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  1. Alcohol-Related Liver Disease

    MedlinePlus

    ... events. Please support us. Donate | Volunteer Alcohol-Related Liver Disease Discussion on Inspire Support Community Join the ... Disease Information > Alcohol-Related Liver Disease Alcohol-Related Liver Disease Explore this section to learn more about ...

  2. HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

    PubMed Central

    Morgan, M Y; Ross, M G; Ng, C M; Adams, D M; Thomas, H C; Sherlock, S

    1980-01-01

    Ninety-two British, caucasian, alcoholic patients with liver disese were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P less than 0.02). Increased measles antibody titres were found in patients without cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of IgM and IgA were were raised in patients with stetosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups. It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcohol-related liver disease are probably secondary phenomena. PMID:7400347

  3. Susceptibility to alcohol-related liver injury.

    PubMed

    Lieber, C S

    1994-01-01

    Alcohol affects the liver through metabolic disturbances associated with its oxidation. Redox changes produced by the hepatic alcohol dehydrogenase pathway affect lipid, carbohydrate and protein metabolism. Ethanol is also oxidized in liver microsomes by the ethanol-inducible cytochrome P4502E1, resulting in ethanol tolerance and selective hepatic perivenular damage. Furthermore, P4502E1 activates various xenobiotics, explaining the increased susceptibility of the heavy drinker to the toxicity of anesthetics, commonly used medications (i.e. isoniazid), analgesics (i.e. acetaminophen), and chemical carcinogens. Induction of microsomal enzymes also contributes to vitamin A depletion, enhances its hepatotoxicity and results in increased acetaldehyde generation from ethanol, with formation of protein adducts, glutathione depletion, free-radical-mediated toxicity, and lipid peroxidation. Chronic ethanol consumption strikingly enhances the number of hepatic collagen-producing activated lipocytes. Both in vivo (in our baboon model of alcoholic cirrhosis) and in vitro (in cultured myofibroblasts and activated lipocytes) ethanol and/or its metabolite acetaldehyde increase collagen accumulation and mRNA for collagen. Gender differences are related, in part, to lower gastric ADH activity (with consequent reduction of first pass ethanol metabolism) in young women, decreased hepatic fatty acid binding protein and increased free-fatty acid levels as well as lesser omega-hydroxylation, all of which result in increased vulnerability to ethanol. Elucidation of the biochemical effects of ethanol are now resulting in improved therapy: in baboons, S-adenosyl-L-methionine attenuates the ethanol-induced glutathione depletion and associated mitochondrial lesions, and polyenylphosphatidylcholine opposes the ethanol-induced hepatic phospholipid depletion, the decrease in phosphatidylethanolamine methyltransferase activity and the activation of hepatic lipocytes, with full prevention of

  4. Ceramide inhibitor myriocin restores insulin/insulin growth factor signaling for liver remodeling in experimental alcohol-related steatohepatitis

    PubMed Central

    Lizarazo, Diana; Zabala, Valerie; Tong, Ming; Longato, Lisa; de la Monte, Suzanne M.

    2015-01-01

    Background and Aim Alcohol-related liver disease (ALD) is mediated in part by insulin resistance. Attendant dysregulation of lipid metabolism increases accumulation of hepatic ceramides that worsen insulin resistance and compromise the structural and functional integrity of the liver. Insulin and insulin growth factor (IGF) stimulate aspartyl-asparaginyl-β-hydroxylase (AAH), which promotes cell motility needed for structural maintenance and remodeling of the liver. AAH mediates its effects by activating Notch, and in ALD, insulin/IGF signaling, AAH, and Notch are inhibited. Method To test the hypothesis that in ALD, hepatic ceramide load contributes to impairments in insulin, AAH, and Notch signaling, control and chronic ethanol-fed adult Long–Evans rats were treated with myriocin, an inhibitor of serine palmitoyl transferase. Livers were used to assess steatohepatitis, insulin/IGF pathway activation, and expression of AAH–Notch signaling molecules. Results Chronic ethanol-fed rats had steatohepatitis with increased ceramide levels; impairments in signaling through the insulin receptor, insulin receptor substrate, and Akt; and decreased expression of AAH, Notch, Jagged, Hairy–Enhancer of Split-1, hypoxiainducible factor 1α, and proliferating cell nuclear antigen. Myriocin abrogated many of these adverse effects of ethanol, particularly hepatic ceramide accumulation, steatohepatitis, and impairments of insulin signaling through Akt, AAH, and Notch. Conclusions In ALD, the histopathology and impairments in insulin/IGF responsiveness can be substantially resolved by ceramide inhibitor treatments, even in the context of continued chronic ethanol exposure. PMID:23802886

  5. Liver disease

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000205.htm Liver disease To use the sharing features on this page, please enable JavaScript. The term "liver disease" applies to many conditions that stop the ...

  6. Liver Diseases

    MedlinePlus

    Your liver is the largest organ inside your body. It helps your body digest food, store energy, and remove poisons. There are many kinds of liver diseases. Viruses cause some of them, like hepatitis ...

  7. A method for estimating alcohol-related liver cirrhosis mortality in Japan.

    PubMed

    Parrish, K M; Higuchi, S; Muramatsu, T; Stinson, F S; Harford, T C

    1991-12-01

    In Japan, per capita alcohol consumption increased sharply during the post World War II period followed by an increase in cirrhosis mortality. The prevalence of alcoholic cirrhosis among hospitalized patients also increased, from 11% in 1969 to 18% in 1985. Despite an increase in the percentage of drinkers among young women, over 80% of women in Japan are still abstainers or light drinkers. Thus, female cirrhosis mortality rates can be used as a proxy measure of non-alcohol-related cirrhosis mortality rates to estimate alcohol-related cirrhosis deaths among Japanese men. Employing this method, we conclude that two-thirds of cirrhosis deaths among men between 24 and 85 years of age and half of all cirrhosis deaths were attributable to alcohol. Two factors are probably responsible for the differences in proportional morbidity and proportional mortality of alcohol-related cirrhosis: differences in survival rates between alcoholic and non-alcoholic cirrhosis patients and detection bias toward post-hepatic cirrhosis. The synergistic effect of alcohol on viral hepatitis may in part explain excess cirrhosis deaths among Japanese men.

  8. Progression of Liver Disease

    MedlinePlus

    ... The Progression of Liver Disease The Progression of Liver Disease There are many different types of liver ... may put your life in danger. The Healthy Liver Your liver helps fight infections and cleans your ...

  9. American Liver Foundation

    MedlinePlus

    ... to Give Join Our Mail List Search: Resources Liver Disease Information Select Info Center Alagille Syndrome Alcohol-Related Liver Disease Alpha-1 Antitrypsin Deficiency Autoimmune Hepatitis Benign ...

  10. Liver disease - resources

    MedlinePlus

    Resources - liver disease ... The following organizations are good resources for information on liver disease : American Liver Foundation -- www.liverfoundation.org Children's Liver Association for Support Services -- www.classkids.org Hepatitis ...

  11. Liver Disease and IBD

    MedlinePlus

    ... Home > Resources > Liver Disease and IBD Go Back Liver Disease and IBD Email Print + Share Several complications ... be necessary to make the definitive diagnosis. FATTY LIVER DISEASE (HEPATCI STEATOSIS) This is the most common ...

  12. Alcoholic disease: liver and beyond.

    PubMed

    Rocco, Alba; Compare, Debora; Angrisani, Debora; Sanduzzi Zamparelli, Marco; Nardone, Gerardo

    2014-10-28

    The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world's third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the "necrosis-fibrosis" sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract.

  13. Autoimmune liver disease panel

    MedlinePlus

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  14. Liver disease in menopause.

    PubMed

    Brady, Carla W

    2015-07-07

    There are numerous physiologic and biochemical changes in menopause that can affect the function of the liver and mediate the development of liver disease. Menopause represents a state of growing estrogen deficiency, and this loss of estrogen in the setting of physiologic aging increases the likelihood of mitochondrial dysfunction, cellular senescence, declining immune responses to injury, and disarray in the balance between antioxidant formation and oxidative stress. The sum effect of these changes can contribute to increased susceptibility to development of significant liver pathology, particularly nonalcoholic fatty liver disease and hepatocellular carcinoma, as well as accelerated progression of fibrosis in liver diseases, as has been particularly demonstrated in hepatitis C virus liver disease. Recognition of the unique nature of these mediating factors should raise suspicion for liver disease in perimenopausal and menopausal women and offer an opportunity for implementation of aggressive treatment measures so as to avoid progression of liver disease to cirrhosis, liver cancer and liver failure.

  15. Alcoholic liver disease

    MedlinePlus

    Liver disease due to alcohol; Cirrhosis or hepatitis - alcoholic; Laennec's cirrhosis ... Alcoholic liver disease occurs after years of heavy drinking. Over time, scarring and cirrhosis can occur. Cirrhosis is the ...

  16. Diet - liver disease

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/002441.htm Diet - liver disease To use the sharing features on this page, please enable JavaScript. Some people with liver disease must eat a special diet. This diet ...

  17. Liver disease in pregnancy

    PubMed Central

    Lee, Noel M; Brady, Carla W

    2009-01-01

    Liver diseases in pregnancy may be categorized into liver disorders that occur only in the setting of pregnancy and liver diseases that occur coincidentally with pregnancy. Hyperemesis gravidarum, preeclampsia/eclampsia, syndrome of hemolysis, elevated liver tests and low platelets (HELLP), acute fatty liver of pregnancy, and intrahepatic cholestasis of pregnancy are pregnancy-specific disorders that may cause elevations in liver tests and hepatic dysfunction. Chronic liver diseases, including cholestatic liver disease, autoimmune hepatitis, Wilson disease, and viral hepatitis may also be seen in pregnancy. Management of liver disease in pregnancy requires collaboration between obstetricians and gastroenterologists/hepatologists. Treatment of pregnancy-specific liver disorders usually involves delivery of the fetus and supportive care, whereas management of chronic liver disease in pregnancy is directed toward optimizing control of the liver disorder. Cirrhosis in the setting of pregnancy is less commonly observed but offers unique challenges for patients and practitioners. This article reviews the epidemiology, pathophysiology, diagnosis, and management of liver diseases seen in pregnancy. PMID:19248187

  18. Diagnosis of alcoholic liver disease

    PubMed Central

    Torruellas, Cara; French, Samuel W; Medici, Valentina

    2014-01-01

    Alcohol is a hepatotoxin that is commonly consumed worldwide and is associated with a spectrum of liver injury including simple steatosis or fatty liver, alcoholic hepatitis, fibrosis, and cirrhosis. Alcoholic liver disease (ALD) is a general term used to refer to this spectrum of alcohol-related liver injuries. Excessive or harmful alcohol use is ranked as one of the top five risk factors for death and disability globally and results in 2.5 million deaths and 69.4 million annual disability adjusted life years. All patients who present with clinical features of hepatitis or chronic liver disease or who have elevated serum elevated transaminase levels should be screened for an alcohol use disorder. The diagnosis of ALD can generally be made based on history, clinical and laboratory findings. However, the diagnosis of ALD can be clinically challenging as there is no single diagnostic test that confirms the diagnosis and patients may not be forthcoming about their degree of alcohol consumption. In addition, clinical findings may be absent or minimal in early ALD characterized by hepatic steatosis. Typical laboratory findings in ALD include transaminase levels with aspartate aminotransferase greater than alanine aminotransferase as well as increased mean corpuscular volume, gamma-glutamyltranspeptidase, and IgA to IgG ratio. In unclear cases, the diagnosis can be supported by imaging and liver biopsy. The histological features of ALD can ultimately define the diagnosis according to the typical presence and distribution of hepatic steatosis, inflammation, and Mallory-Denk bodies. Because of the potential reversible nature of ALD with sobriety, regular screening of the general population and early diagnosis are essential. PMID:25206273

  19. Coffee and Liver Disease

    PubMed Central

    Wadhawan, Manav; Anand, Anil C.

    2016-01-01

    Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality. PMID:27194895

  20. Liver Disease and Pulmonary Hypertension

    MedlinePlus

    Liver Disease Pulmonary & PH Hypertension Did you know that if you have liver disease, you are at risk for pulmonary hypertension? ... tissue diseases (scleroderma and lupus for example), chronic liver disease, congenital heart disease, or HIV infec- tion. ...

  1. Liver transplant for cholestatic liver diseases.

    PubMed

    Carrion, Andres F; Bhamidimarri, Kalyan Ram

    2013-05-01

    Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT.

  2. Pregnancy and liver disease.

    PubMed

    Westbrook, Rachel H; Dusheiko, Geoffrey; Williamson, Catherine

    2016-04-01

    Pregnancy associated liver diseases affect up to 3% of pregnant women and are the most frequent cause of liver dysfunction in pregnancy. When severe, they are associated with significant morbidity and mortality for both mother and infant. A rapid evaluation to distinguish them from non-pregnancy related liver dysfunction is essential, in order to facilitate appropriate management. Liver disease unrelated to pregnancy can present de novo in pregnancy, or pregnancy can occur in women with preexisting liver pathology (Table 1). Research and subsequent advances in medical care have resulted in improved but still not satisfactory maternal and fetal outcomes. In this review we provide an overview of the liver diseases specific to the pregnant state and an update on their pathogenesis, treatment and outcomes. The risks of pregnancy in women with pre-existent liver pathology is detailed and recent advances in our understanding of specific risks and outcomes are discussed.

  3. [Liver diseases and pregnancy].

    PubMed

    Guettrot-Imbert, G; Plessier, A; Hillaire, S; Delluc, C; Leroux, G; Le Guern, V; Costedoat-Chalumeau, N

    2015-03-01

    Liver disease can be observed in pregnant women whether or not related to pregnancy. Liver disorders can be revealed by pruritus, vomiting, jaundice or abnormal liver blood tests during pregnancy. These liver manifestations can lead to the diagnosis of liver disease specifically associated to pregnancy as intrahepatic pregnancy, intrahepatic cholestasis of pregnancy, Hyperemesis gravidarum, acute fatty liver of pregnancy and preeclampsia-induced liver injury. Pregnancy may also be a risk factor for other liver diseases coincident with pregnancy as viral hepatitis, thrombosis, drug toxicity or gallstone. Finally, pre-existing liver disease must be taken into account given the risk of fœto-maternal transmission risk as well as the risk of decompensation of underlying cirrhosis secondary to the hemodynamic changes caused by pregnancy. The aim of this revue is to perform an update on the various situations that can be observed, the principles of management of these liver diseases, in order to reduce the risk of complications and to ensure the best maternal and fetal prognosis.

  4. Liver transplantation for chronic liver disease: advances and controversies in an era of organ shortages

    PubMed Central

    Prince, M; Hudson, M

    2002-01-01

    Since liver transplantation was first performed in 1968 by Starzl et al, advances in case selection, liver surgery, anaesthetics, and immunotherapy have significantly increased the indications for and success of this operation. Liver transplantation is now a standard therapy for many end stage liver disorders as well as acute liver failure. However, while demand for cadaveric organ grafts has increased, in recent years the supply of organs has fallen. This review addresses current controversies resulting from this mismatch. In particular, methods for increasing graft availability and difficulties arising from transplantation in the context of alcohol related cirrhosis, primary liver tumours, and hepatitis C are reviewed. Together these three indications accounted for 42% of liver transplants performed for chronic liver disease in the UK in 2000. Ethical frameworks for making decisions on patients' suitability for liver transplantation have been developed in both the USA and the UK and these are also reviewed. PMID:11884694

  5. Liver Disease and Adult Vaccination

    MedlinePlus

    ... Vaccination Recommendations Adult Vaccination Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet ... critical for people with health conditions such as liver disease. If you have chronic liver disease, talk ...

  6. Alcoholic liver disease

    PubMed Central

    Walsh, K.; Alexander, G.

    2000-01-01

    Alcohol is a major cause of liver cirrhosis in the Western world and accounts for the majority of cases of liver cirrhosis seen in district general hospitals in the UK. The three most widely recognised forms of alcoholic liver disease are alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis. The exact pathogenesis of alcoholic liver injury is still not clear but immune mediated and free radical hepatic injury are thought to be important. There is increasing interest in genetic factors predisposing to hepatic injury in susceptible individuals. Diagnosis is based on accurate history, raised serum markers such as γ-glutamyltransferase, mean corpuscular volume, and IgA and liver histology when obtainable. Abstinence is the most important aspect of treatment. Newer drugs such as acamprosate and naltrexone are used to reduce alcohol craving. Vitamin supplements and nutrition are vital while corticosteroids have a role in acute alcoholic hepatitis where there is no evidence of gastrointestinal haemorrhage or sepsis. Liver transplantation has excellent results in abstinent patients with end stage liver disease but there are concerns about recidivism after transplant.


Keywords: cirrhosis; liver disease; alcohol PMID:10775280

  7. Fatty Liver Disease (Nonalcoholic Steatohepatitis)

    MedlinePlus

    ... History Research Resources Research at NIDDK Meetings & Events Technology Advancement & Transfer Health Information Diabetes Digestive Diseases Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition ...

  8. [Wilson disease: liver form].

    PubMed

    Guerra Montero, Luis; Ortega Álvarez, Félix; Sumire Umeres, Julia; Cok García, Jaime

    2015-01-01

    Wilson disease (WD) is a disorder of copper metabolism that is inherited as an autosomal recessive, which produces toxic copper accumulation mainly in the liver and brain, in general has two ways presentation, liver at early ages and neurological in later ages. We present the case of a female patient of 21 years diagnosed of WD in liver cirrhosis that started with an edematous ascites without any neurological symptoms despite the age. Their laboratory studies showed decrease in serum ceruloplasmin and high cupruria within 24 hours of the disease , characteristic data of WD. Although WD is not a common disease should be suspected in all chronic liver disease of unknown etiology with negative viral markers and autoimmunity with or without neurological manifestations as soon as posible and starting treatment with copper chelating mainly leads to a substantial improvement the prognosis of these patients.

  9. [Autophagy in liver diseases].

    PubMed

    Harada, Masaru

    2011-12-01

    Two major degradation systems exist in cells: the lysosome and proteasome. In the lysosome system, extracellular materials are degraded via endocytosis. Intracellular materials are degraded by autophagy, a cellular pathway crucial for various intracellular events. It has recently been demonstrated that autophagy is involved in the pathogenesis of various liver diseases. In hepatitis B or hepatitis C virus infection, autophagy is enhanced in hepatocytes. In hepatic steatosis, hepatocyte autophagy is inhibited. The expression of the autophagy protein is disrupted in hepatocellular carcinoma. I summarize recent advances in the study of the involvement of autophagy in various liver diseases. The regulation of autophagy in the liver may be a useful therapeutic strategy for various liver diseases.

  10. [Liver diseases in the elderly].

    PubMed

    Bruguera, Miguel

    2014-11-01

    Liver diseases in the elderly have aroused less interest than diseases of other organs, since the liver plays a limited role in aging. There are no specific liver diseases of old age, but age-related anatomical and functional modifications of the liver cause changes in the frequency and clinical behavior of some liver diseases compared with those in younger patients. This review discusses the most important features of liver function in the healthy elderly population, as well as the features of the most prevalent liver diseases in this age group, especially the diagnostic approach to the most common liver problems in the elderly: asymptomatic elevation of serum transaminases and jaundice.

  11. [Probiotics in liver diseases].

    PubMed

    Soriano, Germán; Sánchez, Elisabet; Guarner, Carlos

    2013-01-01

    Alterations in intestinal microbiota and inflammatory response play a key role in disease progression and development of complications in liver diseases, mainly in cirrhosis and non-alcoholic steatohepatitis. Probiotics can be useful to delay disease progression and to prevent development of complications due to their ability to modulate intestinal flora, intestinal permeability and inflammatory response. Several studies have shown the efficacy of probiotics in the treatment of minimal hepatic encephalopathy and the prevention of episodes of overt hepatic encephalopathy. Probiotics have also been observed to prevent postoperative bacterial infections and to improve liver damage in non-alcoholic steatohepatitis. However, more studies are needed in order to confirm the efficacy and safety of probiotics in patients with liver diseases, and to better understanding of the mechanisms implicated in their effects.

  12. Gut microbiota and liver diseases

    PubMed Central

    Minemura, Masami; Shimizu, Yukihiro

    2015-01-01

    Several studies revealed that gut microbiota are associated with various human diseases, e.g., metabolic diseases, allergies, gastroenterological diseases, and liver diseases. The liver can be greatly affected by changes in gut microbiota due to the entry of gut bacteria or their metabolites into the liver through the portal vein, and the liver-gut axis is important to understand the pathophysiology of several liver diseases, especially non-alcoholic fatty liver disease and hepatic encephalopathy. Moreover, gut microbiota play a significant role in the development of alcoholic liver disease and hepatocarcinogenesis. Based on these previous findings, trials using probiotics have been performed for the prevention or treatment of liver diseases. In this review, we summarize the current understanding of the changes in gut microbiota associated with various liver diseases, and we describe the therapeutic trials of probiotics for those diseases. PMID:25684933

  13. Paediatric Autoimmune Liver Disease.

    PubMed

    Liberal, Rodrigo; Vergani, Diego; Mieli-Vergani, Giorgina

    2015-01-01

    In paediatrics, there are 2 liver disorders in which liver damage most likely stems from an autoimmune attack: 'classical' autoimmune hepatitis (AIH) and the AIH/sclerosing cholangitis overlap syndrome (also known as autoimmune sclerosing cholangitis, ASC). The presentation of childhood autoimmune liver disease (AILD) is non-specific and can mimic most other liver disorders. AIH is exquisitely responsive to immunosuppressive treatment, which should be instituted promptly to prevent rapid deterioration and promote remission and long-term survival. Difficult-to-treat or non-responsive patients should be treated with mycophenolate mofetil; if this fails then calcineurin inhibitors can be tried. Persistent failure to respond or lack of adherence to treatment result in end-stage liver disease. These patients, and those with fulminant liver failure at diagnosis, will require liver transplantation. ASC responds to the same immunosuppressive treatment used for AIH when treatment is initiated early. Abnormal liver function tests often resolve within a few months of treatment, although medium- to long-term prognosis is worse than that of AIH because bile duct disease continues to progress despite treatment in approximately 50% of patients. Ursodeoxycholic acid is usually added to conventional treatment regimen in ASC, but whether this actually helps arrest the progression of bile duct disease remains to be established. The pathogenesis of paediatric-onset AILD is not fully understood, although there is mounting evidence that genetic susceptibility, molecular mimicry and impaired immunoregulatory networks contribute to the initiation and perpetuation of the autoimmune attack. Liver damage is thought to be mediated primarily by CD4pos T-cells. While Th1 effector cells are associated with hepatocyte damage in both AIH and ASC, Th17 immune responses predominate in the latter where they correlate with biochemical indices of cholestasis, indicating that IL-17 is involved in the

  14. Systemic abnormalities in liver disease

    PubMed Central

    Minemura, Masami; Tajiri, Kazuto; Shimizu, Yukihiro

    2009-01-01

    Systemic abnormalities often occur in patients with liver disease. In particular, cardiopulmonary or renal diseases accompanied by advanced liver disease can be serious and may determine the quality of life and prognosis of patients. Therefore, both hepatologists and non-hepatologists should pay attention to such abnormalities in the management of patients with liver diseases. PMID:19554648

  15. Autophagy in liver diseases.

    PubMed

    Rautou, Pierre-Emmanuel; Mansouri, Abdellah; Lebrec, Didier; Durand, François; Valla, Dominique; Moreau, Richard

    2010-12-01

    Autophagy, or cellular self-digestion, is a cellular pathway crucial for development, differentiation, survival, and homeostasis. Its implication in human diseases has been highlighted during the last decade. Recent data show that autophagy is involved in major fields of hepatology. In liver ischemia reperfusion injury, autophagy mainly has a prosurvival activity allowing the cell for coping with nutrient starvation and anoxia. During hepatitis B or C infection, autophagy is also increased but subverted by viruses for their own benefit. In hepatocellular carcinoma, the autophagy level is decreased. In this context, autophagy has an anti-tumor role and therapeutic strategies increasing autophagy, as rapamycin, have a beneficial effect in patients. Moreover, in hepatocellular carcinoma, Beclin-1 level, an autophagy protein, has a prognostic significance. In α-1-antitrypsin deficiency, the aggregation-prone ATZ protein accumulates in the endoplasmic reticulum. This activates the autophagic response which aims at degrading mutant ATZ. Some FDA-approved drugs which enhance autophagy and the disposal of aggregation-prone proteins may be useful in α-1-antitrypsin deficiency. Following alcohol consumption, autophagy is decreased in liver cells, likely due to a decrease in intracellular 5'-AMP-activated protein kinase (AMPk) and due to an alteration in vesicle transport in hepatocytes. This decrease in autophagy contributes to the formation of Mallory-Denk bodies and to liver cell death. Hepatic autophagy is defective in the liver in obesity and its upregulation improves insulin sensitivity.

  16. Endocannabinoids in liver disease.

    PubMed

    Tam, Joseph; Liu, Jie; Mukhopadhyay, Bani; Cinar, Resat; Godlewski, Grzegorz; Kunos, George

    2011-01-01

    Endocannabinoids are lipid mediators of the same cannabinoid (CB) receptors that mediate the effects of marijuana. The endocannabinoid system (ECS) consists of CB receptors, endocannabinoids, and the enzymes involved in their biosynthesis and degradation, and it is present in both brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases and contributes to the underlying pathologies. In patients with cirrhosis of various etiologies, the activation of vascular and cardiac CB(1) receptors by macrophage-derived and platelet-derived endocannabinoids contributes to the vasodilated state and cardiomyopathy, which can be reversed by CB(1) blockade. In mouse models of liver fibrosis, the activation of CB(1) receptors on hepatic stellate cells is fibrogenic, and CB(1) blockade slows the progression of fibrosis. Fatty liver induced by a high-fat diet or chronic alcohol feeding depends on the activation of peripheral receptors, including hepatic CB(1) receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB(1) blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB(1) antagonists.

  17. [Liver diseases of infectious aetiology].

    PubMed

    Chalupa, P

    2007-01-01

    Review article is dealing with the problems of infectious diseases of the liver. Attention is paid to the basic infectious agents, jaundice accompanying infectious diseases and focal infections of the liver. Specific infections of the liver are supplemented by brief pathological and anatomical characteristics.

  18. Polycystic Liver Disease

    SciTech Connect

    Linda, Nguyen

    2016-03-25

    A 77-year-old African American male presented with intermittent abdominal pain for one week. He denied nausea, vomiting, diarrhea, constipation, fevers, anorexia, or weight loss. He denied a family history of liver disease, recent travel, or history of intravenous drug abuse. His vital signs were normal. Labs revealed total bilirubin of 1.5 mg/dl, hypoalbuminaemia 3.0 gm/dl and prolonged prothrombin time of 14.8 sec. Computed Tomography of the abdomen and pelvis with contrast showed multiple hepatic cysts with the largest cyst occupying the right abdomen, measuring 20.6 cm (Panel A and). This cyst had predominantly fluid attenuation, but also contained several septations. The patient underwent laparoscopic fenestration of the large hepatic cyst with hepatic cyst wall biopsy. Pathology revealed blood without malignant cells. The patient tolerated the procedure well with improvement of his abdominal pain and normalization of his liver function tests and coagulation profile.

  19. Probiotics in Pediatric Liver Disease.

    PubMed

    Miloh, Tamir

    2015-01-01

    The gut-liver axis involves complex interaction between the intestinal microbiome and the liver parenchyma. Probiotics are live microorganisms that are used in a variety of diseases. With currently only 2 randomized-controlled studies (one with Lactobacillus GG and the other with VSL #3), data are scarce to support the clinical effect of probiotic use in children with nonalcoholic fatty liver disease. There is evidence that probiotics decrease the risk of necrotizing enterocolitis and thereby reduce the prevalence of total parenteral nutrition-induced chronic liver disease. Probiotics are used with a few reported positive outcomes in patients with cystic fibrosis and familial hypercholesterolemia and may be promising in other liver conditions. Probiotics are generally safe and well tolerated in children, premature infants, and in patients after liver transplantation. Large, prospective, randomized clinical trials are needed to evaluate the benefit of probiotics in children with liver diseases.

  20. Screening in liver disease

    PubMed Central

    Poggio, Paolo Del; Mazzoleni, Marzio

    2006-01-01

    A disease is suitable for screening if it is common, if the target population can be identified and reached and if both a good screening test and an effective therapy are available. Of the most common liver diseases only viral hepatitis and genetic hemochromatosis partially satisfy these conditions. Hepatitis C is common, the screening test is good and the therapy eliminates the virus in half of the cases, but problems arise in the definition of the target population. In fact generalized population screening is not endorsed by international guidelines, although some recommend screening immigrants from high prevalence countries. Opportunistic screening (case finding) of individuals with classic risk factors, such as transfusion before 1992 and drug addiction, is the most frequently used strategy, but there is disagreement whether prison inmates, individuals with a history of promiscuous or traumatic sex and health care workers should be screened. In a real practice setting the performance of opportunistic screening by general practitioners is low but can be ameliorated by training programs. Screening targeted to segments of the population or mass campaigns are expensive and therefore interventions should be aimed to improve opportunistic screening and the detection skills of general practitioners. Regarding genetic hemochromatosis there is insufficient evidence for population screening, but individual physicians can decide to screen racial groups with a high prevalence of the disease, such as people in early middle age and of northern European origin. In the other cases opportunistic screening of high risk individuals should be performed, with a high level of suspicion in case of unexplained liver disease, diabetes, juvenile artropathy, sexual dysfunction and skin pigmentation. PMID:16981254

  1. Non-invasive assessment of liver fibrosis in patients with alcoholic liver disease

    PubMed Central

    Lombardi, Rosa; Buzzetti, Elena; Roccarina, Davide; Tsochatzis, Emmanuel A

    2015-01-01

    Alcoholic liver disease (ALD) consists of a broad spectrum of disorders, ranging from simple steatosis to alcoholic steatohepatitis and cirrhosis. Fatty liver develops in more than 90% of heavy drinkers, however only 30%-35% of them develop more advanced forms of ALD. Therefore, even if the current “gold standard” for the assessment of the stage of alcohol-related liver injury is histology, liver biopsy is not reasonable in all patients who present with ALD. Currently, although several non-invasive fibrosis markers have been suggested as alternatives to liver biopsy in patients with ALD, none has been sufficiently validated. As described in other liver disease, the diagnostic accuracy of such tests in ALD is acceptable for the diagnosis of significant fibrosis or cirrhosis but not for lesser fibrosis stages. Existing data suggest that the use of non-invasive tests could be tailored to first tier screening of patients at risk, in order to diagnose early patients with progressive liver disease and offer targeted interventions for the prevention of decompensation. We review these tests and critically appraise the existing evidence. PMID:26494961

  2. Polycystic liver diseases

    PubMed Central

    Onori, P.; Franchitto, A.; Mancinelli, R.; Carpino, G.; Alvaro, D.; Francis, H.; Alpini, G.; Gaudio, E.

    2010-01-01

    Polycystic liver diseases (PCLDs) are genetic disorders with heterogeneous etiologies and a range of phenotypic presentations. PCLD exhibits both autosomal or recessive dominant pattern of inheritance and is characterized by the progressive development of multiple cysts, isolated or associated with polycystic kidney disease, that appear more extensive in women. Cholangiocytes have primary cilia, functionally important organelles (act as mechanosensors) that are involved in both normal developmental and pathological processes. The absence of polycystin-1, 2, and fibrocystin/polyductin, normally localized to primary cilia, represent a potential mechanism leading to cyst formation, associated with increased cell proliferation and apoptosis, enhanced fluid secretion, abnormal cell–matrix interactions, and alterations in cell polarity. Proliferative and secretive activities of cystic epithelium can be regulated by estrogens either directly or by synergizing growth factors including nerve growth factor, IGF1, FSH and VEGF. The abnormalities of primary cilia and the sensitivity to proliferative effects of estrogens and different growth factors in PCLD cystic epithelium provide the morpho-functional basis for future treatment targets, based on the possible modulation of the formation and progression of hepatic cysts. PMID:20138815

  3. Liver Disease in the Alcoholic

    PubMed Central

    Szilagyi, Andrew

    1986-01-01

    The problem of liver damage in alcoholic patients is widespread. This review discusses hepatic damage on the basis of a histologic classification of increasing severity. In the early stages, or with compensated cirrhosis, clinical and laboratory findings may not accurately reflect hepatic involvement. Furthermore, there exists a group of alcoholic patients in whom liver disease may be caused by factors other than alcohol. Nevertheless, in most patients with liver disease, certain biochemical features help to establish an alcoholic etiology. These features and the use of liver biopsy are discussed, and a practical guideline for diagnosis and follow-up is offered. PMID:21267299

  4. Pediatric nonalcoholic fatty liver disease.

    PubMed

    Bozic, Molly A; Subbarao, Girish; Molleston, Jean P

    2013-08-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the pediatric population. Increased recognition of this form of liver disease parallels the dramatic rise in childhood and adolescent obesity over the past 2 decades. Like adults, most children with NAFLD are obese, and comorbidities include insulin resistance, hypertension, and dyslipidemia. Unfortunately, pediatric NAFLD is not always a benign condition, with some children progressing to hepatic fibrosis and even cirrhosis in severe cases. The etiology of nonalcoholic steatohepatitis is not yet fully understood; however, hepatic steatosis in the context of insulin resistance and increased oxidative stress may lead to progressive disease. Although physical examination, laboratory evaluation, and radiographic findings provide clues to the potential presence of fatty liver disease, liver biopsy remains the gold standard for diagnosis. Lifestyle modification, including slow and steady weight loss, improved dietary habits, and increased daily, aerobic physical activity, remains the first-line approach in treating pediatric fatty liver disease. Antioxidant pharmacologic therapy such as use of vitamin E has shown some benefit in patients with biopsy-proven steatohepatitis. Nutrition plays an essential role not only in the development of fatty liver disease but also potentially in the treatment and prevention of progression to more severe disease.

  5. Chronic Liver Disease and Hispanic Americans

    MedlinePlus

    ... Population Profiles > Hispanic/Latino > Chronic Liver Disease Chronic Liver Disease and Hispanic Americans Among the Hispanic/Latino population, chronic liver disease is a leading cause of death. While ...

  6. Human alcohol-related neuropathology

    PubMed Central

    Kril, Jillian J.

    2015-01-01

    Alcohol-related diseases of the nervous system are caused by excessive exposures to alcohol, with or without co-existing nutritional or vitamin deficiencies. Toxic and metabolic effects of alcohol (ethanol) vary with brain region, age/developmental stage, dose, and duration of exposures. In the mature brain, heavy chronic or binge alcohol exposures can cause severe debilitating diseases of the central and peripheral nervous systems, and skeletal muscle. Most commonly, long-standing heavy alcohol abuse leads to disproportionate loss of cerebral white matter and impairments in executive function. The cerebellum (especially the vermis), cortical-limbic circuits, skeletal muscle, and peripheral nerves are also important targets of chronic alcohol-related metabolic injury and degeneration. Although all cell types within the nervous system are vulnerable to the toxic, metabolic, and degenerative effects of alcohol, astrocytes, oligodendrocytes, and synaptic terminals are major targets, accounting for the white matter atrophy, neural inflammation and toxicity, and impairments in synaptogenesis. Besides chronic degenerative neuropathology, alcoholics are predisposed to develop severe potentially life-threatening acute or subacute symmetrical hemorrhagic injury in the diencephalon and brainstem due to thiamine deficiency, which exerts toxic/metabolic effects on glia, myelin, and the microvasculature. Alcohol also has devastating neurotoxic and teratogenic effects on the developing brain in association with fetal alcohol spectrum disorder/fetal alcohol syndrome. Alcohol impairs function of neurons and glia, disrupting a broad array of functions including neuronal survival, cell migration, and glial cell (astrocytes and oligodendrocytes) differentiation. Further progress is needed to better understand the pathophysiology of this exposure-related constellation of nervous system diseases and better correlate the underlying pathology with in vivo imaging and biochemical lesions

  7. Muscle cramps in liver disease.

    PubMed

    Mehta, Shivang S; Fallon, Michael B

    2013-11-01

    Muscle cramps are common in patients with liver disease and adversely influence quality of life. The exact mechanisms by which they occur remain unclear, although a number of pathophysiological events unique to liver disease may contribute. Clinical studies have identified alterations in 3 areas: nerve function, energy metabolism, and plasma volume/electrolytes. Treatments have focused on these particular areas with varied results. This review will focus on the clinical features of muscle cramps in patients with liver disease and review potential mechanisms and current therapies.

  8. Research Areas: Liver Disease

    MedlinePlus

    ... 900 drugs and supplements.​​ Recent discoveries from NIDDK research include: New medication shows promise against liver fibrosis ... linked to biliary atresia in newborn animals Support Research NIDDK invests in basic, clinical and translational research ...

  9. QT prolongation and sudden cardiac death in patients with alcoholic liver disease

    SciTech Connect

    Day, C.P.; James, O.F.W. . Dept. of Medicine); Butler, T.J. . Dept. of Medical Statistics); Campbell, R.W.F. . Dept. of Academic Cardiology)

    1993-06-05

    Cardiovascular death is the most important cause of mortality in alcoholics, yet alcohol may protect against ischemic heart disease. This could be explained if deaths were a consequence of alcohol-related arrhythmias rather than of coronary atheroma. In many conditions, abnormalities of the QT interval are markers of arrhythmia and for risk of sudden death. The authors examined the relation between QT intervals and mortality in patients with alcoholic liver disease.

  10. Coagulation in Liver Disease.

    PubMed

    Hoffman, Maureane

    2015-07-01

    The liver plays a key role in hemostasis as the site of synthesis of many of the proteins involved in the coagulation, antithrombotic and fibrinolytic systems that interact to both establish hemostasis, and preventing thrombosis. The common laboratory tests, prothrombin time (PT) and activated partial thromboplastin time (aPTT), evolved from studies of plasma clotting in test tubes. Such studies laid the basis for the coagulation cascade model of hemostasis. However, thought has evolved to place a greater emphasis on the active roles of cells in localizing and regulating hemostasis. The PT and aPTT do not reflect the roles of cellular elements in hemostasis, nor do they reflect the crucial roles of antithrombotic and fibrinolytic systems. Thus, though the PT may indeed reflect the synthetic capacity of the liver, it does not accurately reflect the risk of bleeding or thrombosis in patients with liver failure.

  11. Extracellular Matrix and Liver Disease

    PubMed Central

    Arriazu, Elena; Ruiz de Galarreta, Marina; Cubero, Francisco Javier; Varela-Rey, Marta; Pérez de Obanos, María Pilar; Leung, Tung Ming; Lopategi, Aritz; Benedicto, Aitor; Abraham-Enachescu, Ioana

    2014-01-01

    Abstract Significance: The extracellular matrix (ECM) is a dynamic microenvironment that undergoes continuous remodeling, particularly during injury and wound healing. Chronic liver injury of many different etiologies such as viral hepatitis, alcohol abuse, drug-induced liver injury, obesity and insulin resistance, metabolic disorders, and autoimmune disease is characterized by excessive deposition of ECM proteins in response to persistent liver damage. Critical Issues: This review describes the main collagenous and noncollagenous components from the ECM that play a significant role in pathological matrix deposition during liver disease. We define how increased myofibroblasts (MF) from different origins are at the forefront of liver fibrosis and how liver cell-specific regulation of the complex scarring process occurs. Recent Advances: Particular attention is paid to the role of cytokines, growth factors, reactive oxygen species, and newly identified matricellular proteins in the regulation of fibrillar type I collagen, a field to which our laboratory has significantly contributed over the years. We compile data from recent literature on the potential mechanisms driving fibrosis resolution such as MF’ apoptosis, senescence, and reversal to quiescence. Future Directions: We conclude with a brief description of how epigenetics, an evolving field, can regulate the behavior of MF and of how new “omics” tools may advance our understanding of the mechanisms by which the fibrogenic response to liver injury occurs. Antioxid. Redox Signal. 21, 1078–1097. PMID:24219114

  12. Liver Disease and IBD

    MedlinePlus

    ... 34% of Crohn’s patients with disease of the terminal ileum (the last segment of the small intestine). ... increased risk for developing gallstones because the diseased terminal ileum cannot absorb bile salts, which are necessary ...

  13. Alcoholic liver disease - the extent of the problem and what you can do about it.

    PubMed

    Hazeldine, Simon; Hydes, Theresa; Sheron, Nick

    2015-04-01

    It takes upwards of ten years for alcohol-related liver disease to progress from fatty liver through fibrosis to cirrhosis to acute on chronic liver failure. This process is silent and symptom free and can easily be missed in primary care, usually presenting with advanced cirrhosis. At this late stage, management consists of expert supportive care, with prompt identification and treatment of bleeding, sepsis and renal problems, as well as support to change behaviour and stop harmful alcohol consumption. There are opportunities to improve care by bringing liver care everywhere up to the standards of the best liver units, as detailed in the Lancet Commission report. We also need a fundamental rethink of the technologies and approaches used in primary care to detect and intervene in liver disease at a much earlier stage. However, the most effective and cost-effective measure would be a proper evidence-based alcohol strategy.

  14. Nonalcoholic fatty liver disease - A multisystem disease?

    PubMed Central

    Mikolasevic, Ivana; Milic, Sandra; Turk Wensveen, Tamara; Grgic, Ivana; Jakopcic, Ivan; Stimac, Davor; Wensveen, Felix; Orlic, Lidija

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians. PMID:27920470

  15. Pleural effusion in liver disease.

    PubMed

    Alonso, José Castellote

    2010-12-01

    Hepatic hydrothorax is the paradigmatic pleural effusion in liver cirrhosis. It is defined as a pleural effusion in a patient with portal hypertension and no cardiopulmonary disease. The estimated prevalence of this complication in patients with liver cirrhosis is 5 to 6%. Its pathophysiology involves movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. Thoracentesis and pleural fluid analysis are necessary for diagnosis. Initial management consists of sodium restriction, diuretics, and therapeutic thoracentesis. A transjugular intrahepatic portosystemic shunt may provide a bridge prior to liver transplantation. Spontaneous bacterial empyema is the infection of a preexisting hydrothorax. The more frequent bacteria involved are ENTEROBACTERIACEAE and gram-positive cocci. Antibiotic therapy is the cornerstone of therapy. This article reviews etiology, clinical manifestations, and therapy of these two complications of liver cirrhosis and portal hypertension.

  16. Gallstones in Patients with Chronic Liver Diseases

    PubMed Central

    2017-01-01

    With prevalence of 10–20% in adults in developed countries, gallstone disease (GSD) is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD) is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients. PMID:28251162

  17. Alcoholic liver disease: The gut microbiome and liver crosstalk

    PubMed Central

    Hartmann, Phillipp; Seebauer, Caroline T.; Schnabl, Bernd

    2015-01-01

    Alcoholic liver disease is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with alcoholic liver disease have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier or preventing cellular responses to microbial products protect from experimental alcoholic liver disease. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of alcoholic liver disease. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship and consequences for alcoholic liver disease. We also discuss how the liver affects the intestinal microbiota. PMID:25872593

  18. Advances in Alcoholic Liver Disease

    PubMed Central

    Beier, Juliane I.; Arteel, Gavin E.

    2013-01-01

    Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States. In studies from the Veterans Administration, patients with cirrhosis and superimposed alcoholic hepatitis had greater than 60% mortality over a 4-year period, with most of those deaths occurring in the first month. Thus, the prognosis for this disease is more ominous than for many common types of cancer (eg, breast, prostate, and colon). Moreover, ALD imposes a significant economic burden from lost wages, health care costs, and lost productivity. Unfortunately, there is still no Food and Drug Administration–approved or widely accepted drug therapy for any stage of ALD. Thus, a pressing need exists for a more detailed understanding of mechanisms of liver injury. This article reviews recent advances in mechanisms and therapy related to five major areas of direct relevance to ALD: oxidative stress; gut-liver axis and cytokine signaling; malnutrition; fibrin/clotting; and stellate cell activation/fibrosis. We also review why therapies related to these mechanisms have performed well in experimental animals and in vitro systems, but have not necessarily translated into effective therapy for humans with ALD. PMID:21088999

  19. Cirrhosis and Liver Disease in Latina Women

    MedlinePlus

    ... Home > Minority Women's Health > Latinas Minority Women's Health Cirrhosis and liver disease Health conditions common in Latinas: More information on cirrhosis and liver disease in English Más recursos en ...

  20. [Liver ultrasound: focal lesions and diffuse diseases].

    PubMed

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed.

  1. Therapy for alcoholic liver disease

    PubMed Central

    Jaurigue, Maryconi M; Cappell, Mitchell S

    2014-01-01

    Alcoholism results in about 2.5 million deaths annually worldwide, representing 4% of all mortality. Although alcoholism is associated with more than 60 diseases, most mortality from alcoholism results from alcoholic liver disease (ALD). ALD includes alcoholic steatosis, alcoholic hepatitis, and alcoholic cirrhosis, in order of increasing severity. Important scoring systems of ALD severity include: Child-Pugh, a semi-quantitative scoring system useful to roughly characterize clinical severity; model for end-stage liver disease, a quantitative, objective scoring system used for prognostication and prioritization for liver transplantation; and discriminant function, used to determine whether to administer corticosteroids for alcoholic hepatitis. Abstinence is the cornerstone of ALD therapy. Psychotherapies, including twelve-step facilitation therapy, cognitive-behavioral therapy, and motivational enhancement therapy, help support abstinence. Disulfiram decreases alcohol consumption by causing unpleasant sensations after drinking alcohol from accumulation of acetaldehyde in serum, but disulfiram can be hepatotoxic. Adjunctive pharmacotherapies to reduce alcohol consumption include naltrexone, acamprosate, and baclofen. Nutritional therapy helps reverse muscle wasting, weight loss, vitamin deficiencies, and trace element deficiencies associated with ALD. Although reduced protein intake was previously recommended for advanced ALD to prevent hepatic encephalopathy, a diet containing 1.2-1.5 g of protein/kg per day is currently recommended to prevent muscle wasting. Corticosteroids are first-line therapy for severe alcoholic hepatitis (discriminant function ≥ 32), but proof of their efficacy in decreasing mortality remains elusive. Pentoxifylline is an alternative therapy. Complications of advanced ALD include ascites, spontaneous bacterial peritonitis, esophageal variceal bleeding, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and

  2. [Pulmonary hypertension in liver diseases].

    PubMed

    Savale, Laurent; Sattler, Caroline; Sitbon, Olivier

    2014-09-01

    Portopulmonary hypertension (PoPH) is defined by the combination of portal hypertension and precapillary pulmonary hypertension (mPAP ≥ 25 mmHg, PCWP < 15 mmHg and PVR > 3 Wood units). PoPH is characterised by pathobiological mechanisms that are similar to other forms of pulmonary arterial hypertension. Prevalence of PoPH is estimated at 0.5-5% among patients with portal hypertension with or without cirrhosis. Treatment strategies most commonly employed for PoPH patients are based on recommendations for idiopathic PAH management. Indeed, the choice of specific PAH treatment must take account the severity of the underlying liver disease. Prognosis of PoPH patients is dependent on both the severity of PAH and of the underlying liver disease. PoPH may be a contraindication for orthotopic liver transplantation (OLT) if mean pulmonary arterial pressure is > 35 mmHg associated with severe right ventricular dysfunction or high level of pulmonary vascular resistance (> 3-4 Wood units). Bridge therapy with specific PAH therapies should be considered in those patients in an attempt to improve pulmonary hemodynamic and thereby allow OLT with acceptable risk. Recent data suggest that stabilize, improve or cure PoPH seems to be possible by combining specific PAH therapies and liver transplantation in selected patients. Clinical and experimental evidences suggest that IFN therapy may be a possible risk factor for PAH.

  3. Pregnancy and Vascular Liver Disease

    PubMed Central

    Bissonnette, Julien; Durand, François; de Raucourt, Emmanuelle; Ceccaldi, Pierre-François; Plessier, Aurélie; Valla, Dominique; Rautou, Pierre-Emmanuel

    2015-01-01

    Vascular disorders of the liver frequently affect women of childbearing age. Pregnancy and the postpartum are prothrombotic states. Pregnancy seems to be a trigger for Budd–Chiari syndrome in patients with an underlying prothrombotic disorder. Whether pregnancy is a risk factor for other vascular liver disorders is unknown. In women with a known vascular liver disorder and a desire for pregnancy, stabilisation of the liver disease, including the use of a portal decompressive procedure when indicated, should be reached prior to conception. The presence of esophageal varices should be screened and adequate prophylaxis of bleeding applied in a manner similar to what is recommended for patients with cirrhosis. Most women likely benefit from anticoagulation during pregnancy and the postpartum. Labor and delivery are best managed by a multidisciplinary team with experience in this situation. Assisted vaginal delivery is the preferred mode of delivery. Although the risk of miscarriage and premature birth is heightened, current management of these diseases makes it very likely to see the birth of a live baby when pregnancy reaches 20 weeks of gestation. PMID:25941432

  4. Alcoholic Liver Disease and Malnutrition

    PubMed Central

    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

  5. Osteoporosis in chronic liver disease.

    PubMed

    Yadav, Anitha; Carey, Elizabeth J

    2013-02-01

    Osteoporosis is a common skeletal complication seen in patients with chronic liver disease. Osteoporosis is usually asymptomatic and, if untreated, can result in fractures and impaired quality of life. For this review, we performed a systematic search of the PubMed database, and all recent peer-reviewed articles regarding the prevalence, pathophysiology, diagnosis, and management of osteoporosis in chronic liver disease were included. The prevalence of osteoporosis varies between 11% and 58% in patients with chronic liver disease and in transplant recipients. The etiology of osteoporosis is multifactorial and only partially understood. Various factors linked to the pathogenesis of bone loss are vitamin D, calcium, insulin growth factor-1, receptor activation of nuclear factor-κB ligand (RANKL), bilirubin, fibronectin, leptin, proinflammatory cytokines, and genetic polymorphisms. Management of osteoporosis involves early diagnosis, identifying and minimizing risk factors, general supportive care, nutrition therapy, and pharmacotherapy. Osteoporosis is diagnosed based on the bone mineral density (BMD) assessment using dual-energy X-ray absorptiometry scan. Measurement of BMD should be considered in all patients with advanced liver disease and in transplant recipients. Vitamin D and calcium supplementation is recommended for all patients with osteoporosis. Specific agents used for treatment of osteoporosis include bisphosphonates, calcitonin, hormonal therapy, and raloxifene. Bisphosphonates have become the mainstay of therapy for osteoporosis prevention and treatment. Prolonged suppression of bone remodeling resulting in atypical fractures has emerged as a significant complication with long-term use of bisphosphonates. Newer treatment agents and better fracture prevention strategies are necessary to prevent and treat osteoporosis.

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

    PubMed Central

    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

  7. [Polycystic liver disease without autosomal dominant polycystic kidney disease].

    PubMed

    Peces, R; González, P; Venegas, J L

    2003-01-01

    Polycystic liver disease is characterized by the presence of multiple bile duct-derived epithelial cysts scattered in the liver parenchyma. The natural history and clinical manifestations of polycystic liver disease are based on the disease as it manifests in patients with autosomal dominant polycystic kidney disease (ADPKD). The occurrence of polycystic liver disease independently from polycystic kidney disease has been known for a long time. More recently, a gene for autosomal dominant polycystic liver disease has been identified on chromosome 19p 13.2-13.1. Isolated polycystic liver disease is underdiagnosed and genetically distinct from polycystic liver disease associated with ADPKD but with similar pathogenesis and clinical manifestations. We report here two men with polycystic liver disease no associated with ADPKD. Ultrasound and computed tomography imaging were effective in documenting the underlying lesions non-invasively.

  8. Nonalcoholic fatty liver disease: diagnosis and management.

    PubMed

    Wilkins, Thad; Tadkod, Altaf; Hepburn, Iryna; Schade, Robert R

    2013-07-01

    Nonalcoholic fatty liver disease is characterized by excessive fat accumulation in the liver (hepatic steatosis). Nonalcoholic steatohepatitis is characterized by steatosis, liver cell injury, and inflammation. The mechanism of nonalcoholic fatty liver disease is unknown but involves the development of insulin resistance, steatosis, inflammatory cytokines, and oxidative stress. Nonalcoholic fatty liver disease is associated with physical inactivity, obesity, and metabolic syndrome. Screening is not recommended in the general population. The diagnosis is usually made after an incidental discovery of unexplained elevation of liver enzyme levels or when steatosis is noted on imaging (e.g., ultrasonography). Patients are often asymptomatic and the physical examination is often unremarkable. No single laboratory test is diagnostic, but tests of liver function, tests for metabolic syndrome, and tests to exclude other causes of abnormal liver enzyme levels are routinely performed. Imaging studies, such as ultrasonography, computed tomography, and magnetic resonance imaging, can assess hepatic fat, measure liver and spleen size, and exclude other diseases. Liver biopsy remains the criterion standard for the diagnosis of nonalcoholic steatohepatitis. Noninvasive tests are available and may reduce the need for liver biopsy. A healthy diet, weight loss, and exercise are first-line therapeutic measures to reduce insulin resistance. There is insufficient evidence to support bariatric surgery, metformin, thiazolidinediones, bile acids, or antioxidant supplements for the treatment of nonalcoholic fatty liver disease. The long-term prognosis is not associated with an increased risk of all-cause mortality, cardiovascular disease, cancer, or liver disease.

  9. Pathogenesis of alcoholic liver disease: Role of oxidative metabolism

    PubMed Central

    Ceni, Elisabetta; Mello, Tommaso; Galli, Andrea

    2014-01-01

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell

  10. Pathogenesis of alcoholic liver disease: role of oxidative metabolism.

    PubMed

    Ceni, Elisabetta; Mello, Tommaso; Galli, Andrea

    2014-12-21

    Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases, resulting in fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma (HCC). Although the pathogenesis of alcoholic liver disease (ALD) involves complex and still unclear biological processes, the oxidative metabolites of ethanol such as acetaldehyde and reactive oxygen species (ROS) play a preeminent role in the clinical and pathological spectrum of ALD. Ethanol oxidative metabolism influences intracellular signaling pathways and deranges the transcriptional control of several genes, leading to fat accumulation, fibrogenesis and activation of innate and adaptive immunity. Acetaldehyde is known to be toxic to the liver and alters lipid homeostasis, decreasing peroxisome proliferator-activated receptors and increasing sterol regulatory element binding protein activity via an AMP-activated protein kinase (AMPK)-dependent mechanism. AMPK activation by ROS modulates autophagy, which has an important role in removing lipid droplets. Acetaldehyde and aldehydes generated from lipid peroxidation induce collagen synthesis by their ability to form protein adducts that activate transforming-growth-factor-β-dependent and independent profibrogenic pathways in activated hepatic stellate cells (HSCs). Furthermore, activation of innate and adaptive immunity in response to ethanol metabolism plays a key role in the development and progression of ALD. Acetaldehyde alters the intestinal barrier and promote lipopolysaccharide (LPS) translocation by disrupting tight and adherent junctions in human colonic mucosa. Acetaldehyde and LPS induce Kupffer cells to release ROS and proinflammatory cytokines and chemokines that contribute to neutrophils infiltration. In addition, alcohol consumption inhibits natural killer cells that are cytotoxic to HSCs and thus have an important antifibrotic function in the liver. Ethanol metabolism may also interfere with cell

  11. Autoimmune liver disease: novelties in management.

    PubMed

    Hadzic, Nedim; Hierro, Loreto

    2014-06-01

    Autoimmune liver disease is the second commonest cause of chronic liver disease in teenagers. There are several forms including autoimmune hepatitis, autoimmune sclerosing cholangitis, primary sclerosing cholangitis and various overlap syndromes, classified on the basis of different serum antibody profiles, histological features and appearances on cholangiography. Treatment with immunosupressants is usually effective, but often required medium to long-term, raising concerns about side effects and adherence to therapy. For a minority of children presenting in acute liver failure or with difficult-to-treat disease liver transplantation is a possible option, although risk of recurrence in the grafted liver remains lifelong.

