Viral hepatitis is still, as it has been for many centuries, a major worldwide cause of acute and chronic liver disease. Outbreaks of jaundice resembling viral hepatitis were described as early as the fifth century bc, and the term epidemic jaundice appeared in the writings of Hippocrates in Greece. Nevertheless, proof of the infectious nature of the disease was established only during and shortly after World War II, in a series of studies that involved feeding contaminated material to human volunteers.<sup>107 MacCallum F.O., Bradley W.H. Transmission of infective hepatitis to human volunteers Lancet 1944 ;  2 : 228  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 134 Paul J.R., Havens W.P., Sabin A.B. Transmission experiments in serum jaundice and infectious hepatitis JAMA 1945 ;  128 : 911

Cliccare qui per andare alla sezione Riferimenti</sup> The successful infection of marmosets with a virus from the feces of patients with infectious hepatitis and the finding of a viral antigen in the feces of such patients<sup>47 Feinstone S.M., Kapikian A.Z., Purcell R.H. Hepatitis A: detection by immune electron microscopy of a virus-like antigen associated with acute illness Science 1973 ;  182 : 1026

Cliccare qui per andare alla sezione Riferimenti, 62 Holmes A.W., Wolfe L., Deinhardt F. , e al. Transmission of human hepatitis to marmosets: Further coded studies J Infect Dis 1971 ;  124 : 520

Cliccare qui per andare alla sezione Riferimenti, 63 Holmes A.W., Wolfe L., Rosenblate H. , e al. Hepatitis in marmosets: Induction of disease with coded specimens from a human volunteer study Science 1969 ;  165 : 816

Cliccare qui per andare alla sezione Riferimenti</sup> led to the identification and the description of the hepatitis A virus (HAV) by Feinstone et al in 1973.<sup>47 Feinstone S.M., Kapikian A.Z., Purcell R.H. Hepatitis A: detection by immune electron microscopy of a virus-like antigen associated with acute illness Science 1973 ;  182 : 1026

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The first description of percutaneously transmitted hepatitis is attributed to Lurman,<sup>106 Lurman A. Eine icterus epidemic Berlin Klin Wochenschr 1885 ;  22 : 20

Cliccare qui per andare alla sezione Riferimenti</sup> who reported 191 cases of jaundice that developed 2 to 8 months after smallpox vaccination with glycerinated human lymph in 1885. Subsequently, many more authors reported similar outbreaks, but the association between the transfusion of blood or plasma and the development of hepatitis was reported for the first time in 1943.<sup>8 Beeson P.B. Jaundice occurring one to four months after transfusion of blood or plasma. Report of 7 cases JAMA 1943 ;  121 : 1332

Cliccare qui per andare alla sezione Riferimenti, 124 Morgan H.V., Williamson D.A.J. Jaundice following administration of human blood products BMJ 1943 ;  1 : 750

Cliccare qui per andare alla sezione Riferimenti</sup> The landmark studies of Krugman and colleagues in the late 1950s and the early 1960s documented the transmissibility of hepatitis by human plasma and confirmed the long-standing clinical observation that both parenteral and enteric transmission could occur.<sup>86 Krugman S., Ward R., Giles J.P. Infectious hepatitis: Detection of virus during the incubation period and in clinically inapparent infections N Engl J Med 1959 ;  261 : 729  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 87 Krugman S., Ward R., Giles J.P. Infectious hepatitis: Studies on the effect of gamma globulin and on the incidence of inapparent infections JAMA 1960 ;  174 : 823

Cliccare qui per andare alla sezione Riferimenti, 88 Krugman S., Ward R., Giles J.P. The natural history of infectious hepatitis Am J Med 1962 ;  32 : 717  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> One of the most important breakthroughs came in the mid-1960s with the discovery of the hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs) by Blumberg and colleagues,<sup>11 Blumberg B.S., Alter H.J., Visnich S. A “new” antigen in leukemia sera JAMA 1965 ;  191 : 541

Cliccare qui per andare alla sezione Riferimenti, 121 Melartin L., Blumberg B.S. Production of antibody against “Australia antigen” in rabbits Nature 1966 ;  210 : 1340

Cliccare qui per andare alla sezione Riferimenti</sup> a discovery that led, in 1977, to their receiving the Nobel prize in Medicine. This discovery also led to the description of the morphologic and immunochemical features of hepatitis B virus (HBV) and, later, to the development of specific passive and active hepatitis B immunoprophylaxis. Soon after the identification of the hepatitis A and B viruses, it became apparent that many cases of posttransfusion hepatitis were neither HBV or HAV. The entity non-A non-B hepatitis was formally introduced in the mid-1970s,<sup>48 Feinstone S.M., Kapikian A.Z., Purcell R.H. , e al. Transfusion associated hepatitis not due to viral hepatitis type A or B N Engl J Med 1975 ;  292 : 767  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti, 147 Prince A.M., Brotman B., Grady G.F. , e al. Long incubation post transfusion hepatitis without serological evidence of exposure to hepatitis B serum Lancet 1974 ;  2 : 241  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> and the hepatitis C virus (HCV) was finally identified in 1989 by Choo and associates.<sup>24 Choo Q.L., Kuo G., Weiner A.J. , e al. Isolation of the cDNA clone derived from a blood borne non-A non-B viral hepatitis genome Science 1989 ;  244 : 359

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