Management of NAFLD

1. Management of NAFLD
Dr. Rahimi gastroenterologist

3. NAFLD
Silymarine??

4. NAFLD
• Refer to hepatologist if diagnosis is unclear, significant
elevation in liver enzymes or evidence of cirrhosis
• weight loss:
• Diet
• Exercise
• Pharmacologic therapy
• bariatric surgery if indicated →reduce NASH progression and
improvement histology including fibrosis in most patient

5. NAFLD
• MetS: (NCEP ATP3) ≥3:
• FBS>100mg/dl or drug treatment for elevated BG
• HDL<40mg/dl for men or <50mg/dl for women or drug treatment
for low HDL-C
• TG≥150mg/dl or drug treatment for elevated TG
• Obesity: weist≥102(90)cm (men) or ≥88(80)cm (women)
• HTN ≥130/85mmhg or drug treatment for HTN
• Treatment of risk factors for CVD (MetS):
• T2DM
• HLP; statin is safe; caution in cirrhosis
• HTN

6. NAFLD
• avoid alcohol consumption
• Heavy drinker:
• consumption >21 standard drinks on average per week in men and >14 in women
• Or consumption ≥30 g/d for men and ≥20 g/d for women
• Or once ≥60 g
• Avoid smoking
• Hepatitis A and B vaccinations
• In NAFLD with high ferritin levels → phlebotomy to reduce iron stores to
near iron deficiency improved the NAS score, without worsening fibrosis
but more data are needed
• pharmacologic therapy

7. Weight loss
• improvement in liver enzymes, serum insulin levels, histology
and quality of life
• combination of a hypocaloric diet (daily reduction by 500-
1,000 kcal) and moderate-intensity exercise
• Some processed foods
• high cholesterol foods
• beverages high in added fructose
• Exercise (aerobic or resistance training)

8. Weight loss
• Weight loss 3%-5% of body weight is necessary to improve
steatosis
• Weight loss 7%-10% of body weight is needed to improve
histopathological features of NASH, including fibrosis (target)
• Exercise alone→prevent or reduce hepatic steatosis, but
other histology?
• 0.5 to 1 kg/week
• faster weight loss → portal brosis

9. Pharmacologic therapies
• Patients without NASH or fibrosis → only diet and physical
activity, no pharmacotherapy
• Indicated in:
• significant fibrosis (stage F2 or F3 and higher)
• progressive NASH
• early-stage NASH with increased risk of fibrosis progression (age
>50 years; diabetes, MetS, persistently increased ALT, active
NASH)

10. Pharmacologic therapies
• Controversial
• Vitamin E
• Pioglitazone
• Duration:
• if increased ALT at baseline, treatment should be stopped if there
is no reduction in aminotransferases after 6 months of therapy
• in patients with normal ALT at baseline, no recommendations can
be made

11. Vitamin E
• ↓oxidative stress
• Liver enzymes (variable)
• Improving histology
• Fibrosis?
• for nondiabetic and without CAD with biopsy-proven NASH
or advanced fibrosis (F≥3)
• With dose of 800 IU/day
• increase in all-cause mortality with high-dose vitamin E (>400
IU/day)

12. pioglitazone
• improve liver biochemical, histology and fibrosis
• weight gain, heart failure
• In biopsy-proven NASH with T2DM
• 30-45mg/d

13. Not recommended
• Metformin: no effect on ALT, BMI and histology
• Liraglutide: resolving NASH, decrease in fibrosis progression,
(an option in future)
• Orlistat:
• no benefit
• only for weight loss
• Ursodeoxycholic acid:
• antiapoptotic and anti-inflammatory effects
• some biochemical improvement
• no histological improvements

14. Not recommended
• Obeticholic acid:
• chenodeoxycholic acid
• improving liver histology
• more studies needed
• Statin: lower liver enzymes, more studies needed
• Pentoxifylline: variable results
• Omega-3 fatty acids: improvement of hepatic steatosis
• Betaine
• losartan

15. silymarine
• extract of Silybum marianum, or milk thistle
• its major active compound is silybin
• used in different liver disorders!
• antioxidant, anti-inflammatory and antifibrotic
• Silymarine in NAFLD → ↓oxidative stress, insulin resistance,
visceral and liver fat accumulation, mitochondrial
dysfunction

16. silymarine
• Silybin alone or with complex → variable result on
ultrasonography of bright liver, liver enzyme levels, HOMA-
IR(Homeostasis Model Assessment of Insulin Resistant),
serum indices of liver fibrosis and histology
• Small trails with no standardization of methods and no well-
structured
• Treatment with silymarin in routine clinical practice is
strongly limited

17. NASH cirrhosis
• management of portal hypertension (R/O esophageal varix,
ascites,…)
• screening of HCC
• LT

18. NASH cirrhosis
Physician should not visit the
patient in this stage!!

20. Liver biopsy
• Peripheral stigmata of chronic liver disease
• Splenomegaly
• Cytopenias
• Serum ferritin >1.5 times the upper limit of normal
(suggestive of NASH and advanced fibrosis)
• Age >45 years with associated obesity or diabetes (increased
risk of advanced fibrosis)

21. Liver biopsy
• repeat liver biopsy 5-7 years or sooner if there is evidence of
worsening liver disease
• Monitoring of fibrosis progression with combination of
biomarkers including HOMA-IR and elastography (requires
validation)