  12. Metabonomics Research Progress on Liver Diseases

    PubMed Central

    2017-01-01

    Metabolomics as the new omics technique develops after genomics, transcriptomics, and proteomics and has rapid development at present. Liver diseases are worldwide public health problems. In China, chronic hepatitis B and its secondary diseases are the common liver diseases. They can be diagnosed by the combination of history, virology, liver function, and medical imaging. However, some patients seldom have relevant physical examination, so the diagnosis may be delayed. Many other liver diseases, such as drug-induced liver injury (DILI), alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD), and autoimmune liver diseases, still do not have definite diagnostic markers; the diagnosis consists of history, medical imaging, and the relevant score. As a result, the clinical work becomes very complex. So it has broad prospects to explore the specific and sensitive biomarkers of liver diseases with metabolomics. In this paper, there are several summaries which are related to the current research progress and application of metabolomics on biomarkers of liver diseases. PMID:28321390

  13. CKD and nonalcoholic fatty liver disease.

    PubMed

    Targher, Giovanni; Chonchol, Michel B; Byrne, Christopher D

    2014-10-01

    The possible link between nonalcoholic fatty liver disease and chronic kidney disease (CKD) recently has attracted considerable scientific interest. Accumulating clinical evidence indicates that the presence and severity of nonalcoholic fatty liver disease is associated significantly with CKD (defined as decreased estimated glomerular filtration rate and/or proteinuria) and that nonalcoholic fatty liver disease predicts the development and progression of CKD, independently of traditional cardiorenal risk factors. Experimental evidence also suggests that nonalcoholic fatty liver disease itself may exacerbate systemic and hepatic insulin resistance, cause atherogenic dyslipidemia, and release a variety of proinflammatory, procoagulant, pro-oxidant, and profibrogenic mediators that play important roles in the development and progression of CKD. However, despite the growing evidence linking nonalcoholic fatty liver disease with CKD, it has not been definitively established whether a causal association exists. The clinical implication for these findings is that patients with nonalcoholic fatty liver disease may benefit from more intensive surveillance or early treatment interventions to decrease the risk of CKD. In this review, we discuss the evidence linking nonalcoholic fatty liver disease with CKD and the putative mechanisms by which nonalcoholic fatty liver disease contributes to kidney damage. We also briefly discuss current treatment options for this increasingly prevalent disease that is likely to have an important future impact on the global burden of disease.

  14. Pathophysiology of Non Alcoholic Fatty Liver Disease

    PubMed Central

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-01-01

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation. PMID:27973438

  15. Cell and tissue engineering for liver disease.

    PubMed

    Bhatia, Sangeeta N; Underhill, Gregory H; Zaret, Kenneth S; Fox, Ira J

    2014-07-16

    Despite the tremendous hurdles presented by the complexity of the liver's structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near- and long-term prospects for such cell-based therapies and the unique challenges for clinical translation.

  16. Pathophysiology of Non Alcoholic Fatty Liver Disease.

    PubMed

    Petta, Salvatore; Gastaldelli, Amalia; Rebelos, Eleni; Bugianesi, Elisabetta; Messa, Piergiorgio; Miele, Luca; Svegliati-Baroni, Gianluca; Valenti, Luca; Bonino, Ferruccio

    2016-12-11

    The physiopathology of fatty liver and metabolic syndrome are influenced by diet, life style and inflammation, which have a major impact on the severity of the clinicopathologic outcome of non-alcoholic fatty liver disease. A short comprehensive review is provided on current knowledge of the pathophysiological interplay among major circulating effectors/mediators of fatty liver, such as circulating lipids, mediators released by adipose, muscle and liver tissues and pancreatic and gut hormones in relation to diet, exercise and inflammation.

  17. Interaction between periodontitis and liver diseases

    PubMed Central

    Han, Pengyu; Sun, Dianxing; Yang, Jie

    2016-01-01

    Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30–50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue. PMID:27588170

  18. Cystic fibrosis-associated liver disease.

    PubMed

    Herrmann, Ulrike; Dockter, Gerd; Lammert, Frank

    2010-10-01

    Liver disease is increasingly common in cystic fibrosis (CF). As new therapeutic options emerge, life expectancy increases and common hepatobiliary manifestations impact on quality of life and survival of CF patients. Hepatobiliary abnormalities in CF vary in nature and range from defects attributable to the underlying CFTR gene defect to those related to systemic disease and malnutrition. Today complications of liver disease represent the third most frequent cause of disease-related death in patients with CF. Here we review molecular and clinical genetics of CF, including genetic modifiers of CF-associated liver disease, and provide practical recommendations for genetic testing, diagnosis and treatment of hepatobiliary manifestations in CF.

  19. Autoantibodies and liver disease: uses and abuses.

    PubMed

    Zeman, Marilyn V; Hirschfield, Gideon M

    2010-04-01

    Confirming whether a patient has autoimmune liver disease is challenging, given its varied presentation and complex definitions. In the continued absence of pathognomonic serum markers, diagnosis requires evaluation of laboratory investigations and, frequently, a liver biopsy - all of which need to be interpreted in the correct clinical context, with an emphasis on exclusion of viral infections, drug toxicity and metabolic disease. However, clear diagnosis is important for appropriate and timely therapy. Autoantibodies remain important tools for clinicians, and were the first proposed serological markers to aid in differentiating viral from chronic autoimmune hepatitis. Their presence is occasionally considered to be synonymous with autoimmune liver disease - a misinterpretation of their clinical significance. The present article summarizes the serum autoantibodies currently investigated in clinical and research practice, along with a description of their value in adult chronic liver diseases, with an emphasis on their appropriate use in the diagnosis and management of patients with autoimmune liver disease.

  20. Management of coagulation abnormalities in liver disease.

    PubMed

    Potze, Wilma; Porte, Robert J; Lisman, Ton

    2015-01-01

    Liver disease is characterized by changes in all phases of hemostasis. These hemostatic alterations were long considered to predispose patients with liver disease towards a bleeding tendency, as they are associated with prolonged conventional coagulation tests. However, these patients may also suffer from thrombotic complications, and we now know that the hemostatic system in patient with liver disease is, in fact, in a rebalanced state. In this review we discuss the concept of rebalanced hemostasis and its implications for clinical management of patients with liver disease. For instance, there is no evidence that the use of prophylactic blood product transfusion prior to invasive procedures reduces bleeding risk. Clinicians should also be aware of the possibility of thrombosis occurring in patients with a liver disease, and regular thrombosis prophylaxis should not be withheld in these patients.

  1. Cirrhosis and autoimmune liver disease: Current understanding

    PubMed Central

    Liberal, Rodrigo; Grant, Charlotte R

    2016-01-01

    Primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC) and autoimmune hepatitis (AIH) constitute the classic autoimmune liver diseases (AILDs). While AIH target the hepatocytes, in PBC and PSC the targets of the autoimmune attack are the biliary epithelial cells. Persistent liver injury, associated with chronic AILD, leads to un-resolving inflammation, cell proliferation and the deposition of extracellular matrix proteins by hepatic stellate cells and portal myofibroblasts. Liver cirrhosis, and the resultant loss of normal liver function, inevitably ensues. Patients with cirrhosis have higher risks or morbidity and mortality, and that in the decompensated phase, complications of portal hypertension and/or liver dysfunction lead to rapid deterioration. Accurate diagnosis and monitoring of cirrhosis is, therefore of upmost importance. Liver biopsy is currently the gold standard technique, but highly promising non-invasive methodology is under development. Liver transplantation (LT) is an effective therapeutic option for the management of end-stage liver disease secondary to AIH, PBC and PSC. LT is indicated for AILD patients who have progressed to end-stage chronic liver disease or developed intractable symptoms or hepatic malignancy; in addition, LT may also be indicated for patients presenting with acute liver disease due to AIH who do not respond to steroids. PMID:27729952

  2. Obesity, nutrition, and liver disease in children.

    PubMed

    Feldstein, Ariel E; Patton-Ku, Dana; Boutelle, Kerri N

    2014-02-01

    In this article, several aspects of childhood obesity are discussed, including epidemiology, associated metabolic complications, management strategies, and therapy with particular attention to the impact of obesity on the liver, resulting in nonalcoholic or metabolic fatty liver disease. The deleterious effects of obesity on the liver and health overall can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. The current evidence is summarized supporting pharmacologic, behavioral, and dietary interventions for the management of obesity and fatty liver disease in children.

  3. Role of liver biopsy in nonalcoholic fatty liver disease

    PubMed Central

    Nalbantoglu, ILKe; Brunt, Elizabeth M

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), defined as abnormal accumulation (> 5%) of hepatic triglyceride without excess alcohol intake, is the most common form of chronic liver disease in adults and children in the United States. NAFLD encompasses a spectrum of histologic findings including uncomplicated steatosis, steatosis with inflammation and steatohepatitis [nonalcoholic steatohepatitis (NASH)]; the latter can advance to cirrhosis and hepatocellular carcinoma. NASH is currently accepted as the hepatic manifestation of the set of cardiovascular risk factors collectively known as metabolic syndrome. In 1999 a system for histologic grading and staging for NASH was proposed; this was revised by the NASH Clinical Research Network in 2005 for the entire spectrum of lesions in NAFLD, including the lesions and patterns of pediatric NAFLD, and for application in clinical research trials. Diagnosis remains distinct from grade and stage. A recent European proposal separates steatosis from activity to derive a numeric diagnosis of NASH. Even though there have been promising advancements in non-invasive testing, these tests are not yet detailed enough to replace the full range of findings provided by liver biopsy evaluation. Limitations of biopsy are acknowledged, but liver biopsy remains the “gold standard” for diagnosis and determination of amounts of necroinflammatory activity, and location of fibrosis, as well as remodeling of the parenchyma in NASH. This review focuses on the specific histologic lesions of NAFLD and NASH, grading and staging, differential diagnoses to be considered, and the continuing role of the liver biopsy in this important liver disease. PMID:25083076

  4. [Auto-antibodies in liver disease].

    PubMed

    Montaño Loza, Aldo J; Angulo, Paul

    2007-01-01

    Autoantibodies are a nonpathogenic manifestation of immune reactivity that may occur in acute and chronic liver diseases. Autoantibodies are the consequence rather than the cause of liver injury, and they can be used as diagnostic tools rather than etiologic markers. Conventional autoantibodies used in the categorization of liver disease are antinuclear antibodies, smooth muscle antibodies, antibodies to liver/kidney microsome type 1, antimitochondrial antibodies, and perinuclear antineutrophil cytoplasmic antibodies. However, the final diagnosis and the treatment strategies do not depend solely on the serological markers. Autoantibodies titles vary overtime and their behavior does not correlate with disease activity. Over-interpretation is the major pitfall in the clinical application of the serological results. Recognition and characterization of new autoantibodies is expected to improve the diagnostic precision, provide diagnostic parameters, and elucidate target autoantigens for the management of liver diseases.

  5. Chronic Liver Disease and Asian Americans/Pacific Islanders

    MedlinePlus

    ... Population Profiles > Asian American > Chronic Liver Disease Chronic Liver Disease and Asian Americans/Pacific Islanders Among Asian Americans, chronic liver disease is a leading cause of death. While ...

  6. Chronic Liver Disease and Native Hawaiian/Pacific Islanders

    MedlinePlus

    ... Hawaiian/Other Pacific Islander > Chronic Liver Disease Chronic Liver Disease and Native Hawaiian/Pacific Islander Native Hawaiian/ ... times more likely to be diagnosed with chronic liver disease in 2006. American Samoans were 8 times ...

  7. Chronic Liver Disease and American Indians/Alaska Natives

    MedlinePlus

    ... American Indian/Alaska Native > Chronic Liver Disease Chronic Liver Disease and American Indians/Alaska Natives Among American Indians and Alaska Natives, chronic liver disease is a leading cause of death. While ...

  8. Advances in Pediatric Nonalcoholic Fatty Liver Disease

    PubMed Central

    Loomba, Rohit; Sirlin, Claude B.; Schwimmer, Jeffrey B.; Lavine, Joel E.

    2009-01-01

    Nonalcoholic fatty liver disease (NAFLD) has emerged as the leading cause of chronic liver disease in children and adolescents in the United States. A two- to three-fold rise in the rates of obesity and overweight in children over the last 2 decades is probably responsible for the epidemic of NAFLD. Emerging data suggest that children with NASH progress to cirrhosis which may ultimately increase liver-related mortality. More worrisome is the recognition that cardiovascular risk and morbidity in children and adolescents is associated with fatty liver. Pediatric fatty liver disease often displays a histologic pattern distinct from that found in adults. Liver biopsy remains the gold standard for diagnosis of NASH. Non-invasive biomarkers are needed to identify individuals with progressive liver injury. Targeted therapies to improve liver histology and metabolic abnormalities associated with fatty liver are needed. Currently, randomized-controlled trials are underway in the pediatric population to define pharmacologic therapy for NAFLD. Public health awareness and intervention are needed to promote healthy diet, exercise, and lifestyle modifications to prevent and reduce the burden of disease in the community. PMID:19637286

  9. Noninvasive Measures of Liver Fibrosis and Severity of Liver Disease

    PubMed Central

    Lucero, Catherine; Brown, Robert S.

    2016-01-01

    Determining the degree of fibrosis is an important step in the assessment of disease severity in patients with chronic liver disease. Liver biopsy has been the gold standard for estimating the extent of inflammation and fibrosis, although the procedure has limitations such as sampling error and variability. Noninvasive testing has been shown to be equally predictive in ruling out fibrosis or ruling in advanced fibrosis. Serum biomarkers and imaging-based tests have more limited predictive ability when classifying intermediate stages, but these tools can help identify which patients should receive antiviral treatment sooner and require ongoing cancer surveillance without the need for biopsy. Using a combination of serum markers and imaging tests may also be helpful in providing functional assessment of portal hypertension in patients with chronic liver disease. PMID:27330502

  10. Cutaneous Manifestations of Common Liver Diseases

    PubMed Central

    Dogra, Sunil; Jindal, Rashmi

    2012-01-01

    Skin functions as a window to our overall health and a number of systemic diseases result in various cutaneous changes. Knowledge of these manifestations helps in suspecting an underlying systemic illness. Cutaneous abnormalities are quite common in patients with liver diseases and this article aims to focus on these dermatoses. Cutaneous manifestations seen in patients with liver disease though common are nonspecific. They can also be seen in patients without liver diseases and generally do not indicate about a specific underlying hepatic disorder. The presence of a constellation of signs and symptoms is more useful in pointing toward an underlying hepatobiliary condition. The commonest symptom in patients with liver disease is pruritus which is often protracted and disabling. Other common features include spider angiomas, palmar erythema, paper money skin, xanthelasmas, pigmentary changes, and nutritional deficiencies. In this article, first the common cutaneous manifestations that may be associated with liver disorders are discussed and then common liver diseases with their specific cutaneous findings are discussed. Cutaneous abnormalities may be the first clue to the underlying liver disease. Identifying them is crucial for early diagnosis and better management. PMID:25755383

  11. GFR Estimating Equations and Liver Disease

    PubMed Central

    Beben, Tomasz; Rifkin, Dena E.

    2015-01-01

    It is important to accurately assess the glomerular filtration rate (GFR) of patients with liver disease in order to deliver care and allocate organs for transplantation in a way that improves outcomes. The most commonly used methods to estimate GFR in this population are based on creatinine, which is biased by these patients’ low creatinine production and potentially by elevated serum bilirubin and decreased albumin levels. None of the creatinine based estimated GFR (eGFR) equations have been specifically modified for a population with liver disease, and even measurement of a 24 hour creatinine clearance has limitations. In liver disease, all creatinine based estimates of GFR overestimate gold standard measured GFR (mGFR), and the degree of overestimation is highest at lower mGFR values and in more severe liver disease. Cystatin C based eGFR has shown promise in general population studies by demonstrating less bias than creatinine based eGFR and improved association with clinically important outcomes, but results in the liver disease population have been mixed and further studies are necessary. Ultimately, specific eGFR equations for liver disease or novel methods for estimating GFR may be necessary. However, for now, the limitations of currently available methods need to be appreciated to understand renal function in liver disease. PMID:26311594

  12. Diagnosis and management of polycystic liver disease.

    PubMed

    Gevers, Tom J G; Drenth, Joost P H

    2013-02-01

    Polycystic liver disease (PLD) is arbitrarily defined as a liver that contains >20 cysts. The condition is associated with two genetically distinct diseases: as a primary phenotype in isolated polycystic liver disease (PCLD) and as an extrarenal manifestation in autosomal dominant polycystic kidney disease (ADPKD). Processes involved in hepatic cystogenesis include ductal plate malformation with concomitant abnormal fluid secretion, altered cell-matrix interaction and cholangiocyte hyperproliferation. PLD is usually a benign disease, but can cause debilitating abdominal symptoms in some patients. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use and multiple pregnancies. Ultrasonography is very useful for achieving a correct diagnosis of a polycystic liver and to differentiate between ADPKD and PCLD. Current radiological and surgical therapies for symptomatic patients include aspiration-sclerotherapy, fenestration, segmental hepatic resection and liver transplantation. Medical therapies that interact with regulatory mechanisms controlling expansion and growth of liver cysts are under investigation. Somatostatin analogues are promising; several clinical trials have shown that these drugs can reduce the volume of polycystic livers. The purpose of this Review is to provide an update on the diagnosis and management of PLD with a focus on literature published in the past 4 years.

  13. Cell and Tissue Engineering for Liver Disease

    PubMed Central

    Bhatia, Sangeeta N.; Underhill, Gregory H.; Zaret, Kenneth S.; Fox, Ira J.

    2015-01-01

    Despite the tremendous hurdles presented by the complexity of the liver’s structure and function, advances in liver physiology, stem cell biology and reprogramming, and the engineering of tissues and devices are accelerating the development of cell-based therapies for treating liver disease and liver failure. This State of the Art Review discusses both the near and long-term prospects for such cell-based therapies and the unique challenges for clinical translation. PMID:25031271

  14. Gut-Liver Axis in Alcoholic Liver Disease

    PubMed Central

    Szabo, Gyongyi

    2014-01-01

    Alcoholic liver disease (ALD) has been amongst the leading causes of liver cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation suggesting a role for gut-derived “toxins” in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that is increasingly recognized as a major factor in ALD. Bacterial endotoxin, LPS, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4 (TLR4). Recent studies also demonstrated that alcohol consumption is associated with alterations in the gut microbiome and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD. PMID:25447847

  15. Managing non-alcoholic fatty liver disease

    PubMed Central

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

    2016-01-01

    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. PMID:27439352

  16. TGF-β signalling and liver disease.

    PubMed

    Fabregat, Isabel; Moreno-Càceres, Joaquim; Sánchez, Aránzazu; Dooley, Steven; Dewidar, Bedair; Giannelli, Gianluigi; Ten Dijke, Peter

    2016-06-01

    The transforming growth factor-beta (TGF-β) family signalling pathways play essential roles in the regulation of different cellular processes, including proliferation, differentiation, migration or cell death, which are essential for the homeostasis of tissues and organs. Because of the diverse and pleiotropic TGF-β functions, deregulation of its pathways contributes to human disease. In the case of the liver, TGF-β signalling participates in all stages of disease progression, from initial liver injury through inflammation and fibrosis, to cirrhosis and cancer. TGF-β has cytostatic and apoptotic effects in hepatocytes, promoting liver differentiation during embryogenesis and physiological liver regeneration. However, high levels of TGF-β, as a consequence of chronic liver damage, result in activation of stellate cells to myofibroblasts and massive hepatocyte cell death, which contributes to the promotion of liver fibrosis and later cirrhosis. During liver tumorigenesis, TGF-β may behave as a suppressor factor at early stages; however, there is strong evidence that overactivation of TGF-β signalling might contribute to later tumour progression, once cells escape from its cytostatic effects. For these reasons, targeting the TGF-β signalling pathway is being explored to counteract liver disease progression. In this review, we aim to shed light on the state-of-the-art in the signalling pathways induced by TGF-β that are involved in different stages of liver physiology and pathology.

  17. [Ultrasound diagnostics of diffuse liver diseases].

    PubMed

    Jung, E M; Wiggermann, P; Stroszczynski, C; Reiser, M F; Clevert, D-A

    2012-08-01

    The current improvements in modern high resolution ultrasound technology, like Tissue Harmonic Imaging (THI), Speckle Reduction Imaging (SRI), partial color coding of B-mode (Color Coded Imaging), and also the advent of ultrasound based elastography as well as contrast-enhanced ultrasound (CEUS) offer fundamentally new ways to characterize diffuse alterations of the liver parenchyma. Besides metabolic disease, disorders of liver fat distribution, infectious and malignant diseases can cause diffuse alterations of the liver parenchyma. In case of liver fibrosis, only a combination of different ultrasound techniques including CEUS, allows the differentiation between benign dysplastic and malignant lesions. Ultrasound elastography allows assessing the extent of the fibrosis. This article focuses on the different ultrasound based diagnostic possibilities in case of diffuse liver disease.

  18. Pediatric Non-alcoholic Fatty Liver Disease.

    PubMed

    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.

  19. Renal Function and Transplantation in Liver Disease.

    PubMed

    Parajuli, Sandesh; Foley, David; Djamali, Arjang; Mandelbrot, Didier

    2015-09-01

    Kidney injury is associated with increased morbidity and mortality in liver transplant recipients. Since the introduction of the model for end-stage liver disease for the allocation of organs for liver transplantation in 2002, the heavy weighting of serum creatinine in the model for end-stage liver disease score has significantly increased the incidence of renal dysfunction seen among patients undergoing liver transplantation. As a result, the frequency of simultaneous liver-kidney (SLK) transplantation compared to liver transplantation alone (LTA) has also increased. The decision to perform SLK rather than LTA is an important one because the benefits to the liver transplant recipient receiving a kidney transplant must be balanced with the benefits of using that organ for a patient with end-stage renal disease. However, predicting whether or not a patient with liver failure has reversible kidney disease, and therefore does not also need a kidney transplant, is difficult. The severity and duration of pretransplant renal dysfunction, hepatitis c, diabetes, and other risk factors for kidney disease are associated with an increased risk of posttransplant end-stage renal disease. However, there are currently no clinical findings that accurately predict renal recovery post liver transplant. As a result, the rate of SLK versus LTA differs significantly between transplant centers. To increase consistency across centers, multiple guidelines have been proposed to guide the decision between SLK and LTA, but their poor predictive value has limited their uniform adoption. Nevertheless, adoption of uniform rules for the allocation of kidneys would reduce the variability between centers in rates of SLK transplant.

  20. Alcoholic liver disease: the gut microbiome and liver cross talk.

    PubMed

    Hartmann, Phillipp; Seebauer, Caroline T; Schnabl, Bernd

    2015-05-01

    Alcoholic liver disease (ALD) is a leading cause of morbidity and mortality worldwide. Alcoholic fatty liver disease can progress to steatohepatitis, alcoholic hepatitis, fibrosis, and cirrhosis. Patients with alcohol abuse show quantitative and qualitative changes in the composition of the intestinal microbiome. Furthermore, patients with ALD have increased intestinal permeability and elevated systemic levels of gut-derived microbial products. Maintaining eubiosis, stabilizing the mucosal gut barrier, or preventing cellular responses to microbial products protect from experimental ALD. Therefore, intestinal dysbiosis and pathological bacterial translocation appear fundamental for the pathogenesis of ALD. This review highlights causes for intestinal dysbiosis and pathological bacterial translocation, their relationship, and consequences for ALD. We also discuss how the liver affects the intestinal microbiota.

  1. [Treatment of parasitic liver diseases].

    PubMed

    Lecuna, V

    1989-01-01

    Most of primary and secondary parasitic liver diseases, at present can be property treated with drugs. Venezuelan pharmaceutic market has some peculiarities that have determined the disappearance from the market of many drugs such as emetine, thiabendazole, quinacrine and niclosamide. Diloxanide never appeared. Venezuela has no commercial international treatises that protect international patents in the pharmaceutical area. In addition, government regulation of cost of drugs is very strict. This is particularly true with old drugs (such as emetine or quinacrine) which had such a low price that is non-commercial for the maker of the drug, usually a large transnational, and is withdrawn from the market. Flexibility of prices is quite easy for new antibiotics which are very expensive. Frequently small national companies import the drug from Italy and Japan which sell the drug independently from international treats. Such companies frequently produce the drug for the government social system, but are unreliable and also frequently they withdraw the drug a variable period of time. The government, through the Ministry of Public Health administer free treatment with drugs for malaria, tuberculosis and leprosy. The severe economic crisis of the country has severely impaired the preventive programs and there is an increase of malaria due to gold mining in the south of the country and falciparum chloroquine resistance and an increase of schistosomiasis in a previous free area. Also administration of drugs for malaria has been severely impaired, mainly for economic reasons. The establishment of a National Government Laboratory is an old (as far as 1946) political goal, but has remained in the political intention.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Vitamin D deficiency in chronic liver disease

    PubMed Central

    Iruzubieta, Paula; Terán, Álvaro; Crespo, Javier; Fábrega, Emilio

    2014-01-01

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required. PMID:25544877

  3. Vitamin D deficiency in chronic liver disease.

    PubMed

    Iruzubieta, Paula; Terán, Álvaro; Crespo, Javier; Fábrega, Emilio

    2014-12-27

    Vitamin D is an important secosteroid hormone with known effect on calcium homeostasis, but recently there is increasing recognition that vitamin D also is involved in cell proliferation and differentiation, has immunomodulatory and anti-inflammatory properties. Vitamin D deficiency has been frequently reported in many causes of chronic liver disease and has been associated with the development and evolution of non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) virus infection. The role of vitamin D in the pathogenesis of NAFLD and CHC is not completely known, but it seems that the involvement of vitamin D in the activation and regulation of both innate and adaptive immune systems and its antiproliferative effect may explain its importance in these liver diseases. Published studies provide evidence for routine screening for hypovitaminosis D in patients with liver disease. Further prospectives studies demonstrating the impact of vitamin D replacement in NAFLD and CHC are required.

  4. Nonalcoholic Fatty Liver Disease in Pediatrics.

    PubMed

    Duncan, Martin; Zong, Wenjing; Biank, Vincent F; Hageman, Joseph R

    2016-02-01

    A 16-year-old Hispanic girl with an elevated body mass index in an otherwise normal state of health presented for her well-child examination. She had signs of metabolic syndrome and insulin resistance including increased waist circumference and acanthosis nigricans. Laboratory results revealed elevated transaminases with otherwise normal hepatic function. Based on the physical examination and laboratory results, she was diagnosed with nonalcoholic fatty liver disease (NAFLD). After further evaluation, she eventually underwent a liver biopsy. The biopsy revealed nonalcoholic steatohepatitis (NASH) with stage 2 fibrosis. This article reviews the definition of NAFLD and NASH, an increasingly prevalent cause of pediatric chronic liver disease associated with obesity and metabolic syndrome. The article also outlines the epidemiology, risk factors, and natural history of NAFLD, which may help identify and prevent high-risk pediatric patients from progressing to irreversible liver disease. Understanding the diagnostic and treatment options offers the best chance at preventing and reversing the early stages of this disease.

  5. Obesity, Nutrition and Liver Disease in Children

    PubMed Central

    Feldstein, Ariel E.; Patton-Ku, Dana; Boutelle, Kerri N.

    2013-01-01

    Synopsis The prevalence of childhood obesity has reached epidemic proportions in the US and many other parts of the world. With obesity comes a variety of adverse health outcomes and metabolic complications. The liver in particular seems to be significantly impacted by fat deposition in the presence of obesity. In this article we discuss several aspects of childhood obesity from epidemiology and associated metabolic complications, to management strategies and therapy with particular attention to the impact of obesity on the liver resulting in non-alcoholic or metabolic fatty liver disease. The deleterious effects of obesity on the liver and health overall can be significantly impacted by a culture that fosters sustained nutritional improvement and regular physical activity. Here we summarize the current evidence supporting pharmacologic, behavioral and dietary interventions for the management of obesity and fatty liver disease in children. PMID:24274876

  6. Heritability of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Schwimmer, Jeffrey B.; Celedon, Manuel A.; Lavine, Joel E.; Salem, Rany; Campbell, Nzali; Schork, Nicholas J.; Shiehmorteza, Masoud; Yokoo, Takeshi; Chavez, Alyssa; Middleton, Michael S.; Sirlin, Claude B.

    2010-01-01

    Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The etiology is believed to be multi-factorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable. Methods Overweight children with biopsy-proven NAFLD and overweight children without NAFLD served as probands. Family members were studied including magnetic resonance imaging to quantify liver fat fraction. Fatty liver was defined as a liver fat fraction ≥ 5%. Etiologies for fatty liver other than NAFLD were excluded. Narrow-sense heritability estimates for fatty liver (dichotomous) and fat fraction (continuous) were calculated using variance components analysis adjusted for covariate effects. Results Fatty liver was present in 17% of siblings and 37% of parents of overweight children without NAFLD. Fatty liver was significantly more common in siblings (59%) and parents (78%) of children with NAFLD. Liver fat fraction was correlated with body mass index (BMI), although the correlation was significantly stronger for families of children with NAFLD than those without NAFLD. Adjusted for age, sex, race, and BMI, heritability of fatty liver was 1.000 and of liver fat fraction 0.386. Conclusion Family members of children with NAFLD should be considered at high risk for NAFLD. These data suggest that familial factors are a major determinant of whether an individual has NAFLD. Studies examining the complex relations between genes and environment in the development and progression of NAFLD are warranted. PMID:19208353

  7. ALDH2 polymorphism and alcohol-related cancers in Asians: a public health perspective.

    PubMed

    Chang, Jeffrey S; Hsiao, Jenn-Ren; Chen, Che-Hong

    2017-03-03

    The occurrence of more than 200 diseases, including cancer, can be attributed to alcohol drinking. The global cancer deaths attributed to alcohol-consumption rose from 243,000 in 1990 to 337,400 in 2010. In 2010, cancer deaths due to alcohol consumption accounted for 4.2% of all cancer deaths. Strong epidemiological evidence has established the causal role of alcohol in the development of various cancers, including esophageal cancer, head and neck cancer, liver cancer, breast cancer, and colorectal cancer. The evidence for the association between alcohol and other cancers is inconclusive. Because of the high prevalence of ALDH2*2 allele among East Asian populations, East Asians may be more susceptible to the carcinogenic effect of alcohol, with most evidence coming from studies of esophageal cancer and head and neck cancer, while data for other cancers are more limited. The high prevalence of ALDH2*2 allele in East Asian populations may have important public health implications and may be utilized to reduce the occurrence of alcohol-related cancers among East Asians, including: 1) Identification of individuals at high risk of developing alcohol-related cancers by screening for ALDH2 polymorphism; 2) Incorporation of ALDH2 polymorphism screening into behavioral intervention program for promoting alcohol abstinence or reducing alcohol consumption; 3) Using ALDH2 polymorphism as a prognostic indicator for alcohol-related cancers; 4) Targeting ALDH2 for chemoprevention; and 5) Setting guidelines for alcohol consumption among ALDH2 deficient individuals. Future studies should evaluate whether these strategies are effective for preventing the occurrence of alcohol-related cancers.

  8. Linking intestinal homeostasis and liver disease

    PubMed Central

    Schnabl, Bernd

    2014-01-01

    Purpose of review Interactions of the gut microbiome with the host are important in health and disease. Microbial translocation releases bacterial products that play a key role in progression of chronic liver disease by promoting hepatic injury and inflammation. Although this has long been recognized, we are just beginning to understand the circumstances under which the gut becomes leaky and to discover bacterial metabolites that promote liver disease. In this review we will summarize recent findings from the last two years. Recent findings Chronic liver disease is associated with an altered microbiome with both qualitative (dysbiosis) and quantitative (overgrowth) differences. This can be viewed as a loss of the symbiotic relationship between the microflora and the host. An imbalanced intestinal homeostasis results in a breach of the gut barrier and subsequent microbial translocation. However, the contribution of the intestinal microflora is beyond simple microbial translocation as pathogenic factor. Bacterial metabolites resulting from an imbalanced homeostasis and dysbiosis play also a crucial role in liver disease. Summary A combination between an initiating liver insult and a disturbance of the gut – host symbiosis synergize in progression of liver disease. PMID:23493073

  9. FastStats: Chronic Liver Disease and Cirrhosis

    MedlinePlus

    ... Submit What's this? Submit Button NCHS Home Chronic Liver Disease and Cirrhosis Recommend on Facebook Tweet Share ... Services Administration American Association for the Study of Liver Diseases American Liver Foundation Get Email Updates To ...

  10. Alcohol-Related Problems of Older Persons.

    ERIC Educational Resources Information Center

    Staples, Pamela A.

    The study of older adults is relatively new for the social sciences. There is a growing awareness of the alcohol-related problems in this population. Between 2 and 10 percent of older social drinkers present severe alcohol-related problems of different kinds. Three terms describe the major consequences of "too much" alcohol: intoxication,…

  11. Micronutrient Antioxidants and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Chen, Guanliang; Ni, Yinhua; Nagata, Naoto; Xu, Liang; Ota, Tsuguhito

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is one of the most important chronic liver diseases worldwide and has garnered increasing attention in recent decades. NAFLD is characterized by a wide range of liver changes, from simple steatosis to nonalcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma. The blurred pathogenesis of NAFLD is very complicated and involves lipid accumulation, insulin resistance, inflammation, and fibrogenesis. NAFLD is closely associated with complications such as obesity, diabetes, steatohepatitis, and liver fibrosis. During the progression of NAFLD, reactive oxygen species (ROS) are activated and induce oxidative stress. Recent attempts at establishing effective NAFLD therapy have identified potential micronutrient antioxidants that may reduce the accumulation of ROS and finally ameliorate the disease. In this review, we present the molecular mechanisms involved in the pathogenesis of NAFLD and introduce some dietary antioxidants that may be used to prevent or cure NAFLD, such as vitamin D, E, and astaxanthin. PMID:27563875

  12. Posttransplant lymphoproliferative disease in liver transplant patients.

    PubMed

    Hartmann, Christina; Schuchmann, Marcus; Zimmermann, Tim

    2011-02-01

    Posttransplant lymphoproliferative disorders (PTLD) are a life-threatening complication following solid organ transplantation. Many posttransplant lymphomas develop from the uncontrolled proliferation of Epstein-Barr virus (EBV)-infected B-cells, whereas EBV-negative PTLDs were increasingly recognized within the past decade. Major risk factors for the development of PTLDs after liver transplantation are immunosuppressive therapy and the type of underlying disease: viral hepatitis, autoimmune liver disease, or alcoholic liver cirrhosis contribute to an increased risk for PTLD. Therapeutic regimens include reduction of immunosuppression, the anti-CD20 antibody rituximab, and chemotherapy, as well as new approaches using interferon-α and anti-interleukin-6 antibodies. Despite the different therapeutic regimens, mortality from PTLD remains high. Therefore, it is of major importance to identify patients at risk at an early stage of the disease. In this review, risk factors for PTLD development after liver transplantation, clinical presentation, diagnosis, and therapy are discussed.

  13. Sialadenosis in Patients with Advanced Liver Disease

    PubMed Central

    Close, John M.; Eghtesad, Bijan

    2009-01-01

    Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis. PMID:19644542

  14. Sialadenosis in patients with advanced liver disease.

    PubMed

    Guggenheimer, James; Close, John M; Eghtesad, Bijan

    2009-06-01

    Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis.

  15. [MRT of the liver in Wilson's disease].

    PubMed

    Vogl, T J; Steiner, S; Hammerstingl, R; Schwarz, S; Kraft, E; Weinzierl, M; Felix, R

    1994-01-01

    To show that Wilson's disease is one likely cause of multiple low-intensity nodules of the liver we obtained MR images in 16 patients with clinically and histopathologically confirmed Wilson's disease. Corresponding to morphological changes MRI enabled the subdivision of the patients into two groups. Using a T2-weighted spin-echo sequence (TR/TE = 2000/45-90) liver parenchyma showed multiple tiny low-intensity-nodules surrounded by high-intensity septa in 10 out of 16 patients. 5 patients had also low-intensity nodules in T1-weighted images (TR/TE = 600/20). In patients of this group histopathology revealed liver cirrhosis (n = 7) and fibrosis (n = 2). Common feature of this patient group was marked inflammatory cell infiltration into fibrous septa, increase of copper concentration in liver parenchyma and distinct pathological changes of laboratory data. In the remaining 6 patients no pathological change of liver morphology was demonstrated by MRI corresponding to slight histopathological changes of parenchyma and normal laboratory data. As low-intensity nodules surrounded by high intensity septa can be demonstrated in patients with marked inflammatory infiltration of liver parenchyma MRI may help to define Wilson patients with poorer prognosis. In patients with low-intensity nodules of the liver and unknown cause of liver cirrhosis laboratory data and histopathology should be checked when searching for disorders of copper metabolism.

  16. Hyaluronic acid concentration in liver diseases.

    PubMed

    Gudowska, Monika; Gruszewska, Ewa; Panasiuk, Anatol; Cylwik, Bogdan; Flisiak, Robert; Świderska, Magdalena; Szmitkowski, Maciej; Chrostek, Lech

    2016-11-01

    The aim of this study was to evaluate the effect of liver diseases of different etiologies and clinical severity of liver cirrhosis on the serum level of hyaluronic acid. The results were compared with noninvasive markers of liver fibrosis: APRI, GAPRI, HAPRI, FIB-4 and Forn's index. Serum samples were obtained from 20 healthy volunteers and patients suffering from alcoholic cirrhosis (AC)-57 patients, non-alcoholic cirrhosis (NAC)-30 and toxic hepatitis (HT)-22. Cirrhotic patients were classified according to Child-Pugh score. Hyaluronic acid concentration was measured by the immunochemical method. Non-patented indicators were calculated using special formulas. The mean serum hyaluronic acid concentration was significantly higher in AC, NAC and HT group in comparison with the control group. There were significant differences in the serum hyaluronic acid levels between liver diseases, and in AC they were significantly higher than those in NAC and HT group. The serum hyaluronic acid level differs significantly due to the severity of cirrhosis and was the highest in Child-Pugh class C. The sensitivity, specificity, accuracy, positive and negative predictive values and the area under the ROC curve for hyaluronic acid and all non-patented algorithms were high and similar to each other. We conclude that the concentration of hyaluronic acid changes in liver diseases and is affected by the severity of liver cirrhosis. Serum hyaluronic acid should be considered as a good marker for noninvasive diagnosis of liver damage, but the combination of markers is more useful.

  17. The gut microbiota and liver disease.

    PubMed

    Llorente, Cristina; Schnabl, Bernd

    2015-05-01

    The leaky gut hypothesis links translocating microbial products with the onset and progression of liver disease, and for a long time was considered one of its major contributors. However, a more detailed picture of the intestinal microbiota contributing to liver disease started to evolve. The gut is colonized by trillions of microbes that aid in digestion, modulate immune response, and generate a variety of products that result from microbial metabolic activities. These products together with host-bacteria interactions influence both normal physiology and disease susceptibility. A disruption of the symbiosis between microbiota and host is known as dysbiosis and can have profound effects on health. Qualitative changes such as increased proportions of harmful bacteria and reduced levels of beneficial bacteria, and also quantitative changes in the total amount of bacteria (overgrowth) have been associated with liver disease. Understanding the link between the pathophysiology of liver diseases and compositional and functional changes of the microbiota will help in the design of innovative therapies. In this review, we focus on factors resulting in dysbiosis, and discuss how dysbiosis can disrupt intestinal homeostasis and contribute to liver disease.

  18. [Alcohol-related problems in primary care].

    PubMed

    Ban, Nobutaro

    2015-09-01

    The approach to treating alcohol-related problems in primary care settings needs: 1) to recognize the incidence of alcohol-related problems in primary care settings; 2) to know the way of screening; 3) to know how to help patients; and 4) to know enough about treating alcoholism to appropriately refer patients for additional help. This article looks research evidence about the incidence of alcohol-related problems in primary care and recognition of incidence and way of screening of alcohol-related problems by primary care physicians in Japan. Then this article describes evidence-based as well as author's experience-based approach to treat the alcohol-related health problems in primary care settings. In line with the newly introduced law to prevent the alcohol-related health problems and the anticipating introduction of new specialty of general medicine, early intervention to alcohol-related problems in primary care settings will be much appreciated. To do so, enough amounts of education and research are needed.

  19. Nutrition in cirrhosis and chronic liver disease.

    PubMed

    Juakiem, Wassem; Torres, Dawn M; Harrison, Stephen A

    2014-02-01

    Nutrition has not been a primary focus of many medical conditions despite its importance in the development and the severity of these diseases. This is certainly the case with nutrition and end-stage liver disease despite the well-established association of nutritional deficiencies and increased rates of complications and mortality in cirrhosis. This review provides an overview of nutrition in chronic liver disease with an emphasis on its pathogenesis as well as ways to assess nutritional status and intervene in an effort to improve nutrition.

  20. [Non-alcoholic fatty liver disease (NAFLD)].

    PubMed

    Rau, Monika; Weiss, Johannes; Geier, Andreas

    2015-07-01

    Non-alcoholic fatty liver disease is the most common chronic liver disease in Europe and in the USA with rising prevalence. Patients with a metabolic syndrome (diabetes mellitus, obesity, dyslipidemia) are patients at risk with the highest prevalence for NAFLD. Progression from a non-alcoholic fatty liver (NAFL) to a non-alcoholic steatohepatitis (NASH) occurs in 5-20% of patients with the potential to develop a liver fibrosis/cirrhosis. NASH patients and NAFLD patients with higher fibrosis should be identified because they are at risk of a higher mortality. A specific treatment for NASH is not available at the moment. Therefore, the treatment of risk factors and metabolic syndrome has high priority.

  1. [Challenges in liver diseases and transplantation].

    PubMed

    Ben Ari, Ziv

    2012-12-01

    In the recent decade the subject of general hepatology has undergone significant upgrading. Several breakthrough discoveries have lead to substantial improvement in the antiviral treatment of viral hepatitis, the therapy of hepatocellular carcinoma and the development of noninvasive diagnosis of the severity of liver disease. Nonalcoholic fatty liver disease (NAFLD] is now established as one of the most common causes of chronic liver disease in the Western world. NAFLD can progress to cirrhosis and its associated complications. This issue of "Harefuah" is dedicated to the current knowledge and challenges in liver disease and transplantation and to novel discoveries in this field. Two new important guidelines of the Israeli Association for the Study of the Liver are published in this issue, the first deals with the management of ascites and its complications and the second relates to the innovative antiviral treatment of chronic hepatitis C virus infection. An extensive review on this latter subject is also included, summarizing the major breakthroughs in this field: the development of the new direct acting antiviraL agents and the role of IL28B polymorphism in the response to treatment. One article argues the concept of the high hepatitis B virus (HBV) vertical transmission in an Arab cohort in Israel, while another paper provides data on a significantly improved response rate to antiviral therapy in HIV-HCV co-infected patients. Increased serum level of lipoprotein-associated phospholipase A2 level, an independent predictor of coronary heart disease, was detected in patients with nonalcohoLic fatty liver disease [NAFLD] in another article. The issue also provides encouraging data showing that following two decades of liver transplantation in Israel, the survival rate has improved. Several additional articles in the issue shed further light on recent discoveries in the field of hepatology.

  2. Lung and Heart Disease Secondary to Liver Disease

    PubMed Central

    Goldberg, David S.; Fallon, Michael B.

    2015-01-01

    Patients with chronic liver disease are at risk of extra-hepatic complications related to cirrhosis and portal hypertension, as well organ-specific complications of certain liver diseases. These complications can compromise quality-of-life, while also increasing morbidity and mortality pre- and post-liver transplantation. Patients with chronic liver disease are at risk for pulmonary complications of hepaotpulmonary syndrome and portopulmonary syndrome; the major cardiac complication falls under the general concept of the cirrhotic cardiomyopathy, which can affect systolic and diastolic function, as well as cardiac conduction. In addition, patients with certain diseases are at risk of lung and/or cardiac complications that are specific to the primary disease (i.e., emphysema in alpha-1-antitrypsin deficiency) or occur with increased incidence in certain conditions (i.e., ischemic heart disease associated with non-alcoholic steatohepatitis. This section will focus on the epidemiology, clinical presentation, pathogenesis, treatment options, and role of transplantation for lung and heart diseases secondary to liver disease, while also highlighting select liver diseases that directly affect the lungs and hearts. PMID:25934564

  3. Developmental origins of nonalcoholic fatty liver disease.

    PubMed

    Brumbaugh, David E; Friedman, Jacob E

    2014-01-01

    Obese pregnant women may transmit their metabolic phenotype to offspring, leading to a cycle of obesity and diabetes over generations. Early childhood obesity predicts nonalcoholic fatty liver disease (NAFLD), the most common chronic human liver disease. The fetus may be vulnerable to steatosis because immature fetal adipose depots are not available to buffer the excess transplacental lipid delivery in maternal obesity. In animal models, in utero high-fat diet exposure results in an increase in the accumulation of liver triglycerides in offspring and increased hepatic oxidative stress and apoptosis, perhaps priming the liver for later development of NAFLD. Innate immune dysfunction and necroinflammatory changes have been observed in postnatal offspring liver of animals born to high-fat-fed dams. Postweaning, livers of offspring exposed to maternal high-fat feeding in utero share pathophysiologic features with human NAFLD, including increased de novo lipogenesis and decreased free fatty acid oxidation. Human studies using magnetic resonance imaging have shown that maternal BMI predicts infant intrahepatocellular lipid storage, as seen in animal models. The generational transfer of NAFLD may occur via epigenetic changes in offspring liver. Transmission of microbiota from mother to infant may impact energy retention and immune function that contribute to a predisposition to NAFLD.

  4. Hemostasis, coagulation abnormalities, and liver disease.

    PubMed

    Mackavey, Carole L; Hanks, Robert

    2013-12-01

    Coagulopathy-related bleeding events are a major concern in the management of acute and chronic liver disease. The liver attempts to maintain a balance between procoagulant and anticoagulant factors, and providers struggle with poor prognostic indicators to manage bleeding and critical complications. Subtle changes in patient presentation that may require extensive provider-directed interventions, such as blood transfusions, intravenous fluid management, mitigating possible sepsis, and evaluating appropriate pharmacologic treatment, are discussed.

  5. [Nonalcoholic fatty liver disease in children].

    PubMed

    Bojórquez-Ramos, María del Carmen

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in children and adolescents in the United States of America (USA) and probably in the entire western hemisphere, due to the increase in the prevalence of overweight and obesity. Steatosis can progress to inflammation, fibrosis and even cirrhosis, which increases the morbidity and mortality associated to liver disease. In every overweight and obese child a thorough analysis should be performed including liver function tests and liver ultrasound, in order to establish a timely diagnosis. The liver biopsy is the most specific study to rule out other potentially treatable entities. It is necessary to count on non-invasive methods to detect children with NAFLD and identify those in risk of progression. Biomarkers related to inflammation, oxidative stress, apoptosis and fibrosis have been reported. The main goal of the treatment is to modify the life style, starting with a healthy diet and an increase of physical activity. Regarding pharmacological treatment, there is evidence of histological improvement with vitamin E use, as opposed to metformin, but more conclusive studies regarding this subject are needed.

  6. Nonmedicinal interventions in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Nanau, Radu M; Cohen, Lawrence B

    2015-01-01

    Unhealthy diet and lack of physical exercise are responsible for fat accumulation in the liver, which may lead to liver disease. Histologically, the severity of the disease has two stages: nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). NAFLD is defined by the presence of steatosis with no evidence of cellular injury such as hepatocyte ballooning. NASH is a distinct entity from NAFLD, and is characterized by the presence of inflammation with hepatocytes damage, with or without fibrosis. While several therapeutic strategies have been proposed to improve this condition, the present review aims to discuss nonmedicinal interventions used to reduce liver involvement or to prevent the disease altogether. The authors investigated dietary patterns and vitamin deficiencies associated with NAFLD, and their role in enhancing disease severity. Additionally, they reviewed the role of exercise and the use of interventions, such as as intragastric balloon and bariatric surgery, for improving disease progression. The authors propose monitoring disease progression or repair by following changes in cytoadipokine levels. PMID:26076224

  7. Complement activation in chronic liver disease.

    PubMed Central

    Munoz, L E; De Villiers, D; Markham, D; Whaley, K; Thomas, H C

    1982-01-01

    Patients with HBsAg positive chronic active liver disease (CALD) and primary biliary cirrhosis (PBC) exhibit increased C3d concentrations and changes in the serum concentrations of the complement components consistent with activation of the classical and alternative pathways. In these patients the concentrations of the regulatory proteins, C3b inactivator (C3bINA) and beta IH globulin, are normal. Patients with HBsAg negative CALD and alcohol induced liver disease (ALD) exhibit no evidence of an increased level of complement system activation. In these patients diminished serum concentrations of complement components appear to be related to diminished hepatic synthetic function. C4 synthesis may be specifically reduced in autoimmune chronic active liver disease. PMID:7083631

  8. Candidates for liver transplantation with alcoholic liver disease: Psychosocial aspects

    PubMed Central

    Telles-Correia, Diogo; Mega, Inês

    2015-01-01

    In Europe, 30% to 50% of liver transplantations are currently due to alcoholic liver disease (ALD). In the United States, this percentage is 17.2%. Post-transplant survival and other predictors of clinical course do not differ significantly from those in other types of transplanted patients, as long as there is no relapse of drinking. However, 20%-25% of these patients lapse or relapse to heavy drinking post-operatively, which has been associated with an increased risk of liver damage and mortality. It is therefore crucial to design specific selection and follow-up strategies aimed at this particular type of patient. Several good and poor prognosis factors that could help to predict a relapse have been suggested, among them the duration of abstinence, social support, a family history of alcoholism, abuse diagnosis versus alcohol dependence, non-acceptance of diagnosis related to alcohol use, presence of severe mental illness, non-adherence in a broad sense, number of years of alcoholism, and daily quantity of alcohol consumption. In this article, we discuss these and other, more controversial factors in selecting ALD patients for liver transplantation. Abstinence should be the main goal after transplantation in an ALD patient. In this article, we review the several definitions of post-transplant relapse, its monitoring and the psychopharmacological and psychotherapeutic treatment. PMID:26494959

  9. Liver transplantation in alcoholic liver disease current status and controversies

    PubMed Central

    Singal, Ashwani K; Chaha, Khushdeep S; Rasheed, Khalid; Anand, Bhupinderjit S

    2013-01-01

    Alcoholic cirrhosis remains the second most common indication for liver transplantation. A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant list. Most transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these patients. Patients with alcohol dependence are at high risk for relapse to alcohol use after transplantation (recidivism). These patients need to be identified and require alcohol rehabilitation treatment before transplantation. Recidivism to the level of harmful drinking is reported in about 15%-20% cases. Although, recurrent cirrhosis and graft loss from recidivism is rare, occurring in less than 5% of all alcoholic cirrhosis-related transplants, harmful drinking in the post-transplant period does impact the long-term outcome. The development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver disease. Surveillance protocols for earlier detection of de novo malignancy are needed to improve the long-term outcome. The need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to corticosteroids. Emerging data from retrospective and prospective studies has challenged the 6 mo rule, and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids. PMID:24106395

  10. Ursodeoxycholic acid in chronic liver disease.

    PubMed Central

    de Caestecker, J S; Jazrawi, R P; Petroni, M L; Northfield, T C

    1991-01-01

    The hydrophilic bile acid ursodeoxycholic acid has recently been shown to reduce biochemical markers of both cholestasis and hepatocellular damage in patients with chronic liver diseases. The most compelling evidence available is for chronic cholestatic liver diseases, in particular primary biliary cirrhosis, primary sclerosing cholangitis, and cholestasis associated with cystic fibrosis. The effects may be less beneficial in patients with advanced liver disease from these conditions. Data from placebo controlled trials are now available in support of earlier uncontrolled observations, but it is not yet clear whether short term benefit results in an improvement in longterm prognosis. The mechanism of action of the compound seems to reside in its displacement of toxic hydrophobic bile acids from both the bile acid pool and hepatocellular membranes. There may be an independent effect on bile flow, which could be of particular importance in cystic fibrosis, and possibly an effect on the immune system. Ursodeoxycholic acid should now be regarded as occupying a central place in the medical management of chronic cholestatic liver diseases, in particular primary biliary cirrhosis, because it improves cholestasis and reduces hepatocellular damage and it is not toxic. Research should now be targeted on whether treatment with ursodeoxycholic acid, initiated early in cholestatic liver conditions, improves the long-term outcome. PMID:1916492

  11. Vitamin D in autoimmune liver disease.

    PubMed

    Smyk, Daniel S; Orfanidou, Timoklia; Invernizzi, Pietro; Bogdanos, Dimitrios P; Lenzi, Marco

    2013-11-01

    The development of autoimmune disease is based on the interaction of genetic susceptibility and environmental causes. Environmental factors include infectious and non-infectious agents, with some of these factors being implicated in several autoimmune diseases. Vitamin D is now believed to play a role in the development (or prevention) of several autoimmune diseases, based on its immunomodulatory properties. As well, the increasing incidence of autoimmune disease as one moves away from the equator, may be due to the lack of sunlight, which is crucial for the maintenance of normal vitamin D levels. A deficiency in vitamin D levels or vitamin D receptors is commonly indicated in autoimmune diseases, with multiple sclerosis (MS) being one of the best-studied and well-known examples. However, the role of vitamin D in other autoimmune diseases is not well defined, including autoimmune liver diseases such as primary biliary cirrhosis, autoimmune hepatitis, and primary sclerosing cholangitis. This review will examine the role of vitamin D as an immunomodulator, followed by a comparison of vitamin D in MS versus autoimmune liver disease. From this comparison, it will become clear that vitamin D likely plays a role in the development of autoimmune liver disease, but this area requires further investigation.

  12. Renal tubular acidosis in chronic liver disease

    PubMed Central

    Golding, Peter L.

    1975-01-01

    Renal tubular acidosis of the gradient or classic type, thought to be due to a disorder of the distal tubule, has been found to occur in 32% of 117 patients with chronic liver disease. Whilst the cause of this disorder is probably multifactorial, immunological mechanisms are considered to play a major role. The presence of this disorder might well be a cause, rather than the result of, the various electrolyte abnormalities seen in patients with chronic liver disease. ImagesFig. 1Fig. 6 PMID:1234340

  13. Pediatric Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Delvin, Edgard; Patey, Natasha; Dubois, Josée; Henderson, Melanie; Lévy, Émile

    2015-01-01

    Summary The rapidly increasing prevalence of childhood obesity and its associated co-morbidities such as hypertriglyceridemia, hyper-insulinemia, hypertension, early atherosclerosis, metabolic syndrome, and non-alcoholic fatty liver disease are major public health concerns in many countries. Therefore the trends in child and adolescent obesity should be closely monitored over time, as in the near future, we may anticipate a major increase of young adults with the stigmata of the metabolic syndrome, and of the related non-alcoholic fatty liver disease (NAFLD), that may lead to non-alcoholic steatohepatitis. PMID:28356817

  14. Autophagy in ethanol-exposed liver disease.

    PubMed

    Wang, Li-Ren; Zhu, Gui-Qi; Shi, Ke-Qing; Braddock, Martin; Zheng, Ming-Hua

    2015-01-01

    Ethanol metabolism in hepatocytes causes the generation of reactive oxygen species, endoplasmic reticulum stress and alterations in mitochondrial energy and REDOX metabolism. In ethanol-exposed liver disease, autophagy not only acts as a cleanser to remove damaged organelles and cytosolic components, but also selectively clears specific targets such as lipid droplets and damaged mitochondria. Moreover, ethanol appears to play a role in protecting hepatocytes from apoptosis at certain concentrations. This article describes the evidence, function and potential mechanism of autophagy in ethanol-exposed liver disease and the controversy surrounding the effects of ethanol on autophagy.

