whs pr symposium - non-alcoholic fatty liver disease

8/10/2019 WHS PR Symposium - Non-Alcoholic Fatty Liver Disease

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Non-Alcoholic Fatty Liver DiseaseNon-Alcoholic Fatty Liver Disease

Barretts EsophagusBarretts Esophagus

Federico Rodrguez-Prez

Gastroenterologist and Hepatologist


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I have no disclosures regarding

this topic

I have no disclosures regarding

this topic


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ObjectivesObjectives

To understand the epidemiology andnatural history of NAFLD

ecogni!e the clinical presentation of

NAFLD "nderstand the strategies for the

diagnosis and treatment of NAFLD

To understand the epidemiology andnatural history of NAFLD

ecogni!e the clinical presentation of

NAFLD "nderstand the strategies for the

diagnosis and treatment of NAFLD


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Non-Alcoholic Fatty Liver Disease

#NAFLD$


#NAFLD$

%hat is it&

%hy care&

%hom to treat&

%hat is it&

%hy care&

%hom to treat&

Non-Alcoholic Fatty i!er "isease #NAF"$Non-Alcoholic Fatty i!er "isease #NAF"$


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NAFLD

%hat is it&

NAFLD

%hat is it&

'vidence of hepatic steatosis either byimaging or histology

No other causes for secondary hepatic fataccumulation

(ignificant alcohol consumption ) * drin+s on any day #) *,gmday$ or ) ./

drin+s per 0ee+ in men ) 1 drin+s on any day #1,gmday$ or ) 2 drin+s

per 0ee+ in 0omen"se of steatogenic medication3ereditary disorders

'vidence of hepatic steatosis either byimaging or histology

No other causes for secondary hepatic fataccumulation

(ignificant alcohol consumption ) * drin+s on any day #) *,gmday$ or ) ./

drin+s per 0ee+ in men ) 1 drin+s on any day #1,gmday$ or ) 2 drin+s

per 0ee+ in 0omen"se of steatogenic medication3ereditary disorders


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NAFLDNAFLD

NAFLD is the most common cause of4LD

(trongly associated 0ith metabolic

ris+ factors5 obesity6 diabetesmellitus6 and dyslipidemia

3istologically categori!ed intosteatosis and steatohepatitis

NAFLD is the most common cause of4LD

(tronglyassociated 0ith metabolic

ris+ factors5 obesity6 diabetesmellitus6 and dyslipidemia

3istologically categori!ed intosteatosis and steatohepatitis


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NAFLD5 A 7lobal 4hallenge

%&'( A)erican

adults areo!er*eight or

o+ese

Pre!alence o,

NAF" in the .

is &/ -0123n .4 (/ )illion

adults )ay ha!eNAF"

567 )illion )ay ha!e

NA.H 88


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3ispanics3ispanics %hites%hites 8lac+s8lac+s

9:;*9:;*

//;.


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NAFLD5 Disease (pectrumNAFLD5 Disease (pectrum

NAF NA.H 4irrhosis

NAF"

.teatosis

#:acro!esicular$

.teatosis

3n,la))ation

Ballooning

Fi+rosis

3n,la))ation

NAF"< Nonalcoholic ,atty li!er disease

NAF< nonalcoholic ,atty li!er

NA.H< nonalcoholic steatohepatitis

Non-Alcoholic Fatty i!er "isease #NAF"$Non-Alcoholic Fatty i!er "isease #NAF"$


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#NAFLD$


#NAFLD$

%hat is it&

%hy care&

%ho to treat&

%hat is it&

%hy care&

%ho to treat&

y # $


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Non-Alcoholic Fatty i!er "isease ;linical 3)plicationsNon-Alcoholic Fatty i!er " isease ;linical 3)plications


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Fe0 symptoms signs oliver disease

8enign course&

@.,< go to cirrhosis

is+ factor for cirrhosis in34> AFLD

.;2< liver related mortality

Fe0 symptoms signs oliver disease

8enign course&

@.,< go to cirrhosis

is+ factor for cirrhosis in34> AFLD

.;2< liver related mortality

Non-Alcoholic Fatty Liver Disease4linical ImplicationsNon-Alcoholic Fatty Liver Disease4linical Implications

(teatosis(teatosis

Non-Alcoholic Fatty i!er "isease ;linical 3)plicationsNon-Alcoholic Fatty i!er "isease ;linical 3)plications


