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Concept: Cirrhosis

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The goal of chronic hepatitis C (CHC) treatment is to achieve a sustained virologic response (SVR). The new generation of direct-acting antivirals (DAAs) offers 90-100% SVR rates. However, access to these treatments is generally limited to patients with advanced liver disease. The aim of this review is to provide an overview of the clinical and economic benefits of achieving SVR and to better understand the full value of CHC treatment in all stages of liver disease.

Concepts: Jaundice, Hepatitis, Hepatitis B, Hepatitis A, Cirrhosis, Hepatitis C

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Acute on chronic liver failure (ACLF) is associated with multi-system organ failure and poor prognosis in hospitalized patients with cirrhosis. We aimed to determine time trends in the epidemiology, economic burden and mortality of ACLF in the United States. The National Inpatient Sample database was queried between 2001 and 2011. ACLF was defined as 2 or more extrahepatic organ failures in patients with cirrhosis. The primary outcomes were trends in hospitalizations, hospital costs and inpatient mortality in ACLF. The number of hospitalizations for cirrhosis in the US nearly doubled from 371,000 in 2001 to 659,000 in 2011. The prevalence of ACLF among those hospitalizations increased from 1.5% (n=5,400) to 5% (n=32,300). The inpatient costs increased 2-fold for cirrhosis ($4.8 billion to $9.8 billion) and 5-fold ($320 million to $1.7 billion) for ACLF. In 2011, the cost per hospitalization for ACLF was 3.5-fold higher than that for cirrhosis ($53,570 vs $15,193). The in-hospital fatality rates decreased from 65% to 50% for ACLF and from 10% to 7% for cirrhosis. The organ failure trends in ACLF showed an increasing proportion of cardiovascular and cerebral and decreasing proportion of respiratory and renal failure. Age, male sex, and the number and types of organ failure were predictors of death in ACLF.

Concepts: Hepatology, Organ failure, Kidney, Hepatic encephalopathy, Cirrhosis, United States, Hospital, Liver

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

Concepts: Steatosis, Nutrition, Hepatitis, Metabolic syndrome, Obesity, Fatty liver, Cirrhosis, Non-alcoholic fatty liver disease

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Primary biliary cholangitis, previously called primary biliary cirrhosis, is a cholestatic autoimmune liver disease that is marked by the progressive lymphocytic destruction of the smallest intralobular bile ducts.(1),(2) In the absence of effective therapy, it progresses inexorably to cirrhosis and liver failure. Ursodiol, a hydrophilic bile acid with an excellent safety profile, was approved by the Food and Drug Administration (FDA) in 1988 for the dissolution of gallstones. On the basis of early promising data in the management of primary biliary cholangitis and the unmet clinical need, the FDA granted ursodiol orphan status in 1991 for the management of . . .

Concepts: Bile, Cirrhosis, Jaundice, Bilirubin, Primary sclerosing cholangitis, Primary biliary cirrhosis, Liver, Hepatology

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Pharmacologic treatments for non-alcoholic steatohepatitis (NASH) are limited. Lifestyle interventions are believed to be effective in reducing features of NASH, although the effect of regular exercise, independent of dietary change, is unclear. We performed a randomized controlled trial to study the effect of exercise on hepatic triglyceride content (HTGC) and biomarkers of fibrosis in patients with NASH.

Concepts: Clinical trial, Efficacy, Effectiveness, Randomized controlled trial, Liver, Glycerol, Obesity, Cirrhosis

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Hepatic steatosis, the first step in the progression of nonalcoholic fatty liver disease, is characterized by triglyceride accumulation in hepatocytes and is highly prevalent in people with obesity. Although initially asymptomatic, hepatic steatosis is an important risk factor for the development of hepatic insulin resistance and type 2 diabetes mellitus and can also progress to more severe pathologies such as nonalcoholic steatohepatitis, liver fibrosis and cirrhosis; hepatic steatosis has, therefore, received considerable research interest in the past 20 years. The lipid accumulation that defines hepatic steatosis disturbs the function of the endoplasmic reticulum (ER) in hepatocytes, thereby generating chronic ER stress that interferes with normal cellular function. Although ubiquitous stress response mechanisms (namely, ER-associated degradation, unfolded protein response and autophagy) are the main processes for restoring cellular proteostasis, these mechanisms are unable to alleviate ER stress in the context of the fatty liver. Furthermore, ER stress and ER stress responses can promote lipid accumulation in hepatocytes in a counter-productive manner and could, therefore, be the origin of a vicious pathological cycle.

