Intervensi Gizi

untuk
Perlemakan
Hati (fatty Liver)
Meike Mayasari, S.Gz, MPH, RD
Registered Dietisien
 Fungsi Organ Hati
Semua darah lewat
Regulasi zat terlarut
dari usus kecil
Dalam darah yang
melalui hati
01 mempengaruhi
fungsi organ lain 02

Penyimpanan dan Metabolisme Metabolisme

metabolisme makronutrien mikronutrien dan ekskresi
03 Protein,
karbohidrat dan
04 Vitamin dan
mineral
05 Obat dan toksin
endogen dan
lipid eksogen
 Perlemakan Hati

Definisi Pada beberapa pasien

Perlemakan hati dapat disertai dengan
Penumpukan trigliserida dan lemak lain peradangan hati dan kematian sel hati
di dalam sel hati. (steatohepatitis)
 Penyebab

01 02 03
Sindrom Metabolik Kelainan Metabolik Obat-obatan
Diabetes tipe II Galaktosemia Amiodaron
Obesitas Homosistinuria Tamoksifen
Hipertrigliseridemia Tirosinemia Matotreksat

04 05
Status Gizi Faktor lain
Kelebihan berat badan Alkohol
Malnutrisi berat Celiac sprue
TPN penyakit Wilson
Starvasi
 TIPE
PERLEMAKAN HATI

NAFLD/ NASH

01
Perlemakan Hati Non-Alkoholik/
Non Alcoholic Fatty Liver
•
Lebih dari 5% akumulasi lemak hati
• Sering terjadi pada seseorang yang tidak
mengkonsumsi alkohol
• Dapat bekembang menjadi sirosis dan gagal hati

PHA

02
Perlemakan Hati Alkoholik/
Alcoholic Fatty Liver/ Alcohol-
Related Liver Disease (ARLD)

penyakit perlemakan hati akibat konsumsi

alkohol secara berlebihan
 Prevalensi NAFLD

90% NAFLD
Dari populasi obesitas

3-5% NASH

25% of the global

Schematic of progression non-alcoholic fatty liver disease (NAFLD)
Normal liver Simple Steatosis NASH/ fibrosis Cirrhosis Liver Cancer

20-30% 15-25% 5-10% 2-5%

➢ Massive steatosis with
➢ Fat accumulation ➢ End stage liver
indications of ➢ Inability of the
in the hepatocyte injury, disease, in which liver to regenerate
hepatocytes, inflammation, most of the of repair (liver
➢ no hepatocellular ➢ ballooning hepatocytes are failure), a
ballooning, degeneration with or replaced by replacement is
➢ no fibrosis without fibrosis, and collagen.
occasionally presence
needed)
➢ Bridging septa,
of mallory bodies.
regenerating
➢ Within 10-20 years, it
may progress to
nodules
cirrhosis
 Faktor Kontributor Progress NAFLD

Obesitas Sleep Apneu

DM Tipe 2 Dysbiosis microba usus

Western Type Diet Psoriasis

Sedentary Lifestyle
 Western diet ?

Rich in … Poor in …
• soda, • cereals,
• frozen junk food, • whole grains,
• juice, • fruit,
• red meat, • vegetables,
• lard, • extra virgin olive oil (EVOO) and fish
• processed meats,
• whole fat dairy foods,
• fatty snack foods,
• take-away foods,
• cakes and biscuits
HOW ?

NAFLD sering menunjukkan

60% pasien DM tipe 2 → NAFLD hiperlipidemia campuran

Konsekuensi : 2,5x lebih tinggi risiko ↑ LDL –C

kematian akibat penyakit hati kronis ≈ ↓ HDL-C dan trigliserida
sindrom metabolik 50% px dislipidemia memiliki NAFLD
 Gejala Fatty Liver

Bisa karena temuan tidak

Tidak ada Tidak spesifik
disengaja

kelelahan/ malaise
Pada pencitraan untuk
Sering tidak bergejala Perasaan penuh/ tidak nyaman di
pemeriksaan tujuan lainnya
sisi kanan abdomen
Treatment
Perubahan Gaya Hidup
untuk NAFLD dan NASH
 NAFLD treatment ?

