Pharmacotherapy of Hepatitis Flashcards Preview

GI > Pharmacotherapy of Hepatitis > Flashcards

Flashcards in Pharmacotherapy of Hepatitis Deck (24):
1

Describe the "natural history" of HCV

From chronic infection it typically takes 20-30 years to become cirrhotic (20%). From there 5% progress to HCC within 1 year.

2

What factors are associated with increased progression of liver injury? Demographic, liver, immune system

Demographic factors: age>40, male, caucasian/hispanic, smoking

Liver injury: alcohol, HBC, obesity, insulin resistance

Immunocompromised: HIV, OLT

3

What are factors that determine likelihood of response of chronic HCV to therapy?

Host: age>40, male, AA, obesity, advanced fibrosis/cirrhosis, HIV, OLT, genetic polymorphism (IL28B)

Viral factors: genotype, viral load

4

What is the gold standard for HCV treatment?

Sustained viral response-- absence of detectable HCV in blood 24wks or 12wks after end of course of therapy

5

What was old mainstay of treatment until 2011?

IFN-alpha
Ribavirin

6

What are the MOAs of IFNalpha? (2)

Immune activation: enhances MHC-I expression, amplifies T lymphocytes/NK cells, enhances macrophage activity

Direct antiviral activity: inhibits HCV attachment and uncaring, activation of cellular RNAses

7

What are AE of IFN alpha? (7)

Flu-like symptoms
Depression/suicide
BM suppression
Activation of autoimmune disease
Weight loss
Bacterial infections
Worsening of liver function in cirrhosis

8

What are MOAs of ribavirin? (4)

Inhibit RNA-dependent RNA polymerase
Induces lethal mutations in HCV RNA
GTP depletion
Modulation of T cell response favoring Th1

9

What are AE of ribavirin? (4)

Non-immune hemolytic anemia
Rash
Dyspnea
Teratogenic

10

What are the differences in genotype in treatment response?

Genotype 1: Longer treatment course (48-72wks), only 40% SVR

Genotype 2/3: 24wks of treatment produces 80% SVR

11

What are categories of currently approved directly acting antiviral drugs? (3)

HCV protease (NS3/4A) inhibitors: telaprevir
Viral RNA-dependent RNA-polymerase (NS5B) inhibitors: Sofosbuvir
Combination pills: Harvoni (ledipasvir+sofosbuvir) and Viekira

12

Describe the current HCV treatment guidelines and the chances of SVR

Genotype 2: sofosbuvir+ribavirin for 12wks
Genotype 3: SOF+RBV for 24wks
SVR=70-90%

Genotype 1: Harvoni/Viekira + ribavirin
SVR=94-99%

13

What is responsible for most of hepatic injury in HBV infection?

Immune response==>the degree of immune tolerance to HBV determines whether a chronic infection will develop

14

Describe phase of immune tolerance in HBV (3)

Normal ALT
High DNA
eAg+, eAb-

15

Describe chronic hepatitis phase of HBV infection

ALT high
High DNA
eAg+, eAb-

16

Describe the changes that occur in eAg seroconversion

ALT transiently high then normal
Low DNA
eAg-/eAb+

17

What is the difference between eAg positive and eAg negative hepatitis B?

eAg negative HBV patients tend to be older (HBV has undergone entire process)

eAg negative HBV infection tends to be harder to treat

18

What are the indications for HBV treatment? (3)

Elevated ALT
Elevated HBV DNA
Patients with cirrhosis and detectable HBV DNA

19

What are endpoints of therapy? (3)

eAg loss (seroconversion associated with decreased risk of hepatic decompensation and HCC)
*DNA suppression*
Others: normalization of ALT, histological response, HBsAG loss

20

What are two most potent viral polymerase inhibitors?

Entecavir
Tenofovir

Both are oral agents

21

Describe the efficacy of treatment for eAg+ chronic HBV

Goal: eAg seroconversion
Oral agents: 20-50% (increases with duration)
IFN: 30%

22

Describe the efficacy of treatment eAg- chronic HBV.

How long do most patients stay on therapy

Goal: long term DNA suppression
Oral agents: 50-90%
IFN: 20%

Note: There is a high relapse rate so most patients stay on therapy long term

23

What are the pros (2) and cons (4) of IFN for HBV therapy?

Pros: finite course, no viral resistance
Cons: high relapse rate in eAg-, limited efficacy, AE, cannot use in patients with decompensated liver disease

24

Describe the pros (3)/cons (3) of nucleoside analogues in chronic HBV therapy?

Pros: well tolerated, useful for eAg neg patients with long term treatment, useful for decompensated cirrhosis

Cons: development of drug-resistant mutants, need long term therapy, occasional post-withdrawal flares