Home Current Issue Previous Issues Published Ahead-of-Print CME Collections Podcasts For Authors Journal Info
Skip Navigation LinksHome > January 2000 - Volume 30 - Issue 1 > Nonalcoholic Steatohepatitis in Children
Journal of Pediatric Gastroenterology & Nutrition:
Original Articles

Nonalcoholic Steatohepatitis in Children

Rashid, Mohsin*; Roberts, Eve A.

Free Access
Article Outline
Collapse Box

Author Information

Division of Gastroenterology and Nutrition, The Hospital for Sick Children, and the University of Toronto, Ontario, Canada

*Current address: Department of Paediatrics, IWK Grace Children's Hospital, Halifax, Nova Scotia, Canada.

Received November 20, 1999;

revised July 29, 1999; accepted September 10, 1999.

Address correspondence and reprint requests to Dr. Eve A. Roberts, Division of Gastroenterology and Nutrition, Room 8267, University Wing, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.

Collapse Box

Abstract

Background: Nonalcoholic steatohepatitis occurs commonly in adults with obesity or diabetes mellitus. There are only a few reports of this condition in children.

Methods: Prospective consecutive clinical series.

Results: Between December 1985 and April 1995, 36 children (21 boys, 15 girls) were diagnosed with nonalcoholic steatohepatitis at the Hospital for Sick Children, Toronto. The median age at diagnosis was 12 years (range, 4–16 years). Most patients were referred because of elevated serum aminotransferases or abnormal hepatic sonogram. Thirty patients (83%) were obese. Two patients had diabetes mellitus at diagnosis, and it developed later in two. Fifteen patients had palpable hepatomegaly, and one of these had splenomegaly. None had physical signs of chronic liver disease. Thirteen of 36 patients had acanthosis nigricans. Serum aminotransferases were elevated in all but one patient. Tests for Wilson disease and chronic hepatitis B and C were negative. Serum lipid profiles were abnormal in 18 patients: 7 had hypercholesterolemia, and 11 had hypertriglyceridemia. Twenty-four of 31 examined had abnormal liver sonograms suggestive of fatty infiltration. Twenty-four patients underwent percutaneous liver biopsy: all showed large-droplet fat. Inflammation was present in 88% and fibrosis-cirrhosis in 75%. One 10-year-old patient had established cirrhosis at diagnosis.

Conclusions: Nonalcoholic steatohepatitis occurs in children, is clinically diverse, and may not be benign.

Nonalcoholic steatohepatitis (NASH) occurs most commonly in adults with obesity, hyperlipidemia, and maturity-onset diabetes (1–5). It has also been described in association with pregnancy, starvation, or chronic treatment with drugs, notably corticosteroids. It may also occur, with elevated serum aminotransferases, in adults in the absence of these risk factors (6–8). Sufficient evidence has accrued to indicate that NASH, as such, occurs in the absence of obvious causative factors such as starvation and that affected patients are not abusing ethanol secretly. Recent observations suggest, however, that the stereotype of the typical NASH patient as middle-aged, massively obese, and female may not be accurate. Moreover, although initially considered a relatively benign disorder, NASH can progress to cirrhosis in adults.

Nonalcoholic steatohepatitis has been reported in children (9–15). Most of these series are small or do not include data from liver biopsies. The purpose of this study was to describe and characterize clinically NASH in children. We report a consecutive prospective series of children with NASH diagnosed at the Hospital for Sick Children during approximately 10 years. This is the one of the largest series of NASH in children reported to date.

Back to Top | Article Outline

PATIENT AND METHODS

All children diagnosed with NASH at the Hospital for Sick Children, Toronto, from December 1985 through April 1995 were included. Patients were excluded if they were receiving concomitant corticosteroid therapy or if they were found to have a metabolic disorder known to cause fatty liver (e.g., Wilson disease, neutral lipid storage disease, or fatty acid oxidation disorders). The first child was diagnosed as having NASH in December 1985 on the basis of clinical obesity and abnormal serum aminotransferase levels, results of laboratory studies excluding other known liver diseases, and results of a percutaneous liver biopsy showing steatosis and inflammation. Thereafter, NASH was included in the differential diagnosis of children with unexplained elevation of aminotransferases, especially if obese. In total, 36 patients were identified. By way of comparison, during this same period, 11 children with symptomatic liver disease were diagnosed as having Wilson disease.

Age, sex, weight, height, initial symptoms, other medical conditions, and medications were noted. Laboratory studies included liver function tests, serology for hepatitis B and C, serum copper and ceruloplasmin, immunoglobulins, nonspecific tissue autoantibodies, random serum glucose, and a fasting lipid profile. A random ethanol level was obtained in one patient.

Thirty-one patients underwent hepatic sonography. A percutaneous liver biopsy was obtained in 24 patients at the time of diagnosis. Follow-up data were available in 21 patients (mean follow-up, 1.5 years; range, 0.2–5.5 years). Statistical analysis was performed with Student's t-test, with P < 0.05 taken as statistically significant.

Back to Top | Article Outline

RESULTS

The median age at diagnosis was 12 years. Thirteen children were less than 11 years old. Most patients had initially reported nonspecific abdominal pain and were referred because of elevated serum aminotransferases or abnormal hepatic sonograms. Two patients had diabetes mellitus at diagnosis (one had been on insulin therapy for many years) and two had later development of insulin-dependent diabetes mellitus. Two brothers had Bardet–Biedl syndrome. One patient had a history of recurrent pancreatitis, one had pustular psoriasis (not treated with methotrexate or corticosteroids), and another had dermatomyositis that had been in remission for several years after anti-inflammatory treatment. Two children had some jaundice. Most children were in good health without other medical illness. No patient had a history of significant drug or medication use, and none used ethanol, according to careful history. None had received a blood transfusion. There was no family history of liver disease; only two patients had a family history of maturity-onset diabetes.

Most patients were obese: 30 of 36 patients had weight in higher than the 97th percentile for age and body weight, more than 120% of ideal weight for height. The mean weight was 147% of ideal body weight (mean weight 71 kg, range 32–138 kg). Sixteen patients had hepatomegaly with the liver edge palpable below the right costal margin, and one of these had hepatosplenomegaly. Thirteen patients had acanthosis nigricans (Fig. 1) observed around the nape of the neck and/or in the axillae; all but one of these were obese. None had typical cutaneous stigmata of chronic liver disease. One had erythema nodosum.

Fig. 1
Fig. 1
Image Tools
Figure 1
Figure 1
Image Tools

One or both serum aminotransferases were elevated at diagnosis in all but one patient. In 35 patients, the mean value for aspartate aminotransferase (AST) was 104 ± 16 U/l (mean ± SEM; normal range, <37 U/l); AST was normal or near normal in 4 patients (range, 26–523 U/l) and was not recorded in 1 patient. In 33 patients tested, alanine aminotransferase (ALT) was 179 ± 31 U/l (normal range, <40 U/l), and 3 patients had normal or near-normal ALT (range, 10–644 U/l). There was no correlation between the severity of obesity and the degree of serum aminotransferase elevation. Alkaline phosphatase was normal for age in all patients. One patient had mild, persistent unconjugated hyperbilirubinemia, and another had mild conjugated hyperbilirubinemia. Serum albumin and prothrombin time were normal in all patients. Serum copper and ceruloplasmin, measured in 34 of 36 patients, were normal. Nonspecific autoantibodies were tested in 21 patients: these were generally not detected. One patient had positive anti-smooth muscle (anti-actin) and anti-mitochondrial antibodies with normal total immunoglobulins; she was also heterozygous for α1-antitrypsin deficiency with phenotype PI MZ. Two patients, including the patient with dermatomyositis, had positive anti-nuclear antibodies. Hepatitis B serology obtained in 33 patients and anti-hepatitis C virus antibody (since availability of the test) in 21 patients were uniformly negative.

Fasting blood lipid profiles were determined in 20 patients and found to be abnormal in 18. Seven patients had hypercholesterolemia and 11 had increased serum triglycerides. Four patients had elevation of both. Fasting serum cholesterol level was 4.43 ± 0.91 mmol/l (m ± SD; normal, 3.20–4.40 mmol/l), and triglyceride was 2.05 ± 1.06 mmol/l (normal, 0.34–1.58 mmol/l). Except in the two patients with diabetes mellitus, random blood glucose was normal in all patients.

Hepatic sonograms were obtained in 31 of 36 patients. Twenty-four showed abnormalities including hepatomegaly and increased echogenicity suggestive of fatty infiltration.

Percutaneous liver biopsy was obtained in 24 patients. All patients had large-droplet steatosis. Most had inflammation (21, or 88%), and many had fibrosis (17, or 71%). There was inflammatory infiltration and fibrosis of varying severity (Fig. 2); the majority showed some degree of both inflammation and fibrosis. Fibrosis was moderately severe in seven patients, including two patients without inflammatory activity. One patient, in addition to these seven, had cirrhosis at diagnosis. None of the biopsy analyses showed any Mallory hyaline. One patient had capillarization of the sinusoids, observed in electron microscopic examination. A comparison of patients with no fibrosis and patients with severe fibrosis-cirrhosis is shown in Table 1. There were no statistically significant differences between these two groups of patients, although, on average, serum aminotransferases were higher in those with severe fibrosis. The patient with normal aminotransferases, however, had extensive fibrosis suggestive of early cirrhosis.

