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Hepatobiliary Surgery and Nutrition 2018年第6期7卷 495-498页

作者： Carlos j.Pirola Silvia Sookoian School of Medicine Institute of Medical Research A LanariUniversity of Buenos AiresCiudad Autonoma de Buenos AiresArgentina Department of Molecular Genetics and Biology of Complex Diseases Institute of Medical Research(IDIM)University of Buenos Aires-National Scientific and Technical Research Council(CONICET)Ciudad Autónoma de Buenos AiresArgentina Department of Clinical and Molecular Hepatology Institute of Medical Research(IDIM)University of Buenos Aires-National Scientific and Technical Research Council(CONICET)Ciudad Autónoma de Buenos AiresArgentina

Nonalcoholic fatty liver disease(NAFLD)is regarded as the most frequent cause of chronic liver damage(1,2).The natural history of the disease presents a complex scenario of potential progression into severe clinical outcomes,including nonalcoholic steatohepatitis(nash),nash-fibrosis,cirrhosis,and hepatocellular carcinoma(1,2).In addition,NAFLD is closely associated with comorbidities of the metabolic syndrome(MetS),including type 2 diabetes,obesity,arterial hypertension,and dyslipidemia,which together aggravate the morbidity and mortality associated with the disease.

关键词： NAFLD liver arterial damage

Nonalcoholic steatohepatitis pharmacotherapy and predictors of response: dual role of aminotransferases as biosensors of metabolism and biomarkers of histological improvement

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Hepatobiliary Surgery and Nutrition 2019年第4期8卷 381-385页

作者： Silvia Sookoian Carlos j.Pirola School of Medicine Institute of Medical Research A.LanariUniversity of Buenos AiresBuenos AiresArgentina Department of Clinical and Molecular Hepatology National Scientific and Technical Research Council(CONICET)and University of Buenos AiresInstitute of Medical Research(IDIM)Buenos AiresCiudad Autónoma de Buenos Aires(C1427ARN)Argentina Department of Molecular Genetics and Biology of Complex Diseases National Scientific and Technical Research Council(CONICET)and University of Buenos AiresInstitute of Medical Research(IDIM)Buenos AiresCiudad Autónoma de Buenos Aires(C1427ARN)Argentina

Nonalcoholic steatohepatitis (nash)—the severe histological form of nonalcoholic fatty liver disease (NAFLD)—is regarded as a major health problem worldwide (1,2). The disease can progress to liver cirrhosis and eventually to hepatocellular carcinoma (1,3). Treatment of nash.and nash-fibrosis is thus increasingly being given priority in the clinical field. Yet, these efforts face challenges not only related to the design and validation of novel pharmacological agents, but also to the need to optimize treatment options as well as improve access to therapies. In fact, while many drugs are currently being tested for safety and efifcacy, only a few approved options for the treatment of nash presently exist (4,5). It is thus expected that, in the near future, emphasis will be given to selecting the right drug for treating nash patients from a wide spectrum of treatment choices. Hence, identiifcation of early predictors of treatment response represents an unmet and relevant need.

关键词： metabolism histological drugs

Considerations for bariatric surgery in patients with cirrhosis

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World journal of Gastroenterology 2018年第28期24卷 3112-3119页

作者： George Boon-Bee Goh Philip R Schauer Arthur j McCullough Department of Gastroenterology and Hepatology Singapore General HospitalSingapore 169608Singapore Duke-NUS Graduate Medical School Singapore 169608Singapore Bariatric and Metabolic Institute Cleveland ClinicClevelandOH 44195United States Department of Gastroenterology Cleveland ClinicClevelandOH 44195United States Department of Pathobiology Cleveland ClinicClevelandOH 44195United States