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(teatohepatitis(teatohepatitis?ore severe metabolic

syndrome

B *,< advanced fibrosis

?ay promote 344

:;C< liver relatedmortality

?ore severe metabolicsyndrome

B *,< advanced fibrosis

?ay promote 344

:;C< liver relatedmortality

?allory body?allory body

balloonedballooned

deaddead


Non-Alcoholic Fatty i!er "isease ;linical 3)plicationsNon-Alcoholic Fatty i!er " isease ;linical 3)plications


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?orbidity mortality significant

liver-relatedco-morbidities

.1;. < liver relatedmortality

344 ris+ high

?orbidity mortality significant

liver-relatedco-morbidities

.1;. < liver relatedmortality

344 ris+ high


4irrhosis #F/$4irrhosis #F/$

NAFLDNAFLD


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(teatosis(teatosis

(teatohepatitis(teatohepatitis

4irrhosis4irrhosis

3epatocellularcarcinoma3epatocellularcarcinoma

NAFLD(pectrum of 3epatic =athologyNAFLD(pectrum of 3epatic =athology


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NA(3 and 344NA(3 and 344

=atients 0ith NA(3 cirrhosis haveincreased ris+ of liver cancer andscreening should be performed

early cumulative incidence is 1;C cirrhoticpatients Diabetes6 older age6 obesity6 alcohol

consumption6 hepatic irondeposition are ris+ factors for the

development of 344

=atients 0ith NA(3 cirrhosis haveincreased ris+ of liver cancer andscreening should be performed

early cumulative incidence is 1;C cirrhoticpatients Diabetes6 older age6 obesity6 alcohol

consumption6 hepatic irondeposition are ris+ factors for the

development of 344Ascha4 Hepatology &/1/

.tarley4 Hepatology &/1/

Bhala et al4 Hepatology &/11


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4onclusion5 %hy care&4onclusion5 %hy care&

Long-term outcomes of patients 0ithNAFLD and NA(35

=atients 0ith NAFLD have increase

overall mortality ?ost common cause of death in

patients 0ith NAFLD and NA(3 is

cardio!ascular disease;

=atients 0ith NA(3 have an increasedris+ of liver-related mortality including

344

Long-term outcomes of patients 0ithNAFLD and NA(35

=atients 0ith NAFLD have increase

overall mortality ?ost common cause of death in

patients 0ith NAFLD and NA(3 is

cardio!ascular disease;

=atients 0ith NA(3 have an increasedris+ of liver-related mortality including

344


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Diagnosis 'valuationDiagnosis 'valuation


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4linical Features5 NAFLD4linical Features5 NAFLD

?ost are asymptomatic #22


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'valuation of Incidentally Discovered

3epatic (teatosis

'valuation of Incidentally Discovered

3epatic (teatosis

=atients 0ith unsuspected hepatic steatosisdetected on imaging5 No symptoms and normal liver biochemistries

rule out significant alcohol consumption or

medications and assess for metabolic ris+factors

Those 0ho have symptoms signsabnormal liverbiochemistriesevaluate as if they havesuspected NAFLD and 0or+-up accordingly;

=atients 0ith unsuspectedhepatic steatosisdetected on imaging5 No symptomsand normal liver biochemistries

rule out significant alcohol consumption or

medications and assess for metabolic ris+factors

Those 0ho have symptomssignsabnormal liverbiochemistriesevaluate as if they havesuspected NAFLD and 0or+-up accordingly;

NAF" Practice guidelines


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Diagnosis 'valuationDiagnosis 'valuation

H. Identify ris+ factors associated

0ith NAFLD #Table .$

H. Identify ris+ factors associated

0ith NAFLD #Table .$

9 +l 1 Ri ? , t i t d ith NAF"


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=uppalanchi R6 Hepatology &//>

9a+le 1< Ris? ,actors associated *ith NAF"

"iagnostic Goal @1 "eter)ine Etiology is F""iagnostic Goal @1 "eter)ine Etiology is F"


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%ho might have NA(3&

9he :eta+olic .yndro)e

3igh prevalence i

patients 0ith

4ryptogenic

cirrhosis

(trong predictorfor NA(3

JJ ?A ID'NTIF=ATI'NT( %IT3

A8NO?AL LI>'T'(T( %3O %ILL

8'N'FIT FO? A

LI>' 8IO=(JJ

; %1/& c) : and 55c)

%1(/'50))hg

%&0/)g'dl

C/ : and 0/

Fasting plas)a glucose le!el

%11/)g'dl


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is+ of NA(3is+ of NA(3

Not D? or 3TN 3TN D? D? K 3TN,

.,

1,

*,

/,

9,

C,

2,

:,

< of =ts 0ith NA(3

Dixon JB, Gastro 2001

1/0 pts lap sD ,or o+esity li!er +D

;o)ponents o, the )eta+olic syndro)e


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ed Flags for NA(3ed Flags for NA(3

