Hepatic Disorders Flashcards

Question 1

Q

Liver
Gross Anatomy

Answer

A

Location:
- From right 5th intercostal space in midclavicular line to just below right costal margin
Size/Weight:
- 10-12cm span
- 1,400-1,600gm (adult weight)
Lobes:
- Visually divides as:
  - Right ⇒ includes right lobe, caudate and quadrate lobes
  - Left
- Physiologic division:
  - Divide into 2 equal parts w/ line extending from IVC to gallbladder

Question 2

Q

Liver
Connections

Answer

A

Glisson’s capsule: CT covering liver
Falciform ligament: connects liver → diaphragm & anterior abdominal wall
- Fetal life: carries umbilical vein
- Later life: carries paraumbilical vein
  - May serve as collateral vessels in portal HTN

Question 3

Q

Liver
Vascular Supply

Answer

A

Inflow:
- Hepatic artery: usually from celiac artery
  - Supplies 30-40% of blood flow
- Portal vein: formed from convergence of superior mesenteric and splenic veins (i.e. most of venous drainage of abdomen)
  - Supplies 60-70% of blood flow
- True infarcts rare d/t dual supply of blood
Venous drainage:
- Extrahepatic veins drain into inferior vena cava

Question 4

Q

Liver
Biliary System

Answer

A

Intrahepatic ducts (lobular and septal) → right and left hepatic ducts (extrahepatic) ⇒ unite to form common hepatic duct

Cystic duct from gallbladder enters ⇒ forms common bile duct (CBD)

Ampulla of Vater: slightly dilated portion of CBD as it empties into second portion of duodenum

Pancreatic duct drains into ampulla in two-thirds of population

Question 5

Q

Liver

Functional Unit Models

Answer

A

Zonation of the parenchyma

Gradient of activity displayed by many hepatic enzymes
Zonal distribution of certain types of hepatic injury
Acinar model ⇒ describes physiologic relationship b/t hepatocytes & vascular supply
Classic lobular model ⇒ describes histopathology of the liver

Question 6

Q

Liver

Lobular Model

Answer

A

Hexagon shaped
- Center ⇒ terminal hepatic veins (“central vein, efferent vein”)
  - Hepatocytes near terminal hepatic vein ⇒ “centrilobular”
- Periphery ⇒ portal tracts
  - Hepatocytes near portal tract ⇒ “periportal”
Pros: easy to define
Cons: not physiologic

Question 7

Q

Liver

Acinar Model

Answer

A

Triangle shaped
- Apex ⇒ central vein
- Distal apices ⇒ terminal hepatic veins (“central vein, efferent vein”)
- Base ⇒ formed by septal venules from portal vein that extend out from portal tracts
Based on blood flow
Parenchyma is divided into three zones
Zones numbered higher as blood flows toward central vein
- Zone 1: adjacent to portal vein
  - Freshest blood flow
- Zone 2: between 1 & 3
- Zone 3: closest to central v.
  - Furthest from afferent blood supply
  - Most susceptible to blood supply problems
    - Ischemia d/t poor portal flow
    - Congestion/ischemia d/t problems w/ blood exiting liver
  - Most susceptible to drug/toxin insults
    - Hepatocytes tend to have active drug metabolizing enzyme systems
    - Susceptible to buildup of toxic metabolite byproducts and injury from toxins in general
Pros: physiologic
Cons: harder to visualize

Question 8

Q

Liver
Portal Tract

Answer

A

Contains 3 structures
- Hepatic artery branch
- Portal vein branch
- Bile duct branch
Connective tissue matrix
Others
- Lymphatic branch
- Scant inflammation
Limiting plate
- Hepatocytes that abut portal tract

Question 9

Q

Hepatocytes

Answer

A

Polygonal eosinophilic cell
Central nucleus, prominent nucleolus
Arranged as 1 cell thick cord after 5 y/o w/ occasional interanastomosis
Surfaces:
- 2 sinusoidal surfaces w/ numerous microvilli facing into Space of Disse
- 1 canalicular surface

Question 10

Q

Hepatocyte and Sinusoids

Arrangement

Question 11

Q

Liver

Bile Flow

Answer

A

Bile flow: canaliculus → bile duct

Bile canaliculus: formed by apposition of two adjacent hepatocytes
Held together by tight junctional complexes
Bile actively transported into canaliculus
Canaliculus → canals of Hering @ border of portal tract → portal bile duct branch

Question 12

Q

Liver

Sinusoid

Answer

A

Formed by fenestrated endothelium w/ no basement membrane
Space of Disse:
- Space between hepatocyte and endothelial cell
- Usually not seen on routine histology
- Contains fibronectin and type I collagen
  - Scaffold of liver architecture
Kupffer cell:
- Resident macrophage sits either on top or between endothelial cells
Ito cells:
- Stellate cells in space of Disse
- Can function as facultative fibroblasts and secrete extracellular matrix components and growth factors
  - When activated, see liver fibrosis and can go on to cirrhosis
- Can store fat

Question 13

Q

Liver Functions

Answer

A

Metabolic
Synthetic
Storage
Catabolic
Excretory

Question 14

Q

Liver Disease

Overview

Answer

A

Mechanisms of injury: metabolic, toxic, microbial, circulatory, and neoplastic
Main primary diseases of the liver: viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC)
Liver can also be damaged by: cardiac decompensation, disseminated cancer, and extrahepatic infections
High functional reserve ⇒ masks impact of mild liver damage
- Insidious process (other than fulminant hepatic failure)
  - Takes place over weeks, months, years
- Hepatic decompensation ⇒ symptoms
Injury is detectable w/ lab tests
Chronic liver disease causes 27k deaths/yr in the US

Question 15

Q

Liver

Response to Injury

Answer

A

Hepatocyte degeneration and intracellular accumulations
Hepatocyte necrosis and apoptosis
Inflammation
Regeneration
Fibrosis

Question 16

Q

Liver Function Tests (LFTs)

Overview

Answer

A

Serologic tests used in the evaluation of liver disease
Commonly include: ALT, AST, Alkaline Phosphatase, GGTP, Total & Direct Bilirubin, Albumin & Total Protein
Many reflect the health of the liver and are not direct measures of its function
Commonly used LFTs may be abnormal even in pts w/ a healthy liver
Liver injury tests (enzymes):
- Serum alanine aminotransferase (ALT)
- Serum aspartate aminotransferase (AST)
- Serum alkaline phosphatase (ALP)
- Serum gamma glutamyl-transferase (GGTP)
Tests of hepatic synthetic function:
- Albumin
- Prothrombin time
Marker of hepatic transport:
- Serum bilirubin

