LIVER DISEASE IN THE ELDERLY
Section snippets
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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Cited by (56)
Obesity and aging: Molecular mechanisms and therapeutic approaches
2021, Ageing Research ReviewsCitation Excerpt :Oxidative stress and inflammation, processes that accompany both aging and obesity, can contribute to the progression of NAFLD to more serious conditions, such as nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). Accordingly, aging has been reported to significantly enhance the progression of NAFLD to NASH and fibrosis, predisposing to increased mortality in elderly subjects with NAFLD (Regev and Schiff, 2001; Frith et al., 2009). Age-associated enhanced fat uptake, increased de novo lipogenesis, decreased β‐oxidation, and/or decreased synthesis/secretion of very-low-density lipoproteins have been proposed to be involved in the liver steatosis that characterizes NAFLD (Cohen et al., 2011).
Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases
2018, International Review of Cell and Molecular BiologyCitation Excerpt :Notably, LDL–cholesterol metabolism rate is decreased by over 30% with age, as a consequence of a decrease in expression of LDL receptors (Miller, 1984). Aging significantly enhances the progression of NAFLD to NASH, and to fibrosis, leading to the conditions that predispose to increase mortality in elderly subjects with NAFLD (Regev, Schiff, 2001). Age-dependent decline of fatty acid β-oxidation and reduced expression of hepatic nuclear receptor peroxisome proliferator–activated receptor may be potential mechanisms (Sanguino et al., 2004).
Cell-autonomous decrease in proliferative competitiveness of the aged hepatocyte
2015, Journal of HepatologyCitation Excerpt :On the other hand, we have also learned over the past several decades that the regenerative potential of the liver declines with age [2–6]. It has been suggested that a delayed regenerative process might play a role in the accelerated progression and worse prognosis of liver disease in the elderly [3,22–25], as well as on the impact of donor age on the outcome of liver transplantation [26], most notably in the case of transplant from a living donor [27,28]. Given the clinical relevance of the issue, the basis for the age-associated impairment of liver regeneration has been the subject of intense investigation.
Liver diseases in the elderly
2014, Gastroenterologia y HepatologiaEpigenome-wide analysis of aging effects on liver regeneration
2023, BMC Biology
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