dr. Salman Paris H.

SpPD
Bagian Ilmu Penyakit Dalam RSUD Budhi Asih/ FK UPN V Jakarta

NAFLD didefinisikan : ditemukannya steatosis

(retensi lemak abnormal di dalam sel) dengan

pemeriksaan imaging atau dengan pemeriksaan
histologi, serta penyebab terjadinya akumulasi
lemak di hati tidak disebabkan oleh konsumsi
alkohol berlebihan, penggunaan obat
steatogenik, atau gangguan hereditas.
NAFLD dikaitkan dengan faktor risiko metabolik,
seperti obesitas, diabetes, dan dislipidemia.
NAFLD dibagi menjadi 2 katergori, yaitu NAFL
(nonalcoholic fatty liver) dan NASH
(nonalcoholic steatohepatitis).

EPIDEMIOLOGY
Prevalence NAFLD is seen worldwide and

is the most common liver disorder in

Western industrialized countries, where the
major risk factors for NAFLD, central
obesity, Type 2 DM, dyslipidemia, and
metabolic are common.
In the US, studies report a prevalence of
NAFLD of 10-46%.
Worldwide, NAFLD has a reported
prevalence of 6-35%.

PREVALENCE
NHANES DATA

Time Period:

NAFLD:
1988-1994
1999-2004
2005-2008

Prevalence of
5.5%
9.8%
11.0%

Accounting for 47, 63 and 75% of chronic liver

disease during those time periods, respectively.

However, it should be noted that the definition of NAFLD used in

the study (elevated serum aminotransferase levels in the absence
of an alternative explanation) could lead to misclassification and
likely underestimated the true prevalence of NAFLD, since patients
with NAFLD may have normal serum aminotransferases.

PREVALENCE
Over the same three time periods, the study also noted

increases in the rates of other components of the

metabolic syndrome, including obesity, Type2 DM and
systemic hypertension.
Obesity
Systemic HTN
1988-1994
1999-2004
2005-2008

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30
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DM2
6
8
9

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ASSOCIATION WITH OTHER

DISORDERS

Patients with NAFLD (particularly those

with NASH) often have one or more
components of the metabolic syndrome:

Obesity

Systemic hypertension

Dyslipidemia

Insulin resistance or overt diabetes

Adipocyte is an Endocrine
Organ

The Two HIT Concept

1st
HIT

2nd
HIT

The Two Hit Concept

Diet
FFA

Fats Burnt
VLDL-TG

Fatty Liver
Susceptibility

1st Hit

Oxidative Stress
Toxins

2nd Hit

Saturated
>
Unsaturat
ed

Inflammatory
Molecules
Damaged Liver

Apoptosis
9

Donnelly et al. J. Clin. Invest. 113: 1343, 2005; Day and James.
Gastroenterol. 114: 842, 1998

These are a Continuum

2nd HIT

1st HIT
FAT >5%

Inflammati
on

Scarring

DCLD

IR and
MS

IR and
MS

CV
Risk
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Natural History of Fatty Liver

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The New Definition of MS

Waist Circum

2 of 5

90 (M), 80 (F)
Triglycerides

>150 mg

HDL

<40 (M) < 50 (F)

Dysglycemia

FPG >100 or DM

Hypertension

>130 or 85

Rx. for any of the above conditions

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Each Perpetuating the Other

NAFLD is the
Hepatic component
of MS

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What is the implication

These are ONE

If we find one
look for the other

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IR

Adiponectin

Leptin,
IL-6
FFA, PC1
Rad, TNF-

Obesity, PPAR-
NEFAs

PC, KC, SC,

LEC

in oxidation
in DAG & TAG

Free radicals
Antioxidants

CC P450 A,E1

TNF-
ATP

Kuffer Cells

Glutathione
PPAR- ,

in oxidative
stress

NO

NF-B

SREBP1a,1c,2

NASH, CV Risk

O2 stress,
Inflmma.

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The Risk Factors

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What Causes Fatty Liver ?

