Copyright ©The Author(s) 2017.
World J Hepatol. Jun 8, 2017; 9(16): 715-732
Published online Jun 8, 2017. doi: 10.4254/wjh.v9.i16.715
Table 1 Non-alcoholic fatty liver disease activity scoring system[121]
Steatosis, grade (0-3)
< 5%0
> 66%3
Lobular inflammation
No foci0
< 2 foci per 200 × field1
2-4 foci per 200 × field2
> 4 foci per 200 × field3
Hepatocyte ballooning
Few balloon cells1
Many cells/prominent ballooning2
Fibrosis stage
Perisinusoidal or periportal1
Mild, zone 3, perisinusoidal1A
Moderate, zone 3, perisinusoidal1B
Perisinusoidal and portal/periportal2
Bridging fibrosis3
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]
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 hepatocytesStage 2
Scattered rare intra-acinar neutrophils with/without associated lymphocytesZone 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 fibrosisStage 3
Portal and intra-acinar chronic inflammationZone 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 neutrophilsStage 4
Neutrophils associated with ballooned hepatocytes with/without chronic inflammationCirrhosis
Chronic portal inflammation-mild or moderate
Table 4 Histologic comparison of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and alcoholic liver disease[129]
CharacteristicNAFLD and NASHAlcoholic liver disease
Disease severityMildVarying
Mallory-Denk bodyPoorly formedWell formed
Glycogenated nucleiCommonLess common
Ductular proliferationLess prominentMore prominent
Fibrosis/cirrhosisLess commonMore common
Sclerosing hyaline necrosisNone/rarePresent
Canalicular cholestasisNone/rarePresent
Foamy degenerationNone/rarePresent
Table 5 Factors to be assessed in the evaluation of a patient with suspected non-alcoholic fatty liver disease[32]
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
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