α-Smooth muscle actin expression predicts the outcome of Kasai portoenterostomy in biliary atresia

Abstract

Background/Aims: Biliary atresia (BA) is a cholangio-destructive disease of the infant liver presenting with features of obstructive cholangiopathy. The Kasai portoenterostomy (KPE) is the first line of management. The aim of our study was to identify the characteristic features of liver histology in BA that impact the outcome of KPE. Patients and Methods: Data from 30 consecutive children was retrieved from our prospectively maintained database of children undergoing KPE. This included basic demographics, laboratory values and histopathological data from liver biopsy. The stages of fibrosis, presence of ductal plate malformation (DPM), giant cell transformation, extramedullary hematopoiesis and area percentage of α-SMA (α-smooth muscle actin) expression was correlated with jaundice clearance after KPE using standard statistical tests. Native liver survival was computed. Results: Overall, 13 (43%) children cleared jaundice in this series and 10 (33%) are alive with native liver. Lower area percent expression of α-SMA correlated with increased probability of jaundice clearance after KPE ( P < 0.001). There was no correlation between stage of fibrosis and jaundice clearance ( P = 0.52). DPM, giant cell transformation and extramedullary hematopoiesis did not correlate with outcome. All children who are alive with native liver had lower expression of α-SMA. Conclusion: α-SMA expression may be a potential predictor of jaundice clearance and native liver survival after KPE.

Biliary Atresia: pathology, Etiology and Pathogenesis

“…The transformation and proliferation of hepatic stellate cells (HSCs) from fat-storing cells to myofibroblasts in BA plays an important role in hepatic fibrogenesis. HSCs are responsible for increased extracellular matrix, which leads to progressive scarring [62]. Expression of an intracellular microfilament protein named α-smooth muscle actin (α-SMA) determines the HSC activity.…”

Peri-Operative Liver Fibrosis and Native Liver Survival in Pediatric Patients with Biliary Atresia: A Systematic Review and Meta-Analysis

“…Characteristics of the 28 studies with 1,171 pediatric patients who had BA and underwent Kasai operation are located in Table 1 . Briefly, there were 25 cohort [ 26 27 28 29 30 31 32 33 34 36 37 39 40 41 45 46 47 48 49 50 51 52 53 54 55 ] and 3 case control studies [ 35 56 57 ]. Six hundred and thirty-one patients survived with their native liver, while 573 required Ltx and 99 reportedly died after Kasai during follow-up.…”

“…Apart from 11 studies that were based on a selected group of users limited to a small sample size, patients were identified via electronic health records or referred to as a consecutive sample later subdivided into ideal vs. non-ideal outcomes [ 28 29 32 35 36 37 39 40 51 54 57 ]. Fourteen studies described pathologists being independently blinded to NLSR status [ 29 31 32 33 34 35 36 39 40 48 49 51 54 57 ]. Length of follow-up was 12 months for capturing survival outcomes in 17 studies [ 26 27 28 29 31 34 35 36 37 46 47 48 50 51 54 56 57 ].…”

“…Fourteen studies described pathologists being independently blinded to NLSR status [ 29 31 32 33 34 35 36 39 40 48 49 51 54 57 ]. Length of follow-up was 12 months for capturing survival outcomes in 17 studies [ 26 27 28 29 31 34 35 36 37 46 47 48 50 51 54 56 57 ]. The studies were mainly scored as ‘poor’ because they did not describe adjusting for confounders in a regression model, such as age at Kasai operation, anatomical pattern, polysplenia syndrome, level of centre experience, sex, albumin, total or direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and/or degree of liver failure.…”

“…Consequently, we extracted the actuarial survival rate at the designated follow-up period (2-, 5-, 10- or 20-years) [ 26 ]. For studies that did not explicitly state NLSR, we extracted data based on how the authors defined “favourable outcome” or “success of operation.” Hence, we extracted the frequency of patients with normal living function without cholangitis or portal hypertension [ 27 ], patients with good quality of life without jaundice relapsing [ 28 ], normal lab parameters and no evidence of medical chronic liver disease [ 29 ], absence of cirrhosis [ 30 31 ] or serum total bilirubin <2 mg/dL at follow-up post-Kasai operation [ 32 33 34 35 36 ].…”