Clinical trial NCT03149289: Hepatitis C Virus Infection in Patients With Hemoglobinopathies
Official title: Treatment of Hepatitis C Virus Infection With Direct-acting Antiviral Drugs in Patients With Hemoglobinopathies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatitis C, Chronic
Hemoglobinopathies
Lead sponsor: Società Italiana Talassemie ed Emoglobinopatie
Sponsor class: OTHER
Collaborators: name: University of Cagliari
name: University of Turin, Italy
name: Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
name: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
name: Ente Ospedaliero Ospedali Galliera
name: University of Campania Luigi Vanvitelli
name: Cardarelli Hospital
name: Reggio Calabria
name: University of Palermo
First posted: 2017-05-11
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patient with hemoglobinopathies with cronic hepatitis C

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in the number of participants with undetectable serum HCV RNA is being assessed at the end of treatment
timeFrame: baseline and 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Palermo, Palermo, Italy
name: Vito Di Marco, MD
role: STUDY_DIRECTOR
References: