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Z Gastroenterol 2020; 58(05): 451-455
DOI: 10.1055/a-1131-8058
Kasuistik

Successful fourth line treatment of a relapse patient with chronic hepatitis C virus infection genotype 3a using sofosbuvir, glecaprevir/pibrentasvir, and ribavirin: a case report

Erfolgreiche Viertlinien-Therapie einer Patientin mit chronischer Hepatitis-C-Virusinfektion mit Sofosbuvir, Glecaprevir/Pibrentasvir und Ribavirin: Ein Fallbericht
Benedikt Bernhard 
1   Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland
2   Department of Cardiology, University Hospital Bern, Switzerland.
,
Felix Stickel 
1   Hepatology Unit, Clinic Beau-Site, Hirslanden Bern, Bern, Switzerland
3   Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland
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Abstract

Background Relapses after therapy with direct-acting antiviral agents (DAA) in chronic hepatitis C virus (HCV) infections are rare due to high efficacy of interferon-free therapy regimens. The presence of resistance-associated substitutions (RAS) in proteins targeted by therapy can lead to lower rates of sustained virological response (SVR) in patients receiving DAA-therapy, and little evidence exists as to how to treat these patients.

Case Summary We present a case of a multi-drug-resistant HCV-genotype-3a-infection in a 50-year-old female without confirmed cirrhosis but with advanced fibrosis (liver stiffness 11.6 kPa) and low viral load. Resistance testing revealed a Y93H mutation in the NS5A gene. Therapies using sofosbuvir and daclatasvir (1st), sofosbuvir, velpatasvir and ribavirin (2nd), and subsequently with sofosbuvir, velpatasvir, and voxilaprevir (3st) did not achieve SVR. Compliance was good with rapid negativity of HCV RNA at 4 weeks of treatment on all 3 occasions. No virological breakthrough was recorded with all regimens. As a rescue attempt, the patient received 24 weeks of sofosbuvir, glecaprevir/pibrentasvir, and weight-based ribavirin at 1000 mg. With this approach, she achieved SVR but developed hepatocellular carcinoma.

Conclusion The combination of sofosbuvir, glecaprevir/pibrentasvir and ribavirin could be a rescue therapy after previous relapses on DAA-therapy, especially in patients with relapse after therapy with sofosbuvir, velpatasvir, and voxilaprevir.

ZusamMenfassung

Hintergrund Rückfälle nach einer Therapie mit direkt antiviral wirkenden Substanzen (DAA) bei Patienten mit chronischer Virushepatitis C (HCV) sind aufgrund der hohen Wirksamkeit dieser Therapeutika selten. Das Auftreten von resistenzassoziierten Substitutionen (RAS) in Proteinen, auf die die Therapie abzielt, kann eine anhaltende Viruselimination (SVR) verhindern, und es existiert wenig Evidenz dazu, wie diese Patienten anschließend behandelt werden sollten.

Fallbeschreibung Wir berichten von einer 50-jährigen Patientin mit einer therapieresistenten HCV-Genotyp-3a-Infektion ohne bestätigte Leberzirrhose, aber mit fortgeschrittener Fibrose (Lebersteifigkeit 11,6 kPa) und niedriger Viruslast. Resistenztestungen zeigten eine Y93H-Mutation im NS5A-Gen des Virus. Mehrere Therapieversuche mit Sofosbuvir und Daclatasvir (1.), Sofosbuvir, Velpatasvir und Ribavirin (2.) und mit Sofosbuvir, Velpatasvir und Voxilaprevir (3.) konnten kein SVR erreichen. Es ergaben sich keine Hinweise auf eine eingeschränkte Compliance, da es jeweils nach vier Wochen zu einer schnellen und über den Therapiezeitraum persistierenden Negativierung der Viruslast kam. Als letzte Alternative erhielt die Patientin eine 24-wöchige Therapie mit Sofosbuvir, Glecaprevir/Pibrentasvir und gewichtsadaptiert 1000 mg Ribavirin. Damit erreichte sie ein SVR, entwickelte aber ein hepatozelluläres Karzinom.

Schlussfolgerung Die Kombination von Sofosbuvir, Glecaprevir/Pibrentasvir und Ribavirin kann eine effektive Therapie nach Rückfällen auf eine vorherige DAA-Therapie darstellen, insbesondere, wenn ein SVR nach Gabe von Sofosbuvir, Velpatasvir und Voxilaprevir ausbleibt.

Key words

chronic hepatitis C virus infection - direct-acting antiviral therapy - resistance-associated species - voxilaprevir relapse - case report

Schlüsselwörter

Chronische Hepatitis-C-Virusinfektion - direkt antiviral wirkende Substanzen - resistenzassoziierte Mutationen - Voxilaprevir - Therapieversagen - Fallbericht


Publication History

Received: 23 January 2020

Accepted: 01 March 2020

Article published online:
11 May 2020

© Georg Thieme Verlag KG
Stuttgart · New York

 

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