Concepts: Steatosis, Diabetes mellitus, Insulin, Cirrhosis, Fatty liver, Metabolic syndrome, Non-alcoholic fatty liver disease, Obesity

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We utilized a disease progression model to predict the number of viraemic infections, cirrhotic cases, and liver-related deaths in the state of Rhode Island (RI) under four treatment scenarios: (1) current HCV treatment paradigm (about 215 patients treated annually, Medicaid reimbursement criteria fibrosis stage ⩾F3); (2) immediate scale-up of treatment (to 430 annually) and less restrictive Medicaid reimbursement criteria (fibrosis stage ⩾F2); (3) immediate treatment scale-up and no fibrosis stage-specific Medicaid reimbursement criteria (⩾F0); (4) an ‘elimination’ scenario (i.e. a continued treatment scale-up needed to achieve >90% reduction in viraemic cases by 2030). Under current treatment models, the number of cirrhotic cases and liver-related deaths will plateau and peak by 2030, respectively. Treatment scale-up with ⩾F2 and ⩾F0 fibrosis stage treatment criteria could reduce the number of cirrhotic cases by 21·7% and 10·0%, and the number of liver-related deaths by 19·3% and 7·4%, respectively by 2030. To achieve a >90% reduction in viraemic cases by 2030, over 2000 persons will need to be treated annually by 2020. This strategy could reduce cirrhosis cases and liver-related deaths by 78·9% and 72·4%, respectively by 2030. Increased HCV treatment uptake is needed to substantially reduce the burden of HCV by 2030 in Rhode Island.

Concepts: Massachusetts, Hepatitis C virus, Hepatitis, Rhode Island, Cirrhosis, Hepatitis C

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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.

Concepts: Medicine, Hepatology, Cirrhosis, Liver, Metabolic syndrome, Non-alcoholic fatty liver disease, Fatty liver, Obesity

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Multiple reports have demonstrated that liver transplantation following donation after circulatory death (DCD) is associated with poorer outcomes when compared with liver transplantation after brain dead donation (DBD). We hypothesized that carefully selected, under-utilized DCD livers recovered from younger donors have excellent outcomes.

Concepts: Legal death, Death, Liver dialysis, Brain death, Liver transplantation, Cirrhosis, Organ transplant, Liver

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Chronic liver disease (CLD) and cirrhosis are major sources of morbidity and mortality in the United States. Little is known about the epidemiology of these two diseases in ethnic minority populations in the United States. We examined the prevalence of CLD and cirrhosis by underlying etiologies among African Americans, Native Hawaiians, Japanese Americans, Latinos and whites in the Multiethnic Cohort. CLD and cirrhosis cases were identified using Medicare claims between 1999 and 2012 among the fee-for-service participants (n=106,458). We used ICD-9 codes, body mass index, history of diabetes mellitus and alcohol consumption from questionnaires to identify underlying etiologies. A total of 5,783 CLD (3,575 CLD without cirrhosis and 2,208 cirrhosis) cases were identified. The prevalence of CLD ranged from 3.9% in African Americans and Native Hawaiians to 4.1% in whites, 6.7% in Latinos and 6.9% in Japanese. Nonalcoholic fatty liver disease (NAFLD) was the most common cause of CLD in all ethnic groups combined (52%), followed by alcoholic liver disease (ALD) (21%). NAFLD was the most common cause of cirrhosis in the entire cohort. By ethnicity, NALFD was the most common cause of cirrhosis in Japanese Americans, Native Hawaiians, and Latinos, accounting for 32% of cases. ALD was the most common cause of cirrhosis in whites (38.2%), while hepatitis C virus was the most common cause in African Americans (29.8%).

Concepts: Fatty liver, Native Americans in the United States, Hepatitis, Non-alcoholic fatty liver disease, Obesity, Race, Cirrhosis, United States