Nonalcoholic steatohepatitis and insulin resistance in children

Table 1 Differences in characteristics of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis between adults and children

	Pediatric-type NASH	Adult-type NASH
Classification by Schwimmer et al[21]	Type 2	Type 1
Incidence	Frequent	Rare
Steatosis	Strong	Weak
	Starting in periportal zone (acinar zone 1)	Starting in perivenular zone (acinar zone 3)
Inflammatory cell infiltration	Portal area	Centrolobular area
Hepatocyte ballooning	None	Prevalent
Fibrosis	None or only in periportal zone (acinar zone 1)	Prevalent in perisinusoidal or perivenular zone (acinar zone 3)
Liver cirrhosis	Present	Present
Epidemiology	More common in overweight, colored race (Hispanic: 73%; Asian: 12%), boys > girls	Hispanic: 41%, White, non-Hispanic: 53%, girls > boys
Ratio in pediatric NAFLD (overlap 16%) by Schwimmer et al[21]	51%	17%
Ratio in pediatric NAFLD (overlap 50%) by Takahashi et al[20]	21%	Not reported

NASH: Nonalcoholic steatohepatitis; NAFLD: Nonalcoholic fatty liver disease.

Table 2 Reports in the literature regarding insulin resistance in pediatric nonalcoholic steatohepatitis /nonalcoholic fatty liver disease

Ref.	Study population and sample size	Age (yr)	Method of diagnosis	Insulin resistance
Santoro et al[32]	229 obese children, including 12 cases of liver biopsy-proven NASH	12.8 ± 2.9	MRI and liver biopsy	No significant correlation between MRI-measured steatosis and whole body insulin sensitivity index
Fitzpatrick et al[33]	40 liver biopsy-proven NAFLD	10-16	Liver biopsy	68% showed insulin resistance. HOMA-R values did not correlate with NAS
Nobili et al[34]	30 NAFLD patients (11:19; without:with steatohepatitis)	8-14	Liver biopsy	HOMA-R values and insulin sensitivity indices did not correlate with steatohepatitis
El-Koofy et al[35]	18 patients with normal histology, 8 simple steatosis patients, and 7 NASH patients	2-15	Liver biopsy	HOMA-R values significantly differed between patients with normal histology and those with steatosis/NASH, and significantly correlated with grading based on US
Patton et al[36]	88 NAFLD patients	6-17	Liver biopsy	NASH vs not NASH: HOMA-R OR = 1.283 (P-value = 0.004) and QUICKI OR = 0.786 (P-value < 0.001)
Ko et al[37]	80 NAFLD patients (18 simple steatosis, 27 type 1 NASH, and 35 type 2 NASH)	10.4 ± 3.9, 12.6 ± 2.4, 12.3 ± 2.3, respectively	Liver biopsy	No differences in HOMA-R values between type 1 and type 2 NASH; HOMA-R values did not correlate with NAS
Manco et al[38]	82 NAFLD patients	3-18	Liver biopsy	HOMA-R and QUICKI values, and HOMA-beta secretion did not correlate with NAS
Nobili et al[39]	72 NAFLD patients	9-18	Liver biopsy	HOMA-R values did not correlate with NAS, steatosis, inflammation, ballooning, or fibrosis
Chan et al[40]	65 fatty liver patients	9.5-14	Liver biopsy and US	HOMA-R and QUICKI values correlated with severity of fatty liver evaluated by US. Higher insulin resistance significantly correlated with fatty liver severity only in male subjects with NASH

NAS: NAFLD activity score; US: Ultrasound; QUICKI: Quantitative insulin sensitivity check index; HOMA-R: Homeostasis model assessment as an index of insulin resistance; NASH: Nonalcoholic steatohepatitis; NAFLD: Nonalcoholic fatty liver disease; MRI: Magnetic resonance imaging.

Table 3 Pathology and homeostasis model assessment as an index of insulin resistance values of pediatric nonalcoholic steatohepatitis patients treated in our department

Patient number	Age (yr)	Matteoni’s criteria	NAS	Brunt’s grading	Brunt’s staging	HOMA-R
1	6	4	7	3	2	40.6
2	9	4	4	2	2	2.72
3	11	4	6	2	3	4.60
4	11	4	6	2	3	5.83
5	12	4	7	3	3	3.65
6	13	4	5	2	3	58.5
7	14	4	5	2	2	20.0
8	14	4	7	2	2	3.36
9	14	4	8	2	3	3.95
10	14	4	3	1	3	67.7
11	15	4	6	2	2	4.89
12	15	4	7	2	3	17.3
13	16	3	7	2	1	19.4

NAS: Nonalcoholic fatty liver disease activity score; HOMA-R: Homeostasis model assessment as an index of insulin resistance.

Table 4 Efficacy of main drugs against nonalcoholic steatohepatitis/nonalcoholic fatty liver disease symptoms

	Drug	Efficacy
Insulin-sensitizing agent	1Metformin[47]	Controversial (effective but no more effective than improvement of lifestyle)
Antioxidants	1Vitamin E[47]	Significant improvements in NASH and NAFLD activity scores
	Vitamin C	No changes in ALT levels or liver inflammation; fibrosis was controlled intentionally
Liver-supporting drugs	Ursodeoxycholic acid	No improvements in serum transaminase and fat levels evaluated by US
	Phosphatidylcholine	No improvement in serum ALT level; improvements in liver echo intensity and insulin resistance
	1Taurine[48]	Decreased serum ALT levels and increased liver CT values in 7 children
Cholesterol-lowering agents	HMG-CoA reductase inhibitor (atorvastatin)	Decrease in serum ALT levels and improvement in liver pathology
	Probucol	Decrease in serum ALT levels

¹Indicate drugs reported for children. US: Ultrasound; NASH: Nonalcoholic steatohepatitis; NAFLD: Nonalcoholic fatty liver disease; CT: Computed tomography; HMG-CoA: 3-hydroxy-3-methylglutaryl-coenzyme A; ALT: Alanine aminotransferase.