328), and NFKB1 3400 A>G (rs4648143) polymorphisms. The study included 301 male alcoholic patients and 156 male healthy volunteers. Polymorphisms were genotyped using TaqMan ® PCR assays for allelic discrimination. Allele and genotype frequencies were compared between groups. Logistic regression analysis was performed to analyze the inheritance model. Analysis of the IL1R1 (rs3917328) polymorphism showed that the proportion of alleleT carriers (CT and TT genotypes) was higher in healthy controls (9.7%) than in alcoholic patients (6.5%; P=.042). However, multivariable logistic regression analyses did not yield a significant result. No differences between groups were found for other analyzed polymorphisms. Our study describes, for the first time, the expected frequencies of certain polymorphisms within miRNA-binding sites in alcoholic patients with and without ALD. Further studies should be developed to clarify the potential relevance of these polymorphisms in alcoholism and ALD development. Copyright © 2018 Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI). All rights reserved.

  14. Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

    DEFF Research Database (Denmark)

    Becker, U; Gluud, C; Farholt, S

    1991-01-01

    , elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione...

  15. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    Science.gov (United States)

    Kirpich, Irina A; Marsano, Luis S; McClain, Craig J

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of diseases involving hepatic fat accumulation, inflammation with the potential progression to fibrosis and cirrhosis over time. NAFLD is often associated with obesity, insulin resistance, and diabetes. The interactions between the liver and the gut, the so-called "gut-liver axis", play a critical role in NAFLD onset and progression. Compelling evidence links the gut microbiome, intestinal barrier integrity, and NAFLD. The dietary factors may alter the gut microbiota and intestinal barrier function, favoring the occurrence of metabolic endotoxemia and low grade inflammation, thereby contributing to the development of obesity and obesity-associated fatty liver disease. Therapeutic manipulations with prebiotics and probiotics to modulate the gut microbiota and maintain intestinal barrier integrity are potential agents for NAFLD management. This review summarizes the current knowledge regarding the complex interplay between the gut microbiota, intestinal barrier, and dietary factors in NAFLD pathogenesis. The concepts addressed in this review have important clinical implications, although more work needs to be done to understand how dietary factors affect the gut barrier and microbiota, and to comprehend how microbe-derived components may interfere with the host's metabolism contributing to NAFLD development. Copyright © 2015 The Canadian Society of Clinical Chemists. All rights reserved.

  16. Dorothy Hodgkin Lecture 2012: non-alcoholic fatty liver disease, insulin resistance and ectopic fat: a new problem in diabetes management.

    Science.gov (United States)

    Byrne, C D

    2012-09-01

    Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome. Non-alcoholic fatty liver disease is a spectrum of fat-associated liver conditions that can result in end-stage liver disease and the need for liver transplantation. Simple steatosis, or fatty liver, occurs early in non-alcoholic fatty liver disease and may progress to non-alcoholic steatohepatitis, fibrosis and cirrhosis with increased risk of hepatocellular carcinoma. Prevalence estimates for non-alcoholic fatty liver disease range from 17 to 33% in the general populations and it has been estimated that non-alcoholic fatty liver disease exists in up to 70% of people with Type 2 diabetes. Non-alcoholic fatty liver disease increases risk of Type 2 diabetes and cardiovascular disease. In people with Type 2 diabetes, non-alcoholic fatty liver disease is the most frequent cause (∼80%) of fatty liver diagnosed by ultrasound. As non-alcoholic fatty liver disease is strongly associated with insulin resistance, the presence of non-alcoholic fatty liver disease with diabetes often contributes to poor glycaemic control. Consequently, strategies that decrease liver fat and improve whole-body insulin sensitivity may both contribute to prevention of Type 2 diabetes and to better glycaemic control in people who already have developed diabetes. This review summarizes the Dorothy Hodgkin lecture given by the author at the 2012 Diabetes UK annual scientific conference, proposing that fatty acid fluxes through the liver are crucial for the pathogenesis of non-alcoholic fatty liver disease and for increasing insulin resistance. © 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.

  17. Association between novel MRI-estimated pancreatic fat and liver histology-determined steatosis and fibrosis in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Patel, N S; Peterson, M R; Brenner, D A; Heba, E; Sirlin, C; Loomba, R

    2013-03-01

    Ectopic fat deposition in the pancreas and its association with hepatic steatosis have not previously been examined in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD). To quantify pancreatic fat using a novel magnetic resonance imaging (MRI) technique and determine whether it is associated with hepatic steatosis and/or fibrosis in patients with NAFLD. This is a cross-sectional study including 43 adult patients with biopsy-proven NAFLD who underwent clinical evaluation, biochemical testing and MRI. The liver biopsy assessment was performed using the NASH-CRN histological scoring system, and liver and pancreas fat quantification was performed using a novel, validated MRI biomarker; the proton density fat fraction. The average MRI-determined pancreatic fat in patients with NAFLD was 8.5% and did not vary significantly between head, body, and tail of the pancreas. MRI-determined pancreatic fat content increased significantly with increasing histology-determined hepatic steatosis grade; 4.6% in grade 1; 7.7% in grade 2; 13.0% in grade 3 (P = 0.004) respectively. Pancreatic fat content was lower in patients with histology-determined liver fibrosis than in those without fibrosis (11.2% in stage 0 fibrosis vs. 5.8% in stage 1-2 fibrosis, and 6.9% in stage 3-4 fibrosis, P = 0.013). Pancreatic fat did not correlate with age, body mass index or diabetes status. In patients with NAFLD, increased pancreatic fat is associated with hepatic steatosis. However, liver fibrosis is inversely associated with pancreatic fat content. Further studies are needed to determine underlying mechanisms to understand if pancreatic steatosis affects progression of NAFLD. © 2013 Blackwell Publishing Ltd.

  18. Fatty acid composition in serum correlates with that in the liver and non-alcoholic fatty liver disease activity scores in mice fed a high-fat diet.

    Science.gov (United States)

    Wang, Xing-He; Li, Chun-Yan; Muhammad, Ishfaq; Zhang, Xiu-Ying

    2016-06-01

    In this study, we investigated the correlation between the serum fatty acid composition and hepatic steatosis, inflammation, hepatocellular ballooning scores, and liver fatty acids composition in mice fed a high-fat diet. Livers were collected for non-alcoholic fatty liver disease score analysis. Fatty acid compositions were analysed by gas chromatography. Correlations were determined by Pearson correlation coefficient. Exposed to a high-fat diet, mice developed fatty liver disease with varying severity without fibrosis. The serum fatty acid variation became more severe with prolonged exposure to a high-fat diet. This variation also correlated significantly with the variation in livers, with the types of fatty acids corresponding to liver steatosis, inflammation, and hepatocellular ballooning scores. Results of this study lead to the following hypothesis: the extent of serum fatty acid variation may be a preliminary biomarker of fatty liver disease caused by high-fat intake. Copyright © 2016. Published by Elsevier B.V.

  19. Peroxisome Proliferator-Activated Receptor and Retinoic X Receptor in Alcoholic Liver Disease

    Directory of Open Access Journals (Sweden)

    Tommaso Mello

    2009-01-01

    Full Text Available A growing number of new studies demonstrate that nuclear receptors are involved in the development of alcoholic liver disease (ALD. Ethanol metabolism and RXR/PPAR functions are tightly interconnected in the liver. Several ethanol metabolizing enzymes are potently regulated by RXR and PPAR after alcohol consumption. The increased ethanol metabolism, in turn, leads to alteration of the redox balance of the cells and impairment of RXR/PPAR functions by direct and indirect effects of acetaldehyde, resulting in deranged lipid metabolism, oxidative stress, and release of proinflammatory cytokines. The use of animal models played a crucial role in understanding the molecular mechanisms of ALD. In this paper we summarize the reciprocal interactions between ethanol metabolism and RXR/PPAR functions. In conclusion, RXR and PPAR play a central role in the onset and perpetuation of the mechanisms underling all steps of the clinical progression in ALD.

