Liver

Age-related changes occurring in the liver may be gross, histologic, biochemical, or related to blood flow or stress. With the exception of changes that affect drug metabolism, most probably have no clinical relevance.

Grossly, the liver becomes more brown and decreases in volume and weight. The color change is attributable to accumulation of lipofuscin (a brown pigment) in hepatocytes as a by-product of lipid and protein metabolism. Capsular and parenchymal fibrosis also increases but does not affect function and does not indicate cirrhosis. Hepatic volume decreases by about 17 to 28% between the ages of 40 and 65; weight decreases by about 25% between the ages of 20 and 70.

Histologically, hepatocytes probably enlarge with aging, and some evidence suggests an increase in nuclear polyploidy and size. The number of mitochondria per hepatic volume decreases with an increase in the number of swollen, vacuolated mitochondria. The numbers of lysosomes and dense bodies also increase.

Biochemically, serum bilirubin levels decrease with aging, although < 0.2% of test results in elderly patients are below the normal range. Protein synthesis also appears to decrease with aging, although the degree varies widely by protein; serum total protein and albumin levels decrease slightly but remain within the normal range.

Phase 1 enzymatic reactions (oxidation, reduction, hydrolysis), which take place in hepatocyte smooth endoplasmic reticulum and which metabolize drugs, decrease linearly with aging. Phase 2 reactions (conjugation) remain essentially unchanged. Phase 1 enzyme activity per gram of liver tissue may actually be preserved, and decreased phase 1 activity may result primarily from an age-related decline in hepatic mass. Why phase 2 reactions are preserved despite the decline in hepatic mass is unclear, but it may be because of compensatory extrahepatic conjugation.

The older liver may also be less responsive to enzyme induction by some agents.

Hepatic blood flow decreases by 35% between the ages of 40 and 65 largely because of a decrease in splanchnic blood flow. The decreased hepatic blood flow, together with decreased hepatic weight, accounts for decreases in hepatic drug elimination of some compounds in the elderly.

Response to physiologic stress may also decrease with aging. Many hepatotoxic drugs cause more severe injury in older people, possibly due to altered drug metabolism, impaired cellular protective mechanisms, and diminished reserve in other organs. Hepatic regeneration is delayed but not greatly impaired. The regulation of regeneration, however, is poorly understood. Some effects are clearly extrahepatic, including decreased serum levels of epidermal growth factor (EGF) and transforming growth factor-. In the elderly, hepatocytes seem less able to respond to hepatotropic growth factors (eg, EGF). Studies have demonstrated a decrease in EGF receptors and their binding capacity for EGF. Therefore, delayed hepatic regeneration is clinically important for elderly patients undergoing liver resections--mortality rates resulting from liver resection are higher in patients > 60 than in those < 60. Postoperative morbidity and mortality, however, are usually not due to liver failure but rather to extrahepatic complications of the surgery. The overall survival of transplanted livers is not dramatically different in older and younger patients, and older patients are increasingly undergoing liver transplantation. Evidence suggests that livers from donors ≥ 65 may be viable for transplantation.

This topic was last updated May 2005.