Non-alcoholic Fatty Liver

Disease Management &

Update.

 DR.DIPTTA BHATTACHARJEE
TMO, DEPT. OF MEDICINE
CHATTAGRAM INTERNATIONAL MEDICAL COLLEGE & HOSPITAL
 NAFLD Basics

Diagnosis and
Staging
Content
Management

Complication
Non-alcoholic mean…
 Alcoholic liver disease :  Non-alcoholic liver disease:
Alcoholic drinks/day (average): No alcohol
Male : 1 drink Alcoholic drinks/day :
Female :more than 2 drink Male : 2
Female :1
 A unit of alcohol contains 8 g of ethanol .
 Nonalcoholic fatty liver disease (NAFLD) is a
condition characterized by excessive
accumulation of lipid (defined as the presence
of lipid in > 5% of hepatocytes )
Definition
There are no causes for secondary hepatic fat
accumulation such as significant alcohol
consumption , use of steatogenic medication
and hereditary disorders .
  Nonalcoholic fatty liver (NAFL) :
Evidence of hepatic steatosis by imaging or
histology .

Subtypes  Nonalcoholic steatohepatitis (NASH):

Presence of hepatic steatosis and inflammation
with hepatocyte injury with or with out fibrosis .
Epidemiology
 Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most
common liver disease worldwide.

 The prevalence of NAFLD

: 80-90% in obese adults.

: 40-70% in patients with diabetes .

: 90% in patients with hyperlipidemia.

 The prevalence of NAFLD among children is 3-10%, rising to 40-70% among

obese children .
Epidemiology
 Prevalence of NAFLD in general population of Bangladesh has been estimated to
vary from 4 to 18.4 %, which jumps up to 49.8% in diabetic patients .

 Overall, NAFLD is estimated to affect 20–30% of the general population in

Western countries and 5–18% in Asia, with about 1 in 10 NAFLD cases exhibiting

NASH. Only a minority of patients will progress to cirrhosis and end-stage liver

disease.
Epidemiology
 With the increasing prevalence of obesity, diabetes, and metabolic syndrome in
the general population, NAFLD has become the most common cause of chronic
liver disease in the western countries as well as lower BMI areas such as in
regions of Asia. Thus, the nature and extent of the problem of NAFLD in the
context of Bangladesh needs to be addressed seriously.

 A Western diet/lifestyle has been associated with weight gain and obesity, and
NAFLD .
Pathogenesis
Insulin resistance is related to obesity and is central to the
pathogenesis of NAFLD

In addition , oxidative stress due to free radicals produced

during fatty acid oxidation

Direct lipotoxicity from fatty acids and other metabolites in the

liver

Endoplasmic reticulum stress

Gut-derived endotoxin

Cytokine release (TNF-α etc.) and immune-mediated

hepatocellular injury.
 Age : Higher risk in 40-50 yrs. old , but is does occur in children

Positive family history-genetic predisposition

Sedentary lifestyle- lack of exercise
Obesity , increased BMI (> 30 kg/m2)
Insulin resistance/metabolic syndrome
Type 2 DM
Risk Hyperlipidemia
Factor Rapid weight loss
Hepatitis C
Total parenteral nutrition
Wilson disease
Obstructive sleep apnea
Nutrition‐related disorders
Drugs and toxins – Amiodarone Tamoxifen ,Synthetic estrogens
Methotrexate ,HAART
How would I know I have NAFLD ?

 Symptoms :  Physical finding :

Asymptomatic. Patient with NAFLD may have hepatomegaly on
physical examination due to fatty infiltration of
Fatigue . the liver .Feature of cirrhosis may present in case
Right sided abdominal pain . of advance disease .
 Lab test :
Elevation of liver ALT>AST

Patient with NAFL may have elevated serum ferritin

concentration or transferrin saturation .
Test to exclude :Viral hepatitis—hepatitis B, hepatitis
Continued.... C , Alcohol-related liver disease. Autoimmune liver
disease. Drug-induced liver disease.
Radiology: Fat can be seen of ultrasound , MRI , or CT scan

Screening of the general population is not currently recommended

by AASLD.EASL recommend screening all patients with obesity or
metabolic syndrome with liver enzymes and ultrasound .
 Noninvasive test
 Fibro scan : Transient Elastography
Requires adequate expertise to produce
reliable results.
Factor that may producer inaccurate
results : obesity , NASH, alcohol use
non fasting state, Hispanic ethnicity

 Non-invasive scores for (NAFLD)/fibrosis

• NAFLD Fibrosis Score (NFS)
• FIB-4 Score
Role of biopsy in NAFLD

GOLD Standard for Diagnosis and

staging.
To Classify NAFLD : NASH VS
NAFL.
Determine stage of fibrosis.