  20. Plasma fibrinogen-like protein 2 levels in patients with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Colak, Yasar; Senates, Ebubekir; Ozturk, Oguzhan; Yilmaz, Yusuf; Coskunpinar, Ender; Kahraman, Ozlem Timirci; Sahin, Onder; Zemheri, Ebru; Enc, Feruze Yilmaz; Ulasoglu, Celal; Kiziltas, Safak; Kurdas, Oya Ovunc; Tuncer, Ilyas

    2011-01-01

    Fibrinogen-like protein 2 (fgl2), has recently been identified as a new member of the fibrinogen-like family of proteins. In this study we assayed plasma levels of fgl2 in patients with biopsy proven non-alcoholic fatty liver disease (NAFLD) and examined their association with clinical, biochemical and histological phenotypes. Levels of plasma fgl2 were measured by enzyme linked immunosorbent assay and compared between the study groups. Moreover, concentrations of fgl2 were assessed in relation to the general characteristics of the study participants and the results of the liver biopsy. Levels of fgl2 were significantly higher in patients with definite non-alcoholic steatohepatitis (NASH) (788±190pg/mL, psubject to future confirmation, our data suggest that fgl2 levels are elevated in the more severe forms of NAFLD.

  1. A case of alcoholic hepatitis demonstrating focal fatty infiltration of the liver on computed tomography

    International Nuclear Information System (INIS)

    Uesaka, Toshihiro; Kato, Masayoshi; Nagai, Tadayuki; Kametani, Tomio; Horigami, Tateyuki; Takimoto, Hiroaki; Tanino, Mikio

    1985-01-01

    Focal fatty infiltration of the liver is a newly recognized entity that may be confused with primary neoplasm or tumor metastasis on computed tomography. We report a 31-year-old woman with a history of chronic alcoholism. Physical examination revealed jaundice, marked hepatomegaly and ascites. Laboratory studies revealed mild elevation of bilirubin, AlP, GOT, γ-GTP and marked leukocytosis. Abdominal CT showed a large area of decreased density in the right lobe. The radionuclide scan demonstrated the area of diminished activity located in the central portion of the right lobe. Ultrasonography demonstrated high echoic mass shadows in the right lobe. The rapid disappearance of the low density area on CT was recognized. The liver biopsy specimen revealed fatty metamorphosis, alcoholic hyaline bodies, pericellular fibrosis and mild lobular disorganization. Focal fatty infiltration can mimic focal hepatic lesions and repeat CT scans are useful in diagnosis. (author)

  2. Effects of Various Drugs on Alcohol-induced Oxidative Stress in the Liver

    Directory of Open Access Journals (Sweden)

    Svetlana Trivic

    2008-09-01

    Full Text Available The major aim of this work was to investigate how alcohol-induced oxidative stress in combined chemotherapy changes the metabolic function of the liver in experimental animals. This research was conducted to establish how bromocriptine, haloperidol and azithromycin, applied to the experimental model, affected the antioxidative status of the liver. The following parameters were determined: reduced glutathione, activities of glutathione peroxidase, glutathione reductase, peroxidase, catalase, xanthine oxidase and lipid peroxidation intensity. Alanine transaminase was measured in serum. Alcohol stress (AO group reduced glutathione and the activity of xanthine oxidase and glutathione peroxidase, but increased catalase and alanine transaminase activity. The best protective effect was achieved with the bromocriptine (AB1 group, while other groups had similar effects on the studied parameters.

  3. Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases

    Directory of Open Access Journals (Sweden)

    Eugene Han

    2017-11-01

    Full Text Available As the number of individuals with non-alcoholic fatty liver disease (NAFLD has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged.

  4. Alcoholic liver injury: defenestration in noncirrhotic livers--a scanning electron microscopic study

    DEFF Research Database (Denmark)

    Horn, T; Christoffersen, P; Henriksen, Jens Henrik Sahl

    1987-01-01

    The fenestration of hepatic sinusoidal endothelial cells in 15 needle biopsies obtained from chronic alcoholics without cirrhosis was studied by scanning electron microscopy. As compared to nonalcoholics, a significant reduction in the number of fenestrae and porosity of the sinusoidal lining wall...

  5. A comparison of liver fat content as determined by magnetic resonance imaging-proton density fat fraction and MRS versus liver histology in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Idilman, Ilkay S; Keskin, Onur; Celik, Azim; Savas, Berna; Elhan, Atilla Halil; Idilman, Ramazan; Karcaaltincaba, Musturay

    2016-03-01

    Many imaging methods have been defined for quantification of hepatic steatosis in non-alcoholic fatty liver disease (NAFLD). However, studies comparing the efficiency of magnetic resonance imaging-proton density fat fraction (MRI-PDFF), magnetic resonance spectroscopy (MRS), and liver histology for quantification of liver fat content are limited. To compare the efficiency of MRI-PDFF and MRS in the quantification of liver fat content in individuals with NAFLD. A total of 19 NAFLD patients underwent MRI-PDFF, MRS, and liver biopsy for quantification of liver fat content. The MR examinations were performed on a 1.5 HDx MRI system. The MRI protocol included T1-independent volumetric multi-echo gradient-echo imaging with T2* correction and spectral fat modeling and MRS with STEAM technique. A close correlation was observed between liver MRI-PDFF- and histology- determined steatosis (r = 0.743, P steatosis (r = 0.712, P hepatic steatosis, a high correlation was observed between the two MRI methods (r = 0.986, P steatosis from mild/no hepatic steatosis (P = 0.007 and 0.013, respectively), with no superiority between them (AUCMRI-PDFF = 0.881 ± 0.0856 versus AUCMRS = 0.857 ± 0.0924, P = 0.461). Both MRI-PDFF and MRS can be used for accurate quantification of hepatic steatosis. © The Foundation Acta Radiologica 2015.

  6. Clinical Characteristics in Patients with Liver Cirrhosis Induced by HBV Infection and Combined with Mild Alcohol Intake

    Directory of Open Access Journals (Sweden)

    Xiaerfuhazi Ha-lida

    2014-09-01

    Full Text Available Objective To investigate the differences of clinical and biochemical characteristics between patients with liver cirrhosis induced by HBV infection combined with and without mild alcohol intake.

  7. [Role of leptin and leptin resistance in non-alcoholic fatty liver disease development in persons with obesity and overweight].

    Science.gov (United States)

    Livzan, M A; Lapteva, I V; Miller, T S

    2014-01-01

    To study the impact of leptin and leptinresistance on formation of non-alcoholic fatty liver disease (NAFLD) of people with obesity and overweight. 105 patients with obesity and overweight were examined, among them 19 men and 86 women, median age 58 (50-63) years. Risk factors development NAFLD, anthropometric indices, biochemical analysis of blood, abdominal ultrasonic studies, levels leptin and its soluble receptor were estimated. examined people with NAFLD were included into 2 groups: main group (patients NAFLD, n = 77) and comparison group (n = 28). Waist volume, body mass index, blood glucose were higher in group of patients with NAFLD (p liver development (rs = (0.376), p obesity and overweight negative correlation of moderate strength (rs = (-0.370), p obesity and excess body weight, phenomenon of leptinresistance arises to patients with obesity and can be considered as predictor of the development and progression of NAFLD among this category of patients.

  8. Dietary Composition Independent of Weight Loss in the Management of Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Tannaz Eslamparast

    2017-07-01

    Full Text Available Poor dietary composition is an important factor in the progression of non-alcoholic fatty liver disease (NAFLD. The majority of NAFLD patients follow diets with overconsumption of simple carbohydrates, total and saturated fat, with reduced intake of dietary fiber and omega-3 rich foods. Although lifestyle modifications including weight loss and exercise remain the keystone of NAFLD management, modifying dietary composition with or without a calorie-restricted diet may also be a feasible and sustainable strategy for NAFLD treatment. In the present review article, we highlight the potential therapeutic role of a “high quality healthy diet” to improve hepatic steatosis and metabolic dysfunction in patients with NAFLD, independent of caloric restriction and weight loss. We provide a literature review evaluating the evidence behind dietary components including fiber-, meat- and omega-3-rich diets and, pending further evidence, we concur with the EASL-EASD-EASO Clinical Guidelines recommendation of the Mediterranean diet as the diet of choice in these patients.