Question 17

Q

Patterns of LFT Abnormalities

Answer

A

Clinically observed patterns of biochemical tests:

Hepatocellular Injury Pattern
- AST/ALT elevated > 5x upper limit of normal
  - Normal for females: < 19 IUs
  - Normal for males: < 30 IUs
- ALP levels elevated ≤ 2-3x upper limit of normal
  - Normal = 38-126
Cholestatic Pattern
- ALP levels elevated 3-5x upper limit of normal
  - AST/ALT elevation minor
Mixed pattern

Question 18

Q

Serum Aminotransferases

Answer

A

Most accurate markers of hepatocellular necrosis

Part of gluconeogenic pathway

Normal levels: < 40 IU/ml

AST: Aspartate Aminotransferase
- Oxaloacetate → Malate
- Found in the mitochondria and cytosol
- Not specific for liver disease
- Found in the liver, heart, skeletal muscles, kidney, brain, pancreas, lungs, leukocytes and erythrocytes
ALT: Alanine Aminotransferase
- Pyruvate → Lactate
- Primarily found in the liver cytosol
- More specific indicator of liver injury than AST

Question 19

Q

Elevated AST/ALT

Interpretation

Answer

A

Mild ⇒ < 3x ULN
- NAFLD; NASH
- Chronic Viral Hepatitis B & C
Moderate ⇒ 3-20x ULN
- Alcoholic Hepatitis (2-3:1 ratio AST:ALT)
- Acute Viral Hepatitis (1:1 ratio)
- Autoimmune hepatitis
High ⇒ > 20x ULN
- Drug toxicity (acetaminophen)
- Acute Viral Hepatitis
- Ischemia
- Autoimmune Hepatitis
- Wilson’s Disease
Ratio AST > ALT
- Alcoholic liver disease
- Cirrhosis of any etiology

Question 20

Q

Serum Alkaline Phosphatase (ALP)

Answer

A

Family of isoenzymes which catalyze hydrolysis of phosphate esters @ alkaline pH
- Reaction requires zinc
- Function in the liver unknown
Four different genes:
- 1 = liver, bone, 1^st trimester placenta and kidney
- 2 = 3^rd trimester placenta and intestine
- 3 = intestine
- 4 = fetal intestine
↑ ALP in liver diseases that involve:
- Inflammation
- Destruction or blockage of large and small intra- and extrahepatic bile ducts
If ALP ↑ ⇒ must ID source
- Gel electrophoresis to separate the various types of ALP
- Measure 5’ nucleotidase or GGTP ⇒ elevated along w/ ALP when 2/2 liver disorder
- ↑ ALP + nl GGTP ⇒ more likely 2/2 bone disorder

Question 21

Q

Elevated Serum Alkaline Phosphatase

Hepatic Etiologies

Answer

A

Chronic cholestatic or infiltrative diseases
Partial bile duct obstruction
Primary biliary cholangitis (PBC) (previously called primary biliary cirrhosis)
Primary sclerosing cholangitis (PSC)
Idiopathic adulthood ductopenia
Drugs ⇒ androgenic steroids; phenytoin
Infiltrative diseases ⇒ sarcoidosis; other granulomatous diseases; metastases

Question 22

Q

Serum Gamma Glutamyltransferase (GGT)

Answer

A

Found in hepatocytes and biliary epithelial cells
Very sensitive indicator of hepatobiliary disease
Usefulness limited by lack of specificity
- Elevated levels also seen in a wide variety of other clinical conditions: pancreatic disease, MI, CKD, COPD, DM, Alcoholism, Phenytoin and Barbiturates
Occult alcohol use ⇒ sensitivity ranges from 52-94%
Clinical uses:
- Evaluate a cause for ↑ ALP
- Support a suspicion of alcohol abuse w/ AST:ALT ratio > 2:1

Question 23

Q

Hepatic Synthetic Function

Tests

Answer

A

Tests measure how well the liver is working:

Serum Albumin
- Most important protein in plasma synthesized by the liver
- Total pool = 500 grams, 12-15 gm synthesized daily
- T ½ = 20 days
  - Not helpful in acute liver disease
- Influenced by nutritional status, hormone balance and osmotic pressure
Prothrombin Time
- Liver synthesizes most coagulation factors
  - Factors II, VII, IX, X, (vitamin K)
- < 50% of normal levels are needed to prolong PT

Question 24

Q

Bile Physiology

Answer

A

Secreted by hepatocytes
Functions:
- Emulsify dietary fats in the duodenum
- Facilitates transport of fat-soluble vitamins (A, D, E, K)
- Rids body of bilirubin
- Enables excretion of cholesterol, lipophilic wates (drugs, toxins)
Contains:
- Water
- Bile salts
- Bilirubin (pigmented)
- Electrolytes (isotonic to plasma)
- Phospholipids and cholesterol

Question 25

Q

Bilirubin

Synthesis & Transport

Answer

A

Heme derived end product
- 85% from senescent RBCs
- 15% from other sources
  - Breakdown of other hepatic hemoproteins
    - Cytochrome P-450 enzymes
  - Premature RBC breakdown in bone marrow
RBC phagocytosed by MΦ in reticuloendothelial system (RES)
- Heme porphyrin ring → biliverdin by microsomal heme oxygenase
- Biliverdin → bilirubin by biliverdin reductase
Unconjugated BRN is released into the plasma
- Majority bound to albumin
  - Insoluble in water ⇒ cannot be excreted in urine or bile
  - Transported to the liver
  - BRN released by albumin and taken up by hepatocytes
- Unbound (free) bilirubin
  - Toxic to brain of newborns ⇒ kernicterus
  - Drugs competing w/ bilirubin for albumin binding sites ↑ free bili

Question 26

Q

Bilirubin

Metabolism & Excretion

Answer

A

Hepatic BRN metabolism__:
- Uptake:
  - Bilirubin dissociates from albumin in the space of Disse
  - Carrier mediated transport of unconjugated BRN across hepatocyte membrane
  - Glutathione-S-Transferase (ligandin) binds bilirubin in the cell
- Conjugation:
  - BRN conjugated w/ glucuronic acid by UDP glucoronyltransferase (UGT) in the ER
  - Forms BRN mono- and diglucuronide ⇒ both water soluble
- Excretion into the bile:
  - Conjugated BRN excreted into bile canaliculus via active transport by MRP2 transport protein
    - Rate limiting step for transhepatic transport of bilirubin
Transport of conjugated BRN__:
- Bile → biliary system → ampulla of Vater → 2^nd portion of the duodenum → large intestine (colon)
- Bacteria convert conjugated BRN → colorless urobilinogens → excreted in the feces
  - Urobilinogens → colored urobilins ⇒ gives stool its color
- 20% of urobilinogens deconjugated by colonic bacteria and reabsorbed by enterohepatic circulation
- 1% is excreted in the urine

