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In the early 1960s, scientists only differentiated between hepatitis A, an acute infection of short incubation period transmitted via the fecal-oral route, and hepatitis B, a potentially chronic infection of long incubation period transmitted via blood exposure. Therefore, the discovery of hepatitis C only occurred with the availability of diagnostic assays in the early 1970s.<ref name="pmid4136143">{{cite journal| author=Prince AM, Brotman B, Grady GF, Kuhns WJ, Hazzi C, Levine RW et al.| title=Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. | journal=Lancet | year= 1974 | volume= 2 | issue= 7875 | pages= 241-6 | pmid=4136143 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4136143  }} </ref><ref name="pmid163436">{{cite journal| author=Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV| title=Transfusion-associated hepatitis not due to viral hepatitis type A or B. | journal=N Engl J Med | year= 1975 | volume= 292 | issue= 15 | pages= 767-70 | pmid=163436 | doi=10.1056/NEJM197504102921502 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=163436  }} </ref><ref name="pmid318578">{{cite journal| author=Seeff LB, Zimmerman HJ, Wright EC, Finkelstein JD, Garcia-Pont P, Greenlee HB et al.| title=A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study. | journal=Gastroenterology | year= 1977 | volume= 72 | issue= 1 | pages= 111-21 | pmid=318578 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=318578  }} </ref> In 1975, the new discovery was termed "non-A, non-B viral hepatitis (NANBH) when serological markers for hepatitis A and B were both absent in patients with signs and symptoms of viral hepatitis. Shortly after, studies scrutinizing into the new discovery revealed that most patients with NANBH were exposed to blood transfusions<ref name="pmid464417">{{cite journal| author=Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA| title=The chronic sequelae of non-A, non-B hepatitis. | journal=Ann Intern Med | year= 1979 | volume= 91 | issue= 1 | pages= 1-6 | pmid=464417 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=464417 }} </ref><ref name="pmid6782484">{{cite journal| author=Aach RD, Szmuness W, Mosley JW, Hollinger FB, Kahn RA, Stevens CE et al.| title=Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study. | journal=N Engl J Med | year= 1981 | volume= 304 | issue= 17 | pages= 989-94 | pmid=6782484 | doi=10.1056/NEJM198104233041701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6782484 }} </ref>, and hepatic cirrhosis ensued in as many as 20% of these patients.<ref name="pmid3929263">{{cite journal| author=Hoofnagle JH, Alter HJ| title=Chronic non-A, non-B hepatitis. | journal=Prog Clin Biol Res | year= 1985 | volume= 182 | issue=  | pages= 63-9 | pmid=3929263 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3929263 }} </ref>
===Discovery of Non-A, Non-B Viral Hepatitis===
 
