Non-alcoholic fatty liver and NASH

Question 1

Epidemiology and NHx of NAFLD and NASH

Answer 1

• 1/4th-1/3rd of people have NAFLD in US
• 10-20% of them have or will develop NASH, and 10-20% of NASH will develop cirrhosis
• Risk factors: obesity, DM2 (or family Hx of DM2), dyslipidemia, metabolic syndrome
• Greatest risk of mortality in NAFLD pts is CVD
• Old age is a risk factor for NASH
• At old age (>65) there is much higher risk for advanced fibrosis/cirrhosis in NAFLD pts

Question 2

Pathogenesis of NAFLD/NASH

Answer 2

• Simple steatosis (NAFLD): fat gets stuck in liver b/c 1) more fat is delivered to liver (diet), 2) increased de novo production of FAs in liver (insulin resistance), 3) TAGs unable to leave liver (lipoprotein packaging impaired)
• To get NASH: must have simple steatosis and one or more hits/conditions that illicit an immune response
• These conditions include: ROS generation, Fe excess, mito dysfxn, JNK/ER stress, genetic predisposition, microbiome

Question 3

Dx of NAFLD/NASH

Answer 3

• NAFLD is ASx, NASH is almost always ASx
• Some Sxs that can be seen in NASH: malaise, fatigue, RUQ discomfort
• PE: abd obesity, enlarged liver, RUQ tenderness
• Labs: consistent w/ metabolic syndrome, elevated AST/ALT (ratio ≤1), bili/AP may be slightly elevated
• Liver biopsy indicated in: high ferritin, positive autoAbs, meds associated w/ DILI (drug-induced liver injury), several risk factors
• Biomarkers of NASH and fibrosis: CRP, IL6, TNFa, Cytokeratin 18 (most important)

Question 4

Rx of NASH/NAFLD

Answer 4

• Weight loss (1-2 lbs per wk), 3-5% improves steatosis but more is needed for inflammation
• Etoh consumption must be reduced
• Insulin sensitizing agens (TZDs, metformin), statins
• Pioglitazone and vitamin E are both used for NASH Rx
• Prospective: FXR agonists, bariatric surgery