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.

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

Folate, Alcohol, and Liver Disease

PubMed Central

Medici, Valentina; Halsted, Charles H.

2013-01-01

Alcoholic liver disease (ALD) is typically associated with folate deficiency, which is the result of reduced dietary folate intake, intestinal malabsorption, reduced liver uptake and storage, and increased urinary folate excretion. Folate deficiency favors the progression of liver disease through mechanisms that include its effects on methionine metabolism with consequences for DNA synthesis and stability and the epigenetic regulation of gene expression involved in pathways of liver injury. This paper reviews the pathogenesis of alcoholic liver disease with particular focus on ethanol-induced alterations in methionine metabolism which may act in synergy with folate deficiency to decrease antioxidant defense as well as DNA stability while regulating epigenetic mechanisms of relevant gene expressions. We also review the current evidence available on potential treatments of alcoholic liver disease based on correcting abnormalities in methionine metabolism and the methylation regulation of relevant gene expressions. PMID:23136133

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

PubMed

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

2015-06-01

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

Clinical epidemiology and disease burden of nonalcoholic fatty liver disease

PubMed Central

Perumpail, Brandon J; Khan, Muhammad Ali; Yoo, Eric R; Cholankeril, George; Kim, Donghee; Ahmed, Aijaz

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) is defined as the presence of hepatic fat accumulation after the exclusion of other causes of hepatic steatosis, including other causes of liver disease, excessive alcohol consumption, and other conditions that may lead to hepatic steatosis. NAFLD encompasses a broad clinical spectrum ranging from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and finally hepatocellular carcinoma (HCC). NAFLD is the most common liver disease in the world and NASH may soon become the most common indication for liver transplantation. Ongoing persistence of obesity with increasing rate of diabetes will increase the prevalence of NAFLD, and as this population ages, many will develop cirrhosis and end-stage liver disease. There has been a general increase in the prevalence of NAFLD, with Asia leading the rise, yet the United States is following closely behind with a rising prevalence from 15% in 2005 to 25% within 5 years. NAFLD is commonly associated with metabolic comorbidities, including obesity, type II diabetes, dyslipidemia, and metabolic syndrome. Our understanding of the pathophysiology of NAFLD is constantly evolving. Based on NAFLD subtypes, it has the potential to progress into advanced fibrosis, end-stage liver disease and HCC. The increasing prevalence of NAFLD with advanced fibrosis, is concerning because patients appear to experience higher liver-related and non-liver-related mortality than the general population. The increased morbidity and mortality, healthcare costs and declining health related quality of life associated with NAFLD makes it a formidable disease, and one that requires more in-depth analysis. PMID:29307986

Liver fibrosis markers in alcoholic liver disease.

PubMed

Chrostek, Lech; Panasiuk, Anatol

2014-07-07

Alcohol is one of the main factors of liver damage. The evaluation of the degree of liver fibrosis is of great value for therapeutic decision making in patients with alcoholic liver disease (ALD). Staging of liver fibrosis is essential to define prognosis and management of the disease. Liver biopsy is a gold standard as it has high sensitivity and specificity in fibrosis diagnostics. Taking into account the limitations of liver biopsy, there is an exigency to introduce non-invasive serum markers for fibrosis that would be able to replace liver biopsy. Ideal serum markers should be specific for the liver, easy to perform and independent to inflammation and fibrosis in other organs. Serum markers of hepatic fibrosis are divided into direct and indirect. Indirect markers reflect alterations in hepatic function, direct markers reflect extracellular matrix turnover. These markers should correlate with dynamic changes in fibrogenesis and fibrosis resolution. The assessment of the degree of liver fibrosis in alcoholic liver disease has diagnostic and prognostic implications, therefore noninvasive assessment of fibrosis remains important. There are only a few studies evaluating the diagnostic and prognostic values of noninvasive biomarkers of fibrosis in patients with ALD. Several noninvasive laboratory tests have been used to assess liver fibrosis in patients with alcoholic liver disease, including the hyaluronic acid, FibroTest, FibrometerA, Hepascore, Forns and APRI indexes, FIB4, an algorithm combining Prothrombin index (PI), α-2 macroglobulin and hyaluronic acid. Among these tests, Fibrotest, FibrometerA and Hepascore demonstrated excellent diagnostic accuracy in identifying advanced fibrosis and cirrhosis, and additionally, Fibrotest was independently associated with survival. Therefore, the use of biomarkers may reduce the need for liver biopsy and permit an earlier treatment of alcoholic patients.

Intestinal microbiota in liver disease.

PubMed

Haque, Tanvir R; Barritt, A Sidney

2016-02-01

The intestinal microbiota have emerged as a topic of intense interest in gastroenterology and hepatology. The liver is on the front line as the first filter of nutrients, toxins and bacterial metabolites from the intestines and we are becoming increasingly aware of interactions among the gut, liver and immune system as important mediators of liver health and disease. Manipulating the microbiota with therapeutic intent is a rapidly expanding field. In this review, we will describe what is known about the contribution of intestinal microbiota to liver homeostasis; the role of dysbiosis in the pathogenesis of liver disease including alcoholic and non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma; and the therapeutic manifestations of altering intestinal microbiota via antibiotics, prebiotics, probiotics and fecal microbiota transplantation. Copyright © 2016. Published by Elsevier Ltd.

Nuclear Receptor Variants in Liver Disease

PubMed Central

Müllenbach, Roman; Weber, Susanne N.; Lammert, Frank

2012-01-01

This review aims to provide a snapshot of the actual state of knowledge on genetic variants of nuclear receptors (NR) involved in regulating important aspects of liver metabolism. It recapitulates recent evidence for the application of NR in genetic diagnosis of monogenic (“Mendelian”) liver disease and their use in clinical diagnosis. Genetic analysis of multifactorial liver diseases such as viral hepatitis or fatty liver disease identifies key players in disease predisposition and progression. Evidence from these analyses points towards a role of NR polymorphisms in common diseases, linking regulatory networks to complex and variable phenotypes. The new insights into NR variants also offer perspectives and cautionary advice for their use as handles towards diagnosis and treatment. PMID:22523693

Anesthesia for Patients With Liver Disease

PubMed Central

Rahimzadeh, Poupak; Safari, Saeid; Faiz, Seyed Hamid Reza; Alavian, Seyed Moayed

2014-01-01

Context: Liver plays an important role in metabolism and physiological homeostasis in the body. This organ is unique in its structure and physiology. So it is necessary for an anesthesiologist to be familiar with various hepatic pathophysiologic conditions and consequences of liver dysfunction. Evidence Acquisition: We searched MEDLINE (Pub Med, OVID, MD Consult), SCOPUS and the Cochrane database for the following keywords: liver disease, anesthesia and liver disease, regional anesthesia in liver disease, epidural anesthesia in liver disease and spinal anesthesia in liver disease, for the period of 1966 to 2013. Results: Although different anesthetic regimens are available in modern anesthesia world, but anesthetizing the patients with liver disease is still really tough. Spinal or epidural anesthetic effects on hepatic blood flow and function is not clearly investigated, considering both the anesthetic drug-induced changes and outcomes. Regional anesthesia might be used in patients with advanced liver disease. In these cases lower drug dosages are used, considering the fact that locally administered drugs have less systemic effects. In case of general anesthesia it seems that using inhalation agents (Isoflurane, Desflurane or Sevoflurane), alone or in combination with small doses of fentanyl can be considered as a reasonable regimen. When administering drugs, anesthetist must realize and consider the substantially changed pharmacokinetics of some other anesthetic drugs. Conclusions: Despite the fact that anesthesia in chronic liver disease is a scary and pretty challenging condition for every anesthesiologist, this hazard could be diminished by meticulous attention on optimizing the patient’s condition preoperatively and choosing appropriate anesthetic regimen and drugs in this setting. Although there are paucity of statistics and investigations in this specific group of patients but these little data show that with careful monitoring and considering the above

Extracorporeal Bioartificial Liver for Treating Acute Liver Diseases

PubMed Central

Kumar, Ashok; Tripathi, Anuj; Jain, Shivali

2011-01-01

Abstract: Liver is a vital organ of the human body performing myriad of essential functions. Liver-related ailments are often life-threatening and dramatically deteriorate the quality of life of patients. Management of acute liver diseases requires adequate support of various hepatic functions. Thus far, liver transplantation has been proven as the only effective solution for acute liver diseases. However, broader application of liver transplantation is limited by demand for lifelong immunosuppression, shortage of organ donors, relative high morbidity, and high cost. Therefore, research has been focused on attempting to develop alternative support systems to treat liver diseases. Earlier attempts have been made to use nonbiological therapies based on the use of conventional detoxification procedures such as filtration and dialysis. However, the absence of liver cells in such techniques reduced the overall survival rate of the patients and led to inadequate essential liver-specific functions. As a result, there has been growing interest in the development of biological therapy-based extracorporeal liver support systems as a bridge to liver transplantation or to support the ailing liver. A bioartificial liver support is an extracorporeal device through which plasma is circulated over living and functionally active hepatocytes packed in a bioreactor with the aim to aid the diseased liver until it regenerates or until a suitable graft for transplantation is available. This review article gives a brief overview of efficacy of various liver support systems that are currently available. Also, the development of advanced liver support systems, which has been analyzed for improving the important system component such as cell source and other culture and circulation conditions for the maintenance of the liver-specific functions, have been described. PMID:22416599

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Microbiota-Liver Axis in Hepatic Disease

PubMed Central

Chassaing, Benoit; Etienne-Mesmin, Lucie; Gewirtz, Andrew T.

2014-01-01

Accumulating evidence indicates that the gut microbiota, long appreciated to be a key determinant of intestinal inflammation, is also playing a key role in chronic inflammatory disease of the liver. Such studies have yielded a general central hypothesis whereby microbiota products activate the innate immune system to drive pro-inflammatory gene expression thus promoting chronic inflammatory disease of the liver. This article reviews the background supporting this hypothesis, outlines how it can potentially explain classic and newly emerging epidemiological chronic inflammatory liver disease, and discusses potential therapeutic means to manipulate the microbiota so as to prevent and/or treat liver disease. PMID:23703735

Hepatitis A and B superimposed on chronic liver disease: vaccine-preventable diseases.

PubMed

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations.

Hepatitis A and B Superimposed on Chronic Liver Disease: Vaccine-Preventable Diseases

PubMed Central

Keeffe, Emmet B

2006-01-01

A number of studies have demonstrated that the acquisition of hepatitis A or hepatitis B in patients with chronic liver disease is associated with high rates of morbidity and mortality. Superimposition of acute hepatitis A in patients with chronic hepatitis C has been associated with a particularly high mortality rate, and chronic hepatitis B virus coinfection with hepatitis C virus is associated with an accelerated progression of chronic liver disease to cirrhosis, decompensated liver disease and hepatocellular carcinoma. With the availability of vaccines against hepatitis B and hepatitis A since 1981 and 1995, respectively, these are vaccine-preventable diseases. Studies have confirmed that hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild to moderate chronic liver disease. However, hepatitis A and B vaccination is less effective in patients with advanced liver disease and after liver transplantation. These observations have led to the recommendation that patients undergo hepatitis A and B vaccination early in the natural history of their chronic liver disease. Vaccination rates are low in clinical practice, and public health and educational programs are needed to overcome barriers to facilitate timely implementation of these recommendations. PMID:18528476

Tuberculosis and liver disease: management issues.

PubMed

Sonika, Ujjwal; Kar, Premashis

2012-01-01

Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.

Coeliac disease in autoimmune liver disease: a cross-sectional study and a systematic review.

PubMed

Mirzaagha, Foroozandeh; Azali, Sepideh Hagh; Islami, Farhad; Zamani, Farhad; Khalilipour, Elias; Khatibian, Morteza; Malekzadeh, Reza

2010-09-01

Several studies have reported an association between coeliac disease and autoimmune liver disease, but there is little information on the prevalence of coeliac disease in certain autoimmune liver diseases, particularly from non-European, non-American countries. To investigate prevalence of coeliac disease in autoimmune liver disease in Iran and to summarize previous literature. We investigated prevalence of coeliac disease among 100 autoimmune liver disease patients and compared it with the prevalence in healthy individuals. We also performed an extensive search of the English literature in PubMed Database. We found substantially elevated prevalence of coeliac disease in patients with overlap syndrome (10-15%) compared to the general population (0.1-1%). To a lesser extent, the prevalence was high in patients with autoimmune hepatitis (2-4%). In our systematic review, prevalence of coeliac disease in autoimmune hepatitis in the majority of studies was 4% or more; several studies also reported such prevalence in primary biliary cirrhosis. Since coeliac disease is common among patients with autoimmune liver disease, screening autoimmune liver disease patients for coeliac disease is indicated. Although the magnitude of benefit from a gluten-free diet in reversing autoimmune liver disease in patients with coeliac disease is controversial, it may reduce the risk of further complications of coeliac disease. Copyright (c) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Effects of Melatonin on Liver Injuries and Diseases

PubMed Central

Zhang, Jiao-Jiao; Meng, Xiao; Li, Ya; Zhou, Yue; Xu, Dong-Ping; Li, Sha; Li, Hua-Bin

2017-01-01

Liver injuries and diseases are serious health problems worldwide. Various factors, such as chemical pollutants, drugs, and alcohol, could induce liver injuries. Liver diseases involve a wide range of liver pathologies, including hepatic steatosis, fatty liver, hepatitis, fibrosis, cirrhosis, and hepatocarcinoma. Despite all the studies performed up to now, therapy choices for liver injuries and diseases are very few. Therefore, the search for a new treatment that could safely and effectively block or reverse liver injuries and diseases remains a priority. Melatonin is a well-known natural antioxidant, and has many bioactivities. There are numerous studies investigating the effects of melatonin on liver injuries and diseases, and melatonin could regulate various molecular pathways, such as inflammation, proliferation, apoptosis, metastasis, and autophagy in different pathophysiological situations. Melatonin could be used for preventing and treating liver injuries and diseases. Herein, we conduct a review summarizing the potential roles of melatonin in liver injuries and diseases, paying special attention to the mechanisms of action. PMID:28333073

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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Nonalcoholic fatty liver disease and vascular disease: State-of-the-art

PubMed Central

Fargion, Silvia; Porzio, Marianna; Fracanzani, Anna Ludovica

2014-01-01

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

Alcoholic Liver Disease: Pathogenesis and Current Management

PubMed Central

Osna, Natalia A.; Donohue, Terrence M.; Kharbanda, Kusum K.

2017-01-01

Excessive alcohol consumption is a global healthcare problem. The liver sustains the greatest degree of tissue injury by heavy drinking because it is the primary site of ethanol metabolism. Chronic and excessive alcohol consumption produces a wide spectrum of hepatic lesions, the most characteristic of which are steatosis, hepatitis, and fibrosis/cirrhosis. Steatosis is the earliest response to heavy drinking and is characterized by the deposition of fat in hepatocytes. Steatosis can progress to steatohepatitis, which is a more severe, inflammatory type of liver injury. This stage of liver disease can lead to the development of fibrosis, during which there is excessive deposition of extracellular matrix proteins. The fibrotic response begins with active pericellular fibrosis, which may progress to cirrhosis, characterized by excessive liver scarring, vascular alterations, and eventual liver failure. Among problem drinkers, about 35 percent develop advanced liver disease because a number of disease modifiers exacerbate, slow, or prevent alcoholic liver disease progression. There are still no FDA-approved pharmacological or nutritional therapies for treating patients with alcoholic liver disease. Cessation of drinking (i.e., abstinence) is an integral part of therapy. Liver transplantation remains the life-saving strategy for patients with end-stage alcoholic liver disease. PMID:28988570

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

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Endocannabinoids in liver disease and hepatic encephalopathy.

PubMed

Magen, Iddo; Avraham, Yosefa; Berry, Elliot; Mechoulam, Raphael

2008-01-01

Chronic liver disease results from a variety of causes such as hepatitis virus infections, autoimmune processes and alcohol consumption. Its complications include fat deposition, hemodynamic changes and fibrosis. Clinically there may be progression to portal-hypertension and porto-systemic encephalopathy. Pioneering research from the laboratory of Kunos at NIH has stressed the importance of endocannabinoids (ECs) as mediators of some of the pathological processes in chronic liver disease. The present review summarizes the literature on the association between ECs and liver disease, as well as the therapeutic potential of ECs and exogenous cannabinoids in liver disease with emphasis on hepatic encephalopathy.

Recurrent viral liver disease (hepatitis B and C) after liver transplantation.

PubMed

Olivera-Martínez, Marco Antonio; Gallegos-Orozco, Juan F

2007-08-01

Hepatitis C represents more than 35% of liver transplant candidates worldwide. Meanwhile, hepatitis B continues to be an important cause of end-stage liver disease and hepatocellular carcinoma in Asia and Africa. Recurrent viral liver disease is a significant event after liver transplantation and continues to be one of the main causes of graft dysfunction and loss in the middle and long-term follow-up. Mechanisms of liver reinfection and disease recurrence vary between these two viruses and pre-emptive as well as the therapeutic approaches are different. Hepatitis B patients can be managed with immune globulin immediately after liver transplant and various agents such as nucleotide and nucleoside analogues can be associated. As a result, disease recurrence has been delayed or prevented in these patients. Individuals transplanted for hepatitis C are known to have universal reinfection and a high rate of disease recurrence has been reported in the literature. Strategies to treat hepatitis C recurrence are limited to the use of pegylated interferon and ribavirin when disease is demonstrated histologically and biochemically, although other strategies have been described with limited or no success. We herein review the mechanisms of disease recurrence and the current as well as the future therapeutic approaches to prevent and to treat these diseases.

Nonalcoholic fatty liver disease, association with cardiovascular disease and 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

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. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Liver Disease in the HIV-Infected Individual

PubMed Central

Price, Jennifer C.; Thio, Chloe L.

2010-01-01

Since the advent of effective antiretroviral therapy (ART) for human immunodeficiency virus-1 (HIV), there has been a substantial decrease in deaths related to acquired immunodeficiency syndrome (AIDS). However, in the ART-era liver disease is now the most common non-AIDS related cause of death among HIV-infected patients, accounting for 14-18% of all deaths in this population and almost half of deaths among hospitalized HIV-infected patients. Just as the burden of non-AIDS morbidity and mortality has changed in the ART-era, the types of liver disease the clinician is likely to encounter among these patients have changed as well. This review will discuss the causes of liver disease in the HIV-infected population in the ART-era, including chronic hepatitis C virus, chronic hepatitis B virus, medication-related hepatotoxicity, alcohol abuse, nonalcoholic fatty liver disease, and AIDS-related liver diseases. PMID:20851211

[Liver involvement in coeliac disease].

PubMed

Riestra, S; Fernández, E; Rodrigo, L

1999-12-01

Coeliac disease is a gluten-sensitive enteropathy in which, genetic, immunologic and environmental factors are implied. Several extradigestive diseases have been described in association with coeliac disease, which share most of the times an immunologic mechanism. The liver is damaged in coeliac disease, and it has been considered by some authors as an extraintestinal manifestation of the disease. In the present revision we discuss the different hepatic diseases related with the coeliac disease, as well as the best approach to diagnosis and therapy of choice. At diagnosis, it is very frequent to find an asymptomatic hipertransaminasemia, which frequently disappears after gluten suppression; the morphological substratum found in this alteration is a non-specific reactive hepatitis in the majority of cases. Coeliac disease is a demonstrated cause of cryptogenic hipertransaminasemia. In a small percentage of patient with coeliac disease an association has been found with other immunological liver diseases, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. Few studies exist that include a large number of patient, and the results on occasions are discordant. Nevertheless, the strongest association is with autoimmune hepatitis and with primary biliary cirrhosis. Several communications of isolated cases of rare hepatic diseases, which probably, only reflect a fortuitous association, have been cited in the literature.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

PubMed

Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

2016-08-01

Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

[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. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Non-Alcoholic Fatty Liver Disease in HIV Infection.

PubMed

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

2017-01-01

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

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. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

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

Survival Outcomes After Intracranial Hemorrhage in Liver Disease.

PubMed

Lagman, Carlito; Nagasawa, Daniel T; Azzam, Daniel; Sheppard, John P; Chen, Cheng Hao Jacky; Ong, Vera; Nguyen, Thien; Prashant, Giyarpuram N; Niu, Tianyi; Tucker, Alexander M; Kim, Won; Kaldas, Fady M; Pouratian, Nader; Busuttil, Ronald W; Yang, Isaac

2018-05-15

Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.

Diet - liver disease

MedlinePlus

... of toxic waste products. Increasing your intake of carbohydrates to be in proportion with the amount of ... severe liver disease include: Eat large amounts of carbohydrate foods. Carbohydrates should be the major source of ...

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

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

Alcoholic liver disease

MedlinePlus

... FF, ed. Ferri's Clinical Advisor 2018 . Philadelphia, PA: Elsevier; 2018:59-60. Carithers RL, McClain C. Alcoholic ... Gastrointestinal and Liver Disease . 10th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 86. Haines EJ, Oyama LC. ...

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

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed Central

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-01-01

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice. PMID:6416437

Psychiatric morbidity in patients with alcoholic liver disease.

PubMed

Ewusi-Mensah, I; Saunders, J B; Wodak, A D; Murray, R M; Williams, R

1983-11-12

Seventy one patients with alcoholic liver disease and an equal number with non-alcoholic liver disease were interviewed using the schedule for affective disorders and schizophrenia. Forty seven (66%) of the group with alcoholic liver disease had or had had psychiatric illnesses compared with 23 (32%) of the control group (p less than 0.001). Affective disorder, particularly major depression, neurotic disorders, and antisocial personality, were all more common among the patients with alcoholic liver disease than the controls. No patient had schizophrenia or other forms of psychosis. Among the patients with alcoholic liver disease 11 men (24%) and 14 women (54%) had an affective or a neurotic disorder that had antedated their heavy drinking, and 30 (77%) of those who had had such a problem at any time had symptoms at the time of interview. Abstinence from alcohol is essential for patients with severe alcoholic liver disease. In view of the high prevalence of psychiatric disorders in these patients psychiatric assessment is important to increase the patients' likelihood of complying with such advice.

Management of alcohol misuse in patients with liver diseases

PubMed Central

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

2017-01-01

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. PMID:27940551

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

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

PubMed Central

Firneisz, Gábor

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients. PMID:25083080

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.

Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease.

PubMed

Targher, Giovanni; Byrne, Christopher D

2017-05-01

Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.

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

The emerging role of mast cells in liver disease.

PubMed

Jarido, Veronica; Kennedy, Lindsey; Hargrove, Laura; Demieville, Jennifer; Thomson, Joanne; Stephenson, Kristen; Francis, Heather

2017-08-01

The depth of our knowledge regarding mast cells has widened exponentially in the last 20 years. Once thought to be only important for allergy-mediated events, mast cells are now recognized to be important regulators of a number of pathological processes. The revelation that mast cells can influence organs, tissues, and cells has increased interest in mast cell research during liver disease. The purpose of this review is to refresh the reader's knowledge of the development, type, and location of mast cells and to review recent work that demonstrates the role of hepatic mast cells during diseased states. This review focuses primarily on liver diseases and mast cells during autoimmune disease, hepatitis, fatty liver disease, liver cancer, and aging in the liver. Overall, these studies demonstrate the potential role of mast cells in disease progression.

Discharge Disposition After Stroke in Patients With Liver Disease.

PubMed

Parikh, Neal S; Merkler, Alexander E; Schneider, Yecheskel; Navi, Babak B; Kamel, Hooman

2017-02-01

Liver disease is associated with both hemorrhagic and thrombotic processes, including an elevated risk of intracranial hemorrhage. We sought to assess the relationship between liver disease and outcomes after stroke, as measured by discharge disposition. Using administrative claims data, we identified a cohort of patients hospitalized with stroke in California, Florida, and New York from 2005 to 2013. The predictor variable was liver disease. All diagnoses were defined using validated diagnosis codes. Ordinal logistic regression was used to analyze the association between liver disease and worsening discharge disposition: home, nursing/rehabilitation facility, or death. Secondarily, multiple logistic regression was used to analyze the association between liver disease and in-hospital mortality. Models were adjusted for demographics, vascular risk factors, and comorbidities. We identified 121 428 patients with intracerebral hemorrhage and 703 918 with ischemic stroke. Liver disease was documented in 13 584 patients (1.7%). Liver disease was associated with worse discharge disposition after both intracerebral hemorrhage (global odds ratio, 1.28; 95% confidence interval, 1.19-1.38) and ischemic stroke (odds ratio, 1.23; 95% confidence interval, 1.17-1.29). Similarly, liver disease was associated with in-hospital death after both intracerebral hemorrhage (odds ratio, 1.33; 95% confidence interval, 1.23-1.44) and ischemic stroke (odds ratio, 1.60; 95% confidence interval, 1.51-1.71). Liver disease was associated with worse hospital discharge disposition and in-hospital mortality after stroke, suggesting worse functional outcomes. © 2016 American Heart Association, Inc.

Oral Anticoagulation in Patients With Liver Disease.

PubMed

Qamar, Arman; Vaduganathan, Muthiah; Greenberger, Norton J; Giugliano, Robert P

2018-05-15

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are "auto-anticoagulated" and thus protected from thrombotic events. Warfarin and non-vitamin K-antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population. Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

PNPLA3 gene in liver diseases.

PubMed

Trépo, Eric; Romeo, Stefano; Zucman-Rossi, Jessica; Nahon, Pierre

2016-08-01

Genome-wide association studies (GWAS) in the field of liver diseases have revealed previously unknown pathogenic loci and generated new biological hypotheses. In 2008, a GWAS performed in a population-based sample study, where hepatic liver fat content was measured by magnetic spectroscopy, showed a strong association between a variant (rs738409 C>G p.I148M) in the patatin-like phospholipase domain containing 3 (PNPLA3) gene and nonalcoholic fatty liver disease. Further replication studies have shown robust associations between PNPLA3 and steatosis, fibrosis/cirrhosis, and hepatocellular carcinoma on a background of metabolic, alcoholic, and viral insults. The PNPLA3 protein has lipase activity towards triglycerides in hepatocytes and retinyl esters in hepatic stellate cells. The I148M substitution leads to a loss of function promoting triglyceride accumulation in hepatocytes. Although PNPLA3 function has been extensively studied, the molecular mechanisms leading to hepatic fibrosis and carcinogenesis remain unclear. This unsuspected association has highlighted the fact that liver fat metabolism may have a major impact on the pathophysiology of liver diseases. Conversely, alone, this locus may have limited predictive value with regard to liver disease outcomes in clinical practice. Additional studies at the genome-wide level will be required to identify new variants associated with liver damage and cancer to explain a greater proportion of the heritability of these phenotypes. Thus, incorporating PNPLA3 and other genetic variants in combination with clinical data will allow for the development of tailored predictive models. This attractive approach should be evaluated in prospective cohorts. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Liver Disease in Cystic Fibrosis: an Update

PubMed Central

Parisi, Giuseppe Fabio; Di Dio, Giovanna; Franzonello, Chiara; Gennaro, Alessia; Rotolo, Novella; Lionetti, Elena; Leonardi, Salvatore

2013-01-01

Context Cystic fibrosis (CF) is the most widespread autosomal recessive genetic disorder that limits life expectation amongst the Caucasian population. As the median survival has increased related to early multidisciplinary intervention, other manifestations of CF have emergedespecially for the broad spectrum of hepatobiliary involvement. The present study reviews the existing literature on liver disease in cystic fibrosis and describes the key issues for an adequate clinical evaluation and management of patients, with a focus on the pathogenetic, clinical and diagnostic-therapeutic aspects of liver disease in CF. Evidence Acquisition A literature search of electronic databases was undertaken for relevant studies published from 1990 about liver disease in cystic fibrosis. The databases searched were: EMBASE, PubMed and Cochrane Library. Results CF is due to mutations in the gene on chromosome 7 that encodes an amino acidic polypeptide named CFTR (cystic fibrosis transmembrane regulator). The hepatic manifestations include particular changes referring to the basic CFTR defect, iatrogenic lesions or consequences of the multisystem disease. Even though hepatobiliary disease is the most common non-pulmonary cause ofmortalityin CF (the third after pulmonary disease and transplant complications), only about the 33%ofCF patients presents clinically significant hepatobiliary disease. Conclusions Liver disease will have a growing impact on survival and quality of life of cystic fibrosis patients because a longer life expectancy and for this it is important its early recognition and a correct clinical management aimed atdelaying the onset of complications. This review could represent an opportunity to encourage researchers to better investigate genotype-phenotype correlation associated with the development of cystic fibrosis liver disease, especially for non-CFTR genetic polymorphisms, and detect predisposed individuals. Therapeutic trials are needed to find strategies of

Liver Disease and Pulmonary Hypertension

MedlinePlus

... Liver disease can cause what is known as “portal hypertension,” meaning increased blood pressure in the veins that ... diagnosed? A specialist can diagnose POPH by identifying portal hypertension (high pressure in the veins of the liver), ...

Liver transplantation for Wilson disease.

PubMed

Catana, Andreea M; Medici, Valentina

2012-01-27

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD.

Liver transplantation for Wilson disease

PubMed Central

Catana, Andreea M; Medici, Valentina

2012-01-01

The aim of this paper is to review the current status of liver transplantation (LT) for Wilson disease (WD), focusing on indications and controversies, especially in patients with neuropsychiatric disease, and on identification of acute liver failure (ALF) cases related to WD. LT remains the treatment of choice for patients with ALF, as initial presentation of WD or when anti-copper agents are stopped, and for patients with chronic liver disease progressed to cirrhosis, unresponsive to chelating medications or not timely treated with copper chelating agents. The indication for LT in WD remains highly debated in patients with progressive neurological deterioration and failure to improve with appropriate medical treatment. In case of Wilsonian ALF, early identification is key as mortality is 100% without emergency LT. As many of the copper metabolism parameters are believed to be less reliable in ALF, simple biochemical tests have been proposed for diagnosis of acute WD with good sensitivity and specificity. LT corrects copper metabolism and complications resulting from WD with excellent 1 and 5 year survival. Living related liver transplantation represents an alternative to deceased donor LT with excellent long-term survival, without disease recurrence. Future options may include hepatocyte transplantation and gene therapy. Although both of these have shown promising results in animal models of WD, prospective human studies are much needed to demonstrate their long-term beneficial effects and their potential to replace the need for medical therapy and LT in patients with WD. PMID:22312450

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. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

High-throughput T-cell receptor sequencing across chronic liver diseases reveals distinct disease-associated repertoires.

PubMed

Liaskou, Evaggelia; Klemsdal Henriksen, Eva Kristine; Holm, Kristian; Kaveh, Fatemeh; Hamm, David; Fear, Janine; Viken, Marte K; Hov, Johannes Roksund; Melum, Espen; Robins, Harlan; Olweus, Johanna; Karlsen, Tom H; Hirschfield, Gideon M

2016-05-01

Hepatic T-cell infiltrates and a strong genetic human leukocyte antigen association represent characteristic features of various immune-mediated liver diseases. Conceptually the presence of disease-associated antigens is predicted to be reflected in T-cell receptor (TCR) repertoires. Here, we aimed to determine if disease-associated TCRs could be identified in the nonviral chronic liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and alcoholic liver disease (ALD). We performed high-throughput sequencing of the TCRβ chain complementarity-determining region 3 of liver-infiltrating T cells from PSC (n = 20), PBC (n = 10), and ALD (n = 10) patients, alongside genomic human leukocyte antigen typing. The frequency of TCRβ nucleotide sequences was significantly higher in PSC samples (2.53 ± 0.80, mean ± standard error of the mean) compared to PBC samples (1.13 ± 0.17, P < 0.0001) and ALD samples (0.62 ± 0.10, P < 0.0001). An average clonotype overlap of 0.85% was detected among PSC samples, significantly higher compared to the average overlap of 0.77% seen within the PBC (P = 0.024) and ALD groups (0.40%, P < 0.0001). From eight to 42 clonotypes were uniquely detected in each of the three disease groups (≥30% of the respective patient samples). Multiple, unique sequences using different variable family genes encoded the same amino acid clonotypes, providing additional support for antigen-driven selection. In PSC and PBC, disease-associated clonotypes were detected among patients with human leukocyte antigen susceptibility alleles. We demonstrate liver-infiltrating disease-associated clonotypes in all three diseases evaluated, and evidence for antigen-driven clonal expansions. Our findings indicate that differential TCR signatures, as determined by high-throughput sequencing, may represent an imprint of distinctive antigenic repertoires present in the different chronic liver diseases

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. © 2014 by the American Association for the Study of Liver Diseases.

Polycystic liver disease with right pleural effusion

NASA Astrophysics Data System (ADS)

Anggreini, A. Y.; Dairi, L. B.

2018-03-01

Polycystic liver disease (PCLD) is a condition in which multiple cysts form in the hepatic parenchyma. The polycystic liver disease is also an autosomal dominant disorder (ADPLD) caused by a mutation in a gene that encodes a protein hepatocystin. PCLD has a prevalence count of 1:200,000 people in the people of America. PCLD occurs ± 24% of patients in the third decade of age to 80% by the sixth decade. Women tend to get larger cysts and more and correlated with the number of pregnancies. The following case report of a woman, 51-years-old who was treated at Haji Adam Malik hospital Medan with a diagnosis of polycystic liver disease with right pleural effusion. Some literature has reported complications of the polycystic liver disease but rarely reported with pleural effusion presentation. The patient had already undergone a puncture of pleural fluid and after three weeks of treatment condition of the patient improved and permitted to be outgoing patient.

