Epigeneticsinliverdisease:frombiologytotherapeuticsTimothyHardy,1,2DerekAMann11FibrosisLaboratories,InstituteofCellularMedicine,NewcastleUniversity,NewcastleuponTyne,UK2DepartmentofGastroenterologyandHepatology,TheNewcastleuponTyneHospitalsNHSFoundationTrust,NewcastleuponTyne,UKCorrespondencetoProfessorDerekAMann,FibrosisLaboratories,InstituteofCellularMedicine,4thFloorWilliamLeechBdg.,NewcastleUniversity,FramlingtonPlace,NewcastleuponTyneNE24HH,UK;derek.mann@ncl.ac.ukReceived28July2016Revised29July2016Accepted1August2016PublishedOnlineFirst13September2016Tocite:HardyT,MannDA.Gut2016;65:1895–1905.ABSTRACTKnowledgeofthefundamentalepigeneticmechanismsgoverninggeneexpressionandcellularphenotypearesufficientlyadvancedthatnovelinsightsintotheepigeneticcontrolofchronicliverdiseasearenowemerging.HepatologistsareintheprocessofsheddinglightontherolesplayedbyDNAmethylation,histone/chromatinmodificationsandnon-codingRNAsinspecificliverpathologies.Alongsidethesediscoveriesareadvancesinthetechnologiesforthedetectionandquantificationofepigeneticbiomarkers,eitherdirectlyfrompatienttissueorfrombodyfluids.Thepremiseforthisreviewistosurveytherecentadvancesinthefieldofliverepigeneticsandtoexploretheirpotentialfortranslationbyindustryandclinicalhepatologistsforthedesignofnoveltherapeuticsanddiagnostic/prognosticbiomarkers.Inparticular,wepresentfindingsinthecontextofhepatocellularcarcinoma,fibrosisandnon-alcoholicfattyliverdisease,wherethereisurgentunmetneedfornewclinicalinterventionsandbiomarkers.INTRODUCTIONIrrespectiveofaetiology,theprogressionofchronicliverdamageandinflammationtocirrhosisand/orcancerishighlyvariablebetweenindividuals.Ifliverdamagepersists,alargepercentageofpatientscanexpecttheirdiseasetoadvanceovertheirlife-time.However,thecourseandrateofprogressionoftheirdiseaseisoftenunpredictableusingprog-nostictoolscurrentlyavailableintheclinic.Asanexample,arecentstudyofpairedbiopsiesfrom108patientswithnon-alcoholicfattyliverdisease(NAFLD)revealedthat42%patientshadfibrosispr...
