{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:45:28Z","timestamp":1765640728495,"version":"3.48.0"},"reference-count":32,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gut"],"published-print":{"date-parts":[[1992,11]]},"abstract":"<jats:p>Hepatocyte expression of pre-S1 and pre-S2 in relation to hepatitis B virus replication (hepatitis B virus-DNA in serum and HBcAg in the liver), histological activity and hepatitis delta virus superinfection was studied by indirect immunofluorescence on frozen sections of liver specimens from 68 patients with chronic hepatitis B virus infection. All 44 patients with chronic type B hepatitis had pre-S1 and pre-S2 display in the liver. The distribution of pre-S1 in the liver was membranous in one, mixed membranous and cytoplasmic in 12, and cytoplasmic in 31. The distribution of pre-S2 was membranous in one, mixed membranous and cytoplasmic in 26, and cytoplasmic in 17. Membranous expression of pre-S1 was significantly more prevalent in patients with active hepatitis B virus replication than in those without (13\/28 v 0\/16, p &lt; 0.001), regardless of the histological activity, as was membranous expression of pre-S2 (27\/28 v 0\/16, p &lt; 0.001). In contrast, a significantly higher extent of cytoplasmic expression of pre-S1 and pre-S2 was noted in patients without active hepatitis B virus replication than in those with. Of 24 patients with chronic type D hepatitis virus, eight had active hepatitis B virus replication, and the other 16 did not. The distribution and quantitative expression of pre-S1 and pre-S2 in the liver in these patients also correlated significantly with the status of hepatitis B virus replication and, moreover, showed little or no difference from those without hepatitis delta virus infection. In conclusion, all patients with chronic type B hepatitis had synthesis and display of pre-S1 and pre-S2 in the liver. The distribution and quantitative expression of pre-S1 and pre-S2, however, were closely related to the status of hepatitis B virus replication, but not to the histological activity. Hepatocyte expression of pre-S1 and pre-S2 in chronic type D hepatitis also correlated significantly with status of hepatitis B virus replication, and was not modulated by concurrent hepatitis delta virus infection.<\/jats:p>","DOI":"10.1136\/gut.33.11.1544","type":"journal-article","created":{"date-parts":[[2007,9,18]],"date-time":"2007-09-18T17:41:31Z","timestamp":1190137291000},"page":"1544-1548","source":"Crossref","is-referenced-by-count":6,"title":["Intrahepatic expression of pre-S1 and pre-S2 antigens in chronic hepatitis B virus infection in relation to hepatitis B virus replication and hepatitis delta virus superinfection."],"prefix":"10.1136","volume":"33","author":[{"given":"C M","family":"Chu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y F","family":"Liaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1992,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/317489a0","article-title":"The hepatitis B virus","volume":"317","author":"Tiollais, P.; Pourcel, C.; Dijean, A.","year":"1985","unstructured":"Tiollais P, Pourcel C, Dijean A. The hepatitis B virus. Nature 1985; 317: 489-95.","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1002\/jmv.1890310106","article-title":"Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma","volume":"31","author":"Robinson, W.S.; Klote, L.; Aoki, N.","year":"1990","unstructured":"Robinson WS, Klote L, Aoki N. Hepadnaviruses in cirrhotic liver and hepatocellular carcinoma. J Med Virol 1990; 31: 18-32.","journal-title":"J Med Virol"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1128\/JVI.52.2.396-402.1984","article-title":"Large surface proteins of hepatitis B virus containing the pre-S sequence","volume":"52","author":"Heermann, K.H.; Goldmann, U.; Schwartz, W.; Seyffarth, T.; Baumgarten, H.; Gerlich, W.H.","year":"1984","unstructured":"Heermann