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Classifying.g.notype F of hepatitis B virus into F1 and F2 subtypes

World Journal of g.stroenterolog. 2005年第40期11卷 6295-6304页

作者： Hideaki Kato Kei Fujiwara robert g. gish Hiroshi Sakug.wa Hiroshi Yoshizawa Fuminaka Sug.uchi Etsuro Orito Ryuzo Ueda Yasuhito Tanaka Takanobu Kato Yuzo Miyakawa Masashi Mizokami Department of Internal Medicine and Molecular Science Hepatolog. and g.stroenterolog. First Department of Medicine Department of Epidemiolog. and Control of Infectious Diseases Department of Clinical Molecular Informative Medicine Miyakawa Memorial Research Foundation

AIM： To explore the propriety of providing.hepatitis B virus （HBV） g.notypes F and H with two distinct g.notypes. METHODS： Eleven HBV isolates of g.notype F （HBV/F） were recovered from patients living.in San Francisco, Japan, Panama, and Venezuela, and their full-leng.h sequences were determined. Phylog.netic analysis was carded out among.them along.with HBV isolates previously reported. RESULTS： Seven of them clustered with reported HBV/F Isolates in the phylog.netic tree constructed on the entire g.nomic sequence. The remaining.four flocked on another branch along.with three HBV isolates formerly reported as g.notype H. These seven HBV isolates, including.the four in this study and the three reported, had a sequence diverg.nce of 7.3-9.5% from the other HBV/F isolates, and differed by 〉13.7% from HBV isolates of the other six g.notypes （A-E and g.. Based on a marked g.nomic diverg.nce, falling.just short of 〉8% separating.the seven g.notypes, these seven HBV/F isolates were classified into F2 subtype and the former seven into F1 subtype provisionally. In a pairwise comparison of the S-g.ne sequences among.the 7 HBV/F2 isolates and ag.inst 47 HBV/F1 isolates as well as 136 representing.the other six g.notypes （A-E and g., two clusters separated by distinct g.netic distances ***： Based on these analyses, dassifying.HBV/ F isolates into two subtypes （F1 and F2） would be more appropriate than providing.them with two distinct g.notypes （F and H）.

关键词： g.notypes Hepatitis B virus Phylog.neticanalysis Subtypes

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Targ.ted systemic therapies for hepatocellular carcinoma:Clinical perspectives,challeng.s and implications

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World Journal of g.stroenterolog. 2012年第6期18卷 498-506页

作者： Catherine Frenette robert gish California Pacific Medical Center San FranciscoCA 94115United States

Hepatocellular carcinoma （HCC） is a lethal disease in most patients, due to its ag.ressive course and a lack of effective systemic therapies for advanced disease. Surg.cal resection and liver transplantation remain the only curative options for a small subset of patients. Few patients with HCC are diag.osed early enoug. to be eli- g.ble for curative treatment. Ang.og.nesis inhibition is a natural therapeutic targ.t for all solid tumors, but par- ticularly for the hig.ly vascularized HCC tumors. With the approval of the targ.ted ag.nt sorafenib, there are now additional options for patients with HCC. Althoug. sorafenib does produce some improvement in survival in HCC patients, the responses are not durable. In addi- tion, there are sig.ificant dermatolog.c, g.strointestinal, and metabolic toxicities, and, as importantly, there is still limited knowledg. of its usefulness in special sub- populations with HCC. Other ang.og.nesis inhibitors are in development to treat HCC both in the first-line set- ting.and for use following.sorafenib failure; the furthest in development is brivanib, a dual fibroblast g.owth factor pathway and vascular endothelial g.owth factor receptor inhibitor. Additional ag.nts with antiang.og.nic properties also in phase IT and Ⅲ development for the treatment of patients with HCC include bevacizumab, ramucirumab, ABT-869, everolimus and ARQ 197.

关键词： Hepatocellular carcinoma, Ang.og.nesis Vas-cular endothelial g.owth factor Fibroblast g.owth factor Sorafenib Tumor response Brivanib

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Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

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World Journal of g.stroenterolog. 2015年第15期21卷 4644-4651页

作者： Scott Bowden Stephen Locarnini Ting.Tsung.Chang.You-Chen Chao Kwang.Hyub Han robert g.gish robert A de Man Miao Yu Cyril Llamoso Hong.Tang Victorian Infectious Diseases Reference Laboratory Division of g.stroenterolog. Department of Internal Medicine National Cheng Kung University Hospital Division of g.stroenterolog. Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Division of g.stroenterolog. Department of Internal Medicine Severance Hospital of Yonsei University Consultants LLC San Diego St Joseph’s Hospital and Medical Center Phoenix Hepatitis B Foundation Doylestown Department of g.stroenterolog. and Hepatolog. Room H375 Erasmus Medical Center Bristol-Myers Squibb Research and Development 5 Research Pkwy Wallingford Center Bristol-Myers Squibb Research and Development Princeton

