Viral hepatitis B and C: virology and treatment principles

Hepatitis B can be controlled but rarely cured; hepatitis C can now be cured with tablets. This page explains why.

Updated Nov 12, 2026

Hepatitis B virus (HBV) and hepatitis C virus (HCV) both cause chronic liver infection that can lead to cirrhosis and liver cancer, but they behave very differently. HBV keeps a stable DNA copy (cccDNA) in the hepatocyte nucleus, so treatment suppresses it, often for life. HCV is an RNA virus that replicates only in the cytoplasm and leaves no archive, so direct-acting antivirals (DAAs) can clear it for good.

Key points

HBV forms covalently closed circular DNA (cccDNA) in the nucleus; no current drug removes it, so cure is not possible and most treated people continue therapy indefinitely.
Preferred HBV drugs are entecavir and tenofovir: potent, well tolerated and with a high barrier to resistance; stopping them can cause a severe hepatitis flare.
Before chemotherapy, rituximab or other strong immunosuppression, people are screened for HBV, because the virus can reactivate.
HCV cure equals a sustained virological response (SVR): no detectable HCV RNA some weeks after treatment ends; current DAAs cure the great majority.
Before HCV treatment everyone is tested for HBV, since clearing HCV can unmask HBV reactivation.
In decompensated cirrhosis (Child-Pugh B or C), NS3/4A protease inhibitor regimens are contraindicated; sofosbuvir-based regimens are used instead.

HBV: genome, life cycle and genotypes

HBV is a small enveloped virus with a partly double-stranded, relaxed circular DNA genome. It attaches to the hepatocyte and enters through the bile acid transporter NTCP. In the nucleus the genome is repaired into cccDNA, which acts as a minichromosome and is the template for all viral RNAs. One long RNA (pregenomic RNA) is packaged with the viral polymerase and copied back into DNA by reverse transcription inside the capsid. Infected cells also release huge excess amounts of empty surface-antigen (HBsAg) particles, which may help exhaust the immune response. HBV has ten genotypes; genotypes F and H circulate among Indigenous peoples of South America, and genotype affects HBeAg loss and response to interferon.

Nucleos(t)ide analogues (entecavir, tenofovir) inhibit the polymerase's reverse-transcriptase step.
Bulevirtide blocks NTCP entry and is used for hepatitis D, which needs HBV to spread.

HBV markers and phases

Chronic HBV moves through phases over a lifetime. HBsAg shows infection; HBeAg usually marks high replication; anti-HBe and falling HBV DNA mark lower activity. Some viruses carry mutations that stop HBeAg production while still replicating actively (HBeAg-negative chronic hepatitis). Age at infection matters most: infection in infancy becomes chronic in most cases, infection in adults rarely does. Treatment is usually reserved for people with high HBV DNA and raised ALT, anyone with cirrhosis, and those about to receive immunosuppressive therapy.

HBV treatment: goals, choice and pitfalls

Because cccDNA persists, the realistic goals are to keep HBV DNA suppressed, promote loss of HBeAg (and, rarely, HBsAg: a functional cure), slow fibrosis, lower the risk of liver cancer and prolong survival. Pegylated interferon is given for a fixed period and works best in some genotypes; nucleos(t)ide analogues are oral and usually continued long term.

Barrier to resistance: lamivudine selects resistance in most people over years, while entecavir and tenofovir rarely do; entecavir is less reliable after prior lamivudine resistance.
Stopping therapy can trigger a severe, sometimes fatal flare, so liver tests are followed after any stop.
Entecavir alone is not used in a person with untreated HIV, because it can select HIV resistance.
Reactivation with immunosuppression: chemotherapy, rituximab and other strong immunosuppressants can wake HBV up, so people are screened (HBsAg, anti-HBc) and many receive prophylactic antivirals.
Tenofovir alafenamide has less effect on kidneys and bone than tenofovir disoproxil; renal function guides dose adjustment of these drugs.

HCV: genome, life cycle and genotypes

HCV is a positive-sense single-stranded RNA virus. Its genome is translated into one long polyprotein that host and viral proteases cut into structural proteins (core, E1, E2) and non-structural proteins. Replication happens entirely in the cytoplasm, on membrane platforms built by the virus; there is no DNA stage and no latent reservoir, which is why HCV is curable. HCV has at least six genotypes, and the high variability of its envelope is one reason there is no vaccine.

NS3/4A protease: cuts the polyprotein; target of the -previr drugs (glecaprevir, voxilaprevir, grazoprevir).
NS5A: organises replication and assembly; target of the -asvir drugs (velpatasvir, ledipasvir, pibrentasvir).
NS5B RNA polymerase: copies the genome; sofosbuvir is a nucleotide prodrug that inhibits it.

HCV: SVR and resistance-associated substitutions

SVR means HCV RNA stays undetectable for a set period (typically twelve weeks, SVR12) after the end of treatment, and it is considered a cure. Modern pangenotypic regimens combine drugs on two targets and cure more than nine in ten people. Resistance-associated substitutions (RASs) are amino-acid changes in the target proteins that reduce drug activity. Some exist before treatment; others emerge in people whose treatment fails. NS5A changes such as Y93H matter most, especially in genotype 3 with cirrhosis, where resistance testing may guide the regimen. Sofosbuvir has a high barrier to resistance.

Liver function (Child-Pugh) and drug choice

The Child-Pugh score grades cirrhosis from A (compensated) to B and C (decompensated, with ascites, encephalopathy or variceal bleeding). It changes drug choice. NS3/4A protease inhibitors reach much higher levels when liver function is poor and have caused serious liver injury, so they are contraindicated in decompensated cirrhosis. Sofosbuvir plus an NS5A inhibitor, often with ribavirin, is used in that setting; even then SVR rates are lower and the liver may not fully recover. For HBV, entecavir and tenofovir can be used in decompensated disease, where suppression can be lifesaving.

Other cautions and context

Amiodarone with sofosbuvir-containing regimens can cause severe slowing of the heart rate; the combination is avoided or closely monitored.
Velpatasvir and ledipasvir need stomach acid for absorption, so acid-reducing drugs need careful timing or avoidance.
Ribavirin causes haemolytic anaemia and is teratogenic.
WHO estimates that about five million people in the Americas live with chronic hepatitis B; vaccination at birth is the key prevention.

Test yourself

Think of the answer, then tap the question to see it.

Why can current drugs cure hepatitis C but not hepatitis B?

HBV keeps cccDNA in the hepatocyte nucleus, which no drug removes; HCV replicates only in the cytoplasm with no DNA stage or latent reservoir.

What does SVR12 mean in hepatitis C treatment?

HCV RNA remains undetectable twelve weeks after the end of treatment; it is treated as a cure.

Why is HBV tested before rituximab or an HCV direct-acting antiviral?

Both strong immunosuppression and clearing HCV can let HBV reactivate and cause severe hepatitis; screening allows monitoring or prophylactic antivirals.

Which HCV regimens are contraindicated in Child-Pugh B or C cirrhosis, and why?

Regimens containing an NS3/4A protease inhibitor, because drug levels rise sharply when the liver fails and serious liver injury has been reported.

What risk follows stopping entecavir or tenofovir in chronic hepatitis B?

A severe, sometimes fatal, acute flare of hepatitis as the virus rebounds; liver function is followed after any stop.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Hepatitis B (World Health Organization, 2026); DailyMed - SOFOSBUVIR AND VELPATASVIR tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); DailyMed - ENTECAVIR tablet (DailyMed (U.S. National Library of Medicine), 2026).

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