Table 1
Table 1
Image Tools
Fig. 2
Fig. 2
Image Tools

Follow-up data were available on 21 patients. The mean duration of follow-up was 18 months (range, 2–65 months). Six patients lost weight, and all had improvement in serum aminotransferase levels. In two of these patients AST and ALT completely normalized. Most patients had great difficulty losing weight. The AST and ALT levels fluctuated in those patients who were not able to achieve weight loss. One patient subsequently had severe hypothyroidism.

Back to Top | Article Outline

DISCUSSION

At the time this study began, whether chronic liver disease resembling alcoholic liver disease but occurring in nonalcoholics actually existed was controversial. Identifying this disease in children provided evidence that NASH as such actually existed. Finding a large number of such patients now suggests that it constitutes a significant problem in pediatric hepatology. The diagnosis of NASH rests in part on histologic findings, and we have accepted steatosis with evidence of necroinflammatory activity as the essential histologic criteria for this diagnosis. In many patients, fibrosis is also present. We believe that the term “nonalcoholic steatohepatitis” is unduly restrictive and prefer the term “nonalcoholic fatty liver disease.” However, the former terminology appears entrenched.

Despite many case series describing NASH in adults, there have been only a few reports of this disorder in children. Moran et al. (9) described three children with obesity and steatohepatitis. In a study of 299 obese children, Kinugasa et al. (10) found 36 (13%) to have abnormal aminotransferases. Liver biopsy was performed in 11 of these children, and results confirmed steatohepatitis. One patient had cirrhosis, along with maturity-onset diabetes mellitus and hyperlipidemia. Vajro et al. (11) reported a series of seven obese children with persistently elevated aminotransferases. These children may have had NASH; however, liver biopsy was obtained in only one patient, and the results showed steatohepatitis. Recently Baldridge et al. (12) reported a series of 14 children with idiopathic hepatic steatosis, identified by retrospective review of results of all liver biopsies performed in a tertiary-care pediatric hospital. All were obese, and most had abnormal AST and ALT. Two patients with test results showing normal liver function were discovered incidentally at laparotomy. In a screening study of 310 obese Japanese children Tazawa et al. (13) found that 24% had elevated serum ALT and 83% had a fatty fibrotic pattern observed on hepatic sonography. This same sonographic appearance was found in 19% of children studied who had normal ALT. Although elevated ALT and fatty liver by ultrasound testing appeared to be somewhat more common in older children with more severe obesity, no statistically significant differences were found in different age groups or with longer duration of obesity. An Italian screening study of 195 obese children found fatty liver by sonography in 55%, elevated serum AST or ALT in 20%, and both features in 15%(14).

In our prospective series of 36 children with NASH, findings were heterogeneous. Obesity was the most common clinical denominator. The average patient had a body weight approximately 50% higher than the ideal for height. Although the mean weight overall was 71 kg, of particular concern was the very obese younger child, specifically, 13 children less than 11 years of age whose average weight was 56 kg. However, six patients were not obese (childhood obesity defined as weight >120% of ideal weight for height). Typically, these children were tall with large bones and proportionately heavy body weight. Unlike some adult series, boys were more common than girls in this series of children. Male predominance was also noted in a Japanese survey of fatty liver detected by sonography in a cohort of 810 children between the ages of 4 and 12 years (16). Approximately half of all patients in the present study had hepatomegaly, and most had elevated serum aminotransferases. Other liver function test results were normal. Eighteen of 20 patients studied had hyperlipidemia; hypertriglyceridemia was more common and more severe.

Long-term follow-up in adults with NASH has shown that the disease is usually slowly progressive but can ultimately lead to cirrhosis in some patients (17,18). Other studies in adults have documented cirrhosis complicating NASH (3–5,8). In this series one patient, a 10 year-old girl with hepatosplenomegaly, had cirrhosis at diagnosis, the second case of cirrhosis in childhood NASH thus far reported. We speculate that some patients with “cryptogenic” cirrhosis occurring in adulthood have in fact had NASH since childhood.

One third of the children in this series had acanthosis nigricans. This association has not been described in other reports of children with NASH. Acanthosis nigricans may be subtle and can be missed without careful examination. Although acanthosis nigricans may occur in simple childhood obesity, it has also been shown to be a cutaneous marker of hyperinsulinemia (19,20). Keratinocytes have receptors for insulin, epidermal growth factor, and insulin-like growth factors. In hyperinsulinemia, circulating insulin, because of its structural similarity to insulin-like growth factor, binds to these receptors and stimulates cell division, leading to acanthosis. Richards et al. (21) reported 22 children with obesity, insulin resistance, acanthosis nigricans, and hyperandrogenemia. Obesity was always the first component of the syndrome to appear. Unfortunately, liver function tests were not obtained in this study.

Other features of the patients in this series suggest that abnormalities of carbohydrate metabolism may be important in the pathogenesis of NASH in children. Two of the patients in our series were known to have diabetes, and two other patients had development of diabetes later. A further patient had insulin-dependent diabetes that developed beyond the period of follow-up for this study at a time when his obesity had resolved and serum aminotransferases were normal. Two patients had Bardet–Biedl syndrome, an inherited syndrome characterized by retinal dystrophy, polydactyly, obesity, renal abnormalities, and male hypogenitalism. Non–insulin-dependent diabetes mellitus (NIDDM) frequently develops, with insulin resistance due to abnormal insulin receptor function (22). Alström syndrome is a rare condition, phenotypically similar to Bardet–Biedl, but distinguished by sensorineural deafness and absence of mental retardation (23). Obesity, hyperlipidemia, NIDDM, and acanthosis nigricans commonly occur in Alström syndrome. Hepatic involvement with mild steatosis, portal inflammation, and moderate fibrosis has been described in one patient (24). Yet another report of a rare syndrome in this Bardet–Biedl/Alström spectrum has been published (25), in which one patient had hepatic steatosis and both patients had decreased insulin receptor binding.

We speculate that abnormal carbohydrate metabolism plays an important role in the pathogenesis of childhood NASH. The high prevalence of acanthosis nigricans suggests that abnormalities in insulin metabolism may be important. Wanless et al. (26) reported hepatic steatosis in a unique subcapsular distribution in patients receiving continuous ambulatory dialysis who took insulin intraperitoneally. In hyperinsulinemia, free fatty acids are preferentially esterified into triglycerides. The resultant hepatic steatosis may incite an inflammatory response, leading to fibrosis. Hypertriglyceridemia was prominent in many of the children in this series. In a few patients tested, hyperinsulinemia was detected. Hyperinsulinemia is characteristic of puberty (27), but recent studies with standardized measurement of insulin levels indicate that obese preadolescent children already have hyperinsulinemia with insulin resistance affecting glucose and lipid metabolism (28). Racial differences, especially relating to decreased hepatic clearance of insulin, may be relevant (29). In a cohort of 228 obese Japanese children in a single prefecture, hyperinsulinemia was found in 32% and by regression analysis appeared to be the major contributor to occurrence of elevated serum ALT, used as a marker for NASH (30). A recent study in obese adolescents documented hyperinsulinemia as well as perturbations to insulin-like growth factor I and its binding proteins (31).

Although chronic hyperinsulinemia coupled with hepatocellular insulin resistance may be important for development of NASH, genetic differences unrelated to carbohydrate and lipid metabolism may account for the heterogeneity of clinical findings in NASH. These include heterozygosity for the HFE gene (32), α1-antitrypsin phenotype (33), adequacy of anti-oxidant defenses such as hepatic glutathione levels, and hepatic cytochrome P450. Hepatocellular concentrations of CYP2E1, an ethanol-inducible cytochrome P450 that activates some xenobiotics to toxic intermediates, were found to be increased in adults with NASH (34). Genes regulating body weight, such as the ob gene (35), may also play a role in the clinical diversity of NASH.

The long-term prognosis of children with NASH remains unknown. In adults, weight reduction can lead to improvement in serum aminotransferase levels (36,37). All six patients in our series who lost weight had a decrease in serum aminotransferases. Although the number was small, the trend was toward improvement. In the series of obese children reported by Vajro et al. (11) persistently elevated aminotransferases normalized in all seven patients after weight reduction, and liver size decreased in those with hepatomegaly. In the only patient in that series with steatohepatitis detected in liver biopsy at diagnosis, inflammation resolved after weight reduction. A more recent report of 38 obese children with fatty liver diagnosed by sonography documents that the liver sonogram improved or became normal in 26 (79%) of the 33 children who lost weight when assessed at 3 months of age. All children who had had elevated aminotransferases had normal aminotransferases at that time (15). Whether improvement in aminotransferase levels always parallels improvement in liver histology is not known, because serial liver biopsies are rarely performed. However, until results of long-term follow-up studies are available in children, it is prudent to recommend a weight loss program for these obese children. We use a combination of energy intake restriction, mainly by reducing fat intake, and increased energy expenditure through aerobic exercise. Other possible treatments include ursodeoxycholic acid (38) or antioxidants such as vitamin E (39), but such treatments have not been evaluated rigorously.

