The document discusses the structure and function of the liver as well as common conditions seen in advanced liver disease. It describes the liver's dual blood supply, role in metabolism and detoxification, and how liver failure can lead to complications like jaundice, portal hypertension, gastroesophageal varices, hepatic encephalopathy, cerebral edema, and ascites. Treatment focuses on correcting underlying causes, reducing complications, and managing symptoms. Liver transplantation may be considered for severe, end-stage liver disease.
2. STRUCTURE OF THE LIVER
• Largest parenchymal organ of the body:
averages 1500 g
• Located in right upper quadrant of
abdomen, beneath diaphragm
• Divided into right and left lobes
• Subdivided according to blood supply and biliary
drainage
3. STRUCTURE OF THE LIVER (CONT.)
• Glisson capsule: connective tissue capsule
covered by visceral peritoneum
• Form suspensory hepatic ligaments
• Demarcate bare area of liver directly in contact
with diaphragm
• Dual blood supply
• Arterial (25%): inflow from aorta via celiac trunk and
hepatic artery
• Remainder from portal vein (75%) drains into
capillary bed of alimentary canal and pancreas
• Rich in substances absorbed and secreted by gut
6. STRUCTURE OF THE LIVER (CONT.)
• Portal circulation
• Afferent blood vessels branch into liver with bile
ducts to form portal triads
• Portal veins
• Hepatic arteries
• Bile ducts
• Blood from hepatic artery and portal vein drains into
hepatic sinusoids
• Surrounded by endothelial and Kupffer cells
• Surround sheets of liver cells or hepatic plates
7. STRUCTURE OF THE LIVER (CONT.)
• Portal circulation
• Blood drains into central veins
• Coalesce into hepatic vein
• Empty in inferior vena cava
9. LIVER FUNCTION
Digestive Organ
• Bile salt secretion for fat digestion
• Processing and storage of fats,
carbohydrates, proteins
• Processing and storage of vitamins and
minerals
10. LIVER FUNCTION (CONT.)
Endocrine Organ
• Regulation of carbohydrate, fat, and protein
metabolism
• Metabolism
• Glucocorticoids
• Mineralocorticoids
• Sex hormones
11. LIVER FUNCTION (CONT.)
Hematologic Organ
• Temporary storage of blood
• Removal of bilirubin from bloodstream
• Hematopoiesis in certain disease states
• Synthesis of blood-clotting factors
12. LIVER FUNCTION (CONT.)
Excretory Organ
• Excretion of bile pigment and cholesterol
• Urea synthesis
• Detoxification of drugs and other foreign
substances
14. HEPATOCELLULAR FAILURE
• Clinical manifestations
• Jaundice
• Muscle wasting
• Ascites
• Impaired absorption of fat-soluble vitamins from GI
tract: vitamins A, D, E, and K
• Osteomalacia (vitamin D)
• Poor blood clotting factor production (vitamin K)
15. HEPATOCELLULAR FAILURE
(CONT.)
• Clinical manifestations
• Abnormal storage and release of glucose in the
form of glycogen
• Hyperglycemia
• Hypoglycemia
• Inadequate protein metabolism
• Decreased production of clotting factors (excessive
bleeding)
• Hypoalbuminemia: generalized edema related to low
serum oncotic pressure
16. HEPATOCELLULAR FAILURE
(CONT.)
• Clinical manifestations
• Impaired processing of endogenous steroid
hormone: estrogen
• Men
• Gynecomastia
• Impotence
• Testicular atrophy
• Female hair distribution
• Women
• Irregular menses
• Palmar erythema
• Spider telangiectasia
17. HEPATOCELLULAR FAILURE
(CONT.)
• Clinical manifestations
• Altered lipoprotein processing
• Dyslipidemias: hypertriglyceridemia
• Impaired clearance of exogenous drugs and toxins
• Conversion of ammonia to urea: hepatic
encephalopathy
20. JAUNDICE (CONT.)
Pathogenesis
• Damaged RBCs lyse and release O2 carrying
Hgb molecules
• RBCs taken up by reticuloendothelial system
• Heme oxygenase separates heme from globin
• Opening of heme ring to release central Fe atom
• Biliverdin (enzyme bilirubin reductase) bilirubin
21. JAUNDICE (CONT.)
Pathogenesis
• Bilirubin (unconjugated) is released into
plasma and transported to liver
• Lipid soluble
• Can be displaced from albumin by fatty acids and
certain organic anions (sulfonamides, salicylates)
• Kernicterus: free unconjugated bilirubin diffuses into
neonate’s brain, leading to encephalopathy
22. JAUNDICE (CONT.)
Pathogenesis
• Special transport proteins in liver extract
unconjugated bilirubin from plasma
• Bilirubin is bound (conjugated) to H2O-soluble
derivatives of glucuronic acid
• Enzyme uridine diphosphate glucuronosyltransferase
(UDPGT)
• Yields H2O-soluble bilirubin monoglucuronide and
diglucuronide—excreted into bile ducts
23. JAUNDICE (CONT.)
Pathogenesis
• Bile is transported through biliary system to
small intestine
• Passes to colon to be broken down to
urobilirubin
• Small fraction absorbed by colon;
