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Enteric‐coated cysteamine for the treatment of paediatric non‐alcoholic fatty liver disease
Author(s) -
Dohil R.,
Schmeltzer S.,
Cabrera B. L.,
Wang T.,
Durelle J.,
Duke K. B.,
Schwimmer J. B.,
Lavine J. E.
Publication year - 2011
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2011.04626.x
Subject(s) - medicine , cysteamine , gastroenterology , clinical endpoint , fatty liver , oxidative stress , body mass index , endocrinology , disease , clinical trial
Aliment Pharmacol Ther 2011; 33: 1036–1044 Summary Background Non‐alcoholic fatty liver disease (NAFLD) is a common cause of liver disease in children. Hepatic fat accumulation and oxidative stress contribute to its pathogenesis. Cysteamine bitartrate readily traverses cellular membranes and is a potent antioxidant. Aim To evaluate the safety and efficacy of enteric‐coated (EC) cysteamine in children with NAFLD. Method Children, aged ≥10 y, meeting screening criteria with biopsy‐proven NAFLD and serum ALT ≥60 IU/L, received twice‐daily EC‐cysteamine for 24 weeks. Monthly ALT, AST, body mass index (BMI) and gastrointestinal symptom scores were measured. Subjects with >50% reduction or normalisation of ALT achieved the primary endpoint. Results Of the 13 children enrolled (mean age 14.0 years), 11 completed EC‐cysteamine therapy (mean dose 15.2 mg/kg/day) and were included in the final analysis. For these 11 subjects, the mean ALT levels at baseline and 24 weeks were 120.2 and 55 IU/L respectively ( P = 0.002), and the AST levels were 60 and 36 IU/L respectively ( P = 0.007). The primary endpoint was reached in 7 and normalisation (≤40 IU/L) of ALT in 5. After 24 week therapy, mean adiponectin levels increased ( P = 0.009) and CK‐18 fragment levels decreased ( P = 0.013), insulin levels remained unchanged ( P = 0.99). Mean leptin levels were decreased in responders ( P = 0.044). Mean BMI was 34.5 at baseline and 34.2 kg/m 2 after treatment ( P = 0.35). Mean symptom scores at baseline (1.1) and at 24 weeks (0.7) were similar. No major adverse events were reported. Conclusions Enteric‐coated cysteamine reduces ALT and AST levels in children with NAFLD without reduction in body mass index. Further studies will evaluate optimal cysteamine therapeutic dose and effect on liver histology in NAFLD (Clinicaltrials.gov protocol ID: 07‐1699).