Back to Top | Article Outline

CONCLUSIONS

We conclude that NASH is not limited to adults. Indeed, it may be fairly common in children. It should certainly be suspected in obese children with mildly elevated serum aminotransferases. Moreover, it can occur in nonobese children. Sonography may suggest the diagnosis of massive fatty infiltration in the liver, but a liver biopsy is needed to assess the degree of chronic damage. Steatohepatitis can be found in other diseases affecting the liver. Wilson disease must be excluded. Chronic viral hepatitis and drug-induced hepatitis must also be considered in the differential diagnosis. Not necessarily a benign disorder, NASH can progress to cirrhosis during childhood and may account for some cases of cirrhosis in adults in whom the cause is obscure. Although there may be diverse causes for NASH in children, we believe that many children have specific and potentially definable disorders of hepatocellular metabolism.

Back to Top | Article Outline

Acknowledgments:

Dr. Rashid was supported by a Duncan Gordon Fellowship from the Hospital for Sick Children Foundation and a grant from Janssen Pharmaceutica. This report is dedicated to the memory of James L. Weber, MD, FRCPC, distinguished paediatrician and liver specialist, in appreciation of his mentorship.

Back to Top | Article Outline

REFERENCES

1. Ludwig J, Viggiano TR, McGill DB, Ott BJ. Nonalcoholic steatohepatitis: Mayo Clinic experience with a hitherto unnamed disease. Mayo Clin Proc 1980; 55:434–8.

2. Adler M, Schaffner F. Fatty liver hepatitis and cirrhosis in obese patients. Am J Med 1979; 67:811–6.

3. Diehl AM, Goodman Z, Ishak KG. Alcohol-like disease in nonalcoholics. Gastroenterology 1988; 95:1056–62.

4. Lee RG. Nonalcoholic steatohepatitis: A study of 49 patients. Hum Pathol 1989; 20:594–8.

5. Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: An autopsy study with analysis of risk factors. Hepatology 1990; 12:1106–10.

6. Schaffner F, Thaler H. Nonalcoholic fatty liver disease. Prog Liver Dis 1986; 8:283–6.

7. Alvarez SZ, Billote J, Ongkingco–Obillos C. Chronic hepatitis with fatty change. J Gastroenterol Hepatol 1990; 5:223–7.

8. Bacon BR, Farahwash MJ, Lanney CG, Neuschwander–Tetri BA. Nonalcoholic steatohepatitis: An expanded clinical entity. Gastroenterology 1994; 107:1103–9.

9. Moran JR, Ghishan FK, Halter SA, Greene HL. Steatohepatitis in obese children: A cause of chronic liver dysfunction. Am J Gastroenterol 1983; 78:374–7.

10. Kinugasa A, Tsunamoto K, Furukawa N, Sawada T, Kusunoki T, Shimada N. Fatty liver and its fibrous changes found in simple obesity of children. J Pediatr Gastroenterol Nutr 1984; 3:408–14.

11. Vajro P, Fontanella A, Perna C, Orso G, Tedesco M, De Vincenzo A. Persistent hypertransaminasemia resolving after weight reduction in obese children. J Pediatr 1994; 125:239–41.

12. Baldridge AD, Perez–Atayde AR, Grame–Cooke F, Higgins L, Lavine JE. Idiopathic steatohepatitis in childhood: A multicenter retrospective study. J Pediatr 1995; 127:700–4.

13. Tazawa Y, Noguchi H, Nishiomiya F, Takada G. Serum alanine aminotransferase activity in obese children. Acta Paediatr 1997; 86:238–41.

14. Bergomi A, Lughetti L, Corciulo N, et al. Italian multicenter study on liver damage in pediatric obesity (abstract). Int J Obes Relat Metab Disord 1998; 22(suppl 4):S22.

15. Franzese A, Vajro P, Argenziano A, et al. Liver involvement in obese children: Ultrasonography and liver enzyme levels at diagnosis and during follow-up in an Italian population. Dig Dis Sci 1997; 42:1428–32.

16. Tominaga K, Kurata JH, Chen YK, et al. Prevalence of fatty liver in Japanese children and relationship to obesity: An epidemiological ultrasonographic survey. Dig Dis Sci 1995; 40:2002–9.

17. Powell EE, Cooksley WGE, Hanson R, Searle J, Halliday JW, Powell LW. The natural history of nonalcoholic steatohepatitis: A follow-up study of forty-two patients for up to 21 years. Hepatology 1990; 11:74–80.

18. Propst A, Propst T, Judmaier G, Vogel W. Prognosis in nonalcoholic steatohepatitis. Gastroenterology 1995; 108:1607.

19. Brockow K, Steinkraus V, Rinninger F, Abeck D, Ring J. Acanthosis nigricans: A marker for hyperinsulinemia. Pediatr Dermatol 1995; 12:323–6.

20. Stuart CA, Gilkison CR, Smith MM, Bosma AM, Keenan BS, Nagamani M. Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr (Phila) 1998; 37:73–9.

21. Richards GE, Cavallo A, Meyer WJ, et al. Obesity, acanthosis nigricans, insulin resistance and hyperandrogenemia: Pediatric perspective and natural history. J Pediatr 1985; 107:893–7.

22. Green JS, Parfrey PS, Harnett JD, et al. The cardinal manifestations of Bardet–Biedl syndrome, a form of Laurence–Moon–Biedl syndrome. N Engl J Med 1989; 321:1002–9.

23. Dyer DS, Wilson ME, Small KW, Pai GS. Alström syndrome: A case misdiagnosed as Bardet–Biedl syndrome. J Pediatr Ophthalmol Strabismus 1994; 31:272–4.

24. Connolly MB, Jan JE, Couch RM, Wong LTK, Dimmick JE, Rigg JM. Hepatic dysfunction in Alström disease. Am J Med Genet 1991; 40:421–4.

25. Boor R, Herwig J, Schrezenmeir J, Pontz BF, Schönberger W. Familial insulin resistant diabetes associated with acanthosis nigricans, polycystic ovaries, hypogonadism, pigmentary retinopathy, labyrinthine deafness, and mental retardation. Am J Med Genet 1993; 45:649–53.

26. Wanless IR, Bargman JM, Oreopoulos DG, Vas SI. Subcapsular steatonecrosis in response to peritoneal insulin delivery: A clue to the pathogenesis of steatonecrosis in obesity. Mod Pathol 1989; 2:69–74.

27. Amiel SA, Caprio S, Sherwin RS, Plewe G, Haymond MW, Tamborlane WV. Insulin resistance of puberty: A defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab 1991; 72:277–82.

28. Caprio S, Bronson M, Sherwin RS, Rife F, Tamborlane WV. Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children. Diabetologia 1996; 39:1489–97.

29. Jiang X, Srinivasan SR, Radhakrishnamurthy B, Dalferes ER, Jr, Berenson GS. Racial (black-white) differences in insulin secretion and clearance in adolescents: The Bogalusa Heart Study. Pediatrics 1996; 97:357–60.

30. Kawasaki T, Hashimoto N, Kikuchi T, Takahashi H, Uchiyama M. The relationship between fatty liver and hyperinsulinemia in obese Japanese children. J Pediatr Gastroenterol Nutr 1997; 31:317–21.

31. Attia N, Tamborlane WV, Heptulla R, et al. The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity. J Clin Endocrinol Metab 1998; 83:1467–71.

32. George DK, Goldwurm S, MacDonald GA, et al. Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis. Gastroenterology 1998; 114:311–8.

33. Czaja AJ. Frequency and significance of phenotypes for alpha1-antitrypsin deficiency in type 1 autoimmune hepatitis. Dig Dis Sci 1998; 43:1725–31.

34. Weltman MD, Farrell GC, Hall P, Ingelman–Sundberg M, Liddle C. Hepatic cytochrome P450 2E1 is increased in patients with nonalcoholic steatohepatitis. Hepatology 1998; 27:128–33.

35. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372:425–32.

36. Palmer M, Schaffner F. Effect of weight reduction on hepatic abnormalities in overweight patients. Gastroenterology 1990; 99:1408–13.

37. Teli MR, James OF, Burt AD, Bennett MK, Day CP. The natural history of nonalcoholic fatty liver: A follow-up study. Hepatology 1995; 22:1714–9.

38. Laurin J, Lindor KD, Crippin JS, et al. Ursodeoxycholic acid or clofibrate in the treatment of non-alcohol-induced steatohepatitis: A pilot study. Hepatology 1996; 23:1464–7.

39. Lavine JE. Treatment of obesity-induced steatohepatitis with vitamin E (abstract). Gastroenterology 1998; 114:A1284–5.

Cited By:

This article has been cited 153 time(s).