Pyogenic Liver Abscess as Endemic Disease, Taiwan

PubMed Central

Tsai, Feng-Chiao; Huang, Yu-Tsung; Chang, Luan-Yin

2008-01-01

Pyogenic liver abscess has become a health problem in Taiwanese society. However, the extent of this problem has remained unclear because of the lack of a population-based study. We therefore performed a nationwide analysis of pyogenic liver abscess in Taiwan from 1996 through 2004. We analyzed 29,703 cases from the Taiwan National Health Insurance database and 506 cases from National Taiwan University Hospital. Our analysis showed that the annual incidence of pyogenic liver abscess increased steadily from 11.15/100,000 population in 1996 to 17.59/100,000 in 2004. Diabetes, malignancy, renal disease, and pneumonia were associated with a higher risk for the disease. By contrast, death due to pyogenic liver abscess decreased over time, although population-based abscess-related death increased slightly. Renal disease, malignancy, pneumonia, and heart disease correlated with higher death rates; Klebsiella pneumoniae infection and therapeutic procedures were related to lower death rates. Diabetes did not significantly change death rates for the 506 patients from the hospital. PMID:18826824

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

PubMed

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

2017-08-01

Non-alcoholic fatty liver disease and non-alcoholic steatohepatitis are the most common causes of chronic liver disease with known negative impact on patients' health-related quality of life. Our aim was to validate a disease-specific health-related quality of life instrument useful for efficacy trials involving patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. From a long item selection questionnaire, we selected relevant items which, by factor analysis, were grouped into domains constituting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version. The developed instrument was subjected to internal validity, test-retest reliability and construct validity assessment using standard methods. For development of the Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument, a 75-item-long item selection questionnaire was administered to 25 patients with non-alcoholic fatty liver disease. After item reduction, factor analysis found that 98.7% of variance in the remaining items would be explained by six factors. Thus, the resulting Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version instrument had 36 items grouped into six domains: Abdominal Symptoms, Activity, Emotional, Fatigue, Systemic Symptoms, and Worry. The independent validation group included another 104 patients with non-alcoholic fatty liver disease. The Cronbach's alphas of 0.74-0.90 suggested good to excellent internal consistency of the domains. Furthermore, the presence of obesity and history of depression were discriminated best by Chronic Liver Disease Questionnaire-Non-Alcoholic Fatty Liver Disease version scores (P<.05). The domains' correlations with the most relevant domains of Short Form-36 exceeded 0.70. Test-retest reliability in a subgroup of patients (N=27) demonstrated no significant within-patient variability with multiple administrations (all median differences were zero, all P>.15

Application of Induced Pluripotent Stem Cells in Liver Diseases

PubMed Central

Yu, Yue; Wang, Xuehao; Nyberg, Scott L.

2014-01-01

Tens of millions of patients are affected by liver disease worldwide. Many of these patients can benefit from therapy involving hepatocyte transplantation. Liver transplantation is presently the only proven treatment for many medically refractory liver diseases including end-stage liver failure and inherited metabolic liver disease. However, the shortage in transplantable livers prevents over 40% of listed patients per year from receiving a liver transplant; many of these patients die before receiving an organ offer or become too sick to transplant. Therefore, new therapies are needed to supplement whole-organ liver transplantation and reduce mortality on waiting lists worldwide. Furthermore, the remarkable regenerative capacity of hepatocytes in vivo is exemplified by the increasing number of innovative cell-based therapies and animal models of human liver disorders. Induced pluripotent stem cells (iPSCs) have similar properties to those of embryonic stem cells (ESCs) but bypass the ethical concerns of embryo destruction. Therefore, generation of hepatocyte-like cells (HLCs) using iPSC technology may be beneficial for the treatment of severe liver diseases, screening of drug toxicities, basic research of several hepatocytic disorders, and liver transplantation. Here we briefly summarize the growing number of potential applications of iPSCs for treatment of liver disease. PMID:26858888

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…

Chronic Liver Diseases in Children: Clinical Profile and Histology.

PubMed

Dhole, Sachin Devidas; Kher, Archana S; Ghildiyal, Radha G; Tambse, Manjusha P

2015-07-01

The main aim of the study is to study the clinical profile of disorders of the liver and hepatobiliary system in paediatric patients and to correlate the histopathology findings of liver biopsy in chronic liver disease. Another aim being to assess the prognosis and to know the outcome and the effects of treatment in chronic liver diseases in paediatric age group. It was a prospective study, included the clinical profile of Chronic Liver Diseases (CLD) in children and the histopathological correlation. A total of 55 children were thoroughly investigated by doing relevant investigations and liver biopsy. A male predominance (60%) was noted with maximum incidence in the age group of 6-12 years. The incidence of CLD was 1.1% of total admissions. The most common presenting complaint was jaundice and abdominal distension. Hepatic encephalopathy was noted in 29% patients. Hepatomegaly was seen in 63% patients and spleenomegaly was seen in 60% patients. The incidence of cirrhosis on liver biopsy was 42% (23cases) in CLD patients. The most common diagnosis on histopathology was Wilson's disease (22%), followed by hepatitis and autoimmune hepatitis. The predominant spectrum of CLD was metabolic liver disease and also the predominant cause of death. As the incidence of CLD is quite low, a very high index of suspicion is required for its diagnosis. Some uncommon causes of CLD in children were seen in our study like neutral lipid storage disease, α1-Antitrypsin deficiency disease, lupus hepatitis, Alagille syndrome and Budd-Chiari syndrome. A patient of CLD with jaundice and hepatomegaly should be treated aggressively as those are the poor prognostic indicators of the disease. Hepatic encephalopathy and cirrhosis are also associated with poor outcome in patients with CLD. Liver biopsy histopathology by an expert and its correlation with laboratory investigations plays an important role in the diagnosis of CLD. The major cause of deaths in patients with CLD is due to end stage

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

Nutrition management in chronic liver disease.

PubMed

Bavdekar, Ashish; Bhave, Sheila; Pandit, Anand

2002-05-01

Liver has a central role in nutritional homeostasis and any liver disease leads to abnormalities in nutrient metabolism and subsequent malnutrition. All children with chronic liver disease (CLD) must undergo a periodic nutritional assessment--medical history, anthropometry esp. skinfold thickness and mid-arm circumference, and biochemical estimation of body nutrients. Nutritional rehabilitation is catered to the individual child but generally the caloric intake is increased to 130% of RDA by adding glucose polymers and/or MCT oil (coconut oil) with essential fatty acid supplementation (sunflower oil). The enteral route is preferred and occasionally nasogastric and/or nocturnal feeding are required to ensure an adequate intake. Proteins rich in branched chain amino acids are given in moderation (2-3 gm/kg/day) in compensated cirrhotics unless encephalopathy occurs when protein restriction may be necessary (1 gm/kg/day). Fat-soluble vitamins are supplemented in large quantities esp. in cholestasis along with other vitamins and minerals. Dietary therapy is the mainstay of management of some metabolic liver diseases and may be curative in disorders like galactosemia, fructosemia and glycogen storage disorders. Pre and postoperative nutritional support is an important factor in improving survival after liver transplantation.

Review article: Probiotics in gastrointestinal and liver diseases.

PubMed

Jonkers, D; Stockbrügger, R

2007-12-01

Probiotics, defined as live micro-organisms with beneficial effects for the host, are widely applied in gastrointestinal and liver diseases. To review the available evidence of clinical trials on probiotics in gastrointestinal and liver diseases, with a major focus on irritable bowel syndrome, inflammatory bowel disease, pancreatitis and chronic liver diseases. Evidence for the therapeutic or preventive application of particular probiotic strains is available for antibiotic-associated diarrhoea, rota-virus-associated diarrhoea and pouchitis. Results are encouraging for irritable bowel syndrome, ulcerative colitis and for reducing side effects by Helicobacter pylori eradication therapies, but are less clear for Crohn's disease, lactose intolerance and constipation. In general, for most of these patient groups, more placebo-controlled methodologically well-designed studies that pay attention to both clinical outcome and mechanistic aspects are required. The application in liver disease and pancreatitis is promising, but more human trials have to be awaited. Possible mechanisms of probiotics include modulation of the intestinal microbiota and the immune system, but different bacterial may have different effects. Further insight into disease entities and the functioning of probiotic strains is required to be able to select disease-specific strains, which have to be tested in well-designed placebo-controlled studies.

Limited Knowledge of Acetaminophen in Patients with Liver Disease.

PubMed

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

2016-12-28

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.

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

The Global Burden of Liver Disease: The Major Impact of China

PubMed Central

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

2016-01-01

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. PMID:25164003

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.

Betaine chemistry, roles, and potential use in liver disease.

PubMed

Day, Christopher R; Kempson, Stephen A

2016-06-01

Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Nutritional Needs and Support for Children with Chronic Liver Disease

PubMed Central

Yang, Christine H.; Yoo, Eric R.; Kerner, John A.

2017-01-01

Malnutrition has become a dangerously common problem in children with chronic liver disease, negatively impacting neurocognitive development and growth. Furthermore, many children with chronic liver disease will eventually require liver transplantation. Thus, this association between malnourishment and chronic liver disease in children becomes increasingly alarming as malnutrition is a predictor of poorer outcomes in liver transplantation and is often associated with increased morbidity and mortality. Malnutrition requires aggressive and appropriate management to correct nutritional deficiencies. A comprehensive review of the literature has found that infants with chronic liver disease (CLD) are particularly susceptible to malnutrition given their low reserves. Children with CLD would benefit from early intervention by a multi-disciplinary team, to try to achieve nutritional rehabilitation as well as to optimize outcomes for liver transplant. This review explains the multifactorial nature of malnutrition in children with chronic liver disease, defines the nutritional needs of these children, and discusses ways to optimize their nutritional. PMID:29035331

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. Accessed ...

Gut Microbiota and Complications of Liver Disease

PubMed Central

Acharya, Chathur; Bajaj, Jasmohan

2016-01-01

Synopsis The epidemic of chronic liver disease and how to combat its complications has been a challenging aspect for many years. New laboratory techniques have made analysis of the human intestinal microbiome easier and also more detailed. With insight into dysbiosis and how this dysbiosis impacts liver disease, scientists have new targets in the intestine and liver. Dysbiosis is associated with endotoxemia and propagates liver injury in NASH and alcoholic cirrhosis. The composition of the microbiota changes with the development of cirrhosis and decompensation Apart from microbes, the role that bile acids play in this arena are also being discovered and newer treatments like FXR receptor agonists are coming into the picture. Altered gut microbiota plays an important role in cirrhosis and its modulation to prevent disease progression changes, and concomitantly bile acid physiology must be regulated or augmented to help prevent cirrhosis and its complications. PMID:28164848

Alpha-1-antitrypsin phenotypes in adult liver disease patients

PubMed Central

Alempijevic, Tamara; Milutinovic, Aleksandra Sokic; Kovacevic, Nada

2009-01-01

Alpha-1-antitrypsin (AAT) is an important serine protease inhibitor in humans. Hereditary alpha-1-antitrypsin deficiency (AATD) affects lungs and liver. Liver disease caused by AATD in paediatric patients has been previously well documented. However, the association of liver disease with alpha-1-antitrypsin gene polymorphisms in adults is less clear. Therefore, we aimed to study AAT polymorphisms in adults with liver disease. We performed a case-control study. AAT polymorphisms were investigated by isoelectric focusing in 61 patients with liver cirrhosis and 9 patients with hepatocellular carcinoma. The control group consisted of 218 healthy blood donors. A significant deviation of observed and expected frequency of AAT phenotypes from Hardy-Weinberg equilibrium (chi-square = 34.77, df 11, P = 0.000) in the patient group was caused by a higher than expected frequency of Pi ZZ homozygotes (f = 0.0143 and f = 0.0005, respectively, P = 0.000). In addition, Pi M homozygotes were more frequent in patients than in controls (63% and 46%, respectively, P = 0.025). Our study results show that Pi ZZ homozygosity in adults could be associated with severe liver disease. Presence of Pi M homozygosity could be associated with liver disease via some mechanism different from Z allele-induced liver damage through accumulation of AAT polymers. PMID:19961268

Liver Biopsy in Chronic Liver Diseases: Is There a Favorable Benefit: Risk Balance?

PubMed

Larrey, Dominique; Meunier, Lucy; Ursic-Bedoya, José

2017-01-01

Liver biopsy is still useful in selected clinical situations in which it is the only tool to obtain information necessary for the diagnosis, the prognosis, and the decision for treatment. Main examples are viral hepatitis with confounding co-morbidities, non alcoholic fatty liver disease, and autoimmune liver diseases.

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

Intestinal fungi contribute to development of alcoholic liver disease.

PubMed

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

2017-06-30

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

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

Nutritional Considerations for Dogs and Cats with Liver Disease.

PubMed

Norton, Rebecca D; Lenox, Catherine E; Manino, Paul; Vulgamott, James C

2016-01-01

The goals of nutritional management of liver disease in the dog and cat are directed at treating the clinical manifestations as opposed to treating the underlying cause. Specifically, the clinician strives to avoid overwhelming the remaining metabolic capacities of the damaged liver while providing sufficient nutrients for regeneration. A brief overview of liver diseases and associated clinical signs encountered in the dog and cat and a review of specific nutrients are discussed as well as amounts and sources of nutrients recommended to meet nutritional goals in the diseased liver.

Current treatment for non-alcoholic fatty liver disease.

PubMed

Moctezuma-Velázquez, C

Non-alcoholic fatty liver disease is the most prevalent hepatopathy, estimated at 30% in the general population. In the coming years, it will likely be the most common indication for liver transplantation and the most frequent cause of hepatocellular carcinoma. Current treatment for non-alcoholic fatty liver disease is based on dietary and exercise interventions that have been shown to be efficacious, even for reverting fibrosis. Unfortunately, compliance with general measures involving lifestyle modifications is very poor, making pharmacologic strategies a necessary option. At present, there are no treatments for non-alcoholic fatty liver disease approved by regulatory agencies, and the only ones with sufficient evidence and recommended by international societies are treatments with pioglitazone and vitamin E, which are not exempt from adverse effects. We review herein the current management of non-alcoholic fatty liver disease, including dietary and physical activity interventions, available treatments, equivocal therapies, emerging treatments, and treatments presently in clinical trials. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

Nonalcoholic fatty liver disease: Evolving paradigms

PubMed Central

Lonardo, Amedeo; Nascimbeni, Fabio; Maurantonio, Mauro; Marrazzo, Alessandra; Rinaldi, Luca; Adinolfi, Luigi Elio

2017-01-01

In the last years new evidence has accumulated on nonalcoholic fatty liver disease (NAFLD) challenging the paradigms that had been holding the scene over the previous 30 years. NAFLD has such an epidemic prevalence as to make it impossible to screen general population looking for NAFLD cases. Conversely, focusing on those cohorts of individuals exposed to the highest risk of NAFLD could be a more rational approach. NAFLD, which can be diagnosed with either non-invasive strategies or through liver biopsy, is a pathogenically complex and clinically heterogeneous disease. The existence of metabolic as opposed to genetic-associated disease, notably including ”lean NAFLD” has recently been recognized. Moreover, NAFLD is a systemic condition, featuring metabolic, cardiovascular and (hepatic/extra-hepatic) cancer risk. Among the clinico-laboratory features of NAFLD we discuss hyperuricemia, insulin resistance, atherosclerosis, gallstones, psoriasis and selected endocrine derangements. NAFLD is a precursor of type 2 diabetes (T2D) and metabolic syndrome and progressive liver disease develops in T2D patients in whom the course of disease is worsened by NAFLD. Finally, lifestyle changes and drug treatment options to be implemented in the individual patient are also critically discussed. In conclusion, this review emphasizes the new concepts on clinical and pathogenic heterogeneity of NAFLD, a systemic disorder with a multifactorial pathogenesis and protean clinical manifestations. It is highly prevalent in certain cohorts of individuals who are thus potentially amenable to selective screening strategies, intensive follow-up schedules for early identification of liver-related and extrahepatic complications and in whom earlier and more aggressive treatment schedules should be carried out whenever possible. PMID:29085206

Non-Alcoholic Fatty Liver Disease: The Emerging Burden in Cardiometabolic and Renal Diseases.

PubMed

Han, Eugene; Lee, Yong Ho

2017-12-01

As the number of individuals with non-alcoholic fatty liver disease (NAFLD) has increased, the influence of NAFLD on other metabolic diseases has been highlighted. Accumulating epidemiologic evidence indicates that NAFLD not only affects the liver but also increases the risk of extra-hepatic diseases such as type 2 diabetes mellitus, metabolic syndrome, dyslipidemia, hypertension, cardiovascular or cerebrovascular diseases, and chronic kidney disease. Non-alcoholic steatohepatitis, an advanced type of NAFLD, can aggravate these inter-organ relationships and lead to poorer outcomes. NAFLD induces insulin resistance and exacerbates systemic chronic inflammation and oxidative stress, which leads to organ dysfunction in extra-hepatic tissues. Although more research is needed to identify the pathophysiological mechanisms and causal relationship between NAFLD and cardiometabolic and renal diseases, screening for heart, brain, and kidney diseases, risk assessment for diabetes, and a multidisciplinary approach for managing these patients should be highly encouraged. Copyright © 2017 Korean Diabetes Association.

Laparoscopic management of cystic disease of the liver.

PubMed

Albrink, M H; McAllister, E W; Rosemurgy, A S; Karl, R C; Carey, L C

1994-04-01

Laparoscopic surgical procedures are increasing in scope and in variety. The benefits of decreased wound morbidity and pain have been well documented for multiple procedures that have traditionally required laparotomy. Although there are few controlled studies to document them, these benefits may be evident from simple clinical observation. Cystic disease of the liver is a condition that is treated largely for symptomatic reasons. The so-called noninvasive or radiographic guided methods of treatment for cystic disease of the liver are fraught with high recurrence rates. We present four cases of cystic disease of the liver treated laparoscopically, followed with pertinent discussion.

Current and Future Burden of Chronic Nonmalignant Liver Disease.

PubMed

Udompap, Prowpanga; Kim, Donghee; Kim, W Ray

2015-11-01

Disease burden is an important indicator of the state of health of a population. It can be measured as the frequency (eg, incidence and prevalence) of a condition or its effects including fatal and non-fatal health loss from disease (eg, disability-adjusted life years) as well as the financial costs (eg, direct healthcare costs and indirect healthcare expenditures related to lost income because of premature death). Accurate disease burden information is essential for policy-making such as prioritization of health interventions and allocation of resources. Chronic liver disease (CLD) causes substantial health and economic burden in the United States, where nearly 2 million deaths annually are attributable to CLD. In the recent past, overall mortality rate of CLD has been increasing. Viral hepatitis and alcoholic liver disease are thought to be the most common etiologies of chronic liver diseases. More recently, the prevalence of nonalcoholic fatty liver disease is rapidly increasing, and nonalcoholic steatohepatitis has become a leading indication for liver transplantation. In this article, we assemble available data on the burden of CLD in the United States, focusing on nonmalignant complications, whereas the impact on mortality and healthcare expenses of hepatocellular carcinoma, an important consequence of CLD, is discussed elsewhere. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

When can nutritional therapy impact liver disease?

PubMed

Bozeman, Matthew C; Benns, Matthew V; McClave, Stephen A; Miller, Keith R; Jones, Christopher M

2014-10-01

This article reviews the current literature regarding nutritional therapy in liver disease, with an emphasis on patients progressing to liver failure as well as surgical patients. Mechanisms of malnutrition and sarcopenia in liver failure patients as well as nutritional assessment, nutritional requirements of this patient population, and goals and methods of therapy are discussed. Additionally, recommendations for feeding, micronutrient, branched chain amino acid supplementation, and the use of pre- and probiotics are included. The impact of these methods can have on patients with advanced disease and those undergoing surgical procedures will be emphasized.

Basal values and changes of liver stiffness predict the risk of disease progression in compensated advanced chronic liver disease.

PubMed

Pons, Mònica; Simón-Talero, Macarena; Millán, Laura; Ventura-Cots, Meritxell; Santos, Begoña; Augustin, Salvador; Genescà, Joan

2016-10-01

Transient elastography has been proposed as a tool to predict the risk of decompensation in patients with chronic liver disease. We aimed to identify risk groups of disease progression, using a combination of baseline liver stiffness measurement (LSM) and its change over time (delta-LSM) in patients with compensated advanced chronic liver disease (cACLD). Ninety-four patients with baseline LSM ≥10kPa, Child-Pugh score 5 and without previous decompensation were included. A second LSM was performed during follow-up and data on liver function and liver-related events were collected. The primary endpoint was a composite that included death, liver decompensation and impairment in at least 1 point in Child-Pugh score. After a median follow-up of 43.6 months, 15% of patients presented the primary endpoint. Multivariate analysis identified baseline LSM (OR 1.12, P=0.002) and delta-LSM (OR 1.02, P=0.048) as independent predictors of the primary endpoint. A high risk group represented by patients with baseline LSM ≥21kPa and delta-LSM ≥10% (risk of progression 47.1%, 95% CI: 23-71%) was identified, while patients with LSM <21kPa and delta-LSM <10% presented zero risk of progression (P=0.03). Simple classification rules using baseline LSM and delta-LSM identify cACLD patients at low or high risk of disease progression. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

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

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

PubMed

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

2015-10-21

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.

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. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Various pathways leading to the progression of chronic liver diseases].

PubMed

Egresi, Anna; Lengyel, Gabriella; Somogyi, Anikó; Blázovics, Anna; Hagymási, Krisztina

2016-02-21

As the result of various effects (viruses, metabolic diseases, nutritional factors, toxic agents, autoimmune processes) abnormal liver function, liver steatosis and connective tissue remodeling may develop. Progression of this process is complex including various pathways and a number of factors. The authors summarize the factors involved in the progression of chronic liver disease. They describe the role of cells and the produced inflammatory mediators and cytokines, as well as the relationship between the disease and the intestinal flora. They emphasize the role of oxidative stress, mitochondrial dysfunction and cell death in disease progression. Insulin resistance and micro-elements (iron, copper) in relation to liver damage are also discussed, and genetic and epigenetic aspects underlying disease progression are summarized. Discovery of novel treatment options, assessment of the effectiveness of treatment, as well as the success and proper timing of liver transplantation may depend on a better understanding of the process of disease progression.

Genetics of nonalcoholic fatty liver disease.

PubMed

Dongiovanni, Paola; Valenti, Luca

2016-08-01

Epidemiological, familial, and twin studies indicate that non-alcoholic fatty liver disease, now the leading cause of liver damage in developed countries, has a strong heritability. The common I148M variant of PNPLA3 impairing hepatocellular lipid droplets remodeling is the major genetic determinant of hepatic fat content. The I148M variant has a strong impact on the full spectrum of liver damage related to fatty liver, encompassing non-alcoholic steatohepatitis, advanced fibrosis, and hepatocellular carcinoma, and influences the response to therapeutic approaches. Common variants in GCKR enhance de novo hepatic lipogenesis in response to glucose and liver inflammation. Furthermore, the low-frequency E167K variant of TM6SF2 and rare mutations in APOB, which impair very low-density lipoproteins secretion, predispose to progressive fatty liver. These and other recent findings reviewed here indicate that impaired lipid handling by hepatocytes has a major role in the pathogenesis of non-alcoholic fatty liver disease by triggering inflammation, fibrogenesis, and carcinogenesis. These discoveries have provided potential novel biomarkers for clinical use and have revealed intriguing therapeutic targets. Copyright © 2016 Elsevier Inc. All rights reserved.

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

Sarcopenia in patients with advanced liver disease.

PubMed

Ponziani, Francesca Romana; Gasbarrini, Antonio

2017-04-28

Sarcopenia is the loss of muscle mass and function, affecting up to 70% of patients with advanced liver disease. Liver cirrhosis is characterized by an altered glucose metabolism, lipid oxidation, ketogenesis and protein catabolism, leading to the loss of adipose and muscle tissue. The gastrointestinal dysfunction of cirrhotic patients results in inadequate nutrients intake and is responsible for muscle weakness thus limiting physical exercise and perpetuating the reduction of muscle mass. Recently, alterations of hormonal pathways involved in muscle growth, increased intestinal permeability and changes in the gut microbiota composition have been reported in cirrhotic patients. Interestingly, a role of intestinal bacteria in maintaining muscle health has been hypothesized through the translocation of bacteria and bacterial products into the bloodstream triggering the production of muscle wasting-associated cytokines. Sarcopenia is associated with severe outcomes in patients with liver cirrhosis, mostly due to the incidence of disease complications. Furthermore, sarcopenia may represent an important prognostic factor for patients with hepatocellular carcinoma and for those undergoing liver transplantation and can be considered a useful additional tool in the global assessment of patients with advanced liver disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

Role of Gut Microbiota in Liver Disease.

PubMed

Brenner, David A; Paik, Yong-Han; Schnabl, Bernd

2015-01-01

Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include: (1) changes in caloric yield of diet; (2) regulation of gut permeability to release bacterial products; (3) modulation of choline metabolism; (4) production of endogenous ethanol; (5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.

Effect of Liver Disease on Hepatic Transporter Expression and Function.

PubMed

Thakkar, Nilay; Slizgi, Jason R; Brouwer, Kim L R

2017-09-01

Liver disease can alter the disposition of xenobiotics and endogenous substances. Regulatory agencies such as the Food and Drug Administration and the European Medicines Evaluation Agency recommend, if possible, studying the effect of liver disease on drugs under development to guide specific dose recommendations in these patients. Although extensive research has been conducted to characterize the effect of liver disease on drug-metabolizing enzymes, emerging data have implicated that the expression and function of hepatobiliary transport proteins also are altered in liver disease. This review summarizes recent developments in the field, which may have implications for understanding altered disposition, safety, and efficacy of new and existing drugs. A brief review of liver physiology and hepatic transporter localization/function is provided. Then, the expression and function of hepatic transporters in cholestasis, hepatitis C infection, hepatocellular carcinoma, human immunodeficiency virus infection, nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and primary biliary cirrhosis are reviewed. In the absence of clinical data, nonclinical information in animal models is presented. This review aims to advance the understanding of altered expression and function of hepatic transporters in liver disease and the implications of such changes on drug disposition. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Role of autoimmunity in nonviral chronic liver disease.

PubMed

Amarapurkar, D N; Amarapurkar, A D

2000-11-01

To evaluate the prevalence and clinical profile of autoimmune hepatitis (AIH) in patients with chronic liver disease. Four hundred and thirty five consecutive patient with chronic liver disease seen in our department from January 1997 to December 1998 were studied with detailed history and clinical examination. All the patients underwent liver function tests, ultrasonography, isotope liver scanning, viral markers, autoimmune markers ANA, ASMA, LKM1 and AMA (by immunofluorescence technique) and liver histology whenever permissible. Appropriate work up for Wilson's disease was done whenever suspected clinically. Diagnosis of autoimmune hepatitis was made by the composite scoring system by international autoimmune hepatitis group. Twenty out of the 435 patients met the criteria of definite autoimmune hepatitis and seven patient had probable autoimmune hepatitis. Forty out of 408 patients showed markers of autoimmunity positive but did not qualify diagnosis of AIH on composite scores. Demographic profile of 27 patients with autoimmune hepatitis was as follows; male:female ratio 1:8, mean age 39.8 +/- 13 years (Range 4-65 years); mode of presentation as cirrhosis 11/27 (40.7%), chronic hepatitis 12/27 (44.4%) and acute hepatitis 4/27 (14.8%). Elevated serum bilirubin levels were seen in 12 (44.4%) patients while mean serum aminotransferases levels were 249 +/- 343 and 262 +/- 418 respectively. Other disease associations seen were as follows: diabetes in 4 (14.8%), rheumatoid arthritis in 3 (11%), hypothyroidism in 2 (7.4%) and ulcerative colitis in 1 (3.7%). The pattern of autoimmune markers was ANA +ve 23/27 (85%) (+ve titres of ANA > 1:80 in adults and 1:20 in children), ASMA +ve in 16/27 (59.2%) (+ve titres of ASMA > 1:40) and LKM1 in 3 patients. AMA in tires less than 1:80 was found in 3 patients. Liver histology changes seen were lymphoplasmacytic infiltrates (100%), bridging necrosis (93%), liver cell rossetting (80%) and fibrosis with or without cirrhosis (50

Portopulmonary Hypertension in Liver Disease Presenting in Childhood.

PubMed

Ecochard-Dugelay, Emmanuelle; Lambert, Virginie; Schleich, Jean-Marc; Duché, Mathieu; Jacquemin, Emmanuel; Bernard, Olivier

2015-09-01

Portopulmonary hypertension (POPH) is a known complication of cirrhosis in adults, but there is little information on its incidence and outcome in children with liver disease. We report 14 patients with POPH and present a synthesis of the medical literature. Diagnosis of POPH in the 14 patients was based on right-sided heart catheterization displaying mean pulmonary artery pressure (mPAP) >25 mmHg, indexed pulmonary vascular resistances >3 Wood units · m, and pulmonary wedge pressure <15 mmHg. A literature review added 84 patients. In our unit, POPH was found in 0.5% of the children with portal hypertension, 0.9% of the children with end-stage liver disease awaiting transplantation, and 3 children with congenital portosystemic shunts (CPSSs). Analysis of 98 reported patients, including the 14 presented here, showed the cause of liver disease to be chronic liver disease or portal cavernoma in 76 instances (34 with a history of surgical portosystemic shunt) and CPSS in 22 instances. There was a precession with proven hypoxemia caused by hepatopulmonary syndrome in 6 patients. Median survival was 3 months in 56 untreated patients. An 80% 5-year probability of survival in 42 patients was treated by CPSS closure, pulmonary vasodilators, and/or liver transplantation. Mean pretransplant mPAP was 34 and 49 mmHg in transplant survivors and nonsurvivors, respectively. POPH is a rare but extremely severe complication of childhood liver disease. Portosystemic shunts, whether congenital or acquired, likely play an important causative role. Early diagnosis is crucial and requires systematic screening by echocardiography in children at risk.

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

Management of cytomegalovirus infection and disease in liver transplant recipients

PubMed Central

Bruminhent, Jackrapong; Razonable, Raymund R

2014-01-01

Cytomegalovirus (CMV) is one of the most common viral pathogens causing clinical disease in liver transplant recipients, and contributing to substantial morbidity and occasional mortality. CMV causes febrile illness often accompanied by bone marrow suppression, and in some cases, invades tissues including the transplanted liver allograft. In addition, CMV has been significantly associated with an increased predisposition to acute and chronic allograft rejection, accelerated hepatitis C recurrence, and other opportunistic infections, as well as reduced overall patient and allograft survival. To negate the adverse effects of CMV infection on transplant outcome, its prevention, whether through antiviral prophylaxis or preemptive therapy, is an essential component to the management of liver transplant recipients. Two recently updated guidelines have suggested that antiviral prophylaxis or preemptive therapy are similarly effective in preventing CMV disease in modest-risk CMV-seropositive liver transplant recipients, while antiviral prophylaxis is the preferred strategy over preemptive therapy for the prevention of CMV disease in high-risk recipients [CMV-seronegative recipients of liver allografts from CMV-seropositive donors (D+/R-)]. However, antiviral prophylaxis has only delayed the onset of CMV disease in many CMV D+/R- liver transplant recipients, and such occurrence of late-onset CMV disease was significantly associated with increased all-cause and infection-related mortality after liver transplantation. Therefore, a search for better strategies for prevention, such as prolonged duration of antiviral prophylaxis, a hybrid approach (antiviral prophylaxis followed by preemptive therapy), or the use of immunologic measures to guide antiviral prophylaxis has been suggested to prevent late-onset CMV disease. The standard treatment of CMV disease consists of intravenous ganciclovir or oral valganciclovir, and if feasible, reduction in pharmacologic immunosuppression

The Natural Course of Non-Alcoholic Fatty Liver Disease

PubMed Central

Calzadilla Bertot, Luis; Adams, Leon Anton

2016-01-01

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. PMID:27213358

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 T reg 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. Copyright © 2016 Elsevier Inc. All rights reserved.

Nonalcoholic fatty liver disease and liver transplantation - Where do we stand?

PubMed Central

Mikolasevic, Ivana; Filipec-Kanizaj, Tajana; Mijic, Maja; Jakopcic, Ivan; Milic, Sandra; Hrstic, Irena; Sobocan, Nikola; Stimac, Davor; Burra, Patrizia

2018-01-01

Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a challenging and multisystem disease that has a high socioeconomic impact. NAFLD/NASH is a main cause of macrovesicular steatosis and has multiple impacts on liver transplantation (LT), on patients on the waiting list for transplant, on post-transplant setting as well as on organ donors. Current data indicate new trends in the area of chronic liver disease. Due to the increased incidence of metabolic syndrome (MetS) and its components, NASH cirrhosis and hepatocellular carcinoma caused by NASH will soon become a major indication for LT. Furthermore, due to an increasing incidence of MetS and, consequently, NAFLD, there will be more steatotic donor livers and less high quality organs available for LT, in addition to a lack of available liver allografts. Patients who have NASH and are candidates for LT have multiple comorbidities and are unique LT candidates. Finally, we discuss long-term grafts and patient survival after LT, the recurrence of NASH and NASH appearing de novo after transplantation. In addition, we suggest topics and areas that require more research for improving the health care of this increasing patient population. PMID:29662288

LiverAtlas: a unique integrated knowledge database for systems-level research of liver and hepatic disease.

