1. Guidelines for the diagnosis and management of Nonalcoholic Fatty Liver Disease (NAFLD): Update in 2012
Sameh M Fakhry MD, Msc, PhD
Consultant of Gastroenterology, Hepatology and Endoscopy
Abu Dhabi Police Medical Services

2. NAFLD
A broad clinico-pathologic spectrum ranging from simple steatosis to NASH LC ESLD ,HCC
NASH:
Steatosis
ballooning degeneration
Mallory bodies
Inflammation
Necrosis & fibrosis.

4. Defining NAFLD
A liver biopsy showing moderate to gross macrovesicular fatty change with or without inflammation (lobular or portal), Mallory bodies, fibrosis, or cirrhosis.
Negligible alcohol consumption
Random blood assays for ethanol should be negative
Absence of serologic evidence of hepatitis B or hepatitis C.

5. Prevalence of NAFLD/NASH
NAFLD is an extremely common liver disease, its prevalence is % of the general population & increases with BMI. NASH affects about 4-5%.
Prevalence of steatosis (BMI>30 kg/m2) & (BMI>35 kg/m2) is estimated at 65–75% & 85–90% respectively.

6. Prevalence of NAFLD/NASH
In obese individuals, the prevalence of NASH increases disproportionately; studies suggest that 15–20% of obese individuals have NASH.
Studies of NASH patients suggest that between 40 & 95% will be obese, > 50% may have II DM & up to 80%may have dyslipidaemia.

8. Causes of NASH/NAFLD Chronic Metabolic Syndrome:
Overweight (Starvation) DM
Dyslipidemia
Drugs and Toxins:
Corticosteroids
Tamoxifen
Amoidarone
Proteases Inhibitors
Industrial solvents

9. Causes of NASH/NAFLD (Cont’d)
Subacute Metabolic Syndromes:
JI By-pass
TPN
Rapid weight loss
Inherited Metabolic Diseases
Liposdystrophy
Abetalipoproteinemia
Celiac Disease
HIV

10. Spectrum of Hepatic Pathology Hepatocellular carcinoma
NAFLD
Spectrum of Hepatic Pathology
Steatohepatitis
Steatosis
NAFLD: Spectrum of Hepatic Pathology
The next several slides illustrate the histopathology of NAFLD. As mentioned earlier, nonalcoholic fatty liver disease (NAFLD) is a spectrum of hepatic pathology that ranges from fatty liver (steatosis) on the most clinically-benign end of the spectrum to cirrhosis on the opposite extreme where most liver-related morbidity and mortality occur. Nonalcoholic steatohepatitis (NASH) is an intermediate form of liver damage that sometimes progresses to cirrhosis. Some individuals who become cirrhotic from NAFLD develop hepatocellular carcinoma.
Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis 2004;24:3-20.
Cirrhosis
Hepatocellular carcinoma

11. Natural History of NAFLD
Unselected population
(100%)
1-4% Over % over
15-20 years years
1.7%
Steatosis
20-30% of total
The Spectrum Of
NAFLD
NASH
2-3% of total
Cirrhosis ??
Death due to
Complication of
cirrhosis
HCC??

13. Ins R Endotoxin The first hit
 Adipose tissue
TNFa/ Ad’nect
 FFA
Ins R
Endotoxin
STEATOSIS
(Ins Resistant)
“Vulnerable”
NORMAL
“Resistant”
The first hit
(Insulin)
 TNF
 Adiponectin
e- flow
FFA oxidizing
enzymes
Hepatic Insulin
resistance
 PPAR-a
FFA oxidation
 CPT I
NASH
The second hits
Oxidative stress
FFA either cause the second hit or sensitise the liver to other second hits

14. NASH—Laboratory Findings
The AST/ALT ratio is usually < 1
ANA positive in ~30%
Increased IgA
Abnormal iron indices in 20% to 60%
Prolonged PT and low albumin with cirrhosis
Alkaline phosphatase is less frequently elevated
Hyperbilirubinemia is uncommon
*Normal labs do not rule out NASH

15. Liver biopsy Liver biopsy and histology in NAFLD/NASH: Limitations
pitfalls and future areas of research in histological definitions

18. How to decide when to do a liver Bx to establish cause of abnormal ALT
Rule out other causes of liver disease
Causes Found No Causes Found
Metabolic Syndrome Present
YES NO
Will Bx Change Rx NO
YES Discuss Risks/Benefits.
Make patient aware of risks of not doing Bx
Consider Bx risks:
FIB4, ELF, fibroscan etc. BX BX

19. Diagnostic Tools and Strategies for NAFLD/NASH
Non-invasive Strategies for NASH and Liver Fibrosis
What are they?
Are they as sensitive as liver biopsy in other words would they replace biopsy

20. Biomarker Characteristics
Sensitive (e.g., lowest level of detection)
Specific (e.g., assay specific to marker, effect)
Reproducible – experimental and population-based conditions
Accurate and relevant (actual marker or surrogate)
Carefully validated in human studies
Can be carried out using small quantity Reliable
Simple
Rapid

21. Many Tests, the most vaildated are: APRI Test Fibro Test
Serum Markers
Many Tests, the most vaildated are:
APRI Test
Fibro Test

22. Fibroscan It is measure for the liver stiffness
Validated in HCV but not in NAFLD

23. US, CT, MRI
US (transient elastography) and CT: detect moderate and sever steatosis
MRI: Detection of all degrees of steatosis with quantification of hepatic fat (MRI spectroscopy, MR elastography)

24. Treatment of NASH Correcting Risk factors for NASH Using drugs
Life style e.g Diet, exercise
Medicines
Surgery
Using drugs
Pioglitazone
Vitamin E
Metformin

25. Conclusions
Steatosis is relatively benign, but NASH has significant morbidity/mortality risk
Insulin resistance and cellular damage are the key pathogenetic mechanisms
Diagnosis is bases on combination of biochemical and histological features
Sustained gradual weight loss and exercise are hallmark therapies
Insulin sensitizers, cytoprotectants, antioxidants may play role in future for those who fail conservative therapy