Impact of distinct antiviral treatment regimens on the long-term outcome after HCV cure – Data from the German Hepatitis C-Registry (DHC-R)

Abstract

Background

Direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infection are endowed with sustained virological response (SVR) rates >95%. However, HCV cure does not completely eliminate the risk of hepatocellular carcinoma (HCC) development and liver decompensation. The present study investigated the impact of the administered DAA regimen on clinical long-time outcomes after SVR.

Methods

Matched-pair survival analyses of 5802 chronically HCV infected patients from the German Hepatitis C-Registry compared the incidence of liver-related events 2.5 years after SVR in patients receiving either sofosbuvir (SOF)-based treatment or NS3/NS4A-protease inhibitor (PI)-containing DAA regimens. Hypothesis driven logistic regression analyses were performed to identify independent predictors for the occurrence of liver-related events.

Results

Matched-pair survival analyses revealed a borderline significant difference in the incidence of liver-related endpoints (except of HCC development) in patients receiving SOF-based treatment (4.1%) compared to PI-containing DAA regimens (2.6%) 2.5 years after SVR (p=0.061). Numerically, a trend towards a benefit of PI-based DAA treatment was observed (PI 65 events vs SOF 102 events). Hypothesis driven logistic regression analyses could not confirm SOF-based treatment as an independent predictor for the occurrence of liver-related events after HCV cure (p=0.072, OR=0.670).

Conclusions

The incidence of liver-related events 2.5 years after HCV cure did not differ significantly between SOF-based DAA treatment and PI-containing regimens. However, numerically a trend towards a benefit of PI-based DAA treatment was observed. Therefore, a minor effect of the applied DAA regimen on the long-term incidence of liver-related events cannot be excluded.

Zusammenfassung

Hintergrund

Direkt wirkende antivirale Agenzien (DAA) zur Behandlung von Hepatitis-C-Virus (HCV)-Infektionen weisen eine hohe virologische Ansprechrate (SVR) von über 95% auf. Die Ausheilung der HCV-Infektion schließt jedoch das Risiko der Entwicklung eines hepatozellulären Karzinoms (HCC) und einer Leberdekompensation nicht vollständig aus. In der vorliegenden Studie wurde untersucht, wie sich das verabreichte DAA-Regime auf klinische Langzeitereignisse nach SVR auswirkt.

Methoden

Mittels Matched-Pair-Überlebensanalysen von 5802 chronisch HCV-infizierten Patienten aus dem Deutschen Hepatitis-C-Register wurde die Inzidenz leberbezogener Ereignisse 2,5 Jahre nach SVR bei Patienten verglichen, die entweder eine Behandlung auf der Basis von Sofosbuvir (SOF) oder eine NS3/NS4A-Proteaseinhibitor (PI)-haltige DAA-Therapie erhielten. Zudem wurden hypothesengesteuerte logistische Regressionsanalysen durchgeführt, um unabhängige Prädiktoren für das Auftreten von leberbedingten Ereignissen zu identifizieren.

Ergebnisse

Matched-Pair-Überlebensanalysen ergaben einen grenzwertig signifikanten Unterschied in der Inzidenz leberbezogener Endpunkte (mit Ausnahme der Entwicklung von HCC) bei Patienten, die eine SOF-basierte Behandlung (4,1%) im Vergleich zu PI-haltigen DAA-Behandlungen (2,6%) 2,5 Jahre nach SVR erhielten (p=0,061). Numerisch wurde ein Trend zu einem Vorteil der PI-basierten DAA-Behandlung beobachtet (PI 65-Ereignisse gegenüber SOF 102-Ereignisse). Hypothesengeleitete logistische Regressionsanalysen konnten die SOF-basierte Behandlung nicht als unabhängigen Prädiktor für das Auftreten von leberbezogenen Ereignissen nach HCV-Heilung bestätigen (p=0,072, OR=0,670).

Schlussfolgerungen

Die Inzidenz leberbezogener Ereignisse 2,5 Jahre nach Ausheilung unterschied sich nicht signifikant zwischen einer SOF-basierten DAA-Behandlung und PI-haltigen Regimen. Zahlenmäßig ergab sich jedoch ein Trend zu einem Vorteil der PI-basierten DAA-Behandlung. Daher kann eine geringfügige Auswirkung des verwendeten DAA-Schemas auf die langfristige Inzidenz leberbedingter Ereignisse nicht ausgeschlossen werden.

Keywords

Liver - hepatitis C - viral hepatitis - direct acting antivirals (DAA) - hepatocellular carcinoma - sustained virological response - liver cirrhosis - long-term follow up - survival

Schlüsselwörter

Leber - Virushepatitis - Hepatitis C - direkt wirkende antivirale Medikamente (DAA) - hepatozelluläres Karzinom - anhaltendes virologisches Ansprechen - Leberzirrhose - Langzeitnachbeobachtung - Überleben

Publikationsverlauf

Eingereicht: 11. November 2024

Angenommen nach Revision: 20. Februar 2025

Artikel online veröffentlicht:
13. Mai 2025

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