Alcohol
Obesity, WC
T2DM
Triglycerides
Medicines*, TPN

Wilsonss Disease
-1 Anti-trypsin
AI Hepatitis
Hepatitis C
Inherited syndromes

* MTX, VA, Acetaminophen, TC, Tamoxifen,

Nefidepine, Amiodarone, CCl4
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Clinical Presentation
Asymptomatic
Routine blood tests
Liver enzymes
Enlarged Liver (1/3)
RUQ periumb. Pain
Fatigue. Malaise

Anorexia, Nausea
> 90% are obese
USG e/o fatty liver
Acanthosis

Nigricans
DM, HTN, Lipid abn.
OSAS, Snoring

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Laboratory Abnormalities
2 - 4 fold GPT &

Normal Albumin. PT
Low ANA + < 1 in

GOT
SGOT: SGPT Ratio <
320
1
Serum Ferritin
AKP slight in 1/3
Iron saturation
Dyslipidemia - TG
SGOT: SGPT Ratio >
FBG and PPBG
1
BUN & Creatinine - N
if Cirrhosis sets in

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Potential Drugs for NAFLD

Insulin Sensitizing Agents

Membrane-Stabilizing

Glitazones; Metformin

Urso deoxy cholic Acid

Lipid-Lowering Agents

Betaine (SAM)

Clofibrate; Gemfibrozil

Anti-Oxidants

Future Potential
Treatments

Vitamin E; Vitamin C

Anti-fibrotics; Probiotics

Vitamin B Complex

Silymarin; Selenium

Lecithin; -Carotene

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Urso deoxy cholic Acid - UDCA

Evidence of efficacy in NASH/NAFLD is equivocal
300 mg bid or 10 mg/kg in two divided doses PO
Given up to 12 to 24 months - depends on response
Cholestasis, PBC, PSC, Acute viral hepatitis, HBV, HCV
Chronic hepatitis, Alcoholic liver disease
Dissolution of cholesterol microliths / gallstones
Class E drug in pregnancy (not to be used in COP)

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There is No Effective Drug Rx.

NAFLD and NASH may resolve with weight loss
Liver fat content ; No effect on fibrosis & Inflam.
Diet and exercise improve insulin sensitivity,

increase oxidative capacity and utilization of FFAs

Weight loss has clear benefits for CV risk & T2DM

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Berikut adalah beberapa rekomendasi

untuk tatalaksana dari pengobatan NAFLD:

1. Penurunan berat badan dapa mengurangi
steatosis hepatik, akan tetapi diperlukan penurunan
berat badan paling sedikit 10% untuk memperbaiki
necroinflammation.
2. Pasien dengan NAFLD tidak disarankan untuk
mengkonsumsi alkohol dalam jumlah yang banyak.
3. Pemberian vitamin E (a-tocopherol) 800 IU/hari
memperbaiki histologi hati pada pasien dewasa
nondiabetik yang telah dibuktikan dengan biopsi
memiliki NASH, sehingga dapat dipertimbangkan
sebagai terapi lini pertama.
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Berikut adalah beberapa rekomendasi

untuk tatalaksana dari pengobatan
NAFLD:
4. Omega-3 dapat dipertimbangkan sebagai terapi lini
pertama pada pasien NAFLD dengan
hipertrigliseridemia.
5. Metformin tidak direkomendasikan sebagai terapi
spesifk untuk penyakit hati pada dewasa dengan NASH.
6. Pioglitazone dapat digunakan sebagai terapi
steatohepatitis pada pasien dengan NASH yang telah
dibuktikan dengan biopsi, akan tetapi data keamanan
dan efikasi jangka panjang belum diketahui.
7. Statin dapat digunakan sebagai terapi dislipidemia
pada pasien dengan NAFLD dan NASH, akan tetapi
tidak direkomendasikan pada pasien dengan spesifik
NASH.(MAR)
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TERIMAKASIH

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Take Home Points

It is the main cause of liver enzymes; Isnt that

benign
Spectrum of disease NAFLD NASH Cirrhosis - HCC
Insulin resistance, MS are the key pathogenic features
DM, TG, Non fatty abdominal obesity, increasing age
Always look for DM, TG, CVD if you see fatty liver
Presently, the management is to improve IR, TG, DM
It is a marker of CV Risk. Rx. improve insulin sensitivity
Modify underlying metabolic risk factors diet, exercise
Use Mayo scoring to predict NASH (fibrosis). No biopsy

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