031716_Nonalcoholic Fatty Liver Disease AY15-16 (1)

8/18/2019 031716_Nonalcoholic Fatty Liver Disease AY15-16 (1)

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Non Alcoholic FattyLiver Disease

(NAFLD) Arifa Toor, MD


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5 million years 50 years


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1995

Obesity Trends* Among U.S. AdultsBRFSS, 1990, 1995, 2005

*B!" #0, or $bout #0 lbs o%er&eig't (or 5) + erson-

2005

1990

No Data


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Obesity Trends* Among !"! Ad#lts$%F""& '0 0

*B!" #0, or / #0 lbs. o%er&eig't (or 5) + erson-

No Data


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NAFLD PrevalenceGeneral US Adult Population

NAFLD PrevalenceGeneral US Adult Population

Dallas Heart Study ( ! "" adults# Assessed NAFLD with liver imaging General prevalence o$ $atty liver %&'

(range ' ) *'#Most individuals (79%) with fatty liver do not exhi it aminotransferase elevations

Dallas Heart Study ( ! "" adults# Assessed NAFLD with liver imaging General prevalence o$ $atty liver %&'

(range ' ) *'#Most individuals (79%) with fatty liver do not exhi it aminotransferase elevations

NHAN+S ,,, (&*! -"" adults#Assessed NAFLD .ith aminotrans$erasesGeneral prevalence o$ NAFLD */*'

NHAN+S ,,, (&*! -"" adults#Assessed NAFLD .ith aminotrans$erasesGeneral prevalence o$ NAFLD */*'

NAFLD Prevalence*/*)%&'

NAFLD Prevalence*/*)%&'

!"#$ x more revalent than

&e atitis '

!"#$ x more revalent than

&e atitis '

NAFLD #revalence: $eneral %S A&ult #o'ulation


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NHAN+S ,,,NHAN+S ,,,

NormalAST! ALT

*/*'*/*' Une0plained HepatitisUne0plained Hepatitis12,3aist circum$erenceTriglycerides

+levated ,nsulin levelsHDL cholesterol

12,3aist circum$erenceTriglycerides

+levated ,nsulin levelsHDL cholesterol

Meta oli yndromeMeta oli yndrome

N AN S ***

'lar*+ ,ran ati+ Diehl- Am . /astro 0$$!1 92394$ 'lar*+ ,ran ati+ Diehl- Am . /astro 0$$!1 92394$


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• Alcohol)li4e liver disease in individuals .hodo not consume e0cessive alcohol

• Histologic spectrum o$ liver damageNAFL 5 $atty liver (steatosis#NASH 5 $atty liver 6 increased hepatocyte

death (steatohepatitis#7irrhosis 5 regenerative nodules 6 $i8rosis

• Diagnosis o$ e0clusion ,lood tests and imaging " insensitive+ non"s e ifi

• Alcohol)li4e liver disease in individuals .hodo not consume e0cessive alcohol

• Histologic spectrum o$ liver damageNAFL 5 $atty liver (steatosis#NASH 5 $atty liver 6 increased hepatocyte

death (steatohepatitis#

7irrhosis 5 regenerative nodules 6 $i8rosis• Diagnosis o$ e0clusion

,lood tests and imaging " insensitive+ non"s e ifi

TerminologyTerminologyNon-Alcoholic FattyLiver Disease

(NAFLD)

N on- A lcoholic F atty Liver D isease

(NAFLD)

Non-Alcoholic Fatty Liver Disease (NAFLD)


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atty ver s assoc ate ith the etabolic

"yndrome"entral + esity*!'aire& fastin lucose

levate& Tri lyceri&esLo. DLTN

of NAFLD 'atients have the full !eta olic syn&ro of NAFLD 'atients have at least one feature

Meta olic Syn&ro!e


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2eta8olic Syndrome2eta8olic Syndrome

A8normal production o$ hormones 9cyto4ines that regulate in$lammatoryresponses

A8normal production o$ hormones 9cyto4ines that regulate in$lammatoryresponses

P:;)in$lammatory

ANT,)in$lammatory

Meta olic Syn&ro!e


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Meta olic Syn&ro!e - "yto ine *! alance

TNFTNF AdiponectinAdiponectin

• ,nhi8its FA upta4e• Stimulates FA o0idation 9 lipid e0port• +nhances insulin sensitivity


• Pro)apoptotic• :ecruits 317=s• Promotes insulin

resistance


resistance

2eta8olic Syndrome7yto4ine ,m8alance


Pro)in$lammatory Anti)in$lammatoryAnti)in$lammatory

Steatosis (NAFL# 6cell death 6 in$lammation (NASH# 9

insulin resistance


insulin resistance


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Meta olic Syn&ro!e - "yto ine *! alance

