Liver & intrahepatic bile ducts

• One of the most important causes of liver disease worldwide in adults and children (Nat Rev Gastroenterol Hepatol 2018;15:11)
• Global prevalence is ~24% (Nat Rev Gastroenterol Hepatol 2018;15:11)
• It largely affects patients with unhealthy metabolic conditions but can occur even in lean individuals (Medicine (Baltimore) 2012;91:319)

• Overweight / obesity, hyperglycemia / type 2 diabetes mellitus and other metabolic disorders (dyslipidemia, insulin resistance, hypertension, etc.) (Hepatology 2023;78:1966, J Hepatol 2020;73:202)

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• Most patients with MASLD are asymptomatic and diagnosed incidentally (Clin Liver Dis 2016;20:277)
• Prevalence of MASLD is high in people of Asian and Hispanic origin (Clin Liver Dis 2018;22:39)
• Fatty livers induced by alternative causes (medications, starvation, inherited disorders of lipid metabolism, etc.) are not MASLD (Hepatology 2023;78:1966)

• Bright liver and increased hepatorenal contrast on ultrasound (US) (Tohoku J Exp Med 1983;139:43)
• Liver / spleen attenuation ratio < 1.1 on computed tomography (CT) (Hepatol Commun 2019;3:1347)
• High signal intensity on T1 weighted magnetic resonance images (MRI)
• Whole hepatic lipid volume is quantifiable by using a special MRI technique (Hepatol Res 2019;49:1374)

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• Presence of fibrosis is a sole prognostic factor in MASLD (Gastroenterology 2015;149:389, Hepatology 2015;61:1547)

• Swollen soft liver with yellowish-brown color
• Surface of the affected liver becomes irregular with progression of fibrosis
• Some cases show cirrhosis or hepatocellular carcinoma

Contributed by Yoshihiro Ikura, M.D.

• Lipid stain methods (oil red O, Sudan black B, filipin, etc.) to detect liver fat can be performed on frozen sections

Contributed by Yoshihiro Ikura, M.D.

• Predominantly macrovesicular steatosis in ≥ 5% hepatocytes under low magnification (4x or lower) is a sole histologic requirement for diagnosis of MASLD
• Disease severity is evaluated separately by grade of activity and stage of fibrosis
• Activity grade is assessed according to nonalcoholic fatty liver disease activity score (NAS) using the sum of 3 components (total 0 - 8 points) (Hepatology 2005;41:1313)
  • Steatosis
    • 0: < 5%
    • 1: 5 - 33%
    • 2: 34 - 66%
    • 3: > 66%
  • Lobular inflammation
    • 0: none
    • 1: < 2 foci/20x field
    • 2: 2 - 4 foci/20x field
    • 3: > 4 foci/20x field
  • Ballooning degeneration
    • 0: none
    • 1: few
    • 2: many
• Fibrosis stage is assessed into 5 levels (Hepatology 2005;41:1313)
  • Stage 0: none
  • Stage 1: perivenular (zone 3) fibrosis
  • Stage 2: perivenular + portal fibrosis
  • Stage 3: bridging fibrosis
  • Stage 4: cirrhosis
• Other characteristic findings are Mallory-Denk bodies, glycogenated nuclei, giant mitochondria (megamitochondria) and lipogranuloma
• Histologic changes of concomitant liver conditions may be seen (Hepatology 2023;78:1966, World J Gastroenterol 2024;30:1949)
• In MASLD associated cirrhosis, steatotic hepatocytes may become depleted, resulting in a loss of visible steatosis; however, the term cryptogenic cirrhosis should not be used for this condition (J Hepatol 2020;73:202)

Contributed by Yoshihiro Ikura, M.D.

• CK18: ballooned hepatocytes are characteristically negative (J Hepatol 2010;53:719)

A 71 year old woman (nondrinker) presented with possible diagnosis of hepatocellular carcinoma and SLD with abdominal ultrasound. Percutaneous liver biopsy was performed for definitive diagnosis. The photomicrograph above shows nontumorous liver tissue (background). What information has the lowest priority for accurate pathologic diagnosis?

1. Autoantibodies
2. Genetic test results
3. Medications
4. Metabolic factors
5. Virus markers

B. Genetic test results. Liver histology shows inflammatory damage associated with lymphoid follicle formation and steatosis. These morphological features are common findings in both autoimmune hepatitis and chronic hepatitis C. Indeed, this case was positive for hepatitis C virus genotype 3. ALD, MASLD and drug induced SLD should always be investigated as possible comorbid pathological mechanisms (Clin Pract 2024;14:2542). Some genetic disorders cause SLD but the incidence is very low. Answer A is incorrect because autoimmune diseases should be ruled out. Answer C is incorrect because steatosis is relatively common in drug induced liver injury. Answer E is incorrect because chronic hepatitis C is most likely in cases with such histology. Answer D is incorrect because MASLD is the most common type of SLD.

Comment Here

Reference: Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH)

Which of the following is correct concerning the intracellular inclusion seen in the figure above (arrow)?

1. Actin positive
2. CK18 negative
3. Related to viral infection
4. Specific for alcoholic liver damage
5. Ubiquitin positive

E. Ubiquitin positive. The inclusion shown is a Mallory-Denk body. It is a ubiquitinated aggregate of keratin filament that occurs in ballooned hepatocytes. Answer A is incorrect because the intracellular inclusion is negative for actin. Answer B is incorrect because the intracellular inclusion is positive for CK18. Answer C is incorrect because the intracellular inclusion is not related to viral infection. Answer D is incorrect because the intracellular inclusion is not restricted to alcohol related liver injury.

Comment Here

Reference: Metabolic dysfunction associated steatotic liver disease (MASLD) / Metabolic dysfunction associated steatohepatitis (MASH)