Hepatitis Antiviral Medications

Hepatitis B: a DNA virus that hides

Hepatitis B virus (HBV) carries a partially double-stranded DNA genome but replicates via an unusual reverse transcriptase step, copying an RNA intermediate back into DNA like a retrovirus. Viral DNA then converts into covalently closed circular DNA (cccDNA), which settles permanently in the hepatocyte nucleus as a durable template for new virus. Nucleoside and nucleotide analogues — entecavir, tenofovir disoproxil fumarate, and tenofovir alafenamide — are incorporated into the growing viral DNA chain by the reverse transcriptase and halt synthesis. This blocks new virion production but does nothing to the cccDNA already in the nucleus. That is why these drugs suppress rather than cure, and why therapy is generally long-term, often indefinite.

Because tenofovir also inhibits HIV's reverse transcriptase, it carries real antiretroviral activity. In unrecognized HIV co-infection, an HBV regimen containing tenofovir alone behaves like inadequate single-agent HIV therapy — enough to pressure the virus, not enough to control it — risking HIV drug resistance. This is why HIV testing must precede hepatitis B antiviral therapy.

These agents carry boxed warnings for lactic acidosis with hepatomegaly and steatosis, a mitochondrial toxicity shared across nucleoside analogues, and for severe hepatitis flares on discontinuation, since stopping suppression lets the immune system resume attacking infected hepatocytes. Peginterferon alfa is an alternative: it boosts the host's antiviral immune response for a finite duration instead of blocking the polymerase, trading simplicity for systemic toxicity — flu-like symptoms, cytopenias, and depression.

Hepatitis C: an RNA virus with no hiding place

Hepatitis C virus (HCV) is a single-stranded RNA virus that replicates in the cytoplasm via its own RNA-dependent RNA polymerase. It never integrates into host DNA and forms no nuclear reservoir like cccDNA, so clearing every infected cell's virus genuinely eliminates the infection rather than merely suppressing it. This is the basis for direct-acting antivirals (DAAs), combinations targeting distinct replication steps: NS5B polymerase inhibitors such as sofosbuvir block RNA synthesis directly; NS5A inhibitors such as ledipasvir, velpatasvir, and pibrentasvir disrupt viral assembly and the replication complex; and NS3/4A protease inhibitors such as glecaprevir and grazoprevir block cleavage of the viral polyprotein. The name stems double as a study aid: "-buvir" for polymerase inhibitors, "-asvir" for NS5A inhibitors, and "-previr" for protease inhibitors.

Modern pangenotypic combinations work across HCV genotypes, allowing short, finite courses with excellent tolerability versus older interferon-based regimens. Two practical issues dominate use. First, DAAs are substrates or modulators of P-glycoprotein and cytochrome P450 enzymes, interacting with amiodarone, statins, acid-suppressing drugs, certain anticonvulsants, and St. John's wort, altering drug levels. Second, patients with underlying hepatitis B can experience HBV reactivation once HCV is suppressed, so screening for hepatitis B precedes hepatitis C treatment.