The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Bernd Schnabl - One of the best experts on this subject based on the ideXlab platform.
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Serum and Fecal Oxylipins in Patients with Alcohol-Related Liver Disease.
Digestive diseases and sciences, 2019Co-Authors: Bei Gao, Sonja Lang, Yi Duan, Yanhan Wang, Debbie L. Shawcross, Alexandre Louvet, Philippe Mathurin, Peter Stärkel, Bernd SchnablAbstract:Alcohol-related Liver Disease is one of the most prevalent chronic Liver Diseases worldwide. Mechanisms involved in the pathogenesis of alcohol-related Liver Disease are not well understood. Oxylipins play a crucial role in numerous biological processes and pathological conditions. Nevertheless, oxylipins are not well studied in alcohol-related Liver Disease. (1) To characterize the patterns of bioactive ω-3 and ω-6 polyunsaturated fatty acid metabolites in alcohol use disorder and alcoholic hepatitis patients and (2) to identify associations of serum oxylipins with clinical parameters in patients with alcohol-related Liver Disease. We performed a comprehensive liquid chromatography with tandem mass spectrometry (LC–MS/MS) analysis of serum and fecal oxylipins derived from ω-6 arachidonic acid, ω-3 eicosapentaenoic acid, and docosahexaenoic acid in a patient cohort with alcohol-related Liver Disease. Our results show profound alterations in the serum oxylipin profile of patients with alcohol use disorder and alcoholic hepatitis compared to nonalcoholic controls. Spearman correlation of the oxylipins with clinical parameters shows a link between different serum oxylipins and intestinal permeability, aspartate aminotransferase, bilirubin, albumin, international normalized ratio, platelet count, steatosis, fibrosis and model for end-stage Liver Disease score. Especially, higher level of serum 20-HETE was significantly associated with decreased albumin, increased hepatic steatosis, polymorphonuclear infiltration, and 90-day mortality. Patients with alcohol-related Liver Disease have different oxylipin profiles. Future studies are required to confirm oxylipins as Disease biomarker or to connect oxylipins to Disease pathogenesis.
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antimicrobial proteins intestinal guards to protect against Liver Disease
Journal of Gastroenterology, 2019Co-Authors: Tim Hendrikx, Bernd SchnablAbstract:Alterations of gut microbes play a role in the pathogenesis and progression of many disorders including Liver and gastrointestinal Diseases. Both qualitative and quantitative changes in gut microbiota have been associated with Liver Disease. Intestinal dysbiosis can disrupt the integrity of the intestinal barrier leading to pathological bacterial translocation and the initiation of an inflammatory response in the Liver. In order to sustain symbiosis and protect from pathological bacterial translocation, antimicrobial proteins (AMPs) such as a-defensins and C-type lectins are expressed in the gastrointestinal tract. In this review, we provide an overview of the role of AMPs in different chronic Liver Disease such as alcoholic steatohepatitis, non-alcoholic fatty Liver Disease, and cirrhosis. In addition, potential approaches to modulate the function of AMPs and prevent bacterial translocation are discussed.
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microbiome as a therapeutic target in alcohol related Liver Disease
Journal of Hepatology, 2019Co-Authors: Shiv Kumar Sarin, Bernd Schnabl, Apurva PandeAbstract:Alcohol-related Liver Disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced Liver Disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related Liver Disease. A major mechanism by which gut microbiota influence the development of alcohol-related Liver Disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the Liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related Liver Disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related Liver Disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related Liver Disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related Liver Disease. These approaches are likely to add to the therapeutic options for alcohol-related Liver Disease independently or in conjunction with steroids.
