Non-alcoholic fatty liver disease: An expanded review

Table 1 Non-alcoholic fatty liver disease activity scoring system[121]

Steatosis, grade (0-3)
< 5%	0
5%-33%	1
34%-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
Hepatocyte 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 2 Steatosis, activity, and fibrosis scoring system[91,124]

Steatosis score (S): Assessed the quantities of large or medium-sized lipid droplets (0-3)

S0: < 5%

S1: 5%-33%

S2: 34%-66%

S3: > 67%

Activity grade (0-4): Sum of scores for ballooning and lobular inflammation

A1: Mild activity

A2: Moderate activity

A3 and A4: Severe activity

Hepatocyte ballooning (0-2)

0: None

1: Foci of hepatocytes with rounded shape, pale or reticulated cytoplasm

2: Foci of hepatocytes with rounded shape, pale or reticulated cytoplasm and enlargement (> 2 × normal size)

Lobular inflammation (0-2)

0: None

1: < 2 foci per 20 × field

2: > 2 foci per 20 × field

Fibrosis stage (F)

F0: No relevant fibrosis

F1: 1a - mild zone 3 perisinusoidal fibrosis

1b - moderate zone 3 perisinusoidal fibrosis

1c - portal fibrosis

F2: Zone 3 perisinusoidal fibrosis with periportal fibrosis

F3: Bridging fibrosis

F4: Cirrhosis

Table 3 Brunt grading and staging of nonalcoholic steatohepatitis[96]

Grading	Staging
Mild (Grade 1)	Stage 1
Steatosis (mostly macrovesicular)	Zone 3 perisinusoidal/pericellular fibrosis (focal or extensive)
Involves up to 66% of biopsy
Occasional ballooned zone 3 hepatocytes	Stage 2
Scattered rare intra-acinar neutrophils with/without associated lymphocytes	Zone 3 perisinusoidal/pericellular fibrosis with associated focal or extensive periportal fibrosis
No/mild portal chronic inflammation
Moderate (Grade 2)
Steatosis-any degree
Ballooning hepatocytes-zone 3
Intra-acinar neutrophils-may be associated with zone 3 pericellular fibrosis	Stage 3
Portal and intra-acinar chronic inflammation	Zone 3 perisinusoidal/pericellular fibrosis and portal fibrosis with associated focal or extensive bridging fibrosis
Severe (Grade 3)
Panacinar steatosis
Ballooning-zone 3
Intra-acinar inflammation with scattered neutrophils	Stage 4
Neutrophils associated with ballooned hepatocytes with/without chronic inflammation	Cirrhosis
Chronic portal inflammation-mild or moderate

Table 4 Histologic comparison of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and alcoholic liver disease[129]

Characteristic	NAFLD and NASH	Alcoholic liver disease
Disease severity	Mild	Varying
Mallory-Denk body	Poorly formed	Well formed
Glycogenated nuclei	Common	Less common
Ductular proliferation	Less prominent	More prominent
Fibrosis/cirrhosis	Less common	More common
Sclerosing hyaline necrosis	None/rare	Present
Phlebosclerosis	None/rare	Present
Canalicular cholestasis	None/rare	Present
Foamy degeneration	None/rare	Present

NASH: Non-alcoholic steatohepatitis; NAFLD: Non-alcoholic fatty liver disease.

Table 5 Factors to be assessed in the evaluation of a patient with suspected non-alcoholic fatty liver disease[32]

Factor

Personal and family history of diabetes, hypertension and CVD

Alcohol use: < 20 g/d (women), < 30 g/d (man)

Waist circumference, BMI, change in body weight

Hepatitis B/C infection

Liver enzymes

History of steatosis-associated drug use

Fast blood glucose, hemoglobin A1c

Serum total and HDL-cholesterol, triacylglycerol, uric acid

Undertaken due to clinical suspicion

Ultrasound

Hemochromatosis testing: Ferritin and transferrin saturation

Celiac disease: IgA and tissue transglutaminase

Thyroid disease: TSH level (T3/T4)

Polycystic ovarian syndrome

Wilson’s disease: Ceruloplasmin

Autoimmune disease: ANA, AMA, SMA

Alpha-1 antitrypsin deficiency: Alpha-1-antitrypsin level

ANA: Anti-nuclear antibody; AMA: Anti-mitochondrial antibody; SMA: Anti-smooth muscle antibody; CVD: Cardiovascular disease; BMI: Body mass index; HDL: High density lipoprotein; TSH: Thyroid stimulating hormone.