Question 27

Q

Bilirubin

Measurement

Answer

A

Total bilirubin = 0.1-1.5 mg/dL
Unconjugated or “indirect” = 0.1-1.0 mg/dL
- Not soluble in water
- Not measured directly in serum
- Indirect BRN = Total – Direct BRN
Conjugated or “direct” = 0-0.3 mg/dL
- Water soluble
- Small amount leaks out from liver
- Directly measured in the serum

Question 28

Q

Excess Bilirubin

Answer

A

Hyperbilirubinemia: ↑ bilirubin concentration in blood (> 1.0 mg/dL)
Jaundice (icterus): yellow skin and sclerae (> 2-2.5 mg/dL)
Cholestasis: visible bile plugs and bile by microscopic examination of liver
Cholestatic jaundice: Cholestasis and hyperbilirubinemia

Question 29

Q

Jaundice

Answer

A

“Icterus”

Yellow discoloration of skin, sclera and mucous membranes
Excess serum bilirubin ⇒ deposited in tissues
- Tissues w/ high [elastin] ⇒ ↑ affinity for serum bilirubin
  - E.g., sclera of the eye
Normal serum bilirubin 0.3-1.5 mg/dL
↑ BRN becomes clinically evident when > 2-4 mg/dL
Other conditions can cause yellow discoloration of the skin but not scleral icterus
- Carotenemia (excess serum carotene from carrots)
- Tanning products
- Side effects of medication (e.g., quinacrine or busulfan)

Question 30

Q

Unconjugated Hyperbilirubinemia

Answer

A

Disorders are not usually ass. w/ significant hepatic disease

Displacement of BRN from albumin by drugs
- Rifampin
Overproduction__:
*Overproduction of BRN** ⇒ exceeds hepatic conjugative capability
- BRN rarely > 5mg/dL
- Jaundice usually mild
- Hemolytic disorders
  - Sickle cell anemia, thalassemia, G6PD deficiency, paroxysmal nocturnal hemoglobinuria
- Ineffective erythropoiesis
  - Fe deficiency, vitamin B12 deficiency, sideroblastic anemia, lead toxicity
- Resorption of large hematomas
Impaired uptake__:
- 1°: Gilbert’s syndrome
- 2°: Certain drugs, e.g., rifampin, may compete w/ BRN uptake
Impaired conjugation__:
- 1°: Crigler-Najjar syndrome
- 2°: Acquired defects in conjugation
  - Drugs (e.g. chloramphenicol)

Question 31

Q

Gilbert’s Syndrome

Answer

A

AD disorder, 3-8% of population
Mutation of bilirubin UDP-GT
- ↓ Uptake of unconjugated BRN by hepatocytes
- Partial defect in BRN conjugation (50% of normal)
Mild unconjugated hyperbilirubinemia
- BRN levels ≤ 6mg/dL
- No other biochemical/histological abnormalities
Pts asymptomatic at baseline
Occasionally exhibit jaundice w/ illness, stress, fatigue, premenstrual state and alcohol abuse
Liver biopsy is not indicated, no specific therapy

Question 32

Q

Crigler-Najjar Syndrome

Answer

A

Unconjugated Hyperbilirubinemia

Impaired conjugation of BRN caused by ∆ UDP glucoronyltransferase activity.

Type 1
- AR disorder
- No UDPGT activity
- Fatal for neonates
  - Severe unconjugated hyperbilirubinemia (> 20 mg/dL)
  - Often die by 18 m/o w/ kernicterus
- Tx: phototherapy, plasmapheresis, liver transplantation
Type 2
- AD disorder
- ↓ UDPGT activity (10% of normal)
- BRN levels 10-16 mg/dL
- No kernicterus
- Tx: Phenobarbital to induce UDPGT activity

Question 33

Q

Neonatal Jaundice

Answer

A

Seen in 70% of full-term newborns
Physiologic in first 5 days of life
D/t incompletely developed hepatic BRN metabolism
- ↓ Ligandin and ↓ UGT
Result in unconjugated hyperbilirubinemia
UGT ↑ by 2 wks of life to adult levels
Bilirubin crosses placenta and is dealt w/ by mom in utero
Other factors:
- RH and ABO blood incompatibilities: hemolytic anemia ⇒ pathologic + physiologic jaundice in newborn
- Hypothyroidism
- Breast milk jaundice resulting from an inhibitor of UDPGT activity in maternal breast milk

Question 34

Q

Conjugated Hyperbilirubinemia

Answer

A

Definition: conjugated BRN level > 30% of total BRN
Congenital causes:
- Dubin-Johnson syndrome
- Rotor’s syndrome
- Progressive familial intrahepatic cholestasis (PFIC) (“Byler’s disease”)
Acquired causes:
- Cholestasis: impaired formation or excretion of all components of bile

Question 35

Q

Dubin-Johnson Syndrome

Answer

A

Conjugated Hyperbilirubinemia

AR condition
Mutated MRP2 transporter
Impaired storage and excretion of BRN
Serum BRN levels 2-5mg/dL
Histological exam reveals a darkly pigmented (black) liver
No specific therapy

Question 36

Q

Rotor’s Syndrome

Answer

A

Conjugated Hyperbilirubinemia

AR condition
Impaired intracellular storage of BRN
Bile salt excretion is normal
BRN levels 2-5mg/dL
Liver is not pigmented
Liver function unaffected
No specific therapy

Question 37

Q

Progressive Familial Intrahepatic Cholestasis (PFIC)

“Byler’s Disease”

Answer

A

Conjugated Hyperbilirubinemia

AR condition
Defective hepatic secretion of bile acids across the canalicular membrane
Particularly affecting the Amish kindred
Pts present w/ severe watery diarrhea, cholestatic jaundice, fat-soluble vitamin deficiency and occasionally pancreatitis

Question 38

Q

Cholestasis

Overview

Answer

A

Impaired formation or excretion of all components of bile
↑ Serum and tissue bilirubin
2 major mechanisms:
- Defect in excretion of BRN from hepatocytes into bile ⇒ intrahepatic cholestasis
- Mechanical obstruction to the flow of bile through the bile ducts ⇒ extrahepatic cholestasis
Biochemical pattern:
- ↑ Serum BRN (usually conjugated)
- ↑ ALP
- ↑ GGTP
- Mild ↑ AST/ALT (≤ 2x ULN)

