Hepatitis C Direct-Acting Antivirals Treatment Pathway
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Direct answer
Hepatitis C direct-acting antivirals are oral drugs that inhibit viral proteins such as NS5A, the NS5B polymerase and the NS3/4A protease, and they cure most patients within 8 to 12 weeks of treatment. Cure is defined as sustained virological response at 12 weeks after stopping treatment, meaning HCV RNA remains undetectable. Sofosbuvir-based regimens are the usual first choice because they work across genotypes.
What you must remember
- Genotypes: Six major genotypes; genotype 3 is common across much of India, with genotype 1 also frequent, and regimen choice depends on genotype and cirrhosis status.
- Sofosbuvir: A nucleotide NS5B polymerase inhibitor that forms the backbone of most current regimens, combined with an NS5A inhibitor.
- SVR12: Undetectable HCV RNA 12 weeks after completing therapy, the marker of cure; normal ALT alone does not establish it.
- Cirrhosis: Longer treatment or ribavirin may be added in selected cirrhotic or previously treated patients, per current guidance, and HCC surveillance continues after cure.
- Extrahepatic disease: Mixed cryoglobulinaemia with vasculitis, membranoproliferative glomerulonephritis, lichen planus, porphyria cutanea tarda and B-cell lymphoma.
- HBV reactivation: Patients who are HBsAg or anti-HBc positive need HBV DNA monitoring during direct-acting antiviral therapy.
A pathway from positive anti-HCV to cure
A 45-year-old man has a positive anti-HCV antibody, which shows exposure rather than active infection.
- Confirm active infection: HCV RNA confirms the diagnosis, because antibody alone does not show that the virus is still active.
- Genotype the virus: Genotyping determines the regimen and duration.
- Stage the liver: Elastography or a non-invasive score assesses fibrosis and checks for cirrhosis, since cirrhosis alters duration and the need for ribavirin.
- Screen for coinfection and interactions: HBsAg and anti-HBc detect hepatitis B coinfection or past infection, HIV testing is done, and interacting drugs such as amiodarone are reviewed, since amiodarone is associated with bradycardia when combined with sofosbuvir.
- Treat and confirm SVR12: HCV RNA is checked during therapy to confirm response and again 12 weeks after the end of treatment. An undetectable result then is SVR12, the endpoint used to declare cure.
- Retreat after failure: Failure after a first course is managed with a different regimen selected by genotype and prior treatment, with specialist input.
Public programmes in India have made direct-acting antiviral treatment available, and access arrangements should be checked locally rather than assumed.
Where the exam tries to catch you
Cure, reactivation and extrahepatic disease are the favourite areas for examiner traps.
- Trap: equating normal ALT with cure. Correct: transaminases can normalise while virus persists, so cure is judged by HCV RNA at SVR12.
- Trap: ignoring genotype 3 in regimen choice. Correct: it is linked to hepatic steatosis and, among genotypes, is the hardest to cure with direct-acting antivirals in cirrhosis, so it matters in regimen choice (genotype 1 was the poor interferon responder, not genotype 3).
- Trap: missing hepatitis B reactivation. Correct: hepatitis B can flare during direct-acting antiviral therapy in people who carry the virus, so HBV status is checked before treatment and monitored during it.
- Trap: missing extrahepatic disease in the stem. Correct: mixed cryoglobulinaemia links to membranoproliferative glomerulonephritis and vasculitis, while lichen planus and porphyria cutanea tarda are common associations.
Frequently asked questions
What defines a cure of hepatitis C after direct-acting antiviral treatment?
Sustained virological response, defined as undetectable HCV RNA 12 weeks after completing therapy, is the marker of cure in hepatitis C. Normal ALT alone does not establish cure, because transaminases can normalise while virus remains detectable.
Which hepatitis C genotype is most common in India?
Genotype 3 is the most frequently cited genotype in much of India, with genotype 1 also found commonly. Regional proportions vary between studies, so the statement is best remembered as a general pattern rather than a fixed figure.
Why must hepatitis B be excluded before starting direct-acting antivirals for hepatitis C?
Hepatitis B reactivation can occur during direct-acting antiviral treatment in patients who are HBsAg positive or anti-HBc positive. Hepatitis B status is therefore checked before starting hepatitis C treatment, and HBV DNA is monitored during therapy.
Which extrahepatic manifestation of hepatitis C is linked to membranoproliferative glomerulonephritis?
Mixed cryoglobulinaemia is the classic extrahepatic manifestation of hepatitis C linked to membranoproliferative glomerulonephritis, vasculitis and purpura. Lichen planus and porphyria cutanea tarda are also associated with hepatitis C.
Is ribavirin still part of standard hepatitis C treatment?
Ribavirin is no longer part of standard first-line regimens and is added only in selected cases, such as some patients with cirrhosis or prior treatment failure, per current guidance. It causes haemolytic anaemia, which limited its use with older interferon-based regimens.