KH, Goldmann U, Schwartz W, Seyffarth T, Baumgarten H, Gerlich WH. Large surface proteins of hepatitis B virus containing the pre-S sequence. J Virol 1984; 52: 396-402.","journal-title":"J Virol"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1128\/JVI.58.2.522-525.1986","article-title":"Pre-SI antigens and antibodies early in the course of acute hepatitis B virus infection","volume":"58","author":"Klinkert, M.Q.; Theilmann, L.; Praff, E.","year":"1986","unstructured":"Klinkert MQ, Theilmann L, Praff E. Pre-SI antigens and antibodies early in the course of acute hepatitis B virus infection. J Virol 1986; 58: 522-5.","journal-title":"J Virol"},{"key":"ref_5","first-page":"45","article-title":"Hepatitis B virus proteins eliciting protective immunity","volume":"4","author":"Neurath, A.R.; Jameson, B.A.; Huima, T.","year":"1987","unstructured":"Neurath AR, Jameson BA, Huima T. Hepatitis B virus proteins eliciting protective immunity. Microbiol Sci 1987; 4:45-51.","journal-title":"Microbiol Sci"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0092-8674(86)90663-X","article-title":"Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus","volume":"46","author":"Neurath, A.R.; Kent, S.B.H.; Strick, N.","year":"1986","unstructured":"Neurath AR, Kent SBH, Strick N. Identification and chemical synthesis of a host cell receptor binding site on hepatitis B virus. Cell 1986; 46: 429-36.","journal-title":"Cell"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1002\/hep.1840060206","article-title":"Detection of pre-SI proteins in serum and liver of HBsAg-positive patients: A new markers for hepatitis B virus infection","volume":"6","author":"Theilmann, L.; Klinkert, M.Q.; Gmelin, K.; Salfeld, J.; Schallor, H.; Pfaff, E.","year":"1986","unstructured":"Theilmann L, Klinkert MQ, Gmelin K, Salfeld J, Schallor H, Pfaff E. Detection of pre-SI proteins in serum and liver of HBsAg-positive patients: A new markers for hepatitis B virus infection. Hepatology 1986; 6: 186-90.","journal-title":"Hepatology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1016\/0016-5085(87)90617-2","article-title":"Pre-S encoded surface proteins in relation to the major surface antigens in acute hepatitis B virus infection","volume":"92","author":"Gerken, G.; Manns, M.; Gerlich, W.H.","year":"1987","unstructured":"Gerken G, Manns M, Gerlich WH. Pre-S encoded surface proteins in relation to the major surface antigens in acute hepatitis B virus infection. Gastroenterology 1987; 92: 1864-8.","journal-title":"Gastroenterology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1111\/j.1600-0676.1989.tb00391.x","article-title":"Expression and clinical significance of pre-S1 and S2 proteins of HBV in sera of patients with chronic liver disease","volume":"9","author":"Hu, K.Q.; Yu, Z.Q.; Li, F.H.; Hao, L.J.","year":"1989","unstructured":"Hu KQ, Yu ZQ, Li FH, Hao LJ. Expression and clinical significance of pre-S1 and S2 proteins of HBV in sera of patients with chronic liver disease. Liver 1989; 9: 146-52.","journal-title":"Liver"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/hep.1840090202","article-title":"Serum titers of pre-S(2) antigen in patients with acute and chronic type B hepatitis: relation to serum aminotransferase activity and other hepatitis B virus markers","volume":"9","author":"Y, Oka H.","year":"1989","unstructured":"Kurai K, Lino K, Koike K, Mitamura K, Endo Y, Oka H. Serum titers of pre-S(2) antigen in patients with acute and chronic type B hepatitis: relation to serum aminotransferase activity and other hepatitis B virus markers. Hepatology 1989; 9:175-9.","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0168-8278(87)80029-6","article-title":"Expression of pre-S gene encoded proteins in liver and serum during chronic hepatitis b virus