Sixty cases with primary knee OA were equally categorized into six groups with EHI (Gs 1, 2, 3) or without (Gs 4, 5, 6). GI included cases with HCV, GII cases with RHS & HCV and GIII cases with a history of non-active schistosomiasis whereas Gs 4, 5 & 6 included cases without EHI. Clinical examination with inclusion criteria of pathological manifestations w\as associated with biochemical evaluation of adhesion molecules (E-selectin, P-selectin, intracellular adhesion molecule-3 "ICAM-3") in plasma and synovial fluid. Synovial fluid indices (IgG, IgA, IgM, & C3) were evaluated as well as indices of inflammation and oxidative stress (Beta 2 microglobulin, Haptaglobulin, fibronectin, total thiol, superoxide dismutase, thiobarbituric acid reactive substance & hyaluronan) in synovial fluid and indices activating fibrogenesis in serum and plasma (procollagen III, plasma prolidase, Interleukin-1 beta, Interleukin-6 & TNF alpha). The results showed a positive relationship between indices activating vascular damage, fibrogenesis and immuno-inflammatory response with higher change magnitude in EHI cases particularly with combined HCV & RHS. This implement the dual role of hepatic insult and intestinal amoebiasis on immune mediated mechanisms activating inflammatory response in OA cases reflecting common signaling pathways associated with pathogenesis of multifaceted origin.