Disposition, layout og vejledning i udformning af kliniske ...
Non-alkoholisk fedtleversygdom (NAFLD): Diagnostik og behandlingForfattere og korrespondanceHenning Gr?nb?k (tovholder), Peter Thielsen, Konstantin Kazankov, Sara Heeb?ll, Sanne Dam Larsen, Synne Semb, Lars Peter Skovgaard Larsen, Peter Holland-Fischer, Th?ger Th?gersen, Jens Meldgaard Bruun (Dansk Endokrinologisk Selskab og Dansk Selskab for Adipositasforskning). Korrespondance: Professor Henning Gr?nb?k, Medicinsk Hepatogastroenterologisk Afdeling, Aarhus Universitetshospital, N?rrebrogade 44, 8000 Aarhus C. E-mail: henngroe@rm.dkStatusF?rste udkast: 01.07.2016Diskuteret p? Hindsgavl: 27.08 2016Korrigeret udkast:20.01 2017Endelig guideline:20.01 2017Guideline skal revideres senest:21.01 2021Afgr?nsning af emnet Non-alkoholisk fedtleversygdom (Non-Alcoholic Fatty Liver Disease, NAFLD) er den hyppigste leversygdom i den vestlige verden. NAFLD omfatter spektret fra simpel steatose (Non-Alcoholic fatty liver, NAFL) til steatohepatitis (Non-alcoholic steatohepatitis, NASH). Patienter med NASH kan udvikle fibrose (der kan progrediere til cirrose) og prim?r leverkr?ft (HCC). Det er vigtigt at diagnostisere NASH og vurdere behov for behandling. Denne guideline omhandler diagnosticering og behandling af NAFLD. Guidelinen omhandler ikke andre former for fedtleversygdom, f.eks. sekund?rt til alkohol, toxisk/medikamentel p?virkning eller sult/malnutrition. Quick-guideNAFLD skal mist?nkes ved udredning for transaminas?mi og steatose p?vist ved UL. Risikofaktorer for metabolisk syndrom (MetS) b?r identificeres og alkoholoverforbrug samt andre differential diagnoser udelukkes. Patienter med MetS b?r udredes for NAFLD.Simpel steatose (NAFL) p?virker ikke d?delighed mens NASH (s?rligt ved fibrose ≥ F2) er associeret med ?get leverrelateret morbiditet og mortalitet. Jo h?jere alder og jo flere risikofaktorer for MetS des st?rre er risikoen for fibrose. Serum fibrose scores (FIB-4 og NAFLD fibrosis score) og elastografi kan benyttes til at vurdere risiko for NASH og fibrose. Leverbiopsi anbefales til diagnostisk vurdering af patienter med h?j risiko for NASH og differentialdiagnoser. Leverbiopsi er den eneste metode, der sikkert kan skelne NAFL fra NASH og kvantitere fibrosegraden. Det anbefales at den histologiske vurdering st?tter sig til ”Steatosis, Activity and Fibrosis” (SAF) score i diagnosticering og NAFLD Activity Score (NAS) til vurdering af behandlingseffekt og opf?lgning. Den prim?re behandling af NAFLD best?r af livsstils?ndring (kost og motion) med henblik p? v?gttab og bedring af MetS. V?gttab > 3-10 % reducerer graden af steatose (> 3 %), inflammation (> 5-10 %) og fibrose (> 10 %).Der foreligger ikke sikker evidens for, at medicinsk behandling har gavnlig effekt p? kliniske endepunkter. Medicinsk behandling kan overvejes til behandling af NASH ved insufficient effekt af livsstilsintervention ved: 1) fibrose ≥ F2, 2) ?get risiko for progression af fibrose (alder > 50 ?r, MetS, ?get ALAT), eller 3) udtalt necroinflammatorisk aktivitet. Vitamin E kan overvejes til patienter uden diabetes. Til NASH patienter med diabetes kan overvejes pioglitazon under hensyntagen til risiko for bivirkninger inklusive v?gt?gning, kongestiv hjertesygdom, bl?recancer og frakturer.Bariatrisk kirurgi overvejes hvis ovenst?ende behandlinger er uden tilstr?kkelig effekt og patienten i ?vrigt opfylder kravene til bariatrisk kirurgi.Behandling af MetS er vigtig for patienter med NAFLD of f?lger g?ldende retningslinjer.NAFLD er associateret med en ?get risiko for udvikling af HCC, men der er ikke sikker evidens for screening for HCC.Figur 1: Flowchart for udredning af patienter med mistanke om NAFLD/NASH1) Levertal: ALAT, ASAT, γ-Glutamyltransferase (γ-GT). 2) Serum fibrose mark?rer (se Tabel 1 Appendiks): FIB-4, NAFLD Fibrosis Score (ELF, FibroTest).3) Vejledning for udredning af NAFLD-patienter.Prim?r udredning:Dispositioner til MetS (diabetes, hypertension, hyperlipid?mi, hjertekarsygdom, polycystisk ovarie syndrom)Taljem?l, h?jde, v?gt, BMI, v?gt?gningAlkohol indtag: < 20 g/dag for kvinder, < 30 g/dag for m?ndMedicin inkl. naturmedicin anamneseH?moglobin, leukocytter, trombocytterSerum total og HDL-kolesterol, triglyceridFaste blodsukker, HbA1c, faste insulin/c-peptidUdelukkelse af hepatitis B og C infektionJern, ferritin og transferrin (jernm?tning)Autoimmune mark?rer (IgG, IgM, IgA, glatmuskelcelle antistof, anti-mitokondrie antistof, antinukl?re antistoffer)Ultralydsskanning af leveren.Udvidet udredningsprogram:Tests for c?liaki og stofskiftesygdom, polycystisk ovarie syndrom;Tests for sj?ldne lever sygdomme hvis relevant (Wilson, α1-antitrypsin mangel, LAL-D).IndledningNAFLD er oftest en langsomt progredierende sygdom og den hyppigste leversygdom i vestlige lande og afficerer 17-46 %. Forekomst og sv?rhedsgrad er ?get hos ?ldre. NAFL uden inflammation og fibrose har en god prognose mens NASH har ?get morbiditet og mortalitet PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TaW5naDwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (1). Det er prim?rt tilstedev?relsen af fibrose i index leverbiopsien, som er korreleret med ?get mortalitet, levertransplantation og leverrelateret sygdom og d?d PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bbmd1bG88L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (4). NAFLD forekommer ogs? hos normalv?gtige, og her kan leversygdommen ogs? v?re progredierende. NAFLD hos normalv?gtige eller let overv?gtige ses is?r i udviklingslandene og er ikke n?dvendigvis ledsaget af MetS ADDIN EN.CITE <EndNote><Cite><Author>Vernon</Author><Year>2011</Year><RecNum>11628</RecNum><DisplayText>(5)</DisplayText><record><rec-number>11628</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463053442">11628</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Vernon, G.</author><author>Baranova, A.</author><author>Younossi, Z. M.</author></authors></contributors><auth-address>Department of Medicine, Center for Liver Diseases, Inova Fairfax Hospital, Falls Church, VA 22042, USA.</auth-address><titles><title>Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults</title><secondary-title>Aliment Pharmacol Ther</secondary-title></titles><periodical><full-title>Aliment Pharmacol Ther</full-title></periodical><pages>274-85</pages><volume>34</volume><number>3</number><keywords><keyword>Adult</keyword><keyword>Biopsy</keyword><keyword>Fatty Liver/diagnosis/*epidemiology</keyword><keyword>Humans</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Prevalence</keyword><keyword>Prognosis</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2011</year><pub-dates><date>Aug</date></pub-dates></dates><isbn>1365-2036 (Electronic)
0269-2813 (Linking)</isbn><accession-num>21623852</accession-num><urls><related-urls><url>;(5).Risikoen for udvikling af HCC ved NASH varierer fra 0,25 % til 7,6 % over 5 ?r. Patienter med NASH-associeret HCC er ?ldre og har hyppigere ko-morbiditet p? diagnose tidspunktet. Amerikanske studier rapporterer en HCC incidens p? 2,6 % hos patienter med NASH-cirrose og med stigende incidens. Et amerikansk populations studie af HCC patienter viser at ca. 60 % af HCC tilf?lde optr?der ved NAFLD og at NAFLD er den n?sthyppigste indikation for HCC-relateret levertransplantation ADDIN EN.CITE <EndNote><Cite><Author>Wong</Author><Year>2014</Year><RecNum>11629</RecNum><DisplayText>(6)</DisplayText><record><rec-number>11629</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463053503">11629</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wong, R. J.</author><author>Cheung, R.</author><author>Ahmed, A.</author></authors></contributors><auth-address>Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA; Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA.</auth-address><titles><title>Nonalcoholic steatohepatitis is the most rapidly growing indication for liver transplantation in patients with hepatocellular carcinoma in the U.S</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>2188-95</pages><volume>59</volume><number>6</number><keywords><keyword>Aged</keyword><keyword>Carcinoma, Hepatocellular/epidemiology/*etiology/surgery</keyword><keyword>Fatty Liver/*complications/epidemiology/surgery</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver Neoplasms/epidemiology/*etiology/surgery</keyword><keyword>Liver Transplantation/*statistics & numerical data</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Retrospective Studies</keyword><keyword>United States/epidemiology</keyword></keywords><dates><year>2014</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>24375711</accession-num><urls><related-urls><url>;(6). Der er ikke evidens for systematisk HCC screening i denne store risikopopulation eller NASH cirrose patienter ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). DefinitionerNAFLD er karakteriseret ved en ?get m?ngde af fedt i leveren (> 5 %) og er associeret med insulin resistens (IR) som led i MetS (Tabel 1). NAFLD omfatter to kliniske enheder: 1) Simpel steatose (NAFL), hvor der alene er fedtophobning i leveren uden eller med kun let lobul?r inflammation og 2) NASH, hvor der udover steatose ses hepatocyt ballooning samt lobul?r inflammation med risiko for udvikling af fibrose, cirrose samt HCC. (Tabel 1) ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7).Tabel 1KarakteristikaNAFLDKan v?re NAFL eller NASH. Associeret med MetS inclusive Taljem?l > 94/> 80 cm for m?nd/kvinderBlodtryk > 130/85 mm Hg eller i behandling for hypertensionFaste glukose > 5.6 mmol/L eller i behandling for diabetesSerum triglycerid > 1.7 mmol/LHDL-kolesterol < 1.0 (m?nd)/< 1.3 mmol/L (kvinder). NAFLGodartet prognose. Histologisk enten ren (simpel) steatose eller steatose og mild lobul?r inflammation.NASH?get lever-associereet mortalitet og morbiditet. ?get risiko for alvorlig hjertesygdom. Hisologisk ses steatose, hepatocyt ballooning, lobul?r inflammation. Fibrosegrad kan v?re ingen (F0), let (F1), signifikant (≥ F2), bro-fibrose (≥ F3) eller svarende til cirrose (F4).DifferentialdiagnoserHyppigeAlkoholToksisk/medikamentel (bl.a. prednisolon, ?strogen, tamoxifen)Kronisk hepatitis B eller CMindre hyppigeH?mokromatoseAutoimmun hepatitisAlfa-1 antitrypsin mangelC?liakiWilson’s sygdomA-/hypo-betalipoprotein?miLysosomal acid lipase deficiency (LAL-d)HypotyroidismeParenteral ern?ring.Tabel 2. EvidensniveauELRGHvilken billedteknik anbefales til at stille diagnosen leversteatose? Ultralydskanning kan anvendes 1bAMR spectroskopi eller kvantitativ MR proton-densitet fedt fraktion har h?jere sensitivitet og specificitet end UL, men anbefales ikke rutinem?ssigt.1bAHvorn?r skal man mist?nke NAFLD og NASH?Det anbefales at screene patienter med IR/MetS for NAFLD. Risiko for NAFLD ?ges successivt jo flere risikofaktorer for MetS som er til stede. 1bADiagnosen kr?ver udelukkelse af andre ?rsager til lever steatose eller leverp?virkning (Tabel 1).1bADiagnosticeringen af NASH giver vigtig prognostisk viden om risikoen for progression af sygdom, behov for monitorering og behandlings indikation.1bAAnvendelse af leverbiopsi i diagnosen NAFL/NASH? Leverbiopsi er eneste sikre metode til at skelne NAFL fra NASH og vurdere fibrosegrad. Ved ?get risiko for NASH anbefales leverbiopsi.1bADet anbefales, at st?tte sig til SAF score mhp. at stille diagnosen og Kleiner fibrose score til at vurdere graden af fibrose. NASH diagnosen stilles ved en leverbiopsi, der viser steatose, hepatocyt ballooning og lobul?r inflammation.1bANAS score anbefales til vurdering af behandlingseffekt og opf?lgning n?r NASH diagnosen er stillet.1bAHvilke non-invasive metoder kan anvendes til vurdering af graden af fibrose ved NASH? Sammensatte fibrose scores (FIB-4 og NAFLD fibrosis score) og elastografi kan anvendes til at identificere patienter med lav eller h?j risiko for betydende fibrose og til at monitorere fibrosegraden.1bAHos patienter med h?j risiko for progression af fibrose anbefales leverbiopsi (se ovenfor).2bBFibrose scores og samtidig elastografi styrker muligvis den diagnostiske n?jagtighed. 2aBKan livsstilsintervention anvendes ved NAFLDV?gttab opn?et via livsstilsintervention (kost og motion) anbefales som den prim?re behandling af NAFL og NASH.1bAHos nogle patienter med NASH kan v?gttab p? mindst 7% medf?re reduktion af fibrose.1bADer er ikke evidens for fysisk tr?ning uden kost?ndring til behandling af NASH.1bAHvilken farmakologisk intervention kan anvendes til behandling af NAFLD?Der er ikke evidens for farmakologisk behandling af patienter med NAFL.2cBMedicinsk behandling af NASH kan overvejes ved fibrose ≥F2 eller risikofaktorer (DM, MetS, ALAT forh?jelse eller betydende necroinflammation). 2bBVitamin E behandling (800 IU/dag) kan overvejes under hensyntagen til risiko for prostata cancer.2bBPioglitazon (30-45 mg/dag) kan overvejes til behandling samtidig diabetes under hensyntagen til risiko for bivirkninger inklusive v?gt?gning, kongestiv hjertesygdom, bl?recancer og frakturer.2aBDet er uafklaret hvor l?nge behandling b?r p?g? og hvilke metoder, der egner sig til behandlingsmonitorering. Man kan overveje at stoppe behandlingen, hvis der ikke ses fald i ALAT hos patienter med transaminas?mi ved behandlingsstart.3BBNon-farmakologisk og farmakologisk behandling af komorbiditet anbefales vedr?rende diabetes, hypertension, hyperlipid?m, overv?gt og isk?misk hjertesygdom.2aADer er ikke tilstr?kkelig evidens for at anbefale rutinem?ssig behandling med obeticholsyre (FXR agonist) eller liraglutid (GLP-1 analog).3BCKan bariatrisk kirurgi anvendes i behandling af NASH?Der er ikke sikker evidens for at tilbyde bariatrisk kirurgi til patienter med NASH med mindre patienterne opfylder de accepterede kriterier.2aBI henhold til Centre for Evidence Based Medicine, University of OxfordEmneopdelt gennemgangHvorn?r skal man mist?nke NAFLD og hvorledes skelner man mellem NAFL og NASH? NAFLD b?r mist?nkes ved tilf?ldigt fund af transaminas?mi i screeningsblodpr?ver, leversteatose ved abdominal UL unders?gelse, eller ved forekomsten af tilstande som er ledsaget af ?get risiko for NAFLD; prim?rt faktorer, der indg?r i MetS (Tabel 1). NAFLD er oftest asymptomatisk eller viser sig ved uspecifikke symptomer som tr?thed og abdominalt ubehag ADDIN EN.CITE <EndNote><Cite><Author>Angulo</Author><Year>2002</Year><RecNum>235</RecNum><DisplayText>(8)</DisplayText><record><rec-number>235</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1309711806">235</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Angulo, P.</author></authors></contributors><titles><title>Nonalcoholic fatty liver disease</title><secondary-title>N.Engl.J.Med.</secondary-title></titles><periodical><full-title>N.Engl.J.Med.</full-title></periodical><pages>1221-1231</pages><volume>346</volume><number>16</number><reprint-edition>NOT IN FILE</reprint-edition><keywords><keyword>Biopsy</keyword><keyword>diagnosis</keyword><keyword>Disease</keyword><keyword>etiology</keyword><keyword>Fatty Liver</keyword><keyword>Gastroenterology</keyword><keyword>Humans</keyword><keyword>Liver</keyword><keyword>Liver Function Tests</keyword><keyword>pathology</keyword><keyword>Prevalence</keyword><keyword>radiography</keyword><keyword>Risk Factors</keyword><keyword>therapy</keyword><keyword>Ultrasonography</keyword><keyword>Weight Loss</keyword></keywords><dates><year>2002</year></dates><urls></urls></record></Cite></EndNote>(8). 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ADDIN EN.CITE.DATA (11, 12). Den histologiske unders?gelse vil endvidere kunne kvantificere graden af levercelleskade (ballooning og apoptose), inflammation (celletype og lokalisation) og fibrose (lokalisation og udbredning). NASH forekommer, n?r der er samtidig forekomst af steatose, ballooning og lobul?r inflammation ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). Disse variabler indg?r i sammensatte scores NAFLD Activity Score (NAS) ADDIN EN.CITE <EndNote><Cite><Author>Kleiner</Author><Year>2005</Year><RecNum>11642</RecNum><DisplayText>(12)</DisplayText><record><rec-number>11642</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463054433">11642</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kleiner, D. E.</author><author>Brunt, E. M.</author><author>Van Natta, M.</author><author>Behling, C.</author><author>Contos, M. J.</author><author>Cummings, O. W.</author><author>Ferrell, L. D.</author><author>Liu, Y. C.</author><author>Torbenson, M. S.</author><author>Unalp-Arida, A.</author><author>Yeh, M.</author><author>McCullough, A. J.</author><author>Sanyal, A. J.</author><author>Nonalcoholic Steatohepatitis Clinical Research, Network</author></authors></contributors><auth-address>Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA. KleinerD@mail.</auth-address><titles><title>Design and validation of a histological scoring system for nonalcoholic fatty liver disease</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>1313-21</pages><volume>41</volume><number>6</number><keywords><keyword>Adult</keyword><keyword>Child</keyword><keyword>Fatty Liver/*pathology</keyword><keyword>Fibrosis</keyword><keyword>Humans</keyword><keyword>Inflammation/pathology</keyword><keyword>Liver/*pathology</keyword><keyword>Logistic Models</keyword><keyword>Observer Variation</keyword><keyword>*Severity of Illness Index</keyword></keywords><dates><year>2005</year><pub-dates><date>Jun</date></pub-dates></dates><isbn>0270-9139 (Print)