With the ever increasing global obesity pandemic, clinical burden from obesity related complications are anticipated in parallel. Bariatric surgery, a treatment approved for weight loss in morbidly obese patients, has reported to be associated with good outcomes, such as reversal of type two diabetes mellitus and reducing all-cause mortality on a long term basis. However, complications from bariatric surgery have similarly been reported. In particular, with the onslaught of non-alcoholic fatty liver disease(NAFLD) epidemic, in associated with obesity and metabolic syndrome, there is increasing prevalence of NAFLD related liver cirrhosis, which potentially connotes more risk of specific complications for surgery. Bariatric surgeons may encounter, either expectedly or unexpectedly, patients with non-alcoholic steatohepatitis(nash) and nash related cirrhosis more frequently. As such, the issues and considerations surrounding their medical care/surgery warrant careful deliberation to ensure the best outcomes. These considerations include severity of cirrhosis, liver synthetic function, portal hypertension and the impact of surgical factors. This review explores these considerations comprehensively and emphasizes the best approach to managing cirrhotic patients in the context of bariatric surgery.

关键词： Cirrhosis Portal hypertension Non-alcoholic fatty liver disease Bariatric surgery Complications

Future Pharmacotherapy for Non-alcoholic Steatohepatitis (nash): Review of Phase 2 and 3 Trials

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journal of Clinical and Translational Hepatology 2018年第3期6卷 264-275页

作者： james j.Connolly Kohtaro Ooka joseph K.Lim Department of Internal Medicine Yale University School of MedicineNew HavenCTUSA Division of Gastroenterology Hepatology and NutritionUniversity of Pittsburgh Medical CenterPittsburghPAUSA Yale Liver Center Section of Digestive DiseasesYale University School of MedicineNew HavenCTUSA

Non-alcoholic steatohepatitis(nash)results from inflammation and hepatocyte injury in the setting of hepatic ***-alcoholic steatohepatitis increases the risk of progression to liver fibrosis and cirrhosis,and is the most rapidly growing etiology for liver failure and indication for liver transplantation in the *** loss and lifestyle modification remain the standard first-line treatment,as no USA Food and Drug Administration-approved pharmacotherapy currently *** past decade has seen an explosion of interest in drug development targeting pathologic pathways in non-alcoholic steatohepatitis,with numerous phase 2 and 3 trials currently in ***,we concisely review the major targets and mechanisms of action by class,summarize results from com-pleted pivotal phase 2 studies,and provide a detailed outline of key active studies with trial data for drugs in development,including obeticholic acid,elafibranor,cenicriviroc and selonsertib.

关键词： Fatty liver Non-alcoholic steatohepatitis Clinical trials Pharmacotherapy Obeticholic acid

Review of nonalcoholic fatty liver disease in women with polycystic ovary syndrome

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World journal of Gastroenterology 2014年第39期20卷 14172-14184页

作者： Carly E Kelley Ann j Brown Anna Mae Diehl Tracy L Setji Department of Medicine Division of Endocrinology Duke University Medical Center Durham NC 27710 United States Department of Medicine Division of Gastroenterology Duke University Medical Center Durham NC 27710 United States

Polycystic ovary syndrome(PCOS) is the most common endocrine disorder in reproductive-aged women. Women with PCOS frequently have metabolic complications including insulin resistance(IR), early diabetes, hypertension and dyslipidemia. Recent studies have demonstrated an association between PCOS and another metabolic complication: nonalcoholic fatty liver disease(NAFLD). NAFLD occurs as a result of abnormal lipid handling by the liver, which sensitizes the liver to injury and inflammation. It can progress to nonalcoholic steatohepatitis(nash), which is characterized by hepatocyte injury and apoptosis. With time and further inflammation, nash can progress to cirrhosis. Thus, given the young age at which NAFLD may occur in PCOS, these women may be at significant risk for progressive hepatic injury over the course of their lives. Many potential links between PCOS and NAFLD have been proposed, most notably IR and hyperandrogenemia. Further studies are needed to clarify the association between PCOS and NAFLD. In the interim, clinicians should be aware of this connection and consider screening for NAFLD in PCOS patients who have other metabolic risk factors. The optimal method of screening is unknown. However, measuring alanine aminotransferase and/or obtaining ultrasound on high-risk patients can be considered. First line treatment consists of lifestyle interventions and weight loss, with possible pharmacologic interventions in some cases.