re-excreted by kidneys and liver
• Jaundice results from dysfunction anywhere
along pathway
25. JAUNDICE (CONT.)
Prehepatic Causes
• Hemolysis
• Ineffective erythropoiesis
• Resorption of large hematomas in patients
with mild liver disease
• Frequent and harmless cause of mild jaundice
related to unconjugated hyperbilirubinemia
26. JAUNDICE (CONT.)
Hepatic Causes
• Dysfunction of each of hepatic steps in
bilirubin metabolism
• UDPGT mutations
• Gilbert syndrome: low levels of unconjugated
hyperbilirubinemia increased by fasting or illness
• Crigler-Najjar types I & 2 syndromes: severe neonatal
unconjugated hyperbilirubinemia
27. JAUNDICE (CONT.)
Posthepatic Causes
• At level of canalicular bilirubin transport
• Dubin-Johnson syndrome
• Rotor syndrome
• Conjugated hyperbilirubinemia
• Phenothiazines
• Sex hormones in women—high levels of normal
pregnancy cause benign cholestasis of pregnancy
34. PORTAL HYPERTENSION
• Etiology
• Sluggish blood flow resulting in increased pressure in
portal circulation
• Congested venous drainage of much of the GI tract
• Symptoms
• Anorexia
• Varices (esophageal, gastric, hemorrhoidal) can
rupture; cause uncontrolled bleeding
• Ascites
36. GASTROESOPHAGEAL VARICES
• Causes
• Results from portal hypertension
• Alcoholic or posthepatic cirrhosis
• Vasoactive hormones
• Increased splanchnic blood flow
• Increased vascular resistance in the liver
37. GASTROESOPHAGEAL
VARICES (CONT.)
• Pathogenesis
• A number of collateral venous pathways that dilate
in response to elevated portal pressure
• In attempt to transport blood from splanchnic bed
around cirrhotic liver and back to heart
• Other common pathways
• Spontaneous spleno-renal shunts
• Variety of deep, asymptomatic portosystemic shunts
38. GASTROESOPHAGEAL
VARICES (CONT.)
• Pathogenesis
• Part of very complex venous network that surrounds
the proximal part of stomach and esophagus lies
just beneath the mucosa
• Increased liability to rupture with critically high portal
pressure; leads to massive, life-threatening upper GI
bleed
40. GASTROESOPHAGEAL
VARICES (CONT.)
• Clinical features
• Affects about half of cirrhotic patients
• 30% experience variceal hemorrhage within 2 years
of diagnosis
• Size is main determinant of risk for bleeding
41. GASTROESOPHAGEAL
VARICES (CONT.)
• Clinical features
• Variceal bleeding
• Main cause of death in patients with long-standing
cirrhosis (20%-30%)
• Mortality 50%
• Two distinct phases of variceal hemorrhage
• Coincident with and shortly after bleeding
• Period of 6-8 weeks following initial bleed
• Greatest risk of rebleed occurs in first 72 hours
42. GASTROESOPHAGEAL
VARICES (CONT.)
• Signs and symptoms
• Hematemesis
• Melena
• Rapid intestinal transit and vigorous bleeding
• Bright red rectal bleeding
• Anemia
43. GASTROESOPHAGEAL
VARICES (CONT.)
• Treatment
• Fluid resuscitation
• Normal saline via large-bore IV lines
• Correcting the coagulopathy and stopping further
bleeding
• Blood components and clotting factors
• Parenteral vitamin K
• FFP
• Platelets
• Recombinant factor VIIa (with failure of above measures)
47. GASTROESOPHAGEAL
VARICES (CONT.)
• Treatment
• Endoscopic ligation of esophageal varices
• Suctioning and ligation of varix
• Endoscopic techniques show mortality benefit
compared to medication
• Fail to control acute bleeding (10%-20%)
• May result in an increase in venous pressure proximal to
area treated
49. GASTROESOPHAGEAL
VARICES (CONT.)
• Treatment
• Balloon tamponade of varices
• Widely used before endoscopic treatment
• Sengstaken-Blakemore tube
• Minnesota tube
• Linton-Nachlas tube
• Gastric tube inflated and held against varices in fundus
• Compression hemostasis and occlusion of blood flow
55. HEPATIC ENCEPHALOPATHY
• Pathogenesis
• Complex neuropsychiatric syndrome
• Associated with hepatic failure or severe chronic
liver disease
• Exact cause is unknown
• Characterized by symptoms ranging from mild
confusion and lethargy to stupor and coma
60. HEPATIC ENCEPHALOPATHY
(CONT.)
• Treatment
• Correcting any identifiable precipitating factors
• Restriction of dietary protein (60 g or less)
• >400 g carbohydrate daily
• May be reintroduced with dropping ammonia levels
• 20 g/day; increase by 10-20 g/day every few days to
highest of 0.75-1 g/kg/daily
61. HEPATIC ENCEPHALOPATHY
(CONT.)
• Treatment
• Peripheral or central glucose infusions along with
vitamins
• Oral antibiotics suppress intestinal flora that break
down dietary protein and release ammonia
• Osmotic diuretics
• Enhance elimination of nitrogenous wastes
• Lactulose: dose titrated = 2 soft, acidic stools/daily
62. CEREBRAL EDEMA
• Pathogenesis
• Swelling of the brain in patients with grade 3 or 4
hepatic encephalopathy
• With increased ICP, blood perfusion of brain is
decreased
• Major cause of death with acute hepatic failure
cerebral perfusion = carotid artery pressure –
intracranial pressure pressure
64. CEREBRAL EDEMA (CONT.)
• Treatment
• IV infusion of mannitol
• Increases serum osmolarity
• Draws H2O from brain to reduce swelling
• Sodium pentothal
• 2nd line agent if mannitol not tolerated
• Position in semi-Fowler position
• Moderate hypothermia
• Survival (60%) with aggressive treatment
65. ASCITES
• Etiology
• The pathologic accumulation of fluid in peritoneal
cavity
• Results from inappropriate osmotic gradient across the
pleura between Na, H2O, and protein
68. CONDITIONS OF ADVANCED
LIVER DISEASE (CONT.)
• Diagnostics
• Abdominal paracentesis
• Fluid examination
• Total protein
• Albumin
• Cell count
• Optional (bacteria, fungi, mycobacteria, cytology,
amylase, glucose, lactate dehydrogenase)
69. CONDITIONS OF ADVANCED
LIVER DISEASE (CONT.)