In the early 1960s, scientists only differentiated between hepatitis A, an acute infection of short incubation period transmitted via the fecal-oral route, and hepatitis B, a potentially chronic infection of long incubation period transmitted via blood exposure. Therefore, the discovery of hepatitis C only occurred with the availability of diagnostic assays in the early 1970s.<ref name="pmid4136143">{{cite journal| author=Prince AM, Brotman B, Grady GF, Kuhns WJ, Hazzi C, Levine RW et al.| title=Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. | journal=Lancet | year= 1974 | volume= 2 | issue= 7875 | pages= 241-6 | pmid=4136143 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4136143  }} </ref><ref name="pmid163436">{{cite journal| author=Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV| title=Transfusion-associated hepatitis not due to viral hepatitis type A or B. | journal=N Engl J Med | year= 1975 | volume= 292 | issue= 15 | pages= 767-70 | pmid=163436 | doi=10.1056/NEJM197504102921502 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=163436  }} </ref><ref name="pmid318578">{{cite journal| author=Seeff LB, Zimmerman HJ, Wright EC, Finkelstein JD, Garcia-Pont P, Greenlee HB et al.| title=A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study. | journal=Gastroenterology | year= 1977 | volume= 72 | issue= 1 | pages= 111-21 | pmid=318578 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=318578  }} </ref> In 1974-5, the works of Alfred Prince, Stephen Feinstone, and Harvey Alter led to the new discovery that was termed "non-A, non-B viral hepatitis (NANBH) when serological markers for hepatitis A and B were both absent in patients with signs and symptoms of viral hepatitis.<ref name="pmid4136143">{{cite journal| author=Prince AM, Brotman B, Grady GF, Kuhns WJ, Hazzi C, Levine RW et al.| title=Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus. | journal=Lancet | year= 1974 | volume= 2 | issue= 7875 | pages= 241-6 | pmid=4136143 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4136143 }} </ref><ref name="pmid163436">{{cite journal| author=Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV| title=Transfusion-associated hepatitis not due to viral hepatitis type A or B. | journal=N Engl J Med | year= 1975 | volume= 292 | issue= 15 | pages= 767-70 | pmid=163436 | doi=10.1056/NEJM197504102921502 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=163436 }} </ref><ref name="pmid53329">{{cite journal| author=Alter HJ, Holland PV, Morrow AG, Purcell RH, Feinstone SM, Moritsugu Y| title=Clinical and serological analysis of transfusion-associated hepatitis. | journal=Lancet | year= 1975 | volume= 2 | issue= 7940 | pages= 838-41 | pmid=53329 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=53329  }} </ref> Shortly after, studies scrutinizing into the new discovery revealed that most patients with NANBH were exposed to blood transfusions<ref name="pmid464417">{{cite journal| author=Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA| title=The chronic sequelae of non-A, non-B hepatitis. | journal=Ann Intern Med | year= 1979 | volume= 91 | issue= 1 | pages= 1-6 | pmid=464417 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=464417  }} </ref><ref name="pmid6782484">{{cite journal| author=Aach RD, Szmuness W, Mosley JW, Hollinger FB, Kahn RA, Stevens CE et al.| title=Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study. | journal=N Engl J Med | year= 1981 | volume= 304 | issue= 17 | pages= 989-94 | pmid=6782484 | doi=10.1056/NEJM198104233041701 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6782484  }} </ref>, and hepatic cirrhosis ensued in as many as 20% of these patients.<ref name="pmid3929263">{{cite journal| author=Hoofnagle JH, Alter HJ| title=Chronic non-A, non-B hepatitis. | journal=Prog Clin Biol Res | year= 1985 | volume= 182 | issue=  | pages= 63-9 | pmid=3929263 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3929263  }} </ref>
 
With no ability to isolate the virus, the infective potential and mode of transmission of NANBH was later confirmed in 1978 when chimpanzees were infected with the virus following injection of human blood from patients confirmed to have the disease.<ref name="pmid76017">{{cite journal| author=Alter HJ, Purcell RH, Holland PV, Popper H| title=Transmissible agent in non-A, non-B hepatitis. | journal=Lancet | year= 1978 | volume= 1 | issue= 8062 | pages= 459-63 | pmid=76017 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=76017  }} </ref><ref name="pmid76018">{{cite journal| author=Tabor E, Gerety RJ, Drucker JA, Seeff LB, Hoofnagle JH, Jackson DR et al.| title=Transmission of non-A, non-B hepatitis from man to chimpanzee. | journal=Lancet | year= 1978 | volume= 1 | issue= 8062 | pages= 463-6 | pmid=76018 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=76018  }} </ref><ref name="pmid632054">{{cite journal| author=Hollinger FB, Gitnick GL, Aach RD, Szmuness W, Mosley JW, Stevens CE et al.| title=Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group. | journal=Intervirology | year= 1978 | volume= 10 | issue= 1 | pages= 60-8 | pmid=632054 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=632054  }} </ref> Chimpanzee models contributed to the discovery of various NANBH variants and agents, and allowed scientists to study the pathological aspects of hepatic injury in these infections.<ref name="pmid451589">{{cite journal| author=Shimizu YK, Feinstone SM, Purcell RH, Alter HJ, London WT| title=Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees. | journal=Science | year= 1979 | volume= 205 | issue= 4402 | pages= 197-200 | pmid=451589 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=451589  }} </ref><ref name="pmid6255037">{{cite journal| author=Hollinger FB, Mosley JW, Szmuness W, Aach RD, Peters RL, Stevens C| title=Transfusion-transmitted viruses study: experimental evidence for two non-A, non-B, hepatitis agents. | journal=J Infect Dis | year= 1980 | volume= 142 | issue= 3 | pages= 400-7 | pmid=6255037 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6255037  }} </ref><ref name="pmid6795310">{{cite journal| author=Trépo C, Vitvitski L, Hantz O| title=Non-A, Non-B hepatitis virus: identification of a core antigen-antibody system that cross reacts with hepatitis B core antigen and antibody. | journal=J Med Virol | year= 1981 | volume= 8 | issue= 1 | pages= 31-47 | pmid=6795310 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6795310  }} </ref>
 