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ADDIN EN.CITE.DATA (13, 14). NAS score har i sig selv ikke nogen prognostisk v?rdi, men er vist effektiv til vurdering af behandlingsrespons. SAF score er enkel at anvende og har ?get reproducerbarheden for at stille diagnosen, men er ikke sikkert prognostisk valideret. Anvendelse af non-invasive metoder til diagnosticering af NASH: Der findes ingen validerede non-invasive metoder til at skelne NAFLD og NASH. Der er udviklet flere sammensatte scores, men disse er typisk d?rlige til at skelne mellem NASH og ikke-NASH eller ikke validerede. For en samlet liste henvises til EASL guideline ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
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ADDIN EN.CITE.DATA (16). Anvendelse af biokemiske tests til bestemmelse af fibrose: Graden af fibrose er en vigtig prognostisk faktor og relaterer sig til forekomsten af lever relaterede komplikationer og mortalitet ADDIN EN.CITE <EndNote><Cite><Author>Ekstedt</Author><Year>2015</Year><RecNum>11614</RecNum><DisplayText>(3)</DisplayText><record><rec-number>11614</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463053253">11614</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ekstedt, M.</author><author>Hagstrom, H.</author><author>Nasr, P.</author><author>Fredrikson, M.</author><author>Stal, P.</author><author>Kechagias, S.</author><author>Hultcrantz, R.</author></authors></contributors><auth-address>Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.</auth-address><titles><title>Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>1547-54</pages><volume>61</volume><number>5</number><keywords><keyword>Cohort Studies</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/complications/*mortality</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Non-alcoholic Fatty Liver Disease/complications/*mortality/*pathology</keyword><keyword>Prognosis</keyword><keyword>Severity of Illness Index</keyword><keyword>Time Factors</keyword></keywords><dates><year>2015</year><pub-dates><date>May</date></pub-dates></dates><isbn>1527-3350 (Electronic)
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ADDIN EN.CITE.DATA (17) og NAFLD Fibrosis Score ADDIN EN.CITE <EndNote><Cite><Author>Shah</Author><Year>2009</Year><RecNum>11652</RecNum><DisplayText>(18)</DisplayText><record><rec-number>11652</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055410">11652</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Shah, A. G.</author><author>Lydecker, A.</author><author>Murray, K.</author><author>Tetri, B. N.</author><author>Contos, M. J.</author><author>Sanyal, A. J.</author><author>Nash Clinical Research, Network</author></authors></contributors><auth-address>Division of Gastroenterology, Department of Internal Medicine, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.</auth-address><titles><title>Comparison of noninvasive markers of fibrosis in patients with nonalcoholic fatty liver disease</title><secondary-title>Clin Gastroenterol Hepatol</secondary-title></titles><periodical><full-title>Clin Gastroenterol Hepatol</full-title></periodical><pages>1104-12</pages><volume>7</volume><number>10</number><keywords><keyword>Adult</keyword><keyword>Age Factors</keyword><keyword>Alanine Transaminase/blood</keyword><keyword>Aspartate Aminotransferases/blood</keyword><keyword>Biomarkers</keyword><keyword>*Diagnostic Techniques and Procedures</keyword><keyword>Fatty Liver/*complications</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/*diagnosis</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Platelet Count</keyword><keyword>Predictive Value of Tests</keyword><keyword>ROC Curve</keyword></keywords><dates><year>2009</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1542-7714 (Electronic)
1542-3565 (Linking)</isbn><accession-num>19523535</accession-num><urls><related-urls><url>;(18) er simple at anvende ud fra standard biokemi og kliniske parametre, og valideret i flere studiepopulationer. F?lles for disse metoder er, at de er bedst til at skelne mellem forekomsten sv?r eller ingen fibrose. Derudover er den negative pr?diktive v?rdi for at ekskludere sv?r (≥ F3) fibrose bedre end den positive pr?diktive v?rdi for forekomsten af fibrose. S?ledes kan disse tests udpege patienter med lav risiko for fibrose, hvorimod identificeringen af patienter med betydende fibrose er beh?ftet med st?rre usikkerhed ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). Der findes to kommercielle assays Enhanced Liver Fibrosis (ELF) score (TIMP-1, PIIINP og hyaluronsyre) og FibroTest (Alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, γ-glutamyltransferase, bilirubin, ALAT) der ogs? er vist at pr?diktere leverrelateret d?delighed ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). Disse anvendes ikke rutinem?ssigt i klinisk praksis. Anvendelse af billedteknikker til bestemmelse af steatose og fibrose: Ingen billeddiagnostisk metode kan vurdere tilstedev?relsen eller graden af NASH, men det er muligt at anvende billeddiagnostik til at vurdere graden af steatose og fibrose. Steatose kan p?vises ved b?de UL, CT- og MR-scanning. MR spectroskopi betragtes som guld standard billedmodalitet for p?visning af lever steatose. MR spectroskopi registrerer data fra en begr?nset omr?de at leveren mens en ny MR teknik, kvantitativ MR proton-density fedt fraktion, kan estimere fedtfraktionen st?rre dele af leveren. Men da UL er den hurtigste, billigste og nemmmeste metode til bestemmelse af steatose, er det den mest anvendte. Ved moderat og sv?r steatose (fedtindhold > 20 %) har ultralyd h?j sensitivitet (85 %) og specificitet (93 %) med AUROC p? 0,93. Dette er p? h?jde med CT og MR ADDIN EN.CITE <EndNote><Cite><Author>Hernaez</Author><Year>2011</Year><RecNum>11606</RecNum><DisplayText>(19)</DisplayText><record><rec-number>11606</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1462915637">11606</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Hernaez, R.</author><author>Lazo, M.</author><author>Bonekamp, S.</author><author>Kamel, I.</author><author>Brancati, F. L.</author><author>Guallar, E.</author><author>Clark, J. M.</author></authors></contributors><auth-address>Department of Medicine The Johns Hopkins School of Medicine, Baltimore, MD 21287, USA. rhernae1@jhmi.edu</auth-address><titles><title>Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>1082-90</pages><volume>54</volume><number>3</number><keywords><keyword>Fatty Liver/pathology/*ultrasonography</keyword><keyword>Humans</keyword><keyword>Reproducibility of Results</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2011</year><pub-dates><date>Sep 2</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>21618575</accession-num><urls><related-urls><url>;(19). Fibrose er den vigtigste mark?r for sv?rhedsgraden af NASH ADDIN EN.CITE <EndNote><Cite><Author>Ekstedt</Author><Year>2015</Year><RecNum>11614</RecNum><DisplayText>(3)</DisplayText><record><rec-number>11614</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463053253">11614</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Ekstedt, M.</author><author>Hagstrom, H.</author><author>Nasr, P.</author><author>Fredrikson, M.</author><author>Stal, P.</author><author>Kechagias, S.</author><author>Hultcrantz, R.</author></authors></contributors><auth-address>Department of Clinical and Experimental Medicine, Linkoping University, Linkoping, Sweden.