TNFTNF AdiponectinAdiponectin




resistance


resistance



Pro)in$lammatory Anti)in$lammatoryAnti)in$lammatory


insulin resistance


insulin resistance

NAFLD: S'ectru! of e'atic #atholo y


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SteatosisSteatosis

SteatohepatitisSteatohepatitis

7irrhosis7irrhosis

Hepatocellular

carcinoma

Hepatocellular

carcinoma

NAFLDSpectrum o$ Hepatic Pathology

NAFLDSpectrum o$ Hepatic Pathology

NAFLD: S ectru! of e atic #atholo y

l f


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• 2ore consistent and rapidprogression to cirrhosis than NAFL

• 2ore consistent and rapidprogression to cirrhosis than NAFL

NAFLNAFL 7irrhosis%'

7irrhosis%'

NASH 6$i8rosisNASH 6$i8rosis

7irrhosis%"'

7irrhosis%"'

#$ years #$ years

:"#$ years:"#$ years

Matteoni et al- /astroenterology #9991 ##43#;#!Matteoni et al- /astroenterology #9991 ##43#;#!

Prognostic ,mplications o$NASH 6 Fi8rosis

Prognostic ,mplications o$NASH 6 Fi8rosis

#ro nostic *!'lications of NAS 4 Fi rosis

Ris Factors for "irrhosis


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:is4 Factors $or 7irrhosis:is4 Factors $or 7irrhosis

• Age > *)*" years•

;8esity• Dia8etes

• Age > *)*" years•

;8esity• Dia8etes

44% revalen e of ridging fi rosisif age :$ years and atient o ese

or dia eti

44% revalen e of ridging fi rosisif age :$ years and atient o eseor dia eti

Ris Factors for irrhosis


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Diagnosing Fatty LiverDisease

No one test can &ia nose thiscon&ition*t5s usually asy!'to!aticLiver tests !ay or !ay not ea nor!al

AST6ALT usually 789 nor!alSteatosis is usually seen onultrasoun& ( ut this &oes note clu&e conco!itant &iseases)


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Diagnosing Fatty LiverDisease

;hat to loo for in the history:#resence of features of !eta olicsyn&ro!e

Alcohol use- 7< &rin 6&ay = , 7>&rin s6&ay ?Me&ications that can cause liver in@uryMe&ications that can cause fatty liver-a!io&orone, MT9, ta!o ifen, steroi&s,

val'roic aci&, * !e&sFa!ily history of liver &isease

a!


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agnos ng atty verDisease

LabsFastin lucose, li'i&s, h A


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agnos ng atty verDisease

+maging%ltrasoun&- Crst line test#ic s u' steatosis .hen //1 ofhe'atocytes are aEecte&

"T6MR* can also e use&, ut notroutinelyMR s'ectrosco'y- not .i&elyavaila le, ut it is the !ost accuratenon invasive !easure of steatosis

Dia nostic $oal / sta lish Severity


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•

7linical prognosis depends on histologySteatosis generally 8enignSteatohepatitis increases ris4 $or cirrhosis7irrhosis is associated .ith signi$icant

mor8idityand mortality

•

7linical prognosis depends on histologySteatosis generally 8enignSteatohepatitis increases ris4 $or cirrhosis7irrhosis is associated .ith signi$icant

mor8idityand mortality

/eneral Message/eneral Message

Diagnostic Goal ? +sta8lishSeverity

Diagnostic Goal ? +sta8lishSeverity



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1lood Tests

+sta8lishing Severity+sta8lishing Severity

• Aminotrans$erase level not use$ul7an 8e normal in advanced disease

• AST


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•

7an=t distinguish $atty liver $romsteatohepatitis or @early cirrhosis

• Stigmata o$ portal HTN or nodular

liver contour suggest cirrhosis• 2ay detect unsuspected H77

•

7an=t distinguish $atty liver $romsteatohepatitis or @early cirrhosis

• Stigmata o$ portal HTN or nodular

liver contour suggest cirrhosis• 2ay detect unsuspected H77


,maging Tests,maging Tests



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• 7linical *)*" 6 o8esity or D2 suggest8ridging $i8rosis

• Fi8rosis mar4ersSimple scoring systems using AST


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F+$-. "corehtt / gihe !com calc#lators he atology 1brosis-.-

score

*N#%T: A$ , AST, ALT, #lateletsFor!ula: ( A e AST ) 6 ( #latelets ( sGr ( ALT ) )