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bacterial translocation and changes in the intestinal microbiome associated with alcoholic Liver Disease
World Journal of Hepatology, 2012Co-Authors: Bernd SchnablAbstract:Alcoholic Liver Disease progresses through several stages of tissue damage, from simple steatosis to alcoholic hepatitis, fibrosis, or cirrhosis. Alcohol also affects the intestine, increases intestinal permeability and changes the bacterial microflora. Liver Disease severity correlates with levels of systemic bacterial products in patients, and experimental alcoholic Liver Disease is dependent on gut derived bacterial products in mice. Supporting evidence for the importance of bacterial translocation comes from animal studies demonstrating that intestinal decontamination is associated with decreased Liver fibrogenesis. In addition, mice with a gene mutation or deletion encoding receptors for either bacterial products or signaling molecules downstream from these receptors, are resistant to alcohol-induced Liver Disease. Despite this strong association, the exact molecular mechanism of bacterial translocation and of how changes in the intestinal microbiome contribute to Liver Disease progression remains largely unknown. In this review we will summarize evidence for bacterial translocation and enteric microbial changes in response to alcoholic Liver injury and chronic alcoholic Liver Disease. We will further describe consequences of intestinal dysbiosis on host biology. We finally discuss how therapeutic interventions may modify the gastrointestinal microflora and prevent or reduce alcoholic Liver Disease progression.
Giulio Marchesini - One of the best experts on this subject based on the ideXlab platform.
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nonalcoholic fatty Liver Disease a precursor of the metabolic syndrome
Digestive and Liver Disease, 2015Co-Authors: Amedeo Lonardo, Giulio Marchesini, Paul Angulo, S Ballestri, Paola LoriaAbstract:Abstract The conventional paradigm of nonalcoholic fatty Liver Disease representing the “hepatic manifestation of the metabolic syndrome” is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty Liver Disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty Liver Disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty Liver Disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty Liver Disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty Liver Disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty Liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty Liver Disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.
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nonalcoholic fatty Liver Disease and the metabolic syndrome
Current Opinion in Lipidology, 2005Co-Authors: Giulio Marchesini, Rebecca Marzocchi, Federica Agostini, Elisabetta BugianesiAbstract:In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive Liver Disease. Nonalcoholic steatosis (nonalcoholic fatty Liver Disease, NAFLD) is now considered a metabolic pathway to advanced Liver Disease, cirrhosis and hepatocellular carcinoma. Liver Disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of Liver Disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different Diseases. We still need to clarify the mechanism(s) responsible for Liver Disease progression from pure fatty Liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal Liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic Liver Disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic Liver Disease.
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Insulin resistance: A metabolic pathway to chronic Liver Disease
Hepatology, 2005Co-Authors: Elisabetta Bugianesi, Arthur J. Mccullough, Giulio MarchesiniAbstract:Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty Liver Disease (NAFLD), one of the most common causes of chronic Liver Disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic Liver Disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the Liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the Liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic Disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the Liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic Liver Disease is associated with multiple features of the metabolic syndrome, and the risk of progressive Liver Disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the Liver (metformin) and in the periphery (thiazolidinediones) are discussed.
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association of nonalcoholic fatty Liver Disease with insulin resistance
The American Journal of Medicine, 1999Co-Authors: Giulio Marchesini, Arthur J. Mccullough, Elisabetta Bugianesi, Mara Brizi, Antonio Maria Morsellilabate, Giampaolo Bianchi, Gabriele Forlani, N MelchiondaAbstract:Abstract BACKGROUND AND PURPOSE: Nonalcoholic fatty Liver Disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal weight. We tested the hypothesis that there is an association between nonalcoholic fatty Liver Disease and insulin resistance that is independent of diabetes and obesity. SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "bright Liver" on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex. RESULTS: Patients with nonalcoholic fatty Liver Disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70], fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty Liver Disease. The exclusion of overweight and obese subjects did not change the results. CONCLUSION: Nonalcoholic fatty Liver Disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.
Elisabetta Bugianesi - One of the best experts on this subject based on the ideXlab platform.