==Discovery of Hepatitis C Virus===
The attempt to discover the first NANBH antibodies was unyielding for several years  . Although the virus was originally described in the early 1970s, the identification of NANBH-specific antibodies did not occur until 1985 by Yohko Shimizu and colleagues.<ref name="pmid2984683">{{cite journal| author=Shimizu YK, Oomura M, Abe K, Uno M, Yamada E, Ono Y et al.| title=Production of antibody associated with non-A, non-B hepatitis in a chimpanzee lymphoblastoid cell line established by in vitro transformation with Epstein-Barr virus. | journal=Proc Natl Acad Sci U S A | year= 1985 | volume= 82 | issue= 7 | pages= 2138-42 | pmid=2984683 | doi= | pmc=PMC397508 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2984683  }} </ref> In 1989, the full isolation of a cDNA clone 5-1-1 derived from NANBH genome was finally successful. Qui-Lim Choo and colleagues were able to construct a random-primed complementary DNA (cDNA) from plasma containing NANBH agent, showing that the virus is an positive-stranded RNA molecule composed of of 10,000 nucleotides.<ref name="pmid2523562">{{cite journal| author=Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M| title=Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. | journal=Science | year= 1989 | volume= 244 | issue= 4902 | pages= 359-62 | pmid=2523562 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2523562  }} </ref> With the isolation of the new agent, hepatitis c virus (HCV) was discovered and the term replaced NANBH in 1989 for the first time.<ref name="pmid2523562">{{cite journal| author=Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M| title=Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. | journal=Science | year= 1989 | volume= 244 | issue= 4902 | pages= 359-62 | pmid=2523562 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2523562  }} </ref> In the early 1990s, HCV was then classified into 6 major genotypes and several subtypes.<ref name="pmid8245854">{{cite journal| author=Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B et al.| title=Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. | journal=J Gen Virol | year= 1993 | volume= 74 ( Pt 11) | issue=  | pages= 2391-9 | pmid=8245854 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8245854  }} </ref> Due to similarity with other RNA viruses, it was considered a type member of the genus ''Hepacivirus'' within the family ''Flavividae''.<ref name="pmid8245854">{{cite journal| author=Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B et al.| title=Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region. | journal=J Gen Virol | year= 1993 | volume= 74 ( Pt 11) | issue=  | pages= 2391-9 | pmid=8245854 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8245854  }} </ref><ref name="pmid7597443">{{cite journal| author=Bukh J, Miller RH, Purcell RH| title=Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes. | journal=Semin Liver Dis | year= 1995 | volume= 15 | issue= 1 | pages= 41-63 | pmid=7597443 | doi=10.1055/s-2007-1007262 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7597443 }} </ref>




In the mid 1970s, [[Harvey J. Alter]], Chief of the Infectious Disease Section in the Department of Transfusion Medicine at the [[National Institutes of Health]] (NIH), and his research team demonstrated that most post-transfusion hepatitis cases were not due to [[hepatitis A]] and [[Hepatitis B|B]] viruses. Despite this discovery, international research effort to identify the virus, initially called ''non-A, non-B hepatitis'' (NANBH), failed for the next decade. In 1987, Michael Houghton, Qui-Lim Choo, and George Kuo at Chiron Corporation utilized [[molecular cloning]] to identify the unknown organism. In 1988, the virus was confirmed by Alter by verifying its presence in a panel of NANBH specimens. In April of 1989, the discovery of the virus, re-named hepatitis C virus (HCV), was published in two articles in the journal ''Science''.


