Gaafar Ragab

Egypt, the single country with highest incidence of HCV infection in the world, has embarked on a government-sponsored mass treatment program using several combinations of DAAs. Recognizing the importance of extrahepatic manifestations, independently of the hepatic, a subcommittee was assigned to develop national guidelines for respective prioritizing indications and protocols. It evaluated the benefit of treating patients with different extrahepatic manifestations, and reviewed relevant clinical trials and guidelines concerning DAA combinations available in Egypt. The latter included Sofosbuvir plus either peg-interferon, Simeprevir, Ledipasvir or daclatasvir, and the Viekera family comprising paritaprevir/ritonavir + ombitasvir with (GT-1) or without (GT-4) Dasabuvir. Any of these protocols may be used with or without Ribavirin according to indication. A blueprint was subjected to peer debate in dedicated workshops in two national meetings and subsequently to an online professional review, eventually leading to a final report that was adopted by the health authorities. Seven compelling and 10 optional indications were identified for treating patients with predominantly extrahepatic manifestations. The former include kidney disease at different stages, cryoglobulinemic vasculitis and non-Hodgkin lymphoma. Selected treatment protocols, were encoded and their use was prioritized on the basis of evidence of efficacy and safety. We concluded that any of the studied protocols may be used, preferably with ribavirin, for 12-week treatment in all patients with extrahepatic manifestations without cirrhosis and with eGFR above 30 ml/min/1.73 sqm. Ribavirin should be included in protocols for treating patients with compensated cirrhosis. Daclatasvir-based protocols are recommended for decompensated cirrhosis, while the Viekera family is recommended in patients with eGFR < 30 ml/min/1.73 sqm, including those on dialysis. In kidney-transplanted patents, caution is due to avoidance of the pharmacokinetic interaction with the Cytochrome-P450 enzyme system, in-between immunosuppressive agents and most DAAs, particularly the Viekera family.

Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors.The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]. It could also potentially transmit infections. The recipient's microbiome contributes, on the other hand, to the tolerance to transfused blood, or to the development of transfusion reactions. Cancer patients are a particularly vulnerable population, often immunosuppressed with a significantly altered microbiota. They are more at risk for transmission of ?dormant? bacteria via blood transfusion. Furthermore, chemotherapy and radiation induce mucositis that likely results in significant translocation of gut microbiota and abnormal immune reactions to transfused blood. It is therefore relevant to revisit transfusion thresholds and consider transfusion-saving strategies in cancer patients.Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors.The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]. It could also potentially transmit infections. The recipient's microbiome contributes, on the other hand, to the tolerance to transfused blood, or to the development of transfusion reactions. Cancer patients are a particularly vulnerable population, often immunosuppressed with a significantly altered microbiota. They are more at risk for transmission of ?dormant? bacteria via blood transfusion. Furthermore, chemotherapy and radiation induce mucositis that likely results in significant translocation of gut microbiota and abnormal immune reactions to transfused blood. It is therefore relevant to revisit transfusion thresholds and consider transfusion-saving strategies in cancer patients.

Avascular necrosis (AVN) is a devastating condition that is rarely reported in patients with immune thrombocytopenia (ITP). Treatment with steroids remains a major risk factor for developing AVN. However, the incidence of AVN in patients with ITP requiring corticosteroid therapy is much less than that observed with other clinical conditions requiring corticosteroids. ITP is a bleeding disorder but can be also be a pro-thrombotic state via different mechanisms and thus could result in AVN. Among the possible causes of this pro-thrombotic state is the presence of antiphospholipid antibodies (aPLs). In this case, we report a patient with refractory ITP who developed multifocal AVN around the time she acquired new aPLs. We also discuss different mechanisms by which risk of thrombosis is increased in ITP and the relationship between ITP, aPLs and antiphospholipid syndrome.