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Concept: Cirrhosis

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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

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In recent years, the treatment options for patients with severe cardiorespiratory failure have been extended by the implementation of mechanical circulatory support (MCS). Identification of patients that benefit most from this cost-intensive treatment modality is of central importance, but is also challenging. Previous studies unravelled certain patient characteristics that should be taken into account, such as age, weight, and underlying pathology, and also the delay until MCS implementation as well as tissue hypoxia as prognostic factors. Relevant comorbidities included neurologic, renal, and hepatic disorders. Of note, baseline liver function tests predicted outcome in patients on extracorporeal life support (ECLS), including short-term and long-term mortality. Most strikingly, increased levels of alkaline phosphatase and total bilirubin indicated unfavourable short-term and long-term survival even after adjustment for age, gender, left ventricular function, and relevant known comorbidities such as impaired renal function and diabetes. Therefore, the assessment of liver function tests may be regarded as another piece in the complex puzzle of our efforts perceiving the ideal ECLS candidate with positive long-term outcome.

Concepts: Bile, Cirrhosis, Blood, Alkaline phosphatase, Hemoglobin, Bilirubin, Liver, Liver function tests

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Hepatitis B virus (HBV) RNA in serum has recently been linked to efficacy and prognosis of chronic hepatitis B (CHB) treatment. This study explored the nature, origin, underlying mechanisms, and potential clinical significance of serum HBV RNA.

Concepts: Interferon, Virus, Hepatitis A, Hepatitis C, Cirrhosis, Hepatitis, Hepatitis B

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Response-guided therapy has been confirmed to be an effective strategy for the treatment of chronic hepatitis C in the peginterferon (PegIFN) era, but no randomized trial utilizing this strategy has been conducted in chronic hepatitis B.

Concepts: Interferon, Hepatitis D, Hepatitis A, Cirrhosis, Hepatocellular carcinoma, Hepatitis, Hepatitis B, Hepatitis C

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p62 is a ubiquitin-binding autophagy receptor and signaling protein that accumulates in premalignant liver diseases and most hepatocellular carcinomas (HCCs). Although p62 was proposed to participate in the formation of benign adenomas in autophagy-deficient livers, its role in HCC initiation was not explored. Here we show that p62 is necessary and sufficient for HCC induction in mice and that its high expression in non-tumor human liver predicts rapid HCC recurrence after curative ablation. High p62 expression is needed for activation of NRF2 and mTORC1, induction of c-Myc, and protection of HCC-initiating cells from oxidative stress-induced death.

Concepts: Cell nucleus, Necessary and sufficient condition, Liver, DNA, Gene, Cirrhosis, Glucose, Cancer