{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:09:01Z","timestamp":1790856541627,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"published-print":{"date-parts":[[1996,12]]},"abstract":"<jats:p>AIMS: To assess which pathological features are associated with a sensitive marker of liver fibrogenesis and thus of the potential development of fibrosis in hepatitis C. METHODS: The degree of liver fibrogenesis was evaluated by quantification of type I collagen mRNA and transforming growth factor (TGF) beta 1 mRNA (a major profibrogenic cytokine) in liver biopsy specimens from 28 patients with chronic hepatitis C and five controls, using a quantitative reverse transcription polymerase chain reaction (RT-PCR) assay. Results of mRNA quantification were correlated with histological lesions scored semiquantitatively in the same specimens. RESULTS: Type I collagen mRNA was more strongly expressed in patients than in controls and correlated with the degree of fibrosis, but not with any of the necro-inflammatory lesions (portal inflammation, piecemeal necrosis, and lobular necrosis). TGF beta 1 mRNA concentration was higher in patients than in controls and correlated with histological grade of activity and lobular necrosis. This result was confirmed by in situ hybridisation experiments which showed that TGF beta 1 mRNA was mainly expressed in areas of focal lobular necrosis in chronic hepatitis C. CONCLUSION: This study shows that fibrosis, rather than necro-inflammatory lesions or activity scores, is associated with fibrogenesis and thus with potential aggravation of the fibrous deposit in chronic hepatitis C. Lobular necrosis is an important predictor of prognosis in chronic hepatitis C, as shown by its strong association with TGF beta 1 mRNA expression.<\/jats:p>","DOI":"10.1136\/jcp.49.12.998","type":"journal-article","created":{"date-parts":[[2007,6,9]],"date-time":"2007-06-09T00:50:46Z","timestamp":1181350246000},"page":"998-1004","source":"Crossref","is-referenced-by-count":35,"title":["Histological features predictive of liver fibrosis in chronic hepatitis C infection."],"prefix":"10.1136","volume":"49","author":[{"given":"V","family":"Paradis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Mathurin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Laurent","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F","family":"Charlotte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Vidaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Poynard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Opolon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Bedossa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[1996,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/S0140-6736(95)90470-0","article-title":"Genetic diversity of hepatitis C virus: implications for pathogenesis, treatment, and prevention","volume":"345","author":"Soni, P.; Duseiko, G.M.; Harrison, T.J.; Dhillon, A.P.","year":"1995","unstructured":"Soni P, Duseiko GM, Harrison TJ, Dhillon AP. Genetic diversity of hepatitis C virus: implications for pathogenesis, treatment, and prevention. Lancet 1995;345:562-6.","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1002\/hep.1840190629","article-title":"Classification of chronic hepatitis: diagnosis, grading and staging","volume":"19","author":"Desmet, V.J.; Gerber, M.; Hoofnagle, J.H.; Manns, M.; Scheuer, P.J.","year":"1994","unstructured":"Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 1994;19:1513-19.","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/hep.1840080310","article-title":"The development of cirrhosis in patients with chronic type B hepatitis: a prospective study","volume":"8","author":"Liaw, Y.-F.; Tai, D.-I.; Chu, C.-M.; Chen, T.