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

Abstract

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 ¼ 0.010; Exp(B) ¼ 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.

Digital image analysis of collagen assessment of progression of fibrosis in recurrent HCV after liver transplantation

“…In previous studies, CPA in recurrent HCV post-LT correlated with both Ishak stage scores and HVPG, with greater percentage changes in CPA than in HVPG in early portal hypertension [6]. CPA at 1-year biopsy post-LT for HCV cirrhosis was highly predictive of clinical outcome and better than Ishak stage or HVPG [7]. Lastly, CPA allows subclassification of cirrhosis [8] and this potentially increases the possibility of using histological parameters in cirrhosis to predict clinical outcomes.…”

“…CPA at one time point is a histological measurement that quantifies fibrosis, and relates to clinical outcomes [6,7]. CPA also correlates with HVPG with wider range of values in patients with Ishak stage 5/6, showing that cirrhosis can be subclassified [8].…”

“…These are described in detail in a previous publication [7], but in essence comprise a period of three randomized studies; initially CYA vs. TAC monotherapy [24]; then the TMC study, where a cohort received either CYA or TAC-based triple drug immunosuppression [25]. After the TMC study, patients transplanted for HCV cirrhosis, in a randomized study received triple immunosuppression therapy with corticosteroids, TAC and azathioprine (AZA), or TAC monotherapy, adjusting TAC dosing as previously described [26].…”

Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

“…These numbers are not arithmetically proportionate, i.e., stage 2 is not half of stage 4 (19,20). The need for an objective method, has led to the increasing use of digital image analysis (DIA) technology with collagen quantification using collagen proportionate area (CPA) for liver fibrosis assessment (21)(22)(23)(24)(25). As the number of hepatocytes decreases with increasing number of collagen deposition, the functional reserve is diminished accordingly (26).…”

What is the benefit of computer-assisted image analysis of liver fibrosis area?

“…They also reported that CPA at 1-year post-transplantation in hepatitis C virus-infected patients predicts subsequent clinical decompensation more accurately than Ishak stage or HVPG [5]. They conclude that CPA should be the histological parameter with which to compare LSM and other non-invasive fibrosis markers and also be used to subclassify cirrhosis.…”