Javier Ampuero1, Carlota Jimeno2, Rosa Quiles3, José Miguel Rosales4, Susana Llerena5, Nieves Palomo6, Patricia Cordero7, Francisco Javier Serrano8, Juan José Urquijo9, José María Moreno-Planas10, Guillermo Ontanilla11, Marta Hernández12, Aída Ortega-Alonso13, Marta Maraver14, Martín Bonacci15, Ángela Rojas16, Blanca Figueruela2, Xavier Forns15, Raúl J Andrade13, José Luis Calleja12, Moisés Diago9, Isabel Carmona7, Manuel de la Mata8, María Buti6, Javier Crespo5, Juan Manuel Pascasio16, José María Navarro4, Javier Salmerón3, Manuel Romero-Gómez17. 1. Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Institute of Biomedicine of Seville and University of Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: javi.ampuero@gmail.com. 2. Unit for the Clinical Management of Digestive Diseases, Valme University Hospital, Sevilla, Spain. 3. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit, Complejo Hospitalario de Granada, Spain. 4. Gastroenterology Department, Agencia Sanitaria Costa del Sol, Marbella, Spain. 5. Liver Unit, Hospital Universitario Marqués de Valdecilla, Santander, Spain. 6. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Hepatology Unit, Hospital Universitario Vall d'Hebrón, Barcelona, Spain. 7. Inter-Centre Unit of Digestive Diseases, Virgen Macarena University Hospitals, Sevilla, Spain. 8. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Gastroenterology Department, Hospital Universitario Reina Sofia, Córdoba, Spain. 9. Liver Unit, Hospital General de Valencia, Spain. 10. Digestive Department, Complejo Hospitalario Universitario de Albacete, Spain. 11. Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain. 12. Gastroenterology Department, Hospital Universitario Puerta de Hierro, Madrid, Spain. 13. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain. 14. Gastroenterology Department, Hospital Universitario Juan Ramón Jiménez, Huelva. 15. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Liver Unit, Hospital Clinic and IDIBAPS, Barcelona, Spain. 16. Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Institute of Biomedicine of Seville and University of Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. 17. Unit of Digestive Diseases, Virgen del Rocio University Hospital, Sevilla, Spain; Institute of Biomedicine of Seville and University of Sevilla, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain. Electronic address: mromerogomez@us.es.
Abstract
BACKGROUND & AIMS: Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model. METHODS: This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes. RESULTS: A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups. CONCLUSIONS: The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy. LAY SUMMARY: The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.
BACKGROUND & AIMS:Patients with advanced liver fibrosis remain at risk of cirrhosis-related outcomes and those with severe comorbidities may not benefit from hepatitis C (HCV) eradication. We aimed to collect data on all-cause mortality and relevant clinical events within the first two years of direct-acting antiviral therapy, whilst determining the prognostic capability of a comorbidity-based model. METHODS: This was a prospective non-interventional study, from the beginning of direct-acting antiviral therapy to the event of interest (mortality) or up to two years of follow-up, including 14 Spanish University Hospitals. Patients with HCV infection, irrespective of liver fibrosis stage, who received direct-acting antiviral therapy were used to build an estimation and a validation cohort. Comorbidity was assessed according to Charlson comorbidity and CirCom indexes. RESULTS: A total of 3.4% (65/1,891) of individuals died within the first year, while 5.4% (102/1,891) died during the study. After adjusting for cirrhosis, platelet count, alanine aminotransferase and sex, the following factors were independently associated with one-year mortality: Charlson index (hazard ratio [HR] 1.55; 95% CI 1.29-1.86; p = 0.0001), bilirubin (HR 1.39; 95% CI 1.11-1.75; p = 0.004), age (HR 1.06 95% CI 1.02-1.11; p = 0.005), international normalized ratio (HR 3.49; 95% CI 1.36-8.97; p = 0.010), and albumin (HR 0.18; 95% CI 0.09-0.37; p = 0.0001). HepCom score showed a good calibration and discrimination (C-statistics 0.90), and was superior to the other prognostic scores (model for end-stage liver disease 0.81, Child-Pugh 0.72, CirCom 0.68) regarding one- and two-year mortality. HepCom score identified low- (≤5.7 points: 2%-3%) and high-risk (≥25 points: 56%-59%) mortality groups, both in the estimation and validation cohorts. The distribution of clinical events was similar between groups. CONCLUSIONS: The HepCom score, a combination of Charlson comorbidity index, age, and liver function (international normalized ratio, albumin, and bilirubin) enables detection of a group at high risk of one- and two-year mortality, and relevant clinical events, after starting direct-acting antiviral therapy. LAY SUMMARY: The prognosis of patients with severe comorbidities may not benefit from HCV viral clearance. An algorithm to decide who will benefit from the treatment is needed to manage the chronic HCV infection better.
Authors: Patricia Amoros-Reboredo; Dolors Soy; Marta Hernandez-Hernandez; Sabela Lens; Conxita Mestres Journal: Int J Environ Res Public Health Date: 2020-05-26 Impact factor: 3.390