The Aging Liver

Abstract

Background/Objective: Numerous age-related changes in hepatic structure and function have been described, although liver function seems to be quite well maintained in old age. Few consistent and reproducible observations and a lack of correlation between structural and functional data characterize the present state of our knowledge. In contrast to renal clearance, no equally reliable method exists to estimate hepatic drug clearance. The contribution of age to altered drug clearance in the elderly is difficult to assess as drug interactions, numbers and types of drugs taken at a time, underlying disease and increased interindividual variability are superimposed to the aging process. Methods: A comprehensive computer-assisted search of the literature. Results: A decline in liver volume and blood flow and a reduction in in vitro and in vivo metabolic capacity have been shown in older subjects, and the physiologic basis of reduced hepatic drug clearance in this age group. Conclusions: After decades of research into the matter, the old and well-known aphorism ‘start lower – go slower’ is valid more than ever in the field of geriatric prescribing. Not only renally excreted drugs but also substances which are metabolized and excreted by the liver should be used at a starting dose which is 30–40% smaller than the average dose used in middle-aged adults.

Renal transplantation in the elderly

“…The reduced renal clearance of drugs that occurs with normal aging has been well described, and this phenomenon is likely to be more marked in aging recipients of older kidneys. Less appreciated are the changes that occur in hepatic metabolic capacity with age that may impact on hepatic drug clearance in older transplant recipients [97]. However, the extent of the impact of a given drug or drug protocol on the immune system affected by age is not currently known.…”

Increasing hepatic arteriole wall thickness and decreased luminal diameter occur with increasing age in normal livers

“…However, in rat and human studies it has been shown that with older age there is decreasing liver volume and blood flow [8][9][10][11]. Older livers may have impaired regenerative capabilities associated with shortened telomere length as well as altered oxidative and metabolic capacities [12][13][14][15][16].…”

Pharmacologic Issues in Geriatric Emergency Medicine

“…Metabolism and clearance of drugs are also changed in the elderly [12][13][14][15][16] (Table 2). Unfortunately, because elderly patients with comorbid conditions are excluded from many drug trials, the knowledge of drug metabolism is limited.…”

“…Hepatic metabolism in the elderly is not only related to age, but to lifestyle, genotype, hepatic blood flow, hepatic disease, and interactions with other medications. It may be reduced up to 30% to 50% in the elderly [14][15][16]. Hepatic metabolism occurs through one of two biotransformation systems.…”

“…Medications that induce the P450 system lead to decreased levels of medications metabolized by the liver. Phase II metabolism, which includes acetylation, sulfonation, conjugation, and glucuronidation, is minimally affected in the older population [14]. Cigarette smoking, alcohol use, and caffeine may also affect hepatic metabolism.…”