PubMed

Zhang, Yanqiong; Yang, Chunyuan; Wang, Shaochuang; Chen, Tao; Li, Mansheng; Wang, Xue; Li, Dongsheng; Wang, Kang; Ma, Jie; Wu, Songfeng; Zhang, Xueli; Zhu, Yunping; Wu, Jinsheng; He, Fuchu

2013-09-01

A large amount of liver-related physiological and pathological data exist in publicly available biological and bibliographic databases, which are usually far from comprehensive or integrated. Data collection, integration and mining processes pose a great challenge to scientific researchers and clinicians interested in the liver. To address these problems, we constructed LiverAtlas (http://liveratlas.hupo.org.cn), a comprehensive resource of biomedical knowledge related to the liver and various hepatic diseases by incorporating 53 databases. In the present version, LiverAtlas covers data on liver-related genomics, transcriptomics, proteomics, metabolomics and hepatic diseases. Additionally, LiverAtlas provides a wealth of manually curated information, relevant literature citations and cross-references to other databases. Importantly, an expert-confirmed Human Liver Disease Ontology, including relevant information for 227 types of hepatic disease, has been constructed and is used to annotate LiverAtlas data. Furthermore, we have demonstrated two examples of applying LiverAtlas data to identify candidate markers for hepatocellular carcinoma (HCC) at the systems level and to develop a systems biology-based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC differential diagnosis. LiverAtlas is the most comprehensive liver and hepatic disease resource, which helps biologists and clinicians to analyse their data at the systems level and will contribute much to the biomarker discovery and diagnostic performance enhancement for liver diseases. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Pulmonary Vascular Complications of Liver Disease

PubMed Central

Fritz, Jason S.; Fallon, Michael B.

2013-01-01

Hepatopulmonary syndrome and portopulmonary hypertension are two pulmonary vascular complications of liver disease. The pathophysiology underlying each disorder is distinct, but patients with either condition may be limited by dyspnea. A careful evaluation of concomitant symptoms, the physical examination, pulmonary function testing and arterial blood gas analysis, and echocardiographic, imaging, and hemodynamic studies is crucial to establishing (and distinguishing) these diagnoses. Our understanding of the pathobiology, natural history, and treatment of these disorders has advanced considerably over the past decade; however, the presence of either still increases the risk of morbidity and mortality in patients with underlying liver disease. There is no effective medical treatment for hepatopulmonary syndrome. Although liver transplantation can resolve hepatopulmonary syndrome, there appears to be worse survival even with transplantation. Liver transplantation poses a very high risk of death in those with significant portopulmonary hypertension, where targeted medical therapies may improve functional status and allow successful transplantation in a small number of select patients. PMID:23155142

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

Nonalcoholic fatty liver disease in spinal and bulbar muscular atrophy

PubMed Central

Guber, Robert D.; Takyar, Varun; Kokkinis, Angela; Fox, Derrick A.; Alao, Hawwa; Kats, Ilona; Bakar, Dara; Remaley, Alan T.; Hewitt, Stephen M.; Kleiner, David E.; Liu, Chia-Ying; Hadigan, Colleen; Fischbeck, Kenneth H.; Rotman, Yaron

2017-01-01

Objective: To determine the prevalence and features of fatty liver disease in spinal and bulbar muscular atrophy (SBMA). Methods: Two groups of participants with SBMA were evaluated. In the first group, 22 participants with SBMA underwent laboratory analysis and liver imaging. In the second group, 14 participants with SBMA were compared to 13 female carriers and 23 controls. Liver biopsies were done in 4 participants with SBMA. Results: Evidence of fatty liver disease was detected by magnetic resonance spectroscopy in all participants with SBMA in the first group, with an average dome intrahepatic triacylglycerol of 27% (range 6%–66%, ref ≤5.5%). Liver dome magnetic resonance spectroscopy measurements were significantly increased in participants with SBMA in the second group relative to age- and sex-matched controls, with average disease and male control measurements of 17% and 3%, respectively. Liver biopsies were consistent with simple steatosis in 2 participants and nonalcoholic steatohepatitis in 2 others. Conclusions: We observed evidence of nonalcoholic liver disease in nearly all of the participants with SBMA evaluated. These observations expand the phenotypic spectrum of the disease and provide a potential biomarker that can be monitored in future studies. PMID:29142082

Clinical approaches to non-alcoholic fatty liver disease

PubMed Central

Schwenger, Katherine JP; Allard, Johane P

2014-01-01

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

Physicians’ practices for diagnosing liver fibrosis in chronic liver diseases: A nationwide, Canadian survey

PubMed Central

Sebastiani, Giada; Ghali, Peter; Wong, Philip; Klein, Marina B; Deschenes, Marc; Myers, Robert P

2014-01-01

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians’ characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians’ main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better

Neural net classification of liver ultrasonogram for quantitative evaluation of diffuse liver disease

NASA Astrophysics Data System (ADS)

Lee, Dong Hyuk; Kim, JongHyo; Kim, Hee C.; Lee, Yong W.; Min, Byong Goo

1997-04-01

There have been a number of studies on the quantitative evaluation of diffuse liver disease by using texture analysis technique. However, the previous studies have been focused on the classification between only normal and abnormal pattern based on textural properties, resulting in lack of clinically useful information about the progressive status of liver disease. Considering our collaborative research experience with clinical experts, we judged that not only texture information but also several shape properties are necessary in order to successfully classify between various states of disease with liver ultrasonogram. Nine image parameters were selected experimentally. One of these was texture parameter and others were shape parameters measured as length, area and curvature. We have developed a neural-net algorithm that classifies liver ultrasonogram into 9 categories of liver disease: 3 main category and 3 sub-steps for each. Nine parameters were collected semi- automatically from the user by using graphical user interface tool, and then processed to give a grade for each parameter. Classifying algorithm consists of two steps. At the first step, each parameter was graded into pre-defined levels using neural network. in the next step, neural network classifier determined disease status using graded nine parameters. We implemented a PC based computer-assist diagnosis workstation and installed it in radiology department of Seoul National University Hospital. Using this workstation we collected 662 cases during 6 months. Some of these were used for training and others were used for evaluating accuracy of the developed algorithm. As a conclusion, a liver ultrasonogram classifying algorithm was developed using both texture and shape parameters and neural network classifier. Preliminary results indicate that the proposed algorithm is useful for evaluation of diffuse liver disease.

Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

PubMed

Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

2018-02-09

Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

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

PubMed

Zhao, Yingying; Xing, Huichun

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.

Diabetes mellitus and renal involvement in chronic viral liver disease.

PubMed

Iovanescu, V F; Streba, C T; Ionescu, M; Constantinescu, A F; Vere, C C; Rogoveanu, I; Moța, E

2015-01-01

Chronic viral liver disease is often associated with other conditions. Diabetes mellitus (DM) is frequently reported in this context and may play a role in the progression of the liver disease to hepatocellular carcinoma (HCC). Renal disease is also an important extrahepatic manifestation of hepatitis viral infection and its presence is associated with poor prognosis and management issues. Our study had multiple purposes: to determine the frequency of the association between chronic viral liver disease and diabetes mellitus, evaluate the potential of diabetes mellitus as a risk factor for HCC and assess an eventual renal involvement. We included in our study a number of 246 patients with chronic liver disease, from whom 136 were diagnosed with chronic viral hepatitis and 110 with viral liver cirrhosis. These patients were assessed by using a clinical examination and a series of tests, including serum transaminase levels, serum bilirubin, serum albumin, markers of cholestasis, fasting plasma glucose levels, serum creatinine, urea, albuminuria, Addis-Hamburger test, electrophoresis of urinary proteins, abdominal ultrasound and, in some cases, CT examination. We obtained the following results: diabetes mellitus is often associated with chronic liver disease of viral etiology, having been identified in 18.29% of the patients in our study. Age above 60 in patients with chronic hepatitis (p=0.013<0.05) and presence of hepatitis C virus were particularly correlated with the presence of diabetes mellitus. Renal disease was present in 13.4% of the patients with chronic liver disease and it was especially associated with liver cirrhosis and hepatitis C virus. The most common form of renal injury was glomerulonephritis. Acute kidney injury was diagnosed only in cirrhotic patients as hepatorenal syndrome, occurring in 7.27% of the subjects, while chronic kidney disease was identified only in two cases of chronic viral hepatitis. Four patients in our study were diagnosed with

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

Emerging roles of SIRT1 in fatty liver diseases

PubMed Central

Ding, Ren-Bo; Bao, Jiaolin; Deng, Chu-Xia

2017-01-01

Fatty liver diseases, which are commonly associated with high-fat/calorie diet, heavy alcohol consumption and/or other metabolic disorder causes, lead to serious medical concerns worldwide in recent years. It has been demonstrated that metabolic homeostasis disruption is most likely to be responsible for this global epidemic. Sirtuins are a group of conserved nicotinamide adenine dinucleotide (NAD+) dependent histone and/or protein deacetylases belonging to the silent information regulator 2 (Sir2) family. Among seven mammalian sirtuins, sirtuin 1 (SIRT 1) is the most extensively studied one and is involved in both alcoholic and nonalcoholic fatty liver diseases. SIRT1 plays beneficial roles in regulating hepatic lipid metabolism, controlling hepatic oxidative stress and mediating hepatic inflammation through deacetylating some transcriptional regulators against the progression of fatty liver diseases. Here we summarize the latest advances of the biological roles of SIRT1 in regulating lipid metabolism, oxidative stress and inflammation in the liver, and discuss the potential of SIRT1 as a therapeutic target for treating alcoholic and nonalcoholic fatty liver diseases. PMID:28808418

Association between liver fibrosis and coronary heart disease risk in patients with nonalcoholic fatty liver disease.

PubMed

Dogan, Serkan; Celikbilek, Mehmet; Yilmaz, Yunus K; Sarikaya, Savas; Zararsiz, Gokmen; Serin, Halil I; Borekci, Elif; Akyol, Lütfi; Pirti, Ilyas; Davarci, Sena E

2015-03-01

Nonalcoholic fatty liver disease (NAFLD) is being increasingly recognized as the most common cause of chronic liver disease worldwide. It has been shown that NAFLD in adults is associated with increased risk of coronary heart disease (CHD). Because of the limitations of liver biopsy, noninvasive scoring indexes such as the NAFLD fibrosis score (NFS) were developed. The Framingham risk score (FRS) provides an estimate of CHD risk. In our study we aimed to investigate whether the severity of liver fibrosis estimated with the NFS is associated with a higher risk of CHD among individuals with ultrasonography-diagnosed NAFLD. A total of 155 patients and controls (81 patients with NAFLD and 74 controls) with ages ranging from 18 to 70 years were enrolled in this cross-sectional prospective study. Demographic, anthropometric, clinical, and laboratory data were obtained from each individual. The NAFLD patients were divided into subgroups on the basis of the severity of fatty liver. The FRS and NFS were adopted to predict the risk of CHD and the severity of hepatic fibrosis. In our study, we found that the FRS was higher in NAFLD patients than in controls (P<0.05). According to the FRS category, NFSs were higher in the intermediate/high probability CHD risk group in NAFLD (P<0.05). In multiple models, only age, sex, cholesterol, and HDL were independently associated with intermediate/high CHD risk (P<0.05). We also found a positive correlation between the NFS and the FRS (r=0.373, P<0.001). The optimum NFS cutoff point for identifying intermediate/high CHD risk in NAFLD patients was -2.1284, with a sensitivity and specificity of 95.20 and 48.30%, respectively. The predictive performance of the NFS in the determination of intermediate/high CHD risk in NAFLD patients was found to be 72% based on the area under the curve value. The FRS is associated with the NFS in NAFLD. The assessment of liver fibrosis may be useful for the risk stratification of CHD in the absence of liver

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.

[Coffee can be beneficial for patients with liver diseases].

PubMed

Kjærgaard, Maria; Thiele, Maja; Krag, Aleksander

2014-10-20

Coffee is one of the most commonly consumed beverages in the world. Consequently, it is important to consider the impact of coffee on health and disease. A daily intake of at least three cups of coffee is likely to have beneficial health effects, especially in patients at risk of liver diseases. Coffee has been associated with decreased liver inflammation, prevention of cirrhosis, reduced steatosis and lower incidence of hepatocellular carcinoma. It is not yet possible to make clear recommendations, but coffee can likely be included as part of a healthy diet for patients with liver diseases.

New Insights from Rodent Models of Fatty Liver Disease

PubMed Central

2011-01-01

Abstract Rodent models of fatty liver disease are essential research tools that provide a window into disease pathogenesis and a testing ground for prevention and treatment. Models come in many varieties involving dietary and genetic manipulations, and sometimes both. High-energy diets that induce obesity do not uniformly cause fatty liver disease; this has prompted close scrutiny of specific macronutrients and nutrient combinations to determine which have the greatest potential for hepatotoxicity. At the same time, diets that do not cause obesity or the metabolic syndrome but do cause severe steatohepatitis have been exploited to study factors important to progressive liver injury, including cell death, oxidative stress, and immune activation. Rodents with a genetic predisposition to overeating offer yet another model in which to explore the evolution of fatty liver disease. In some animals that overeat, steatohepatitis can develop even without resorting to a high-energy diet. Importantly, these models and others have been used to document that aerobic exercise can prevent or reduce fatty liver disease. This review focuses primarily on lessons learned about steatohepatitis from manipulations of diet and eating behavior. Numerous additional insights about hepatic lipid metabolism, which have been gained from genetically engineered mice, are also mentioned. Antioxid. Redox Signal. 15, 535–550. PMID:21126212

Role of folate in nonalcoholic fatty liver disease.

PubMed

Sid, Victoria; Siow, Yaw L; O, Karmin

2017-10-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of chronic liver conditions that are characterized by steatosis, inflammation, fibrosis, and liver injury. The global prevalence of NAFLD is rapidly increasing in proportion to the rising incidence of obesity and type 2 diabetes. Because NAFLD is a multifaceted disorder with many underlying metabolic abnormalities, currently, there is no pharmacological agent that is therapeutically approved for the treatment of this disease. Folate is a water-soluble B vitamin that plays an essential role in one-carbon transfer reactions involved in nucleic acid biosynthesis, methylation reactions, and sulfur-containing amino acid metabolism. The liver is the primary organ responsible for storage and metabolism of folates. Low serum folate levels have been observed in patients with obesity and diabetes. It has been reported that a low level of endogenous folates in rodents perturbs folate-dependent one-carbon metabolism, and may be associated with development of metabolic diseases such as NAFLD. This review highlights the biological role of folate in the progression of NAFLD and its associated metabolic complications including obesity and type 2 diabetes. Understanding the role of folate in metabolic disease may position this vitamin as a potential therapeutic for NAFLD.

Mediterranean diet and nonalcoholic fatty liver disease.

PubMed

Anania, Caterina; Perla, Francesco Massimo; Olivero, Francesca; Pacifico, Lucia; Chiesa, Claudio

2018-05-21

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease, and is characterized by a wide spectrum of fat-liver disorders that can result in severe liver disease and cirrhosis. Inflammation and oxidative stress are the major risk factors involved in the pathogenesis of NAFLD. Currently, there is no consensus concerning the pharmacological treatment of NAFLD. However, lifestyle interventions based on exercise and a balanced diet for quality and quantity, are considered the cornerstone of NAFLD management. Mediterranean diet (MD), rich in polyunsaturated fats, polyphenols, vitamins and carotenoids, with their anti-inflammatory and anti-oxidant effects, has been suggested to be effective in preventing cardiovascular risk factors. In adults, MD has also been demonstrated to be efficacious in reducing the risk of metabolic syndrome. However, few studies are available on the effects of the MD in both adult and pediatric subjects with NAFLD. Thus, the aims of the present narrative review are to analyze the current clinical evidence on the impact of MD in patients with NAFLD, and to summarize the main mechanisms of action of MD components on this condition.

Immunology in the liver--from homeostasis to disease.

PubMed

Heymann, Felix; Tacke, Frank

2016-02-01

The liver is a central immunological organ with a high exposure to circulating antigens and endotoxins from the gut microbiota, particularly enriched for innate immune cells (macrophages, innate lymphoid cells, mucosal-associated invariant T (MAIT) cells). In homeostasis, many mechanisms ensure suppression of immune responses, resulting in tolerance. Tolerance is also relevant for chronic persistence of hepatotropic viruses or allograft acceptance after liver transplantation. The liver can rapidly activate immunity in response to infections or tissue damage. Depending on the underlying liver disease, such as viral hepatitis, cholestasis or NASH, different triggers mediate immune-cell activation. Conserved mechanisms such as molecular danger patterns (alarmins), Toll-like receptor signalling or inflammasome activation initiate inflammatory responses in the liver. The inflammatory activation of hepatic stellate and Kupffer cells results in the chemokine-mediated infiltration of neutrophils, monocytes, natural killer (NK) and natural killer T (NKT) cells. The ultimate outcome of the intrahepatic immune response (for example, fibrosis or resolution) depends on the functional diversity of macrophages and dendritic cells, but also on the balance between pro-inflammatory and anti-inflammatory T-cell populations. As reviewed here, tremendous progress has helped to understand the fine-tuning of immune responses in the liver from homeostasis to disease, indicating promising targets for future therapies in acute and chronic liver diseases.

Autophagy in alcohol-induced liver diseases

PubMed Central

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

2013-01-01

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 pathologic 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. PMID:22551004

The healthcare burden imposed by liver disease in aging Baby Boomers.

PubMed

Davis, Gary L; Roberts, William L

2010-02-01

The Baby Boomer generation is composed of 78 million Americans who are just beginning to reach their retirement years. Most Boomers have at least one chronic health problem, and these significantly increase the expense of providing medical care. Liver disease is the 12th most common cause of death in the United States, representing a relatively small portion of overall healthcare costs compared with cardiovascular disease and malignancy. Nonetheless, hepatitis C and fatty liver disease are more common in the Boomers and may play a more dominant role as they age. As a consequence, primary liver cancer is likely to become more prevalent. As with most chronic illnesses, prevention rather than disease management is likely to have the greatest impact. For those already afflicted by chronic liver disease, recognition and treatment can reduce the incidence of late complications, as was clearly demonstrated with chronic hepatitis B and C. Perhaps obesity is the greatest threat to our future health, and fatty liver disease, although likely preventable, will probably become the disease that fills the waiting rooms of future hepatologists.

[Current epidemiological status of causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital within the past 20 years].

PubMed

Zhao, R H; Ma, K; Hu, J; Chen, C X; Qi, J Y

2018-02-20

Objective: To investigate the causes of disease among patients with liver disease hospitalized in Department of Infectious Diseases in our hospital and the changes in such causes within the past 20 years. Methods: A retrospective analysis was performed for the clinical data of 7570 patients who were admitted to our hospital from January 1995 to December 2015. The chi-square test was used for the statistical analysis of constituent ratio. Results: Of all 7570 patients with liver disease, 4930 (65.13%) had viral hepatitis, 332 (4.39%) had immune disease, 215 (2.84%) had drug-induced liver injury, 192 (2.54%) had fatty liver disease, 88 (1.16%) had schistosome-induced liver disease, 160 (2.11%) had inherited metabolic diseases, and 20 (0.13%) had vascular disease; 689 (9.1%) still had no clear cause of disease at discharge. The proportion of patients with viral hepatitis was 77.61% in the first 10 years and 59.19% in the last 10 years ( P < 0.01). As for liver disease caused by hepatotropic virus, there were significant increases in the proportion of patients with hepatitis C or hepatitis E from the first to the last 10 years (hepatitis C: 2.24% vs 15.56%, P < 0.01; hepatitis E: 18.61% vs 23.07%, P < 0.05), while there were significant reductions in the proportion of patients with hepatitis B (68.14% vs 60.01%, P < 0.05) or hepatitis A (10.7% vs 1.36%, P < 0.05). The proportion of patients with immune diseases was 0.82% in the first 10 years and 6.08% in the last 10 years ( P < 0.01). There were also certain changes in the proportion of patients with liver disease caused by other reasons. Conclusion: There is a large proportion of patients with viral hepatitis among patients with liver disease hospitalized in Department of Infectious Diseases in a large general hospital, especially hepatitis B and E caused by hepatotropic virus. There is a certain change in the epidemiology of liver disease within the past 20 years, with a reduction in the proportion of patients with

Correlation Of Deviance In Arterial Oxygenation With Severity Of Chronic Liver Disease.

PubMed

Shaukat, Al-Aman; Zar, Adnan; Zuhaid, Muhammad; Afridi, Safa Saadat

2016-01-01

Hepatitis B and C related chronic liver diseases have led to development of a serious threat to the people of South Asia. The main aim of this study was to evaluate the correlation of magnitude of arterial deoxygention to the severity of liver disease. It was a hospital based cross-sectional descriptive study, carried out in the Medical Department of Khyber Teaching Hospital Peshawar. All in all 115 patients were assessed for the severity of the liver diseases and were correlated with arterial deoxygenation using linear regression models. Male to female ratio was 1.5:1. Males infected with hepatitis B, hepatitis C and both were 9, 60 and 1, while females suffered from hepatitis B, Hepatitis C and both were 2, 42 and 1 respectively. The linear relationship between A-a DO2 with severity of liver disease showed positive correlation while PO2 showed negative correlation with severity of liver disease. There was a positive correlation between A-a DO2 and severity of liver diseases while PO2 and severity of liver diseases showed negative correlation.

The Enhanced liver fibrosis score is associated with clinical outcomes and disease progression in patients with chronic liver disease.

PubMed

Irvine, Katharine M; Wockner, Leesa F; Shanker, Mihir; Fagan, Kevin J; Horsfall, Leigh U; Fletcher, Linda M; Ungerer, Jacobus P J; Pretorius, Carel J; Miller, Gregory C; Clouston, Andrew D; Lampe, Guy; Powell, Elizabeth E

2016-03-01

Current tools for risk stratification of chronic liver disease subjects are limited. We aimed to determine whether the serum-based ELF (Enhanced Liver Fibrosis) test predicted liver-related clinical outcomes, or progression to advanced liver disease, and to compare the performance of ELF to liver biopsy and non-invasive algorithms. Three hundred patients with ELF scores assayed at the time of liver biopsy were followed up (median 6.1 years) for liver-related clinical outcomes (n = 16) and clear evidence of progression to advanced fibrosis (n = 18), by review of medical records and clinical data. Fourteen of 73 (19.2%) patients with ELF score indicative of advanced fibrosis (≥9.8, the manufacturer's cut-off) had a liver-related clinical outcome, compared to only two of 227 (<1%) patients with ELF score <9.8. In contrast, the simple scores APRI and FIB-4 would only have predicted subsequent decompensation in six and four patients respectively. A unit increase in ELF score was associated with a 2.53-fold increased risk of a liver-related event (adjusted for age and stage of fibrosis). In patients without advanced fibrosis on biopsy at recruitment, 55% (10/18) with an ELF score ≥9.8 showed clear evidence of progression to advanced fibrosis (after an average 6 years), whereas only 3.5% of those with an ELF score <9.8 (8/207) progressed (average 14 years). In these subjects, a unit increase in ELF score was associated with a 4.34-fold increased risk of progression. The ELF score is a valuable tool for risk stratification of patients with chronic liver disease. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

To screen or not to screen? Celiac antibodies in liver diseases

PubMed Central

Narciso-Schiavon, Janaína Luz; Schiavon, Leonardo Lucca

2017-01-01

Celiac disease (CD) is a systemic immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals. The typical symptoms are anemia, diarrhea, fatigue, weight loss, and abdominal pain. CD has been reported in patients with primary sclerosing cholangitis, primary biliary cholangitis, autoimmune hepatitis, aminotransferase elevations, nonalcoholic fatty liver disease, hepatitis B, hepatitis C, portal hypertension and liver cirrhosis. We evaluate recommendations for active screening for CD in patients with liver diseases, and the effect of a gluten-free diet in these different settings. Active screening for CD is recommended in patients with liver diseases, particularly in those with autoimmune disorders, steatosis in the absence of metabolic syndrome, noncirrhotic intrahepatic portal hypertension, cryptogenic cirrhosis, and in the context of liver transplantation. In hepatitis C, diagnosis of CD can be important as a relative contraindication to interferon use. Gluten-free diet ameliorates the symptoms associated with CD; however, the associated liver disease may improve, remain the same, or progress. PMID:28223722

The Pathogenesis of Autoimmune Liver Disease.

PubMed

Arndtz, Katherine; Hirschfield, Gideon M

Autoimmune liver disease (AILD) encompasses 3 main distinct clinical diseases: autoimmune hepatitis, primary biliary cholangitis (formally known as cirrhosis, PBC) and primary sclerosing cholangitis (PSC). These conditions are an important, yet under-appreciated cause of patient morbidity and mortality with ongoing unmet needs for further research and clinical advances. There is observational evidence for genetic predisposition, with all 3 conditions being more common in first degree relatives. AILD is associated with the presence of auto-antibodies and higher risks of other non-hepatic auto-immune conditions. Genetic risk association studies have identified HLA and non-HLA risk loci for the development of disease, with some HLA loci providing prognostic information. This re-enforces the concept that genetic predisposition to autoimmunity is important, likely in the context of environmental exposures. Such environmental triggers are unclear but relevant risks include smoking, drug and xenobiotic exposure as well as the complexities of the microbiome. There is evidence for a loss of immune tolerance to self-antigens playing a part in the development of these conditions. In particular the IL-2 and IL-12 regulatory pathways have been implicated in pre-disposing to an unopposed inflammatory response within the liver. Main immunological themes revolve around loss of immune tolerance leading to T-cell mediated injury, imbalance in the regulation of immune cells and defective immune response to foreign antigens. For PBC and PSC, there is then the added complexity of the consequences of cholestasis on hepato-biliary injury, immune regulation and liver fibrosis. Whilst specific disease causes and triggers are still lacking, AILD arises on the background of collective genetic and environmental risk, leading to chronic and abnormal hepato-biliary immune responses. Effective and more rational therapy will ultimately be developed when the multiple pathways to liver injury are

Herbal medicines for liver diseases in India.

PubMed

Thyagarajan, S P; Jayaram, S; Gopalakrishnan, V; Hari, R; Jeyakumar, P; Sripathi, M S

2002-12-01

The use of natural remedies for the treatment of liver diseases has a long history, starting with the Ayurvedhic treatment, and extending to the Chinese, European and other systems of traditional medicines. The 21st century has seen a paradigm shift towards therapeutic evaluation of herbal products in liver diseases by carefully synergizing the strengths of the traditional systems of medicine with that of the modern concept of evidence-based medicinal evaluation, standardization of herbal products and randomized placebo controlled clinical trials to support clinical efficacy. The present review provides the status report on the scientific approaches made to herbal preparations used in Indian systems of medicine for the treatment of liver diseases. In spite of the availability of more than 300 preparations for the treatment of jaundice and chronic liver diseases in Indian systems of medicine using more than 87 Indian medicinal plants, only four terrestrial plants have been scientifically elucidated while adhering to the internationally acceptable scientific protocols. In-depth studies have proved Sylibum marianum to be anti-oxidative, antilipidperoxidative, antifibrotic, anti-inflammatory, immunomodulating and liver regenerative. Glycyrrhiza glabra has been shown to be hepatoprotective and capable of inducing an indigenous interferon. Picrorhiza kurroa is proved to be anti-inflammatory, hepatoprotective and immunomodulatory. Extensive studies on Phyllanthus amarus have confirmed this plant preparation as being anti-viral against hepatitis B and C viruses, hepatoprotective and immunomodulating, as well as possessing anti-inflammatory properties. For the first time in the Indian systems of medicine, a chemo-biological fingerprinting methodology for standardization of P. amarus preparation has been patented. Copyright 2002 Blackwell Publishing Asia Pty Ltd

Perioperative management of liver surgery-review on pathophysiology of liver disease and liver failure.

PubMed

Gasteiger, Lukas; Eschertzhuber, Stephan; Tiefenthaler, Werner

2018-01-01

An increasing number of patients present for liver surgery. Given the complex pathophysiological changes in chronic liver disease (CLD), it is pivotal to understand the fundamentals of chronic and acute liver failure. This review will give an overview on related organ dysfunction as well as recommendations for perioperative management and treatment of liver failure-related symptoms.

Progesterone, prolactin, and gynaecomastia in men with liver disease.

PubMed Central

Farthing, M J; Green, J R; Edwards, C R; Dawson, A M

1982-01-01

Plasma progesterone was raised in 36 of 50 (72%) men with liver disease compared with 20 healthy male control subjects. Plasma progesterone was significantly higher in men with non-alcoholic cirrhosis with gynaecomastia than those without, but no similar relationship was found in men with alcoholic fatty change and alcoholic cirrhosis. Hyperprolactinaemia was found in 14% of men with liver disease but levels were unrelated to the presence of gynaecomastia. Increased circulating levels of progesterone and prolactin alone do not explain the development of gynaecomastia in patients with liver disease, but progesterone may be an additional factor acting in association with the known disturbances of other sex steroids. PMID:7076004

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

PubMed Central

Stål, Per

2015-01-01

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. PMID:26494963

The intersection of nonalcoholic fatty liver disease and obesity.

PubMed

Woo Baidal, Jennifer A; Lavine, Joel E

2016-01-27

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and recently emerged as the most rapidly increasing indication for liver transplant. Although obesity is a risk factor for NAFLD, overlap between these two entities is incompletely understood. We highlight recent insights into the pathogenesis of human NAFLD in relation to obesity and discuss advances in the diagnosis and treatment of NAFLD. Copyright © 2016, American Association for the Advancement of Science.

Stratifying the risks of oral anticoagulation in patients with liver disease.

PubMed

Efird, Lydia M; Mishkin, Daniel S; Berlowitz, Dan R; Ash, Arlene S; Hylek, Elaine M; Ozonoff, Al; Reisman, Joel I; Zhao, Shibei; Jasuja, Guneet K; Rose, Adam J

2014-05-01

Chronic liver disease presents a relative contraindication to warfarin therapy, but some patients with liver disease nevertheless require long-term anticoagulation. The goal is to identify which patients with liver disease might safely receive warfarin. Among 102 134 patients who received warfarin from the Veterans Affairs from 2007 to 2008, International Classification of Diseases-Ninth Revision codes identified 1763 patients with chronic liver disease. Specific diagnoses and laboratory values (albumin, aspartate aminotransferase, alanine aminotransferase, creatinine, and cholesterol) were examined to identify risk of adverse outcomes, while controlling for available bleeding risk factors. Outcomes included percent time in therapeutic range, a measure of anticoagulation control, and major hemorrhagic events, by International Classification of Diseases-Ninth Revision codes. Patients with liver disease had lower mean time in therapeutic range (53.5%) when compared with patients without (61.7%; P<0.001) and more hemorrhages (hazard ratio, 2.02; P<0.001). Among patients with liver disease, serum albumin and creatinine levels were the strongest predictors of both outcomes. We created a 4-point score system: patients received 1 point each for albumin (2.5-3.49 g/dL) or creatinine (1.01-1.99 mg/dL), and 2 points each for albumin (<2.5 g/dL) or creatinine (≥2 mg/dL). This score predicted both anticoagulation control and hemorrhage. When compared with patients without liver disease, those with a score of zero had modestly lower time in therapeutic range (56.7%) and no increase in hemorrhages (hazard ratio, 1.16; P=0.59), whereas those with the worst score (4) had poor control (29.4%) and high hazard of hemorrhage (hazard ratio, 8.53; P<0.001). Patients with liver disease receiving warfarin have poorer anticoagulation control and more hemorrhages. A simple 4-point scoring system using albumin and creatinine identifies those at risk for poor outcomes. © 2014 American

Organ allocation for chronic liver disease: model for end-stage liver disease and beyond.

PubMed

Asrani, Sumeet K; Kim, W Ray

2010-05-01

Implementation of the model for end-stage liver disease (MELD) score has led to a reduction in waiting list registration and waitlist mortality. Prognostic models have been proposed to either refine or improve the current MELD-based liver allocation. The model for end-stage liver disease - sodium (MELDNa) incorporates serum sodium and has been shown to improve the predictive accuracy of the MELD score. However, laboratory variation and manipulation of serum sodium is a concern. Organ allocation in the United Kingdom is now based on a model that includes serum sodium. An updated MELD score is associated with a lower relative weight for serum creatinine coefficient and a higher relative weight for bilirubin coefficient, although the contribution of reweighting coefficients as compared with addition of variables is unclear. The D-MELD, the arithmetic product of donor age and preoperative MELD, proposes donor-recipient matching; however, inappropriate transplantation of high-risk donors is a concern. Finally, the net benefit model ranks patients according to the net survival benefit that they would derive from the transplant. However, complex statistical models are required and unmeasured characteristics may unduly affect the model. Despite their limitations, efforts to improve the current MELD-based organ allocation are encouraging.

Dietary fructose in nonalcoholic fatty liver disease.

