Hepatic sinusoidal obstruction syndrome due to herbal ingestion in South African children - An 8 year review
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1 UNIVERSITY OF PRETORIA Hepatic sinusoidal obstruction syndrome due to herbal ingestion in South African children - An 8 year review L. Hendricks, A. Meyer, A. Terblanche Dept of paediatric gastroenterology Steve Biko Academic Hospital 1
2 No disclaimers or conflicts of interests 2
3 Introduction Uncommon chronic liver disease Affect children and adults Incidence 1-70% in adults Incidence unknown in children West: Stem cell Transplants, GvHD Africa, Asia, Middle East: Herbal medicine
4 Pyrrolizidine alkaloids 3% world s plant species contain PA Heliotropium, Senecio, Crotalaria, Symphytum, Tusanqi species Toxic when PA s undergo metabolic oxidation by hepatocytes Damage dose and duration dependent mg/kg/day for 3-7 weeks - WHO: safest intake 1mg/ day in adults
5 Nakanuma et al, 5
6 Pathophysiology Metabolic oxidation to toxic pyrrole protein adducts Oxidised by cytochrome P450 3A4 biotransformation Results in oxidative stress reaction, mitochondrial injury and apoptosis At sinusoidal level: - PA more selectively toxic to endothelial cells than hepatocytes - Loss of sinusoidal wall integrity with detachment of endothelial lining - Embolization of central zones of hepatic lobule, centrilobular necrosis, perisinusoidal fibrosis, peliosis and nodular regenerative hyperplasia CIRCULATORY OBSTRUCTION PRECEDES HEPATOCYTE DYSFX 6
7 Objectives Characterize children with SOS due to herbal ingestion Document complications and long term outcomes of patients with SOS
8 Method Descriptive study Folder review Inclusion criteria - all patients with SOS - 01/01/2008 to 01/04/ years of age at time of presentation - Steve Biko Academic Hospital Paediatric Gastroenterology service Exclusion criteria - incomplete medical records - other causes of chronic liver disease, excluding SOS - > 13 years of age at time of presentation
9 25 29 patients <1 yr age 1-5 yrs age >5 yrs age male female Median age of presentation 63,5mo
10 14% Geographical distribution SOS 72% Mpumalanga Limpopo Gauteng Eastern Cape no. patients
11 History of ingestion Ave duration 15 mo traditional meds pharmaceutical meds homeopathic meds unknown no. of patients
12 presenting symptoms RUQ pain Upper GI bleed Hepatomegaly Acute liver failure Wasting Jaundice 62% HSM 79% Ascites 80%
13 presenting symptoms RUQ pain Upper GI bleed Hepatomegaly Acute liver failure Wasting presenting symptoms Jaundice HSM Ascites
14 16 Common presenting symptoms <1 yr 1-5 yrs >5 yrs
15 16 Common presenting symptoms <1 yr 1-5 yrs >5 yrs
16 16 Common presenting symptoms <1 yr 1-5 yrs >5 yrs
17 Biochemical markers CMV positive coagulopathy Raised GGT raised AST no. of patients raised ALT raised bili
18 Bili > 50 ALT > 30AST > 69 GGT > 22 INR > 1,3 PT > 16 Albumin < 29 0 Bili >50 ALT > 30 AST > 69 GGT > 22 INR > 1,3 PT > 16 Albumin < 29 <1 yr initial bloods 1-5 yrs initial bloods >5 yrs initial bloods <1yr 1-5 yrs > 5 yrs Initial blood results Last recorded blood results
19 ultrasound ascites thickened GB hepar hepatic a RI raised cirrhosis other
20 14 US findings Ascites Thickened GB Hepar Hepatic artery RI Cirrhosis Other <1 yr 1-5 yrs >5 yrs
21
22 Progressive disease Static disease Improvement in condition 100% recovery 10 (35%) 7 (24%) 3 (10%) 5 (17%) Initial PELD 10 Latest PELD 4 Initial PELD 13 Latest PELD 5 Initial PELD 12 Latest PELD - 4 Initial PELD 8 Latest PELD outcomes outcomes
23 6 Age related outcomes static disease progressive disease improved 100% recovery palliation death <1 yr 1-5 yrs >5 yrs
24 poor prognostic factors severe ascites weight gain severe hyperbilirubinemia portal vein thrombosis multi organ failure hepatic venous pressure > 20
25 Poor Px factors multi organ failure portal v thrombosis hyperbilirubinemia ascites >5 yrs 1-5 yrs <1 yr
26 Conclusion Seems to be more prevalent in rural environments Typically in younger children 0-5 yrs of age Typically present with ascites, jaundice, HSM and PHT - infants seem to present with more complicated disease but are also more likely to respond to supportive treatment PELD scores generally improved on supportive management alone More studies needed to determine incidence, prevalence and prognostic markers Communication imperative!
27 Thank you!
28 28
29 Histology findings ZONAL NECROSIS NARROWING OF SINUSOIDS STEATOSIS BILE DUCT INJURY+NECROSIS VASCULAR INJURY SUBENDOTHELIAL FIBROSIS CENTROLOBULAR NECROSIS >5 yrs 1-5 yrs <1 yr
30 7 Histology findings compared to PELD scores centrolobular necrosis subendothelial fibrosis vascular injury bile duct injury and necrosis steatosis narrowing of sinusoids zonal necrosis PELD -5 to 5 5 to to to 20 >20
31 PELD -5 to 5 Initial PELD score 6 to to >20 <1 yr 1-5 yrs >5 yrs Neonates and infants presented with higher PELD scores initially The neonatal and infant group had the most improvement in PELD scores at follow up. >5 yr age group showed deterioration in PELD scores over time PELD -5 to 5 Follow up PELD score 6 to to to 20 >20 <1 yr 1-5 yrs >5 yrs
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