Hepatitis B: A timeline of key dates

A timeline of key events behind the growing understanding about hepatitis B as a disease, its prevention and treatment.

1600-01-01T00:00:00+000040,000 cases recorded1861-01-01T00:00:00+0000R. Virchow, 'Ueber das Vockommn und den Nacweis des hepatogenen. inspersondere des katarrhalischen Icterus', Vichows Arch Pathol Anat, (1865), 32, 117-25.1865-01-01T00:00:00+0000The outbreak was probably caused by blood contamination of the lymph used in the smallpox vaccination. Of 1129 vaccinated shipworkers, 191 developed jaundice. A. Lurman, 'Eine icterusepidemic', Berl Klin Wehnschr, 22 (1885), 20-23; J. Jehn, 'Eine Ikterusepidemie in wahrscheinlichem. Zusam-menhang mit vorausgegangener Revaccination', Dtsch Med.Wochenschr, 11 (1885), 339.1885-01-01T00:00:00+0000S. McDonald, 'Acute yellow atrophy', Edinburgh Medical Journal, 15 (1908), 208.1908-01-01T00:00:00+0000Hilleman, a microbiologist, is credited with having saved more children's lives than any other medical scientist in the 20th century. He pioneered eight out of the fourteen vaccines routinely recommended for children today. This includes the vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and Haemophilus influenzae bacteria. Hilleman developed these vaccines as head of Merck & Co's virus and cell biology research department. 1919-08-30T00:00:00+0000The authors considered a range of factors causing the outbreak, including an infectious agent. J Stokes, R Ruedemann, W Lemon, 'Epidemic infectious jaundice and its relation to the therapy of syphilis', Arch Intern Med, 26 (1920), 521-33.1920-01-01T00:00:00+0000Blumberg was a physician and geneticist who won the Nobel Prize in 1976 for his discovery of a surface antigen for the hepatitis B virus. He found the antigen while conducting work on blood samples from different populations from around the world to understand genetic variations in susceptibility to disease. The antigen was first spotted testing a blood sample from a haemophiliac patient in New York against blood taken from a visiting Korean physician. Blumberg's discovery paved the way to the development of the first screen test for hepatitis B to prevent its spread in blood donations. His research also helped in the creation of the first vaccine against the disease, which to this day is the gold standard in the management of the disease. 1925-07-28T00:00:00+0000They noted the use of lancets being used repeatedly to obtain blood samples from patients. A Flaum, H Malmros, E Persson, 'Eine nosocomiale Ikterusepidemie', Acta Med Scand, 16 (Suppl.) (1926), 544–53.1926-01-01T00:00:00+0000GM Findlay, JL Dunlop, HC Brown, 'Observations on epidemic catarrhal jaundice', Trans R Soc Trop Med Hyg, 25 (1931), 7–28.1931-05-21T00:00:00+00001937-01-01T00:00:00+0000E Polack, 'Chronic hepatitis in young persons, with or without intermittent jaundice', Acta Med Scand, 93 (1937), 14-22; A Kornberg, 'Latent liver disease in persons recovered from catarrhal jaundice and in otherwise normal medical students as revealed by the bilirubin excretion test', Journal Clinical Investigation, 21 (1941), 299-308.1937-12-31T00:00:00+0000The plasma was a standard means of preventing measles and mumps in the 1930s. In one case seven young children resident in a long-term institution became jaundiced 78-82 days after being inoculated with the plasma. S.A. Propert, 'Hepatitis after prophylactic serum', BMJ, 2 (1938), 677-678. Another epidemic involved 41 cases of jaundice with 8 deaths following the administration of pooled measles convelescent serum from 26 donors. AS MacNalty, Annual Report of the Chief Medical Officer of the Ministry of Health for the Year 1937 (London, 1938); P Beeson, G Chesney, A McFarlan, 'Hepatitis following injection of mumps convalescent plasma', Lancet, 1 (1944), 814-21.1938-01-01T00:00:00+0000Vaccination against yellow fever was introduced in the 1930s. The first British vaccine produced using a mixture of live, mouse-brain passaged virus with human immune serum together with normal serum. Between 1933 and 1938 89 cases of jaundice were observed among 3100 vaccines, about 3% of recipients. Most cases developed the jaundice 2-3 months after vaccination. GM Findlay, F.O. MacCallum, ' Hepatitis and jaundice associated with immunization against certain virus diseases: (section of comparative medicine)', Proc R Soc Med, 31/7 (1938), 799-806.1938-01-01T00:00:00+0000The biopsies were done on 38 patients. K Roholm, P Iversen, 'Changes in the liver in acute epidemic hepatitis (catarrhal jaundice) based on 38 aspiration biopsies', Acta Pathol Microbiol Scand, 16 (1939), 427-42.1939-01-01T00:00:00+000028,585 US soldiers were affected, 62 died. WA Sawyer, et al. 