2005 Fiscal Year Final Research Report Summary
Non Alcoholic Steathepatitis in Children : cause and factors of development of disease.
| Project/Area Number |
15591108
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | National University Corporation Tottori University |
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Principal Investigator |
NAGATA Ikuo Tottori University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (50252846)
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| Co-Investigator(Kenkyū-buntansha) |
MURAKAMI Jun Tottori University, University Hospital, Research Associate, 医学部附属病院, 助手 (90362889)
IITSUKA Toshiyuki Tottori University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (70271046)
KANZAKI Susumu Tottori University, Faculty of Medicine, Professor, 医学部, 教授 (90224873)
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| Project Period (FY) |
2003 – 2005
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| Keywords | NASH / fatty change / developmental hepatic disease / central pattern / diffuse pattern |
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| Research Abstract |
To elucidate clinical features, mechanisms and contributing factors for nonalcoholic steatohepatitis (NASH) in childhood, we analyzed the clinical course, liver histology and serum data in eitht cases of children with NASH.
[Methods 'Eight childhood NASH cases (8-13 years old, 7 males, one female) were examined as to clinical and histological features, inflammatory cytolcines, leptin levels and endotoxin concentrations. The body mass index, body fat percentage and serum levels of ALT and fern tin were measured over time in each patient, with an oral glucose tolerance test (OGTT) performed during the course.
[Results] 1) All male patients were moderately or severely obese and presented with acanthosis nigricans. Liver function returned to the normallange in 3 patients in whom obesity and body fat levels decreased. 2) Histological findings included moderate to severe steatosis of liver cells, inflammatory cell infiltration in the portal area and mild to moderate fibrosis. 3) OGTT values sh
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owed that 3 patients were normal type, another 3 were borderline type and 1 was diabetic type, according to the Japan Diabetes Society criteria, with all patients showing elevated baseline concentrations of immunoreactive insulin. ALT values varied among patients; in some patients, values at around 50 IU/L persisted, while in others, values fluctuated periodically within a range of 200 to 400 IU/L. The course of ALT values was well correlated with obesity level, body fat percentage and serum ferritin level. The female patient had also been diagnosed as having Alstrom syndrome, who exhibited elevated ALT values and hyperinsulinemia although not obese. 4) Tumor necrosis factor-_levels were determinable in 5 patients; in each of them the value was < 5 ng/mL. While interleukin-6 (IL-6) was increased in 1 patient at 8.2 ng/mL, it was measured at < 4 ng/mL in the other 7. IL-10 was < 2 ng/mL in 4 patients and was elevated to 16 ng/mL in 1 patient. Endotoxin concentration was < 5 ng/mL in 4 patients, whereas a marked increase to 19.9 ng/mL was noted in 1 patient (with Alstrom syndrome). Serum leptin levels were measurable in 6 patients: 5.6 ng/mL in 1 patient and elevated levels ranging from 14.2 to 18.3 ng/mL in 5 patients. 5) Two patients exhibited a decreasing trend in the transaminase level following administration of urodeoxycholic 'acid and vitamin E and polyenphosphatidylcholine.
[Discussion and conclusions] Involvement of hyperinsulinemia is suspected as a background factor in childhood NASH. Elevation of inflammatory cytokines and endotoxin have been noted in some children with NASH. Decrease in body fat percentage and obesity level is a useful indication for improvement in liver function. Treatment with medications with antioxidant action and lipid metabolism regulation may be effective. Less
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