  15. Autoimmune hepatitis: a classic autoimmune liver disease.

    PubMed

    Moy, Libia; Levine, Jeremiah

    2014-12-01

    AIH is characterized by chronic inflammation of the liver, interface hepatitis, hypergammaglobulinemia, and production of autoantibodies. Based on the nature of the serum autoantibodies, two types of AIH are recognized: type 1 (AIH-1), positive for ANA and/or anti-smooth muscle antibody, and type 2 (AIH-2), defined by the positivity for anti-liver kidney microsomal type 1 antibody or for anti-liver cytosol type 1 antibody. AIH demonstrates a female preponderance with the female-to-male ratio of 4:1 in AIH-1 and 10:1 in AIH-2. Several genes confer susceptibility to AIH and influence clinical manifestation, response to treatment, and overall prognosis. Most are located within the human leukocyte antigen (HLA) region, which is involved in the presentation of antigenic peptides to T cells and thus in the initiation of adaptive immune responses. The strongest associations are found within the HLA-DRB1 locus. In patients with increased genetic susceptibility to AIH, immune responses to liver autoantigens could be triggered by molecular mimicry. Because of molecular mimicry, different environmental agents, drugs, and viruses might produce AIH. In AIH, T cells are numerically and functionally impaired, permitting the perpetuation of effector immune responses with ensuing persistent liver destruction. AIH is rare but highly treatable inflammatory condition of the liver. Subclinical and asymptomatic disease is common. AIH therefore needs to be considered in the differential diagnosis of all patients with elevated liver enzymes. Clinical response to immunosuppressive therapy is characteristic and supports the diagnosis.

  16. Lipoprotein metabolism in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui Gordon; Robson, Simon C.; Yao, Zemin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD), an escalating health problem worldwide, covers a spectrum of pathologies characterized by fatty accumulation in hepatocytes in early stages, with potential progression to liver inflammation, fibrosis, and failure. A close, yet poorly understood link exists between NAFLD and dyslipidemia, a constellation of abnormalities in plasma lipoproteins including triglyceride-rich very low density lipoproteins. Apolipoproteins are a group of primarily liver-derived proteins found in serum lipoproteins; they not only play an extracellular role in lipid transport between vital organs through circulation, but also play an important intracellular role in hepatic lipoprotein assembly and secretion. The liver functions as the central hub for lipoprotein metabolism, as it dictates lipoprotein production and to a significant extent modulates lipoprotein clearance. Lipoprotein metabolism is an integral component of hepatocellular lipid homeostasis and is implicated in the pathogenesis, potential diagnosis, and treatment of NAFLD. PMID:23554788

  17. Vinyl chloride-associated liver disease.

    PubMed

    Berk, P D; Martin, J F; Young, R S; Creech, J; Selikoff, I J; Falk, H; Watanabe, P; Popper, H; Thomas, L

    1976-06-01

    Although polyvinyl chloride has been produced from vinyl chlride monomer for more than 40 years, recognition of toxicity among vinyl chloride polymerization workers is more recent. In the mid 1960s, workers involved in cleaning polymerization tanks were found to have acro-osteolysis. In 1974, the same population of workers was found to be at risk for an unusual type of hepatic fibrosis and angiosarcoma of the liver. We describe two cases of vinyl chloride-associated liver injury, one of hepatic fibrosis and one of angiosarcoma. Histologic features of these lesions are similar to the hepatic fibrosis and angiosarcomas resulting from chronic exposure to inorganic arsenicals. Preliminary studies suggest that the toxicity of vinyl chloride may result from formation, during high-dose exposure, of active metabolites by mixed function oxidases of the liver. Epidemiologic studies indicate an increased incidence not only of liver disease, but also of cancers of the brain, lung, and possibly other organs.

  18. Role of Osteopontin in Liver Diseases

    PubMed Central

    Wen, Yankai; Jeong, Seogsong; Xia, Qiang; Kong, Xiaoni

    2016-01-01

    Osteopontin (OPN), a multifunctional protein, is involved in numerous pathological conditions including inflammation, immunity, angiogenesis, fibrogenesis and carcinogenesis in various tissues. Extensive studies have elucidated the critical role of OPN in cell signaling such as regulation of cell proliferation, migration, inflammation, fibrosis and tumor progression. In the liver, OPN interacts with integrins, CD44, vimentin and MyD88 signaling, thereby induces infiltration, migration, invasion and metastasis of cells. OPN is highlighted as a chemoattractant for macrophages and neutrophils during injury in inflammatory liver diseases. OPN activates hepatic stellate cells (HSCs) to exert an enhancer in fibrogenesis. The role of OPN in hepatocellular carcinoma (HCC) has also generated significant interests, especially with regards to its role as a diagnostic and prognostic factor. Interestingly, OPN acts an opposing role in liver repair under different pathological conditions. This review summarizes the current understanding of OPN in liver diseases. Further understanding of the pathophysiological role of OPN in cellular interactions and molecular mechanisms associated with hepatic inflammation, fibrosis and cancer may contribute to the development of novel strategies for clinical diagnosis, monitoring and therapy of liver diseases. PMID:27570486

  19. Complications in patients with alcohol-associated liver disease who undergo liver transplantation.

    PubMed

    Gaglio, Paul J; Gaglio, Paul J

    2012-11-01

    Cirrhosis caused by alcohol-associated liver disease is a common indication for liver transplantation worldwide. Patients with alcohol-associated liver disease who undergo liver transplantation face multiple challenging comorbid medical issues that enhance the potential for perioperative and postoperative complications. Awareness of these issues and appropriate therapeutic intervention may minimize the negative effect of these complications on posttransplantation survival. This article reviews important posttransplantation problems in patients transplanted for alcohol-associated liver disease.

  20. The Differentiation of Intestinal-Failure-Associated Liver Disease from Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis.

    PubMed

    Buchman, Alan L; Naini, Bita V; Spilker, Bert

    2017-02-01

    Intestinal failure-associated liver disease (IFALD), formerly known as parenteral nutrition-associated liver disease has often been listed in textbooks as an example of nonalcoholic fatty liver disease (NAFLD). However, the etiology, pathophysiology, epidemiology, histology, and progression differ substantially between the conditions defined as NAFLD and the disease, IFALD. Therefore, IFALD should not be defined or considered as a type or a cause of nonalcoholic fatty liver or nonalcoholic steatohepatitis, but rather as a distinct disease.

  1. Management of thrombocytopenia in advanced liver disease.

    PubMed

    Gangireddy, V G R; Kanneganti, P C; Sridhar, S; Talla, S; Coleman, T

    2014-11-01

    Thrombocytopenia (defined as a platelet count <150×10(9)) is a well-known complication in patients with liver cirrhosis and has been observed in 76% to 85% of patients. Significant thrombocytopenia (platelet count <50×10(9) to 75×10(9)) occurs in approximately 13% of patients with cirrhosis. Thrombocytopenia can negatively impact the care of patients with severe liver disease by potentially interfering with diagnostic and therapeutic procedures. Multiple factors can contribute to the development of thrombocytopenia including splenic platelet sequestration, immunological processes, bone marrow suppression by chronic viral infection, and reduced levels or activity of the hematopoietic growth factor thrombopoietin. The present review focuses on the etiologies and management options for severe thrombocytopenia in the setting of advanced liver disease.

  2. Alcohol-Related Problems in High-Risk Groups. EURO Reports and Studies 109. Report on a WHO Study.

    ERIC Educational Resources Information Center

    Plant, Martin, Ed.

    Alcohol consumption has risen dramatically in many countries since the Second World War. Accompanying this rise has been a rise in alcohol-related problems, including liver cirrhosis mortality, alcohol dependence, and alcohol-related crimes and accidents. Alcohol misuse presents huge health, social, and legal problems throughout most of Europe and…

  3. Genetic predisposition in nonalcoholic fatty liver disease

    PubMed Central

    Sookoian, Silvia; Pirola, Carlos J.

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease whose prevalence has reached global epidemic proportions. Although the disease is relatively benign in the early stages, when severe clinical forms, including nonalcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma, occur, they result in worsening the long-term prognosis. A growing body of evidence indicates that NAFLD develops from a complex process in which many factors, including genetic susceptibility and environmental insults, are involved. In this review, we focused on the genetic component of NAFLD, with special emphasis on the role of genetics in the disease pathogenesis and natural history. Insights into the topic of the genetic susceptibility in lean individuals with NAFLD and the potential use of genetic tests in identifying individuals at risk are also discussed. PMID:28268262

  4. Circadian rhythms in liver metabolism and disease.

    PubMed

    Ferrell, Jessica M; Chiang, John Y L

    2015-03-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease.

  5. Circadian rhythms in liver metabolism and disease

    PubMed Central

    Ferrell, Jessica M.; Chiang, John Y.L.

    2015-01-01

    Mounting research evidence demonstrates a significant negative impact of circadian disruption on human health. Shift work, chronic jet lag and sleep disturbances are associated with increased incidence of metabolic syndrome, and consequently result in obesity, type 2 diabetes and dyslipidemia. Here, these associations are reviewed with respect to liver metabolism and disease. PMID:26579436

  6. Overlap syndromes among autoimmune liver diseases.

    PubMed

    Rust, Christian; Beuers, Ulrich

    2008-06-07

    The three major immune disorders of the liver are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Variant forms of these diseases are generally called overlap syndromes, although there has been no standardised definition. Patients with overlap syndromes present with both hepatitic and cholestatic serum liver tests and have histological features of AIH and PBC or PSC. The AIH-PBC overlap syndrome is the most common form, affecting almost 10% of adults with AIH or PBC. Single cases of AIH and autoimmune cholangitis (AMA-negative PBC) overlap syndrome have also been reported. The AIH-PSC overlap syndrome is predominantly found in children, adolescents and young adults with AIH or PSC. Interestingly, transitions from one autoimmune to another have also been reported in a minority of patients, especially transitions from PBC to AIH-PBC overlap syndrome. Overlap syndromes show a progressive course towards liver cirrhosis and liver failure without treatment. Therapy for overlap syndromes is empiric, since controlled trials are not available in these rare disorders. Anticholestatic therapy with ursodeoxycholic acid is usually combined with immunosuppressive therapy with corticosteroids and/or azathioprine in both AIH-PBC and AIH-PSC overlap syndromes. In end-stage disease, liver transplantation is the treatment of choice.

  7. Autophagy in alcohol-induced liver diseases.

    PubMed

    Dolganiuc, Angela; Thomes, Paul G; Ding, Wen-Xing; Lemasters, John J; Donohue, Terrence M

    2012-08-01

    Alcohol is the most abused substance worldwide and a significant source of liver injury; the mechanisms of alcohol-induced liver disease are not fully understood. Significant cellular toxicity and impairment of protein synthesis and degradation occur in alcohol-exposed liver cells, along with changes in energy balance and modified responses to pathogens. Autophagy is the process of cellular catabolism through the lysosomal-dependent machinery, which maintains a balance among protein synthesis, degradation, and recycling of self. Autophagy is part of normal homeostasis and it can be triggered by multiple factors that threaten cell integrity, including starvation, toxins, or pathogens. Multiple factors regulate autophagy; survival and preservation of cellular integrity at the expense of inadequately folded proteins and damaged high-energy generating intracellular organelles are prominent targets of autophagy in pathological conditions. Coincidentally, inadequately folded proteins accumulate and high-energy generating intracellular organelles, such as mitochondria, are damaged by alcohol abuse; these alcohol-induced pathological findings prompted investigation of the role of autophagy in the pathogenesis of alcohol-induced liver damage. Our review summarizes the current knowledge about the role and implications of autophagy in alcohol-induced liver disease.

  8. Radiologic evaluation of nonalcoholic fatty liver disease

    PubMed Central

    Lee, Seung Soo; Park, Seong Ho

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a frequent cause of chronic liver diseases, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH)-related liver cirrhosis. Although liver biopsy is still the gold standard for the diagnosis of NAFLD, especially for the diagnosis of NASH, imaging methods have been increasingly accepted as noninvasive alternatives to liver biopsy. Ultrasonography is a well-established and cost-effective imaging technique for the diagnosis of hepatic steatosis, especially for screening a large population at risk of NAFLD. Ultrasonography has a reasonable accuracy in detecting moderate-to-severe hepatic steatosis although it is less accurate for detecting mild hepatic steatosis, operator-dependent, and rather qualitative. Computed tomography is not appropriate for general population assessment of hepatic steatosis given its inaccuracy in detecting mild hepatic steatosis and potential radiation hazard. However, computed tomography may be effective in specific clinical situations, such as evaluation of donor candidates for hepatic transplantation. Magnetic resonance spectroscopy and magnetic resonance imaging are now regarded as the most accurate practical methods of measuring liver fat in clinical practice, especially for longitudinal follow-up of patients with NAFLD. Ultrasound elastography and magnetic resonance elastography are increasingly used to evaluate the degree of liver fibrosis in patients with NAFLD and to differentiate NASH from simple steatosis. This article will review current imaging methods used to evaluate hepatic steatosis, including the diagnostic accuracy, limitations, and practical applicability of each method. It will also briefly describe the potential role of elastography techniques in the evaluation of patients with NAFLD. PMID:24966609

  9. Mitochondrial dysfunction in cholestatic liver diseases.

    PubMed

    Arduini, Alessandro; Serviddio, Gaetano; Tormos, Ana M; Monsalve, Maria; Sastre, Juan

    2012-01-01

    Cholestatic liver diseases are characterized by blockade of bile flow from the liver to the intestine, and accumulation of hydrophobic bile acids in the liver and plasma. As a consequence an inflammatory response evolves associated with increased apoptosis, oxidative stress, and eventually fibrosis. Cholestasis is associated with profound metabolic changes, alterations in the mitochondrial function, decreased fatty acid oxidation, and increased glycolisis. Mitochondria play a central role in the development of this liver disease because they mediate death receptor signaling - triggered by inflammatory cytokines or bile acids - and contribute to oxidative damage, metabolic disorder, and onset of fibrosis. During the pathogenesis of biliary cirrhosis mitochondria's need for renewal is hampered by a blunted mitochondrial biogenesis. Lack of stimulation of mitochondrial renewal helps to explain mitochondrial impairment in long-term cholestasis. The marked depletion of mitochondrial DNA and occurrence of mitochondrial DNA deletions are probably relevant contributors to the progression of this severe disease. All these findings certainly support the consideration of long-term cholestasis as a secondary mitochondrial hepatopathy.

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

    MedlinePlus

    ... Genetics Home Health Conditions NAFLD non-alcoholic fatty liver disease Enable Javascript to view the expand/collapse ... Open All Close All Description Non-alcoholic fatty liver disease ( NAFLD ) is a buildup of excessive fat ...

  11. New Advances in Polycystic Liver Diseases.

    PubMed

    Santos-Laso, A; Izquierdo-Sánchez, L; Lee-Law, P Y; Perugorria, M J; Marzioni, M; Marin, J J G; Bujanda, L; Banales, J M

    2017-02-01

    Polycystic liver diseases (PLDs) include a heterogeneous group of congenital disorders inherited as dominant or recessive genetic traits; they are manifested alone or in association with polycystic kidney disease. Ductal plate malformation during embryogenesis and the loss of heterozygosity linked to second-hit mutations may promote the dilatation and/or development of a large number (> 20) of biliary cysts, which are the main cause of morbidity in these patients. Surgical procedures aimed to eliminate symptomatic cysts show short-term beneficial effects, but are not able to block the disease progression. Therefore, liver transplantation is the only curative option. Intense studies on the molecular mechanisms involved in the pathogenesis of PLDs have resulted in different clinical trials, some of them with promising outcomes. Here the authors summarize the key aspects of PLD etiology, pathogenesis, and therapy, highlighting the most recent advances and future research directions.

  12. Liver disease and “natural” hepatotoxins

    PubMed Central

    Schoental, R.

    1963-01-01

    The author discusses the role of “natural” hepatotoxic substances, derived from plants and fungi, in the etiology of liver disease, especially in tropical and subtropical countries. The hazards involved in even the occasional use of natural hepatotoxins and the difficulty in tracing the causative factors of chronic diseases are illustrated by the example of the pyrrolizidine (Senecio) alkaloids. The ingestion by rats of a single dose of these alkaloids can induce chronic liver lesions and even hepatoma which, however, may not become apparent for 1½-2½ years. It is suggested that, however varied the chemical structures of the various hepatocarcinogens, they may all affect an essential cell constituent (e.g., a “mitotic hormone”), possibly of a steroidal nature, each substance interfering with a particular stage of its biosynthesis. “Natural” toxic factors may also be responsible for some other chronic diseases, especially those which are mainly encountered in, or restricted to, certain pastoral communities. In view of the greater susceptibility of the suckling young and the foetus than of adults to hepatotoxins, it would appear more promising to attempt to trace the causative agents of liver disease in children than in adults, in whom disease takes much longer to develop. ImagesFIG. 1FIG. 3FIG. 4FIG. 5FIG. 6FIG. 7FIG. 8FIG. 9FIG. 10 PMID:14107756

  13. Endocrine causes of nonalcoholic fatty liver disease

    PubMed Central

    Marino, Laura; Jornayvaz, François R

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the industrialized world. The prevalence of NAFLD is increasing, becoming a substantial public health burden. NAFLD includes a broad spectrum of disorders, from simple conditions such as steatosis to severe manifestations such as fibrosis and cirrhosis. The relationship of NAFLD with metabolic alterations such as type 2 diabetes is well described and related to insulin resistance, with NAFLD being recognized as the hepatic manifestation of metabolic syndrome. However, NAFLD may also coincide with endocrine diseases such as polycystic ovary syndrome, hypothyroidism, growth hormone deficiency or hypercortisolism. It is therefore essential to remember, when discovering altered liver enzymes or hepatic steatosis on radiological exams, that endocrine diseases can cause NAFLD. Indeed, the overall prognosis of NAFLD may be modified by treatment of the underlying endocrine pathology. In this review, we will discuss endocrine diseases that can cause NALFD. Underlying pathophysiological mechanisms will be presented and specific treatments will be reviewed. PMID:26494962

  14. Interleukin-1 Family Cytokines in Liver Diseases

    PubMed Central

    Tsutsui, Hiroko; Cai, Xianbin; Hayashi, Shuhei

    2015-01-01

    The gene encoding IL-1 was sequenced more than 30 years ago, and many related cytokines, such as IL-18, IL-33, IL-36, IL-37, IL-38, IL-1 receptor antagonist (IL-1Ra), and IL-36Ra, have since been identified. IL-1 is a potent proinflammatory cytokine and is involved in various inflammatory diseases. Other IL-1 family ligands are critical for the development of diverse diseases, including inflammatory and allergic diseases. Only IL-1Ra possesses the leader peptide required for secretion from cells, and many ligands require posttranslational processing for activation. Some require inflammasome-mediated processing for activation and release, whereas others serve as alarmins and are released following cell membrane rupture, for example, by pyroptosis or necroptosis. Thus, each ligand has the proper molecular process to exert its own biological functions. In this review, we will give a brief introduction to the IL-1 family cytokines and discuss their pivotal roles in the development of various liver diseases in association with immune responses. For example, an excess of IL-33 causes liver fibrosis in mice via activation and expansion of group 2 innate lymphoid cells to produce type 2 cytokines, resulting in cell conversion into pro-fibrotic M2 macrophages. Finally, we will discuss the importance of IL-1 family cytokine-mediated molecular and cellular networks in the development of acute and chronic liver diseases. PMID:26549942

  15. Treatment of nonalcoholic fatty liver disease

    PubMed Central

    Siebler, Juergen; Galle, Peter R

    2006-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause for elevated liver enzymes in the developed nations. Beyond prevention programs which are of particular interest because of the increasing number of overweight children, treatment should be focussed on the most important risk factors, obesity and insulin resistance. As a consequence of elucidating the pathomechanisms of NAFLD, the number of potential therapeutic options increased. However, many studies investigating the therapeutic effect show shortcomings in at least one of the following points: lack of a serial liver biopsy, short term of treatment and limited number of included patients. The second generation insulin sensitizer pioglitazone and rosiglitazone show the most promising improvements in NAFLD, but weight gain and potential hepatotoxicity calls for attention. In conclusion, a general recommendation for the application of specific drugs cannot be given. Besides controlled clinical trials, weight reduction and physical activity to improve insulin sensitivity in obese patients should be the priority objective. PMID:16610015

  16. Vitamin E reduces liver stiffness in nonalcoholic fatty liver disease

    PubMed Central

    Fukui, Aiko; Kawabe, Naoto; Hashimoto, Senju; Murao, Michihito; Nakano, Takuji; Shimazaki, Hiroaki; Kan, Toshiki; Nakaoka, Kazunori; Ohki, Masashi; Takagawa, Yuka; Takamura, Tomoki; Kamei, Hiroyuki; Yoshioka, Kentaro

    2015-01-01

    AIM: To evaluate the efficacy of vitamin E treatment on liver stiffness in nonalcoholic fatty liver disease (NAFLD). METHODS: Thirty-eight NAFLD patients were administered vitamin E for > 1 year. The doses of vitamin E were 150, 300, or 600 mg; three times per day after each meal. Responses were assessed by liver enzyme levels [aspartate aminotransferase (AST), alanine aminotranferease (ALT), and γ-glutamyl transpeptidase (γ-GTP)], noninvasive scoring systems of hepatic fibrosis-4 [FIB-4 index and aspartate aminotransferase-to-platelet index (APRI)], and liver stiffness [velocity of shear wave (Vs)] measured by acoustic radiation force impulse elastography. Vs measurements were performed at baseline and 12 mo after baseline. The patients were genotyped for the patatin-like phospholipase domain containing 3 (PNPLA3) polymorphisms and then divided into either the CC/CG or GG group to examine each group’s responses to vitamin E treatment. RESULTS: We found marked differences in the platelet count, serum albumin levels, alkaline phosphatase levels, FIB-4 index, APRI, and Vs at baseline depending on the PNPLA3 polymorphism. AST, ALT, and γ-GTP levels (all P < 0.001); FIB-4 index (P = 0.035); APRI (P < 0.001); and Vs (P < 0.001) significantly decreased from baseline to 12 mo in the analysis of all patients. In the subset analyses of PNPLA3 genotypes, AST levels (P = 0.011), ALT levels (P < 0.001), γ-GTP levels (P = 0.005), APRI (P = 0.036), and Vs (P = 0.029) in genotype GG patients significantly improved, and AST and ALT levels (both P < 0.001), γ-GTP levels (P = 0.003), FIB-4 index (P = 0.017), and APRI (P < 0.001) in genotype CC/CG patients. CONCLUSION: One year of vitamin E treatment improved noninvasive fibrosis scores and liver stiffness in NAFLD patients. The responses were similar between different PNPLA3 genotypes. PMID:26644818

  17. Obesity, fatty liver disease and intestinal microbiota

    PubMed Central

    Arslan, Nur

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disorder that is increasing in prevalence with the worldwide epidemic of obesity. NAFLD is the hepatic manifestation of the metabolic syndrome. The term NAFLD describes a spectrum of liver pathology ranges from simple steatosis to steatosis with inflammation nonalcoholic steatohepatitis and even cirrhosis. Metabolic syndrome and NAFLD also predict hepatocellular carcinoma. Many genetic and environmental factors have been suggested to contribute to the development of obesity and NAFLD, but the exact mechanisms are not known. Intestinal ecosystem contains trillions of microorganisms including bacteria, Archaea, yeasts and viruses. Several studies support the relationship between the intestinal microbial changes and obesity and also its complications, including insulin resistance and NAFLD. Given that the gut and liver are connected by the portal venous system, it makes the liver more vulnerable to translocation of bacteria, bacterial products, endotoxins or secreted cytokines. Altered intestinal microbiota (dysbiosis) may stimulate hepatic fat deposition through several mechanisms: regulation of gut permeability, increasing low-grade inflammation, modulation of dietary choline metabolism, regulation of bile acid metabolism and producing endogenous ethanol. Regulation of intestinal microbial ecosystem by diet modifications or by using probiotics and prebiotics as a treatment for obesity and its complications might be the issue of further investigations. PMID:25469013

  18. Lower Muscle Endurance in Patients with Alcoholic Liver Disease

    ERIC Educational Resources Information Center

    Andersen, Henning; Aagaard, Niels K.; Jakobsen, Johannes; Dorup, Inge; Vilstrup, Hendrik

    2012-01-01

    Patients with alcoholic liver disease often complain of restricted physical capacity, which could be due to decreased muscle endurance. The aim of this study was to assess the muscular endurance in patients with alcoholic liver disease. In a cross sectional study, 24 patients with alcoholic liver disease and 22 controls were evaluated using…

  19. Hypoxia-inducible factors as molecular targets for liver diseases.

    PubMed

    Ju, Cynthia; Colgan, Sean P; Eltzschig, Holger K

    2016-06-01

    Liver disease is a growing global health problem, as deaths from end-stage liver cirrhosis and cancer are rising across the world. At present, pharmacologic approaches to effectively treat or prevent liver disease are extremely limited. Hypoxia-inducible factor (HIF) is a transcription factor that regulates diverse signaling pathways enabling adaptive cellular responses to perturbations of the tissue microenvironment. HIF activation through hypoxia-dependent and hypoxia-independent signals have been reported in liver disease of diverse etiologies, from ischemia-reperfusion-induced acute liver injury to chronic liver diseases caused by viral infection, excessive alcohol consumption, or metabolic disorders. This review summarizes the evidence for HIF stabilization in liver disease, discusses the mechanistic involvement of HIFs in disease development, and explores the potential of pharmacological HIF modifiers in the treatment of liver disease.

  20. Targeting autophagy for the treatment of liver diseases.

    PubMed

    Ni, Hong-Min; Williams, Jessica A; Yang, Hua; Shi, Ying-Hong; Fan, Jia; Ding, Wen-Xing

    2012-12-01

    Autophagy is a lysosomal degradation pathway that can degrade bulk cytoplasm and superfluous or damaged organelles, such as mitochondria, to maintain cellular homeostasis. It is now known that dysregulation of autophagy can cause pathogenesis of numerous human diseases. Here, we discuss the critical roles that autophagy plays in the pathogenesis of liver diseases such as non-alcoholic and alcoholic fatty liver, drug-induced liver injury, protein aggregate-related liver diseases, viral hepatitis, fibrosis, aging and liver cancer. In particular, we discuss the emerging therapeutic potential by pharmacological modulation of autophagy for these liver diseases.

  1. Biomarkers in nonalcoholic fatty liver disease

    PubMed Central

    Neuman, Manuela G; Cohen, Lawrence B; Nanau, Radu M

    2014-01-01

    BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver condition characterized by insulin resistance, type 2 diabetes and fat accumulation in the liver that may cause hepatic inflammation and progressive scarring leading to nonalcoholic steatohepatitis (NASH) and irreversible liver damage (cirrhosis). As a result, there has been increased recognition of the need to assess and closely monitor individuals for risk factors of components of NAFLD and NASH, as well as the severity of these conditions using biomarkers. AIM: To review the biomarkers used to diagnose and define the severity of NAFLD and NASH. METHODS: A comprehensive PubMed and Google Scholar literature search was performed using the terms “non-alcoholic fatty liver disease”, “non-alcoholic steatohepatitis”, as well as the name of each biomarker known to be used. Articles indexed between 2004 and 2014 were used. Each author read the publications separately and the results were discussed. RESULTS: Biomarkers offer a potential prognostic or diagnostic indicator for disease manifestation, progression or both. Serum biomarkers, including total cholesterol, triglycerides, insulin resistance and C-peptide, have been used for many years. Emerging biomarkers, such as apolipoprotein A1, apolipoprotein B, leptin, adiponectin, free fatty acids, ghrelin and tumour necrosis factor-alpha, have been proposed as tools that could provide valuable complementary information to that obtained from traditional biomarkers. Moreover, markers of cell death and mitochondrial dysfunction (cytokeratins) represent powerful predictors of risk. For biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in sex and ethnic origin are a necessity. CONCLUSIONS: The present review attempts to provide a comprehensive analysis of the emerging risk biomarkers of NAFLD and NASH, and to use the clinical significance and analytical

  2. Psoriasis and Nonalcoholic Fatty Liver Disease.

    PubMed

    Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A

    2017-03-16

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.

  3. Pediatric Parenteral Nutrition-Associated Liver Disease.

    PubMed

    Israelite, Jill C

    Pediatric parenteral nutrition-associated liver disease (PNALD) is typically defined as a decrease in bile flow that is independent of a mechanical obstruction and of any other underlying liver disease. It is most often seen in pediatric patients receiving parenteral nutrition support. Up to 50% to 66% of children receiving long-term parenteral nutrition are reported to be diagnosed with PNALD. The goal of treatment for PNALD is advancement to full enteral nutrition and elimination of dependence on parenteral nutrition support. Achieving this goal is not always possible, especially in patients with short bowel syndrome. The following review article highlights some of the current treatment strategies focused on prevention or correction of PNALD as noted in current American Society for Parenteral and Enteral Nutrition guidelines.

  4. Targeting Dysbiosis for the Treatment of Liver Disease.

    PubMed

    Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

    2016-02-01

    The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets.

  5. Challenges in transplantation for alcoholic liver disease.

    PubMed

    Berlakovich, Gabriela A

    2014-07-07

    Transplantation for the treatment of alcoholic cirrhosis is more controversially discussed than it is for any other indication. The crucial aspect in this setting is abstinence before and after liver transplantation. We established pre-transplant selection criteria for potential transplant candidates. Provided that the underlying disease can be treated, there is no reason to withhold liver transplantation in a patient suffering from alcoholic cirrhosis. Evaluation of the patient by a multidisciplinary team, including an addiction specialist, is considered to be the gold standard. However, several centers demand a specified period of abstinence - usually 6 mo- irrespective of the specialist's assessment. The 6-mo rule is viewed critically because liver transplantation was found to clearly benefit selected patients with acute alcoholic hepatitis; the benefit was similar to that achieved for other acute indications. However, the discussion may well be an academic one because the waiting time for liver transplantation exceeds six months at the majority of centers. The actual challenge in liver transplantation for alcoholic cirrhosis may well be the need for lifelong post-transplant follow-up rather than the patient's pre-transplant evaluation. A small number of recipients experience a relapse of alcoholism; these patients are at risk for organ damage and graft-related death. Post-transplant surveillance protocols should demonstrate alcohol relapse at an early stage, thus permitting the initiation of adequate treatment. Patients with alcoholic cirrhosis are at high risk of developing head and neck, esophageal, or lung cancer. The higher risk of malignancies should be considered in the routine assessment of patients suffering from alcoholic cirrhosis. Tumor surveillance protocols for liver transplant recipients, currently being developed, should become a part of standard care; these will improve survival by permitting diagnosis at an early stage. In conclusion, the key

  6. MicroRNAs and liver disease

    PubMed Central

    Kerr, Thomas A.; Korenblat, Kevin M.; Davidson, Nicholas O.

    2011-01-01

    Post-transcriptional regulation of gene expression is now recognized as an important contributor to disease pathogenesis, among whose mechanisms include alterations in the function of stability and translational elements within both coding and non-coding regions of messenger RNA. A major component in this regulatory paradigm is the binding both to RNA stability and also to translational control elements by microRNAs (miRNAs). miRNAs are non-coding endogenously transcribed RNAs that undergo a well characterized series of processing steps that generate short single stranded (~20–22) RNA fragments that bind to complementary regions within a range of targets and in turn lead to mRNA degradation or attenuated translation as a result of trafficking to processing bodies. This article will highlight selected advances in the role of miRNAs in liver disease including non-alcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma and will briefly discuss the utility of miRNAs as biomarkers of liver injury and neoplasia. PMID:21420035

  7. Nuclear receptors and nonalcoholic fatty liver disease.

    PubMed

    Cave, Matthew C; Clair, Heather B; Hardesty, Josiah E; Falkner, K Cameron; Feng, Wenke; Clark, Barbara J; Sidey, Jennifer; Shi, Hongxue; Aqel, Bashar A; McClain, Craig J; Prough, Russell A

    2016-09-01

    Nuclear receptors are transcription factors which sense changing environmental or hormonal signals and effect transcriptional changes to regulate core life functions including growth, development, and reproduction. To support this function, following ligand-activation by xenobiotics, members of subfamily 1 nuclear receptors (NR1s) may heterodimerize with the retinoid X receptor (RXR) to regulate transcription of genes involved in energy and xenobiotic metabolism and inflammation. Several of these receptors including the peroxisome proliferator-activated receptors (PPARs), the pregnane and xenobiotic receptor (PXR), the constitutive androstane receptor (CAR), the liver X receptor (LXR) and the farnesoid X receptor (FXR) are key regulators of the gut:liver:adipose axis and serve to coordinate metabolic responses across organ systems between the fed and fasting states. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and may progress to cirrhosis and even hepatocellular carcinoma. NAFLD is associated with inappropriate nuclear receptor function and perturbations along the gut:liver:adipose axis including obesity, increased intestinal permeability with systemic inflammation, abnormal hepatic lipid metabolism, and insulin resistance. Environmental chemicals may compound the problem by directly interacting with nuclear receptors leading to metabolic confusion and the inability to differentiate fed from fasting conditions. This review focuses on the impact of nuclear receptors in the pathogenesis and treatment of NAFLD. Clinical trials including PIVENS and FLINT demonstrate that nuclear receptor targeted therapies may lead to the paradoxical dissociation of steatosis, inflammation, fibrosis, insulin resistance, dyslipidemia and obesity. Novel strategies currently under development (including tissue-specific ligands and dual receptor agonists) may be required to separate the beneficial effects of nuclear receptor activation from unwanted metabolic

  8. Nursing care for end-stage liver disease.

    PubMed

    Clements, Amanda; Greenslade, Lynda

    Nurses are seeing more and more patients with liver disease, many of whom are under 65. Most common causes are avoidable and, as liver disease may take up to 30 years to develop, identifying those at risk is key. Patients with liver disease often have a fluctuating course of complications that needs a team approach to care. Improving end-of-life care can also reduce the number of these patients who die in hospital. This article, the first in a two-part series, explores some common complications of liver disease and best practice for nurses treating patients with end-stage liver disease.

  9. AISF position paper on liver disease and pregnancy.

    PubMed

    2016-02-01

    The relationship between liver disease and pregnancy is of great clinical impact. Severe liver disease in pregnancy is rare; however, pregnancy-related liver disease is the most frequent cause of liver dysfunction during pregnancy and represents a severe threat to foetal and maternal survival. A rapid differential diagnosis between liver disease related or unrelated to pregnancy is required in women who present with liver dysfunction during pregnancy. This report summarizes the recommendation of an expert panel established by the Italian Association for the Study of the Liver (AISF) on the management of liver disease during pregnancy. The article provides an overview of liver disease occurring in pregnancy, an update on the key mechanisms involved in its pathogenesis, and an assessment of the available treatment options. The report contains in three sections: (1) specific liver diseases of pregnancy; (2) liver disease occurring during pregnancy; and (3) pregnancy in patients with pre-existing chronic liver disease. Each topic is discussed considering the most relevant data available in literature; the final statements are formulated according to both scientific evidence and clinical expertise of the involved physicians, and the AISF expert panel recommendations are reported.

  10. [Veno-occlusive disease of the liver].

    PubMed

    Rybicka, Malwina; Krysiak, Robert; Okopień, Bogusław

    2009-01-01

    Veno-occlusive disease (VOD) is seen most often in the group of bone marrow transplant recipients. The essence of this disease is the obstruction of the hepatic sinusoidal and centrolobular venous outflow, because of the injury to the endothelium of the liver vessels. It results in congestion of the liver and hepatomegaly. The typical clinical symptoms of VOD are: jaundice, portal hypertension with peripheral oedemas and the weight gain. Depending on the extent of the injury of the hepatic vessels, VOD is divided into three grades: mild, moderate and severe. The clinical markers that inform about the severity of the disease are: the rate of the serum bilirubin growth and the rate of the weight gain growth within the first 2 weeks since the beginning of the disease. Severe VOD is the third of the most often cause of death among people who underwent bone marrow transplantation. The mortality rate is diverse and depends on severity of the disease. The effectiveness of the VOD therapy is limited, so it is worth putting greater pressure on the prophylaxis of VOD or on finding more effective modes of treatment.

  11. [Nonalcoholic fatty liver disease, association with cardiovascular disease and treatment (II). The treatment of nonalcoholic fatty liver disease].

    PubMed

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández-Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    2016-09-27

    Disease nonalcoholic fatty liver disease (NAFLD) comprises a series of histologically similar to those induced by alcohol consumption in people with very little or no liver damage same. The importance of NAFLD is its high prevalence in our Western societies, from the point of view liver in its progressive evolution from steatosis to steatohepatitis, cirrhosis and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with accelerated atherosclerosis and cardiovascular events, the leading cause of morbidity and mortality. This updated January 2016 revision consists of two parts. In this second part, the treatment of NAFLD and its influence on cardiovascular disease and drugs used in the control of cardiovascular risk factors showing a beneficial effect on the liver disease will be reviewed.

  12. The ascending pathophysiology of cholestatic liver disease.

    PubMed

    Jansen, Peter L M; Ghallab, Ahmed; Vartak, Nachiket; Reif, Raymond; Schaap, Frank G; Hampe, Jochen; Hengstler, Jan G

    2017-02-01

    In this review we develop the argument that cholestatic liver diseases, particularly primary biliary cholangitis and primary sclerosing cholangitis (PSC), evolve over time with anatomically an ascending course of the disease process. The first and early lesions are in "downstream" bile ducts. This eventually leads to cholestasis, and this causes bile salt (BS)-mediated toxic injury of the "upstream" liver parenchyma. BS are toxic in high concentration. These concentrations are present in the canalicular network, bile ducts, and gallbladder. Leakage of bile from this network and ducts could be an important driver of toxicity. The liver has a great capacity to adapt to cholestasis, and this may contribute to a variable symptom-poor interval that is often observed. Current trials with drugs that target BS toxicity are effective in only about 50%-60% of primary biliary cholangitis patients, with no effective therapy in PSC. This motivated us to develop and propose a new view on the pathophysiology of primary biliary cholangitis and PSC in the hope that these new drugs can be used more effectively. These views may lead to better stratification of these diseases and to recommendations on a more "tailored" use of the new therapeutic agents that are currently tested in clinical trials. Apical sodium-dependent BS transporter inhibitors that reduce intestinal BS absorption lower the BS load and are best used in cholestatic patients. The effectiveness of BS synthesis-suppressing drugs, such as farnesoid X receptor agonists, is greatest when optimal adaptation is not yet established. By the time cytochrome P450 7A1 expression is reduced these drugs may be less effective. Anti-inflammatory agents are probably most effective in early disease, while drugs that antagonize BS toxicity, such as ursodeoxycholic acid and nor-ursodeoxycholic acid, may be effective at all disease stages. Endoscopic stenting in PSC should be reserved for situations of intercurrent cholestasis and

  13. Tyrosine Metabolism in Patients with Liver Disease*

    PubMed Central

    Levine, Robert J.; Conn, Harold O.

    1967-01-01

    Plasma levels of tyrosine were assayed in the fasting state and after oral administration of either tyrosine (tyrosine tolerance test) or phenylalanine (phenlyalanine conversion test) in normal subjects and in patients with hepatitis, biliary obstruction, or cirrhosis. Fasting tyrosine levels tended to be slightly increased in patients with hepatitis and biliary obstruction and markedly increased in patients with cirrhosis. Tyrosine tolerance tests in patients with cirrhosis were characterized by larger than normal increments in tyrosine levels and by delayed returns toward fasting levels. The results of phenylalanine conversion tests were abnormal in approximately one-half of patients with either hepatitis or biliary obstruction and four-fifths of patients with cirrhosis. Abnormalities were characterized by elevated fasting plasma tyrosine levels, or small and delayed increments in tyrosine levels, or both. Abnormal phenylalanine conversion test results in patients with cirrhosis did not correlate closely with any clinical feature of cirrhosis or with the results of any standard liver function test; there was positive correlation only with abnormal ammonia tolerance, a test of portalsystemic shunting. Tests of tyrosine metabolism do not appear to be useful for routine clinical assessment of liver function. Tyrosine tolerance tests and phenylalanine conversion tests done for purposes of diagnosis of other diseases may yield misleading results in patients with liver disease. PMID:6074004

  14. Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases

    PubMed Central

    Gao, Bin; Radaeva, Svetlana; Park, Ogyi

    2009-01-01

    Hepatic lymphocytes are enriched in NK and NKT cells that play important roles in antiviral and antitumor defenses and in the pathogenesis of chronic liver disease. In this review, we discuss the differential distribution of NK and NKT cells in mouse, rat, and human livers, the ultrastructural similarities and differences between liver NK and NKT cells, and the regulation of liver NK and NKT cells in a variety of murine liver injury models. We also summarize recent findings about the role of NK and NKT cells in liver injury, fibrosis, and repair. In general, NK and NKT cells accelerate liver injury by producing proinflammatory cytokines and killing hepatocytes. NK cells inhibit liver fibrosis via killing early-activated and senescent-activated stellate cells and producing IFN-γ. In regulating liver fibrosis, NKT cells appear to be less important than NK cells as a result of hepatic NKT cell tolerance. NK cells inhibit liver regeneration by producing IFN-γ and killing hepatocytes; however, the role of NK cells on the proliferation of liver progenitor cells and the role of NKT cells in liver regeneration have been controversial. The emerging roles of NK/NKT cells in chronic human liver disease will also be discussed. Understanding the role of NK and NKT cells in the pathogenesis of chronic liver disease may help us design better therapies to treat patients with this disease. PMID:19542050

  15. Infectious diseases in end-stage liver disease patients.

    PubMed

    Mehta, Aneesh K; Lyon, G Marshall

    2010-09-01

    Patients with chronic liver diseases sustain impairment to immune systems, which worsens over time. These defects in their host defense lead to risks of bacterial infections and increased morbidity. Providers should have heightened surveillance for infectious diseases and suspect one with any acute change in status. Patient history may reveal rare infections and allow initiation of early appropriate therapy. There should be a low threshold for obtaining diagnostic cultures and peritoneal fluid samples and discussing possible causes with an infectious diseases consultant or a microbiology laboratory. These maneuvers will maximize therapy in patients at high risk for death due to infectious disease.

  16. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    PubMed

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD.

  17. [Metastatic disease of the liver: surgical perspective].

    PubMed

    Mercado, M A; Medina, H; Rossano, A; Acosta, E; Rodríguez, M; Chan, C; Orozco, H

    1997-01-01

    Approximately half of patients with colorectal cancer will develop hepatic metastases and it is estimated that up to 10% of that group will have resectable liver disease. Surgical resection remains the first line treatment option of metastatic liver tumors and has yielded a 20 to 40% five year survival rate. Selection of appropriate patients for resection is critical to a successful outcome. The best results are obtained in patients with isolated metastases. Factors that are associated with a poorer results are the presence of four or more lesions or a surgical margin less than 1 cm. Endocrine metastases can be resected in a palliative fashion but each case has to be individualized. This is also true for non colorectal-nonendocrine metastases. For this tumors the experience is anecdotal and confined to limited reported series. Adjuvant treatment (infusional chemotherapy and chemoembolization) can also have a role in treatment as well as cryotherapy.

  18. Herbal medicines and nonalcoholic fatty liver disease.

    PubMed

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-08-14

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future.

  19. Herbal medicines and nonalcoholic fatty liver disease

    PubMed Central

    Yao, Hong; Qiao, Yu-Jie; Zhao, Ya-Li; Tao, Xu-Feng; Xu, Li-Na; Yin, Lian-Hong; Qi, Yan; Peng, Jin-Yong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), which is characterized by excessive fat accumulation in the liver of patients who consume little or no alcohol, becomes increasingly common with rapid economic development. Long-term excess fat accumulation leads to NAFLD and represents a global health problem with no effective therapeutic approach. NAFLD is considered to be a series of complex, multifaceted pathological processes involving oxidative stress, inflammation, apoptosis, and metabolism. Over the past decades, herbal medicines have garnered growing attention as potential therapeutic agents to prevent and treat NAFLD, due to their high efficacy and low risk of side effects. In this review, we evaluate the use of herbal medicines (including traditional Chinese herbal formulas, crude extracts from medicinal plants, and pure natural products) to treat NAFLD. These herbal medicines are natural resources that can inform innovative drug research and the development of treatments for NAFLD in the future. PMID:27570425

  20. Therapeutic RNA Manipulation in Liver Disease

    PubMed Central

    Kerr, Thomas A.; Davidson, Nicholas O.

    2010-01-01

    Summary Posttranscriptional regulation of gene expression is increasingly recognized as a model for inherited and acquired disease. Recent work has expanded understanding of the range of mechanisms that regulate several of these distinct steps including mRNA splicing, trafficking, and/or stability. Each of these pathways is implicated in disease pathogenesis and each represent important avenues for therapeutic intervention. This review will summarize important mechanisms controlling mRNA processing and the regulation of mRNA degradation, including the role of miRNAs and RNA binding proteins. These pathways provide important opportunities for therapeutic targeting directed at splicing and degradation in order to attenuate genetic defects in RNA metabolism. We will highlight developments in vector development and validation for therapeutic manipulation of mRNA expression with a focus on potential applications in metabolic and immune-mediated liver disease. PMID:19918970

  1. Sirtuins and nonalcoholic fatty liver disease

    PubMed Central

    Nassir, Fatiha; Ibdah, Jamal A

    2016-01-01

    Mammalian sirtuins are seven members belonging to the silent information regulator 2 family, a group of Class III histone/protein deacetylases. Sirtuins (SIRT 1-7) have different subcellular localization and function and they regulate cellular protein function through various posttranslational modifications. SIRT1 and 3, the most studied sirtuins, use the product of cellular metabolism nicotinamide adenine dinucleotide as a cofactor to post-translationally deacetylate cellular proteins and consequently link the metabolic status of the cell to protein function. Sirtuins have been shown to play a key role in the development and rescue of various metabolic diseases including non-alcoholic fatty liver disease (NAFLD). NAFLD is currently the most chronic liver disease due mainly to high-calorie consumption and lower physical activity. No pharmacological approach is available to treat NAFLD, the current recommended treatment are lifestyle modification such as weight loss through calorie restriction and exercise. Recent studies have shown downregulation of sirtuins in human as well as animal models of NAFLD indicating an important role of sirtuins in the dynamic pathophysiology of NAFLD. In this review, we highlight the recent knowledge on sirtuins, their role in NAFLD and their unique potential role as novel therapeutic target for NAFLD treatment. PMID:28028356

  2. Reluctance to Accept Alcohol Treatment by Alcoholic Liver Disease Transplant Patients: A Qualitative Study

    PubMed Central

    Heyes, Cathy M.; Schofield, Toni; Gribble, Robert; Day, Carolyn A.; Haber, Paul S.

    2016-01-01

    Background Liver transplantation (LT) is the optimum treatment for patients with end-stage alcoholic liver disease (ALD). However, despite a recognized risk of relapse to harmful drinking, ALD transplant patients are reluctant to use speciality alcohol treatment to support their abstinence, even when offered within the LT context. This study aimed to understand and identify factors contributing to alcohol treatment reluctance by ALD patients undergoing transplantation. Methods We conducted an in-depth qualitative study of ALD transplant patients. Minimally structured face-to-face interviews explored participants' alcohol-related experiences and their reasons for not using alcohol treatment during the course of their transplantation. Thematic analysis was used to analyze and interpret interview data to understand treatment reluctance based on participants' experiences. Results Five major themes were identified among 3 subgroups of patients (pretransplant and posttransplant abstainers and posttransplant relapsers): (i) the “contract” of mandatory abstinence, (ii) the “gap in the program” involving the lack of candour between patient and staff about alcohol-related matters and the lack of addiction services, (iii) a preference by participants to self-manage their alcohol use disorder, (iv) social support as a facilitator of abstinence and the risk of relapse when social support is diminished, and (v) the fear of stigmatization. Each of these factors were dynamically interrelated and differed slightly for each subgroup. Conclusions The LT services may benefit from the inclusion of integrated specialist addiction services in their model of care. Such an approach may enhance the acceptability of alcohol treatment and reduce the risk of relapse among ALD transplant participants, especially for those whose social supports have diminished. PMID:27795986

  3. Management of alcohol misuse in patients with liver diseases.

    PubMed

    Peng, Jennifer L; Patel, Milan Prakash; McGee, Breann; Liang, Tiebing; Chandler, Kristina; Tayarachakul, Sucharat; O'Connor, Sean; Liangpunsakul, Suthat

    2017-03-01

    Excessive alcohol use not only causes alcoholic liver disease (ALD) but also increases the risk of liver-related mortality in patients who already have other chronic liver diseases. Screening for alcohol misuse or alcohol use disorder (AUD) among patients with underlying liver disease is essential. This clinical review covers what is known about ALD, the impact of alcohol in patients with underlying liver diseases, current management of alcohol misuse and AUD, and the management of alcohol misuse and AUD specifically in patients with liver diseases. Several treatment options for alcohol misuse and AUD exist such as psychosocial intervention and behavioral and pharmacological therapies. The strategies used in the treatment of alcohol misuse and AUD are still applicable in those who consume alcohol and have underlying liver disease. However, certain medications still need to be carefully used due to potentially worsening already compromised liver function. Screening of ongoing alcohol use in subjects with liver disease is important, and prompt intervention is needed to prevent the associated morbidity and mortality from the detrimental effects of continued alcohol use on underlying liver disease. Considering alcoholism is a complex disease, probably a multidisciplinary approach combining psychotherapy and comprehensive medical care will be the most effective. Future research could focus on identifying additional treatment options for addressing the psychotherapy component since the self-determination and will to quit drinking alcohol can play such a crucial role in promoting abstinence.

  4. The Role of Akt in Chronic Liver Disease and Liver Regeneration.

    PubMed

    Morales-Ruiz, Manuel; Santel, Ansgar; Ribera, Jordi; Jiménez, Wladimiro

    2017-02-01

    The liver is continuously exposed to diverse insults, which may culminate in pathological processes causing liver disease. An effective therapeutic strategy for chronic liver disease should control the causal factors of the disease and stimulate functional liver regeneration. Preclinical studies have shown that interventions aimed at maintaining Akt activity in a dysfunctional liver meet most of the criteria. Although the central function of Akt is cell survival, other cellular aspects such as glucose uptake, glycogen synthesis, cell-cycle progression, and lipid metabolism have been shown to be prominent functions of Akt in the context of hepatic physiology. In this review, the authors describe the benefits of the Akt signaling pathway, emphasizing its importance in coordinating proper cellular growth and differentiation during liver regeneration, hepatic function, and liver disease.

  5. Hemorheological Alteration in Patients Clinically Diagnosed with Chronic Liver Diseases

    PubMed Central

    2016-01-01

    Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient’s history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P < 0.001) in male patients, but not in female patients. In correlation analysis, there were inverse relationships between both systolic and diastolic whole blood viscosity and liver stiffness (systolic: r = −0.25, diastolic: r = −0.22). Whole blood viscosity was significantly lower in male patients with LC than NAFLD or chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases. PMID:27822933

  6. Hemorheological Alteration in Patients Clinically Diagnosed with Chronic Liver Diseases.

    PubMed

    Jang, Bohyun; Han, Ji Won; Sung, Pil Soo; Jang, Jeong Won; Bae, Si Hyun; Choi, Jong Young; Cho, Young I; Yoon, Seung Kew

    2016-12-01

    Since liver function is changed by chronic liver diseases, chronic liver disease can lead to different hemorheological alterations during the course of the progression. This study aims to compare alterations in whole blood viscosity in patients with chronic liver disease, focusing on the gender effect. Chronic liver diseases were classified into three categories by patient's history, serologic markers, and radiologic findings: nonalcoholic fatty liver disease (NAFLD) (n = 63), chronic viral hepatitis B and C (n = 50), and liver cirrhosis (LC) (n = 35). Whole blood viscosity was measured by automated scanning capillary tube viscometer, while liver stiffness was measured by transient elastography using FibroScan®. Both systolic and diastolic whole blood viscosities were significantly lower in patients with LC than NAFLD and chronic viral hepatitis (P < 0.001) in male patients, but not in female patients. In correlation analysis, there were inverse relationships between both systolic and diastolic whole blood viscosity and liver stiffness (systolic: r = -0.25, diastolic: r = -0.22). Whole blood viscosity was significantly lower in male patients with LC than NAFLD or chronic viral hepatitis. Our data suggest that whole blood viscosity test can become a useful tool for classifying chronic liver disease and determining the prognosis for different types of chronic liver diseases.

  7. Fractionation of gamma-glutamyltransferase in patients with nonalcoholic fatty liver disease and alcoholic liver disease

    PubMed Central

    Sueyoshi, Shigeo; Sawai, Setsu; Satoh, Mamoru; Seimiya, Masanori; Sogawa, Kazuyuki; Fukumura, Atsushi; Tsutsumi, Mikihiro; Nomura, Fumio

    2016-01-01

    AIM To assess how serum gamma-glutamyltransferase (GGT) fractions vary in patients with alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD). METHODS Serum samples were obtained from 14 patients with biopsy-proven alcoholic liver diseases and 9 patients with biopsy proven non-alcoholic fatty liver disease. In addition to these biopsy-proven cases, 16 obese (body mass index > 25) patients without any history of alcohol consumption but with a fatty liver on ultrasound examination and with elevated GGT were included for an additional analysis. Serum GGT fractionation was conducted by high-performance gel filtration liquid chromatography and was separated into the four fractions, big-GGT, medium-GGT, small-GGT (s-GGT), and free-GGT (f-GGT). RESULTS The results were expressed as a ratio of each fraction including the total GGT (t-GGT). The s-GGT/t-GGT ratios were lowest for the control group and highest for the ALD group. The differences between the control and NAFLD groups and also between the NAFLD and ALD groups were statistically significant. In contrast, the f-GGT/t-GGT ratios were highest in the control group and lowest in the ALD group, with the differences being statistically significant. As a result, the s-GGT/f-GGT ratios were markedly increased in the NAFLD group as compared with the control group. The increase of the s-GGT/t-GGT ratios, the decrease of the f-GGT/t-GGT ratios, and the increase of s-GGT/F-GGT ratios as compared with the control group subjects were also found in obese patients with clinically diagnosed fatty change of the liver. CONCLUSION Serum GGT fractionation by high-performance gel filtration liquid chromatography is potentially useful for the differential diagnosis of ALD and NAFLD. PMID:28083083

  8. Hepatocellular Carcinoma in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Ur Rahman, Zia; Hurairah, Abu

    2016-01-01

    Our objective was to study nonalcoholic fatty liver disease (NAFLD) as a relevant risk factor associated with hepatocellular carcinoma (HCC) in patients with and without cirrhosis. HCC is a common cancer worldwide that predominantly involves patients with hepatic cirrhosis. HCC has recently been linked to NAFLD, the hepatic manifestation of obesity and related metabolic disorders. This association is alarming due to the high prevalence of NAFLD globally, which may contribute to the rising incidence of HCC. A 31-year-old female with a history of dyslipidemia, hypertension, and diabetes mellitus presented with abdominal pain that persisted for six months. The pain was associated with gastrointestinal symptoms and weight loss. She was drug-free and a nonalcoholic and a nonsmoker. The physical examination was unremarkable. The abdominal exam showed a soft and non-tender abdomen, with no organomegaly or ascites. The laboratory evaluation was unremarkable. The imaging studies showed a hypodense lesion in the right hepatic lobe with strong arterial enhancement. Subsequently, the patient underwent a liver biopsy. The histopathology results were consistent with HCC. The patient underwent an uneventful segment VI liver resection and tumor-free margins were achieved. In our patient, NAFLD was designated as an independent etiology for HCC, without cirrhosis. Our patient recovered well and has been disease free for over a year. HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk of HCC. These results provide new targets for surveillance, prevention, early recognition, and effective treatment of HCC associated with NAFLD. PMID:27733959

  9. Thyroid dysfunction and nonalcoholic fatty liver disease.

    PubMed

    Efstathiadou, Zoe A; Kita, Marina D; Polyzos, Stergios A

    2017-02-09

    Thyroid hormones are crucial for hepatic lipid and glucose metabolism. Nonalcoholic fatty liver disease (NAFLD), a very common and potentially serious disease of modern society, shares common clinical features with hypothyroidism, such as obesity, insulin resistance and dyslipidemia. Furthermore, in certain studies, increased prevalence of hypothyroidism was observed in patients with NAFLD. However, whether there is a linear relationship between thyroid hormone levels and NAFLD incidence and severity, including values within or in proximity to the reference range remains a contradictory subject in the literature. On the other hand, attempts to treat NAFLD with thyromimetic drugs remain at an early stage. In this review, data derived from observational studies along with evidence on possible treatment with thyroid hormone analogues are presented.

  10. Ideal Experimental Rat Models for Liver Diseases.

    PubMed

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok; Kim, Kyung Sik

    2011-05-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes.