  9. Association of non-alcoholic fatty liver disease with renal stone disease detected on computed tomography

    International Nuclear Information System (INIS)

    Nam, In Chul

    2016-01-01

    To evaluate the association between Non-alcoholic fatty liver disease (NAFLD) with renal stone disease detected on computed tomography (CT). A total 1812 patients who underwent abdomen-pelvis CT in July 2015 were included in this study. The inclusion criteria for NAFLD were as follows: (i) lower average Hounsfield unit (HU) of hepatic right lobe, left medial and lateral segment when compared with that of spleen, (ii) patients who having urolithiasis in kidneys, ureters and urinary bladder, and (iii) patients underwent abdomen-pelvis CT including noncontrast image. The statistical significance of the association between NAFLD and renal stone disease was assessed using Chi Square Test. The Odds ratios and 95% CI were calculated to assess the propensity of renal stones disease for NAFLD by using Logistic Regression analysis. The frequency of renal stone disease in patients with NAFLD was higher approximately 19% than those who having renal stone disease without NAFLD. In addition, the presence of NAFLD was linked with renal stone disease showing that detection rate of renal stone disease in patients with NAFLD was markedly high (odds ratio: 5, 95% CI, 3–8.2) (p < 0.05) in multivariate analysis. The presence of significant association between NAFLD with renal stone disease and NAFLD may be considered to be an independent variable as a risk factor for renal stone disease

  10. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    Mônica Rodrigues de Araújo Souza

    2012-03-01

    Full Text Available CONTEXT: Non-alcoholic fatty liver disease (NAFLD, hepatic manifestation of metabolic syndrome, has been considered the most common liver disease nowadays, which is also the most frequent cause of elevated transaminases and cryptogenic cirrhosis. The greatest input of fatty acids into the liver and consequent increased beta-oxidation contribute to the formation of free radicals, release of inflammatory cytokines and varying degrees of hepatocytic aggression, whose histological expression may vary from steatosis (HS to non-alcoholic steatohepatitis (NASH. The differentiation of these forms is required by the potential risk of progression to cirrhosis and development of hepatocellular carcinoma. OBJECTIVE: To review the literature about the major risk factors for NAFLD in the context of metabolic syndrome, focusing on underlying mechanisms and prevention. METHOD: PubMed, MEDLINE and SciELO data basis analysis was performed to identify studies describing the link between risk factors for metabolic syndrome and NAFLD. A combination of descriptors was used, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, metabolic syndrome and risk factors. At the end, 96 clinical and experimental studies, cohorts, meta-analysis and systematic reviews of great impact and scientific relevance to the topic, were selected. RESULTS: The final analysis of all these data, pointed out the central obesity, type 2 diabetes, dyslipidemia and hypertension as the best risk factors related to NAFLD. However, other factors were highlighted, such as gender differences, ethnicity, genetic factors and the role of innate immunity system. How these additional factors may be involved in the installation, progression and disease prognosis is discussed. CONCLUSION: Risk factors for NAFLD in the context of metabolic syndrome expands the prospects to 1 recognize patients with metabolic syndrome at high risk for NAFLD, 2 elucidate pathways common to other co-morbidities, 3

  11. Can Diet Help Non-Obese Individuals with Non-Alcoholic Fatty Liver Disease (NAFLD)?

    OpenAIRE

    Merchant, Hamid A.

    2017-01-01

    Subjects diagnosed with non-alcoholic fatty liver disease (NAFLD) or hepatic steatosis are usually obese or overweight. NAFLD has also been reported in many non-obese healthy subjects as an incidental finding during imaging. Subjects with early-stage NAFLD who are otherwise healthy are often left unmanaged in current clinical practice; it is not clear if an early intervention in those individuals would be of any benefit in preventing NAFLD progression to more serious conditions. Since many of...

  12. Lipid droplet-associated proteins in alcoholic liver disease: a potential linkage with hepatocellular damage

    OpenAIRE

    Ikura, Yoshihiro; Caldwell, Stephen H

    2015-01-01

    Steatosis is a characteristic morphological change of alcoholic liver disease, but its pathologic significance is still obscure. Regardless of cell types, intracellular lipid droplets are coated with a phospholipid monolayer, on which many kinds of lipid droplet-associated proteins are present. These proteins, such as the perilipin family of proteins and the cell death inducing DNA fragmentation factor (DFF) 45-like effectors, are recognized to play important roles in lipid metabolism in the ...

  13. Influence of hyperglycemia on liver inflammatory conditions in the early phase of non-alcoholic fatty liver disease in mice.

    Science.gov (United States)

    Harada, Shinichi; Miyagi, Kei; Obata, Tokio; Morimoto, Yasuko; Nakamoto, Kazuo; Kim, Ke Ih; Kim, Soo Ki; Kim, Soo Ryang; Tokuyama, Shogo

    2017-06-01

    A non-alcoholic fatty liver disease (NAFLD) has high prevalence and now important issue of public health. In general, there exists strong interaction between NAFLD and diabetes, but the detailed mechanism is unclear. In this study, we determined the effects of hyperglycemia on progression in the early phase of NAFLD in mice. Male ddY mice were fed a choline-deficient, l-amino acid-defined, high-fat diet (CDAHFD) consisting of 60% of kcal from fat and 0.1% methionine by weight. Hyperglycemic condition was induced by streptozotocin (STZ) treatment. The assessment of liver function used serum AST and ALT levels, and histological analysis. Hepatic tumour necrosis factor (TNF)-α mRNA levels was estimated by qRT-PCR. During the 3-42 days that the mice were fed CDAHFD, the livers gradually caused accumulation of fat, and infiltration of inflammation cells gradually increased. Serum AST and ALT levels and significantly increased after being fed CDAHFD for 3 days and were exacerbated by the STZ-induced hyperglycemic condition. In addition, hepatic TNF-α mRNA also significantly increased. These phenomena reversed by insulin administration. The results showed that progression in the early phase of NAFLD may be exacerbated by hyperglycemia-induced exacerbation of inflammation. © 2017 Royal Pharmaceutical Society.

  14. Prevalence of metabolic risk factors in non-alcoholic fatty liver disease

    International Nuclear Information System (INIS)

    Ashraf, N.; Sarfraz, T.; Mumtaz, Z.; Rizwan, M.

    2017-01-01

    Objective: To determine the frequency of factors leading to metabolic syndrome among non-alcoholic fatty liver disease (NAFLD) patients at a tertiary care hospital. Study Design: Descriptive cross sectional study. Place and Duration of Study: Department of Medicine, Combined Military Hospital, Kharian. Study was carried out over a period of six months from Jan 2015 to Jun 2015. Material and Methods: A total of 110 patients were included in this study. Past history was taken to rule out alcohol intake, viral and drug induced etiology, to determine the presence of co-morbidities like obesity, type 2 diabetes mellitus, arterial hypertension and dyslipidemia. Physical examination was carried to determine the arterial blood pressure and to determine anthropometric data that is weight, height, body mass index (BMI) and abdominal obesity by measuring waist circumference. Results: Mean age of the patients was 49.95 +- 8.86 years. There were 72 male patients (65.5%) while 38 (34.5%) patients were female. Different metabolic factors were central obesity in 82 patients (74.5%), raised high density lipoprotein (HDL) in 19 patients (17.3%), raised cholesterol in 87 patients (79.1%), raised blood pressure in 65 patients (59.1%) and raised fasting plasma glucose in 82 patients (74.5%). Mean BMI was 26.31 kg/m2 +- 2.68, mean waist circumference was 109.82 cm +- 18.41, mean cholesterol was 237.50 +- 48.47mg/dl, mean systolic blood pressure was 148.88mmHg +- 22.10, mean diastolic blood pressure was 90.41mmHg +- 12.25 and mean fasting plasma glucose was 113.28mg/dl +- 22.80. Stratification with regard to age was carried out. Conclusion: A considerable number of patients with NAFLD had metabolic syndrome. There was a close correlation between NAFLD and metabolic syndrome. (author)

  15. Systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease.

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    Silvia Sookoian

    Full Text Available The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD. Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein-protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a

  16. [Non-alcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases].