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nonalcoholic fatty Liver Disease and the metabolic syndrome
Current Opinion in Lipidology, 2005Co-Authors: Giulio Marchesini, Rebecca Marzocchi, Federica Agostini, Elisabetta BugianesiAbstract:In the last 15 years evidence has been accumulating suggesting that hepatic steatosis may be the starting point for a progressive Liver Disease. Nonalcoholic steatosis (nonalcoholic fatty Liver Disease, NAFLD) is now considered a metabolic pathway to advanced Liver Disease, cirrhosis and hepatocellular carcinoma. Liver Disease of other etiology, namely hepatitis C virus, may interact with NAFLD, although the underlying mechanism(s) have not been fully elucidated. Type 2 diabetes mellitus, obesity and dyslipidemia are the principal factors associated with NAFLD, which is now considered the hepatic expression of metabolic syndrome (MS). Several studies have dealt with the relationship of NAFLD and MS, the risk of Liver Disease associated with the classical features of MS, the importance of insulin resistance as the common soil of different Diseases. We still need to clarify the mechanism(s) responsible for Liver Disease progression from pure fatty Liver, to steatohepatitis and to cirrhosis, and the reason(s) why only a few NAFLD cases progress to terminal Liver failure while others (the majority) will have a cardiovascular outcome. The epidemics of obesity and diabetes of Western countries is expected to produce a significant increase of metabolic Liver Disease in the next years. Prevention and intervention programs based on lifestyle are therefore mandatory to reduce the burden of metabolic Liver Disease.
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Insulin resistance: A metabolic pathway to chronic Liver Disease
Hepatology, 2005Co-Authors: Elisabetta Bugianesi, Arthur J. Mccullough, Giulio MarchesiniAbstract:Insulin resistance (IR) is the pathophysiological hallmark of nonalcoholic fatty Liver Disease (NAFLD), one of the most common causes of chronic Liver Disease in Western countries. We review the definition of IR, the methods for the quantitative assessment of insulin action, the pathophysiology of IR, and the role of IR in the pathogenesis of chronic Liver Disease. Increased free fatty acid flux from adipose tissue to nonadipose organs, a result of abnormal fat metabolism, leads to hepatic triglyceride accumulation and contributes to impaired glucose metabolism and insulin sensitivity in muscle and in the Liver. Several factors secreted or expressed in the adipocyte contribute to the onset of a proinflammatory state, which may be limited to the Liver or more extensively expressed throughout the body. IR is the common characteristic of the metabolic syndrome and its related features. It is a systemic Disease affecting the nervous system, muscles, pancreas, kidney, heart, and immune system, in addition to the Liver. A complex interaction between genes and the environment favors or enhances IR and the phenotypic expression of NAFLD in individual patients. Advanced fibrotic Liver Disease is associated with multiple features of the metabolic syndrome, and the risk of progressive Liver Disease should not be underestimated in individuals with metabolic disorders. Finally, the ability of insulin-sensitizing, pharmacological agents to treat NAFLD by reducing IR in the Liver (metformin) and in the periphery (thiazolidinediones) are discussed.
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association of nonalcoholic fatty Liver Disease with insulin resistance
The American Journal of Medicine, 1999Co-Authors: Giulio Marchesini, Arthur J. Mccullough, Elisabetta Bugianesi, Mara Brizi, Antonio Maria Morsellilabate, Giampaolo Bianchi, Gabriele Forlani, N MelchiondaAbstract:Abstract BACKGROUND AND PURPOSE: Nonalcoholic fatty Liver Disease is frequently associated with type 2 diabetes mellitus, obesity, and dyslipidemia, but some patients have normal glucose tolerance or normal weight. We tested the hypothesis that there is an association between nonalcoholic fatty Liver Disease and insulin resistance that is independent of diabetes and obesity. SUBJECTS AND METHODS: We measured anthropometric and metabolic variables in 46 patients with chronically elevated serum aminotransferase levels, "bright Liver" on ultrasound scan, and normal glucose tolerance. Indexes of insulin resistance and secretion were determined using the homeostasis model assessment method. They were compared with 92 normal subjects who were matched for age and sex. RESULTS: Patients with nonalcoholic fatty Liver Disease were characterized by fasting and glucose-induced hyperinsulinemia, insulin resistance, postload hypoglycemia, and hypertriglyceridemia. Insulin resistance [odds ratio (OR) = 15 per percent increase, 95% confidence interval (CI): 3.0 to 70], fasting triglyceride level (OR = 3.1 per mmol/liter increase, 95% CI: 1.1 to 8.9), 180-minute blood glucose level (OR = 4.3 per mmol/liter decrease, 95% CI: 1.6 to 12), and average insulin concentration in response to oral glucose (OR = 3.0 per 100 pmol/liter increase, 95% CI: 1.5 to 6.2) were independently associated with nonalcoholic fatty Liver Disease. The exclusion of overweight and obese subjects did not change the results. CONCLUSION: Nonalcoholic fatty Liver Disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance. Genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.