  11. Ideal Experimental Rat Models for Liver Diseases

    PubMed Central

    Lee, Sang Woo; Kim, Sung Hoon; Min, Seon Ok

    2011-01-01

    There are many limitations for conducting liver disease research in human beings due to the high cost and potential ethical issues. For this reason, conducting a study that is difficult to perform in humans using appropriate animal models, can be beneficial in ascertaining the pathological physiology, and in developing new treatment modalities. However, it is difficult to determine the appropriate animal model which is suitable for research purposes, since every patient has different and diverse clinical symptoms, adverse reactions, and complications due to the pathological physiology. Also, it is not easy to reproduce identically various clinical situations in animal models. Recently, the Guide for the Care and Use of Laboratory Animals has tightened up the regulations, and therefore it is advisable to select the appropriate animals and decide upon the appropriate quantities through scientific and systemic considerations before conducting animal testing. Therefore, in this review article the authors examined various white rat animal testing models and determined the appropriate usable rat model, and the pros and cons of its application in liver disease research. The authors believe that this review will be beneficial in selecting proper laboratory animals for research purposes. PMID:26421020

  12. [Immunity and malnutrition in alcoholic liver diseases].

    PubMed

    Hevia Ojanguren, C; Fanjul Cabeza, B; González Vázquez, M I; Linares Rodríguez, A; Rodrigo Sáez, L

    1994-10-01

    Assessment of immunity was performed in 150 patients with alcoholic liver disease (15 steatosis, 30 hepatitis and 105 cirrhosis: 34 in grade A, 34 in grade B and 37 in grade C, according to Child-Pugh classification). This assessment was based on the total lymphocyte count and a delayed hypersensitivity skin multiple test. Likewise, nutritional status of patients was studied using anthropometric and biochemical parameters (triceps skinfold thickness, arm muscle circumference and serum albumin). The association between alcoholic liver disease, malnutrition and immunity was analyzed. The results show that lymphopenia and disorders in cell-mediate immunity were more common in those patients with cirrhosis, increasing the number of anergic patients while the degree of hepatocellular insufficiency worsens (8.8% in grade A, 11.8% in grade B and 32.4% in grade C). Although there where significantly more alterations of delayed cutaneous hypersensitivity in cirrhotics with malnutrition (hypoergy: 55.2% and anergy: 37.9%) than in those well nourished (hypoergy: 23.7% and anergy: 10.5%, p < 0.01), lymphopenia didn't show differences between these groups. We think that immunity mus'nt be considered a parameter in nutritional assessment.

  13. Hepatitis C: What Happens in End-Stage Liver Disease?

    MedlinePlus

    ... diseases or liver diseases (hepatologist). Newer, more-effective hepatitis C treatments can eliminate the virus in many people, reducing the risk of end-stage liver disease. With Michael F. Picco, ... and natural history of hepatitis C virus infection. http://www.uptodate.com/home. ...

  14. Psychotropic drugs and liver disease: A critical review of pharmacokinetics and liver toxicity

    PubMed Central

    Telles-Correia, Diogo; Barbosa, António; Cortez-Pinto, Helena; Campos, Carlos; Rocha, Nuno B F; Machado, Sérgio

    2017-01-01

    The liver is the organ by which the majority of substances are metabolized, including psychotropic drugs. There are several pharmacokinetic changes in end-stage liver disease that can interfere with the metabolization of psychotropic drugs. This fact is particularly true in drugs with extensive first-pass metabolism, highly protein bound drugs and drugs depending on phase I hepatic metabolic reactions. Psychopharmacological agents are also associated with a risk of hepatotoxicity. The evidence is insufficient for definite conclusions regarding the prevalence and severity of psychiatric drug-induced liver injury. High-risk psychotropics are not advised when there is pre-existing liver disease, and after starting a psychotropic agent in a patient with hepatic impairment, frequent liver function/lesion monitoring is advised. The authors carefully review the pharmacokinetic disturbances induced by end-stage liver disease and the potential of psychopharmacological agents for liver toxicity. PMID:28217372

  15. The Role of Oxidative Stress and Antioxidants in Liver Diseases.

    PubMed

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-11-02

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed.

  16. The Role of Oxidative Stress and Antioxidants in Liver Diseases

    PubMed Central

    Li, Sha; Tan, Hor-Yue; Wang, Ning; Zhang, Zhang-Jin; Lao, Lixing; Wong, Chi-Woon; Feng, Yibin

    2015-01-01

    A complex antioxidant system has been developed in mammals to relieve oxidative stress. However, excessive reactive species derived from oxygen and nitrogen may still lead to oxidative damage to tissue and organs. Oxidative stress has been considered as a conjoint pathological mechanism, and it contributes to initiation and progression of liver injury. A lot of risk factors, including alcohol, drugs, environmental pollutants and irradiation, may induce oxidative stress in liver, which in turn results in severe liver diseases, such as alcoholic liver disease and non-alcoholic steatohepatitis. Application of antioxidants signifies a rational curative strategy to prevent and cure liver diseases involving oxidative stress. Although conclusions drawn from clinical studies remain uncertain, animal studies have revealed the promising in vivo therapeutic effect of antioxidants on liver diseases. Natural antioxidants contained in edible or medicinal plants often possess strong antioxidant and free radical scavenging abilities as well as anti-inflammatory action, which are also supposed to be the basis of other bioactivities and health benefits. In this review, PubMed was extensively searched for literature research. The keywords for searching oxidative stress were free radicals, reactive oxygen, nitrogen species, anti-oxidative therapy, Chinese medicines, natural products, antioxidants and liver diseases. The literature, including ours, with studies on oxidative stress and anti-oxidative therapy in liver diseases were the focus. Various factors that cause oxidative stress in liver and effects of antioxidants in the prevention and treatment of liver diseases were summarized, questioned, and discussed. PMID:26540040

  17. Non-alcoholic fatty liver disease in children.

    PubMed

    Chaturvedi, Kanupriya; Vohra, Pankaj

    2012-09-01

    A cross sectional study was conducted in 100 children, aged 5 to 12 years, to find the prevalence of non-alcoholic fatty liver diseases (NAFLD), at New Delhi. Those with fatty liver on ultrasonography with no apparent etiology, were labeled as NAFLD. Three (3%) children had evidence of fatty liver on ultrasonography.

  18. Liver abnormalities in drug and substance abusers.

    PubMed

    Pateria, Puraskar; de Boer, Bastiaan; MacQuillan, Gerry

    2013-08-01

    Drug and substance abuse remains a major medical problem. Alcohol use, abuse and dependence are highly prevalent conditions. Alcohol related liver disease can present as simple steatosis, steatohepatitis, alcoholic hepatitis or liver cirrhosis. Paracetamol hepatotoxicity secondary to accidental or deliberate overdose is another common problem. While the adverse cardiovascular, neurological, renal and psychiatric consequences of various illicit substance abuses are widely studied and publicized, less attention has been directed towards possible hepatotoxic effects. Illicit drug abuse can cause a range of liver abnormalities ranging from asymptomatic derangement of liver function tests to fulminant hepatic failure. This article reviews the epidemiology, risk factors, clinical manifestations, pathogenesis, investigations, management and prognostic factors of alcohol related liver disease and paracetamol hepatotoxicity as well as the current knowledge pertaining to hepatotoxicity of the more commonly used illicit substances including cannabis, amphetamine type stimulants, cocaine, khat chewing and complementary and alternate medicine.

  19. Drug-Induced Liver Disease: Clinical Course.

    PubMed

    Saithanyamurthi, Hemamala; Faust, Alison Jazwinski

    2017-02-01

    Drug-induced liver injury (DILI) is a term used to describe a spectrum of clinical presentations and severity that ranges from mild elevation of liver enzymes on routine blood work to acute liver failure and death. Approximately 10% of all patients with DILI develop acute liver failure resulting in death or liver transplantation. DILI may be prolonged with persistence of elevated liver enzymes for longer than 6 months in approximately 5% to 20% of cases. Cirrhosis and long-term liver-related morbidity and mortality have also been described but are rare, occurring in 1% to 3% of cases.

  20. Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases

    PubMed Central

    Yarygin, Konstantin N.

    2017-01-01

    The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable. PMID:28210629

  1. Cellular Mechanisms of Liver Regeneration and Cell-Based Therapies of Liver Diseases.

    PubMed

    Kholodenko, Irina V; Yarygin, Konstantin N

    2017-01-01

    The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role. Participation of blood-borne cells of the bone marrow origin in liver parenchyma regeneration has been proven but does not exceed 1-2% of newly formed hepatocytes. Liver regeneration is activated spontaneously after injury and can be further stimulated by cell therapy with hepatocytes, hematopoietic stem cells, or mesenchymal stem cells. Further studies aimed at improving the outcomes of cell therapy of liver diseases are underway. In case of liver failure, transplantation of engineered liver can become the best option in the foreseeable future. Engineering of a transplantable liver or its major part is an enormous challenge, but rapid progress in induced pluripotency, tissue engineering, and bioprinting research shows that it may be doable.

  2. Growth Differentiation Factor 15 Predicts Chronic Liver Disease Severity

    PubMed Central

    Lee, Eaum Seok; Kim, Seok Hyun; Kim, Hyun Jin; Kim, Kyung Hee; Lee, Byung Seok; Ku, Bon Jeong

    2017-01-01

    Background/Aims Growth differentiation factor 15 (GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is emerging as a biomarker for several diseases. The aim of this study was to determine the clinical performances of GDF-15 for the prediction of liver fibrosis and severity in chronic liver disease. Methods The serum GDF-15 levels were examined via enzyme immunoassay in 145 patients with chronic liver disease and 101 healthy individuals. The patients with chronic liver disease consisted of 54 patients with chronic hepatitis, 44 patients with compensated liver cirrhosis, and 47 patients with decompensated liver cirrhosis. Results Of the patients with chronic liver diseases, the decompensated liver cirrhosis patients had an increased serum GDF-15 (3,483 ng/L) level compared with the patients with compensated liver cirrhosis (1,861 ng/L) and chronic hepatitis (1,232 ng/L). The overall diagnostic accuracies of GDF-15, as determined by the area under the receiver operating characteristic curves, were as follows: chronic hepatitis=0.656 (>574 ng/L, sensitivity, 53.7%; specificity, 79.2%), compensated liver cirrhosis=0.886 (>760 ng/L, sensitivity, 75.6%; specificity, 92.1%), and decompensated liver cirrhosis=0.984 (>869 ng/L, sensitivity, 97.9%; specificity, 94.1%). Conclusions This investigation represents the first study to demonstrate the availability of GDF-15 in chronic liver disease. GDF-15 comprised a useful biomarker for the prediction of liver fibrosis and severity in chronic liver disease. PMID:27728964

  3. Zebrafish Models of Human Liver Development and Disease

    PubMed Central

    Wilkins, Benjamin J.; Pack, Michael

    2016-01-01

    The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease. PMID:23897685

  4. Is There a Role for Probiotics in Liver Disease?

    PubMed Central

    Lo, Robert S.; Austin, Andrew S.; Freeman, Jan G.

    2014-01-01

    Intestinal microbiota plays an important role in health and disease. Alteration in its healthy homeostasis may result in the development of numerous liver disorders including complications of liver cirrhosis. On the other hand, restoration and modulation of intestinal flora through the use of probiotics is potentially an emerging therapeutic strategy. There is mounting evidence that probiotics are effective in the treatment of covert and overt hepatic encephalopathy, as well as in the prevention of recurrence of encephalopathy. The beneficial effect of probiotics also extends to liver function in cirrhosis, nonalcoholic fatty liver disease, and alcoholic liver disease. On the other hand, data associating probiotics and portal hypertension is scanty and conflicting. Probiotic therapy has also not been shown to prevent primary or secondary spontaneous bacterial peritonitis. Larger clinical studies are required before probiotics can be recommended as a treatment modality in liver diseases. PMID:25436233

  5. Monogenic diseases that can be cured by liver transplantation.

    PubMed

    Fagiuoli, Stefano; Daina, Erica; D'Antiga, Lorenzo; Colledan, Michele; Remuzzi, Giuseppe

    2013-09-01

    While the prevalence of most diseases caused by single-gene mutations is low and defines them as rare conditions, all together, monogenic diseases account for approximately 10 in every 1000 births according to the World Health Organisation. Orthotopic liver transplantation (LT) could offer a therapeutic option in monogenic diseases in two ways: by substituting for an injured liver or by supplying a tissue that can replace a mutant protein. In this respect, LT may be regarded as the correction of a disease at the level of the dysfunctional protein. Monogenic diseases that involve the liver represent a heterogeneous group of disorders. In conditions associated with predominant liver parenchymal damage (i.e., genetic cholestatic disorders, Wilson's disease, hereditary hemochromatosis, tyrosinemia, α1 antitrypsin deficiency), hepatic complications are the major source of morbidity and LT not only replaces a dysfunctional liver but also corrects the genetic defect and effectively cures the disease. A second group includes liver-based genetic disorders characterised by an architecturally near-normal liver (urea cycle disorders, Crigler-Najjar syndrome, familial amyloid polyneuropathy, primary hyperoxaluria type 1, atypical haemolytic uremic syndrome-1). In these defects, extrahepatic complications are the main source of morbidity and mortality while liver function is relatively preserved. Combined transplantation of other organs may be required, and other surgical techniques, such as domino and auxiliary liver transplantation, have been attempted. In a third group of monogenic diseases, the underlying genetic defect is expressed at a systemic level and liver involvement is just one of the clinical manifestations. In these conditions, LT might only be partially curative since the abnormal phenotype is maintained by extrahepatic synthesis of the toxic metabolites (i.e., methylmalonic acidemia, propionic acidemia). This review focuses on principles of diagnosis, management

  6. How to Face Chronic Liver Disease: The Sinusoidal Perspective

    PubMed Central

    Fernández-Iglesias, Anabel; Gracia-Sancho, Jordi

    2017-01-01

    Liver microcirculation plays an essential role in the progression and aggravation of chronic liver disease. Hepatic sinusoid environment, mainly composed by hepatocytes, liver sinusoidal endothelial cells, Kupffer cells, and hepatic stellate cells, intimately cooperate to maintain global liver function and specific phenotype of each cell type. However, continuous liver injury significantly deregulates liver cells protective phenotype, leading to parenchymal and non-parenchymal dysfunction. Recent data have enlightened the molecular processes that mediate hepatic microcirculatory injury, and consequently, opened the possibility to develop new therapeutic strategies to ameliorate liver circulation and viability. The present review summarizes the main cellular components of the hepatic sinusoid, to afterward focus on non-parenchymal cells phenotype deregulation due to chronic injury, in the specific clinical context of liver cirrhosis and derived portal hypertension. Finally, we herein detail new therapies developed at the bench-side with high potential to be translated to the bedside. PMID:28239607

  7. Gut microbiota and probiotics in chronic liver diseases.

    PubMed

    Cesaro, Claudia; Tiso, Angelo; Del Prete, Anna; Cariello, Rita; Tuccillo, Concetta; Cotticelli, Gaetano; Del Vecchio Blanco, Camillo; Loguercio, Carmelina

    2011-06-01

    There is a strong relationship between liver and gut: the portal system receives blood from the gut, and intestinal blood content activates liver functions. The liver, in turn, affects intestinal functions through bile secretion into the intestinal lumen. Alterations of intestinal microbiota seem to play an important role in induction and promotion of liver damage progression, in addition to direct injury resulting from different causal agents. Bacterial overgrowth, immune dysfunction, alteration of the luminal factors, and altered intestinal permeability are all involved in the pathogenesis of complications of liver cirrhosis, such as infections, hepatic encephalopathy, spontaneous bacterial peritonitis, and renal failure. Probiotics have been suggested as a useful integrative treatment of different types of chronic liver damage, for their ability to augment intestinal barrier function and prevent bacterial translocation. This review summarizes the main literature findings about the relationships between gut microbiota and chronic liver disease, both in the pathogenesis and in the treatment by probiotics of the liver damage.

  8. An Update on Laboratory Diagnosis of Liver Inherited Diseases

    PubMed Central

    Elce, Ausilia; Amato, Felice

    2013-01-01

    Liver inherited diseases are a group of genetically determined clinical entities that appear with an early chronic liver involvement. They include Wilson's disease (hepatolenticular degeneration), hereditary hemochromatosis, and alpha-1-antitrypsin deficiency. In addition, cystic fibrosis, although it is not specifically a liver disease, may cause a severe liver involvement in a significant percentage of cases. For all these pathologies, the disease gene is known, and molecular analysis may contribute to the unequivocal diagnosis. This approach could avoid the patient invasive procedures and limit complications associated with a delay in diagnosis. We review liver inherited diseases on the basis of the genetic defect, focusing on the contribution of molecular analysis in the multistep diagnostic workup. PMID:24222913

  9. Hemostatic issues in pregnancy-induced liver disease.

    PubMed

    Lisman, Ton; Bernal, William

    2017-03-01

    Liver diseases may be accompanied by profound changes in the hemostatic system including thrombocytopenia, decreased plasma levels of pro- and anticoagulants, and alterations in plasma levels of fibrinolysis. The net effect of the hemostatic changes in chronic and acute liver diseases is a hemostatic system that is in relative balance due to the simultaneous decline in pro- and antihemostatic drivers. A unique category of liver diseases are those induced by pregnancy. In acute fatty liver of pregnancy, profound hemostatic changes occur, which may be caused by a combination of liver failure and disseminated intravascular coagulation. Hemostatic changes in preeclampsia and HELLP syndrome are dominated by thrombocytopenia, although alterations in plasmatic coagulation may also occur. Post-partum bleeds, bleeding from cesarean section wounds, and hepatobiliary bleeds may occur in both patient groups. Patients with intrahepatic cholestasis of pregnancy do not show clinically relevant hemostatic alterations, despite biochemical evidence of liver injury.

  10. Assessment of fibrotic liver disease with multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Lu, Fake; Zheng, Wei; Tai, Dean C. S.; Lin, Jian; Yu, Hanry; Huang, Zhiwei

    2010-02-01

    Liver fibrosis is the excessive accumulation of extracellular matrix proteins such as collagens, which may result in cirrhosis, liver failure, and portal hypertension. In this study, we apply a multimodal nonlinear optical microscopy platform developed to investigate the fibrotic liver diseases in rat models established by performing bile duct ligation (BDL) surgery. The three nonlinear microscopy imaging modalities are implemented on the same sectioned tissues of diseased model sequentially: i.e., second harmonic generation (SHG) imaging quantifies the contents of the collagens, the two-photon excitation fluorescence (TPEF) imaging reveals the morphology of hepatic cells, while coherent anti-Stokes Raman scattering (CARS) imaging maps the distributions of fats or lipids quantitatively across the tissue. Our imaging results show that during the development of liver fibrosis (collagens) in BDL model, fatty liver disease also occurs. The aggregated concentrations of collagen and fat constituents in liver fibrosis model show a certain correlationship between each other.

  11. Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome.

    PubMed

    Lonardo, Amedeo; Ballestri, Stefano; Marchesini, Giulio; Angulo, Paul; Loria, Paola

    2015-03-01

    The conventional paradigm of nonalcoholic fatty liver disease representing the "hepatic manifestation of the metabolic syndrome" is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty liver disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty liver disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty liver disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty liver disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty liver disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty liver disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.

  12. Itch in Liver Disease: Facts and Speculations

    PubMed Central

    Ghent, Cameron N.; Bloomer, Joseph R.

    1979-01-01

    Pruritus in hepatobiliary disease is commonly believed to be caused by retention of bile acids with their sequestration in the skin. HOwever, we have recently demonstrated that skin levels of bile acids in patients with cholestasis correlate poorly with pruritus. In this report, we present additional data concerning the relationship of pruritus to bile acid retention: (1) the urinary excretion of sulfated and nonsulfated bile acids was not significantly different in patients with cholestasis who itched compared to those who did not; (2) one patient with itch associated with a liver abscess had normal levels of bile acids in serum, skin, and urine; (3) patients with primary biliary cirrhosis who itched had lower serum bile acid levels than patients with mechanical biliary obstruction who did not itch. These studies support our premise that pruritus in hepatobiliary diseases is not directly related to bile acid retention. They suggest that the type of cholestatic disorder, and not simply the magnitude of the cholestasis, as estimated by the elevation of serum bile acids, is important. We propose that the agent responsible for pruritus is produced in response to cholestasis, possibly through activation of the alternate pathway of bile acid synthesis. Properties of the hypothetical pruritogen are discussed. PMID:452625

  13. Autoimmune liver disease in Noonan Syndrome.

    PubMed

    Loddo, Italia; Romano, Claudio; Cutrupi, Maria Concetta; Sciveres, Marco; Riva, Silvia; Salpietro, Annamaria; Ferraù, Valeria; Gallizzi, Romina; Briuglia, Silvana

    2015-03-01

    Noonan Syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. The incidence of NS is estimated to be between 1:1000 and 1:2500 live births. The syndrome is transmitted as an autosomal dominant trait. In approximately 50% of cases, the disease is caused by missense mutations in the PTPN11 gene on chromosome 12, resulting in a gain of function of the non-receptor protein tyrosine phosphatase SHP-2 protein. Autoimmune Hepatitis (AIH) is a cryptogenic, chronic and progressive necroinflammatory liver disease. Common features of AIH are hypergammaglobulinemia (IgG), presence of circulating autoantibodies, histological picture of interface hepatitis and response to immunosuppressant drugs. Conventional treatment with Prednisone and Azathioprine is effective in most patients. We describe the case of a 6 years-old girl with Noonan Syndrome and Autoimmune Hepatitis type 1. Molecular analysis of PTPN11 gene showed heterozygous mutation c.923A>G (Asn308Ser) in exon 8. Though association between NS and autoimmune disorders is known, this is the second case of association between Noonan Syndrome and Autoimmune Hepatitis type 1 described in literature. In the management of NS, an accurate clinical evaluation would be recommended. When there is a clinical suspicion of autoimmune phenomena, appropriate laboratory tests should be performed with the aim of clarifying whether the immune system is involved in NS. We think that autoimmunity represents a characteristic of NS, even if the etiopathogenesis is still unknown.

  14. Low vitamin D status is associated with advanced liver fibrosis in patients with nonalcoholic fatty liver disease.

    PubMed

    Yang, Bing-Bing; Chen, Yuan-Hua; Zhang, Cheng; Shi, Chang-E; Hu, Kai-Feng; Zhou, Ju; Xu, De-Xiang; Chen, Xi

    2017-02-01

    Several studies explored the association between vitamin D status and nonalcoholic fatty liver disease with contradictory results. We aimed to investigate the association between vitamin D status, inflammatory cytokines and liver fibrosis in nonalcoholic fatty liver disease patients. Two hundred nineteen nonalcoholic fatty liver disease patients and 166 age- and gender- matched healthy controls were recruited for this study. Serum 25(OH)D was measured by radioimmunoassay. Serum interleukin-8 and transforming growth factor-β1 were measured using ELISA. Serum 25(OH)D was only marginally decreased in nonalcoholic fatty liver disease patients. Interestingly, serum 25(OH)D was markedly reduced in nonalcoholic fatty liver disease patients with advanced liver fibrosis compared to nonalcoholic fatty liver disease patients with indeterminate liver fibrosis and no advanced fibrosis. Logistic regression analysis showed that there was an inverse association between serum 25(OH)D and severity of liver fibrosis in nonalcoholic fatty liver disease patients. Further analysis showed that serum interleukin-8 was elevated in nonalcoholic fatty liver disease patients, the highest interleukin-8 in patients with advanced fibrosis. An inverse correlation between serum 25(OH)D and interleukin-8 was observed in nonalcoholic fatty liver disease patients with and without liver fibrosis. Although serum transforming growth factor-β1 was slightly elevated in nonalcoholic fatty liver disease patients, serum transforming growth factor-β1 was reduced in nonalcoholic fatty liver disease patients with advanced fibrosis. Unexpectedly, a positive correlation between serum 25(OH)D and transforming growth factor-β1 was observed in nonalcoholic fatty liver disease patients with advanced fibrosis. In conclusion, low vitamin D status is associated with advanced liver fibrosis in nonalcoholic fatty liver disease patients. Interleukin-8 may be an important mediator for hepatic fibrosis in nonalcoholic

  15. Nonalcoholic Fatty Liver Disease: Key Considerations Before and After Liver Transplantation

    PubMed Central

    Patel, Yuval A.; Berg, Carl L.

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common etiology of chronic liver disease in developed countries and is on trajectory to become the leading indication for liver transplantation in the USA and much of the world. Patients with NAFLD cirrhosis awaiting liver transplant face unique challenges and increased risk for waiting list stagnation and dropout due to burdensome comorbidities including obesity, diabetes, cardiovascular disease, and kidney disease. Thus far, patients transplanted for NAFLD cirrhosis have excellent mid- and long-term patient and graft survival, but concerns regarding short-term morbidity and mortality continue to exist. Post-liver transplantation, NAFLD occurs as both a recurrent and de novo manifestation, each with unique outcomes. NAFLD in the donor population is of concern given the growing demand for liver transplantation and mounting pressure to expand the donor pool. This review addresses key issues surrounding NAFLD as an indication for transplantation, including its increasing prevalence, unique patient demographics, outcomes related to liver transplantation, development of post-liver transplantation NAFLD, and NAFLD in the liver donor population. It also highlights exciting areas where further research is needed, such as the role of bariatric surgery and preconditioning of marginal donor grafts. PMID:26815171

  16. Non-alcoholic fatty liver disease in children.

    PubMed

    Janczyk, Wojciech; Socha, Piotr

    2012-06-01

    Non-alcoholic fatty liver disease is increasingly prevalent in children, together with obesity. Transaminases, tests for insulin resistance, ultrasonography and MRI are variably used as surrogates markers of steatosis. Other liver diseases, such as Wilson disease, should be excluded. A liver biopsy is performed in selected cases: young children, familial history of severe disease, inconclusive tests for other pathologies, suspected advanced fibrosis, hypertransaminasemia despite weight loss and in clinical trials. Weight reduction, and changes in lifestyle, are the front-line treatment. Drug therapy is under evaluation.

  17. Controlling alcohol-related global health problems.

    PubMed

    Lam, Tai Hing; Chim, David

    2010-07-01

    Alcohol's adverse public health impact includes disease, injury, violence, disability, social problems, psychiatric illness, drunk driving, drug use, unsafe sex, and premature death. Furthermore, alcohol is a confirmed human carcinogen. The International Agency for Research on Cancer concluded that alcohol causes cancer of the oral cavity, pharynx, larynx, esophagus, liver, colon-rectum, and breast. World Cancer Research Fund/American Institute for Cancer Research concluded that the evidence justifies recommending avoidance of consuming any alcohol, even in small quantities. Despite being responsible for 3.8% of global deaths (2,255,000 deaths) and 4.6% of global disability-adjusted life years in 2004, alcohol consumption is increasing rapidly in China and Asia. Contrary to the World Health Assembly's call for global control action, Hong Kong has reduced wine and beer taxes to zero since 2008. An International Framework Convention on Alcohol Control is urgently needed. Increasing alcohol taxation and banning alcohol advertisement and promotion are among the most effective policies.

  18. Genetic Diseases That Predispose to Early Liver Cirrhosis

    PubMed Central

    Liguori, Renato

    2014-01-01

    Inherited liver diseases are a group of metabolic and genetic defects that typically cause early chronic liver involvement. Most are due to a defect of an enzyme/transport protein that alters a metabolic pathway and exerts a pathogenic role mainly in the liver. The prevalence is variable, but most are rare pathologies. We review the pathophysiology of such diseases and the diagnostic contribution of laboratory tests, focusing on the role of molecular genetics. In fact, thanks to recent advances in genetics, molecular analysis permits early and specific diagnosis for most disorders and helps to reduce the invasive approach of liver biopsy. PMID:25132997

  19. Low Serum Hepcidin in Patients with Autoimmune Liver Diseases.

    PubMed

    Lyberopoulou, Aggeliki; Chachami, Georgia; Gatselis, Nikolaos K; Kyratzopoulou, Eleni; Saitis, Asterios; Gabeta, Stella; Eliades, Petros; Paraskeva, Efrosini; Zachou, Kalliopi; Koukoulis, George K; Mamalaki, Avgi; Dalekos, George N; Simos, George

    2015-01-01

    Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

  20. Study on Assessment of Renal Function in Chronic Liver Disease

    PubMed Central

    Das, Nupur; Paria, Baishakhi; Sarkar, Sujoy

    2015-01-01

    Introduction: Renal dysfunction is common in chronic liver disease. The cause of this renal dysfunction is either multi-organ involvement in acute conditions or secondary to advanced liver disease. Objectives: The study was undertaken to assess the renal function in chronic liver diseases and find out the association of alteration of renal function with gradation of liver disease. (assessed by child-pugh criteria) and to find out the association of alteration of renal function among the cases of chronic liver disease of different aetiology. Materials and Methods: This cross-sectional, observational study was undertaken in Department of General Medicine, Calcutta National Medical College & Hospital, Kolkata during March 2012 to July 2013 with 50 admitted patients of chronic liver disease after considering the exclusion criteria. The patients were interviewed with a pre-designed and pre-tested schedule, examined clinically, followed by some laboratory investigations relevant to diagnose the aetiology of chronic liver disease, and to assess the severity of liver and renal dysfunction. Data was analysed by standard statistical method. Results: Eighty six percent of the patients were male and the mean age of study population was 43.58 y, 68% patients suffered from alcoholic liver disease, followed by 14% patients had chronic Hepatitis-B, 10% patients developed acute kidney injury, 20% had hepato renal syndrome and 14% had IgA deposition. The distribution of serum urea and creatinine across the categories of Child Pugh classification tested by Mann-Whitney test and the distribution was statistically significant. Conclusion: The present study has found significant association between severity of liver dysfunction and certain parameters of renal dysfunction. PMID:25954647

  1. Inequalities in Alcohol-Related Mortality in 17 European Countries: A Retrospective Analysis of Mortality Registers

    PubMed Central

    Mackenbach, Johan P.; Kulhánová, Ivana; Bopp, Matthias; Borrell, Carme; Deboosere, Patrick; Kovács, Katalin; Looman, Caspar W. N.; Leinsalu, Mall; Mäkelä, Pia; Martikainen, Pekka; Menvielle, Gwenn; Rodríguez-Sanz, Maica; Rychtaříková, Jitka; de Gelder, Rianne

    2015-01-01

    Background Socioeconomic inequalities in alcohol-related mortality have been documented in several European countries, but it is unknown whether the magnitude of these inequalities differs between countries and whether these inequalities increase or decrease over time. Methods and Findings We collected and harmonized data on mortality from four alcohol-related causes (alcoholic psychosis, dependence, and abuse; alcoholic cardiomyopathy; alcoholic liver cirrhosis; and accidental poisoning by alcohol) by age, sex, education level, and occupational class in 20 European populations from 17 different countries, both for a recent period and for previous points in time, using data from mortality registers. Mortality was age-standardized using the European Standard Population, and measures for both relative and absolute inequality between low and high socioeconomic groups (as measured by educational level and occupational class) were calculated. Rates of alcohol-related mortality are higher in lower educational and occupational groups in all countries. Both relative and absolute inequalities are largest in Eastern Europe, and Finland and Denmark also have very large absolute inequalities in alcohol-related mortality. For example, for educational inequality among Finnish men, the relative index of inequality is 3.6 (95% CI 3.3–4.0) and the slope index of inequality is 112.5 (95% CI 106.2–118.8) deaths per 100,000 person-years. Over time, the relative inequality in alcohol-related mortality has increased in many countries, but the main change is a strong rise of absolute inequality in several countries in Eastern Europe (Hungary, Lithuania, Estonia) and Northern Europe (Finland, Denmark) because of a rapid rise in alcohol-related mortality in lower socioeconomic groups. In some of these countries, alcohol-related causes now account for 10% or more of the socioeconomic inequality in total mortality. Because our study relies on routinely collected underlying causes of

  2. Interactions Between the Intestinal Microbiome and Liver Diseases

    PubMed Central

    Schnabl, Bernd; Brenner, David A.

    2014-01-01

    The human intestine harbors a diverse community of microbes that promote metabolism and digestion in their symbiotic relationship with the host. Disturbance of its homeostasis can result in disease. We review factors that disrupt intestinal homeostasis and contribute to non-alcoholic fatty liver disease (NAFLD), steatohepatitis (NASH), alcoholic liver disease, and cirrhosis. Liver disease has long been associated with qualitative and quantitative (overgrowth) dysbiotic changes in the intestinal microbiota. Extrinsic factors, such as the Western diet and alcohol, contribute to these changes. Dysbiosis results in intestinal inflammation, a breakdown of the intestinal barrier, and translocation of microbial products in animal models. However, the contribution of the intestinal microbiome to liver disease goes beyond simple translocation of bacterial products that promote hepatic injury and inflammation. Microbial metabolites produced in a dysbiotic intestinal environment and host factors are equally important in the pathogenesis of liver disease. We review how the combination of liver insult and disruptions in intestinal homeostasis contribute to liver disease. PMID:24440671

  3. Genetics of liver disease: From pathophysiology to clinical practice.

    PubMed

    Karlsen, Tom H; Lammert, Frank; Thompson, Richard J

    2015-04-01

    Paralleling the first 30 years of the Journal of Hepatology we have witnessed huge advances in our understanding of liver disease and physiology. Genetic advances have played no small part in that. Initial studies in the 1970s and 1980s identified the strong major histocompatibility complex associations in autoimmune liver diseases. During the 1990 s, developments in genomic technologies drove the identification of genes responsible for Mendelian liver diseases. Over the last decade, genome-wide association studies have allowed for the dissection of the genetic susceptibility to complex liver disorders, in which also environmental co-factors play important roles. Findings have allowed the identification and elaboration of pathophysiological processes, have indicated the need for reclassification of liver diseases and have already pointed to new disease treatments. In the immediate future genetics will allow further stratification of liver diseases and contribute to personalized medicine. Challenges exist with regard to clinical implementation of rapidly developing technologies and interpretation of the wealth of accumulating genetic data. The historical perspective of genetics in liver diseases illustrates the opportunities for future research and clinical care of our patients.

  4. Periodontal disease and liver cirrhosis: A systematic review

    PubMed Central

    2015-01-01

    Objectives: Studies suggest that periodontal disease, a source of subclinical and persistent infection, may be associated with various systemic conditions, including liver cirrhosis. The aim of this study was to examine the literature and determine the relationship between periodontal disease and liver cirrhosis and to identify opportunities and directions for future research in this area. Methods: A systematic review of English articles in the PubMed, EMBASE, and Scopus databases was conducted using search terms including ‘liver cirrhosis’, ‘end-stage liver disease’, ‘liver diseases’, ‘oral health’, ‘periodontal disease’, ‘mouth disease’, ‘gingivitis’, and ‘periodontitis’. Results: Thirteen studies published between 1981 and 2014 were found to include data on oral health and periodontal disease in cirrhotic patients. Studies indicated an increased incidence of periodontal disease in patients with liver cirrhosis, measured with several different periodontal indices. The reported prevalence of periodontal disease in cirrhosis patients ranged from 25.0% to 68.75% in four studies and apical periodontitis was found in 49%–79% of the patients. One study found that mortality was lower among patients who underwent dental treatment versus non-treated patients. Another study suggested an association between periodontal disease and the progression of liver cirrhosis, but data are sparse and conflicting as to whether periodontal disease is correlated to cirrhosis aetiology and severity. Conclusion: Despite the clinical reality of periodontal disease in liver cirrhosis patients, there are few published studies. Before clinical implications can be addressed, more data on the prevalence of and correlation between periodontal disease and liver cirrhosis aetiology, duration, and progression are needed. PMID:26770799

  5. Zebrafish: An Important Tool for Liver Disease Research

    PubMed Central

    Goessling, Wolfram; Sadler, Kirsten C.

    2016-01-01

    As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration. PMID:26319012

  6. Zebrafish: an important tool for liver disease research.

    PubMed

    Goessling, Wolfram; Sadler, Kirsten C

    2015-11-01

    As the incidence of hepatobiliary diseases increases, we must improve our understanding of the molecular, cellular, and physiological factors that contribute to the pathogenesis of liver disease. Animal models help us identify disease mechanisms that might be targeted therapeutically. Zebrafish (Danio rerio) have traditionally been used to study embryonic development but are also important to the study of liver disease. Zebrafish embryos develop rapidly; all of their digestive organs are mature in larvae by 5 days of age. At this stage, they can develop hepatobiliary diseases caused by developmental defects or toxin- or ethanol-induced injury and manifest premalignant changes within weeks. Zebrafish are similar to humans in hepatic cellular composition, function, signaling, and response to injury as well as the cellular processes that mediate liver diseases. Genes are highly conserved between humans and zebrafish, making them a useful system to study the basic mechanisms of liver disease. We can perform genetic screens to identify novel genes involved in specific disease processes and chemical screens to identify pathways and compounds that act on specific processes. We review how studies of zebrafish have advanced our understanding of inherited and acquired liver diseases as well as liver cancer and regeneration.

  7. Limited Knowledge of Acetaminophen in Patients with Liver Disease

    PubMed Central

    Saab, Sammy; Konyn, Peter G.; Viramontes, Matthew R.; Jimenez, Melissa A.; Grotts, Jonathan F.; Hamidzadah, Wally; Dang, Veronica P.; Esmailzadeh, Negin L.; Choi, Gina; Durazo, Francisco A.; El-Kabany, Mohamed M.; Han, Steven-Huy B.; Tong, Myron J.

    2016-01-01

    Abstract Background and Aims: Unintentional acetaminophen overdose remains the leading cause of acute liver failure in the United States. Patients with underlying liver disease are at higher risk of poor outcomes from acetaminophen overdose. Limited knowledge of acetaminophen may be a preventable contributor to elevated rates of overdose and thus acute liver failure. The purpose of this study is to assess knowledge of acetaminophen dosing and presence of acetaminophen in common combination products in patients with liver disease. Methods: We performed a cross-sectional study of patients with liver disease at the Pfleger Liver Institute at the University of California, Los Angeles between June 2015 and August 2016. Patients completed a demographic questionnaire and an acetaminophen knowledge survey. Additional information was obtained from the medical record. Results: Of 401 patients with liver disease, 30 (15.7%) were able to correctly identify that people without liver disease can safely take up to 4 g/day of acetaminophen. The majority of patients (79.9%–86.8%) did not know that Norco® (hydrocone/acetaminophen), Vicodin® (hydrocone/acetaminophen) and Percocet® (oxycodone/acetaminophen) contained acetaminophen. Only 45.3% of the patients knew that Tylenol® #3 contained acetaminophen. Conclusions: We conclude that patients with liver disease have critically low levels of knowledge of acetaminophen, putting them at risk both of acetaminophen overdose, as well as undermedication, and inadequate management of chronic pain. We recommend an increase in education efforts regarding acetaminophen dosage and its safety in the setting of liver disease. Increasing education for those at risk of low acetaminophen knowledge is essential to minimizing acetaminophen overdose rates and optimizing pain management. PMID:28097095

  8. Disposition of nitrendipine in patients with chronic liver diseases.

    PubMed

    Zilly, W; Rämsch, K D; Gothe, M

    1988-01-01

    Metabolism of nitrendipine occurs principally in the liver. Therefore, an alteration of pharmacokinetics has to be discussed in patients with hepatic impairment. To evaluate steady-state plasma concentrations and pharmacokinetics, a low dose of nitrendipine (5 mg/day for 3 weeks) was administered orally to patients with different chronic liver diseases (fatty liver, n = 3; chronic hepatitis, n = 2; and cirrhosis of the liver, n = 5). Nitrendipine plasma concentrations were analyzed by using a gas-liquid chromatography procedure. Twenty-two days after beginning the study, steady-state plasma concentrations were lower than 1.0 microgram/L in one patient without liver disease and in seven patients with chronic liver diseases, in contrast to three patients with alcoholic cirrhosis (5.5, 1.3, and 2.9 micrograms/L). The maximum concentration (Cmax) was 2.3 micrograms/L in the patient without liver disease and 8.3 +/- 3.9 micrograms/L in the hepatic patients. The elimination half-life was prolonged in three of five patients with cirrhosis of the liver (35, 67, and 43 h), whereas in the other patients the half-life was in a normal range (4.2-21.3 h). The area under the concentration-time curve (AUC) was enhanced in three patients with liver cirrhosis (387, 69, and 126 h/micrograms/L); in the other seven hepatic patients, results were normal (35-49 h/micrograms/L). There were no alterations observed in any patient in blood pressure and laboratory data. Oral administration of a low dose of nitrendipine resulted in slightly enhanced steady state plasma concentrations only in patients with advanced cirrhosis of the liver. The half-life, AUC, and bioavailability also seem to be altered only in a more severe state of liver disease.

  9. Role of the Intestinal Microbiome in Cholestatic Liver Disease.

    PubMed

    LaRusso, Nicholas F; Tabibian, James H; O'Hara, Steven P

    2017-01-01

    Hepatobiliary health and disease is influenced by multiple factors including genetics, epigenetics, and the environment. Recently, multiple lines of evidence suggest that the microbiome also plays a central role in the initiation and/or progression of several liver diseases. Our current understanding of the dynamic interplay between microbes, microbial products and liver health and pathophysiology is incomplete. However, exciting insights are continually being made that support both a central role of the microbiome and a need for further interrogation of the microbes or microbe-associated molecules involved in the initiation and progression of select liver diseases.

  10. Human Immunodeficiency Virus and Liver Disease Forum 2010: Conference Proceedings

    PubMed Central

    Sherman, Kenneth E.; Thomas, David L.; Chung, Raymond T.

    2013-01-01

    Liver disease continues to represent a critical mediator of morbidity and mortality in those with human immunodeficiency virus (HIV) infection. The frequent presence and overlap of concomitant injurious processes, including hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of immunosuppression lead to rapid fibrotic progression and early development of end-stage liver disease. This conference summary describes the proceedings of a state-of-the-art gathering of international experts designed to highlight the status of current research in epidemiology, natural history, pathogenesis, and treatment of HIV and liver disease. PMID:21898501

  11. NONALCOHOLIC FATTY LIVER DISEASE BRAZILIAN SOCIETY OF HEPATOLOGY CONSENSUS.

    PubMed

    Cotrim, Helma P; Parise, Edison R; Figueiredo-Mendes, Cláudio; Galizzi-Filho, João; Porta, Gilda; Oliveira, Claudia P

    2016-01-01

    The prevalence of obesity-related metabolic syndrome has rapidly increased in Brazil, resulting in a high frequency of nonalcoholic fatty liver disease, that didn't receive much attention in the past. However, it has received increased attention since this disease was identified to progress to end-stage liver diseases, such as cirrhosis and hepatocellular carcinoma. Clinical practice guidelines for the diagnosis and treatment of nonalcoholic fatty liver disease have not been established in Brazil. The Brazilian Society of Hepatology held an event with specialists' members from all over Brazil with the purpose of producing guideline for Nonalcoholic Fatty Liver Disease based on a systematic approach that reflects evidence-based medicine and expert opinions. The guideline discussed the following subjects: 1-Concepts and recommendations; 2-Diagnosis; 3-Non-medical treatment; 4-Medical treatment; 5-Pediatrics - Diagnosis; 6-Pediatrics - Non-medical treatment; 7-Pediatrics - Medical treatment; 8-Surgical treatment.

  12. Membranous Nephropathy Associated With Immunological Disorder-Related Liver Disease

    PubMed Central

    Dauvergne, Maxime; Moktefi, Anissa; Rabant, Marion; Vigneau, Cécile; Kofman, Tomek; Burtey, Stephane; Corpechot, Christophe; Stehlé, Thomas; Desvaux, Dominique; Rioux-Leclercq, Nathalie; Rouvier, Philippe; Knebelmann, Bertrand; Boffa, Jean-Jacques; Frouget, Thierry; Daugas, Eric; Jablonski, Mathieu; Dahan, Karine; Brocheriou, Isabelle; Remy, Philippe; Grimbert, Philippe; Lang, Philippe; Chazouilleres, Oliver; Sahali, Dil; Audard, Vincent

    2015-01-01

    Abstract The association between membranous nephropathy (MN) and immunological disorder-related liver disease has not been extensively investigated, and the specific features of this uncommon association, if any, remain to be determined. We retrospectively identified 10 patients with this association. We aimed to describe the clinical, biological, and pathological characteristics of these patients and their therapeutic management. The possible involvement of the phospholipase A2 receptor (PLA2R) in these apparent secondary forms of MN was assessed by immunohistochemistry with renal and liver biopsy specimens. The mean delay between MN and liver disease diagnoses was 3.9 years and the interval between the diagnosis of the glomerular and liver diseases was <1.5 years in 5 patients. MN was associated with a broad spectrum of liver diseases including primary biliary cirrhosis (PBC), autoimmune hepatitis (AIH), and primary sclerosing cholangitis (PSC). AIH whether isolated (n = 3) or associated with PBC (n = 2) or PSC (n = 2) was the most frequent autoimmune liver disease. Circulating PLA2R antibodies were detected in 4 out of 9 patients but the test was performed under specific immunosuppressive treatment in 3 out of 9 patients. Seven of the 9 patients with available renal tissue specimens displayed enhanced expression of PLA2R in glomeruli whereas PLA2R was not expressed in liver parenchyma from these patients or in normal liver tissue. The study of immunoglobulin (Ig) subclasses of deposits in glomeruli revealed that the most frequent pattern was the coexistence of IgG1 and IgG4 immune deposits with IgG4 predominating. Detection of PLA2R antibodies in glomeruli but not in liver parenchyma is a common finding in patients with MN associated with autoimmune liver disease, suggesting that these autoantibodies are not exclusively detected in idiopathic MN. PMID:26222864

  13. Nuclear Accident Crisis and Liver Disease: A Summary on Evidences

    PubMed Central

    Wiwanitkit, Viroj

    2013-01-01

    The present global concern is on the adverse effect due to exposure to nuclides expelled from the disrupted nuclear power plant accident in Japan. The exposure can induce several adverse effects. In this specific brief review, the author summarizes the evidences on the effect on liver. Discussion is focused on several liver diseases. PMID:25125994

  14. Non-alcoholic fatty liver disease and childhood obesity.

    PubMed

    Mathur, Prashant; Das, Manoja K; Arora, Narendra K

    2007-04-01

    Obesity has emerged as a significant global health problem in the pediatric population. Pediatric liver disease is a serious complication of childhood obesity. Non-alcoholic steatohepatitis (NASH) is an entity in the spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from fat in the liver--simple steatosis, NASH/ steatohepatitis--fat with in.ammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. Children get NAFLD, and the incidence of this pediatric liver disease is rising as childhood obesity becomes increasingly prevalent. Although much remains to be learned about pediatric NAFLD, it is already evident that children with NASH risk progressive liver damage, including cirrhosis. Liver biopsy is required for definitive diagnosis, and other causes of fatty liver in childhood must be excluded. Gradual weight loss through increased regular exercise and a low-fat, low-refined carbohydrate diet appears to be effective. Drug treatments are being developed. The important message is that childhood obesity poses important health problems, including but not limited to potentially severe chronic liver disease. Early diagnosis of children who are only overweight is a worthy goal so that strategies to limit obesity can be instituted as early as possible. Identification of genetic risks is important, but management will invariably require changes in environmental factors. In addition to individual treatment, a multifaceted, societal initiative is required for solving the childhood obesity epidemic.

  15. Non-alcoholic fatty liver disease in 2015

    PubMed Central

    Ahmed, Monjur

    2015-01-01

    There is worldwide epidemic of non-alcoholic fatty liver disease (NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. PMID:26085906

  16. Role of the Nrf2-ARE Pathway in Liver Diseases

    PubMed Central

    Yang, Ji Hye; Ki, Sung Hwan

    2013-01-01

    The liver is a central organ that performs a wide range of functions such as detoxification and metabolic homeostasis. Since it is a metabolically active organ, liver is particularly susceptible to oxidative stress. It is well documented that liver diseases including hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma are highly associated with antioxidant capacity. NF-E2-related factor-2 (Nrf2) is an essential transcription factor that regulates an array of detoxifying and antioxidant defense genes expression in the liver. It is activated in response to electrophiles and induces its target genes by binding to the antioxidant response element (ARE). Therefore, the roles of the Nrf2-ARE pathway in liver diseases have been extensively investigated. Studies from several animal models suggest that the Nrf2-ARE pathway collectively exhibits diverse biological functions against viral hepatitis, alcoholic and nonalcoholic liver disease, fibrosis, and cancer via target gene expression. In this review, we will discuss the role of the Nrf2-ARE pathway in liver pathophysiology and the potential application of Nrf2 as a therapeutic target to prevent and treat liver diseases. PMID:23766860

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

    PubMed

    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.

  18. Hepatocyte xenotransplantation for treating liver disease.

    PubMed

    Bonavita, André Gustavo; Quaresma, Kátia; Cotta-de-Almeida, Vinícius; Pinto, Marcelo Alves; Saraiva, Roberto Magalhães; Alves, Luiz Anastácio

    2010-01-01

    The treatment of acute and chronic liver failure is still a challenge despite modern therapeutic innovations. While liver transplantation can restore liver function and improve patient survival, donor shortages limit this treatment to a small number of patients. Cellular xenotransplantation has emerged as an alternative for treating liver failure. Xenohepatocytes could be readily available in sufficient quantities to treat patients in critical condition and thereby reduce the donor shortage. The use of isolated encapsulated or non-encapsulated cells can reduce the immunorejection response. Several studies using animal models of acute or chronic liver failure have demonstrated improved survival and recovery of liver function after xenotransplantation of adult hepatocytes. Porcine liver cells are a potential source of xenohepatocytes due to similarities with human physiology and the great number of hepatocytes that can be obtained. The recent development of less immunogenic transgenic pigs, new immunosuppressive drugs, and cellular encapsulation systems represents important advances in the field of cellular xenotransplantation. In this study, we review the work carried out in animal models that deals with the advantages and limitations of hepatocyte xenotransplantation, and we propose new studies needed in this field.

  19. Encephalopathy in Wilson Disease: Copper Toxicity or Liver Failure?

    PubMed Central

    Ferenci, Peter; Litwin, Tomasz; Seniow, Joanna; Czlonkowska, Anna

    2015-01-01

    Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis. PMID:26041965

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

    PubMed

    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.

  1. [Hepatic cell transplantation: a new therapy in liver diseases].

    PubMed

    Pareja, Eugenia; Cortés, Miriam; Martínez, Amparo; Vila, Juan José; López, Rafael; Montalvá, Eva; Calzado, Angeles; Mir, José

    2010-07-01

    Liver transplantation has been remarkably effective in the treatment in patients with end-stage liver disease. However, disparity between solid-organ supply and increased demand is the greatest limitation, resulting in longer waiting times and increase in mortality of transplant recipients. This situation creates the need to seek alternatives to orthotopic liver transplantation.Hepatocyte transplantation or liver cell transplantation has been proposed as the best method to support patients. The procedure consists of transplanting individual cells to a recipient organ in sufficient quantity to survive and restore the function. The capacity of hepatic regeneration is the biological basis of hepatocyte transplantation. This therapeutic option is an experimental procedure in some patients with inborn errors of metabolism, fulminant hepatic failure and acute and chronic liver failure, as a bridge to orthotopic liver transplantation. In the Hospital La Fe of Valencia, we performed the first hepatocyte transplantation in Spain creating a new research work on transplant program.

  2. Chronic liver disease: evaluation by magnetic resonance

    SciTech Connect

    Stark, D.D.; Goldberg, H.I.; Moss, A.A.; Bass, N.M.

    1984-01-01

    Magnetic resonance (MR) imaging distinguished hepatitis from fatty liver and cirrhosis in a woman with a history of alcohol abuse. Anatomic and physiologic manifestations of portal hypertension were also demonstrated by MR.

  3. Role of spleen elastography in patients with chronic liver diseases

    PubMed Central

    Giunta, Mariangela; Conte, Dario; Fraquelli, Mirella

    2016-01-01

    The development of liver cirrhosis and portal hypertension (PH), one of its major complications, are structural and functional alterations of the liver, occurring in many patients with chronic liver diseases (CLD). Actually the progressive deposition of hepatic fibrosis has a key role in the prognosis of CLD patients. The subsequent development of PH leads to its major complications, such as ascites, hepatic encephalopathy, variceal bleeding and decompensation. Liver biopsy is still considered the reference standard for the assessment of hepatic fibrosis, whereas the measurement of hepatic vein pressure gradient is the standard to ascertain the presence of PH and upper endoscopy is the method of choice to detect the presence of oesophageal varices. However, several non-invasive tests, including elastographic techniques, are currently used to evaluate the severity of liver disease and predict its prognosis. More recently, the measurement of the spleen stiffness has become particularly attractive to assess, considering the relevant role accomplished by the spleen in splanchnic circulation in the course of liver cirrhosis and in the PH. Moreover, spleen stiffness as compared with liver stiffness better represents the dynamic changes occurring in the advanced stages of cirrhosis and shows higher diagnostic performance in detecting esophageal varices. The aim of this review is to provide an exhaustive overview of the actual role of spleen stiffness measurement as assessed by several elastographic techniques in evaluating both liver disease severity and the development of cirrhosis complications, such as PH and to highlight its potential and possible limitations. PMID:27672283

  4. Decreased S100B expression in chronic liver diseases

    PubMed Central

    Baik, Su Jung; Kim, Tae Hun; Yoo, Kwon; Moon, Il Hwan; Choi, Ju Young; Chung, Kyu Won; Song, Dong Eun

    2017-01-01

    Background/Aims Hepatic innervation in liver diseases is not fully understood. We here evaluated S100B expression as a marker of hepatic nerves in patients with various chronic liver diseases, topographically and semi-quantitatively. Methods Liver specimens were obtained from 70 subjects (three controls, and 32 chronic hepatitis B, 14 chronic hepatitis C, 14 liver cirrhosis, and seven hepatocellular carcinoma patients). The hepatic nerve density was calculated based on immunohistochemical staining of S100B protein in the portal tracts and hepatic lobules. S100B mRNA levels were semi-quantitatively assessed as the S100B/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA ratio. Results The densities of the hepatic nerves in portal tracts of chronic liver diseases were not significantly different from those of normal controls but the hepatic nerve densities in lobular areas of liver cirrhosis were significantly decreased (p = 0.025). Compared to the control, the S100B/GAPDH mRNA ratio was significantly decreased in chronic liver diseases (p = 0.006) and most decreased in chronic hepatitis C patients (p = 0.023). In chronic liver diseases, The S100B/GAPDH mRNA ratio tended to decrease as the fibrosis score > 0 (p = 0.453) but the overall correlation between the S100B/GAPDH mRNA ratio and fibrosis score was not statistically significant (r = 0.061, p = 0.657). Conclusions Hepatic innervation is decreased in cirrhotic regenerating nodules compared to the control group and seems to decrease in early stages of fibrosis progression. Further studies are needed to clarify the association between changes of hepatic innervation and chronic liver disease progression. PMID:27255110

  5. Innate immune signaling and gut-liver interactions in non-alcoholic fatty liver disease

    PubMed Central

    Trautwein, Christian

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome and covers a disease spectrum ranging from steatosis to inflammation, fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The innate immune response in the liver plays an important role during NAFLD progression. In addition, changes in the intestinal microbial balance and bacterial translocation can further affect disease progression. Immune cells in the liver recognize cell damage or pathogen invasion with intracellular or surface-expressed pattern recognition receptors (PRRs), subsequently initiating signaling cascades that trigger the release of factors promoting the inflammatory response during NAFLD progression. Therefore, mechanisms by which cells of the immune system are activated and recruited into the liver and how these cells cause injury and stress are important for understanding the inflammatory response during NAFLD. PMID:25568861

  6. Clinical Presentation and Patient Evaluation in Nonalcoholic Fatty Liver Disease.

    PubMed

    Patel, Vaishali; Sanyal, Arun J; Sterling, Richard

    2016-05-01

    Nonalcoholic fatty liver disease (NAFLD) is a diagnosis of exclusion. Most patients are asymptomatic and diagnosed incidentally. Most patients remain undiagnosed. A high index of suspicion and serologic work-up to rule out alternative causes of liver disease is required. In NALFD, fibrosis correlates with outcomes, including mortality. To diagnose, assess severity, and monitor fibrosis, 2 noninvasive methods can be used. However, noninvasive tests are more helpful at extremes of fibrosis: excluding it or diagnosing advanced fibrosis. Liver biopsy is usually reserved for cases whereby noninvasive tests fail to accurately determine the degree of fibrosis or the diagnosis is unclear.

