Topic 7-Agents against Hepatitis Viruses

Question 1

What is the goal of treatment in viral hepatitis?

Answer 1

1.) Total suppression of virus 2.) Replication seroconversion (AB negativity) 3.)normalizing of enzyme levels and tissue picture
Total eradication not yet possible

In the case of HCV there are more combination therapies dependent on genotype. With a combined therapy we can reach SVR (12 weeks undecetable viral level – 97-100% chance of eradication) often without relapse.

Question 2

Interferon alpha mechanism

Answer 2

Complex antiviral activity (induces production of more than 20 antiviral proteins)

Question 3

What helps increase the kinetic properties of interferon alpha

Answer 3

Polyethylenglycol

Question 4

Adverse effect of interferon alpha

Answer 4

Flu like symptoms, suppression of hematopoeisis, GI problems, liver, and kidney function disorders, CNS issues

Question 5

Which 3 nucleoside/nucleotide analogues are used for Hepatitis B

Answer 5

Lamivudin
Entecavir
Tenofovir

Question 6

How is the resistance to nucleoside and nucleotide analogues for hep B

Answer 6

Entecavir is well tolerated
Lamivudin has some resistance
Tenofovir is more potent and has no resistance

Question 7

Main points of treatment of Hep. B

Answer 7

Development of resistance in HBV is highly depends on initial viral count (as higher then faster)

• Decrease of the count should be so fast as possible
• Constant suppression is very important
• The most often used lamivudin is not really good choice
• For postexposure prophylaxis: anti-HBV immunglobulin

Question 8

When should treatment be initiated for hepatitis B

Answer 8

1. )Cirrhosis
   - Decompensated: every case, only nucleosides are possible
   - Compensated: if HBV-DNA is >104 / ml yes, if it is lower, then it can be also recomennded
2. )Immunactive phase (HBe AG positiv)
   - In case of newly diagnostisized patients treatment can be delayed with 3-6 Month
   - If HBV-DNA >105 / ml and GPT high (>60 IU (male) >38 IE (female)
   - If GPT is lower but other findings (clinical or histological) show active disease
   - Peg-INF treatment 1 year or nucleoside 1 year after Hbe AG negativity
3. )Hbe negative phase
   - If HBV-DNA is >104 and GPT is high (>60 IU (male) >38 IE (female)
   - Peg-INF treatment 1 year or nucleoside until HBs AG negtivity (many years or lifelong)
   - Patient with low GPT should be observed to notice the activation of the disease
4. )In case of HDV coinfection only INF treatment is effective

Question 9

Ribavirin treats HCV via what mechanism
Administration
Adverse effects
HCV duration

Answer 9

Guanosine ananlogue
Broad spectrum 
P.O., iv, and aerosol
Adverse effects: normocytic anemia, in high dose bone marrow suppression, possible it is carcinogenic and teratogenic. CNS (fatigue, insomnia, asthenia) and skin problems, coughing, are possible. Inhaled form can cause conjunctivitis.
HCV treatment is 12-48 weeks orally

Question 10

Treatment of HCV

NS5B polymerase inhibitor

Answer 10

Sofosbuvir

Question 11

Sofosbuvir info?

Answer 11

TMP analogue, causes chain termination

• Effective on genotypes 1,2,3,4,5,6 (no data for others)
• Resistance still not registered
• Low toxicity: headache, nausea, insomnia, fatigue possible