A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis

Authors

  • Roberta D'Ambrosio,

    Corresponding author
    1. A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
    2. Department of Pathology and INSERM U773, Beaujon Hospital, University Paris-Diderot, Clichy, France
    • First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via F. Sforza 35, 20122 Milan, Italy
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    • fax: 39-0250320410

  • Alessio Aghemo,

    1. A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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  • Maria Grazia Rumi,

    1. Division of Hepatology, Ospedale San Giuseppe, Università degli Studi di Milano, Milan, Italy
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  • Guido Ronchi,

    1. A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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  • Maria Francesca Donato,

    1. A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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  • Valerie Paradis,

    1. Department of Pathology and INSERM U773, Beaujon Hospital, University Paris-Diderot, Clichy, France
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  • Massimo Colombo,

    1. A.M. and A. Migliavacca Center for Liver Disease, First Division of Gastroenterology, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milan, Italy
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  • Pierre Bedossa

    1. Department of Pathology and INSERM U773, Beaujon Hospital, University Paris-Diderot, Clichy, France
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  • Potential conflict of interest: Alessio Aghemo is on an advisory committee for Roche. Maria Grazia Rumi is on advisory committees for Tibotec, Roche, and Janssen Cilag. Massimo Colombo has received grant and research support from Merck, Roche, BMS, and Gilead Science; is on advisory committees for Merck, Roche, Novartis, Bayer, BMS, Gilead Science, Tibotec, Vertex, and Achillion; and has received speaking and teaching engagements from Tibotec, Roche, Novartis, Bayer, BMS, Gilead Science, and Vertex.

  • Dr. D'Ambrosio received a research grant from Università degli Studi di Milano (FSE, Regione Lombardia).

Abstract

Although annular fibrosis is the hallmark of cirrhosis, other microscopic changes that affect liver function such as sinusoid capillarization or loss of metabolic zonation are common. A sustained virological response (SVR) may halt fibrosis deposition in hepatitis C virus (HCV)-infected patients, but its impact on the other cirrhosis-associated lesions is unknown. The aim of this study was to assess the impact of an SVR on cirrhosis-related histopathological features. Paired pre- and posttreatment liver biopsies from 38 HCV patients with cirrhosis with an SVR were analyzed. Fibrosis was staged using the METAVIR scoring system, and the area of fibrosis was measured using morphometry. Ductular proliferation, metabolic zonation, sinusoid capillarization, and hepatic stellate cell activation were assessed by anti-cytokeratin-7, anti-glutamine synthetase (GS), anti-cytochrome P4502E1 (CYP2E1), anti-CD34, and anti α-smooth muscle actin (αSMA). After 61 months from an SVR, cirrhosis regression was observed in 61%, and the collagen content decreased in 89%. Although periportal and lobular necroinflammation vanished, portal inflammation persisted in 66%. Ductular proliferation decreased in 92%. Before treatment, metabolic zonation was lost, as shown by GS and CYP2E1, in 71% and 88%, respectively, with normalization in 79% and 73%, after an SVR. Conversely, no changes in sinusoidal capillarization were observed after treatment, as assessed by CD34 (P = 0.41) and αSMA (P = 0.95). Finally, no differences in all the immunohistochemical scores emerged whether or not cirrhosis persisted. Conclusion: Cirrhosis regression and decreased fibrosis are frequently observed among HCV patients with cirrhosis with an SVR. Despite ductular proliferation vanishing and lobular zonation restoration, portal inflammation and sinusoidal capillarization may not regress after viral eradication. (HEPATOLOGY 2012)

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