• Treatment
• Dietary sodium restriction to 88 mEq/day
• Bed rest
• Diuretics
• Goal is loss of 0.5 kg of body weight daily
• Free H2O restriction if hyponatremia
• 25% albumin infusions
• No response to Na restriction and diuretics
72. SPONTANEOUS BACTERIAL
PERITONITIS
• Etiology
• Bacterial infection in the peritoneal cavity
• Single infecting organism of gut origin
• Risks
• Cirrhosis, ascites
• Causes
• Diminished opsonic activity of ascitic fluid
• Diminished reticuloendothelial function
• Transmigration of gut bacteria across intestinal wall
into the ascites
75. HEPATORENAL SYNDROME
• Etiology
• Acute and progressive disease
• Normal kidney with disturbed intrarenal blood flow
related to imbalance between vasoconstricting
and vasodilating mechanisms
• Causes
• Overly, vigorous diuretic therapy or paracentesis
• Severe diarrhea
• NSAIDs
• Variceal bleeding
• Sepsis
77. ACUTE VIRAL HEPATITIS
• Pathogenesis
• Inflammation of the liver parenchyma
• Caused by many viruses
• Cytomegalovirus, Epstein-Barr
• “Viral hepatitis”
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Delta agent: defective RNA virus that requires the
helper function of hepatitis B virus
81. HEPATITIS A (HAV) (CONT.)
• Treatment
• Supportive (rest, nutritious diet)
• Avoid ETOH, acetaminophen, other hepatotoxins
• Prevention
• Careful hand washing
• Segregation
• Cleaning of laundry and personal items
• Immunization
82. HEPATITIS B (HBV)
• Pathogenesis
• Partially double-stranded DNA virus
• Spread by parenteral contact with infected blood
or blood products
• Includes contaminated needles and sexual contact
• Life-threatening illness with high mortality
• 300 million (5%) of world population have chronic
infection
• 1 to 1.25 million in United States
83. HEPATITIS B (HBV) (CONT.)
• Risk factors
• Health care settings (3%)
• Transfusions and dialysis (1%)
• Acupuncture
• Tattooing
• Extended overseas travel
• Residence in an institution
84. HEPATITIS B (HBV) (CONT.)
• Clinical manifestations
• Incubation period of 2-6 months
• Prodromal period
• Ranges from no symptoms to complex issues
• Rashes
• Arthralgia and arthritis
• Angioedema
• Serum sickness
• Glomerulonephritis
• Jaundice (lasting 2 weeks on average)
85. HEPATITIS B (HBV) (CONT.)
• Diagnosis
• Serologic testing
• Surface antigen (HBsAg): early/active infection
• Surface antibody (HbcAg): resolution and immunity
• Core antigen (HBsAg): chronic infection
• Core antibody (HBsAg)
• Seroconversion to core antibody (HBcAg)
• Hepatitis B e antigen (HBeAg): viral replication and
infectivity
86. HEPATITIS B (HBV) (CONT.)
• Treatment
• Supportive
• Most nonfulminant infections resolve spontaneously
• About 5% progress to chronic infection
• Aggressive treatment in fulminant hepatitis for
coagulopathy, encephalopathy, cerebral edema,
and other manifestations
• Liver transplant
87. HEPATITIS B (HBV) (CONT.)
• Treatment
• Interferon-alpha
• 24-48 weeks of therapy
• Response rate of 33%
• Lamivudine
• Adefovir
• Entecavir
• Response rate of 67%
• Extremely expensive
• Telbivudine
88. HEPATITIS B (HBV) (CONT.)
• Prevention
• Immunizations (HBV)
• Doses given at 0, 1, and 6 months
• 95% response rate
• Lower in obese, smokers, men, cirrhosis, CRF, organ
transplant recipients, children with celiac disease,
immunosuppression
89. HEPATITIS B (HBV) (CONT.)
• Prevention
• Administration of HBIG postinoculation
• Given within 7 days of exposure
• Indications
• Neonates born to HBsAg-positive mothers
• Prophylaxis after needlestick or sexual exposure in
nonimmune persons
• After liver transplantation in patients who are HBsAg + prior
to transplantation
90. HEPATITIS C (HCV)
• Pathogenesis
• Single-stranded RNA virus that belongs to
Flaviviridae family
• Spread through IV drug use or blood transfusions
prior to 1990
• Lack of knowledge related to extremely high
mutation rate in laboratory
• 3% worldwide infected
• Leading cause of end-stage liver disease with
cirrhosis in U.S.
• Most common in U.S. but lower response rate to
treatment
91. HEPATITIS C (HCV) (CONT.)
• Clinical manifestations
• Acute HCV infection
• Usually asymptomatic
• Transaminase rarely exceeds 1000 international units/L
• Only 15% resolve
• Course is erratic with wide fluctuations on liver enzymes
• Extrahepatic manifestations
• Medium-vessel vasculitis (polyarteritis nodosa)
• Essential mixed cryoglobulinemia
• Membranoproliferative glomerulonephritis
92. HEPATITIS C
• Pathogenesis
• Chronic HBV Infection
• Course is erratic with wide fluctuations on liver enzymes
• Progression to liver disease (20%)
• Extrahepatic manifestations
• Medium-vessel vasculitis (polyarteritis nodosa)
