Digital image analysis of liver collagen predicts clinical outcome of recurrent hepatitis C Virus 1 year after liver transplantation

Clinical outcomes of recurrent hepatitis C virus after liver transplantation are difficult to predict. We evaluated collagen proportionate area (CPA), a quantitative histological index, at 1 year with respect to the first episode of clinical decompensation. Patients with biopsies at 1 year after liver transplantation were evaluated by Ishak stage/grade, and biopsy samples stained with Sirius red for digital image analysis were evaluated for CPA. Cox regression was used to evaluate variables associated with first appearance of clinical decompensation. Receiver operating characteristic (ROC) curves were also used. A total of 135 patients with median follow‐up of 76 months were evaluated. At 1 year, median CPA was 4.6% (0.2%‐36%) and Ishak stage was 0‐2 in 101 patients, 3‐4 in 23 patients, and 5‐6 in 11 patients. Decompensation occurred in 26 (19.3%) at a median of 61 months (15‐138). Univariately, CPA, tacrolimus monotherapy, and Ishak stage/grade at 1 year were associated with decompensation; upon multivariate analysis, only CPA was associated with decompensation (P = 0.010; Exp(B) = 1.169; 95%CI, 1.037‐1.317). Area under the ROC curve was 0.97 (95%CI, 0.94‐0.99). A cutoff value of 6% of CPA had 82% sensitivity and 95% specificity for decompensation. In the 89 patients with hepatic venous pressure gradient (HVPG) measurement, similar results were obtained. When both cutoffs of CPA > 6% and HVPG ≥ 6 mm Hg were used, all patients decompensated. Thus, CPA at 1‐year biopsy after liver transplantation was highly predictive of clinical outcome in patients infected with hepatitis C virus who underwent transplantation, better than Ishak stage or HVPG. Liver Transpl 17:178–188, 2011. © 2011 AASLD.

[1]  E. Cholongitas,et al.  Outcome of recurrent hepatitis C virus after liver transplantation in a randomized trial of tacrolimus monotherapy versus triple therapy , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[2]  Chihiro Morishima,et al.  Fibrosis progression in chronic hepatitis C: Morphometric image analysis in the HALT‐C trial , 2009, Hepatology.

[3]  J. Rakela,et al.  Natural history of post–liver transplantation hepatitis C: A review of factors that may influence its course , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[4]  L. Pape,et al.  Prognostic value of computerized quantification of liver fibrosis in children with biliary atresia , 2009, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[5]  R. Standish,et al.  Computer‐assisted image analysis of liver collagen: Relationship to Ishak scoring and hepatic venous pressure gradient , 2009, Hepatology.

[6]  M. Muñoz-Fernandez,et al.  Serum levels of fibrosis biomarkers measured early after liver transplantation are associated with severe hepatitis C virus recurrence , 2009, Transplant infectious disease : an official journal of the Transplantation Society.

[7]  A. Burroughs,et al.  Clinical outcome of HCV‐related graft cirrhosis and prognostic value of hepatic venous pressure gradient , 2009, Transplant international : official journal of the European Society for Organ Transplantation.

[8]  Charles M. Miller,et al.  The significance of metabolic syndrome in the setting of recurrent hepatitis C after liver transplantation , 2008, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[9]  R. Fontana,et al.  Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C , 2008, Hepatology.

[10]  E. Cholongitas,et al.  Hepatic venous pressure gradient to assess fibrosis and its progression after liver transplantation for HCV cirrhosis , 2007, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[11]  Ramon Planas,et al.  Hepatic venous pressure gradient predicts clinical decompensation in patients with compensated cirrhosis. , 2007, Gastroenterology.

[12]  U. Neumann,et al.  Influence of Donor Histology on Outcome in Patients Undergoing Transplantation for Hepatitis C , 2007, Transplantation.

[13]  R. Becker,et al.  Progression of fibrosis in advanced chronic hepatitis C: Evaluation by morphometric image analysis , 2007, Hepatology.

[14]  U. Neumann,et al.  Fibrosis progression in hepatitis C positive liver recipients after sustained virologic response to antiviral combination therapy (interferon-ribavirin therapy). , 2007, Transplantation.

[15]  E. Cholongitas,et al.  Transjugular liver biopsy: how good is it for accurate histological interpretation? , 2006, Gut.

[16]  R. Standish,et al.  An appraisal of the histopathological assessment of liver fibrosis , 2006, Gut.

[17]  X. Forns,et al.  Hepatic venous pressure gradient identifies patients at risk of severe hepatitis C recurrence after liver transplantation , 2006, Hepatology.

[18]  E. Lyden,et al.  Recurrent hepatitis C posttransplant: Early preservation injury may predict poor outcome , 2006, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[19]  Ramon Planas,et al.  Beta-blockers to prevent gastroesophageal varices in patients with cirrhosis. , 2005, The New England journal of medicine.

[20]  C. Ripoll,et al.  Influence of hepatic venous pressure gradient on the prediction of survival of patients with cirrhosis in the MELD Era , 2005, Hepatology.

