fatty liver disease with diabetes mellitus [bangladesh]
TRANSCRIPT
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WELCOME
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Nonalcoholic Fatty Liver Disease In Diabetes
Mellitus
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A 52 years old female was found to have elevated liver enzyme [AST= 80U/L and ALT = 94 U/L] on routine blood check up. Viral hepatitis panel was negative. Ultrasonography of whole abdomen shows fatty infiltration of liver. Her medical history reveals that she is diabetic for 8 years and hypertensive for 5 years.
The patient came to the hospital for further evaluation. She was overweight [BMI=29.5 kg/m2] and to have mild hepatomegaly with no sign of cirrhosis. After excluding other potential cause of patient’s liver enzymes elevation, NAFLD is considered the likely cause.
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What is Fatty Liver Disease? The definition of nonalcoholic fatty liver disease (NAFLD) requires that
(a) There is evidence of hepatic steatosis, either by imaging or by histology and
(b) There are no causes for secondary hepatic fat accumulation such as significant alcohol consumption, use of steatogenic medication or hereditary disorders.
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Usually seen in people who are overweight or
obese
Some fat in your liver is normal
More than 5%-10% of the organ's weight, you
may have fatty liver disease
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What Are the Types of Nonalcoholic Fatty Liver disease?
1. Nonalcoholic fatty liver (NAFL)
• the presence of hepatic steatosis with no evidence of hepatocellular injury in the form of ballooning of the hepatocytes.
2. Nonalcoholic steatohepatitis (NASH)
• presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning) with or without fibrosis.
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What are the other causes of fatty liver disease?
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Who's at Risk for Fatty Liver?
Conditions with established association
Conditions with emerging association
Obesity Polycystic ovary syndrome
Type 2 diabetes mellitus Hypothyroidism
Dyslipidemia Obstructive Sleep apnea
Metabolic syndrome Hypopituitarism
Hypogonadism
Pancreato-duodenal resection
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A patient having fatty liver gave history that he used to drink
occasionally
Is it Alcoholic Fatty Liver disease or
Nonalcoholic Fatty Liver disease??
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MALE•>21 drinks per week
FEMALE•>14 drinks per week
Over a 2-year period prior to baseline liver histology
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What is Diabetes mellitus?
Diabetes mellitus is a clinical syndrome characterized by an increase in plasma blood glucose (hyperglycaemia).
Diabetes has many causes, but is most commonly due to type 1 or type 2 diabetes.
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Mechanism of Lipid accumulation/steatosis
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Pathogenesis of NASH
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Pathogenesis of NASH
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Pathogenesis of NASH
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# What is fatty liver disease?
# What are the spectrums of fatty liver disease?
# What is diabetes mellitus?
# How diabetes causes fatty liver disease?
ANSWERED
ANSWERED
ANSWERED
ANSWERED
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Prevalence of NAFLD
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Global prevalence NAFLD
25.24%Lowest
Africa
Highest
Middle east and southern
America
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T2 DM
22.51%
Obesity
51.34%
Hyperlipidemia
69.16%
Metabolic Syndrome
42.54%
Hypertension
39.34%
Global prevalence NAFLD
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ASIA
15-20%
China, Japan, Korea = 12-24%
Hong kong = 16%
Taiwan = 12%
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India
General population
• 9-32 %
Type 2 DM
•56.5%
Female
•60%
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BANGLADESH
1.1-7.6%Liver
disease patients
NAFLD
Study in DMCH13%
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Prevalence of NASH among NAFLD patients in BANGLADESH
Absent
10%
Borderline
52.6%
Present 42.4%
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How can a diabetic patient with NAFLD presents??
• Feeling tired• Loss of weight or appetite• Weakness• Nausea• Confusion, poor judgment, or
trouble concentrating.• Pain in the center or right upper part
of abdomen.
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Criteria of diagnosis of NAFLD
Hepatic steatosis
by imaging or
histology
No co-existing
causes for CLD
No competing etiologies
for hepatic steatosis
No significant
alcohol consumption
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How Is Fatty Liver Diagnosed?
Routine Blood test
Imaging
Histopathology
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Routine tests for diabetic patients having NAFLD
The liver enzymes (AST,
ALT) may higher than
normal
Fasting lipid profile shows dyslipidemia
High blood sugar profile
HbA1C is above normal
level
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Ultrasound
Healthy liver in Ultrasound Fatty liver in Ultrasound
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CT Scan and MRI of Fatty liver
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MRS in Fatty liver
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Liver biopsy
Liver biopsy remains the best diagnostic tool for confirming NAFLD and evaluating necroinflammation/fibrosis, as well as the most sensitive and specific means of providing important prognostic information.