First line on
therapy :
Diet & exercise
intervention

No clear Simple,
multidisiplinary,
pharmalogical nutritional
treatment guidelines are
needes
It is clear → Has not ben
focus on clearly
lifestyle established :
modification extent &
composition of
the diet
 NAFLD dietary patterns/food/nutrients chart
Berná, G., & Romero‐Gomez, M. (2020). The role of nutrition in non‐alcoholic fatty liver disease:
Pathophysiology and management. Liver International, 40(S1), 102–108. doi:10.1111/liv.14360

❑ X Western diet dikaitkan dengan

kejadian NAFLD

✓ Diet Mediterania dan Diet DASH

s memiliki efek
pada NAFLD
menguntungkan
Diet Mediterania

Tinggi proporsi asam lemak tidak jenuh

(MUFA dan PUFA) Definisi tidak seragam

Sayuran, buah-buahan, gandum utuh

biji-bijian, ikan berlemak, rendah daging merah, produk
susu rendah lemak, tinggi kacang-kacangan dan polong-
polongan
Sumber

• Lemak sedang (32 sd 35%)

• Rendah lemak jenuh ( 9-10%)
• Tinggi asam lemak tak jenuh ganda (terutama omega 3) Pola diet MeD
• Tinggi serat (27 sd 37 gram/hari)

Mahan & Raymond. 2017. Krause’s Food & The Nutrition Care Process 14th edition. Elsevier Inc.All rights Reserved
Diet DASH (dietary approaches to stop hypertension)

Tinggi mineral kalsum, potassium dan

magnesium

Rendah lemak dan tinggi serat

• Tinggi buah-buahan dan sayuran, produk susu rendah

lemak
• Kaya bji-bijian, ikan dan kacang-kacangan Pola diet DASH
• Rendah protein hewani dan gula

Mahan & Raymond. 2017. Krause’s Food & The Nutrition Care Process 14th edition. Elsevier Inc.All rights Reserved
Treatment of NAFLD with diet, physical activity and exercise
Manuel Romero-Gómez1,⇑, Shira Zelber-Sagi2,3, Michael Trenell4
Journal of Hepatology 2017 vol. 67 j 829–846
 The association between coffee or caffeine consumption and NAFLD
Improvement in Improvement in
Author Type of coffee Sample size
steatosis fibrosis

All caffeinated coffee

Zelber-Sagi 2015 80 347 No Yes (Fibrotest)
types

Caffeinated and
Bambha 2013 82 782 No Yes
decaffeinated

Regular coffee, not

Anty 2012 81 195 NE Yes
espresso

Birerdinc 2012 84 Caffeine intake 41,658 Yes NE

Molloy 2012 79 Regular coffee 306 No Yes

Catalano 2010 83 Only espresso coffee 245 Yes NE

NE, not evaluated

Gomez, et al.. Journal of Hepatology, volume 67, issue 4, P829-846
 Coffee Consumption and Non-alcoholic Fatty Liver Disease:
An Umbrella Review and a Systematic Review and Meta-analysis
Chayanis Kositamongkol, Sukrit Kanchanasurakit, Chiraphong Auttamalang, Nutkamon Inchai, Thanatchaporn Kabkaew, Sarunporn Kitpark,
Nathorn Chaiyakunapruk, Acharaporn Duangjai, Surasak Saokaew and Pochamana Phisalprapa
Frontiers in Pharmacology | www.frontiersin.org. December 2021 | Volume 12 | Article 786596

Hasil kontras pada populasi umum

✓ 4 SMRS dlm studi payung → individu
dalam populasi umum yang secara teratur
minum kopi secara signifikan terkait
dengan kejadian NAFLD yang lebih rendah
✓ 9 studi → konsumsi kopi tidak
berhubungan dengan insiden NAFLD yang
lebih rendah pd populasi umum
✓ Heterogenitas studi tinggi