</auth-address><titles><title>Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>1547-54</pages><volume>61</volume><number>5</number><keywords><keyword>Cohort Studies</keyword><keyword>Female</keyword><keyword>Follow-Up Studies</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/complications/*mortality</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Non-alcoholic Fatty Liver Disease/complications/*mortality/*pathology</keyword><keyword>Prognosis</keyword><keyword>Severity of Illness Index</keyword><keyword>Time Factors</keyword></keywords><dates><year>2015</year><pub-dates><date>May</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>25125077</accession-num><urls><related-urls><url>;(3). Der findes flere forskellig ultralydsbaserede elastografiske metoder til fibrosevurdering ved NASH, og den meste udbredte er transient elastografi (TE) evt. med Fibroscan?. Elastografi er p?virkelig af faktorer som f?deindtag (< 4 timer) forud for elastografi, p?g?ende inflammation, kolestase og h?jresidigt hjertesvigt, der kan ?ge leverens stivhed og give et falsk positivt resultat ADDIN EN.CITE <EndNote><Cite><Author>Castera</Author><Year>2010</Year><RecNum>11607</RecNum><DisplayText>(20)</DisplayText><record><rec-number>11607</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1462915731">11607</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Castera, L.</author><author>Foucher, J.</author><author>Bernard, P. H.</author><author>Carvalho, F.</author><author>Allaix, D.</author><author>Merrouche, W.</author><author>Couzigou, P.</author><author>de Ledinghen, V.</author></authors></contributors><auth-address>Services d'Hepato-gastroenterologie, Centre Hospitalo-Universitaire de Bordeaux, Hopital Haut Leveque, Avenue Magellan, 33604 Pessac, France. laurent.castera@chu-bordeaux.fr</auth-address><titles><title>Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>828-35</pages><volume>51</volume><number>3</number><keywords><keyword>*Elasticity Imaging Techniques/standards/statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver/*physiopathology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prospective Studies</keyword><keyword>Reproducibility of Results</keyword><keyword>Time Factors</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>20063276</accession-num><urls><related-urls><url>;(20). Det er endnu ikke entydigt vist om steatose i sig selv giver ?get stivhed ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). I en metaanalyse med NAFLD patienter viste TE f?lgende: For F ≥ 2 med cut-off 6.7-7.7 kPa var sensitivitet 67–94 %, specificitet 61–84 % (AUROC 0.79–0.87). For F ≥ 3 med cut-off 8.0–10.4 kPa var sensitivitet 65–100 % og specificitet 75–97 % (AUROC 0.76– 0.98). For F4 med cut-off 10.3–17.5 kPa var sensitivitet 78–100 %, specificitet 82–98 % (AUROC 0.91–0.99). Samlet estimat for diagnostisk sikkerhed var: F ≥ 2: sensitivitet 79 % og specificitet 75 %; F ≥ 3: sensitivitet 85 % og specificitet 85 %; og F4: sensitivitet 92 % og specificitet 92 % ADDIN EN.CITE <EndNote><Cite><Author>Kwok</Author><Year>2014</Year><RecNum>11858</RecNum><DisplayText>(21)</DisplayText><record><rec-number>11858</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1474915083">11858</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Kwok, R.</author><author>Tse, Y. K.</author><author>Wong, G. L.</author><author>Ha, Y.</author><author>Lee, A. U.</author><author>Ngu, M. C.</author><author>Chan, H. L.</author><author>Wong, V. W.</author></authors></contributors><auth-address>Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China; Department of Gastroenterology and Hepatology, Concord Repatriation Hospital, Sydney, Australia.</auth-address><titles><title>Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments</title><secondary-title>Aliment Pharmacol Ther</secondary-title></titles><periodical><full-title>Aliment Pharmacol Ther</full-title></periodical><pages>254-69</pages><volume>39</volume><number>3</number><keywords><keyword>Biomarkers/metabolism</keyword><keyword>Biopsy</keyword><keyword>Elasticity Imaging Techniques/*methods</keyword><keyword>Fatty Liver/*diagnosis/pathology</keyword><keyword>Humans</keyword><keyword>Keratin-18/*blood</keyword><keyword>Liver Cirrhosis/diagnosis/pathology</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Obesity/complications</keyword><keyword>Sensitivity and Specificity</keyword></keywords><dates><year>2014</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1365-2036 (Electronic)
0269-2813 (Linking)</isbn><accession-num>24308774</accession-num><urls><related-urls><url>;(21). Mest optimale cut-off for for at finde patienter med betydelig fibrose ved TE ligger s?ledes omkring 7,0-9.0 kPA. Der kan opn?s h?jere succesrate ved brug af XL-probe hos adip?se patienter, men pr?cisionen bedres ikke signifikant og det er bekymrende at op til 20 % af unders?gelserne har vist usikre fund ADDIN EN.CITE <EndNote><Cite><Author>Castera</Author><Year>2010</Year><RecNum>11607</RecNum><DisplayText>(20)</DisplayText><record><rec-number>11607</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1462915731">11607</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Castera, L.</author><author>Foucher, J.</author><author>Bernard, P. H.</author><author>Carvalho, F.</author><author>Allaix, D.</author><author>Merrouche, W.</author><author>Couzigou, P.</author><author>de Ledinghen, V.</author></authors></contributors><auth-address>Services d'Hepato-gastroenterologie, Centre Hospitalo-Universitaire de Bordeaux, Hopital Haut Leveque, Avenue Magellan, 33604 Pessac, France. laurent.castera@chu-bordeaux.fr</auth-address><titles><title>Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>828-35</pages><volume>51</volume><number>3</number><keywords><keyword>*Elasticity Imaging Techniques/standards/statistics & numerical data</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver/*physiopathology</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prospective Studies</keyword><keyword>Reproducibility of Results</keyword><keyword>Time Factors</keyword></keywords><dates><year>2010</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>20063276</accession-num><urls><related-urls><url>;(20). TE er dog en sikker metode til eksklusion af sv?r fibrose og cirrose med en negativ pr?diktiv v?rdi omkring 90 % ADDIN EN.CITE <EndNote><Cite><Author>Wong</Author><Year>2010</Year><RecNum>11663</RecNum><DisplayText>(22)</DisplayText><record><rec-number>11663</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463057091">11663</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Wong, V. W.</author><author>Vergniol, J.</author><author>Wong, G. L.</author><author>Foucher, J.</author><author>Chan, H. L.</author><author>Le Bail, B.</author><author>Choi, P. C.</author><author>Kowo, M.</author><author>Chan, A. W.</author><author>Merrouche, W.</author><author>Sung, J. J.</author><author>de Ledinghen, V.</author></authors></contributors><auth-address>Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China.</auth-address><titles><title>Diagnosis of fibrosis and cirrhosis using liver stiffness measurement in nonalcoholic fatty liver disease</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>454-62</pages><volume>51</volume><number>2</number><keywords><keyword>*Elasticity Imaging Techniques</keyword><keyword>Fatty Liver/*complications</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Liver Cirrhosis/*complications/*diagnosis</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Prospective Studies</keyword><keyword>Reproducibility of Results</keyword><keyword>Risk Factors</keyword></keywords><dates><year>2010</year><pub-dates><date>Feb</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>20101745</accession-num><urls><related-urls><url>;(22). ?vrige ultralydsbaserede elastografiske metoder har den fordel, at man samtidig kan visualisere det omr?de, ”region of interest” (ROI), hvor der udf?res fibrosem?linger. Metoderne er integreret i et almindeligt ultralydsapparat og er baseret p? ”shear wave” elastografi. De mest anvendte principper er Acoustic-Radiation-Force-Impulse imaging (ARFI) og 2D-Shear Wave Elastography (SWE). Der er kun f? og sm? studier, der sammenligner ARFI, SWE og TE, men studierne viser, at metoderne tilsyneladende er ligev?rdige i vurderingen af fibrosegrad ved NAFLD PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Zb25lZGE8L0F1dGhvcj48WWVhcj4yMDEwPC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (23, 24). Vedr. elastografiske unders?gelser skal man v?re opm?rksom p? at v?rdierne er afh?ngige af den anvendte teknik og at der er forskel p? cut-off mellem fibroskanning med standard eller XL-probe lige som man ikke kan sammenligne v?rdier direkte med ARFI og SWE teknik. Et studie har vist at MR elastografi (MRE) til vurdering af fibrose ved NAFLD er mere pr?cis end TE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JbWFqbzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl
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ADDIN EN.CITE PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5JbWFqbzwvQXV0aG9yPjxZZWFyPjIwMTY8L1llYXI+PFJl
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b3RlPn==
ADDIN EN.CITE.DATA (25). Pris og den mere ufleksible unders?gelsesteknik har hidtidigt gjort modaliteten mindre egnet i daglig klinisk praksis. Kliniske rekommandationer 1 (se Tabel 2)Fund af NAFLD b?r f?re til udredning for MetS og omvendt.UL anbefales til at stille NAFLD diagnosen, da det er den enkleste og billigste metode at anvende.Diagnosen NAFLD stilles ved fund af steatose (billedunders?gelser eller leverbiopsi) og samtidig udelukkelse af andre ?rsager.Hos patienter med stor risiko for NASH og betydende fibrose anbefales leverbiopsi, der er den eneste sikre metode til at skelne NAFL fra NASH og til at vurdere fibrosegrad. NASH diagnosen stilles ved en leverbiopsi, der viser steatose, hepatocyt ballooning og lobul?r inflammation. Det anbefales under diagnosticering at st?tte sig SAF score og Kleiner fibrose score. Det anbefales at anvende NAS score til monitorering.Sammensatte fibrose scores (FIB-4 og NAFLD fibrosis score) eller elastografi kan identificere patienter med lav eller h?j risiko for betydende fibrose og til at monitorere fibrosegraden hos patienter med NASH. Samtidig anvendelse af fibrose scores og samtidig elastografi styrker muligvis den diagnostiske n?jagtighed. Kan livsstilsintervention anvendes til behandling af NASH? NAFLD betragtes som den hepatiske manifestation af MetS. NAFLD er t?t associeret med overv?gt og fysisk inaktivitet PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJjaGVzaW5pPC9BdXRob3I+PFllYXI+MTk5OTwvWWVh
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ADDIN EN.CITE.DATA (26). Livsstilsinterventioner i form af kost?ndringer og ?get fysisk aktivitet med henblik p? v?gttab og bedret metabolisk profil har derfor v?ret afpr?vet som behandlingsmuligheder for NAFLD og NASH. Prospektive unders?gelser har vist en positiv effekt af v?gttab p? fedtindholdet i leveren, og p? leverenzymer hos patienter med NAFLD ADDIN EN.CITE <EndNote><Cite><Author>Thoma</Author><Year>2012</Year><RecNum>362</RecNum><DisplayText>(27)</DisplayText><record><rec-number>362</rec-number><foreign-keys><key app="EN" db-id="sxdxa9s0vtx2ffett92xdzslxpxf29p5z5rp" timestamp="1461451565">362</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Thoma, C.</author><author>Day, C. P.</author><author>Trenell, M. I.</author></authors></contributors><auth-address>Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK.</auth-address><titles><title>Lifestyle interventions for the treatment of non-alcoholic fatty liver disease in adults: a systematic review</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><pages>255-66</pages><volume>56</volume><number>1</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Clinical Trials as Topic</keyword><keyword>Combined Modality Therapy</keyword><keyword>Diet Therapy</keyword><keyword>Exercise Therapy</keyword><keyword>Fatty Liver/pathology/physiopathology/*therapy</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Life Style</keyword><keyword>Lipid Metabolism</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Motor Activity</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Prospective Studies</keyword><keyword>Weight Reduction Programs</keyword></keywords><dates><year>2012</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>21723839</accession-num><urls><related-urls><url>;(27). Gennemg?ende har disse studier vist en signifikant reduktion i fedtindholdet i leveren ved et v?gttab p? 3-5 % af kropsv?gten, og med st?rre grad af reduktion med st?rre v?gttab. Studierne er prim?rt hospitalsbaserede og vurderet ved lever biopsi, men det er ogs? vist at v?re effektivt i prim?r sektoren vurderet ved MR spectroscopi. Livsstilintervention i form af kost?ndring, ?get fysisk aktivitet og ?ndring af adf?rd for opn?else af v?gttab har ogs? vist effekt p? NASH. Dette er vist i et randomiseret fors?g ADDIN EN.CITE <EndNote><Cite><Author>Promrat</Author><Year>2010</Year><RecNum>231</RecNum><DisplayText>(28)</DisplayText><record><rec-number>231</rec-number><foreign-keys><key app="EN" db-id="sxdxa9s0vtx2ffett92xdzslxpxf29p5z5rp" timestamp="1456696818">231</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Promrat, K.</author><author>Kleiner, D. E.</author><author>Niemeier, H. M.</author><author>Jackvony, E.</author><author>Kearns, M.</author><author>Wands, J. R.</author><author>Fava, J. L.</author><author>Wing, R. R.</author></authors></contributors><auth-address>Division of Gastroenterology and Hepatology, The Warren Alpert Medical School of Brown University, Providence, RI 02903, USA. Kittichai_Promrat@Brown.edu</auth-address><titles><title>Randomized controlled trial testing the effects of weight loss on nonalcoholic steatohepatitis</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>121-129</pages><volume>51</volume><number>1</number><reprint-edition>NOT IN FILE</reprint-edition><keywords><keyword>Adult</keyword><keyword>Body Mass Index</keyword><keyword>complications</keyword><keyword>diet therapy</keyword><keyword>Fatty Liver</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>Inflammation</keyword><keyword>Life Style</keyword><keyword>Liver</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>Obesity</keyword><keyword>pathology</keyword><keyword>therapy</keyword><keyword>Weight Loss</keyword></keywords><dates><year>2010</year></dates><work-type>10.1002/hep.23276 doi</work-type><urls><related-urls><url>PM:19827166</url></related-urls></urls></record></Cite></EndNote>(28) og et kohorte studie PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5WaWxhci1Hb21lejwvQXV0aG9yPjxZZWFyPjIwMTU8L1ll
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ADDIN EN.CITE.DATA (30). Baseret p? prospektive studier anbefales NAFLD patienter en hypokalorisk di?t ADDIN EN.CITE <EndNote><Cite><Author>American Diabetes</Author><Year>2014</Year><RecNum>378</RecNum><DisplayText>(31)</DisplayText><record><rec-number>378</rec-number><foreign-keys><key app="EN" db-id="sxdxa9s0vtx2ffett92xdzslxpxf29p5z5rp" timestamp="1462539215">378</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>American Diabetes, Association</author></authors></contributors><titles><title>Standards of medical care in diabetes--2014</title><secondary-title>Diabetes Care</secondary-title></titles><periodical><full-title>Diabetes Care</full-title></periodical><pages>S14-80</pages><volume>37 Suppl 1</volume><keywords><keyword>Delivery of Health Care/*standards</keyword><keyword>Diabetes Mellitus/*diagnosis/*therapy</keyword><keyword>Humans</keyword></keywords><dates><year>2014</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1935-5548 (Electronic)
0149-5992 (Linking)</isbn><accession-num>24357209</accession-num><urls><related-urls><url>;(31) f.eks. med underskud af 500–1000 kcal/dag. Til vedligeholdelse af v?gttab kan almindelig varieret kost anbefales og med nedsat forbrug af cholesterol, m?ttede fedtsyrer, trans-fedtsyrer (findes i ”junkfood”) og fruktose, som bla findes i l?skedrikke. Det anbefales at kombinere di?t og fysisk aktivitet. En metaanalyse fra 2012 af 12 studier, viste en mulig effekt af fysisk tr?ning p? fedtindholdet i leveren ADDIN EN.CITE <EndNote><Cite><Author>Keating</Author><Year>2012</Year><RecNum>136</RecNum><DisplayText>(32)</DisplayText><record><rec-number>136</rec-number><foreign-keys><key app="EN" db-id="sxdxa9s0vtx2ffett92xdzslxpxf29p5z5rp" timestamp="1456696817">136</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Keating, S. E.</author><author>Hackett, D. A.</author><author>George, J.</author><author>Johnson, N. A.</author></authors></contributors><auth-address>Discipline of Exercise and Sport Science, University of Sydney, Australia</auth-address><titles><title>Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis</title><secondary-title>J.Hepatol.</secondary-title></titles><periodical><full-title>J.Hepatol.</full-title></periodical><pages>157-166</pages><volume>57</volume><number>1</number><reprint-edition>NOT IN FILE</reprint-edition><keywords><keyword>Adult</keyword><keyword>Australia</keyword><keyword>Diet</keyword><keyword>Exercise</keyword><keyword>Exercise Therapy</keyword><keyword>Fatty Liver</keyword><keyword>Humans</keyword><keyword>Liver</keyword><keyword>methods</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Obesity</keyword><keyword>physiology</keyword><keyword>physiopathology</keyword><keyword>Resistance Training</keyword><keyword>therapy</keyword><keyword>Weight Loss</keyword><keyword>Weight Reduction Programs</keyword></keywords><dates><year>2012</year></dates><work-type>S0168-8278(12)00210-3 pii ;10.1016/j.jhep.2012.02.023 doi</work-type><urls><related-urls><url>PM:22414768</url></related-urls></urls></record></Cite></EndNote>(32). Den fysiske aktivitet kan b?de best? af konditionstr?ning og styrketr?ning og to randomiserede studier har vist effekt p? steatose, leverenzymer, IR og den metaboliske profil uafh?ngigt af v?gttab PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5TdDwvQXV0aG9yPjxZZWFyPjIwMDk8L1llYXI+PFJlY051