Dr. D.W. Bradley filed suit against Chiron, challenging the status of U.S. patent 5,350,671 covering HCV clones, diagnostics, and vaccines. Dr. Bradley sought to invalidate the patent, have himself included as a co-inventor, and receive damages and royalty income from Chiron. Dr. Bradley claimed he supplied Chiron with HCV-infected plasma that was instrumental in Chiron's isolation and cloning of HCV, that he developed critical findings about the virus, and that he provided Chiron with assistance regarding cloning methods. Dr. Bradley began work on what was then called non-A, non-B hepatitis in 1977 and the dispute between Dr. Bradley and Chiron can be traced back to 1986 when the parties failed to agree on terms for Dr. Bradley to provide infected plasma to Chiron.  <!--
  --><ref name="chiron">[http://www.chiron.com Chiron Corporation] ''Chiron Hepatitis C Research Honored with 2000 Lasker Award for Clinical Medical Research'' Press release, [[18 September]] [[2000]].</ref><!--
  --><ref name="choo">{{cite journal | author = Choo Q, Kuo G, Weiner A, Overby L, Bradley D, Houghton M | title = Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. | journal = Science | volume = 244 | issue = 4902 | pages = 359-62 | year = 1989 | id = PMID 2523562}}</ref><!--
  --><ref name="kuo">{{cite journal | author = Kuo G, Choo Q, Alter H, Gitnick G, Redeker A, Purcell R, Miyamura T, Dienstag J, Alter M, Stevens C | title = An assay for circulating antibodies to a major etiologic virus of human non-A, non-B hepatitis. | journal = Science | volume = 244 | issue = 4902 | pages = 362-4 | year = 1989 | id = PMID 2496467}}</ref><!--
  --><ref name="houghton">Houghton, M., Q.-L. Choo, and G. Kuo. ''NANBV Diagnostics and Vaccines.''  European Patent No. EP-0-3 18-216-A1. European Patent Office (filed [[18 November]] [[1988]], published [[31 May]] [[1989]]).</ref>
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}

Revision as of 22:29, 27 July 2014

Discovery of Non-A, Non-B Viral Hepatitis

In the early 1960s, scientists only differentiated between hepatitis A, an acute infection of short incubation period transmitted via the fecal-oral route, and hepatitis B, a potentially chronic infection of long incubation period transmitted via blood exposure. Therefore, the discovery of hepatitis C only occurred with the availability of diagnostic assays in the early 1970s.[1][2][3] In 1974-5, the works of Alfred Prince, Stephen Feinstone, and Harvey Alter led to the new discovery that was termed "non-A, non-B viral hepatitis (NANBH) when serological markers for hepatitis A and B were both absent in patients with signs and symptoms of viral hepatitis.[1][2][4] Shortly after, studies scrutinizing into the new discovery revealed that most patients with NANBH were exposed to blood transfusions[5][6], and hepatic cirrhosis ensued in as many as 20% of these patients.[7]

With no ability to isolate the virus, the infective potential and mode of transmission of NANBH was later confirmed in 1978 when chimpanzees were infected with the virus following injection of human blood from patients confirmed to have the disease.[8][9][10] Chimpanzee models contributed to the discovery of various NANBH variants and agents, and allowed scientists to study the pathological aspects of hepatic injury in these infections.[11][12][13]

Discovery of Hepatitis C Virus=

The attempt to discover the first NANBH antibodies was unyielding for several years . Although the virus was originally described in the early 1970s, the identification of NANBH-specific antibodies did not occur until 1985 by Yohko Shimizu and colleagues.[14] In 1989, the full isolation of a cDNA clone 5-1-1 derived from NANBH genome was finally successful. Qui-Lim Choo and colleagues were able to construct a random-primed complementary DNA (cDNA) from plasma containing NANBH agent, showing that the virus is an positive-stranded RNA molecule composed of of 10,000 nucleotides.[15] With the isolation of the new agent, hepatitis c virus (HCV) was discovered and the term replaced NANBH in 1989 for the first time.[15] In the early 1990s, HCV was then classified into 6 major genotypes and several subtypes.[16] Due to similarity with other RNA viruses, it was considered a type member of the genus Hepacivirus within the family Flavividae.[16][17]