• Essential mixed cryoglobulinemia
• Membranoproliferative glomerulonephritis
93. HEPATITIS C (CONT.)
• Treatment
• Supportive and expectant
• Unless complications or subacute hepatic failure
• Early treatment not recommended
• 20%-40% of acute seropositive patients will convert to
seronegativity and an undetectable viral load during
1st 6 months after infection
• Chronic infection
• Assessed by a viral load and viral genotype
• Liver biopsy to stage disease activity
94. HEPATITIS C (HCV)
• Treatment
• Pegylated interferon-alpha
• 60% response rate
• More common type 1 infection (45%)
• Less common type 2 and 3 (85%)
• 5%-10% drop out of treatment because of side effects
and cost (expensive)
• Length
• Type 1: 48 weeks
• Other types: 24 weeks
95. HEPATITIS D (DELTA)
• Pathogenesis
• Fulminant hepatitis (HDV)
• Incomplete viral organism that requires presence of
HBV for replication
• Occurs coincident with or subsequent to initial
infection with Hep B
• Transmitted parenterally and intimate contact
• Diagnosis
• Anti-HDV IgM and IgG enzyme linked immunosorbent
assay (ELISA)
96. HEPATITIS D (DELTA) (CONT.)
• Treatment
• No specific vaccine or treatment
• Prevention
• Safe sexual practices
• Screening of blood products
• Avoidance of IV drug use
• Vaccination of susceptible persons with HBV
vaccine
97. HEPATITIS E (HEV)
• Pathogenesis
• RNA virus spread via fecal-oral route
• Contaminated H2O
• Parenteral transmission
• One of most common in developing countries
• Cases related to recent travel
98. HEPATITIS E (HEV) (CONT.)
• Clinical manifestations
• Incubation period is 2-9 weeks
• Prodromal and icteric illness
• Usually last only 2 weeks
• Similar to HAV infection
• Diagnosis
• None available
99. HEPATITIS E (HEV) (CONT.)
• Treatment
• Supportive
• No vaccine available
• Prevention
• Careful hand washing
• Avoidance of undercooked foods
• Drinking of safe H2O and beverages
100. CHRONIC HEPATITIS
• Pathogenesis
• Chronic low-grade liver inflammation of any cause
(also called “triaditis” or “transaminitis”)
• Inflammation confined to portal triads without
destruction of normal liver structures with elevated
serum transaminase levels
• Clinical manifestations
• Asymptomatic
• Mild, nonspecific symptoms
101. CHRONIC HEPATITIS (CONT.)
• Progression
• No progressive liver disease
• No drug treatment needed
• Excellent prognosis
• Classification schemes
• Etiologic factor
• Histologic grade
• Stage in terms of fibrosis
102. CHRONIC ACTIVE HEPATITIS
• Pathogenesis
• Progressive, destructive inflammatory disease of the
liver lasting >6 months
• Extends beyond the portal triad to hepatic lobule
(piecemeal necrosis)
• Symptoms
• Typical of acute hepatitis are often seen
103. CHRONIC ACTIVE HEPATITIS
(CONT.)
• Complications
• Spontaneous arrest with any degree of fibrosis
• Progression to macronodular or micronodular
cirrhosis
• Autoimmune disease
• Viral hepatitis (B and C)
• Toxins
• Metabolic disease
104. CHRONIC ACTIVE HEPATITIS
(CONT.)
• Subgroups
• Minority of newly infected HBV patients but majority
of those will progress to chronic active hepatitis
• Manifestation of autoimmune hepatitis
• Exhibit a variety of immunologic markers
• Antinuclear antibodies
• Anti–smooth muscle antibodies
• Usually suffer from a second autoimmune disease
(e.g., Hashimoto)
105. CHRONIC ACTIVE HEPATITIS
(CONT.)
• Subgroups
• Induced by therapeutic agents
• Mostly women
• Minocycline
• Nitrofurantoin
• Have a metabolic liver disorder
• “Cryptogenic cirrhosis”
• Wilson disease
• Hemochromatosis
106. CHRONIC ACTIVE HEPATITIS
(CONT.)
• Diagnosis
• Clinical setting
• Laboratory
• Abnormal liver enzymes
• Serologic studies
• Serum Fe and ferritin (hemochromatosis)
• Serum ceruloplasmin (Wilson disease)
• Liver biopsy
• Confirms diagnosis
• Grading and staging
108. CHRONIC ACTIVE HEPATITIS
(CONT.)
• Autoimmune hepatitis
• Diagnosis
• Several autoantibodies
• Polyclonal hypergammaglobulinemia
• Positive ANA (high level)
• High levels of ASMA
• Management
• Stopping the offending drug
109. BILIARY CIRRHOSIS
• Etiology
• End result of continuous, ongoing inflammation of
bile ducts caused by macroscopic or microscopic
biliary obstruction
• Primary biliary cirrhosis (PBC)
• Autoimmune condition often associated with systemic
lupus erythematosus and other autoimmune illnesses
• + ANA, AMA
110. BILIARY CIRRHOSIS (CONT.)
• Pathogenesis
• Persistent biliary obstruction results in inflammation
and scarring of liver with obliteration of bile ductules
• Result is diffuse and widespread fibrosis with nodule
formation
111. BILIARY CIRRHOSIS (CONT.)
• Pathogenesis
• Examples of large-duct obstruction
• Gallstone disease
• Primary sclerosing cholangitis (PSC)
• Chronic biliary fluke infestation
• Immigrants from infected areas are at an increased risk
• Opisthorchis and Clonorchis species—Asian
endemic acquired by eating raw fish that carry
larval cysts
116. PRIMARY SCLEROSING
CHOLANGITIS (PSC) (CONT.)
• Diagnosis
• ERCP shows typical beaded and atrophic
appearance of biliary tree
• Liver biopsy performed for staging of disease
• Treatment
• Medical and endoscopic treatments are for
palliative treatment
• Liver transplant
117. ALCOHOLIC FATTY LIVER
• Pathogenesis
• “Alcoholic steatohepatitis”
• Accumulation of fat in the liver cells
• Causes
• More fat is delivered to hepatocyte than it can
normally metabolize; defect in fat metabolism
within the cell
• Alcohol, drugs
• Protein malnutrition
• Diabetes mellitus, obesity
• Total parenteral nutrition (TPN)
119. ALCOHOLIC FATTY LIVER
(CONT.)
