{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T02:49:01Z","timestamp":1782874141568,"version":"3.54.5"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":4079,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"German Network of Competence on Viral Hepatitis (\u201cHep-Net\u201d; project 10.2.2)"},{"name":"BMBF (German Ministry for Science and Education)"},{"name":"Essex Pharma (Munich, Germany)"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,7]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Early treatment of acute hepatitis C infection with interferon alfa-2b (IFN-\u03b1-2b) prevents chronicity in almost all patients. So far, no data are available on the long-term outcome after interferon (IFN) therapy of acute hepatitis C. The aim of this study was to assess the clinical, virological, and immunological long-term outcome of 31 successfully treated patients with acute hepatitis C infection who were followed for a median of 135 weeks (52-224 weeks) after end of therapy. None of the individuals had clinical evidence of liver disease. Alanine aminotransferase (ALT) levels were normal in all but 1 patient. Serum hepatitis C virus (HCV) RNA was negative throughout follow-up, even when investigated with the highly sensitive transcription-mediated amplification (TMA) assay (cutoff 5-10 IU\/mL). In addition, no HCV RNA was detected in peripheral blood mononuclear cells (PBMC) of 15 cases tested. The patients\u2019 overall quality-of-life scores as determined by the SF-36 questionnaire did not differ from the German reference control cohort. <jats:italic toggle=\"yes\">Ex vivo<\/jats:italic> interferon gamma (IFN-\u03b3) ELISPOT analysis detected HCV-specific CD4<jats:sup>+<\/jats:sup> T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8<jats:sup>+<\/jats:sup> T-cell responses were found in 4 of 5 <jats:italic toggle=\"yes\">HLA<\/jats:italic>-A2-positive individuals. Anti-HCV antibody levels decreased significantly during and after therapy in all individuals. <jats:underline>In conclusion<\/jats:underline>, early treatment of symptomatic acute hepatitis C with IFN-\u03b1-2b leads to a long-term virological, biochemical, and clinical response. Waning of anti-HCV humoral immunity and presence of HCV-specific CD8<jats:sup>+<\/jats:sup> (but not CD4<jats:sup>+<\/jats:sup>) T cells highlights the complexity of T-cell and B-cell memory to HCV, which might be significantly altered by IFN treatment. (Hepatology 2004;40:98-107.)<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.20291","type":"journal-article","created":{"date-parts":[[2004,7,2]],"date-time":"2004-07-02T07:03:11Z","timestamp":1088751791000},"page":"98-107","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":76,"title":["Long-term follow-up after successful interferon therapy of acute hepatitis C"],"prefix":"10.1097","volume":"40","author":[{"given":"Johannes","family":"Wiegand","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elmar","family":"J\u00e4ckel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Cornberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Hinrichsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manfred","family":"Dietrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Kroeger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang P.","family":"Fritsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Kubitschke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuray","family":"Aslan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans L.","family":"Tillmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael Peter","family":"Manns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiner","family":"Wedemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"issue":"Suppl 1","key":"R1-17-20241201","first-page":"S1S2","article-title":"National Institutes of Health Consensus Development Conference: management of hepatitis C: 2002.","volume":"36","author":"Seeff","year":"2002","journal-title":"HEPATOLOGY"},{"issue":"Suppl 1","key":"R2-17-20241201","first-page":"S21S29","article-title":"Course and outcome of hepatitis