Question 39

Q

Differentiating

Cholestasis

Answer

A

Considerable overlap in biochemical pattern seen in intrahepatic and extrahepatic causes
Additional testing to look for an extrahepatic cause
- Abdominal US
- CT
- MRCP (magnetic resonance cholangiopancreatography)
  - MRI of the biliary and pancreatic trees
- ERCP (endoscopic retrograde cholangiopancreatography)
  - Endoscopic contrast study of the biliary tree
Obstruction in the biliary tree (gallstone, pancreatic tumor or malignant biliary tract CA) ⇒ bile ducts will appear dilated on imaging

Question 40

Q

Intrahepatic Cholestasis

Etiologies

Answer

A

Bile canaliculus
- Hepatocellular injury
  - Viral and alcoholic hepatitis
  - Sepsis
  - Prolonged total parenteral nutrition
  - Congestive hepatopathy (from right heart failure)
  - Infiltrative disorders (sarcoidosis, amyloidosis, lymphoma etc.)
  - Graft-versus-host disease (after bone marrow transplant)
- Drugs
  - Steroid hormones, chlorpromazine, OCP, NSAIDs etc.
- Benign post-operative cholestasis
- Pregnancy
Bile ductule
- ? Drugs
Portal tract bile duct
- Primary biliary cholangitis (PBC) (“Primary biliary cirrhosis”)
- Intrahepatic biliary atresia
Medium and large interlobular bile ducts
- Sclerosing cholangitis
- Cholangiocarcinoma
- Parasite
- Vanishing bile duct syndrome (idiopathic adulthood ductopenia, chronic rejection)

Question 41

Q

Intrahepatic Cholestasis

Morphologic Features

Answer

A

Cholestasis & cell necrosis

Early cholestasis
- Preferential localization in zone 3
- See bile in hepatocytes
Late cholestasis
- Bile plugs in zone 1
- Feathery degeneration
  - Swelling
  - Bile pigment
  - Reticulation of cytoplasm
- Mallory hyaline
- Fibrosis/Cirrhosis

Question 42

Q

Extrahepatic Cholestasis
Etiologies

Answer

A

Choledocholithiasis (gallstones impacted in common bile duct)
Sclerosis and strictures of biliary tree
- Sclerosing cholangitis
- Secondary causes
Neoplasia
- Cholangiocarcinoma (bile ducts)
- Pancreatic adenocarcinoma
- Ampullary carcinoma
- Duodenal neoplasm
- Metastases to hepatic hilum
- Portal LN involvement by any neoplasm
HIV cholangiopathy
Haemobilia (blood clots in biliary tree)
Infectious cholangiopathy: worms impacted in bile ducts (Clonorchis, Ascaris, Fasciola)
Chronic pancreatitis
Benign biliary strictures (post-cholecystectomy, post liver transplant, related to PSC, ischemic)
Pediatric pts
- Extrahepatic biliary atresia
- Choledochal cysts

Question 43

Q

Extrahepatic Cholestasis

Morphologic Features

Answer

A

Cholestasis & Cell Necrosis

Plus

Portal tract edema
Bile duct proliferation
Neutrophils
Bile infarct
Extravasated bile

Question 44

Q

Cholestasis

Clinical Manifestations

Answer

A

Dark urine ⇒ “tea colored”
Light stools ⇒ “clay colored”
Pruritus
- D/t retention of bile salts and other products
- Tx w/ bile salt binders (cholestyramine)
Abd pain
Weight loss
Fat malabsorption (steatorrhea)
Fat soluble vitamin deficiency states:
- Vit A ⇒ night blindness
- Vit D ⇒ osteomalacia
- Vit K ⇒ coagulopathy
High cholesterol ⇒ xanthomas
Secondary biliary cirrhosis

Question 45

Q

Predictable

Hepatotoxins

Answer

A

Fundamental property of toxin
Injury in majority of people
Dose dependent
Zonal necrosis
Two mechanisms:
- Direct
- Indirect

Question 46

Q

Carbon Tetrachloride Toxicity

Question 47

Q

Unpredictable

Hepatotoxins

Answer

A

Idiosyncratic reaction
Host dependent
Non-dose dependent
Non-zonal
Two mechanisms:
- Hypersensitivity
- Metabolic aberration

Question 48

Q

Acute and Chronic Hepatitis

Common Causes

Answer

A

Viral
Drug/Toxin
Alcohol
Non-Alcoholic Fatty Liver
Autoimmune Related Disorders
Metabolic Disorders
Ischemic/Congestive
Extrahepatic biliary obstruction

Question 49

Q

Hepatic Injury

Morphologic Patterns

Question 50

Q

Confluent Necrosis

Subtypes

Answer

A

Bridging: Bands of necrosis linking landmark structures (portal tracts and central veins)
Submassive: Necrosis of entire lobules or groups of lobules
Massive: Necrosis of virtually all the hepatocytes

Question 51

Q

Acute Viral Hepatitis

Pathology

Answer

A

Similar in all forms of viral hepatitis:

Lobular disarray
Liver cell necrosis
- Apoptosis
- Ballooning degeneration
Inflammation
- Lymphocytes
- Macrophages
- Neutrophils
Regeneration
± Cholestasis and phlebitis

Question 52

Q

Chronic Hepatitis

Answer

A

Definition: Presence of necrosis and inflammation in the liver for > 6 months
Liver biopsy can be done to establish degree of disease
Expressed as ‘grade’ and ‘stage’
- Grade describes the amount of acute disease and takes into account:
  - Interface necrosis
  - Lobular activity
  - Portal inflammation
- Stage describes the level of fibrosis:
  - No fibrosis
  - Portal fibrosis
  - Bridging fibrosis
  - Cirrhosis

Question 53

Q

Autoimmune Hepatitis

Answer

A

Chronic hepatitis of unknown cause

~20% of all cases of chronic hepatitis in Western countries
More common in women, usually middle age
Ass. w/ circulating auto-Ab and high levels of immunoglobulins
Ass. w/ other autoimmune diseases
Suspected mechanism of injury:
- Ab-dependent cell-mediated cytotoxicity
- Defective suppressor T cell function
Type I: Anti-smooth muscle, Anti-actin, anti-asiaoglycoprotein receptor Ab
Type II: Liver/kidney microsomes and anti-liver cytosolic protein Ab
Pathology: Like chronic viral hepatitis, often plasma cell rich infiltrate
Clinical features: Ranges from asymptomatic to fulminant disease
Treatment: steroid and immune suppression responsive
Must distinguish from other causes of chronic hepatitis