PubMed

Vos, Miriam B; Lavine, Joel E

2013-06-01

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in adults and children. A number of genetic and environmental factors are known to predispose individuals to NAFLD. Certain dietary sugars, particularly fructose, are suspected to contribute to the development of NAFLD and its progression. The increasing quantity of fructose in the diet comes from sugar additives (most commonly sucrose and high fructose corn syrup) in beverages and processed foods. Substantial links have been demonstrated between increased fructose consumption and obesity, dyslipidemia, and insulin resistance. Growing evidence suggests that fructose contributes to the development and severity of NAFLD. In human studies, fructose is associated with increasing hepatic fat, inflammation, and possibly fibrosis. Whether fructose alone can cause NAFLD or if it serves only as a contributor when consumed excessively in the setting of insulin resistance, positive energy balance, and sedentary lifestyle is unknown. Sufficient evidence exists to support clinical recommendations that fructose intake be limited through decreasing foods and drinks high in added (fructose-containing) sugars. Copyright © 2013 American Association for the Study of Liver Diseases.

The Role of Celiac Disease in Severity of Liver Disorders and Effect of a Gluten Free Diet on Diseases Improvement

PubMed Central

Rostami-Nejad, Mohammad; Haldane, Thea; AlDulaimi, David; Alavian, Seyed Moayed; Zali, Mohammad Reza; Rostami, Kamran

2013-01-01

Context Celiac disease (CD) is defined as a permanent intolerance to ingested gluten. The intolerance to gluten results in immune-mediated damage of small intestine mucosa manifested by villous atrophy and crypt hyperplasia. These abnormalities resolve with initiationa gluten-free diet. Evidence Acquisition PubMed, Ovid, and Google were searched for full text articles published between 1963 and 2012. The associated keywords were used, and papers described particularly the impact of celiac disease on severity of liver disorder were identified. Results Recently evidence has emerged revealingthat celiac disease not only is associated with small intestine abnormalities and malabsorption, but is also a multisystem disorder affecting other systems outside gastrointestinal tract, including musculo-skeletal, cardiovascular and nervous systems. Some correlations have been assumed between celiac and liver diseases. In particular, celiac disease is associated with changes in liver biochemistry and linked to alter the prognosis of other disorders. This review will concentrate on the effect of celiac disease and gluten-free diets on the severity of liver disorders. Conclusions Although GFD effect on the progression of CD associated liver diseases is not well defined, it seems that GFD improves liver function tests in patients with a hypertransaminasemia. PMID:24348636

Steatorrhea in patients with liver disease

PubMed Central

Williams, C. N.; Sidorov, J. J.

1971-01-01

Intestinal function was studied in 26 patients with seven types of acute and chronic liver disease, documented by liver biopsy. Steatorrhea, defined by a stool fat higher than 6 g. per day, was present in 18 of 23 consecutive patients studied, an incidence of 78.3%. Two patients with infectious hepatitis associated with steatorrhea studied previously were added and the 20 cases were analyzed. The malabsorption found was confined to fat and fat-soluble vitamins; stool excretion varied from 6.1 to 22 g. per day in the seven groups studied. No histological abnormality was seen on jejunal biopsy, serum vitamin B12, D-xylose and Schilling tests were normal, and no radiological findings associated with malabsorption were detected in the small bowel. It is concluded that steatorrhea is a common finding in a wide variety of acute and chronic liver diseases and cannot be attributed to a primary defect of the small bowel. PMID:5150072

Advanced MRI Methods for Assessment of Chronic Liver Disease

PubMed Central

Taouli, Bachir; Ehman, Richard L.; Reeder, Scott B.

2010-01-01

MRI plays an increasingly important role for assessment of patients with chronic liver disease. MRI has numerous advantages, including lack of ionizing radiation and the possibility of performing multiparametric imaging. With recent advances in technology, advanced MRI methods such as diffusion-, perfusion-weighted MRI, MR elastography, chemical shift based fat-water separation and MR spectroscopy can now be applied to liver imaging. We will review the respective roles of these techniques for assessment of chronic liver disease. PMID:19542391

Non-alcoholic fatty liver disease phenotypes in patients with inflammatory bowel disease.

PubMed

Sartini, Alessandro; Gitto, Stefano; Bianchini, Marcello; Verga, Maria Chiara; Di Girolamo, Maria; Bertani, Angela; Del Buono, Mariagrazia; Schepis, Filippo; Lei, Barbara; De Maria, Nicola; Villa, Erica

2018-01-24

Non-alcoholic fatty liver disease (NAFLD) can be detected in up to 33.6% of inflammatory bowel disease (IBD) patients, often in absence of metabolic risk factors. Nevertheless, most of previous studies on such issue were conducted within the IBD population only. The primary aim of this study was to compare clinical and metabolic features of NAFLD in patients with and without IBD (w/o IBD) and to identify specific NAFLD phenotypes within the IBD population. Among 223 NAFLD patients, 78 patients with IBD were younger compared to 145 without (w/o) IBD, were less likely to have altered liver enzymes, had lower mean body weight, smaller waist circumference and lower body mass index (BMI); at the same time, MetS was more prevalent among patients w/o IBD (56.6 vs. 23.1%, p < 0.001). Within IBD population, patients with severe IBD showed more often severe steatosis (S3) at ultrasound (US) (32.1 vs. 16.6%, p = 0.01), compared to mild-to-moderate disease. Independent risk factors for S3 US steatosis in IBD patients at the multivariate logistic regression analysis were: more than 1 IBD relapse per year during disease history (OR 17.3, 95% CI 3.6-84), surgery for IBD (OR 15.1, 95% CI 3.1-73.7) and more extensive intestinal involvement (OR 19.4, 95% CI 3.4-110.9); the ongoing anti-Tumor Necrosis Factor alpha (antiTNFα) therapy was the only independent factor which protect toward the presence of altered liver enzymes (OR 0.15, 95% CI 0-0.8, p = 0.02). In conclusion, NAFLD in IBD patients is different from that in patients w/o IBD, who seem to develop different NAFLD phenotypes according to intestinal disease clinical course. More severe IBD seem to predict the presence of more severe steatosis. Therapy with antiTNFα antibodies could prevent alteration of liver enzymes in such population.

Management of Neurologic Manifestations in Patients with Liver Disease.

PubMed

Ferro, José M; Viana, Pedro; Santos, Patrícia

2016-08-01

Liver disease, both in its acute and chronic forms, can be associated with a wide spectrum of neurologic manifestations, both central and peripheral, ranging in severity from subclinical changes to neurocritical conditions. Neurologists are frequently consulted to participate in their management. In this review, we present an overview of management strategies for patients with hepatic disease whose clinical course is complicated by neurologic manifestations. Type A hepatic encephalopathy (HE), which occurs in acute liver failure, is a neurologic emergency, and multiple measures should be taken to prevent and treat cerebral edema. In Type C HE, which occurs in chronic liver disease, management should be aimed at correcting precipitant factors and hyperammonemia. There is an increasing spectrum of drug treatments available to minimize ammonia toxicity. Acquired hepatocerebral degeneration is a rare complication of the chronic form of HE, with typical clinical and brain MRI findings, whose most effective treatment is liver transplantation. Epilepsy is frequent and of multifactorial cause in patients with hepatic disease, and careful considerations should be made regarding choice of the appropriate anti-epileptic drugs. Several mechanisms increase the risk of stroke in hepatic disease, but many of the drugs used to treat and prevent stroke are contraindicated in severe hepatic failure. Hepatitis C infection increases the risk of ischemic stroke. Hemorrhagic stroke is more frequent in patients with liver disease of alcoholic etiology. Viral hepatitis is associated with a wide range of immune-mediated complications, mostly in the peripheral nervous system, which respond to different types of immunomodulatory treatment. Several drugs used to treat hepatic disease, such as the classical and the new direct-acting antivirals, may have neurologic complications which in some cases preclude its continued use.

Is alveolar hydatid disease of the liver incurable?

PubMed Central

Mosimann, F

1980-01-01

The etiologic agent of alveolar hydatid disease is Echinococcus multilocularis. Infestation of the liver by the larvae of this Cestode results in an infiltrative mass that behaves biologically very much like a malignant tumor. From 1955 to 1978, 13 patients with alveolar hydatid disease of the liver were investigated, operated and followed at the University Medical Center of Lausanne, Switzerland. Due to the extension of the lesions, six patients had exploratory laparotomy with biopsy only; the other seven were submitted to hepatic resection. Follow-up demonstrated that the disease progresses slowly and that a resection, even if incomplete, can afford long-lasting relief. However the present data suggest that surgical cure of alveolar hydatid disease must be very rare. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:7406556

Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease

PubMed Central

Razavi, Homie; Loomba, Rohit; Younossi, Zobair; Sanyal, Arun J.

2017-01-01

Nonalcoholic fatty liver disease (NAFLD) and resulting nonalcoholic steatohepatitis (NASH) are highly prevalent in the United States, where they are a growing cause of cirrhosis and hepatocellular carcinoma (HCC) and increasingly an indicator for liver transplantation. A Markov model was used to forecast NAFLD disease progression. Incidence of NAFLD was based on historical and projected changes in adult prevalence of obesity and type 2 diabetes mellitus (DM). Assumptions were derived from published literature where available and validated using national surveillance data for incidence of NAFLD‐related HCC. Projected changes in NAFLD‐related cirrhosis, advanced liver disease, and liver‐related mortality were quantified through 2030. Prevalent NAFLD cases are forecasted to increase 21%, from 83.1 million (2015) to 100.9 million (2030), while prevalent NASH cases will increase 63% from 16.52 million to 27.00 million cases. Overall NAFLD prevalence among the adult population (aged ≥15 years) is projected at 33.5% in 2030, and the median age of the NAFLD population will increase from 50 to 55 years during 2015‐2030. In 2015, approximately 20% of NAFLD cases were classified as NASH, increasing to 27% by 2030, a reflection of both disease progression and an aging population. Incidence of decompensated cirrhosis will increase 168% to 105,430 cases by 2030, while incidence of HCC will increase by 137% to 12,240 cases. Liver deaths will increase 178% to an estimated 78,300 deaths in 2030. During 2015‐2030, there are projected to be nearly 800,000 excess liver deaths. Conclusion: With continued high rates of adult obesity and DM along with an aging population, NAFLD‐related liver disease and mortality will increase in the United States. Strategies to slow the growth of NAFLD cases and therapeutic options are necessary to mitigate disease burden. (Hepatology 2018;67:123‐133). PMID:28802062

Cell Death and Cell Death Responses in Liver Disease: Mechanisms and Clinical Relevance

PubMed Central

Luedde, Tom; Kaplowitz, Neil; Schwabe, Robert F.

2015-01-01

Summary Hepatocellular death is present in almost all types of human liver disease and is used as a sensitive parameter for the detection of acute and chronic liver disease of viral, toxic, metabolic, or autoimmune origin. Clinical data and animal models suggest that hepatocyte death is the key trigger of liver disease progression, manifested by the subsequent development of inflammation, fibrosis, cirrhosis, and hepatocellular carcinoma. Modes of hepatocellular death differ substantially between liver diseases. Different modes of cell death such as apoptosis, necrosis, and necroptosis trigger specific cell death responses and promote progression of liver disease through distinct mechanisms. In this review, we first discuss molecular mechanisms by which different modes of cell death, damage-associated molecular patterns, and specific cell death responses contribute to the development of liver disease. We then review the clinical relevance of cell death, focusing on biomarkers; the contribution of cell death to drug-induced, viral, and fatty liver disease and liver cancer; and evidence for cell death pathways as therapeutic targets. PMID:25046161

An epidemiological study of the association of coffee with chronic liver disease.

PubMed

Walton, H B; Masterton, G S; Hayes, P C

2013-11-01

Chronic liver disease affects 855 people per million in the UK. Previous studies have reported that coffee appears protective against the development of abnormal liver enzymes, hepatic fibrosis and cirrhosis. The aim of this study, the first in a Scottish population, was to compare coffee consumption in patients with liver disease and that of control populations to determine correlations between coffee intake and the incidence of non-cancerous liver disease and with Child's-Pugh and model for end-stage liver disease (MELD) scores. Two hundred and eighty-six patients attending the liver outpatient department at the Royal Infirmary of Edinburgh completed a questionnaire regarding coffee consumption and lifestyle factors. Control questionnaires were also completed by 100 orthopaedic outpatients and 120 medical students. Patients with cirrhosis (n = 95) drank significantly less coffee than those without cirrhosis (p = <0.001). There was no correlation between Child's-Pugh (-0.018) and MELD scores (-0.132) with coffee consumption. Coffee drinking is associated with a reduced prevalence of cirrhosis in patients with chronic liver disease. However, there was no significant difference in the amount of coffee drunk by liver patients and the control groups. It is possible that by changing the amount of coffee drunk, the development of cirrhosis in liver disease could be postponed.

Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

PubMed

Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

2014-04-01

Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

Screening for Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Diseases: A Cohort Study Using Transient Elastography.

PubMed

Saroli Palumbo, Chiara; Restellini, Sophie; Chao, Che-Yung; Aruljothy, Achuthan; Lemieux, Carolyne; Wild, Gary; Afif, Waqqas; Lakatos, Peter L; Bitton, Alain; Cocciolillo, Sila; Ghali, Peter; Bessissow, Talat; Sebastiani, Giada

2018-06-07

Inflammatory bowel disease (IBD) patients may be at risk for nonalcoholic fatty liver disease (NAFLD) due to chronic inflammation, hepatotoxic drugs, and alteration of the gut microbiota. Prospective data using accurate diagnostic methods are lacking. We prospectively investigated prevalence and predictors of NAFLD and liver fibrosis by transient elastography (TE) with associated controlled attenuation parameter (CAP) in IBD patients as part of a routine screening program. NAFLD was defined as CAP ≥248 dB/m. Significant liver fibrosis (stage 2 or higher out of 4) was defined as TE measurement ≥7.0 kPa. Predictors of NAFLD and significant liver fibrosis were determined by logistic regression analysis. A total of 384 patients (mean age 42.4 years, 45.0% male, 64.6% with Crohn's disease) with no significant alcohol intake were included. Prevalence of NAFLD and significant liver fibrosis was 32.8% and 12.2%, respectively. Independent predictors of NAFLD were older age (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.15-1.82), higher body mass index (BMI; aOR, 1.31; 95% CI, 1.20-1.42) and higher triglycerides (aOR, 1.45; 95% CI, 1.01-2.09). Significant liver fibrosis was independently predicted by older age (aOR, 1.38; 95% CI, 1.12-1.64) and higher BMI (aOR, 1.14; 95% CI, 1.07-1.23). Extrahepatic diseases were more common in IBD patients with NAFLD compared with those without, namely chronic kidney disease (10.3 vs 2.3%; P < 0.001) and cardiovascular diseases (11.3 vs 4.7%; P = 0.02). NAFLD diagnosed by TE with CAP is a frequent comorbidity in IBD patients and is associated with extrahepatic diseases. Noninvasive screening strategies could help early diagnosis and initiation of interventions, including weight loss, correction of dyslipidemia, and linkage to care. 10.1093/ibd/izy200_video1izy200.video15794817619001.

Altered plasma lipidome profile of dairy cows with fatty liver disease.

PubMed

Gerspach, C; Imhasly, S; Gubler, M; Naegeli, H; Ruetten, M; Laczko, E

2017-02-01

Fatty liver disease is a common health problem of dairy cows occurring during the transition from pregnancy to lactation. It is a direct response to fat mobilization due to negative energy balance. Accumulation of lipids in the liver occurs if the uptake of non-esterified fatty acids by the liver exceeds the capacity of lipid oxidation or secretion by the liver. Currently, the diagnosis of fatty liver disease requires confirmation through biopsies to determine the hepatic lipid content. In view of this lack of a practical diagnostic tool, we compared the plasma lipidome of diseased dairy cows using liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Multivariate data analysis yielded 20 m/z values that were able to distinguish between dairy cows with no hepatic lipidosis and those exhibiting different stages of the disease. Based on the chromatography retention time and m/z ratios, we identified phosphatidylcholines with reduced plasma abundances in cows with fatty liver disease. The abundances of different bile acids tended to be increased. In addition, we detected two metabolites related to inflammation, resolvin E1 and palmitoyl-ethanolamine (PEA), which need to be further investigated in cattle. These results indicate that the measurement of specific representatives of phosphatidylcholines in plasma may provide a novel diagnostic biomarker of fatty liver disease in dairy cows. Copyright © 2016 Elsevier Ltd. All rights reserved.

Targeting nuclear receptors for the treatment of fatty liver disease.

PubMed

Tanaka, Naoki; Aoyama, Toshifumi; Kimura, Shioko; Gonzalez, Frank J

2017-11-01

Ligand-activated nuclear receptors, including peroxisome proliferator-activated receptor alpha (PPARα), pregnane X receptor, and constitutive androstane receptor, were first identified as key regulators of the responses against chemical toxicants. However, numerous studies using mouse disease models and human samples have revealed critical roles for these receptors and others, such as PPARβ/δ, PPARγ, farnesoid X receptor (FXR), and liver X receptor (LXR), in maintaining nutrient/energy homeostasis in part through modulation of the gut-liver-adipose axis. Recently, disorders associated with disrupted nutrient/energy homeostasis, e.g., obesity, metabolic syndrome, and non-alcoholic fatty liver disease (NAFLD), are increasing worldwide. Notably, in NAFLD, a progressive subtype exists, designated as non-alcoholic steatohepatitis (NASH) that is characterized by typical histological features resembling alcoholic steatohepatitis (ASH), and NASH/ASH are recognized as major causes of hepatitis virus-unrelated liver cirrhosis and hepatocellular carcinoma. Since hepatic steatosis is basically caused by an imbalance between fat/energy influx and utilization, abnormal signaling of these nuclear receptors contribute to the pathogenesis of fatty liver disease. Standard therapeutic interventions have not been fully established for fatty liver disease, but some new agents that activate or inhibit nuclear receptor signaling have shown promise as possible therapeutic targets. In this review, we summarize recent findings on the roles of nuclear receptors in fatty liver disease and discuss future perspectives to develop promising pharmacological strategies targeting nuclear receptors for NAFLD/NASH. Copyright © 2017 Elsevier Inc. All rights reserved.

Cardiac Diseases Among Liver Transplant Candidates.

PubMed

Gitman, Marina; Albertz, Megan; Nicolau-Raducu, Ramona; Aniskevich, Stephen; Pai, Sher-Lu

2018-05-27

Improvements in early survival after liver transplant (LT) have allowed for the selection of LT candidates with multiple comorbidities. Cardiovascular disease is a major contributor to post-LT complications. We performed a literature search to identify the causes of cardiac disease in the LT population and to describe techniques for diagnosis and perioperative management. Since no definite guidelines for preoperative assessment (except for pulmonary heart disease) are currently available, we recommend an algorithm for preoperative cardiac work-up. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Chronic Liver Disease in the Hispanic Population of the United States

PubMed Central

Carrion, Andres F.; Ghanta, Ravi; Carrasquillo, Olveen; Martin, Paul

2014-01-01

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease. PMID:21628000

Nonalcoholic fatty liver disease and polycystic ovary syndrome.

PubMed

Vassilatou, Evangeline

2014-07-14

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD.

Nonalcoholic fatty liver disease and polycystic ovary syndrome

PubMed Central

Vassilatou, Evangeline

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease, in patients without significant alcohol consumption. Increased prevalence of NAFLD has been reported in patients with polycystic ovary syndrome (PCOS), one of the most common endocrinopathies in premenopausal women, which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the syndrome. Obesity, in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in PCOS. Moreover, existing data support that androgen excess, which is the main feature of PCOS and is interrelated to insulin resistance, may be an additional contributing factor to the development of NAFLD. Although the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients, limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with NAFLD. PCOS patients, particularly obese patients with features of the metabolic syndrome, should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal ultrasound. Lifestyle modifications including diet, weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with NAFLD. When pharmacologic therapy is considered, metformin may be used, although currently there is no medical therapy of proven benefit for NAFLD. Long-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation, follow-up protocol and optimal treatment for PCOS patients with NAFLD. PMID:25024594

The Impact of Liver Cell Injury on Health-Related Quality of Life in Patients with Chronic Liver Disease

PubMed Central

Alt, Yvonne; Grimm, Anna; Schlegel, Liesa; Grambihler, Annette; Kittner, Jens M.; Wiltink, Jörg; Galle, Peter R.; Wörns, Marcus A.; Schattenberg, Jörn M.

2016-01-01

Background Patients with chronic liver disease often suffer from unspecific symptoms and report severe impairment in the quality of life. The underlying mechanisms are multifactorial and include disease-specific but also liver related causes. The current analysis evaluated the association of hepatocellular apoptosis in non-viral chronic liver disease and health-related quality of life (HRQL). Furthermore we examined factors, which influence patient's physical and mental well-being. Methods A total of 150 patients with non-infectious chronic liver disease were included between January 2014 and June 2015. The German version of the Chronic Liver Disease Questionnaire (CLDQ-D), a liver disease specific instrument to assess HRQL, was employed. Hepatocellular apoptosis was determined by measuring Cytokeratin 18 (CK18, M30 Apoptosense ELISA). Results Female gender (5.24 vs. 5.54, p = 0.04), diabetes mellitus type II (4.75 vs. 5.46, p<0.001) and daily drug intake (5.24 vs. 6.01, p = 0.003) were associated with a significant impairment in HRQL. HRQL was not significantly different between the examined liver diseases. Levels of CK18 were the highest in patients with NASH compared to all other disease entities (p<0.001). Interestingly, CK18 exhibited significant correlations with obesity (p<0.001) and hyperlipidemia (p<0.001). In patients with cirrhosis levels of CK18 correlated with the MELD score (r = 0.18, p = 0.03) and were significantly higher compared to patients without existing cirrhosis (265.5 U/l vs. 186.9U/l, p = 0.047). Additionally, CK18 showed a significant correlation with the presence and the degree of hepatic fibrosis (p = 0.003) and inflammation (p<0.001) in liver histology. Finally, there was a small negative association between CLDQ and CK18 (r = -0.16, p = 0.048). Conclusion Different parameters are influencing HRQL and CK18 levels in chronic non-viral liver disease and the amount of hepatocellular apoptosis correlates with the impairment in HRQL in

Preclinical Models for Investigation of Herbal Medicines in Liver Diseases: Update and Perspective

PubMed Central

Tan, Hor-Yue; San-Marina, Serban; Wang, Ning; Hong, Ming; Li, Sha; Li, Lei; Cheung, Fan; Wen, Xiao-Yan; Feng, Yibin

2016-01-01

Liver disease results from a dynamic pathological process associated with cellular and genetic alterations, which may progress stepwise to liver dysfunction. Commonly, liver disease begins with hepatocyte injury, followed by persistent episodes of cellular regeneration, inflammation, and hepatocyte death that may ultimately lead to nonreversible liver failure. For centuries, herbal remedies have been used for a variety of liver diseases and recent studies have identified the active compounds that may interact with liver disease-associated targets. Further study on the herbal remedies may lead to the formulation of next generation medicines with hepatoprotective, antifibrotic, and anticancer properties. Still, the pharmacological actions of vast majority of herbal remedies remain unknown; thus, extensive preclinical studies are important. In this review, we summarize progress made over the last five years of the most commonly used preclinical models of liver diseases that are used to screen for curative herbal medicines for nonalcoholic fatty liver disease, liver fibrosis/cirrhosis, and liver. We also summarize the proposed mechanisms associated with the observed liver-protective, antifibrotic, and anticancer actions of several promising herbal medicines and discuss the challenges faced in this research field. PMID:26941826

Nonalcoholic Fatty Liver Disease in Inflammatory Bowel Disease: Prevalence and Risk Factors.

PubMed

Mariabeatrice, Principi; Andrea, Iannone; Giuseppe, Losurdo; Michela, Mangia; Endrit, Shahini; Francesca, Albano; Rizzi, Salvatore Fabio; La Fortezza, Rosa Federica; Rosa, Lovero; Antonella, Contaldo; Michele, Barone; Gioacchino, Leandro; Enzo, Ierardi; Alfredo, Di Leo

2018-04-23

Nonalcoholic fatty liver disease (NAFLD) is common in inflammatory bowel diseases (IBD). Herein, NAFLD prevalence and risk factors in a large IBD cohort were evaluated and compared to that of a non-IBD sample. Crohn's disease/ulcerative colitis outpatients referred to IBD service of our Gastroenterology Unit were enrolled. Subjects affected by functional and motor gastrointestinal disorders, in whom IBD was ruled out, referred to general outpatient service in the same area, were considered as nonIBD group. Exclusion criteria were based on previous diagnosis of nonNAFLD chronic liver diseases and secondary causes of fat liver overload. Characteristics of IBD and liver status were collected. Risk factors for metabolic syndrome were analyzed. Ultrasonographic presence and degree of steatosis were assessed. Data were examined by univariate and multivariate analyses. For this study 465 IBD and 189 non-IBD subjects were consecutively enrolled. NAFLD was found in 28.0% and 20.1% in IBD and non-IBD subjects, respectively (P = 0.04). IBD patients with NAFLD were younger than non-IBD ones. There was no significant difference in steatosis grade and association between NAFLD and IBD behavior, extension, activity, and drugs. In the IBD group, multivariate analysis demonstrated that NAFLD was independently associated to metabolic syndrome (OR=2.24, 95%CI 1.77-28.81), diabetes (OR=1.71, 95%CI 1.43-12.25), fasting blood glucose (OR=1.36, 95%CI 1.13-1.68), and abdominal circumference (OR=1.68, 95%CI 1.15-14.52). NAFLD is more common and occurs at a younger age in IBD than in nonIBD subjects. However, further investigation is required to ascertain possible NAFLD pathogenic IBD-related factors other than conventional/metabolic ones. 10.1093/ibd/izy051_video1izy051.video15774874877001.

Quality of life following liver transplantation: a comparative study between Familial Amyloid Neuropathy and liver disease patients

PubMed Central

2009-01-01

Background It has been demonstrated in many studies that quality of life can be improved after liver transplantation in patients with liver disease. Nevertherless quality of life improvement in specific groups of transplantated patients such as those with Familial Amyloid Polineuropathy hasn't yet been explored. The present study aimed to compare the change in quality of life following liver transplantation between patients with Familial Amyloid Polineuropathy (FAP) and patients with liver disease. Results Patient's mental quality of life showed an improvement in all liver disease patients, and a worsening in FAP patients, resulting in a significant difference between the two groups. Regarding physical quality of life, although a similar improvement was seen in both groups, FAP patients had significantly less improvement than the sub-group of decompensated liver disease (Child-Pugh B and C). Conclusion It is concluded that liver transplantation has a less beneficial impact in FAP patient's physical quality of life, probably because they are not so much disabled by their disease at the moment of liver transplantation. The lesser improvement in mental quality of life of FAP patients may be due to their particular psychological profile and greater expectations towards transplantation. PMID:19604387

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

PubMed

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M

2016-09-28

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

PubMed Central

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

2016-01-01

Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids

Beneficial effects of naringenin in liver diseases: Molecular mechanisms

PubMed Central

Hernández-Aquino, Erika; Muriel, Pablo

2018-01-01

Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix (ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor (TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells (HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase (MAPK), toll-like receptor (TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease (NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor (VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases. PMID:29713125

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS).

PubMed

Sheron, Nick; Moore, Michael; O'Brien, Wendy; Harris, Scott; Roderick, Paul

2013-10-01

In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. A community feasibility study in nine general practice sites in Hampshire. Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives. Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking.

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

Diagnosis of non-alcoholic fatty liver disease (NAFLD).

PubMed

Yki-Järvinen, Hannele

2016-06-01

Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT ≈30 U/l in men and ≈20 U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1 , and by John Jones, DOI: 10.1007/s00125

[Non-alcoholic fatty liver disease, as a component of the metabolic syndrome, and its causal correlations with other extrahepatic diseases].

PubMed

Halmos, Tamás; Suba, Ilona

2017-12-01

Non-alcoholic fatty liver disease is the most common non-infectious chronic liver-disease in our age, and is a spectrum of all the diseases associated with increased fat accumulation in the hepatocytes. Its development is promoted by sedentary life-style, over-feeding, and certain genetic predisposition. Prevalence in the adult population, even in Hungary is ~30%. In a part of cases, this disease may pass into non-alcoholic steatohepatitis, later into fibrosis, rarely into primary hepatocellular cancer. Fatty liver is closely and bidirectionally related to the metabolic syndrome and type 2 diabetes, and nowadays there is a general consensus that fatty liver is the hepatic manifestation of the metabolic sycndrome. The importance of the fatty liver has been highly emphasized recently. In addition to the progression into steatohepatitis, its causal relationship with numerous extrahepatic disorders has been discovered. In our overview, we deal with the epidemiology, pathomechanism of the disease, discuss the possibilities of diagnosis, its relationship with the intestinal microbiota, its recently recognized correlations with bile acids and their receptors, and its supposed correlations with the circadian CLOCK system. Hereinafter, we overview those extrahepatic disorders, which have been shown to be causal link with the non-alcoholic fatty liver disease. Among these, we emphasize the metabolic syndrome/type 2 diabetes, cardiovascular disorders, chronic kidney disease, sleep apnea/hypoventilation syndrome, inflammatory bowel disease, Alzheimer's disease, osteoporosis, and psoriasis, as well. Based on the above, it can be stated, that high risk individuals with non-alcoholic fatty liver disease need systemic care, and require the detection of other components of this systemic pathological condition. While currently specific therapy for the disease is not yet known, life-style changes, adequate use of available medicines can prevent disease progression. Promising research

Role of scavenger receptors in the pathophysiology of chronic liver diseases.

PubMed

Armengol, Carolina; Bartolí, Ramon; Sanjurjo, Lucía; Serra, Isabel; Amézaga, Núria; Sala, Margarita; Sarrias, Maria-Rosa

2013-01-01

Scavenger receptors comprise a large family of structurally diverse proteins that are involved in many homeostatic functions. They recognize a wide range of ligands, from pathogen-associated molecular patterns (PAMPs) to endogenous, as well as modified host-derived molecules (DAMPs). The liver deals with blood micro-organisms and DAMPs released from injured organs, thus performing vital metabolic and clearance functions that require the uptake of nutrients and toxins. Many liver cell types, including hepatocytes and Kupffer cells, express scavenger receptors that play key roles in hepatitis C virus entry, lipid uptake, and macrophage activation, among others. Chronic liver disease causes high morbidity and mortality worldwide. Hepatitis virus infection, alcohol abuse, and non-alcoholic fatty liver are the main etiologies associated with this disease. In this context, continuous inflammation as a result of liver damage leads to hepatic fibrosis, which frequently brings about cirrhosis and ultimately hepatocellular carcinoma. In this review, we will summarize the role of scavenger receptors in the pathophysiology of chronic liver diseases. We will also emphasize their potential as biomarkers of advanced liver disease, including cirrhosis and cancer.

[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.

Chronic liver disease in the Hispanic population of the United States.

PubMed

Carrion, Andres F; Ghanta, Ravi; Carrasquillo, Olveen; Martin, Paul

2011-10-01

Chronic liver disease is a major cause of morbidity and mortality among Hispanic people living in the United States. Environmental, genetic, and behavioral factors, as well as socioeconomic and health care disparities among this ethnic group have emerged as important public health concerns. We review the epidemiology, natural history, and response to therapy of chronic liver disease in Hispanic patients. The review covers nonalcoholic fatty liver disease, viral hepatitis B and C, coinfection of viral hepatitis with human immunodeficiency virus, alcoholic cirrhosis, hepatocellular carcinoma, autoimmune hepatitis, and primary biliary cirrhosis. For most of these disorders, the Hispanic population has a higher incidence and more aggressive pattern of disease and overall worse treatment outcomes than in the non-Hispanic white population. Clinicians should be aware of these differences in caring for Hispanic patients with chronic liver disease. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

Hepatic protoporphyrin metabolism in patients with advanced protoporphyric liver disease.

PubMed Central

Bloomer, J. R.