• Treatment
• Stopping alcohol intake
• Providing appropriate nutrition
• Nonalcoholic steatohepatitis (NASH)
• Weight reduction
• Control of diabetes or hyperlipidemia
• Treat underlying cause
• If untreated, 3%-5% will progress to liver fibrosis and
cirrhosis
120. ALCOHOLIC HEPATITIS
• Pathogenesis
• Active inflammation of the centrilobular region of
the liver
• Liver cells show pathologic changes of hepatocyte
necrosis with neutrophilic infiltration and intracellular
inclusions
• Mallory bodies
• Causes
• Alcoholics binge in larger quantities than usual
121. ALCOHOLIC HEPATITIS (CONT.)
• Clinical manifestations
• Illness ranges from mild to severe
• Severe case
• Hepatomegaly
• Fever
• Signs of acute liver failure
• Encephalopathy
124. HEREDITARY
HEMOCHROMATOSIS (HH)
• Etiology
• One of most common autosomal recessive disorders
in the world
• Metal storage disease
• European population
• 1:10 heterozygous carrier
• 0.3% homozygous
• U.S. prevalence of homozygosity
• 0.44% Caucasian
• 0.027% Hispanics
• 0.014% African Americans
125. • Pathogenesis
• Activity of mutant gene (HFE) allows excessive and
uncontrolled Fe absorption by GI tract
• Common mutation is C282Y
• Mutations cause Fe deposition in numerous organs
• Advanced disease: >20 g Fe in liver, pancreas, and
heart
Hereditary Hemochromatosis (HH)Hereditary Hemochromatosis (HH)
(Cont.)(Cont.)
126. HEREDITARY
HEMOCHROMATOSIS (HH)
(CONT.)
• Pathogenesis
• Secondary hemochromatosis
• Causes
• Occurs with chronic hereditary dyserythropoietic states
• Alcoholic patients with liver disease
• Patients with excessive Fe ingestion over many years
• Hemochromatosis related to anemias
• Related to repeated blood transmissions and Fe intake
129. HEREDITARY
HEMOCHROMATOSIS (HH)
(CONT.)
• Diagnosis
• Early diagnosis and treatment are critical
• Clinical features and family history
• Laboratory
• Elevated plasma Fe and transferrin saturation
• Serum ferritin dramatically elevated to several mg/L
• Genetic analysis for HFE gene
• Liver biopsy
130. HEREDITARY
HEMOCHROMATOSIS (HH)
(CONT.)
• Treatment
• Deferoxamine (IM/SQ) chelates Fe and facilitates its
renal excretion
• Repeated phlebotomy
• 500 ml (1 unit) of whole blood until Hct drops below 37%
• Maintenance therapy of 1 unit every 2-3 months
• Liver transplant
• Pts with irreversible cirrhosis
131. WILSON DISEASE
• Etiology
• Rare autosomal recessive disorder
• Metal storage disease
• Presents <30 years
• Hepatic dysfunction
• Neuropsychiatric illness
• Always have occult compensated cirrhosis at time of
diagnosis
• Excessive amounts of copper accumulate in live
and other organs
132. WILSON DISEASE (CONT.)
• Etiology
• Linked to specific abnormal protein (ATP7B)
• Results in retention of copper in liver
• Impaired incorporation of copper into ceruloplasmin
• Most patients are compound heterozygotes with
several mutations
133. WILSON DISEASE (CONT.)
• Clinical manifestations
• More common in children
• Hepatomegaly
• Fatty infiltration of liver
• Elevated liver enzymes
• Renal tubular acidosis
• Fanconi-like syndrome
• Cardiomyopathy
• Hypogonadism
• Metabolic bone disease (vitamin D–resistant rickets)