Eliminate other cause of liver disease . Steatosis +

necroinflammation
(ballooning, Mallory
bodies,
Megamitochondria)
Flowchart
represents how to
approach to
diagnose NAFLD
Management
Lifestyle modification :
Lifestyle modification, which includes changes in
dietary pattern and composition as well as increasing
physical activity levels improve insulin sensitivity ,
is the first step and cornerstone of NAFLD
management. Decreasing overall sedentary time and
breaking up sedentary time throughout the day is a
useful treatment strategy for all people with
NAFLD/NASH.
Lifestyle modification

Weight loss :
weight reduction of >5% is usually necessary to reduce liver fat, 7–
10% to improve liver inflammation and >10% to improve
fibrosis/scarring, although even lower reductions can be helpful .
Research has shown that weight loss is an effective treatment for
NAFLD across the disease spectrum.
 Exercise :
Any increase in physical activity is useful, even without weight
loss. In order to induce significant changes, over 150 min/week of
moderate intensity physical activity over 3-5 sessions including a
combination of aerobic (“cardio” e.g., brisk walking, cycling,
swimming) and resistance training are recommended .
Lifestyle modification :

Diet :
Portion control and simple carbohydrate
avoidance . Avoid fructose sweetened beverage .
Home-cooked meals are preferable .The
Mediterranean diet is one of the most studied and
beneficial. Even without weight loss, a healthier
food pattern, especially the Mediterranean diet
can result in NAFLD improvement.
Treatment of Metabolic Syndrome in NAFLD

 Statin : CVD is the most common cause of death in

NAFLD and NASH . Safe For use in NAFLD . So, they
may be used to treat dyslipidemia.

 Vitamin –E : Vitamin E has anti-cell death and antioxidant properties.

Therefore, it has been proposed for the treatment of NAFLD, vitamin E was
significantly better than placebo at improving steatohepatitis, but it had no
significant effects on fibrosis . The use of vitamin E is indicated by the U.S.
guidelines in patients with biopsy-assessed NASH .
Treatment of Metabolic Syndrome in
NAFLD
 Pioglitazones : Pioglitazone was particularly effective for the treatment of
NASH in patients with pre-diabetes or T2DM. Pioglitazone is an anti-
diabetic drug able to modulate several responses, including insulin
sensitivity. Several studies and a meta-analysis have consistently
demonstrated an improvement in liver blood tests and in liver biopsy
features following pioglitazone Administration . How ever long-term safety
and efficacy not been established .
 Bariatric surgery :
Patients unresponsive to lifestyle changes and pharmacotherapy, bariatric surgery is
an option for reducing weight and metabolic complications. The effect of bariatric
surgery on body weight largely exceeds the 10% weight loss target associated with
liver fat clearance, NASH resolution and fibrosis reversal, as reported in several
studies .
Cirrhosis is not an absolute contraindication to bariatric surgery, but a precise
evaluation of hepatic and cardiovascular function should be performed prior to
surgery
 Liver Transplantation : Patients with NAFLD in whom
end stage liver disease develop should be evaluated for liver
transplantation . The outcomes of liver transplantation in
well selected patients with NAFLD are generally good but
comorbidities such as Diabetes , Cardiovascular diseases
often limit transplant candidacy .
 Consequences
Disease progressing from
NAFLD to NASH to
cirrhosis/liver failure and HCC.
Concurrence of NAFLD with
Hep-c worsen their prognosis
and decrease their response to
therapy .

Cause of mortality in cirrhotic NASH patient :

Cardiovascular diseasae

Liver failure

HCC
  Accurate Diagnosis
Make sure no other form of Liver disease.
Determination
When to see a of Sub type of NAFLD you
may have (NAFL or NASH) .
Hepatologist if I Evaluate for liver scar(fibrosis).

have NAFLD ? Liver biopsy may be needed.

 Monitoring

Look for signs of worsening of liver scar

Special monitoring if cirrhosis present

Monitoring FOLLOW-UP RECOMMENDED

Evaluate weight loss, exercise, After 6 months

Strategy diet and lifestyle changes
Blood and platelet count 2 × annually
Liver biochemical tests 2 × annually
Disease progression and Consult hepatologist At 6 months and then
complications can be detected yearly, depending on the
response
during the follow-up as Screening for cardiovascular Every 1–2 years,
indicated in Table risk depending on risk factors

Liver biopsy Every 3–5 years,

depending on response

Imaging tests When indicated

 NAFLD has become one of the most common liver conditions throughout the
world .
NAFLD is an umbrella term that include NAFL & NASH

Biopsy needed to categorize the NAFLD

Leading cause of death in NAFLD is Heart Disease

Summary Management hinges on weight loss exercise avoiding excess
carbohydrate , metabolic syndrome control
Vitamin E For Biopsy proven NASH

Many drug in the therapeutic trial for liver targeted

pharmacological treatments .
If NAFLD is detected and managed early enough, it is possible
to reduce the amount of fat in your liver, which may slow down
or even stop the damage, and eventually allow your liver to fully
recover.
 References

• Davidson's Principles and Practice of Medicine ,23rd

Edition .

• Harrison's Principles of Internal Medicine , 20th

edition

• EASL Clinical Practice Guidelines for the

management of non-alcoholic fatty liver disease

• WGO Practice Guideline NAFLD & NASH

  Dr. Mohammad Kamrul Islam
Acknowledgement Associate prof. Dept. of Medicine
CIMCH
Thank You