Kopi pada NAFLD

✓ 5 studi → pasien dengan NAFLD, konsumsi
kopi signifikan penurunan fibrosis hati (OR
0,67)
✓ 4 studi → Tidak ada perbedaan konsumsi
kopi pd populasi umum dan pasien
dengan NAFLD atau pasien dengan fibrosis
ringan dan fibrosis signifikan
Lifestyle modification in NAFLD/NASH: Facts and figures
Kate Hallsworth , Leon A Adams.
JHEP. Rep. 2019 Nov 5;1(6):468-479. doi: 10.1016/j.jhepr.2019.10.008
Intervensi Diet dan NAFLD ? ( systematic review dr 8 study)

Diet mediterania tanpa pembatasan energi Diet Hipokalorik dengan diet tinggi asam
• Menurunkan kandungan lipid intrahepatatal lemak tak jenuh
• Tidak ada perubahan alanin transaminase (ALT)
• Tidak ada perubahan konsentrasi gamma- • Menurunkan ALT
glutamyl transpeptidase (gGT), total • Menurunkan aspartate
cholesterol, LDL-C, HDL-C, triglyceride, glukosa aminotransferase (AST)
puasa / insulin, atau asesmen homeostasis
untuk resisitensi insulin
Makronutrien dan NAFLD
FAT
SFA dan trans fat MUFA, PUFA
Merusak hati Efek menguntungkan untuk hati

SFA
• Meningkatnya lemak hati terkait
lipogenesis + meningkatnya PUFA
lipolysis jaringan adiposa • Suplementasi Omega 3 ,
• Berkaitan dengan gangguan menurunkan kandungan lemak
metabolisme glutathione + hati dan skor steatosis
meningkatnya stress oksidatif → • Diet hiperkalori jangka panjang
perkembangan NAFLD yang kaya PUFA ( omega 3 dan
• Belum jelas sumber SFA (susu vs omega 6), mencegah akumulasi
daging) apakah ada efek beda fatty liver pada overweight
pd kandungan fatty liver

Kolesterol MUFA ex EVOO extra virgin olive oil

• Kontribusi pada NAFLD belum • Konsumsi 20 g/ hari selama 12
jelas minggu + diet hipokalori →
• beberapa studi → Memperbaiki fatty liver
meningkatnya kolesterol
Berná, G., & Romero‐Gomez, M. (2020). The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management. Liver
terkait perkembangan NAFLD International, 40(S1), 102–108. doi:10.1111/liv.14360
 The influence of olive oil on fatty liver
Constituent Mechanism of action
Anti-inflammatory and immunomodulatory
Oleic acid Phenols
effects
Phenols: Hydroxytyrosol Oleuropein
Decreased lipid oxidation Decreased DNA
Caffeic acid O-coumaric acid Vanillic acid
damage
3,4-Dihydroxyphenyl ethanol
Oleic acid Decreased synthesis of arachidonic acid

Hydroxytyrosol Inhibits lipo-oxygense

Inhibits HMG-CoA reductase Inhibits RAS
Squalene
activation
Decreased membrane permeability and
Oleic acid Lignans
oxidation
Protocatechuic acid Decreased synthesis of arachidonic acid

Kargulewicz, et al.. Dietary recommendations for patients with non-alcoholic fatty liver disease. Prz Gastroenterol.2014 ; 9(1): 18–23
Makronutrien dan NAFLD
Karbohidrat

Gula tambahan (sukrosa, fruktosa dan sirup

Hubungan ? jagung tinggi fruktosa) dengan NAFLD

Ex : cakes, soft drink dan snack manis →

Tinggi fruktosa meningkatkan risiko NAFLD

Pasien dewasa Konsumsi tinggi fruktosa, meningkatnya

fibrosis dan pembengkakan hati
dengan NAFLD

Efek serat ?
Berná, G., & Romero‐Gomez, M. (2020). The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management. Liver
International, 40(S1), 102–108. doi:10.1111/liv.14360
 Serat dan NAFLD ?