1997-01-01

Protoporphyria is a genetic disorder in which liver damage is caused by the toxic effect of protoporphyrin accumulation in the liver. In this study protoporphyrin was measured in the resected livers of 7 patients who had liver transplantation and an additional patient from whom liver tissue was obtained post mortem. Comparison of liver, erythrocyte and serum protoporphyrin levels demonstrated a marked gradient between these compartments: erythrocyte, 5781 +/- 655 micrograms/dl; serum, 384 +/- 102 micrograms/dl; liver 377,238 +/- 55,568 micrograms/100 gm wet weight, (mean +/- SE). Protoporphyrin levels in bile of 3 patients were 55,559, and 1,153 micrograms/dl, indicating a gradient between liver and bile as well. Examination of the livers by polarization microscopy and electron microscopy demonstrated protoporphyrin pigment crystals. In one patient who had recurrent liver disease after transplantation, the protoporphyrin concentration in the graft at the time of death was similar to that in the resected liver. These data indicate that liver protoporphyrin levels in patients with advanced protoporphyric liver disease are much higher than levels in blood and bile, in part because protoporphyrin forms crystalline deposits in liver tissue. Thus, progressive hepatic accumulation of protoporphyrin occurs in the face of impaired biliary excretion. An intrinsic defect in hepatic excretion of protoporphyrin is probably not necessary for this condition to develop because liver disease can occur in the graft following transplantation. PMID:9626752

[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

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

Non-alcoholic fatty liver disease: Pathophysiology and management

PubMed Central

Carr, Rotonya M.; Oranu, Amanke; Khungar, Vandana

2016-01-01

Abstract/Summary NAFLD is an important cause of morbidity and mortality worldwide both because of cardiovascular, hepatic and oncologic sequelae as well as because it is rapidly becoming the leading cause of end stage liver disease and liver transplant. With a prevalence of 30% in the US, it has reached epidemic proportions. While the metabolic syndrome is a common risk factor, there are differences among racial and ethnic groups, suggesting the complex interaction between hormonal, nutritional and genetic factors at play in disease pathogenesis. The clinical syndrome of NAFLD spans from bland steatosis to steatohepatitis which can progress to fibrosis and cirrhosis. The pathogenesis including roles of hormones, nutritional and intestinal dysbiosis, insulin resistance, lipotoxicity, and hepatic inflammation, and genes are examined. Non-invasive testing and liver biopsy indications are reviewed. Approved and investigational therapies for NAFLD and NASH are outlined in this review of a disease that is currently an area of great interest to the hepatology community. PMID:27837778

Endocannabinoids in Liver Disease

PubMed Central

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

2010-01-01

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 is present both in brain and peripheral tissues, including the liver. The hepatic ECS is activated in various liver diseases, which contributes to the underlying pathologies. In cirrhosis of various etiologies, activation of vascular and cardiac CB1 receptors by macrophage- and platelet-derived endocannabinoids contribute to the vasodilated state and cardiomyopathy, which can be reversed by CB1 blockade. In mouse models of liver fibrosis, activation of CB1 receptors on hepatic stellate cells is fibrogenic, and CB1 blockade slows the progression of fibrosis. Fatty liver induced by high-fat diets or chronic alcohol feeding depend on activation of peripheral, including hepatic CB1 receptors, which also contribute to insulin resistance and dyslipidemias. Although the documented therapeutic potential of CB1 blockade is limited by neuropsychiatric side effects, these may be mitigated by using novel, peripherally restricted CB1 antagonists. PMID:21254182

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.

Epstein-Barr viral load before a liver transplant in children with chronic liver disease.

PubMed

Shakibazad, Nader; Honar, Naser; Dehghani, Seyed Mohsen; Alborzi, Abdolvahab

2014-12-01

Many children with chronic liver disease require a liver transplant. These patients are prone to various infections, including Epstein-Barr virus infection. This study sought to measure the Epstein-Barr viral load by polymerase chain reaction before a liver transplant. This cross-sectional study was done at the Shiraz University of Medical Sciences, Shiraz, Iran, in 2011. All patients were aged younger than 18 years with chronic liver disease and were candidates for a liver transplant at the Shiraz Nemazee Hospital Organ Transplant Center. They had been investigated regarding their demographic characteristics, underlying disease, laboratory findings, and Epstein-Barr viral load by real-time TaqMan polymerase chain reaction. Ninety-eight patients were studied and the mean age was 6.5 ± 5.9 years. Cryptogenic cirrhosis was the most-prevalent reason for liver transplant, and the death rate before a transplant was 15%. Among the study subjects, 6 had measurable Epstein-Barr viral load by polymerase chain reaction before the transplant, and 4 of them had considerably higher Epstein-Barr viral loads (more than 1000 copies/mL). With respect to the close prevalence of posttransplant lymphoproliferative disease (6%) and the high Epstein-Barr viral load in the patients before a transplant (4%), high pretransplant Epstein-Barr viral load can be considered a risk factor for posttransplant lymphoproliferative disorder.

Rodent Models of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis

PubMed Central

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

2013-01-01

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. PMID:24192824

Non-Alcoholic Fatty Liver Disease.

PubMed

Engin, Atilla

2017-01-01

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

Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.

PubMed

Niemietz, Christoph; Chandhok, Gursimran; Schmidt, Hartmut

2015-09-30

The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

[Disease burden of liver cancer in the Chinese population, in 1990 and 2013].

PubMed

Wang, L J; Yin, P; Liu, Y N; Liu, J M; Qi, J L; Zhou, M G

2016-06-01

To analyze the disease burden of liver cancer in the Chinese population in 1990 and 2013. Data from Global Burden of Diseases 2013 (GBD2013) was used to analyze the disease burden of liver cancer in China. The main outcome measurements would include mortality and disability-adjusted life years (DALY). Again, GBD global standard population in 2013 was used as the reference population to calculate the age-standardized rate. Related changes on percentage from 1990 to 2013 were calculated to analyze the changing patterns of disease burden for liver cancer in China. In 2013, a total of 358 100 people died of liver cancer, with the crude death rate as 25.85/100 000, in China. Number of deaths due to liver cancer secondary to hepatitis B was 163 600 (accounting for 45.69%). Number of deaths due to liver cancer secondary to hepatitis C was 134 200 (accounting for 37.48%) with DALY due to liver cancer appeared as 40.80 million person years. In 2013, the leading causes of DALY related to liver cancer was liver cancer secondary to hepatitis B, followed by liver cancer secondary to hepatitis C, liver cancer secondary to alcohol use, other liver cancers, with related DALYs as 4 652.0, 3 394.3, 964.3 and 592.1 thousands person years, respectively. The disease burdens of liver cancer secondary to various kinds of liver cancer were significantly higher in males than in females. Compared with 1990, the standardized mortality of liver cancer reduced by 25.00%, the DALY attributable to liver cancer increased by 16.95% and the standardized DALY rate attributable to liver cancer reduced by 33.47%. The burden of liver cancer secondary to hepatitis C became more serious and the standardized death rate increased by 106.18%, together with the standardized DALY rate increased by 91.68% in the past 23 years. Disease burden of liver cancer among young adults and the elderly were most serious. When comparing with the data in 1990, the standardized DALY rate showed declining trend in all the

Platelets in liver disease, cancer and regeneration.

PubMed

Kurokawa, Tomohiro; Ohkohchi, Nobuhiro

2017-05-14

Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease (CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.

Outcomes of liver transplantation for end-stage biliary disease: A comparative study with end-stage liver disease.

PubMed

Lai, Yan-Hua; Duan, Wei-Dong; Yu, Qiang; Ye, Sheng; Xiao, Nian-Jun; Zhang, Dong-Xin; Huang, Zhi-Qiang; Yang, Zhan-Yu; Dong, Jia-Hong

2015-05-28

To evaluate the outcomes of patients with end-stage biliary disease (ESBD) who underwent liver transplantation, to define the concept of ESBD, the criteria for patient selection and the optimal operation for decision-making. Between June 2002 and June 2014, 43 patients with ESBD from two Chinese organ transplantation centres were evaluated for liver transplantation. The causes of liver disease were primary biliary cirrhosis (n = 8), cholelithiasis (n = 8), congenital biliary atresia (n = 2), graft-related cholangiopathy (n = 18), Caroli's disease (n = 2), iatrogenic bile duct injury (n = 2), primary sclerosing cholangitis (n = 1), intrahepatic bile duct paucity (n = 1) and Alagille's syndrome (n = 1). The patients with ESBD were compared with an end-stage liver disease (ESLD) case control group during the same period, and the potential prognostic values of multiple demographic and clinical variables were assessed. The examined variables included recipient age, sex, pre-transplant clinical status, pre-transplant laboratory values, operation condition and postoperative complications, as well as patient and allograft survival rates. Survival analysis was performed using Kaplan-Meier curves, and the rates were compared using log-rank tests. All variables identified by univariate analysis with P values < 0.100 were subjected to multivariate analysis. A Cox proportional hazard regression model was used to determine the effect of the study variables on outcomes in the study group. Patients in the ESBD group had lower model for end-stage liver disease (MELD)/paediatric end-stage liver disease (PELD) scores and a higher frequency of previous abdominal surgery compared to patients in the ESLD group (19.2 ± 6.6 vs 22.0 ± 6.5, P = 0.023 and 1.8 ± 1.3 vs 0.1 ± 0.2, P = 0.000). Moreover, the operation time and the time spent in intensive care were significantly higher in the ESBD group than in the ESLD group (527.4 ± 98.8 vs 443.0 ± 101.0, P = 0.000, and 12.74 ± 6.6 vs 10

Methods to determine intestinal permeability and bacterial translocation during liver disease

PubMed Central

Wang, Lirui; Llorente, Cristina; Hartmann, Phillipp; Yang, An-Ming; Chen, Peng; Schnabl, Bernd

2015-01-01

Liver disease is often times associated with increased intestinal permeability. A disruption of the gut barrier allows microbial products and viable bacteria to translocate from the intestinal lumen to extraintestinal organs. The majority of the venous blood from the intestinal tract is drained into the portal circulation, which is part of the dual hepatic blood supply. The liver is therefore the first organ in the body to encounter not only absorbed nutrients, but also gut-derived bacteria and pathogen associated molecular patterns (PAMPs). Chronic exposure to increased levels of PAMPs has been linked to disease progression during early stages and to infectious complications during late stages of liver disease (cirrhosis). It is therefore important to assess and monitor gut barrier dysfunction during hepatic disease. We review methods to assess intestinal barrier disruption and discuss advantages and disadvantages. We will in particular focus on methods that we have used to measure increased intestinal permeability and bacterial translocation during experimental liver disease models. PMID:25595554

Pathophysiology and Mechanisms of Nonalcoholic Fatty Liver Disease.

PubMed

Haas, Joel T; Francque, Sven; Staels, Bart

2016-01-01

Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver disorders characterized by abnormal hepatic fat accumulation, inflammation, and hepatocyte dysfunction. Importantly, it is also closely linked to obesity and the metabolic syndrome. NAFLD predisposes susceptible individuals to cirrhosis, hepatocellular carcinoma, and cardiovascular disease. Although the precise signals remain poorly understood, NAFLD pathogenesis likely involves actions of the different hepatic cell types and multiple extrahepatic signals. The complexity of this disease has been a major impediment to the development of appropriate metrics of its progression and effective therapies. Recent clinical data place increasing importance on identifying fibrosis, as it is a strong indicator of hepatic disease-related mortality. Preclinical modeling of the fibrotic process remains challenging, particularly in the contexts of obesity and the metabolic syndrome. Future studies are needed to define the molecular pathways determining the natural progression of NAFLD, including key determinants of fibrosis and disease-related outcomes. This review covers the evolving concepts of NAFLD from both human and animal studies. We discuss recent clinical and diagnostic methods assessing NAFLD diagnosis, progression, and outcomes; compare the features of genetic and dietary animal models of NAFLD; and highlight pharmacological approaches for disease treatment.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

Metabolic Syndrome: Nonalcoholic Fatty Liver Disease.

PubMed

Williams, Tracy

2015-08-01

Although nonalcoholic fatty liver disease (NAFLD) is not one of the defining criteria for metabolic syndrome, it is a common hepatic manifestation. NAFLD includes a spectrum of histologic findings ranging from simple steatosis, known as nonalcoholic fatty liver, to nonalcoholic steatohepatitis (NASH). To make the diagnosis of NAFLD, other etiologies of steatosis or hepatitis, such as hepatotoxic drugs, excessive alcohol intake, congenital errors of metabolism, or viral hepatitis, must be ruled out. After ruling out other conditions, the diagnosis of NAFLD often is made clinically, but a definitive diagnosis of NASH requires liver biopsy. As with other complications of metabolic syndrome, insulin resistance is thought to be an underlying etiology of NAFLD. Management strategies attempt to reverse or improve insulin resistance while minimizing liver damage. The strongest evidence supports lifestyle modifications with weight loss, but there is some evidence to support bariatric surgery, medical therapy with insulin-sensitizing agents, and/or pharmacotherapy to promote weight loss. Cardiovascular disease is the major cause of mortality in patients with NAFLD, so management must include modification of cardiovascular risk factors. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Psoriasis and Nonalcoholic Fatty Liver Disease.

PubMed

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

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. Copyright © 2017 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

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

Feasibility of detection and intervention for alcohol-related liver disease in the community: the Alcohol and Liver Disease Detection study (ALDDeS)

PubMed Central

Sheron, Nick; Moore, Michael; O’Brien, Wendy; Harris, Scott; Roderick, Paul

2013-01-01

Background In the past 15 years mortality rates from liver disease have doubled in the UK. Brief alcohol advice is cost effective, but clinically meaningful reductions in alcohol consumption only occur in around 1 in 10 individuals. Aim To provide evidence that detecting early liver disease in the community is feasible, practical, and that feedback of liver risk can increase the proportion of subjects reducing alcohol consumption. Design and setting A community feasibility study in nine general practice sites in Hampshire. Method Hazardous and harmful drinkers were identified by WHO AUDIT questionnaire and offered screening for liver fibrosis. Results In total, 4630 individuals responded, of whom 1128 (24%) hazardous or harmful drinkers were offered a liver fibrosis check using the Southampton Traffic Light (STL) test; 393 (38%) attended and test results were returned by post. The STL has a low threshold for liver fibrosis with 45 (11%) red, 157 (40%) amber, and 191 (49%) green results. Follow-up AUDIT data was obtained for 303/393 (77%) and 76/153 (50%) subjects with evidence of liver damage reduced drinking by at least one AUDIT category (harmful to hazardous, or hazardous to low risk) compared with 52/150 (35%, P<0.011) subjects without this evidence; in the subset of harmful drinkers patterns (AUDIT >15), 22/34 (65%) of STL positives, reduced drinking compared with 10/29 (35%, P<0.017) STL negatives. Conclusion Detection of liver disease in the community is feasible, and feedback of liver risk may reduce harmful drinking. PMID:24152485

Burden of Gastrointestinal and Liver Diseases in Iran: Estimates Based on the Global Burden of Disease, Injuries, and Risk Factors Study, 2010.

PubMed

Malekzadeh, Fatemeh; Sepanlou, Sadaf Ghajarieh; Poustchi, Hossein; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza

2015-07-01

BACKGROUND Gastrointestinal and liver diseases (GILD) constitute a noteworthy portion of causes of death and disability in Iran. However, data on their prevalence and burden is sparse in Iran. The Global Burden of Disease (GBD) study in 2010 has provided invaluable comprehensive data on the burden of GILD in Iran. METHODS Estimations of death, years of life lost due to premature death (YLL), years of life lost due to disability (YLD), disability-adjusted life years (DALY), life expectancy, and healthy life expectancy have been reported for 291 diseases, 67 risk factors, 1160 sequelae, for both sexes and 19 age groups, form 1990 to 2010 for 187 countries. In the current paper, 5 major categories of gastrointestinal (GI) and liver diseases have been investigated as follows: GI infectious diseases, GI and liver cancers, liver infections, chronic end stage liver disease, and other digestive diseases. RESULTS Among women, 7.6% of all deaths and 3.9% of all DALYs were due to digestive and liver diseases in 2010. The respective figures in men were 7.8% of deaths and 4.6% of DALYs. The most important cause of death among children under 5 is diarrhea. Among adults between 15 to 49 years old, the main causes of death are GI and liver cancers and cirrhosis, while diarrhea still remains a major cause of DALY. Among adults 50 years and above, GI and liver cancers and cirrhosis are the main causes of both deaths and DALYs. Gastritis and duodenitis, diarrheal diseases, gall bladder and bile duct diseases, acute hepatitis A, peptic ulcer disease, appendicitis, and acute hepatitis A mainly cause disability rather than death. CONCLUSION GBD study provides invaluable source of data on burden of GILD in Iran. However, there exist limitations, namely overestimation of burden of liver cancer and underestimation of the burden of GI diseases that are usually diagnosed in outpatient settings. The collaboration of scientists across the world and specifically those from developing countries

Trend of Gastrointestinal and Liver Diseases in Iran: Results of the Global Burden of Disease Study, 2010.

PubMed

Sepanlou, Sadaf Ghajarieh; Malekzadeh, Fatemeh; Naghavi, Mohsen; Forouzanfar, Mohammad Hossein; Shahraz, Saeid; Moradi-Lakeh, Maziar; Malekzadeh, Reza; Poustchi, Hossein

2015-07-01

BACKGROUND The general pattern of epidemiologic transition from communicable to noncommunicable diseases is also observed for gastrointestinal and liver diseases (GILD), which constitute a heterogeneous array of causes of death and disability. We aimed to describe the trend of GILD in Iran based on the global burden of disease (GBD2010) study from 1990 to 2010. METHODS The trend of number of deaths, disability, adjusted life years (DALYs) and their age-standardized rates caused by 5 major GILD have been reported. The change in the rankings of major causes of death and DALY has been described as well. RESULTS The age standardized rates of death and DALYs in both sexes have decreased from 1990 to 2010 for most GILD. The most prominent decreases in death rates are observed for diarrheal diseases, gastritis and duodenitis, and peptic ulcer disease. Positive trends are observed for liver cancer, pancreatic cancer, and gall bladder cancer. Diarrheal diseases have retained their 1st rank among children under 5. Among adults, decreased ranks are observed for diarrheal diseases, appendicitis, gastritis and duodenitis, gall bladder diseases, pancreatitis, and all types of cirrhosis. The trends in age standardized rates of DALYs, deaths, and YLLs are negative for almost all GILD, and especially for diarrheal diseases. However, there is no upward or downward trend in rates of years lost due to disability (YLDs) for most diseases. Total numbers of DALYs and deaths due to acute hepatitis C, stomach cancer, and liver cancers are rising. The total DALYs due to overall digestive diseases except cirrhosis and DALYs due to cirrhosis are both somehow stable. No data has been reported for GILD that are mainly diagnosed in outpatient settings, including gastroesophageal reflux disease, irritable bowel syndrome, and non-alcoholic fatty liver disease. CONCLUSION The results of GBD 2010 demonstrate that the rates of most GILD are decreasing in Iran but total DALYs are somehow stable

Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

PubMed

Maan, Raoel; de Knegt, Robert J; Veldt, Bart J

2015-11-01

Thrombocytopenia (platelet count <150 × 10(9)/L) often complicates chronic liver disease, impeding optimal management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

Non-alcoholic fatty liver disease: What the clinician needs to know

PubMed Central

Machado, Mariana Verdelho; Cortez-Pinto, Helena

2014-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver disease in the Western world. Furthermore, it is increasing worldwide, paralleling the obesity pandemic. Though highly frequent, only about one fifth of affected subjects are at risk of developing the progressive form of the disease, non-alcoholic steatohepatitis with fibrosis. Even in the latter, liver disease is slowly progressive, though, since it is so prevalent, it is already the third cause of liver transplantation in the United States, and it is predicted to get to the top of the ranking in few years. Of relevance, fatty liver is also associated with increased overall mortality and particularly increased cardiovascular mortality. The literature and amount of published papers on NAFLD is increasing as fast as its prevalence, which makes it difficult to keep updated in this topic. This review aims to summarize the latest knowledge on NAFLD, in order to help clinicians understanding its pathogenesis and advances on diagnosis and treatment. PMID:25278691

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2014-12-15

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies.Date of the most recent search of the Group's trials register: 29 May 2014. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. Ten trials have been identified, of which three trials involving 118 participants were included; the dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30 participants from two trials. Improvement in biliary excretion was reported in only one trial and no significant change after treatment was shown. There were no data available for analysis for long-term outcomes such as death or need for liver transplantation. There are few

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

Liver cirrhosis in selected autoimmune diseases: a nationwide cohort study in Taiwan.

PubMed

Tung, Chien-Hsueh; Lai, Ning-Seng; Lu, Ming-Chi; Lee, Ching-Chih

2016-02-01

The association between autoimmune diseases and liver cirrhosis has rarely been explored in Asian populations, an endemic area of viral hepatitis. The aim of this study was to investigate the comparative risk of liver cirrhosis among a group of selective autoimmune diseases in Taiwanese patients and to identify groups of high risk. This retrospective study was a nationwide, population-based study and used Taiwan's National Health Insurance Research Database. A total of 29,856 patients with definite diagnosis of selected autoimmune diseases (Registry of Taiwan Catastrophic Illness Database, ACR classification) at the starting time point of January 1, 2005, were enrolled in this study. After tracked for a 5-year period, the endpoints were diagnosis of liver cirrhosis (in accordance with International Classification of Diseases, Ninth Revision, Clinical Modification, ICD-9-CM codes 571). The control group was composed of other patients in the same database and consisted of randomly selected 753,495 sex- and age-matched non-autoimmune disease patients. The Cox proportional hazard regression model was used to calculate the risk of liver cirrhosis after adjusting for certain variables such as comorbidity, living area, and socioeconomic status. Among the patients with selected autoimmune diseases, 1987 liver cirrhosis were observed. Patients with psoriasis had a significantly increased risk of liver cirrhosis (HR 1.87, 95 % CI 1.25-2.81) than control group without psoriasis. The risk of liver cirrhosis was significantly lower in patients with rheumatoid arthritis (HR 0.29, 95 % CI 0.19-0.44). There is a gradient of risk of liver cirrhosis among the autoimmune diseases; the specific risks need to be investigated on the basis of hypotheses. Conventional immunosuppressive drug administration should be carefully implemented by regular monitoring of liver condition in order to avoid causing an adverse effect of chronic liver fibrosis.

Significance of increased expression of decoy receptor 3 in chronic liver disease.

PubMed

Kim, S; Kotoula, V; Hytiroglou, P; Zardavas, D; Zhang, L

2009-08-01

Considerable evidence has indicated that apoptosis plays an important role in hepatocyte death in chronic liver disease. However, the cellular and molecular mechanisms underlying liver regeneration in these diseases are largely unknown. Plausibly, certain molecules expressed to counteract apoptosis might provide survival advantage of certain liver cells. Therefore, we investigated a possible expression of decoy receptor 3 of the tumour necrosis factor receptor family in chronic liver diseases since decoy receptor 3 is known to inhibit apoptosis mediated by pro-apoptotic tumour necrosis factor family ligands including Fas ligand. A series of liver biopsies from patients with different stages of fibrosis were subjected to immunohistochemistry and in situ hybridization. Both decoy receptor 3 protein and mRNA were mainly expressed in biliary epithelial cells and infiltrating lymphocytes in the diseased livers. Most noticeably, intense decoy receptor 3 expression was observed in newly developing biliary ductules in regenerative nodules as well as dysplastic nodules of cirrhotic livers. In addition, decoy receptor 3 secretion in hepatocellular carcinoma cells in culture was via the activation of mitogen-activated protein kinases. Decoy receptor 3 was specifically expressed in chronic liver diseases and hepatocellular carcinoma cells, and decoy receptor 3 might facilitate the survival of liver cells by exerting its anti-apoptotic activity during the progression of liver cirrhosis and hepatocarcinogenesis.

Polycystic Liver Disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linda, Nguyen, E-mail: nguyenli@einstein.edu

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.more » 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.« less

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease.

PubMed

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; Dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-08-07

To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. The median (25(th)-75(th) centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child-Pugh score (P = 0

Serum proinflammatory cytokines and nutritional status in pediatric chronic liver disease

PubMed Central

Santetti, Daniele; de Albuquerque Wilasco, Maria Inês; Dornelles, Cristina Toscani Leal; Werlang, Isabel Cristina Ribas; Fontella, Fernanda Urruth; Kieling, Carlos Oscar; dos Santos, Jorge Luiz; Vieira, Sandra Maria Gonçalves; Goldani, Helena Ayako Sueno

2015-01-01

AIM: To evaluate the nutritional status and its association with proinflammatory cytokines in children with chronic liver disease. METHODS: We performed a cross-sectional study with 43 children and adolescents, aged 0 to 17 years, diagnosed with chronic liver disease. All patients regularly attended the Pediatric Hepatology Unit and were under nutritional follow up. The exclusion criteria were fever from any etiology at the time of enrollment, inborn errors of the metabolism and any chronic illness. The severity of liver disease was assessed by Child-Pugh, Model for End-stage Liver Disease (MELD) and Pediatric End Stage Liver Disease (PELD) scores. Anthropometric parameters were height/age, body mass index/age and triceps skinfold/age according to World Health Organization standards. The cutoff points for nutritional status were risk of malnutrition (Z-score < -1.00) and malnutrition (Z-score < -2.00). Interleukin-1β (IL-1β), IL-6 and tumor necrosis factor-α levels were assessed by commercial ELISA kits. For multivariate analysis, linear regression was applied to assess the association between cytokine levels, disease severity and nutritional status. RESULTS: The median (25th-75th centile) age of the study population was 60 (17-116)-mo-old, and 53.5% were female. Biliary atresia was the main cause of chronic liver disease (72%). With respect to Child-Pugh score, cirrhotic patients were distributed as follows: 57.1% Child-Pugh A, a mild presentation of the disease, 34.3% Child-Pugh B, a moderate stage of cirrhosis and 8.6% Child-Pugh C, were considered severe cases. PELD and MELD scores were only above the cutoff point in 5 cases. IL-6 values ​​were increased in patients at nutritional risk (34.9%) compared with those who were well-nourished [7.12 (0.58-34.23) pg/mL vs 1.63 (0.53-3.43) pg/mL; P = 0.02], correlating inversely with triceps skinfold-for-age z-score (rs = -0.61; P < 0.001). IL-6 levels were associated with liver disease severity assessed by Child

Hepatitis B virus pre-S/S variants in liver diseases.

PubMed

Chen, Bing-Fang

2018-04-14

Chronic hepatitis B is a global health problem. The clinical outcomes of chronic hepatitis B infection include asymptomatic carrier state, chronic hepatitis (CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC). Because of the spontaneous error rate inherent to viral reverse transcriptase, the hepatitis B virus (HBV) genome evolves during the course of infection under the antiviral pressure of host immunity. The clinical significance of pre-S/S variants has become increasingly recognized in patients with chronic HBV infection. Pre-S/S variants are often identified in hepatitis B carriers with CH, LC, and HCC, which suggests that these naturally occurring pre-S/S variants may contribute to the development of progressive liver damage and hepatocarcinogenesis. This paper reviews the function of the pre-S/S region along with recent findings related to the role of pre-S/S variants in liver diseases. According to the mutation type, five pre-S/S variants have been identified: pre-S deletion, pre-S point mutation, pre-S1 splice variant, C-terminus S point mutation, and pre-S/S nonsense mutation. Their associations with HBV genotype and the possible pathogenesis of pre-S/S variants are discussed. Different pre-S/S variants cause liver diseases through different mechanisms. Most cause the intracellular retention of HBV envelope proteins and induction of endoplasmic reticulum stress, which results in liver diseases. Pre-S/S variants should be routinely determined in HBV carriers to help identify individuals who may be at a high risk of less favorable liver disease progression. Additional investigations are required to explore the molecular mechanisms of the pre-S/S variants involved in the pathogenesis of each stage of liver disease.

Epidemiology and Natural History of Non-alcoholic Fatty Liver Disease

PubMed Central

Mishra, Alita; Younossi, Zobair M

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is an important cause of liver disease burden across the world. By definition, although the histopathologic features of NAFLD are identical to that of alcoholic liver disease, its diagnosis requires absence of significant alcohol use and absence of other causes of chronic liver disease. We now know that NAFLD is not simply a disease of the Western world. It is manifested across the world, in varying rates, across gender, across varying ethnicities, and in its association with other host factors. In this review article, the definition of NAFLD, its spectrum, ranging from mild steatosis to hepatocellular injury and inflammation defined as non-alcoholic steatohepatitis (NASH) is discussed. Mild steatosis is generally a stable disease whereas NASH can be progressive. Based on current published literature, current incidence and prevalence of NAFLD and NASH are discussed. It is also accepted that these processes will continue to increase in prevalence with the rise of obesity, type II diabetes, and associated metabolic syndrome. Some of the risk factors have been well-established and are discussed. In addition, this review also presents emerging associations with other risk factors for NAFLD. Natural history of NAFLD is variable depending upon the histologic subtypes and other underlying comorbidities and is discussed in this review as well. PMID:25755422

The increasing burden of potentially preventable liver disease among adult liver transplant recipients: A comparative analysis of liver transplant indication by era in Australia and New Zealand.

PubMed

Howell, Jessica; Balderson, Glenda; Hellard, Margaret; Gow, Paul; Strasser, Simone; Stuart, Katherine; Wigg, Alan; Jeffrey, Gary; Gane, Ed; Angus, Peter W

2016-02-01

Hepatitis C (HCV), hepatitis B (HBV), alcohol-related liver disease (ALD), and non-alcohol-related fatty liver disease (NAFLD) are leading indications for adult liver transplantation in Australia and New Zealand. However, these diseases are potentially preventable through effective primary and/or secondary prevention strategies. This study evaluates the relative contribution of potentially preventable liver diseases to liver transplant numbers in Australia and New Zealand over time. Prospectively recorded clinical, demographic, and outcome data were collected from the Australian and New Zealand Liver Transplant Registry for all primary adult liver transplants performed in Australia and New Zealand from 1 January 1985 until 31 December 2012. Potentially preventable liver disease was defined as HBV, HCV, NAFLD, ALD, and HCC. The etiology of liver disease leading to liver transplantation and the proportion of preventable liver disease-related liver transplantation was compared between Era 1 (1985-1993), Era 2 (1994-2003), and Era 3 (2004-2012). Overall, 1252 of 3266 adult primary liver transplants (38.3%) were performed for potentially preventable liver disease. There was a significant increase in the proportion of liver transplants because of preventable liver disease from 21.2% (93 of 439) in Era 1, to 49.8% (623 of 1252) in Era 2 and 63.5% (1000 of 1575) in Era 3 (P < 0.0001). Over time, there was a significant increase in HCV (P < 0.0001), ALD (P = 0.002), and NAFLD (P < 0.0001) as a primary indication for adult liver transplant, whereas HBV has significantly decreased from Era 1 to Era 3 as an indication for transplant (P < 0.0001). The number of transplants performed for HCC also increased across Eras (P < 0.0001), with 84% due to underlying potentially preventable liver disease. Since 2004, the majority of primary adult liver transplants within Australia and New Zealand have been because of potentially preventable liver diseases and the

Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: An Italian position statement

PubMed Central

Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

2014-01-01

Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the “6-mo rule”. Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The “Group of Italian Regions” suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

Silymarin/Silybin and Chronic Liver Disease: A Marriage of Many Years.

PubMed

Federico, Alessandro; Dallio, Marcello; Loguercio, Carmelina

2017-01-24

Silymarin is the extract of Silybum marianum , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.

Acute hepatitis A and B in patients with chronic liver disease: prevention through vaccination.

PubMed

Keeffe, Emmet B

2005-10-01

Retrospective and prospective studies have demonstrated that the occurrence of acute hepatitis A in patients with chronic liver disease is associated with higher rates of morbidity and mortality than in previously healthy individuals with acute hepatitis A. The mortality associated with acute hepatitis A may be particularly high in patients with preexisting chronic hepatitis C. Although acute hepatitis B in patients with preexisting chronic liver disease is less well studied, worse outcomes than in previously healthy individuals are apparent. However, numerous studies convincingly demonstrate that chronic hepatitis B virus coinfection with hepatitis C virus (or hepatitis D virus) is associated with an accelerated natural history of liver disease and worse outcomes. These observations led to studies that demonstrated the safety and efficacy of hepatitis A and hepatitis B vaccination in patients with mild-to-moderate chronic liver disease. Hepatitis A and B vaccination is less effective in patients with advanced liver disease, especially after decompensation, such as in patients awaiting liver transplantation, and in liver transplant recipients. The emerging lower rates of inherent immunity in younger individuals, higher morbidity and mortality of acute hepatitis A or B superimposed on chronic liver disease, and greater vaccine efficacy in milder forms of chronic liver disease suggest that it is a reasonable policy to recommend hepatitis A and B vaccination in patients early in the natural history of chronic liver disease.

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

Anesthetic management in pediatric orthotopic liver transplant for fulminant hepatic failure and end-stage liver disease.

PubMed

Camkıran, Aynur; Araz, Coşkun; Seyhan Ballı, Sevgi; Torgay, Adnan; Moray, Gökhan; Pirat, Arash; Arslan, Gülnaz; Haberal, Mehmet

2014-03-01

We assessed the anesthetic management and short-term morbidity and mortality in pediatrics patients who underwent an orthotopic liver transplant for fulminant hepatic failure or end-stage liver disease in a university hospital. We retrospectively analyzed the records of children who underwent orthotopic liver transplant from May 2002 to May 2012. Patients were categorized into 2 groups: group fulminant hepatic failure (n=22) and group end-stage liver disease (n=19). Perioperative data related to anesthetic management and intraoperative events were collected along with information related to postoperative course and survival to hospital discharge. Mean age and weight for groups fulminant hepatic failure and end-stage liver disease were 8.6 ± 2.7 years and 10.8 ± 3.8 years (P = .04) and 29.2 ± 11.9 kg and 33.7 ± 16.9 kg (P = .46). There were no differences between the groups regarding length of anhepatic phase (65 ± 21 min vs 73 ± 18 min, P = .13) and operation time (9.1 ± 1.6 h vs 9.5 ± 1.8 h, P = .23). When compared with the patients in group fulminant hepatic failure, those in group end-stage liver disease more commonly had a Glasgow Coma score of 7 or less (32% vs 6%, P = .04). Compared with patients in group fulminant hepatic failure, those in group end-stage liver disease were more frequently extubated in the operating room (31.8% versus 89.5% P < .001). Postoperative duration of mechanical ventilation (2.78 ± 4.02 d vs 2.85 ± 10.21 d, P = .05), and the mortality rates at 1 year after orthotopic liver transplant (7.3% vs 0%, P = .09) were similar between the groups. During pediatric orthotopic liver transplant, those children with fulminant hepatic failure require more intraoperative fluids and more frequent perioperative mechanical ventilation than those with end-stage liver disease.

