title: A morphometric and immunohistochemical study to assess the benefit of a sustained virological response in hepatitis C virus patients with cirrhosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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. roberta.dambrosio@unimi.it
authors.forename: Roberta
authors.initials: R
authors.lastname: D'Ambrosio
authors.forename: Alessio
authors.initials: A
authors.lastname: Aghemo
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Rumi
authors.forename: Guido
authors.initials: G
authors.lastname: Ronchi
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Donato
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.forename: Pierre
authors.initials: P
authors.lastname: Bedossa
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D000998:Antiviral Agents / Q000627:therapeutic use; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005974:Glutamate-Ammonia Ligase / Q000276:immunology; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7 / Q000378:metabolism; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012074:Remission Induction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D018952:Antigens, CD34; D000998:Antiviral Agents; D053552:Keratin-7; D019392:Cytochrome P-450 CYP2E1; D000410:Alanine Transaminase; D005974:Glutamate-Ammonia Ligase