infection in comparison to other markers of active viral replication","volume":"5","author":"Hadziyannis, S.; Raimondo, G.; Papaioannou, C.; Anastassakos, C.; Wong, D.; Sninsky, J.","year":"1987","unstructured":"Hadziyannis S, Raimondo G, Papaioannou C, Anastassakos C, Wong D, Sninsky J, et al. Expression of pre-S gene encoded proteins in liver and serum during chronic hepatitis b virus infection in comparison to other markers of active viral replication. J Hepatol 1987; 5: 253-9.","journal-title":"J Hepatol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1002\/hep.1840060615","article-title":"Demonstration of pre-S polypeptides of chronic hepatitis B virus carriers","volume":"6","author":"Thung, S.N.; Gerber, M.A.; Kasamblides, E.J.; Gilja, B.A.; Keh, W.; Gerlich, W.H.","year":"1986","unstructured":"Thung SN, Gerber MA, Kasamblides EJ, Gilja BA, Keh W, Gerlich WH. Demonstration of pre-S polypeptides of chronic hepatitis B virus carriers. Hepatology 1986; 6: 1315-8.","journal-title":"Hepatology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/j.1600-0676.1987.tb00352.x","article-title":"Relationship of pre-S encoded antigens in liver and clinical manifestation of chronic hepatitis B infection","volume":"7","author":"Hess, G.; Gerlich, W.H.; Gerken, G.; Manns, M.; Meyer Zum Buschenfelde, K.H.","year":"1987","unstructured":"Hess G, Gerlich WH, Gerken G, Manns M, Meyer Zum Buschenfelde KH. Relationship of pre-S encoded antigens in liver and clinical manifestation of chronic hepatitis B infection. Liver 1987; 7: 245-50.","journal-title":"Liver"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0168-8278(88)80477-X","article-title":"Expression of pre-S1 in liver of chronic hepatitis B virus carriers","volume":"7","author":"Fraiese, A.; Pontisso, P.; Cavalletto, D.; Fattovich, G.; Alberti, A.","year":"1988","unstructured":"Fraiese A, Pontisso P, Cavalletto D, Fattovich G, Alberti A. Expression of pre-S1 in liver of chronic hepatitis B virus carriers. JHepatol 1988; 7: 157-63.","journal-title":"JHepatol"},{"key":"ref_15","first-page":"1538","article-title":"Intrahepatic expression of pre-S proteins of hepatitis B virus and its possible relation to liver cell necrosis","volume":"84","author":"Hu, K.Q.; Hao, L.J.; Zhang, Y.Y.; Wang, Y.K.","year":"1989","unstructured":"Hu KQ, Hao LJ, Zhang YY, Wang YK. Intrahepatic expression of pre-S proteins of hepatitis B virus and its possible relation to liver cell necrosis. Am J Gastroenterol 1989; 84: 1538-42.","journal-title":"Am J Gastroenterol"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1111\/j.1600-0676.1989.tb00420.x","article-title":"Ultrastructural localization of pre-S2 polypeptides in the liver tissues of patients with chronic hepatitis B virus infection","volume":"9","author":"Saito, T.; Kamimura, T.; Asakura, H.; Ishikawa, M.","year":"1989","unstructured":"Saito T, Kamimura T, Asakura H, Ishikawa M. Ultrastructural localization of pre-S2 polypeptides in the liver tissues of patients with chronic hepatitis B virus infection. Liver 1989; 9: 329-37.","journal-title":"Liver"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1016\/0016-5085(90)90028-Y","article-title":"Hepatic expression patterms of the large and middle hepatitis B virus surface proteins in viremic and nonviremic chronic hepatitis B","volume":"98","author":"Dienes, H.P.; Gerlich, W.H.; Worsdorfer, M.; Gerken, G.; Bianchi, L.; Hess, G.","year":"1990","unstructured":"Dienes HP, Gerlich WH, Worsdorfer M, Gerken G, Bianchi L, Hess G, et al. Hepatic expression patterms of the large and middle hepatitis B virus surface proteins in viremic and nonviremic chronic hepatitis B. Gastroenterology 1990; 98: 1017-23.","journal-title":"Gastroenterology"},{"key":"ref_18","first-page":"343","article-title":"Immunohistochemical study of pre-S(2) antigen in liver and serum of patients with chronic hepatitis B","volume":"25","author":"Takaguchi, K.; Yamada, G.; Tsuji","year":"1990","unstructured":"Takaguchi K, Yamada G, Tsuji. Immunohistochemical study of pre-S(2) antigen in liver and serum of patients with chronic hepatitis B. GastroenterolJtpn 1990; 25: 343-9.","journal-title":"GastroenterolJtpn"},{"key":"ref_19","first-page":"364","article-title":"Expression of pre-S1, pre-S2 and X peptides in relation to viral replication in livers with chronic hepatitis B","volume":"355","author":"Suzuki, K.; Udrida, T.; Shikata, T.; Moiryama, M.; Arakawa, Y.; Mizokami, M.","year":"1990","unstructured":"Suzuki K, Udrida T, Shikata T, Moiryama M, Arakawa Y, Mizokami M, et al. Expression of pre-S1, pre-S2 and X peptides in relation to viral replication in livers with chronic hepatitis B. Liver 1990; 355: 364.","journal-title":"Liver"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1038\/305336a0","article-title":"Signals regulating hepatitis B surface antigen transcription","volume":"305","author":"Cattaneo, R.; Will, H.; Hernandez, N.; Schaller, H.","year":"1983","unstructured":"Cattaneo R, Will H, Hernandez N, Schaller H. Signals regulating hepatitis B surface antigen transcription. Nature 1983; 305: 336-8.","journal-title":"Nature"},{"key":"ref_21","first-page":"83","article-title":"Hybrid hepatitis B virus-host transcripts in a","volume-title":"human hepatoma cell. Proc Natl Acad Sci USA","volume":"82","author":"Ou, J.H.; Rutter, W.J.","year":"1985","unstructured":"Ou JH, Rutter WJ. Hybrid hepatitis B virus-host transcripts in a human hepatoma cell. Proc Natl Acad Sci USA 1985; 82: 83-7."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9338","DOI":"10.1073\/pnas.83.24.9338","article-title":"Assembly of viral particles in Xenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle","volume":"83","author":"Standring, D.N.; Ou, J.H.; Rutter, W.J.","year":"1986","unstructured":"Standring DN, Ou JH, Rutter WJ. Assembly of viral particles in Xenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle. Proc Natl Acad Sci USA 1986; 83: 9338-42.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1126\/science.3787251","article-title":"Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide","volume":"234","author":"Persing, D.H.; Vermus, H.E.; Ganem, D.","year":"1986","unstructured":"Persing DH, Vermus HE, Ganem D. Inhibition of secretion of hepatitis B surface antigen by a related presurface polypeptide. Science 1986; 234: 1388-91.","journal-title":"Science"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/0016-5085(87)90863-8","article-title":"Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic\/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis","volume":"92","author":"Chu, C.M.; Liaw, Y.F.","year":"1987","unstructured":"Chu CM, Liaw YF. Intrahepatic distribution of hepatitis B surface and core antigens in chronic hepatitis B virus infection. Hepatocyte with cytoplasmic\/membranous hepatitis B core antigen as a possible target for immune hepatocytolysis. Gastroenterology 1987; 92: 220-5.","journal-title":"Gastroenterology"},{"key":"ref_25","first-page":"590602","article-title":"Transmission of the hepatitis B virus-associated delta antigen to chimpanzee. J7 Infect Dis","volume":"141","author":"Rizzetto, M.; Canese, M.G.; Gerin, J.L.; London, W.T.; Siy, D.L.; Purcell, R.H.","year":"1980","unstructured":"Rizzetto M, Canese MG, Gerin JL, London WT, Siy DL, Purcell RH. Transmission of the hepatitis B virus-associated delta antigen to chimpanzee. J7 Infect Dis 1980; 141: 590602."