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    Halmos, Tamás; Suba, Ilona

    2017-12-01

    Non-alcoholic fatty liver disease is the most common non-infectious chronic liver-disease in our age, and is a spectrum of all the diseases associated with increased fat accumulation in the hepatocytes. Its development is promoted by sedentary life-style, over-feeding, and certain genetic predisposition. Prevalence in the adult population, even in Hungary is ~30%. In a part of cases, this disease may pass into non-alcoholic steatohepatitis, later into fibrosis, rarely into primary hepatocellular cancer. Fatty liver is closely and bidirectionally related to the metabolic syndrome and type 2 diabetes, and nowadays there is a general consensus that fatty liver is the hepatic manifestation of the metabolic sycndrome. The importance of the fatty liver has been highly emphasized recently. In addition to the progression into steatohepatitis, its causal relationship with numerous extrahepatic disorders has been discovered. In our overview, we deal with the epidemiology, pathomechanism of the disease, discuss the possibilities of diagnosis, its relationship with the intestinal microbiota, its recently recognized correlations with bile acids and their receptors, and its supposed correlations with the circadian CLOCK system. Hereinafter, we overview those extrahepatic disorders, which have been shown to be causal link with the non-alcoholic fatty liver disease. Among these, we emphasize the metabolic syndrome/type 2 diabetes, cardiovascular disorders, chronic kidney disease, sleep apnea/hypoventilation syndrome, inflammatory bowel disease, Alzheimer's disease, osteoporosis, and psoriasis, as well. Based on the above, it can be stated, that high risk individuals with non-alcoholic fatty liver disease need systemic care, and require the detection of other components of this systemic pathological condition. While currently specific therapy for the disease is not yet known, life-style changes, adequate use of available medicines can prevent disease progression. Promising research

  17. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers

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    Claudia Sanna

    2016-05-01

    Full Text Available Non-alcoholic fatty liver disease (NAFLD is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas and extra-intestinal sites (kidney in men, and breast in women. Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC, but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  18. Non-Alcoholic Fatty Liver Disease and Extra-Hepatic Cancers.

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    Sanna, Claudia; Rosso, Chiara; Marietti, Milena; Bugianesi, Elisabetta

    2016-05-12

    Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease but the second cause of death among NAFLD patients are attributed to malignancies at both gastrointestinal (liver, colon, esophagus, stomach, and pancreas) and extra-intestinal sites (kidney in men, and breast in women). Obesity and related metabolic abnormalities are associated with increased incidence or mortality for a number of cancers. NAFLD has an intertwined relationship with metabolic syndrome and significantly contributes to the risk of hepatocellular carcinoma (HCC), but recent evidence have fuelled concerns that NAFLD may be a new, and added, risk factor for extra-hepatic cancers, particularly in the gastrointestinal tract. In this review we critically appraise key studies on NAFLD-associated extra-hepatic cancers and speculate on how NAFLD may influence carcinogenesis at these sites.

  19. Non-Alcoholic Fatty Liver Disease in Children: Focus on Nutritional Interventions

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    Min Yang

    2014-10-01

    Full Text Available With increasing prevalence of childhood obesity, non-alcoholic fatty liver disease (NAFLD has emerged as the most common cause of liver disease among children and adolescents in industrialized countries. It is generally recognized that both genetic and environmental risk factors contribute to the pathogenesis of NAFLD. Recently, there has been a growing body of evidence to implicate altered gut microbiota in the development of NAFLD through the gut-liver axis. The first line of prevention and treatment of NAFLD in children should be intensive lifestyle interventions such as changes in diet and physical activity. Recent advances have been focused on limitation of dietary fructose and supplementation of antioxidants, omega-3 fatty acids, and prebiotics/probiotics. Convincing evidences from both animal models and human studies have shown that reduction of dietary fructose and supplement of vitamin E, omega-3 fatty acids, and prebiotics/probiotics improve NAFLD.

  20. What is the role of adiponectin in obesity related non-alcoholic fatty liver disease?

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    Finelli, Carmine; Tarantino, Giovanni

    2013-02-14

    Non-alcoholic fatty liver disease (NAFLD) is recognized as the most common type of chronic liver disease in Western countries. Insulin resistance is a key factor in the pathogenesis of NAFLD, the latter being considered as the hepatic component of insulin resistance or obesity. Adiponectin is the most abundant adipose-specific adipokine. There is evidence that adiponectin decreases hepatic and systematic insulin resistance, and attenuates liver inflammation and fibrosis. Adiponectin generally predicts steatosis grade and the severity of NAFLD; however, to what extent this is a direct effect or related to the presence of more severe insulin resistance or obesity remains to be addressed. Although there is no proven pharmacotherapy for the treatment of NAFLD, recent therapeutic strategies have focused on the indirect upregulation of adiponectin through the administration of various therapeutic agents and/or lifestyle modifications. In this adiponectin-focused review, the pathogenetic role and the potential therapeutic benefits of adiponectin in NAFLD are analyzed systematically.

  1. Non-alcoholic fatty liver disease and its associated risk factors in Brazilian postmenopausal women.

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    Bruno, A de Souza; Rodrigues, M H; Alvares, M C B; Nahas-Neto, J; Nahas, E A Petri

    2014-08-01

    To evaluate the prevalence and risk factors of non-alcoholic fatty liver disease (NAFLD) in postmenopausal women. A cross-sectional study was carried involving 188 women (age ≥ 45 years and amenorrhea ≥ 12 months) attending the outpatient unit in south-eastern Brazil. Exclusion criteria were liver disease (hepatitis B and C, cholestatic disease, liver insufficiency), use of drugs that affect liver metabolism; alcoholics; AIDS or cancer history; and morbid obesity. NAFLD was diagnosed by abdominal ultrasound. Clinical, anthropometric (body mass index, waist circumference) and biochemical variables were measured. Of the 188 women, 73 (38.8%) had NAFLD. Blood pressure, waist circumference, body mass index, LDL cholesterol, triglycerides and glucose were significantly higher in NAFLD patients when compared with women without NAFLD (control group) (p NAFLD group (6.1 ± 4.6 vs. 2.4 ± 1.4 in control group, p NAFLD, and 46.1% of the control group (p NAFLD, were: high waist circumference (odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.13), insulin resistance (OR 3.81, 95% CI 2.01-7.13), and presence of metabolic syndrome (OR 8.68, 95% CI 3.3-24.1). NAFLD showed a high prevalence among postmenopausal women. The presence of metabolic syndrome, abdominal obesity and IR were indicators of risk for the development of NAFLD.

  2. Protective function of complement against alcohol-induced rat liver damage.

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    Bykov, Igor L; Väkevä, Antti; Järveläinen, Harri A; Meri, Seppo; Lindros, Kai O

    2004-11-01

    The complement system can promote tissue damage or play a homeostatic role in the clearance and disposal of damaged tissue. We assessed the role of the terminal complement pathway in alcohol-induced liver damage in complement C6 (C6-/-) genetically deficient rats. C6-/- and corresponding C6+/+ rats were continuously exposed to ethanol by feeding ethanol-supplemented liquid diet for six weeks. Liver samples were analyzed for histopathology and complement component deposition by immunofluorescence microscopy. Prostaglandin E receptors and cytokine mRNA levels were analyzed by RT-PCR and plasma cytokines by ELISA. Deposition of complement components C1, C3, C8 and C9 was observed in C6+/+ rats, but not in C6-/- animals. The histopathological changes, the liver weight increase and the elevation of the plasma pro-/anti-inflammatory TNF-alpha/IL-10 ratio were, on the other hand, more marked in C6-/- rats. Furthermore, ethanol enhanced the hepatic mRNA expression of the prostaglandin E receptors EP2R and EP4R exclusively in the C6-/- rats. Our results indicate that a deficient terminal complement pathway predisposes to tissue injury and promotes a pro-inflammatory cytokine response. This suggests that an intact complement system has a protective function in the development of alcoholic liver damage.

