NAFLD and NASH

Question 1

The MC chronic liver disease in many parts of the world

Answer 1

NONALCOHOLIC FATTY LIVER DISEASE (NAFLD)

*strongly associated with OVERWEIGHT/OBESITY and INSULIN RESISTANCE

Question 2

Risk of advance liver fibrosis is highest in individuals with NASH who are:

Answer 2

aged 45-50
overweight/obese
type 2 diabetes

Question 3

Gene that encodes an enzyme involved in INTRACELLULAR TRAFFICKING OF LIPIDS

Answer 3

PNPLA3

*correlates w/ susceptibility to HEPATIC STEATOSIS, CIRRHOSIS and LIVER CANCER

Question 4

Occurs when hepatocyte mechanisms for triglyceride synthesis (lipid uptake and de novo lipogenesis) overwhelm metabolisms for triglyceride disposal (degradative metabolis and lipoprotein export) –> ACCUMULATION OF FAT

Answer 4

Hepatic Steatosis

Question 5

Stimulates hepatocyte TGL accumulation by altering the intestinal microbiota to enhance both energy harvest from dietary sources and intestinal permeability

Answer 5

Obesity

Question 6

Insulin resistance promotes HYPERGLYCEMIA –> drives the pancreas to produce more insulin to maintain glucose homeostasis

Answer 6

HYPERINSULINEMIA –> promotes lipid uptake, fat synthesis and fat storage –> hepatic triglyceride accumulation - STEATOSIS

Question 7

Morphologic manifestation of lipotoxicity and resultant wound healing

Answer 7

NASH

Question 8

Potential outcomes of chronic NASH

Answer 8

Cirrhosis and Liver cancer

Question 8

Potential outcomes of chronic NASH

Answer 8

Cirrhosis and Liver cancer

Question 9

Results from FUTILE REPAIR (progressive accumulation of wound healing cells, fibrous matrix and abnormal vasculature (scarring) rather than efficient reconstruction/regeneration of healthy hepatic parenchyma

Answer 9

CIRRHOSIS

Question 10

Develop when malignantly transformed liver cells escape mechanisms that normally control regenerative growth

Answer 10

Primary Liver Cancers

Question 11

Diagnosing NAFLD requires demonstration of

Answer 11

Increased liver fat in the absence of hazardous levels of alcohol consumption

Question 12

NAFLD Risk Factors

Answer 12

BMI
Insulin Resistance/Type 2 DM
Other parameters indicative of Metabolic Syndrome

Question 13

Critically important because it is necessary to define PROGNOSIS and determine treatment recommendations

Answer 13

STAGING

Question 14

Staging approaches can be separated into

Answer 14

NONINVASIVE - blood testing, physical examination and imaging

INVASIVE - liver biopsy

Question 15

Suggest Diagnosis of ADVANCED NAFLD

Answer 15

Blood test evidence of HEPATIC DYSFUNCTION - hyperbilirubinemia, hypoalbuminemia, prothrombin time prolongation) or PORTAL HPN (thrombocytopenia)

Stigmata of PORTAL HPN on PE
spider angiomata
palmar erythema
splenomegaly
ascites
clubbing 
encephalopathy

Question 16

The GOLD STANDARD for establishing the severity of liver injury and fibrosis because it is both more sensitive and specific

Answer 16

LIVER BIOPSY

*2 cm or longer

Question 17

Foundation for NAFLD treatment

Answer 17

Diet and Exercise

Question 18

Weight loss decrease to improve serum aminotransferases and hepatic steatosis

Answer 18

3-5 % body weight - improve STEATOSIS

> 10 % body weight - improve STEATOHEPATITIS

Question 19

1st line pharmacotherapy for nondiabetic NASH patients

Answer 19

Vitamin E

Question 20

Treat Dyslipidemia in patients with NAFLD/NASH

Answer 20

Statins

Question 21

Most clinically benign extreme of the spectrum

Answer 21

HEPATIC STEATOSIS - simplest accumulation of triglyceride w/n hepatocytes