Seminars in Liver Disease
Clinical features and natural history of nonalcoholic steatosis syndromes
Falck-Ytter, Y; Younossi, ZM; Marchesini, G; McCullough, AJ
Seminars in Liver Disease, 21(1): 17-26.

Journal of Gastroenterology and Hepatology
Non-alcoholic steatohepatitis: What is it, and why is it important in the Asia-Pacific region?
Farrell, GC
Journal of Gastroenterology and Hepatology, 18(2): 124-138.

Alimentary Pharmacology & Therapeutics
Non-alcoholic fatty liver disease
Alba, LM; Lindor, K
Alimentary Pharmacology & Therapeutics, 17(8): 977-986.
10.1046/j.0269-2813.2003.01493.x
CrossRef
Seminars in Liver Disease
Obesity and the liver: Developmental perspectives
Hoppin, AG
Seminars in Liver Disease, 24(4): 381-387.

Pediatric Gastroenterology 2004
Treatment of pediatric non-alcoholic steatohepatitis
Vajro, P; Broccoletti, T; Lenta, S; Migliaro, F
Pediatric Gastroenterology 2004, (): 199-205.

Postgraduate Medical Journal
Treatment of non-alcoholic fatty liver disease
Adams, LA; Angulo, P
Postgraduate Medical Journal, 82(): 315-322.
10.1136/pgmj.2005.042200
CrossRef
Pediatrics
Active healthy living: Prevention of childhood obesity through increased physical activity
McCambridge, TM; Bernhardt, DT; Brenner, JS; Congeni, JA; Gomez, JE; Gregory, AJM; Gregory, DB; Griesemer, BA; Reed, FE; Rice, SG; Small, EW; Stricker, PR; Frankowski, BL; Gereige, RS; Grant, LM; Hyman, D; Magalnick, H; Mears, CJ; Monteverdi, GJ; Murray, RD; Evan, GP; Roland, MM; Young, TL
Pediatrics, 117(5): 1834-1842.
10.1542/peds.2006-0472
CrossRef
Annals Academy of Medicine Singapore
Consequences of Childhood Obesity
Lee, YS
Annals Academy of Medicine Singapore, 38(1): 75-81.

Clinics in Liver Disease
Nonalcoholic Fatty Liver Disease: A Practical Approach to Evaluation and Management
Rafiq, N; Younossi, ZM
Clinics in Liver Disease, 13(2): 249-+.
10.1016/j.cld.2009.02.009
CrossRef
Hepatology International
Fatty liver disease in children: eat now pay later
De Bruyne, RML; Fitzpatrick, E; Dhawan, A
Hepatology International, 4(1): 375-385.
10.1007/s12072-009-9160-z
CrossRef
Hepatology
NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome
Chitturi, S; Abeygunasekera, S; Farrell, GC; Holmes-Walker, J; Hui, JM; Fung, C; Karim, R; Lin, R; Samarasinghe, D; Liddle, C; Weltman, M; George, J
Hepatology, 35(2): 373-379.
10.1053/jhep.2002.30692
CrossRef
Journal of Pediatric Endocrinology & Metabolism
Cirrhotic outcome in patients with craniopharyngioma
Altuntas, B; Ozcakar, B; Bideci, A; Cinaz, P
Journal of Pediatric Endocrinology & Metabolism, 15(7): 1057-1058.

American Journal of Gastroenterology
Obese children with steatohepatitis can develop cirrhosis in childhood
Molleston, JP; White, F; Teckman, J; Fitzgerald, JF
American Journal of Gastroenterology, 97(9): 2460-2462.
PII S0002-9270(02)04360-5
CrossRef
Clinical Pediatrics
Non-alcoholic fatty liver disease in a toddler
Fishbein, M; Cox, S
Clinical Pediatrics, 43(5): 483-485.

Hepatology
Design and validation of a histological scoring system for nonalcoholic fatty liver disease
Kleiner, DE; Brunt, EM; Van Natta, M; Behling, C; Contos, MJ; Cummings, OW; Ferrell, LD; Liu, YC; Torbenson, MS; Unalp-Arida, A; Yeh, M; McCullough, AJ; Sanyal, AJ
Hepatology, 41(6): 1313-1321.
10.1002/hep.20701
CrossRef
International Journal of Molecular Medicine
Evaluation of fatty acid metabolism-related gene expression in nonalcoholic fatty liver disease
Nakamuta, M; Kohjima, M; Morizono, S; Kotoh, K; Yoshimoto, T; Miyagi, I; Enjoji, M
International Journal of Molecular Medicine, 16(4): 631-635.

Medical Journal of Australia
Non-alcoholic steatohepatitis in children and adolescents
Manton, ND; Lipsett, J; Moore, DJ; Davidson, GP; Bourne, AJ; Couper, RTL
Medical Journal of Australia, 173(9): 476-479.

Seminars in Liver Disease
Etiopathogenesis of nonalcoholic steatohepatitis
Chitturi, S; Farrell, GC
Seminars in Liver Disease, 21(1): 27-41.

Pediatrics
Prevalence of fatty liver in children and adolescents
Schwimmer, JB; Deutsch, R; Kahen, T; Lavine, JE; Stanley, C; Behling, C
Pediatrics, 118(4): 1388-1393.
10.1542/peds.2006-1212
CrossRef
Journal of Diabetes and Its Complications
Diazoxide prevents abdominal adiposity and fatty liver in obese OLETF rats at prediabetic stage
Guo, ZY; Bu, SZ; Yu, YW; Ghatnekar, G; Wang, MJ; Chen, L; Bu, M; Yang, LH; Zhu, BG; Feng, ZK; Huang, Q
Journal of Diabetes and Its Complications, 22(1): 46-55.
10.1016/j.jdiacomp.2006.08.005
CrossRef
Journal of the American Academy of Nurse Practitioners
Fatty liver in adolescents on the US-Mexico border
Sharp, DB; Santos, LA; Cruz, ML
Journal of the American Academy of Nurse Practitioners, 21(4): 225-230.
10.1111/j.1745-7599.2009.00397.x
CrossRef
Best Practice & Research in Clinical Gastroenterology
Steatohepatitis in obese individuals
Youssef, WI; McCullough, AJ
Best Practice & Research in Clinical Gastroenterology, 16(5): 733-747.
10.1053/bega.2002.0334
CrossRef
Cleveland Clinic Journal of Medicine
Nonalcoholic fatty liver disease and the epidemic of obesity
Collantes, R; Ong, JP; Younossi, ZM
Cleveland Clinic Journal of Medicine, 71(8): 657-664.

Pediatric and Developmental Pathology
Viral diseases of the liver in children: Diagnostic and differential diagnostic considerations
White, FV; Dehner, LR
Pediatric and Developmental Pathology, 7(6): 552-567.
10.1007/s10024-004-8101-z
CrossRef
European Journal of Pediatrics
Prolonged hepatitis caused by cytomegalovirus and non-alcoholic steatohepatitis in 16-year-old obese boy
Kanda, T; Yokosuka, O; Suzuki, Y
European Journal of Pediatrics, 164(4): 212-215.
10.1007/s00431-004-1584-9
CrossRef
Canadian Medical Association Journal
Nonalcoholic fatty liver disease
Mager, D; Roberts, E
Canadian Medical Association Journal, 173(7): 735.
10.1503/cmaj.1050122
CrossRef
Hepatology
NAFLD in children: A prospective clinical-pathological study and effect of lifestyle advice
Nobili, V; Marcellini, M; Devito, R; Ciampalini, P; Piemonte, F; Comparcola, D; Sartorelli, MR; Angulo, P
Hepatology, 44(2): 458-465.
10.1002/hep.21262
CrossRef
Clinical Nutrition
Update on non-alcoholic fatty liver disease in children
Papandreou, D; Rousso, I; Mavromichalis, L
Clinical Nutrition, 26(4): 409-415.
10.1016/j.clnu.2007.02.002
CrossRef
Chest
Elevated serum aminotransferase levels in children at risk for obstructive sleep apnea
Kheirandish-Gozal, L; Capdevila, OS; Kheirandish, E; Gozal, D
Chest, 133(1): 92-99.
10.1378/chest.07-0773
CrossRef
Diabetes Research and Clinical Practice
Effect of a hypocaloric diet in transaminases in nonalcoholic fatty liver disease and obese patients, relation with insulin resistance
de Luis, DA; Aller, R; Izaola, O; Sagrado, MG; Conde, R; Gonzalez, JM
Diabetes Research and Clinical Practice, 79(1): 74-78.
10.1016/j.diabres.2007.07.015
CrossRef
Alimentary Pharmacology & Therapeutics
Review article: epidemiology, pathogenesis and potential treatments of paediatric non-alcoholic fatty liver disease
Barshop, NJ; Sirlin, CB; Schwimmer, JB; Lavine, JE
Alimentary Pharmacology & Therapeutics, 28(1): 13-24.
10.1111/j.1365-2036.2008.03703.x
CrossRef
Clinical Pediatrics
Age- and Ethnic-Specific Elevation of ALT Among Obese Children at Risk for Nonalcoholic Steatohepatitis (NASH): Implications for Screening
Leung, DH; Williams, K; Fraley, JK; Klish, WJ
Clinical Pediatrics, 48(1): 50-57.
10.1177/0009922808321678
CrossRef
Journal of Pediatrics
Vitamin E treatment of nonalcoholic steatohepatitis in children: A pilot study
Lavine, JE
Journal of Pediatrics, 136(6): 734-738.

