Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. It is characterized by hepatic steatosis without significant alcohol consumption and ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH). The pathogenesis involves insulin resistance and oxidative stress leading to steatosis and liver damage in genetically predisposed individuals. Diagnosis involves testing to exclude other causes and may require liver biopsy. Treatment focuses on lifestyle modifications like weight loss through diet and exercise while supplements and medications aim to reduce insulin resistance and oxidative stress.

1. NON ALCOHOLIC FATTY
LIVER DISEASE
ANILA SAJJAD
MBS 163010

2. OUTLINE OF PRESENTATION
• INTRODUCTION AND DEFINITIONS
• PATHOGENESIS AND RISK FACTORS
• DIAGNOSIS
• PROGNOSIS AND COMPLICATIONS
• MANAGEMENT
• TREATMENT
• MONITORING
• SUMMARY

3. Nonalcoholic Fatty Liver Disease (NAFLD)
Most common of All liver Disorders
 Most frequent cause of chronic liver disease most
common cause of End stage Liver Disorder Needing liver
transplantation.
Present in up to 75% of individuals with obesity and type
2 Diabetes
 Present in 3% of children and > 50%obese children.

4. Nonalcoholic Fatty Liver (NAFL)
Evidence of Hepatic steatosis either by imaging or Histology (>
5% of hepatocytes histologically) without any other Cause for
secondary Fat Accumulation with no evidence of hepatocellular
injury in the form of ballooning of the hepatocytes or no
evidence of fibrosis.
The risk of progression to cirrhosis and liver failure is minimal.
Nonalcoholic steatohepatitis (NASH)
Presence of hepatic steatosis and inflammation with hepatocyte
injury (ballooning) with or without fibrosis.
This can progress to cirrhosis, liver failure and rarely liver
cancer

5. SPECTRUM OF NAFLD

6. NAFLD -DEFINITION
1) EVIDENCE OF HEPATIC STEATOSIS (IMAGING/HISTOLOGY)
2) NO CAUSE FOR SECONDARY FAT ACCUMULATION (SIGNIFICANT ALCOHOL
CONSUMPTION, DRUGS, HEREDITARY CONDITIONS)
WORKING CLASSIFICATION OF NAFLD
NNFL(NON NASH FATTY LIVER)
TYPE 1 : ONLY STEATOSIS
TYPE 2 : STEATOSIS + NON SPECIFIC LOBULAR INFLAMMATION
NASH( NON ALCOHOLIC STEATOHEPATITIS)
TYPE 3 : STEATOSIS + INFLAMMATION +/- FIBROSIS OF VARIABLE LEVELS
TYPE 4 : STEATOSIS + INFLAMMATION + HEPATOCYTE BALLOONING + FIBROSIS/MALLORY DENK BODIES

7. Fatty liver (Steatosis)
Steatohepatitis
- inflammation
- fibrosis
Cirrhosis
Normal liver
NON-ALCOHOLIC FATTY LIVER DISEASE
(NAFLD)

8. NFLD : A BURDEN WORLDWIDE

10. ENVIRONMENTAL FACTORS FOR A FATTY
WORLD

11. CAUSES OF NAFLD
• ACQUIRED METABOLIC DISORDER(DM,OBESITY ,HYPERLIPIDEMIA,STARVATION)
• CYTOTOXIC & CYTOSTATIC DRUGS
• METALS(SB,P,U)
• INBORN ERROR OFMETABOLISM(ABETALIPOPROTEINEMIA, GALACTOCEMIA)
• SURGICAL PROCEDURE( GASTRIC BYPASS,JEJUNOILEAL BYPASS)
• MISCELLANEOUS(IBD,SEVERE ANEMIA,TPN)

12. PATHOPHYSIOLOGY
Salgado W, et al. Acta Cir. Bras. 2006;
21.

13. PATHOGENESIS AND RISK FACTORS
INSULIN RESISTANCE IS RELATED TO OBESITY AND IS CENTRAL TO THE PATHOGENESIS OF
NAFLD.
IN ADDITION, OXIDATIVE STRESS AND CYTOKINES ARE IMPORTANT CONTRIBUTING FACTORS,
TOGETHER RESULTING IN STEATOSIS AND PROGRESSIVE LIVER DAMAGE IN GENETICALLY
SUSCEPTIBLE INDIVIDUALS.
KEY HISTOLOGIC COMPONENTS OF NASH ARE STEATOSIS, HEPATOCELLULAR BALLOONING,
AND LOBULAR INFLAMMATION

14. PATHOGENESIS
DIRECTED BY “2 HIT HYPOTHESIS”

15. DIAGNOSIS
WHEN TO SUSPECT NAFLD???
• HISTORY : NO SYMPTOMS ,FATIGUE, MALAISE AND ABDOMINAL
DISCOMFORT.
• THE PRESENCE OF ANY OF THE FOLLOWING, ESPECIALLY WITH A
HISTORY OF ABNORMAL AST/ALT, SHOULD LEAD TO A WORK-UP
FOR NAFLD/NASH:
1. PRESENCE OF OBESITY, ESPECIALLY MORBID OBESITY (BMI > 35)
2. DIAGNOSIS OF TYPE 2 DIABETES MELLITUS
3. DIAGNOSIS OF METABOLIC SYNDROME
4. HISTORY OF OBSTRUCTIVE SLEEP APNEA
5. PRESENCE OF INSULIN RESISTANCE
6. CHRONIC ELEVATION OF AST/ALT, OTHERWISE UNEXPLAINED

16. DIAGNOSIS
• DETAILED PATIENT HISTORY OF ALCOHOL CONSUMPTION—THRESHOLD <
20 G/DAY IN WOMEN, < 30 G/DAY IN MEN.
• PHYSICAL EXAMINATION :
1. CENTRAL OBESITY CORRELATES WITH SEVERITY OF INFLAMMATION ON BIOPSY
2. DORSOCERVICAL LIPOHYPERTROPHY (BUFFALO HUMP) CORRELATES WITH
HEPATOCYTE INJURY.
3. ADVANCED LIVER DISEASE: SPIDER ANGIOMAS, ASCITES, HEPATOMEGALY,
SPLENOMEGALY, PALMAR ERYTHEMA, JAUNDICE, HEPATIC
ENCEPHALOPATHY.