-J.","year":"1988","unstructured":"Liaw Y-F, Tai D-I, Chu C-M, Chen T-J. The development of cirrhosis in patients with chronic type B hepatitis: a prospective study. Hepatology 1988;8:493-6.","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/hep.1840060302","article-title":"The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis","volume":"6","author":"Cooksley, W.G.E.; Bradbear, R.A.; Robinson, W.; Harrison, M.; Halliday, J.W.; Powell, L.W.","year":"1986","unstructured":"Cooksley WGE, Bradbear RA, Robinson W, Harrison M, Halliday JW, Powell LW, et al. The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis. Hepatology 1986;6:345-8.","journal-title":"Hepatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1002\/hep.1840150402","article-title":"The pathology of hepatitis C","volume":"15","author":"Scheuer, P.J.; Ashrafzadeh, P.; Sherlock, S.; Brown, D.; Dusheiko, G.M.","year":"1992","unstructured":"Scheuer PJ, Ashrafzadeh P, Sherlock S, Brown D, Dusheiko GM. The pathology of hepatitis C. Hepatology 1992;15: 567-71.","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/hep.1840150403","article-title":"Thung SH, Schaffner F. The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis","volume":"15","author":"Bach, N.","year":"1992","unstructured":"Bach N, Thung SH, Schaffner F. The histological features of chronic hepatitis C and autoimmune chronic hepatitis: a comparative analysis. Hepatology 1992;15:572-7.","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/0016-5085(93)90432-C","article-title":"Pathological diagnosis of chronic hepatitis C. A multicenter comparative study with chronic hepatitis B","volume":"104","author":"Lefkowitch, J.H.; Schiff, E.R.; Davis, G.L.; Perrilo, R.P.; Lindsay, K.; Bodenheimer, H.C.","year":"1993","unstructured":"Lefkowitch JH, Schiff ER, Davis GL, Perrilo RP, Lindsay K, Bodenheimer HC, et al. Pathological diagnosis of chronic hepatitis C. A multicenter comparative study with chronic hepatitis B. Gastroenterology 1993;104:595-603.","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1055\/s-2008-1040452","article-title":"Structure of the extracellular matrix in normal and fibrotic liver: Collagens and glycoproteins","volume":"10","author":"Schuppan, D.","year":"1990","unstructured":"Schuppan D. Structure of the extracellular matrix in normal and fibrotic liver: Collagens and glycoproteins. Semin Liver Dis 1990;10:1-10.","journal-title":"Semin Liver Dis"},{"key":"ref_9","first-page":"710","article-title":"Collagen types in normal","volume-title":"and cirrhotic liver. Gastroenterology 1985; 76","author":"Rojkind, M.; Giambrone, M.A.; Biempica, L.","unstructured":"Rojkind M, Giambrone MA, Biempica L. Collagen types in normal and cirrhotic liver. Gastroenterology 1985;76:710-19."},{"key":"ref_10","first-page":"1833","article-title":"Cellular distribution of transforming growth factor-P1 and procollagen types I, III and IV transcripts in carbon tetrachloride-induced rat liver fibrosis","volume":"5","author":"Nakatsukasa, H.; Nagy, P.; Evarts, R.P.; Hsia, C.; Marsden, E.; Thorgeirsson, S.","year":"1990","unstructured":"Nakatsukasa H, Nagy P, Evarts RP, Hsia C, Marsden E, Thorgeirsson S. Cellular distribution of transforming growth factor-P1 and procollagen types I, III and IV transcripts in carbon tetrachloride-induced rat liver fibrosis. 7 Clin Invest 1990;5:1833-43."},{"key":"ref_11","first-page":"115","article-title":"Liver fibrosis and extracellular matrix","volume":"8","author":"Biagini, G.","year":"1989","unstructured":"Biagini G. Liver fibrosis and extracellular matrix. _7 Hepatol 1989;8:115-24."},{"key":"ref_12","first-page":"99","article-title":"The use of molecular hybridization techniques as tools to evaluate hepatic fibrogenesis","volume-title":"Coninective tissue in health and disease","author":"Rojkind, M.","year":"1990","unstructured":"Zern MA, Czaja MJ, Weiner FR. The use of molecular hybridization techniques as tools to evaluate hepatic fibrogenesis. In: Rojkind M, ed. Coninective tissue in health and disease. Boca Raton, FL: CRC Press, 1990:99-122."