  7. Utility of Noninvasive Markers of Fibrosis in Cholestatic Liver Diseases.

    PubMed

    Corpechot, Christophe

    2016-02-01

    Methods of liver fibrosis assessment have changed considerably in the last 20 years, and noninvasive markers now have been recognized as major first-line tools in the management of patients with chronic viral hepatitis infection. But what about the efficiency and utility of these surrogate indices for the more uncommon chronic cholestatic liver diseases, namely primary biliary cirrhosis and primary sclerosing cholangitis? This article provides clinicians with a global overview of what is currently known in the field. Both diagnostic and prognostic aspects of noninvasive markers of fibrosis in cholestatic liver diseases are presented and discussed.

  8. Opioid Drugs in Patients With Liver Disease: A Systematic Review

    PubMed Central

    Soleimanpour, Hassan; Safari, Saeid; Shahsavari Nia, Kavous; Sanaie, Sarvin; Alavian, Seyed Moayed

    2016-01-01

    Context The liver, one of the most important organs of the body, is known to be responsible for several functions. The functional contribution of the liver to the metabolism of carbohydrates, protein, drugs and toxins, fats and cholesterol and many other biological processes are still unknown. Liver disorders are classified into two types: acute and chronic. Different drugs are used in liver diseases to treat and control pain. Most pain relief medications such as opioids are metabolized via the liver; therefore, the adverse reactions of drugs are probably higher for patients with liver disease. The current study aimed to evaluate the effects of opioid drugs on patients with liver disease; therefore, it is necessary to select suitable opioids for such patients. Evidence Acquisition This review was written by referring to research literature including 70 articles and four textbooks published from 1958 to 2015 on various reputable sites. Searches were carried out on the key phrases of narcotic pain relievers (opioids), acute and chronic hepatic failure, opioid adverse drug reactions, drug-induced liver injury (DILI) and other similar keywords. References included a variety of research papers (descriptive and analytical), intervention and review articles. Results In patients with liver disease, administration of opioid analgesics should be observed, accurately. As a general rule, lower doses of drugs should be administered at regular intervals based on the signs of drug accumulation. Secondly, the interactions of opioid drugs with different levels of substrates of the P450 cytochrome enzyme should be considered. Conclusions Pain management in patients with liver dysfunction is always challenging to physicians because of the adverse reactions of drugs, especially opioids. Opioids should be used cautiously since they can cause sedation, constipation and sudden encephalopathy effects. Since the clearance of these drugs in patients with hepatic insufficiency is decreased

  9. Autophagy in chronic liver diseases: the two faces of Janus.

    PubMed

    Gual, Philippe; Gilgenkrantz, Hélène; Lotersztajn, Sophie

    2017-03-01

    Alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are the leading causes of cirrhosis and increase the risk of hepatocellular carcinoma and liver-related death. ALD and NAFLD share common pathogenic features extending from isolated steatosis to steatohepatitis and steatofibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms of the progression of NAFLD and ALD are complex and still unclear. Important links between the regulation of autophagy (macroautophagy and chaperone-mediated autophagy) and chronic liver diseases have been reported. Autophagy may protect against steatosis and progression to steatohepatitis by limiting hepatocyte injury and reducing M1 polarization, as well as promoting liver regeneration. Its role in fibrosis and hepatocarcinogenesis is more complex. It has pro- and antifibrogenic properties depending on the hepatic cell type concerned, and beneficial and deleterious effects on hepatocarcinogenesis at initiating and late phases, respectively. This review summarizes the latest advances on the role of autophagy in different stages of fatty liver disease progression and describes its divergent and cell-specific effects during chronic liver injury.

  10. Management of Alcohol Dependence in Patients with Liver Disease

    PubMed Central

    Addolorato, Giovanni; Mirijello, Antonio; Leggio, Lorenzo; Ferrulli, Anna; Landolfi, Raffaele

    2016-01-01

    Alcohol dependence represents a chronic and relapsing disease affecting nearly 10% of the general population both in the United States and in Europe, with a widespread burden of morbidity and mortality. Alcohol dependence represents the most common cause of liver damage in the Western Countries. Although alcoholic liver disease is associated primarily with heavy drinking, continued alcohol consumption, even in low doses after the onset of liver disease, increases the risk of severe consequences, including mortality. Consequently the ideal treatment of patients affected by alcohol dependence and alcoholic liver disease should aim at achieving long-term total alcohol abstinence and preventing relapse. The aim of the present review is to provide an update on the management of alcohol dependence in patients with alcoholic liver disease. Increasing evidences suggests the usefulness of psychosocial interventions and medications combined in order to reduce alcohol intake, promote abstinence and prevent relapse in alcohol dependent patients. Disulfiram, naltrexone and acamprosate have been approved for this indication; gamma-hydroxybutyric acid (GHB) is approved in Italy and Austria. However, these drugs have not been tested in patients with advanced liver disease. Amongst other emerging pharmacotherapies for alcoholism, topiramate, ondansetron, and baclofen seem the most promising ones. Both topiramate and ondansetron hold a safe profile in alcoholic patients; however, none of them has been tested in alcoholic patients with advanced liver disease. To date, baclofen represents the only anti-craving medication formally tested in a randomized clinical trial in alcoholic patients affected by liver cirrhosis, although additional confirmatory studies are warranted. PMID:23456576

  11. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 5 2014-10-01 2014-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  12. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  13. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  14. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 5 2011-10-01 2011-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  15. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  16. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 5 2010-10-01 2010-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  17. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  18. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 5 2012-10-01 2012-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  19. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  20. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  1. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  2. 49 CFR 382.505 - Other alcohol-related conduct.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 5 2013-10-01 2013-10-01 false Other alcohol-related conduct. 382.505 Section 382... SUBSTANCES AND ALCOHOL USE AND TESTING Consequences for Drivers Engaging in Substance Use-Related Conduct § 382.505 Other alcohol-related conduct. (a) No driver tested under the provisions of subpart C of...

  3. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  4. 49 CFR 655.35 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Other alcohol-related conduct. 655.35 Section 655... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PREVENTION OF ALCOHOL MISUSE AND PROHIBITED DRUG USE IN TRANSIT OPERATIONS Prohibited Alcohol Use § 655.35 Other alcohol-related conduct. (a) No employer shall permit...

  5. 49 CFR 199.237 - Other alcohol-related conduct.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Other alcohol-related conduct. 199.237 Section 199... MATERIALS SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) PIPELINE SAFETY DRUG AND ALCOHOL TESTING Alcohol Misuse Prevention Program § 199.237 Other alcohol-related conduct. (a) No operator...

  6. Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice

    PubMed Central

    Satishchandran, Abhishek; Iracheta-Vellve, Arvin; Ambade, Aditya; Kodys, Karen; Catalano, Donna; Ward, Doyle V.; Szabo, Gyongyi

    2017-01-01

    Background Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology. Materials and methods Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated. Results Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfα), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST). Conclusions Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an

  7. Nonalcoholic Fatty Liver Disease Review: Diagnosis, Treatment, and Outcomes.

    PubMed

    Ahmed, Aijaz; Wong, Robert J; Harrison, Stephen A

    2015-11-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal serum aminotransferase levels in both developed and developing countries. Patients with nonalcoholic steatohepatitis (NASH), a subset of NAFLD, are at risk for progressive liver disease and in need of effective treatment options. A practical approach may be pursued by identifying patients with NAFLD with the highest likelihood for histologic evidence of NASH. Despite decades of clinical trials, no single treatment can be recommended to all patients with NASH. Importantly, there is no evidence that pioglitazone or vitamin E improves fibrosis. Bariatric surgeries may improve hepatic histology in morbidly obese patients with NASH, although randomized clinical trials are lacking. Currently, NASH is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States. The primary and secondary prevention of NAFLD may require aggressive strategies for managing obesity, diabetes, and metabolic syndrome.

  8. Non-alcoholic Fatty Liver Disease (NAFLD)--A Review.

    PubMed

    Karim, M F; Al-Mahtab, M; Rahman, S; Debnath, C R

    2015-10-01

    Non-alcoholic fatty liver disease (NAFLD) is an emerging problem in Hepatology clinics. It is closely related to the increased frequency of overweight or obesity. It has recognised association with metabolic syndrome. Central obesity, diabetes mellitus, dyslipidemia are commonest risk factors. Association with hepatitis C genotype 3 is also recognised. NAFLD is an important cause of cyptogenic cirrhosis of liver. It affects all populations and all age groups. Most patients with NAFLD are asymptomatic or vague upper abdominal pain. Liver function tests are mostly normal or mild elevation of aminotranferases. Histological features almost identical to those of alcohol-induced liver damage and can range from mild steatosis to cirrhosis. Two hit hypothesis is prevailing theory for the development of NAFLD. Diagnosis is usually made by imaging tools like ultrasonogram which reveal a bright liver while liver biopsy is gold standard for diagnosis as well as differentiating simple fatty liver and non-alcoholic steatohepatitis (NASH). Prognosis is variable. Simple hepatic steatosis generally has a benign long-term prognosis. However, one to two third of NASH progress to fibrosis or cirrhosis and may have a similar prognosis as cirrhosis from other liver diseases. Treatment is mostly control of underlying disorders and dietary advice, exercise, insulin sensitizers, antioxidants, or cytoprotective agents. The prevalence of NAFLD is increasing. So it needs more research to address this problem.

  9. MR imaging features of focal liver lesions in Wilson disease.

    PubMed

    Dohan, Anthony; Vargas, Ottavia; Dautry, Raphael; Guerrache, Youcef; Woimant, France; Hamzi, Lounis; Boudiaf, Mourad; Poujois, Aurelia; Faraoun, Sid Ahmed; Soyer, Philippe

    2016-09-01

    Hepatic involvement in Wilson disease (WD) manifests as a diffuse chronic disease in the majority of patients. However, in a subset of patients focal liver lesions may develop, presenting with a wide range of imaging features. The majority of focal liver lesions in patients with WD are benign nodules, but there are reports that have described malignant liver tumors or dysplastic nodules in these patients. Because of the possibility of malignant transformation of liver nodules, major concerns have been raised with respect to the management and follow-up of patients with WD in whom focal liver lesions have been identified. The assessment of liver involvement in patients with WD is generally performed with ultrasonography. However, ultrasonography conveys limited specificity so that magnetic resonance (MR) imaging is often performed to improve lesion characterization. This review was performed to illustrate the spectrum of MR imaging features of focal liver lesions that develop in patients with WD. It is assumed that familiarity with the MR imaging presentation of focal liver lesions in WD may help clarify the actual nature of hepatic nodules in patients with this condition.

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

    PubMed

    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.

  11. Questions and controversies: the role of necroptosis in liver disease

    PubMed Central

    Dara, Lily; Liu, Zhang-Xu; Kaplowitz, Neil

    2016-01-01

    Acute and chronic liver injury results in hepatocyte death and turnover. If injury becomes chronic, the continuous cell death and turnover leads to chronic inflammation, fibrosis and ultimately cirrhosis and hepatocellular carcinoma. Controlling liver cell death both in acute injury, to rescue the liver from acute liver failure, and in chronic injury, to curb secondary inflammation and fibrosis, is of paramount importance as a therapeutic strategy. Both apoptosis and necrosis occur in the liver, but the occurrence of necroptosis in the liver and its contribution to liver disease is controversial. Necroptosis is a form of regulated necrosis which occurs in certain cell types when caspases (+/−cIAPs) are inhibited through the RIPK1-RIPK3 activation of MLKL. The occurrence of necroptosis in the liver has recently been examined in multiple liver injury models with conflicting results. The aim of this review is to summarize the published data with an emphasis on the controversies and remaining questions in the field. PMID:27924226

  12. Effects of Phlebotomy on Liver Enzymes and Histology of Patients with Nonalcoholic Fatty Liver Disease

    PubMed Central

    Khodadoostan, Mahsa; Zamanidoost, Maryam; Shavakhi, Ahmad; Sanei, Hosein; Shahbazi, Masood; Ahmadian, Mehdi

    2017-01-01

    Background: Nonalcoholic fatty liver disease (NAFLD), defined as excessive liver fat deposition and one of end-stage liver disease causes. Increased ferritin levels are associated with insulin resistance and a higher hepatic iron and fat content. Hyperferritinemia has been associated with severity of liver damage in NAFLD. The study aimed to evaluate the effects of phlebotomy on liver enzymes and histology in such patients. Materials and Methods: Thirty-two eligible patients who had NAFLD and after 6 months of lifestyle modification still had NAFLD, and whose ferritin serum was above 250 mg/dl, were enrolled in this clinical trial study. After written informed consent was obtained, each patient's blood serum was taken for aspartate transaminase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALK-P), complete blood count (CBC), total iron-binding capacity (TIBC), iron, and ferritin. Then the patients underwent liver biopsy. After that patients underwent phlebotomy, giving 350 cc blood monthly. Before every phlebotomy, hemoglobin and ferritin were checked. If they were in the goal range, phlebotomy was discontinued and the patient underwent liver biopsy. A serum sample was taken for testing at the beginning of the study. The results before and after phlebotomy were compared. The maximum duration of the study was 6 months. Results: Thirty-two patients (26 males and 6 females) were enrolled, and the mean average age was 33.7 ± 6.74 years. Phlebotomy improved liver enzymes and histology of liver significantly (P < 0.001) and induced reduction of ferritin. Conclusion: Phlebotomy is effective for the improvement of liver enzymes and histology in patients with NAFLD and hyperferritinemia. PMID:28299304

  13. Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases.

    PubMed

    Wang, Yini; Yu, Xiaopeng; Chen, Ermei; Li, Lanuan

    2016-05-12

    Mesenchymal stem cells (MSCs) represent an attractive cell type for research and therapy due to their ability to proliferate, differentiate, modulate immune reactions, and secrete trophic factors. MSCs exist in a multitude of tissues, including bone marrow, umbilical cord, and adipose tissues. Moreover, MSCs have recently been isolated from the liver. Compared with other MSC types, liver-derived human MSCs (LHMSCs) possess general morphologies, immune functions, and differentiation capacities. Interestingly, LHMCSs produce higher levels of pro-angiogenic, anti-inflammatory, and anti-apoptotic cytokines than those of bone marrow-derived MSCs. Thus, these cells may be a promising therapeutic source for liver diseases. This paper summarizes the biological characteristics of LHMSCs and their potential benefits and risks for the treatment of liver diseases.

  14. Time spent in hospital after liver transplantation: Effects of primary liver disease and comorbidity

    PubMed Central

    Tovikkai, Chutwichai; Charman, Susan C; Praseedom, Raaj K; Gimson, Alexander E; van der Meulen, Jan

    2016-01-01

    AIM To explore the effect of primary liver disease and comorbidities on transplant length of stay (TLOS) and LOS in later admissions in the first two years after liver transplantation (LLOS). METHODS A linked United Kingdom Liver Transplant Audit - Hospital Episode Statistics database of patients who received a first adult liver transplant between 1997 and 2010 in England was analysed. Patients who died within the first two years were excluded from the primary analysis, but a sensitivity analysis was also performed including all patients. Multivariable linear regression was used to evaluate the impact of primary liver disease and comorbidities on TLOS and LLOS. RESULTS In 3772 patients, the mean (95%CI) TLOS was 24.8 (24.2 to 25.5) d, and the mean LLOS was 24.2 (22.9 to 25.5) d. Compared to patients with cancer, we found that the largest difference in TLOS was seen for acute hepatic failure group (6.1 d; 2.8 to 9.4) and the largest increase in LLOS was seen for other liver disease group (14.8 d; 8.1 to 21.5). Patients with cardiovascular disease had 8.5 d (5.7 to 11.3) longer TLOS and 6.0 d (0.2 to 11.9) longer LLOS, compare to those without. Patients with congestive cardiac failure had 7.6 d longer TLOS than those without. Other comorbidities did not significantly increase TLOS nor LLOS. CONCLUSION The time patients spent in hospital varied according to their primary liver disease and some comorbidities. Time spent in hospital of patients with cancer was relatively short compared to most other indications. Cardiovascular disease and congestive cardiac failure were the comorbidities with a strong impact on increased LOS. PMID:28058226

  15. Nonalcoholic fatty liver disease: Synopsis of current developments.

    PubMed

    Onyekwere, C A; Ogbera, A O; Samaila, A A; Balogun, B O; Abdulkareem, F B

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) which is defined as the accumulation of fat>5% of liver weight is increasingly becoming an important cause of chronic liver disease. This article tries to chronicle advances that have occurred in the understanding of the pathogenesis, pathology as well as the management of this disease. We have done a Medline search on published work on the subject and reviewed major conference proceedings in the preceding years. The Pathogenesis involves a multi-hit process in which increased accumulation of triglycerides in face of insulin resistance results in increased susceptibility to inflammatory damage mediated by increased expression of inflammatory cytokines and adipokines, oxidative stress and mitochondrial dysfunction, endoplasmic reticulum stress and gut derived endotoxemia. An interplay of multiple metabolic genetic expression and environmental factors however determine which patient with NAFLD will progress from simple steatosis to non-alcoholic steatohepatitis (NASH) and liver cirrhosis. The minimum criteria for diagnosis of NASH are steatosis, ballooning and lobular inflammation; fibrosis is not required. The NASH Clinical Research Network (CRN), histological scoring system is used to grade and stage the disease for standardization. The management of NAFLD consists of treating liver disease as well as associated metabolic co-morbidities such as obesity, hyperlipidaemia, insulin resistance and type 2 diabetes mellitus (T2DM). Patient education is important as their insight and commitment is pivotal, and lifestyle modification is the first line of treatment. Improvement in liver histology in non-diabetic NASH patients has been reported with use of Vitamin E. Other liver-related therapies under investigations include pentoxyfiylins, Caspar inhibitors, Resveratrol as well as probiotics. The prognosis (both overall and liver-related mortality) for simple steatosis is not different from that of the general population however.

  16. Automated segmentation of liver and liver cysts from bounded abdominal MR images in patients with autosomal dominant polycystic kidney disease

    NASA Astrophysics Data System (ADS)

    Kim, Youngwoo; Bae, Sonu K.; Cheng, Tianming; Tao, Cheng; Ge, Yinghui; Chapman, Arlene B.; Torres, Vincente E.; Yu, Alan S. L.; Mrug, Michal; Bennett, William M.; Flessner, Michael F.; Landsittel, Doug P.; Bae, Kyongtae T.

    2016-11-01

    Liver and liver cyst volume measurements are important quantitative imaging biomarkers for assessment of disease progression in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). To date, no study has presented automated segmentation and volumetric computation of liver and liver cysts in these populations. In this paper, we proposed an automated segmentation framework for liver and liver cysts from bounded abdominal MR images in patients with ADPKD. To model the shape and variations in ADPKD livers, the spatial prior probability map (SPPM) of liver location and the tissue prior probability maps (TPPMs) of liver parenchymal tissue intensity and cyst morphology were generated. Formulated within a three-dimensional level set framework, the TPPMs successfully captured liver parenchymal tissues and cysts, while the SPPM globally constrained the initial surfaces of the liver into the desired boundary. Liver cysts were extracted by combined operations of the TPPMs, thresholding, and false positive reduction based on spatial prior knowledge of kidney cysts and distance map. With cross-validation for the liver segmentation, the agreement between the radiology expert and the proposed method was 84% for shape congruence and 91% for volume measurement assessed by the intra-class correlation coefficient (ICC). For the liver cyst segmentation, the agreement between the reference method and the proposed method was ICC  =  0.91 for cyst volumes and ICC  =  0.94 for % cyst-to-liver volume.

  17. Automated segmentation of liver and liver cysts from bounded abdominal MR images in patients with autosomal dominant polycystic kidney disease.

    PubMed

    Kim, Youngwoo; Bae, Sonu K; Cheng, Tianming; Tao, Cheng; Ge, Yinghui; Chapman, Arlene B; Torres, Vincente E; Yu, Alan S L; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P; Bae, Kyongtae T

    2016-11-21

    Liver and liver cyst volume measurements are important quantitative imaging biomarkers for assessment of disease progression in autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD). To date, no study has presented automated segmentation and volumetric computation of liver and liver cysts in these populations. In this paper, we proposed an automated segmentation framework for liver and liver cysts from bounded abdominal MR images in patients with ADPKD. To model the shape and variations in ADPKD livers, the spatial prior probability map (SPPM) of liver location and the tissue prior probability maps (TPPMs) of liver parenchymal tissue intensity and cyst morphology were generated. Formulated within a three-dimensional level set framework, the TPPMs successfully captured liver parenchymal tissues and cysts, while the SPPM globally constrained the initial surfaces of the liver into the desired boundary. Liver cysts were extracted by combined operations of the TPPMs, thresholding, and false positive reduction based on spatial prior knowledge of kidney cysts and distance map. With cross-validation for the liver segmentation, the agreement between the radiology expert and the proposed method was 84% for shape congruence and 91% for volume measurement assessed by the intra-class correlation coefficient (ICC). For the liver cyst segmentation, the agreement between the reference method and the proposed method was ICC  =  0.91 for cyst volumes and ICC  =  0.94 for % cyst-to-liver volume.

  18. Therapeutic potential of green tea in nonalcoholic fatty liver disease.

    PubMed

    Masterjohn, Christopher; Bruno, Richard S

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a constellation of progressive liver disorders that are closely related to obesity, diabetes, and insulin resistance and may afflict over 70 million Americans. NAFLD may occur as relatively benign, nonprogressive liver steatosis, but in many individuals it may progress in severity to nonalcoholic steatohepatitis, fibrosis, cirrhosis, and liver failure or hepatocellular carcinoma. No validated treatments currently exist for NAFLD except for weight loss, which has a poor long-term success rate. Thus, dietary strategies that prevent the development of liver steatosis or its progression to nonalcoholic steatohepatitis are critically needed. Green tea is rich in polyphenolic catechins that have hypolipidemic, thermogenic, antioxidant, and anti-inflammatory activities that may mitigate the occurrence and progression of NAFLD. This review presents the experimental evidence demonstrating the hepatoprotective properties of green tea and its catechins and the proposed mechanisms by which these targeted dietary agents protect against NAFLD.

  19. [Liver disease associated with hereditary defects of hepatobiliary transporters].

    PubMed

    Wendum, Dominique

    2010-12-01

    The identification of biliary tranporters has enhanced our understanding of bile formation and some liver diseases. In this review, we first describe the main hepatobiliary transporters and their function. Then, some liver diseases related to mutations of biliary tranporters (FIC1/ATP8B1, BSEP/ABCB11, MDR3 /ABCB4 and MRP2/ABCC2) will be described with a focus on the pathological aspects. These diseases include progressive familial intrahepatic cholestasis (PFIC), benign recurrent intrahepatic cholestasis (BRIC), intrahepatic cholestasis of pregnancy, Dubin-Johnson's syndrome and low phospholipid associated cholelithiasis (LPAC).

  20. Nonalcoholic fatty liver disease: the concept and confusion.

    PubMed

    Sanal, M G

    2011-12-01

    Nonalcoholic fatty liver disease (NAFLD) is generally considered as a disease associated with diabetes mellitus type 2. But on a closer evaluation we realize a host of confusion associated with this from the nomenclature, diagnosis to pathogenesis. The term refers to a spectrum ranging from steatosis to steatosis with inflammation (NASH) to cirrhosis in the absence of alcohol abuse. But in fact NAFLD is a vague term for a spectrum of diseases which differ not only in the clinical presentation but also in the etiology. NAFLD is loose to incorporate so many etiologies excluding alcoholism and few other "known" etiologies, presenting as fat in liver. Considering the diverse etiologies there is a need for personalized management in NAFLD, which at present is difficult. Currently fatty liver disease could be considered as an added Hepato-cardiovascular-renal and cancer risk factor rather than a specific diagnosis.

  1. Cell Therapy for Liver Disease Using Bioimaging Rats

    PubMed Central

    Haga, Junko; Enosawa, Shin; Kobayashi, Eiji

    2017-01-01

    Advances in stem cell research suggest that cell therapy is a potential alternative to liver transplantation. The use of individualized and minimally invasive cell therapy is desirable to avoid rejection and reduce patient burden. While allo-hepatocyte transplantation has been performed for metabolic hepatic disease, auto-bone marrow transplantation (BMT) has shifted toward mesenchymal stem cells (MSCs) transplantation for liver cirrhosis. In this article, an overview of cell transplantation research for liver disease is provided through our recent rat studies. We have developed various kinds of rat imaging models and have evaluated the effect of cell therapy for liver disease. Bone marrow cells (BMCs) of the Alb-DsRed2 rat were transplanted via the portal vein (PV) in acute and chronic liver damage models. The number of Alb-DsRed2+ albumin-producing cells increased, and the size of the cells increased in the chronic liver damage model as well as in the acute liver damage model. Luciferase transgenic (luc-Tg) rat hepatocytes were transplanted into the hepatectomized LEW rat via the PV. Luminescence intensity lasted for 2 months in the hepatectomized rat. BMCs obtained from green fluorescent protein (GFP) Tg rats were transplanted repeatedly via the PV using an implanted catheter with a port. Repeated BMT via the PV reduced the liver fibrosis. Adipocyte-derived MSCs from the luc-Tg rat were transplanted into the hepatectomized rat model via the PV after ischemic reperfusion. MSCs inhibited hepatocyte apoptosis and promoted liver regeneration. Transplanting the optimal number of cells by an effective and safe way is important for clinical application. Bioimaging rats are a powerful tool for cell transplantation research because it makes observation of the in vivo kinetics of transplanted cells possible. Cell transplantation research using bioimaging rats contributes greatly to evaluating effective methods of cell therapy. PMID:28174669

  2. Pharmacokinetics and metabolism of theophylline in patients with liver diseases.

    PubMed

    Staib, A H; Schuppan, D; Lissner, R; Zilly, W; von Bomhard, G; Richter, E

    1980-11-01

    In patients with acute hepatitis, cholestasis, and compensated or decompensated liver cirrhosis the kinetics and urinary excretion of theophylline and metabolites were investigated following intravenous administration (193 mg). Significant decreases of plasma clearance and a prolongation of the plasma elimination half-life were found only in cases with decompensated liver cirrhosis and to a lesser extent in cases of acute hepatitis. The metabolite pattern in urine was changed in all disease groups compared to controls, i.e., increased excretion of 1-methyl uric acid and a concomitant decrease of 1,3-dimethyl uric acid and particularly of 3-methylxanthine. These results allow the following conclusions. In liver disease the 1-demethylation of theophylline is inhibited; this inhibition appears to be compensated by a shift towards 1-methyl uric acid formation. The monitoring of plasma levels of theophylline is indicated, especially in therapy of patients wtih decompensated liver cirrhosis.

  3. Epigenetics in liver disease: from biology to therapeutics

    PubMed Central

    Hardy, Timothy; Mann, Derek A

    2016-01-01

    Knowledge of the fundamental epigenetic mechanisms governing gene expression and cellular phenotype are sufficiently advanced that novel insights into the epigenetic control of chronic liver disease are now emerging. Hepatologists are in the process of shedding light on the roles played by DNA methylation, histone/chromatin modifications and non-coding RNAs in specific liver pathologies. Alongside these discoveries are advances in the technologies for the detection and quantification of epigenetic biomarkers, either directly from patient tissue or from body fluids. The premise for this review is to survey the recent advances in the field of liver epigenetics and to explore their potential for translation by industry and clinical hepatologists for the design of novel therapeutics and diagnostic/prognostic biomarkers. In particular, we present findings in the context of hepatocellular carcinoma, fibrosis and non-alcoholic fatty liver disease, where there is urgent unmet need for new clinical interventions and biomarkers. PMID:27624887

  4. The Effect of Inflammatory Cytokines in Alcoholic Liver Disease

    PubMed Central

    Kawaratani, Hideto; Tsujimoto, Tatsuhiro; Douhara, Akitoshi; Takaya, Hiroaki; Moriya, Kei; Namisaki, Tadashi; Noguchi, Ryuichi; Yoshiji, Hitoshi; Fujimoto, Masao; Fukui, Hiroshi

    2013-01-01

    Alcohol is the most common cause of liver disease in the world. Chronic alcohol consumption leads to hepatocellular injury and liver inflammation. Inflammatory cytokines, such as TNF-α and IFN-γ, induce liver injury in the rat model of alcoholic liver disease (ALD). Hepatoprotective cytokines, such as IL-6, and anti-inflammatory cytokines, such as IL-10, are also associated with ALD. IL-6 improves ALD via activation of the signal transducer and activator of transcription 3 (STAT3) and the subsequent induction of a variety of hepatoprotective genes in hepatocytes. IL-10 inhibits alcoholic liver inflammation via activation of STAT3 in Kupffer cells and the subsequent inhibition of liver inflammation. Alcohol consumption promotes liver inflammation by increasing translocation of gut-derived endotoxins to the portal circulation and activating Kupffer cells through the LPS/Toll-like receptor (TLR) 4 pathways. Oxidative stress and microflora products are also associated with ALD. Interactions between pro- and anti-inflammatory cytokines and other cytokines and chemokines are likely to play important roles in the development of ALD. The present study aims to conduct a systemic review of ALD from the aspect of inflammation. PMID:24385684

  5. [Drug metabolism in patients with liver disease (author's transl)].

    PubMed

    Richter, E; Epping, J; Fuchshofen-Röckel, M; Heusler, H; Zilly, W

    1980-10-01

    Patients with acute hepatitis and patients with compensated or decompensated cirrhosis of the liver have a decreased plasma clearance of hexobarbital. This however could not been demonstrated in patients with intra- or extrahepatic cholestasis and patients with primary biliary cirrhosis of the liver. The plasma clearance of methohexital, - a high clearance drug - is not changed in the same way. Also there is no evidence as yet, that patients with liver disease and without a collateral portal circulation do have an increased bioavailability of oral high clearance drugs.

  6. Alpha 1-antitrypsin deficiency and infantile liver disease.

    PubMed Central

    McPhie, J L; Binnie, S; Brunt, P W

    1976-01-01

    Infantile liver disease with deficiency of serum alpha1-antitrypsin is illustrated by a description of the clinical, biochemical, and pathological findings in two affected families. The simplicity of the diagnostic tests is emphasized. Review of 61 biopsies of liver from children and adolescents provided a further 3 cases. It is prudent to exclude this metabolic defect in children with a history of "neonatal hepatitis". Images FIG. 1 FIG. 2 PMID:1085610

  7. The promise of gene therapy in gastrointestinal and liver diseases

    PubMed Central

    Prieto, J; Herraiz, M; Sangro, B; Qian, C; Mazzolini, G; Melero, I; Ruiz, J

    2003-01-01

    Gene therapy consists of the transfer of genetic material to cells to achieve a therapeutic goal. In the field of gastroenterology and hepatology gene therapy has produced considerable expectation as a potential tool in the management of conditions that lack effective therapy including non-resectable neoplasms of the liver, pancreas and gastrointestinal tract, chronic viral hepatitis unresponsive to interferon therapy, liver cirrhosis, and inflammatory bowel disease. PMID:12651882

  8. Mutations in TJP2 cause progressive cholestatic liver disease

    PubMed Central

    Sambrotta, Melissa; Strautnieks, Sandra; Papouli, Efterpi; Rushton, Peter; Clark, Barnaby E.; Parry, David A.; Logan, Clare V.; Newbury, Lucy J.; Kamath, Binita M.; Ling, Simon; Grammatikopoulos, Tassos; Wagner, Bart E.; Magee, John C.; Sokol, Ronald J.; Mieli-Vergani, Giorgina; Smith, Joshua D.; Johnson, Colin A.; McClean, Patricia; Simpson, Michael A.; Knisely, A.S.; Bull, Laura N.; Thompson, Richard J.

    2014-01-01

    The elucidation of genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Protein-truncating mutations in the tight junction protein 2 gene (TJP2) are shown to cause failure of protein localisation, with disruption of tight-junction structure leading to severe cholestatic liver disease. This contrasts with the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species. PMID:24614073

  9. Combined 'en bloc' liver and pancreas transplantation in patients with liver disease and type 1 diabetes mellitus.

    PubMed

    Pirenne, Jacques; Deloose, Koen; Coosemans, Willy; Aerts, Raymond; Van Gelder, Frank; Kuypers, Dirk; Maes, Bart; Verslype, Chris; Yap, Paul; Van Steenbergen, Werner; Roskams, Tania; Mathieu, Chantal; Fevery, Johan; Nevens, Frederik

    2004-11-01

    Liver disease alters the glucose metabolism and may cause diabetes, but this condition is potentially reversible with liver transplantation (LTx). Type 1 diabetes mellitus may be coincidentally present in a LTx candidate and immunosuppressive drugs will aggravate diabetes and make its management more difficult for posttransplant. In addition, diabetes negatively influences outcome after LTx. Therefore, the question arises as to why not transplanting the pancreas in addition to the liver in selected patients suffering from both liver disease and Type 1 diabetes. We report two cases of en bloc combined liver and pancreatic transplantation, a technique originally described a decade ago in the treatment of upper abdominal malignancies but rarely used for the treatment of combined liver disease and Type 1 diabetes. Both recipients are currently liver disease-free and insulin-free more than 2 and 4 years posttransplant, respectively. Surgical, medical and immunological aspects of combined liver-pancreas transplantation are discussed in the light of the existing relevant literature.

  10. Nonalcoholic Fatty Liver Disease Management: Dietary and Lifestyle Modifications.

    PubMed

    Nguyen, Vi; George, Jacob

    2015-08-01

    Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of abnormalities that can range from bland liver fat (steatosis), to hepatic inflammation and liver injury (steatohepatitis). It is estimated that NAFLD will become the principal cause of liver disease in Western nations and the leading indication for liver transplantation. Advancements in disease recognition and management are therefore paramount. Although the development of new, reliable drug therapies is vital, lifestyle interventions remain the most effective treatment modality. In addition to weight loss as a primary measure of treatment success, there is growing recognition that other endpoints, including the prevention or delay of diabetes onset, reduced cardiovascular events, prevention of cancer, and improved overall mortality, are equally important outcomes that can be independently modified by lifestyle change. Moreover, NAFLD is inextricably part of a complex, systemic disease process that is linked with deeply entrenched maladaptive lifestyle behaviors. Thus, a holistic, multidisciplinary, and individualized approach to disease management will be the key to achieving any realistic population-level change.

  11. Liver Disease Secondary to Intestinal Failure

    PubMed Central

    Abu-Wasel, Bassam

    2014-01-01

    IFALD is a common and potentially life-threatening condition for patients with SBS requiring long-term PN. There exists the potential for decreasing its incidence by optimizing the composition and the rate of infusion of parenteral solutions, by advocating a multidisciplinary approach, and by early referral for intestinal-liver transplantation to ensure long-term survival of patients with SBS. PMID:24551858

  12. Preventing Alcohol-Related Problems Through Health Policy Research

    PubMed Central

    Voas, Robert B.; Fell, James C.

    2010-01-01

    Alcohol-related health policy research is responsible for guiding the implementation of laws and public health policies that have reduced alcohol-related highway injuries and deaths, as well as other alcohol-related problems over the last 40 years. This research, which tests theories about potential policy changes and responds to specific problems, has examined a vast array of prevention programs. This article briefly identifies 10 program categories and highlights four programs to illustrate the scope and complexity of the individual health policy areas within the categories. PMID:23579933

  13. Managing alcohol related aggression in the emergency department (Part I).

    PubMed

    Ferns, Terry; Cork, Alison

    2008-01-01

    Internationally, violence in the emergency department (ED) is of a constant concern to emergency practitioners. Frequently, both original research papers and anecdotal reports emphasise the phenomenon of alcohol related aggression in the ED. In this first paper, we highlight the literatures discussion of alcohol related violence in the emergency department and the potential psychological effects of alcohol intoxication. In the second we offer personal and organisational strategies clinical nursing staff may consider appropriate to minimise the risk of assault when caring for service users projecting alcohol related aggression.

  14. Acute Fatty Liver of Pregnancy and its Differentiation from Other Liver Diseases in Pregnancy.

    PubMed

    Maier, J T; Schalinski, E; Häberlein, C; Gottschalk, U; Hellmeyer, L

    2015-08-01

    Background: There are a number of threatening liver diseases that occur during pregnancy. Acute fatty liver of pregnancy is a rare disease associated with high maternal and foetal mortality. Case Report: We report on a young gravida 1 woman who presented to our level 1 perinatal centre in the 36 + 5 week of pregnancy with an isolated elevation of transaminases together with diffuse upper abdominal complaints. After comprehensive diagnostic work-up we performed an emergency delivery by Caesarean section. This was followed by interdisciplinary management. Discussion: The differentiation from other liver diseases seems not to be obvious in all cases. Here we consider the following differential diagnoses: hyperemesis gravidarum, intrahepatic gestational cholestasis, preeclampsia, HELLP syndrome. Conclusion: Rapid diagnosis and delivery as well as interdisciplinary aftercare are necessary in order to reduce maternal and foetal mortality.

  15. Liver transplantation for nonalcoholic fatty liver disease: new challenges and new opportunities.

    PubMed

    Shaker, Mina; Tabbaa, Adam; Albeldawi, Mazen; Alkhouri, Naim

    2014-05-14

    Nonalcoholic fatty liver disease (NAFLD) is becoming rapidly one of the most common indications for orthotopic liver transplantation in the world. Development of graft steatosis is a significant problem during the post-transplant course, which may happen as a recurrence of pre-existing disease or de novo NAFLD. There are different risk factors that might play a role in development of graft steatosis including post-transplant metabolic syndrome, immune-suppressive medications, genetics and others. There are few studies that assessed the effects of NAFLD on graft and patient survival; most of them were limited by the duration of follow up or by the number of patients. With this review article we will try to shed light on post-liver transplantation NAFLD, significance of the disease, how it develops, risk factors, clinical course and treatment options.

  16. Cat scratch disease causing hepatic masses after liver transplant.

    PubMed

    Thudi, Kavitha R; Kreikemeier, Jeffrey T; Phillips, Nancy J; Salvalaggio, Paolo R; Kennedy, Donald J; Hayashi, Paul H

    2007-02-01

    Hepatic cat scratch disease is rarely reported in liver transplant recipients and has never been reported with discrete liver lesions in the graft. A 52-year-old woman was transplanted for hepatitis C cirrhosis and hepatocellular carcinoma. Her posttransplant course was uneventful. She presented 2.7 years after transplantation with fever of unknown origin and went on to develop multiple and diffuse discrete liver lesions. Despite an extensive work-up including percutaneous and laparoscopic biopsies, a subsegmental resection that included one of these masses was required to make the diagnosis of Bartonella henselae infection. Serologic tests were equivocal. Histology was consistent with cat scratch disease of the liver, and polymerase chain reaction (PCR) testing of the resected tissue confirmed the diagnosis. Response to doxycycline was rapid. Fevers resolved within 7 days. Repeat abdominal CT scan showed reduction of the liver masses. Cat scratch disease should be considered in postliver transplant patients presenting with fever and liver lesions, especially if close contact with cats has occurred. Diagnosis by PCR testing of involved tissue is preferred when serologies are equivocal due to immunosuppression.

  17. Pediatric fatty liver disease: Role of ethnicity and genetics

    PubMed Central

    Marzuillo, Pierluigi; Miraglia del Giudice, Emanuele; Santoro, Nicola

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprehends a wide range of conditions, encompassing from fatty liver or steatohepatitis with or without fibrosis, to cirrhosis and its complications. NAFLD has become the most common form of liver disease in childhood as its prevalence has more than doubled over the past 20 years, paralleling the increased prevalence of childhood obesity. It currently affects between 3% and 11% of the pediatric population reaching the rate of 46% among overweight and obese children and adolescents. The prevalence of hepatic steatosis varies among different ethnic groups. The ethnic group with the highest prevalence is the Hispanic one followed by the Caucasian and the African-American. This evidence suggests that there is a strong genetic background in the predisposition to fatty liver. In fact, since 2008 several common gene variants have been implicated in the pathogenesis of fatty liver disease. The most important is probably the patatin like phospholipase containing domain 3 gene (PNPLA3) discovered by the Hobbs’ group in 2008. This article reviews the current knowledge regarding the role of ethnicity and genetics in pathogenesis of pediatric fatty liver. PMID:24966605

  18. Functions of autophagy in normal and diseased liver

    PubMed Central

    Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

    2013-01-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

  19. Functions of autophagy in normal and diseased liver.

    PubMed

    Czaja, Mark J; Ding, Wen-Xing; Donohue, Terrence M; Friedman, Scott L; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J; Lemoine, Antoinette; Lin, Jiandie D; Ou, Jing-hsiung James; Perlmutter, David H; Randall, Glenn; Ray, Ratna B; Tsung, Allan; Yin, Xiao-Ming

    2013-08-01

    Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases.

  20. Novel strategies to mine alcoholism-related haplotypes and genes by combining existing knowledge framework.

    PubMed

    Zhang, RuiJie; Li, Xia; Jiang, YongShuai; Liu, GuiYou; Li, ChuanXing; Zhang, Fan; Xiao, Yun; Gong, BinSheng

    2009-02-01

    High-throughout single nucleotide polymorphism detection technology and the existing knowledge provide strong support for mining the disease-related haplotypes and genes. In this study, first, we apply four kinds of haplotype identification methods (Confidence Intervals, Four Gamete Tests, Solid Spine of LD and fusing method of haplotype block) into high-throughout SNP genotype data to identify blocks, then use cluster analysis to verify the effectiveness of the four methods, and select the alcoholism-related SNP haplotypes through risk analysis. Second, we establish a mapping from haplotypes to alcoholism-related genes. Third, we inquire NCBI SNP and gene databases to locate the blocks and identify the candidate genes. In the end, we make gene function annotation by KEGG, Biocarta, and GO database. We find 159 haplotype blocks, which relate to the alcoholism most possibly on chromosome 1 approximately 22, including 227 haplotypes, of which 102 SNP haplotypes may increase the risk of alcoholism. We get 121 alcoholism-related genes and verify their reliability by the functional annotation of biology. In a word, we not only can handle the SNP data easily, but also can locate the disease-related genes precisely by combining our novel strategies of mining alcoholism-related haplotypes and genes with existing knowledge framework.

  1. Fatal liver cyst rupture in polycystic liver disease complicated with autosomal dominant polycystic kidney disease: A case report.

    PubMed

    Tong, Fang; Liang, Yue; Zhang, Lin; Li, Wenhe; Chen, Peng; Duan, Yijie; Zhou, Yiwu

    2016-05-01

    A 59-year-old man was struck in the abdomen and later presented to the emergency room. His blood pressure dropped and eventually died 16h post trauma and just before emergency exploratory laparotomy. Autopsy revealed two polycystic kidneys and a giant polycystic liver with two ruptures. Blood (2225g) was observed in the peritoneum and the body-surface injury was minor. Genetic testing was performed to confirm that the man had an autosomal dominant polycystic kidney disease (ADPKD) complicated by polycystic liver disease (PLD). Autopsy, histopathology and medical history showed that the cause of death was the ruptures of liver cysts due to trauma. In this communication, we describe a fatal case and hope to increase awareness and recognition of PLD and ADPKD. We also wish to indicate that due to the fragile condition of liver cysts, trauma should be considered even if the body-surface injury is minor in fatal cases of PLD patient with a traumatic history.

  2. Comparison of CT scanning and radionuclide imaging in liver disease

    SciTech Connect

    Friedman, M.L.; Esposito, F.S.

    1980-01-01

    Early experience with body CT suggested its usefulness in many diagnostic problems; jaundice, renal and pancreatic masses, and in the evaluation of relatively inaccessible parts of the body, such as the retroperitineum, mediastinum, and pelvis. Investigation of hepatic disease by CT was not unexpectedly compared to radionuclide liver scanning, the major preexisting modality for imaging the liver. In the evaluation of the jaundiced patient, CT rapidly assumed a major role, providing more specific information about the liver than the RN liver scan, as well as demonstrating adjacent organs. CT differentiate obstructive from non-obstructive jaundice. With respect to mass lesions of the liver, the RN liver scan is more sensitive than CT but less specific. The abnormalities on an isotope image of the liver consist of normal variants in configuration, extrinsic compression by adjacent structures, cysts, hemangiomata, abscesses, and neoplasms. These suspected lesions may then be better delineated by the CT image, and a more precise diagnosis made. The physiologic information provided by the RN liver scan is an added facet which is helpful in the patient with diffuse hepatic disease. The CT image will be normal in many of these patients, however, hemochromatosis and fatty infiltration lend themselves especially to density evaluation by CT. The evaluation of lymphoma is more thorough with CT. Structures other than the liver, such as lymph nodes, are visualized. Gallium, however, provides additional isotopic information in patients with lymphoma, and in addition, is known to be useful in the investigation of a febrile patient with an abscess. Newer isotopic agents expand hepatic imaging in other directions, visualizing the biliary tree and evaluating the jaundiced patient.

  3. Mitochondrial genome architecture in non-alcoholic fatty liver disease.

    PubMed

    Sookoian, Silvia; Flichman, Diego; Scian, Romina; Rohr, Cristian; Dopazo, Hernán; Gianotti, Tomas Fernández; Martino, Julio San; Castaño, Gustavo O; Pirola, Carlos J

    2016-12-01

    Non-alcoholic fatty liver disease (NAFLD) is associated with mitochondrial dysfunction, a decreased liver mitochondrial DNA (mtDNA) content, and impaired energy metabolism. To understand the clinical implications of mtDNA diversity in the biology of NAFLD, we applied deep-coverage whole sequencing of the liver mitochondrial genomes. We used a multistage study design, including a discovery phase, a phenotype-oriented study to assess the mutational burden in patients with steatohepatitis at different stages of liver fibrosis, and a replication study to validate findings in loci of interest. We also assessed the potential protein-level impact of the observed mutations. To determine whether the observed changes are tissue-specific, we compared the liver and the corresponding peripheral blood entire mitochondrial genomes. The nuclear genes POLG and POLG2 (mitochondrial DNA polymerase-γ) were also sequenced. We observed that the liver mtDNA of patients with NAFLD harbours complex genomes with a significantly higher mutational (1.28-fold) rate and degree of heteroplasmy than in controls. The analysis of liver mitochondrial genomes of patients with different degrees of fibrosis revealed that the disease severity is associated with an overall 1.4-fold increase in mutation rate, including mutations in genes of the oxidative phosphorylation (OXPHOS) chain. Significant differences in gene and protein expression patterns were observed in association with the cumulative number of OXPHOS polymorphic sites. We observed a high degree of homology (∼98%) between the blood and liver mitochondrial genomes. A missense POLG p.Gln1236His variant was associated with liver mtDNA copy number. In conclusion, we have demonstrated that OXPHOS genes contain the highest number of hotspot positions associated with a more severe phenotype. The variability of the mitochondrial genomes probably originates from a common germline source; hence, it may explain a fraction of the 'missing heritability

  4. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    PubMed

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  5. Albumin liver dialysis as pregnancy-saving procedure in cholestatic liver disease and intractable pruritus.

    PubMed

    Lemoine, Maud; Revaux, Aurelie; Francoz, Claire; Ducarme, Guillaume; Brechignac, Sabine; Jacquemin, Emmanuel; Uzan, Michele; Ganne-Carrie, Nathalie

    2008-11-14

    Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare cholestatic liver disease. Such liver disease can get worse by female hormone disorder. Albumin dialysis or Molecular Adsorbent Recirculating System (MARS) has been reported to reverse severe cholestasis-linked pruritus. Here, we report the first use of MARS during a spontaneous pregnancy and its successful outcome in a patient with PFIC3 and intractable pruritus. Albumin dialysis could be considered as a pregnancy-saving procedure in pregnant women with severe cholestasis and refractory pruritus.

  6. Reversal of hypertriglyceridemia, fatty liver disease, and insulin resistance by a liver-targeted mitochondrial uncoupler.

    PubMed

    Perry, Rachel J; Kim, Taehan; Zhang, Xian-Man; Lee, Hui-Young; Pesta, Dominik; Popov, Violeta B; Zhang, Dongyan; Rahimi, Yasmeen; Jurczak, Michael J; Cline, Gary W; Spiegel, David A; Shulman, Gerald I

    2013-11-05

    Nonalcoholic fatty liver disease (NAFLD) affects one in three Americans and is a major predisposing condition for the metabolic syndrome and type 2 diabetes (T2D). We examined whether a functionally liver-targeted derivative of 2,4-dinitrophenol (DNP), DNP-methyl ether (DNPME), could safely decrease hypertriglyceridemia, NAFLD, and insulin resistance without systemic toxicities. Treatment with DNPME reversed hypertriglyceridemia, fatty liver, and whole-body insulin resistance in high-fat-fed rats and decreased hyperglycemia in a rat model of T2D with a wide therapeutic index. The reversal of liver and muscle insulin resistance was associated with reductions in tissue diacylglycerol content and reductions in protein kinase C epsilon (PKCε) and PKCθ activity in liver and muscle, respectively. These results demonstrate that the beneficial effects of DNP on hypertriglyceridemia, fatty liver, and insulin resistance can be dissociated from systemic toxicities and suggest the potential utility of liver-targeted mitochondrial uncoupling agents for the treatment of hypertriglyceridemia, NAFLD, metabolic syndrome, and T2D.

  7. Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

    PubMed Central

    Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

    2014-01-01

    Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

  8. Circulating microRNAs in nonalcoholic fatty liver disease.

    PubMed

    DiStefano, Johanna K; Gerhard, Glenn S

    2016-01-01

    Liver biopsy is currently recognized as the most accurate method for diagnosing and staging nonalcoholic fatty liver disease (NAFLD). However, this procedure is typically performed when disease has progressed to clinically significant stages, thereby limiting early diagnosis of patients who are at high risk for development of liver- and cardiovascular-related morbidity and mortality. Recently, microRNAs (miRNAs), short, noncoding RNAs that regulate gene expression, have been associated with histological features of NAFLD and are readily detected in the circulation. As such, miRNAs are emerging as potentially useful noninvasive markers with which to follow the progression of NAFLD. In this article, we present the evidence linking circulating miRNAs with NAFLD and discuss the potential value of circulating miRNA profiles in the development of improved methods for NAFLD diagnosis and clinical monitoring of disease progression.

  9. Circulating microRNAs in nonalcoholic fatty liver disease

    PubMed Central

    Gerhard, Glenn S.

    2016-01-01

    Summary Liver biopsy is currently recognized as the most accurate method for diagnosing and staging nonalcoholic fatty liver disease (NAFLD). However, this procedure is typically performed when disease has progressed to clinically significant stages, thereby limiting early diagnosis of patients who are at high risk for development of liver- and cardiovascular-related morbidity and mortality. Recently, microRNAs (miRNAs), short, noncoding RNAs that regulate gene expression, have been associated with histological features of NAFLD and are readily detected in the circulation. As such, miRNAs are emerging as potentially useful noninvasive markers with which to follow the progression of NAFLD. In this article, we present the evidence linking circulating miRNAs with NAFLD and discuss the potential value of circulating miRNA profiles in the development of improved methods for NAFLD diagnosis and clinical monitoring of disease progression. PMID:26606259

  10. Telomere and telomerase in chronic liver disease and hepatocarcinoma.

    PubMed

    Carulli, Lucia; Anzivino, Claudia

    2014-05-28

    The pathogenesis of liver cirrhosis is not completely elucidated. Although in the majority of patients, the risk factors may be identified in B and C viral hepatitis, alcohol intake, drugs or fatty liver disease, there is a small percentage of patients with no apparent risk factors. In addition, the evolution of chronic liver disease is highly heterogeneous from one patient to another. Among patient with identical risk factors, some rapidly progress to cirrhosis and hepatocellular carcinoma (HCC) whereas others have a benign course. Therefore, a genetic predisposition may contribute to the development of cirrhosis and HCC. Evidence supporting the role of genetic factors as a risk for cirrhosis has been accumulating during the past years. In addition to the results from epidemiological studies, polymorphisms studies and data on twins, the concept of telomere shortening as a genetic risk factor for chronic liver disease and HCC has been proposed. Here we review the literature on telomerase mutations, telomere shortening and liver disease including hepatocellular carcinoma.

  11. Pediatric nonalcoholic fatty liver disease: A clinical and laboratory challenge

    PubMed Central

    Pacifico, Lucia; Poggiogalle, Eleonora; Cantisani, Vito; Menichini, Guendalina; Ricci, Paolo; Ferraro, Flavia; Chiesa, Claudio

    2010-01-01

    The true prevalence of pediatric nonalcoholic fatty liver disease (NAFLD) is unknown. Challenges in determining the population prevalence of NAFLD include the type of test (and the reference intervals used to define normal and abnormal), the type of population (general population, hospital series), the demographic characteristics of the population sampled, and the nature of the study design. The natural history of pediatric NAFLD remains uncertain. The issue of when to perform a liver biopsy in children with suspected NAFLD remains controversial. Children with NAFLD but normal alanine aminotransferase are rarely investigated. However, evidence of alterations in glucose metabolism parameters should prompt a better understanding of the natural history of pediatric NAFLD not only in terms of the progression of liver disease but also regarding its potential relationship with other health outcomes such as type 2 diabetes mellitus and cardiovascular disease. This evidence could make liver biopsy mandatory in the majority of cases at risk of progressive and severe hepatic and extrahepatic disease. This conclusion, however, raises the question of the feasibility of liver biopsy assessment in an extremely large at risk population, and of the cost/effectiveness of this policy. There is a considerable, continuous interest in reliable, noninvasive alternatives that will allow the prognosis of pediatric NAFLD to be followed in large community or population-based studies. PMID:21161009

  12. A Different Perspective for Management of Diabetes Mellitus: Controlling Viral Liver Diseases

    PubMed Central

    2017-01-01

    Knowing how to prevent and treat diabetes mellitus (DM) earlier is essential to improving outcomes. Through participating in synthesis and catabolism of glycogen, the liver helps to regulate glucose homeostasis. Viral related liver diseases are associated with glycometabolism disorders, which means effective management of viral liver diseases may be a therapeutic strategy for DM. The present article reviews the correlation between DM and liver diseases to give an update of the management of DM rooted by viral liver diseases. PMID:28352640

  13. Correlates of alcohol-related regretted sex among college students.

    PubMed

    Orchowski, Lindsay M; Mastroleo, Nadine R; Borsari, Brian

    2012-12-01

    The prevalence of alcohol-related regretted sex in college students warrants a better understanding of the characteristics of students who report such experiences. Therefore, the present study examined correlates of regretted sexual experiences involving alcohol use among 2 specific high-risk college student samples: students mandated to alcohol intervention (n = 522) and volunteer 1st-year students transitioning to college (n = 481). Results indicated that alcohol-related regretted sex occurred at similar rates in mandated and volunteer students, with approximately 25% of the students reporting at least 1 occurrence in the past month. Women were more likely to report alcohol-related regretted sex compared with men. The belief that alcohol use would result in "liquid courage" was associated with alcohol-related regretted sex among college students, even after accounting for greater alcohol use and problem alcohol use behaviors. These findings have significant implications for intervention efforts and future research.

  14. Correlates of Alcohol-Related Regretted Sex among College Students

    PubMed Central

    Orchowski, Lindsay M.; Mastroleo, Nadine R.; Borsari, Brian

    2012-01-01

    The prevalence of alcohol-related regretted sex in college students warrants a better understanding of the characteristics of students who report such experiences. Therefore, the present study examined correlates of regretted sexual experiences involving alcohol use among two specific high-risk college student samples: Students mandated to alcohol intervention (N = 522) and volunteer first-year students transitioning to college (N = 481). Results indicated that alcohol-related regretted sex occurred in similar rates in mandated and volunteer students, with approximately 25% of the students reporting at least one occurrence in the past month. Women were more likely to report alcohol-related regretted sex compared to men. The belief that alcohol use would result in “liquid courage” was associated with alcohol-related regretted sex among college students, even after accounting for greater alcohol use and problem alcohol use behaviors. These findings have significant implications for intervention efforts and future research. PMID:22448762

  15. Protective Behavioral Strategies, Social Norms, and Alcohol-Related Outcomes.

    PubMed

    Arterberry, Brooke J; Smith, Ashley E; Martens, Matthew P; Cadigan, Jennifer M; Murphy, James G

    2014-01-01

    The present study examined the unique contributions of protective behavioral strategies and social norms in predicting alcohol-related outcomes. Participants were 363 students from a large public university in the Midwest who reported at least one binge-drinking episode (5+/4+ drinks for men/women in one sitting) in the past 30 days. Data were collected 1/2010-3/2011. We used SEM to test models where protective behavioral strategies (PBS) and social norms were predictors of both alcohol use and alcohol-related problems, after controlling for the effects of gender. Both PBS and descriptive norms had relationships with alcohol use. PBS also had a relationship with alcohol-related problems. Overall, the findings suggest that PBS and social norms have unique associations with distinct alcohol-related outcomes.

