Gaafar Ragab

Behcet's disease is a chronic multi-system disorder of unknown etiology with protean manifestations. Venous thromboembolism is more common than arterial thrombosis, with deep vein thrombosis being the most frequent. Endothelial dysfunction resulting from vascular inflammation is considered to be an important factor of thrombosis, although the endothelial injury itself cannot completely explain the hypercoagulable state of the disease because other vasculitis syndromes do not increase the risk of thrombosis. The aim of this study is to evaluate the prevalence of activated protein C resistance (APC-R) in Egyptian patients with Behcet's disease. Also, to detect hyperhomocysteinemia in selected cases (with vascular complications) to assess their relationship with thromboembolic complications. The APC resistance ratio mean in the group of patients with vascular involvement was 2.6 ± 0.8 which was less than the group with no vascular involvement 2.8 ± 0.6, with non- significant P-value (0.5). There was more incidence of ocular lesions in the group of patients with high homocysteine level than the group of patients with normal homocytsteine level with significant P-value (0.08).

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.

OBJECTIVE: Limited data are available on the genetics of rheumatoid arthritis (RA) in Egyptians. Therefore, we investigated whether the confirmed genetic risk factors for RA in Europeans and/or Asians contribute to RA susceptibility in Egyptians.

SUBJECTS AND METHODS: A set of seven single-nucleotide polymorphisms (SNPs) in the vicinity of CD28, TNFAIP3, PTPN22, PADI4 and HLA-DRA were tested in a large multi-centric RA cohort in Egypt, consisting of 394 cases and 398 matched controls. Patients were stratified based on the positivity of either anti-citrullinated protein antibodies (ACPAs) or rheumatoid factor (RF).

RESULTS: Significant association was evident for three SNPs in this cohort: the CD28 (rs1980422) variant showed a strong association in the whole cohort (P=0.000119) and in seropositive subsets of the disease (PACPA+=0.004; PRF+=0.0005). Upon stratification, the PTPN22 (rs2476601) and TNFAIP3(rs5029939) variants showed association only with ACPA positive (PACPA+=0.00573) and negative (PACPA-=0.00999) phenotypes, respectively.

CONCLUSION: Our results suggest that CD28(rs1980422) and PTPN22(rs2476601) contribute to RA-susceptibility in Egyptians. Failure to replicate the association of PADI4(rs2240340)/(PADI4_94) in Egyptian RA patients provides further support for the notion that genetic architecture of RA is different in multiple populations of European, Asian, African, and Middle Eastern ancestries. Further investigation using large-scale studies is thus needed to maximize the power of genetic association.