'Jaundice in Army personnel in the western region of the United States and its relation to vaccination against yellow fever', American Journal of Epidemiology, 39/3 (1944), 337-430; RH Turner, et al., 'Some clinical studies of acute hepatitis occurring in soldiers after inoculation with yellow fever vaccine', Annals Internal Medicine, 20 (1944), 193-218. Alarmed by the report the British government decided not to vaccine the Prime Minister, Winston Churchill, against yellow fever. 1942-01-01T00:00:00+0000Voegt conducted the experiment at the University Hospital in Vienna. The volunteers were given blood, urine and duodenal juice collected from patients with infective hepatitis. This was done either by injection or via the oral route. Voegt was a member of the clinic of Hans Eppinger, an Austrian physician who later became infamous for his experiments on prisoners at the Dachau concentration camp. Eppinger never accepted the validity of Voegt's findings and his work was ignored in English-speaking countries. Voegt published his experimernt in 'Zur Aetiologie der Hepatitis epidemica', Munch Med.Wschr, 89 (1942), 76–9.1942-01-01T00:00:00+0000Nine out of 56 patients treated with large volumes of pooled serum for a variety of conditions developed jaundice 49-107 days after treatment. It was observed that these cases resembled the cases that occurred after yellow fever vaccination. HV Morgan, D Williamson, 'Jaundice following administration of human blood products', BMJ, 1/4302 (1943), 750-531943-01-01T00:00:00+0000Clinicians at Grady Hospital in Atlanta reported seven cases developed 1–4 months after receivbing transfusion of whole blood or plasma. P Beeson, 'Jaundice occurring one to four months after transfusion of blood or plasma', JAMA, 121 (1943), 1332-35. Clinicians working at large Army hospital identified 103 patients who developed hepatitis after receiving blood transfusions. EB Grossman, S Stewart, JJ Stokes, 'Post-transfusion hepatitis in battle casualties', JAMA, 129 (1945), 991-94.1943-01-01T00:00:00+0000MOH, 'Homologous serum jaundice: memorandum prepared by medical officers of the Ministry of Health', Lancet, 241 (1943), 83-88. 1943-01-01T00:00:00+0000J. Beattie, J. Marshall, ' Aetiology of post-arsphenamine jaundice', BMJ, 1/4346 (1944), 547-50.1944-01-01T00:00:00+0000Researchers showed the agent survived being heated to 56 degrees celsius for 30 mins and being chlorinated. It also survived in frozen samples for more than a year. They also showed it could be transmitted by feeding or inoculation of fecal extracts, blood or urine taken from symptomatic patients. FO MacCallum, DW Bradley, 'Transmission of infective hepatitis to human volunteers', Lancet, 2 (1944), 228; WP Havens, 'Properties of the etiologic agent of infectious hepatitis', Proc Soc Exp Biol Med, 58 (1945), 203-04; GM Findlay, RR Willcox, 'Infective hepatitis; transmission by faeces and urine', Lancet, 2 (6378) (1945), 594-97. 1944-01-01T00:00:00+0000OD Ratnoff, A Patek, 'Natural history of Laennec's cirrhosis of liver', Medicine, 21 (1942), 207-68.1944-01-01T00:00:00+0000Serum taken from a soldier who had developed hepatitis 14 weeks after receiving arsenical therapy was inoculated into 10 volunteers, 7 of whom became jaundiced 42-70 days later. FO MacCallum, DW Bradley, 'Transmission of infective hepatitis to human volunteers', Lancet, 2 (1944), 228. 1945-01-01T00:00:00+0000This was established as a result of an experiment with volunteers. Serum taken from a soldier who developed jaundice during 14th weeks of arsenical therapy was inoculated into 10 volunteers, 7 of whom became jaundiced 42-70 days later, of which three died. Volunteers who were administered nasopharyngeal washings from those affected did not contract the disease, confirming serum to be the source of the infection. F.O. MacCallum, 'Transmission of arsenotherapyjaundice by blood,' Lancet, 1 (1945), 342.1945-01-01T00:00:00+0000EB Grossman, S Stewart, JJ Stokes, 'Post-transfusion hepatitis in battle casualties', JAMA, 129/15 (1945), 991-94.1945-12-08T00:00:00+000050,000 US Army personal were hospitalised after receiving contaminated batches of yellow fever vaccine. The epidemic affected 300,000 American troops. G. Freeman, 'Epidemiology and incubation period of jaundice following yellow fever vaccination', American Journal Tropical Medicine & Hygiene s26/1 (1946), 15-32.1946-01-01T00:00:00+0000Anon, 'Transfusion jaundice', BMJ, 225 (1946), 423-24,1946-01-01T00:00:00+0000Stool specimens taken from patient during the active illness found to be highly infectious, but less so in patients incubating or recovering from the disease. WP Havens Jr, 'Period of infectivity of patients with experimentally induced infectious hepatitis', J Exp Med, 83 (1946), 251-58; T Francis Jr, AW Frisch, JJ Quilligan Jr, 'Demonstration of infectious hepatitis virus in presymptomatic period after transfer by transfusion', Proc Soc Exp Biol Med, 61 (1946), 276-80.1946-01-01T00:00:00+0000JR Neefe, SS Gellis, J Stokes Jr, 'Homologous serum hepatitis and infectious (epidemic) hepatitis; studies in volunteers bearing on immunological and other characteristics of the etiological agents', Am J Med, 1 (1946), 3-22.1946-01-01T00:00:00+0000F O MacCallum, Paper to the International Congress of Physicians, 1947; Anon, 'Homologous serum hepatitis', Lancet. 