Physiological and Anatomical Alterations in Children with Liver Cirrhosis

Abstract Objective To evaluate physiological and anatomical changes in children with liver cirrhosis supporting the development of physiologically based pharmacokinetic (PBPK) models. Methods A literature review was conducted (December 2023–May 2024) using PubMed and Google Scholar to identify studies reporting physiological and anatomical parameters in children (< 18 years) with liver cirrhosis. Parameters were analyzed in relation to disease severity (Child–Pugh and/or MELD/PELD scores), stratified by age, and compared to adult data. This study examined parameters modified in adult liver cirrhosis PBPK models to assess if similar changes occur in children. Results Parameters such as albumin, α1-acid glycoprotein, glomerular filtration rate, functional liver mass, portal blood flow, hepatic arterial blood flow, renal blood flow, and cardiac index showed either comparable alterations or lacked sufficient pediatric data to confirm differences from adult data. Hematocrit was significantly lower in children aged 2 to < 6 years ( P = 0.022), with up to 25% greater fractional decline compared to adults, possibly due to developmental and nutritional factors. Conclusion While children with liver cirrhosis exhibit physiological trends similar to adults, hematocrit shows a clear age-specific difference. For other parameters, limited pediatric data prevents firm conclusions, highlighting the need for age-specific studies to improve PBPK models and guide pediatric drug therapy. Graphical Abstract Key pharmacokinetic alterations in children with liver cirrhosis compared to adults. Created with BioRender.com, incorporating data from Edginton et al. (2008). Abbreviations: CP Child–Pugh. = Parameter is similar as observed in adults. ≠ Parameter is different as observed in adults.