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When should we do Liver biopsy ?
• Patients with NAFLD who are at increased risk to have steatohepatitis and advanced fibrosis.
• 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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Limitations of Liver biopsy
cost
Procedure related morbidity
and mortality
sampling error
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Emerging diagnostic tools
• Imaging by transient elastography
• Plasma biomarkers - plasma cytokeratin-18 fragments (marker of hepatocyte apoptosis)
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If NAFLD discovered incidentally on imaging, should we evaluate in all cases?
asymptomaticnormal liver
biochemistries
No need to further
evaluation
lack any liver-
related symptoms
or signs
normal liver biochemistries
assess for metabolic risk
factors and alternate causes for
hepatic steatosis
symptomaticabnormal liver biochemistries
worked-up
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Should we screen all the diabetic patients ??
NO
uncertainties surrounding diagnostic tests
lack of knowledge related to the long-term benefits
Lack of treatment options
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Should we screen the family members of a diabetic patient having NAFLD?
CURRENTLY NOT RECOMMENDED
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What Is the Long-Term Outlook for Fatty Liver?
Fortunately, many cases of fatty liver don’t develop into liver disease. The liver can repair itself, if we take the necessary steps to treat high cholesterol, diabetes.
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Who should be treated?
All diabetic patient having NAFLD
Lifestyle intervention
treatments aimed at improving liver disease should be limited to those with NASH
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Lifestyle intervention
Hypocaloricdiet
Physical activity
Weight loss
Improve steatosis
Improve necroinflammation
3-5%
5-10%
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Weight reduction
OrlistateImprove
liver enzymeBut not
histology
Exercise aloneMay reduce
steatosisUnknown
about histology
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Management of body weight and obesity
Goal is sustained weight loss of 7-10% of body weight
Weight loss of up to 1 kg/week is considered to be safe
Rapid weight loss can result in worsening of the liver disease
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Medical management
• Metformin
• Thiazolidinediones (TZDs)
• Glucagon-like peptide-1 (GLP-1) analogs
• Dipeptidyl peptidase-4 (DPP-4) inhibitors
Anti diabetic agents
Others
• Statins• Vitamin E• Ursodeoxycholic acid
(UDCA)• Omega-3 fattyacids
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Antidiabetic agents for NAFLD patients
Metformin+ life style modification
Not major improvement of
aminotransferase and histology
Not recommended as a specific
treatment for NASH
PioglitazoneCan be used
to treat NASH
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GLP-1 analogs
Improved glucose tolerance and a small decrease in BMI
Improved steatosis and NASH histology
Antidiabetic agents for NAFLD patients
DPP-4 inhibitors
Improvement in HbA1c levels and a decrease BMI
Decreases in alanine aminotransferase levels and
improved liver histology
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Statin use in patients with NAFLD and NASH
• Statins can be used to treat dyslipidemia in patients with NAFLD and NASH.
• Statins should not be used to specifically treat NASH.
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Vitamin E (a-tocopherol)
• improves liver histology
• considered as a first-line pharmacotherapy
Non-diabetic patients
• Not recommendedDiabetic patients
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Ursodeoxycholic acid (UDCA)
•Not recommended for the treatment of NAFLD or NASH
Omega-3 fatty acids
•Considered as the first line agents to treat hypertriglyceridemia in patients with NAFLD
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Is blood glucose control helps in NAFLD improvement?
Studies shows that decrease in hemoglobin A1c and the use of insulin were associated with an improvement in hepatic fibrosis.
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What Else should be done?
• Upper GI Endoscopy
• HCC screening
• Routinely repeating a liver biopsy is not recommended.
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Prognosis of NAFLD
NAFLBenign
conditionImprove naturally
NASH
Cirrhosis
Liver cancerLiver failure
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Type 2 diabetics, presence of NAFLD
Increased total mortality,
regardless of classic risk
factors
Have twice risk mortality
compared with nondiabetics
without NAFLD
More common causes of
death malignancy
(33% of death)
More liver related
complications (19% of death)
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Conclusion
The identification of NAFLD should be sought as part of routine assessment of diabetic patients, because it is essential for the early diagnosis and proper implementation of lifestyle and pharmaceutical interventions.
Diet, exercise, and weight loss provide significant clinical benefits and must be considered of first line for treating NAFLD/NASH.
There is significant research effort in developing noninvasive monitoring of disease progression and effective treatment for the betterment of patients health.
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