,2 lanation o3 %es#lt /For NA"4 / Fi score 7 HJK I F/-FFor 467 ith or itho#t4+7 / Fi score 7


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• Sampling error • :is4• +0pense

• Sampling error

• :is4• +0pense


Liver 1iopsy B Gold standardLiver 1iopsy B Gold standard

LimitationsLimitations


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,stablishing "everity Fibroscan

Eective non-invasive tool to!easure liver stiEness .hichcorrelates .ith severity of C rosis

Sensitivity6S'eciCcity201 for F/6F

Allo.s ris stratiCcation of'atients#re&ictive tool for co!'licationsof cirrhosis%se& co!'li!entary to liver

io'sy


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O#r A roachto ,stablishing "everity Revie. i!a in , asic la s for anysi ns of cirrhosis#erfor! C roscan*f result a''ears consistent .ithclinical 'icture no io'sy*f C roscan non &ia nostic orinconsistent .ith clinical 'icture -'erfor! liver io'sy to assessseverity

*f conco!itant liver &isease


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Treatment

At 'resent, there is no one stan&ar&reco!!en&ation for the treat!ent ofNAFLD6NAS

There is evi&ence to su''ort:Lifestyle !o&iCcations to lose .ei ht(all 'atients)

ita!in (non &ia etic, non cirrhotic'atients)Treat the !eta olic syn&ro!e (o esity,&ia etes, &ys'li'i&e!ia) in all NAS

'atients


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2anagement strategies in non)alcoholic $atty liver disease(NAFLD#/

C Dyson et al/ Frontline GastroenteroldoiE&"/&&%


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Li3estyle odi1cationDiet ,2ercise


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+ndivid#ali9ing Thera y Diet

Avoi& hi h fructosecorn syru'(su are& soft

&rin s) Avoi& trans-fattyaci&s ('artiallyhy&ro enate& oils)"oEee !ay e

eneCciale'atolo y >0 88(>): >2- /J


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$ariatric "#rgery

Several series sho. re ression ofsteatosis an& necroin3a!!atorychan es after sur ery ($astroenterolo y>00J )

A !eta-analysis of


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Treating the etabolic"yndrome

Dia etesMetfor!in Crst line treat!ent after &iet#io litaOone secon& line

*nsulin6sulfonylureas last choicey'ertension A" * an& ARB5s !ay i!'rove he'aticC rosis an& transa!inases

y'erli'i&e!iaStatins are enerally safe

Liver Directed


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Liver Directededications

"onsi&er in 'atients .ith io'sy'roven NAS .ho have faile&lifestyle !o&iCcation#io litaOone has sho.n resolution ofsteatohe'atitis co!'are& to 'lace oSanyal N M >00

Plon ter! safety- " F, la&&er "a

+'ti!u! &uration un no.n ita!in - antio i&antH Sho.ni!'rove steatohe'atitis at 00*%6&ay

#otential &o.nsi&es Qall cause!ortalit , stro e, rostate ca

NAFLD: Thera'eutic A''roach


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SteatosisSteatosis 7irrhosis7irrhosisSteatohepatitisSteatohepatitis

;vert 2eta8olic Syndrome (2S#;vert 2eta8olic Syndrome (2S#

es es NoNo

Treat 2S3t loss

:0 D2Anti)HTN

Lo.er lipids

Treat 2S

3t loss:0 D2

Anti)HTNLo.er lipids

Treat NAFLDTreat NAFLD

2onitor $or NAFLD ProgressionPhysical e0ams (portal HTN#

1lood tests (platelets! AST


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:eight Loss thro#gh Li3estyle odi1cation "igni1cantly%ed#ces Feat#res o3 Non Alcoholic "teatohe atitis

(A) &resence o+ base'ine+ibrosis

(B) absence o+ base'ine+ibrosis,

./0 atients1. 2ee3sDiet- 153ca' 'ess than dai'!ener"! needE6ercise .557in82ee3 b!2a'3in"

astroentero'o"! 9o'u7e :4/ Issue . .5:1 0;


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$ariatric "#rgery in ;atients ithNon Alcoholic "teatohe atitis

Distribution o+ +ibrosis sta"e be+ore and : !ear a+ter sur"er!>$etavir score, (+ibrosis sta"ed 2ith $etavir score) (n ? =5 8=.) 2ith aired 'iver bio sies be+ore and : !ear a+ter sur"er!∗

031716_Nonalcoholic Fatty Liver Disease AY15-16 (1)

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