  3. Proteomic and genomic studies of non-alcoholic fatty liver disease - clues in the pathogenesis

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    Lim, Jun Wei; Dillon, John; Miller, Michael

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a widely prevalent hepatic disorder that covers wide spectrum of liver pathology. NAFLD is strongly associated with liver inflammation, metabolic hyperlipidaemia and insulin resistance. Frequently, NAFLD has been considered as the hepatic manifestation of metabolic syndrome. The pathophysiology of NAFLD has not been fully elucidated. Some patients can remain in the stage of simple steatosis, which generally is a benign condition; whereas others can develop liver inflammation and progress into non-alcoholic steatohepatitis, fibrosis, cirrhosis and hepatocellular carcinoma. The mechanism behind the progression is still not fully understood. Much ongoing proteomic researches have focused on discovering the unbiased circulating biochemical markers to allow early detection and treatment of NAFLD. Comprehensive genomic studies have also begun to provide new insights into the gene polymorphism to understand patient-disease variations. Therefore, NAFLD is considered a complex and mutifactorial disease phenotype resulting from environmental exposures acting on a susceptible polygenic background. This paper reviewed the current status of proteomic and genomic studies that have contributed to the understanding of NAFLD pathogenesis. For proteomics section, this review highlighted functional proteins that involved in: (1) transportation; (2) metabolic pathway; (3) acute phase reaction; (4) anti-inflammatory; (5) extracellular matrix; and (6) immune system. In the genomic studies, this review will discuss genes which involved in: (1) lipolysis; (2) adipokines; and (3) cytokines production. PMID:25024592

  4. Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease.

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    Kawano, Yuki; Cohen, David E

    2013-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation in the absence of excess alcohol intake. NAFLD is the most common chronic liver disease, and ongoing research efforts are focused on understanding the underlying pathobiology of hepatic steatosis with the anticipation that these efforts will identify novel therapeutic targets. Under physiological conditions, the low steady-state triglyceride concentrations in the liver are attributable to a precise balance between acquisition by uptake of non-esterified fatty acids from the plasma and by de novo lipogenesis, versus triglyceride disposal by fatty acid oxidation and by the secretion of triglyceride-rich lipoproteins. In NAFLD patients, insulin resistance leads to hepatic steatosis by multiple mechanisms. Greater uptake rates of plasma non-esterified fatty acids are attributable to increased release from an expanded mass of adipose tissue as a consequence of diminished insulin responsiveness. Hyperinsulinemia promotes the transcriptional upregulation of genes that promote de novo lipogenesis in the liver. Increased hepatic lipid accumulation is not offset by fatty acid oxidation or by increased secretion rates of triglyceride-rich lipoproteins. This review discusses the molecular mechanisms by which hepatic triglyceride homeostasis is achieved under normal conditions, as well as the metabolic alterations that occur in the setting of insulin resistance and contribute to the pathogenesis of NAFLD.

  5. Early life programming and the risk of non-alcoholic fatty liver disease.

    Science.gov (United States)

    Lynch, C; Chan, C S; Drake, A J

    2017-06-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease and can be considered the hepatic manifestation of the metabolic syndrome. NAFLD represents a spectrum of disease, from the relatively benign simple steatosis to the more serious non-alcoholic steatohepatitis, which can progress to liver cirrhosis, hepatocellular carcinoma and end-stage liver failure, necessitating liver transplantation. Although the increasing prevalence of NAFLD in developed countries has substantial implications for public health, many of the precise mechanisms accounting for the development and progression of NAFLD are unclear. The environment in early life is an important determinant of cardiovascular disease risk in later life and studies suggest this also extends to NAFLD. Here we review data from animal models and human studies which suggest that fetal and early life exposure to maternal under- and overnutrition, excess glucocorticoids and environmental pollutants may confer an increased susceptibility to NAFLD development and progression in offspring and that such effects may be sex-specific. We also consider studies aimed at identifying potential dietary and pharmacological interventions aimed at reducing this risk. We suggest that further human epidemiological studies are needed to ensure that data from animal models are relevant to human health.

  6. Curcumin: Reintroduced Therapeutic Agent from Traditional Medicine for Alcoholic Liver Disease

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    Hamid Reza Rahimi

    2015-03-01

    Full Text Available Alcoholic liver disease (ALD is the main cause of chronic liver disease across the world and can lead to fibrosis and cirrhosis. The etiopathogenesis of ALD is related to ethanol-induced oxidative stress, glutathione reduction, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. Curcumin is an active ingredient of the rhizome of turmeric. The substance is shown to have minor adverse effects. As the substance possess low bioavailability in free formulation, different strategies has been conducted to improve its bioavailability which resulted in production of nanomiscels and nanoparticles. Curcumin can provide protection for the liver against toxic effects of alcohol use. Several studies showed curcumin blocks endotoxin-mediated activation of NF-κB and suppresses the expression of cytokines, chemokines, COX-2, and iNOS in Kupffer cells. According to the molecular studies, curcumin inhibits NF-κB signaling pathway, regulates cytokines production and modulates immune response. It has been shown that curcumin can suppress gene expression, especially cytokines genes resulting in down-regulation of tumor necrosis factor-α (TNF-α, interleukin 1 (IL-1, IL-6, IL-8, adhesion molecules (ICAM, VCAM and C-reactive protein. Hence, curcumin can have therapeutic effects on the majority of chronic inflammatory diseases such as asthma, bronchitis, inflammatory bowel disease, rheumatoid arthritis, ALD, fatty liver, and allergy.

  7. Hypothalamic-pituitary-gonadal function in relation to liver function in men with alcoholic cirrhosis

    DEFF Research Database (Denmark)

    Gluud, C; Bahnsen, M; Bennett, Patrick

    1983-01-01

    Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20). No signi......Serum concentrations of oestrone, oestradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) were significantly (P less than 0.01) raised in men with alcoholic liver cirrhosis (no. = 42) compared with age-matched controls (no. = 20...... affected liver function (no. = 18) had significantly (P less than 0.05) raised serum concentrations of testosterone, FSH, and LH when compared with both controls and patients with severely affected liver function (no. = 13). Serum concentrations of testosterone, FSH, and LH in the latter group showed...... groups of patients. Dexamethasone suppression did not change the concentration of testosterone significantly, but oestrone and oestradiol concentrations decreased significantly (P less than 0.01) in controls and patients. In patients, but not in controls, a significant (P less than 0.01) increase in FSH...

  8. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study.

    Science.gov (United States)

    Jang, Eun Sun; Jeong, Sook-Hyang; Hwang, Sung Ho; Kim, Hyun Young; Ahn, So Yeon; Lee, Jaebong; Lee, Sang Hyub; Park, Young Soo; Hwang, Jin Hyeok; Kim, Jin-Wook; Kim, Nayoung; Lee, Dong Ho

    2012-10-18

    Liver function tests (LFTs) can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Coffee consumption was closely related to male gender, high body mass index (BMI), alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST). On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT) level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  9. Effects of coffee, smoking, and alcohol on liver function tests: a comprehensive cross-sectional study

    Directory of Open Access Journals (Sweden)

    Jang Eun

    2012-10-01

    Full Text Available Abstract Background Liver function tests (LFTs can be affected by many factors and the proposed effects of coffee on LFT require a comprehensive evaluation. The aim of this study was to elucidate whether drinking coffee, smoking, or drinking alcohol have independent effects on LFTs in Korean health-check examinees. Methods We used the responses of 500 health-check examinees, who had participated in a self-administered questionnaire survey about coffee, alcohol drinking, and smoking habits. Results Coffee consumption was closely related to male gender, high body mass index (BMI, alcohol drinking, and smoking. On univariable and multivariable analyses, drinking coffee lowered serum levels of total protein, albumin, and aspartate aminotransferases (AST. On multivariable analyses, smoking raised serum γ-glutamyl transferase (GGT level and decreased serum protein and albumin levels, while alcohol drinking raised GGT level after adjustment for age, gender, regular medication, BMI, coffee and alcohol drinking amounts, and smoking. Conclusions Coffee consumption, smoking, and alcohol drinking affect the individual components of LFT in different ways, and the above 3 habits each have an impact on LFTs. Therefore, their effects on LFTs should be carefully interpreted, and further study on the mechanism of the effects is warranted.