2 (1947), 691-92.1947-01-01T00:00:00+0000WHO, Technical Report Series, No. 62 (1953)1953-01-01T00:00:00+0000JR Neefe, et al., 'Carriers of hepatitis virus in the blood and viral hepatitis in whole blood recipients. I. Studies on donors suspected as carriers of hepatitis virus and as sources of post-transfusion viral hepatitis', JAMA, 154/13 (1954), 1066-71; R Murray, et al., 'Carriers of hepatitis virus in the blood and viral hepatitis in whole blood recipients. II. Confirmation of carrier state by transmission experiments in volunteers', JAMA, 154/13 (1954), 1072-741954-01-01T00:00:00+0000J Stokes Jr., et al, 'The carrier state in viral hepatitis', JAMA, 154/13 (1954), 1059-65.1954-01-01T00:00:00+0000Using starch gel electrophoresis, Blumberg tested the serum samples against blood taken from haemophiliacs who had received multiple transfusions, looking for antibody-antigen reactions. Blumberg did the work with the help of W Thomas Dublin. 1957-01-01T00:00:00+00001957-01-01T00:00:00+0000Blumberg found the antigen after observing an unusual cross reaction between the two samples of blood. 1964-01-01T00:00:00+0000WHO Technical Report Series, No. 285 (1964).1964-01-01T00:00:00+0000Blumberg and his team found the antigen to common in 1 in 10 leukaemia patients. By contrast it was rare in healthy individuals (1 in 1,000). BS Blumberg, HJ Alter, S Visnich, A new antigen in leukemia sera, JAMA, 191 (1965), 541-6.1965-01-01T00:00:00+0000The patient was James Blair, a twelve year old. Six months before he tested negative for the disease1966-07-20T00:00:00+0000She made a full recovery1967-04-01T00:00:00+0000Carried out with more than 700 mentally disabled children, the experiments were later criticised for being unethical. The research, however, revealed hepatitis was made up of A & B strains, that HBsAG could provide means for a hepatitis B vaccine and gamma globulin antibodies from hepatitis patients' blood could help treat hepatitis B. The experiment had both an an experimental and a control group. Those in experimental group were children already housed at Willowbrook. They were injected with protective antibodies. The control group involved newly admitted children. This group had a subset of children deliberately infected with hepatitis A obtained from sick children with remainder being given nothing. S Krugman, JP Giles, J, Hammond, 'Infectious hepatitis. Evidence of two distinct clinical, epidemiological and immunological types of infection', JAMA, 200 (1967), 365–73.1967-05-01T00:00:00+0000AM Prince, 'An antigen detected in the blood during the incubation period of serum hepatitis', Proc. Natl Acad. Sci. USA, 60 (1968), 814–21.1968-01-01T00:00:00+0000This was done using an agar gel diffusion assay Prince developed. 1968-01-01T00:00:00+00001968-01-01T00:00:00+0000Hilleman launched the work based on sample HBsAg supplied to him by Alfred Prince1968-01-01T00:00:00+0000JB Smith, BS Blumberg, 'Viral hepatitis, postnecrotic cirrhosis, and hepatocellular carcinoma', Lancet, 2/7627 (1969), 953; AI. Sutnick, et al, 'The role of Australia antigen in viral hepatitis and other diseases', Annual Review Medicine, 23 (1972), 161-76.1969-01-01T00:00:00+0000Four members of staff and seven patients died. The outbreak prompted Kenneth Murray to launch project to genetically engineer vaccine against hepatits B. 1969-01-01T00:00:00+0000Baruch Blumberg and Irving Millman appled for the patent following pressure from the Federal government to show applications from basic research. BS Blumberg, I Millman 'Vaccine against viral hepatitis and process', US patent 3636191A1969-10-08T00:00:00+00001970-01-01T00:00:00+00001970-01-01T00:00:00+0000DS Dane, CH Cameron, M Briggs, 'Virus-like particles in serum of patients with Australia-antigen-associated hepatitis', Lancet, 1 (1970), 695–8.1970-04-04T00:00:00+00001971-01-01T00:00:00+0000Hilleman achieved this on the basis of collecting blood from homosexual men and drug users, mainly living in flophouses, stairwells and fire escapes in the Bowery neighbourhood of New York. 1971-01-01T00:00:00+0000Known as the solid-phase sandwich radioimmunosassay, the test combined the specificity of the biological antigen-antibody interaction with the high sensitivity of modern physicochemical analytical method. It used lablelled antigens or antibodies with radioactive substances such as iodine-15. CM Ling, LR Overby, 'Prevalence of hepatitis B virus antigen as revealed by direct radioimmune assay with 125 I-antibody', Journal Immunology, 20 (1972), 834–41.1972-01-01T00:00:00+00001972-01-01T00:00:00+0000BS Blumberg, I Millman 'Vaccine against viral hepatitis and process', US patent 3636191A1972-01-18T00:00:00+0000JE