C.","volume":"36","author":"Hoofnagle","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R3-17-20241201","doi-asserted-by":"crossref","first-page":"958965","DOI":"10.1016\/S0140-6736(01)06102-5","article-title":"Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial.","volume":"358","author":"Manns","year":"2001","journal-title":"Lancet"},{"key":"R4-17-20241201","doi-asserted-by":"crossref","first-page":"975982","DOI":"10.1056\/NEJMoa020047","article-title":"Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection.","volume":"347","author":"Fried","year":"2002","journal-title":"N Engl J Med"},{"key":"R5-17-20241201","doi-asserted-by":"crossref","first-page":"14521457","DOI":"10.1056\/NEJMoa011232","article-title":"Treatment of acute hepatitis C with interferon alfa-2b.","volume":"345","author":"Jaeckel","year":"2001","journal-title":"N Engl J Med"},{"key":"R6-17-20241201","doi-asserted-by":"crossref","first-page":"14951496","DOI":"10.1053\/jhep.2003.50237","article-title":"Prediction of spontaneous viral clearance in acute hepatitis C by viral load measurements.","volume":"37","author":"Berg","year":"2003","journal-title":"HEPATOLOGY"},{"issue":"Suppl 1","key":"R7-17-20241201","first-page":"3640","article-title":"Role of the specific T-cell response for clearance and control of hepatitis C virus.","volume":"6","author":"Pape","year":"1999","journal-title":"J Viral Hepat"},{"key":"R8-17-20241201","doi-asserted-by":"crossref","first-page":"5765","DOI":"10.1016\/S1286-4579(01)01510-6","article-title":"Immunity to hepatitis C virus: stunned but not defeated.","volume":"4","author":"Klenerman","year":"2002","journal-title":"Microbes Infect"},{"key":"R9-17-20241201","doi-asserted-by":"crossref","first-page":"595601","DOI":"10.1002\/hep.510300312","article-title":"Pathogenesis of chronic hepatitis C: immunological features of hepatic injury and viral persistence.","volume":"30","author":"Cerny","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R11-17-20241201","doi-asserted-by":"crossref","first-page":"578582","DOI":"10.1038\/75063","article-title":"Cellular immune responses persist and humoral responses decrease two decades after recovery from a single-source outbreak of hepatitis C.","volume":"6","author":"Takaki","year":"2000","journal-title":"Nat Med"},{"key":"R12-17-20241201","doi-asserted-by":"crossref","first-page":"267276","DOI":"10.1053\/jhep.2001.21162","article-title":"Differential CD4() and CD8() T-cell responsiveness in hepatitis C virus infection.","volume":"33","author":"Chang","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R13-17-20241201","doi-asserted-by":"crossref","first-page":"61046113","DOI":"10.1128\/JVI.76.12.6104-6113.2002","article-title":"Comprehensive analysis of CD8()-T-cell responses against hepatitis C virus reveals multiple unpredicted specificities.","volume":"76","author":"Lauer","year":"2002","journal-title":"J Virol"},{"key":"R14-17-20241201","doi-asserted-by":"crossref","first-page":"34473458","DOI":"10.4049\/jimmunol.169.6.3447","article-title":"Impaired effector function of hepatitis C virus-specific CD8 T cells in chronic hepatitis C virus infection.","volume":"169","author":"Wedemeyer","year":"2002","journal-title":"J Immunol"},{"key":"R15-17-20241201","doi-asserted-by":"crossref","first-page":"1139211400","DOI":"10.1128\/JVI.75.23.11392-11400.2001","article-title":"Cross-reactivity between hepatitis C virus and influenza A virus determinant-specific cytotoxic T cells.","volume":"75","author":"Wedemeyer","year":"2001","journal-title":"J Virol"},{"key":"R16-17-20241201","first-page":"299325","article-title":"Cell mediated immune response to the hepatitis C virus.","volume":"242","author":"Rehermann","year":"2000","journal-title":"Curr Top Microbiol Immunol"},{"key":"R17-17-20241201","doi-asserted-by":"crossref","first-page":"40474053","DOI":"10.4049\/jimmunol.147.12.4047","article-title":"The minimum peptide epitope from the influenza virus matrix protein. Extra and intracellular loading of HLA-A2.","volume":"147","author":"Bednarek","year":"1991","journal-title":"J Immunol"},{"key":"R18-17-20241201","doi-asserted-by":"crossref","first-page":"244256","DOI":"10.1002\/hep.510300141","article-title":"Mutational pattern of hepatitis B virus on sequential therapy with famciclovir and lamivudine in patients with hepatitis B virus reinfection occurring under HBIg immunoglobulin after liver transplantation.","volume":"30","author":"Tillmann","year":"1999","journal-title":"HEPATOLOGY"},{"key":"R19-17-20241201","doi-asserted-by":"crossref","first-page":"159168","DOI":"10.1016\/S0166-0934(01)00433-5","article-title":"Quantitation of hepatitis C virus RNA by third generation