❏ Belum dipelajari ekstensif Konsumsi rendah serat

❏ Konsumsi rendah serat + pola diet lain
terkait NAFLD
❏ Perubahan microbiota usus

diamati terjadi pada pasien Menginduksi disbiosis

NAFLD
❏ Asupan prebiotic →

meningkatkan fenotip hati Memodifikasi mikrobiota

pada NAFLD Menginduksi endotoksemia
Peradangan sistemik
Resistensi insulin
Peradangan & kesusakan hati
Makronutrien dan NAFLD
Protein

Bagaimana?
● Peran protein terhadap perkembangan
NAFLD belum jelas

● Konsumsi protein hewani ??

Berná, G., & Romero‐Gomez, M. (2020). The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management. Liver
International, 40(S1), 102–108. doi:10.1111/liv.14360
 Mikronutrien dan NAFLD

Mikronutrien terlibat Peran Pada NAFLD dilaporkan …

➢ Zink ✓ Sebagai antioksidan, ▪ Terjadi penurunan serum zink,

➢ Copper ✓ antifibrotik, copper, vitamin A, C,D,E dan
➢ Iron ✓ efek imunomodulator, karotenoid
➢ Selenium ✓ efek lipoprotektif ▪ Kelebihan selenium dan iron
➢ Magnesium berperan dalam keparahan NAFLD
➢ Vitamin A, C, D, E
➢ Karotenoid Berná, G., & Romero‐Gomez, M. (2020). The role of nutrition in non‐alcoholic fatty liver disease: Pathophysiology and management. Liver
International, 40(S1), 102–108. doi:10.1111/liv.14360
 Studi tentang efek probiotik terhadap area lemak
visceral (VFA) dan fraksi lemak intrahepatik (IHF)
pada NAFLD.

➢ 65 pasien NAFLD obesitas diacak untuk diberikan

probiotik (campuran 6 spesies bakteri) dan kelompok www.nature.com/scientificreports. (2019) 9:5688 | https://doi.org/10.1038/s41598-019-42059-3

plasebo selama 12 minggu.

➢ Berat badan dan total lemak tubuh berkurang dalam
probiotik kelompok tetapi tidak dalam kelompok plasebo.
➢ Fraksi IHF rata-rata berkurang setelah 12 minggu
pengobatan pada kelompok probiotik dibandingkan
dengan pada awal
➢ Pengurangan trigliserida lebih besar pada kelompok
perlakuan probiotik dibandingkan kelompok placebo
➢ Pengobatan dengan probiotik selama 12 minggu
menghasilkan penurunan yang signifikan pada IHF dan
berat badan pada pasien NAFLD obesitas
 Probiotics may restore intestinal barrier
NAFLD and probiotic-related beneficial mechanisms integrity, positively acting on ZO-1
expression, mucus thickness and
commensal bacteria proportion (eubiosis).

Moreover, they participate to the

shutdown of bowel inflammation, enrolling
T regulatory cells, DCs and macrophages
to secrete anti-inflammatory cytokines
(TGF-β and IL10).

In the liver, the reduction of endotoxemia

halts hepatic damage, as shown by lower
aminotransferases (ALT and AST) and
contributes to the recovery of the hepatic
functions, affecting the lipid

Meroni, M., Longo, M., & Dongiovanni, P. (2019). The Role of

Probiotics in Nonalcoholic Fatty Liver Disease: A New Insight
into Therapeutic Strategies. Nutrients, 11(11),
2642. doi:10.3390/nu11112642
Gut microbiome-targeted therapeutic strategies against NAFLD

Dysbiosis promotes the process of

nonalcoholic fatty liver disease via
multiple pathways

Gut microbiome-targeted therapeutic

strategies include probiotic, prebiotic,
synbiotic, and fecal microbiota
transplantation

