Pathology of alcoholic liver disease, can it be differentiated from nonalcoholic steatohepatitis?

Table 1 Histopathologic abnormalities in nonalcoholic steatohepatitis[4]

Necessary components

Steatosis, macro > micro; accentuated in Zone 3

Lobular inflammation, mild; scattered polymorphonuclear leukocytes as well as mononuclear cells

Ballooning of hepatocytes; most apparent near steatotic liver cells, in Zone 3

Usually present but not necessary

Zone 3 perisinusoidal fibrosis

Zone 1 hepatocellular glycogenated nuclei

Lipogranulomas in the lobules; usually small

Occasional acidophil bodies or periodic acid Schiff-stained Kupffer cells

Fat cysts

May be present, not necessary

Mallory’s hyaline in ballooned hepatocytes - usually Zone 3; typically poorly formed, may require immunostaining for ubiquitin, p62 or CK 7, 18, 19 to confirm

Hepatocellular iron, usually grade 1

Megamitochondria in hepatocytes

Table 2 Grading system for alcoholic liver disease[6]

Grade 0-11

Steatosis

0-3 as in NIDDK NASH CRN

Lobular inflammation

0-3 as in NIDDK NASH CRN

Cell death

0 none

1 focal apoptosis

2 many acidophil bodies

3 confluent necrosis

Ballooning

0-2 as in NIDDK NASH CRN

Fibrosis stages 0-6

Stage 1 mild Zone 3 pericellular and/or perivenular

Stage 2 marked Zone 3 fibrosis in most zones 3

Stage 3 fibrous linkage HV to septa

Stage 4 fibrous linkage HV, PT and septa

Stage 5 incomplete or probable cirrhosis

Stage 6 definite cirrhosis

NASH CRN: Nonalcoholic Steatohepatitis Research Network; NIDDK: National Institute of Diabetes and Digestive and Kidney Diseases; HV: Hepatic venule; PT: Portal tracts.

Table 3 Non-alcoholic fatty liver disease activity score as defined by nonalcoholic steatohepatitis clinical research network[16]

Item	Definition	Score
Steatosis (grade)	Low to medium power evaluation of parenchymal involvement by steatosis
	< 5%	0
	5%-33%	1
	> 33%-66%	2
	> 66%	3
Lobular Inflammation	Overall assessment of all inflammatory foci
	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
Fibrosis stage
	None	0
	Perisinusoidal or periportal	1
	Mild, Zone 3, perisinusoidal	1A
	Moderate, Zone 3, perisinusoidal	1B
	Portal/periportal	1C
	Perisinusoidal and portal/periportal	2
	Bridging fibrosis	3
	Cirrhosis	4

Table 4 Differences in histologic features of nonalcoholic steatohepatitis and alcoholic liver disease

NAFLD (NASH)	ALD
Usually mild disease	Varying severity
Bridging necrosis rare	Bridging necrosis common
Poorly formed MH	Well formed MH
-/rare	Sclerosing hyaline necrosis
-/rare	Phlebosclerosis
-/rare	Canalicular cholestasis
Not described	Foamy degeneration
Nuclear vacuolation - more common	Nuclear vacuolation - less common
Presence of Iron/hemosiderin is less frequent	Presence of Iron/hemosiderin is more frequent
Ductular reaction is less frequent/prominent	Ductular reaction is more frequent/prominent
Fibrosis/cirrhosis - less common	Fibrosis/cirrhosis - more common

NAFLD: Non-alcoholic fatty liver disease; ALD: Alcoholic liver disease; NASH: Nonalcoholic steatohepatitis; MH: Mallory hyaline.