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Clinical outcome and hemodynamic changes following HCV eradication with oral antiviral therapy in patients with clinically significant portal hypertension

  • Author Footnotes
    † Both authors share first co-authorship.
    Sabela Lens
    Footnotes
    † Both authors share first co-authorship.
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Author Footnotes
    † Both authors share first co-authorship.
    Anna Baiges
    Footnotes
    † Both authors share first co-authorship.
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Edilmar Alvarado-Tapias
    Affiliations
    Gastroenterology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Elba LLop
    Affiliations
    Liver Unit, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Majadahonda, Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Javier Martinez
    Affiliations
    Servicio de Gastroenterologia y Hepatología, Hospital Universitario Ramon y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Jose Ignacio Fortea
    Affiliations
    Digestive Diseases Department, Marqués de Valdecilla University Hospital, IDIVAL, Santander, Spain
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  • Luís Ibáñez-Samaniego
    Affiliations
    Liver Unit, Hospital Gregorio Marañón, Facultad de Medicina, Universidad Complutense Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Zoe Mariño
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Sergio Rodríguez-Tajes
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Adolfo Gallego
    Affiliations
    Gastroenterology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Rafael Bañares
    Affiliations
    Liver Unit, Hospital Gregorio Marañón, Facultad de Medicina, Universidad Complutense Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Ángela Puente
    Affiliations
    Digestive Diseases Department, Marqués de Valdecilla University Hospital, IDIVAL, Santander, Spain
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  • Agustín Albillos
    Affiliations
    Servicio de Gastroenterologia y Hepatología, Hospital Universitario Ramon y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Jose Luis Calleja
    Affiliations
    Liver Unit, Hospital Universitario Puerta de Hierro, Universidad Autónoma de Madrid, Majadahonda, Madrid, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Xavier Torras
    Affiliations
    Gastroenterology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Virginia Hernández-Gea
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Jaume Bosch
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)

    Hepatology, Inselspital, Bern University, Bern, Switzerland
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  • Cándid Villanueva
    Affiliations
    Gastroenterology Department, Hospital Santa Creu i Sant Pau, Barcelona, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Juan Carlos García-Pagán
    Correspondence
    Corresponding author. Address: Head Barcelona Hepatic Hemodynamic Lab, Senior Consultant in Hepatology, Associate Professor University of Barcelona, Liver Unit, Hospital Clínic, Villarroel 170, Barcelona (08036), Spain. Tel.: (+34)93 2275753.
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
    Search for articles by this author
  • Xavier Forns
    Affiliations
    Liver Unit, Hospital Clínic, Barcelona, Universidad de Barcelona, IDIBAPS, Spain

    Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD)
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  • Author Footnotes
    † Both authors share first co-authorship.

      Highlights

      • HVPG ≥10 mmHg persists 2 years after therapy in 53–65% of patients with HCV-related cirrhosis despite HCV eradication.
      • Changes in liver stiffness do not correlate with changes in HVPG after a sustained virological response.
      • Baseline HVPG ≥16 mmHg and ascites identify patients with persistent CSPH and risk of decompensation.

      Background & Aims

      Clinically significant portal hypertension (CSPH), defined as a hepatic venous pressure gradient (HVPG) ≥10 mmHg, persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct-acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population.

      Methods

      We conducted a prospective multicenter study in 226 patients with HCV-related cirrhosis and CSPH who achieved SVR after antiviral therapy. Patients with CSPH 24 weeks after end of treatment (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96).

      Results

      All patients were clinically evaluated. Out of 176 patients with CSPH at SVR24, 117 (66%) underwent an HVPG measurement at SVR96. At SVR96, 55/117 (47%) patients had HVPG <10 mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥16 mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13 kPa) but did not correlate with HVPG changes (30% of patients with liver stiffness measurement <13.6 kPa still had CSPH). Seventeen (7%) patients presented with de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥16 mmHg and history of ascites.

      Conclusions

      Patients achieving SVR experienced a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53–65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.

      Lay summary

      As a major complication of cirrhosis, clinically significant portal hypertension (CSPH) is associated with adverse clinical outcomes. Herein, we show that CSPH persists at 96 weeks in just over half of patients with HCV-related cirrhosis, despite HCV elimination by direct-acting antivirals. Despite viral cure, patients with CSPH at the start of antiviral treatment remain at long-term risk of hepatic complications and should be managed accordingly.

      Graphical abstract

      Keywords

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