branched DNA-based signal amplification assay.","volume":"101","author":"Ross","year":"2002","journal-title":"J Virol Methods"},{"key":"R20-17-20241201","doi-asserted-by":"crossref","first-page":"714718","DOI":"10.1136\/gut.48.5.714","article-title":"Low frequency of HLA-DRB111 in hepatitis C virus induced end stage liver disease.","volume":"48","author":"Tillmann","year":"2001","journal-title":"Gut"},{"key":"R21-17-20241201","first-page":"XVIIXXVII","article-title":"Assessment of health related quality of life with the SF-36 Health Survey. in German.","volume":"35","author":"Bullinger","year":"1996","journal-title":"Rehabilitation (Stuttg)"},{"key":"R22-17-20241201","first-page":"10621068","article-title":"Perihepatic lymphadenopathy: a marker of response to interferon alpha in chronic hepatitis C.","volume":"45","author":"Wedemeyer","year":"1998","journal-title":"Hepatogastroenterology"},{"key":"R23-17-20241201","doi-asserted-by":"crossref","first-page":"467472","DOI":"10.1002\/hep.510260230","article-title":"Enlargement of perihepatic lymph nodes in relation to liver histology and viremia in patients with chronic hepatitis C.","volume":"26","author":"Dietrich","year":"1997","journal-title":"HEPATOLOGY"},{"key":"R24-17-20241201","doi-asserted-by":"crossref","first-page":"12281233","DOI":"10.1056\/NEJM199904223401602","article-title":"Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group.","volume":"340","author":"Kenny-Walsh","year":"1999","journal-title":"N Engl J Med"},{"key":"R25-17-20241201","doi-asserted-by":"crossref","first-page":"321327","DOI":"10.1053\/jhep.2001.22112","article-title":"Acute hepatitis C.","volume":"33","author":"Orland","year":"2001","journal-title":"HEPATOLOGY"},{"key":"R26-17-20241201","first-page":"6064","article-title":"Spontaneous viral clearance in patients with acute hepatitis C can be predicted by repeated measurements of serum viral load.","volume":"37","author":"Hofer","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R27-17-20241201","first-page":"8088","article-title":"Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance.","volume":"125","author":"Gerlach","year":"2003","journal-title":"Gastroenterology"},{"key":"R28-17-20241201","doi-asserted-by":"crossref","first-page":"12011203","DOI":"10.1002\/hep.20221","article-title":"Whom? When? How? Another piece of evidence for early treatment of acute hepatitis C.","volume":"39","author":"Wedemeyer","year":"2004","journal-title":"HEPATOLOGY"},{"key":"R29-17-20241201","doi-asserted-by":"crossref","first-page":"12451249","DOI":"10.1002\/hep.510250530","article-title":"Early antibody response against hypervariable region 1 is associated with acute self-limiting infections of hepatitis C virus.","volume":"25","author":"Zibert","year":"1997","journal-title":"HEPATOLOGY"},{"key":"R30-17-20241201","doi-asserted-by":"crossref","first-page":"41894199","DOI":"10.4049\/jimmunol.151.8.4189","article-title":"Hepatitis C virus-specific CTL responses in the liver of chimpanzees with acute and chronic hepatitis C.","volume":"151","author":"Erickson","year":"1993","journal-title":"J Immunol"},{"key":"R31-17-20241201","doi-asserted-by":"crossref","first-page":"883895","DOI":"10.1016\/S1074-7613(01)00245-X","article-title":"The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes.","volume":"15","author":"Erickson","year":"2001","journal-title":"Immunity"},{"key":"R32-17-20241201","doi-asserted-by":"crossref","first-page":"933941","DOI":"10.1016\/S0016-5085(99)70353-7","article-title":"Recurrence of hepatitis C virus after loss of virus-specific CD4() T-cell response in acute hepatitis C.","volume":"117","author":"Gerlach","year":"1999","journal-title":"Gastroenterology"},{"key":"R33-17-20241201","doi-asserted-by":"crossref","first-page":"1566915674","DOI":"10.1073\/pnas.202608199","article-title":"Genomic analysis of the host response to hepatitis C virus infection.","volume":"99","author":"Su","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R34-17-20241201","doi-asserted-by":"crossref","first-page":"13951406","DOI":"10.1084\/jem.194.10.1395","article-title":"Determinants of viral clearance and persistence during acute hepatitis C virus infection.","volume":"194","author":"Thimme","year":"2001","journal-title":"J Exp