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170

10 ( )

,

( )

()

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70 /

140/

5%

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Non alcoholic fatty liver disease / NAFLD

. Accumulation of fat in liver cells.

. Doesnt damage the liver.

. Common in patients who are obese orhave DM type 2.

. Treatment depents on the cause.

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6

, ,

40% 510%

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Nonalcoholic fatty liver ( NAFL ) atau

PERJALANAN PENYAKIT ?( Disease Progression )

Simple steatosis

Nonalcoholic steatohepatitis ( NASH ).

BUKU AJAR Ed.IV.2007.Hal.462.dr.Irsan Hasan SpPDKGEH

Fibrosis

Sirosis hepatis

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OBESITAS

SENTRAL

ADIPONECTIN TNF-

RESISTENSIINSULIN

ESlain

Adiponectin berfungsi :.Memacu oksidasi asamlemak.

.Menurunkan TG..Meningkatkan sensitifitasinsulin..Menekan respon inflamasi

endotel..Menghambat proliferasi otot

ADIPOCYTOKINES

.Leptin..PAI -1.*.Adipsin..Resistin

PAI-1 *= Plasminogen Activator InhibitorDiabetes update,Prof.Dr.dr.Darmono. SpPD-KEMD,10-11 Sept 2005

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KERJA INSULIN

FFA

GLUKOSA

Glukoneogene

sis

Re-esterifikasi

TGJar adiposa

Khilomikron.

VLDL LDLFFA

darah

INSULIN

SEL

LIVER

Diabetes update,Prof.Dr.dr,Sri Hartini KS Kariadi SpPD-KEMD,10-11 Sept 2005

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PATOGENESIS TERJADINYA

FATTY LIVER ?

>>>FFA

GLUKOSA

Glukoneogene

sis

Re-esterifikasi>>

>>TGJar adiposa

Khilomikron.

VLDL LDL>>>FFA

darah

RESISTENSI INSULINSEL

LIVER

TNF-

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Fatcontent

increasesUCP2

increases

Macrophage function

reduced

First Hit

Influx of free fattyacids

Oxidative stress

Ischemia

Second Hit

Fatty liverHigh-calorie

diet Obesity

Activation

of lipidperoxidation

ATP in livertissue decreases

Increased

sensitivity toendotoxins

Steatohepati

tis Fibrosis

Cirrhosis

The two-hit hypothesis is the pathogenesis

of NASH

UCP2 = uncoupling protein 2

First Hit: Development of fatty liver

Second Hit: Increased sensitivity to stress,

endotoxins amd ischemia

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PerlemakanPerlemakan HatiHati

((steatosissteatosis makrovesikularmakrovesikular))

11stst HitHit

Stres oksidatifKepekaan

Makanan

berlemak(FFA)*

Akumulasi lemak(trigliserida) di

hepatosit

PATOGENESIS

NASHNASH

SirosisSirosis

2nd Hit

ToksinMediator inflamasi

(sitokin: IL, TNF)

Donnelly et al. J. Clin. Invest. 113: 1343, 2005

Day and James. Gastroenterol. 114: 842, 1998

Toksin: Toksin bakterial Zat besi Leptin*FFA = Free Fatty Acids

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Influence of free radicals and cytokines on the development of NASH

TNF

TGF

TGF TGF IL 8

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PENATALAKSANAAN

1. Atasi faktor risiko.

. Turunkan berat badan. Untuk mengoreksi resistensi insu

. Metformin Menambah sensitifitas insulin,menekan gluk

genesis.( Konsensus pengelolaan DM tipe 2,2002,PERKENI ).. Tiazolidindion.Menambah sensitifitas insulin.

( Konsensus pengelolaan DM tipe 2,2002,PERKENI ).

. .

( Penatalaksanaan dislipidemia 2004 PB.PERKENI ).

. Antioksidan Mencegah progresi NAFLD NASH & FibrN-asetilsistein ( Fluimucil ),vit.E,vit.C,betain.( Buku ajar Ed.IV.2007,hal.467.dr.Irsan Hasan.SpPD-KGEH ).

2. Hepatoprotektor :Ursochol ( Ursodeoxycholic acid / UDCA ).

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TERIMA KASIHTERIMA KASIHTERIMA KASIHTERIMA KASIH