NAFLD Histology and Score

Yaniv Zohar, M.D. Ph.D

Dept. of Pathology

RAMBAM – Health Care Campus

November 2016

Nonalcoholic Liver Disease (NAFLD)

• Most common type of chronic liver disease in majority of developed countries

• A spectrum of disorders including simple steatosis, nonalcoholic steatohepatitis (NASH) and cirrhosis

• While simple steatosis is benign and stable, NASH is a more aggressive form of NAFLD progressing to cirrhosis

Morphological Features of NAFLD

• No single histological feature for diagnosis of the disease

• Diagnosis of NAFLD/NASH is based on several morphological changes:

– Macrovesicular steatosis

– Lobular inflammation

– Hepatocellular ballooning

– Fibrosis

– Miscellaneous findings (Mallory-Denk bodies, portal inflammation, lipogranulomas etc.)

• None of the above changes is specific to NASH

Liver biopsy – Yes or No?

• Liver biopsy remains the gold standard for characterizing liver histology in patients with NAFLD

• Non-invasive methods are limited in assessing:

– Degree of steatosis

– Degree of inflammation

– Degree of fibrosis

– Other liver diseases

• Biopsy is recommended for pts. at high risk of steatohepatitis, advanced fibrosis, or with concurrent chronic liver disease of other etiology

Milestones in NASH Diagnosis

Ikura Y., World J Hepatol. 2014 Dec 27;6(12):894-900

Milestones in NASH Diagnosis

Am J Gastroenterol. 1999 Sep;94(9):2467-74.

Milestones in NASH Diagnosis

Hepatology. 2005 Jun;41(6):1313-21.

NAFLD Activity Score (NAS)

• A histological scoring system addressing the full spectrum of NAFLD

• Initially 14 features, 4 semi-quantitative features:

– Steatosis

– Lobular inflammation

– Hepatocellular ballooning

– Fibrosis

• Additional 9 features (present/absent)

Hepatology. 2005 Jun;41(6):1313-21.

NAFLD Activity Score (NAS)

• A simple, non weighted scoring system to be used in clinical trials

• Utilizes only H&E and Masson Trichrome staining

• Reproducible with interrater agreement of 0.61 for adult NASH

• Less reproducible in pediatric NASH (different histology)

Hepatology. 2005 Jun;41(6):1313-21.

Grading Steatosis

• Score 0 – <5% (minimal)

• Score 1 – 5-33% (mild)

• Score 2 – 34-66% (moderate)

• Score 3 - >66% (severe)

Grading Lobular Inflammation

• Score 0 – none

• Score 1 – <2 foci / 20x field

• Score 2 – 2-4 foci / 20x field

• Score 3 – >4 foci / 20x field

Grading Hepatocellular Ballooning

• Score 0 – none

• Score 1 – few (mild)

• Score 2 – many (moderate-marked)

Hepatocellular Ballooning IHC

Cytokeratin 18 Ubiquitin

Ikura Y., World J Hepatol. 2014 Dec 27;6(12):894-900

Staging Fibrosis

• Score 0 – none

• Score 1 – perisinusoidal or periportal – 1a – mild, zone 3, perisinusoidal

– 1b – moderate, zone 3, perisinusoidal

– 1c – portal/periportal

• Score 2 – perisinusoidal and portal/periportal

• Score 3 – bridging fibrosis

• Score 4 – cirrhosis

Staging Fibrosis

Staging Fibrosis

NAFLD Activity Score (NAS)

Steatosis (0-3)

+ Lobular inflammation (0-3)

+ Hepatocellular ballooning (0-2)

NAS score = (0-8)

NASH CRN fibrosis (0-4)

Differential Diagnosis

• Alcoholic steatohepatitis (Neutrophils, Mallory-Denk)

• Autoimmune hepatitis (plasma cells)

• Hepatitis C (G3)

• Drug induced liver injury

• Wilson disease

Clinical and laboratory information is crucial!

Clinical Significance

• Original NASH CRN committee did not discuss correlation between NAS and steatohepatitis

• NAS ≥4 is generally agreed to distinguish simple steatosis from steatohepatitis and its consequences

Hjelkrem et al, Aliment Pharmacol Ther. 2011 Jul;34(2):214-8