An 80-year-old man participates in a study designed to evaluate the effects of aging on the liver. He has undergone a liver biopsy every 10 years since age 40 so that researchers can identify age-related histologic changes. The subject is healthy and has no relevant family history. He does not use alcohol or illicit drugs. BMI is 21.5 kg/m². Physical examination is unremarkable; laboratory studies, including complete blood count, liver function tests, cholesterol levels, and hemoglobin A1c, are within normal limits. Which of the following histologic changes has most likely developed over time in this individual?

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11ec160b_3cbf_64ce_9249_17a6fdff5da7_MD0001_00 Several important age-related changes develop in the liver over time. The size of the liver shrinks, associated with a decrease in perfusion. In addition, the regenerative capabilities of the liver slow, increasing susceptibility to toxic and ischemic injury. At the cellular level, the overall number of hepatocytes decreases, and the remaining hepatocytes usually increase in size, associated with polyploidy and enlarged mitochondria. Their ability to clear intracellular debris decreases, allowing a lysosomal degradation product called lipofuscin to accumulate over time; the presence of these yellowish-brown inclusions within hepatocytes is sometimes referred to as brown atrophy. Other cellular changes of aging include a decrease in size and number of fenestrations within endothelial cells, formation of lipid droplets within stellate cells, and decreased phagocytic activity of Kupffer cells. (Choice A) Senile (eg, age-related) systemic amyloidosis is characterized by transthyretin deposition in the extracellular space. Although amyloidosis can involve the liver, affected patients frequently have hepatomegaly and elevated alkaline phosphatase levels. (Choice B) Hereditary hemochromatosis is an autosomal recessive disorder characterized by excessive iron absorption and hemosiderin deposition in hepatocytes and other tissues. This patient has no family history of hemochromatosis, and abnormalities in liver transaminases (eg, AST, ALT) would be expected. (Choice C) Mallory-Denk bodies are intracytoplasmic hyaline inclusions found within damaged hepatocytes in the setting of alcoholic hepatitis and other liver diseases (eg, nonalcoholic steatohepatitis). This patient has no medical conditions that predispose to their formation. (Choice E) Chronic hepatic injury activates stellate cells, leading to collagen production and ultimately cirrhosis. This would not occur in a healthy individual. Educational objective: Normal age-related changes in the liver include decreased size, decreased perfusion, slower regenerative capability, and the development of yellowish-brown lipofuscin inclusions within hepatocytes. __________ References: Hallmarks of aging in the liver. (http://www.ncbi.nlm.nih.gov/pubmed/31462971) The peculiar aging of human liver: a geroscience perspective within transplant context. (http://www.ncbi.nlm.nih.gov/pubmed/30772626) Liver physiology and liver diseases in the elderly. (http://www.ncbi.nlm.nih.gov/pubmed/24379563)

An 80-Year-Old Man Participates in a Study Designed to Evaluate