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ADDIN EN.CITE.DATA (35, 36). Det er vist, at patienter med NAFLD har en meget forskellig og generelt ringe parathed til livsstils?ndringer og v?gttab ADDIN EN.CITE <EndNote><Cite><Author>Centis</Author><Year>2013</Year><RecNum>358</RecNum><DisplayText>(37)</DisplayText><record><rec-number>358</rec-number><foreign-keys><key app="EN" db-id="sxdxa9s0vtx2ffett92xdzslxpxf29p5z5rp" timestamp="1461443046">358</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Centis, E.</author><author>Moscatiello, S.</author><author>Bugianesi, E.</author><author>Bellentani, S.</author><author>Fracanzani, A. L.</author><author>Calugi, S.</author><author>Petta, S.</author><author>Dalle Grave, R.</author><author>Marchesini, G.</author></authors></contributors><auth-address>Unit of Metabolic Diseases and Clinical Dietetics, Alma Mater Studiorum University, Bologna, Italy.</auth-address><titles><title>Stage of change and motivation to healthier lifestyle in non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><pages>771-7</pages><volume>58</volume><number>4</number><keywords><keyword>Adult</keyword><keyword>Aged</keyword><keyword>Diet</keyword><keyword>Fatty Liver/*psychology/*therapy</keyword><keyword>Female</keyword><keyword>Health Behavior</keyword><keyword>Humans</keyword><keyword>*Life Style</keyword><keyword>Male</keyword><keyword>Middle Aged</keyword><keyword>*Motivation</keyword><keyword>Motor Activity</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Young Adult</keyword></keywords><dates><year>2013</year><pub-dates><date>Apr</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>23201248</accession-num><urls><related-urls><url>;(37), og det kr?ver en koordineret indsats fra sundhedspersonale at informere patienterne grundigt om sygdomsenheden NAFLD/NASH og motivere dem til livstils?ndringer; muligvis skal tv?rfaglig indsats med f.eks. di?tister tages i brug.Kliniske rekommandationer 2Livsstilsintervention, der omfatter kost?ndringer (hypokalorisk di?t med underskud af 500–1000 kcal/dag) og fysisk aktivitet (konditionstr?ning eller styrketr?ning 150-200 min/uge) m?lrettet mod v?gttab kan anbefales til alle patienter med NAFLD; V?gttab p? > 5 % kan v?re tilstr?kkeligt for patienter med NAFLD mens patienter med NASH og fibrose b?r opn? et v?gttab > 10 %;Fysisk tr?ning uden v?gttab kan muligvis reducere fedtindholdet i leveren; der er ikke evidens for forbedring i inflammation eller fibrose ved fysisk tr?ning uden di?t.Hvilken medicinsk behandling kan anvendes til NASH?M?let for medicinsk behandling er at forbedre patienternes livskvalitet og prognose og kan overvejes hvis livsstilsintervention alene ikke har haft tilstr?kkelig effekt. Vigtige endepunkter er udvikling af cirrose, HCC og lever-relateret og cardiovaskul?r d?d. Derfor er der ikke indikation for behandling af NAFL. Risikoen ?get mortalitet og morbiditet er s?rligt ?get hos patienter med NASH og fibrose PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Bbmd1bG88L0F1dGhvcj48WWVhcj4yMDE1PC9ZZWFyPjxS
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ADDIN EN.CITE.DATA (38). Af samme ?rsag er det aktuelt vanskeligt at give specifikke behandlings rekommandationer ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). De gennemf?rte randomiserede fors?g har v?ret alt for korte til at estimere effekt p? kliniske endepunkter. Der er hverken fundet effekt af behandling p? udvikling af cirrose, HCC eller d?d. P? baggrund af naturhistorien er det vanskeligt at gennemf?re fors?g der har tilstr?kkeligt lang follow up og derfor er den kliniske relevans foreksllige endepunkter og surrogat endepunkter diskuteret ADDIN EN.CITE <EndNote><Cite><Author>Sanyal</Author><Year>2011</Year><RecNum>10099</RecNum><DisplayText>(39)</DisplayText><record><rec-number>10099</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1315519607">10099</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sanyal, A. J.</author><author>Brunt, E. M.</author><author>Kleiner, D. E.</author><author>Kowdley, K. V.</author><author>Chalasani, N.</author><author>Lavine, J. E.</author><author>Ratziu, V.</author><author>McCullough, A.</author></authors></contributors><auth-address>Department of Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA. asanyal@mcvh-vcu.edu</auth-address><titles><title>Endpoints and clinical trial design for nonalcoholic steatohepatitis</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>344-53</pages><volume>54</volume><number>1</number><edition>2011/04/27</edition><dates><year>2011</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>21520200</accession-num><urls><related-urls><url>;(39). Det prim?re accepterede surrogat endepunkt er histologi med hovedv?gt p? fibrosegrad ADDIN EN.CITE <EndNote><Cite><Author>Sanyal</Author><Year>2011</Year><RecNum>10099</RecNum><DisplayText>(39)</DisplayText><record><rec-number>10099</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1315519607">10099</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Sanyal, A. J.</author><author>Brunt, E. M.</author><author>Kleiner, D. E.</author><author>Kowdley, K. V.</author><author>Chalasani, N.</author><author>Lavine, J. E.</author><author>Ratziu, V.</author><author>McCullough, A.</author></authors></contributors><auth-address>Department of Gastroenterology, Virginia Commonwealth University, Richmond, VA, USA. asanyal@mcvh-vcu.edu</auth-address><titles><title>Endpoints and clinical trial design for nonalcoholic steatohepatitis</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>344-53</pages><volume>54</volume><number>1</number><edition>2011/04/27</edition><dates><year>2011</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1527-3350 (Electronic)
0270-9139 (Linking)</isbn><accession-num>21520200</accession-num><urls><related-urls><url>;(39). Der foreligger ingen valide data for monitorering af behandling eller varighed ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7).Vitamin EVitamin E (α-tocopherol) modvirker oxidativt stress, der anses som en grundl?ggende faktor i NASH patogenesen. I Danmark forhandles E vitamin i h?ndk?b som kapsler af 300-350 mg, sv. t. 500-525 IU pr kapsel. Effekten af E-vitamin i kombination med andre stoffer eller som monoterapi er unders?gt i en metaanalysesom ikke fandt overbevisende evidens ADDIN EN.CITE <EndNote><Cite><Author>Musso</Author><Year>2010</Year><RecNum>10084</RecNum><DisplayText>(40)</DisplayText><record><rec-number>10084</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1315519062">10084</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Musso, G.</author><author>Gambino, R.</author><author>Cassader, M.</author><author>Pagano, G.</author></authors></contributors><auth-address>Gradenigo Hospital, Turin, Italy. giovanni_musso@yahoo.it</auth-address><titles><title>A meta-analysis of randomized trials for the treatment of nonalcoholic fatty liver disease</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>79-104</pages><volume>52</volume><number>1</number><edition>2010/06/26</edition><keywords><keyword>Adult</keyword><keyword>Antioxidants/therapeutic use</keyword><keyword>Child</keyword><keyword>Fatty Liver/*drug therapy/pathology/radionuclide imaging</keyword><keyword>Humans</keyword><keyword>Middle Aged</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Thiazolidinediones/therapeutic use</keyword><keyword>Treatment Outcome</keyword></keywords><dates><year>2010</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1527-3350 (Electronic)