Journal of Gastroenterology and Hepatology
Non-alcoholic fatty liver disease
Angulo, P; Lindor, KD
Journal of Gastroenterology and Hepatology, 17(): S186-S190.

Jama-Journal of the American Medical Association
Treatment of pediatric and adolescent obesity
Yanovski, JA; Yanovski, SZ
Jama-Journal of the American Medical Association, 289(): 1851-1853.

Gastroenterology
Mice heterozygous for a defect in mitochondrial trifunctional protein develop hepatic steatosis and insulin resistance
Ibdah, JA; Perlegas, P; Zhao, YW; Angdisen, J; Borgerink, H; Shadoan, MK; Wagner, JD; Matern, D; Rinaldo, P; Cline, JM
Gastroenterology, 128(5): 1381-1390.
10.1053/j.gastro.2005.02.001
CrossRef
Pediatrics
Health status and health care expenditures in a nationally representative sample: how do overweight and healthy-weight children compare?
Skinner, AC; Mayer, ML; Flower, K; Weinberger, M
Pediatrics, 121(2): E269-E277.
10.1542/peds.2007-0874
CrossRef
Digestive Diseases
Epidemiology of Non-Alcoholic Fatty Liver Disease
Bellentani, S; Scaglioni, F; Marino, M; Bedogni, G
Digestive Diseases, 28(1): 155-161.
10.1159/000282080
CrossRef
Hepatology
The histopathology of pediatric nonalcoholic fatty liver disease
Molleston, JP
Hepatology, 42(3): 536-538.
10.1002/hep.20873
CrossRef
Paediatrics & Child Health
Anthropometric and metabolic characteristics in children with clinically diagnosed nonalcoholic fatty liver disease
Mager, DR; Ling, SM; Roberts, EA
Paediatrics & Child Health, 13(2): 111-117.

Pediatric Diabetes
Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents
Nadeau, KJ; Ehlers, LB; Zeitler, PS; Love-Osborne, K
Pediatric Diabetes, 10(1): 5-13.
10.1111/j.1399-5448.2008.00450.x
CrossRef
New England Journal of Medicine
Medical progress - Nonalcoholic fatty liver disease
Angulo, P
New England Journal of Medicine, 346(): 1221-1231.

Canadian Journal of Gastroenterology
Nonalcoholic steatohepatitis: More than just being fat
Shaffer, EA
Canadian Journal of Gastroenterology, 16(5): 318-321.

International Journal of Obesity
Hepatic steatosis in obese Chinese children
Chan, DFY; Li, AM; Chu, WCW; Chan, MHM; Wong, EMC; Liu, EKH; Chan, IHS; Yin, J; Lam, CWK; Fok, TF; Nelson, EAS
International Journal of Obesity, 28(): 1257-1263.
10.1038/sj.ijo.0802734
CrossRef
Contemporary Clinical Trials
Treatment of nonalcoholic fatty liver disease in children: TONIC trial design
Lavine, JE; Schwimmer, JB; Molleston, JP; Scheimann, AO; Murray, KF; Abrams, SH; Rosenthal, P; Sanyal, AJ; Robuck, PR; Brunt, EM; Unalp, A; Tonascia, J
Contemporary Clinical Trials, 31(1): 62-70.
10.1016/j.cct.2009.09.001
CrossRef
Saudi Medical Journal
A stereological and histological analysis of spleen on obese female rats, fed with high fat diet
Altunkaynak, BZ; Ozbek, E; Altunkaynak, ME
Saudi Medical Journal, 28(3): 353-357.

Nutrition in Clinical Practice
Nonalcoholic fatty liver disease and obesity
Saadeh, S
Nutrition in Clinical Practice, 22(1): 1-10.

European Review for Medical and Pharmacological Sciences
Relationship of insulin resistance and adipocytokines on serum alanine aminotransferase in presurgical morbid obese patients
de Luis, DA; Aller, R; Izaola, O; Sagrado, MG; Conde, R; de la Fuente, B; Castrillon, JLP
European Review for Medical and Pharmacological Sciences, 13(6): 413-418.

Seminars in Liver Disease
Nonalcoholic steatohepatitis: Definition and pathology
Brunt, EM
Seminars in Liver Disease, 21(1): 3-16.

Best Practice & Research in Clinical Gastroenterology
Treatment of non-alcoholic steatohepatitis
Angulo, P; Lindor, KD
Best Practice & Research in Clinical Gastroenterology, 16(5): 797-810.
10.1053/bega.2002.0327
CrossRef
Clinical Pediatrics
Undetected hepatomegaly in obese children by primary care physicians: A pitfall in the diagnosis of pediatric nonalcoholic fatty liver disease
Fishbein, M; Mogren, J; Mogren, C; Cox, S; Jennings, R
Clinical Pediatrics, 44(2): 135-141.

Annals of Nutrition and Metabolism
Serum Leptin as a Predictor of Fatty Liver in 7-Year-Old Korean Children
Kim, IK; Kim, J; Kang, JH; Song, J
Annals of Nutrition and Metabolism, 53(2): 109-116.
10.1159/000165360
CrossRef
Pediatrics and Neonatology
Risk Factors for Liver Steatosis in Obese Children and Adolescents
Lin, YC; Chang, PF; Yeh, SJ; Liu, K; Chen, HC
Pediatrics and Neonatology, 51(3): 149-154.

Gut
Non-alcoholic steatohepatitis (NASH): where are we now and where are we going?
Day, CP
Gut, 50(5): 585-588.

Hepatology
Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C
Hui, JM; Kench, JG; Chitturi, S; Sud, A; Farrell, GC; Byth, K; Hall, P; Khan, M; George, J
Hepatology, 38(2): 420-427.
10.1053/jhep.2003.50320
CrossRef
Digestive and Liver Disease
Non-alcoholic fatty liver disease: a multicentre clinical study by the Italian Association for the Study of the Liver
Loguercio, C; De Simone, T; D'Auria, MV; de Sio, I; Federico, A; Tuccillo, C; Abbatecola, AM; Blanco, CD
Digestive and Liver Disease, 36(6): 398-405.
10.1016/j.dld.2004.01.022
CrossRef
Acta Endoscopica
Non-alcoholic fatty liver disease: from steatosis to cirrhosis
Leclercq, I; Sempoux, C
Acta Endoscopica, 36(3): 299-314.

Digestive Diseases and Sciences
Influence of insulin resistance and adipokines in the grade of steatosis of nonalcoholic fatty liver disease
Aller, R; de Luis, DA; Fernandez, L; Calle, F; Velayos, B; Olcoz, JL; Izaola, O; Sagrado, MG; Conde, R; Gonzalez, JM
Digestive Diseases and Sciences, 53(4): 1088-1092.
10.1007/s10620-007-9981-3
CrossRef
European Journal of Gastroenterology & Hepatology
Role of liver biopsy in the assessment of non-alcoholic fatty liver disease
Hubscher, SG
European Journal of Gastroenterology & Hepatology, 16(): 1107-1115.

Frontiers in Bioscience
Non-alcoholic fatty liver disease (NAFLD) in children
Roberts, EA
Frontiers in Bioscience, 10(): 2306-2318.

Acta Paediatrica
The association between non-alcoholic fatty liver disease and insulin resistance in 20 obese children and adolescents
Ciba, I; Widhalm, K
Acta Paediatrica, 96(1): 109-112.
10.1111/j.1651-2227.2007.00031.x
CrossRef
Przeglad Gastroenterologiczny
Nonalcoholic steatohepatitis
Deron, W; Krawczyk, K; Malecka-Panas, E
Przeglad Gastroenterologiczny, 3(2): 118-124.

Hepatology International
Advanced hepatic fibrosis and cirrhosis due to nonalcoholic fatty liver disease in Sri Lankan children: a preliminary report
Rajindrajith, S; Dassanayake, AS; Hewavisenthi, J; de Silva, HJ
Hepatology International, 2(2): 209-212.
10.1007/s12072-008-9062-5
CrossRef
Journal of Pediatrics
Metabolic, hormonal, oxidative, and inflammatory factors in pediatric obesity-related liver disease
Mandato, C; Lucariello, S; Licenziati, MR; Franzese, A; Spagnuolo, MI; Ficarella, R; Pacilio, M; Amitrano, M; Capuano, G; Meli, R; Vajro, P
Journal of Pediatrics, 147(1): 62-66.
10.1016/j.jpeds.2005.02.028
CrossRef
American Journal of Clinical Nutrition
Relation between elevated serum alanine aminotransferase and metabolic syndrome in Korean adolescents
Park, HS; Han, JH; Choi, KM; Kim, SM
American Journal of Clinical Nutrition, 82(5): 1046-1051.

