WELCOME

DR. SYEDA NUR-E- JANNAT

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AASLD PRACTICE GUIDELINE

THE DIAGNOSIS AND MANAGEMENT OF NON-

ALCOHOLIC FATTY LIVER DISEASE : PRACTICE
GUIDELINE BY AMERICAN ASSOCIATION FOR THE
STUDY OF LIVER DISEASE,AMERICAN COLLEGE OF
GASTROENTEROLOGY, AND THE AMERICAN
GASTROENTEROLOGICAL ASSOCIATION

HEPATOLOGY,
Official journal of the American Association For The
Study Of Liver Disease,
Vol. 55 , Issue 6 ,page 2005-2023,June 2012

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THESE RECOMMENDATIONS ARE BASED ON FOLLOWING :

•Formal review and analysis of the recently published

world literature on the topic [medline search up to June
2011]
•American College OF Physicians’ manual for assessing
health practices and designing practice guideline
•Guideline policies of the three socities approving this
document.
•The experience of the authers and independent reviewers
with regards to NAFLD

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HIGHLIGHTS

 DEFINITIONS -NAFLD,NAFL,NASH,NASH CIRRHOSIS

NATURAL HISTORY

INCIDENCE AND PREVALANCE

EVALUATION OF NAFLD

MANAGEMENT OF PATIENTS WITH NAFLD

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DEFINITIONS

NAFLD: The entire spectrum of fatty liver disease in individual

without significant alcohol consumption, ranging from fatty liver to
steatohepatitis and cirrhosis.

NAFL: Presence of hepatic steatosis with no evidence of

hepatocellular injury in the form of ballooning of hepatocytes or no
evidence of fibrosis.

NASH: Presence of hepatic steatosis AND inflammation with

hepatocyte injury (ballooning) with or without fibrosis

NASH Cirrhosis: presence of cirrhosis with current or previous

histological evidence of steatosis or steatohepatitis

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NAFLD
(a) evidence of hepatic steatosis, either by
imaging or by histology
and
(b) no causes for secondary hepatic fat
accumulation .

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COMMON CAUSES OF SECONDARY HEPATIC
STEATOSIS
Macrovesicular steatosis-
Excessive alcohol consumption- ongoing or recent consumption of significant
quantities of alcohol >21 drinks per week in men
>14 drinks per week in women over a 2-year period
Hepatitis C (genotype 3)
Wilson's disease
Medications (e.g., amiodarone, methotrexate, tamoxifen, corticosteroids)
Lipodystrophy
Starvation
Parenteral nutrition
Abetalipoproteinemia

Microvesicular steatosis-
Medications (valproate, anti-retroviral medicines)
Acute fatty liver of pregnancy
HELLP syndrome
Reye's syndrome
Inborn errors of metabolism (e.g., LCAT deficiency, cholesterol ester storage
disease, Wolman disease) 7
RISK FACTORS ASSOCIATED WITH NAFLD

Conditions with established association

Obesity

Type2 diabetes mellitus

Dyslipidemia

Metabolic syndrome

Conditions with emerging association

Hypothyroidism

Polycystic ovary syndrome

Obstructive Sleep Apnea

Hypopituitarism

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THE METABOLIC SYNDROME

The Adult Treatment Panel III clinical definition :

three or more of the following features:
(1) waist circumference > 102 cm in men or
> 88 cm in women;
(2) triglyceride level ≥ 150 mg/dL
(3) HDL cholesterol level < 40 mg/dL in men and
< 50 mg/dL in women;
(4) blood pressure ≥ 130 / 85 mm Hg
(5) fasting plasma glucose level ≥ 110 mg/dL

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INCIDENCE AND PREVALENCE

General Population
Incidence
Two Japanese studies 31 and 86 cases of suspected NAFLD per 1,000 person-years
respectively

Prevalence

NAFLD - 6.3% to 33% (WORLDWIDE)

median of 20% in general population
NASH -3 to 5%.
NASH cirrhosis -not known.

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INCIDENCE AND PREVALENCE
PREVALENCE IN HIGH RISK GROUP
OBESITY: severe obesity undergoing bariatric surgery
NAFLD - 90%
unsuspected cirrhosis- 5%

T2DM: NAFLD - 69%(USG)

87%(USG+BIOPSY)

DYSLIPIDEMIA- NAFLD -50%

Age
Gender
ethnicity

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NATURAL HISTORY

NAFL : Minimal risk of progression to cirrhosis

and liver failure .