Maynard, et al., 'Experimental infection of chimpanzees with the virus of hepatitis B', Nature, 237/5357 (1972), 514-15; LF Barker, et al., 'Transmission of type B viral hepatitis to chimpanzees', Journal Infectious Diseases, 127/6 (1973), 648-62.1972-06-01T00:00:00+00001972-12-01T00:00:00+00001975-01-01T00:00:00+0000AU Bertland, AA Tytell, GP Lampson, E Buynak, 'Method for purifying hepatitis B antigen'm US Patent US4017360A. The patent was granted 12 April 1977.1975-05-14T00:00:00+0000WJ McAleer, EH Wamuth, 'Process for isolating hepatitis b antigen', US Patent 4024243. The patent was granted 17 May 1977.1975-06-16T00:00:00+0000The study carried out in 12 chimpanzees indicated the vaccine would be safe to test in humans, MR Hilleman, EB Buynak, RR Roehm, AA Tytell, AU Bertland, 'Purified and inactivated hepatitis vaccine: Progress Report', American Journal of Medical Sciences, 279/2 (1975), 401-4.1975-09-01T00:00:00+0000Conducted among 1,083 gay men in New York. Gay men were ten times more likely to get hepatitis B than the normal population. Men injected with the vaccine were found to be 75% less likely to get hepatitis B than those who didn't get the vaccine. The trial was done by Wolf Szmuness at New York Medical Center using the vaccine produced by Hilleman at Merck. 1978-01-01T00:00:00+0000The vaccine was developed by Alfred Prince in partnership with John Vnek. Together they devised easier and less expensive purification steps than those used by Merck. The new vaccine required a tenth of the dose than Merck's vaccine. All these measures helped reduce the cost of the vaccine, which was 50 cents per dose. This compared with $90 to $100 for 3 doses of the Merck plasma vaccine. The low cost vaccine was licensed to Cheil Division of Samsung, Korea, Wuhan Institute in China and the Ministry of Healthy in Burma. 1978-01-01T00:00:00+0000The patent was filed on the basis of work undertaken by Kenneth Murray. 1978-12-22T00:00:00+0000The work, funded by Biogen, was undertaken as part of a project to develop recombinant hepatitis B vaccine. It was published in CJ Burrell, P Mackay, PJ Greenaway, PH Hofsneider, K Murray, 'Expression in Escheria Coli of hepatitis B virus DNA sequences cloned in plasmid pBR322', Nature, 279/5708 (1979), 43-47. 1979-02-01T00:00:00+0000F Galibert, E Mandart, F Fitoussi, P Tiollais, P Charnay, , 'Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature, 281/5733 (1979), 646-50; P. Charnay, C Pourcel, A Louise, A Fritsch, P Tiollais, 'Cloning in Escherichia coli and physical structure of hepatitis B virion DNA', PNAS USA, 76/5 (1979), 2222-26; P Charnay, E Mandart, A Hampe, F Fitoussi, P Tiollais, F Galibert, 'Localization on the viral genome and nucleotide sequence of the gene coding for the two major polypeptides of the hepatitis B surface antigen (HBs Ag)', Nucleic Acids Research, 7/2 (1979), 335-46.1979-05-01T00:00:00+0000The research was funded by Merck with the aim of developing a recombinant vaccine against hepatitis B. It was published in P Valenzuela, P Gray, M Quiroga, J Zaldivar, H M Goodman, WJ Rutter, 'Nucleotide sequence of the gene coding for the major protein of hepatitis B virus surface antigen', Nature, 280/5725 (1979), 815e819.1979-08-30T00:00:00+0000The patent was based on the work of Kenneth Murray. It was granted in July 1990 as European Patent (UK) No 0182442. 1979-12-21T00:00:00+00001980-01-01T00:00:00+0000JC Edman, P Gray, P Valenzuela, LB Rall, WJ Rutter, 'Integration of hepatitis B virus sequences and their expression in a human hepatoma cell', Nature, 286/5772 (1980), 535-38.1980-07-31T00:00:00+00001981-01-01T00:00:00+00001981-07-01T00:00:00+0000The vaccines were made with HBsAg purified from plasma of people with chronic hepatitis B. The vaccines were Hevac B Pasteur - made by Merieux and the Pasteur Institute and Hepatavax made by Maurice Hilleman at Merck.1982-01-01T00:00:00+0000The programme, called the Hepatitis B eradication 5-year programme, used plasma-derived vaccines developed by Korean companies: Korean Green Cross, Cheil, and LG Industry. 1982-01-01T00:00:00+0000WHO, WHO Technical Report Series, No. 691 (Geneva: WHO, 1983).1983-01-01T00:00:00+0000The trial was done with 37 healthy adult volunteers. The vaccine was made using HBsAg cloned in yeast. EM Scolnick, AA McLean, DJ West, WJ McAleer WJ Miller, EB Buynak, 'Clinical evaluation in healthy adults of a hepatitis B vaccine made by recombinant DNA', JAMA 251/21 (1984), 2812-15. 1984-06-01T00:00:00+00001984-07-01T00:00:00+0000The vaccine, Hepatabox, was developed by Green Cross using Prince and Vnek's technique. 1986-01-01T00:00:00+0000The vaccine was first approved in West Germany, in May, and then in the US in July. The vaccine was regarded as a breakthrough because it was made from a genetically engineered sub-particle of the virus. This made it much safer than the original vaccine which used the virus sub-particle sourced from the blood of hepatitis B sufferers. The vaccine heralded a new era for the production of vaccines and is a major weapon against one of the most infectious diseases. 