• Arthritis
134. WILSON DISEASE (CONT.)
• Clinical manifestations
• Neurologic
• Movement disorder
• Rigid dystonia
• Primarily psychiatric symptoms
135. WILSON DISEASE (CONT.)
• Diagnosis
• Clinical signs and symptoms
• Slit-lamp examination
• Brownish Kayser-Fleischer rings at margin of cornea
• Genetic analysis
• Laboratory
• Low serum ceruloplasmin
• Elevated 24-hour urinary copper excretion
• Liver biopsy
136. WILSON DISEASE (CONT.)
• Treatment
• Lifelong treatment
• Noncompliance leads to definite progression
• Dietary modification
• Elimination copper-rich foods
• Organ meats, shellfish, nuts, chocolate, mushrooms
• Copper removal therapy
• Testing home H2O sources and filtering
137. WILSON DISEASE (CONT.)
• Treatment
• Oral chelation therapy
• Trientine
• Fewer side effects
• Penicillamine
• Zinc
• Neurologic disease
• Ammonium tetrathiomolybdate
• Not associated with early transient neurologic deterioration
138. ACETAMINOPHEN POISONING
• Etiology
• Responsible for 39% of cases of acute hepatic
failure
• Acute ingestion of acetaminophen >140 mg/kg
exposes liver to high levels of toxic metabolite
• Clinical manifestations
• Patients surviving 1 week generally experience
complete recovery
• Nausea, vomiting, diarrhea within several hours of
ingestion
144. LIVER ABSCESS (CONT.)
• Diagnosis
• Ultrasound/CT
• Ultrasound/CT-guided thin-needle aspiration
• Laboratory
• Gram stain and cultures of material
• Blood cultures
145. LIVER ABSCESS (CONT.)
• Treatment
• Surgical drainage
• Large (2 cm) solitary or multiple liver abscesses
• CT/ultrasound-guided percutaneous drainage tube
• Antibiotic therapy
• Placed with minimal morbidity and discomfort
• Remain in until drainage resolved
146. TRAUMA
• Etiology
• Injury by penetrating abdominal trauma
• Gunshot or stab wounds
• Rib fractures
• Common injuries to the liver
• Simple and multiple lacerations
• Avulsions
• Crush injuries
147. TRAUMA (CONT.)
• Pathogenesis
• Highly vascular organ
• Receives approximately 29% of body’s cardiac output
• Massive blood loss with trauma
148. TRAUMA (CONT.)
• Clinical manifestations
• Typical signs of hemorrhagic shock
• Hypotension, tachycardia, tachypnea, pallor,
diaphoresis, confusion
• Right upper quadrant pain
• Exaggerated by deep breathing
• Referred to shoulder (may indicate diaphragmatic
irritation)
• Abdominal tenderness
• Distention
• Guarding
• Rigidity
149. MALIGNANCY
• Etiology
• Liver is a common site for metastasis of primary
cancers
• Related to vascularity and lymphatic drainage
• Rare in United States
• Primary liver tumors
• HCCs
• Cholangiocarcinoma
• Angiosarcoma
• Hepatoblastoma (most common in children)
• Lymphoma (especially T cell)
• Benign tumors are less common
150. MALIGNANCY:
HEPATOCELLULAR
CARCINOMA (HCC)
• Most common form of primary hepatic
malignancy
• Referred to as “hepatoma”
• Uncommon in middle-aged
• Men > women
• Increase in United States related to increased
HBV and HCV prevalence
153. MALIGNANCY (CONT.)
• Treatment
• Hepatic resection
• Not usually possible with advanced diffuse liver disease
or multifocal tumors
• Partial resection
• Complete hepatectomy followed by liver
transplantation
• Radical option for tumor localized to liver
• Chemotherapy
154. MALIGNANCY (CONT.)
• Treatment
• Nonpalliative treatments
• Hepatic artery ligation
• Direct percutaneous injection of alcohol into tumor
• Cryotherapy
• Thermal techniques
158. EVALUATION OF TRANSPLANT
PATIENT
• Identified risk factors
• Uncontrolled bacterial sepsis
• Failure of major organ systems
• Extrahepatic malignancy
• Portal vein thrombosis
• Previous protosystemic shunt operations
• Current alcohol/drug addiction
• Poor psychosocial support system
• Psychological instability
• HIV
• End-stage liver disease
159. EVALUATION OF TRANSPLANT
PATIENT (CONT.)
• Patients with viral hepatitis are particularly
susceptible to recurrence
• Must be managed with care
• Indefinite treatment with high-dose HBIG has
lowered recurrence rates and increased survival
• No effective regimen to prevent recurrent HCV
infection
162. EVALUATION OF TRANSPLANT
PATIENT (CONT.)
• Patient identified as candidate + donor
organ procured
• Surgery (8-22 hours to complete)
• 5 anastomoses
• Suprahepatic inferior vena cava
• Infrahepatic vena cava
• Portal vein
• Hepatic artery
• Biliary tract
163. POST-TRANSPLANTATION
MANAGEMENT
• Immunosuppression
• Prevents rejection of transplant graft
• Rejection response most often occurs between postop
days 4-10
• Immunosuppressive drugs
• Cyclosporine
• Prednisone
• Tacrolimus (instead of cyclosporine)
• Main consequence is immune suppression and increased
risk of infection
164. POST-TRANSPLANTATION
MANAGEMENT (CONT.)
• Clinical manifestations of organ rejection
• Tachycardia
• Fever
• Right upper quadrant or flank pain
• Diminished bile flow/change in color through T-tube
• Laboratory findings
• Elevated serum bilirubin, transaminase, alkaline
phosphatase levels
• Increased PT
165. POST-TRANSPLANTATION
MANAGEMENT (CONT.)
• Critical post-transplantation period issues
• Infection
• Hypertension
• Renal dysfunction
• Hyperlipidemia and cardiovascular disease
• Obesity
• Osteoporosis
• Increased risk for cancer
• Psychological issues
166. POST-TRANSPLANTATION
MANAGEMENT (CONT.)
• Critical post-transplantation period issues
• Chronic rejection
• Progressive ductopenia and recurrence of primary
pretransplantation liver disease
• Causes graft failure with time
• Actuarial survival at 5 years
• 88% of patients with cholestatic liver disease
• 78% of patients with noncholestatic liver disease + HCV
negative
• 70% of patients with HCV
167. ABNORMAL BILIRUBIN
METABOLISM IN THE
NEONATAL PERIOD
• Physiologic jaundice of the newborn
• Harmless condition lasting no longer than 2 weeks
after delivery
• Causes
• Immature bilirubin conjugation and transport
mechanisms
• Increased gut absorption of bilirubin
• Breast-fed > bottle-fed babies
• Congenital hemolytic disorders
168. • Physiologic jaundice of the newborn
• Causes
• Crigler-Najjar syndrome
• Hypothyroidism
• Congenital pyloric stenosis
• Sepsis
• Resorbing hematomas
• B-glucuronidase in breast milk results in increased
unconjugated bilirubin in the gut
Abnormal Bilirubin Metabolism inAbnormal Bilirubin Metabolism in
the Neonatal Period (Cont.)the Neonatal Period (Cont.)
169. ABNORMAL BILIRUBIN
METABOLISM IN THE
NEONATAL PERIOD (CONT.)
• Kernicterus: brain injury related to
hyperbilirubinemia
• Immature blood-brain barrier allows free
unconjugated bilirubin to enter brain;
encephalopathy
• Yellowish staining of permanently damaged brain
tissue in basal ganglia and thalamus
• Serious complication of neonatal period r/t
premature birth, neonatal jaundice, hemolytic
disease
170. ABNORMAL BILIRUBIN
METABOLISM IN THE
NEONATAL PERIOD (CONT.)
