Prediction of Liver-related Outcomes After HCV Cure

Development of a Predictive Model of Liver Complications Emergence in Patients With Advanced Fibrosis Who Achieve Sustained Virological Response With Direct-acting Antivirals-based Therapy

Objectives: To develop and validate a predictive model, applicable to daily practice, of liver complications emergence in hepatitis C virus (HCV)-infected patients and advanced fibrosis, who have achieved sustained viral response (SVR) with direct-acting antivirals (DAA)-based therapy.

Methods:

Design: Mulsite prospective multicenter cohort study. Study subjects: HCV-monoinfected and HIV/HCV-coinfected individuals recruited from two parallel cohorts (GEHEP-MONO Cohort clinicaltrials.gov ID: NCT02333292(HEPAVIR-DAA Cohort clinicaltrials.gov ID: NCT02057003). These cohorts enrolled patients with HCV infection, treated with DAA-based regimens after October 2011, at the units of infectious diseases of 18 hospitals throughout Spain. Patients who fullfilled the following inclusion criteria are included in this study: 1) Have received a regimen with one or more DAA; 2) Have achieved SVR 12 weeks after treatment; 3) Have an evaluable liver stiffness (LS) of more than 9.5 kPa in the three months prior to the start of treatment.

Follow-up: The baseline time point is the date of SVR. All participants are evaluated by a common protocol every six months. At every visit, clinical and laboratory examination focusing on the early detection of liver complications are carried out. LS is assessed by vibration-controlled transient elastography, according to a standardized procedure, every 12 months. In patients with cirrhosis, liver ultrasound and plasma alpha-fetoprotein determination are conducted for hepatocellular carcinoma screening, every six months.

Variables and data analysis: The primary outcome variable of the study will be the emergence of liver complication (hepatic decompensation or hepatocellular carcinoma) or liver transplant. Predictive models will be develop with clinical, analytical, and genetic variables independently associated with the primary variable in a Cox regression for competitive risks applied to a developmental subpopulation. The performance of the model will be evaluated using COR curves. Sensitivity, specificity, and positive and negative predictive values will be calculated, both in the developmental population and in a validation population.

Study Overview

• Status: Unknown
• Conditions: Hepatocellular Carcinoma; Hepatitis C, Chronic; Hepatic Decompensation; Sustained Virological Response; Direct-acting Antivirals

• Study Type: Observational
• Enrollment (Anticipated): 1035

Contacts and Locations

Study Locations

• Spain
  • Sevilla, Spain, 41014
    • Recruiting
    • Hospital Universitario de Valme
    • Contact: ANAIS CORMA-GOMEZ, MD; Phone Number: 0034955015799; Email: anais.corgo@gmail.com
    • Principal Investigator: ANAIS CORMA-GOMEZ, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

HIV/HCV-coinfected and HCV-monoinfected individuals from two parallel cohorts (HEPAVIR-DAA Cohort clinicaltrials.gov ID: NCT02057003; GEHEP-MONO Cohort clinicaltrials.gov ID: NCT02333292). These cohorts enrolled patients with HCV infection, treated with DAA-based regimens after October 2011, at the units of infectious diseases of 18 hospitals throughout Spain. Subjects were included if they fulfilled the inclusion criteria.

Description

Inclusion Criteria:

• Had achieved SVR 12 weeks after DAA-based regimen, either with or without Peg-interferon
• Showed liver stiffness (LS) value ≥9.5 kPa prior to treatment
• Had LS measurement available at SVR time-point

Exclusion Criteria:

• Individuals seropositive for HBsAg
• Individuals who refuse to participate
• Individuals under 18 years old

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver complications emergence	Appearance of hepatocellular carcinoma, portal hypertensive gastrointestinal bleeding, ascites, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorrenal syndrome and acute on chronic liver failure after SVR	From the inclusion until death, liver transplant, HCV reinfection or the censoring date (final study date)

Collaborators and Investigators

• Sponsor: Hospital Universitario de Valme
• Collaborators: Instituto de Salud Carlos III

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): December 31, 2021

Study Registration Dates

• First Submitted: July 2, 2020
• First Submitted That Met QC Criteria: July 2, 2020
• First Posted (Actual): July 7, 2020

Study Record Updates

• Last Update Posted (Actual): July 7, 2020
• Last Update Submitted That Met QC Criteria: July 2, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: GEHEP-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No