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ADDIN EN.CITE.DATA (42), hvilket antyder at ALAT kan bruges som biomark?r for histologisk behandlingseffekt. For patienter med transaminas?mi foresl?s s?ledes, at E vitamin seponeres hvis der ikke ses et signifikant fald i ALAT ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). Bivirkninger: Et Cochrane review fandt at h?jdosis E vitamin behandling generelt kan medf?re overd?delighed ADDIN EN.CITE <EndNote><Cite><Author>Bjelakovic</Author><Year>2012</Year><RecNum>244</RecNum><DisplayText>(43)</DisplayText><record><rec-number>244</rec-number><foreign-keys><key app="EN" db-id="v0dawfxe5ftswoear5yv5spfrrretdpatpdt" timestamp="1461182106">244</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Bjelakovic, G.</author><author>Nikolova, D.</author><author>Gluud, L. L.</author><author>Simonetti, R. G.</author><author>Gluud, C.</author></authors></contributors><auth-address>Department of InternalMedicine,Medical Faculty, University ofNis,Nis, Serbia. goranb@junis.ni.ac.rs.</auth-address><titles><title>Antioxidant supplements for prevention of mortality in healthy participants and patients with various diseases</title><secondary-title>Cochrane Database Syst Rev</secondary-title></titles><periodical><full-title>Cochrane Database Syst Rev</full-title></periodical><pages>CD007176</pages><volume>3</volume><keywords><keyword>Antioxidants/*administration & dosage/adverse effects</keyword><keyword>Ascorbic Acid/administration & dosage/adverse effects</keyword><keyword>Female</keyword><keyword>Health Status</keyword><keyword>Humans</keyword><keyword>Male</keyword><keyword>*Mortality</keyword><keyword>Primary Prevention/*methods</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Secondary Prevention/*methods</keyword><keyword>Selenium/administration & dosage/adverse effects</keyword><keyword>Vitamin A/administration & dosage/adverse effects</keyword><keyword>Vitamin E/administration & dosage/adverse effects</keyword><keyword>beta Carotene/administration & dosage/adverse effects</keyword></keywords><dates><year>2012</year></dates><isbn>1469-493X (Electronic)
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ADDIN EN.CITE.DATA (44). ThiazolidinedionerThiazolidinedioner er peroxisome proliferator-activated receptor (PPAR)-γ agonister, som is?r bedrer insulinf?lsomheden i fedtv?v og reducerer fris?tning af frie fedtsyrer til leveren. Pioglitazon er det eneste indregistrerede pr?parat, og det er godkendt til behandling af type 2 diabetes, sk?nt sj?ldent ordineret pga. risiko for bivirkninger. Effekten af pioglitazon er unders?gt i randomiserede studier med non-diabetiske og diabetiske NASH patienter ADDIN EN.CITE <EndNote><Cite><Author>Boettcher</Author><Year>2012</Year><RecNum>11677</RecNum><DisplayText>(45)</DisplayText><record><rec-number>11677</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1464338861">11677</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boettcher, E.</author><author>Csako, G.</author><author>Pucino, F.</author><author>Wesley, R.</author><author>Loomba, R.</author></authors></contributors><auth-address>Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.</auth-address><titles><title>Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis</title><secondary-title>Aliment Pharmacol Ther</secondary-title></titles><periodical><full-title>Aliment Pharmacol Ther</full-title></periodical><pages>66-75</pages><volume>35</volume><number>1</number><keywords><keyword>Fatty Liver/complications/*drug therapy</keyword><keyword>Humans</keyword><keyword>Hypoglycemic Agents/*therapeutic use</keyword><keyword>Liver/*drug effects</keyword><keyword>Liver Cirrhosis/*drug therapy</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Thiazolidinediones/*therapeutic use</keyword></keywords><dates><year>2012</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1365-2036 (Electronic)
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ADDIN EN.CITE.DATA (42). Studiet fandt ikke signifikant effekt p? det histologiske score. En meta-analyse som inkluderede tre randomiserede studier (pioglitazon 30-45 mg/dag) fandt en mulig effekt p? histologisk inflammation, men ikke fibrose ADDIN EN.CITE <EndNote><Cite><Author>Boettcher</Author><Year>2012</Year><RecNum>11677</RecNum><DisplayText>(45)</DisplayText><record><rec-number>11677</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1464338861">11677</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Boettcher, E.</author><author>Csako, G.</author><author>Pucino, F.</author><author>Wesley, R.</author><author>Loomba, R.</author></authors></contributors><auth-address>Division of Gastroenterology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA.</auth-address><titles><title>Meta-analysis: pioglitazone improves liver histology and fibrosis in patients with non-alcoholic steatohepatitis</title><secondary-title>Aliment Pharmacol Ther</secondary-title></titles><periodical><full-title>Aliment Pharmacol Ther</full-title></periodical><pages>66-75</pages><volume>35</volume><number>1</number><keywords><keyword>Fatty Liver/complications/*drug therapy</keyword><keyword>Humans</keyword><keyword>Hypoglycemic Agents/*therapeutic use</keyword><keyword>Liver/*drug effects</keyword><keyword>Liver Cirrhosis/*drug therapy</keyword><keyword>Non-alcoholic Fatty Liver Disease</keyword><keyword>Randomized Controlled Trials as Topic</keyword><keyword>Thiazolidinediones/*therapeutic use</keyword></keywords><dates><year>2012</year><pub-dates><date>Jan</date></pub-dates></dates><isbn>1365-2036 (Electronic)
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ADDIN EN.CITE.DATA (47) og frakturer ADDIN EN.CITE <EndNote><Cite><Author>Billington</Author><Year>2015</Year><RecNum>243</RecNum><DisplayText>(48)</DisplayText><record><rec-number>243</rec-number><foreign-keys><key app="EN" db-id="v0dawfxe5ftswoear5yv5spfrrretdpatpdt" timestamp="1461158757">243</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Billington, E. O.</author><author>Grey, A.</author><author>Bolland, M. J.</author></authors></contributors><auth-address>Division of Endocrinology, University of Calgary, Calgary, Canada. e.billington@auckland.ac.nz.
Bone & Joint Research Group, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1010, New Zealand. e.billington@auckland.ac.nz.
Bone & Joint Research Group, Faculty of Medical and Health Sciences, University of Auckland, 85 Park Road, Grafton, Auckland, 1010, New Zealand.</auth-address><titles><title>The effect of thiazolidinediones on bone mineral density and bone turnover: systematic review and meta-analysis</title><secondary-title>Diabetologia</secondary-title></titles><periodical><full-title>Diabetologia</full-title></periodical><pages>2238-46</pages><volume>58</volume><number>10</number><keywords><keyword>Bone density</keyword><keyword>Diabetes mellitus</keyword><keyword>Meta-analysis</keyword><keyword>Pioglitazone</keyword><keyword>Rosiglitazone</keyword><keyword>Systematic review</keyword><keyword>Thiazolidinediones</keyword></keywords><dates><year>2015</year><pub-dates><date>Oct</date></pub-dates></dates><isbn>1432-0428 (Electronic)
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ADDIN EN.CITE.DATA (49). Fors?get fandt at NASH forsvandt hos 39 % af liraglutid patienter og 9 % af placebo patienter og at f?rre patienter i liraglutid gruppen havde progression af fibrose under behandlingen. Der afventes st?rre og l?ngere studier. Liraglutid er associeret med v?gttab, bedre metabolisk regulation (blandt personer med diabetes), faldende blodtryk og lipider.Bivirkninger De hyppigste bivirkninger er gastrointestinale og inkluderer b?de kvalme, opkastning og diarre eller obstipation og flere studier har vist en stigning i puls. Der er rejst mistanke om ?get risiko for pankreatitis. Det b?r n?vnes at pr?paratet er dyrt for patienter, som ikke opfylder kriterier for tilskud. Obetichol syreObetichol syre (obeticholic acid) er en syntetisk galdesyre, som aktiverer farnesoid X nuclear receptoren (FXR). FXR aktivering ?ger insulin sensitivitet og s?nker hepatisk gluconeogenese og plasma triglycerid. Et randomiseret fase 2 studie med 283 NASH og borderline NASH patienter unders?gte effekten af 72 ugers placebo eller obetichol syre behandling, 25 mg/dag PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5OZXVzY2h3YW5kZXItVGV0cmk8L0F1dGhvcj48WWVhcj4y