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1172\/JCI115561","article-title":"Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblast-like cells. A potential mechanism of self perpetuation in liver fibrogenesis","volume":"89","author":"Bachem, M.; Meyer, D.; Melchior, R.; Sell, K.M.; Gressner, A.M.","year":"1992","unstructured":"Bachem M, Meyer D, Melchior R, Sell KM, Gressner AM. Activation of rat liver perisinusoidal lipocytes by transforming growth factors derived from myofibroblast-like cells. A potential mechanism of self perpetuation in liver fibrogenesis. _J Clin Invest 1992;89:19-27.","journal-title":"_J Clin Invest"},{"key":"ref_14","first-page":"244","article-title":"Analysis of HCV genotypes by a fluorescent competitive oligonucleotide priming PCR","volume":"20","author":"Sajus, M.; Olivi, M.; Vidaud, D.; Mathurin, P.; Opolon, P.; Poynard, T.","year":"1994","unstructured":"Sajus M, Olivi M, Vidaud D, Mathurin P, Opolon P, Poynard T, et al. Analysis of HCV genotypes by a fluorescent competitive oligonucleotide priming PCR (COP-PCR) [abstract]. Hepatology 1994;20:244a.","journal-title":"(COP-PCR)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/hep.1840200104","article-title":"The METAVIR cooperative group. Interand intraobserver variation in the assessment of liver biopsy of chronic hepatitis C","volume":"20","year":"1994","unstructured":"The METAVIR cooperative group. Interand intraobserver variation in the assessment of liver biopsy of chronic hepatitis C. Hepatology 1994;20:15-20.","journal-title":"Hepatology"},{"issue":"431 -5","key":"ref_16","article-title":"Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis","volume":"1","author":"Knodell, K.G.; Ishak, K.G.; Black, W.C.; Chen, T.S.; Craig, R.; Kaplowitz, N.","year":"1981","unstructured":"Knodell KG, Ishak KG, Black WC, Chen TS, Craig R, Kaplowitz N, et al. Formulation and application of a numerical scoring system for assessing histological activity in asymptomatic chronic active hepatitis. Hepatology 1981; 1:431 -5.","journal-title":"Hepatology"},{"key":"ref_17","first-page":"156","article-title":"Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski, P.; Sacchi, N.","year":"1987","unstructured":"Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Analyt Biocheml 1987;162:156-9.","journal-title":"Analyt Biocheml"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/0168-9525(93)90137-7","article-title":"Quantitation of RNA using the polymerase chain reaction","volume":"9","author":"Foley, K.P.; Leonard, M.W.; Engel, J.D.","year":"1993","unstructured":"Foley KP, Leonard MW, Engel JD. Quantitation of RNA using the polymerase chain reaction. Trends Genet 1993;9: 380-5.","journal-title":"Trends Genet"},{"key":"ref_19","first-page":"760","article-title":"TGF 1 mRNA, protein and receptors in normal human liver, cirrhosis and hepatocellular carcinomas","volume":"21","author":"Bedossa, P.; Peltier, E.; Franco, D.; Poynard, T.; Lemaigre, G.","year":"1995","unstructured":"Bedossa P, Peltier E, Franco D, Poynard T, Lemaigre G. TGF 1 mRNA, protein and receptors in normal human liver, cirrhosis and hepatocellular carcinomas. Hepatologv 1995;21:760-6.","journal-title":"Hepatologv"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1056\/NEJM199104043241401","article-title":"Transforming growth factor-, B1 and a in chronic liver disease","volume":"324","author":"Castilla, A.; Prieto, J.; Fausto, N.","year":"1991","unstructured":"Castilla A, Prieto J, Fausto N. Transforming growth factor-,B1 and a in chronic liver disease. N Eigl\/ Med 1991;324:933-6.","journal-title":"N Eigl\/ Med"},{"key":"ref_21","first-page":"259","article-title":"Increased transforming growth factor-1 gene expression in human liver disease","volume":"14","author":"Annoni, G.; Weiner, F.; Zern, M.A.","year":"1992","unstructured":"Annoni G, Weiner F, Zern MA. Increased transforming growth factor-1 gene expression in human liver disease. _7 Hepatol 1992;14:259-64."