ìCirrhosisFrom30000meters

TheoHellerTranslationalHepatologySectionLiverDiseasesBranch,NIDDK,NIH

Patient

Patient

Patient

Patient

WhyCare?

ì Global

ì Society

ì Family

ì Personal

WhatDoesTheLiverDo?

ì Choresì Makesì Breaksì Storesì Repackagesì Cleansì Protectsì Immunecentral

Progression

LiverDiseasesViralHepatitisNASHAlcoholAutoimmune

AccelerantsHIVAlcoholDiabetes

http://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/natural-history/core-concept/all

Histology

DavidKleiner

Histology

DavidKleiner

Whathappens?

The most important organ in the body!

GUT

Help!!!!!

Ascites

Infection

ìHUGE!

Other

ì Encephalopathy

ì Cytopenias

ì Osteoporosis

Research?

ì Whydoesliverdiseaseprogress?

ì Whydosomeprogressmorethanothers?

Definition?

ì Whatisit?ì Causeofillnessanddeath?

ì Defineì Whattomeasure?ì Howtomeasure?ì Whentomeasure?

Options

OutcomeBiopsy

PortalPressure

Imaging Blood

BreathTests

TransientElastography

Predictionisverydifficult,especiallyaboutthefuture.

Niels Bohr

Biopsy

R.A.Standish,etal.2006Gut,555695780017-5749

TransientElastography

Dr.ASAlawad

CoolestFact

ìFibrosiscanreverse

HDVtreatedfor12years

Daryl T.-Y. Lau, David E. Kleiner, Yoon Park, Adrian M. di Bisceglie, Jay H. Hoofnagle. Gastroenterology, Volume 117, Issue 5, 1999, 1229–1233

Also

ì HCV

ì HBV

ì PBC

ì AIH

ì Alcohol

ì Hemochromatosis

SotoStudyProgression?

ì Approachì Patientsarethereasontodoresearchì Itisnotthatwedoresearchsoneedpatients!

TwoProngedApproach

ì Rarediseases- commonapproach

ì Rareapproach - commondiseases

ì Searchforuniversal truth

ì Aimtounderstandandultimatelyhaltprogressionofliverdisease!

NodularRegenerativeHyperplasia

DavidKleiner

ConceptBreak

ì Allgutbloodflowsthroughtheliver

ì Infectionisacommoncauseofdeathinliverdisease,typicallywithgutorganisms

ì Microbialtranslocationfromthegutisassociatedwithadvancedliverdisease

ì Dysbiosis occursasliverdiseaseprogresses

ì Doesthemicrobiome andtheresponsetoitalterthecourseofliverdisease?

Questions

ì Whatishappening?ì Constanttranslocation?ì Pressureandtranslocation?ì Microbiome content?

ì QinetalNature2015

ì Shunting?Vs.Hepaticfunction?ì Beforetheliverprocessesanything?

Approach

ìDirectportalveinsampling?

ì Privilegedvessel

ì Pre-existingexpertise

StudyOutline15–DK-0100

ì Samplelivertissue,portalandperipheralblood

ì Placeincontextof:ì Hepaticfunctionì Shuntingì Microbiomeì Inflammationì Immunity

BenchtoBedsideAward

ConceptStudy

ì SickleCellpatientswithliverdisease

ì Studyreversalafterbonemarrowtransplant

ì 13-DK-0196

ì CourtneyFitzhugh,MattHsieh,JohnTisdale

EpilogueandPrologue

ìStartedwithpatients

ìLedtoideas

ìLedtoprotocols/projects

ìPatientsaretheframeofreference

ìTakesomethingbacktopatients

Concepts

ì UniqueenvironmentattheNIH

ì Laydowntheroad;benchvs.bedsideirrelevant

ì Boutiquetothebroad

ì Opportunitytolearnaboutallendstageliverdisease

ì Universaltruths

ì Allwhiletakingcareofpeoplewhodesperatelyneedcare

Acknowledgmentsì LiverDiseasesBranch

ì Patients,Nurses,Fellows

ì ChristopherKohì Ohad Etzionì Hawwa Alaoì Devika Kapuriaì Yaron Rotman

ì MarcGhany

ì BarbaraRehermann

ì DavidKleiner

ì JayHoofnagle

ì T.JakeLiang

ì JamesBalow

ì IraLevin

ì MichaelKrause

ì Collaboratorsì NIAID,NHLBI,NIAMS,NCHD,

NCI,CC,NHGRI,Stanford,Indiana,HepQuant,Eiger

ì TranslationalHepatologySectionì Rabab Aliì LizTownsendì GraceZhang