Gut microbiome can reverse dysbiosis

and mitigate the process of NAFLD
✓ 28 clinical trials enrolling 1555 criterion proven NAFLD patients with the
use of probiotics from 4 to 28 weeks were included.
▪ Probiotik → penurunan regulasi lipogenik, oksidatif, dan sinyal inflamasi.
Probiotic therapy had beneficial effects on body mass, alanine ▪
aminotransferase, aspartate transaminase , gamma-glutamyl, insulin, Probiotik memodulasi komposisi mikrobiota usus dan produknya, dan
homeostasis model assessment-insulin, and total cholesterol, but not in permeabilitas usus.
fasting blood sugar, lipid profiles, or tumor necrosis factor-alpha.
Conclusion. ▪ Probiotik juga menghasilkan glikemik yang lebih baik mengontrol dan
mengurangi berat hati.
The systematic review and meta-analysis support that probiotics are superior
to placebo in NAFLD patients and could be utilized as a common ▪ Potensi hepatoprotektif probiotik terhadap NAFLD
complementary therapeutic approach
 Benefits of exercise
and physical activity
in NAFLD

Keterangan :
EDV : end diastolic volume;
SV : stroke volume;
EF : ejection fraction;
Romero-Gómez, M., Zelber-Sagi, S., & Trenell, M. (2017). Treatment of FMD : flow-modulated dilatation; VLDL
NAFLD with diet, physical activity and exercise. Journal of : very low density lipoprotein.
Hepatology, 67(4), 829–846. doi:10.1016/j.jhep.2017.05.016
 Extrahepatic benefits of
physical activity and exercise
for patients with NAFLD

✓ Physical activity and exercise offer a host

of extrahepatic benefits for patients with
NAFLD across the disease spectrum and
are useful tools to aid weight-loss
maintenance.

✓ Increasing cardiorespiratory fitness and

muscle strength can help to maintain and
improve the ability to perform day-to-day
activities and thus improve quality of life..

Kate Hallsworth, Leon A Adams. 2019. Lifestyle modification in NAFLD/NASH: Facts and figures
JHEP. Rep. 2019 Nov 5;1(6):468-479. doi: 10.1016/j.jhepr.2019.10.008
 Probability of reaching NASH resolution, fibrosis regression (at least one stage) and steatosis
improvement in patients with NASH under lifestyle intervention according to percentage of weight loss

Romero-Gómez, M., Zelber-Sagi, S., & Trenell, M. (2017). Treatment of NAFLD with diet, physical
activity and exercise. Journal of Hepatology, 67(4), 829–846. doi:10.1016/j.jhep.2017.05.016
The role of the multidisciplinary approach and behavioural therapy in
the lifestyle treatment of NASH

Ask Advise Asses Assist Arrange

5A Model
➢ May be useful as a tool to assist clinicians advising NAFLD patients to modify their behaviour,
➢ assessing their interest in doing so,
➢ assisting in their efforts to change,
➢ and arranging appropriate follow-up.

Romero-Gómez, M., Zelber-Sagi, S., & Trenell, M. (2017). Treatment of NAFLD with diet, physical
activity and exercise. Journal of Hepatology, 67(4), 829–846. doi:10.1016/j.jhep.2017.05.016
Useful techniques to support patients to Practical tips on how to support patients to
make and sustain lifestyle changes make lifestyle changes for clinicians

1. Explain what NAFLD is and that it is reversible with lifestyle change;

address any misconceptions e.g. alcohol being the cause of NAFLD
2. Explain energy balance in relation to body weight changes
3. Set a SMART (see Fig) weight loss target
4. Use appropriate interventions e.g. regular meal patterns, reduced
snacking, portion control
5. Encourage use of self-regulation/self-monitoring tools e.g.
Regular weighing
a. Count daily calories to track food intake using a diary,
smartphone app or internet websites
b. Use of pedometers/activity trackers
c. Read nutrition information labels to check, compare & choose
healthier options
d. Develop skills in meal planning, shopping, food preparation &
cooking
6. Sign posting to local Exercise Schemes, community gyms, weight
management programmes, walking groups

Kate Hallsworth, Leon A Adams. 2019. Lifestyle modification in NAFLD/NASH: Facts and figures
JHEP. Rep. 2019 Nov 5;1(6):468-479. doi: 10.1016/j.jhepr.2019.10.008
Thankyou