Alcohol & Metabolic Liver Diseases

Question 1

ddx for abnormal AST and ALT (alcohol & metabolic causes)

Answer 1

*alcohol
*metabolic dysfunction-associated steatotic liver disease (MASLD) [formerly, non-alcoholic fatty liver disease]
*hemochromatosis
*Wilson’s disease
*alpha-1 antitrypsin

Question 2

ddx for abnormal alkaline phopshatase (alcohol & metabolic causes)

Answer 2

*choledocholithiasis
*tumor

Question 3

imaging for abnormal LFTs

Answer 3

1. ULTRASOUND should be the first test
   -more sensitive than CT for gallstones
   -equally sensitive for dilated ducts
   -portable, cheap, no radiation, no IV contrast
2. CT if the ultrasound is negative

Question 4

acute alcoholic hepatitis - clinical features

Answer 4

*history: significant alcohol exposure, RUQ pain, fever, jaundice
*PE: fever, RUQ tenderness, hepatomegaly
*labs: AST/ALT > 2:1, AST < 300
*liver biopsy: MALLORY BODIES, steatosis, PMNs, ballooning

Question 5

LFTs for acute alcoholic hepatitis

Answer 5

AST / ALT > 2:1, AST < 300

Question 6

mallory bodies

Answer 6

*histology finding indicative of acute alcoholic hepatitis

Question 7

acute alcoholic hepatitis - treatment

Answer 7

*alcohol abstinence
*nutritional support
*prophylaxis against gastric mucosal bleeding (PPIs)

Question 8

alcoholic cirrhosis - clinical features

Answer 8

*history: significant alcohol exposure (50 gm EtOH per day x 20-30 years for males; half of that for females)

*exam:
-spider angiomata, palmar erythema
-Dupuytren’s contractures
-parotid enlargement
-gynecomastia
-testicular atrophy
-peripheral neuropathy

*LABS:
-AST/ALT > 2:1
-increased GGT
-increased MCV (large RBCs)

Question 9

metabolic dysfunction-associated steatotic liver disease (MASLD) - epidemiology

Answer 9

*more common in men & Hispanics
*associated conditions:
-obesity
-diabetes mellitus
-hyperlipidemia (TG and/or cholesterol)

note - this is NON-ALCOHOLIC FATTY LIVER DISEASE

Question 10

metabolic dysfunction-associated steatotic liver disease (MASLD) - diagnosis

Answer 10

*AST/ALT < 1
*exclude other causes (HBV, HCV, hereditary hemochromatosis)
*liver ultrasound
*liver biopsy good but rarely used

Question 11

metabolic dysfunction-associated steatotic liver disease (MASLD) - treatment

Answer 11

*diet, exercise, weight loss
*treat associated conditions (DM, hyperlipidemia)
*bariatric surgery
*GLP-1 agonists?

Question 12

hereditary hemochromatosis - etiology

Answer 12

*autosomal recessive mutation of HFE gene
*caused by reduced hepatic release (or activity) of hepcidin

Question 13

hereditary hemochromatosis - clinical manifestations

Answer 13

*after age 40 in men, 50 in women
*fatigue, arthropathy, diabetes, impotence, hyperpigmentation, cardiomyopathy

Question 14

hereditary hemochromatosis - diagnosis

Answer 14

*transferrin saturation > 50%
*ferritin > 200
*genetic testing C282Y/C282Y

Question 15

hereditary hemochromatosis - treatment

Answer 15

phlebotomy to ferritin < 50

Question 16

secondary hemochromatosis - etiology

Answer 16

*due to excess iron intake:
-ineffective erythropoiesis (sideroblastic anemia)
-repeated blood transfusions for chronic anemia
-beer brewing in iron drums (Africa)

Question 17

secondary hemochromatosis - treatment

Answer 17

desferoxamine

Question 18

alpha-1 antitrypsin disease - pathophysiology

Answer 18

*liver disease caused by accumulation of MISFOLDED alpha-1 antitrypsin protein (“gain of function”)
*mutations cause the alpha1-AT protein to polymerize in the ER of hepatocytes

*absence of alpha-1 antitrypsin (alpha-1 AT) is the primary mechanism for premature development of pulmonary emphysema or COPD in affected patients (“loss of function”)

Question 19

alpha-1 antitrypsin disease - clinical manifestations

Answer 19

*liver damage & dyspnea in young patients
*lung disease (inadequate protease inhibitor activity)
*liver disease (accumulation of variant A1AT in hepatocytes)
*normal phenotype: MM ; pathogenic: ZZ (autosomal codominant inheritance pattern)
*presentations: hx of NEONATAL HEPATITIS, INCREASED LFTs, hepatitis, cirrhosis
*treatment: liver transplant

Question 20

Wilson’s Disease - etiology

Answer 20

*autosomal recessive problem with copper transport (AT7B gene mutation causes failure of apoceruloplasmin transporter)
*leads of copper accumulation in many organs

Question 21

Wilson’s Disease - clinical manifestations

Answer 21

*LIVER DISEASE + NEUROPSYCHIATRIC FEATURES
*chronic hepatitis or fulminant hepatitis
*associated clinical features:
-neuropsychiatric disease (tremor, EPS sx)
-hemolytic anemia
*PE: Kayser-Fleischer rings

Question 22

Wilson’s Disease - diagnosis

Answer 22

*decreased ceruloplasmin
*increased urinary copper

Question 23

Wilson’s Disease - treatment

Answer 23

*d-penicillamine (chelates copper)

Question 24

Kayser-Fleischer rings

Answer 24

*indicative of Wilson’s disease