Hepatitis C Virus Infection in Patients With Hemoglobinopathies

Treatment of Hepatitis C Virus Infection With Direct-acting Antiviral Drugs in Patients With Hemoglobinopathies

Progression of liver fibrosis in patients with hemoglobinopathies is strongly related to the severity of iron overload and the presence of chronic hepatitis C virus (HCV) infection. Effective iron chelation therapy and HCV infection eradication are efficacy to prevent liver complications. EASL and AASLD guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. However, data regarding the use of direct-acting antiviral drugs (DAAs) in this patient population are very few This large, observational study evaluated the safety and efficacy of standard therapy with DAAs in a large Italian cohort of with hemoglobinopathies, chronic HCV infection and advanced liver fibrosis.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic; Hemoglobinopathies
• Intervention / Treatment: Drug: Antiviral drugs

Detailed Description

Many patients with hemoglobinopathies have been infected with hepatitis C virus (HCV) through blood transfusion, mostly before screening of blood donors was introduced in 1992. The reported prevalence of anti-HCV-positive thalassemia patients varies between 4.4% in Turkey and 85.4% in Italy. HCV infection is associated with decompensated cirrhosis, hepatocellular carcinoma and other liver complications, especially if left untreated. Prevalence of cirrhosis in thalassemia patients up to 32% have been reported.

Thalassemia patients with cirrhosis have an increased risk of death. Progression of liver fibrosis is strongly related to the presence of chronic HCV infection and extent of iron overload. Thalassemia patients with elevated serum aminotransferase levels for >6 months should be tested for HCV infection and, in the event of HCV infection, HCV genotyping is recommended in order to plan antiviral therapy and the likelihood of response. Noninvasive transient elastography (FibroScan®) can be used to determine the presence of fibrosis in thalassemia patients with HCV infection.

Effective chelation therapy and treatment of HCV infection are needed in order to prevent liver complications and decrease morbidity and mortality. For many years, pegylated interferon (peg-IFN) plus ribavirin was the standard of care for the treatment of chronic HCV infection and decompensated cirrhosis. Studies of peg-IFN plus ribavirin have demonstrated sustained virological response (SVR) rates of 25-64% in patients with thalassemia and HCV infection. However, peg-IFN and ribavirin are both associated with anemia. Ribavirin-associated hemolysis leads to an increased requirement for blood transfusions, which in turn can lead to worsening of iron overload. Therefore, European Association for the Study of the Liver (EASL) 2015 guidelines recommend interferon-free regimens for the treatment of HCV infection in patients with hemoglobinopathies. The aim of this study was to evaluate the safety and efficacy of DAA standard regimens in patients with hemoglobinopathies and chronic HCV liver disease treated in Italy.

Antiviral treatments were administered according to Italian Medicines Agency (AIFA) guidelines.

• Study Type: Observational
• Enrollment (Actual): 168

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

Patient with hemoglobinopathies with cronic hepatitis C

Description

Inclusion Criteria:

• Patients with hemoglobinopathies, chronic hepatitis due to HCV and the presence of fibrosis (defined as Fibroscan® stiffness ≥10 kPa) or a bioptic evaluation of cirrhosis (same ISHAK fibrosis score) determined within 6 months previously. Patients with extrahepatic manifestations of chronic hepatitis C virus infection (cryoglobulinemia with organ damage, B-lymphoproliferative disorders) were also included.

Exclusion Criteria:

• Patients with active cancer, including hepatocellular carcinoma, and pregnant or lactating females were excluded from the study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
HCV RNA positive; hemoglobinopathies with hepatites C treated with antiviral drugs	Drug: Antiviral drugs; sofosbuvir, ribavirin, daclatasvir, ledipasvir, simeprevir, paritaprevir, dasabuvir, ombitasvir; Other Names: Direct-acting antiviral drugs'

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the number of participants with undetectable serum HCV RNA is being assessed at the end of treatment	The quantification of hepatitis virus particles in serum is assessed and expressed in IU/mL (IU, international units ) through quantitation of virus ribonucleic acid by real time polymerase chain reaction (PCR).	baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Società Italiana Talassemie ed Emoglobinopatie
• Collaborators: University of Palermo; University of Campania "Luigi Vanvitelli"; Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico; University of Turin, Italy; University of Cagliari; Reggio Calabria; Ente Ospedaliero Ospedali Galliera; Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello; Cardarelli Hospital
• Investigators: Study Director: Vito Di Marco, MD, University of Palermo, Palermo, Italy

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: April 14, 2017
• First Submitted That Met QC Criteria: May 9, 2017
• First Posted (Actual): May 11, 2017

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: May 9, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Hematologic Diseases; Liver Diseases; Genetic Diseases, Inborn; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis C, Chronic; Hemoglobinopathies; Anti-Infective Agents; Antiviral Agents
• Other Study ID Numbers: HCV-SITE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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