Question 54

Q

Drug-related Chronic Hepatitis

Answer

A

Many drugs reported to cause chronic hepatitis
May be indistinguishable from viral and autoimmune disease histologically
Requires exclusion of other causes serologically and clinical history

Question 55

Q

Alcoholic Liver Disease

Stages

Answer

A

Fatty Liver (Steatosis)
- Yellow, enlarged, heavy liver
- Fat first accumulates in zone 3
- Enlarged mitochondria, SER hyperplasia
- If discontinue drinking, can lose the fat
- Cause of progression to next step is unclear
Steatohepatitis
- 10-30% mortality
- > 30% who continue to drink for 1-2 yrs more will develop next step
- Necrosis of hepatocytes
- Neutrophilic infiltrate
- Mallory hyaline and fat
- Perivenular and pericellular fibrosis
Cirrhosis
- Thin and thick bands of fibrosis circumscribing nodules of regenerating hepatocytes
- Central and pericellular fibrosis

Important to realize that any of these manifestations may coexist

Do not need to see one to proceed to the next

Question 56

Q

Non-Alcoholic Fatty Liver (NAFL)

Associations

Answer

A

Obesity
Diabetes
Drug related: corticosteroids
Metabolic disease/disorder
- Wilson’s disease
- Kwashiorkor

Question 57

Q

Primary Biliary Cholangitis (PBC)

Overview

Answer

A

“Primary Biliary Cirrhosis”

Chronic progressive cholestatic liver disease characterized by destruction of intrahepatic bile ducts

Autoimmune disease (presumably)
> 85% have at least one other autoimmune disease:
- Chronic thyroiditis, RA, scleroderma, Sjogren’s, SLE
> 95% have elevated antimitochondrial Ab
- Elevated Ig, other Abs present
Presumed attack of ducts by cytotoxic T cells
Middle age women (range 30-65yrs)
F:M ratio is 10:1
Other labs: elevated alkaline phosphatase, ↑ serum cholesterol

Question 58

Q

Primary Biliary Cholangitis (PBC)

Stages

Answer

A

Stage I: Destruction of small and medium sized bile ducts (focal, segmental)
- Granulomas are the characteristic portal infiltrate
- All types of inflammatory cells are seen
- Plasma cell and eosinophils may be prominent
Stage II: Periportal inflammation and ductular proliferation
Stage III: Bridging fibrosis
- Mallory hyaline
- ↑ Copper deposition
Stage IV: Cirrhosis

Question 59

Q

Primary Sclerosing Cholangitis (PSC)

Answer

A

Chronic cholestatic liver disease of unknown cause

Inflammatory and fibrosing process narrows and eventually obstructs intrahepatic and extrahepatic bile ducts

Associations:
- Ulcerative colitis (seen in 2/3)
- Less commonly: Crohn’s disease, lymphoma, retroperitoneal fibrosis
Hypergammaglobulinemia
Antineutrophilic cytoplasmic Ab (ANCA)
More common in men in 3-4th decade
↑ risk of cholangiocarcinoma
- Up to 10% of PSC patients
Liver transplant is curative

Question 60

Q

Iron Overload

Etiologies

Answer

A

↑ Iron absorption
- HHC
- Chronic liver disease
- Porphyria cutanea tarda
- Congenital diseases
- Dietary iron overload
- Excess medicinal iron
Parenteral iron overload
- Multiple blood transfusions
- Injectable medicinal iron
Focal iron overload
- Idiopathic pulmonary hemosiderosis
- Renal hemosiderosis

Question 61

Q

Hereditary Hemochromatosis (HHC)

Pathogenesis

Answer

A

Inherited disorder of iron metabolism
Iron deposition toxic to involved organs
Autosomal recessive
HFE gene on short arm of chromosome 6
Linked to the HLA locus of the MHC
- 70% of homozygotes have HLA-A3

Question 62

Q

Hereditary Hemochromatosis (HHC)

Clinical Features

Answer

A

↑ Iron absorption in duodenum
↑ Serum iron, ferritin, and transferrin saturation
Clinical manifestations:
- Diabetes
- Skin pigmentation
- Cardiac failure
- Cirrhosis

Question 63

Q

Wilson Disease

Answer

A

Genetic disorder in which excess copper builds up in the body.

Symptoms are typically related to the brain and liver.

Question 64

Q

Cystic Fibrosis

Hepatic Effects

Answer

A

Tenacious bile due to CF
Similar change in viscosity seen in other bodily secretions
Newborns may present w/ obstructive jaundice
15% of young adults w/ CF have symptomatic liver disease, can develop cirrhosis

Answer 62

A

Defective secretion of mutant protein made in the liver
Co-dominant inheritance: > 75 variants
- PIMM normal
- PIZZ phenotype ⇒ abnormal folding
Liver and lung disease
- Emphysema: due to lack of protease inhibitor
- Hepatitis, Cholestasis and Cirrhosis: due to accumulation of abnormal protein
  - Seen as globules in hepatocyte
  - ↑ risk of hepatocellular carcinoma
Most common genetic cause of liver disease in infants and children
- 1/2000 live births
- Only 10-15% of those develop liver dz
Liver transplant curative

Answer 63

A

Cardiac disease: any disease ass. w/ right heart failure
- Congestive heart failure (most common cause)
- Tricuspid valvular disease
- Constrictive pericarditis
Venous obstruction
- Budd-Chiari: occlusion of intra and/or extrahepatic veins w/ congestive liver damage
  - Hypercoagulable states
- Hepatic veno-occlusive disease: occlusion of the central venules and small branches of the hepatic veins
  - Bush tea
  - Chemotherapeutic agents

Answer 64

A

Definition: Liver cannot perform metabolic, synthetic, detoxifying activities sufficiently for body’s needs
Usually end-stage of chronic progressive damage
- Steady destruction of hepatocytes
- Repetitive waves of parenchymal damage
Rarely d/t sudden, massive liver destruction ⇒ fulminant hepatic failure
Criterion: Need to lose 80-90% of liver functional capacity
Without a transplant, 80% of pts w/ hepatic failure will die

Answer 65

A

Acute liver illness w/ encephalopathy within 6 months after dx
- Fulminant if within 2 weeks jaundice onset
- Sub-fulminant if within 3 months of jaundice onset
Caused by massive hepatic necrosis
- Mechs include direct toxic damage or combo of toxicity and immune-mediated hepatic destruction
Etiologies:
- Usu. from drugs or toxins
  - Halothane, antimycobacterial drugs, chemicals
- Hepatitis A, Hepatitis B, autoimmune hepatitis