  10. Gene expression in brain and liver produced by three different regimens of alcohol consumption in mice: comparison with immune activation.

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    Elizabeth Osterndorff-Kahanek

    Full Text Available Chronically available alcohol escalates drinking in mice and a single injection of the immune activator lipopolysaccharide can mimic this effect and result in a persistent increase in alcohol consumption. We hypothesized that chronic alcohol drinking and lipopolysaccharide injections will produce some similar molecular changes that play a role in regulation of alcohol intake. We investigated the molecular mechanisms of chronic alcohol consumption or lipopolysaccharide insult by gene expression profiling in prefrontal cortex and liver of C57BL/6J mice. We identified similar patterns of transcriptional changes among four groups of animals, three consuming alcohol (vs water in different consumption tests and one injected with lipopolysaccharide (vs. vehicle. The three tests of alcohol consumption are the continuous chronic two bottle choice (Chronic, two bottle choice available every other day (Chronic Intermittent and limited access to one bottle of ethanol (Drinking in the Dark. Gene expression changes were more numerous and marked in liver than in prefrontal cortex for the alcohol treatments and similar in the two tissues for lipopolysaccharide. Many of the changes were unique to each treatment, but there was significant overlap in prefrontal cortex for Chronic-Chronic Intermittent and for Chronic Intermittent-lipopolysaccharide and in liver all pairs showed overlap. In silico cell-type analysis indicated that lipopolysaccharide had strongest effects on brain microglia and liver Kupffer cells. Pathway analysis detected a prefrontal cortex-based dopamine-related (PPP1R1B, DRD1, DRD2, FOSB, PDNY network that was highly over-represented in the Chronic Intermittent group, with several genes from the network being also regulated in the Chronic and lipopolysaccharide (but not Drinking in the Dark groups. Liver showed a CYP and GST centered metabolic network shared in part by all four treatments. We demonstrate common consequences of chronic alcohol

  11. Concomitant Psychiatric and Nonalcohol-Related Substance Use Disorders Among Hospitalized Patients with Alcoholic Liver Disease in the United States.

    Science.gov (United States)

    Jinjuvadia, Raxitkumar; Jinjuvadia, Chetna; Puangsricharoen, Pimpitcha; Chalasani, Naga; Crabb, David W; Liangpunsakul, Suthat

    2018-02-01

    Despite that the epidemiological studies on the comorbidity of alcohol misuse and psychiatric disorders have been studied, less is known about the magnitude of these disorders among patients with alcoholic liver disease (ALD). Our aim was to determine the prevalence of psychiatric and substance use disorders among hospitalized ALD patients in the United States. We utilized a single-level clinical classification software to identify patients with ALD and psychiatric/substance use disorders from the 2011 National Inpatient Sample data. The primary outcome was the prevalence of these disorders among hospitalized patients with ALD (n = 74,972) compared to those with chronic liver diseases not caused by alcohol (n = 350,140) and those without underlying liver diseases (n = 1,447,063). The prevalence of adjustment disorder, anxiety disorder, posttraumatic stress disorder, and depression was significantly higher among hospitalized patients with ALD when compared to those with chronic liver diseases not caused by alcohol (all with p-values psychiatric/substance use disorders among hospitalized patients with ALD. Hospitalized patients with ALD have significantly high prevalence of concomitant psychiatric and substance abuse disorders when compared to those with chronic liver diseases not caused by alcohol and those without underlying liver diseases. Screening and appropriate intervention should be implemented as part of routine clinical care for these patients. Copyright © 2017 by the Research Society on Alcoholism.

  12. Kidney, lower limb and whole-body uptake and release of catecholamines in alcoholic liver disease

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Ring-Larsen, H; Christensen, N J

    1988-01-01

    Regional (kidney, lower limb) and whole-body kinetics of endogenous noradrenaline (NA) and tritium-labelled L-noradrenaline (3H-NA) were determined in patients with alcoholic liver disease (one alcoholic hepatitis, 12 cirrhosis) and in control subjects (n = 6) in order to get information on the s......Regional (kidney, lower limb) and whole-body kinetics of endogenous noradrenaline (NA) and tritium-labelled L-noradrenaline (3H-NA) were determined in patients with alcoholic liver disease (one alcoholic hepatitis, 12 cirrhosis) and in control subjects (n = 6) in order to get information...... to controls and non-ascitic patients (1.2 and 1.0 pmol/min.g, respectively. Patients and control kidneys and limbs extracted almost the same fraction of 3H-NA (0.34 vs. 0.32 NS and 0.34 vs. 0.37 NS, respectively). Whole-body clearance of 3H-NA was not significantly different in cirrhotics and controls (median...... 0.89 vs. 0.91 l/min.m2), indicating that the raised NA in decompensated cirrhosis reflects enhanced sympatho-adrenal activity rather than decreased metabolism of this amine. Our results do not point towards a uniform sympatho-adrenal overactivity in decompensated cirrhosis, but rather indicate...

  13. Rat Strain Differences in Susceptibility to Alcohol-Induced Chronic Liver Injury and Hepatic Insulin Resistance

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    Sarah M. DeNucci

    2010-01-01

    Full Text Available The finding of more severe steatohepatitis in alcohol fed Long Evans (LE compared with Sprague Dawley (SD and Fisher 344 (FS rats prompted us to determine whether host factors related to alcohol metabolism, inflammation, and insulin/IGF signaling predict proneness to alcohol-mediated liver injury. Adult FS, SD, and LE rats were fed liquid diets containing 0% or 37% (calories ethanol for 8 weeks. Among controls, LE rats had significantly higher ALT and reduced GAPDH relative to SD and FS rats. Among ethanol-fed rats, despite similar blood alcohol levels, LE rats had more pronounced steatohepatitis and fibrosis, higher levels of ALT, DNA damage, pro-inflammatory cytokines, ADH, ALDH, catalase, GFAP, desmin, and collagen expression, and reduced insulin receptor binding relative to FS rats. Ethanol-exposed SD rats had intermediate degrees of steatohepatitis, increased ALT, ADH and profibrogenesis gene expression, and suppressed insulin receptor binding and GAPDH expression, while pro-inflammatory cytokines were similarly increased as in LE rats. Ethanol feeding in FS rats only reduced IL-6, ALDH1–3, CYP2E1, and GAPDH expression in liver. In conclusion, susceptibility to chronic steatohepatitis may be driven by factors related to efficiency of ethanol metabolism and degree to which ethanol exposure causes hepatic insulin resistance and cytokine activation.

  14. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

    Science.gov (United States)

    Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

    2017-01-10

    There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females ( p liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness ( p = 0.044). Tea consumption had no effect ( p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

  15. Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B

    Directory of Open Access Journals (Sweden)

    Alexander Hodge

    2017-01-01

    Full Text Available There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD, hepatitis C virus (HCV, and hepatitis B virus (HBV infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE. We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV. Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females (p < 0.05. Patients with HBV had lower liver stiffness than those with HCV and NAFLD. After adjustment for age, gender, smoking, alcohol consumption, M or XL probe, and disease state (NAFLD, HCV, and HBV status, those who drank 2 or more cups of coffee per day had a lower liver stiffness (p = 0.044. Tea consumption had no effect (p = 0.9. Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

  16. Hepatic overproduction of 13-HODE due to ALOX15 upregulation contributes to alcohol-induced liver injury in mice.

    Science.gov (United States)

    Zhang, Wenliang; Zhong, Wei; Sun, Qian; Sun, Xinguo; Zhou, Zhanxiang

    2017-08-21

    Chronic alcohol feeding causes lipid accumulation and apoptosis in the liver. This study investigated the role of bioactive lipid metabolites in alcohol-induced liver damage and tested the potential of targeting arachidonate 15-lipoxygenase (ALOX15) in treating alcoholic liver disease (ALD). Results showed that chronic alcohol exposure induced hepatocyte apoptosis in association with increased hepatic 13-HODE. Exposure of 13-HODE to Hepa-1c1c7 cells induced oxidative stress, ER stress and apoptosis. 13-HODE also perturbed proteins related to lipid metabolism. HODE-generating ALOX15 was up-regulated by chronic alcohol exposure. Linoleic acid, but not ethanol or acetaldehyde, induced ALOX15 expression in Hepa-1c1c7 cells. ALOX15 knockout prevented alcohol-induced liver damage via attenuation of oxidative stress, ER stress, lipid metabolic disorder, and cell death signaling. ALOX15 inhibitor (PD146176) treatment also significantly alleviated alcohol-induced oxidative stress, lipid accumulation and liver damage. These results demonstrated that activation of ALOX15/13-HODE circuit critically mediates the pathogenesis of ALD. This study suggests that ALOX15 is a potential molecular target for treatment of ALD.

