Treatment of Chronic Hepatitis C with Decompensated Cirrhosis After Prior DAA Treatment Failure

This protocol covers adults with chronic hepatitis C infection who also have decompensated cirrhosis and a history of sofosbuvir- or NS5A inhibitor-based direct-acting antiviral (DAA) treatment failure — a clinically distinct population with constrained retreatment options.

Clinical Scenario

The patient has chronic hepatitis C with decompensated cirrhosis and has previously failed a sofosbuvir- or NS5A inhibitor-based DAA regimen. Retreatment in this setting is limited by the inability to use NS3/4A protease inhibitors given the decompensated hepatic state, which significantly narrows the therapeutic landscape.

Treatment Goal

Sustained virologic response 12 weeks after completion of therapy (SVR12) — confirmed undetectable HCV RNA.

Retreatment Approach (partial overview)

Guidelines support a combination antiviral regimen incorporating ribavirin, with regimen selection guided by HCV genotype and the degree of hepatic decompensation. Complete regimen details are available in the structured protocol below.

Instant Access to Structured Evidence-Based Regimens
References
DOI: 10.1093/cid/ciad319

Retreatment of persons with decompensated cirrhosis and a history of DAA-based treatment failure is limited by the inability to use an NS3/4A protease inhibitor (eg, glecaprevir, grazoprevir, voxilaprevir) in the setting of decompensated cirrhosis.

Recommendations to retreat with a 24-week course of either sofosbuvir/velpatasvir plus weight-based ribavirin or ledipasvir/sofosbuvir plus weight-based ribavirin are based on the relatively favorable SVR rates (91% to 100%) with these regimens among patients with compensated cirrhosis and prior DAA failure.

Low initial dose of ribavirin (600 mg) is recommended for patients with CTP class C cirrhosis; increase as tolerated.

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