Page 33 - EASL POSTGRADUATE COURSE
P. 33
Table 1. Completed RCTs for the treatment of pediatric NAFLD with effective drugs. Adapted
from Della Corte et al. [10].
Drug Type of Clinical-Trial. Patients Intervention Endpoints Results
study gov identifier
Vitamin E 3-20 years Alpha Improvement Negative
+ ascorbic Double NCT Biopsy proven tocopherol serum levels of Negative
acid blind RCT 00655018 NAFLD 600 IU/day aminotransferase, Positive
+ insulin-sensitivity,
TONIC Double NCT 8-17 years Ascorbic acid body weight and
blind RCT 00063635 Biopsy 500 mg/d liver histology
Cystea-mine confirmed
Open label NCT NAFLD Metformin Reduction of 50%
DHA –preliminary 00799578 ALT >60 U/L 500 mg BID or less of serum
study ALT levels from
NCT ≥10 years Vitamin E baseline or 40
Double 00885313 Biopsy proven 400 IU BID IU/L or less
blind RCT NAFLD
ALT > 60 1 gr/mg body Normalization or
U/L surface area >50% of serum
(maximum ALT levels from
4-16 years 100 mg BID) baseline
Biopsy proven
NAFLD 1° exptl arm: Improvement of Negative
250 mg/day ALT levels
Positive
2° exptl arm: Improvement of
500 mg/day serum levels of Positive
triglycerides (LDL-
Gluco- Double NCT 4-16 years 5 gr/day chollesterol)
mannan blind RCT 01553500 Echographic Improvement in Negative
evidence lipid metabolism
of hepatic
steatosis Improvement in
glucose
metabolism
Treatment
Lifestyle modification represents the current first-line therapy for pediatric NAFLD, even though it
is not known to improve NAFLD-associated liver damage [9]. As guidelines for the management of
NAFLD in children are still lacking, the identification of effective treatments represents a challenge
for pediatric hepatologists in the near future. Based on new risk factor and pathogenesis knowledge,
several studies have evaluated the effects of different molecules (e.g. insulin-sensitizers, anti-oxidants,
and cytoprotective agents) in the treatment of pediatric fatty liver. Several drug-based therapies (e.g.
vitamin E, metformin) and dietary supplementation (e.g. VSL#3, docosahexaenoic acid) have been
shown to be effective on ballooning, steatosis and inflammation, but fibrotic lesions are refractory to
treatments [10]. For these reasons many clinical trials for the treatment of pediatric NAFLD have been
proposed, some of which have been completed (Table 1), while others are still in progress (Table 2)
(clinical trials registered on ClinicalTrial.gov as of December 2014) [10].
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 33
from Della Corte et al. [10].
Drug Type of Clinical-Trial. Patients Intervention Endpoints Results
study gov identifier
Vitamin E 3-20 years Alpha Improvement Negative
+ ascorbic Double NCT Biopsy proven tocopherol serum levels of Negative
acid blind RCT 00655018 NAFLD 600 IU/day aminotransferase, Positive
+ insulin-sensitivity,
TONIC Double NCT 8-17 years Ascorbic acid body weight and
blind RCT 00063635 Biopsy 500 mg/d liver histology
Cystea-mine confirmed
Open label NCT NAFLD Metformin Reduction of 50%
DHA –preliminary 00799578 ALT >60 U/L 500 mg BID or less of serum
study ALT levels from
NCT ≥10 years Vitamin E baseline or 40
Double 00885313 Biopsy proven 400 IU BID IU/L or less
blind RCT NAFLD
ALT > 60 1 gr/mg body Normalization or
U/L surface area >50% of serum
(maximum ALT levels from
4-16 years 100 mg BID) baseline
Biopsy proven
NAFLD 1° exptl arm: Improvement of Negative
250 mg/day ALT levels
Positive
2° exptl arm: Improvement of
500 mg/day serum levels of Positive
triglycerides (LDL-
Gluco- Double NCT 4-16 years 5 gr/day chollesterol)
mannan blind RCT 01553500 Echographic Improvement in Negative
evidence lipid metabolism
of hepatic
steatosis Improvement in
glucose
metabolism
Treatment
Lifestyle modification represents the current first-line therapy for pediatric NAFLD, even though it
is not known to improve NAFLD-associated liver damage [9]. As guidelines for the management of
NAFLD in children are still lacking, the identification of effective treatments represents a challenge
for pediatric hepatologists in the near future. Based on new risk factor and pathogenesis knowledge,
several studies have evaluated the effects of different molecules (e.g. insulin-sensitizers, anti-oxidants,
and cytoprotective agents) in the treatment of pediatric fatty liver. Several drug-based therapies (e.g.
vitamin E, metformin) and dietary supplementation (e.g. VSL#3, docosahexaenoic acid) have been
shown to be effective on ballooning, steatosis and inflammation, but fibrotic lesions are refractory to
treatments [10]. For these reasons many clinical trials for the treatment of pediatric NAFLD have been
proposed, some of which have been completed (Table 1), while others are still in progress (Table 2)
(clinical trials registered on ClinicalTrial.gov as of December 2014) [10].
The International Liver Congress™ 2015 • Vienna, Austria • April 22–23, 2015 33