1986-05-01T00:00:00+0000HepataxinB was developed by Cheil Sugar using the technique licensed from Alfred Prince and John Vnek.1986-11-01T00:00:00+00001986-12-01T00:00:00+0000JH Hoofnagle, KD Mullen, B Jones, et al, 'Treatment of chornic non-A, non and non-B hepatitis with recombinant human alpha interferon' NEJM, 315 (1986), 1575-78.1986-12-18T00:00:00+0000The technology was developed at Merck's plant in Montgomery County, Philadelphia. The deal was initiated by Roy Vagelos, Merck's CEO. The aim was to help China deal with its major hepatitis B problem.1989-01-01T00:00:00+00001989-01-01T00:00:00+00001989-05-01T00:00:00+00001990-01-01T00:00:00+00001992-01-01T00:00:00+0000The drug was developed by Schering Plough. The drug helps suppress the replication of the hepatitis B virus. 1992-07-13T00:00:00+00001993-01-01T00:00:00+00001994-01-01T00:00:00+00001994-01-01T00:00:00+0000Developed by GlaxoSmithKline, the drug was originally approved for HIV. The drug does not offer a cure but helps block infected cell replication, thereby helping to reduce liver inflammation and delay scarring of the liver caused by hepatitis B. 1998-12-09T00:00:00+00001999-01-01T00:00:00+00002001-01-01T00:00:00+00002001-01-01T00:00:00+0000The drug was originally developed by Gilead Sciences for the treatment of HIV. The drug works by blocking an enzyme, reverse transcriptase, the heptitis B virus needs to reproduce in the body. 2002-09-20T00:00:00+0000This included 6 member states that had policies for vaccinating adolescents. Of the 89 member states with historically high prevalences of chronic hepatitis B infection, 64 (72%) had adopted universal infant hepatitis B vaccination.2003-05-01T00:00:00+00002003-05-01T00:00:00+00002005-03-30T00:00:00+0000Hilleman, an American microbiologist, is credited with having saved more children's lives than any other medical scientist in the 20th century. He pioneered eight out of the fourteen vaccines routinely recommended for children today. This included the vaccines for measles, mumps, hepatitis A, hepatitis B, chickenpox, meningitis, pneumonia and Haemophilus influenzae bacteria. Hilleman developed these vaccines as head of Merck & Co's virus and cell biology research department. 2005-04-11T00:00:00+00002005-05-13T00:00:00+00002006-10-25T00:00:00+00002007-01-01T00:00:00+0000The drug is also used to treat HIV.2008-08-11T00:00:00+0000Blumberg was an American physician and geneticist who won the Nobel Prize in 1976 for his discovery of a surface antigen for the hepatitis B virus. He found the antigen while conducting work on blood samples from different populations from around the world to understand genetic variations in susceptibility to disease. The antigen was first spotted testing a blood sample from a haemophiliac patient in New York against blood taken from a visiting Korean physician. Blumberg's discovery paved the way to the development of the first screen test for hepatitis B to prevent its spread in blood donations. His research also helped in the creation of the first vaccine against the disease, which to this day is the gold standard in the management of the disease.2011-04-05T00:00:00+0000The trials undertaken from 2013 used a drug that interferes with RNA. The drug was developed by Arrowhead Pharmaceuticals. The aim of the drug is to reduce the surface antigens (HBsAg) created by chronic hepatitis B infections. The trials showed the experimental drug was safe and effective enough to be tested in people. The drug is designed to deliver a molecule to the liver where it binds to a receptor, and then another molecule, derived from bee venom, helps break through the membranes in the liver cells to deliver the medicine directly into the cells. The drug interferes with the the expression of the hepatitis B messager RNA that produces HBsAg. 2015-01-01T00:00:00+00002016-11-09T00:00:00+0000The company's shares fell from a high of $6.18 on November 8, 2016, to an $1.20 on December 21, 2016. 2016-11-09T00:00:00+00002017-08-01T00:00:00+0000World Hepatitis Alliance,' Study shows universal vaccination has wiped out hepatitis B and associated liver cancer in Alaska's young people', MedicalXpress, August 10 2017. The study was carried out by Brian McMahon and colleagues at the Alaska Native Tribal Health Consortium (ANTHC) Hepatitis Program. The results was reported to the World Indigenous Peoples' Conference on Viral Hepatitis in Anchorage, Alaska. 2017-08-08T00:00:00+0000The vaccine was developed by Dynavax2017-11-01T00:00:00+00002018-02-01T00:00:00+0000The aim of the drug is to mute hepatitis B genes to give the immune system a chance to fight the hepatitis B infection.2018-03-27T00:00:00+0000Developed by Arrowhead Pharmaceuticals, the drug, ARC-520, is administered with the antiviral entecavir. The treatment cleared the HBsAg from one patient and substantially reduced it in the remaining patients. The results were presented to the European Association for the Study of the Liver. 2018-05-02T00:00:00+0000
