LIVER DISEASE IN THE ELDERLY

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A substantial percentage of morbidity and mortality in the elderly is attributable to liver disease. The number of patients older than 65 years old with chronic liver disease has increased owing, in part, to improved management of chronic liver disease and cirrhosis as well as advances in the management of extrahepatic systemic diseases. The number of elderly patients with chronic hepatitis C is increasing because of the large cohort of middle-aged patients with hepatitis C virus (HCV) infection who are growing older.

Chronic liver disease, including cirrhosis, was the ninth commonest cause of death in the United States in 198917 and in 1998,63a respectively. Mortality from cirrhosis in the United States accounted for 7.9 deaths per 100,000 population in 1993.78 The rate of mortality from chronic liver disease was highest among patients aged 65 to 74 years (49 per 100,000 men, 26.7 per 100,000 women). These rates are 3.2 and 5.6 fold higher than those for men and women aged 35 to 44 years.17 Although there are no liver diseases specific to advanced age, the presentation, clinical course, and management of liver disease in the elderly may differ in important respects from those for younger individuals.

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AGE-RELATED CHANGES IN LIVER STRUCTURE

Few comprehensive studies describe the nature and extent of changes that occur in the structure and function of the aging human liver. The most cited changes are a decline in liver volume and a reduction in hepatic blood flow.55, 5, 107, 115 Several studies have shown a significant inverse correlation between age and liver volume and liver blood flow. A significant inverse correlation exists between apparent liver blood flow per unit volume of liver (liver perfusion) and age (Fig. 1). Despite

LIVER FUNCTION AND BIOCHEMICAL TESTS

Although there is some evidence that aging affects hepatic function, most relevant studies failed to identify significant age-related deficits in liver function in humans.67, 94Many pharmacokinetic studies have documented a decline in the clearance of drugs undergoing liver metabolism in aging individuals.34, 35, 97, 106, 108 The clearance of drugs such as antipyrine, aminopyrine, imipramine, many benzodiazepines, and caffeine has been shown to be reduced by 10% to 50% with age. This decline

Hepatitis A Virus

Hepatitis A virus (HAV) infection is usually a mild disease, particularly in children, in whom it is frequently anicteric and often subclinical. Acute liver failure occurs in less than 0.35% of adult patients. Acute hepatitis A is encountered rarely in patients older than age 65. Middle-aged and older people have been shown to be more susceptible to severe HAV infections and are more likely to have serious complications. Older people have a higher incidence of acute liver failure and a higher

DRUG-INDUCED LIVER DISEASE

The elderly as a group consume disproportionately large amounts of drugs compared with younger persons. Increased drug consumption and multiple drug use (polypharmacy) common in older patients are major factors contributing to adverse drug events in the elderly.19 Alteration in pharmacodynamics and pharmacokinetics with advancing age may alter the response to drugs.35, 66

Drug-induced liver disease occurs with increased frequency in the elderly. In Denmark, the overall incidence of drug-induced

CIRRHOSIS AND PORTAL HYPERTENSION

Although cirrhosis is a major factor influencing prognosis in elderly patients with chronic liver disease, the impact of concurrent diseases, unrelated to the liver, on mortality is also important. In a Japanese study, 135 patients who were aged 80 years or older and had chronic liver disease were followed for a median of 3.4 years (range, 0.5–10.8 y).40 Of these patients, 54% had cirrhosis, and 90% had various concomitant chronic diseases. Of the 52 patients who died during observation, only

PRIMARY BILIARY CIRRHOSIS

Primary biliary cirrhosis is predominantly a disease of middle-aged women but may present in patients older than age 65 in 30% to 40% of cases.3, 37, 61 According to the analysis of Hospitalization Registry data in Denmark, the incidence of primary biliary cirrhosis peaks between age 70 and 79 (Fig. 4).3 In England, more than one third of patients with primary biliary cirrhosis are older than 65, and the median age at the date of diagnosis is 62 to 63.41, 61 Several studies have shown that when

AUTOIMMUNE HEPATITIS

Autoimmune hepatitis originally was described in the early 1950s in young women. Although it occurs most frequently in women between the ages of 10 and 30 or in late middle age, autoimmune hepatitis can affect both sexes and all age groups. The presentation of autoimmune hepatitis in older subjects, although uncommon, has been described by several authors.65, 86 Newton et al65 reviewed all the patients diagnosed with autoimmune hepatitis in a single medical center during a 15-year period and

HEPATOCELLULAR CARCINOMA

Although the peak incidence of hepatocellular carcinoma (HCC) in China and sub-Saharan Africa occurs during early to middle adulthood, in Europe and North America HCC is predominantly a disease of the elderly.90, 113 In Western countries, more than 50% of affected patients are older than age 60 at presentation, and 40% are older than 70. In a retrospective review of 110 cases of HCC in England, 47% presented at age 65 or older.15 In a large prospective study, Ikeda et al42 showed that the

LIVER TRANSPLANTATION

The extremes of age traditionally have been considered relative contraindications to liver transplantation because of the technical difficulties of surgery and anesthesia in the very young and the general physical state of the elderly. These age boundaries are not fixed and continually are being extended. During the early experience with liver transplantation, an age of 50 to 55 years was used arbitrarily by most transplant programs as the upper limit for transplantation.56 More recently, with

LIVER TRANSPLANTATION FROM ELDERLY DONORS

A shortage of donor organs has become a major problem in liver transplantation, and the discrepancy between the number of liver transplant candidates and donors is growing constantly. This situation has led to important changes in traditional organ selection criteria to meet the need for donor livers. Historically an age greater than 50 years was considered to be a relative contraindication to organ donation. Several studies published in the early 1990s have shown, however, that livers from

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    Address reprint requests to Arie Regev, MD Division of Hepatology Center for Liver Diseases Jackson Medical Towers, Suite 1101 1500 NW 12th Avenue Miami, FL 33136 e-mail: [email protected]

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    Division of Hepatology, Center for Liver Diseases, University of Miami School of Medicine, Miami, Florida

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