Answer 66

A

Most common route

End point of chronic hepatitis that ends in cirrhosis

Answer 67

A

Hepatocytes are viable, but can’t function normally

Examples: Tetracycline toxicity, pregnancy

Answer 68

A

Fatty liver disease
- Alcohol (ASH), Non-alcoholic steatohepatitis (NASH) / Non-alcoholic fatty liver disease (NALD)
Viral hepatitis
- Hep C, B (w/ or w/o D)
Autoimmune diseases
- Autoimmune hepatitis, Primary biliary cirrhosis, Primary sclerosing cholangitis
Genetic liver diseases
- Hemochromatosis, Wilson’s disease, α-1 anti-trypsin deficiency, cystic fibrosis
Vascular causes
- R heart failure, Budd Chiari syndrome, veno-occlusive disease
Rare causes
- Drugs
  - Methotrexate, amiodarone, methyldopa
- Toxins, herbal supplements
- Secondary biliary cirrhosis
  - Ass. w/ chronic cholestasis
Cryptogenic (unknown)
- 10-15% of cases

Answer 69

A

Irreversible end result of chronic liver disease
- Death of hepatocytes, ECM deposition, vascular reorganization
Characterized histologically by regenerative nodules surrounded by fibrous tissue
Caused by a variety of inflammatory, toxic, metabolic and/or congestive insults
- Hepatitis, hepatopathy, cholestasis

Answer 70

A

Pathologically ⇒ gross pattern of architectural distortion
- Micronodular
  - Regenerative nodules < 3 mm
  - Often due to alcoholic cirrhosis
- Macronodular
  - Nodules > 3 mm
  - Commonly related to chronic viral hepatitis
- Mixed
Clinically
- Compensated
  - No complications
- Decompensated
  - One or more complications (ex. ascites, encephalopathy or variceal bleeding)
  - Liver transplantation considered

Answer 71

A

May be dx @ at the asymptomatic stage
General decline in health (most ubiquitous feature)
Non-specific complaints:
- Anorexia, wt loss, malaise, fatigue, weakness
Loss of normal bile flow
- Jaundice
- Pruritus
Loss of detoxification
- Neurological sx
- Hepatorenal
Loss of synthetic function
- Albumin
- Clotting factors
Advanced disease may present w/ complications of portal HTN
- Esophageal varices
- Ascites
- Splenomegaly
- Portosystemic shunting (varicosities)
- Encephalopathy
Cancer risk
- Hepatocellular Carcinoma

Answer 72

A

Cutaneous stigmata and endocrine features:

Jaundice
Splenomegaly and ascites ⇒ suggest portal HTN
Spider angiomata
Palmar erythema
Leukonychia (white nails)
Gynecomastia
Testicular atrophy
Caput medusae

Answer 73

A

Hepatic insufficiency (synthetic dysfunction):
- Low serum albumin
- Prolonged prothrombin time (INR)
- High bilirubin
Portal HTN (due to hypersplenism):
- Thrombocytopenia
- Anemia
- Leukopenia

Answer 74

A

US, CT, and MRI may all be used

Characteristic features include:

Small, shrunken, nodular liver
Recanalized paraumbilical vein
Enlarged caudate lobe of the liver
Prominent vessels (varices) around the esophagus, stomach or in the mesentery
Splenomegaly
Free abdominal fluid (ascites)
Enlarged portal vein

Answer 75

A

Non-invasive:
- Bloodwork
  - HCV – fibrosure
  - NASH – fibrosure
- Imaging
  - US w/ elastography
  - Fibroscan
  - MR elastography
Invasive:
- Liver biopsy
  - Gold standard
  - Often not necessary if complications (e.g. varices or ascites) present or radiologic imaging diagnostic
  - Performed percutaneously or via trans-jugular route (allows for measurement of portal pressures)

Answer 76

A

Cirrhosis = end histological stage resulting from chronic liver injury of various etiologies
Initially, cirrhosis is compensated
- Median survival 10-12 yrs
Decompensated stage marked by onset of variceal hemorrhage, ascites, hepatic encephalopathy and/or jaundice
- 60% risk over 10 yrs
- Ascites most common
- ↑ risk of death from liver disease
- Median survival 2-4 yrs

Answer 77

A

Portal HTN
Hepatic encephalopathy
- Variety of neurological signs and sx in pts who suffer chronic liver failure or in who the portal circulation is diverted –has 4 stages, ending in coma
Hepatorenal syndrome
- Renal failure featuring renal hypoperfusion: oliguria, azotemia and ↑ plasma creatinine levels
- Usually kidneys function normally
- Seems to be d/t ↓ in renal blood flow
Hepatopulmonary Syndrome
- Clinical liver disease, hypoxemia, intra-pulmonary vascular dilations

Answer 78

A

Portal circulation follow Ohm’s Law: P = R x F
Portal venous system ⇒ low-pressure system
Cirrhosis:
- Nodular regeneration and fibrosis in the space of Disse
  - ↑ resistance to flow
- ↓ tone in the splanchnic arterioles (possibly related to nitric oxide) ⇒ ↑ splanchnic blood flow
  - ↑ portal venous inflow
Portal pressure gradient = effective intrasinusoidal pressure
- Difference between hepatic vein and portal vein pressure
- Normally < 5 mmHg
- Clinically significant elevation: > 12 mmHg
Not all PHTN is due to cirrhosis
PHTN is classified according to the site of increased resistance

Answer 79

A

Pre-hepatic causes:
- Portal vein thrombosis, splenic vein thrombosis, splenomegaly, arterioportal fistula
Intra-hepatic causes:
- Presinusoidal (Schistosomiasis), sinusoidal (cirrhosis), post-sinusoidal (veno-occlusive disease)
- Primary Biliary Cirrhosis (pre-cirrhosis)
- Congenital hepatic fibrosis
- Cystic disease of the liver
- Nodular transformation
- Metastatic or primary carcinoma
- Toxins
Post-hepatic causes:
- Budd-Chiari syndrome (thrombosis of hepatic v.), IVC web/obstruction, constrictive pericarditis, right heart failure
Idiopathic

Answer 80

A

Portal HTN ⇒ dilation of pre-existing connections ⇒ portal-systemic collaterals
Most important: Esophago-gastric collaterals (Esophagogastric varices)
- Coronary vein ↔︎ esophageal veins
- Drains blood into azygos vein
- Could cause life-threatening hemorrhage
Other sites of portosystemic collaterals:
- Umbilicus (caput medusae)
  - Splenic bed via short gastric veins (gastric fundic varices)
  - Retroperitoneum
- Rectum (rectal varices)
- Small and large intestine (ectopic varices)