Med"},{"key":"R35-17-20241201","doi-asserted-by":"crossref","first-page":"1566115668","DOI":"10.1073\/pnas.202608299","article-title":"Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.","volume":"99","author":"Thimme","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"key":"R36-17-20241201","doi-asserted-by":"crossref","first-page":"14991512","DOI":"10.1084\/jem.191.9.1499","article-title":"Analysis of successful immune responses in persons infected with hepatitis C virus.","volume":"191","author":"Lechner","year":"2000","journal-title":"J Exp Med"},{"key":"R37-17-20241201","doi-asserted-by":"crossref","first-page":"24792487","DOI":"10.1002\/1521-4141(200009)30:9<2479::AID-IMMU2479>3.0.CO;2-B","article-title":"CD8 T lymphocyte responses are induced during acute hepatitis C virus infection but are not sustained.","volume":"30","author":"Lechner","year":"2000","journal-title":"Eur J Immunol"},{"key":"R38-17-20241201","doi-asserted-by":"crossref","first-page":"55505558","DOI":"10.1128\/JVI.75.12.5550-5558.2001","article-title":"Sustained dysfunction of antiviral CD8 T lymphocytes after infection with hepatitis C virus.","volume":"75","author":"Gruener","year":"2001","journal-title":"J Virol"},{"key":"R39-17-20241201","doi-asserted-by":"crossref","first-page":"15281536","DOI":"10.1086\/315450","article-title":"Association of hepatitis C virus-specific CD8() T cells with viral clearance in acute hepatitis C.","volume":"181","author":"Gruner","year":"2000","journal-title":"J Infect Dis"},{"key":"R40-17-20241201","doi-asserted-by":"crossref","first-page":"659662","DOI":"10.1126\/science.1088774","article-title":"HCV persistence and immune evasion in the absence of memory T cell help.","volume":"302","author":"Grakoui","year":"2003","journal-title":"Science"},{"key":"R41-17-20241201","doi-asserted-by":"crossref","first-page":"346355","DOI":"10.1016\/S0016-5085(00)70217-4","article-title":"Hepatitis C virus-specific T-cell reactivity during interferon and ribavirin treatment in chronic hepatitis C.","volume":"118","author":"Cramp","year":"2000","journal-title":"Gastroenterology"},{"key":"R42-17-20241201","doi-asserted-by":"crossref","first-page":"743754","DOI":"10.1053\/jhep.2002.35344","article-title":"The dynamics of T-lymphocyte responses during combination therapy for chronic hepatitis C virus infection.","volume":"36","author":"Barnes","year":"2002","journal-title":"HEPATOLOGY"},{"key":"R43-17-20241201","doi-asserted-by":"crossref","first-page":"173178","DOI":"10.1126\/science.271.5246.173","article-title":"Immunology taught by viruses.","volume":"271","author":"Zinkernagel","year":"1996","journal-title":"Science"},{"key":"R44-17-20241201","doi-asserted-by":"crossref","first-page":"32153218","DOI":"10.4049\/jimmunol.161.7.3215","article-title":"Detection of a high frequency of virus-specific CD4 T cells during acute infection with lymphocytic choriomeningitis virus.","volume":"161","author":"Varga","year":"1998","journal-title":"J Immunol"},{"key":"R45-17-20241201","doi-asserted-by":"crossref","first-page":"60116019","DOI":"10.1128\/jvi.71.8.6011-6019.1997","article-title":"Immunodominant CD4 T-cell epitope within nonstructural protein 3 in acute hepatitis C virus infection.","volume":"71","author":"Diepolder","year":"1997","journal-title":"J Virol"},{"key":"R46-17-20241201","doi-asserted-by":"crossref","first-page":"16451655","DOI":"10.1084\/jem.20030239","article-title":"Memory CD8 T cells are required for protection from persistent hepatitis C virus infection.","volume":"197","author":"Shoukry","year":"2003","journal-title":"J Exp Med"},{"key":"R47-17-20241201","doi-asserted-by":"crossref","first-page":"15541561","DOI":"10.4049\/jimmunol.166.3.1554","article-title":"Independent regulation of lymphocytic choriomeningitis virus-specific T cell memory pools: relative stability of CD4 memory under conditions of CD8 memory T cell loss.","volume":"166","author":"Varga","year":"2001","journal-title":"J Immunol"}],"container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fhep.20291","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200407000-00017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T12:00:40Z","timestamp":1733054440000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200407000-00017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7]]},"references-count":46,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004]]}},"URL":"https:\/\/doi.org\/10.1002\/hep.20291","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2004,7]]}}}