Functional Liver Tests and Treatment of Chronic Hepatitis

Question 1

What is the common location and clinical implications of abnormal levels of Aspartate Aminotransferase (AST)?

Answer 1

Location: 
Cytosol and mitochondria of hepatocytes
Heart
Skeletal Muscle
Blood

Clinical Implications:
Hepatocellular damage
May result from non-hepatic injury as well

Question 2

What is the common location and clinical implications of abnormal levels of Alanine Aminotransferase (ALT)?

Answer 2

Location:
Cytosol of all hepatocytes

Clinical Implications:
Hepatocellular damage

Question 3

What is the common location and clinical implications of abnormal levels of bilirubin?

Answer 3

Location:
Heme degradation product conjugated in ER of hepatocytes, excreted in bile

Clinical Implications:
Cholestasis, impaired conjugation, biliary obstruction
Elevated indirect bilirubin = hemolysis
Elevated direct bilirubin = bile duct obstruction

Question 4

What is the common location and clinical implications of abnormal levels of Alkaline Phosphatase?

Answer 4

Location:
Bile canaliculi microvilli
Serum Alk Phos is primarily from liver and bone

Clinical Implications:
Cholestasis, infiltrative disease, biliary obstruction
Non-Hepatic implications: 
Bone disease
Pregnancy

Question 5

What is the common location and clinical implications of abnormal levels of Albumin?

Answer 5

Location:
Synthesized in liver

Clinical Implications:
Synthetic Dysfunction

Question 6

What is the common location and clinical implications of abnormal levels of Prothrombin time?

Answer 6

Location:
Many blood coagulation factors are synthesized in the liver

Clinical Implications:
Synthetic dysfunction

Question 7

What is the normal ratio of AST:ALT, what do common abnormalities indicate, and what levels signify a mild vs severe abnormality?

Answer 7

Normal ratio AST:ALT = 0.8
Ratio >1 is seen in cirrhosis
Ratio >2 suggests alcoholic liver disease
- Low ALT from B6 malabsorption
- High AST from alcohol preferentially damaging AST rich mitochondria
Normal levels of each ~50 Units/L
Mild elevation of AST or ALT = 15 times normal levels

Question 8

Describe the etiology of jaundice

Answer 8

Jaundice is the result of elevated bilirubin. Bilirubin is a normal heme degradation product. It is normally taken up into hepatocytes and conjugated (glucoronidation) by the enzyme bilirubin-UGT in the ER to a water soluble form that is excreted into the bile canaliculi. Elevations in bilirubin may manifest as either conjugated (direct) hyperbilirubinemia or unconjugated (indirect) hyperbilirubinemia.

Question 9

Name and describe three causes of unconjugated (indirect) hyperbilirubinemia

Answer 9

Gilbert’s Syndrome: benign disease resulting from decreased expression of bilirubin-UGT. Patients have normal AST, ALT, and Alk Phos levels. Jaundice results from stress, and may be protective.

Crippler-Najjar syndrome: A more severe disease than Gilbert’s resulting from mutation (Type II) or complete absence (Type I) of UGT. Type I = neurologic impairment

Hemolysis: Increased heme breakdown (i.e. Hemolytic anemia)

Question 10

Name and describe four causes of conjugated (direct) hyperbilirubinemia

Answer 10

Extra hepatic obstruction of bile flow

Intrahepatic cholestasis: a functional impairment of bile formation within the hepatocyte

Hepatitis

Cirrhosis

Question 11

What are the four main patterns of disease that liver tests can detect?

Answer 11

Hepatocellular injury or necrosis
Cholestatic disease
Infiltrative disease
Synthetic Dysfunction

Question 12

What are the hepatic and non-hepatic etiologies associated with mildly elevated AST or ALT?

Answer 12

Hepatic:
Chronic HBV and HCV
Acute Viral hepatitis (including EBV and CMV)
Steatohepatitis
Alcohol -related liver injury
Hemochromatosis
Autoimmune Hepatitis
a-1-antitrypsin deficiency
Wilson's disease
Celiac disease
Cirrhosis

Non-hepatic:
Hemolysis
Myopathy
Thyroid disease
Strenuous exercise

Question 13

What are the etiologies associated with severely elevated AST or ALT?

Answer 13

Acute viral hepatitis (Hep A-E, herpes)
Medications/toxins
Ischemic hepatitis
Autoimmune hepatitis
Wilson's disease
Acute Budd-Chiari syndrome
Hepatic artery ligation or thrombosis

Question 14

What are the etiologies associated with elevated alkaline phosphatase?

Answer 14

HEPATOBILIARY:
Bile duct obstruction
Primary biliary cirrhosis (PBC)
Primary Sclerosing Cholangitis (PSC)
Medications
Hepatitis
Cirrhosis
Infiltrating Disease of liver

NON-HEPATIC:
Bone disease
Pregnancy
Chronic renal failure
Lymphoma/other malignancies
Congestive heart failure
Infection and inflammation

Question 15

What are some infiltrating diseases of the liver that cause elevated Alk Phos levels?

Answer 15

Sarcoidosis
Tuberculosis
Fungal Infection
Other granulomatous diseases
Amyloidosis
Lymphoma
Metastatic malignancy
Hepatocellular carcinoma

Question 16

What are all of the HBV serological markers and what do they indicate?

Answer 16

HBsAg = Hepatitis B surface antigen
Pos indicates active HBV infection

HBeAg = Hepatitis B envelope antigen
Pos indicates a high viral load

HBsAb = Hepatitis B surface antibody
Pos Indicates prior exposure, either infection or immunization

HBcAb = Hepatitis B core antibody
Pos Indicates prior infection only

HBeAb = Hepatitis B envelope antibody
Pos indicates low viral load

HBV DNA
Pos indicates active viral replication

Question 17

What is the goal of HBV treatment?

Answer 17

Seroconversion
Loss of HBeAg and development of HBeAb associated with negative HBV DNA when treatment is stopped

Prevention of decompensated cirrhosis in those with advanced fibrosis

Note: loss of HBsAg rarely occurs (infection is still present, but not in high quantities

Question 18

What are the treatment options for HBV?

Answer 18

Interferon therapy:

Finite duration of therapy

Question 19

What is the goal of HCV treatment?

Answer 19

Chronic HCV infection is defined as HCV RNA presence >6mo after infection

Goal of antiviral therapy is to clear HCV RNA such that patients remain HCV RNA clear 12 weeks after stopping therapy.
Sustained virological response = cure

Question 20

What is the treatment for Hereditary Hemochromatosis?

Answer 20

HH - Inherited disorder resulting in increased iron absorption in duodenum, accumulating in liver
Therapeutic phlebotomy or chelation therapy with desfuroxamine

Question 21

What is the treatment for autoimmune hepatitis?

Answer 21

AH - Chronic hepatitis characterized by immunologic and autoimmune features.
Treatment is based on immune suppression:
Corticosteroids
Azathioprine
Relapse typically occurs if treatment is stopped after liver enzymes normalize

Question 22

What is the treatment for Primary Biliary Cirrhosis?

Answer 22

PBC - Immune mediated disease causing damage to small intrahepatic bile ducts.
Treatment is ursodeoxycolic acid (UDCA):
A secondary bile acid produced by intestinal bacteria
Improves bile acid transport, detoxifies bile, provides cytoprotection

Question 23

What is the treatment for Primary Sclerosing Cholangitis?

Answer 23

asdf