Paul Angulo - One of the best experts on this subject based on the ideXlab platform.
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nonalcoholic fatty Liver Disease a precursor of the metabolic syndrome
Digestive and Liver Disease, 2015Co-Authors: Amedeo Lonardo, Giulio Marchesini, Paul Angulo, S Ballestri, Paola LoriaAbstract:Abstract The conventional paradigm of nonalcoholic fatty Liver Disease representing the “hepatic manifestation of the metabolic syndrome” is outdated. We identified and summarized longitudinal studies that, supporting the association of nonalcoholic fatty Liver Disease with either type 2 diabetes mellitus or metabolic syndrome, suggest that nonalcoholic fatty Liver Disease precedes the development of both conditions. Online Medical databases were searched, relevant articles were identified, their references were further assessed and tabulated data were checked. Although several cross-sectional studies linked nonalcoholic fatty Liver Disease to either diabetes and other components of the metabolic syndrome, we focused on 28 longitudinal studies which provided evidence for nonalcoholic fatty Liver Disease as a risk factor for the future development of diabetes. Moreover, additional 19 longitudinal reported that nonalcoholic fatty Liver Disease precedes and is a risk factor for the future development of the metabolic syndrome. Finally, molecular and genetic studies are discussed supporting the view that aetiology of steatosis and lipid intra-hepatocytic compartmentation are a major determinant of whether fatty Liver is/is not associated with insulin resistance and metabolic syndrome. Data support the novel paradigm of nonalcoholic fatty Liver Disease as a strong determinant for the development of the metabolic syndrome, which has potentially relevant clinical implications for diagnosing, preventing and treating metabolic syndrome.
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nonalcoholic fatty Liver Disease
Canadian Medical Association Journal, 2005Co-Authors: Leon A Adams, Paul Angulo, Keith D LindorAbstract:NONALCOHOLIC FATTY Liver Disease is emerging as the most common chronic Liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated Liver enzyme levels to cirrhosis with complications of Liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty Liver Disease as well as approaches to its management.
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nonalcoholic fatty Liver Disease
Encyclopedia of Gastroenterology, 2004Co-Authors: Paul AnguloAbstract:Nonalcoholic fatty Liver Disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive Liver Disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the Disease requires a Liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular Disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive Liver Disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.
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non alcoholic fatty Liver Disease
Journal of Gastroenterology and Hepatology, 2002Co-Authors: Paul Angulo, Keith D LindorAbstract:Non-alcoholic fatty Liver Disease (NAFLD) is a chronic Liver Disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but Liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the Liver Disease. Weight reduction, when achieved and sustained, may improve the Liver Disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying Liver Disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after Liver transplantation.
Byron W Marks - One of the best experts on this subject based on the ideXlab platform.
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autosomal dominant polycystic Liver Disease a second family
Clinical Genetics, 2008Co-Authors: Gabriel Berrebi, Robert P Erickson, Byron W MarksAbstract:An autosomal dominant pattern of transmission has been established for polycystic kidney Disease. The degree of cystic involvement of other organs has been variable. The genetic pattern of transmission of polycystic Liver Disease independent of cystic kidney Disease has never been established. We present a second family with polycystic Liver Disease without kidney Disease. The lack of renal cysts is unlikely to be due to variable expressivity and penetrance of the gene for polycystic kidney Disease. The Liver cysts may be of late onset since none of the proband's four children demonstrate cysts. Alternatively, none of these four individuals may have received the gene for polycystic Liver Disease from their affected mother. The family described supports an autosomal dominant pattern of inheritance for polycystic Liver Disease.