American Journal of Roentgenology
The frequency of radiology reporting of childhood obesity
Strife, JL; Decanio, RE; Donnelly, LF; Johnson, ND
American Journal of Roentgenology, 186(3): 833-836.
10.2214/AJR.04.1563
CrossRef
Ageing Research Reviews
Lipotoxicity, overnutrition and energy metabolism in aging
Slawik, M; Vidal-Puig, AJ
Ageing Research Reviews, 5(2): 144-164.
10.1016/j.arr.2006.03.004
CrossRef
Nature Clinical Practice Gastroenterology & Hepatology
Evaluation and management of obesity-related nonalcoholic fatty liver disease
Nugent, C; Younossi, ZM
Nature Clinical Practice Gastroenterology & Hepatology, 4(8): 432-441.
10.1038/ncpgasthep0879
CrossRef
American Journal of Orthodontics and Dentofacial Orthopedics
Childhood obesity and skeletal maturation assessed with Fishman's hand-wrist analysis
Akridge, M; Hilgers, KK; Silveira, AM; Scarfe, W; Scheetz, JP; Kinane, DF
American Journal of Orthodontics and Dentofacial Orthopedics, 132(2): 185-190.
10.1016/j.ajodo.2005.12.034
CrossRef
World Journal of Pediatrics
Nonalcoholic fatty liver disease in children living in the obeseogenic society
A-Kader, HH
World Journal of Pediatrics, 5(4): 245-254.
10.1007/s12519-009-0048-8
CrossRef
Steatohepatitis (Nash and Ash)
Non-alcoholic steatohepatitis: grading and staging the histological lesions
Brunt, EM
Steatohepatitis (Nash and Ash), 121(): 26-33.

Best Practice & Research in Clinical Gastroenterology
Pathology of steatohepatitis
Brunt, EM; Tiniakos, DG
Best Practice & Research in Clinical Gastroenterology, 16(5): 691-707.
10.1053/bega.2002.0326
CrossRef
Expert Opinion on Pharmacotherapy
Current best treatment for nonalcoholic fatty liver disease
Angulo, P
Expert Opinion on Pharmacotherapy, 4(5): 611-623.

Journal of Clinical Investigation
Molecular mediators of hepatic steatosis and liver injury
Browning, JD; Horton, JD
Journal of Clinical Investigation, 114(2): 147-152.
10.1172/JCI200422422
CrossRef
Pediatrics
Influence of gender, race, and ethnicity on suspected fatty liver in obese adolescents
Schwimmer, JB; McGreal, N; Deutsch, R; Finegold, MJ; Lavine, JE
Pediatrics, 115(5): E561-E565.
10.1542/peds.2004-1832
CrossRef
Journal of Gastroenterology and Hepatology
Non-alcoholic steatohepatitis in the Asia-Pacific region: Future shock?
Chitturi, S; Farrell, GC; George, J
Journal of Gastroenterology and Hepatology, 19(4): 368-374.

Archives of Disease in Childhood
Fatty liver disease in children
Marion, AW; Baker, AJ; Dhawan, A
Archives of Disease in Childhood, 89(7): 648-652.
10.1136/adc.2003.029942
CrossRef
Revista Espanola De Enfermedades Digestivas
Non-alcoholic steatohepatitis: physiopathological, clinical and therapeutic implications
Perez-Aguilar, F; Benlloch, S; Berenguer, M; Beltran, B; Berenguer, J
Revista Espanola De Enfermedades Digestivas, 96(9): 628-648.

Current Science
Non-alcoholic fatty liver disease: an under-recognized cause with emerging importance
Das, SK; Mukherjee, S; Vasudevan, DM
Current Science, 90(5): 659-665.

Clinical Gastroenterology and Hepatology
Nonalcoholic fatty liver disease in children: A single center experience
A-Kader, HH; Henderson, J; Vanhoesen, K; Ghishan, F; Bhattacharyya, A
Clinical Gastroenterology and Hepatology, 6(7): 799-802.
10.1016/j.cgh.2008.03.001
CrossRef
International Journal of Food Sciences and Nutrition
Is there any association between high-density lipoprotein, insulin resistance and non-alcoholic fatty liver disease in obese children?
Papandreou, D; Rousso, I; Economou, I; Makedou, A; Moudiou, T; Malindretos, P; Pidonia, I; Pantoleon, A; Mavromichalis, I
International Journal of Food Sciences and Nutrition, 60(4): 312-318.
10.1080/09637480701780088
CrossRef
Acta Paediatrica
Nonalcoholic fatty liver disease in overweight children and adolescents
Sagi, R; Reif, S; Neuman, G; Webb, M; Phillip, M; Shalitin, S
Acta Paediatrica, 96(8): 1209-1213.
10.1111/j.1651-2227.2007.00399.x
CrossRef
Archives of Disease in Childhood
Lifestyle intervention in obese children with nonalcoholic fatty liver disease: 2-year follow-up study
Reinehr, T; Schmidt, C; Toschke, AM; Andler, W
Archives of Disease in Childhood, 94(6): 437-442.

Bmc Medicine
The pediatric NAFLD fibrosis index: a predictor of liver fibrosis in children with non-alcoholic fatty liver disease
Nobili, V; Alisi, A; Vania, A; Tiribelli, C; Pietrobattista, A; Bedogni, G
Bmc Medicine, 7(): -.
ARTN 21
CrossRef
Mayo Clinic Proceedings
Nonalcoholic steatohepatitis
Kumar, KS; Malet, PF
Mayo Clinic Proceedings, 75(7): 733-739.

Best Practice & Research in Clinical Gastroenterology
Steatohepatitis in children
Roberts, EA
Best Practice & Research in Clinical Gastroenterology, 16(5): 749-765.
10.1053/bega.2002.0331
CrossRef
Pediatrics
Prevention of pediatric overweight and obesity
Krebs, NF; Baker, RD; Greer, FR; Heyman, MB; Jaksic, T; Lifshitz, F; Jacobson, MS
Pediatrics, 112(2): 424-430.

Archives of Medical Research
Influence of insulin resistance and adipocytokines on elevated serum alanine aminotransferase in obese patients
de Luis, DA; Aller, R; Izaola, O; Sagrado, MG; Conde, R; Bellido, D
Archives of Medical Research, 39(1): 110-114.
10.1016/j.arcmed.2007.06.009
CrossRef
Seminars in Liver Disease
Hepatic, Cardiovascular, and Endocrine Outcomes of the Histological Subphenotypes of Nonalcoholic Fatty Liver Disease
Rubinstein, E; Lavine, JE; Schwimmer, JB
Seminars in Liver Disease, 28(4): 380-385.
10.1055/s-0028-1091982
CrossRef
Annals Academy of Medicine Singapore
The Risk Factors for Ultrasound-diagnosed Non-alcoholic Fatty Liver Disease Among Adolescents
Fu, CC; Chen, MC; Li, YM; Liu, TT; Wang, LY
Annals Academy of Medicine Singapore, 38(1): 15-21.

Hepatology
Nonalcoholic Steatohepatitis in Children: A Multicenter Clinicopathological Study
Carter-Kent, C; Yerian, LM; Brunt, EM; Angulo, P; Kohli, R; Ling, SC; Xanthakos, SA; Whitington, PF; Charatcharoenwitthaya, P; Yap, J; Lopez, R; McCullough, AJ; Feldstein, AE
Hepatology, 50(4): 1113-1120.
10.1002/hep.23133
CrossRef
Zeitschrift Fur Gastroenterologie
Histopathological Diagnose of Non-alcoholic and Alcoholic Fatty Liver Disease
Tannapfel, A; Denk, H; Dienes, HP; Langner, C; Schirmacher, P; Trauner, M; Flott-Rahmel, B
Zeitschrift Fur Gastroenterologie, 48(4): 486-498.
10.1055/5-0029-1245278
CrossRef
Acta Paediatrica
MRI and ultrasound for hepatic fat quantification: relationships to clinical and metabolic characteristics of pediatric nonalcoholic fatty liver disease
Pacifico, L; Celestre, M; Anania, C; Paolantonio, P; Chiesa, C; Laghi, A
Acta Paediatrica, 96(4): 542-547.
10.1111/j.1651-2227.2007.00186.x
CrossRef
Critical Reviews in Clinical Laboratory Sciences
Mechanisms of liver injury relevant to pediatric hepatology
Tanner, MS
Critical Reviews in Clinical Laboratory Sciences, 39(1): 1-61.

Hepatology
Nonalcoholic steatohepatitis: Summary of an AASLD Single Topic Conference
Neuschwander-Tetri, BA; Caldwell, SH
Hepatology, 37(5): 1202-1219.
10.1053/jhep.2003.50193
CrossRef
Qjm-An International Journal of Medicine
Non-alcoholic fatty liver: a common manifestation of a metabolic disorder
Malnick, SDH; Beergabel, M; Knobler, H
Qjm-An International Journal of Medicine, 96(): 699-709.
10.1093/qjmed/hcg120
CrossRef
Nash and Nutritional Therapy
Nonalcoholic fatty liver (NAFL): Overview
Caldwell, SH; Al-Osaimi, A; Chang, C; Davis, C; Hespenheide, EE; Krugner-Higby, L; Hylton, AI; Iezzoni, JC; Le, TH; Nakamoto, RK; Redick, J; Peterson, T
Nash and Nutritional Therapy, (): 1-43.