关键词： Polycystic ovary syndrome Fatty liver Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis

Impact of COVID-19 on Liver Transplant Activity in the USA: Variation by Etiology and Cirrhosis Complications

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journal of Clinical and Translational Hepatology 2023年第1期11卷 130-135页

作者： Yong-Fang Kuo Paul Kwo Robert j Wong Ashwani K.Singal Department of Biostatistics University of Texas Medical BranchGalvestonTXUSA Division of Gastroenterology and Hepatology Veterans Affairs Palo Alto Healthcare SystemStanford University School of MedicinePalo AltoCAUSA University of South Dakota Sanford School of MedicineVermillionSDUSA Avera Transplant Institute Sioux FallsSDUSA

Background and Aims:The COVID-19 pandemic has impacted the care of patients with liver *** examined impact of COVID-19 on liver transplant(LT)activity in the ***:LT listings in the United Network for Organ Sharing(UNOS)database(April 2018–May 2021)were analyzed to examine the impact of COVID-19 pandemic on the LT activity based on etiology:hepatitis C virus(HCV),alcohol-associated liver disease(ALD),alcoholic hepatitis(AH),and nonalcoholic steatohepatitis(nash)complications:hepatocellular carcinoma(HCC)and acute-on-chronic liver failure(ACLF)grade 2 or 3 and Model for End-Stage Liver Disease(MELD)*** regression models assessed time trend changes on a log ***:Of 23,871 recipients(8,995 in the COVID era,April 2018–February 2020),mean age 52 years,62% men,61% Caucasian,32%ALD,15%HCC,30%ACLF grades 2–3,and mean MELD score 20.5,monthly LT changes were a decrease of 3.4%for overall LTs and 22%for HCC after September 2020,and increase of 4.5%for ALD since 11/2020 and 17%since 03/2021 for ACLF grade 2–*** MELD scores increased by 0.7 and 0.36 after june 2020 for HCV and HCC ***:The COVID-19 pandemic has impacted LT activity,with a decrease of LTs especially for HCC,and an increase of LTs for ALD and severe *** are needed to reorganize cirrhosis patients to overcome the aftereffects of COVID-19 pandemic.

关键词： COVID-19 UNOS OLT Region Public policies

Non-alcoholic fatty liver disease: a narrative review of genetics

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The journal of Biomedical Research 2018年第6期32卷 389-400页

作者： Christopher j.Danford Zemin Yao Z.Gordon jiang Division of Gastroenterology and Hepatology Beth Israel Deaconess Medical Center Department of Biochemistry Microbiology and Immunology Ottawa Institute of Systems Biology University of Ottawa

Non-alcoholic fatty liver disease(NAFLD) is now the most common cause of chronic liver diseases worldwide. It encompasses a spectrum of disorders ranging from isolated hepatic steatosis to nonalcoholic steatohepatitis(nash),fibrosis, cirrhosis, and hepatocellular carcinoma. One of the key challenges in NAFLD is identifying which patients will progress. Epidemiological and genetic studies indicate a strong pattern of heritability that may explain some of the variability in NAFLD phenotype and risk of progression. To date, at least three common genetic variants in the PNPLA3, TM6 SF2, and GCKR genes have been robustly linked to NAFLD in the population. The function of these genes revealed novel pathways implicated in both the development and progression of NAFLD. In addition,candidate genes previously implicated in NAFLD pathogenesis have also been identified as determinants or modulators of NAFLD phenotype including genes involved in hepatocellular lipid handling, insulin resistance,inflammation, and fibrogenesis. This article will review the current understanding of the genetics underpinning the development of hepatic steatosis and the progression of nash. These newly acquired insights may transform our strategy to risk-stratify patients with NAFLD and to identify new potential therapeutic targets.

关键词： NAFLD nash genetics PNPLA3 TM6SF2 GCKR MBOAT7

Beyond the liver in patients with non-alcoholic fatty liver disease (NAFLD)——cause for concern?