Age 7ender

3ispanic

3TN

Obesity Diabetes

ALT and A(T level

A(TALT

Insulin level

Age 7ender

3ispanic

3TN

Obesity Diabetes ALT and A(T level

A(TALT

Insulin level

No la+ test or i)aging study

*ill +e a+le to predict *ith

1//2 accuracy

9he )ore ris? ,actors the

)ore li?ely the patient has

NA.H


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H1 'clude significant alcoholconsumption and competing etiologies

for hepatic steatosis #Table 1$

H1 'clude significant alcoholconsumption and competing etiologies

for hepatic steatosis #Table 1$


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NAF" Practice guidelines


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H* 'clude coeistent causes for4LD

H* 'clude coeistent causes for4LD


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Initial 'valuationInitial 'valuation

Negative viral autoimmune genetic mar+ers

=atients 0ith NAFLD can present 0ith mild elevation of

ferritin;

8ut patients 0ith persistent increased ferritin level and

increase iron saturation in the contet of homo!ygous or

hetero!ygous 41:1 3F' mutations liver biopsy;

1.< of patients 0ith NAFLD can present 0ith mild

elevations of autoantibodies level #ANA .5.C,M A(?A .5/,

3igh serum titers of autoantibodies 0ith other

features of autoimmune liver diseasecomplete

0or+up

Negative viral autoimmune genetic mar+ers

=atients 0ith NAFLD can present 0ith mild elevation of

ferritin;

8ut patients 0ith persistent increased ferritin level and

increase iron saturation in the contet of homo!ygous or

hetero!ygous 41:1 3F' mutations liver biopsy;

1.< of patients 0ith NAFLD can present 0ith mild

elevations of autoantibodies level #ANA .5.C,M A(?A .5/,

3igh serum titers of autoantibodies 0ith other

features of autoimmune liver diseasecomplete

0or+up


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Diagnostic ToolsDiagnostic Tools

Diagnostic evaluation5 LiverDiagnostic evaluation5 Liver


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Diagnostic evaluation5 Liver

=rofile

Diagnostic evaluation5 Liver=rofile

ALT andor A(T are only mildly-moderatelyelevated

19-*,< 0ith en!ymes may have fibrosis or

cirrhosis

Normal liver biochemistry results do not

eclude advance fibrosis

A(TALT ratio @ . but this ratio increases as

fibrosis advances K- increase in al+aline phosphatase and 77T

ALT andor A(T are only mildly-moderatelyelevated

19-*,< 0ith en!ymes may have fibrosis or

cirrhosis

Normal liver biochemistry results do not

eclude advance fibrosis

A(TALT ratio @ . but this ratio increases as

fibrosis advances K- increase in al+aline phosphatase and 77T

Non-Invasive ?ar+ers ofNon-Invasive ?ar+ers of


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Non-Invasive ?ar+ers of

Fibrosis

Non Invasive ?ar+ers of

Fibrosis

NAFLD Fibrosis (core#http5nafldscore;com$

Age6 8?I6 hyperglycemia6 platelet count6

albumin6 A(TALT ratio

@ -.;/99 had ,< sensitivity and C,Qvelocity

=Qdensity of tissue

(tiffness is measured in +ilopascals


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7oals of Liver biopsy7oals of Liver biopsy

Identify NA(3 #ballooning6 inflammation6 etc$

'stablish diagnosis

4linical trials

(tage fibrosis

ule out concomitant liver disease #iron

loading6 etc$

=rognosis

Identify NA(3 #ballooning6 inflammation6 etc$

'stablish diagnosis

4linical trials

(tage fibrosis

ule out concomitant liver disease #iron

loading6 etc$

=rognosis

4 l i4 l i


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4onclusions4onclusions

As? yoursel, *hat it is that you *ant to ?no*3, NA.H !s not NA.H

4onsider liver biopsy

9he )ore the ris? ,actors4 the greater the li?elihood the

patient has NA.H

3, )ild ,i+rosis !s ad!anced ,i+rosis

4onsider Fibroscan

As? yoursel, *hat it is that you *ant to ?no*3, NA.H !s not NA.H

4onsider liver biopsy

9he )ore the ris? ,actors4 the greater the li?elihood the

patient has NA.H

3, )ild ,i+rosis !s ad!anced ,i+rosis

4onsider Fibroscan


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?anagement of NAFLD?anagement of NAFLD


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Lifestyle ?odificationsLifestyle ?odifications