• Kernicterus
• Most infants die of condition
• Survivors often suffer from cerebral palsy, movement
disorders, and mental retardation
• Treatment
• Drugs that displace bilirubin from albumin seriously
worsen condition
• Early recognition
• Exchange transfusions
• Phenobarbital (increase UDPGT levels)
• Phototherapy (bili-lights)
171. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
• Acute hepatitis A infection
• Mild or asymptomatic
• Prevalence correlates with quality of sanitation and
hygiene
• Treatment is supportive
• Prevention
• Careful hand washing
• Segregation
• Cleaning of laundry and personal items
• Supportive
• Vaccination
172. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
(CONT.)
• Hepatitis B infection
• Common childhood disease
• Vertical transmission from an HBsAg-positive mother to
infant
• Infected blood products and drugs
• Less-developed areas
• Complications
• Immune complex diseases
• Fever
• Papular acrodermatitis
• Renal disease
• Hematologic complications
173. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
(CONT.)
• Hepatitis B infection
• Incidence of chronic infection is higher after
neonatal or childhood infections
• Grave long-term consequences
• Passive immunization
• Given within 12 hours of birth to children of HBsAg
positive mothers or children of high-risk mothers
• Series of injections at birth, 1, and 6 months of age
174. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
(CONT.)
• Hepatitis C virus
• Less commonly spread vertically
• Effective screening of blood products has greatly
reduced risk of infection
• Hepatitis delta virus
• Spread by intrafamily route as a coinfector with
hepatitis B
175. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
(CONT.)
• Hepatitis E virus
• Common in adolescents and young adults
• High mortality rate in pregnant women
• Most common cause of childhood hepatitis; indirect
cause of infant mortality
• Causes
• Many viruses may cause biochemical or clinical
hepatitis in pediatric population
• Epstein-Barr
• Cytomegalovirus
• Herpesvirus
• Adenovirus
176. INFECTIOUS AND ACQUIRED
HEPATIDITES IN CHILDREN
(CONT.)
• Hepatitis E virus
• Finding of an enlarged liver and elevated
transaminases necessitates a search for congenital
infection
• Part of the so-called TORCH syndrome
• Causes
• Cytomegalovirus
• Herpesvirus
• Varicella
• Toxoplasma
• Syphilis
177. REYE SYNDROME
• Primarily a disease of children
• Occurs shortly after a viral illness such as
influenza or chickenpox
• Mortality as high as 40%
• Characterized by fatty infiltration of liver with
severe hepatic dysfunction
• Encephalopathy
• Coagulopathy
• Elevated levels of hepatocellular enzymes
178. REYE SYNDROME (CONT.)
• Pathophysiologic mechanism is unknown
• Significant mitochondrial dysfunction of
hepatocytes
• Strong association with aspirin use during preceding
viral illness
• Treatment is supportive
• If child survives, recovery is complete
• Liver transplant reserved for irreversible disease
179. Α1-ANTITRYPSIN DEFICIENCY
• Pathogenesis
• Autosomal recessive condition found mainly
in children and young adults
• α1-Antitrypsin is an enzyme inhibitor found in
many tissues
• Prevents elastase and collagenase from damaging
tissues
• Genetically controlled by a gene with many allelic
variations
• PiZZ (protein inhibitor Z variant) produces α1-ATZ protein
180. Α1-ANTITRYPSIN DEFICIENCY
(CONT.)
• Pathogenesis
• Defective α1-antitrypsin protein accumulates in liver
and produces diagnostic granules seen
microscopically
• Clinical manifestations
• Centrilobular emphysema
• Pancreatic insufficiency
• Cirrhosis
• Treatment
• Liver transplant
• Gene therapy
181. CYSTIC FIBROSIS
• Pathogenesis
• Autosomal recessive condition primarily known as a
cause of lung disease in children
• Complications
• Pancreatic insufficiency
• Intestinal obstruction
• Gallstone disease
• Neonatal giant cell hepatitis
• Bile duct obstruction
• Biliary cirrhosis
182. CYSTIC FIBROSIS (CONT.)
• Treatment
• Directed at complications
• Gene therapy
• Ursodeoxycholic acid
• Improves biochemical indices of liver injury
183. CEREBROTENDINOUS
XANTHOMATOSIS
• Pathogenesis
• Disorder of bilirubin metabolism related to steroid
hydroxylase deficiency
• Peroxisomes are responsible for B oxidation in final
steps of bile acid synthesis
• Numerous hereditary peroxisomopathies have been
described
• X-linked adrenal leukodystrophy
• Progressive neurologic dysfunction and adrenal
insufficiency
184. CEREBROTENDINOUS
XANTHOMATOSIS (CONT.)
• Clinical manifestations
• Premature atherosclerosis
• Encephalopathy
• Treatment
• Ineffective but investigational therapies have been
tried
• Chenodeoxycholic acid shows marked
improvement
185. GILBERT SYNDROME
• Pathogenesis
• Disorder of bile acid transport
• Very common (10% Caucasian population in United
States)
• Benign, autosomal dominant condition
• Results in mild unconjugated hyperbilirubinemia
• Caused by decreased bilirubin glucuronidation
186. CRIGLER-NAJJAR SYNDROME
• Pathogenesis
• Rare, autosomal recessive disorder marked by
significant unconjugated hyperbilirubinemia
• Type 1
• Presents shortly after birth
• Neonates usually die of kernicterus or suffer irreversible
neurologic damage
• Near total absence of bilirubin conjugation
• Results in high levels of unconjugated bilirubin crossing
the immature blood-brain barrier
187. CRIGLER-NAJJAR SYNDROME
(CONT.)
• Type 1
• Treatment
• Liver transplant after phototherapy
• Plasma exchange transfusion (life saving in rare
instances)
188. CRIGLER-NAJJAR SYNDROME
(CONT.)
• Type 2
• Some conjugating capacity exists; enhanced by
administration of phenobarbital
• Rarely experience bilirubin encephalopathy
• Can lead normal lives
• Treatment
• Phototherapy
• Phenobarbital
• Potentially liver transplantation
• Gene therapy
190. PROGRESSIVE FAMILIAL
INTRAHEPATIC CHOLESTASIS
(PFIC) (CONT.)