Turkish Journal of Pediatrics
Fatty liver in obese children: prevalence and correlation with anthropometric measurements and hyperlipidemia
Arslan, N; Buyukgebiz, B; Ozturk, Y; Cakmakci, H
Turkish Journal of Pediatrics, 47(1): 23-27.

Journal of Hepatology
Pediatric nonalcoholic fatty liver disease (NAFLD): A "growing" problem?
Roberts, EA
Journal of Hepatology, 46(6): 1133-1142.
10.1016/j.jhep.2007.03.003
CrossRef
Monatsschrift Kinderheilkunde
Non-alcoholic fatty liver disease (NAFLD). Non-alcoholic steatohepatitis - NASH
Keller, KM
Monatsschrift Kinderheilkunde, 152(8): 864-869.
10.1007/s0004-0995-z
CrossRef
Journal of Alternative and Complementary Medicine
The role of optimal healing environments in the management of childhood obesity
Freedman, MR; Stern, JS
Journal of Alternative and Complementary Medicine, 10(): S231-S244.

Hepatology
Histopathology of pediatric nonalcoholic fatty liver disease
Schwinnner, JB; Behling, C; Newbury, R; Deutsch, R; Nievergelt, C; Schork, NJ; Lavine, JE
Hepatology, 42(3): 641-649.
10.1002/hep.20842
CrossRef
Annual Review of Nutrition
Pediatric obesity and insulin resistance: Chronic disease risk and implications for treatment and prevention beyond body weight modification
Cruz, ML; Shaibi, GQ; Weigensberg, MJ; Spruijt-Metz, D; Ball, GDC; Goran, MI
Annual Review of Nutrition, 25(): 435-468.
10.1146/annurev.nutr.25.050304.092625
CrossRef
Indian Journal of Pediatrics
Non-alcoholic fatty liver disease and childhood obesity
Mathur, P; Das, MK; Arora, NK
Indian Journal of Pediatrics, 74(4): 401-407.

Digestive and Liver Disease
Relationship between nonalcoholic fatty liver disease prevalence and visceral fat in obese adolescents
Damaso, AR; do Prado, WL; de Piano, A; Tock, L; Caranti, DA; Lofrano, MC; Carnier, J; Cristofalo, DJM; Lederman, H; Tufik, S; de Mello, MT
Digestive and Liver Disease, 40(2): 132-139.
10.1016/j.dld.2007.09.009
CrossRef
Seminars in Liver Disease
Clinical aspects of fatty liver disease
Choudhury, J; Sanyal, AJ
Seminars in Liver Disease, 24(4): 349-362.

Seminars in Liver Disease
Effects of weight loss surgeries on liver disease
Blackburn, GL; Mun, EC
Seminars in Liver Disease, 24(4): 371-379.

World Journal of Gastroenterology
Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis
Iacobellis, A; Marcellini, M; Andriulli, A; Perri, F; Leandro, G; Devito, R; Nobili, V
World Journal of Gastroenterology, 12(): 7821-7825.

European Review for Medical and Pharmacological Sciences
Influence of insulin resistance in obese patients on elevated serum alanine aminotransferase
De Luis, DA; Aller, R; Izaola, O; Sagrado, MG; Conde, R; Hernandez, JMG
European Review for Medical and Pharmacological Sciences, 11(1): 21-25.

Harvard Review of Psychiatry
Pediatric obesity: Parallels with addiction and treatment recommendations
Acosta, MC; Manubay, J; Levin, FR
Harvard Review of Psychiatry, 16(2): 80-96.
10.1080/10673220802069764
CrossRef
Anales De Pediatria
Fatty liver disease, insulin resistance and adiponectin in an obese pediatric population
Lopez-Capape, M; Lopez-Bermejo, A; Blanco, MA; Orejas, EL; Blasco, JC; Castellanos, RB
Anales De Pediatria, 71(6): 495-501.
10.1016/j.anpedi.2009.07.037
CrossRef
Journal of Pediatrics
Pediatric Nonalcoholic Fatty Liver Disease in 2009
Alisi, A; Manco, M; Vania, A; Nobili, V
Journal of Pediatrics, 155(4): 469-474.
10.1016/j.jpeds.2009.06.014
CrossRef
Gut
The natural history of non-alcoholic fatty liver disease in children: a follow-up study for up to 20 years
Feldstein, AE; Charatcharoenwitthaya, P; Treeprasertsuk, S; Benson, JT; Enders, FB; Angulo, P
Gut, 58(): 1538-1544.
10.1136/gut.2008.171280
CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Obesity in children and adolescents worldwide: Current views and future directions - Working group report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Koletzko, B; Girardet, JP; Klish, W; Tabacco, O
Journal of Pediatric Gastroenterology and Nutrition, 35(): S205-S212.
10.1097/01.MPG.0000027010.95204.B9
CrossRef
Journal of Gastroenterology and Hepatology
Non-alcoholic fatty liver disease
Angulo, P; Lindor, KD
Journal of Gastroenterology and Hepatology, 17(): S186-S190.

Postgraduate Medical Journal
Managing liver failure
Kelly, DA
Postgraduate Medical Journal, 78(): 660-667.

Journal of Pediatrics
Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease
Schwimmer, JB; Deutsch, R; Rauch, JB; Behling, C; Newbury, R; Lavine, JE
Journal of Pediatrics, 143(4): 500-505.
10.1067/0022-3476(03)00325-1
CrossRef
Journal of Pediatric Endocrinology & Metabolism
Non-alcoholic fatty-liver disease in pediatric populations
Chavez-Tapia, NC; Sanchez-Avila, F; Vasquez-Fernandez, F; Torres-Machorro, A; Tellez-Avilal, FI; Uribe, M
Journal of Pediatric Endocrinology & Metabolism, 20(): 1059-1073.

Journal of Hepatology
Independent associations of alanine aminotransferase (ALT) levels with cardiovascular risk factor clustering in Chinese adolescents
Kong, APS; Choi, KC; Cockram, CS; Ho, CS; Chan, MHM; Ozaki, R; Wong, GWK; Ko, GTC; So, WY; Tong, PCY; Lam, CWK; Lau, JTF; Chow, FCC; Chan, JCN
Journal of Hepatology, 49(1): 115-122.
10.1016/j.jhep.2008.02.014
CrossRef
Liver International
Changing aetiology of liver dysfunction in the new generation of a hepatitis B and C-endemic area: cross-sectional studies on adolescents born in the first 10 years after universal hepatitis B vaccination
Kao, JT; Wang, JH; Hung, CH; Hu, TH; Lee, CM; Hung, SF; Lu, SN
Liver International, 28(9): 1298-1304.
10.1111/j.1478-3231.2008.01844.x
CrossRef
Surgery for Obesity and Related Diseases
Selection of electrical algorithms to treat obesity with intermittent vagal block using an implantable medical device
Camilleri, M; Toouli, J; Herrera, MF; Kow, L; Pantoja, JP; Billington, CJ; Tweden, KS; Wilson, RR; Moody, FG
Surgery for Obesity and Related Diseases, 5(2): 224-229.
10.1016/j.soard.2008.09.006
CrossRef
Archives of Pathology & Laboratory Medicine
Recent Developments in Liver Pathology
Yan, BC; Hart, JA
Archives of Pathology & Laboratory Medicine, 133(7): 1078-1086.

Seminars in Pediatric Surgery
Diagnosis and treatment of pediatric nonalcoholic steatohepatitis and the implications for bariatric surgery
Pardee, PE; Lavine, JE; Schwimmer, JB
Seminars in Pediatric Surgery, 18(3): 144-151.
10.1053/j.sempedsurg.2009.04.004
CrossRef
Best Practice & Research in Clinical Gastroenterology
Non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH): diagnosis and clinical course
Cortez-Pinto, H; Camilo, ME
Best Practice & Research in Clinical Gastroenterology, 18(6): 1089-1104.
10.1016/j.bpg.2004.06.021
CrossRef
Endocrinology and Metabolism Clinics of North America
Type 2 diabetes in children and youth
Kaufman, FR
Endocrinology and Metabolism Clinics of North America, 34(3): 659-+.
10.1016/j.ecl.2005.04.010
CrossRef
Pediatric Dentistry
Association between childhood obesity and smooth-surface caries in posterior teeth: A preliminary study
Hilgers, KK; Kinane, DE; Scheetz, JP
Pediatric Dentistry, 28(1): 23-28.

Pediatric Annals
Nonalcoholic fatty liver disease
Alfie, ME; Treem, WR
Pediatric Annals, 35(4): 290-+.