Risk of seizures and status epilepticus in older patients with liver disease.

PubMed

Alkhachroum, Ayham M; Rubinos, Clio; Kummer, Benjamin R; Parikh, Neal S; Chen, Monica; Chatterjee, Abhinaba; Reynolds, Alexandra; Merkler, Alexander E; Claassen, Jan; Kamel, Hooman

2018-06-06

Seizures can be provoked by systemic diseases associated with metabolic derangements, but the association between liver disease and seizures remains unclear. We performed a retrospective cohort study using inpatient and outpatient claims between 2008 and 2015 from a nationally representative 5% sample of Medicare beneficiaries. The primary exposure variable was cirrhosis, and the secondary exposure was mild, noncirrhotic liver disease. The primary outcome was seizure, and the secondary outcome was status epilepticus. Diagnoses were ascertained using validated International Classification of Diseases, Ninth Edition, Clinical Modification codes. Survival statistics were used to calculate incidence rates, and Cox proportional hazards models were used to examine the association between exposures and outcomes while adjusting for seizure risk factors. Among 1 782 402 beneficiaries, we identified 10 393 (0.6%) beneficiaries with cirrhosis and 19 557 (1.1%) with mild, noncirrhotic liver disease. Individuals with liver disease were older and had more seizure risk factors than those without liver disease. Over 4.6 ± 2.2 years of follow-up, 49 843 (2.8%) individuals were diagnosed with seizures and 25 patients (0.001%) were diagnosed with status epilepticus. Cirrhosis was not associated with seizures (hazard ratio [HR] = 1.1, 95% confidence interval [CI] = 1.0-1.3), but there was an association with status epilepticus (HR = 1.9, 95% CI = 1.3-2.8). Mild liver disease was not associated with a higher risk of seizures (HR = 0.8, 95% CI = 0.6-0.9) or status epilepticus (HR = 1.1, 95% CI = 0.7-1.5). In a large, population-based cohort, we found an association between cirrhosis and status epilepticus, but no overall association between liver disease and seizures. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Drug-induced Liver Disease in Patients with Diabetes Mellitus.

PubMed

Iryna, Klyarytskaya; Helen, Maksymova; Elena, Stilidi

2015-01-01

The study presented here was accomplished to assess the course of drug-induced liver diseases in patient's rheumatoid arthritis receiving long-term methotrexate therapy. Diabetes mellitus was revealed as the most significant risk factor. The combination of diabetes mellitus with other risk factors (female sex) resulted in increased hepatic fibrosis, degree of hepatic encephalopathy and reduction of hepatic functions. The effectiveness and safety of ursodeoxycholic acid and cytolytic type-with S-Adenosyl methionine was also evaluated. 13C-MBT: 13C-methacetin breath test; ALT: alanine aminotransferase; AP: alkaline phosphatase; AST: aspartic transaminase; DILD: drug-induced liver disease; DM: diabetes mellitus; HE: hepatic encephalopathy; HFM: hepatic functional mass; SAMe: S-Adenosyl methionine; UDCA: ursodeoxycholic acid. Iryna K, Helen M, Elena S. Drug-induced Liver Disease in Patients with Diabetes Mellitus. Euroasian J Hepato-Gastroenterol 2015;5(2):83-86.

Cadmium Exposure and Liver Disease among US Adults

PubMed Central

Hyder, Omar; Chung, Michael; Cosgrove, David; Herman, Joseph M.; Li, Zhiping; Firoozmand, Amin; Gurakar, Ahmet; Koteish, Ayman; Pawlik, Timothy M.

2014-01-01

Background Effects of chronic cadmium exposure on liver disease and liver-related mortality are unknown. We evaluated the association of creatinine-corrected urinary cadmium levels with hepatic necroinflammation, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), liver-related mortality, and liver cancer mortality in the US general population. Methods We analyzed the relationship of individuals in the top quartile for urinary cadmium measured in 12,732 adults who participated in the Third National Health and Nutrition Examination Survey in 1988–1994 (NHANES III), and hepatic necroinflammation, NAFLD, and NASH. Associations between cadmium, liver-related mortality, and liver cancer mortality were evaluated in the NHANES III mortality follow-up study. Results The cutoffs for highest quartile of urinary cadmium per gram of urinary creatinine were 0.65 and 0.83 μg/g for men and women, respectively (P<0.001). After multivariate adjustment for other factors including smoking, the odds ratios [95 % confidence intervals (CI)] for hepatic necroinflammation, NAFLD, and NASH associated with being in the top quartile of cadmium levels by gender, were 2.21 (95 % CI, 1.64–3.00), 1.30 (95 % CI, 1.01–1.68) and 1.95 (95 % CI, 1.11–3.41) for men and 1.26 (95 % CI, 1.01–1.57), 1.11 (95 % CI, 0.88–1.41) and 1.34 (95 % CI, 0.72–2.50) for women, respectively. The hazard ratios for liver-related mortality and liver cancer mortality for both genders were 3.42 (95 % CI, 1.12–10.47) and 1.25 (95 % CI, 0.37–4.27). Conclusions Environmental cadmium exposure was associated with hepatic necroinflammation, NAFLD, and NASH in men, and hepatic necroinflammation in women. Individuals in the top quartile of creatinine-corrected urinary cadmium had over a threefold increased risk of liver disease mortality but not in liver cancer related mortality. PMID:23636881

[Prolyl hydroxylase activity in liver specimens in chronic liver diseases (author's transl)].

PubMed

Langness, U; Clausnitzer, H; Verspohl, M; Grasedyck, K

1978-08-25

100 patients were laparoscopied, liver tissue specimens taken from atypically altered areas. Prolyl hydroxylase was determined in the specimen, in parallel tissue was examined by light microscope. 8 groups of patients could be differentiated: Patients 1. with active, 2, with inactive cirrhosis, 3. with fatty infiltrations, 4. with fatty infiltration and mesenchymal reaction, 5. with aggressive, 6. with persistent, 7. with reactive hepatitis, 8. patients without histological changes. In the case of connective tissue increase in the liver prolyl hydroxylase activities were statistically significant above normal. In addition, there was a statistically significant difference between the enzyme activities of each group. A correlation could be found between prolyl hydroxylase activity and morphologically estimated connective tissue formation, but not the serum enzyme activities usually determined in liver diseases. Therefore, could be concluded that prolyl hydroxylase activity is an index of actual collagen biosynthesis in chronic liver diseases.

The association of coffee intake with liver cancer incidence and chronic liver disease mortality in male smokers.

PubMed

Lai, G Y; Weinstein, S J; Albanes, D; Taylor, P R; McGlynn, K A; Virtamo, J; Sinha, R; Freedman, N D

2013-09-03

Coffee intake is associated with reduced risk of liver cancer and chronic liver disease as reported in previous studies, including prospective ones conducted in Asian populations where hepatitis B viruses (HBVs) and hepatitis C viruses (HCVs) are the dominant risk factors. Yet, prospective studies in Western populations with lower HBV and HCV prevalence are sparse. Also, although preparation methods affect coffee constituents, it is unknown whether different methods affect disease associations. We evaluated the association of coffee intake with incident liver cancer and chronic liver disease mortality in 27,037 Finnish male smokers, aged 50-69, in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, who recorded their coffee consumption and were followed up to 24 years for incident liver cancer or chronic liver disease mortality. Multivariate relative risks (RRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazard models. Coffee intake was inversely associated with incident liver cancer (RR per cup per day=0.82, 95% CI: 0.73-0.93; P-trend across categories=0.0007) and mortality from chronic liver disease (RR=0.55, 95% CI: 0.48-0.63; P-trend<0.0001). Inverse associations persisted in those without diabetes, HBV- and HCV-negative cases, and in analyses stratified by age, body mass index, alcohol and smoking dose. We observed similar associations for those drinking boiled or filtered coffee. These findings suggest that drinking coffee may have benefits for the liver, irrespective of whether coffee was boiled or filtered.

Association of nonalcoholic fatty liver disease and liver cancer

PubMed Central

Schulz, Perla Oliveira; Ferreira, Fabio Gonçalves; Nascimento, Maria de Fátima Araújo; Vieira, Andrea; Ribeiro, Mauricio Alves; David, André Ibrahim; Szutan, Luiz Arnaldo

2015-01-01

AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson’s disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson’s trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the

Gut-Liver Axis Derangement in Non-Alcoholic Fatty Liver Disease.

PubMed

Poeta, Marco; Pierri, Luca; Vajro, Pietro

2017-08-02

Non-alcoholic fatty liver disease (NAFLD) is the most frequent type of chronic liver disease in the pediatric age group, paralleling an obesity pandemic. A "multiple-hit" hypothesis has been invoked to explain its pathogenesis. The "first hit" is liver lipid accumulation in obese children with insulin resistance. In the absence of significant lifestyle modifications leading to weight loss and increased physical activity, other factors may act as "second hits" implicated in liver damage progression leading to more severe forms of inflammation and hepatic fibrosis. In this regard, the gut-liver axis (GLA) seems to play a central role. Principal players are the gut microbiota, its bacterial products, and the intestinal barrier. A derangement of GLA (namely, dysbiosis and altered intestinal permeability) may promote bacteria/bacterial product translocation into portal circulation, activation of inflammation via toll-like receptors signaling in hepatocytes, and progression from simple steatosis to non-alcoholic steato-hepatitis (NASH). Among other factors a relevant role has been attributed to the farnesoid X receptor, a nuclear transcriptional factor activated from bile acids chemically modified by gut microbiota (GM) enzymes. The individuation and elucidation of GLA derangement in NAFLD pathomechanisms is of interest at all ages and especially in pediatrics to identify new therapeutic approaches in patients recalcitrant to lifestyle changes. Specific targeting of gut microbiota via pre-/probiotic supplementation, feces transplantation, and farnesoid X receptor modulation appear promising.

Mechanisms and cell signaling in alcoholic liver disease

PubMed Central

Beier, Juliane I.; McClain, Craig J.

2013-01-01

Alcoholic liver disease (ALD) remains a major cause of morbidity and mortality worldwide. For example, the Veterans Administration Cooperative Studies reported that patients with cirrhosis and superimposed alcoholic hepatitis had a 4-year mortality of >60%. The poor prognosis of ALD implies that preventing disease progression would be more effective than treating end-stage liver disease. An obvious avenue of prevention would be to remove the damaging agent; however, the infamously high rate of recidivism in alcoholics makes maintaining abstinence a difficult treatment goal to prevent ALD. Indeed, although the progression of ALD is well-characterized, there is no universally accepted therapy available to halt or reverse this process in humans. With better understanding of the mechanism(s) and risk factors that mediate the initiation and progression of ALD, rational targeted therapy can be developed to treat or prevent ALD. The purpose of this review is to summarize the established and proposed mechanisms by which chronic alcohol abuse damages the liver and to highlight key signaling events known or hypothesized to mediate these effects. PMID:20868231

How predictive quantitative modelling of tissue organisation can inform liver disease pathogenesis.

PubMed

Drasdo, Dirk; Hoehme, Stefan; Hengstler, Jan G

2014-10-01

From the more than 100 liver diseases described, many of those with high incidence rates manifest themselves by histopathological changes, such as hepatitis, alcoholic liver disease, fatty liver disease, fibrosis, and, in its later stages, cirrhosis, hepatocellular carcinoma, primary biliary cirrhosis and other disorders. Studies of disease pathogeneses are largely based on integrating -omics data pooled from cells at different locations with spatial information from stained liver structures in animal models. Even though this has led to significant insights, the complexity of interactions as well as the involvement of processes at many different time and length scales constrains the possibility to condense disease processes in illustrations, schemes and tables. The combination of modern imaging modalities with image processing and analysis, and mathematical models opens up a promising new approach towards a quantitative understanding of pathologies and of disease processes. This strategy is discussed for two examples, ammonia metabolism after drug-induced acute liver damage, and the recovery of liver mass as well as architecture during the subsequent regeneration process. This interdisciplinary approach permits integration of biological mechanisms and models of processes contributing to disease progression at various scales into mathematical models. These can be used to perform in silico simulations to promote unravelling the relation between architecture and function as below illustrated for liver regeneration, and bridging from the in vitro situation and animal models to humans. In the near future novel mechanisms will usually not be directly elucidated by modelling. However, models will falsify hypotheses and guide towards the most informative experimental design. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Circulating Extracellular Vesicles with Specific Proteome and Liver MicroRNAs Are Potential Biomarkers for Liver Injury in Experimental Fatty Liver Disease

PubMed Central

Povero, Davide; Eguchi, Akiko; Li, Hongying; Johnson, Casey D.; Papouchado, Bettina G.; Wree, Alexander; Messer, Karen; Feldstein, Ariel E.

2014-01-01

Background & Aim Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy. Design Choline Deficient L-Amino Acid (CDAA) and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens. Results We observed statistically significant differences in the level of extracellular vesicles (EVs) in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05), fibrosis (r2 = 0.66, p<0.05) and pathological angiogenesis (r2 = 0.71, p<0.05). Extensive characterization of blood EVs identified both microparticles (MPs) and exosomes (EXO) present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192 - two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver. Conclusions These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD. PMID:25470250

Is the iron regulatory hormone hepcidin a risk factor for alcoholic liver disease?

PubMed Central

Harrison-Findik, Duygu Dee

2009-01-01

Despite heavy consumption over a long period of time, only a small number of alcoholics develop alcoholic liver disease. This alludes to the possibility that other factors, besides alcohol, may be involved in the progression of the disease. Over the years, many such factors have indeed been identified, including iron. Despite being crucial for various important biological processes, iron can also be harmful due to its ability to catalyze Fenton chemistry. Alcohol and iron have been shown to interact synergistically to cause liver injury. Iron-mediated cell signaling has been reported to be involved in the pathogenesis of experimental alcoholic liver disease. Hepcidin is an iron-regulatory hormone synthesized by the liver, which plays a pivotal role in iron homeostasis. Both acute and chronic alcohol exposure suppress hepcidin expression in the liver. The sera of patients with alcoholic liver disease, particularly those exhibiting higher serum iron indices, have also been reported to display reduced prohepcidin levels. Alcohol-mediated oxidative stress is involved in the inhibition of hepcidin promoter activity and transcription in the liver. This in turn leads to an increase in intestinal iron transport and liver iron storage. Hepcidin is expressed primarily in hepatocytes. It is noteworthy that both hepatocytes and Kupffer cells are involved in the progression of alcoholic liver disease. However, the activation of Kupffer cells and TNF-α signaling has been reported not to be involved in the down-regulation of hepcidin expression by alcohol in the liver. Alcohol acts within the parenchymal cells of the liver to suppress the synthesis of hepcidin. Due to its crucial role in the regulation of body iron stores, hepcidin may act as a secondary risk factor in the progression of alcoholic liver disease. The clarification of the mechanisms by which alcohol disrupts iron homeostasis will allow for further understanding of the pathogenesis of alcoholic liver disease. PMID

Drug metabolism alterations in nonalcoholic fatty liver disease

PubMed Central

Merrell, Matthew D.; Cherrington, Nathan J.

2013-01-01

Drug-metabolizing enzymes play a vital role in the elimination of the majority of therapeutic drugs. The major organ involved in drug metabolism is the liver. Chronic liver diseases have been identified as a potential source of significant interindividual variation in metabolism. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States, affecting between 60 and 90 million Americans, yet the vast majority of NAFLD patients are undiagnosed. NAFLD encompasses a spectrum of pathologies, ranging from steatosis to nonalcoholic steatohepatitis and fibrosis. Numerous animal studies have investigated the effects of NAFLD on hepatic gene expression, observing significant alterations in mRNA, protein, and activity levels. Information on the effects of NAFLD in human patients is limited, though several significant investigations have recently been published. Significant alterations in the activity of drug-metabolizing enzymes may affect the clearance of therapeutic drugs, with the potential to result in adverse drug reactions. With the enormous prevalence of NAFLD, it is conceivable that every drug currently on the market is being given to patients with NAFLD. The current review is intended to present the results from both animal models and human patients, summarizing the observed alterations in the expression and activity of the phase I and II drug-metabolizing enzymes. PMID:21612324

The Role of Innate Lymphoid Cells in Immune-Mediated Liver Diseases

PubMed Central

Liu, Meifang; Zhang, Cai

2017-01-01

Innate lymphoid cells (ILCs) are a recently identified group of innate immune cells lacking antigen-specific receptors that can mediate immune responses and regulate tissue homeostasis and inflammation. ILCs comprise group 1 ILCs, group 2 ILCs, and group 3 ILCs. These ILCs usually localize at mucosal surfaces and combat pathogens by the rapid release of certain cytokines. However, the uncontrolled activation of ILCs can also lead to damaging inflammation, especially in the gut, lung, and skin. Although the physiological and pathogenic roles of ILCs in liver diseases have been attracting increasing attention recently, there has been no systematic review regarding the roles of ILCs in immune-mediated liver diseases. Here, we review the relationships between the ILC subsets and their functions in immune-mediated liver diseases, and discuss their therapeutic potential based on current knowledge about the functional roles of these cells in liver diseases. PMID:28659927

Risk stratification in autoimmune cholestatic liver diseases: Opportunities for clinicians and trialists

PubMed Central

Trivedi, Palak J.; Corpechot, Christophe; Pares, Albert

2015-01-01

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are infrequent autoimmune cholestatic liver diseases, that disproportionate to their incidence and prevalence, remain very important causes of morbidity and mortality for patients with liver disease. Mechanistic insights spanning genetic risks and biological pathways to liver injury and fibrosis have led to a renewed interest in developing therapies beyond ursodeoxycholic acid that are aimed at both slowing disease course and improving quality of life. International cohort studies have facilitated a much greater understanding of disease heterogeneity, and in so doing highlight the opportunity to provide patients with a more individualized assessment of their risk of progressive liver disease, based on clinical, laboratory, or imaging findings. This has led to a new approach to patient care that focuses on risk stratification (both high and low risk); and furthermore allows such stratification tools to help identify patient subgroups at greatest potential benefit from inclusion in clinical trials. In this article, we review the applicability and validity of risk stratification in autoimmune cholestatic liver disease, highlighting strengths and weaknesses of current and emergent approaches. (Hepatology 2016;63:644–659) PMID:26290473

Enzymatic liver function capacity correlates with disease severity of patients with liver cirrhosis: a study with the LiMAx test.

PubMed

Malinowski, Maciej; Jara, Maximilian; Lüttgert, Katja; Orr, James; Lock, Johan Friso; Schott, Eckart; Stockmann, Martin

2014-12-01

Assessment and quantification of actual liver function is crucial in patients with chronic liver disease to monitor disease progression and predict individual prognosis. Mathematical models, such as model for end-stage liver disease, are used for risk stratification of patients with chronic liver disease but do not include parameters that reflect the actual functional state of the liver. We aimed to evaluate the potential of a (13)C-based liver function test as a stratification tool by comparison with other liver function tests and clinical parameters in a large sample of healthy controls and cirrhotic patients. We applied maximum liver function capacity (LiMAx) to evaluate actual liver function in 347 patients with cirrhosis and in 86 controls. LiMAx showed strong negative correlation with Child-Pugh Score (r = -0.707; p < 0.001), MELD (r = -0.686; p < 0.001) and liver function tests. LiMAx was lower in patients with liver cirrhosis compared to healthy controls [99 (57-160) µg/kg/h vs. 412 (365-479) µg/kg/h, p < 0.001] and differed among Child-Pugh classes [a: 181 (144-227) µg/kg/h, b: 96 (62-132) µg/kg/h and c: 52 (37-81) µg/kg/h; p < 0.001]. When stratified patients according to disease severity, LiMAx results were not different between cirrhotic patients and cirrhotic patients with transjugular intrahepatic portosystemic shunt. LiMAx appears to provide reliable information on remnant enzymatic liver function in chronic liver disease and allows graduation of disease severity.

[Comparison of various noninvasive serum markers of liver fibrosis in chronic viral liver disease].

PubMed

Kim, Sun Min; Sohn, Joo Hyun; Kim, Tae Yeob; Roh, Young Wook; Eun, Chang Soo; Jeon, Yong Cheol; Han, Dong Soo; Oh, Young Ha

2009-12-01

The aim of this study was to determine the clinical performances of noninvasive serum markers for the prediction of liver fibrosis in chronic viral liver diseases. We analyzed a total of 225 patients with chronic viral liver diseases (180 with hepatitis B virus, 43 with hepatitis C virus, and 2 with hepatitis B+C virus) who underwent a liver biopsy procedure at the Hanyang University Guri Hospital between March 2002 and February 2007. Serum was also obtained at the time of liver biopsy. Liver fibrosis was staged according to the scoring system proposed by the Korean Study Group for the Pathology of Digestive Diseases. Various noninvasive serum markers were evaluated, including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet (AP) index, AST/platelet ratio index (APRI), cirrhosis discriminant score (CDS), platelet count, hyaluronic acid (HA), and type IV collagen. There were 17, 40, 61, 74, and 33 patients at stages F0, F1, F2, F3, and F4, respectively. The overall diagnostic accuracies of each marker, as determined by the area under receiver operating characteristics curves, were APRI=0.822, CDS=0.776, platelet count=0.773, AP index=0.756, HA=0.749, type IV collagen=0.718, and AAR=0.642 for predicting significant fibrosis (> or =F2); and CDS=0.835, platelet count=0.795, AP index=0.794, HA=0.766, AAR=0.711, type IV collagen=0.697, and APRI=0.691 for predicting extensive fibrosis (> or =F3). All noninvasive serum markers evaluated in this study were useful for predicting significant or extensive liver fibrosis in chronic viral liver diseases. In particular, APRI was most useful for the prediction of significant fibrosis, and CDS was most useful for the prediction of extensive fibrosis.

Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

PubMed Central

Demirdal, Umit Secil; Ciftci, Ihsan Hakkı; Kavuncu, Vural

2010-01-01

INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X‐ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti‐liver/kidney microsomal autoantibodies1, liver‐specific protein, anti‐smooth muscle antibodies, and anti‐mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1‐L4 T‐scores and femur total T‐scores were ‐3,08±0,58 and ‐1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3%) were antinuclear antibodies, four (2.7%) were liver membrane antibodies, three (2.0%) were anti‐liver/kidney microsomal autoantibodies1, and two (1.3%) were liver‐specific protein positive. None of the patients had anti‐mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver‐specific protein, and anti‐liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings. PMID:21120296

Non-alcoholic fatty liver disease and dyslipidemia: An update.

PubMed

Katsiki, Niki; Mikhailidis, Dimitri P; Mantzoros, Christos S

2016-08-01

Non-alcoholic fatty liver (NAFLD) is the most common liver disease worldwide, progressing from simple steatosis to necroinflammation and fibrosis (leading to non-alcoholic steatohepatitis, NASH), and in some cases to cirrhosis and hepatocellular carcinoma. Inflammation, oxidative stress and insulin resistance are involved in NAFLD development and progression. NAFLD has been associated with several cardiovascular (CV) risk factors including obesity, dyslipidemia, hyperglycemia, hypertension and smoking. NAFLD is also characterized by atherogenic dyslipidemia, postprandial lipemia and high-density lipoprotein (HDL) dysfunction. Most importantly, NAFLD patients have an increased risk for both liver and CV disease (CVD) morbidity and mortality. In this narrative review, the associations between NAFLD, dyslipidemia and vascular disease in NAFLD patients are discussed. NAFLD treatment is also reviewed with a focus on lipid-lowering drugs. Finally, future perspectives in terms of both NAFLD diagnostic biomarkers and therapeutic targets are considered. Copyright © 2016 Elsevier Inc. All rights reserved.

Ursodeoxycholic acid in the treatment of liver diseases.

PubMed Central

Saksena, S.; Tandon, R. K.

1997-01-01

Ursodeoxycholic acid is a dihydroxy bile acid with a rapidly expanding spectrum of usage in acute and chronic liver diseases. The various mechanisms of action of this hydrophilic bile acid include direct cytoprotection, detergent action on dysfunctional microtubules, immunomodulation and induction of hypercholeresis. Its efficacy in primary biliary cirrhosis and primary sclerosing cholangitis as an adjunct to medical therapy has been well established. Newer indications include its use in the management of chronic hepatitis, cirrhosis, post liver transplant rejection, graft-versus-host disease and acute viral hepatitis, where it not only relieves symptoms of cholestasis but also arrests ongoing hepatocyte necrosis. PMID:9122101

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

PubMed Central

French, Samuel W.

2013-01-01

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

"Immune activation, aging and gender" and progression of liver disease.

PubMed

Nasta, Paola

2011-08-01

Hepatitis C is the predominant cause of liver disease in the HIV-positive population and the most important of the non-AIDS-related causes of death. HCV disease tends to become chronic more frequently in HIV-positive subjects, and to evolve more rapidly into cirrhosis of the liver. The rapidity of the evolution varies considerably from one individual to the next and, if in HIV-negative subjects cirrhosis manifests itself after approx. 40-50 years of disease, in HIV-positive subjects it emerges 10-15 years earlier (1, 2). The severity of the fibrosis is not a gradual event and can be worsened by many factors. Age, sex, duration of the infection and assumption of alcohol are the most well-known variables; obesity, diabetes, steatosis and metabolic disorders are equally important factors that affect the progression of liver disease (3). The severity of the liver disease is very different in men compared to women. Being male is undoubtedly one of the factors most closely related to the gravity of fibrosis (4). In HCV mono-infected women, cirrhosis appears from the age of 60 onwards. With the onset of the menopause, in fact, the progression of liver disease accelerates and the risk of developing cirrhosis or cancer of the liver becomes particularly significant in women over 50. The conditions of menopause or of amenorrhea, irrespective of age, are therefore correlated with the progression of liver disease (5). This evidence led researchers to theorize on the possible anti-fibrogenic role of estrogens. In fact, estrogens in physiological doses in the plasma of women in fertile age contribute to controlling the progression of liver disease through antioxidant mechanisms and lipid peroxidation control mechanisms (6). The reduction of estrogens during the menopause is closely linked to the increase of metabolic disorders. During the menopause, steatosis and cardiovascular diseases increase in parallel with the increase of atherogenic lipoproteins, the accumulation ofintra

Risk for development of severe liver disease in lean patients with nonalcoholic fatty liver disease: A long-term follow-up study.

PubMed

Hagström, Hannes; Nasr, Patrik; Ekstedt, Mattias; Hammar, Ulf; Stål, Per; Hultcrantz, Rolf; Kechagias, Stergios

2018-01-01

Most patients with nonalcoholic fatty liver disease (NAFLD) are overweight or obese. However, a significant proportion of patients have a normal body mass index (BMI), denoted as lean NAFLD. The long-term prognosis of lean NAFLD is unclear. We conducted a cohort study of 646 patients with biopsy-proven NAFLD. Patients were defined as lean (BMI < 25.0), overweight (BMI 25.0-29.9), or obese (BMI ≥ 30.0) at the time of biopsy. Each case was matched for age, sex, and municipality to 10 controls. Overall mortality and development of severe liver disease were evaluated using population-based registers. Cox regression models adjusted for age, sex, type 2 diabetes, and fibrosis stage were used to examine the long-term risk of mortality and liver-related events in lean and nonlean NAFLD. Lean NAFLD was seen in 19% of patients, while 52% were overweight and 29% were obese. Patients with lean NAFLD were older, had lower transaminases, lower stages of fibrosis, and lower prevalence of nonalcoholic steatohepatitis at baseline compared to patients with a higher BMI. During a mean follow-up of 19.9 years (range 0.4-40 years) representing 12,631 person years and compared to patients who were overweight, patients with lean NAFLD had no increased risk for overall mortality (hazard ratio 1.06; P =  0.73) while an increased risk for development of severe liver disease was found (hazard ratio 2.69; P =  0.007). Conclusion : Although patients with lean NAFLD have lower stages of fibrosis, they are at higher risk for development of severe liver disease compared to patients with NAFLD and a higher BMI, independent of available confounders. ( Hepatology Communications 2018;2:48-57).

Non-alcoholic Fatty Liver Disease: East Versus West

PubMed Central

Agrawal, Swastik; Duseja, Ajay K

2012-01-01

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

Diagnosis and Management of Alcoholic Liver Disease.

PubMed

Dugum, Mohannad; McCullough, Arthur

2015-06-28

Alcohol is a leading cause of liver disease and is associated with significant morbidity and mortality. Several factors, including the amount and duration of alcohol consumption, affect the development and progression of alcoholic liver disease (ALD). ALD represents a spectrum of liver pathology ranging from fatty change to fibrosis to cirrhosis. Early diagnosis of ALD is important to encourage alcohol abstinence, minimize the progression of liver fibrosis, and manage cirrhosis-related complications including hepatocellular carcinoma. A number of questionnaires and laboratory tests are available to screen for alcohol intake. Liver biopsy remains the gold-standard diagnostic tool for ALD, but noninvasive accurate alternatives, including a number of biochemical tests as well as liver stiffness measurement, are increasingly being utilized in the evaluation of patients with suspected ALD. The management of ALD depends largely on complete abstinence from alcohol. Supportive care should focus on treating alcohol withdrawal and providing enteral nutrition while managing the complications of liver failure. Alcoholic hepatitis (AH) is a devastating acute form of ALD that requires early recognition and specialized tertiary medical care. Assessment of AH severity using defined scoring systems is important to allocate resources and initiate appropriate therapy. Corticosteroids or pentoxifylline are commonly used in treating AH but provide a limited survival benefit. Liver transplantation represents the ultimate therapy for patients with alcoholic cirrhosis, with most transplant centers mandating a 6 month period of abstinence from alcohol before listing. Early liver transplantation is also emerging as a therapeutic measure in specifically selected patients with severe AH. A number of novel targeted therapies for ALD are currently being evaluated in clinical trials.

The Potential and Action Mechanism of Polyphenols in the Treatment of Liver Diseases

PubMed Central

Li, Sha; Cheung, Fan

2018-01-01

Liver disease, involving a wide range of liver pathologies from fatty liver, hepatitis, and fibrosis to cirrhosis and hepatocellular carcinoma, is a serious health problem worldwide. In recent years, many natural foods and herbs with abundant phytochemicals have been proposed as health supplementation for patients with hepatic disorders. As an important category of phytochemicals, natural polyphenols have attracted increasing attention as potential agents for the prevention and treatment of liver diseases. The striking capacities in remitting oxidative stress, lipid metabolism, insulin resistance, and inflammation put polyphenols in the spotlight for the therapies of liver diseases. It has been reported that many polyphenols from a wide range of foods and herbs exert therapeutic effects on liver injuries via complicated mechanisms. Therefore, it is necessary to have a systematical review to sort out current researches to help better understand the potentials of polyphenols in liver diseases. In this review, we aim to summarize and update the existing evidence of natural polyphenols in the treatment of various liver diseases by in vitro, in vivo, and clinical studies, while special attention is paid to the action mechanisms. PMID:29507653

Hepatic cholesterol ester hydrolase in human liver disease.

PubMed

Simon, J B; Poon, R W

1978-09-01

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

HFE Genotyping in Patients with Elevated Serum Iron Indices and Liver Diseases

PubMed Central

Evangelista, Andreia Silva; de Araújo, Thiago Ferreira; Abrantes-Lemos, Clarice Pires; Deguti, Marta Mitiko; Cançado, Eduardo Luiz Rachid

2015-01-01

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population. PMID:25654085

[Nutritional Assessment and Management for Patients with Chronic Liver Disease].

PubMed

Lee, Tae Hee

2018-04-25

When liver disease is severe, the prognosis can be worse if the patient is malnourished. Adequate nutritional support for patients with liver diseases can improve the patient's condition and prognosis. In the case of liver cirrhosis, malnutrition can occur due to a variety of causes, including poor oral intake, maldigestion, malabsorption, associated renal disease, and metabolic abnormalities. For a nutritional assessment, it is important to check the dietary intake, change in body composition, including anthropometry, and a functional assessment of muscle. Counselling and oral or enteral nutrition is preferred over parenteral nutrition as in other diseases. If esophageal varices are present, care should be taken when installing a feeding tube, but if there are ascites, percutaneous endoscopic gastrostomy is contraindicated because of the risk of complications. Calories of 30-35 kcal/kg/day and protein from 1.2 to 1.5 g/kg/day are appropriate. Protein restriction is unnecessary unless the hepatic encephalopathy is severe. A late evening snack and branched chain amino acids can be helpful. In the case of cholestasis, the supply of manganese and copper should be restricted. Sarcopenia in patients with liver cirrhosis is also prevalent and associated with the prognosis.

Valproic acid and nonalcoholic fatty liver disease: A possible association?

PubMed Central

Farinelli, Edoardo; Giampaoli, David; Cenciarini, Anja; Cercado, Ephraim; Verrotti, Alberto

2015-01-01

Valproic acid (VPA) is one of the most prescribed drugs in children with newly diagnosed epilepsy. Weight gain and obesity have been observed as side effects of VPA. These are often linked with other metabolic disturbances such as development of insulin resistance, dyslipidemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease or nonalcoholic fatty liver disease (NAFLD). NAFLD refers to a group of liver disorders with marked hepatic steatosis. It is associated with an increased incidence of cardiovascular diseases and overall reduced life expectancy. NAFLD occurs in 20%-25% of the general population and it is known to be the most common cause of chronic liver disease. NAFLD therefore represents a major public health issue worldwide. This study reviews and summarizes relevant literature that supports the existence of an association between VPA therapy and the development of NAFLD in children. Long-term VPA-therapy appears to be associated with an increased risk of developing NAFLD. Further studies are needed to clarify the pathogenic mechanisms that lie behind this association and to standardize the options for the use of this drug in overweight patients and in those with risks for developing MetS and NAFLD. PMID:26019740

Gut Microbiota of Nonalcoholic Fatty Liver Disease.

