Our comparative analysis of the N-glycans and glycoproteins derived from the circulation of animals and people as a function of liver disease has helped identify a set of fucosylated proteins that may help in early disease detection and even suggest unsuspected etiological cofactors. In addition, we have determined that specific, viral glycoproteins, such as hepatitis B surface antigen, have a great tendency to rapidly oligomerize helping evade proteaosmal degradation and detection by the immune system. These glycoproteins appear to have obligate requirements for endoplasmic reticular (ER) glucosidase, presumably calnexin, mediated protein folding. Hepatitis B and C, for example, appear to be dependent upon this pathway. Inhibitors of ER glucosidases may have therapeutic value and are being clinically tested. The molecular basis of the dependency of these proteins upon calnexin will be discussed, as well as the early detection of cancer and hepatitis C clinical trials.