Answer 81

A

> 50% of pts w/ cirrhosis develop gastroesophageal varices
Varices form and enlarge at a rate of 7-8%/year
Endoscopy to ID pts w/ medium-large varices @ high risk for bleeding
Primary prophylaxis (prevention of first bleed)
- Non-selective β-blocker (e.g. nadolol or propranolol) ⇒ ↓ intra-variceal pressure
- Endoscopic banding

Answer 82

A

Medical emergency
10-30% of pts every year
Each episode associated w/ up to 50% mortality
Presentation:
- Hematemesis
- Melena and/or hematochezia
- Typically leads to hemodynamic compromise
Predictors of bleeding:
- Larger variceal size
- Red signs on the varices
- More advanced liver disease (Childs B-C)
Treatment:
- Hemodynamic resuscitation w/ IV fluid
- Blood and/or FFP transfusion
- Pharmacologic therapy
  - Somatostatin or its synthetic analog (octreotide)
  - Abx
- Endoscopic therapy
  - Band ligation or injection sclerotherapy
- Transjugular intrahepatic portosystemic shunt (TIPS stent)
  - Creates a communication between portal (portal vein) and systemic (hepatic vein) circulation
  - For refractory bleeding

Answer 83

A

Pathological accumulation of excess fluid in the peritoneal cavity
Cirrhosis causes 75% of cases
Classification: serum ascites-albumin gradient (SAAG)
- Elevated SAAG > 1.1 g/dL ⇒ portal HTN, right heart failure, massive liver metastases
Clinically detectable w/ > 500 mL
- Shifting dullness to percussion
- Fluid wave
- Bulging of the flanks
- Everted umbilicus
- Umbilical hernia
Detectable w/ US @ > 250 mL

Answer 84

A

Cirrhosis (portal HTN):

Hepatic venous outflow block
- Anatomical: fibrosis and regenerative nodules
- Functional: ↑intrahepatic vascular tone, predominantly post-sinusoidal ⇒ ↑ sinusoidal pressure
Splanchnic and systemic arteriolar vasodilation
- Decreased effective arterial blood volume
- Upregulation of sodium-retaining hormones
- Sodium and water retention
- Plasma volume expansion
- Dilutional hyponatremia and renal failure from hepatorenal syndrome
Sinusoidal hypertension
- Drives fluid out of the sinusoids and into peritoneal cavity
- Intravascular fluid continuously replenished by plasma volume expansion

Answer 85

A

Sodium restriction (< 2g/day)
Fluid restriction [when hyponatremia (Na < 125mEq/L) occurs]
Diuretics
- Spironolactone (aldosterone antagonist)
- Furosemide (loop diuretic)
Refractory ascites (~10% of pts w/ cirrhosis)
- Fluid overload that recurs rapidly after therapeutic paracentesis
- Unresponsive to high dose diuretic treatment and sodium restricted diet
- Treatment includes repeated large-volume paracentesis, TIPS or liver transplantation

Answer 86

A

Ascitic fluid infection w/ growth of a single organism and ascitic fluid neutrophil count > 250 cells/μL w/o e/o a surgically remediable intra-abd cause
Dx by paracentesis w/ analysis of fluid cell count and culture
For all practical purposes, SBP occurs only in the setting of liver disease

Answer 87

A

Severe liver disease ⇒ failure of local and systemic immune defenses ⇒ ↑ bacterial translocation
RES = main defense system vs bacteremia and other hematogenous infectious
- Most RES activity located in the liver
- Kupffer cells (tissue MΦ) are the major components
Cirrhosis ⇒ ↓ bactericidal activity of Kupffer cells and impaired reticuloendothelial system (RES) activity
- Porto-systemic shunting bypasses the liver
  - Escaping the action of the RES
Impaired RES ⇒ prolonged bacteremia
In the presence of ascites, bacterial colonization occurs
In pts w/ ↓ local defense mechanisms (e.g. low ascites complement levels) ⇒ overt ascites infection develops (SBP)

Answer 88

A

Predominant sx: fever, jaundice and abdominal pain
- Pts can present atypically w/ encephalopathy, shock or renal failure
- Up to ⅓ of pts may be entirely asymptomatic
Treatment:
- Third generation cephalosporin (e.g. cefotaxime) IV for 5 days
- High rates of SBP recurrence (70% at 1 year w/o abx)
- Secondary prophylaxis w/ long-term abx is indicated

Answer 89

A

Occurs in pts w/ advanced cirrhosis
Functional renal failure
- Extreme peripheral vasodilatation ⇒ renal vasoconstriction
- Kidneys w/o significant histological abnl
Renal dysfunction characterized by:
- ↓ GFR
- Oliguria
- Low urine sodium (<10mEq/L)
- Absence of intrinsic renal disease or other renal insults ⇒ nl urinary sediment & nl renal US
Tx:
- Withdrawing diuretics and nephrotoxins
- Volume expansion w/ saline or albumin
- Liver transplantation is the only effective cure
  - If liver transplant is done early enough, kidneys should begin working properly again

Answer 90

A

Neuropsychiatric manifestations of hepatic cirrhosis

Proposed pathogenesis:
- ↓ Clearance of gut-derived neurotoxins, including ammonia
- Ammonia ⤭ BBB ⇒ ↑ astrocytic peripheral-type benzodiazepine receptors
  - Most potent stimulants of neurosteroid production
- Neurosteroids ⇒ major modulators of GABA
- GABA ⇒ cortical depression and hepatic encephalopathy
Dx: based on hx and PE findings
- Ammonia levels are unreliable
  - Poor correlation b/t stage of encephalopathy and serum [ammonia]
Clinical features: subtle changes in personality/affect → deep coma
- Flapping tremor or “asterixis” ⇒ cardinal feature
  - Due to inability to maintain posture of the outstretched hands
Treatment:
- ID and address precipitating factors
  - GI hemorrhage, infections, electrolyte abnl, new-onset renal insufficiency, TIPS placement, medication non-compliance
- Therapy is directed at altering the colonic microenvironment
  - ↓ ammonia production in the gut
    - Lactulose
    - Non-absorbable abx such as rifaximin

Answer 91

A

98% of Hepatic Malignancies in US
Carcinoma
- Lung, Breast, Colon, Pancreas
Hematopoietic Malignancies
- Non-Hodgkin lymphoma
- Hodgkin lymphoma
- Leukemia
- Sarcoma