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ADDIN EN.CITE.DATA (38). Studiet en effekt p? inflammation og fibrose. Der er desuden v?gttab og bedring af den metaboliske regulation for patienter med diabetes. Der afventes fase III studier.Bivirkninger Pr?paratet er kun godkendt for nyligt og erfaringerne ringe. De prim?re bivirkninger angives at v?re hudkl?e og dyslipid?mi. Andre pr?paraterEffekten af UDCA p? NASH er unders?gt i flere studier med skuffende resultater og kan derfor ikke anbefales ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7). Effekten af metformin p? NASH er ogs? skuffende ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
0168-8278 (Linking)</isbn><accession-num>27062661</accession-num><urls><related-urls><url>;(7), men behandlingen er indiceret hvis patienten har en samtidig diabetes. Retrospektive studier tyder desuden p?, at metformin modvirker udviklingen af HCC ADDIN EN.CITE <EndNote><Cite><Author>Zhang</Author><Year>2012</Year><RecNum>241</RecNum><DisplayText>(50)</DisplayText><record><rec-number>241</rec-number><foreign-keys><key app="EN" db-id="v0dawfxe5ftswoear5yv5spfrrretdpatpdt" timestamp="1461157738">241</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>Zhang, Z. J.</author><author>Zheng, Z. J.</author><author>Shi, R.</author><author>Su, Q.</author><author>Jiang, Q.</author><author>Kip, K. E.</author></authors></contributors><auth-address>Department of Epidemiology, School of Public Health, Shanghai Jiao Tong University, 227 South Chongqing Road, Shanghai 200025, China. zhang.zj@</auth-address><titles><title>Metformin for liver cancer prevention in patients with type 2 diabetes: a systematic review and meta-analysis</title><secondary-title>J Clin Endocrinol Metab</secondary-title></titles><periodical><full-title>J Clin Endocrinol Metab</full-title><abbr-1>The Journal of clinical endocrinology and metabolism</abbr-1></periodical><pages>2347-53</pages><volume>97</volume><number>7</number><keywords><keyword>Algorithms</keyword><keyword>Carcinoma, Hepatocellular/complications/epidemiology/*prevention & control</keyword><keyword>Chemoprevention/methods</keyword><keyword>Diabetes Mellitus, Type 2/complications/*drug therapy/epidemiology</keyword><keyword>Humans</keyword><keyword>Hypoglycemic Agents/therapeutic use</keyword><keyword>Liver Neoplasms/complications/epidemiology/*prevention & control</keyword><keyword>Metformin/*therapeutic use</keyword></keywords><dates><year>2012</year><pub-dates><date>Jul</date></pub-dates></dates><isbn>1945-7197 (Electronic)
0021-972X (Linking)</isbn><accession-num>22523334</accession-num><urls><related-urls><url>;(50) hvorfor der stadig afventes studier.Behandling af komorbide tilstandeAlle NAFLD patienter b?r tilbydes diagnostik og behandling af de hyppigt forekommende komorbide tilstande, som dyslipid?mi, hypertension, type 2 diabetes mellitus og s?vnapn? ADDIN EN.CITE <EndNote><Cite><Author>European Association for the Study of the Liver . Electronic address</Author><Year>2016</Year><RecNum>11653</RecNum><DisplayText>(7)</DisplayText><record><rec-number>11653</rec-number><foreign-keys><key app="EN" db-id="f92ps2fpaf0dp9eavabv59stz9t5sxw9ttww" timestamp="1463055554">11653</key></foreign-keys><ref-type name="Journal Article">17</ref-type><contributors><authors><author>European Association for the Study of the Liver . Electronic address, easloffice easloffice eu</author><author>European Association for the Study of, Diabetes</author><author>European Association for the Study of, Obesity</author></authors></contributors><titles><title>EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease</title><secondary-title>J Hepatol</secondary-title></titles><periodical><full-title>J Hepatol</full-title></periodical><dates><year>2016</year><pub-dates><date>Mar 10</date></pub-dates></dates><isbn>1600-0641 (Electronic)
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ADDIN EN.CITE.DATA (40, 51, 52). Kliniske rekommandationer 3Ingen l?gemidler har vist effekt p? kliniske endepunkter og anbefalinger om behandling af patienter med NAFLD er vejledendePrognosen ved NAFL er god og der er ikke evidens for at tilbyde medicinsk behandling ved denne tilstandMedicinsk behandling af NASH overvejes, hvis der er fibrose ≥ F2 risikofaktorer best?ende af diabetes, MetS, vedvarende ALAT-forh?jelse, eller betydende histologisk inflammationVitamin E behandling (800 IU/dag) kan overvejes til is?r non-diabetiske NASH patienter under hensyntagen til mulige bivirkninger; metoder til behandlingsmonitorering og varighed er uafklaret; blandt personer med transaminas?mi kan overvejes seponering ved manglende ALAT fald efter seks m?nederPioglitazon (30-45 mg/dag) kan overvejes til behandling af NASH patienter s?rligt ved samtidig diabetes under hensyntagen til mulige bivirkninger; metoder til behandlingsmonitorering og varighed er uafklaretDiagnosticering og behandling af komorbiditet inklusive diabetes, hypertension, hyperlipid?mi, isk?misk hjertesygdom understreges.Kan bariatrisk kirurgi anvendes til behandling af NAFLD?I Danmark anvendes bariatrisk kirurgi til behandling af patienter med sv?r fedme og alder mellem 25-60 ?r, hvor de ikke-kirurgiske behandlingstilbud kan anses for at v?re udt?mte. Personer som indstilles til bariatrisk kirurgi skal opfylde et af f?lgende to kriterier: 1) BMI > 50 kg/m2 eller 2) BMI > 35 kg/m2 med type 2 diabetes, sv?r regulerbar hypertension, dokumenteret s?vnapn? eller polycystisk ovariesyndrom. NAFLD/NASH er ikke en godkendt indikation i Danmark. Et systematisk review fandt at flere patienter, der opn?ede en BMI reduktion p? > 15 kg/m2 ved bariatrisk kirurgi havde forbedret histologisk inflammation og fibrose PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Cb3dlcjwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+PFJl
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ADDIN EN.CITE.DATA (53). Der blev dog ikke fundet ?ndringer i graden af steatohepatitis. Kliniske rekommandationer 4Bariatrisk kirurgi b?r ikke rutinem?ssigt tilbydes patienter med NAFLD med mindre, patienten allerede opfylder standardkriterierne for bariatrisk kirurgi. Litteraturs?gningLitteratur s?gning (April 2016): S?geord: Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, vitamin E, insulin sensitizers, pioglitazone, obeticholic acid, liraglutide, bariatric surgery. Referencer ADDIN EN.REFLIST 1.Singh S, Allen AM, Wang Z, Prokop LJ, Murad MH, Loomba R. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 2015;13(4):643-54 e1-9; quiz e39-40.2.Angulo P, Kleiner DE, Dam-Larsen S, Adams LA, Bjornsson ES, Charatcharoenwitthaya P, et al. Liver Fibrosis, but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015;149(2):389-97 e10.3.Ekstedt M, Hagstrom H, Nasr P, Fredrikson M, Stal P, Kechagias S, et al. Fibrosis stage is the strongest predictor for disease-specific mortality in NAFLD after up to 33 years of follow-up. Hepatology. 2015;61(5):1547-54.4.Yamazaki H, Tsuboya T, Tsuji K, Dohke M, Maguchi H. Independent Association Between Improvement of Nonalcoholic Fatty Liver Disease and Reduced Incidence of Type 2 Diabetes. Diabetes Care. 2015;38(9):1673-9.5.Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011;34(3):274-85.6.Wong RJ, Cheung R, Ahmed A. 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Obes Surg. 2015;25(12):2280-9.Appendiks:Fibrose scoresUdregning og tolkningFibrosis 4 calculator (FIB-4) FIB-4 =alder x ASATtrombocyttal x √ALATresultat< 1,45: forudsiger ingen signifikant fibrose (F0-F2)1,45 og 3,25: gr?zone> 3,25: forudsiger signifikant fibrose (F3-F4)NAFLD fibrosis score (NFS)-1,675 + 0,037 x alder (?r) + 0,094 x BMI (kg/m2) +1,13 x forekomst af DM/IGT (ja = 1, nej = 0) + 0,99 x AST/ALT ratio -0,013 x trombocyttal (x109/l) - 0,066 x albumin (g/l)resultat< -1,455: forudsiger ingen signifikant fibrose (F0-F2 fibrosis)-1,455 og 0,675: gr?zone (indeterminate score)> 0,675: forudsiger signifikant fibrose (F3-F4 fibrose)Begge kan udregnes online p? henholdsvis og DM = diabetes mellitus; IGT = nedsat glukose toleranceTabel 3 og 4: NAFLD Activity ScoreKarakteristikaScoreVurderingSteatose0<5%15-33%2>33-66%3>66%Lobul?r Inflammation0Ingen foci1<2 foci/200x22-4 foci/200x3>4 foci/200xHepatocyt Ballooning0Ingen1F? balloon celler2Mange celler/prominent ballooningSteatose BalloneringLobul?r inflammation Diagnose19939020955000019886594422Steatose019939099695019886594422119886594422Steatose219886594422Steatose1949451905019939020891500019886594422Steatose1, 2, 31981201003300019886594422119939099695019886594422119886594422NASH219886594422NASH19939020955000019886594422Steatose219939099695019886594422119886594422NASH219886594422NASH ................
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