Novel Histologic Scoring System for Long-Term Allograft Fibrosis After Liver Transplantation in Children

Abstract

The existing systems for scoring fibrosis were not developed to evaluate transplanted livers. Our aim was to design and validate a novel fibrosis scoring system specifically adapted to assess liver allograft fibrosis (LAF). Clinical data, histology, transient elastography (TE) and AST/platelet ratio index (APRI) were reviewed in 38 pediatric liver transplant (LT) recipients. Protocol liver biopsies performed at 6 months and 7 years post-LT were reviewed by three pathologists who assessed LAF using the METAVIR and Ishak systems. LAF was also scored separately in portal (0-3), sinusoidal (0-3) and centrolobular areas (0-3). Scoring evaluations were correlated with fibrosis quantification using morphometry, and also with TE and APRI. Statistical correlations between morphometry and METAVIR were 0.571 (p < 0.000) and 0.566 (p < 0.000) for the Ishak system. The novel score (0-9) for separate assessment of portal, sinusoidal and centrolobular fibrosis showed a better correlation with morphometry (0.731; p < 0.000) and high intra-/interobserver agreement (0.966; p < 0.000 and 0.794; p < 0.000, respectively). No correlation was found between TE or APRI and morphometry or the three histologic scores. In conclusion, this novel semiquantitative fibrosis scoring system seems to more accurately reflect LAF than the existing scoring system and may become a practical tool for staging fibrosis in LT.

Progressive Fibrosis is Driven by Genetic Predisposition, Allo-Immunity, and Inflammation in Pediatric Liver Transplant Recipients

“…on different hepatic parenchyma zones using LAFSc (Venturi et al, 2012). This zone-specific analysis enabled us to decipher cause-specific inflammation and fibrosis patterns, resulting in a scheme for PB interpretation (Fig.…”

“…Fibrosis was assessed using the liver allograft fibrosis score (LAFSc) on Masson's trichrome-stained slides, with scores assigned to portal, sinusoidal, and central areas, as reported (Venturi et al, 2012). This is well accepted and a validated fibrosis scoring system in the context of pediatric allograft fibrosis.…”

“…Protocol biopsies (PBs) from LT recipient children revealed frequent allograft inflammation and fibrosis (Evans et al, 2006;Scheenstra et al, 2009;Hubscher, 2011;Venturi et al, 2012Venturi et al, , 2014Gurevich et al, 2015), in stable LT recipients without predisposing factors (Evans et al, 2006;Venturi et al, 2014;Gurevich et al, 2015;Miyagawa-Hayashino et al, 2012). The etiopathogenesis of these "idiopathic" changes is unknown, while graft age, subclinical rejection and medication non-compliance have been considered as possible aetiologies (Hubscher, 2011;Venturi et al, 2014;Miyagawa-Hayashino et al, 2012).…”

Safety and Tolerance of Donor-Derived Mesenchymal Stem Cells in Pediatric Living-Donor Liver Transplantation: The MYSTEP1 Study

“…Additionally, we will perform protocol liver biopsies routinely every 5 years after LT. Liver tissue will be processed for immunohistochemistry (hematoxylin and eosin staining; staining for CD3, CD4, and CD20). Biopsies will be scored according to the Banff criteria and the liver allograft fibrosis scoring system [44]. Further, expression of anti- and proinflammatory cytokines will be measured by real-time RT-PCR in liver tissue.…”

Limitations and opportunities of non-invasive liver stiffness measurement in children

“…This score has been used to evaluate adult patients with hepatitis B and C[19] and paediatric patients after liver transplantation[22], biliary atresia[23], intestinal failure[24] and total parenteral nutrition[25]; (2) the grading score of Ishak et al[20] assesses fibrosis qualitatively on a 0-6 scale. The Ishak score has been used in paediatric populations with various liver diseases, and including children after liver transplantation[26] or cardiovascular surgery[27]; (3) the grading score of Desmet et al[17] assesses fibrosis qualitatively on a 0-4 scale, with F0 indicating absence of fibrosis, F1 indicating portal fibrosis, F2 indicating fibrosis with septa without distortion of the liver architecture, F3 indicating septal fibrosis with severe distortion of the liver architecture, and F4 indicating cirrhosis. It has been used to evaluate adult patients with chronic hepatitis C[28]; and (4) the semi-quantitative severity score of Chevalier et al[21] has been used in children[29] and adults with hepatitis B[30] and C[31].…”