NASH: can progress to cirrhosis, liver failure and

rarely liver cancer.

NASH Cirrhosis: increased risk for HCC.

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The long term outcomes:

(a) patients with NAFLD have increased overall mortality compared

to matched control populations

(b) the most common cause of death in patients with NAFLD,

NAFL and NASH is cardiovascular disease

(c) patients with NASH (but not NAFL) have an increased liver-
related mortality rate.

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NATURAL HISTORY OF NASH CIRRHOSIS VERSUS
HEPATITIS C CIRRHOSIS

•lowerrate of decompensation and mortality in patients

with NASH cirrhosis

•overall10-year survival was not different from matched

patients with hepatitis C cirrhosis.

•NASH cirrhosis are at significantly lower risk for HCC than

patients with hepatitis C cirrhosis.

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EVALUATION OF INCIDENTALLY DISCOVERED
HEPATIC STEASOSIS

1. symptoms or signs of liver disease

OR abnormal LFT

evaluate as suspected NAFLD and worked up

accordingly

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EVALUATION OF INCIDENTALLY DISCOVERED
HEPATIC STEASOSIS

2. NO liver-related symptoms or signs

and normal LFT

assess
1. metabolic risk factors(e.g., obesity, glucose
intolerance, dyslipidemia)
2 alternate causes for hepatic steatosis – significant
alcohol consumption or medications.

liver biopsy not recommended

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SCREENING

NAFLD:

In Primary Care, Diabetes, and Obesity Clinic

(higher-risk individuals)
Family Member

not advised

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SCREENING

NASH CIRRHOSIS

gastroesophageal varices
HCC screening

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INITIAL EVALUATION

exclude :
1. competing etiologies for steatosis
2. co-existing common chronic liver disease
hemochromatosis
autoimmune liver disease
chronic viral hepatitis
Wilson's disease.
PBC

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ASSESSMENT OF STEATOHEPATITIS AND
ADVANCED FIBROSIS IN NAFLD

Non-invasive
Serum aminotransferase levels
ultrasound, CT, and MRI
NAFLD Fibrosis Score
Enhanced Liver Fibrosis (ELF) panel
Transient elastography.
serum/plasma cytokeratin-18 (CK18 )

Invasive
Liver biopsy

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 NAFLD FIBROSIS SCORE

This based on six readily available variables

(age, BMI, hyperglycemia, platelet count, albumin, AST/ALT ratio)

calculated using the published formula (http://nafldscore.com)

Score sensitivity specificity

< −1.455 90% 60% exclude advanced fibrosis
> 0.676 67% 97% presence of advanced fibrosis.

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PLASMA CK18

sensitivity of 78%
specificity of 87%,

promising biomarker to identify steatohepatitis

not recommend in routine clinical practice

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LIVER BIOPSY

GOLD STANDARD

WHOM TO DO ?
1. patients with NAFLD who are at increased risk to have
steatohepatitis and advanced fibrosis.

- metabolic syndrome with persistently abnormal LFT

- NAFLD Fibrosis Score

2. suspected NAFLD in whom competing etiologies for hepatic

steatosis and co-existing chronic liver diseases cannot be
excluded without a liver biopsy.

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MANAGEMENT OF PATIENTS WITH NAFLD

LIFE STYLE INTERVENTION

Weight loss : hypocaloric diet

increased physical activity.

3-5% of bw improve steatosis,

10% improve hepatic necroinflammation.

Exercise alone may reduce hepatic steatosis

improvement in other aspects of liver histology -unknown.

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 DRUG TREATMENT

METFORMIN :

has no significant effect on liver histology ,hepatic

insulin sensitivity ,aminotransferase.

not recommended as a specific treatment for NASH.

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THIAZOLIDINEDIONES

rosiglitazone :
Improved aminotransferases and
hepatic steatosis
but not necroinflammation or fibrosis
increased risk of coronary events

NOT RECOMMENDED

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PIOGLITAZONE
significantly improve steatosis and inflammation but not
fibrosis .

