Histopathology of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Table 1 Histopathological abnormalities in nonalcoholic steatohepatitis[7]

Histopathological abnormalities
Necessary components
Steatosis (macro > micro; accentuated in zone 3)
Lobular inflammation (mixed, mild; scattered polymorphonuclear leukocytes as well as mononuclear cells)
Hepatocellular ballooning (most apparent near steatotic liver cells, typically in zone 3)
Usually present; but not necessary for diagnosis
Perisinusoidal fibrosis (in zone 3)
Hepatocellular glycogenated nuclei (in zone 1)
Lipogranulomas (in the lobules; of varying size, but usually small)
Acidophil bodies or periodic acid-Schiff-stained Kupffer cells
Fat cysts
May be present but not necessary for diagnosis
Mallory-Denk bodies (in ballooned hepatocytes)
Iron deposition (in hepatocytes or sinusoidal lining cells)
Megamitochondria (in hepatocytes)

Table 2 Grading and staging system for nonalcoholic steatohepatitis[13]

Grading and staging
Grading
Grade 1 (mild)	Steatosis: up to 66%
	Ballooning: occasional in zone 3
	Intralobular inflammation: scattered polymorphs ± lymphocytes
	Portal inflammation: no or mild
Grade 2 (moderate)	Steatosis: any degree
	Ballooning: obvious, predominantly zone 3
	Intralobular inflammation: polymorphs and chronic inflammation noted
	Portal inflammation: mild to moderate
Grade 3 (severe)	Steatosis: panacinar
	Ballooning: ballooning and disarray obvious, predominantly in zone 3
	Intralobular inflammation: scattered polymorphs ± mild chronic inflammation
	Portal inflammation: mild or moderate
Staging
Stage 1	Zone 3 perisinusoidal/pericellular fibrosis, focal or extensive
Stage 2	Zone 3 perisinusoidal/pericellular fibrosis + focal or extensive periportal fibrosis
Stage 3	Zone 3 perisinusoidal/pericellular fibrosis + portal fibrosis + bridging fibrosis
Stage 4	Cirrhosis

Table 3 Components of nonalcoholic fatty liver disease activity score[14]

Item	Definition	Score
Steatosis	< 5%	0
	5%-33%	1
	> 33%-66%	2
	> 66%	3
Lobular inflammation	No foci	0
	< 2 foci per 200 × field	1
	2-4 foci per 200 × field	2
	> 4 foci per 200 × field	3
Ballooning	None	0
	Few balloon cells	1
	Many cells/prominent ballooning	2

Table 4 Histopathological features of pediatric and adult nonalcoholic fatty liver disease cases n (%)

Item	Score/code	Pediatric (n = 34)	Adult (n = 23)
Steatosis
Grade	0 (< 5%)	0 (0)	0 (0)
	1 (5%-33%)	10 (29)	7 (30)
	2 (> 33%-66%)	15 (45)	14 (61)
	3 (> 66%)	9 (26)	2 (9)
Location	Zone 3	12 (35)	14 (61)
	Zone 1	0 (0)	0 (0)
	Azonal	5 (15)	4 (17)
	Panacinar	17 (50)	5 (22)
Fibrosis
Perisinusoidal1	0 (none)	19 (56)	6 (26)
	1 (mild)	10 (29)	8 (35)
	2 (moderate)	5 (15)	9 (39)
Periportal	0 (none)	18 (53)	13 (57)
	1 (mild)	13 (38)	6 (26)
	2 (moderate)	2 (6)	2 (9)
	3 (severe)	1 (3)	1 (4)
	4 (cirrhosis)	0 (0)	1 (4)
Stage	0 (none)	12 (34)	6 (26)
	1A (mild, zone 3, perisinusoidal)	4 (12)	5 (22)
	1B (moderate, zone 3, perisinusoidal)	2 (6)	2 (9)
	1C (periportal)	7 (21)	0 (0)
	2 (perisinusoidal + periportal)	6 (18)	5 (22)
	3 (bridging fibrosis)	3 (9)	4 (17)
	4 (cirrhosis)	0 (0)	1 (4)
Inflammation
Lobular	0 (no foci)	7 (21)	2 (9)
	1 (< 2 foci per 200 × field)	18 (52)	13 (56)
	2 (2-4 foci per 200 × field)	7 (21)	6 (26)
	3 (> 4 foci per 200 × field)	2 (6)	2 (9)
Portal	0 (none)	11 (32)	10 (43)
	1 (mild)	14 (42)	11 (48)
	2 (moderate)	9 (26)	2 (9)
	3 (severe)	0 (0)	0 (0)
Ballooning	0 (none)	16 (47)	6 (26)
	1 (few)	10 (29)	13 (57)
	2 (many/prominent)	8 (24)	4 (17)
Diagnosis	Not NASH	8 (24)	4 (17)
	Borderline zone 1 NASH	7 (21)	2 (9)
	Borderline zone 3 NASH	5 (15)	5 (22)
	Definite NASH	14 (40)	12 (52)

¹Perisinusoidal fibrosis was significantly milder in pediatric cases than in adult cases. Borderline zone 1 NASH corresponds to type 2 NASH[52]. NASH: Nonalcoholic steatohepatitis.