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Hepatobiliary Surgery and Nutrition 2018年第2期7卷 138-142页

作者： Matthew j.Armstrong Geoffrey Haydon Wing-Kin Syn Liver Unit Queen Elizabeth University Hospital BirminghamBirminghamUK Centre for Liver Research NIHR Biomedical Research CentreUniversity of BirminghamBirminghamUK Section of Gastroenterology Ralph H Johnson Veterans Affairs Medical CenterCharlestonSouth CarolinaUSA Division of Gastroenterology and Hepatology Department of MedicineMedical University of South CarolinaCharlestonSouth CarolinaUSA

Non-alcoholic fatty liver disease(NAFLD)is a global public health problem and is the most common cause of chronic liver disease *** prevalence of NAFLD is approximately 30%,irrespective of ethnicity,and parallels the exponential rise of the obesity and diabetes *** active inflammatory and cell injury component of NAFLD,known as non-alcoholic steatohepatitis(nash),increases the risk of liver-related mortality by 5 to 10 times;but this is largely dependent on the extent of fibrosis(1,2).Despite this,cardiovascular disease(CVD)and extra-hepatic malignancy remain the commonest causes of death in these ***,non-surprisingly the last decade has seen the clinical focus switch from NAFLD as a solitary organ entity to a multi-systemic disease.

关键词： NAFLD liver mortality

Nuclear receptors and non-alcoholic fatty liver disease:An update

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Liver Research 2020年第2期4卷 88-93页

作者： Xiao Yang Frank j.Gonzalez Min Huang Huichang Bi Guangdong Provincial Key Laboratory of New Drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhouChina Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNIHBethesdaMDUSA

Non-alcoholic fatty liver disease(NAFLD)has become the leading cause of chronic liver disease in adults and children *** symptoms of NAFLD range from simple steatosis and non-alcoholic stea-tohepatitis(nash)to hepatic fibrosis or cirrhosis,even ultimately develops to hepatocellular *** receptors(NRs)are a superfamily of ligand-activated transcription factors,most of which are ligand-activated that control cellular homeostasis in the liver and other tissues.A growing number of studies demonstrated the important role of NRs in *** this review,the current findings on the role of NRs in NAFLD are summarized and future perspectives to target NRs for NAFLD are discussed.

关键词： Nuclear receptors(NRs) Non-alcoholic fatty liver disease(NAFLD) Pregnane X receptor(PXR) Constitutive androstane receptor(CAR) Farnesoid X receptor(FXR) Peroxisome proliferator activated receptor (PPAR) Liver X receptor(LXR)

Current Modalities of Fibrosis Assessment in Non-alcoholic Fatty Liver Disease

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journal of Clinical and Translational Hepatology 2017年第3期5卷 261-271页

作者： Mark CC Cheah Arthur j McCullough George Boon-Bee Goh Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Department of Gastroenterology Cleveland Clinic Ohio USA Department of Pathobiology Cleveland Clinic Ohio USA Department of Gastroenterology & Hepatology Singapore General Hospital Singapore Duke-NUS Medical School Singapore

Non-alcoholic fatty liver disease (NAFLD) is a burgeoning global health *** the subset of NAFLD patients with non-alcoholic steatohepatitis (nash),the presence of significant fibrosis at index assessment is associated with poor prognosis and increased ***,there is a growing need to accurately assess and stage *** biopsy,the current gold standard,has limitations with sampling error and is invasive,with associated inherent *** has led to a host of non-invasive means of assessing fibrosis,which has garnered relevance in a disease that requires serial assessment of fibrosis longitudinally over *** review discusses,comprehensively,the various tools available to the clinician for the assessment of fibrosis,including the various scoring systems used in liver biopsy,the non-invasive means of serum biomarkers,such as the highly-validated NAFLD fibrosis score,and the imaging-based modalities,such as transient elastography and magnetic resonance elastography.

关键词： NAFLD Fibrosis assessment Modalities