  16. Cholesterol metabolism in cholestatic liver disease and liver transplantation: From molecular mechanisms to clinical implications

    PubMed Central

    Nemes, Katriina; Åberg, Fredrik; Gylling, Helena; Isoniemi, Helena

    2016-01-01

    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein (LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X (Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers - such as cholesterol precursor sterols, plant sterols, and cholestanol - may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation. PMID:27574546

  17. Reducing Alcohol-Related Sexual Assault in the Marine Corps

    DTIC Science & Technology

    2013-04-10

    REDUCING ALCOHOL-RELATED SEXUAL ASSAULT IN THE MARINE CORPS 5a.&CONTRACT&NUMBER! N/A 5b.&GRANT&NUMBER! N/A 5c.&PROGRAM&ELEMENT&NUMBER! N/A 6...reduce alcohol-related sexual assault in the Marine Corps. It advocates more emphasis and training on the interplay between alcohol and sexual ...assault, as well as male and female-specific training on the issue. 15.&SUBJECT&TERMS! Sexual Assault, Alcohol, Incapacitation, Marine Corps

  18. Managing alcohol related aggression in the emergency department (Part II).

    PubMed

    Cork, Alison; Ferns, Terry

    2008-04-01

    Violence in the emergency department (ED) is a global problem. In our first paper, we highlighted the potential psychological effects of alcohol intoxication, the literatures discussion of alcohol related violence in the emergency department and the importance of developing positive nurse/service user relationships. In this second paper, we discuss personal and organisational strategies clinical nursing staff may consider appropriate to minimise the risk of assault when caring for service users projecting alcohol related aggression.

  19. Pathogenesis of veno-occlusive liver disease after radiation

    SciTech Connect

    Fajardo, L.F.; Colby, T.V.

    1980-11-01

    Radiation-induced liver disease is characterized structurally by progressive fibrous obliteration of central veins (veno-occlusive disease (VOD)). The pathogenesis is unknown. Samples of liver from 11 patients with radiation-induced VOD were studied by light and electron microscopy for evidence of central vein thrombosis. The patients had received fractionated radiation with total doses of 1850 to 4050 rads, or single doses of 1000 rads. In addition, six patients had received chemotherapy. We postulate that ionizing radiation injures preferentially the endothelial cells of central veins, which leads to focal deposition of fibrin. The resulting fibrin network is eventually replaced by collagen, causing fibrous occlusion.

  20. Autophagy in the liver: functions in health and disease.

    PubMed

    Ueno, Takashi; Komatsu, Masaaki

    2017-03-01

    The concept of macroautophagy was established in 1963, soon after the discovery of lysosomes in rat liver. Over the 50 years since, studies of liver autophagy have produced many important findings. The liver is rich in lysosomes and possesses high levels of metabolic-stress-induced autophagy, which is precisely regulated by concentrations of hormones and amino acids. Liver autophagy provides starved cells with amino acids, glucose and free fatty acids for use in energy production and synthesis of new macromolecules, and also controls the quality and quantity of organelles such as mitochondria. Although the efforts of early investigators contributed markedly to our current knowledge of autophagy, the identification of autophagy-related genes represented a revolutionary breakthrough in our understanding of the physiological roles of autophagy in the liver. A growing body of evidence has shown that liver autophagy contributes to basic hepatic functions, including glycogenolysis, gluconeogenesis and β-oxidation, through selective turnover of specific cargos controlled by a series of transcription factors. In this Review, we outline the history of liver autophagy study, and then describe the roles of autophagy in hepatic metabolism under healthy and disease conditions, including the involvement of autophagy in α1-antitrypsin deficiency, NAFLD, hepatocellular carcinoma and viral hepatitis.

  1. Notch signaling and new therapeutic options in liver disease.

    PubMed

    Morell, Carola Maria; Strazzabosco, Mario

    2014-04-01

    Notch signaling is a crucial determinant of cell fate decision during development and disease in several organs. Notch effects are strictly dependent on the cellular context in which it is activated. In the liver, Notch signaling is involved in biliary tree development and tubulogenesis. Recent advances have shed light on Notch as a critical player in liver regeneration and repair, as well as in liver metabolism and inflammation and cancer. Notch signaling is finely regulated at several levels. The complexity of the pathway provides several possible targets for development of therapeutic agents able to inhibit Notch. Recent reports have shown that persistent activation of Notch signaling is associated with liver malignancies, particularly hepatocellular with stem cell features and cholangiocarcinoma. These novel findings suggest that interfering with the aberrant activation of the Notch pathway may have therapeutic relevance. However, further studies are needed to clarify the mechanisms regulating physiologic and pathologic Notch activation in the adult liver, to better understand the mechanistic role(s) of Notch in liver diseases and to develop safe and specific therapeutic agents.

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

    PubMed

    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

  3. [Nonalcoholic fatty liver disease, association with cardiovascular disease snd treatment. (I). Nonalcoholic fatty liver disease and its association with cardiovascular disease].

    PubMed

    Brea, Ángel; Pintó, Xavier; Ascaso, Juan F; Blasco, Mariano; Díaz, Ángel; González-Santos, Pedro; Hernández Mijares, Antonio; Mantilla, Teresa; Millán, Jesús; Pedro-Botet, Juan

    2016-09-27

    Non-alcoholic fatty liver disease (NAFLD) comprises a series of histologically lesions similar to those induced by alcohol consumption in people with very little or no liver damage. The importance of NAFLD is its high prevalence in the Western world and, from the point of view of the liver, in its gradual progression from steatosis to steatohepatitis, cirrhosis, and liver cancer. During the last decade it has been observed that NAFLD leads to an increased cardiovascular risk with acceleration of arteriosclerosis and events related to it, being the main cause of its morbidity and mortality. This review, updated to January 2016, consists of two parts, with the first part analysing the association of NAFLD with cardiovascular disease.

  4. Non-alcoholic fatty liver disease and liver transplantation: Outcomes and advances

    PubMed Central

    Said, Adnan

    2013-01-01

    Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide. In the last decade it has become the third most common indication for liver transplantation in the United States. Increasing prevalence of NAFLD in the general population also poses a risk to organ donation, as allograft steatosis can be associated with non-function of the graft. Post-transplant survival is comparable between NAFLD and non-NAFLD causes of liver disease, although long term outcomes beyond 10 year are lacking. NAFLD can recur in the allograft frequently although thus far post transplant survival has not been impacted. De novo NAFLD can also occur in the allograft of patients transplanted for non-NAFLD liver disease. Predictors for NAFLD post-transplant recurrence include obesity, hyperlipidemia and diabetes as well as steroid dose after liver transplantation. A polymorphism in PNPLA3 that mediates triglyceride hydrolysis and is linked to pre-transplant risk of obesity and NAFLD has also been linked to post transplant NAFLD risk. Although immunosuppression side effects potentiate obesity and the metabolic syndrome, studies of immunosuppression modulation and trials of specific immunosuppression regimens post-transplant are lacking in this patient population. Based on pre-transplant data, sustained weight loss through diet and exercise is the most effective therapy for NAFLD. Other agents occasionally utilized in NAFLD prior to transplantation include vitamin E and insulin-sensitizing agents. Studies of these therapies are lacking in the post-transplant population. A multimodality and multidisciplinary approach to treatment should be utilized in management of post-transplant NAFLD. PMID:24409043

  5. [Role of autophagy in the pathogenesis of liver diseases].

    PubMed

    Werling, Klára

    2011-12-04

    Autophagy is a self-digestion process that plays an important role in the development, differentiation and homeostasis of cells, helping their survival during starvation and hypoxia. Accumulated mutant proteins in the endoplasmic reticulum can be degraded by autophagy in alpha-1 antitrypsin deficiency. Hepatitis C and B virus may exploit the autophagy pathway to escape the innate immune response and to promote their own replication. Autophagy is decreased in response to chronic alcohol consumption, likely due to a decrease in 5'-adenosine monophosphate-activated protein kinase, increase in mTOR activity and due to an alteration in vesicle transport in hepatocytes. In obesity and alcoholic liver disease the decreased function of autophagy causes formation of Mallory-Denk bodies and cell death. The deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress, and to progression of liver disease. Autophagy defect in hepatocellular carcinoma suggests that it can serve a tumor-suppressor function. The autophagy protein Beclin-1 levels have prognostic significance in liver tumors. Understanding of the molecular mechanism and the role of autophagy may lead to more effective therapeutic strategies in liver diseases in the future.

  6. Gut Microbiota and Host Reaction in Liver Diseases

    PubMed Central

    Fukui, Hiroshi

    2015-01-01

    Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD), especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD) and its progression to nonalcoholic steatohepatitis (NASH). There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases. PMID:27682116

  7. [Alphafetoprotein in hepatic tumours and benign liver diseases].

    PubMed

    Forones, N M; Queiroz, L A; Ferraz, M L; Parise, E R

    1995-01-01

    AFP is an oncofetal protein found in increased levels in hepatocellular carcinoma, liver metastasis and other benign liver diseases. PURPOSE--To know the behaviour of this protein in each of these clinical situations would undoubtedly help us to discriminate between hepatocellular carcinoma and benign diseases. PATIENTS--A hundred forty nine patients were divided into 4 groups: 1. acute hepatitis (AH) n = 24, 2. chronic liver disease, viral or alcoholic (CLD) n = 81, 3. hepatic metastasis (HM) n = 29, 4. hepatocellular carcinoma (HCC) n = 15. AFP assays were done by ELISA (Abbott Diagnostica, ref. value: 15ng/mL). RESULTS--The results observed were as follows: AFP < 15ng/mL: AH 75%, CLD 86.4%, HM 79.3%, HCC 6.6%, AFP > 15 e < 100ng/mL: AH 25%, CLD 8.6%, HM 20.6%, HCC 20%, AFP > 100ng/mL: AH zero, CLD 4.9%, HM zero, HCC 49%. It is clear that depending on the cut off level, there is a decrease of sensibility which is paralleled by an increase in specificity. CONCLUSIONS--AFP levels are increased in benign liver diseases (AH, CLD) and HM, how ever levels above 100ng/mL occur much more frequently in HCC. In our sample, 93.3% of the HCC showed high levels of AFP, probably because most of the patients had advanced clinical stages of the disease.

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

    PubMed Central

    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

  9. Probiotic as a Novel Treatment Strategy Against Liver Disease

    PubMed Central

    Imani Fooladi, Abbas Ali; Mahmoodzadeh Hosseini, Hamideh; Nourani, Mohammad Reza; Khani, Soghra; Alavian, Seyed Moayed

    2013-01-01

    Context A symbiotic relationship between the liver and intestinal tract enables the healthy status of both organs. Microflora resident in intestinal lumen plays a significant role in hepatocytes function. Alterations to the type and amount of microorganisms that live in the intestinal tract can result in serious and harmful liver dysfunctions such as cirrhosis, nonalcoholic fatty liver disease, alcoholic liver disease, and hepatic encephalopathy. An increased number of pathogens, especially enterobacteriaceae, enterococci, and streptococci species causes the elevation of intestinal permeability and bacterial translocation. The presence of high levels of lipopolysaccharide (LPS) and bacterial substances in the blood result in a portal hypertension and ensuing hepatocytes damage. Several methods including the usage of antibiotics, prebiotics, and probiotics can be used to prevent the overgrowth of pathogens. Compared to prebiotic and antibiotic therapy, probiotics strains are a safer and less expensive therapy. Probiotics are "live microorganisms (according to the FAO/WHO) which when administered in adequate amounts confer a health benefit on the host”. Evidence Acquisitions Data from numerous preclinical and clinical trials allows for control of the flora bacteria quantity, decreases in compounds derived from bacteria, and lowers proinflammatory production such as TNF-α, IL-6 and IFN-γ via down-regulation of the nuclear factor kappa B (NF-κ B). Results On the other hand, probiotic can reduce the urease activity of bacterial microflora. Furthermore, probiotic decreases fecal pH value and reduces ammonia adsorption. In addition, the serum level of liver enzymes and other substances synthesized by the liver are modulated subsequent to probiotic consumption. Conclusions According to our knowledge, Probiotic therapy as a safe, inexpensive and a noninvasive strategy can reduce pathophysiological symptoms and improve different types of liver diseases without side

  10. Variations in human liver fucosyltransferase activities in hepatobiliary diseases.

    PubMed

    Jezequel-Cuer, M; Dalix, A M; Flejou, J F; Durand, G

    1992-06-01

    The hyperfucosylation of a number of glycoconjugates observed in liver diseases involves the action of several specific fucosyltransferases (F.T.) notably responsible for synthesizing histo-blood group antigens. We determined the activities of alpha 3, alpha 2 and alpha 3/4 F.T. in 35 liver biopsy samples from patients with fatty liver, alcoholic or post-hepatic liver cirrhosis, primary or secondary biliary cirrhosis, acute hepatitis or a normal liver. F.T. activities were measured by transfer of GDP [14C] fucose to asialotransferrin for alpha 3 F.T., to phenyl beta-D-galactoside for alpha 2 F.T. and to 2' fucosyllactose for alpha 3/4 F.T. The diseased liver extracts showed an early increase in non-Le gene-associated alpha 3 F.T. activity (p = 0.001), which was related to the number of steatosic hepatocytes and the degree of intralobular inflammatory infiltration. Overexpression of this alpha 3 F.T. provides an explanation for the strong expression of 3-fucosyl lactosamine structures described in several hepatobiliary diseases. alpha 2 F.T. levels were significantly elevated in the two groups of liver cirrhosis and acute hepatitis (p = 0.05), but not enough to consider alpha 2 F.T. as a sensitive feature of mesenchymal cell injury. All Lewis-positive biopsies displaying biliary alterations showed increased Le gene-encoded alpha 3/4 F.T. activity (p = 0.001), which was related to the intensity of neoductular proliferation. Elevated levels of alpha 3/4 F.T. may be a very early sign of biliary regeneration.

  11. Non alcoholic fatty liver disease and metabolic syndrome

    PubMed Central

    Paschos, P; Paletas, K

    2009-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinicopathologic entity increasingly recognized as a major health burden in developed countries. It includes a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and rarely, progression to cirrhosis. Recent studies emphasize the role of insulin resistance, oxidative stress and subsequent lipid peroxidation, proinflammatory cytokines, adipokines and mitochondrial dysfunction in the development and progression of NAFLD. Furthermore, accumulating evidence supports an association between NAFLD and metabolic syndrome. Although the data are mainly epidemiological, the pathogenesis of NAFLD and metabolic syndrome seems to have common pathophysiological mechanisms, with focus on insulin resistance as a key factor. This review summarizes the current knowledge on the epidemiology, pathophysiology and diagnosis of both NAFLD and metabolic syndrome and the findings that strongly support the association of nonalcoholic fatty liver disease as a possible component in the cluster of metabolic syndrome. PMID:19240815

  12. Insulin resistance in clinical and experimental alcoholic liver disease

    PubMed Central

    Carr, Rotonya M.; Correnti, Jason

    2015-01-01

    Alcoholic liver disease (ALD) is the number one cause of liver failure worldwide; its management costs billions of health care dollars annually. Since the advent of the obesity epidemic, insulin resistance and diabetes have become common clinical findings in patients with ALD; and the development of insulin resistance 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. PMID:25998863

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

    PubMed Central

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

    2016-01-01

    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. PMID:27347998

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

    PubMed

    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.

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

    PubMed

    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.

  16. Rodent models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Imajo, Kento; Yoneda, Masato; Kessoku, Takaomi; Ogawa, Yuji; Maeda, Shin; Sumida, Yoshio; Hyogo, Hideyuki; Eguchi, Yuichiro; Wada, Koichiro; Nakajima, Atsushi

    2013-11-04

    Research in nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), has been limited by the availability of suitable models for this disease. A number of rodent models have been described in which the relevant liver pathology develops in an appropriate metabolic context. These models are promising tools for researchers investigating one of the key issues of NASH: not so much why steatosis occurs, but what causes the transition from simple steatosis to the inflammatory, progressive fibrosing condition of steatohepatitis. The different rodent models can be classified into two large groups. The first includes models in which the disease is acquired after dietary or pharmacological manipulation, and the second, genetically modified models in which liver disease develops spontaneously. To date, no single rodent model has encompassed the full spectrum of human disease progression, but individual models can imitate particular characteristics of human disease. Therefore, it is important that researchers choose the appropriate rodent models. The purpose of the present review is to discuss the metabolic abnormalities present in the currently available rodent models of NAFLD, summarizing the strengths and weaknesses of the established models and the key findings that have furthered our understanding of the disease's pathogenesis.

  17. Autoimmune Liver Disease Post-Liver Transplantation: A Summary and Proposed Areas for Future Research.

    PubMed

    Edmunds, Catherine; Ekong, Udeme D

    2016-03-01

    Autoimmune liver diseases (AILD) are rare diseases with a reported prevalence of less than 50 per 100 000 population. As the research landscape and our understanding of AILDs and liver transplantation evolves, there remain areas of unmet needs. One of these areas of unmet needs is prevention of disease recurrence after liver transplantation. Disease recurrence is not an insignificant event because allograft loss with the need for retransplantation can occur. Patients transplanted for AILD are more likely to experience acute rejection compared to those transplanted for non-AILD, and the reason(s) behind this observation is unclear. Tasks for the future include a better understanding of the pathogenesis of AILD, definition of the precise pathogenetic mechanisms of recurrent AILD, and development of strategies that can identify recipients at risk for disease recurrence. Importantly, the role of crosstalk between alloimmune responses and autoimmune responses in AILD is an important area that needs further study.This article reviews the relevant literature of de novo autoimmune hepatitis, recurrent autoimmune hepatitis, recurrent primary sclerosing cholangitis, and recurrent primary biliary cirrhosis in terms of the clinical entity, the scientific advancements, and future scientific goals to enhance our understanding of these diseases.

  18. Animals models of gastrointestinal and liver diseases. Animal models of alcohol-induced liver disease: pathophysiology, translational relevance, and challenges.

    PubMed

    Mathews, Stephanie; Xu, Mingjiang; Wang, Hua; Bertola, Adeline; Gao, Bin

    2014-05-15

    Over the last four decades, chronic ethanol feeding studies in rodents using either ad libitum feeding or intragastric infusion models have significantly enhanced our understanding of the pathogenesis of alcoholic liver disease (ALD). Recently, we developed a chronic plus binge alcohol feeding model in mice that is similar to the drinking patterns of many alcoholic hepatitis patients: a history of chronic drinking and recent excessive alcohol consumption. Chronic+binge ethanol feeding synergistically induced steatosis, liver injury, and neutrophil infiltration in mice, which may be useful for the study of early alcoholic liver injury and inflammation. Using this chronic+binge model, researchers have begun to identify novel mechanisms that participate in the pathogenesis of alcoholic liver injury, thereby revealing novel therapeutic targets. In this review article, we briefly discuss several mouse models of ALD with a focus on the chronic+binge ethanol feeding model.

  19. Assessment of thyroid and gonadal function in liver diseases

    PubMed Central

    Kharb, Sandeep; Garg, M. K.; Puri, Pankaj; Brar, Karninder S.; Pandit, Aditi; Srivastava, Sharad

    2015-01-01

    Introduction: Liver is involved with the synthesis of carrier proteins and metabolism of various hormones and liver diseases may, therefore, be associated with various endocrine disturbances. This study was conducted to assess thyroid and gonadal function in subjects with acute hepatitis (AH), chronic liver disease (CLD), and those who had undergone liver transplantation (LT). Materials and Methods: Patients with AH, CLD with Child-Pugh stage A (CLD-1) and Child-Pugh stage B or C (CLD-2), and LT seen at our tertiary level hospital were assessed clinically, biochemically, and for thyroid and gonadal functions besides 25 healthy controls. Results: Thyroid dysfunction and hypogonadism were present in 14 (16%) and 24 (28%) patients with liver diseases respectively. Among thyroid dysfunction, the commonest was sick euthyroid syndrome six (7%), followed by subclinical hypothyroidism in three patients (3.5%), subclinical hyperthyroidism and thyrotoxicosis in two patients each (2.3%) and overt hypothyroidism in one patient. Among patients with LT and AH groups, the only abnormality was significantly lower total T3 compared with healthy controls. The CLD2 group had significantly lower levels of all thyroid hormones compared with controls and CLD1 group. Hypogonadism was commonest in patients with CLD-2 (14; 50%) followed by LT (3; 33%), CLD-1 (4; 20%), and AH (3; 14%). Hypogonadism was predicted by older age, lower levels of serum albumin, total cholesterol, and triglycerides and higher levels of plasma glucose, serum bilirubin, aspartate transaminases, and international normalized ratio. Gonadal functions showed recovery following LT. Conclusions: Thyroid dysfunction and hypogonadism form an important part of the spectrum of acute and CLD, and patients with LT. Deterioration of synthetic functions of liver disease predicts presence of hypogonadism. PMID:25593833

  20. Statins in nonalcoholic fatty liver disease and steatohepatitis: updated review.

    PubMed

    Nseir, William; Mahamid, Mahmud

    2013-03-01

    Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that refers to the presence of hepatic steatosis without significant intake of alcohol. NAFLD is an asymptomatic disease that can progress to nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma. The most common cause of mortality in patients with NAFLD or NASH is cardiovascular disease (CVD). Currently, the treatment of NAFLD focuses on gradual weight loss and life style modifications. However, multifactorial treatment of NAFLD or NASH risk factors may be needed to reduce the likelihood of these patients developing CVD. This review discusses the mechanisms that link hyperlipidemia and NAFLD. In addition, the review focuses on the safety and efficacy of statins in patients with NAFLD or NASH, and their effect on the extent of hepatic steatosis and fibrosis based on human studies.

  1. Alcoholism and liver disease in Mexico: genetic and environmental factors.

    PubMed

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

    2013-11-28

    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.

  2. Structural and functional hepatocyte polarity and liver disease

    PubMed Central

    Gissen, Paul; Arias, Irwin M.

    2015-01-01

    Summary Hepatocytes form a crucially important cell layer that separates sinusoidal blood from the canalicular bile. They have a uniquely organized polarity with a basal membrane facing liver sinusoidal endothelial cells, while one or more apical poles can contribute to several bile canaliculi jointly with the directly opposing hepatocytes. Establishment and maintenance of hepatocyte polarity is essential for many functions of hepatocytes and requires carefully orchestrated cooperation between cell adhesion molecules, cell junctions, cytoskeleton, extracellular matrix and intracellular trafficking machinery. The process of hepatocyte polarization requires energy and, if abnormal, may result in severe liver disease. A number of inherited disorders affecting tight junction and intracellular trafficking proteins have been described and demonstrate clinical and pathophysiological features overlapping those of the genetic cholestatic liver diseases caused by defects in canalicular ABC transporters. Thus both structural and functional components contribute to the final hepatocyte polarity phenotype. Many acquired liver diseases target factors that determine hepatocyte polarity, such as junctional proteins. Hepatocyte depolarization frequently occurs but is rarely recognized because hematoxylin-eosin staining does not identify the bile canaliculus. However, the molecular mechanisms underlying these defects are not well understood. Here we aim to provide an update on the key factors determining hepatocyte polarity and how it is affected in inherited and acquired diseases. PMID:26116792

  3. Current Status of Therapy in Nonalcoholic Fatty Liver Disease

    PubMed Central

    McNear, Scott

    2009-01-01

    The obesity epidemic has now spread worldwide. With increase in weight, there is an increase in dysregulated energy metabolism ultimately leading to dysfunction of multiple organ systems recognized as the metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease worldwide, and is thought to be the hepatic manifestation of metabolic syndrome. It is a nondiscriminating disease affecting both children and adults and no socioeconomic class is spared. There is a well-defined increase in both liver-related and all-cause mortality. Current projections foresee a continued worsening in prevalence, especially with the increased rate of childhood obesity. Prevention would be the ultimate goal, but with continued trends in obesity, therapeutic options are needed to manage this chronic liver disease and prevent its complications of cirrhosis and even hepatocellular carcinoma. Therapies will need to be affordable, tolerable, and safe to be useful on such a large scale. This article will discuss some of the basic understanding of NAFLD, as well as review the currently tested therapies, some novel therapies, and potential future therapeutic options. PMID:21180532

  4. Palliative care for patients with end-stage liver disease.

    PubMed

    Larson, Anne M

    2015-05-01

    Liver disease results in over four million physician visits and over 750,000 hospitalizations per year in the USA. Those with chronic liver disease frequently progress to cirrhosis, end-stage liver disease (ESLD), and death. Patients with ESLD experience numerous complications, including muscle cramps, confusion (hepatic encephalopathy), protein calorie malnutrition, muscle wasting, fluid overload (ascites, edema), bleeding (esophagogastric variceal hemorrhage), infection (spontaneous bacterial peritonitis), fatigue, anxiety, and depression. Despite significant improvements in palliation of these complications, patients still suffer reduced quality of life and must confront the fact that their disease will often inexorably progress to death. Liver transplantation is a valid option in this setting, increasing the duration of survival and palliating many of the symptoms. However, many patients die waiting for an organ or are not candidates for transplantation due to comorbid illness. Others receive a transplant but succumb to complications of the transplant itself. Patients and families must struggle with simultaneously hoping for a cure while facing a life-threatening illness. Ideally, the combination of palliative care with life-sustaining therapy can maximize the patients' quality and quantity of life. If it becomes clear that life-sustaining therapy is no longer an option, these patients are then already in a system to help them with end-of-life care.

  5. Management of non-alcoholic fatty liver disease in 2015

    PubMed Central

    Malhotra, Neel; Beaton, Melanie D

    2015-01-01

    There is no single pharmacologic therapy that has been approved to treat nonalcoholic fatty liver disease in the general population. The backbone of therapy currently includes intensive lifestyle modification with established targets for diet and weight loss. The use of unsweetened, unfiltered coffee along with limiting high fructose corn syrup have emerged as beneficial dietary recommendations. The use of empiric oral hypoglycemic agents and vitamin E, however, has not been widely accepted. Developing bariatric surgical techniques are promising, but additional studies with long-term follow up are needed before it can be widely recommended. Finally, liver transplantation is an increasingly frequent consideration once complications of end-stage disease have developed. The future treatment of those with nonalcoholic fatty liver disease will likely involve a personalized approach. The importance of the gut microbiome in mediating hepatocyte inflammation and intestinal permeability is emerging and may offer avenues for novel treatment. The study of anti-fibrotic agents such as pentoxifylline and FXR agonists hold promise and new pathways, such as hepatocyte cannabinoid receptor antagonists are being studied. With the incidence of obesity and the metabolic syndrome increasing throughout the developed world, the future will continue to focus on finding novel agents and new applications of existing therapies to help prevent and to mediate the progression of nonalcoholic fatty liver disease. PMID:26730275

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

    PubMed Central

    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

  7. Current and future therapies for inherited cholestatic liver diseases

    PubMed Central

    van der Woerd, Wendy L; Houwen, Roderick HJ; van de Graaf, Stan FJ

    2017-01-01

    Familial intrahepatic cholestasis (FIC) comprises a group of rare cholestatic liver diseases associated with canalicular transport defects resulting predominantly from mutations in ATP8B1, ABCB11 and ABCB4. Phenotypes range from benign recurrent intrahepatic cholestasis (BRIC), associated with recurrent cholestatic attacks, to progressive FIC (PFIC). Patients often suffer from severe pruritus and eventually progressive cholestasis results in liver failure. Currently, first-line treatment includes ursodeoxycholic acid in patients with ABCB4 deficiency (PFIC3) and partial biliary diversion in patients with ATP8B1 or ABCB11 deficiency (PFIC1 and PFIC2). When treatment fails, liver transplantation is needed which is associated with complications like rejection, post-transplant hepatic steatosis and recurrence of disease. Therefore, the need for more and better therapies for this group of chronic diseases remains. Here, we discuss new symptomatic treatment options like total biliary diversion, pharmacological diversion of bile acids and hepatocyte transplantation. Furthermore, we focus on emerging mutation-targeted therapeutic strategies, providing an outlook for future personalized treatment for inherited cholestatic liver diseases. PMID:28223721

  8. Crosstalk between the gut and the liver via susceptibility loci: Novel advances in inflammatory bowel disease and autoimmune liver disease.

    PubMed

    Li, Xinyang; Shen, Jun; Ran, Zhihua

    2017-02-01

    Inflammatory bowel disease (IBD) is an autoimmune disorder characterized by chronic, relapsing intestinal inflammation. Autoimmune liver disease (AILD) may be involved in IBD as an extra-intestinal manifestation (EIM). Epidemiologic and anatomic evidence have demonstrated an intimate crosstalk between the gut and the liver. In this review, we briefly introduced nine groups of susceptibility loci shared by inflammatory bowel and autoimmune liver disease for the first time. The genome-wide association studies (GWAS) evidence of pathways involving crosstalk between the gut and the liver is clarified and explained. It has been found that HNF4-α, GPR35, MST1R, CARD9, IL2/IL21/IL2R, BACH2, TNFRSF14, MAdCAM-1, and FUT2 are the genes involved in tight junction formation, macrophage function, T helper cell or Treg cell cycle and function, TNF secretion, lymphocyte homing or intestinal dysbiosis, respectively. The intimate crosstalk between the gut and liver in immunity is also highlighted and discussed in this review.

  9. Chlorpromazine-induced cholestatic liver disease with ductopenia.

    PubMed

    Chlumská, A; Curík, R; Boudová, L; Mukensnabl, P; Klvana, P

    2001-07-01

    We describe a 30-year-old pregnant woman in whom cholestatic liver disease developed 16 resp. 18 days after the medication of chlorprothixeni hydrochloridum and chlorpromazine treatment in the 33rd week of pregnancy. Clinically, the course was characterized by severe jaundice lasting 10 months, fever, pruritus, high serum alkaline phosphatase level, transient aminotransferase elevation, and hypercholesterolemia. The pregnancy was terminated in the 35th week by cesarean section with the birth of a premature female newborn without any signs of liver damage. The histological examination of the mother's liver revealed ductopenia, defined by the absence of interlobular bile ducts in at least 50% of the small portal tracts, and long-standing cholestasis with pseudoxanthomatous transformation of hepatocytes and ductular epithelia, and small lobular xanthomas. The jaundice resolved very slowly after ursodeoxycholic acid therapy. The liver function tests 26 months after the onset of jaundice showed only a slight elevation of alkaline phosphatase and aminotransferases. In the control liver biopsy, non-active periportal and septal fibrosis without signs of cholestasis was seen. To our knowledge this is the sixth report to document chlorpromazine-induced ductopenia in pregnancy and the first to describe a newborn without any liver damage.

  10. Recent developments in the management of idiopathic cholestatic liver disease.

    PubMed

    Imam, Mohamad H; Weeding, Emma; Lindor, Keith D

    2012-01-01

    In recent years, the clinical management of patients with idiopathic cholestatic liver disease has shown significant progress. Advancement of diagnostic and therapeutic approaches and better understanding of the pathophysiology underlying these diseases have all contributed considerably to this progress. In this review, we aim to touch briefly on several developments that have occurred in this regard and to discuss novel findings and interventions valuable to clinical practice.

  11. Genome-Wide Association Studies and Liver Disease

    PubMed Central

    Speliotes, Elizabeth K.

    2016-01-01

    Sequencing of the human genome has opened up many opportunities to learn about our own genetic susceptibilities to disease. In this Foreword to this issue of Seminars in Liver Disease, I provide some required background to understanding genome-wide association analyses in general, including a list of terms (Table 1) often used in such studies. Five areas of particular significance are then reviewed in detail in the articles that follow. PMID:26676811

  12. Gut-Liver Axis, Nutrition, and Non Alcoholic Fatty Liver Disease

    PubMed Central

    Kirpich, Irina A.; Marsano, Luis S.; McClain, Craig J.

    2015-01-01

    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. PMID:26151226

  13. Gut-liver axis, nutrition, and non-alcoholic fatty liver disease.

    PubMed

    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.

  14. A case of veno-occlusive disease following liver transplantation.

    PubMed

    Chen, Hong; Wang, Xu; Fan, Tieyan; Li, Jun; Wang, Letian; Shen, Zhongyang

    2014-01-01

    The present case report describes the diagnosis and treatment of a patient with veno-occlusive disease (VOD) following liver transplantation. Combining the clinical data and relevant literature, the study aimed to consider the causes of VOD following liver transplantation, and the pathogenesis, clinical diagnosis and auxiliary examination features of VOD. A 42-year-old man who had a long history of taking traditional Chinese medicine (essential components unknown) underwent an orthotropic liver transplantation on January 14, 2011, due to small venous occlusion disease of the liver. The patient was treated with tacrolimus as an antirejection therapy following the surgery, and gradually developed right upper quadrant pain and fatigue. The examination results were consistent with the diagnostic standards for VOD. Following treatment with methylprednisolone, the patient was treated with alprostadil and Danhong injections. Forty days later, the patient's total bilirubin (TBIL) level was observed to have decreased significantly, the liver function had returned to normal and the ascites had decreased, but had not completely disappeared. The patient then underwent a transjugular intrahepatic portosystemic shunt (TIPS) procedure, following which the ascites were shown to have completely disappeared.

  15. Management of Non-alcoholic Fatty Liver Disease and Steatohepatitis

    PubMed Central

    Le, Thuy-Anh; Loomba, Rohit

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) is the most common cause of abnormal liver enzymes and chronic liver disease in the US with expected rise in incidence paralleling the epidemic of obesity. A subset of patients with NAFLD have the progressive form of NAFLD that is termed non-alcoholic steatohepatitis (NASH), which is characterized by specific features on liver histology including hepatocellular ballooning degeneration, lobular inflammation, and zone-3 steatosis with or without peri-sinusoidal fibrosis. Non-alcoholic steatohepatitis can progress to cirrhosis and result in liver-related death. Insulin resistance is commonly seen in patients with NASH and often co-exists with other features of the metabolic syndrome including hypertension, hyperlipidemia, and obesity. Although weight loss through lifestyle modifications including dietary changes and increased physical exercise remains the backbone of management of NASH, it has proved challenging for patients to achieve and maintain weight loss goals. Thus, it is often necessary to couple lifestyle changes with another pharmacologic treatment for NASH. Insulin sensitizers including the biguanides (metformin), thiazolidinediones (pioglitazone and rosiglitazone), and glucagon-like peptide-1 receptor agonists (exenatide) are large groups of medications that have been studied for the treatment of NASH. Other agents with anti-inflammatory, anti-apoptotic, or anti-fibrotic properties which have been studied in NASH include vitamin E, pentoxifylline, betaine, and ursodeoxycholic acid. This review will provide a detailed summary on the clinical data behind the full spectrum of treatments that exist for NASH and suggest management recommendations. PMID:25755424

  16. Pathophysiology and Management of Alcoholic Liver Disease: Update 2016

    PubMed Central

    Stickel, Felix; Datz, Christian; Hampe, Jochen; Bataller, Ramon

    2017-01-01

    Alcoholic liver disease (ALD) is a leading cause of cirrhosis, liver cancer, and acute and chronic liver failure and as such causes significant morbidity and mortality. While alcohol consumption is slightly decreasing in several European countries, it is rising in others and remains high in many countries around the world. The pathophysiology of ALD is still incompletely understood but relates largely to the direct toxic effects of alcohol and its main intermediate, acetaldehyde. Recently, novel putative mechanisms have been identified in systematic scans covering the entire human genome and raise new hypotheses on previously unknown pathways. The latter also identify host genetic risk factors for significant liver injury, which may help design prognostic risk scores. The diagnosis of ALD is relatively easy with a panel of well-evaluated tests and only rarely requires a liver biopsy. Treatment of ALD is difficult and grounded in abstinence as the pivotal therapeutic goal; once cirrhosis is established, treatment largely resembles that of other etiologies of advanced liver damage. Liver transplantation is a sound option for carefully selected patients with cirrhosis and alcoholic hepatitis because relapse rates are low and prognosis is comparable to other etiologies. Still, many countries are restrictive in allocating donor livers for ALD patients. Overall, few therapeutic options exist for severe ALD. However, there is good evidence of benefit for only corticosteroids in severe alcoholic hepatitis, while most other efforts are of limited efficacy. Considering the immense burden of ALD worldwide, efforts of medical professionals and industry partners to develop targeted therapies in ALF has been disappointingly low. PMID:28274107

  17. The global burden of liver disease: the major impact of China.

    PubMed

    Wang, Fu-Sheng; Fan, Jian-Gao; Zhang, Zheng; Gao, Bin; Wang, Hong-Yang

    2014-12-01

    Liver disease is a major cause of illness and death worldwide. In China alone, liver diseases, primarily viral hepatitis (predominantly hepatitis B virus [HBV]), nonalcoholic fatty liver disease, and alcoholic liver disease, affect approximately 300 million people. The establishment of the Expanded Program on Immunization in 1992 has resulted in a substantial decline in the number of newly HBV-infected patients; however, the number of patients with alcoholic and nonalcoholic fatty liver diseases is rising at an alarming rate. Liver cancer, one of the most deadly cancers, is the second-most common cancer in China. Approximately 383,000 people die from liver cancer every year in China, which accounts for 51% of the deaths from liver cancer worldwide. Over the past 10 years, China has made some significant efforts to shed its "leader in liver diseases" title by investing large amounts of money in funding research, vaccines, and drug development for liver diseases and by recruiting many Western-trained hepatologists and scientists. Over the last two decades, hepatologists and scientists in China have made significant improvements in liver disease prevention, diagnosis, management, and therapy. They have been very active in liver disease research, as shown by the dramatic increase in the number of publications in Hepatology. Nevertheless, many challenges remain that must be tackled collaboratively. In this review, we discuss the epidemiology and characteristics of liver diseases and liver-related research in China.

  18. The emerging role of autophagy in alcoholic liver disease.

    PubMed

    Ding, Wen-Xing; Manley, Sharon; Ni, Hong-Min

    2011-05-01

    Autophagy is a highly conserved intracellular catabolic pathway that degrades cellular long-lived proteins and organelles. Autophagy is normally activated in response to nutrient deprivation and other stresses as a cell survival mechanism. Accumulating evidence indicates that autophagy plays a critical role in liver pathophysiology, in addition to maintaining hepatic energy and nutrient balance. Alcohol consumption causes hepatic metabolic changes, oxidative stress, accumulation of lipid droplets and damaged mitochondria; all of these can be regulated by autophagy. This review summarizes the recent findings about the role and mechanisms of autophagy in alcoholic liver disease (ALD), and the possible intervention for treating ALD by modulating autophagy.

  19. Marchiafava-Bignami and Alcohol Related Acute Polyneuropathy: The Cooccurrence of Two Rare Entities

    PubMed Central

    Boloursaz, Samine; Nekooei, Sirous; Seilanian Toosi, Farrokh; Rezaei-Dalouei, Hossein; Davachi, Behrooz; Kazemi, Sahar

    2016-01-01

    Objectives. The aim of this article is to represent the first reported case with cooccurrence of two rare alcohol related complications. Case Report. We report a 38-year-old man with chronic alcoholism who presented with both cranial and peripheral nerve palsy. On MRI examination characteristic findings of Marchiafava-Bignami disease were recognized. Discussion. Marchiafava-Bignami disease (MBD) is a rare complication of long-term, heavy alcohol abuse that has characteristic MRI findings. Acute alcohol related polyneuropathy (AARP) is another rare and not-well-understood complication of chronic alcohol abuse. We could not find any previous report of the cooccurrence of these two complications in the literature. PMID:27668107

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

    SciTech Connect

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

    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.

  1. Pathophysiology of lipid droplet proteins in liver diseases.

    PubMed

    Carr, Rotonya M; Ahima, Rexford S

    2016-01-15

    Cytosolic lipid droplets (LDs) are present in most cell types, and consist of a core comprising neutral lipids, mainly triglycerides and sterol esters, surrounded by a monolayer of phospholipids. LDs are heterogeneous in their structure, chemical composition, and tissue distribution. LDs are coated by several proteins, including perilipins and other structural proteins, lipogenic enzymes, lipases and membrane-trafficking proteins. Five proteins of the perilipin (PLIN) family (PLIN1 (perilipin), PLIN2 (adipose differentiation-related protein), PLIN3 (tail-interacting protein of 47kDa), PLIN4 (S3-12), and PLIN5 (myocardial lipid droplet protein)), are associated with LD formation. More recently, the CIDE family of proteins, hypoxia-inducible protein 2 (HIG2), and patanin-like phospholipase domain-containing 3 (PNPLA3) have also gained attention in hepatic LD biology. Evidence suggests that LD proteins are involved in the pathophysiology of fatty liver diseases characterized by excessive lipid accumulation in hepatocytes. This review article will focus on how hepatic LDs and their associated proteins are involved in the pathogenesis of three chronic liver conditions: hepatitis C virus infection, non-alcoholic fatty liver disease, and alcoholic liver disease.

  2. NK Cell Subtypes as Regulators of Autoimmune Liver Disease

    PubMed Central

    2016-01-01

    As major components of innate immunity, NK cells not only exert cell-mediated cytotoxicity to destroy tumors or infected cells, but also act to regulate the functions of other cells in the immune system by secreting cytokines and chemokines. Thus, NK cells provide surveillance in the early defense against viruses, intracellular bacteria, and cancer cells. However, the effecter function of NK cells must be exquisitely controlled to prevent inadvertent attack against normal “self” cells. In an organ such as the liver, where the distinction between immunotolerance and immune defense against routinely processed pathogens is critical, the plethora of NK cells has a unique role in the maintenance of homeostasis. Once self-tolerance is broken, autoimmune liver disease resulted. NK cells act as a “two-edged weapon” and even play opposite roles with both regulatory and inducer activities in the hepatic environment. That is, NK cells act not only to produce inflammatory cytokines and chemokines, but also to alter the proliferation and activation of associated lymphocytes. However, the precise regulatory mechanisms at work in autoimmune liver diseases remain to be identified. In this review, we focus on recent research with NK cells and their potential role in the development of autoimmune liver disease. PMID:27462349

  3. Stem cells for the treatment of liver disease.

    PubMed

    Allen, K J; Buck, N E; Williamson, R

    2005-12-01

    Stem cells tantalise. They alone have the capacity to divide exponentially, recreate the stem cell compartment as well as create differentiated cells to build tissues. They should be the natural candidates to provide a renewable source of cells for transplantation. Does the reality support the promise of this exciting alternative to conventional therapies for metabolic and degenerative liver disease? Can techniques be developed to provide the large number of cells that could be required? Must there be "space" in the liver to accept the cells? To what extent is the liver immunoprivileged, and is immunosuppression necessary for stem cell therapy? Is it better to use haematopoietic stem cells, fetal stem cells, mesenchymal cells, embryonic stem cells, hepatocytes or all of the above, but for different disease indications? This paper discusses why the exploration of stem cells for the treatment of liver disease is of great potential, and delineates some of the hurdles that need to be overcome before patients see benefits from laboratory-based research into stem cell transplantation and function.

  4. Glucocorticoids and non-alcoholic fatty liver disease.

    PubMed

    Woods, Conor P; Hazlehurst, Jonathon M; Tomlinson, Jeremy W

    2015-11-01

    Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the global obesity and metabolic disease epidemic and is rapidly becoming the leading cause of liver cirrhosis and indication for liver transplantation worldwide. The hallmark pathological finding in NAFLD is excess lipid accumulation within hepatocytes, but it is a spectrum of disease ranging from benign hepatic steatosis to steatohepatitis through to fibrosis, cirrhosis and risk of hepatocellular carcinoma. The exact pathophysiology remains unclear with a multi-hit hypothesis generally accepted as being required for inflammation and fibrosis to develop after initial steatosis. Glucocorticoids have been implicated in the pathogenesis of NAFLD across all stages. They have a diverse array of metabolic functions that have the potential to drive NAFLD acting on both liver and adipose tissue. In the fasting state, they are able to mobilize lipid, increasing fatty acid delivery and in the fed state can promote lipid accumulation. Their action is controlled at multiple levels and in this review will outline the evidence base for the role of GCs in the pathogenesis of NAFLD from cell systems, rodent models and clinical studies and describe interventional strategies that have been employed to modulate glucocorticoid action as a potential therapeutic strategy.

  5. Liver Transplant

    MedlinePlus

    ... Home > Your Liver > Liver Disease Information > Liver Transplant Liver Transplant Explore this section to learn more about ... resource. www.paulcox.com.au Why is the liver important? The liver is the second largest organ ...

  6. A novel cause for abnormal liver function tests in pregnancy and the puerperium: non-alcoholic fatty liver disease.

    PubMed

    Page, L M; Girling, J C

    2011-11-01

    Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease in the western world, but has never been reported in pregnancy before. We suggest that NAFLD should also be considered as a cause for abnormal liver function tests during pregnancy. As NAFLD is driven by insulin resistance, it is biologically plausible that pregnancy may reveal previously subclinical disease. Obstetricians have a vital role in optimising maternal health during and after pregnancy and therefore we need to include NAFLD in the differential diagnosis for abnormal liver function tests and recommend lifestyle modifications that may prevent progression to cirrhosis and hepatocellular carcinoma.

  7.  Most overweight and obese Indian children have nonalcoholic fatty liver disease.

    PubMed

    Pawar, Sunil V; Zanwar, Vinay G; Choksey, Ajay S; Mohite, Ashok R; Jain, Samit S; Surude, Ravindra G; Contractor, Qais Q; Rathi, Pravin M; Verma, Ravi U; Varthakavi, Premlata K

     Background and rationale. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of pediatric liver disease in western countries. Its prevalence in Indian subcontinent is not well studied.

  8. Fatty Liver Disease is Associated with Underlying Cardiovascular Disease in HIV-Infected Persons

    PubMed Central

    Crum-Cianflone, Nancy; Krause, David; Wessman, Dylan; Medina, Sheila; Stepenosky, James; Brandt, Carolyn; Boswell, Gilbert

    2010-01-01

    Background Cardiovascular disease is an increasing concern among HIV-infected persons and their providers. We determined if fatty liver disease is a marker for underlying coronary atherosclerosis among HIV-infected persons. Methods We performed a cross-sectional study among HIV-infected adults to evaluate the prevalence of and factors, including fatty liver disease, associated with subclinical coronary atherosclerosis. All participants underwent computed tomography for determination of coronary artery calcium (CAC; positive defined as a score >0) and fatty liver disease (defined as a liver-to-spleen ratio <1.0). Factors associated with CAC were determined using multivariate logistic regression models. Results We studied 223 HIV-infected adults with a median age of 43 years (IQR 36–50), 96% were male, and 49% were Caucasian. Median CD4 count was 586 cells/mm3, and 83% were receiving antiretroviral medications. Seventy-five (34%) had a positive CAC score, and 29 (13%) subjects had fatty liver disease. Among those with CAC scores of 0, 1–100, >100, the percentage with concurrent fatty liver disease was 8%, 18%, and 41%, respectively (p=0.001). In the multivariate model, CAC was associated with increasing age (OR 4.3 per 10 years, p<0.01), hypertension (OR 2.6, p<0.01), and fatty liver disease (OR 3.8, p<0.01). Conclusions Coronary atherosclerosis as detected by CAC is prevalent among young HIV-infected persons. The detection of fatty liver disease among HIV-infected adults should prompt consideration for assessment for underlying cardiovascular disease and risk factor reduction. PMID:21251186

  9. NHE1 deficiency in liver: implications for non-alcoholic fatty liver disease.

    PubMed

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

    2014-07-25

    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.

  10. Assessment of Liver Viscoelasticity for the Diagnosis of Early Stage Fatty Liver Disease Using Transient Elastography

    NASA Astrophysics Data System (ADS)

    Remenieras, Jean-Pierre; Dejobert, Maelle; Bastard, Cécile; Miette, Véronique; Perarnau, Jean-Marc; Patat, Frédéric

    Nonalcoholic fatty liver disease (NAFLD) is characterized by accumulation of fat within the Liver. The main objective of this work is (1) to evaluate the feasibility of measuring in vivo in the liver the shear wave phase velocity dispersion cs(ω) between 20 Hz and 90 Hz using vibration-controlled transient elastography (VCTE); (2) to estimate through the rheological Kelvin-Voigt model the shear elastic μ and shear viscosity η modulus; (3) to correlate the evolution of these viscoelastic parameters on two patients at Tours Hospital with the hepatic fat percentage measured with T1-weighted gradient-echo in-and out-phase MRI sequence. For the first volunteer who has 2% of fat in the liver, we obtained μ = 1233 ± 133 Pa and η = 0.5 ± 0.4 Pa.s. For the patient with 22% of fat, we measure μ = 964 ± 91 Pa and η = 1.77 ± 0.3 Pa.s. In conclusion, this novel method showed to be sensitive in characterizing the visco-elastic properties of fatty liver.

  11. Nutrition and Physical Activity in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Oliveira, Claudia P.; de Lima Sanches, Priscila; de Abreu-Silva, Erlon Oliveira; Marcadenti, Aline

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and it is associated with other medical conditions such as diabetes mellitus, metabolic syndrome, and obesity. The mechanisms of the underlying disease development and progression are not completely established and there is no consensus concerning the pharmacological treatment. In the gold standard treatment for NAFLD weight loss, dietary therapy, and physical activity are included. However, little scientific evidence is available on diet and/or physical activity and NAFLD specifically. Many dietary approaches such as Mediterranean and DASH diet are used for treatment of other cardiometabolic risk factors such as insulin resistance and type-2 diabetes mellitus (T2DM), but on the basis of its components their role in NAFLD has been discussed. In this review, the implications of current dietary and exercise approaches, including Brazilian and other guidelines, are discussed, with a focus on determining the optimal nonpharmacological treatment to prescribe for NAFLD. PMID:26770987

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

    PubMed Central

    Li, Fengyuan; Duan, Kangmin; Wang, Cuiling; McClain, Craig; Feng, Wenke

    2016-01-01

    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. PMID:26839540

  13. 47Calcium absorption in parenchymatous and biliary liver disease

    PubMed Central

    Whelton, Michael J.; Kehayoglou, A. K.; Agnew, J. E.; Turnberg, L. A.; Sherlock, Sheila

    1971-01-01

    As measured by whole body retention of isotopic calcium given in milk, absorption of calcium was impaired in 10 patients with chronic parenchymal non-biliary liver disease who were icteric. Mean absorption was normal in 15 patients with parenchymal liver disease who were anicteric although some individual patients absorbed less than any of the controls. Depressed absorption of calcium was seen in 10 patients with primary biliary cirrhosis and seven patients with intra- or extra-hepatic biliary obstructive disease. The most likely cause for this malabsorption is reduced bile salt secretion into the intestinal lumen which impairs vitamin D and fat absorption. The finding that parenteral vitamin D increased calcium absorption to normal levels in five patients with primary biliary cirrhosis suggests that deficiency of this vitamin is a major and correctable factor leading to calcium malabsorption in such patients. Precipitation of calcium salts by excess intraluminal fat appears to be a further possible factor reducing calcium absorption in these patients. These findings emphasize the importance of parenteral vitamin D therapy in patients with chronic obstructive biliary diseases. They also suggest that certain patients with chronic parenchymatous liver disease, particularly those who are icteric, may also occasionally require therapy with vitamin D. PMID:5171934

  14. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    PubMed Central

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. PMID:22654421

  15. Animal models of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Takahashi, Yoshihisa; Soejima, Yurie; Fukusato, Toshio

    2012-05-21

    Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages.

  16. Apoptosis as a Mechanism for Liver Disease Progression

    PubMed Central

    Guicciardi, Maria Eugenia; Gores, Gregory J.

    2011-01-01

    Hepatocyte injury is ubiquitous in clinical practice, and the mode of cell death associated with this injury is often apoptosis, especially by death receptors. Information from experimental systems demonstrates that hepatocyte apoptosis is sufficient to cause liver hepatic fibrogenesis. The mechanisms linking hepatocyte apoptosis to hepatic fibrosis remain incompletely understood, but likely relate to engulfment of apoptotic bodies by professional phagocytic cells and stellate cells, and release of mediators by cells undergoing apoptosis. Inhibition of apoptosis with caspase inhibitors has demonstrated beneficial effects in murine models of hepatic fibrosis. Recent studies implicating Toll-like receptor 9 (TLR9) in liver injury and fibrosis are also of particular interest. Engulfment of apoptotic bodies is one mechanism by which the TLR9 ligand (CpG DNA motifs) could be delivered to this intracellular receptor. These concepts suggest therapy focused on interrupting the cellular mechanisms linking apoptosis to fibrosis would be useful in human liver diseases. PMID:20960379

  17. Role of bioactive fatty acids in nonalcoholic fatty liver disease.

    PubMed

    Juárez-Hernández, Eva; Chávez-Tapia, Norberto C; Uribe, Misael; Barbero-Becerra, Varenka J

    2016-08-02

    Nonalcoholic fatty liver disease (NAFLD) is characterized by fat deposition in hepatocytes, and a strong association with nutritional factors. Dietary fatty acids are classified according to their biochemical properties, which confer their bioactive roles. Monounsaturated fatty acids have a dual role in various human and murine models. In contrast, polyunsaturated fatty acids exhibit antiobesity, anti steatosic and anti-inflammatory effects. The combination of these forms of fatty acids-according to dietary type, daily intake and the proportion of n-6 to n-3 fats-can compromise hepatic lipid metabolism. A chemosensory rather than a nutritional role makes bioactive fatty acids possible biomarkers for NAFLD. Bioactive fatty acids provide health benefits through modification of fatty acid composition and modulating the activity of liver cells during liver fibrosis. More and better evidence is necessary to elucidate the role of bioactive fatty acids in nutritional and clinical treatment strategies for patients with NAFLD.

  18. Assessing an AI knowledge-base for asymptomatic liver diseases.

    PubMed

    Babic, A; Mathiesen, U; Hedin, K; Bodemar, G; Wigertz, O

    1998-01-01

    Discovering not yet seen knowledge from clinical data is of importance in the field of asymptomatic liver diseases. Avoidance of liver biopsy which is used as the ultimate confirmation of diagnosis by making the decision based on relevant laboratory findings only, would be considered an essential support. The system based on Quinlan's ID3 algorithm was simple and efficient in extracting the sought knowledge. Basic principles of applying the AI systems are therefore described and complemented with medical evaluation. Some of the diagnostic rules were found to be useful as decision algorithms i.e. they could be directly applied in clinical work and made a part of the knowledge-base of the Liver Guide, an automated decision support system.

  19. Chronic cholestatic liver diseases: clues from histopathology for pathogenesis.

    PubMed

    Pollheimer, Marion J; Fickert, Peter; Stieger, Bruno

    2014-06-01

    Chronic cholestatic liver diseases include fibrosing cholangiopathies such as primary biliary cirrhosis or primary sclerosing cholangitis. These and related cholangiopathies clearly display pathologies associated with (auto)immunologic processes. As the cholangiocyte's apical membrane is exposed to the toxic actions of the bile fluid, the interaction of bile with cholangiocytes and the biliary tree in general must be considered to completely understand the pathogenesis of cholangiopathies. While the molecular processes involved in the hepatocellular formation of bile are well understood in both normal and pathophysiologic conditions, those in the bile ducts of normal liver and in livers with cholangiopathies lag behind. This survey highlights key mechanisms known to date that are important for the formation of bile by hepatocytes and its modification by the biliary tree. It also delineates the clinical pathophysiologic findings for cholangiopathies and puts them in perspective with current experimental models to reveal the pathogenesis of cholangiopathies and develop novel therapeutic approaches.