EDieting vs E3ealthy 'ating

(ugarstac+s;com

3arvard 3ealthy 'ating =lates and3elathy 'ating =yramid 0ebsite

%eight 0atchers

EDieting vs E3ealthy 'ating

(ugarstac+s;com

3arvard 3ealthy 'ating =lates and3elathy 'ating =yramid 0ebsite

%eight 0atchers


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Lifestyle ?odificationsLifestyle ?odifications

'ercise

?etabolic benefit vs 0eight loss

7ym

Trainer Dancing

%al+ing5 * times to 9 times per 0ee+

'ercise

?etabolic benefit vs 0eight loss

7ym

Trainer Dancing

%al+ing5 * times to 9 times per 0ee+


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Other ?anagement AdvicesOther ?anagement Advices

4hec+ 3epatitis A8

Identify >it D deficiency

Treat sleep apnea

Limit acetaminophen inta+e5 notmore than 1,,, mg per day

Allo0 statin use if necessary tocontrol elevated cholesterol

4hec+ 3epatitis A8

Identify >it D deficiency

Treat sleep apnea

Limit acetaminophen inta+e5 notmore than 1,,, mg per day

Allo0 statin use if necessary tocontrol elevated cholesterol


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4ardiovascular disease in NAFLD4ardiovascular disease in NAFLD

4ardiovascular disease is the leading causeof death

=atients 0 NAFLD should be ris+ stratified for4> d! and managed accordingly

Statins can be used safely to treatdyslipidemia since there is no evidence that

patients with CLD are at higher risk forserious liver injury than those w/o liver dz

(!" ##SLD guidelines$

4ardiovascular disease is the leading causeof death

=atients 0 NAFLD should be ris+ stratified for4> d! and managed accordingly

Statins can be used safely to treatdyslipidemia since there is no evidence that

patients with CLD are at higher risk forserious liver injury than those w/o liver dz

(!" ##SLD guidelines$


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8ariatric (urgery8ariatric (urgery

Foregut bariatric surgery can beeffective in improving hepatichistology in selected patients#severely obese$ 0ithout liver failureor portal 3TN

%ot contraindicated in obesepatients with %#&LD w/o cirrhosisbut type' safety' and efficacy not

established in cirrhotics

Foregut bariatric surgery can beeffective in improving hepatichistology in selected patients#severely obese$ 0ithout liver failureor portal 3TN

%ot contraindicated in obesepatients with %#&LD w/o cirrhosisbut type' safety' and efficacy not

established in cirrhotics:u))adi et al6 &//54 &/1& AA." guideline


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?anagement of NA(3?anagement of NA(3


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=harmacotherapy for NA(3=harmacotherapy for NA(3

No drugs have been approved

=harmacotherapy is based on trial

data

No drugs have been approved

=harmacotherapy is based on trial

data


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=I>'N( (tudy=I>'N( (tudy

Further analysis sho0ed that bestresults 0ere seen in patients 0hotoo+ >itamin ' and also achieved0eight loss

>itamin ' may increasecardiovascular ris+ and prostatecancer

Further analysis sho0ed that bestresults 0ere seen in patients 0hotoo+ >itamin ' and also achieved0eight loss

>itamin ' may increasecardiovascular ris+ and prostatecancer


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Farnesoid R #nuclear$ eceptorFarnesoid R #nuclear$ eceptor


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Farnesoid R #nuclear$ eceptor

#FR$

Farnesoid R #nuclear$ eceptor

#FR$

Activation5

Inhibits hepatic de novo lipogenesis

Increases insulin sensitivity =rotects hepatocytes against bile acid

induced cytotoicity

Agonists may be useful in NA(3

Activation5

Inhibits hepatic de novo lipogenesis

Increases insulin sensitivity

=rotects hepatocytes against bile acid

induced cytotoicity

Agonists may be useful in NA(3


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FLINT 4linical TrialFLINT 4linical Trial

NI3 funded trial in 1:* patients

Obeticholic acid 19 mg po d vsplacebo for 21 0ee+s

Non-cirrhotics Improvement in NAFLD Activity

(core5

#/C< in O4A vs 1.< in placebo$

(ide effects5 severe pruritus *itamin ' may be used in selected patients

Obeticholic Acid may be considered in the future

Dietary modifications and eercise play an importantrole in management of patients 0ith NAFLD

Drug therapy of NA(3 must only be provided in those0ith documented and established NA(3

>itamin ' may be used in selected patients

Obeticholic Acid may be considered in the future

Dietary modifications and eercise play an importantrole in management of patients 0ith NAFLD

whs pr symposium - non-alcoholic fatty liver disease

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