Date Event People Places
1600 - 1900Outbreaks of jaundice common in urban populations and armies during wars 
1861 - 1865Outbreaks of of jaundice noted in Union troops during American Civil War 
1865Rudolf Virchow, renowned pathologist, argued jaundice caused by deranged cellular functionVirchow 
1885Jaundice outbreaks recorded among German shipworkers and inmates in an asylum several months after receiving smallpox vaccination containing human lymphLurman 
1908Stuart McDonald, a pathologist, argued fulminant hepatitis could be an infectious disease transmitted by a virusMcDonaldUniversity of Durham
30 Aug 1919Maurice Hilleman was born in Miles City, Montana, USAHillemanMerck & Co
1920Sudden increase in jaundice observed in patients treated for syphilis StokesMayo Clinic
28 Jul 1925Baruch S. Blumberg born in New York NY, USABlumbergFox Chase Cancer Center, University of Pennsylvania
1926Flaum and co-workers link jaundice epidemic in patients attending a Swedish diabetes clinic to virus transmitted between humansFlaum, Malmros, Persson 
May 1931Human bodily fluid suggested to contain filterable agent causing hepatitisFindlay, Dunlop, BrownWellcome Bureau of Scientific Research
1937 - 1940Growing recognition of chronic hepatitis in patients with 'catarrhal jaundice' 
1937 - 1941Persistent hepatic inflammation detected in patients who otherwise appeared to recover from jaundicePolack, Kornberg 
1938 - 1947Outbreaks of jaundice linked to prophylactic injections of plasma drawn from convalescent measles and mumps patientsPropert, Beeson, Chesney, McFarlan 
1938Jaundice and hepatitis found in 3% of 3100 recipients of yellow fever vaccineFindlay, MacCallum 
1939 - 1942Danish clinicians undertaking liver biopsies detected hepatic inflammation in patients with jaundice, undermining 'catarrhal' origin ideaRoholm, Iversen 
1942Yellow fever vaccine containing human serum caused massive jaundice outbreak in US armySawyer, Turner 
1942Hans Voegt reported first deliberate transmission of viral hepatitis to human volunteersVoegtUniversity Hospital Vienna
1943Blood transfusion and treatment with normal immune globulin linked to jaundiceMorgan, WilliamsonSt Bartholomew's Hospital
1943 - 1945Jaundice linked to blood transfusionBeeson, Grossmanb, Stewart, Stokes 
1943British Ministry of Health introduced the term 'homologous serum jaundice' to decribe jaundice following innoculation with blood products 
1944Jaundice outbreak among syphilitic patients linked to inoculation with salvarsan with an 'infective agent'Marshall, Beattie 
1944 - 1945Infectious hepatitis shown to be caused by a filterable agent in fecal matter and blood, and to be resistant to heat and chlorineMacCallum, Bradley, Havens, Findlay, WilcoxMRC Jaundice Committee, Yale University
1944Cirrhosis found in several deceased patients with no history of alcoholic liver disease who had recovered from jaundiceRatnoff, PatekColumbia University, Welfare Hospital
1945Serum shown to be source of hepatitis infection MacCallum, Bradley 
1945First evidence that jaundice caused by infectious agent in bloodMacCallum 
8 Dec 1945Gamma-globulin observed to help patients who developed hepatitis after receiving blood transfusionsGrossman, Stewart, Stokes 
January 1946Largest outbreak of serum hepatitis recorded following yellow vaccine campaign 
1946British Medical Journal editorial advises against use of blood products because of risk of jaundice 
1946Infectious hepatitis found to have incubation period of 20-30 daysHavens, Francis, Frisch, Quilligan 
1946Evidence emerged that infectious hepatitis caused by more than one causative agentNeefe, Gellis, Stokes 
1947'Infectious hepatitis' renamed hepatitis A, and 'serum hepatitis' renamed hepatitis BMacCallum 
1953WHO Expert Committee published report epidemic and serum hepatitis 
1954Chronic viral carriers identified in human volunteer studiesKeefe, Norris, Reinhold, Mitchell, Howell, Roderick MurrayUniversity of Pennsylvania, National Institutes of Health
1954Researchers estimated 0.2-0.5% US population carry hepatitis B virus in their bloodStokesTemple University, Albert Einstein Medical Center, Children's Hospital of Philadelphia
1957 - 1964Baruch Blumberg launched study of variation in serum proteins in blood samples from different populations to understand individual disease susceptibilityBlumberg, DublinFox Chase Cancer Center
1957Maurice Hilleman started researching hepatitisHillemanWalter Reed Army Medical Center
1964Blumberg discovered unusual protein in serum from New York haemophliac patient and an AborigineBlumbergFox Chase Cancer Center
1964WHO issued second report on hepatitis 
