Hepatitis B & C Treatment Prophylactic Measures Vaccination

Hepatitis B & C Treatment

Prophylactic Measures Vaccination against HBV absent in case of HCV! Avoid any exposure to blood or any body fluid of an infected person. This could be happen in cases of : sharing personal hygiene items (razors , toothbrushes …) Avoid sex with an infected person . Undergo a hepatitis test before any planned pregnancy

Pharmacotherapy Two Groups of Antiviral Drugs : Interferons Nucleoside & Nucleotide analogs (both used together in combination)

Interferons It is a family of naturally occurring glycoproteins that interfere with the ability of virus to infect cells . Inhibit the growth of many viruses in vitro ,this activity in vivo is disappointing. They are synthetized by recombinant DNA technologies .

Interferon There are at least 3 types of interferons : Αlpha α ( hepatitis B,C ) Beta β ( Relapsing remitting multiple sclerosis ) Gamma γ (Chronic granulomatous disease ) for treatment of hepatitis we use two of the 15 alpha interferons : - interferon α-2a - interferon α-2b

Interferon Interferons are used in so called “pegylated “ formulations . Pegylation is the process of covalent attachment of polyethylene glycol to enlarge the molecular size of the drug . ( the larger molecular size delays absorption and lengthens the duration of action )

Mode of action The antiviral mechanism is not completely understood , it appears to involve the induction of the host enzyme that inhibits viral RNA translation leading to the degradation of viral mRNA ad tRNA

Pharmacokinetics Its not active orally . administrated : intralesionally , subcutaneously , or intravenously . Absent in plasma , because of cellular uptake and metabolism by the liver and kidneys . Negligible renal elimination occurs .

Adverse Effects Flu-like symptoms mainly : fever , chills , myalgias and arthralgias. GIT disturbances . Fatigue and mental depressions . Bone marrow suppression and sometimes weight loss and thyroiditis .

Nucleoside & Nucleotide analogs Ribavirin : is a guanosine analog , which inhibits guanosine triphosphate formation preventing viral mRNA capping , and blocks RNA polymerase . Taken orally or intravenously in combination with an interferon ,absorption is increased when taken with fatty meal. It is eliminated in urine . Adverse effects : dose dependent transient anemia , elevation of bilirubin. It is contraindicated in pregnancy .

Lamivudine is a cytosine analog Inhibits HBV DNA polymerase without any effect on the host DNA . Intracellular half-life is hours longer than its plasma half-life . Lamivudine is well absorbed orally (half-life is 9 hours ) Excreted in urine . Dose reduction is necessary in case of renal insufficiency (if creatinine clearance is less than 50ml/min) . Rare occurrence of headache and dizziness .

Adefovir is a nucleotide analog Binds to viral DNA and stops replication . Taken orally once a day . Excreted in urine . Clearance is influenced by renal function . Discontinuation of adefovir results in severe exacerbation of hepatitis . No drug interactions .

Entecavir is a guanosine analog It competes with the natural substrate (deoxyguanosine triphosphate) of the virus and blocks viral reverse transcriptase . Effective against Lumivudine resistant strains of hepatitis . Improves liver inflammation and scarring . Given once a day. Discontinuation of Entecavir also results in severe exacerbation of hepatitis . Drugs with renal toxicity should be avoided.

Telbivudine is a thymidine analog It terminates elongation of viral DNA . Given orally once a day. Eliminated by glomerular filtration . Dose must be adjusted in case of renal failure.

References : - lippincott pharmacology 5th edition -harrison principles of internal medicine 18th edition.