[21]  C. Sabin,et al.  Immunosuppression and donor age with respect to severity of HCV recurrence after liver transplantation , 2005, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[22]  U. Neumann,et al.  Fibrosis progression after liver transplantation in patients with recurrent hepatitis C. , 2004, Journal of hepatology.

[23]  R. Groszmann,et al.  The hepatic venous pressure gradient: Anything worth doing should be done right , 2004, Hepatology.

[24]  U. Neumann,et al.  Long-term outcome of liver transplants for chronic hepatitis C: a 10-year follow-up , 2004, Transplantation.

[25]  V. Paradis,et al.  Sampling variability of liver fibrosis in chronic hepatitis C , 2003, Hepatology.

[26]  A. Demetris,et al.  Progression of liver fibrosis in patients with chronic hepatitis C after orthotopic liver transplantation , 2003, Transplantation.

[27]  M. Berenguer Host and donor risk factors before and after liver transplantation that impact HCV recurrence , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[28]  J. Lake The role of immunosuppression in recurrence of hepatitis C , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[29]  R. Wiesner,et al.  Report of the First International Liver Transplantation Society Expert Panel Consensus Conference on Liver Transplantation and Hepatitis C , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[30]  R. Gish,et al.  A model to predict severe HCV‐related disease following liver transplantation , 2003, Hepatology.

[31]  P. Angus,et al.  Liver transplantation for HCV‐associated liver cirrhosis: Predictors of outcomes in a population with significant genotype 3 and 4 distribution , 2003, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[32]  D. Elbourne,et al.  Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial , 2002, The Lancet.

[33]  M. Vivarelli,et al.  Slowly tapering off steroids protects the graft against hepatitis C recurrence after liver transplantation , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[34]  A. Burroughs Induction immunosuppression for patients who underwent transplantation for cirrhosis caused by hepatitis C? The answer is no! , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[35]  G. Everson Impact of immunosuppressive therapy on recurrence of hepatitis C , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[36]  P. Gow,et al.  Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C , 2002, Gut.

[37]  A. Moya,et al.  Contribution of donor age to the recent decrease in patient survival among HCV‐infected liver transplant recipients , 2002, Hepatology.

[38]  K. Batts,et al.  Impact of cytomegalovirus infection, year of transplantation, and donor age on outcomes after liver transplantation for hepatitis C , 2002, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[39]  J. Berlin,et al.  The association between hepatitis C infection and survival after orthotopic liver transplantation. , 2002, Gastroenterology.

[40]  A. Dhillon,et al.  THE ROLE OF DIFFERENT IMMUNOSUPPRESSION IN THE LONG-TERM HISTOLOGICAL OUTCOME OF HCV REINFECTION AFTER LIVER TRANSPLANTATION FOR HCV CIRRHOSIS , 2001, Transplantation.

[41]  A. Burroughs,et al.  THE INFLUENCE OF CYTOMEGALOVIRUS VIRAEMIA ON THE OUTCOME OF RECURRENT HEPATITIS C AFTER LIVER TRANSPLANTATION12 , 2000, Transplantation.

[42]  K. Batts,et al.  Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation , 2000, Hepatology.

[43]  B. Davidson,et al.  A pilot study of immunosuppressive monotherapy in liver transplantation: tacrolimus versus microemulsified cyclosporin. , 1999, Transplantation.

[44]  Xi-Zhang Lin,et al.  The normal adult human liver biopsy: A quantitative reference standard , 1998, Hepatology.

[45]  J. Rodés,et al.  Clinical events after transjugular intrahepatic portosystemic shunt: correlation with hemodynamic findings. , 1998, Gastroenterology.

[46]  A. Burroughs,et al.  Hepatic venous pressure measurement: An old test as a new prognostic marker in cirrhosis? , 1997, Hepatology.

[47]  K. Ishak,et al.  Histological grading and staging of chronic hepatitis. , 1995 .

[48]  A. Dhillon,et al.  Grading of cellular rejection after orthotopic liver transplantation , 1995, Hepatology.

[49]  D. Pillay,et al.  PROVISION OF PROGNOSTIC INFORMATION IN IMMUNOCOMPROMISED PATIENTS BY ROUTINE APPLICATION OF THE POLYMERASE CHAIN REACTION FOR CYTOMEGALOVIRUS , 1993, Transplantation.

[50]  W. Jiménez,et al.  Measurement of fibrosis in needle liver biopsies: Evaluation of a colorimetric method , 1985, Hepatology.

[51]  R. Groszmann,et al.  Portal pressure, presence of gastroesophageal varices and variceal bleeding , 1985, Hepatology.

[52]  R. Groszmann,et al.  Current management of portal hypertension. , 2003, Journal of hepatology.

[53]  L. Blendis,et al.  Is sinusoidal portal hypertension a necessary factor for the development of hepatic ascites? , 1992, Journal of hepatology.