Hepatitis Viruses

Hepatitis A (HAV)

Genome: RNA

Transmission: Fec*l-Oral

Chronicity: Acute only

Vaccine Status: Yes

Hepatitis B (HBV)

Genome: DNA

Transmission: Blood / Sexual / Perinatal

Chronicity: Acute & Chronic

Vaccine Status: Yes

Hepatitis C (HCV)

Genome: RNA

Transmission: Blood-Borne

Chronicity: High Chronicity (80%)

Vaccine Status: No (Curable)

Hepatitis D (HDV)

Genome: RNA (Defective)

Transmission: Blood / Co-infection

Chronicity: Requires HBV

Vaccine Status: HBV Vaccine

Hepatitis E (HEV)

Genome: RNA

Transmission: Fec*l-Oral

Chronicity: Acute (Severe in pregnancy)

Vaccine Status: No

HAV & HEV ("The Vowels")

Hit the bowels. Fecal-oral transmission. They do not cause chronic hepatitis. Crucial note: HEV carries a high mortality rate in pregnant women.

HBV

The only DNA virus among them. It uses a unique reverse transcriptase during its replication cycle (a prime target for pharmacotherapy).

HCV

An RNA virus notorious for lacking a proofreading RNA polymerase, leading to frequent mutations and "quasispecies." This is why there is no vaccine, but it is the leading indication for liver transplantation.

HDV

A "defective" RNA virus. It absolutely requires the Hepatitis B surface antigen (HBsAg) to assemble its viral envelope. Therefore, vaccinating against HBV guarantees protection against ‘blank’.

HBsAg (Surface Antigen)

The hallmark of infection. If it is positive, the virus is currently in the patient's body (either acute or chronic).

Anti-HBs (Surface Antibody)

The hallmark of immunity. If it is positive, the patient is protected, either from past infection or vaccination.

Anti-HBc (Core Antibody)

The hallmark of natural exposure

• IgM anti-HBc: Acute, recent infection.

• IgG anti-HBc: Chronic or past resolved infection.

HBeAg (Envelope Antigen)

A marker of active viral replication and high infectivity.

Susceptible (Give the vaccine!)

HBsAg: Negative

Anti-HBs: Negative

Anti-HBc: Negative

Immune due to natural infection

HBsAg: Negative

Anti-HBs: Positive

Anti-HBc: Positive (IgG)

Immune due to vaccination (They only saw the surface antigen)

HBsAg: Negative

Anti-HBs: Positive

Anti-HBc: Negative

Acute Infection

HBsAg: Positive

Anti-HBs: Negative

Anti-HBc: Positive (IgM)

Chronic Infection

HBsAg: Positive

Anti-HBs: Negative

Anti-HBc: Positive (IgG)

Hepatitis B (HBV) Treatment

_{^{The goal of HBV therapy is viral suppression (preventing cirrhosis and hepatocellular carcinoma), not complete eradication, because HBV integrates its DNA into the host nucleus as covalently closed circular DNA (cccDNA).}}

Nucleos(t)ide Analogue Reverse Transcriptase Inhibitors (NRTIs)

Pegylated Interferon alfa-2a (Peg-IFN)

Nucleos(t)ide Analogue Reverse Transcriptase Inhibitors (NRTIs)

• Drugs of Choice: Tenofovir (TDF or TAF) and Entecavir.

• Mechanism: They act as false building blocks. The viral HBV DNA polymerase (which has reverse transcriptase activity) incorporates the drug into the growing viral DNA strand, causing premature chain termination.

• _{^{Pharmacy Pearl: Tenofovir Alafenamide (TAF) is preferred over Tenofovir Disoproxil Fumarate (TDF) in patients with osteoporosis or renal impairment because TAF achieves higher intracellular concentrations with less systemic bone/renal toxicity.}}

Pegylated Interferon alfa-2a (Peg-IFN)

• Mechanism: Enhances the host immune response and inhibits viral protein synthesis.

• Drawback: Administered subcutaneously with a heavy side-effect profile (flu-like symptoms, profound depression, bone marrow suppression). Generally avoided unless treating a young patient with well-compensated liver disease for a finite duration.

Hepatitis C (HCV) Treatment

_{^{The paradigm for HCV has shifted from immune modulation to a complete, highly successful cure using Direct-Acting Antivirals (DAAs).}}

_{^{Therapy always involves combining 2 or 3 DAAs with different mechanisms to prevent resistance. You can identify the drug class by its suffix:}}

NS3/4A Protease Inhibitors (Suffix: "-previr")

NS5A Replication Complex Inhibitors (Suffix: "-asvir")

NS5B Polymerase Inhibitors (Suffix: "-buvir")

Classic Regimens: Epclusa (Sofosbuvir + Velpatasvir) or Mavyret (Glecaprevir + Pibrentasvir).

NS3/4A Protease Inhibitors (Suffix: "-previr")

• Examples: Glecaprevir, Grazoprevir, Voxilaprevir.

• Mechanism: Inhibit the viral protease enzyme responsible for cleaving the HCV polyprotein into functional individual proteins.

NS5A Replication Complex Inhibitors (Suffix: "-asvir")

• Examples: Ledipasvir, Velpatasvir, Pibrentasvir.

• Mechanism: Block a vital structural protein required for viral assembly and replication.

NS5B Polymerase Inhibitors (Suffix: "-buvir")

• Examples: Sofosbuvir.

• Mechanism: Nucleotide analogue that causes chain termination of the viral RNA polymerase.

Amiodarone

Pharmacy Safety Pearl: ‘blank’ is strictly contraindicated with Sofosbuvir-containing regimens due to the risk of severe, fatal symptomatic bradycardia.