Viral Hepatitis B and C Infection in Patients With Idiopathic Thrombocytopenic Purpura Treated With Triple Therapy

Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia in the absence of other causes.ITP is mediated by antiplatelet autoantibodies. Antibody-coated platelets are phagocytosed by macrophages in the reticuloendothelial system, leading to accelerated platelet clearance. Macrophages also act as antigen-presenting cells interacting with CD8+ and CD4+ T cells that in turn stimulate antibody-producing B cells.This pathogenic loop sustains autoantibody production. T cell-mediated platelet lysis and megakaryocyte immunoinjury contribute to the diverse pathobiology of ITP.

Single-agent treatments have not been successful at inducing prolonged remission.With immunosuppressive monotherapy, ITP patients usually require prolonged treatment, leading to unpleasant and sometimes serious side effects.

Recent studies combining dexamethasone and rituximab in short courses have reported encouraging results.it is postulated that adding cyclosporine to this combination may induce a more enduring remission by also targeting T cells and thereby briefly suppressing all 3 immune cell types implicated in sustaining the pathogenic loop.

Suppressing these cells simultaneously has a risk of predisposing to serious infections.it is considered it appropriate to conduct a pilot study on a small number of patients with the aim of investigating the safety and efficacy of the triple therapy.

Infectious complications, mainly caused by the use of corticosteroids and other immunosuppressive agents, are a major cause of morbidity in patients with cITP. Moreover, infections may trigger autoimmune diseases and, at least theoretically, may be a complication of an already impaired immune system. It has been reported that children have an increased incidence of infection before diagnosis of ITP.

Hepatitis B (HBV) and C (HCV) virus infections are blood-borne viruses that pose major public health threats worldwide. The World Health Organization (WHO) report released in April 2017 on the status of hepatitis worldwide documented that 1.75 million new cases of HCV infection occurred in 2015, with about 71 million people already infected, the Eastern Mediterranean region has the highest HCV prevalence rate in the world According to WHO, in 2017 Egypt had the highest HCV prevalence rate in the world . According to the IHME in 2016, there were 4,002,706 men and 3,757,236 women with chronic HCV. HCV prevalence was estimated to be 11.9% among the general population (populations at relatively low risk of exposure to HCV, such as healthy children, blood donors, antenatal clinic attendees and pregnant women), 55.6% among populations at high risk (PWID, hemodialysis, multitransfused individuals and hemophiliacs), 14.3% among populations at intermediate risk (household contacts of HCV-infected individuals, prisoners, individuals with diabetes and healthcare workers), 56.0% among populations with liver-related conditions (acute viral hepatitis, liver cirrhosis, chronic liver disease, hepatocellular carcinoma and non-Hodgkin's lymphoma) and 35.0% among special clinical populations (dermatological manifestations, rheumatologic disorders and non-liver-related malignancies Thrombocytopenia can also complicate bleeding manifestations such as variceal bleeding. It may impede the initiation and continuation of antiviral therapy, potentially decreasing the probability of successful HCV reatment.Recent studies have evaluated the underlying mechanism of thrombocytopenia in chronic HCV infection and assessed the usefulness of several therapeutic options.

Besides hepatic complications, chronic HCV infection is also associated with several extra-hepatic manifestations including thrombocytopenia. Thrombocytopenia in chronic Hcv infection is a major problem, particularly in patients with advanced liver disease. The risk of serious bleeding with severe thrombocytopenia can prevent invasive procedures including biopsies for staging.

The pathophysiology of thrombocytopenia in patients with HCV infection is thought to be multifactorial. Besides inducing an autoimmune reaction with production of antiplatelet antibodies, the virus also causes direct bone marrow suppression with resulting thrombocytopenia , chronic HCV infection induced liver fibrosis and cirrhosis leads to portal hypertension with subsequent hypersplenism and sequestration of platelets, decreased the production of thrombopoeitin, and endothelial dysfunction, all of which can contribute to thrombocytopenia.Although uncommonly used in developed countries, interferon (IFN) and ribavirin used as part of anti-HCV therapy can also contribute to low platelet count.Hepatitis B virus (HBV) infection represents a significant global health problem, since almost one third of the worlds population has serological signs of previous or present infection, and that 240 million individuals are chronic hepatitis B surface antigen (HBsAg) carriers. Worldwide, low rates of serological HBsAg positivity (0.2%-0.5%) and signs of previous HBV contact [4%-6% HBsAg negative/anti-hepatitis B core antigen antibodies (anti-HBc)positive subjects] are registered in north western and central Europe, north America and Australia. On the contrary, the highest prevalences are reported in China, Southeast Asia and tropical Africa (chronicinfection 8%-20%, and previous exposure 70%-95%,respectively).

It is presently well known that medications such as glucocorticoids and anticancer treatments can interfere with the host immune system and blunt the control that it exerts over HBV replication, with the potential to cause viral reactivation (HBVr) in both HBsAg positive patients and individuals with serological signs of previous resolved HBV exposure. HBVr can assume various manifestations, spanning from asymptomatic hepatitis to life threatening fulminant liver failure. This risk is most common among patients undergoing treatment for hematological tumors or those receiving hematopoietic stem cell transplantation (HSCT). Nevertheless, also patients with solid tumors, immunological diseases and inflammatory bowel diseases are exposed to the risk of HBVr.The existence of an effective vaccination and a mature treatment schedule for HBV suggests that the potential for elimination of this virus as a major public health problem in Egypt exists. In a challenging economic climate, effective targeting of prevention and treatment strategies for both HBV and HCV is essential to make best use of limited resources in Egypt, however. Recent modelling work on HCV illustrates the potential power of intervention targeting in both reducing the risk of infection spread, and improving treatment outcomes, in the Egyptian context.