{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:36:43Z","timestamp":1777631803088,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,12,7]],"date-time":"2005-12-07T00:00:00Z","timestamp":1133913600000},"content-version":"vor","delay-in-days":4024,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[1994,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The case of a young female patient with chronic active hepatitis B, vasculitic purpura, edema, and circulating immune complexes due to mixed Cryoglobulinemia is described. Serum transami\u2010nases were elevated. Serological assays showed hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti\u2010HBe), and antibody to hepatitis B core antigen (anti\u2010HBc) antibodies but no antibody to hepatitis C virus (anti\u2010HCV) or antibody to hepatitis delta virus (anti\u2010HDV) antibodies. Using hepatitis B virus\u2010polymerase chain reaction (HBV\u2010PCR) and direct sequencing a precore\/core (preC\/C) mutant unable to synthesize HBeAg was detected in serum. HBV antigens were demonstrated in the circulating immune complexes. Following 1 month of treatment with interferon\u2010a 2b 3 miu three times weekly, alanine aminotransferases returned to normal levels while cryoglobulins and immune complexes disappeared from serum. In addition, 2 months after the onset of treatment serum HBV\u2010DNA was no longer detectable by PCR.<\/jats:p><jats:p>Prior to treatment the analysis of cellular immune reactions of peripheral blood mononu\u2010clear cells showed a major proliferative response to HBcAg, preS1Ag and HBxAg and a minor response to HBeAg and HBsAg. One month after conclusion of treatment a decline in T\u2010cell reactivity against all HBV antigens was observed. During clinical response to the therapy, however, a strong proliferative response of T cells to HBcAg and HBeAg was demonstrated.<\/jats:p><jats:p>In conclusion, immune complex disease may complicate chronic hepatitis B in patients expressing HBe\u2010minus HBV mutants. Treatment with interferon\u2010a was found to be effective in mixed Cryoglobulinemia even in the presence of HBe\u2010minus HBV mutants. Antiviral effects of interferon\u2010a induce a decrease in specific T\u2010cell recognition of HBV antigens. Clinical response and virus elimination were, however, accompanied by a reconstitution of cellular immune responses to HBV core antigens, i.e., HBcAg and HBeAg. The response to certain T cell epitopes on these antigens may be of pathogenetic relevance for virus elimination. \u00a9 1994 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jmv.1890440404","type":"journal-article","created":{"date-parts":[[2007,3,3]],"date-time":"2007-03-03T00:27:44Z","timestamp":1172881664000},"page":"330-335","source":"Crossref","is-referenced-by-count":22,"title":["Mixed cryoglobulinemia type II in chronic hepatitis B associated with HBe\u2010minus HBV mutant: Cellular immune reactions and response to interferon treatment"],"prefix":"10.1002","volume":"44","author":[{"given":"Hanns","family":"L\u00f6hr","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernd","family":"Goergen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wolfgang","family":"Weber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Werner","family":"Godderz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karl\u2010Hermann Meyer","family":"zum B\u00fcschenfelde","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Gerken","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199211193272104"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(90)90130-J"},{"key":"e_1_2_1_4_1","doi-asserted-by":"crossref","first-page":"2650","DOI":"10.4049\/jimmunol.143.8.2650","article-title":"Recognition of hepatitis B virus envelope proteins by liver\u2010infiltrating T lymphocytes in chronic HBV infection","volume":"143","author":"Barnaba V","year":"1989","journal-title":"Journal of Immunology"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.1980.20280169957.x"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199211193272111"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(86)90395-1"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(87)90904-1"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840100213"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90903-P"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)90713-7"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)92715-E"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90861-6"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01316786"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1063929"},{"key":"e_1_2_1_16_1","doi-asserted-by":"crossref","unstructured":"DienstagJL BhanAK AlterHJ FeinstoneSM PurcellRH(1979):Circulating immune complexes in non\u2010A non\u2010B hepatitis. Lancet1265\u20131267.","DOI":"10.1016\/S0140-6736(79)92228-1"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/165.4.778"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115581"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840080630"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840150405"},{"key":"e_1_2_1_21_1","doi-asserted-by":"crossref","first-page":"539","DOI":"10.4049\/jimmunol.139.2.539","article-title":"Functional characterization of cloned intrahepatic, hepatitis B virus nucleoprotein\u2010specific helper T cell lines","volume":"139","author":"Ferrari C","year":"1987","journal-title":"Journal of Immunology"},{"key":"e_1_2_1_22_1","first-page":"599","article-title":"Cryoglobulins in acute and chronic liver diseases","volume":"16","author":"Florin\u2010Christensen A","year":"1974","journal-title":"Clinical and Experimental Immunology"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.1890290408"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(91)90984-J"},{"key":"e_1_2_1_25_1","doi-asserted-by":"crossref","unstructured":"GoergenB Meyer zum BuschenfeldeK\u2010H GerkenG(1993):Mutation specific PCR and direct solid phase sequencing assay for the detection of HBV preC\/C mutants in anti\u2010HBe positive chronic hepatitis B. Journal of Medical Virology (in press).","DOI":"10.1002\/jmv.1890430118"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6822(92)90315-G"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1990.32"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199302183280703"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(91)90074-L"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(91)90196-5"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197706302962605"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-111-6-479"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1991.tb08164.x"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/168.5.1133"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(91)80021-Z"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016-5085(93)90862-7"},{"key":"e_1_2_1_37_1","first-page":"489","article-title":"Does the immune response play a role in the pathogenesis of chronic liver disease?","volume":"112","author":"Mondelli M","year":"1988","journal-title":"Archives of Pathology and Laboratory Medicine"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.1986.tb02162.x"},{"key":"e_1_2_1_39_1","first-page":"484","article-title":"Acute immune complex disease associated with hepatitis","volume":"100","author":"Ozawa T","year":"1976","journal-title":"Archives of Pathology and Laboratory Medicine"},{"key":"e_1_2_1_40_1","doi-asserted-by":"crossref","first-page":"3147","DOI":"10.4049\/jimmunol.137.10.3147","article-title":"Immunologic effects of interferon\u2010alpha in man: Treatment with human recombinant interferon\u2010alpha suppresses in vitro im\u2010munoglobulin production in patients with chronic type B hepatitis","volume":"137","author":"Peters M","year":"1986","journal-title":"Journal of Immunology"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/309801a0"},{"key":"e_1_2_1_42_1","doi-asserted-by":"crossref","first-page":"3566","DOI":"10.1128\/jvi.65.7.3566-3574.1991","article-title":"Emergence of and takeover by hepatitis B virus (HBV) with rearrangements in the preS\/S and preC\/C genes during chronic HBV infection","volume":"65","author":"Tran A","year":"1991","journal-title":"Journal of Virology"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115590"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1159\/000200935"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmv.1890440404","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.1890440404","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T04:05:59Z","timestamp":1698206759000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.1890440404"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12]]},"references-count":43,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1994,12]]}},"alternative-id":["10.1002\/jmv.1890440404"],"URL":"https:\/\/doi.org\/10.1002\/jmv.1890440404","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12]]}}}