Viral Hepatitis 21 Hepatitis A

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Hepatitis A (HAV) is an RNA virus in the picornavirus family (see Table 2). The virus is easily transmitted by the fecal-oral route. In countries where the virus is endemic and sanitation is poor, most people become infected in early childhood when the disease is mild and life-long immunity results (59). Recently, a shift in the prevalence of cases from childhood to adulthood has occurred, presumably due to improved living conditions. In the United States and other industrialized nations, the prevalence of anti-HAV antibodies increases with advancing age (60). Seroprevalence in an ambulatory geriatric population (mean age 75) in New York was 94%. In a 1994 serologic study from Colorado, the prevalence of anti-HAV antibodies at ages 60, 70, and 80 was 40%, 60%, and 80%, respectively (59). The steady increase in seroprevalence with age is seen in men and women and in all races and ethnic groups.

The clinical manifestations of acute hepatitis A become more severe and are associated with prolonged cholestasis with advancing age (61,62). In the United States, the overall case fatality rate for HAV infection is 1/1000; however, it rises to 27/1000 in persons 50 yr or older (61). Approx 100 HAV-related deaths occur in the U.S. each year of which 70% are in persons over age 49 (63). The increased death rates in the older population is attributable to higher rates of fulminant hepatitis since chronic infection does not occur (59).

Table 2

Viral Hepatitis

Table 2

Viral Hepatitis

Virus

Transmission

Incubation range in days (average)

Clinical characteristics in older persons

Chronic infection

A

Fecal-oral

14-50

Prolonged cholestasis

No

(28)

Increased mortality

B

Parenteral

45-160

Milder acute infection, but chronic

Yes

Sexual

(120)

infection more common. Sequelae:

cancer and cirrhosis

C

Parenteral

15-150

Same as hepatitis B virus (HBV)

Yes

Other ?

(42)

D

Parenteral

45-130

May worsen existing cirrhosis

Yes

Sexual

from HBV

E

Fecal-oral

14-60

No data

No

G

Parenteral

Limited data

Clinical significance unknown

Yes

An inactivated hepatitis A vaccine has been available since 1993, and clinical studies have shown the vaccine to be safe, very well tolerated, and highly immunogenic in all age groups (64). Similar to young adults, seroconversion rates are 100% in older adults (40-61 yr) (65). Immunogenicity in frail elderly persons, such as residents of long-term care, has not been reported. Although disease may be more severe in older adults current vaccination policies do not specifically target the elderly. However, vaccination is recommended for older travelers who plan to visit countries endemic for HAV.

2.2. Hepatitis B

Hepatitis B (HBV) is a complex deoxyribonucleic acid (DNA) virus composed of double-stranded DNA, core antigen (HBcAg), surface antigen (HBSAg), and soluble nucleocapsid antigen (HBeAg). Hepatitis B surface antigen is detectable during acute illness and disappears when antibody to HBSAg develops. Transmission of HBV is by percutaneous and mucous membrane exposure to infectious body fluids. Serum, saliva, and semen have been shown to contain HBSAg. Hepatitis D (HDV), also known as Delta agent, is a small single-stranded, circular RNA particle that is coated with HBSAg. Infection with HDV requires either simultaneous infection with HBV or chronic HBV infection. The co-infection may result in fulminant hepatitis (60).

Infection with HBV accounts for approx 20% of cases of acute viral hepatitis in older adults (60,66). Because the primary risk group in the U.S. and Europe is intravenous drug abusers, a group not highly represented in the elderly population, acute infection is not common in this age group. Transfusion-related HBV infection from contaminated blood in the window period of detection is a now an uncommon event with risk estimated to be 1 in 63,000 transfusions (67). Long-term care facilities were at one time considered a risk area for HBV when several outbreaks occurred during the 1970s-1980s (60). However, recent surveys of geriatric hospitals indicate the prevalence of HBSAg is similar to the general geriatric population (<1%) (60,68).

Acute HBV in older adults is usually mild and many cases are subclinical or present with a cholestatic picture (66). In addition to the typical symptoms of jaundice, anorexia, and fatigue, diarrhea is a common complaint in elderly persons (66). Complaints reflecting immune complex disease such as myalgias and arthalgias are rare in older adults. Although acute HBV is generally not a severe disease in older adults, the mortality from fulminant HBV increases with age (60). In a multivariant analysis of prognostic factors in 115 patients with HBV, age was an independent predictor of survival. Chronic carriage rates also increase when individuals are infected at older ages. Compared with a 10% carriage rate in young adults, approx 60% of older persons become chronic carriers (60). However, most elderly HBV chronic carriers were infected early in life and have carried the virus for a prolonged period and, although HBSAg is detected, there is little evidence of active viral replication as determined by the presence of HBeAg or viral DNA in the serum (60).

