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Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia.

ABSTRACT: BACKGROUND:Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation. METHODS:Ki67 (clone, MIB-1) liver parenchyma expression was measured by immunohistochemical staining of samples from living donors and patients with biliary atresia to assess its value in predicting outcomes after KP. RESULTS:Of 35 children with biliary atresia, 13 were native liver survivors (NLS), 17 were non-NLS, and five had primary LT. The median proportion of Ki67 immunostained areas in donors and patients with biliary atresia at KP was 0·06 and 0·99 per cent respectively. Univariable analysis identified a high proportion of Ki67 areas, high Ki67 cell numbers and high Ki67-positive/leucocyte common antigen-positive cell numbers at KP as significant predictors of poor native liver survival after KP (hazard ratio 9·29, 3·37 and 12·17 respectively). The proportion of Ki67 areas in the non-NLS group was significantly higher than that in the NLS group (1·29 versus 0·72 per cent respectively; P = 0·001), and then decreased at LT (0·32 per cent versus 1·29 per cent at KP; P?

SUBMITTER: Yoshii D

PROVIDER: S-EPMC7528526 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia.

Yoshii D D Inomata Y Y Komohara Y Y Shimata K K Honda M M Hayashida S S Oya Y Y Yamamoto H H Yamamoto H H Sugawara Y Y Hibi T T

BJS open 20200616 5

<h4>Background</h4>Biliary atresia is a rare paediatric biliary obliteration disease with unknown aetiology, and is the most common indication for paediatric liver transplantation (LT). However, no consensus for predicting Kasai portoenterostomy (KP) outcomes using liver histological findings exists. Ki67 is a popular biomarker for measuring and monitoring cellular proliferation.<h4>Methods</h4>Ki67 (clone, MIB-1) liver parenchyma expression was measured by immunohistochemical staining of sample ...[more]

PMID: 32543770

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Project description:Background and aimsBiliary atresia (BA) is a cholestatic, fibro-obliterative cholangiopathy of unknown etiology. BA is primarily treated by a surgical approach, that is, the Kasai portoenterostomy (KPE), to obtain clearance of jaundice (COJ). The gut microbiota (GM) composition has been associated with the course of several cholestatic liver diseases. It is largely unknown, however, whether GM composition associates with the outcome of KPE. We compared the GM composition of BA patients and controls and assessed if GM composition before KPE was related to COJ after KPE.MethodsWe compared feces of term-born BA patients before KPE and controls (patients undergoing inguinal hernia repair) by 16S rRNA sequencing. Composition and alpha diversity of the GM were compared between BA and controls before KPE and after KPE, between patients with COJ versus without COJ (total serum bilirubin < or ≥20 μmol/L <6 months post-KPE).ResultsAlpha diversity was comparable between BA (n = 12, age 1.6 [1.3-1.8] months) and controls (n = 6, age 2.0 [1.4-2.1] months; P = 0.22). Compared with controls, BA patients had lower abundances of Bifidobacteriaceae (β = -1.98, P < 0.001) and Lachnospiraceae (β = -1.84, P = 0.007), and higher abundances of Streptococcus (β = -1.13, P = 0.003). The alpha diversity before KPE correlated negatively with COJ (R = -0.63, P = 0.03). Lower alpha diversity pre-KPE was associated with COJ [+] (βlogit = -0.64, P = 0.04). We observed greater abundances of genus Acinetobacter (β = 1.27, P = 0.03) and family Clostridiaceae (β = 1.45, P = 0.03) and lower abundances of the family Enterobacteriaceae (genera Klebsiella (β = -1.21, P = 0.01), Salmonella (β = -1.57, P = 0.02)) in COJ [+] versus COJ [-].ConclusionsThe GM of BA patients before Kasai portoenterostomy associates with outcome, clearance of jaundice, suggestive of predictive, and mechanistic roles of the gut microbiota composition in bile homeostasis.

Project description:Background Good outcomes of biliary atresia (BA) are conventionally achieved after early Kasai portoenterostomy (KP). However, in some recent pieces of literature, there are discrepancies in the influence of age in Kasai procedure on postoperative short-term prognosis. This meta-analysis aims to evaluate the effects of earlier KP on short-term surgical prognosis of BA and clarify these discrepancies in recent studies. Methods To identify related studies, PubMed, Embase, Web of Science, Cochrane, and the Chinese National Knowledge Infrastructure database were searched up to March 2022. Data for the impact of age at KP on clinical prognosis were extracted, including jaundice clearance rate (JCR) and native liver survival rate (NLSR). Results A total of 14 articles were included in the present study, which involve a total of 3,276 patients with BA who underwent Kasai procedure. Compared with patients older than 91 days of age, patients 90 days of age or younger exhibited significantly better JCR [odds ratio (OR), 3.05; 95% confidence interval (CI), 2.23–4.17; P < .001] and a more favorable NLSR (OR, 1.72; 95% CI, 1.37–2.15; P < .001). The NLSR of patients younger than 60 days of age was significantly higher than those of patients from 61 to 90 days of age (OR, 1.41; 95% CI, 1.18–1.68; P < .001). There was no significant difference in JCRs between patients aged 60 days of age or younger and those aged 61–90 days of age (OR, 1.31; 95% CI, 0.95–1.81; P = 0.10). Among patients 30 days of age or younger, 31–45 days of age, and 46–60 days of age, there were also no significant differences in JCR. Conclusion A significantly better short-term JCR and NLSRs were achieved among patients with BA treated using a KP procedure at ≤90 days of age compared with those treated at >90 days of age. There was no further improvement in the short-term JCR when the procedure was performed at ≤60 days compared with those treated at 61–90 days of age. However, treatment at ≤60 days of age was associated with a significant improvement in NLSR. Therefore, the timing of KP does exert an important effect on short-term clinical outcomes of patients with BA.

Dataset Information

Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia.

Publications

Ki67 expression at Kasai portoenterostomy as a prognostic factor in patients with biliary atresia.

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