non-alcoholic steatohepatitis

Synopsis

1. heptocytic steatosis
· >5% (beyond physiologic level)

2. steatohepatitis
· ballooned hepatocytes
· Mallory-Denk bodies
· damaged IF within hepatocytes; CAM5.2+
· portal neutrophilic infiltrate

3. steatofibrosis
· acinar zone 3 fibrosis (perivenular fibrosis/pericellular fibrosis) may progress to central-portal bridging cirrhosis

Etiology

 obesity
 diabetes mellitus
 metabolic syndrome X
 jejunoileal bypass
 intestinal resection
 total parenteral nutrition (TPN)
 lipodystrophy
 small bowel diverticulosis
 metabolic diseases
 hyperlipidemia
 gastrointestinal surgery for obesity (by-pass surgery)
 drugs

• glucocorticoids
• perhexilene maleate (Pexid)
• 4’4’-diethylaminoethoxyhexoestrol
• amiodarone
• tamoxifen
• nifedipine (Adalate)

 chemicals

• petrochemicals

Differential diagnosis

Centrizonal arteries can cause central zones to be mistaken for portal tracts, especially in the setting of centrizonal ductular reaction, and result in either missed diagnosis or inaccurate staging of NASH.

The presence of centrizonal arteries must be recognized to allow for correct orientation to liver architecture in NASH and, together with the finding of increased CD34-positive microvessel formation in higher-stage fibrosis, suggests a possible association between neoangiogenesis and NASH progression to cirrhosis.

Types

 TPN-induced steatohepatitis
 glycogenoses (glycogen storage diseases, GSDs)

See also

 steatohepatitis

• alcoholic steatohepatitis

 non-alcoholic fatty liver disease (NAFLD)

References

 Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C. Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol Med. 2008 Feb;14(2):72-81. PMID: 18218340

 Videla LA, Rodrigo R, Araya J, Poniachik J. Insulin resistance and oxidative stress interdependency in non-alcoholic fatty liver disease. Trends Mol Med. 2006 Dec;12(12):555-8. PMID: 17049925

 Zafrani ES. Non-alcoholic fatty liver disease: an emerging pathological spectrum. Virchows Arch. 2004 Jan;444(1):3-12. PMID: 14685853

 Centrizonal arteries and microvessels in nonalcoholic steatohepatitis. Gill RM, Belt P, Wilson L, Bass NM, Ferrell LD. Am J Surg Pathol. 2011 Sep;35(9):1400-4. PMID: 21836480