Seminars in Liver Disease
Definitive diagnosis and assessment of risk for nonalcoholic fatty liver disease in children and adolescents
Schwimmer, JB
Seminars in Liver Disease, 27(3): 312-318.
10.1055/s-2007-985075
CrossRef
Pediatric Diabetes
Comorbidities and microvascular complications of type 2 diabetes in children and adolescents
Dean, HJ; Sellers, EAC
Pediatric Diabetes, 8(): 35-41.

Histopathology
Histological assessment of non-alcoholic fatty liver disease
Hubscher, SG
Histopathology, 49(5): 450-465.
10.1111/j.1365-2559.2006.02416.x
CrossRef
World Journal of Gastroenterology
A rabbit model of pediatric nonalcoholic steatohepatitis: The role of adiponectin
Fu, JF; Fang, YL; Liang, L; Wang, CL; Hong, F; Dong, GP
World Journal of Gastroenterology, 15(8): 912-918.
10.3748/wjg.15.912
CrossRef
Journal of the American Academy of Nurse Practitioners
Parental disconnect between perceived and actual weight status of children: A metasynthesis of the current research
Doolen, J; Alpert, PT; Miller, SK
Journal of the American Academy of Nurse Practitioners, 21(3): 160-166.
10.1111/j.1745-7599.2008.00382.x
CrossRef
Metabolism-Clinical and Experimental
Association between leptin and transaminases: 1-year follow-up study in 180 overweight children
Reinehr, T; Schmidt, C; de Sousa, G; Andler, W
Metabolism-Clinical and Experimental, 58(4): 497-503.
10.1016/j.metabol.2008.11.007
CrossRef
Best Practice & Research Clinical Endocrinology & Metabolism
Obesity and liver disease
Scheen, AJ; Luyckx, FH
Best Practice & Research Clinical Endocrinology & Metabolism, 16(4): 703-716.
10.1053/beem.2002.0225
CrossRef
Pediatric Transplantation
Non-alcoholic steatohepatitis in children
Nanda, K
Pediatric Transplantation, 8(6): 613-618.
10.1111/j.1399-3046.2004.00241.x
CrossRef
Current Opinion in Pediatrics
Nonalcoholic steatohepatitis in a teenage girl with type 2 diabetes
Nadeau, K; Klingensmith, G; Sokol, RJ
Current Opinion in Pediatrics, 15(1): 127-131.

PDF (535)
Current Opinion in Pediatrics
The metabolic syndrome and nonalcoholic fatty liver disease in children
Sundaram, SS; Zeitler, P; Nadeau, K
Current Opinion in Pediatrics, 21(4): 529-535.
10.1097/MOP.0b013e32832cb16f
PDF (137) | CrossRef
Current Opinion in Pediatrics
Nonalcoholic fatty liver disease (NAFLD) in children
Sathya, P; Martin, S; Alvarez, F
Current Opinion in Pediatrics, 14(5): 593-600.

PDF (546)
Current Opinion in Pediatrics
Nonalcoholic fatty liver disease in the pediatric population: a review
Wieckowska, A; Feldstein, AE
Current Opinion in Pediatrics, 17(5): 636-641.

PDF (77)
European Journal of Gastroenterology & Hepatology
The role of nutritional profile in the orexigenic neuropeptide secretion in nonalcoholic fatty liver disease obese adolescents
Lederman, HM; Ernandes, R; de Mello, MT; Tufik, S; Dâmaso, A; de Piano, A; Tock, L; Carnier, J; Foschini, D; de Lima Sanches, P; Corrêa, FA; Oyama, LM; do Nascimento, CM
European Journal of Gastroenterology & Hepatology, 22(5): 557-563.
10.1097/MEG.0b013e3283346df2
PDF (189) | CrossRef
Journal of Clinical Gastroenterology
Update on Nonalcoholic Fatty Liver Disease
McCullough, AJ
Journal of Clinical Gastroenterology, 34(3): 255-262.

PDF (559)
Journal of Pediatric Gastroenterology and Nutrition
The Spectrum of Fatty Liver in Obese Children and The Relationship of Serum Aminotransferases to Severity of Steatosis
Fishbein, MH; Miner, M; Mogren, C; Chalekson, J
Journal of Pediatric Gastroenterology and Nutrition, 36(1): 54-61.

PDF (698)
Journal of Pediatric Gastroenterology and Nutrition
Vitamin E Treatment in Pediatric Obesity-Related Liver Disease: A Randomized Study
Vajro, P; Mandato, C; Franzese, A; Ciccimarra, E; Lucariello, S; Savoia, M; Capuano, G; Migliaro, F
Journal of Pediatric Gastroenterology and Nutrition, 38(1): 48-55.

PDF (389)
Journal of Pediatric Gastroenterology and Nutrition
Risk for Nonalcoholic Fatty Liver Disease in Hispanic Youth With BMI ≥95th Percentile
Quirós-Tejeira, RE; Rivera, CA; Ziba, TT; Mehta, N; Smith, CW; Butte, NF
Journal of Pediatric Gastroenterology and Nutrition, 44(2): 228-236.
10.1097/MPG.0b013e31802d4acc
PDF (153) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Overweight Children and Adolescents: A Clinical Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Baker, S; Barlow, S; Cochran, W; Fuchs, G; Klish, W; Krebs, N; Strauss, R; Tershakovec, A; Udall, J
Journal of Pediatric Gastroenterology and Nutrition, 40(5): 533-543.

PDF (110)
Journal of Pediatric Gastroenterology and Nutrition
Pharmacological Interventions for Nonalcoholic Fatty Liver Disease in Adults and in Children: A Systematic Review
Socha, P; Horvath, A; Vajro, P; Dziechciarz, P; Dhawan, A; Szajewska, H
Journal of Pediatric Gastroenterology and Nutrition, 48(5): 587-596.
10.1097/MPG.0b013e31818e04d1
PDF (1325) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Trends in Nonalcoholic Fatty Liver Disease–related Hospitalizations in US Children, Adolescents, and Young Adults
Punyanitya, M; Quinn, VP; Jacobsen, SJ; Koebnick, C; Getahun, D; Reynolds, K; Coleman, KJ; Porter, AH; Lawrence, JM
Journal of Pediatric Gastroenterology and Nutrition, 48(5): 597-603.
10.1097/MPG.0b013e318192d224
PDF (322) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Type 2 Diabetes in Children is Frequently Associated with Elevated Alanine Aminotransferase
Nadeau, KJ; Klingensmith, G; Zeitler, P
Journal of Pediatric Gastroenterology and Nutrition, 41(1): 94-98.

PDF (139)
Journal of Pediatric Gastroenterology and Nutrition
Alanine Amino Transferase Concentrations Are Linked to Folate Intakes and Methylenetetrahydrofolate Reductase Polymorphism in Obese Adolescent Girls
Frelut, M; Emery-Fillon, N; Guilland, J; Dao, HH; de Courcy, GP
Journal of Pediatric Gastroenterology and Nutrition, 43(2): 234-239.
10.1097/01.mpg.0000228110.83616.92
PDF (145) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Association of Raised Liver Transaminases With Physical Inactivity, Increased Waist–Hip Ratio, and Other Metabolic Morbidities in Severely Obese Children
Lee, YS; Kek, BL; Poh, LK; Saw, SM; Loke, KY
Journal of Pediatric Gastroenterology and Nutrition, 47(2): 172-178.
10.1097/MPG.0b013e318162a0e5
PDF (258) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
Acute Fatty Liver Disease after Suprasellar Tumor Resection
Evans, HM; Shaikh, MG; McKiernan, PJ; Hockley, AD; Crowne, EC; Kirk, JM; Kelly, DA
Journal of Pediatric Gastroenterology and Nutrition, 39(3): 288-291.

PDF (318)
Journal of Pediatric Gastroenterology and Nutrition
Pediatric Nonalcoholic Fatty Liver Disease: A Critical Appraisal of Current Data and Implications for Future Research
Patton, HM; Sirlin, C; Behling, C; Middleton, M; Schwimmer, JB; Lavine, JE
Journal of Pediatric Gastroenterology and Nutrition, 43(4): 413-427.
10.1097/01.mpg.0000239995.58388.56
PDF (4432) | CrossRef
Journal of Pediatric Gastroenterology and Nutrition
MRI in Identifying Hepatic Steatosis in Obese Children and Relation to Ultrasonography and Metabolic Findings
Pozzato, C; Radaelli, G; Dall'Asta, C; Verduci, E; Villa, A; Villa, C; Scaglioni, S; Riva, E; Pontiroli, AE; Cornalba, G; Giovannini, M
Journal of Pediatric Gastroenterology and Nutrition, 47(4): 493-499.
10.1097/MPG.0b013e31817b6e10
PDF (345) | CrossRef
Back to Top | Article Outline
Keywords:

Acanthosis nigricans; Fatty liver; Fibrosis; Obesity; Steatohepatitis

© 2000 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Images

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.

Connect With Us

 

 

Twitter

twitter.com/JPGNonline

 

Visit JPGN.org on your smartphone. Scan this code (QR reader app required) with your phone and be taken directly to the site.