In addition to cirrhosis from chronic active hepatitis, one of the major complications of HBV infection is hepatocellular carcinoma. The length of time infected is an important factor in the development of cancer and, thus, elderly persons who have been infected for many years are at greatest risk (69). The rate of hepatocellular carcinoma rises from 197/100,000 in 30- to 39-yr olds to 927/100,000 in 60- to 69-yr-old chronic HBV carriers (62).

The treatment of elderly persons with chronic HBV is largely supportive. Although a-interferon shows evidence of suppressing viral replication and may decrease the risk of progression to cirrhosis or cancer, side effects of therapy increase with advancing age (60). Therapy should be reserved for patients in overall good health except for their liver disease and who have evidence of active viral replication. Lamivudine, a nucleoside analogue, holds promise as a new anti-HBV agent.

The currently licensed hepatitis B vaccine is a genetic recombinant vaccine consisting of highly purified HBSAg particles expressed in yeast. The vaccine is very well tolerated and highly immunogenic with excellent protective efficacy in children and young adults. However, response rates to HBV vaccine diminish significantly with increased age. Ninety percent of persons under age 40 achieve an adequate seroresponse compared with only 50% in persons over age 60.

2.3. Hepatitis C

Hepatitis C (HCV) is an RNA virus in the flavivirus family and accounts for the majority of cases of acute viral hepatitis in the older adults. The virus is transmitted parenterally and accounts for approx 90% of new cases of posttransfusion hepatitis. Other exposures to contaminated blood, either via occupation or intravenous drug abuse, may also transmit HCV. Although 40-50% of community-acquired HCV cases do not report a parenteral exposure, nonparenteral transmission of HCV is not well understood. Sexual transmission, if it occurs, is not efficient (61). The major risk factor for HCV in older persons is transfusion and most became infected with HCV prior to 1990 when routine screening of the blood supply began (60). The current risk of acquiring HCV from transfusion is approx 1 in 103,000 (67). The seroprevalence of HCV increases with advancing age from 0.6% among 18- to 25-yr olds to 2.5% of persons over age 60. The increased prevalence in older persons is likely due to a greater chance of transfusion (60). The seroprevalence in long-term care facilities is approx that of the general elderly population. In a Canadian and an Italian chronic care facility, the prevalences of anti-HCV antibodies were 1.4% and 2.2%, respectively, both reflecting rates similar to the community at large (68,70).

The clinical manifestations of acute HCV are generally mild and nonspecific. In a series of 20 older people with acute non-A non-B hepatitis, approx 30-40% had fever, abdominal pain, and jaundice (60). Fulminant hepatitis is rare with HCV, but development of chronic liver disease is very common (61,66,71). Virtually all persons become chronically infected and a significant number develop chronic liver disease. Chronic active hepatitis or cirrhosis develops in 29-76%, on average 20 yr after initial infection (71). In older patients with chronic HCV, the HCV-RNA titer is significantly higher than in younger patients, and there is evidence that disease progression is more rapid (60). Hepatocellular carcinoma is clearly associated with chronic HCV infection, and the relative risk of cancer from HCV may be even greater than that from HBV (52 vs. 15) (69). In a study of 25 older persons with HCV in the U.K., 36% developed hepatocellular carcinoma (71).

Alpha interferon is administered to patients with chronic HCV infection as an attempt to prevent progression to cirrhosis and possibly liver cancer. Persons with high viral load and viral genotype 1 have a low response rate to a-interferon, and many patients who do have an initial response relapse when therapy is discontinued (60). Most studies of interferon treatment of HCV have not included older participants. In one study from Japan, interferon was administered to 19 patients aged 65 and older with HCV, and the response rate was 26% compared with 33% in younger persons. Of note, the older subjects had higher HCV-RNA titers and more severe fibrosis on liver biopsy compared with young subjects. Response rates in elderly persons correlated with lower HCV-RNA titers (72). Because older persons have more side effects and a lower response rate to interferon, therapy should be reserved for those persons with a low RNA titer, viral genotypes other than 1, and minimal fibrosis on biopsy (60).

2.4. Hepatitis E

Hepatitis E virus (HEV) is an enterically transmitted virus found in Africa, Asia, and Mexico. Attack rates of HEV are highest in persons ages 15-40, and mortality is high in pregnant women. Seroprevalence increases with age, reaching 70% in persons over age 60 living in endemic areas (60). No cases of HEV have been reported in the United States.

2.5. Hepatitis G

Hepatitis G virus (HGV) is a recently discovered novel agent belonging to the flavivirus family and is distantly related to HCV. The epidemiology and clinical significance of this HGV is still being defined, but it is felt to be a possible cause of the transfusion-associated hepatitis (73). The pattern of HGV seroprevalence is similar to HCV and increases with age, peaking in the sixties (60). In 105 elderly Italian persons with a mean age of 73, anti-HGV antibodies were found in 24%, and 3% were viremic. No subject had clinical evidence of hepatitis (73).

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