Week 4: Liver - ALD, MAFLD, and Inherited Liver Diseases

Question 1

What are histological findings in Alcoholic Liver Disease (ALD) and Metabolic Associated Fatty Liver Disease (MAFLD)

Answer 1

• Steatosis
• Steatohepatitis

Question 2

Clinical findings in Alcoholic Liver Disease (ALD)

Answer 2

• Hepatomegaly
• Jaundice
• Malaise
• Anorexia
• Weight Loss
• Abdominal Discomfort

Question 3

Expected lab values of bilirubin, AST, and ALT in Alcohol Liver Disease

Answer 3

• Hyperbilirubinemia
• Both elevated; AST:ALT ratio > 2:1

Question 4

Treatment for Alcoholic Liver Disease (ALD)

Answer 4

Cessation of alcohol use

Question 5

Hepatic steatosis in patients w/out heavy alcohol use or another cause of secondary steatosis (ex: Wilson disease)

Answer 5

Metabolic Associated Fatty Liver Disease (MAFLD)

Question 6

What are risk factors for Metabolic Associated Fatty Liver Disease (MAFLD)

Answer 6

• Obesity
• Diabetes Mellitus
• Hypertension
• Hyperlipidemia
• Hypothyroidism
• Smoking
• PCOS

Question 7

Treatment for Metabolic Associated Fatty Liver Disease (MAFLD)

Answer 7

• correction of underlying risk factor
• liver transplant (end-stage)

Question 8

ID

Answer 8

Steatosis

Question 9

ID

Answer 9

Steatohepatitis

steatosis - orange arrow
inflammatory cells - yellow arrows

Question 10

What are two features of Steatohepatitis

Answer 10

• Ballooned Hepatocytes
• Mallory-Denk bodies or Mallory hyaline

Question 11

ID

Answer 11

Ballooned Hepatocytes

Question 12

What causes Mallory-Denk bodies or Mallory hyaline?

Answer 12

aggregates of damaged keratin filaments

Question 13

ID

Answer 13

Mallory-Denk bodies or Mallory hyaline

eosinophilic, ropey, or globular material within the cytoplasm representing aggregates of damaged keratin (8 and 18) filaments

Question 14

ID

Answer 14

Alcoholic hepatitis

clusters of inflammatory cells (dark blue)
Mallory-Denk bodies or Mallory hyaline (black arrow)

Question 15

ID

Answer 15

Ballooned Hepatocytes (black arrow head) and clusters of inflammatory cells (orange arrow)

Question 16

ID

Answer 16

Mallory-Denk Body

immunostaining for keratins 8 and 18 (brown color) and in the
ballooned cell (dotted lines) the ubiquinated keratins are collapsed into Mallory hyaline, leaving the cytoplasm “empty.” (black arrow)

Question 17

ID

Answer 17

Steatohepatitis

Pericellular fibrosis, a ‘spidery’ fibrosis blue pattern (yellow arrows) around the central vein (orange arrow)

Question 18

What are three inherited Liver Diseases

Answer 18

• Hereditary hemochromatosis
• Alpha-1 Antitrypsin (A1AT) Deficiency
• Wilson Disease

Question 19

Impaired ability of the body to inhibit iron absorption resulting in excess iron stores in body tissues

Answer 19

Hemochromatosis

Question 20

What is excess iron deposition in the liver termed in a patient with hemochromatosis or another condition called?

Answer 20

Hepatic siderosis

Question 21

What lab values of ferritin, iron, and transferrin saturation would you expect in a patient with hemochromatosis

Answer 21

Increase in all 3 of these values

Question 22

How do you treat hereditary hemochromatosis

Answer 22

Therapeutic phlebotomy (vein drainage)

Question 23

What is the genetics and mutation of Hereditary Hemochromatosis

Answer 23

Autosomal Recessive and Mutation in HFE

“Heavy Fe (Iron)” is HFE gene that when mutated decreases hepcidin

Question 24

What chromosome is HFE on?

Answer 24

Chromosome 6

Fe for iron. F is the 6th letter of the alphabet

Question 25

What does hepcidin bind?

Answer 25

Ferroportin

iron channel of enterocytes and macrophages, resulting in its degradation and lowers iron transport

Question 26

ID and the staining

Answer 26

Hereditary Hemochromatosis and HE stain

iron deposits in hepatocytes (black arrows)

Question 27

ID and the staining

Answer 27

Hereditary Hemochromatosis and Perls Prussian Blue stain

Question 28

What genetic mutation is associated with Alpha-1 Antitrypsin (A1AT) Deficiency

Answer 28

Pi*ZZ

“P”an Ac “I” nar Emphy “ZZ” ma

Pi” stands for “protease inhibitor,” which is another name for the alpha-1 antitrypsin protein, and “Z” represents a specific genetic variant of that protein, with “ZZ” indicating a homozygous condition

Question 29

ID and staining

Answer 29

normal liver and periodic acid Schiff (PAS) stain

Question 30

ID and staining

Answer 30

Diastese digestion (D) and periodic acid Schiff (PAS) stain - Normal hepatocyte response

Called PASD - see absence of red granules in normal liver tissue

Question 31

ID and staining

Answer 31

Alpha-1 Antitrypsin (A1AT) Deficiency and periodic acid Schiff (PAS) stain

globular red granules are seen which are diastase resistant. These are the aggregates of misfolded A1AT protein (black arrows) which could not be secreted and therefore accumulated in hepatocytes

Question 32

ID

Answer 32

Alpha-1 Antitrypsin (A1AT) Deficiency

A genetic condition affecting both the LUNGS and LIVER. Buzz statement for A1AT Deficiency

Question 33

ID

Answer 33

Alpha-1 Antitrypsin (A1AT) Deficiency

A - red aggregates of misfolded A1AT protein in PAS
B - EM showing aggregates of misfolded A1AT protein

Question 34

What is the genetics and mutation of Wilson Disease

Answer 34

Autosomal Recessive and mutation in ATP7B

Question 35

ID

Answer 35

Wilson Disease

Kayser-Fleischer rings (yellow arrow) encircling the iris

Question 36

What are the expected lab values of urine copper and Ceruloplasmin in Wilson Disease?

Answer 36

High urine copper
Decreased Ceruloplasmin

Cerulo- is blue in latin and the copper ring around the eye decreases the blue or color of the iris.

Question 37

ID and staining

Answer 37

Wilson Disease and Rhodanine stain

Copper stains bright orange to brown in granules (yellow arrows) on Rhodanine stain