T2DM- significant reduction (∼18%) in the primary outcome of

death, myocardial infarction, or stroke
higher rate of CHF
Significant weight gain.

Pioglitazone can be used to treat steatohepatitis in patients

with biopsy-proven NASH.

long term safety and efficacy of pioglitazone in patients with

NASH is not established.

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VITAMIN E (Α-TOCOPHEROL)
decrease aminotransferases improve steatosis, inflammation,
ballooning and resolution of steatohepatitis
no effect on hepatic fibrosis.

daily dose of 800 IU/day

Increase risk of prostate cancer in relatively healthy man (400 IU/day)

in non-diabetic adults with biopsy-proven NASH a first-line

pharmacotherapy

vitamin E is not recommended to treat

NASH in diabetic patients
NAFLD without liver biopsy
NASH cirrhosis
cryptogenic cirrhosis

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URSODEOXYCHOLIC ACID (UDCA) :
not recommended to treat NAFLD or NASH.

OMEGA-3 FATTY ACIDS:

first line agents to treat hypertriglyceridemia
in patients with NAFLD.
Not recommend for the specific treatment of
NAFLD or NASH

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STATIN

Patients with NAFLD and NASH are at increased risk for

cardiovascular disease

(a) statins are safe in patients with liver disease

(b) there is no evidence that patients with CLD including NAFLD
and NASH are at higher risk for serious liver injury from statins than
those without liver disease.

To treat dyslipidemia in patients with NAFLD and NASH.

not recommended for specific treatment of NASH.

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BARIATRIC SURGERY

majority of patients undergoing bariatric surgery for

severe obesity have associated fatty liver disease

Foregut bariatric surgery is not contraindicated in

eligible obese individuals with NAFLD or NASH (but
without established cirrhosis)

with established NASH cirrhosis - The type, safety and

efficacy of foregut bariatric surgery are not established.

foregut bariatric surgery is not an established option to

treat NASH specifically.

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NAFLD IN PATIENTS WITH OTHER CHRONIC LIVER
DISEASES

Coexistent hepatic steatosis is common in

1 chronic hepatitis C (HCV) infection (strongly

associated with more advanced liver disease).
2. primary biliary cirrhosis (PBC)
3. obese and/or diabetic patients with
autoimmune liver disease

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When steatosis and steatohepatitis are evident
in patients with other types of chronic liver disease
then assess for
metabolic risk factors and
alternate etiologies for hepatic steatosis.

vitamin E or pioglitazone
NOT RECOMMENDED

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SUMMARY

The diagnosis of NAFLD

(a) hepatic steatosis by imaging or histology
(b) no significant alcohol consumption
(c) no competing etiologies for hepatic steatosis
(d) no co-existing causes for chronic liver disease

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Incidentally Discovered Hepatic Steatosis having symptoms or signs of liver
disease or abnormal LFT -evaluate as suspected NAFL

If no symptoms or signs with norma LFT -assess for metabolic risk factors and
alternate causes for hepatic steatosis .liver biopsy not recommended.

Screening for NAFLD in adults is not advised

NASH cirrhosis-screen for gastroesophageal varices,HCC.

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NAFLD Fibrosis Score is a clinically useful tool for identifying NAFLD patients
with higher fibrosis.
serum/plasma CK18 is a promising biomarker for identifying steatohepatitis

metabolic syndrome and NAFLD Fibrosis Score predicts the presence of

steatohepatitis -its presence can be used to target patients for a liver biopsy.

Liver biopsy should be considered in patients with suspected NAFLD in whom

competing etiologies for hepatic steatosis and co-existing chronic liver
diseases cannot be excluded without a liver biopsy.

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Weight Loss 3-5% of bw improve steatosis up to 10 % improve
necroinflammation

Metformin ,rosiglitazone.UDCA is not recommended as a specific treatment

for NASH.

Pioglitazone ,vitamin E 800 IU/day -to treat steatohepatitis

with biopsy-proven NASH.

vitamin E or pioglitazone not recommended to treat steatohepatits with

other type of CLD who have coexisting NAFLD and NASH .

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-
omega-3 fatty acids first line agents to treat hypertriglyceridemia
statins - to treat dyslipidemia

vitamin E is not recommended to treat NASH in diabetic patients, NAFLD

without liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis

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THANK YOU

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