PubMed

Abdou, Reham M; Zhu, Lixin; Baker, Robert D; Baker, Susan S

2016-05-01

The prevalence of nonalcoholic fatty liver disease has been rapidly increasing worldwide. It has become a leading cause of liver transplantation. Accumulating evidence suggests a significant role for gut microbiota in its development and progression. Here we review the effect of gut microbiota on developing hepatic fatty infiltration and its progression. Current literature supports a possible role for gut microbiota in the development of liver steatosis, inflammation and fibrosis. We also review the literature on possible interventions for NAFLD that target the gut microbiota.

Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) in HIV.

PubMed

Rockstroh, Jürgen Kurt

2017-04-01

Abnormal liver enzymes (LE) are common in patients infected with the human immunodeficiency virus (HIV) even in the absence of viral hepatitis or alcohol abuse. With availability of antiretroviral combination therapy, life expectancy has improved dramatically and as a consequence the spectrum of liver disease is changing. Increased reports on the development of non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) in HIV coinfected patients raise questions around prevalence, clinical manifestations, and clinical outcome of these liver diseases in HIV coinfection. Moreover, the potential impact of combination antiretroviral therapy as well as direct HIV effects on the emergence of non-alcoholic fatty liver disease needs to be explored. This review summarizes the recent literature on NAFLD and NASH in HIV.

Hepatic Dendritic Cells, the Tolerogenic Liver Environment, and Liver Disease.

PubMed

Dou, Lei; Ono, Yoshihiro; Chen, Yi-Fa; Thomson, Angus W; Chen, Xiao-Ping

2018-05-01

The unique liver immune microenvironment favors resistance to inflammation that promotes normal physiological function. At the same time, it endows the liver with tolerogenic properties that may promote pathological processes. Hepatic dendritic cells (HDCs) initiate and orchestrate immune responses depending on signals they receive from the local environment and are thought to contribute to liver tolerance. Thus, HDCs facilitate impaired T cell responses that are observed in persistent hepatitis C virus (HCV) infection, hepatocellular carcinoma progression, and liver allograft transplantation. HDCs also participate in anti-inflammatory responses in liver ischemia-reperfusion injury (IRI). Moreover, they promote the regression of fibrosis from various fibrogenic liver injuries. These findings suggest that HDCs regulate intrahepatic immune responses, allowing the liver to maintain homeostasis and integrity even under pathological conditions. This review focuses on the tolerogenic properties of HDCs based on recent research and in relation to liver disease pathogenesis and its therapy. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

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

PubMed

Augustin, Salvador; Graupera, Isabel; Caballeria, Juan

2017-12-20

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

Quantitative characterization of fatty liver disease using x-ray scattering

NASA Astrophysics Data System (ADS)

Elsharkawy, Wafaa B.; Elshemey, Wael M.

2013-11-01

Nonalcoholic fatty liver disease (NAFLD) is a dynamic condition in which fat abnormally accumulates within the hepatocytes. It is believed to be a marker of risk of later chronic liver diseases, such as liver cirrhosis and carcinoma. The fat content in liver biopsies determines its validity for liver transplantation. Transplantation of livers with severe NAFLD is associated with a high risk of primary non-function. Moreover, NAFLD is recognized as a clinically important feature that influences patient morbidity and mortality after hepatic resection. Unfortunately, there is a lack in a precise, reliable and reproducible method for quantification of NAFLD. This work suggests a method for the quantification of NAFLD. The method is based on the fact that fatty liver tissue would have a characteristic x-ray scattering profile with a relatively intense fat peak at a momentum transfer value of 1.1 nm-1 compared to a soft tissue peak at 1.6 nm-1. The fat content in normal and fatty liver is plotted against three profile characterization parameters (ratio of peak intensities, ratio of area under peaks and ratio of area under fat peak to total profile area) for measured and Monte Carlo simulated x-ray scattering profiles. Results show a high linear dependence (R2>0.9) of the characterization parameters on the liver fat content with a reported high correlation coefficient (>0.9) between measured and simulated data. These results indicate that the current method probably offers reliable quantification of fatty liver disease.

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.

Albumin in chronic liver disease: structure, functions and therapeutic implications.

PubMed

Spinella, Rosaria; Sawhney, Rohit; Jalan, Rajiv

2016-01-01

Human serum albumin is a critical plasma protein produced by the liver with a number of accepted clinical indications in chronic liver disease including management of circulatory and renal dysfunction in patients with ascites. Advanced cirrhosis is characterised by reduced albumin concentration as well as impaired albumin function as a result of specific structural changes and oxidative damage. Traditionally, the biologic and therapeutic role of albumin in liver disease was attributed to its oncotic effects but it is now understood that albumin has a wide range of other important physiologic functions such as immunomodulation, endothelial stabilisation, antioxidant effects and binding multiple drugs, toxins and other molecules. This review discusses the multifunctional properties of albumin and, in particular, the biologic and clinical implications of structural and functional changes of albumin that are associated with cirrhosis. Based on these insights, we explore the current and potential future therapeutic uses of albumin in liver disease.

Liver transplantation for Wilson's disease in pediatric patients: decision making and timing.

PubMed

Narumi, S; Umehara, M; Toyoki, Y; Ishido, K; Kudo, D; Kimura, N; Kobayashi, T; Sugai, M; Hakamada, K

2012-03-01

Transplantation for Wilson's disease occupies 1/3 of the cases for metabolic diseases in Japan. At the end of 2009, 109 transplantations had been performed including three deceased donor cases in the Japanese registry. We herein discuss problems of transplantation for Wilson's disease as well as its indication, timing, and social care. We retrospectively reviewed four fulminant cases and two chronic cases who underwent living donor liver transplantation. There were two boys and two girls. Four adolescents of average age 11.3 years underwent living donor liver transplantation. Duration from onset to transplantation ranged from 10 to 23 days. Average Model for End-stage Liver Disease (MELD) score was 27.8 (range=24-31). All patients were administrated chelates prior to transplantation. MELD, New Wilson's index, Japanese scoring for liver transplantation, and liver atrophy were useful tools for transplantation decision making; however, none of them was an independent decisive tool. Clinical courses after transplantation were almost uneventful. One girl, however, developed an acute rejection episode due to noncompliance at 3 years after transplantation. All patients currently survive without a graft loss. No disease recurrence had been noted even using living related donors. Two adults evaluated for liver transplantation were listed for deceased donor liver transplantation. Both candidates developed cirrhosis despite long-term medical treatment. There were no appropriate living donors for them. There are many problems in transplantation for Wilson's disease. The indications for liver transplantation should be considered individually using some decision-making tools. The safety of the living donor should be paid the most attention. Copyright © 2012 Elsevier Inc. All rights reserved.

Chylous ascites in a cheetah (Acinonyx jubatus) with venoocclusive liver disease.

PubMed

Terrell, Scott P; Fontenot, Deidre K; Miller, Michele A; Weber, Martha A

2003-12-01

An 11-yr-old female cheetah (Acinonyx jubatus) was diagnosed clinically with hepatic and renal disease and euthanatized after an extended illness. Postmortem examination revealed 8-10 L of milky white fluid in the abdominal cavity and markedly dilated lymphatic vessels within the intestinal mesentery. The abdominal fluid was a chylous effusion based on the cytologic predominance of lymphocytes and macrophages and comparison of cholesterol and triglyceride levels in the fluid and in serum. Gross and histopathologic lesions in the liver were consistent with a diagnosis of venoocclusive liver disease. Chylous ascites is uncommon with human chronic liver disease and is rarely identified in animals.

Library of molecular associations: curating the complex molecular basis of liver diseases.

PubMed

Buchkremer, Stefan; Hendel, Jasmin; Krupp, Markus; Weinmann, Arndt; Schlamp, Kai; Maass, Thorsten; Staib, Frank; Galle, Peter R; Teufel, Andreas

2010-03-20

Systems biology approaches offer novel insights into the development of chronic liver diseases. Current genomic databases supporting systems biology analyses are mostly based on microarray data. Although these data often cover genome wide expression, the validity of single microarray experiments remains questionable. However, for systems biology approaches addressing the interactions of molecular networks comprehensive but also highly validated data are necessary. We have therefore generated the first comprehensive database for published molecular associations in human liver diseases. It is based on PubMed published abstracts and aimed to close the gap between genome wide coverage of low validity from microarray data and individual highly validated data from PubMed. After an initial text mining process, the extracted abstracts were all manually validated to confirm content and potential genetic associations and may therefore be highly trusted. All data were stored in a publicly available database, Library of Molecular Associations http://www.medicalgenomics.org/databases/loma/news, currently holding approximately 1260 confirmed molecular associations for chronic liver diseases such as HCC, CCC, liver fibrosis, NASH/fatty liver disease, AIH, PBC, and PSC. We furthermore transformed these data into a powerful resource for molecular liver research by connecting them to multiple biomedical information resources. Together, this database is the first available database providing a comprehensive view and analysis options for published molecular associations on multiple liver diseases.

Nonalcoholic fatty liver disease in Asia: emerging perspectives.

PubMed

Seto, Wai-Kay; Yuen, Man-Fung

2017-02-01

As in the West, nonalcoholic fatty liver disease (NAFLD) is the commonest chronic liver disease in Asia, with a prevalence higher than 40 % in some countries. The risk factors for NAFLD development are similar to those in Western countries, including increased body mass index, diabetes, insulin resistance, and metabolic syndrome. NAFLD in Asians is associated with different extrahepatic manifestations involving the cardiovascular, gastrointestinal, and renal systems. A considerable proportion of Asians with NAFLD are described as having "lean" NAFLD. Present in approximately 20 % of the Asian population, lean NAFLD is closely linked with insulin resistance, diabetes, and other metabolic complications, but its association with disease progression to nonalcoholic steatohepatitis and cirrhosis remains to be defined. There is emerging evidence of the interactions of NAFLD with hepatitis B virus and hepatitis C virus infection in Asia. Unlike in Western countries, NAFLD constitutes only a minority of cirrhosis and hepatocellular carcinoma cases in Asia. Possible explanations are the lower prevalence of obesity and the overwhelming problem of viral hepatitis in Asia. With aging of the obesity cohort in Asia, NAFLD-related liver complications are expected to increase.

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

Iron overload and HFE gene mutations in Czech patients with chronic liver diseases.

PubMed

Dostalikova-Cimburova, Marketa; Kratka, Karolina; Stransky, Jaroslav; Putova, Ivana; Cieslarova, Blanka; Horak, Jiri

2012-01-01

The aim of the study was to identify the prevalence of HFE gene mutations in Czech patients with chronic liver diseases and the influence of the mutations on iron status. The presence of HFE gene mutations (C282Y, H63D, and S65C) analyzed by the PCR-RFLP method, presence of cirrhosis, and serum iron indices were compared among 454 patients with different chronic liver diseases (51 with chronic hepatitis B, 122 with chronic hepatitis C, 218 with alcoholic liver disease, and 63 patients with hemochromatosis). Chronic liver diseases patients other than hemochromatics did not have an increased frequency of HFE gene mutations compared to controls. Although 33.3% of patients with hepatitis B, 43% of patients with hepatitis C, and 73.2% of patients with alcoholic liver disease had elevated transferrin saturation or serum ferritin levels, the presence of HFE gene mutations was not significantly associated with iron overload in these patients. Additionally, patients with cirrhosis did not have frequencies of HFE mutations different from those without cirrhosis. This study emphasizes the importance, not only of C282Y, but also of the H63D homozygous genetic constellation in Czech hemochromatosis patients. Our findings show that increased iron indices are common in chronic liver diseases but {\\it HFE} mutations do not play an important role in the pathogenesis of chronic hepatitis B, chronic hepatitis C, and alcoholic liver disease.

Diagnosis of liver disease in domestic ferrets (Mustela putorius).

PubMed

Huynh, Minh; Laloi, Flora

2013-01-01

Liver disease in ferrets is often subclinical and underdiagnosed. Clinical pathology and diagnostic imaging are needed to guide clinicians but definite diagnosis is based on histopathologic lesions. Inflammatory digestive conditions can lead to ascending tract infection and hepatobiliary inflammation. Ferrets have a specific sensitivity to hepatic lipidosis. Incidence of hepatic neoplasia is high in ferrets. After a summary of anatomy and physiology of the ferret liver, hepatic diseases known in ferret species are reviewed with their subsequent diagnostic procedures. Copyright © 2013 Elsevier Inc. All rights reserved.

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

Perioperative liver and spleen elastography in patients without chronic liver disease.

PubMed

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-02-27

To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s ( P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more ( P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy ( n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin ( R 2 = 0.154, Pearson's r = 0.392, P = 0.032) and international normalized ratio ( R 2 = 0.285, Pearson's r = 0.534, P = 0.003). Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease.

Perioperative liver and spleen elastography in patients without chronic liver disease

PubMed Central

Eriksson, Sam; Borsiin, Hanna; Öberg, Carl-Fredrik; Brange, Hannes; Mijovic, Zoran; Sturesson, Christian

2018-01-01

AIM To investigate changes in hepatic and splenic stiffness in patients without chronic liver disease during liver resection for hepatic tumors. METHODS Patients scheduled for liver resection for hepatic tumors were considered for enrollment. Tissue stiffness measurements on liver and spleen were conducted before and two days after liver resection using point shear-wave elastography. Histological analysis of the resected liver specimen was conducted in all patients and patients with marked liver fibrosis were excluded from further study analysis. Patients were divided into groups depending on size of resection and whether they had received preoperative chemotherapy or not. The relation between tissue stiffness and postoperative biochemistry was investigated. RESULTS Results are presented as median (interquartile range). 35 patients were included. The liver stiffness increased in patients undergoing a major resection from 1.41 (1.24-1.63) m/s to 2.20 (1.72-2.44) m/s (P = 0.001). No change in liver stiffness in patients undergoing a minor resection was found [1.31 (1.15-1.52) m/s vs 1.37 (1.12-1.77) m/s, P = 0.438]. A major resection resulted in a 16% (7%-33%) increase in spleen stiffness, more (P = 0.047) than after a minor resection [2 (-1-13) %]. Patients who underwent preoperative chemotherapy (n = 20) did not differ from others in preoperative right liver lobe [1.31 (1.16-1.50) vs 1.38 (1.12-1.56) m/s, P = 0.569] or spleen [2.79 (2.33-3.11) vs 2.71 (2.37-2.86) m/s, P = 0.515] stiffness. Remnant liver stiffness on the second postoperative day did not show strong correlations with maximum postoperative increase in bilirubin (R2 = 0.154, Pearson’s r = 0.392, P = 0.032) and international normalized ratio (R2 = 0.285, Pearson’s r = 0.534, P = 0.003). CONCLUSION Liver and spleen stiffness increase after a major liver resection for hepatic tumors in patients without chronic liver disease. PMID:29492187

Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic

PubMed Central

Hassan, Kareem; Bhalla, Varun; Ezz El Regal, Mohammed; A-Kader, H Hesham

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is quickly becoming one of the most prominent causes of liver disease worldwide. The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it. Current efforts to elucidate the mechanism and causes of the disease have answered some questions, but much remains unknown about NAFLD. The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease, as well as the current and future diagnostic, preventative, and therapeutic options available to clinicians for the management of NAFLD. PMID:25232245

Glutathione S-transferases in neonatal liver disease.

PubMed Central

Mathew, J.; Cattan, A. R.; Hall, A. G.; Hines, J. E.; Nelson, R.; Eastham, E.; Burt, A. D.

1992-01-01

AIMS: To investigate the distribution of alpha and pi class glutathione S-transferases (GST) in normal fetal, neonatal, and adult liver; and to examine changes in GST expression in neonatal liver disease. METHODS: alpha and pi class GST were immunolocalised in sections of formalin fixed liver tissue obtained from human fetuses (n = 21), neonates (n = 8), young children (n = 9) and adults (n = 10), and from neonates with extrahepatic biliary atresia (n = 15) and neonatal hepatitis (n = 12). Monospecific rabbit polyclonal antibodies were used with a peroxidase-antiperoxidase method. RESULTS: Expression of pi GST was localised predominantly within biliary epithelial cells of developing and mature bile ducts of all sizes from 16 weeks' gestation until term and in neonatal and adult liver. Coexpression of pi and alpha GST was seen in hepatocytes of developing fetal liver between 16 and 34 weeks' gestation. Although pi GST was seen in occasional hepatocytes up to six months of life, this isoenzyme was not expressed by hepatocytes in adult liver. By contrast, alpha GST continued to be expressed by hepatocytes in adult liver; this isoenzyme was also seen in some epithelial cells of large bile ducts in adult liver. No change was observed in the distribution of alpha GST in either neonatal hepatitis or extrahepatic biliary atresia. However, aberrant expression of pi GST was identified in hepatocytes of all but one case of extrahepatic biliary atresia but in only two cases of neonatal hepatitis. CONCLUSIONS: The phenotypic alterations noted in extrahepatic biliary atresia may result from the effect of cholate stasis. Evaluation of the pattern of pi and alpha GST distribution by immunohistochemical staining may provide valuable information in distinguishing between these two forms of neonatal liver disease. Images PMID:1401176

Progress and challenges in the prevention and control of nonalcoholic fatty liver disease.

PubMed

Cai, Jingjing; Zhang, Xiao-Jing; Li, Hongliang

2018-05-30

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide. Individuals with NAFLD have a high frequency of developing progressive liver disease and metabolism-related comorbidities, which result from of a lack of awareness and poor surveillance of the disease and a paucity of approved and effective therapies. Managing the complications of NAFLD has already begun to place a tremendous burden on health-care systems. Although efforts to identify effective therapies are underway, the lack of validated preclinical NAFLD models that represent the biology and outcomes of human disease remains a major barrier. This review summarizes the characteristics and prevalence of the disease and the status of our understanding of its mechanisms and potential therapeutic targets. © 2018 Wiley Periodicals, Inc.

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

Platelets: No longer bystanders in liver disease

PubMed Central

Adams, David H.; Watson, Steve P.; Lalor, Patricia F.

2016-01-01

Growing lines of evidence recognize that platelets play a central role in liver homeostasis and pathobiology. Platelets have important roles at every stage during the continuum of liver injury and healing. These cells contribute to the initiation of liver inflammation by promoting leukocyte recruitment through sinusoidal endothelium. They can activate effector cells, thus amplifying liver damage, and by modifying the hepatic cellular and cytokine milieu drive both hepatoprotective and hepatotoxic processes. Conclusion: In this review we summarize how platelets drive such pleiotropic actions and attempt to reconcile the paradox of platelets being both deleterious and beneficial to liver function; with increasingly novel methods of manipulating platelet function at our disposal, we highlight avenues for future therapeutic intervention in liver disease. (Hepatology 2016;64:1774‐1784) PMID:26934463

A shift in paradigm towards human biology-based systems for cholestatic-liver diseases.

PubMed

Noor, Fozia

2015-12-01

Cholestatic-liver diseases (CLDs) arise from diverse causes ranging from genetic factors to drug-induced cholestasis. The so-called diseases of civilization (obesity, diabetes, metabolic disorders, non-alcoholic liver disease, cardiovascular diseases, etc.) are intricately implicated in liver and gall bladder diseases. Although CLDs have been extensively studied, there seem to be important gaps in the understanding of human disease. Despite the fact that many animal models exist and substantial clinical data are available, translation of this knowledge towards therapy has been disappointingly limited. Recent advances in liver cell culture such as in vivo-like 3D cultivation of human primary hepatic cells, human induced pluripotent stem cell-derived hepatocytes; and cutting-edge analytical techniques such as 'omics' technologies and high-content screenings could play a decisive role in deeper mechanistic understanding of CLDs. This Topical Review proposes a roadmap to human biology-based research using omics technologies providing quantitative information on mechanisms in an adverse outcome/disease pathway framework. With modern sensitive tools, a shift in paradigm in human disease research seems timely and even inevitable to overcome species barriers in translation. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Fibrosis Assessment in Nonalcoholic Fatty Liver Disease (NAFLD) in 2016.

PubMed

Kaswala, Dharmesh H; Lai, Michelle; Afdhal, Nezam H

2016-05-01

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver pathologies characterized by hepatic steatosis with a history of little to no alcohol consumption or secondary causes of hepatic steatosis. The prevalence of NAFLD is 20-25 % of the general population in the Western countries and is associated with metabolic risk factors such as obesity, diabetes mellitus, and dyslipidemia. The spectrum of disease ranges from simple steatosis to nonalcoholic steatohepatitis, fibrosis, and cirrhosis. Advanced fibrosis is the most significant predictor of mortality in NAFLD. It is crucial to assess for the presence and degree of hepatic fibrosis in order to make therapeutic decisions and predict clinical outcomes. Liver biopsy, the current gold standard to assess the liver fibrosis, has a number of drawbacks such as invasiveness, sampling error, cost, and inter-/intra-observer variability. There are currently available a number of noninvasive tests as an alternative to liver biopsy for fibrosis staging. These noninvasive fibrosis tests are increasingly used to rule out advanced fibrosis and help guide disease management. While these noninvasive tests perform relatively well for ruling out advanced fibrosis, they also have limitations. Understanding the strengths and limitations of liver biopsy and the noninvasive tests is necessary for deciding when to use the appropriate tests in the evaluation of patients with NAFLD.

Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease.

PubMed

Aqel, Bashar; DiBaise, John K

2015-12-01

The incidence of nonalcoholic fatty liver disease (NAFLD) continues to increase with prevalence estimates ranging from 17%-33%, making it is the most common cause of chronic liver disease in North America. Its importance is due to not only its prevalence but also its association with increased cardiovascular morbidity and progression to cirrhosis in a subset of patients. NAFLD encompasses a pathologic spectrum of disease, from relatively benign accumulation of lipid (steatosis) to progressive nonalcoholic steatohepatitis associated with inflammation, fibrosis, and necrosis. Nonalcoholic steatohepatitis remains an important phenotypic state because this subgroup of patients is deemed at high risk for developing cirrhosis and progressing to liver failure requiring transplantation or to death. Gut microbiota has recently been identified as regulators of energy homeostasis and fat deposition, thereby implicating them in the development of obesity and associated metabolic diseases. The growing evidence that alteration in gut microbiota (dysbiosis) may affect liver pathology may allow for a better understanding of its role in the pathogenesis of NAFLD, help to identify patients at risk of progression, and expose a microbial target for prevention and therapeutic intervention. In this review, we discuss the growing evidence that highlights the relationship between gut microbiota and its association with NAFLD. © 2015 American Society for Parenteral and Enteral Nutrition.

[Comprehensive characteristics of the pulmonary syndrome in chronic liver diseases].

PubMed

Pashchenko, I G; Romanov, A A; Zhumanbaeva, R M; Osmolovskiĭ, V S; Faliushina, N V

1988-01-01

Combined investigations have shown that the pulmonary syndrome in chronic liver diseases is a group of changes (heterogeneous in their structure and origin), most of which are of intercurrent nature (chronic bronchitis and its complications, chronic pneumonia), the lesser part of them is related directly to an inflammatory liver process and constitutes the true pulmonary syndrome (interstitial pneumonitis, fibrosing alveolitis). In view of the fact that chronic liver pathology is attended by concomitant disorders of pulmonary ventilation, hemodynamics and immunologic homestasis, the authors propose that they should be regarded as a risk factor contributing to the development of respiratory diseases.

Nonalcoholic fatty liver disease: diagnosis, pathogenesis, and management.

PubMed

Başaranoğlu, Metin; Örmeci, Necati

2014-04-01

Nonalcoholic fatty liver disease (NAFLD) is an umbrella term that covers both a relatively benign condition, which is simple steatosis, and nonalcoholic steatohepatitis (NASH). NASH is characterized by a chronic and progressive liver pathology that may progress to cirrhosis, end-stage liver disease, hepatocellular carcinoma, and liver transplantation. Despite the growing body of evidence, one of the important and unresolved problems is the pathogenesis of NASH. It might be a metabolic disturbance as a primary abnormality in NAFLD. Insulin resistance is at the center of these metabolic abnormalities. Then, hepatocyte injury might be induced by oxidative stress. This ongoing process progresses to NASH, even to cirrhosis in some patients. In addition to oxidative stress, possibilities for the next hit are lipid peroxidation, reactive metabolites, adipose tissue products, transforming growth factor-β₁, Fas ligand, mitochondrial dysfunction, respiratory chain deficiency, and intestinal microbiota. Currently, there is no well-established and approved therapy. Recommendations are to improve existing co-morbidities, such as obesity, hyperlipidemia, or type 2 diabetes, and lifestyle modification with weight loss and exercise.

Cognitive Abilities of Children With Neurological and Liver Forms of Wilson Disease.

PubMed

Favre, Emilie; Lion-François, Laurence; Canton, Marie; Vanlemmens, Claire; Bonneton, Marjorie; Bouillet, Lise; Brunet, Anne-Sophie; Lachaux, Alain

2017-03-01

Cognitive impairment in adult patients experiencing Wilson disease is now more clearly described, even in liver forms of the disease. Although this condition can appear during childhood, the cognitive abilities of children have not yet been reported in a substantial case series. This retrospective study included 21 children with Wilson disease who had undergone general cognitive assessment. The results argue in favor of a poor working memory capacity in the liver form of the disease, and more extensive cognitive impairments in its neurological form. Extensive neuropsychological investigations on all children experiencing Wilson disease are thus required.

Non-invasive Diagnosis of Fibrosis in Non-alcoholic Fatty Liver Disease

PubMed Central

Arora, Anil; Sharma, Praveen

2012-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed as well as in developing countries. Its prevalence continues to rise currently affecting approximately 20-30% of adults and 10% of children in the United States. Non-alcoholic fatty liver disease represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign non-progressive clinical course, to non-alcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Liver biopsy remains the gold standard for evaluating the degree of hepatic necroinflammation and fibrosis; however, several non-invasive investigations, such as serum biomarkers, have been developed to establish the diagnosis and also to evaluate treatment response. There has been a substantial development of non-invasive risk scores, biomarker panels, and radiological modalities to identify at risk patients with NAFLD without recourse to liver biopsy on a routine basis. Examples include combination of serum markers like NAFLD fibrosis score (NFS), BARD score, fibrometer, FIB4, and non-invasive tools like fibroscan which assess fibrosis in patients with NAFLD. Other markers of fibrosis that have been evaluated include high-sensitivity C-reactive protein, plasma pentraxin 3, interleukin-6, and cytokeratin-18. This review focuses on the methods currently available in daily clinical practice in hepatology and touches briefly on the potential future markers under investigation. PMID:25755423

[Bio-ecological control of chronic liver disease and encephalopathy].

PubMed

Bengmark, S; Di Cocco, P; Clemente, K; Corona, L; Angelico, R; Manzia, T; Famulari, A; Pisani, F; Orlando, G

2011-08-01

Minimal encephalopathy was originally associated with chronic liver disease but is increasingly associated with most other chronic diseases and particularly with diabetes and also chronic disorders in other organs: kidneys, lungs, thyroid and with obesity. It is increasingly with dramatically increased and more or less permanent increase in systemic inflammation, most likely a result of Western lifestyle. Frequent physical exercise and intake of foods rich in vitamins, antioxidants, fibres, lactic acid bacteria etc in combination with reduction in intake of refined and processed foods is known to reduce systemic inflammation and prevent chronic diseases. Some lactic acid bacteria, especially Lb paracasei, lb plantarum and pediococcus pentosaceus have proven effective to reduce inflammation and eliminate encephalopathy. Significant reduction in blood ammonia levels and endotoxin levels were reported in parallel to improvement of liver disease. Subsequent studies with other lactic acid bacteria seem to demonstrate suppression of inflammation and one study also provides evidence of clinical improvement.

Factors influencing health-related quality of life in chronic liver disease

PubMed Central

Sobhonslidsuk, Abhasnee; Silpakit, Chatchawan; Kongsakon, Ronnachai; Satitpornkul, Patchareeya; Sripetch, Chaleaw; Khanthavit, Anya

2006-01-01

AIM: To investigate the factors contributing to health-related quality of life (HRQL) in chronic liver disease (CLD). METHODS: Patients with CLD and age- and sex-matched normal subjects performed the validated Thai versions of the short-form 36 (SF-36) by health survey and chronic liver disease questionnaire (CLDQ). Stepwise multiple regression analysis was used to assess the impact of disease severity, demography, causes of CLD, socioeconomic factors, and self-rating health perception on HRQL. RESULTS: Two-hundred and fifty patients with CLD and fifty normal subjects were enrolled into the study. Mean age and the numbers of low educated, unemployed, blue-collar career and poor health perception increased significantly from chronic hepatitis to Child’s Classes A to B to C. Advanced stage of CLD was related to deterioration of HRQL. Increasing age and female reduced physical health area. Low socioeconomic factors and financial burden affected multiple areas of HRQL. In overall, the positive impact of self-rating health perception on HRQL was consistently showed. CONCLUSION: Advanced stages of chronic liver disease, old age, female sex, low socioeconomic status and financial burden are important factors reducing HRQL. Good health perception improves HRQL regardless of stages of liver disease. PMID:17203521

Association of PNPLA3 I148M Variant With Chronic Viral Hepatitis, Autoimmune Liver Diseases and Outcomes of Liver Transplantation

PubMed Central

Geng, Ning; Xin, Yong-Ning; Xia, Harry Hua-Xiang; Jiang, Man; Wang, Jian; Liu, Yang; Chen, Li-Zhen; Xuan, Shi-Ying

2015-01-01

Context: The PNPLA3 I148M variant has been recognized as a genetic determinant of liver fat content and a genetic risk factor of liver damage progression associated with steatohepatitis. The I148M variant is associated with many chronic liver diseases. However, its potential association with inflammatory and autoimmune liver diseases has not been established. Evidence Acquisition: We systemically reviewed the potential associations of I148M variant with chronic viral hepatitis, autoimmune liver diseases and the outcome of liver transplantation, explored the underlying molecular mechanisms and tried to translate them into more individualized decision-making and personalized medicine. Results: There were associations between I148M variant and chronic viral hepatitis and autoimmune liver diseases and differential associations of I148M variant in donors and recipients with post-liver transplant outcomes. I148M variant may activate the development of steatosis caused by host metabolic disorders in chronic viral hepatitis, but few researches were found to illustrate the mechanisms in autoimmune liver diseases. The peripherally mediated mechanism (via extrahepatic adipose tissue) may play a principal role in triglyceride accumulation regardless of adiponutrin activity in the graft liver. Conclusions: Evidences have shown the associations between I148M variant and mentioned diseases. I148M variant induced steatosis may be involved in the mechanism of chronic viral hepatitis and genetic considered personalized therapies, especially for PSC male patients. It is also crucial to pay attention to this parameter in donor selection and prognosis estimation in liver transplantation. PMID:26034504

Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

PubMed

Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

2014-04-01

Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Expression and function of methylthioadenosine phosphorylase in chronic liver disease.

PubMed

Czech, Barbara; Dettmer, Katja; Valletta, Daniela; Saugspier, Michael; Koch, Andreas; Stevens, Axel P; Thasler, Wolfgang E; Müller, Martina; Oefner, Peter J; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

2013-01-01

To study expression and function of methylthioadenosine phosphorylase (MTAP), the rate-limiting enzyme in the methionine and adenine salvage pathway, in chronic liver disease. MTAP expression was analyzed by qRT-PCR, Western blot and immunohistochemical analysis. Levels of MTA were determined by liquid chromatography-tandem mass spectrometry. MTAP was downregulated in hepatocytes in murine fibrosis models and in patients with chronic liver disease, leading to a concomitant increase in MTA levels. In contrast, activated hepatic stellate cells (HSCs) showed strong MTAP expression in cirrhotic livers. However, also MTA levels in activated HSCs were significantly higher than in hepatocytes, and there was a significant correlation between MTA levels and collagen expression in diseased human liver tissue indicating that activated HSCs significantly contribute to elevated MTA in diseased livers. MTAP suppression by siRNA resulted in increased MTA levels, NFκB activation and apoptosis resistance, while overexpression of MTAP caused the opposite effects in HSCs. The anti-apoptotic effect of low MTAP expression and high MTA levels, respectively, was mediated by induced expression of survivin, while inhibition of survivin abolished the anti-apoptotic effect of MTA on HSCs. Treatment with a DNA demethylating agent induced MTAP and reduced survivin expression, while oxidative stress reduced MTAP levels but enhanced survivin expression in HSCs. MTAP mediated regulation of MTA links polyamine metabolism with NFκB activation and apoptosis in HSCs. MTAP and MTAP modulating mechanisms appear as promising prognostic markers and therapeutic targets for hepatic fibrosis.

Ursodeoxycholic acid for cystic fibrosis-related liver disease.