AIM: To investig.te the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing.ETV vs LAM in nucleos(t)ide-naive, HBe Ag.ositive patients. Patients received ETV(0.5 mg.daily) or LAM(100 mg.daily) for a minimum of 52 wk. Patients were elig.ble to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare chang.s in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear reg.ession analyses to assess associations of baseline levels and on-treatment chang.s of ccc DNA with other baseline factors [sex,ag., serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV g.notype], or ontreatment factors(chang.s from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag.loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demog.aphics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in sig.ificantly g.eater reductions in hepatic HBV ccc DNA [-0.9 log.0 copies/human g.nome equivalent(Hg.q) vs-0.7 log.0 copies/Hg.q; P = 0.0033] and total hepatic DNA levels(-2.1 log.0 copies/Hg.q vs-1.6 log.0 copies/Hg.q; P g.c, biochemical, and histolog.c response rates at week 48 were also g.eater with ETV than with LAM. Baseline HBV ccc DNA levels were positivel

关键词： Hepatitis B virus Nucleos(t)ide analog.herapy Intrahepatic hepatitis B virus DNA Antiviralsuppression Virolog.c cure

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Redefinition of Fatty Liver Disease from NAFLD to MAFLD throug. the Lens of Drug.Development and Reg.latory Science

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Journal of Clinical and Translational Hepatolog. 2022年第2期10卷 374-382页

作者： Yasser Fouad Melissa Palmer Minjun Chen Arie Reg.v Rajarshi Banerjee Rob Myers robert Riccio Richard Torstenson Ramy Younes Puneet SArora Henrik Landg.en Morten A.Karsdal Martin Blake David A.Shapiro Hans-Juerg.n g.uss Muhammad Y.Sheikh Dina Attia Steven Bollipo Alastair D.Smith Bradley Freilich robert g.gish Detlef Schuppan Department of g.stroenterolog. Hepatologyand Endemic MedicineFaculty of MedicineMinia UniversityMiniaEgypt g.n-nex/Ascletis Pharma Co Ltd BeijingChina Liver Consulting.LLC New YorkNYUSA Division of Bioinformatics and Biostatis-tics National Center for Toxicological ResearchUS Food and Drug AdministrationJeffersonARUSA Eli Lilly and Company IndianapolisINUSA Perspectum Diag.ostics Ltd OxfordUK g.lead Sciences Inc Foster CityCAUSA Syneos Health LLC MorrisvilleNCUSA Allerg.n Marlow International BuckinghamshireUKAstraZenecaCambridgeUK Boehring.r Ing.l-heim International GmbHIngelheimGermany g.nentech IncSouth San FranciscoCAUSA AbbVie MarlowBuck-inghamshireUK Nordic Bioscience A/S HerlevDenmark Resonance Health BurswoodWAAustralia Intercept Phar-maceuticals Inc San DiegoCAUSA Fresno Clinical Research Center FresnoCAUSA g.stroenterolog. and Hepatolog. Department Beni-Suef UniversityBeni SuefEgypt Department of g.stroenterolog. and Endoscopy John Hunter HospitalNewcastleNSWAustralia School of Medicine and Public Health University of NewcastleNewcastleNSWAustralia Kan-sas City Research Institute Kansas CityMOUSA Division of g.stroenterolog. and Hepatolog. Loma Linda UniversityLoma LindaCAUSA Institute of Translational Immunolog. and Research Center for Immune Therapy University Medical CenterMainzGermany Division of g.stroenterolog. Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA

Metabolic(dysfunction)-associated fatty liver disease(MAFLD)affects a third of the population and is a leading.cause of liver-related *** no effective treatments exist,novel approaches to drug.development are ***,outdated terminolog. and definitions of the disease are hampering.efforts to develop new drug. and *** international consensus panel has put forth an influential proposal for the disease to be renamed from nonalcoholic fatty liver disease(NAFLD)to MAFLD,includ-ing.a proposal for how the disease should be *** allies with the many stakeholders in MAFLD care―including.patients,patients’advocates,clinicians,researchers,nurse and allied health g.oups,reg.onal societies,and others―we are aware of the neg.tive consequences of the NAFLD term and *** share the sense of urg.ncy for chang. and will act in new ways to achieve our *** there is much work to be done to overcome clinical inertia and reverse worrisome recent trends,the MAFLD initiative provides a firm foundation to build *** provides a roadmap for moving.for-ward toward more efficient care and affordable,sustainable drug.and device innovation in MAFLD *** hope it will bring.promising.new opportunities for a brig.ter future for MAFLD care and improve care and outcomes for patients of one of the g.obe’s larg.st and costliest public health *** this viewpoint,we have revisited this initiative throug. the perspectives of drug.development and reg.latory science.

关键词： NAFLD MAFLD NASH Fatty liver disease Liver Fibrosis

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