Successful retreatment with glecaprevir/pibrentasvir after sofosbuvir/velpatasvir failure in a patient with hepatitis C-related decompensated cirrhosis complicated by hepatocellular carcinoma.

Direct-acting antivirals (DAAs) markedly improve sustained virologic response (SVR) rates in chronic hepatitis C virus (HCV) infection, including decompensated cirrhosis. However, retreatment options remain limited in patients with decompensated cirrhosis after DAA failure. We experienced a case of decompensated cirrhosis that was successfully retreated with glecaprevir/pibrentasvir (GLE/PIB) after sofosbuvir/velpatasvir (SOF/VEL) failure. The patient was a woman in her 70 s with HCV genotype 1b and an HCV RNA level of 7.1 log IU/mL. The Child-Pugh classification was class B, with a score of 7. The albumin-bilirubin (ALBI) score was - 1.99, with a modified ALBI grade of 2b. Screening prior to antiviral therapy detected multifocal hepatocellular carcinoma (HCC). She initially underwent treatment for HCC and esophageal varices, achieving a cancer-free status. SOF/VEL was subsequently initiated, but virologic relapse occurred. Resistance testing detected NS5A substitutions (L31I/M and Y93H) without P32 deletion. Seven months after completing SOF/VEL, the patient's Child-Pugh score had improved to 6, although she was still receiving oral branched-chain amino acids. Because established retreatment options for decompensated cirrhosis after SOF/VEL failure are scarce, she underwent GLE/PIB therapy after institutional ethics approval and achieved SVR. This case highlights the practical challenges of managing DAA failure in patients with decompensated cirrhosis and suggests that carefully selected retreatment may be feasible after stabilization of hepatic decompensation, although safety considerations remain paramount.