PubMed

Cheng, Katharine; Ashby, Deborah; Smyth, Rosalind L

2017-09-11

Abnormal biliary secretion leads to the thickening of bile and the formation of plugs within the bile ducts; the consequent obstruction and abnormal bile flow ultimately results in the development of cystic fibrosis-related liver disease. This condition peaks in adolescence with up to 20% of adolescents with cystic fibrosis developing chronic liver disease. Early changes in the liver may ultimately result in end-stage liver disease with people needing transplantation. One therapeutic option currently used is ursodeoxycholic acid. This is an update of a previous review. To analyse evidence that ursodeoxycholic acid improves indices of liver function, reduces the risk of developing chronic liver disease and improves outcomes in general in cystic fibrosis. We searched the Cochrane CF and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearches of relevant journals and abstract books of conference proceedings. We also contacted drug companies and searched online trial registries.Date of the most recent search of the Group's trials register: 09 April 2017. Randomised controlled trials of the use of ursodeoxycholic acid for at least three months compared with placebo or no additional treatment in people with cystic fibrosis. Two authors independently assessed trial eligibility and quality. The authors used GRADE to assess the quality of the evidence. Twelve trials have been identified, of which four trials involving 137 participants were included; data were only available from three of the trials (118 participants) since one cross-over trial did not report appropriate data. The dose of ursodeoxycholic acid ranged from 10 to 20 mg/kg/day for up to 12 months. The complex design used in two trials meant that data could only be analysed for subsets of participants. There was no significant difference in weight change, mean difference -0.90 kg (95% confidence interval -1.94 to 0.14) based on 30

Chronic Kidney Disease and Related Long-term Complications Following Liver Transplantation

PubMed Central

Sharma, Pratima; Bari, Khurram

2015-01-01

Liver transplantation (LT) is the standard of care for patients with decompensated cirrhosis. LT recipients have excellent short-term and long-term outcomes including patient and graft survival. Since the adoption of model for end-stage liver disease (MELD) - based allocation policy, the incidence of post-transplant end stage renal disease has risen significantly. Occurrence of stage 4 chronic kidney disease and end stage renal disease substantially increase the risk of post-transplant deaths. Since majority of late post-transplant mortality is due to non-hepatic post-transplant comorbidities, personalized care directed towards risk factor modification may further improve post-transplant survival. PMID:26311603

Non-alcoholic fatty liver disease, to struggle with the strangle: Oxygen availability in fatty livers.

PubMed

Anavi, Sarit; Madar, Zecharia; Tirosh, Oren

2017-10-01

Nonalcoholic fatty liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue durability, mainly in highly metabolic tissues, such as the liver. Accumulating evidence from the past few decades provides strong support for the existence of interruptions in oxygen availability in fatty livers. This outcome may be the consequence of both, impaired systemic microcirculation and cellular membrane modifications which occur under steatotic conditions. This review summarizes current knowledge regarding the main factors which can affect oxygen supply in fatty liver. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Microbiome alterations observed in liver diseases present opportunities for potential fecal transplantation.

PubMed

Heath, Ryan D; Mir, Fazia; Ibdah, Jamal A; Tahan, Veysel

2016-11-01

Many disease processes lead to chronic liver disease, however, progress has been made regarding common findings amongst these disease processes that may suggest a path forward for treatment. In particular, common alterations in the intestinal microflora of patients with different etiologies of liver disease may provide a clue as to the pathogenesis of these disorders as well a potential therapy. Data is still scant at this point, however, what is available suggests a promising opportunity for future studies to expand upon what has been demonstrated.

Nonalcoholic fatty liver disease: molecular mechanisms for the hepatic steatosis.

PubMed

Koo, Seung-Hoi

2013-09-01

Liver plays a central role in the biogenesis of major metabolites including glucose, fatty acids, and cholesterol. Increased incidence of obesity in the modern society promotes insulin resistance in the peripheral tissues in humans, and could cause severe metabolic disorders by inducing accumulation of lipid in the liver, resulting in the progression of non-alcoholic fatty liver disease (NAFLD). NAFLD, which is characterized by increased fat depots in the liver, could precede more severe diseases such as non-alcoholic steatohepatitis (NASH), cirrhosis, and in some cases hepatocellular carcinoma. Accumulation of lipid in the liver can be traced by increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, or the increased incidence of de novo lipogenesis. In this review, I would like to focus on the roles of individual pathways that contribute to the hepatic steatosis as a precursor for the NAFLD.

Nutritional Management of Insulin Resistance in Nonalcoholic Fatty Liver Disease (NAFLD)

PubMed Central

Conlon, Beth A.; Beasley, Jeannette M.; Aebersold, Karin; Jhangiani, Sunil S.; Wylie-Rosett, Judith

2013-01-01

Nonalcoholic fatty liver disease (NAFLD) is an emerging global health concern. It is the most common form of chronic liver disease in Western countries, affecting both adults and children. NAFLD encompasses a broad spectrum of fatty liver disease, ranging from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH), and is strongly associated with obesity, insulin resistance, and dyslipidemia. First-line therapy for NAFLD includes weight loss achieved through diet and physical activity. However, there is a lack of evidenced-based dietary recommendations. The American Diabetes Association’s (ADA) recommendations that aim to reduce the risk of diabetes and cardiovascular disease may also be applicable to the NAFLD population. The objectives of this review are to: (1) provide an overview of NAFLD in the context of insulin resistance, and (2) provide a rationale for applying relevant aspects of the ADA recommendations to the nutritional management of NAFLD. PMID:24152749

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

PubMed Central

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

2014-01-01

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

Liver disease in patients with cystic fibrosis.

PubMed

Kamal, Natasha; Surana, Pallavi; Koh, Christopher

2018-05-01

The aim of this study was to provide an overview of the current understanding of the pathophysiology, diagnosis and management of cystic fibrosis-liver disease (CFLD). CFLD has a variety of manifestations. Previously, it was thought that patients progressed from mild cholestatic disease to cirrhosis to decompensated cirrhosis with portal hypertension. Newer evidence suggests that some patients may develop cirrhosis while others develop noncirrhotic portal hypertension. Advances in our understanding of the pathophysiology of disease necessitate modifications to the current diagnostic criteria. Both fibroscan and noninvasive biomarkers can be used to identify patients with cirrhosis and portal hypertension. Ursodeoxycholic acid remains the mainstay of therapy despite a paucity of rigorous studies supporting its use. Novel therapeutic agents such as CF transmembrane conductance regulator (CFTR) modulators and potentiators are encouraging but need to be evaluated specifically in CFLD. A better understanding of the pathophysiology of disease is critical to developing more disease-specific diagnostics and therapeutics.

Alcoholic Liver Disease: Pathogenesis and New Therapeutic Targets

PubMed Central

GAO, BIN; BATALLER, RAMON

2011-01-01

Alcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide and can lead to fibrosis and cirrhosis. The latest surveillance report published by the National Institute on Alcohol Abuse and Alcoholism showed that liver cirrhosis was the 12th leading cause of death in the United States, with a total of 29,925 deaths in 2007, 48% of which were alcohol related. The spectrum of ALD includes simple steatosis, alcoholic hepatitis, fibrosis, cirrhosis, and superimposed hepatocellular carcinoma. Early work on the pathogenesis of the disease focused on ethanol metabolism–associated oxidative stress and glutathione depletion, abnormal methionine metabolism, malnutrition, and production of endotoxins that activate Kupffer cells. We review findings from recent studies that have characterized specific intracellular signaling pathways, transcriptional factors, aspects of innate immunity, chemokines, epigenetic features, microRNAs, and stem cells that are associated with ALD, improving our understanding of its pathogenesis. Despite this progress, no targeted therapies are available. The cornerstone of treatment for alcoholic hepatitis remains as it was 40 years ago: abstinence, nutritional support, and corticosteroids. There is an urgent need to develop new pathophysiology-oriented therapies. Recent translational studies of human samples and animal models have identified promising therapeutic targets. PMID:21920463

Ethnicity and the diagnosis gap in liver disease: a population-based study.

PubMed

Alazawi, William; Mathur, Rohini; Abeysekera, Kushala; Hull, Sally; Boomla, Kambiz; Robson, John; Foster, Graham R

2014-11-01

Liver disease is a major cause of morbidity and mortality worldwide. Large numbers of liver function tests (LFTs) are performed in primary care, with abnormal liver biochemistry a common finding. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. Metabolic syndrome, common in people from South Asia, is an important risk factor for NAFLD. It is hypothesised that a large gap exists between numbers of patients with abnormal LFTs and those with recorded liver diagnoses, and that NAFLD is more common among adults of South Asian ethnic groups. A cross-sectional study of 690,683 adults in coterminous general practices in a region with high ethnic diversity. Data were extracted on LFTs, liver disease, and process of care measures from computerised primary care medical records. LFTs were performed on 218,032 patients, of whom 31 627 had elevated serum transaminases. The prevalence of abnormal LFTs was highest among individuals of Bangladeshi ethnicity. Of the patients with abnormal LFTs, 88.4% did not have a coded liver diagnosis. NAFLD was the most frequently recorded liver disease and was most common among Bangladeshi patients. In a multivariate analysis, independent risk factors for NAFLD included Bangladeshi ethnicity, diabetes, raised BMI, hypertension, and hypercholesterolaemia. Abnormal LFTs are common in the population, but are underinvestigated and often remain undiagnosed. Bangladeshi ethnicity is an important independent risk factor for NAFLD. © British Journal of General Practice 2014.

Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease.

PubMed

Veropalumbo, Claudio; Campanozzi, Angelo; De Gregorio, Fabiola; Correra, Antonio; Raia, Valeria; Vajro, Pietro

2015-02-01

Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. Copyright © 2014. Published by Elsevier Masson SAS.

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

PubMed

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

2017-07-01

The diagnosis of non-alcoholic steatohepatitis and fibrosis staging are central to non-alcoholic fatty liver disease assessment. We evaluated multiparametric magnetic resonance in the assessment of non-alcoholic steatohepatitis and fibrosis using histology as standard in non-alcoholic fatty liver disease. Seventy-one patients with suspected non-alcoholic fatty liver disease were recruited within 1 month of liver biopsy. Magnetic resonance data were used to define the liver inflammation and fibrosis score (LIF 0-4). Biopsies were assessed for steatosis, lobular inflammation, ballooning and fibrosis and classified as non-alcoholic steatohepatitis or simple steatosis, and mild or significant (Activity ≥2 and/or Fibrosis ≥2 as defined by the Fatty Liver Inhibition of Progression consortium) non-alcoholic fatty liver disease. Transient elastography was also performed. Magnetic resonance success rate was 95% vs 59% for transient elastography (P<.0001). Fibrosis stage on biopsy correlated with liver inflammation and fibrosis (r s =.51, P<.0001). The area under the receiver operating curve using liver inflammation and fibrosis for the diagnosis of cirrhosis was 0.85. Liver inflammation and fibrosis score for ballooning grades 0, 1 and 2 was 1.2, 2.7 and 3.5 respectively (P<.05) with an area under the receiver operating characteristic curve of 0.83 for the diagnosis of ballooning. Patients with steatosis had lower liver inflammation and fibrosis (1.3) compared to patients with non-alcoholic steatohepatitis (3.0) (P<.0001); area under the receiver operating characteristic curve for the diagnosis of non-alcoholic steatohepatitis was 0.80. Liver inflammation and fibrosis scores for patients with mild and significant non-alcoholic fatty liver disease were 1.2 and 2.9 respectively (P<.0001). The area under the receiver operating characteristic curve of liver inflammation and fibrosis for the diagnosis of significant non-alcoholic fatty liver disease was 0

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts

PubMed Central

Ma, Jiantao; Fox, Caroline S.; Jacques, Paul F.; Speliotes, Elizabeth K.; Hoffmann, Udo; Smith, Caren E.; Saltzman, Edward; McKeown, Nicola M.

2016-01-01

Background & Aims Non-alcoholic fatty liver disease affects ~30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Methods Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/-day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. Results After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend = 0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend = 0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. Conclusion In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. PMID:26055949

Sugar-sweetened beverage, diet soda, and fatty liver disease in the Framingham Heart Study cohorts.

PubMed

Ma, Jiantao; Fox, Caroline S; Jacques, Paul F; Speliotes, Elizabeth K; Hoffmann, Udo; Smith, Caren E; Saltzman, Edward; McKeown, Nicola M

2015-08-01

Non-alcoholic fatty liver disease affects ∼30% of US adults, yet the role of sugar-sweetened beverages and diet soda on these diseases remains unknown. We examined the cross-sectional association between intake of sugar-sweetened beverages or diet soda and fatty liver disease in participants of the Framingham Offspring and Third Generation cohorts. Fatty liver disease was defined using liver attenuation measurements generated from computed tomography in 2634 participants. Alanine transaminase concentration, a crude marker of fatty liver disease, was measured in 5908 participants. Sugar-sweetened beverage and diet soda intake were estimated using a food frequency questionnaire. Participants were categorized as either non-consumers or consumers (3 categories: 1 serving/month to <1 serving/week, 1 serving/week to <1 serving/day, and ⩾1 serving/day) of sugar-sweetened beverages or diet soda. After adjustment for age, sex, smoking status, Framingham cohort, energy intake, alcohol, dietary fiber, fat (% energy), protein (% energy), diet soda intake, and body mass index, the odds ratios of fatty liver disease were 1, 1.16 (0.88, 1.54), 1.32 (0.93, 1.86), and 1.61 (1.04, 2.49) across sugar-sweetened beverage consumption categories (p trend=0.04). Sugar-sweetened beverage consumption was also positively associated with alanine transaminase levels (p trend=0.007). We observed no significant association between diet soda intake and measures of fatty liver disease. In conclusion, we observed that regular sugar-sweetened beverage consumption was associated with greater risk of fatty liver disease, particularly in overweight and obese individuals, whereas diet soda intake was not associated with measures of fatty liver disease. Copyright © 2015 European Association for the Study of the Liver. All rights reserved.

Alcoholic liver disease confers a worse prognosis than HCV infection and non-alcoholic fatty liver disease among patients with cirrhosis: An observational study

PubMed Central

Marot, Astrid; Henrion, Jean; Knebel, Jean-François; Moreno, Christophe

2017-01-01

Background Cirrhosis is a heterogeneous clinical condition that includes patients at wide-ranging stages of severity. The role of the underlying liver disease on patient prognosis remains unclear. Aim To assess the impact of the underlying liver disease on the occurrence of hepatocellular carcinoma (HCC) and death. Methods Data related to the occurrence of HCC and death were collected during a 21-year period among patients with cirrhosis related to alcoholic liver disease (ALD) (n = 529), chronic hepatitis C virus (HCV) infection (n = 145) or non-alcoholic fatty liver disease (NAFLD) (n = 78). Results At inclusion, ALD patients were younger than HCV and NAFLD patients (56 vs. 67 vs. 63 years; p<0.001) and had worse liver function (percent of patients with Child-Pugh stages B or C: 48% vs. 8% vs. 17%; p<0.001). During follow-up, 85 patients developed HCC and 379 died. The 10-year cumulative incidence rate of HCC was lower in ALD patients than in HCV and NAFLD patients (8.4% vs. 22.0% vs. 23.7%; p<0.001). The 10-year cumulative incidence rates of mortality were not statistically different between ALD, HCV and NAFLD patients (58.1% vs. 47.7% vs. 49.9%; p = 0.078). Alcohol abstinence and viral eradication were associated with reduced mortality among ALD and HCV patients, respectively. In multivariate analyses, ALD was associated with a reduced risk of HCC (0.39; 95% CI, 0.20–0.76; p = 0.005) but with a higher risk of mortality (1.53; 95% CI, 1.20–1.95; p<0.001). ALD patients died more frequently from decompensation of cirrhosis. Conclusion Despite a lower incidence of HCC, patients with ALD-related cirrhosis have a worse outcome than those with chronic HCV infection or NAFLD-related cirrhosis. PMID:29077714

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.

Natural Medicines Used in the Traditional Tibetan Medical System for the Treatment of Liver Diseases

PubMed Central

Li, Qi; Li, Hai-Jiao; Xu, Tong; Du, Huan; Huan Gang, Chen-Lei; Fan, Gang; Zhang, Yi

2018-01-01

Liver disease is one of the most risk factors threatening human health. It is of great significance to find drugs that can treat liver diseases, especially for acute and chronic hepatitis, non-alcoholic fatty liver disease, and liver cancer. The search for drugs with good efficacy from traditional natural medicines has attracted more and more attention. Tibetan medicine, one of the China's traditional medical systems, has been widely used by the Tibetan people for the prevention and treatment of liver diseases for hundreds of years. The present paper summarized the natural Tibetan medicines that have been used in Tibetan traditional system of medicine to treat liver diseases by bibliographic investigation of 22 Tibetan medicine monographs and drug standards. One hundred and ninety three species including 181 plants, 7 animals, and 5 minerals were found to treat liver diseases in traditional Tibetan medicine system. The most frequently used species are Carthamus tinctorius, Brag-zhun, Swertia chirayita, Swertia mussotii, Halenia elliptica, Herpetospermum pedunculosum, and Phyllanthus emblica. Their names, families, medicinal parts, traditional uses, phytochemicals information, and pharmacological activities were described in detail. These natural medicines might be a valuable gift from the old Tibetan medicine to the world, and would be potential drug candidates for the treatment of liver diseases. Further studies are needed to prove their medicinal values in liver diseases treatment, identify bioactive compounds, elucidate the underlying mechanism of action, and clarify their side effects or toxicity with the help of modern phytochemical, pharmacological, metabonomics, and/or clinical trial methods. PMID:29441019

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

Similarities and differences between pediatric and adult nonalcoholic fatty liver disease.

PubMed

Crespo, Maricruz; Lappe, Sara; Feldstein, Ariel E; Alkhouri, Naim

2016-08-01

Nonalcoholic fatty liver disease (NAFLD) is highly common and potentially serious in children and adolescents. The term NAFLD refers to a spectrum of diseases ranging from accumulation of fat in the liver (simple steatosis or nonalcoholic fatty liver "NAFL") to the potentially progressive form of nonalcoholic steatohepatitis (NASH) characterized by hepatocyte ballooning, inflammation, and often associated with fibrosis. While large prospective longitudinal studies in pediatric NAFLD are still lacking, growing evidence suggests that children with NAFL are at increased risk for cardiometabolic complications, while those with NASH and advance fibrosis are also at risk for significant liver-related morbidity including cirrhosis and its complications. Pediatric NAFLD shares features of adult NAFLD but also shows many different characteristics in terms of prevalence, histology, diagnosis and management. Translational studies suggest that NAFLD is a highly heritable disease in which genetic variations and environment closely interact to determine the disease phenotype and the progression to the more advanced forms of the disease. Changes in lifestyle, targeting gradual weight reduction, and physical exercise continue to be the mainstay of treatment for NAFLD in children. Recent advances in development of noninvasive diagnostic modalities and the potential for identifying effective pharmacological interventions may result in significant progress in the management of NAFLD in the pediatric population. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression and Function of Methylthioadenosine Phosphorylase in Chronic Liver Disease

PubMed Central

Czech, Barbara; Dettmer, Katja; Valletta, Daniela; Saugspier, Michael; Koch, Andreas; Stevens, Axel P.; Thasler, Wolfgang E.; Müller, Martina; Oefner, Peter J.; Bosserhoff, Anja-Katrin; Hellerbrand, Claus

2013-01-01

To study expression and function of methylthioadenosine phosphorylase (MTAP), the rate-limiting enzyme in the methionine and adenine salvage pathway, in chronic liver disease. Design MTAP expression was analyzed by qRT-PCR, Western blot and immunohistochemical analysis. Levels of MTA were determined by liquid chromatography-tandem mass spectrometry. Results MTAP was downregulated in hepatocytes in murine fibrosis models and in patients with chronic liver disease, leading to a concomitant increase in MTA levels. In contrast, activated hepatic stellate cells (HSCs) showed strong MTAP expression in cirrhotic livers. However, also MTA levels in activated HSCs were significantly higher than in hepatocytes, and there was a significant correlation between MTA levels and collagen expression in diseased human liver tissue indicating that activated HSCs significantly contribute to elevated MTA in diseased livers. MTAP suppression by siRNA resulted in increased MTA levels, NFκB activation and apoptosis resistance, while overexpression of MTAP caused the opposite effects in HSCs. The anti-apoptotic effect of low MTAP expression and high MTA levels, respectively, was mediated by induced expression of survivin, while inhibition of survivin abolished the anti-apoptotic effect of MTA on HSCs. Treatment with a DNA demethylating agent induced MTAP and reduced survivin expression, while oxidative stress reduced MTAP levels but enhanced survivin expression in HSCs. Conclusion MTAP mediated regulation of MTA links polyamine metabolism with NFκB activation and apoptosis in HSCs. MTAP and MTAP modulating mechanisms appear as promising prognostic markers and therapeutic targets for hepatic fibrosis. PMID:24324622

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

PubMed Central

Zhang, Chi; Austin, Christine; Amarasiriwardena, Chitra; Arora, Manish

2018-01-01

ABSTRACT The rapid increase in fatty liver disease (FLD) incidence is attributed largely to genetic and lifestyle factors; however, environmental toxicants are a frequently overlooked factor that can modify the effects of more common causes of FLD. Chronic exposure to inorganic arsenic (iAs) is associated with liver disease in humans and animal models, but neither the mechanism of action nor the combinatorial interaction with other disease-causing factors has been fully investigated. Here, we examined the contribution of iAs to FLD using zebrafish and tested the interaction with ethanol to cause alcoholic liver disease (ALD). We report that zebrafish exposed to iAs throughout development developed specific phenotypes beginning at 4 days post-fertilization (dpf), including the development of FLD in over 50% of larvae by 5 dpf. Comparative transcriptomic analysis of livers from larvae exposed to either iAs or ethanol revealed the oxidative stress response and the unfolded protein response (UPR) caused by endoplasmic reticulum (ER) stress as common pathways in both these models of FLD, suggesting that they target similar cellular processes. This was confirmed by our finding that arsenic is synthetically lethal with both ethanol and a well-characterized ER-stress-inducing agent (tunicamycin), suggesting that these exposures work together through UPR activation to cause iAs toxicity. Most significantly, combined exposure to sub-toxic concentrations of iAs and ethanol potentiated the expression of UPR-associated genes, cooperated to induce FLD, reduced the expression of as3mt, which encodes an arsenic-metabolizing enzyme, and significantly increased the concentration of iAs in the liver. This demonstrates that iAs exposure is sufficient to cause FLD and that low doses of iAs can potentiate the effects of ethanol to cause liver disease. This article has an associated First Person interview with the first author of the paper. PMID:29361514

A Systematic Review and Meta-Analysis on the Strength and Consistency of the Associations between Dupuytren Disease and Diabetes Mellitus, Liver Disease, and Epilepsy.

PubMed

Broekstra, Dieuwke C; Groen, Henk; Molenkamp, Sanne; Werker, Paul M N; van den Heuvel, Edwin R

2018-03-01

The role of diabetes mellitus, liver disease, and epilepsy as risk factors for Dupuytren disease remains unclear. In this systematic review and meta-analysis, the strength and consistency of these associations were examined. The MEDLINE, EMBASE, and Web of Science databases were searched for articles reporting an association between Dupuytren disease and diabetes mellitus, liver disease, and epilepsy published before September 26, 2016. The frequencies of Dupuytren disease and diabetes mellitus, liver disease, and epilepsy were extracted, as was information on potential confounders. Generalized linear mixed models were applied to estimate pooled odds ratios, adjusted for confounders. Heterogeneity between studies was quantified using an intraclass correlation coefficient and was accounted for by a random effect for study. One thousand two hundred sixty unique studies were identified, of which 32 were used in the meta-analyses. An association between Dupuytren disease and diabetes mellitus was observed (OR, 3.06; 95 percent CI, 2.69 to 3.48, adjusted for age), which was stronger for type 1 diabetes mellitus than for type 2 diabetes mellitus but was not statistically significant (p = 0.24). An association between Dupuytren disease and liver disease was observed (OR, 2.92; 95 percent CI, 2.08 to 4.12, adjusted for sex). Dupuytren disease and epilepsy were associated, yielding an OR of 2.80 (95 percent CI, 2.49 to 3.15). Heterogeneity between studies was moderate to low. These findings demonstrate an association between Dupuytren disease and diabetes mellitus, liver disease, and epilepsy. Prospective, longitudinal studies are needed to elucidate the pathways causing these associations.

Thermoneutral housing exacerbates non-alcoholic fatty liver disease in mice and allows for sex-independent disease modeling

PubMed Central

Giles, Daniel A; Moreno-Fernandez, Maria E; Stankiewicz, Traci E; Graspeuntner, Simon; Cappelletti, Monica; Wu, David; Mukherjee, Rajib; Chan, Calvin C; Lawson, Matthew J; Klarquist, Jared; Sünderhauf, Annika; Softic, Samir; Kahn, C Ronald; Stemmer, Kerstin; Iwakura, Yoichiro; Aronow, Bruce J; Karns, Rebekah; Steinbrecher, Kris A; Karp, Christopher L; Sheridan, Rachel; Shanmukhappa, Shiva K; Reynaud, Damien; Haslam, David B; Sina, Christian; Rupp, Jan; Hogan, Simon P; Divanovic, Senad

2017-01-01

Non-alcoholic fatty liver disease (NAFLD), a common prelude to cirrhosis and hepatocellular carcinoma, is the most common chronic liver disease worldwide. Defining the molecular mechanisms underlying the pathogenesis of NAFLD has been hampered by a lack of animal models that closely recapitulate the severe end of the human disease spectrum, including bridging hepatic fibrosis. Here, we demonstrate that a novel experimental model employing thermoneutral housing, as opposed to standard housing, resulted in lower stress-driven production of corticosterone, augmented mouse proinflammatory immune responses and markedly exacerbated high fat diet (HFD)-induced NAFLD pathogenesis. Disease exacerbation at thermoneutrality was conserved across multiple mouse strains and was associated with augmented intestinal permeability, an altered microbiome and activation of inflammatory pathways associated with human disease. Depletion of Gram-negative microbiota, hematopoietic cell deletion of Toll-like receptor 4 (TLR4) and inactivation of the interleukin-17 (IL-17) axis resulted in altered immune responsiveness and protection from thermoneutral housing-driven NAFLD amplification. Finally, female mice, typically resistant to HFD-induced obesity and NAFLD, develop full-blown disease at thermoneutrality. Thus, thermoneutral housing provides a sex-independent model of exacerbated NAFLD in mice and represents a novel approach for interrogation of the cellular and molecular mechanisms underlying disease pathogenesis. PMID:28604704

Characteristics and outcome of autoimmune liver disease in Asian children.

PubMed

Lee, Way S; Lum, Su H; Lim, Chooi B; Chong, Sze Y; Khoh, Kim M; Ng, Ruey T; Teo, Kai M; Boey, Christopher C M; Pailoor, Jayalakshmi

2015-04-01

Little is known about autoimmune liver disease (AILD) in Asian children. We studied the clinical features and predictors of outcome in childhood AILD in an Asian population. Retrospective review of AILD [autoimmune hepatitis type 1 and 2 (AIH1, AIH2), primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC)] seen at two pediatric liver units in Malaysia. At presentation, 17 (56%) of the 32 children [19 females, 59%; median (range) age 7.7 (1.8-15.5) years] with AILD (AIH1 = 18, AIH2 = 5, PSC = 0, ASC = 9) had liver cirrhosis. At final review [median (range) duration of follow-up 4.8 (0.4-12) years], 24 patients (75%) survived with a native liver. Twenty-one (66%) were in remission; 19 (AIH1 = 11; AIH2 = 4, ASC = 4) were on prednisolone and/or azathioprine, one on cyclosporine and another on mycophenolate mofetil. Three (AIH1 = 3) were in partial remission. Of the two who underwent liver transplantation (LT; 6.5%; both ASC), one died of primary graft failure after LT. Six patients (19%) died without LT (acute liver failure, n = 1; end-stage liver disease, n = 5). The overall survival rate (native liver and survival post-LT) was 78%. A delay in seeking treatment adversely affected the final outcome [survival with native liver vs. LT or death (duration between onset of disease and treatment; median ± standard error) = 2.5 ± 2.9 months vs. 24.0 ± 13.3 months; p = 0.012]. Although remission was achieved in the majority of patients with prednisolone and/or azathioprine therapy, delay in seeking diagnosis and treatment adversely affects the outcome of childhood AILD in Malaysia.

New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases.

PubMed

Ji, Cheng

2014-01-01

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.

Burden of liver disease in Europe: epidemiology and analysis of risk factors to identify prevention policies.

PubMed

Pimpin, Laura; Cortez-Pinto, Helena; Negro, Francesco; Corbould, Emily; Lazarus, Jeffrey V; Webber, Laura; Sheron, Nick

2018-05-16

The burden of liver disease in Europe continues to grow. We aimed to describe the epidemiology of liver diseases and their risk factors in European countries, and identify public health interventions that could impact on these risk factors to reduce the burden of liver disease. As part of the HEPAHEALTH project, commissioned by EASL, we extracted information on historical and current prevalence and mortality from national and international literature and databases on liver disease in 35 countries in the WHO European region, as well as historical and recent prevalence data on their main determinants; alcohol consumption, obesity and hepatitis B and C virus infections. We extracted information from peer-reviewed and grey literature to identify public health interventions targeting these risk factors. The epidemiology of liver disease is diverse and countries cluster with similar pictures, although the exact composition of diseases and the trends in risk factors which drive them is varied. Prevalence and mortality data indicate that increasing cirrhosis and liver cancer may be linked to dramatic increases in harmful alcohol consumption in Northern European countries, and viral hepatitis epidemics in Eastern and Southern European countries. Countries with historically low levels of liver disease may experience an increase in non-alcoholic fatty liver disease in the future, given the rise of obesity across the majority of European countries. Interventions exist for curbing harmful alcohol use, reducing obesity, preventing or treating viral hepatitis, and screening for liver disease at an early stage. Liver disease in Europe is a serious issue, with increasing cirrhosis and liver cancer. The public health and hepatology communities are uniquely placed to implement measures aimed at reducing their causes: harmful alcohol consumption, child and adult obesity prevalence and chronic infection with hepatitis viruses, which will in turn reduce the burden of liver disease. The

High incidence of zinc deficiency among Filipino children with compensated and decompensated liver disease.

PubMed

Umusig-Quitain, Perlina; Gregorio, Germana V

2010-02-01

The role of zinc in the nutrition and growth of children with chronic liver disease is poorly defined. The present study determined the serum zinc levels of children with compensated liver disease (CLD) and decompensated liver disease (DLD) and compared this with healthy children. Zinc levels were also correlated with the severity of liver disease as measured by Child-Pugh scores. The study comprised of 60 children 0-10 years of age with chronic liver disease, defined as CLD (n = 30) if the Child-Pugh score was < 6, and DLD (n = 30) if the Child-Pugh score was > or = 6. Thirty healthy children 0-10 years served as controls. Serum zinc levels were measured by atomic absorption spectrometry. The 90 patients included 30 with CLD (mean age: 4.54 years: 21 boys; mean Child-Pugh score: 5.83), 30 with DLD (mean age: 1.39 years; 17 boys; mean Child-Pugh score: 9.53) and 30 healthy children (mean age: 4.6; 16 boys). Zinc levels of patients with CLD were significantly lower compared with the healthy controls (Mean [standard deviation]: 68.07 [31.55]vs 89.9 [25.9]microg/dL, P = 0.000), but significantly higher compared to the patients with DLD (48.8 [26.8]microg/dL). Correlation studies showed that the higher the Child-Pugh score, the lower the zinc levels (r = -0.460) Children with chronic liver disease, whether in a compensated or decompensated state, had lower serum zinc levels compared with the healthy controls. As the severity of liver disease worsened, the zinc levels decreased. The study suggests that zinc supplementation should constitute part of the micronutrient intake of children with chronic liver disease.

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

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

Senescence in chronic liver disease: Is the future in aging?

PubMed

Aravinthan, Aloysious D; Alexander, Graeme J M

2016-10-01

Cellular senescence is a fundamental, complex mechanism with an important protective role present from embryogenesis to late life across all species. It limits the proliferative potential of damaged cells thus protecting against malignant change, but at the expense of substantial alterations to the microenvironment and tissue homeostasis, driving inflammation, fibrosis and paradoxically, malignant disease if the process is sustained. Cellular senescence has attracted considerable recent interest with recognition of pathways linking aging, malignancy and insulin resistance and the current focus on therapeutic interventions to extend health-span. There are major implications for hepatology in the field of fibrosis and cancer, where cellular senescence of hepatocytes, cholangiocytes, stellate cells and immune cells has been implicated in chronic liver disease progression. This review focuses on cellular senescence in chronic liver disease and explores therapeutic opportunities. Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

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

Computed tomography of the liver and kidneys in glycogen storage disease.

PubMed

Doppman, J L; Cornblath, M; Dwyer, A J; Adams, A J; Girton, M E; Sidbury, J

1982-02-01

Glycogen, in concentrations encountered in von Gierke's disease, has computed tomography (CT) attenuation coefficients in the 50 to 70 Hounsfield unit (HU: 1,000 scale) range and accounts for the increased density of the liver. However, in eight patients with Type I glycogen storage disease, simultaneous hepatic infiltration with fat and glycogen led to a range of liver CT densities from 13 to 80 HU. Fatty infiltration may facilitate the demonstration of hepatic tumors in older patients with this disease. Half the patients showed increased attenuation coefficients of the renal cortex, indicating glycogen deposition in the kidneys.