Other Inflammatory Liver Diseases

Question 1

NAFLD Risks

Answer 1

• dir proportional to body wt; associated w/ metabolic syndrome
• Others: obesity, DM, rapid wt loss, TPN, acute starvation, jejunal-ileal bypass; inborn errors of metabolism (Wilson’s, abetalipoproteinemia, etc)
• Drugs/toxins: amiodarone, glucocorticoids, tamoxifen, methotrexate, Ca blockers, estrogens

Question 2

NAFLD Epidemiology

Answer 2

1/3 US adult population

highest in Hispanics

men > women

Question 3

NAFLD Pathophysiology

Answer 3

• combo of genetic/environ perpetuating factors vs. regenerative responses
• Fat-derived pro-inflammatory factors - TNFalpha
• Inc hepatic free fatty acids –> TNFalpha and dec adiponectin –> inc hepatocyte lipid accumulation (steatosis) and insulin resistance
• Efforts to remove excess lipids –> ROS geenration –> oxidative stress –> hepatocyte death

Question 4

NAFLD Dx

Answer 4

• No specific serological marker; r/o other liver diseases and look for markers of metabolic syndrome (hyperlipidemia, hyperglycemia)
• Imaging - US (brighter), CT (liver less dense then spleen), MRI (bright fat on T2)to see steatosis
• Use history to distinguish b/n alcoholic and non-alcoholic (>21/wk men and >14 /wk women in last 2 yrs)
• BIOPSY - gold std to determine severity (ballooning hepatocyte degeneration and necrosis is characteristic of NASH; fibrosis and Mallory bodies
• Eval for fibrosis w/ VCTE (fibroscans), US elastoraphy, MR elastography

Question 5

NAFLD Presentation

Answer 5

• usually asymptomatic or non-specific fatigue/RUQ pain or mild elevation in AST/ALT
• progression: NAFL –> NASH (steatohepatitis) –> fibrosis –> cirrhosis
• Once fibrosis/ NASH develops than inc rate and chance of progression to cirrhosis

Question 6

NAFLD Tx

Answer 6

• focus on lifestyle mod
• treat metabolic syndrome
• consider bariatric surgery
• Drugs - Vit E (anti-oxidant) and Pioglitazine (insulin sensitizer that removes fat from liver but causes inc wt gain); rarely used

Question 7

2 General Types of Hemochromatosis (how to distinguish via labs)

Answer 7

• Hereditary (HH) - most commonly auto recessive mutation in HFE gene
• *inc ferritin AND inc transferrin saturation
• Secondary (Acquired) - alcohol abuse, acute liver injury, Hep C< NAFLD, etc
• *inc ferritin BUT normal transferrin saturation

Question 8

HH Pathophysiology

Answer 8

• Partial or total loss hepcidin (produced by liver) which normally inhibits iron from entering circulation–> transferrin saturated in serum (cannot buffer iron) –> non-transferrin bound iron in liver and other organs (cirrhosis, hypogonadism, cardiomyopathy, arthritis, hyperpigmentation)
• 1/250 w/ but not everyone has symptoms (dep on genetic, host and environ factors)

Question 9

HH Presentation

Answer 9

• Asymptomatic w/ abnormal inc iron / LFTs
• Non-specific fatigue, wt loss, weakness
• Specific Findings
  
  • ab pain, arthralgias, amenorrhea, loss of libido, CHF, arrhythmias, hepatomegaly, splenomegaly, spider angiomas, arthritis (specifically MCP joints), DM, skin bronzing from iron deposits, testicular atrophy, bacteremia, gonadotropins (pituitary)

Question 10

HH Tx (+ when to treat)

Answer 10

(only treat if symptomatic OR asymptomatic w/ elevated ferritin)

• Weekly/biweekly phlebotomy until ferritin < 100
• THEN maintenance phlebotomy every 3-4 mo
• Avoid alcohol, high iron diet
• Screen for hepatocellular carcinoma regularly (US and serum AFP)
• If anemic (cannot do phlebotomy) use chelating agents instead