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Published on: May 18, 2021
Oxidative stress parameters in paediatric non-alcoholic fatty liver disease
Valerio Nobili1, Maurizio Parola, Anna Alisi
1Department of Hepatogastroenterology, Bambino Gesu Children's Hospital, Rome, Italy. nobili66@yahoo.it
Insights
Oxidative stress is prevalent in children with non-alcoholic fatty liver disease (NAFLD), indicated by elevated markers like protein carbonyls and 8-hydroxy-2-deoxyguanosine (8-OHG). This stress is linked to more severe inflammation in pediatric NAFLD cases.
Area of Science:
- Pediatric Gastroenterology and Hepatology
- Biochemistry and Molecular Biology
- Oxidative Stress Research
Background:
- Non-alcoholic fatty liver disease (NAFLD) is a growing concern in pediatric populations.
- The role of oxidative stress in the pathogenesis and progression of pediatric NAFLD requires further elucidation.
- Understanding oxidative stress markers can offer insights into disease severity and clinical implications.
Purpose of the Study:
- To investigate the presence and clinical significance of oxidative stress in children diagnosed with NAFLD.
- To evaluate specific oxidative stress biomarkers, including serum protein carbonyls, hepatic 8-hydroxy-2-deoxyguanosine (8-OHG), and anti-malondialdehyde adducted human serum albumin (MDA-HSA) antibodies.
- To correlate these oxidative stress markers with histological features and disease activity in pediatric NAFLD.
Main Methods:
- Observational study design involving 40 children with biopsy-proven NAFLD.
- Measurement of serum protein carbonyls, hepatic 8-OHG expression, and circulating anti-MDA-HSA IgG.
- Analysis of correlations between biomarker levels and NAFLD activity score (NAS), including steatosis, lobular inflammation, hepatocyte ballooning, and fibrosis.
Main Results:
- Elevated serum protein carbonyls were observed in 83% of pediatric NAFLD patients, independent of obesity and insulin resistance.
- Increased hepatic 8-OHG expression was significantly associated with elevated circulating protein carbonyls (p=0.006).
- Anti-MDA-HSA IgG was detected in 63% of patients; higher levels correlated with significantly increased lobular inflammation (p=0.019) and a 13-fold increased risk of NAS ≥5 (p=0.013).
Conclusions:
- Oxidative stress is highly prevalent in children with NAFLD.
- Specific oxidative stress markers, particularly anti-MDA-HSA IgG, are associated with increased hepatic inflammation and disease severity in pediatric NAFLD.
- These findings highlight the potential role of oxidative stress as a contributor to steatohepatitis progression in children.
Abstract:
We have investigated the presence and the possible clinical implications of oxidative stress in children with non-alcoholic fatty liver disease (NAFLD). The present study was an observational study of oxidative stress parameters in the progression of paediatric NAFLD. We observed the role of oxidative stress in children diagnosed with NAFLD by evaluating: serum protein carbonyls, hepatic expression of 8-hydroxy-2-deoxyguanosine (8-OHG), and circulating antibody against malondialdehyde adducted human serum albumin (MDA-HSA). Forty consecutive children with biopsy-proven NAFLD (27 male; 13 female) referred to Bambino Gesù Children's Hospital, Rome, Italy, from January 2007 to April 2008 were included in the study. Serum variations of protein carbonyls, 8-OHG, and circulating antibody against MDA-HSA were evaluated. Elevated protein carbonyls were evident in 33 subjects (83%) irrespective of obesity and insulin resistance. Moreover, liver biopsies of NAFLD patients positive for circulating protein carbonyls also showed a significant increase in the nuclear staining for 8-OHG (p=0.006; 95% CI 3.1-17.7). Anti-MDA-HSA IgG above control threshold was detected in 25 (63%) children. Although protein carbonyl levels were unrelated with disease severity, patients with elevated anti-MDA-HSA IgG had scores for lobular inflammation significantly higher (p=0.019) than subjects with antibodies within the control range, while steatosis, hepatocyte ballooning and fibrosis were similar. High anti-MDA-HSA reactivity was also associated with a 13-fold increased risk (OR=12.9; 95= CI 1.5-113.8; p=0.013) of a NAFLD activity score (NAS) >or=5. These results demonstrate that oxidative stress has an high prevalence in children with NAFLD and is associated with an increased severity of steatohepatitis.