  20. Accumulation of NKT cells in Progressive Nonalcoholic Fatty Liver Disease

    PubMed Central

    Syn, Wing-Kin; Oo, Ye Htun; Pereira, Thiago A; Karaca, Gamze F; Jung, Youngmi; Omenetti, Alessia; Witek, Rafal P; Choi, Steve S; Guy, Cynthia D; Fearing, Caitlin M; Teaberry, Vanessa; Pereira, Fausto E L; Adams, David H; Diehl, Anna Mae

    2010-01-01

    Liver inflammation is greater in nonalcoholic steatohepatitis (NASH) than steatosis, suggesting that immune responses contribute to NAFLD progression. Livers normally contain many natural killer T (NKT) cells which produce factors that modulate inflammatory and fibrogenic responses. Such cells are relatively depleted in steatosis, but their status in more advanced NAFLD is uncertain. We hypothesized that NKT cells accumulate and promote fibrosis progression in NASH. We aimed to determine if livers become enriched with NKT cells during NASH-related fibrosis; identify responsible mechanisms; and assess if NKT cells stimulate fibrogenesis. NKT cells were analyzed in wild type mice and Ptc+/-mice with an overly-active Hedgehog (Hh) pathway, before and after feeding methionine choline deficient (MCD) diets to induce NASH-related fibrosis; effects of NKT cell-derived factors on hepatic stellate cells (HSC) were examined and fibrogenesis was evaluated in CD1d-deficient mice which lack NKT cells; NKT cells were quantified in human cirrhotic and non-diseased livers. During NASH-related fibrogenesis in wild-type mice, Hh pathway activation occurred, leading to induction of factors that promoted NKT cell recruitment, retention and viability, plus liver enrichment with NKT cells. Ptc+/- mice accumulated more NKT cells and developed worse liver fibrosis; CD1d-deficient mice which lack NKT cells were protected from fibrosis. NKT cell-conditioned medium stimulated HSC to become myofibroblastic. Liver explants were 2-fold enriched with NKT cells in patients with non-NASH cirrhosis, and 4-fold enriched in patients with NASH-cirrhosis. In conclusion, Hh pathway activation leads to hepatic enrichment with NKT cells that contribute to fibrosis progression in NASH. PMID:20512988

  1. Altered Arsenic Disposition in Experimental Nonalcoholic Fatty Liver Disease

    PubMed Central

    Canet, Mark J.; Hardwick, Rhiannon N.; Lake, April D.; Kopplin, Michael J.; Scheffer, George L.; Klimecki, Walter T.; Gandolfi, A. Jay

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is represented by a spectrum of liver pathologies ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Liver damage sustained in the progressive stages of NAFLD may alter the ability of the liver to properly metabolize and eliminate xenobiotics. The purpose of the current study was to determine whether NAFLD alters the disposition of the environmental toxicant arsenic. C57BL/6 mice were fed either a high-fat or a methionine-choline-deficient diet to model simple steatosis and NASH, respectively. At the conclusion of the dietary regimen, all mice were given a single oral dose of either sodium arsenate or arsenic trioxide. Mice with NASH excreted significantly higher levels of total arsenic in urine (24 h) compared with controls. Total arsenic in the liver and kidneys of NASH mice was not altered; however, NASH liver retained significantly higher levels of the monomethyl arsenic metabolite, whereas dimethyl arsenic was retained significantly less in the kidneys of NASH mice. NASH mice had significantly higher levels of the more toxic trivalent form in their urine, whereas the pentavalent form was preferentially retained in the liver of NASH mice. Moreover, hepatic protein expression of the arsenic biotransformation enzyme arsenic (3+ oxidation state) methyltransferase was not altered in NASH animals, whereas protein expression of the membrane transporter multidrug resistance-associated protein 1 was increased, implicating cellular transport rather than biotransformation as a possible mechanism. These results suggest that NASH alters the disposition of arsenical species, which may have significant implications on the overall toxicity associated with arsenic in NASH. PMID:22699396

  2. Liver disease associated with occupational exposure to the solvent dimethylformamide

    SciTech Connect

    Redlich, C.A.; Beckett, W.S.; Sparer, J.; Barwick, K.W.; Riely, C.A.; Miller, H.; Sigal, S.L.; Shalat, S.L.; Cullen, M.R.

    1988-05-01

    An attempt is made to characterize an outbreak of liver disease among workers in a fabric coating factory; and to determine the outbreak's cause and natural history and strategies for clinical recognition, treatment, and prevention. Fifty-eight of sixty-six workers participated in the study. All had standard liver function tests at least once. Forty-six workers completed a questionnaire; 27 had more extensive clinical evaluation for recognized liver abnormalities. A plant-wide outbreak of liver disease was recognized after a new employee presented with signs and symptoms of hepatitis. Evaluation of the worksite showed that dimethylformamide, a widely used industrial solvent and known hepatotoxin, was being used to coat fabric in poorly ventilated areas without appropriate skin protection. No other major hepatotoxic exposure was identified. Overall, 36 of 58 (62%) workers tested had elevations of either aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels. Enzyme abnormalities occurred almost exclusively in production workers (35 of 46 were abnormal), whereas only 1 of 12 nonproduction workers showed any elevations in enzyme levels (P less than 0.0001). Serologic tests excluded known infectious causes of hepatitis in all but 2 workers and changes characteristic of toxic liver injury were confirmed by histologic examinations of biopsy specimens from 4 workers. The ratio of AST to ALT levels was one or less in all but 1 worker. After modification of work practices and removal of workers most severely affected from exposure, improvement in liver enzyme abnormalities and symptoms in most patients were seen, although some patients showed persistent elevations of enzyme levels.

  3. Update on Berberine in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Liu, Yang; Zhang, Li; Song, Haiyan

    2013-01-01

    Berberine (BBR), an active ingredient from nature plants, has demonstrated multiple biological activities and pharmacological effects in a series of metabolic diseases including nonalcoholic fatty liver disease (NAFLD). The recent literature points out that BBR may be a potential drug for NAFLD in both experimental models and clinical trials. This review highlights important discoveries of BBR in this increasing disease and addresses the relevant targets of BBR on NAFLD which links to insulin pathway, adenosine monophosphate-activated protein kinase (AMPK) signaling, gut environment, hepatic lipid transportation, among others. Developing nuanced understanding of the mechanisms will help to optimize more targeted and effective clinical application of BBR for NAFLD. PMID:23843872

  4. Liver biopsy histopathology for diagnosis of Johne's disease in sheep.

    PubMed

    Smith, S L; Wilson, P R; Collett, M G; Heuer, C; West, D M; Stevenson, M; Chambers, J P

    2014-09-01

    Sheep with Johne's disease develop epithelioid macrophage microgranulomas, specific to Mycobacterium avium subsp. paratuberculosis (Map) infection, in the terminal ileum, mesenteric lymph nodes, and organs distant to the alimentary tract such as the liver. The objectives of this study were to determine whether liver pathology was present in ewes affected by Map and whether liver cores provide adequate tissue for this potential diagnostic marker. One hundred and twenty-six adult, low body condition ewes were euthanized, necropsied, and underwent simulated liver biopsy. Ileal lesions typical of Map were found in 60 ewes. Hepatic epithelioid microgranulomas were observed in all ewes with Type 3b (n = 40) and 82% (n = 11) with Type 3c ileal lesions. None were found in ewes unaffected by Map or with Type 1, 2, or 3a ileal lesions. Liver biopsy core samples provided adequate tissue for histopathology with a sensitivity and specificity of 96% (95% confidence interval [CI], 0.87-0.99) and 100% (95% CI, 0.95-1), respectively for detection of types 3b and 3c ileal lesions.

  5. Stereotactic ablative radiotherapy for oligometastatic disease in liver.

    PubMed

    Kim, Myungsoo; Son, Seok Hyun; Won, Yong Kyun; Kay, Chul Seung

    2014-01-01

    Liver metastasis in solid tumors, including colorectal cancer, is the most frequent and lethal complication. The development of systemic therapy has led to prolonged survival. However, in selected patients with a finite number of discrete lesions in liver, defined as oligometastatic state, additional local therapies such as surgical resection, radiofrequency ablation, cryotherapy, and radiotherapy can lead to permanent local disease control and improve survival. Among these, an advance in radiation therapy made it possible to deliver high dose radiation to the tumor more accurately, without impairing the liver function. In recent years, the introduction of stereotactic ablative radiotherapy (SABR) has offered even more intensive tumor dose escalation in a few fractions with reduced dose to the adjacent normal liver. Many studies have shown that SABR for oligometastases is effective and safe, with local control rates widely ranging from 50% to 100% at one or two years. And actuarial survival at one and two years has been reported ranging from 72% to 94% and from 30% to 62%, respectively, without severe toxicities. In this paper, we described the definition and technical aspects of SABR, clinical outcomes including efficacy and toxicity, and related parameters after SABR in liver oligometastases from colorectal cancer.

  6. Intrahepatic synthese of immunoglobulin G in chronic liver disease.

    PubMed

    Kronborg, I J; Knopf, P M

    1980-04-01

    A method has been developed to measure the in vitro production of immunoglobulin (Ig) by liver biopsy specimens. Five to 30 mg of liver tissue was cultured for 24 h in Dulbecco's modified Eagle's medium/10% foetal calf serum (FCS) containing radiolabelled leucine (L-[4,5-3H] leucine). The culture medium was collected, centrifuged and the supernatant dialysed to remove labelled leucine. The residual radioactivity was a measure of newly synthesized 3H-labelled proteins released into the medium. The quantity of IgG was determined by immunoprecipitation with monospecific antisera to IgG heavy chains. The presence of IgG in the supernatant was confirmed by chromatography on protein-A Sepharose column. In 6 biopsies without evidence of active inflammation (4 normal and 2 fatty liver by histological criteria) less than 1% of the protein synthesized was IgG. In contrast in the presence of active inflammation in 4 cases of alcoholic hepatitis the IgG percentage ranged from 2 to 6%. Maximal levels of IgG production were detected in 3 cases of chronic active hepatitis (CAH) and ranged from 5 to 30%. The increased Ig synthesis by the liver in alcoholic hepatitis and CAH is presumed to be an index of the intrahepatic host response and may have important implications for mechanisms of liver damage in these diseases.

  7. Alcoholic Liver Disease: Update on the Role of Dietary Fat

    PubMed Central

    Kirpich, Irina A.; Miller, Matthew E.; Cave, Matthew C.; Joshi-Barve, Swati; McClain, Craig J.

    2016-01-01

    Alcoholic liver disease (ALD) spans a spectrum of liver pathology, including fatty liver, alcoholic steatohepatitis, and cirrhosis. Accumulating evidence suggests that dietary factors, including dietary fat, as well as alcohol, play critical roles in the pathogenesis of ALD. The protective effects of dietary saturated fat (SF) and deleterious effects of dietary unsaturated fat (USF) on alcohol-induced liver pathology are well recognized and documented in experimental animal models of ALD. Moreover, it has been demonstrated in an epidemiological study of alcoholic cirrhosis that dietary intake of SF was associated with a lower mortality rates, whereas dietary intake of USF was associated with a higher mortality. In addition, oxidized lipids (dietary and in vivo generated) may play a role in liver pathology. The understanding of how dietary fat contributes to the ALD pathogenesis will enhance our knowledge regarding the molecular mechanisms of ALD development and progression, and may result in the development of novel diet-based therapeutic strategies for ALD management. This review explores the relevant scientific literature and provides a current understanding of recent advances regarding the role of dietary lipids in ALD pathogenesis. PMID:26751488

  8. Olive oil consumption and non-alcoholic fatty liver disease.

    PubMed

    Assy, Nimer; Nassar, Faris; Nasser, Gattas; Grosovski, Maria

    2009-04-21

    The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

  9. GENETIC MODIFIERS OF LIVER DISEASE IN CYSTIC FIBROSIS

    PubMed Central

    Bartlett, Jaclyn R.; Friedman, Kenneth J.; Ling, Simon C.; Pace, Rhonda G.; Bell, Scott C.; Bourke, Billy; Castaldo, Giuseppe; Castellani, Carlo; Cipolli, Marco; Colombo, Carla; Colombo, John L.; Debray, Dominique; Fernandez, Adriana; Lacaille, Florence; Macek, Milan; Rowland, Marion; Salvatore, Francesco; Taylor, Christopher J.; Wainwright, Claire; Wilschanski, Michael; Zemková, Dana; Hannah, William B.; Phillips, M. James; Corey, Mary; Zielenski, Julian; Dorfman, Ruslan; Wang, Yunfei; Zou, Fei; Silverman, Lawrence M.; Drumm, Mitchell L.; Wright, Fred A.; Lange, Ethan M.; Durie, Peter R.; Knowles, Michael R.

    2013-01-01

    Context A subset (~3–5%) of patients with cystic fibrosis (CF) develops severe liver disease (CFLD) with portal hypertension. Objective To assess whether any of 9 polymorphisms in 5 candidate genes (SERPINA1, ACE, GSTP1, MBL2, and TGFB1) are associated with severe liver disease in CF patients. Design, Setting, and Participants A 2-stage design was used in this case–control study. CFLD subjects were enrolled from 63 U.S., 32 Canadian, and 18 CF centers outside of North America, with the University of North Carolina at Chapel Hill (UNC) as the coordinating site. In the initial study, we studied 124 CFLD patients (enrolled 1/1999–12/2004) and 843 CF controls (patients without CFLD) by genotyping 9 polymorphisms in 5 genes previously implicated as modifiers of liver disease in CF. In the second stage, the SERPINA1 Z allele and TGFB1 codon 10 genotype were tested in an additional 136 CFLD patients (enrolled 1/2005–2/2007) and 1088 CF controls. Main Outcome Measures We compared differences in distribution of genotypes in CF patients with severe liver disease versus CF patients without CFLD. Results The initial study showed CFLD to be associated with the SERPINA1 (also known as α1-antiprotease and α1-antitrypsin) Z allele (P value=3.3×10−6; odds ratio (OR) 4.72, 95% confidence interval (CI) 2.31–9.61), and with transforming growth factor β-1 (TGFB1) codon 10 CC genotype (P=2.8×10−3; OR 1.53, CI 1.16–2.03). In the replication study, CFLD was associated with the SERPINA1 Z allele (P=1.4×10−3; OR 3.42, CI 1.54–7.59), but not with TGFB1 codon 10. A combined analysis of the initial and replication studies by logistic regression showed CFLD to be associated with SERPINA1 Z allele (P=1.5×10−8; OR 5.04, CI 2.88–8.83). Conclusion The SERPINA1 Z allele is a risk factor for liver disease in CF. Patients who carry the Z allele are at greater odds (OR ~5) to develop severe liver disease with portal hypertension. PMID:19738092

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

    PubMed

    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

  11. Non-alcoholic fatty liver disease and type 2 diabetes mellitus: the liver disease of our age?

    PubMed

    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.

  12. 78 FR 46351 - Trial Designs and Endpoints for Liver Disease Secondary to Nonalcoholic Steatohepatitis; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-31

    ... HUMAN SERVICES Food and Drug Administration Trial Designs and Endpoints for Liver Disease Secondary to... Research in cosponsorship with the American Association for the Study of Liver Diseases (AASLD) is announcing a 2-day public workshop entitled ``Trial Designs and Endpoints for Liver Disease Secondary...

  13. Pharmacologic therapy for nonalcoholic fatty liver disease in adults.

    PubMed

    Malinowski, Scott S; Byrd, Jennifer S; Bell, Allison M; Wofford, Marion R; Riche, Daniel M

    2013-02-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of triglycerides in hepatocytes in the absence of excessive alcohol intake, ranging in severity from simple steatosis to nonalcoholic steatohepatitis (NASH). Nonalcoholic steatohepatitis can ultimately progress to cirrhosis and hepatocellular carcinoma. NAFLD is associated with cardiometabolic risk factors and is the most common chronic liver disease among adults in the Western Hemisphere. Although simple steatosis is generally considered a self-limiting disease, evidence suggests an increased risk of cardiovascular disease, and, less conclusively, mortality, among individuals with NAFLD and/or NASH. The current standard of care for the treatment of patients with NAFLD focuses on lifestyle interventions, particularly diet and exercise. There is a lack of consensus regarding the most effective and appropriate pharmacologic therapy. A PubMed search was conducted using the medical subject heading terms "fatty liver" and "steatohepatitis." This review focuses on the current pharmacologic options available for treating adults with NAFLD and/or NASH. Continued investigation of drugs or combinations that improve NAFLD progression is crucial. Clinicians, particularly pharmacists, must take an active role in identification and appropriate selection of pharmacotherapy for NAFLD.

  14. Redox Control of Liver Function in Health and Disease

    PubMed Central

    Marí, Montserrat; Colell, Anna; Morales, Albert; von Montfort, Claudia; Garcia-Ruiz, Carmen

    2010-01-01

    Abstract Reactive oxygen species (ROS), a heterogeneous population of biologically active intermediates, are generated as by-products of the aerobic metabolism and exhibit a dual role in biology. When produced in controlled conditions and in limited quantities, ROS may function as signaling intermediates, contributing to critical cellular functions such as proliferation, differentiation, and cell survival. However, ROS overgeneration and, particularly, the formation of specific reactive species, inflicts cell death and tissue damage by targeting vital cellular components such as DNA, lipids, and proteins, thus arising as key players in disease pathogenesis. Given the predominant role of hepatocytes in biotransformation and metabolism of xenobiotics, ROS production constitutes an important burden in liver physiology and pathophysiology and hence in the progression of liver diseases. Despite the recognized role of ROS in disease pathogenesis, the efficacy of antioxidants as therapeutics has been limited. A better understanding of the mechanisms, nature, and location of ROS generation, as well as the optimization of cellular defense strategies, may pave the way for a brighter future for antioxidants and ROS scavengers in the therapy of liver diseases. Antioxid. Redox Signal. 12, 1295—1331. PMID:19803748

  15. Protein-protein interaction network analysis of cirrhosis liver disease

    PubMed Central

    Safaei, Akram; Rezaei Tavirani, Mostafa; Arefi Oskouei, Afsaneh; Zamanian Azodi, Mona; Mohebbi, Seyed Reza; Nikzamir, Abdol Rahim

    2016-01-01

    Aim: Evaluation of biological characteristics of 13 identified proteins of patients with cirrhotic liver disease is the main aim of this research. Background: In clinical usage, liver biopsy remains the gold standard for diagnosis of hepatic fibrosis. Evaluation and confirmation of liver fibrosis stages and severity of chronic diseases require a precise and noninvasive biomarkers. Since the early detection of cirrhosis is a clinical problem, achieving a sensitive, specific and predictive novel method based on biomarkers is an important task. Methods: Essential analysis, such as gene ontology (GO) enrichment and protein-protein interactions (PPI) was undergone EXPASy, STRING Database and DAVID Bioinformatics Resources query. Results: Based on GO analysis, most of proteins are located in the endoplasmic reticulum lumen, intracellular organelle lumen, membrane-enclosed lumen, and extracellular region. The relevant molecular functions are actin binding, metal ion binding, cation binding and ion binding. Cell adhesion, biological adhesion, cellular amino acid derivative, metabolic process and homeostatic process are the related processes. Protein-protein interaction network analysis introduced five proteins (fibroblast growth factor receptor 4, tropomyosin 4, tropomyosin 2 (beta), lectin, Lectin galactoside-binding soluble 3 binding protein and apolipoprotein A-I) as hub and bottleneck proteins. Conclusion: Our result indicates that regulation of lipid metabolism and cell survival are important biological processes involved in cirrhosis disease. More investigation of above mentioned proteins will provide a better understanding of cirrhosis disease. PMID:27099671

  16. Autophagy and non-alcoholic fatty liver disease.

    PubMed

    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.

  17. A nontumorigenic variant of FGF19 treats cholestatic liver diseases.

    PubMed

    Luo, Jian; Ko, Brian; Elliott, Michael; Zhou, Mei; Lindhout, Darrin A; Phung, Van; To, Carmen; Learned, R Marc; Tian, Hui; DePaoli, Alex M; Ling, Lei

    2014-07-30

    Hepatic accumulation of bile acids is central to the pathogenesis of cholestatic liver diseases. Endocrine hormone fibroblast growth factor 19 (FGF19) may reduce hepatic bile acid levels through modulation of bile acid synthesis and prevent subsequent liver damage. However, FGF19 has also been implicated in hepatocellular carcinogenesis, and consequently, the potential risk from prolonged exposure to supraphysiological levels of the hormone represents a major hurdle for developing an FGF19-based therapy. We describe a nontumorigenic FGF19 variant, M70, which regulates bile acid metabolism and, through inhibition of bile acid synthesis and reduction of excess hepatic bile acid accumulation, protects mice from liver injury induced by either extrahepatic or intrahepatic cholestasis. Administration of M70 in healthy human volunteers potently reduces serum levels of 7α-hydroxy-4-cholesten-3-one, a surrogate marker for the hepatic activity of cholesterol 7α-hydroxylase (CYP7A1), the enzyme responsible for catalyzing the first and rate-limiting step in the classical bile acid synthetic pathway. This study provides direct evidence for the regulation of bile acid metabolism by FGF19 pathway in humans. On the basis of these results, the development of nontumorigenic FGF19 variants capable of modulating CYP7A1 expression represents an effective approach for the prevention and treatment of cholestatic liver diseases as well as potentially for other disorders associated with bile acid dysregulation.

  18. Emerging roles of Notch signaling in liver disease

    PubMed Central

    Geisler, Fabian; Strazzabosco, Mario

    2014-01-01

    This review critically discusses the most recent advances on the role of Notch signaling in liver development, homeostasis and disease. It is now clear that the significance of Notch in determining mammalian cell fates and functions extends beyond development, and Notch is a major regular of organ homeostasis. Moreover, Notch signaling is reactivated upon injury and regulates the complex interactions between the distinct cellular types involved in the repair process. Notch is also involved in the regulation of liver metabolism, inflammation and cancer. The net effects of Notch signaling are highly variable and finely regulated at multiple levels, but also depend on the specific cellular context in which Notch is activated. Persistent activation of Notch signaling is associated with liver malignancies, such as hepatocellular carcinoma with stem cell features and intrahepatic cholangiocarcinoma. The complexity of the pathway provides several possible targets for agents able to inhibit Notch. However, further cell- and context-specific in depth understanding of Notch signaling in liver homeostasis and disease will be essential to translate these concepts into the clinical practice and be able to predict benefits and risks of evolving therapies. PMID:24930574

  19. Role of the intestinal microbiome in liver disease.

    PubMed

    Henao-Mejia, Jorge; Elinav, Eran; Thaiss, Christoph A; Licona-Limon, Paula; Flavell, Richard A

    2013-10-01

    The liver integrates metabolic outcomes with nutrient intake while preventing harmful signals derived from the gut to spread throughout the body. Direct blood influx from the gastrointestinal tract through the portal vein makes the liver a critical firewall equipped with a broad array of immune cells and innate immune receptors that recognize microbial-derived products, microorganisms, toxins and food antigens that have breached the intestinal barrier. An overwhelming amount of evidence obtained in the last decade indicates that the intestinal microbiota is a key component of a wide variety of physiological processes, and alterations in the delicate balance that represents the intestinal bacterial communities are now considered important determinants of metabolic syndrome and immunopathologies. Moreover, it is now evident that the interaction between the innate immune system and the intestinal microbiota during obesity or autoimmunity promotes chronic liver disease progression and therefore it might lead to novel and individualized therapeutic approaches. In this review, we discuss a growing body of evidence that highlights the central relationship between the immune system, the microbiome, and chronic liver disease initiation and progression.

  20. Liver Stem Cells: Experimental Findings and Implications for Human Liver Disease.

    PubMed

    Michalopoulos, George K; Khan, Zahida

    2015-10-01

    Evidence from human histopathology and experimental studies with rodents and zebrafish has shown that hepatocytes and cholangiocytes may function as facultative stem cells for each other in conditions of impaired regeneration. The interpretation of the findings derived from these studies has generated considerable discussion and some controversies. This review examines the evidence obtained from the different experimental models and considers implications that these studies may have for human liver disease.

  1. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis

    PubMed Central

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K.; Mukherjee, Rathin; Reddy, Duvvur N.; Rao, Padaki N.

    2015-01-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed. PMID:26155043

  2. The Riddle of Nonalcoholic Fatty Liver Disease: Progression From Nonalcoholic Fatty Liver to Nonalcoholic Steatohepatitis.

    PubMed

    Sharma, Mithun; Mitnala, Shasikala; Vishnubhotla, Ravi K; Mukherjee, Rathin; Reddy, Duvvur N; Rao, Padaki N

    2015-06-01

    Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.

  3. Computer-aided diagnosis of alcoholism-related EEG signals.

    PubMed

    Acharya, U Rajendra; S, Vidya; Bhat, Shreya; Adeli, Hojjat; Adeli, Amir

    2014-12-01

    Alcoholism is a severe disorder that affects the functionality of neurons in the central nervous system (CNS) and alters the behavior of the affected person. Electroencephalogram (EEG) signals can be used as a diagnostic tool in the evaluation of subjects with alcoholism. The neurophysiological interpretation of EEG signals in persons with alcoholism (PWA) is based on observation and interpretation of the frequency and power in their EEGs compared to EEG signals from persons without alcoholism. This paper presents a review of the known features of EEGs obtained from PWA and proposes that the impact of alcoholism on the brain can be determined by computer-aided analysis of EEGs through extracting the minute variations in the EEG signals that can differentiate the EEGs of PWA from those of nonaffected persons. The authors advance the idea of automated computer-aided diagnosis (CAD) of alcoholism by employing the EEG signals. This is achieved through judicious combination of signal processing techniques such as wavelet, nonlinear dynamics, and chaos theory and pattern recognition and classification techniques. A CAD system is cost-effective and efficient and can be used as a decision support system by physicians in the diagnosis and treatment of alcoholism especially those who do not specialize in alcoholism or neurophysiology. It can also be of great value to rehabilitation centers to assess PWA over time and to monitor the impact of treatment aimed at minimizing or reversing the effects of the disease on the brain. A CAD system can be used to determine the extent of alcoholism-related changes in EEG signals (low, medium, high) and the effectiveness of therapeutic plans.

  4. Cryoglobulins in acute and chronic liver diseases

    PubMed Central

    Florin-Christensen, A.; Roux, María E. B.; Arana, R. M.

    1974-01-01

    Cryoglobulins were detected in the sera of thirteen patients with acute viral hepatitis and of twelve with chronic hepatic diseases (active chronic hepatitis, primary biliary cirrhosis and cryptogenic cirrhosis). Their nature and antibody activity was studied. In both groups, most of them consisted of mixed cryoimmunoglobulins (IgM, IgG and/or IgA), but some were single-class immunoglobulins with one or both types of light chains. Unusual components were also found. α1-fetoprotein was present in four cryoprecipitates: in two as the single constituent and in two associated to immunoglobulins; hepatitis-associated antigen co-existed in one of the latter. Some cryoglobulins showed antibody activity against human IgG, smooth muscle and mitochondrial antigens. In one case, the IgM-kappa of the cryoprecipitate had antibody activity against α1-fetoprotein; this antigen was also present in the cryoprecipitate, suggesting immune-complex formation. Autoantibodies were also looked for in the sera of the twenty-five patients; apart from the most common ones, antibodies to α1-fetoprotein were found in two patients. PMID:4143195

  5. Investigating Nonalcoholic Fatty Liver Disease in a Liver-on-a-Chip Microfluidic Device

    PubMed Central

    Simonelli, Maria Chiara; Giannitelli, Sara Maria; Businaro, Luca; Trombetta, Marcella; Rainer, Alberto

    2016-01-01

    Background and Aim Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease worldwide, ranging from simple steatosis to nonalcoholic steatohepatitis, which may progress to cirrhosis, eventually leading to hepatocellular carcinoma (HCC). HCC ranks as the third highest cause of cancer-related death globally, requiring an early diagnosis of NAFLD as a potential risk factor. However, the molecular mechanisms underlying NAFLD are still under investigation. So far, many in vitro studies on NAFLD have been hampered by the limitations of 2D culture systems, in which cells rapidly lose tissue-specific functions. The present liver-on-a-chip approach aims at filling the gap between conventional in vitro models, often scarcely predictive of in vivo conditions, and animal models, potentially biased by their xenogeneic nature. Methods HepG2 cells were cultured into a microfluidically perfused device under free fatty acid (FFA) supplementation, namely palmitic and oleic acid, for 24h and 48h. The device mimicked the endothelial-parenchymal interface of a liver sinusoid, allowing the diffusion of nutrients and removal of waste products similar to the hepatic microvasculature. Assessment of intracellular lipid accumulation, cell viability/cytotoxicity and oxidative stress due to the FFA overload, was performed by high-content analysis methodologies using fluorescence-based functional probes. Results The chip enables gradual and lower intracellular lipid accumulation, higher hepatic cell viability and minimal oxidative stress in microfluidic dynamic vs. 2D static cultures, thus mimicking the chronic condition of steatosis observed in vivo more closely. Conclusions Overall, the liver-on-a-chip system provides a suitable culture microenvironment, representing a more reliable model compared to 2D cultures for investigating NAFLD pathogenesis. Hence, our system is amongst the first in vitro models of human NAFLD developed within a microfluidic device in a sinusoid

  6. Procoagulant therapeutics in liver disease: a critique and clinical rationale.

    PubMed

    Shah, Neeral L; Intagliata, Nicolas M; Northup, Patrick G; Argo, Curtis K; Caldwell, Stephen H

    2014-11-01

    The complex nature of haemostasis in patients with liver disease can result in bleeding and/or thrombosis. These opposing outcomes, which have multiple contributing factors, can pose diagnostic and therapeutic dilemmas for physicians. With the high rate of haemorrhagic complications in patients with cirrhosis, we examine the various procoagulants available for use in this population. In this Review, we describe the clinical and current rationale for using each of the currently available procoagulants-vitamin K, fresh frozen plasma (FFP), cryoprecipitate, platelets, recombinant factor VIIa (rFVIIa), antifibrinolytics, prothrombin concentrate complexes (PCC), desmopressin and red blood cells. By examining the evidence and use of these agents in liver disease, we provide a framework for targeted, goal-directed therapy with procoagulants.

  7. Glycosyltransferases and non-alcoholic fatty liver disease

    PubMed Central

    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

  8. Glycosyltransferases and non-alcoholic fatty liver disease.

    PubMed

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

    2016-02-28

    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.

  9. Nonalcoholic fatty liver disease and metabolic syndrome in postmenopausal women.

    PubMed

    Rodrigues, Marcio H; Bruno, Anderson S; Nahas-Neto, Jorge; Santos, Maria Emilia S; Nahas, Eliana A P

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) is considered the most common cause of chronic liver disease in the Western countries. NAFLD includes a spectrum ranging from a simple steatosis to a nonalcoholic steatohepatitis (NASH) which is defined by the presence of inflammatory infiltrate, cellular necrosis, hepatocyte ballooning, and fibrosis and cirrhosis that can eventually develop into hepatocellular carcinoma. Studies emphasize the role of insulin resistance, oxidative stress, pro-inflammatory cytokines, adipokines in the development and progression of NAFLD. It seems to be independently associated with type II diabetes mellitus, increased triglycerides, decreased HDL-cholesterol, abdominal obesity and insulin resistance. These findings are in accordance with the criteria used in the diagnosis of metabolic syndrome (MetS). Here, we will discuss the current knowledge on the epidemiology, pathophysiology and diagnosis of NAFLD and the association of metabolic syndrome in postmenopausal women.

  10. Probiotics and gut health: a special focus on liver diseases.

    PubMed

    Gratz, Silvia Wilson; Mykkanen, Hannu; El-Nezami, Hani S

    2010-01-28

    Probiotic bacteria have well-established beneficial effects in the management of diarrhoeal diseases. Newer evidence suggests that probiotics have the potential to reduce the risk of developing inflammatory bowel diseases and intestinal bacterial overgrowth after gut surgery. In liver health, the main benefits of probiotics might occur through preventing the production and/or uptake of lipopolysaccharides in the gut, and therefore reducing levels of low-grade inflammation. Specific immune stimulation by probiotics through processes involving dendritic cells might also be beneficial to the host immunological status and help prevent pathogen translocation. Hepatic fat metabolism also seems to be influenced by the presence of commensal bacteria, and potentially by probiotics; although the mechanisms by which probiotic might act on the liver are still unclear. However, this might be of major importance in the future because low-grade inflammation, hepatic fat infiltration, and hepatitis might become more prevalent as a result of high fat intake and the increased prevalence of obesity.

  11. Function of Autophagy in Nonalcoholic Fatty Liver Disease.

    PubMed

    Czaja, Mark J

    2016-05-01

    Autophagy is a lysosomal degradative pathway that functions to promote cell survival by supplying energy in times of stress or by removing damaged organelles and proteins after injury. The involvement of autophagy in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) was first suggested by the finding that this pathway mediates the breakdown of intracellular lipids in hepatocytes and therefore may regulate the development of hepatic steatosis. Subsequent studies have demonstrated additional critical functions for autophagy in hepatocytes and other hepatic cell types such as macrophages and stellate cells that regulate insulin sensitivity, hepatocellular injury, innate immunity, fibrosis, and carcinogenesis. These findings suggest a number of possible mechanistic roles for autophagy in the development of NAFLD and progression to NASH and its complications. The functions of autophagy in the liver, together with findings of decreased hepatic autophagy in association with conditions that predispose to NAFLD such as obesity and aging, suggest that autophagy may be a novel therapeutic target in this disease.

  12. [Pediatric nonalcoholic fatty liver disease/nonalcoholic steatohepatitis].

    PubMed

    Takahashi, Yoshihisa; Fukusato, Toshio; Inui, Ayano; Fujisawa, Tomoo

    2012-10-01

    Nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is a hepatic disease associated with metabolic syndrome. In recent years, pediatric NAFLD has increased in line with the increased prevalence of pediatric obesity. The estimated prevalence of pediatric NAFLD is 2.6-9.6%. With regard to the pathogenesis of NAFLD/ NASH, the "two-hit" or "multiple-hit" hypothesis is widely accepted, and many genetic and environmental factors are associated with the development of NAFLD/NASH. Liver biopsy is regarded as the gold standard for the diagnosis of NAFLD/NASH. Pediatric NAFLD has different histopathological characteristics from those of adult NAFLD. Although pharmacotherapy has been studied in clinical trials, lifestyle modification by diet and exercise remains the mainstay of treatment for NAFLD/NASH.

  13. Pharmacokinetic drug interactions in liver disease: An update

    PubMed Central

    Palatini, Pietro; De Martin, Sara

    2016-01-01

    Inhibition and induction of drug-metabolizing enzymes are the most frequent and dangerous drug-drug interactions. They are an important cause of serious adverse events that have often resulted in early termination of drug development or withdrawal of drugs from the market. Management of such interactions by dose adjustment in clinical practice is extremely difficult because of the wide interindividual variability in their magnitude. This review examines the genetic, physiological, and environmental factors responsible for this variability, focusing on an important but so far neglected cause of variability, liver functional status. Clinical studies have shown that liver disease causes a reduction in the magnitude of interactions due to enzyme inhibition, which is proportional to the degree of liver function impairment. The effect of liver dysfunction varies quantitatively according to the nature, reversible or irreversible, of the inhibitory interaction. The magnitude of reversible inhibition is more drastically reduced and virtually vanishes in patients with advanced hepatocellular insufficiency. Two mechanisms, in order of importance, are responsible for this reduction: decreased hepatic uptake of the inhibitory drug and reduced enzyme expression. The extent of irreversible inhibitory interactions is only partially reduced, as it is only influenced by the decreased expression of the inhibited enzyme. Thus, for appropriate clinical management of inhibitory drug interactions, both the liver functional status and the mechanism of inhibition must be taken into consideration. Although the inducibility of drug-metabolizing enzymes in liver disease has long been studied, very conflicting results have been obtained, mainly because of methodological differences. Taken together, the results of early animal and human studies indicated that enzyme induction is substantially preserved in compensated liver cirrhosis, whereas no definitive conclusion as to whether it is

  14. Regulation of microRNAs and their role in liver development, regeneration and disease.

    PubMed

    Finch, Megan L; Marquardt, Jens U; Yeoh, George C; Callus, Bernard A

    2014-09-01

    Since their discovery more than a decade ago microRNAs have been demonstrated to have profound effects on almost every aspect of biology. Numerous studies in recent years have shown that microRNAs have important roles in development and in the etiology and progression of disease. This review is focused on microRNAs and the roles they play in liver development, regeneration and liver disease; particularly chronic liver diseases such as alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, viral hepatitis and primary liver cancer. The key microRNAs identified in liver development and chronic liver disease will be discussed together with, where possible, the target messenger RNAs that these microRNAs regulate to profoundly alter these processes. This article is part of a Directed Issue entitled: The Non-coding RNA Revolution.

  15. From the liver to the heart: Cardiac dysfunction in obese children with non-alcoholic fatty liver disease

    PubMed Central

    Di Sessa, Anna; Umano, Giuseppina Rosaria; Miraglia del Giudice, Emanuele; Santoro, Nicola

    2017-01-01

    In the last decades the prevalence of non-alcoholic fatty liver disease (NAFLD) has increased as a consequence of the childhood obesity world epidemic. The liver damage occurring in NAFLD ranges from simple steatosis to steatohepatitis, fibrosis and cirrhosis. Recent findings reported that fatty liver disease is related to early atherosclerosis and cardiac dysfunction even in the pediatric population. Moreover, some authors have shown an association between liver steatosis and cardiac abnormalities, including rise in left ventricular mass, systolic and diastolic dysfunction and epicardial adipose tissue thickness. In this editorial, we provide a brief overview of the current knowledge concerning the association between NAFLD and cardiac dysfunction. PMID:28144387

  16. Pleiotropic effects of statins in the diseases of the liver

    PubMed Central

    Janicko, Martin; Drazilova, Sylvia; Pella, Daniel; Fedacko, Jan; Jarcuska, Peter

    2016-01-01

    Statins are a class of molecules that inhibit HMG CoA reductase. They are usually prescribed as a lipid lowering medication. However, there is accumulating evidence that statins have multiple secondary effects both related and unrelated to their lipid-lowering effect. This narrative review of the literature aims to provide the reader with information from clinical studies related to the effect of statin and statins’ potential use in patients with liver diseases. In patients with advanced liver disease due to any etiology, statins exhibit an antifibrotic effect possibly through the prevention of hepatic sinusoidal microthrombosis. Two randomized controlled trials confirmed that statins decrease hepatic vein pressure gradient in patients with portal hypertension and improve the survival of patients after variceal bleeding. Lower rates of infections were observed in patients with cirrhosis who received statin treatment. Statins decrease the risk of hepatocellular carcinoma (HCC) in patients with advanced liver disease in general but particularly in patients with chronic hepatitis B and C. Statins in patients with chronic hepatitis C likely increase the virological response to the treatment with pegylated interferon and ribavirin and have the potential to decrease the rate of fibrosis. Finally, data from randomized controlled trials also confirmed that the addition of statin prolongs the survival of patients with advanced HCC even more than sorafenib. Statins are a very promising group of drugs especially in patients with liver disease, where therapeutic options can often be limited. Some indications, such as the prevention of re-bleeding from esophageal varices and the palliative treatment of HCC have been proven through randomized controlled trials, while additional indications still need to be confirmed through prospective studies. PMID:27468210

  17. Nonalcoholic fatty liver disease: molecular pathways and therapeutic strategies

    PubMed Central

    2013-01-01

    Along with rising numbers of patients with metabolic syndrome, the prevalence of nonalcoholic fatty liver disease (NAFLD) has increased in proportion with the obesity epidemic. While there are no established treatments for NAFLD, current research is targeting new molecular mechanisms that underlie NAFLD and associated metabolic disorders. This review discusses some of these emerging molecular mechanisms and their therapeutic implications for the treatment of NAFLD. The basic research that has identified potential molecular targets for pharmacotherapy will be outlined. PMID:24209497

  18. Carnitine metabolism in patients with chronic liver disease.

    PubMed

    Krähenbühl, S; Reichen, J

    1997-01-01

    Carnitine metabolism was studied in 79 patients with chronic liver disease, including 22 patients with noncirrhotic liver disease and 57 patients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared with 28 control subjects. In comparison with control subjects, patients with noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas patients with cirrhosis had a 29% increase in the long-chain acylcarnitine concentration. Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration. In this group of patients, the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration. Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liver disease and control patients. However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase in the fractional excretion of both free carnitine and short-chain acylcarnitine. The current studies show that patients with cirrhosis are normally not carnitine deficient. Patients with alcohol-induced cirrhosis have increased plasma carnitine concentrations, which may result from increased carnitine biosynthesis because of increased skeletal muscle protein turnover. The increase in the fractional carnitine excretion in patients with primary biliary cirrhosis may result from competition of bile acids and

  19. Nonalcoholic fatty liver disease and vascular disease: state-of-the-art.

    PubMed

    Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

    2014-10-07

    Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular

  20. Adenocarcinoma in Caroli's Disease Treated by Liver Transplantation

    PubMed Central

    Margarit, C.; Murio, E.; Lazaro, J. L.; Charco, R.; Vidal, M. T.; Bonnin, J.

    1993-01-01

    Caroli's disease is characterized by congenital cystic dilatation of the intrahepatic bile ducts. In 7% of casea a malignant tumor develops complicating the course of the disease. We report the case of a 25 year-old woman in whom Caroli's disease was diagnosed at the age of 11. From that time on, she had several episodes of cholangitis. In 1989, the abdominal ultrasound and CT scan showed dilatation of the intrahepatic bile ducts, intracystic lithiasis and a solid mass. FNA cytology showed a papillary adenocarcinoma. At laparotomy a tumor was found occupying both hepatic lobes, and intraoperative US showed another two nodules in the left lobe. The tumor was considered unresectable. Examination of the hilar lymph nodes was tumor-negative. Two weeks later, the patient underwent an ortothopic liver transplantation (OLT). The pathological examination confirmed Caroli's disease with adenocarcinoma. Two years after OLT, the patient is alive with normal liver function and no evidence of disease. To our knowledge this is the first case report of adenocarcinoma in Caroli's disease treated by OLT. PMID:8260439

  1. Acute Kidney Disease After Liver and Heart Transplantation.

    PubMed

    Rossi, Ana P; Vella, John P

    2016-03-01

    After transplantation of nonrenal solid organs, an acute decline in kidney function develops in the majority of patients. In addition, a significant number of nonrenal solid organ transplant recipients develop chronic kidney disease, and some develop end-stage renal disease, requiring renal replacement therapy. The incidence varies depending on the transplanted organ. Acute kidney injury after nonrenal solid organ transplantation is associated with prolonged length of stay, cost, increased risk of death, de novo chronic kidney disease, and end-stage renal disease. This overview focuses on the risk factors for posttransplant acute kidney injury after liver and heart transplantation, integrating discussion of proteinuria and chronic kidney disease with emphasis on pathogenesis, histopathology, and management including the use of mechanistic target of rapamycin inhibition and costimulatory blockade.

  2. Ohio solid organ transplantation consortium criteria for liver transplantation in patients with alcoholic liver disease

    PubMed Central

    Hajifathalian, Kaveh; Humberson, Annette; Hanouneh, Mohamad A; Barnes, David S; Arora, Zubin; Zein, Nizar N; Eghtesad, Bijan; Kelly, Dympna; Hanouneh, Ibrahim A

    2016-01-01

    AIM To evaluate risk of recidivism on a case-by-case basis. METHODS From our center’s liver transplant program, we selected patients with alcoholic liver disease who were listed for transplant based on Ohio Solid Organ Transplantation Consortium (OSOTC) exception criteria. They were considered to have either a low or medium risk of recidivism, and had at least one or three or more months of abstinence, respectively. They were matched based on gender, age, and Model for End-Stage Liver Disease (MELD) score to controls with alcohol-induced cirrhosis from Organ Procurement and Transplant Network data. RESULTS Thirty six patients with alcoholic liver disease were approved for listing based on OSOTC exception criteria and were matched to 72 controls. Nineteen patients (53%) with a median [Inter-quartile range (IQR)] MELD score of 24 (13) received transplant and were followed for a median of 3.4 years. They were matched to 38 controls with a median (IQR) MELD score of 25 (9). At one and five years, cumulative survival rates (± standard error) were 90% ± 7% and 92% ± 5% and 73% ± 12% and 77% ± 8% in patients and controls, respectively (Log-rank test, P = 0.837). Four (21%) patients resumed drinking by last follow-up visit. CONCLUSION Compared to traditional criteria for assessment of risk of recidivism, a careful selection process with more flexibility to evaluate eligibility on a case-by-case basis can lead to similar survival rates after transplantation. PMID:27721920

  3. Experimental Alcohol-Related Peripheral Neuropathy: Role of Insulin/IGF Resistance

    PubMed Central

    Nguyen, Van Anh; Le, Tran; Tong, Ming; Mellion, Michelle; Gilchrist, James; de la Monte, Suzanne M.

    2012-01-01

    The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies. Chronic ethanol feeding slowed nerve conduction in the tibial (p = 0.0021) motor nerve, and not plantar sensory nerve, but it did not affect amplitude. Histological studies of the sciatic nerve revealed reduced nerve fiber diameters with increased regenerative sprouts, and denervation myopathy in ethanol-fed rats. qRT-PCR analysis demonstrated reduced mRNA levels of insulin, IGF-1, and IGF-2 polypeptides, IGF-1 receptor, and IRS2, and ELISAs revealed reduced immunoreactivity for insulin and IGF-1 receptors, IRS-1, IRS-4, myelin-associated glycoprotein, and tau in sciatic nerves of ethanol-fed rats (all p < 0.05 or better). The findings suggest that ALPN is characterized by (1) slowed conduction velocity with demyelination, and a small component of axonal degeneration; (2) impaired trophic factor signaling due to insulin and IGF resistance; and (3) degeneration of myelin and axonal cytoskeletal proteins. Therefore, ALPN is likely mediated by molecular and signal transduction abnormalities similar to those identified in alcoholic liver and brain degeneration. PMID:23016131

  4. Alcohol-related content of animated cartoons: a historical perspective.

    PubMed

    Klein, Hugh; Shiffman, Kenneth S

    2013-01-01

    This study, based on a stratified (by decade of production) random sample of 1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks to determine the prevalence of alcohol-related content; how, if at all, the prevalence changed between 1930 and 1996 (the years spanned by this research); and the types of messages that animated cartoons convey about beverage alcohol and drinking in terms of the characteristics that are associated with alcohol use, the contexts in which alcohol is used in cartoons, and the reasons why cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was found to contain alcohol-related content, indicating that the average child or adolescent viewer is exposed to approximately 24 alcohol-related messages each week just from the cartoons that he/she watches. Data indicated that the prevalence of alcohol-related content declined significantly over the years. Quite often, alcohol consumption was shown to result in no effects whatsoever for the drinker, and alcohol use often occurred when characters were alone. Overall, mixed, ambivalent messages were provided about drinking and the types of characters that did/not consume alcoholic beverages.

  5. Family Supports for Children Who Have Alcohol-Related Disabilities

    ERIC Educational Resources Information Center

    Brown, James D.

    2004-01-01

    Since the first publication on fetal alcohol syndrome appeared in the scientific literature over 30 years ago, there has been a great deal of research interest in the topic. This paper reviews findings within the past 10 years related to causes, frequency, and diagnosis of alcohol-related disabilities, before turning to the impact these…

  6. Alcohol-Related Content of Animated Cartoons: A Historical Perspective

    PubMed Central

    Klein, Hugh; Shiffman, Kenneth S.

    2013-01-01

    This study, based on a stratified (by decade of production) random sample of 1,221 animated cartoons and 4,201 characters appearing in those cartoons, seeks to determine the prevalence of alcohol-related content; how, if at all, the prevalence changed between 1930 and 1996 (the years spanned by this research); and the types of messages that animated cartoons convey about beverage alcohol and drinking in terms of the characteristics that are associated with alcohol use, the contexts in which alcohol is used in cartoons, and the reasons why cartoon characters purportedly consume alcohol. Approximately 1 cartoon in 11 was found to contain alcohol-related content, indicating that the average child or adolescent viewer is exposed to approximately 24 alcohol-related messages each week just from the cartoons that he/she watches. Data indicated that the prevalence of alcohol-related content declined significantly over the years. Quite often, alcohol consumption was shown to result in no effects whatsoever for the drinker, and alcohol use often occurred when characters were alone. Overall, mixed, ambivalent messages were provided about drinking and the types of characters that did/not consume alcoholic beverages. PMID:24350176

  7. Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition.

    PubMed

    Zaloga, Gary P

    2015-09-01

    Phytosterols are plant-derived sterols that are structurally and functionally analogous to cholesterol in vertebrate animals. Phytosterols are found in many foods and are part of the normal human diet. However, absorption of phytosterols from the diet is minimal. Most lipid emulsions used for parenteral nutrition are based on vegetable oils. As a result, phytosterol administration occurs during intravenous administration of lipid. Levels of phytosterols in the blood and tissues may reach high levels during parenteral lipid administration and may be toxic to cells. Phytosterols are not fully metabolized by the human body and must be excreted through the hepatobiliary system. Accumulating scientific evidence suggests that administration of high doses of intravenous lipids that are high in phytosterols contributes to the development of parenteral nutrition-associated liver disease. In this review, mechanisms by which lipids and phytosterols may cause cholestasis are discussed. Human studies of the association of phytosterols with liver disease are reviewed. In addition, clinical studies of lipid/phytosterol reduction for reversing and/or preventing parenteral nutrition associated liver disease are discussed.

  8. Genetic background in nonalcoholic fatty liver disease: A comprehensive review.

    PubMed

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-10-21

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.

  9. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    PubMed Central

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  10. Toll-like receptors in pathophysiology of liver diseases

    PubMed Central

    Kiziltas, Safak

    2016-01-01

    Toll-like receptors (TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte (i.e., hepatocellular injury and regeneration) or hepatic stellate cell (i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases. PMID:27917262

  11. Nonalcoholic fatty liver disease and cholesterol gallstones: which comes first?

    PubMed

    Ahmed, Mohamed H; Ali, Asif

    2014-05-01

    Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GD) are both highly prevalent in the general population and are associated with obesity, insulin resistance, dyslipidemia, and high dietary cholesterol intake. Insulin resistance is a key feature of both NAFLD and GD. Hepatic insulin resistance provides a crucial link between the metabolic syndrome, NAFLD, and increased cholesterol gallstone susceptibility. Hepatic insulin resistance is not only associated with accumulation of hepatic fat but also has a crucial role in supersaturation and excessive production of bile salts. It is not yet clear whether NAFLD is a precursor of GD or whether the presence of GD possibly indicates the presence of long-standing features of metabolic syndrome that accelerates the progression of NAFLD. Recent reports suggested the association between gallstones and nonalcoholic steatohepatitis and liver fibrosis. Importantly, both NAFLD and GD are both associated with high incidence of cardiovascular disease (CVD) and mortality. Emerging evidence suggests a potential benefit of statin therapy in NAFLD and GD. Further research is needed to determine (i) how the presence of NAFLD and GD is associated with CVD (ii) and whether the presence of GD in association with NAFLD increases the risk of liver fibrosis, and (iii) the impact of therapy of NAFLD in the incidence of GD.

  12. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them.

  13. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  14. The heart-liver metabolic axis: defective communication exacerbates disease

    PubMed Central

    Baskin, Kedryn K; Bookout, Angie L; Olson, Eric N

    2014-01-01

    The heart has been recognized as an endocrine organ for over 30 years (de Bold, 2011); however, little is known about how the heart communicates with other organs in the body, and even less is known about this process in the diseased heart. In this issue of EMBO Molecular Medicine, Magida and Leinwand (2014) introduce the concept that a primary genetic defect in the heart results in aberrant hepatic lipid metabolism, which consequently exacerbates hypertrophic cardiomyopathy (HCM). This study provides evidence in support of the hypothesis that crosstalk occurs between the heart and liver, and that this becomes disrupted in the diseased state. PMID:24623378

  15. Importance of Endocytic Pathways in Liver Function and Disease

    PubMed Central

    Schroeder, Barbara; McNiven, Mark A.

    2015-01-01

    Hepatocellular endocytosis is a highly dynamic process responsible for the internalization of a variety of different receptor ligand complexes, trophic factors, lipids, and, unfortunately, many different pathogens. The uptake of these external agents has profound effects on seminal cellular processes including signaling cascades, migration, growth, and proliferation. The hepatocyte, like other well-polarized epithelial cells, posses a host of different endocytic mechanisms and entry routes to ensure the selective internalization of cargo molecules. These pathways include receptor-mediated endocytosis, lipid raft associated endocytosis, caveolae, or fluid-phase uptake although there are likely many others. Understanding and defining the regulatory mechanisms underlying these distinct entry routes, sorting and vesicle formation, as well as the postendocytic trafficking pathways is of high importance especially in the liver, as their mis-regulation can contribute to aberrant liver pathology and liver diseases. Further, these processes can be “hijacked” by a variety of different infectious agents and viruses. This review provides an overview of common components of the endocytic and postendocytic trafficking pathways utilized by hepatocytes. It will also discuss in more detail how these general themes apply to liver-specific processes including iron homeostasis, HBV infection, and even hepatic steatosis. PMID:25428849

  16. Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

    PubMed Central

    Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L’Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

    2015-01-01

    Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development. PMID:25621497

  17. Soft drinks consumption and nonalcoholic fatty liver disease.

    PubMed

    Nseir, William; Nassar, Fares; Assy, Nimer

    2010-06-07

    Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD.

  18. Soft drinks consumption and nonalcoholic fatty liver disease

    PubMed Central

    Nseir, William; Nassar, Fares; Assy, Nimer

    2010-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a common clinical condition which is associated with metabolic syndrome in 70% of cases. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress combine to increase free fatty acid delivery to the liver, and increased hepatic triglyceride accumulation contributes to fatty liver. Regular soft drinks have high fructose corn syrup which contains basic sugar building blocks, fructose 55% and glucose 45%. Soft drinks are the leading source of added sugar worldwide, and have been linked to obesity, diabetes, and metabolic syndrome. The consumption of soft drinks can increase the prevalence of NAFLD independently of metabolic syndrome. During regular soft drinks consumption, fat accumulates in the liver by the primary effect of fructose which increases lipogenesis, and in the case of diet soft drinks, by the additional contribution of aspartame sweetener and caramel colorant which are rich in advanced glycation end products that potentially increase insulin resistance and inflammation. This review emphasizes some hard facts about soft drinks, reviews fructose metabolism, and explains how fructose contributes to the development of obesity, diabetes, metabolic syndrome, and NAFLD. PMID:20518077

  19. Microbiota-based treatments in alcoholic liver disease

    PubMed Central

    Sung, Hotaik; Kim, Seung Woo; Hong, Meegun; Suk, Ki Tae

    2016-01-01

    Gut microbiota plays a key role in the pathogenesis of alcoholic liver disease (ALD). Consumption of alcohol leads to increased gut permeability, small intestinal bacterial overgrowth, and enteric dysbiosis. These factors contribute to the increased translocation of microbial products to the liver via the portal tract. Subsequently, bacterial endotoxins such as lipopolysaccharide, in association with the Toll-like receptor 4 signaling pathway, induce a gamut of damaging immune responses in the hepatic milieu. Because of the close association between deleterious inflammation and ALD-induced microbiota imbalance, therapeutic approaches that seek to reestablish gut homeostasis should be considered in the treatment of alcoholic patients. To this end, a number of preliminary studies on probiotics have confirmed their effectiveness in suppressing proinflammatory cytokines and improving liver function in the context of ALD. In addition, there have been few studies linking the administration of prebiotics and antibiotics with reduction of alcohol-induced liver damage. Because these preliminary results are promising, large-scale randomized studies are warranted to elucidate the impact of these microbiota-based treatments on the gut flora and associated immune responses, in addition to exploring questions about optimal delivery. Finally, fecal microbiota transplant has been shown to be an effective method of modulating gut microbiota and deserve further investigation as a potential therapeutic option for ALD. PMID:27547010

  20. Surgical outcomes following laparoscopic major hepatectomy for various liver diseases

    PubMed Central

    Kang, Sung-Hwa; Kim, Ki-Hun; Shin, Min-Ho; Yoon, Young-In; Kim, Wan-Jun; Jung, Dong-Hwan; Park, Gil-Chun; Ha, Tae-Yong; Lee, Sung-Gyu

    2016-01-01

    Abstract The aim of the study was to report surgical outcomes (efficacy and safety) of laparoscopic major hepatectomy for various liver diseases. Although the number of laparoscopic liver resections has increased, expansion of laparoscopic major hepatic resection remains limited, mainly owing to the technical difficulties for the procedure as compared to open surgery. We describe our experiences with laparoscopic major hepatectomy for various liver diseases. We retrospectively reviewed the medical records of 192 patients who underwent laparoscopic major hepatectomy between October 2007 and March 2015 at Asan Medical Center, Korea. The mean age of the patients was 54 ± 11.6 years, and their mean body mass index was 23.5 kg/m2. The most common preoperative diagnosis was hepatocellular carcinoma (n = 82, 42.7%), followed by intrahepatic duct stones (n = 51, 26.6%). We performed 108 left hepatectomies, 55 right hepatectomies, 18 right posterior sectionectomies, 6 right anterior sectionectomies, 2 central bisectionectomies, and 3 donor right hepatectomies. The conversion rate was 1.6% (3 cases) due to bleeding, bile leakage, and uncontrolled hypercapnea during the operation. The mean operation time was 272 ± 80.2 minutes, and the mean estimated blood loss was 300.4 ± 252.2 mL. The mean postoperative hospital stay was 9.8 days. All resection margins were tumor-free in cases of malignant tumors. The morbidity rate was 3.1% (n = 6), including for case of biliary stricture. There were no deaths. Laparoscopic major hepatectomy, including donor hepatectomy, is a safe and feasible option for various liver diseases when careful selection criteria are used by a surgeon experienced with the relevant surgical techniques. PMID:27787374

  1. Recommendations for Diagnosis, Referral for Liver Biopsy, and Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis.

    PubMed

    Spengler, Erin K; Loomba, Rohit

    2015-09-01

    Nonalcoholic fatty liver disease (NAFLD) is the primary cause of chronic liver disease in the United States, afflicting an estimated 80 to 100 million Americans. Nonalcoholic fatty liver disease is a spectrum of liver diseases composed of nonalcoholic fatty liver and nonalcoholic steatohepatitis (NASH). Although nonalcoholic fatty liver has a negligible risk of progression, patients with NASH often develop cirrhosis or hepatocellular carcinoma. Although liver biopsy is required to diagnose NASH, only patients with a high risk of NASH or advanced fibrosis require this evaluation. Despite the high prevalence of NAFLD, well-defined screening recommendations are currently lacking. In this review, suggestions for screening, diagnosis, and initial work-up of NAFLD are given on the basis of established guidelines and recent publications. Proposed drug treatments of NASH are also discussed, highlighting the study outcomes, as well as proposed uses and limitations of these drugs. The literature was searched in PubMed using search terms nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, with filters of "English language." A date range of January 1, 2000, to May 1, 2015, was used for the search. The bibliographies of key references were also searched manually, and seminal publications before the year 2000 were included.