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1002\/hep.1840050404","article-title":"Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers","volume":"5","author":"Hadziyannis, S.J.; Sherman, M.; Liberman, H.M.; Shafritz, D.O.","year":"1985","unstructured":"Hadziyannis SJ, Sherman M, Liberman HM, Shafritz DO. Liver disease activity and hepatitis B virus replication in chronic delta antigen-positive hepatitis B virus carriers. Hepatology 1985; 5: 544-7.","journal-title":"Hepatology"},{"key":"ref_27","first-page":"914","article-title":"Acute and chronic hepatitis revisited","volume":"ii:","author":"Group, International","year":"1977","unstructured":"International Group. Acute and chronic hepatitis revisited. Lancet 1977; ii: 914-5.","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/hep.1840070102","article-title":"Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis","volume":"7","author":"Liaw, Y.F.; Pao, C.C.; Chu, C.M.; Sheen, I.S.; Huang, M.J.","year":"1987","unstructured":"Liaw YF, Pao CC, Chu CM, Sheen IS, Huang MJ. Changes of serum hepatitis B virus DNA in two types of clinical events preceding spontaneous hepatitis B e antigen seroconversion in chronic type B hepatitis. Hepatology 1987; 7: 1-3.","journal-title":"Hepatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1002\/jmv.1890300307","article-title":"Intrahepatic expression of HBcAg and delta antigen in anti-HBe positive HBsAg carriers with acute exacerbation or chronic liver disease","volume":"30","author":"Chu, C.M.; Liaw, Y.F.; Sheen, I.S.; Chen, T.J.","year":"1990","unstructured":"Chu CM, Liaw YF, Sheen IS, Chen TJ. Intrahepatic expression of HBcAg and delta antigen in anti-HBe positive HBsAg carriers with acute exacerbation or chronic liver disease.J Med Virol 1990; 30: 181-6.","journal-title":"J Med Virol"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5071","DOI":"10.1073\/pnas.75.10.5071","article-title":"Asymmentric budding of viruses in epithelial monolayers: a model system for epithelial polarity","volume":"75","author":"Rodriguez-Boulan, E.; Sabatini, D.D.","year":"1978","unstructured":"Rodriguez-Boulan E, Sabatini DD. Asymmentric budding of viruses in epithelial monolayers: a model system for epithelial polarity. Proc Natl Acad Sci USA 1978; 75: 5071-5.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.4049\/jimmunol.129.6.2773","article-title":"Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes","volume":"129","author":"Mondelli, M.; Mieli-Vergani, G.; Alberti, A.; Vergani, G.; Portmann, P.; Eddleston, L.W.F.","year":"1982","unstructured":"Mondelli M, Mieli-Vergani G, Alberti A, Vergani G, Portmann P, Eddleston LWF, et al. Specificity of T lymphocyte cytotoxicity to autologous hepatocytes in chronic hepatitis B virus infection: evidence that T cells are directed against HBV core antigen expressed on hepatocytes.JImmunol 1982; 129: 2773-8.","journal-title":"JImmunol"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/jmv.1890340104","article-title":"Pre-SI and pre-S2 gene encoded proteins in liver and serum in chronic hepatitis delta infection","volume":"34","author":"Hadziyannis, S.J.; Georgopoulou, U.; Psalidaki, E.; Budkowska, A.","year":"1991","unstructured":"Hadziyannis SJ, Georgopoulou U, Psalidaki E, Budkowska A. Pre-SI and pre-S2 gene encoded proteins in liver and serum in chronic hepatitis delta infection. J Med Virol 1991; 34: 14-9.","journal-title":"J Med Virol"}],"container-title":["Gut"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/gut.33.11.1544","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T15:40:52Z","timestamp":1765640452000},"score":1,"resource":{"primary":{"URL":"https:\/\/gut.bmj.com\/lookup\/doi\/10.1136\/gut.33.11.1544"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1992,11]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1992,11,1]]},"published-print":{"date-parts":[[1992,11]]}},"alternative-id":["10.1136\/gut.33.11.1544"],"URL":"https:\/\/doi.org\/10.1136\/gut.33.11.1544","relation":{},"ISSN":["0017-5749","1468-3288"],"issn-type":[{"type":"print","value":"0017-5749"},{"type":"electronic","value":"1468-3288"}],"subject":[],"published":{"date-parts":[[1992,11]]}}}