Answer 92

A

Malignant tumor that arises from hepatocytes

Low incidence regions: Western industrialized countries
- Age of onset: 6-7th decade
- M:F ratio: 3:1
- % CA deaths: 0.5-2
High incidence regions: Sub-Saharan Africa, Southeast Asia, Japan
- Age of onset: 3-5th decade
- M:F ratio: 9:1
- % CA deaths: 20-40%
Worldwide – Hepatocellular Carcinoma is either the #1 or #2 most common malignancy

Answer 93

A

Incidence of HCC ↑↑↑ in pts w/ cirrhosis

Viral
- Hepatitis B Virus
- Hepatitis C Virus
  - HCC in 1-3% of HCV-infected pts over 20-30 yr follow up
Metabolic disorders
- Hemochromatosis
- α-1 antitrypsin
Exposures
- Alcohol
- Thorotrast
- Aflatoxins
- Anabolic steroids

Answer 94

A

Symptoms
- Abdominal pain
- Fullness
- Mass
- Decompensated cirrhosis
- Paraneoplastic sx
Serology
- ↑ alpha-fetoprotein
Outcome
- Poor
- 50% have metastases @ autopsy

Answer 95

A

Microtrabecular vs Macrotrabecular

Answer 96

A

Screen at-risk individuals w/ US every 6 months
Treatment:
- Pts w/ well-compensated disease ⇒ surgical resection
- Pts w/ advanced cirrhosis ⇒ liver transplantation
- Non-surgical options:
  - Microwave or radiofrequency ablation
  - Trans-arterial chemotherapy

Answer 97

A

Variant of HCC w/ unique features

Arises in normal liver (not a cirrhotic liver like other HCC)
Affects adolescents and young adults
Not ass. w/ elevated AFP
Better prognosis
Histology:
- Large eosinophilic hepatocytes
- Delicate collagen in lamellar arrangement

Answer 98

A

Adenocarcinoma of bile duct origin
Affects primarily 6th-7th decade, M=F
Location:
- Intrahepatic (Peripheral): within the liver
- Extrahepatic: outside the liver
  - R & L hepatic duct
    - If @ convergence ⇒ hilar or Klatskin tumor
  - CBD
  - Cystic duct
Differential diagnosis (microscopic look-alikes, i.e. other adenocarcinomas)
- Pancreatic carcinoma
- Ampullary carcinoma
- Gallbladder carcinoma

Answer 99

A

Signs and symptoms related to site:
- Painless jaundice
- Pruritus
- Palpably enlarged gallbladder
- Pancreatitis
- Anorexia, weight loss
Clinical course
- Similar to gallbladder carcinoma
Outcome
- Dismal

Answer 100

A

Biliary disease
- PSC/UC
- Chronic biliary infection
- C. sinensis (liver fluke)
- Choledochal cysts
- Caroli’s disease
- Congenital hepatic fibrosis
Other exposures
- Hemochromatosis
- Thorotrast

Answer 101

A

Intrahepatic
- Glands within desmoplastic stroma
- May combine w/ HCC, results in cholangiohepatocellular carcinoma
Extrahepatic
- Small sclerosing tumor obliterating lumen
- Tumor spreading along wall of duct
- Intraductal papillary variant

Answer 102

A

Malignant tumor of the liver
Seen mainly in young children, age 0-3 yrs
Clinical manifestations:
- Abdominal enlargement
- Vomiting
- Failure to thrive
- Paraneoplastic syndromes
Elevated AFP
May be cured by resection
Pathology
- Hemorrhagic, circumscribed mass, up to 25cm
- Epithelial cells
  - Embryonal appearance
  - Fetal appearance
- Mesenchymal component
- Extramedullary hematopoiesis

Answer 103

A

Rare (< 1% of all hepatic malignancies)
Angiosarcoma
- Malignant neoplasm of blood vessels
Risk factors (present in ~ 1/3)
- Thorium dioxide
- Vinyl chloride
- Inorganic arsenic
- Anabolic steroids
Clinical:
- Peak: 6-7th decade
- Rapidly fatal

Answer 104

A

Benign neoplasm of blood vessels

Answer 105

A

Benign neoplasm of hepatocytes

Women in reproductive yrs
- Highly ass. w/ oral contraceptives
  - Incidence ↓ w/ low dose oral contraceptives
Rare cases in men w/ anabolic steroid use
Complication:
- Bleeding into peritoneal cavity
Treatment:
- Resection
- May disappear w/ discontinuation of OCPs

Answer 106

A

75% solitary, 25% multiple
Up to 40cm size
Mass lesion composed of compressed benign hepatocytes without normal portal areas
Prominent vascular spaces

Answer 107

A

Non-neoplastic nodular lesion that looks like cirrhosis
- Mass lesion: must be distinguished from others
F>M
Pathology:
- Central fibrous scar containing large vessels w/ radiating septa
- No portal areas, proliferating bile ductules
Treatment: None required

Answer 108

A

Hyperplastic nodules without fibrous scarring

Two forms:
- Partial nodular transformation
  - Partially involves liver
  - Located predominantly in hilar region
- Nodular regenerative hyperplasia
  - Diffuse involvement of liver
Clinical Importance:
- Portal Hypertension in the absence of cirrhosis

Answer 109

A

Bile duct microhamartomas

Anomalous, small cystic bile ducts in stroma

Answer 110

A

Solitary or multiple simple cysts (Polycystic Liver Disease)

Sporadic or can be ass. w/ adult polycystic disease of the kidney

Answer 111

A

Autosomal recessive
Enlarged portal tracts w/ extensive fibrosis w/o regenerative nodules
Numerous bile ductules that communicate w/ the biliary tree
Complication: portal hypertension

Answer 112

A

Larger ducts are segmentally dilated
May contain thickened bile
↑ risk of cholangiocarcinoma

Answer 113

A

Highly successful procedure in pts w/ advanced liver disease
Indications:
- Cirrhosis (all causes)
- Intrahepatic malignancy (ex. localized hepatocellular carcinoma)
- Acute liver failure
- Metabolic diseases (ex. Wilson’s disease)
1-year post transplant pt survival is ~90%
LT evaluation includes detailed medical and psychosocial assessment
Several prognostic indicators have been developed

Answer 114

A

Rejection
- Early
  - Cholangitis
  - Cholestasis
  - Endothelialitis (inflammatory response within endothelium of vessels)
- Late
  - Paucity of bile ducts
  - Arteropathy
  - Subintimal foam cells
  - Myointimal hyperplasia
Infection
- CMV
- HSV
Disease recurrence
EBV ass. lymphoproliferative disease