Management of HCV-Related Liver Disease in Hemophilia and Thalassemia

Abstract

Chronic infection with the hepatitis C virus (HCV) has long been the dominant complication of substitution therapy in patients with inherited blood disorders and the cause of anticipated death due to end-stage liver disease. In hemophilia, transmission of HCV with clotting factors concentrates started to be curbed in the mid-1980s following the adoption of procedures of virus inactivation of concentrates based on heat, whereas in the 1990s treatment of HCV infection with interferon monotherapy was attempted, however, with little success. The advent of combination therapy of interferon with ribavirin led to a substantial improvement of treatment outcome (40% rate of cure), that however was still of limited efficacy in patients with advanced liver disease, those with high load of HCV genotype 1, and patients coinfected with the human immunodeficiency virus. In this latter population, while the course of hepatitis C was accelerated as a consequence of immunodeficiency, the advent of highly active antiretroviral therapy led acquired immunodeficiency syndrome (AIDS) to decline and hepatitis C to progressively emerge as a dominant cause of mortality, in parallel. In patients with thalassemia, transfusion-related transmission of HCV was efficiently interrupted in 1992 with the advent of sensitive screening tests for testing donors for HCV, whereas treatment with interferon and ribavirin of infected thalassemics was constrained by an increased risk of anemia due to the hemolytic properties of ribavirin coupled with interferon-induced bone marrow suppression. The advent of safe and potent regimens based on the oral administration of direct antiviral agents has revolutionized therapy of HCV in patients with congenital blood diseases, providing substantial clinical benefits and making elimination of infection in these populations, possible.

Effectiveness of implementing a decentralized delivery of hepatitis C virus treatment with direct-acting antivirals: A systematic review with meta-analysis

“…People with HIV and/or HBV coinfections and other comorbidities (e.g. haemophilia, thalassemia, kidney disfunction) should be referred to specialists [42,43].…”

“…Specialists will be necessary to manage patients with specific clinical conditions (e.g. cirrhosis, coinfections, and comorbidities) to reduce the adverse events and improve the treatment efficacy in these cases [40,42,43]. Innovative decentralization strategies could be implemented to improve access to HCV treatment, especially in resource-limited settings, contributing to the achievement of HCV elimination targets.…”

Iron chelating properties of Eltrombopag: Investigating its role in thalassemia-induced osteoporosis

“…We demonstrated that iron overload, through up-regulation of TRAP expression, causes overactivity of osteoclasts (OCs) in TM and that normal functional levels can be restored with chelation therapy, suggesting the possibility that oral chelation could alleviate TM-associated OP [5]. TM patients are exposed to an high risk of hepatitis C (HCV) due to the frequent blood transfusions [17]. HCV infection causes an abnormal thrombocyte function and has been shown to be associated with a low platelet count [16].…”

“…In general, HCV infection is associated with a reduced platelet count [16]. Chronic infection with the HCV has been for long time the major co-morbidity in patients with inherited blood disorders such as TM [17]. Another property of ELT is to bind to metal ions and in particular to iron (III).…”

HCV Infection in Thalassemia Syndromes and Hemoglobinopathies: New Perspectives

“…The remaining 75-85% of them make the infection chronic, developing cirrhosis that can be complicated by liver failure and hepatocellular carcinoma. In several studies from different population of thalassemic patients (United States, Italy and Greece) the prevalence of cirrhosis ranged from 10 to 20% and the incidence of HCC in thalassemia patients was progressively increasing (Voskaridou et al, 2012;Borgna-Pignatti et al, 2014;Chung et al, 2015;Moukhadder et al, 2017;Rumi et al, 2018;Hodroj et al, 2019). These data have made an intervention to eradicate HCV infection more urgent.…”