Observational Study
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World J Gastroenterol. Jun 7, 2014; 20(21): 6638-6650
Published online Jun 7, 2014. doi: 10.3748/wjg.v20.i21.6638
Protocol liver biopsy is the only examination that can detect mid-term graft fibrosis after pediatric liver transplantation
Yukihiro Sanada, Koshi Matsumoto, Taizen Urahashi, Yoshiyuki Ihara, Taiichi Wakiya, Noriki Okada, Naoya Yamada, Yuta Hirata, Koichi Mizuta
Yukihiro Sanada, Taizen Urahashi, Yoshiyuki Ihara, Taiichi Wakiya, Noriki Okada, Naoya Yamada, Yuta Hirata, Koichi Mizuta, Department of Transplant Surgery, Jichi Medical University, Tochigi 329-0498, Japan
Koshi Matsumoto, Department of Clinical Pathology, Ebina General Hospital, Kanagawa Prefecture 243-0433, Japan
Author contributions: Sanada Y participated in making the research design, analyzing data, and writing the article; Urahashi T, Ihara Y, Wakiya T, Okada N, Yamada N and Hirata Y participated in the data collection, data analysis and writing of the discussion; Matsumoto K and Mizuta K participated in the research design, writing of the discussion and review of the article.
Correspondence to: Yukihiro Sanada, MD, PhD, Department of Transplant Surgery, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke City, Tochigi 329-0498, Japan. yuki371@jichi.ac.jp
Telephone: +81-285-587069 Fax: +81-285-587069
Received: July 24, 2013
Revised: November 12, 2013
Accepted: November 28, 2013
Published online: June 7, 2014
Processing time: 317 Days and 4.2 Hours
Abstract

AIM: To assessed the clinical significance of protocol liver biopsy (PLB) in pediatric liver transplantation (LT).

METHODS: Between July 2008 and August 2012, 89 and 55 PLBs were performed in pediatric patients at two and five years after LT, respectively. We assessed the histopathological findings using the Metavir scoring system, including activity (A) and fibrosis (F), and we identified factors associated with scores of ≥ A1 and ≥ F1. Our results clarified the timing and effectiveness of PLB.

RESULTS: The incidences of scores of ≥ A1 and ≥ F1 were 24.7% and 24.7%, respectively, at two years after LT and 42.3% and 34.5%, respectively, at five years. Independent risk factors in a multivariate analysis of a score of ≥ A1 at two years included ≥ 2 h of cold ischemic time, no acute cellular rejection and an alanine amino transaminase (ALT) level of ≥ 20 IU/L (P = 0.028, P = 0.033 and P = 0.012, respectively); however, no risk factors were identified for a score of ≥ F1. Furthermore, no independent risk factors associated with scores of ≥ A1 and ≥ F1 at five years were identified using multivariate analysis. A ROC curve analysis of ALT at two years for a score of ≥ A1 demonstrated the recommended cutoff value for diagnosing ≥ A1 histology to be 20 IU/L. The incidence of scores of ≥ A2 or ≥ F2 at two years after LT was 3.4% (three cases), and all patients had an absolute score of ≥ A2. In contrast to that observed for PLBs at five years after LT, the incidence of scores of ≥ A2 or ≥ F2 was 20.0% (11 cases), and all patients had an absolute score of ≥ F2. In all cases, the dose of immunosuppressants was increased after the PLB, and all ten patients who underwent a follow-up liver biopsy improved to scores of ≤ A1 or F1.

CONCLUSION: PLB at two years after LT is an unnecessary examination, because the serum ALT level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.

Keywords: Protocol liver biopsy; Graft fibrosis; Immunosuppression; Liver function test; Pediatric liver transplantation

Core tip: Few studies have investigated the impact of the timing and effectiveness of post-transplant protocol liver biopsy (PLB). We assessed the histopathological findings of these biopsies using the Metavir scoring system, and our results clarified the timing and effectiveness of PLB. PLB at two years after pediatric liver transplantation is an unnecessary examination, because the serum alanine amino transaminase (ALT) level reflects portal inflammation. In addition, immunosuppressive therapy should be modulated to maintain the ALT concentration at a level less than 20 IU/L. PLB at five years is an excellent examination for the detection of early reversible graft fibrosis because no serum markers reflect this finding.