• Type 1 (PFIC) or Byler syndrome
• Caused by single-gene mutation
• Traces back to Amish kindred descended from
Jacob Byler
• Treatment
• Ursodeoxycholic acid
• Biliary diversion procedures (decreases bile acid pool)
• Liver transplant
191. INBORN ERRORS OF
METABOLISM
• Pathogenesis
• Enzyme abnormalities resulting from singe-gene
mutations
• Generally autosomally recessive
• May show up in children
• Result in abnormal processing of lipids,
lipopolysaccharides, glycogen, amino acids,
proteins
• Errors in neonatal period fatal unless immediate
treatment
• Errors in infancy and later years may be amenable
to specific therapies
192. • Pathogenesis
• Error results from excessive accumulation of
precursor substances in target organs (brain, spinal
cord)
• Liver is main site of processing and may be target of
toxic accumulation
• Hepatomegaly
• Liver enzyme elevation
• Jaundice
Inborn Errors of MetabolismInborn Errors of Metabolism
(Cont.)(Cont.)
193. INBORN ERRORS OF
METABOLISM (CONT.)
• Treatment
• Liver or bone marrow transplantation
• Prompt and thorough investigation of family history
and genetic counseling and testing of family
members
194. INTRAHEPATIC HOMEOSTATIC
CONDITIONS
• Cholestatic liver disease in which pathologic
process is confined to the liver
• Extrahepatic biliary system is normal
• Causes
• Neonatal hepatitis
• Conditions in which number of bile ducts is
decreased and inadequate
• Unable to accommodate normal bile metabolism and
transport
195. INTRAHEPATIC HOMEOSTATIC
CONDITIONS (CONT.)
• Alagille syndrome
• Arteriohepatic dysplasia
• Most common form of inherited intrahepatic
cholestasis
• Autosomal dominant condition has complete
penetrance and expressivity
• Typical bony malformations
• Cardiovascular malformation
• Paucity of intrahepatic bile ducts
196. INTRAHEPATIC HOMEOSTATIC
CONDITIONS (CONT.)
• Alagille syndrome
• Slow progression
• Complications
• Pruritus
• Hypercholesterolemia
• Xanthomas
• Neurologic complication
• Related to vitamin E deficiency
• Treatment
• Ursodeoxycholic acid until liver transplant
197. EXTRAHEPATIC CHOLESTATIC
CONDITIONS (BILIARY
ATRESIA)
• Pathogenesis
• “Progressive obliterative cholangiopathy”
• Congenital or acquired
• Common birth defect
• 1/10,000 – 1/15,000 live births
• Occurs in certain autoimmune illnesses
• Principal form of chronic rejection of a transplanted
liver allograft
198. EXTRAHEPATIC CHOLESTATIC
CONDITIONS (BILIARY
ATRESIA) (CONT.)
• Clinical manifestations
• Progressive cholestasis with all the usual features
• Pruritus
• Malabsorption with growth retardation
• Fat-soluble vitamin deficiencies
• Hyperlipidemia
• Cirrhosis with portal hypertension
• Recurrent episodes of bacterial cholangitis
199. EXTRAHEPATIC CHOLESTATIC
CONDITIONS (BILIARY
ATRESIA) (CONT.)
• Diagnosis
• Cholangiogram assesses possibility of a correctable
obstruction
• Kasai procedure creates hepatoportoenteric
connection
• Allows adequate bile drainage
• Not usually curative but “buys time”
• Liver transplant
200. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
• Liver size and blood flow decrease with aging
• Careful monitoring of medications that affect
hepatic blood flow and processed by
cytochromes
• Routine liver blood tests are not changed by
aging
201. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Hepatocellular carcinoma (HCC) is more
often seen in older people
• Related to alcohol or chronic viral hepatitis
• Prognosis is dismal
202. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Ischemic hepatitis
• Usually associated with cardiovascular disease and
episodes of hypotension (surgery or sepsis)
• More common in older patients
• Clinical manifestations
• Rapid elevation of serum transaminases
• Prolonged PT
203. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Ischemic hepatitis
• Treatment
• Recovery may be rapid
• Prognosis depends on severity of underlying disorder
• Complications
• Right-sided heart failure in passive hepatic congestion
with ascites and liver failure
204. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Hemochromatosis in women
• Occurs after menopause
• Presentations
• New-onset DM
• Heart failure
• Arthritis
• Cirrhosis
• HCC
205. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Autoimmune liver diseases
• Chronic active hepatitis may be cause of
“cryptogenic” cirrhosis in older women
• Primary sclerosing cholangitis (PSC)
• Affects older persons with long-standing ulcerative
colitis, even those with colectomies performed
many years earlier
206. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Alcohol abuse
• Patients bear cumulative injury of years of exposure;
show signs of advanced disease
• Clinical manifestations
• Intoxication and hepatic encephalopathy may be
confused with senile dementia and concomitant drug
use
• Treatment
• Same as younger patient
• Note social circumstances, intercurrent medical
problems
207. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Acute viral hepatitis
• More difficult related to nonspecific symptoms and
decreased clinical suspicion
• Acute HAV infection
• Less common related to higher incidence of immunity
• More severe s/s with higher mortality rates in elderly
208. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Acute viral hepatitis
• Treatment
• Close monitoring with standard treatments
• Related to comorbid medical problems, intolerance of side
effects; advanced liver disease may preclude treatment
209. LIVER DISEASES AND
GERIATRIC CONSIDERATIONS
(CONT.)
• Indications for liver transplantation
• No change with advancing years; no arbitrary age
limits have been set
• Barriers
• Allocation of organs remains highly controversial
• Individual evaluation regarding propriety of transplantation
and success likelihood
