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Liver histology and hepatic progenitor cell activity in pediatric acute liver failure: Implications for clinical
Kalpana Panda1, Vikrant Sood1, Bikrant Bihari Lal1
1Department of Pediatric Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Insights
In pediatric acute liver failure (PALF), severe hepatocyte loss and increased hepatic progenitor cell (HPC) activation correlate with poor outcomes. Reduced hepatocyte proliferation and increased senescence also indicate a worse prognosis in these children.
Area of Science:
- Hepatology
- Pediatric Gastroenterology
- Regenerative Medicine
Background:
- Pediatric acute liver failure (PALF) presents complex challenges in understanding hepatic progenitor cell (HPC) activity and liver regeneration.
- The clinicopathological correlations between liver histology, HPC activity, and patient outcomes in PALF require further elucidation.
Purpose of the Study:
- To investigate the relationship between liver histology, HPC activity, and clinical outcomes in children with PALF.
- To identify histological predictors of outcome in pediatric acute liver failure.
Main Methods:
- Analysis of hepatic histological specimens from PALF patients.
- Assessment of hepatocyte loss, HPC activity (CK7, CK19, SOX9, EpCAM), hepatocyte proliferation (Ki67), and senescence (p53, p21).
Main Results:
- Ninety-four children were included; 23.4% survived with native liver (SNL), while 35.1% died and 41.5% received liver transplants (LT).
- The SNL group showed less severe hepatocyte loss, fewer HPCs, more proliferating hepatocytes, and less senescent hepatocytes compared to the poor outcome group (p < .05).
- Hepatocyte loss severity (adjusted OR: 9.95) was an independent predictor of poor outcome; 80% of children with >50% hepatocyte loss had poor outcomes within 10 days.
Conclusions:
- In PALF, severe hepatocyte loss, increased HPC activation, reduced hepatocyte proliferation, and elevated hepatocyte senescence are associated with poor outcomes.
- Loss of over 50% of hepatocytes is a significant independent predictor of poor outcomes in pediatric acute liver failure.
Background:
Hepatic progenitor cell (HPC) activity and regenerative process that follows pediatric acute liver failure (PALF) is still not well understood. This clinicopathological study was thus conducted with an aim to study the correlation of liver histology and HPC activity with outcomes in PALF.
Methods:
All PALF patients with available hepatic histological specimens were included and specimens were analyzed for hepatocyte loss, HPC activity [using cytokeratin (CK) 7, CK19, sex-determining region Y-related high mobility group box(SOX)9 and epithelial cell adhesion molecule (EpCAM)], hepatocyte proliferation (using Ki67), and hepatocyte senescence (using p53 and p21).
Results:
Ninety-four children were included: 22 (23.4%) survived with native liver (SNL) (i.e., the good outcome group) while rest (i.e., the poor outcome group) either died [33%, 35.1%] or received liver transplant (LT) [39%, 41.5%]. When compared to subjects with poor outcomes, those in the SNL group exhibited significantly less severe hepatocyte loss, fewer HPC/hpf, more proliferating hepatocytes, and less senescent hepatocytes (p < .05). Increasing severity of hepatocyte loss (adjusted OR: 9.95, 95% CI: 4.22-23.45, p < .001) was identified as an independent predictor of poor outcome. Eighty percent children with >50% native hepatocyte loss had poor outcome within 10 days of hospitalization.
Conclusion:
In PALF, more severe hepatocyte loss, higher number of HPC activation, lesser number of proliferating hepatocytes, and greater number of senescent hepatocytes are associated with a poor outcome. Loss of >50% hepatocytes is an independent predictor of poor outcome in PALF.
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