The liver is remarkable in its ability to preserve its function despite advanced age. Elderly patients are at an increased risk of more severe hepatic injury when exposed to hepatic insults. This increased risk is likely related to the liver's age-related decrease in regenerative capacity. We will review the hepatic changes that are known to occur with aging and their pathologic consequences of liver disease in elderly patients (Table 90-1).
Table 90-1 Effects of Age on the Liver |Favorite Table|Download (.pdf)
Table 90-1 Effects of Age on the Liver
Liver chemistry tests: unaffected by age
Coagulation factors: unaffected by age
Serum albumin: slightly decreased but within the normal range
Serum cholesterol and triglycerides: increase with age
Phase I drug metabolism: significantly decreased with age
Phase II metabolism: unaffected by age
Hepatic proliferation after surgical resection: diminished by age
Hepatotoxicity: (hepatitis viruses, acetaminophen, isoniazid) more severe in the elderly
Liver volume significantly decreases with age, as shown in both postmortem and in vivo ultrasound studies. This decline, which can reach 40% of maximal healthy mass, occurs mostly after the sixth decade of life and is greater in men than in women. There is also a contemporaneous decrease in hepatic blood flow by approximately 35% to 40%. The cause of decreased blood flow is likely multifactorial—as a result of changes in cardiovascular output, diminished splanchnic blood flow, reduced portal vein blood flow, and increased resistance to portal flow. Hepatocytes accumulate lipofuscin with age while undergoing a decrease in the number of mitochondria, the concentration of smooth endoplasmic reticulum (SER), telomere length, and the activity of several liver microsomal enzymes.
Despite the observed changes in volume and blood flow, age-related changes to hepatic function are less evident in clinical practice (see Table 90-1). The capacity to sustain liver function during aging is reflected in the ability to successfully transplant livers from older deceased donors. Traditional liver chemistry tests, including serum aminotransferases, bilirubin, alkaline phosphatase, and gamma-glutamyl transpeptidase, do not change with age. Likewise, there are no significant changes in coagulation factors. Serum albumin slightly decreases with age, but typically remains within the normal range. Serum cholesterol and triglycerides increase with age as there is a gradual decline in the metabolism of low-density lipoprotein (LDL) cholesterol.
There are age-related changes in the hepatic metabolism of certain medications, which is important since more than 30% of prescription drugs are prescribed to elderly men and women. The incidence of adverse drug reactions significantly increases with increasing age. Phase I drug metabolism relies on microsomal enzymes and results in metabolism by oxidation, reduction, demethylation, and hydrolysis. Phase II drug metabolism relies on cytosolic enzymes and results in metabolism by conjugation with several different polar ligands. Phase I reactions are usually catalyzed ...