1965Blumberg called newly found protein 'Austalian antigen' and saw it as genetic marker for leukaemiaBlumberg, Alter, VischFox Chase Cancer Center
20 Jul 1966Boy with Down Syndrome found to have chronic hepatitis whose blood 6 months before tested positive for Australian antigenBlumbergFox Chase Cancer Center
April 1967Barbara G Werner, technician working in Blumberg's laboratory developed hepatitis after working with Australian antigenWerner, BlumbergFox Chase Cancer Center
1 May 1967Willowbrook State School experiments offered new understandings about hepatitis, its treatment and preventionKrugman, Giles, HammondNew York University, Willbrook State School
1968Alfred Prince, virologist, showed Australian antigen part of hepatitis B virusPrinceNew York Blood Center
1968Prince set up scheme to test donor's blood for hepatitis B at New York Blood CenterPrinceNew York Blood Center
January 1968Collaboration set up between Blumberg's team and Philadelphia General Hospital to test donor's blood for Australian antigenBlumbergPhiladelphia General Hospital, Fox Chase Cancer Center
1968Maurice Hilleman began investigating use of HBsAg to develop hepatitis B vaccine HillemanMerck
1969 - 1972Chronic hepatitis B linked to the development of liver cancerSmith, Blumberg, Sutnick, Millman, LondonFox Chase Cancer Center
1969 - 1971Severe outbreak of hepatitis B in dialysis unit at Edinburgh Royal Infirmary 
8 Oct 1969Blumberg and Millman applied for patent to use HBsAg to produce hepatitis B vaccineBlumberg, MillmanFox Chase Cancer Center
1970US blood banks started using screening test for hepatitis B carriers 
1970WHO Bulletin recommended the detection and exclusion of blood donors carrying the Australian antigen 
4 Apr 1970David Dane and colleagues showed Australian antigen is a surface particle - rename it Hepatitis B surface antigen (HBsAg)Dane, Cameron, BriggsCentral Middlesex Hospital
1971New York State passed legislation requiring testing for hepatitis B for all blood donors 
1971HBsAG purified for first timeHillemanMerck
1 Jan 1972Scientists at Abbott Laboratories published a new highly sensitive test, Austria 125, for detecting hepatitis BLing, OverbyAbbott Laboratories
1972Abbott marketed the first adequate hepatitis B diagnostic testAbbott Laboratories
18 Jan 1972Patent granted to Blumberg and Millman for making hepatitis B vaccineBlumberg, Millman 
1972 - 1973Hepatitis B found to be transmitted to chimpanzeesBarker, MaynardFDA, Hazleton Laboratories, Hammersmith Hospital, Scripps Clinic and Research Foundation, University North Carolina, Pohenix Laboratories, National Institute of Health
December 1972UK introduced testing to screen for HBsAg for all blood donations 
1975Pasteur Institute scientists started to develop fractionation method to purify HBsAg from plasma to produce hepatitis B vaccineTiollaisPasteur Institute
14 May 1975Merck filed US patent for technique to purify hepatitis B antigenBertland, Tytell, Lampson, BuynakMerck
16 Jun 1975Merck filed US patent for process to isolate hepatitis B antigenMcAleer, WasmuthMerck
September 1975Merck reported positive results from chimpanzee trials with hepatitis B vaccine containing inactivated HBsAg antigenHilleman, Buynak, Roehm, Tytell, BertlandMerck
1978 - 1980First clinical trials with plasma vaccine against hepatitis BSzmuness, HillemanNew York Medical Center
1978 - 1986Low-cost plasma hepatitis B vaccine developedPrince, VnekNew York Blood Center
December 1978Biogen filed preliminary UK patent for technique to clone hepatitis B DNA and antigensKenneth MurrayBiogen, University of Edinburgh
February 1979University of Edinburgh scientists published the successful isolation and cloning DNA fragments of the hepatitis B virus in Escherichia coliBurrell, Mackay, Greenaway, Hofschneider, K MurrayUniversity of Edinburgh, Microbiological Research Establishment, Biogen
May 1979 - October 1979Pasteur Institute scientists reported successful cloning of hepatitis B DNA in Escherichia coliGalibert, Mandart, Fitoussi, Tiollais, Charnay, HampePasteur Institute
30 Aug 1979UCSF scientists announced the successful cloning and expression of HBsAg in Escherichia coliValenzuela, Gray, Quiroga, Zaldivar, Goodman, RutterUniversity of California San Francisco, Merck
21 Dec 1979Biogen applied for European patent to clone fragment of DNA displaying hepatitis B antigen specificityMurrayBiogen
1980Pasteur Institute filed for US patent for fractionation method to purify HBsAg from plasma to produce hepatitis B vaccineTiollaisPasteur Institute
31 Jul 1980UCSF scientists published method to culture HBsAg antigens in cancer cellsEdman, Gray, Valenzuela, Rall, RutterUniversity of California San Francisco
1981 - 1991US hepatitis B vaccination programme directed towards people identified at high risk 
July 1981UCSF and Merck filed patent to snthesise HBsAg in recombinant yeastRutterUniversity of California San Francisco, Merck
