Chronic Hepatitis C With Multiple Therapeutic Failures: Case Report With Virological Resistance, Advanced Cirrhosis, and Possible Sustained Response After a Third Direct-Acting Antiviral Regimen

Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver. Generally transmitted through contact with contaminated blood, infection may remain silent for years and progress to liver cirrhosis, liver failure, and hepatocellular carcinoma. Modern treatment with direct-acting antivirals (DAAs) has significantly improved prognosis, but some cases of resistance and relapse, such as the present one, remain a clinical challenge. This report describes the case of a 54-year-old man diagnosed with chronic hepatitis C 10 years earlier. Genotype 1a, treatment-naïve until 2021. Former substance and tobacco user, abstinent for 8 years. Initial clinical assessment showed METAVIR F4 by liver elastography, alpha-fetoprotein of 25 ng/mL, and hepatitis C viral load of 917,533 copies/mL in September 2021. Laboratory tests showed hepatic and hematological impairment, with thrombocytopenia and elevated liver enzymes. Imaging studies revealed chronic cholecystitis and portal hypertension. Treatment was initiated in November 2021 with ledipasvir 90 mg, sofosbuvir 400 mg, and ribavirin 500 mg for 24 weeks, resulting in negative PCR immediately after treatment completion. However, relapse occurred in November 2022, with viral load of 1,256,646 copies/mL. In 2023, the patient was treated with sofosbuvir and velpatasvir for 24 weeks, achieving temporary PCR negativity, followed by viral load rebound in August 2023 to 167,680 copies/mL. Despite relapse and failure to achieve sustained response, the patient refused liver transplantation. Endoscopic examinations revealed esophageal varices, treated with repeated elastic band ligation. In December 2023, a new treatment with glecaprevir and pibrentasvir was initiated and completed in September 2024. Six months after treatment completion, HCV PCR remained negative, suggesting possible cure. The patient remains under observation with regular monitoring of viral load and liver function while awaiting transplant eligibility. Viral resilience and resistance required successive therapeutic adjustments and consideration for inclusion in a liver transplantation protocol. Case reports such as this emphasize the complexity of hepatitis C treatment in patients with multiple treatment failures, underscoring the importance of careful follow-up and individualized therapeutic approaches.