17. DIAGNOSIS
LABORATORY TESTS
• ELEVATED ALT AND AST:
• IN 10% OF NASH PATIENTS, ALT AND AST MAY BE NORMAL, ESPECIALLY WITH SIMPLE STEATOSIS.
• AN ABNORMAL FERRITIN LEVEL IN THE PRESENCE OF NORMAL TRANSFERRIN SATURATION SHOULD ALWAYS SUGGEST A
NEED TO RULE OUT NASH.
• AST/ALT RATIO < 1—THIS RATIO IS USUALLY > 2 IN ALCOHOLIC HEPATITIS.
IMAGING TESTS
 ULTRASOUND IS THE USUAL SCREENING TEST FOR FATTY LIVER.
 THE MAGNETIC RESONANCE IMAGING (MRI) TEST HAS A QUANTITATIVE VALUE, BUT CANNOT DISTINGUISH BETWEEN
NASH AND ASH.
 NO IMAGING STUDY CAN IDENTIFY FAT ACCURATELY IF IT IS < 33% OR DISTINGUISH NASH FROM ASH.

19. Elevated lever enzyme or
Heptomegaly
Exclude excessive alcohol
and other form of liver
disease by history & lab
tests
Image liver by US , CT or
MRI
Normal Fatty Liver
present
Liver
Biopsy
Consider
Liver biopsy to
stage dis&
define risk of

20. WHEN TO OBTAIN A LIVER BIOPSY?
LIVER BIOPSY: “GOLD STANDARD” TO GRADE AND STAGE THE DISEASE, AND TO RULE OUT
OTHER DIAGNOSES IN THE PRESENCE OF ONE OR MORE OF THE FOLLOWING FINDINGS
1. ABNORMAL SERUM FERRITIN IN THE ABSENCE OF AN ELEVATED TRANSFERRIN SATURATION
2. CYTOPENIA
3. SPLENOMEGALY
4. CLINICAL SIGNS OF CHRONIC LIVER DISEASE
5. DIABETES AND ABNORMAL PERSISTENTLY ELEVATED AST/ALT OBESITY AND AGE > 45 OR
ABNORMAL AST/ALT
6. UNEXPLAINED HEPATOMEGALY

21. PROGNOSIS AND COMPLICATIONS
• DISEASE PROGRESSION FROM NAFLD TO NASH TO CIRRHOSIS/LIVER FAILURE AND HCC.
• CONCURRENCE OF NAFLD WITH HEPATITIS C OR HUMAN IMMUNODEFICIENCY VIRUS (HIV)
WORSENS THEIR PROGNOSES AND DECREASES THEIR RESPONSES TO THERAPY.
• LIVER BIOPSY MAY INDICATE THE SEVERITY OF DISEASE, BUT ONLY FIBROSIS, AND NOT
INFLAMMATION OR NECROSIS, HAS BEEN CONFIRMED TO PREDICT THE DISEASE PROGNOSIS.
• END-STAGE NASH IS AN OFTEN UNDER-RECOGNIZED CAUSE OF CRYPTOGENIC CIRRHOSIS
• NASH-RELATED (CRYPTOGENIC) CIRRHOSIS INCREASES THE RISK OF HEPATOCELLULAR
CARCINOMA (HCC).

23. MANAGEMENT
• TARGETS FOR THERAPY : INSULIN RESISTANCE AND OXIDATIVE STRESS
• GOALS OF TREATMENT: REDUCE THE HISTOLOGIC FEATURES AND IMPROVE INSULIN
RESISTANCE AND LIVER ENZYME LEVELS.
• GENERAL APPROACH TO THE PATIENT:
1. WEIGHT LOSS
2. VACCINATIONS
3. TREATMENT OF RISK FACTORS FOR CARDIOVASCULAR DISEASES
4. AVOID ALCOHOL CONSUMPTIONS

24. TREATMENT
• LIFESTYLE MODIFICATION
• DIET AND EXERCISE
• WEIGHT REDUCTION
• INSULIN SENSITIZERS
• METFORMIN
• TROGLITAZONE
• ROSIGLITAZONE
• PIOGLITAZONE
• LIPID LOWERING AGENTS
• ANTIOXIDANTS
• VITAMIN E
• VITAMIN C
• HEPATOPROTECTIVE AGENTS
• BETAINE
• URSODEOXYCHOLIC ACID
• PENTOXYFYLLINE
• ANGIOTENSIN-CONVERTING ENZYME INHIBITORS
• PROBUCOL

25. MONITORING STRATEGY
DISEASE PROGRESSION AND COMPLICATIONS CAN BE DETECTED DURING THE FOLLOW-UP AS
INDICATED

26. SUMMARY
• NAFLD IS MORE COMMON THAN ALCOHOLIC FATTY LIVER DISEASE
• INSULIN RESISTANCE AND FREE RADICAL OXIDATIVE DAMAGE IS THE CULPRIT
FOR PATHOGENESIS
• DIAGNOSIS OF EXCLUSION
• DIET CONTROL AND EXERCISE IS THE HOPE FOR FUTURE
• SUPPLEMENT THERAPIES HAVE GOT SOME ROLE