NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD)
Speaker: Gaurav Singhvi MD, MBA
Clinical Assistant Professor of Medicine at UCLA DAVID GEFFEN SCHOOL OF MEDICINE
CME MEETING WEDNESDAY, JUNE 19, 2019
Spice Affair, Beverly Hills
Topic: NON-ALCOHOLIC FATTY LIVER DISEASE-(NAFLD) & NASH- (NON-ALCOHOLIC STEATOHEPATITIS)- WITH INFLAMMATION
Speaker: Gaurav Singhvi MD, MBA
Clinical Assistant Professor of Medicine at UCLA David Geffen School of Medicine
The original hist-pathologic. description of NAFLD ascribed to a group of obese patients. The term NASH was introduced by Ludwig and his colleagues in 1958.
NAFLD characterized by macrovesicular steatosis of liver, Progression to NASH to fibrosis, and advanced cirrhosis.
Increasing prevalence in the world.
Hispanics-45%, Caucasians- 33%, African-Americans-31%, Asians-31%
Insulin resistance is the prevalent pathophysiological abnormality.
Prevalence at BMI <25 is 16%. BMI>30-75%
Non-vegetarian food, fried foods, spicy food and tea linked to NAFLD
Obesity, glucose intolerance, hypertension, hypertriglyceridemia, and low HDL cholesterol.
Secondary to drug usage: Corticosteroids, Tamoxifen Diltiazem, Aspirin, HAART, Valproic Acid, Amiodarone, Methotrexate, and total parenteral nutrition.
Viruses: Hepatitis C, HIV.
Metabolic: Hyperproteinemia, lipodystrophy, hypopituitarism, Weber Christian syndrome, and Reyes syndrome etc
Toxins: organic solvents, mushroom toxins.
Nutritional: Rapid weight loss, intestinal bypass surgery, and starvation.
Hepatic Steatosis; increased lipolysis, increased lipogenesis, decreased apoB-100, decreased leptin, and increased TNF-alpha
Progression to NASH- increase in reactive oxygen species, lipid peroxidation, depletion of natural antioxidant pool, intestinal microbes, , pro-inflammatory cytokines, endotoxin and apoptosis.
The Stellate cell stimulation leads to collagen-secreting myelofibroblast like cells and eventual hepatic fibrosis.
Mixed inflammatory infiltrates, hepatocyte necrosis, ballooning, mallory’s hyaline, glycjogenated nuclei, and fibrosis.
NATURAL HISTORY OF NAFLD
Major concern- progression to cirrhosis and hepatic cellular carcinoma.
The risk of disease progression is not clear.
Those with simple steatosis on biopsy are at low risk fore progression while those with steatohepatitis are at higher risk.
Some patients with fibrosis can show regression.
RISK FACTORS FOR PROGRESSION
Elevated AST and ALT
Presence of Ballooning degeneration plus fibrosis on biopsy
BMI > 28
Higher visceral adiposity
Coffee consumption associated with lower progression. Tea drinking with higher progression.
Risk of HCC to develop in cirrhosis is 12% over 3 years.
CLINICAL FEATURES OF NAFLD
Malaise, & fatigue
RUQ abdominal discomfort
Obesity and features of metabolic syndrome
Abnormal sleep patterns
ALCOHOLIC STEATOHEPATITIS VERSUS NASH
Alcohol consumption history
AST to ALT ratio >2
Cholestasis often present
Inflammation, Mallory Bodies present
Central vein lesions seen.
Alcohol history absent
AST to ALT ratio- <1
Common Glycogen nuclei
Patchy inflammation, with few mallory bodies.
Central vein lesions rare.
Modest ALT level raise. Rarely over 300 IUL
AST to ALT ratio typically <1
Elevated Alkaline Phosphtase may be only abnormality in some cases.
Elevated blood glucose, hypertriglyceridemia, and/or low HDL cholesterol.
Elevated Ferritin level: 40-58%;
Ultrasound- Hyperechoic, sensitivity- 85-95%, Specificity-62%
CT Scan: Non-contrast sensitivity- 33%. Specificity- 100%
MRI; Quantification- sensitivity-88%. Specificity 63%.
MR Elastography and Fibroscan promising outcomes
Most accurate for Diagnosis
Weight Loss and increased physical activity: Lead to sustained improvement in liver enzyme activity, histology, insulin levels and improved life quality.
Weight loss of a pound a week. Exercise target of 30-60 minutes daily burning 300-400 kcal.
Bariatric Surgery: Shows improvement correcting metabolic syndrome features.
Vitamin E and Insulin sensitizers most common being studied.
Currently about 50 drugs being studied.
Other pharmacologic options include:
Reversible inhibitor of gastric and pancreatic lipase, with 5-10% decrease in body weight in 6-12 months. Improved LFTs and histologic changes in 9 months post treatment. Well tolerated in 80% of patients
80% of NAFLD patients have dyslipidemia, but no significant changes in biochemistry or histology in NAFLD patients withy long term use.
OMEGA 3 FTTY ACIDS
Associated with improved steatosis and inflammation, used especially for hypertriglyceridemia.
Shown to be antifibrogenic, withnixproved insulin resistance, BP and serum biochemistry.
A synthetic variant of bile acid promotes insulin sensitivity and decreased triglycerides. May improve histology. In phase 3 trials.
Multiple other chemical pathways are being studied.
PARVIN D. SYAL MD