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Scenarios where tier-2 evaluation by liver biopsy may be appropriate for establishing the presence of
NASH:

a) Presumably, patients with LSM >9.6 kPa (M probe) and >9.3 kPa (XL probe) should be considered
for the next level of liver disease staging with a percutaneous liver biopsy.

b) An anxious patient who will not be reassured until absence of NASH is firmly established with a liver
biopsy.

c) Persistently elevated ALT despite attempts to lose weight and exercise – this perhaps is the most
common scenario for recommending liver biopsy at a community level practice, but it is not known
that persistently abnormal ALT is sufficiently predictive of the presence of NASH.

d) Tender hepatomegaly – rarely patients may exhibit tender hepatomegaly. This phenomenon appears
to occur in patients with co-existing functional bowel disorders or poorly controlled diabetes.

e) Unexplained fatigue.

Percutaneous liver biopsy is required to firmly establish the presence of NASH. Below are some
comments with regards to the standards for obtaining a liver biopsy:

• 16 gauge (or wider) liver biopsy needle should be used at all times.

• ≥15 mm core is required. Longer cores minimize the risk of sampling variability. Fragmented or
fibrotic samples diminish histological yield.

• Transjugular needle biopsy specimens may not yield sufficient amount of tissue for firm characterization
of liver histology.

• Liver histology should be reviewed by a pathologist with expertise in liver pathology.

• Pathologist should evaluate the liver biopsy in a systematic fashion and address all histological elements
of NAFLD (steatosis – extent, location; inflammation – extent, location, cell type; ballooning – extent
and location; fibrosis – extent, location; other features such as MDBs, Kupffer cells, iron deposition.

References
[1] Castera L, Vilgrain V, Angulo P. Noninvasive evaluation of NAFLD. Nat Rev Gastroenterol

Hepatol 2013;10:666-675.
[2] Chalasani N,Younossi Z, Lavine JE, et al. The diagnosis and management of non-alcoholic fatty

liver disease: Practice Guideline by the American Association for the Study of Liver Diseases,
American College of Gastroenterology, and the American Gastroenterological Association.
Hepatology 2012;55:2005-2023.
[3] Nascimbeni F, Loria P, Ratziu V. Non-alcoholic fatty liver disease: diagnosis and investigation. Dig
Dis 2014;32:586-596.

18 Postgraduate Course Syllabus • Metabolic Liver Disease
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