Functional Liver Tests and Treatment of Chronic Hepatitis

Question 1

what can cause Prolongation of PT (INR)

Answer 1

Significant hepatocellular dysfunction

Vitamin K deficiency

Question 2

how can you differentiate liver Dysfunction vs. Vit K deficiency?

Answer 2

Administer subcutaneous vitamin K and assess response
No correction = liver dysfunction
Normalization = vitamin K deficiency

Question 3

predominately elevated AST and ALT would indicate what pattern of disease?

Answer 3

Hepatocellular Injury or Necrosis

Question 4

predominately elevated alk phos would indicate what pattern of disease?

Answer 4

Cholestatic Pattern

Question 5

where in AST located in the hepatocyte?

Answer 5

Cytosol and mitochondria

Question 6

where is ALT located in the hepatocyte?

Answer 6

Cytosol

Question 7

what organs express AST?

Answer 7

liver, heart, muscle, blood

Question 8

what organs express ALT

Answer 8

Liver only

Question 9

what is a Typical AST:ALT ratio

Answer 9

<1

Question 10

AST:ALT Ratio >1 is seen in _____

Answer 10

cirrhosis

Question 11

AST:ALT Ratio >2 is suggestive of ________

Answer 11

alcoholic liver disease

Question 12

what is alkaline phosphatase

Answer 12

Hydrolase enzyme responsible for removing phosphate groups from nucleotides, proteins and alkaloids

Question 13

alkaline phosphatase can be elavated in

Answer 13

Cholestatic or infiltrative diseases of liver
Obstruction of biliary system
Bone disease
Pregnancy

Question 14

what do glutamyltransferase (GGT) lab values represent

Answer 14

GGT is Not present in bone
so if GGT is elevated and alk phos is elevated then you know the origin is the liver

Is Elevated after alcohol consumption and almost all types of liver disease

Question 15

what are 7 hepatobiliary causes of increased alk phos?

Answer 15

Bile duct obstruction
Primary biliary cholangitis (PBC)
Primary sclerosing cholangitis (PSC)
Medications
Hepatitis
Cirrhosis
Infiltrating disease

Question 16

what are 6 non-hepatic causes of elevated alk phos?

Answer 16

Bone disease
Pregnancy
Chronic renal failure
Lymphoma and other malignancies
Congestive heart failure
Infection and inflammation

Question 17

what are 3 things that can cause Unconjugated (indirect) hyperbilirubinemia

Answer 17

Gilbert’s syndrome
Hemolysis (increased heme breakdown)
Crigler-Najjar syndrome

Question 18

what 4 things can cause conjugated hyperbilirubinemia

Answer 18

Extrahepatic obstruction of bile flow
Intrahepatic cholestasis
Hepatitis
Cirrhosis

Question 19

what is HBsAg and what does it indicate?

Answer 19

Hepatitis B surface antigen
Marker of active infection
Presence for >6 months defines chronic hepatitis B infection

Question 20

what is HBsAb (or anti-HBs) and what does it indicate?

Answer 20

Antibody to HBsAg

Marker of immunity to hepatitis B

Question 21

what is HBcAb and what does it indicate?

Answer 21

Hepatitis B core antibody

Marker of active or prior infection

Question 22

what is HBeAg and what does it indicate?

Answer 22

Hepatitis B “e” antigen

Surrogate marker of high viral load

Question 23

what is HBeAb (or anti-Hbe) and what does it indicate

Answer 23

Antibody to hepatitis B “e” antigen

Associated with lower viral load

Question 24

what does HBV DNA indicate on lab tests

Answer 24

Presence means active viral replication

Question 25

what are the goals of HBV treatment?

Answer 25

HBeAg seroconversion -> Loss of HBeAg and development of HBeAb associated with negative HBV DNA when treatment stopped. Prevention of decompensated cirrhosis in those with advanced fibrosis

Question 26

what are the 3 indications for treatment of chronic HBV

Answer 26

1) HBsAg(+) > 6 months* 2) Serum HBV DNA >105 copies/mL 3) Persistent or intermittent elevation in ALT and AST levels Likelihood of HBeAg seroconversion with normal ALT is very low

Question 27

what are 2 treatment options for HBV

Answer 27

1) Interferon Finite duration of therapy (1 year) Absence of resistant mutations More durable response 2) Nucleoside/tide analogues Fewer side effects Resistant mutations

Question 28

Chronic HCV defined as presence of HCV RNA in blood ____ months after infection

Answer 28

>6

Question 29

Goal of antiviral therapy is to clear HCV RNA such that they remain HCV RNA negative ______ after stopping therapy.

Answer 29

12 weeks

Question 30

what is a current Tx option For HCV

Answer 30

NS5B polymerase inhibitor (SOFOSBUVIR) + NS5A inhibitor (LEDIPASVIR) For 12 weeks

Question 31

what is hereditary hemochromatosis

Answer 31

Inherited disorder resulting in increased intestinal iron absorption

Question 32

what is the treatment of hereditary hemochromatosis

Answer 32

Therapeutic phlebotomy 500 mL of whole blood = 200-250 mg iron Endpoint is serum ferritin 50 ng/mL Maintenance phlebotomy to keep ferritin 50-100 ng/mL

Question 33

what is the tx for hereditary hemochromatosis in anemic patients not able to tolerate phlebotomy?

Answer 33

chelation therapy with desfuroxamine

Question 34

for diagnosis of hereditary hemochromatosis, Initial iron studies are ordered; what results would make you proceed with a gene test?

Answer 34

% iron saturation is >45% OR | ferritin (>500 ng/mL)

Question 35

what is the mutation seen in hereditary hemochromatosis

Answer 35

HFE Gene mutation -> C282Y, H63D, S65C

Question 36

If gene testing comes back positive for hereditary hemochromatosis, what should be the next step?

Answer 36

Evaluate for end organ involvement Liver -> MRI Heart -> Cardiac MRI Pancreas, gonads, thyroid, joints

Question 37

Primary Biliary Cholangitis

Answer 37

Immune mediated disease causing damage to small intrahepatic bile ducts

Question 38

what is the treatment for Primary Biliary Cholangitis

Answer 38

``` ursodeoxycolic acid (UDCA) -> Improves bile acid transport, “detoxifies” bile and providing cytoprotection ```

Question 39

what is Primary Sclerosing Cholangitis

Answer 39

Inflammatory disease of the intra- and EXTRAHEPATIC large bile ducts -> Leads to strictures and obstruction of bile ducts and can ultimately result in cirrhosis

Question 40

what is the Tx of Primary Sclerosing Cholangitis

Answer 40

Treatment focused on management of complications of bile duct obstruction 1) Stenting strictures 2) Antibiotics for cholangitis

Question 41

what is wilsons disease?

Answer 41

Autosomal recessive disorder | Decreased hepatocullar copper excretion resulting in hepatic copper accumulation and injury

Question 42

what is the Tx of wilson's disease

Answer 42

copper chelation -> D-penicillamine, Trientine Maintenance therapy with zinc

Question 43

what is Non-Alcoholic Steatohepatitis (NASH)

Answer 43

NASH is presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning with or without fibrosis

Question 44

what is the Tx of Non-Alcoholic Steatohepatitis (NASH)

Answer 44

Treatment focused on modifying risk factors Obesity Diabetes mellitus type 2 Dyslipidemia