  17. Hepatic fat quantification using the two-point Dixon method and fat color maps based on non-alcoholic fatty liver disease activity score.

    Science.gov (United States)

    Hayashi, Tatsuya; Saitoh, Satoshi; Takahashi, Junji; Tsuji, Yoshinori; Ikeda, Kenji; Kobayashi, Masahiro; Kawamura, Yusuke; Fujii, Takeshi; Inoue, Masafumi; Miyati, Tosiaki; Kumada, Hiromitsu

    2017-04-01

    The two-point Dixon method for magnetic resonance imaging (MRI) is commonly used to non-invasively measure fat deposition in the liver. The aim of the present study was to assess the usefulness of MRI-fat fraction (MRI-FF) using the two-point Dixon method based on the non-alcoholic fatty liver disease activity score. This retrospective study included 106 patients who underwent liver MRI and MR spectroscopy, and 201 patients who underwent liver MRI and histological assessment. The relationship between MRI-FF and MR spectroscopy-fat fraction was used to estimate the corrected MRI-FF for hepatic multi-peaks of fat. Then, a color FF map was generated with the corrected MRI-FF based on the non-alcoholic fatty liver disease activity score. We defined FF variability as the standard deviation of FF in regions of interest. Uniformity of hepatic fat was visually graded on a three-point scale using both gray-scale and color FF maps. Confounding effects of histology (iron, inflammation and fibrosis) on corrected MRI-FF were assessed by multiple linear regression. The linear correlations between MRI-FF and MR spectroscopy-fat fraction, and between corrected MRI-FF and histological steatosis were strong (R 2  = 0.90 and R 2  = 0.88, respectively). Liver fat variability significantly increased with visual fat uniformity grade using both of the maps (ρ = 0.67-0.69, both P Hepatic iron, inflammation and fibrosis had no significant confounding effects on the corrected MRI-FF (all P > 0.05). The two-point Dixon method and the gray-scale or color FF maps based on the non-alcoholic fatty liver disease activity score were useful for fat quantification in the liver of patients without severe iron deposition. © 2016 The Japan Society of Hepatology.

  18. Ultrasonography for diagnosis of alcoholic cirrhosis in people with alcoholic liver disease

    DEFF Research Database (Denmark)

    Pavlov, Chavdar S; Casazza, Giovanni; Semenistaia, Marianna

    2016-01-01

    text, and reference standard, we judged the two studies at high risk of bias. Participants in both studies had undergone both liver biopsy and ultrasonography investigations. The studies shared only a few comparable clinical signs and symptoms (index tests).We decided to not perform a meta-analysis due...

  19. Epigenetic regulation of hepatocellular carcinoma in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Tian, Yuan; Wong, Vincent Wai-Sun; Chan, Henry Lik-Yuen; Cheng, Alfred Sze-Lok

    2013-12-01

    Emerging evidence that epigenetics converts alterations in nutrient and metabolism into heritable pattern of gene expression has profound implications in understanding human physiology and diseases. Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome including obesity and diabetes which elevate the risk of hepatocellular carcinoma (HCC) especially in male. This review focuses on the molecular connections between metabolic dysfunction and aberrant epigenetic alterations in the development of HCC in NAFLD. The metabolites derived from excessive insulin, glucose and lipid may perturb epigenetic gene regulation through DNA methylation, histone modifications, and RNA interference, leading to activation of pro-inflammatory signaling and deregulation of metabolic pathways. The interplay and crosstalk of chromatin-modifying enzymes, microRNAs, signaling pathways and the downstream transcription factors result in epigenomic reprogramming that drives hepatocellular transformation. The interactions between sex hormone pathways and the epigenetic machineries that influence chromatin states in NAFLD provide potential molecular mechanisms of gender disparity in HCC. A deeper understanding of these connections and comprehensive molecular catalog of hepatocarcinogenesis may shed light in the identification of druggable epigenetic targets for the prevention and treatment of HCC in obese or diabetic patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis.

    Science.gov (United States)

    Darmawan, Guntur; Hamijoyo, Laniyati; Hasan, Irsan

    2017-04-01

    non-alcoholic fatty liver disease (NAFLD) is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). All data were analyzed using REVIEW MANAGER 5.3. eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; puric acid levels and severity of NAFLD. No publication bias was observed. our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

  1. Association between Serum Uric Acid and Non-Alcoholic Fatty Liver Disease: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Guntur Darmawan

    2017-04-01

    Full Text Available Background: non-alcoholic fatty liver disease (NAFLD is known to be associated with some metabolic disorders. Recent studies suggested the role of uric acid in NAFLD through oxidative stress and inflammatory process. This study is aimed to evaluate the association between serum uric acid and NAFLD. Methods: a systematic literature review was conducted using Pubmed and Cochrane library. The quality of all studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE. All data were analyzed using REVIEW MANAGER 5.3. Results: eleven studies from America and Asia involving 100,275 subjects were included. The pooled adjusted OR for NAFLD was 1.92 (95% CI: 1.66-2.23; p<0.00001. Subgroup analyses were done based on study design, gender, non-diabetic subjects, non-obese subjects. All subgroup analyses showed statistically significant adjusted OR and most of which having low to moderate heterogeneity. Two studies revealed relationship between increased serum uric acid levels and severity of NAFLD. No publication bias was observed. Conclusion: our study demonstrated association between serum uric acid level and NAFLD. This finding brings a new insight of uric acid in clinical practice. Increased in serum uric acid levels might serve as a trigger for physician to screen for NAFLD.

  2. Characteristics of hepatocellular carcinoma in cirrhotic and non-cirrhotic non-alcoholic fatty liver disease.

    Science.gov (United States)

    Leung, Christopher; Yeoh, Sern Wei; Patrick, Desmond; Ket, Shara; Marion, Kaye; Gow, Paul; Angus, Peter W

    2015-01-28

    To determine characteristics and prognostic predictors of patients with hepatocellular carcinoma (HCC) in association with non-alcoholic fatty liver disease (NAFLD). We reviewed the records of all patients with NAFLD associated HCC between 2000 and 2012. Data collected included demographics; histology; presence or absence of cirrhosis, size and number of HCC, alpha-fetoprotein, body mass index (BMI), and the presence of diabetes, hypertension, or dyslipidaemia. Fifty-four patients with NAFLD associated HCC were identified. Mean age was 64 years with 87% male. Fifteen percent (8/54) were not cirrhotic. 11%, 24% and 50% had a BMI of <25 kg/m2, 25-29 kg/m2 and ≥30 kg/m2 respectively. Fifty-nine percent were diabetic, 44% hypertensive and 26% hyperlipidaemic. Thirty-four percent of the patients had ≤1 of these risk factors. Non-cirrhotics had a significantly larger mean tumour diameter at diagnosis than cirrhotics (P=0.041). Multivariate analysis did not identify any other patient characteristics that predicted the size or number of HCC. HCC can develop in NAFLD without cirrhosis. At diagnosis such tumours are larger than those in cirrhotics, conferring a poorer prognosis.

  3. The Role of Dietary Sugars and De novo Lipogenesis in Non-Alcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    J. Bernadette Moore

    2014-12-01

    Full Text Available Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD. Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL, stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.