  2. When to consider liver transplant during the management of chronic liver disease.

    PubMed

    Fox, Rena K

    2014-01-01

    The decision to perform liver transplantation for a particular patient is never the decision of one single individual, although a single individual could preclude transplant as an option if the opportunity for referral is missed. Every physician treating patients with cirrhosis, including primary care physicians and primary gastroenterologists, should watch for the essential turning points at which a patient may become eligible for a transplant referral. Timing of referral could be assessed according to either the type of liver disease or non–disease-specific measures of disease severity. Although the MELD score is an easily accessible and convenient tool it is not as well known as CTP classification, and many cirrhotic patients under long-term management may not be being allocated a MELD score regularly calculated by their primary physicians. Because a slow progression in MELD score may occur without a change in symptoms, reaching the MELD score acceptable for transplant referral may go unrecognized. As generalists face the rising prevalence of NAFLD and the rising prevalence of cirrhosis and HCC from HCV, there will be an increasing need for education in the management of liver disease. It will be necessary for specialists and health care systems to better inform primary care physicians about the recommendations on criteria for transplant referral and the critical windows of opportunity within which they can act. Although there is a recognized knowledge gap that needs to be addressed, once a patient is in medical care, inadequate physician knowledge should never be the cause for late timing or missing the opportunity for referral.

  3. Exploring College Students' Use of General and Alcohol-Related Social Media and Their Associations with Alcohol-Related Behaviors

    ERIC Educational Resources Information Center

    Hoffman, Eric W.; Pinkleton, Bruce E.; Weintraub Austin, Erica; Reyes-Velázquez, Wanda

    2014-01-01

    Objective: Alcohol marketers have increasingly moved their advertising efforts into digital and social media venues. As a result, the purpose of this study is to investigate associations between students' use of social media, their exposure to alcohol marketing messages through social media, and their alcohol-related beliefs and behaviors.…

  4. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

    PubMed Central

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH. PMID:25400438

  5. Bile acid receptors and nonalcoholic fatty liver disease

    PubMed Central

    Yuan, Liyun; Bambha, Kiran

    2015-01-01

    With the high prevalence of obesity, diabetes, and other features of the metabolic syndrome in United States, nonalcoholic fatty liver disease (NAFLD) has inevitably become a very prevalent chronic liver disease and is now emerging as one of the leading indications for liver transplantation. Insulin resistance and derangement of lipid metabolism, accompanied by activation of the pro-inflammatory response and fibrogenesis, are essential pathways in the development of the more clinically significant form of NAFLD, known as nonalcoholic steatohepatitis (NASH). Recent advances in the functional characterization of bile acid receptors, such as farnesoid X receptor (FXR) and transmembrane G protein-coupled receptor (TGR) 5, have provided further insight in the pathophysiology of NASH and have led to the development of potential therapeutic targets for NAFLD and NASH. Beyond maintaining bile acid metabolism, FXR and TGR5 also regulate lipid metabolism, maintain glucose homeostasis, increase energy expenditure, and ameliorate hepatic inflammation. These intriguing features have been exploited to develop bile acid analogues to target pathways in NAFLD and NASH pathogenesis. This review provides a brief overview of the pathogenesis of NAFLD and NASH, and then delves into the biological functions of bile acid receptors, particularly with respect to NASH pathogenesis, with a description of the associated experimental data, and, finally, we discuss the prospects of bile acid analogues in the treatment of NAFLD and NASH. PMID:26668692

  6. Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

    PubMed Central

    Nakajima, Kei

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain. PMID:23304532

  7. Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

    PubMed

    Takahashi, Yoshihisa; Fukusato, Toshio

    2014-11-14

    Nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is the most common chronic liver disease, and the prevalence is rapidly increasing worldwide. Nonalcoholic steatohepatitis (NASH), the severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma (HCC). Although noninvasive clinical scores and image-based diagnosis for NAFLD have improved, histopathological evaluation of biopsy specimens remains the gold standard for diagnosing NAFLD/NASH. Steatosis, lobular inflammation, and hepatocellular ballooning are all necessary components for the diagnosis of NASH; fibrosis is also typically observed. Other histopathological abnormalities commonly observed in NASH include hepatocellular glycogenated nuclei, lipogranulomas, and acidophil bodies. The characteristics of pediatric NAFLD/NASH differ from adult NAFLD/NASH. Specifically, steatosis and portal inflammation are more severe in pediatric NAFLD, while intralobular inflammation and perisinusoidal fibrosis are milder. Although interobserver agreement for evaluating the extent of steatosis and fibrosis is high, agreement is low for intralobular and portal inflammation. A recently reported histological variant of HCC, steatohepatitic HCC (SH-HCC), shows features that resemble non-neoplastic steatohepatitis, and is thought to be strongly associated with underlying NASH. In this report, we review the histopathological features of NAFLD/NASH.

  8. Gender-based differences in the relationship between fatty liver disease and atherosclerosis

    PubMed Central

    Kim, Hyun-Jin; Lim, Chae-Wan; Lee, Jae hyuk; Park, Hyung-Bok; Suh, Yongsung; Cho, Yoon-Hyeong; Choi, Tae-Young; Hwang, Eui-Seok; Cho, Deok-Kyu; Kim, Hyun-Jin

    2016-01-01

    Summary Background Carotid intima–media thickness (CIMT) is a surrogate of subclinical atherosclerosis. Fatty liver disease is also linked to increased risk of cardiovascular events. The aim of this study was to evaluate the association between fatty liver disease and CIMT according to gender. Methods Patients who had undergone carotid and abdominal ultrasound between June 2011 and December 2013 were retrospectively evaluated. The differences between the CIMT values measured in the common carotid artery and the prevalence of carotid plaque in patients with fatty liver disease and those with normal livers were investigated. Results Out of a total of 1 121 patients, the men had more fatty liver disease than the women. The mean CIMT of the men was significantly higher than that of the women, and the men had more plaque than the women. The women with fatty liver disease had a significantly higher mean CIMT value and more plaque than the women with normal livers. The differences between the men with fatty liver and those with normal livers in mean CIMT values and in the prevalence of plaque were not significant. In the women, multivariate analysis showed that fatty liver disease was independently associated with subclinical atherosclerosis [adjusted hazards ratio (HR) 1.65, 95% confidence interval (CI) 1.007–2.697, p = 0.047]. Conclusions The men had more fatty liver disease, carotid plaque and higher CIMT values than the women. Fatty liver disease was a useful predictor of atherosclerosis, especially for the female study patients. PMID:26972662

  9. Steatohepatitis and liver fibrosis are predicted by the characteristics of very low density lipoprotein in nonalcoholic fatty liver disease

    PubMed Central

    Jiang, Zhenghui G.; Tapper, Elliot B.; Connelly, Margery A.; Pimentel, Carolina F. M. G.; Feldbrügge, Linda; Kim, Misung; Krawczyk, Sarah; Afdhal, Nezam; Robson, Simon C.; Herman, Mark A.; Otvos, James D.; Mukamal, Kenneth J.; Lai, Michelle

    2016-01-01

    Background & Aims A major challenge in the management of nonalcoholic fatty liver disease (NAFLD) is to identify patients with nonalcoholic steatohepatitis (NASH) and early liver fibrosis. The progression of NAFLD is accompanied by distinctive changes in very low density lipoprotein (VLDL), a lipoprotein particle produced exclusively in the liver. Herein, we sought to determine the characteristics of VLDL profiles associated with NASH and liver fibrosis. Methods We evaluated VLDL profiles of 128 patients from a single centre NAFLD registry, and examined VLDL size, total and subclass VLDL concentrations in relation to NAFLD activity score (NAS), steatohepatitis and liver fibrosis as determined by liver biopsy. Results A near linear relationship was observed between mean VLDL particle size and NAFLD activity score (NAS). In multivariate models, VLDL particle size was significantly associated with both NAS and NASH, after adjustment for BMI and diabetes. A decrease in small VLDL particle concentration was associated with more advanced liver fibrosis. In receiver operative characteristic analyses, mean VLDL size performed similarly to cytokeratin 18 in predicting NASH, whereas small VLDL particle concentration had similar performance to NAFLD fibrosis score in predicting stage 2 or above liver fibrosis. Conclusions The increase in mean VLDL size in NASH and decrease in small VLDL particle concentration in liver fibrosis likely reflect changes in the number and state of hepatocytes associated with NASH and fibrosis. In addition to its value in risk stratification of cardiovascular diseases, circulating VLDL profile may provide information for the staging of NAFLD disease severity. PMID:26815314

  10. Private troubles to public issue: empowering communities to reduce alcohol-related harm in Sabah, Malaysia.

    PubMed

    Lasimbang, Helen Benedict; Shoesmith, Wendy; Mohd Daud, Mohd Nazri Bin; Kaur, Nirmal; Jin, Margaret Chin Pau; Singh, Jaswant; John, Wilfred; Salumbi, Edna; Amir, Lidwina

    2015-09-27

    Alcohol is the number three contributor to the burden of disease worldwide so must remain a priority health promotion issue internationally. Malaysia is a Muslim country and alcohol-related harm was not seen as a priority until recently, because it only affects a minority of the population. Sabah has more than 30 different ethnic groups, and alcohol has a traditional role in the cultural practices of many of these groups. In 2009, the Intervention Group for Alcohol Misuse (IGAM) was formed, under the umbrella of Mercy Malaysia by a group of healthcare workers, academics, members of the Clergy and people who were previously alcohol-dependent concerned about the harmful effects of excessive alcohol consumption. IGAM in collaboration with other bodies have organized public seminars, visited villages and schools, encouraged the formation of a support group and trained healthcare professionals in health promotion intervention. The focus later changed to empowering communities to find solutions to alcohol-related harm in their community in a way which is sensitive to their culture. A standard tool-kit was developed using WHO materials as a guide. Village committees were formed and adapted the toolkit according to their needs. This strategy has been shown to be effective, in that 90% of the 20 committees formed are actively and successfully involved in health promotion to reduce alcohol-related harm in their communities.

  11. Nrf2: A Potential Target for New Therapeutics in Liver Disease

    PubMed Central

    Bataille, AM; Manautou, JE

    2013-01-01

    Nuclear erythroid 2–related factor 2 (Nrf2) is an oxidative stress–mediated transcription factor with a variety of downstream targets aimed at cytoprotection. Nrf2 has recently been implicated as a new therapeutic target for the treatment of liver disease. Here, we focus on the most common liver diseases—nonalcoholic fatty liver disease/steatohepatitis, alcoholic liver disease, and drug-induced liver injury—and highlight areas in the development of these conditions where activation of Nrf2 may alleviate disease progression. PMID:22871994

  12. Epigenetic Modifications in the Biology of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Pirola, Carlos J.; Scian, Romina; Gianotti, Tomas Fernández; Dopazo, Hernán; Rohr, Cristian; Martino, Julio San; Castaño, Gustavo O.; Sookoian, Silvia

    2015-01-01

    Abstract The 5-Hydroxymethylcytosine (5-hmC) is an epigenetic modification whose role in the pathogenesis of metabolic-related complex diseases remains unexplored; 5-hmC appears to be prevalent in the mitochondrial genome. The Ten-Eleven-Translocation (TET) family of proteins is responsible for catalyzing the conversion of 5-methylcytosine to 5-hmC. We hypothesized that epigenetic editing by 5-hmC might be a novel mechanism through which nonalcoholic fatty liver disease (NAFLD)-associated molecular traits could be explained. Hence, we performed an observational study to explore global levels of 5-hmC in fresh liver samples of patients with NAFLD and controls (n = 90) using an enzyme-linked-immunosorbent serologic assay and immunohistochemistry. We also screened for genetic variation in TET 1–3 loci by next generation sequencing to explore its contribution to the disease biology. The study was conducted in 2 stages (discovery and replication) and included 476 participants. We observed that the amount of 5-hmC in the liver of both NAFLD patients and controls was relatively low (up to 0.1%); a significant association was found with liver mitochondrial DNA copy number (R = 0.50, P = 0.000382) and PPARGC1A-mRNA levels (R = −0.57, P = 0.04). We did not observe any significant difference in the 5-hmC nuclear immunostaining score between NAFLD patients and controls; nevertheless, we found that patients with NAFLD (0.4 ± 0.5) had significantly lower nonnuclear-5-hmC staining compared with controls (1.8 ± 0.8), means ± standard deviation, P = 0.028. The missense p.Ile1123Met variant (TET1-rs3998860) was significantly associated with serum levels of caspase-generated CK-18 fragment-cell death biomarker in the discovery and replication stage, and the disease severity (odds ratio: 1.47, 95% confidence interval: 1.10–1.97; P = 0.005). The p.Ile1762Val substitution (TET2-rs2454206) was associated with liver PPARGC1A-methylation and

  13. Acute liver failure: A curable disease by 2024?

    PubMed

    Bernal, William; Lee, William M; Wendon, Julia; Larsen, Fin Stolze; Williams, Roger

    2015-04-01

    Over the last three decades acute liver failure (ALF) has been transformed from a rare and poorly understood condition with a near universally fatal outcome, to one with a well characterized phenotype and disease course. Complex critical care protocols are now applied and emergency liver transplantation (ELT) is an established treatment option. These improvements in care are such that the majority of patients may now be expected to survive (Fig. 1). Key features of the condition have changed dramatically over time, with a remarkable fall in the incidence of cerebral edema and intracranial hypertension, a much feared complication. In this review, we summarize the current understanding of key aspects of the classification, pathophysiology and management of ALF, and discuss the foreseeable challenges that will need to be addressed for further improvements to be achieved.

  14. Regenerative medicine using dental pulp stem cells for liver diseases

    PubMed Central

    Ohkoshi, Shogo; Hara, Hajime; Hirono, Haruka; Watanabe, Kazuhiko; Hasegawa, Katsuhiko

    2017-01-01

    Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes. A point worthy of special mention is that dental pulp can be obtained from deciduous teeth during childhood and can be subsequently harvested when necessary after deposition in a tooth bank. MSCs have not only a regenerative capacity but also act in an anti-inflammatory manner via paracrine mechanisms. Promising efficacies and difficulties with the use of MSC derived from teeth are summarized in this review. PMID:28217369

  15. Probiotics in Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, and Cirrhosis.

    PubMed

    Qamar, Amir A

    2015-01-01

    With the growing epidemic of obesity, the incidence of both nonalcoholic fatty liver disease (NAFL) and nonalcoholic steatohepatitis (NASH) is increasing. The intestinal microbiota differs between individuals who are obese or have normal body mass indices. Animal studies have shown increased intestinal permeability in NAFL, NASH, and cirrhosis. This increases the risk of oxidative and inflammatory injury to the liver from intestinal microbacteria. It may also increase the risk of fatty acid injury and fatty deposition. Bacterial translocation is associated with increased portal hypertension and hepatic encephalopathy in cirrhosis. By preventing bacterial adhesion and translocation, probiotics may have a role in the management of patients with NAFL, NASH, and cirrhosis. Multiple small studies have suggested that probiotics improve some of the clinical markers of activity in patients with NAFL and NASH. Controlled studies have also shown improved outcomes in patients with cirrhosis who were treated with probiotics.

  16. Autophagy and microRNA dysregulation in liver diseases.

    PubMed

    Kim, Kyu Min; Kim, Sang Geon

    2014-01-01

    Autophagy is a catabolic process through which organelles and cellular components are sequestered into autophagosomes and degraded via fusion with lysosomes. Autophagy plays a role in many physiological processes, including stress responses, energy homeostasis, elimination of cellular organelles, and tissue remodeling. In addition, autophagy capacity changes in various disease states. A series of studies have shown that autophagy is strictly controlled to maintain homeostatic balance of energy metabolism and cellular organelle and protein turnover. These studies have also shown that this process is post-transcriptionally controlled by small noncoding microRNAs that regulate gene expression through complementary base pairing with mRNAs. Conversely, autophagy regulates the expression of microRNAs. Therefore, dysregulation of the link between autophagy and microRNA expression exacerbates the pathogenesis of various diseases. In this review, we summarize the roles of autophagy and microRNA dysregulation in the course of liver diseases, with the aim of understanding how microRNAs modify key autophagic effector molecules, and we discuss how this dysregulation affects both physiological and pathological conditions. This article may advance our understanding of the cellular and molecular bases of liver disease progression and promote the development of strategies for pharmacological intervention.

  17. Metabolic aspects of adult patients with nonalcoholic fatty liver disease

    PubMed Central

    Abenavoli, Ludovico; Milic, Natasa; Di Renzo, Laura; Preveden, Tomislav; Medić-Stojanoska, Milica; De Lorenzo, Antonino

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease and it encompasses a spectrum from simple steatosis to steatohepatitis, fibrosis, or cirrhosis. The mechanisms involved in the occurrence of NAFLD and its progression are probably due to a metabolic profile expressed within the context of a genetic predisposition and is associated with a higher energy intake. The metabolic syndrome (MS) is a cluster of metabolic alterations associated with an increased risk for the development of cardiovascular diseases and diabetes. NAFLD patients have more than one feature of the MS, and now they are considered the hepatic components of the MS. Several scientific advances in understanding the association between NAFLD and MS have identified insulin resistance (IR) as the key aspect in the pathophysiology of both diseases. In the multi parallel hits theory of NAFLD pathogenesis, IR was described to be central in the predisposition of hepatocytes to be susceptible to other multiple pathogenetic factors. The recent knowledge gained from these advances can be applied clinically in the prevention and management of NAFLD and its associated metabolic changes. The present review analyses the current literature and highlights the new evidence on the metabolic aspects in the adult patients with NAFLD. PMID:27610012

  18. Fructose, high fructose corn syrup, sucrose, and non-alcoholic liver disease

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nonalcoholic fatty liver disease (NAFLD), formerly called nonalcoholic steatohepatitis, is characterized by hepatic steatosis and abnormal triglyceride accumulation in liver cells. Its etiology, pathophysiology, and pathogenesis are still poorly understood. Some have suggested that the increased in...

  19. Liver-specific magnetic resonance contrast medium in the evaluation of chronic liver disease

    PubMed Central

    dos Reis, Marcio Augusto Correia Rodrigues; Baroni, Ronaldo Hueb

    2015-01-01

    ABSTRACT The hepatobiliary-specific contrast medium (gadoxetic acid – Primovist®) is primarily used to improve detection and characterization of focal hepatic lesions, such as in chronic liver disease patients with suspected hepatocellular carcinoma. Since the contrast medium is selectively taken up by functioning hepatocytes in the late hepatobiliary phase, it helps to detect typical hepatocellular carcinoma, which show low signal intensity on this phase. This imaging feature also assists in differentiating regenerative/dysplastic nodules from early hepatocellular carcinomas (with over 90% accuracy), as well as hypervascular hepatocellular carcinomas from arterial pseudo-enhancement foci. Future perspectives include its use in quantification of hepatic function and fibrosis. PMID:26154554

  20. How is the liver primed or sensitized for alcoholic liver disease?

    PubMed

    Tsukamoto, H; Takei, Y; McClain, C J; Joshi-Barve, S; Hill, D; Schmidt, J; Deaciuc, I; Barve, S; Colell, A; Garcia-Ruiz, C; Kaplowitz, N; Fernandez-Checa, J C; Yokoyama, H; Okamura, Y; Nakamura, Y; Ishii, H; Chawla, R K; Barve, S; Joshi-Barve, S; Watson, W; Nelson, W; Lin, M; Ohata, M; Motomura, K; Enomoto, N; Ikejima, K; Kitamura, T; Oide, H; Hirose, M; Bradford, B U; Rivera, C A; Kono, H; Peter, S; Yamashina, S; Konno, A; Ishikawa, M; Shimizu, H; Sato, N; Thurman, R

    2001-05-01

    This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hidekazu Tsukamoto and Yoshiyuki Takei. The presentations were (1) Tribute to Professor Rajendar K. Chawla, by Craig J. McClain; (2) Dysregulated TNF signaling in alcoholic liver disease, by Craig J. McClain, S. Joshi-Barve, D. Hill, J Schmidt, I. Deaciuc, and S. Barve; (3) The role of mitochondria in ethanol-mediated sensitization of the liver, by Anna Colell, Carmen Garcia-Ruiz, Neil Kaplowitz, and Jose C. Fernandez-Checa; (4) A peroxisome proliferator (bezafibrate) can prevent superoxide anion release into hepatic sinusoid after acute ethanol administration, by Hirokazu Yokoyama, Yukishige Okamura, Yuji Nakamura, and Hiromasa Ishii; (5) S-adenosylmethionine affects tumor necrosis factor-alpha gene expression in macrophages, by Rajendar K. Chawla, S. Barve, S. Joshi-Barve, W. Watson, W. Nelson, and C. McClain; (6) Iron, retinoic acid and hepatic macrophage TNFalpha gene expression in ALD, by Hidekazu Tsukamoto, Min Lin, Mitsuru Ohata, and Kenta Motomura; and (7) Role of Kupffer cells and gut-derived endotoxin in alcoholic liver injury, by N. Enomoto, K. Ikejima, T. Kitamura, H. Oide, Y. Takei, M. Hirose, B. U. Bradford, C. A. Rivera, H. Kono, S. Peter, S. Yamashina, A. Konno, M. Ishikawa, H. Shimizu, N. Sato, and R. Thurman.

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

    PubMed Central

    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

  2. Gut-liver axis and probiotics: their role in non-alcoholic fatty liver disease.

    PubMed

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

    2014-11-14

    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.

  3. Personal strivings, binge drinking, and alcohol-related problems.

    PubMed

    Simons, Jeffrey S; Christopher, Michael S; McLaury, Ann E

    2004-06-01

    This study examined relations between personal strivings and alcohol use among college students. Personal strivings are ongoing goals that individuals are characteristically trying to achieve through their behavior. Participants generated lists of personal strivings following standard instructions and then completed an assessment of alcohol use and related problems. Participants returned to complete a follow-up assessment of drinking behavior after 30 days. Personal strivings were coded into content categories by trained raters using a coding manual. Four content categories were examined for this study: achievement, affiliation, health, and self-presentation. A series of t tests revealed that participants endorsing achievement strivings reported less alcohol-related problems and marginally fewer instances of binge drinking during the 30-day follow-up period. In contrast, participants endorsing self-presentation strivings reported more alcohol-related problems during the follow-up period.

  4. The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease.

    PubMed

    Pastori, Daniele; Polimeni, Licia; Baratta, Francesco; Pani, Arianna; Del Ben, Maria; Angelico, Francesco

    2015-01-01

    Non-alcoholic fatty liver disease is an emerging liver disease in Western countries and the most frequent cause of incidental elevation of serum liver enzymes. Dyslipidaemia is frequently observed in patients with non-alcoholic fatty liver disease, and treatment of dyslipidaemia plays a critical role in the overall management of these patients. Moreover, coronary artery disease remains the most common cause of death. Statins are effective lipid-lowering agents, associated with a lowering the risk of cardiovascular events in several interventional randomized clinical trials. However, statins are often underused in patients with non-alcoholic fatty liver disease and many physicians are concerned about the prescription of statins to patients with unexplained persistent elevation of liver enzymes or active liver disease. Based on currently available data, statin therapy, at low-to-moderate doses, seems to be safe and has low liver toxicity. Treatment of dyslipidaemia in patients with non-alcoholic fatty liver disease is recommended and may also improve liver function tests. In these patients, the risks of not taking statins could outweigh the risks of taking the drug. Conversely, the usefulness of statins for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis is still a matter of debate and randomized clinical trials of adequate size and duration are required.

  5. Interleukin-34 as a fibroblast-derived marker of liver fibrosis in patients with non-alcoholic fatty liver disease.

    PubMed

    Shoji, Hirotaka; Yoshio, Sachiyo; Mano, Yohei; Kumagai, Erina; Sugiyama, Masaya; Korenaga, Masaaki; Arai, Taeang; Itokawa, Norio; Atsukawa, Masanori; Aikata, Hiroshi; Hyogo, Hideyuki; Chayama, Kazuaki; Ohashi, Tomohiko; Ito, Kiyoaki; Yoneda, Masashi; Nozaki, Yuichi; Kawaguchi, Takumi; Torimura, Takuji; Abe, Masanori; Hiasa, Yoichi; Fukai, Moto; Kamiyama, Toshiya; Taketomi, Akinobu; Mizokami, Masashi; Kanto, Tatsuya

    2016-07-01

    Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic non-viral liver disease. Activation of macrophages and hepatic stellate cells is a critical step that promotes liver fibrosis. We aimed to explore the feasibility of interleukin-34 (IL-34), a key regulator of macrophages, as a fibrosis marker in patients with NAFLD. We enrolled 197 liver biopsy-proven NAFLD patients. We evaluated the serum levels of IL-34, macrophage-colony stimulating factor (M-CSF), soluble CD163 (sCD163), 40 cytokines/chemokines, hyaluronic acid, type IV collagen 7s, and clinically-approved fibrosis scores. IL-34 increased with the progression of fibrosis and was an independent marker for liver fibrosis. Immunostaining experiments, using resected liver specimens from NAFLD patients, revealed that IL-34 was mainly expressed on liver fibroblasts. IL-34 based fibrosis score (0.0387*IL-34 (pg/ml) + 0.3623*type IV collagen 7s (ng/ml) + 0.0184*age (year)-1.1850) was a practical predictive model of liver fibrosis. Using receiver-operating characteristic analyses, the area under the curve, sensitivity, and specificity of IL-34 based fibrosis score were superior or comparable to the other fibrosis biomarkers and scores. In conclusion, the IL-34 based fibrosis score, including serum IL-34, type IV collagen 7s and age, is a feasible diagnostic marker of liver fibrosis in NAFLD patients.

  6. The role of tourism in alcohol-related highway fatalities.

    PubMed

    Colón, I

    1985-04-01

    Tourism and fatal single motor vehicle accidents, an index of alcohol-related motor accidents, are examined in a cross-sectional analysis of the 50 states of the Union and the District of Columbia. A multiple regression model is employed in which average mileage driven, percent of metropolitan residents, and number of licensed drivers are statistically controlled. Tourism is found to be positively associated with the single motor vehicle fatality rate. Further research and policy implications are discussed.

  7. Drug dosage recommendations in patients with chronic liver disease.

    PubMed

    Periáñez-Párraga, Leonor; Martínez-López, Iciar; Ventayol-Bosch, Pere; Puigventós-Latorre, Francesc; Delgado-Sánchez, Olga

    2012-04-01

    Chronic liver diseases (CLD) alter the kinetics of drugs. Despite dosage adjustment is based on Child-Pugh scores, there are no available recommendations and/or algorithms of reference to facilitate dosage regimens. A literature review about dose adjustment of the drugs from the hospital guide -which are included in the list of the WHO recommended drugs to be avoided or used with caution in patients with liver disease- was carried out. The therapeutic novelties from the last few years were also included. In order to do so, the summary of product characteristics (SPC), the database DrugDex-Micromedex, the WHO recommendations and the review articles from the last 10 years in Medline were reviewed. Moreover, the kinetic parameters of each drug were calculated with the aim of establishing a theoretical recommendation based on the proposal of Delcò and Huet. Recommendations for 186 drugs are presented according to the SPC (49.5%), DrugDex-Micromedex (26.3%) and WHO (18.8%) indications; six recommendations were based on specific publications; the theoretical recommendation based on pharmacokinetic parameters was proposed in four drugs. The final recommendations for clinical management were: dosage modification (26.9%), hepatic/analytical monitoring of the patient (8.6%), contraindication (18.8%), use with caution (19.3%) and no adjustment required (26.3%). In this review, specific recommendations for the practical management of patients with chronic liver disease are presented. It has been elaborated through a synthesis of the published bibliography and completed by following a theoretical methodology.

  8. The prevalence of nonalcoholic fatty liver disease in the Americas.

    PubMed

    López-Velázquez, Jorge A; Silva-Vidal, Karen V; Ponciano-Rodríguez, Guadalupe; Chávez-Tapia, Norberto C; Arrese, Marco; Uribe, Misael; Méndez-Sánchez, Nahum

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) is an alarming public health problem. The disease is one of the main causes of chronic liver disease worldwide and is directly linked to the increased prevalence of obesity and type 2 diabetes mellitus (T2DM) in the general population. The worldwide prevalence of NAFLD has been estimated at 20-30%, but the prevalence is unknown in the Americas because of a lack of epidemiological studies. However, given the trends in the prevalence of diabetes and obesity, the prevalence of NAFLD and its consequences are expected to increase in the near future. The aim of the present study is to present the current data on the prevalence of NAFLD in the Americas. We performed an electronic search of the main databases from January 2000 to September 2013 and identified 356 reports that were reviewed. We focused on the epidemiology and prevalence of known NAFLD risk factors including obesity, T2DM, and the metabolic syndrome (MS). The prevalence of the MS was highest in the United States, Mexico, Costa Rica, Puerto Rico, Chile, and Venezuela. In addition, Puerto Rico, Guyana, and Mexico have the highest prevalence of T2DM in the Americas, while USA has the most people with T2DM. In conclusion, the prevalence rates of NAFLD and obesity were highest in the United States, Belize, Barbados, and Mexico.

  9. MicroRNAs in Nonalcoholic Fatty Liver Disease

    PubMed Central

    Baffy, György

    2015-01-01

    Nonalcoholic fatty liver disease (NAFLD) has become the most common liver disorder. Strongly linked to obesity and diabetes, NAFLD has the characteristics of complex diseases with substantial heterogeneity. Accordingly, our ability to predict the risk of advanced NAFLD and provide efficient treatment may improve by a better understanding of the relationship between genotype and phenotype. MicroRNAs (miRNAs) play a major role in the fine-tuning of gene expression and they have recently emerged as novel biomarkers and therapeutic tools in the management of NAFLD. These short non-coding RNA sequences act by partial repression or degradation of targeted mRNAs. Deregulation of miRNAs has been associated with different stages of NAFLD, while their biological role in the pathogenesis remains to be fully understood. Systems biology analyses based on predicted target genes have associated hepatic miRNAs with molecular pathways involved in NAFLD progression such as cholesterol and lipid metabolism, insulin signaling, oxidative stress, inflammation, and pathways of cell survival and proliferation. Moreover, circulating miRNAs have been identified as promising noninvasive biomarkers of NAFLD and linked to disease severity. This rapidly growing field is likely to result in major advances in the pathomechanism, prognostication, and treatment of NAFLD. PMID:26690233

  10. Non-alcoholic fatty liver disease, diet and gut microbiota

    PubMed Central

    Finelli, Carmine; Tarantino, Giovanni

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is a severe liver disease that is increasing in prevalence with the worldwide epidemic of obesity and its related insulin-resistance state. Evidence for the role of the gut microbiota in energy storage and the subsequent development of obesity and some of its related diseases is now well established. More recently, a new role of gut microbiota has emerged in NAFLD. The gut microbiota is involved in gut permeability, low-grade inflammation and immune balance, it modulates dietary choline metabolism, regulates bile acid metabolism and produces endogenous ethanol. All of these factors are molecular mechanisms by which the microbiota can induce NAFLD or its progression toward overt non-alcoholic steatohepatitis. Modification of the gut microbiota composition and/or its biochemical capacity by specific dietary or pharmacological interventions may advantageously affect host metabolism. Large-scale intervention trials, investigating the potential benefit of prebiotics and probiotics in improving cardiometabolic health in high-risk populations, are fervently awaited. PMID:26417275

  11. The lymphatic vascular system in liver diseases: its role in ascites formation.

    PubMed

    Chung, Chuhan; Iwakiri, Yasuko

    2013-06-01

    The lymphatic system is part of the circulatory system and plays a key role in normal vascular function. Its failure plays a crucial role in the development and maintenance of various diseases including liver diseases. Lymphangiogenesis (the growth of lymphatic vessels) and changes in the properties of lymphatic vessels are associated with pathogenesis of tumor metastases, ascites formation, liver fibrosis/cirrhosis and portal hypertension. Despite its significant role in liver diseases and its importance as a potential therapeutic target for those diseases, the lymphatic vascular system of the liver is poorly understood. Therefore, how the lymphatic vascular system in general and lymphangiogenesis in particular are mechanistically related to the pathogenesis and maintenance of liver diseases are largely unknown. This article summarizes: 1) the lymphatic vascular system; 2) its role in liver tumors, liver fibrosis/cirrhosis and portal hypertension; and 3) its role in ascites formation.

  12. New advances in molecular mechanisms and emerging therapeutic targets in alcoholic liver diseases

    PubMed Central

    Williams, Jessica A; Manley, Sharon; Ding, Wen-Xing

    2014-01-01

    Alcoholic liver disease is a major health problem in the United States and worldwide. Chronic alcohol consumption can cause steatosis, inflammation, fibrosis, cirrhosis and even liver cancer. Significant progress has been made to understand key events and molecular players for the onset and progression of alcoholic liver disease from both experimental and clinical alcohol studies. No successful treatments are currently available for treating alcoholic liver disease; therefore, development of novel pathophysiological-targeted therapies is urgently needed. This review summarizes the recent progress on animal models used to study alcoholic liver disease and the detrimental factors that contribute to alcoholic liver disease pathogenesis including miRNAs, S-adenosylmethionine, Zinc deficiency, cytosolic lipin-1β, IRF3-mediated apoptosis, RIP3-mediated necrosis and hepcidin. In addition, we summarize emerging adaptive protective effects induced by alcohol to attenuate alcohol-induced liver pathogenesis including FoxO3, IL-22, autophagy and nuclear lipin-1α. PMID:25278688

  13. Non-alcoholic Fatty liver disease in children.

    PubMed

    Singer, Cristina; Stancu, Polixenia; Coşoveanu, Simona; Botu, Alina

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pathogeny, clinical and paraclinical findings, and treatment of NAFLD in children.

  14. Non-Alcoholic Fatty Liver Disease in Children

    PubMed Central

    SINGER, CRISTINA; STANCU, POLIXENIA; COŞOVEANU, SIMONA; BOTU, ALINA

    2014-01-01

    In the last years, there has been extremely much information which reveals an alarming increase of obesity in children and, at the same time, an increase of the incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD implies a wide range of affections starting from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH); the latter can evolve to cirrhosis and hepatic carcinoma. All these affections were noticed in children, too. The article presents data on the epidemiology, pathogeny, clinical and paraclinical findings, and treatment of NAFLD in children. PMID:25729601

  15. Malnutrition and Nutritional Support in Alcoholic Liver Disease: a Review.

    PubMed

    Chao, Andrew; Waitzberg, Dan; de Jesus, Rosangela Passos; Bueno, Allain A; Kha, Victor; Allen, Karen; Kappus, Matthew; Medici, Valentina

    2016-12-01

    Malnutrition is associated with alcoholic liver disease (ALD) and related complications such as hepatic encephalopathy and increased rate of infections. Avoidance of prolonged fasting and overly restrictive diets is important to avoid poor nutrition. Adequate intake of calories, protein, and micronutrients via frequent small meals and evening supplements and/or enteral and parenteral nutrition when indicated has been associated with reduced mortality and morbidity in patients with ALD. Modification of protein/fat sources and composition in addition to probiotic supplementation are promising interventions for decreased progression of ALD and its complications.

  16. Current Pharmacologic Therapy for Nonalcoholic Fatty Liver Disease.

    PubMed

    Ganesh, Swaytha; Rustgi, Vinod K

    2016-05-01

    Weight loss, regular exercise, and diet composition modification seem to improve biochemical and histologic abnormalities. Other therapies directed at insulin resistance, oxidative stress, cytoprotection, and fibrosis may also offer benefits. Insulin sensitizers and vitamin E seem to be the most promising; however, they cause side effects. A multifaceted approach of lifestyle modifications, weight loss, and pharmacotherapy can be used in combination, but no single treatment approach has proved universally applicable to the general population with nonalcoholic steatohepatitis (NASH). Continuous clinical and preclinical studies on existing and potential drugs are needed to improve treatment of nonalcoholic fatty liver disease/NASH.

  17. Cystic fibrosis-related liver disease: a single-center experience.

    PubMed

    Costa, Paula Catarino; Barreto, Celeste Canha; Pereira, Luisa; Lobo, Maria Luisa; Costa, Maria Adília; Lopes, Ana Isabel Gouveia

    2011-06-30

    Prospective studies concerning liver disease in pediatric cystic fibrosis patients are scarce. The present study aimed to describe the prevalence and clinical expression of cystic fibrosis - related liver disease, in a cohort of 62 pediatric patients. Descriptive study, resulting from the prospective evaluation, between 1994 and 2009, of 62 pediatric patients (age <18 years) with cystic fibrosis. The follow-up protocol included a clinical assessment every 2 months, liver function tests every 6 months and annual liver ultrasonography. The cumulative prevalence of liver disease was 11.2% (7/62 cases). All patients had ΔF508 mutation and pancreatic insufficiency, none had meconium ileus. The liver involvement became clinically evident at a mean age of 8 years (3-15 years), revealed by hepatomegaly or hepatosplenomegaly (3 cases) and/ or abnormalities of liver function tests (3 cases) changes of liver ultrasound (7 cases) with evidence of portal hypertension (2 cases). Four patients were submitted to liver biopsy; biliary fibrosis was documented in one case, focal biliary cirrhosis in 2 cases and multilobular cirrhosis in another case. Within a median 11.6 years follow-up period (all patients under UDCA therapy after liver disease diagnosis), progression of liver disease was observed in 2 patients; one patient developed refractory variceal bleeding and progressive hepatic failure, requiring liver transplant. The results of the present study agree with those of previous pediatric studies, further documenting clinical expression of liver disease in CF patients, which is usually detected in the first decade of life and emphasize the contribution of ultrasound to early diagnosis of liver involvement. Moreover, although advanced liver disease is a relatively rare event, early isolated liver transplantation may have to be considered at this age group.

  18. Risk of alcohol use relapse after liver transplantation for alcoholic liver disease

    PubMed Central

    Onishi, Yasuharu; Kimura, Hiroyuki; Hori, Tomohide; Kishi, Shinichi; Kamei, Hideya; Kurata, Nobuhiko; Tsuboi, Chisato; Yamaguchi, Naoko; Takahashi, Mayu; Sunada, Saki; Hirano, Mitsuaki; Fujishiro, Hiroshige; Okada, Takashi; Ishigami, Masatoshi; Goto, Hidemi; Ozaki, Norio; Ogura, Yasuhiro

    2017-01-01

    AIM To investigate factors, including psychosocial factors, associated with alcoholic use relapse after liver transplantation (LT) for alcoholic liver disease (ALD). METHODS The clinical records of 102 patients with ALD who were referred to Nagoya University Hospital for LT between May 2003 and March 2015 were retrospectively evaluated. History of alcohol intake was obtained from their clinical records and scored according to the High-Risk Alcoholism Relapse scale, which includes duration of heavy drinking, types and amount of alcohol usually consumed, and previous inpatient treatment history for alcoholism. All patients were assessed for eligibility for LT according to comprehensive criteria, including Child-Pugh score, Model for End-Stage Liver Disease score, and psychosocial criteria. RESULTS Of the 102 patients with ALD referred for LT, seven (6.9%) underwent LT. One (14.3%) of these seven patients returned to heavy drinking, but that patient was able to successfully quit drinking following an immediate intervention, consisting of psychotherapeutic education and supportive psychotherapy, by a psychiatrist. A comparison between the transplantation/registration (T/R) group, consisting of the seven patients who underwent LT and 10 patients listed for deceased donor LT, and 50 patients who did not undergo LT and were not listed for deceased donor LT (non-T/R group), showed statistically significant differences in duration of abstinence period (P < 0.01), duration of heavy drinking (P < 0.05), adherence to medical treatment (P < 0.01), and declaration of abstinence (P < 0.05). CONCLUSION Patients with ALD referred for LT require comprehensive evaluation, including evaluation of psychosocial criteria, to prevent alcoholic recidivism. PMID:28223731

  19. Fatty Liver Index and Lipid Accumulation Product Can Predict Metabolic Syndrome in Subjects without Fatty Liver Disease

    PubMed Central

    Cheng, Yuan-Lung; Wang, Yuan-Jen; Lan, Keng-Hsin; Huo, Teh-Ia; Hsieh, Wei-Yao; Hou, Ming-Chih; Lee, Fa-Yauh; Wu, Jaw-Ching; Lee, Shou-Dong

    2017-01-01

    Background. Fatty liver index (FLI) and lipid accumulation product (LAP) are indexes originally designed to assess the risk of fatty liver and cardiovascular disease, respectively. Both indexes have been proven to be reliable markers of subsequent metabolic syndrome; however, their ability to predict metabolic syndrome in subjects without fatty liver disease has not been clarified. Methods. We enrolled consecutive subjects who received health check-up services at Taipei Veterans General Hospital from 2002 to 2009. Fatty liver disease was diagnosed by abdominal ultrasonography. The ability of the FLI and LAP to predict metabolic syndrome was assessed by analyzing the area under the receiver operating characteristic (AUROC) curve. Results. Male sex was strongly associated with metabolic syndrome, and the LAP and FLI were better than other variables to predict metabolic syndrome among the 29,797 subjects. Both indexes were also better than other variables to detect metabolic syndrome in subjects without fatty liver disease (AUROC: 0.871 and 0.879, resp.), and the predictive power was greater among women. Conclusion. Metabolic syndrome increases the cardiovascular disease risk. The FLI and LAP could be used to recognize the syndrome in both subjects with and without fatty liver disease who require lifestyle modifications and counseling. PMID:28194177

  20. [The comparison of algorithms on the CT image retrieval of Xinjiang local liver hydatid disease].

    PubMed

    Yan, Chuanbo; Hamit, Murat; Li, Li; Chen, Jianjun; Hu, Yahting; Kong, Dewei; Zhou, Jingjing

    2013-10-01

    Xinjiang local liver hydatid disease is an infectious parasitic disease in Xinjiang pastoral areas. Based on the image features, selecting the appropriate distance algorithms to retrieve the image quickly and accurately, different distance algorithms have been induced in this area, which can greatly assist the doctors to early detect, diagnose and cure the liver hydatid disease. This paper compared the performance of different distance algorithms to retrieve the image when using the liver hydatid disease medical image texture features. The results showed that: for the liver hydatid disease medical images retrieval based on gray level cocurrence matrix (GLCM) texture features, the Mahalanobis distance algorithm is superior to other distance algorithms.

  1. Current treatment options for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

    PubMed

    Beaton, Melanie D

    2012-06-01

    Nonalcoholic fatty liver disease is the leading cause of liver disease in western society. It is a cause of end-stage liver disease, with increased mortality secondary to cirrhosis and its complications. It is also recognized that cardiovascular disease is a significant cause of death in these patients. Significant work evaluating various treatments has been performed in recent years; however, to date, no ideal therapy exists. Lifestyle modification remains the cornerstone of management. The present article reviews the current status of various treatment modalities evaluated in nonalcoholic fatty liver disease.

  2. A comparison of the fibrotic potential of nonalcoholic fatty liver disease and chronic hepatitis C.

    PubMed

    Charlotte, Fréderic; Le Naour, Gilles; Bernhardt, Carole; Poynard, Thierry; Ratziu, Vlad

    2010-08-01

    In nonalcoholic fatty liver disease the amount of fibrosis for individual histologic stages is unknown. To better understand the fibrotic potential of nonalcoholic fatty liver disease, we compared the amount of fibrosis in nonalcoholic fatty liver disease versus chronic hepatitis C virus patients. The area of fibrosis for equivalent fibrosis stages was measured by micromorphometry in 70 nonalcoholic fatty liver disease and 70 matched, untreated, chronic hepatitis C virus controls. The area of fibrosis correlated with Brunt stage (r = 0.71; P < .001) in nonalcoholic fatty liver disease and METAVIR stage (r = 0.58; P < .001) in chronic hepatitis C virus. Mean area of fibrosis was similar in nonalcoholic fatty liver disease and chronic hepatitis C virus patients (7.77% versus 7.70%). Although chronic hepatitis C virus patients displayed higher area of fibrosis in early disease (no or mild fibrosis), nonalcoholic fatty liver disease and chronic hepatitis C virus patients had similar area of fibrosis in more advanced disease (7.83% versus 8.06%, respectively; P = .86 for bridging fibrosis; and 16.62% versus 12.98%, respectively; P = .29 for cirrhosis). The area of fibrosis was similar in Brunt stage 3 nonalcoholic fatty liver disease and METAVIR stage 2 chronic hepatitis C virus, the usual threshold for initiating therapy. The area of steatosis declined with increasing fibrosis stages confirming the early loss of liver fat with progressive fibrosis in nonalcoholic fatty liver disease. Fibrosis is as abundant in nonalcoholic fatty liver disease as in chronic hepatitis C virus, especially in the advanced stages of the disease. The fibrotic potential of nonalcoholic fatty liver disease is as severe as that of chronic hepatitis C virus.

  3. American Association for the Study of Liver Diseases

    MedlinePlus

    ... Special Interest Groups Governing Board Member Committees Emerging Liver Scholars Resident Program Fellows Program New Trainees Worksites Events and Professional Development Calendar The Liver Meeting® Webinars LiverLearning® Continuing Medical Education Program GI/ ...

  4. Cannabinoid receptor type 2 functional variant influences liver damage in children with non-alcoholic fatty liver disease.

    PubMed

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco; Miraglia del Giudice, Emanuele; Nobili, Valerio

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis.Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD.CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage.We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02).Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage.

  5. Cannabinoid Receptor Type 2 Functional Variant Influences Liver Damage in Children with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Rossi, Francesca; Bellini, Giulia; Alisi, Anna; Alterio, Arianna; Maione, Sabatino; Perrone, Laura; Locatelli, Franco

    2012-01-01

    Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of disease ranging from simple steatosis to inflammatory steatohepatitis (NASH) with different degrees of fibrosis that can ultimately progress to cirrhosis. Accumulating evidence suggests the involvement of the endocannabinoid-system in liver disease and related complications. In particular, hepatoprotective properties for Cannabinoid Receptor type 2 (CB2) have been shown both through experimental murine models of liver injury and association study between a CB2 functional variant, Q63R, and liver enzymes in Italian obese children with steatosis. Here, in order to clarify the role of CB2 in severity of childhood NAFLD, we have investigated the association of the CB2 Q63R variant, with histological parameters of liver disease severity in 118 Italian children with histologically-proven NAFLD. CB2 Q63R genotype was assigned performing a TaqMan assay and a general linear model analysis was used to evaluate the association between the polymorphism and the histological parameters of liver damage. We have found that whereas CB2 Q63R variant is not associated with steatosis or fibrosis, it is associated with the severity of the inflammation (p = 0.002) and the presence of NASH (p = 0.02). Our findings suggest a critical role for CB2 Q63R variant in modulating hepatic inflammation state in obese children and in the consequent increased predisposition of these patients to liver damage. PMID:22927922

  6. Insights from Genome-Wide Association Analyses of Nonalcoholic Fatty Liver Disease

    PubMed Central

    Kahali, Bratati; Halligan, Brian; Speliotes, Elizabeth K.

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is caused by hepatic steatosis, which can progress to nonalcoholic steatohepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma in the absence of excessive alcohol consumption. Nonalcoholic fatty liver disease will become the number one cause of liver disease worldwide by 2020. Nonalcoholic fatty liver disease is correlated albeit imperfectly with obesity and other metabolic diseases such as diabetes, hyperlipidemia, and cardiovascular disease, but exactly how having one of these diseases contributes to the development of other metabolic diseases is only now being elucidated. Development of NAFLD and related metabolic diseases is genetically influenced in the population, and recent genome-wide association studies (GWASs) have discovered genetic variants that associate with these diseases. These GWAS-associated variants cannot only help us to identify individuals at high risk of developing NAFLD, but also to better understand its pathophysiology so that we can develop more effective treatments for this disease and related metabolic diseases in the future. PMID:26676813

  7. Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases.

    PubMed

    Chu, Andrew S; Perlmutter, David H; Wang, Yan

    2014-01-01

    Alpha-1-antitrypsin deficiency (ATD) is one of the most common genetic causes of liver disease and is a prototype of liver diseases caused by the pathologic accumulation of aggregated mutant alpha-1-antitrypsin Z (ATZ) within liver cells. In the case of ATD-associated liver disease, the resulting "gain-of-function" toxicity can lead to serious clinical manifestations, including cirrhosis and hepatocellular carcinoma. Currently, the only definitive therapy for ATD-associated liver disease is liver transplantation, but recent efforts have demonstrated the exciting potential for novel therapies that target disposal of the mutant protein aggregates by harnessing a cellular homeostasis mechanism called autophagy. In this review, we will summarize research advances on autophagy and genetic liver diseases. We will discuss autophagy enhancer strategies for liver disease due to ATD and another genetic liver disease, inherited hypofibrinogenemia, caused by the proteotoxic effects of a misfolded protein. On the basis of recent evidence that autophagy plays a role in cellular lipid degradation, we also speculate about autophagy enhancer strategies for treatment of hepatic lipid storage diseases such as cholesterol ester storage disease.

  8. Does the Intestinal Microbiota Explain Differences in the Epidemiology of Liver Disease between East and West?

    PubMed

    Nakamoto, Nobuhiro; Schnabl, Bernd

    2016-04-01

    Changes in bacterial communities are associated with the pathogenesis of many diseases including inflammatory bowel disease and liver disease. Dysbiosis can induce intestinal inflammation resulting in increased intestinal permeability and bacterial translocation. The majority of chronic liver diseases are associated with bacterial translocation resulting in or enhancing an inflammatory response in the liver. Intestinal inflammation and a dysfunctional intestinal barrier are not sufficient to cause liver disease in the absence of an additional liver insult. In this article, the authors summarize differences in intestinal microbiota composition between Eastern and Western countries. The authors specifically discuss whether differences in microbiota composition could explain the epidemiological differences in liver disease found in Asia and Europe/the USA.

  9. Non-alcoholic fatty liver disease: a new epidemic in children.

    PubMed

    Ciocca, Mirta; Ramonet, Margarita; Álvarez, Fernando

    2016-12-01

    Non-alcoholic fatty liver disease is considered one of the most common causes of liver disease in adults and children, consistent with the increased prevalence of obesity in both populations worldwide. It is a multifactorial condition involving a broad spectrum of liver diseases than range from simple steatosis to steatohepatitis, and characterized by histological findings of inflammation and fibrosis. Its pathogenesis and progression are not fully understood yet, and a more complete understanding of liver disease may aid in developing new therapies and noninvasive diagnostic tools. Liver biopsy remains the gold standard for disease staging. Although lifestyle and diet modifications are the keys in non-alcoholic fatty liver disease treatment, the development of new drugs may be promising for patients failing first-line therapy.

  10. Does the Intestinal Microbiota Explain Differences in the Epidemiology of Liver Disease between East and West?

    PubMed Central

    Nakamoto, Nobuhiro; Schnabl, Bernd

    2016-01-01

    Changes in bacterial communities are associated with the pathogenesis of many diseases including inflammatory bowel disease and liver disease. Dysbiosis can induce intestinal inflammation resulting in increased intestinal permeability and bacterial translocation. The majority of chronic liver diseases are associated with bacterial translocation resulting in or enhancing an inflammatory response in the liver. Intestinal inflammation and a dysfunctional intestinal barrier are not sufficient to cause liver disease in the absence of an additional liver insult. In this article, the authors summarize differences in intestinal microbiota composition between Eastern and Western countries. The authors specifically discuss whether differences in microbiota composition could explain the epidemiological differences in liver disease found in Asia and Europe/the USA. PMID:27243019

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

    PubMed Central

    Lu, Kuan-Hung; Liu, Chun-Ting; Raghu, Rajasekaran; Sheen, Lee-Yan

    2012-01-01

    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. PMID:24716123

  12. Leptospira Exposure and Patients with Liver Diseases: A Case-Control Seroprevalence Study

    PubMed Central

    Alvarado-Esquivel, Cosme; Sánchez-Anguiano, Luis Francisco; Hernández-Tinoco, Jesús; Ramos-Nevárez, Agar; Margarita Cerrillo-Soto, Sandra; Alberto Guido-Arreola, Carlos

    2016-01-01

    The seroepidemiology of Leptospira infection in patients suffering from liver disease has been poorly studied. Information about risk factors associated with infection in liver disease patients may help in the optimal planning of preventive measures. We sought to determine the association of Leptospira IgG seroprevalence and patients with liver diseases, and to determine the characteristics of the patients with Leptospira exposure. We performed a case-control study of 75 patients suffering from liver diseases and 150 age- and gender-matched control subjects. Diagnoses of liver disease included liver cirrhosis, steatosis, chronic hepatitis, acute hepatitis, and amoebic liver abscess. Sera of participants were analyzed for the presence of anti- Leptospira IgG antibodies using a commercially available enzyme immunoassay. Anti-Leptospira IgG antibodies were found in 17 (22.7%) of 75 patients and in 15 (10.0%) of 150 control subjects (OR = 2.32; 95% CI: 1.09-4.94; P=0.03). This is the first age- and gender-matched case control study about Leptospira seroprevalence in patients with liver diseases. Results indicate that Leptospira infection is associated with chronic and acute liver diseases. Results warrants for additional studies on the role of Leptospira exposure in chronic liver disease. PMID:27493589

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

    PubMed

    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.

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

    PubMed Central

    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

  15. The Role of Iron and Iron Overload in Chronic Liver Disease

    PubMed Central

    Milic, Sandra; Mikolasevic, Ivana; Orlic, Lidija; Devcic, Edita; Starcevic-Cizmarevic, Nada; Stimac, Davor; Kapovic, Miljenko; Ristic, Smiljana

    2016-01-01

    The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models. PMID:27332079

  16. Herbal Products: Benefits, Limits, and Applications in Chronic