Biliary atresia liver histopathological determinants of early post-Kasai outcome

Nguyen, Anh-Hoa Pham; Pham, Yen; Vu, Giap H.; Nguyen, My Ha; Hoang, Thach Ngoc; Holterman, Ai Xuan

doi:10.1016/j.jpedsurg.2021.03.039

Cited by 14 publications

(13 citation statements)

References 34 publications

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“…The intrahepatic bile duct and biliary system in the inv mice show markedly proliferative biliary ductules surrounding the portal vein like the DPM of some human BA [ 7 ]. DPM has also been observed in 20–40% of infants with BA with some prognostic relevance [ 7 , 29 , 31 , 32 , 34 , 107 , 108 , 109 ]. However, the extrahepatic bile duct does not show any evidence of ischemia or inflammation.…”

Section: Resultsmentioning

confidence: 99%

Biliary Atresia Animal Models: Is the Needle in a Haystack?

Pal

Joy

Sergi

2022

IJMS

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Biliary atresia (BA) is a progressive fibro-obliterative process with a variable degree of inflammation involving the hepatobiliary system. Its consequences are incalculable for the patients, the affected families, relatives, and the healthcare system. Scientific communities have identified a rate of about 1 case per 10,000–20,000 live births, but the percentage may be higher, considering the late diagnoses. The etiology is heterogeneous. BA, which is considered in half of the causes leading to orthotopic liver transplantation, occurs in primates and non-primates. To consolidate any model, (1) more transport and cell membrane studies are needed to identify the exact mechanism of noxa-related hepatotoxicity; (2) an online platform may be key to share data from pilot projects and new techniques; and (3) the introduction of differentially expressed genes may be useful in investigating the liver metabolism to target the most intricate bilio-toxic effects of pharmaceutical drugs and toxins. As a challenge, such methodologies are still limited to very few centers, making the identification of highly functional animal models like finding a “needle in a haystack”. This review compiles models from the haystack and hopes that a combinatorial search will eventually be the root for a successful pathway.

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Section: Resultsmentioning

confidence: 99%

Biliary Atresia Animal Models: Is the Needle in a Haystack?

Pal

Joy

Sergi

2022

IJMS

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“…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.…”

Section: Resultsmentioning

confidence: 99%

“…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 ].…”

Section: Methodsmentioning

confidence: 99%

“…We followed a similar method for organizing all other histopathological features, where 0 indicated absence of that feature and 1–3 as increasing intensity [ 26 39 ]. Bile duct proliferation/destruction was defined as: (1) mild, 5–9 bile ducts per portal tract; (2) moderate, ≥10 bile ducts per portal tract; and (3) severe, ≥10 bile ducts per portal tract and the ducts are elongated attenuated and angulated [ 30 33 40 ]. Cholestasis was defined as: (1) absent; (2) mild, accumulation of bile in centrilobular hepatocytes; (3) moderate, accumulation of bile in centrilobular and periportal hepatocytes or even in portal tracts; and (4) severe, presence of bile infarcts.…”

Section: Methodsmentioning

confidence: 99%

“…Portal inflammation was defined as: (1) mild, cells are present in <1/3 portal tracts; (2) moderate, cells are present in >1/3–2/3 portal tracts; and (3) severe, dense packing of cells present in >2/3 portal tracts. Giant cell transformation was grouped into positive vs. negative categories [ 30 33 40 ].…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

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

Jahangirnia

Oltean

Nasr

et al. 2022

Pediatr Gastroenterol Hepatol Nutr

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No systematic review to date has examined histopathological parameters in relation to native liver survival in children who undergo the Kasai operation for biliary atresia (BA). A systematic review and meta-analysis is presented, comparing the frequency of native liver survival in peri-operative severe vs. non-severe liver fibrosis cases, in addition to other reported histopathology parameters. Records were sourced from MEDLINE, Embase, and CENTRAL databases. Studies followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and compared native liver survival frequencies in pediatric patients with evidence of severe vs. non-severe liver fibrosis, bile duct proliferation, cholestasis, lobular inflammation, portal inflammation, and giant cell transformation on peri-operative biopsies. The primary outcome was the frequency of native liver survival. A random effects meta-analysis was used. Twenty-eight observational studies were included, 1,171 pediatric patients with BA of whom 631 survived with their native liver. Lower odds of native liver survival in the severe liver fibrosis vs. non-severe liver fibrosis groups were reported (odds ratio [OR], 0.16; 95% confidence interval [CI], 0.08–0.33; I 2 =46%). No difference in the odds of native liver survival in the severe bile duct destruction vs. non-severe bile duct destruction groups were reported (OR, 0.17; 95% CI, 0.00–63.63; I 2 =96%). Lower odds of native liver survival were documented in the severe cholestasis vs. non-severe cholestasis (OR, 0.10; 95% CI, 0.01–0.73; I 2 =80%) and severe lobular inflammation vs. non-severe lobular inflammation groups (OR, 0.02; 95% CI, 0.00–0.62; I 2 =69%). There was no difference in the odds of native liver survival in the severe portal inflammation vs. non-severe portal inflammation groups (OR, 0.03; 95% CI, 0.00–3.22; I 2 =86%) or between the severe giant cell transformation vs. non-severe giant cell transformation groups (OR, 0.15; 95% CI, 0.00–175.21; I 2 =94%). The meta-analysis loosely suggests that the presence of severe liver fibrosis, cholestasis, and lobular inflammation are associated with lower odds of native liver survival in pediatric patients after Kasai.

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IL13 and periostin in active fibrogenic areas of the extrahepatic bile ducts in biliary atresia patients

et al. 2022

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Background: The leading pathology of biliary atresia (BA) is in ammatory and brous obstruction of extrahepatic bile duct, butthe pathogenesis remains unclear.IL13 is a cytokine associated with allergies and in ammatory brosis, and periostin induces brogenesis by stimulation with IL13. We analyzed the involvement of IL13 and periostin in in ammatory brosis in the extrahepatic bile duct of BA patients.Materials and Methods: Surgically resected tissues from the hepatic hilar area of BA patients were immunostained with CD45, α-SMA, IL13 and periostin and statistically analyzed. Fibroblasts from the resected tissue were cultured with recombinant IL13, and periostin production was analyzed by quantitative polymerase chain reaction and Western blotting.Results: IL13 was stained in 93% of large and micro bile ducts, and 92.1% matched with the CD45 location (p=0.006) around the large bile ducts. Periostin staining correlated with the localization of IL13 and αSMA (p<0.001) around the large bile ducts. Periostin mRNA and protein were up regulated by IL13 stimulation in cultured broblasts.Conclusion: IL13 was associated with induced periostin expression by broblasts, playing a vital role in the pathogenesis of brogenesis around the extrahepatic bile duct in BA.

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Biliary atresia liver histopathological determinants of early post-Kasai outcome

Cited by 14 publications

References 34 publications

Biliary Atresia Animal Models: Is the Needle in a Haystack?

Biliary Atresia Animal Models: Is the Needle in a Haystack?

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

IL13 and periostin in active fibrogenic areas of the extrahepatic bile ducts in biliary atresia patients

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