  4. Non-alcoholic Fatty Liver Disease in Lean Subjects: Characteristics and Implications.

    Science.gov (United States)

    Kumar, Ramesh; Mohan, Shantam

    2017-09-28

    Non-alcoholic fatty liver disease (NAFLD) is commonly diagnosed in obese subjects; however, it is not rare among lean individuals. Given the absence of traditional risk factors, it tends to remain under-recognised. The metabolic profiles of lean NAFLD patients are frequently comparable to those of obese NAFLD patients. Though results from several studies have been mixed, it has been generally revealed that lean subjects with NAFLD have minor insulin resistance compared to that in obese NAFLD. Several genetic variants are associated with NAFLD without insulin resistance. Some data suggest that the prevalence of steatohepatitis and advanced fibrosis do not differ significantly between lean and obese NAFLD; however, the former tend to have less severe disease at presentation. The underlying pathophysiology of lean NAFLD may be quite different. Genetic predispositions, fructose- and cholesterol-rich diet, visceral adiposity and dyslipidaemia have potential roles in the pathogenic underpinnings. Lean NAFLD may pose a risk for metabolic disturbances, cardiovascular morbidity or overall mortality. Secondary causes of hepatic steatosis are also needed to be ruled out in lean subjects with NAFLD. The effectiveness of various treatment modalities, such as exercise and pharmacotherapy, on lean NAFLD is not known. Weight loss is expected to help lean NAFLD patients who have visceral obesity. Further investigation is needed for many aspects of lean NAFLD, including mechanistic pathogenesis, risk assessment, natural history and therapeutic approach.

  5. Binding of ligands to the catalytic zinc ion in horse liver alcohol dehydrogenase.

    Science.gov (United States)

    Syvertsen, C; McKinley-McKee, J S

    1984-01-01

    The affinity of nitrogen and sulfur ligands for the catalytic zinc ion in horse liver alcohol dehydrogenase has been investigated by their influence on the affinity labeling reaction with iodoacetate. All the nitrogen compounds including ammonia, a primary and a secondary amine, and heterocycles containing a pyridine-type nitrogen with the exception of 2,2-dipyridyl were found to activate the affinity labeling reaction. Activation results from inner-sphere ligand coordination to the catalytic zinc ion. Closely related pyridine compounds gave a regular increase in affinity for the enzyme with increasing basicity, as expected for coordination to a metal ion. The sulfur compounds penicillamine and mercaptoethanol also activated the affinity labeling reaction, but dimercaptopropanol bound very tightly as a bidentate inhibited the reaction. The anions hydrosulfide, diethyldithiocarbamate, and cyanide coordinated to the catalytic zinc ion, whereas azide, thiocyanate, tetrazole, and iodide complexed the anion-binding site. The anionic metal ligands increased the rate of inactivation of the enzyme with iodoacetamide by binding to the catalytic zinc ion, while the binding of iodoacetate to the anion-binding site was prevented.

  6. Could metabolic syndrome lead to hepatocarcinoma via non-alcoholic fatty liver disease?

    Science.gov (United States)

    Scalera, Antonella; Tarantino, Giovanni

    2014-07-28

    It was estimated that from 2002 to 2008 the risk of developing cancer increased a quarter-fold in men and two-fold in women due to excessive BMI. Obesity, metabolic syndrome and type 2 diabetes mellitus are strictly related and are key pathogenetic factors of non-alcoholic fatty liver disease (NAFLD), the most frequent liver disease worldwide. The most important consequence of the "metabolic epidemics" is the probable rise in the incidence of hepatocarcinoma (HCC), and NAFLD is the major causative factor. Adipose tissue is not merely a storage organ where lipids are preserved as an energy source. It is an active organ with important endocrine, paracrine, and autocrine actions in addition to immune functions. Adipocytes produce a wide range of hormones, cytokines, and growth factors that can act locally in the adipose tissue microenvironment and systemically. In this article, the main roles of insulin growth factor (IGF)-1 and IGF-2 are discussed. The role of IGF-2 is not only confined to HCC, but it may also act in early hepato-carcinogenesis, as pre-neoplastic lesions express IGF-2 mRNA. IGF-1 and IGF-2 interact with specific receptors (IGF-1R and IGF-2R). IGF-1R is over-expressed in in vitro and in animal models of HCC and it was demonstrated that IGF ligands exerted their effects on HCC cells through IGF-1R and that it was involved in the degeneration of pre-neoplastic lesions via an increase in their mitotic activity. Both IGF-2R and TGF β, a growth inhibitor, levels are reduced in human HCC compared with adjacent normal liver tissues. Another key mechanism involves peroxisome proliferator-activated receptor (PPAR)γ. In in vitro studies, PPARγ inhibited various carcinomas including HCC, most probably by regulating apoptosis via the p21, p53 and p27 pathways. Finally, as a clinical consequence, to improve survival, efforts to achieve a "healthier diet" should be promoted by physicians and politicians.

  7. Higher free triiodothyronine is associated with non-alcoholic fatty liver disease in euthyroid subjects : The Lifelines Cohort Study

    NARCIS (Netherlands)

    van den Berg, Eline H.; van Tienhoven-Wind, Lynnda J. N.; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, Hans; Dullaart, Robin P. F.

    Objective. Overt hypothyroidism confers an increased risk of non-alcoholic fatty liver disease (NAFLD). The liver plays a crucial role in the metabolism of cholesterol and triglycerides; thyroid hormones interact on hepatic lipid homeostasis. Thyroid function within the euthyroid range affects a

  8. Free triiodothyronine as determinant of non-alcoholic fatty liver disease in euthyroid subjects: The lifelines cohort study

    NARCIS (Netherlands)

    Van Den Berg, Eline; van Tienhoven-Wind, Lynnda; Amini, Marzyeh; Schreuder, Tim C.M.A.; Faber, Klaas Nico; Blokzijl, H.; Dullaart, Robin P.F.

    2016-01-01

    Background: Non-alcoholic fatty live disease (NAFLD) is becoming the leading cause of chronic liver disease in de Western world. The liver plays a crucial role in the metabolism of cholesterol and triglycerides and thyroid hormones interact on hepatic lipid homeostasis. Given the importance of

  9. [Two cases of rapidly progressive nephritic syndrome complicated with alcoholic liver cirrhosis].

    Science.gov (United States)

    Kaneko, Tomohiro; Arima, Ryuji; Arakawa, Yusuke; Aoki, Michiko; Fukuda, Kumiko; Fukui, Megumi; Hirama, Akio; Fujita, Emiko; Mii, Akiko; Utsumi, Koichi; Shimizu, Akira; Iino, Yasuhiko

    2011-01-01

    It has been reported that glomerulosclerosis with IgA deposition is likely to be complicated with alcoholic liver cirrhosis. On the other hand, it is said that complications of nephrotic syndrome or rapidly progressive glomerulonephritis (RPGN) are relatively rare. We experienced two patients with alcoholic liver cirrhosis complicated with RPGN syndrome who had obtained favorable outcomes through the use of steroids and immune system suppressors. Case 1 was a 55-year-old male. He was being treated for alcoholic liver cirrhosis, but as bloody urine was noticed macroscopically, his renal function rapidly decreased. Specimens from a renal biopsy showed endocapillary proliferative lesions accompanying necrotic lesions. Granular deposition of IgA (IgA1) and C3 was seen along the capillary walls and in the mesangial areas. After the combined treatments of bilateral palatotonsillectomy, three courses of steroid semi-pulse therapy and post-therapy with steroids and mizoribin (MZR)were started, his hematuria and proteinuria disappeared and renal function improved markedly. Case 2 was a 37-year-old male with alcoholic liver cirrhosis complicated with hepatic encephalopathy. Although he was being treated at another hospital, nephritic syndrome occurred with rapidly worsening renal function and massive ascites. After continuous drainage of the ascites, we performed a renal biopsy. Mild proliferative lesions and notable wrinkling, thickening and doubling of the basal membrane were seen. Crescent formations were found in about half of the glomeruli. The fluorescent antibody technique showed positive pictures of IgA (IgA1) and C3. When three