1982First plasma vaccines against hepatitis B licensed for market in US and EuropeHillemanMerieux, Institute Pasteur, Merck
1982South Korea government launched nationwide hepatitis B immunisation programme  
1983WHO argued hepatitis B virus second only to tobacco as cause of cancer 
1 Jun 1984Genetically engineered vaccine against hepatitis B reported to have positive trial resultsScolnick, McLean, West, McAleer , Miller, BuynakMerck, University California San Francisco
July 1984Taiwan launched nationwide hepatitis B vaccination programme 
1986Low-cost plasma vaccine against hepatitis B approved in Indonesia 
1986First genetically engineered vaccine against hepatitis B approvedScolnickMerck
November 1986Low-cost plasma hepatitis B vaccine gained approval in South KoreaPrince, VnekCheil Sugar
December 1986Genetically engineered hepatitis B vaccine, Engerix-B, approved in BelgiumSmithKline Biologicals
18 Dec 1986Results released from first small-scale clinical trial of recombinant interferon-alpha therapy for post-transfusion chronic hepatitis BHoofnagle, Mullen, Jones, Rustgi, Di Bisceglie, Peters, Waggoner, ParkNational Institutes of Health
1989Merck sold hepatitis B vaccination manufacturing technology to Chinese government for $7millionVagelosMerck
January 1989Genetically engineered hepatitis B vaccine, Engerix-B, approved in USSmithKline Biologicals
May 1989Genetically engineered hepatitis B vaccine, GenHevac, approved in FrancePasteur Vaccins
1990Hepatitis B vaccine cost US$3 per dose 
1992WHO recommended all countries integrate hepatitis B vaccination into their universal childhood vaccination programmes by 1997 
13 Jul 1992FDA approved the use of genetically engineered interferon-alpha, Intron A, for the treatment of hepatitis BSchering-Plough
1993Hepatitis B vaccination manufacturing plant opened in Beijing, aided by MerckMerck
1994Ten years after rolling out its nationwide hepatitis B vaccination programme Taiwan reported its children's HBsAg carrier rate had reduced from 10% to less than 1% 
1994Hepatitis B vaccination manufacturing plant opened in Shenzhen, aided by Merck 
9 Dec 1998FDA approved the first antiviral drug, lamivudine, for treating chronic hepatitis BGlaxoSmithKline
1999Global Alliance for Vaccines and Immunization (GAVI) and the Vaccine Fund (VF) launched programme to support poor countries roll-out hepatitis B vaccination 
2001WHO recorded that 126 (66%) of its 191 member states had universal infant or childhood hepatitis B vaccination programmes 
2001Hepatitis B vaccine cost US$0.30 per dose 
20 Sep 2002FDA approved adefovir, an antiviral drug, dipivoxil for treatment of chronic hepatitis BGilead Sciences
May 2003WHO recorded that 151 (79%) of 192 member states had adopted universal childhood hepatitis B vaccination programmes 
May 2003GAVI/VF reported that 48 (64%) of poor countries eligible for their support had received funding to introduce hepatitits B vaccine 
30 Mar 2005FDA approved entecavir, an antiviral drug, for treatment of chronic hepatitis B in adults and children under 2 years old 
11 Apr 2005Maurice Hilleman diedHillemanMerck & Co
13 May 2005FDA approved peginterferon alfa-2a, an antiviral drug, for patients with chronic hepatitis B who failed previous antiviral treatmentRoche
25 Oct 2006FDA approved telbivudine, an antiviral drug, for the treatment of hepatitis B infectionNovartis, Idenix
2007WHO reported that 71 (89%) of its 193 member states had initiated a hepatitis B vaccination programme 
11 Aug 2008FDA approved tenofovir disoproxil fumarate, an antiviral drug, to treat chronic hepatitis BGilead Sciences
5 Apr 2011Baruch S. Blumberg diedblumbergFox Chase Cancer Center, University of Pennsylvania
2015Chimpanzee trials indicated that gene silencing drug could treat hepatitis B Arrowhead Pharmaceuticals
9 Nov 2016FDA halted phase II trials with RNA interference drug, ARC-520, due to multiple deaths of non-human primates treated with high dosesArrowhead Pharmaceuticals
9 Nov 2016 - December 21, 2016Arrowhead Pharmaceuticals shares fell following hold on clinical trials with RNAi drug to treat hepatitis BArrowhead Pharmaceuticals
August 2017UK, one of the last countries in Europe, rolled out hepatitis B vaccination programme for infants 
8 Aug 2017Universal hepatitis B vaccination introduced for all newborns in 1980s reported to have wiped out hepatitis B infection and associated liver cancer cases in Alaskan indigenous population 
November 2017FDA approved a two-dose hepatitis B vaccine for use in adults aged 18 and overDynavax
February 2018Hepatitis B Foundation Drug Watch listed 36 drugs at various development stages for chronic hepatitis B 
27 Mar 2018Dosing trial launched with humans to test use of RNA interference drug to treat hepatitis BArrowhead Pharmaceuticals
2 May 2018Positive results for RNAi drug for treating chronic hepatitis b reported from 8-person clinical trialArrowhead Pharmaceuticals