},{"key":"ref_22","first-page":"171","article-title":"Transforming growth factor beta 1 and type I procollagen transcripts during regeneration and early fibrosis in rat liver","volume":"63","author":"Nakatsukasa, H.; Evarts, R.P.; Hsia, C.; Thorgeirsson, S.S.","year":"1990","unstructured":"Nakatsukasa H, Evarts RP, Hsia C, Thorgeirsson SS. Transforming growth factor beta 1 and type I procollagen transcripts during regeneration and early fibrosis in rat liver. Lab Invest 1990;63: 171-80.","journal-title":"Lab Invest"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9717","DOI":"10.1073\/pnas.86.24.9717","article-title":"Quantitation of mRNA by the polymerase chain reaction","volume":"86","author":"Wang, A.M.; Doyle, M.V.; Mark, D.F.","year":"1989","unstructured":"Wang AM, Doyle MV, Mark DF. Quantitation of mRNA by the polymerase chain reaction. Proc Natl Acad Sci USA 1989;86:9717-21.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2725","DOI":"10.1073\/pnas.87.7.2725","article-title":"Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction","volume":"87","author":"Gilliland, G.; Perrin, S.; Blanchard, K.; Bunn, H.F.","year":"1990","unstructured":"Gilliland G, Perrin S, Blanchard K, Bunn HF. Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction. Proc Natl Acad Sci USA 1990;87:2725-29.","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0016-5085(95)90019-5","article-title":"Growth factor and procollagen type I expression in human liver disease","volume":"108","author":"Malizia, G.; Brunt, E.M.; Peters, M.G.; Rizzo, A.; Broekelmann, T.J.; McDonald, J.A.","year":"1995","unstructured":"Malizia G, Brunt EM, Peters MG, Rizzo A, Broekelmann TJ, McDonald JA. Growth factor and procollagen type I expression in human liver disease. Gastroenterologv 1995; 108:145-56.","journal-title":"Gastroenterologv"},{"key":"ref_26","first-page":"1221","article-title":"Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease","volume":"139","author":"Milani, S.; Herbst, H.; Schuppan, D.; Surrenti, C.","year":"1991","unstructured":"Milani S, Herbst H, Schuppan D, Surrenti C. Transforming growth factors beta 1 and beta 2 are differentially expressed in fibrotic liver disease. Anj7 Pathol 1991;139:1221-29."},{"key":"ref_27","first-page":"298","article-title":"Quantitative analysis of transforming growth factor PI messenger RNA in the liver of patients with chronic hepatitis C: Absencc of correlation between high levels and severity of disease","volume":"21","author":"Roulot, D.; Durand, H.; Coste, T.; Rautureau, J.; Strosberg, A.D.; Benarous, R.","year":"1995","unstructured":"Roulot D, Durand H, Coste T, Rautureau J, Strosberg AD, Benarous R, et al. Quantitative analysis of transforming growth factor PI messenger RNA in the liver of patients with chronic hepatitis C: Absencc of correlation between high levels and severity of disease. Hepato\/og3 1995;21:298-304."},{"key":"ref_28","first-page":"1050","article-title":"Pretreatment serum hepatitis C virus RNA levels and hepatitis C genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C","volume":"22","author":"Martinot-Peignoux, M.; Marcellin, P.; Pouteau, M.; Castelnau, C.; Boyer, N.; Poliquin, M.","year":"1995","unstructured":"Martinot-Peignoux M, Marcellin P, Pouteau M, Castelnau C, Boyer N, Poliquin M, et al. Pretreatment serum hepatitis C virus RNA levels and hepatitis C genotype are the main and independent prognostic factors of sustained response to interferon alfa therapy in chronic hepatitis C. Hepatology 1995;22:1050-7.","journal-title":"Hepatology"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp.49.12.998","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:57:58Z","timestamp":1758790678000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp.49.12.998"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12]]},"references-count":28,"journal-issue":{"issue":"12","published-online":{"date-parts":[[1996,12,1]]},"published-print":{"date-parts":[[1996,12]]}},"alternative-id":["10.1136\/jcp.49.12.998"],"URL":"https:\/\/doi.org\/10.1136\/jcp.49.12.998","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"value":"0021-9746","type":"print"},{"value":"1472-4146","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12]]}}}