References

  1. ↑ 1.0 1.1 Prince AM, Brotman B, Grady GF, Kuhns WJ, Hazzi C, Levine RW; et al. (1974). "Long-incubation post-transfusion hepatitis without serological evidence of exposure to hepatitis-B virus". Lancet. 2 (7875): 241–6. PMID 4136143.
  2. ↑ 2.0 2.1 Feinstone SM, Kapikian AZ, Purcell RH, Alter HJ, Holland PV (1975). "Transfusion-associated hepatitis not due to viral hepatitis type A or B." N Engl J Med. 292 (15): 767–70. doi:10.1056/NEJM197504102921502. PMID 163436.
  3. ↑ Seeff LB, Zimmerman HJ, Wright EC, Finkelstein JD, Garcia-Pont P, Greenlee HB; et al. (1977). "A randomized, double blind controlled trial of the efficacy of immune serum globulin for the prevention of post-transfusion hepatitis. A Veterans Administration cooperative study". Gastroenterology. 72 (1): 111–21. PMID 318578.
  4. ↑ Alter HJ, Holland PV, Morrow AG, Purcell RH, Feinstone SM, Moritsugu Y (1975). "Clinical and serological analysis of transfusion-associated hepatitis". Lancet. 2 (7940): 838–41. PMID 53329.
  5. ↑ Berman M, Alter HJ, Ishak KG, Purcell RH, Jones EA (1979). "The chronic sequelae of non-A, non-B hepatitis". Ann Intern Med. 91 (1): 1–6. PMID 464417.
  6. ↑ Aach RD, Szmuness W, Mosley JW, Hollinger FB, Kahn RA, Stevens CE; et al. (1981). "Serum alanine aminotransferase of donors in relation to the risk of non-A,non-B hepatitis in recipients: the transfusion-transmitted viruses study". N Engl J Med. 304 (17): 989–94. doi:10.1056/NEJM198104233041701. PMID 6782484.
  7. ↑ Hoofnagle JH, Alter HJ (1985). "Chronic non-A, non-B hepatitis". Prog Clin Biol Res. 182: 63–9. PMID 3929263.
  8. ↑ Alter HJ, Purcell RH, Holland PV, Popper H (1978). "Transmissible agent in non-A, non-B hepatitis". Lancet. 1 (8062): 459–63. PMID 76017.
  9. ↑ Tabor E, Gerety RJ, Drucker JA, Seeff LB, Hoofnagle JH, Jackson DR; et al. (1978). "Transmission of non-A, non-B hepatitis from man to chimpanzee". Lancet. 1 (8062): 463–6. PMID 76018.
  10. ↑ Hollinger FB, Gitnick GL, Aach RD, Szmuness W, Mosley JW, Stevens CE; et al. (1978). "Non-A, non-B hepatitis transmission in chimpanzees: a project of the transfusion-transmitted viruses study group". Intervirology. 10 (1): 60–8. PMID 632054.
  11. ↑ Shimizu YK, Feinstone SM, Purcell RH, Alter HJ, London WT (1979). "Non-A, non-B hepatitis: ultrastructural evidence for two agents in experimentally infected chimpanzees". Science. 205 (4402): 197–200. PMID 451589.
  12. ↑ Hollinger FB, Mosley JW, Szmuness W, Aach RD, Peters RL, Stevens C (1980). "Transfusion-transmitted viruses study: experimental evidence for two non-A, non-B, hepatitis agents". J Infect Dis. 142 (3): 400–7. PMID 6255037.
  13. ↑ Trépo C, Vitvitski L, Hantz O (1981). "Non-A, Non-B hepatitis virus: identification of a core antigen-antibody system that cross reacts with hepatitis B core antigen and antibody". J Med Virol. 8 (1): 31–47. PMID 6795310.
  14. ↑ Shimizu YK, Oomura M, Abe K, Uno M, Yamada E, Ono Y; et al. (1985). "Production of antibody associated with non-A, non-B hepatitis in a chimpanzee lymphoblastoid cell line established by in vitro transformation with Epstein-Barr virus". Proc Natl Acad Sci U S A. 82 (7): 2138–42. PMC 397508. PMID 2984683.
  15. ↑ 15.0 15.1 Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M (1989). "Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome". Science. 244 (4902): 359–62. PMID 2523562.
  16. ↑ 16.0 16.1 Simmonds P, Holmes EC, Cha TA, Chan SW, McOmish F, Irvine B; et al. (1993). "Classification of hepatitis C virus into six major genotypes and a series of subtypes by phylogenetic analysis of the NS-5 region". J Gen Virol. 74 ( Pt 11): 2391–9. PMID 8245854.
  17. ↑ Bukh J, Miller RH, Purcell RH (1995). "Genetic heterogeneity of hepatitis C virus: quasispecies and genotypes". Semin Liver Dis. 15 (1): 41–63. doi:10.1055/s-2007-1007262. PMID 7597443.

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