Viral Hepatitis in the Elderly

Andres F Carrion MD; Paul Martin MD; FACG

Disclosures

Am J Gastroenterol. 2012;107(5):691-697. 

In This Article

Hepatitis B

The NHANES III indicated that the prevalence of chronic hepatitis B virus (HBV) infection, defined in that cohort as detectable total anti-hepatitis B-core antibody and hepatitis B surface antigen (HBsAg), is 0.42% in the United States. Adults older than 50 years of age have on average a 1.5 to twofold higher prevalence of this infection across different ethnic groups compared with younger individuals.[27] The NHANES (1999–2006) showed an overall seroprevalence of past/present HBV infection in the United States of 4.7% (defined as positive total anti-hepatitis B-core). These data also show marked variations of the seroprevalence of the disease among different age groups with adults aged ≥50 having a 1.7 and 12.8 times higher seroprevalence of past/present infection than individuals aged 20–49 and 6–19 years, respectively. When compared with the prior NHANES survey (1988–1994), there was a significant decrease in the seroprevalence of past/present HBV infection in younger individuals but elderly adults had a non-significant increase.[28] Furthermore, there was a non-significant decrease in the seroprevalence of chronic HBV infection in all age groups when data from both surveys were compared.[28] Importantly, these surveys exclude the incarcerated, homeless, institutionalized, and recent immigrants; therefore, the seroprevalence estimates of past/present and chronic HBV infection are likely to be underestimated.[29] As expected foreign-born individuals living in the United States have a 4.4 higher prevalence of HBV infection compared with US born individuals.[27]

Clinical manifestations of acute HBV infection in the elderly may be different than in younger adults. During an outbreak of acute HBV in elderly nursing home residents, most infected individuals were asymptomatic with only a few presenting with jaundice and non-specific symptoms such as anorexia, nausea, and vomiting. No fatalities or individuals requiring hospitalization were reported during the outbreak.[30]

The natural course of chronic HBV infection is determined by multiple variables including age.[31] The risk of progression to chronic hepatitis B is inversely related to age at the time of infection. For example, progression to chronic hepatitis B has been reported in >90% of infants, 25–50% of children aged 1–5 years, and <5% of older children and young adults following an episode of acute HBV infection.[30] However, the rate of progression to chronic hepatitis B is higher in elderly individuals than in younger adults. Data from an outbreak of acute HBV infection in a nursing home in Japan showed that 59% of patients older than 65 years of age developed chronic infection.[30] The rate of spontaneous HBsAg seroclearance is also different in younger and elderly adults with chronic HBV infection. Individuals older than 60 years of age have a greater than twofold and 1.75 higher rates of cumulative HBsAg seroclearance compared with adults aged 40–49 years and 50–59 years, respectively (adjusted for several variables such as sex, baseline HBV-DNA level, baseline alanine aminotransferase (ALT) level, ethnicity, and body mass index). Importantly, this difference is even more pronounced when elderly and younger adults with HBV-DNA levels >10,000 copies/ml are compared.[32] Elderly individuals with acute HBV infection have similar rates of hepatitis B e antigen (HBeAg) positivity as younger adults (~77% for both groups) but significantly lower rates of antibodies to hepatitis e antigen (5.5% vs. 18.6%, respectively).[33] Among individuals with chronic HBV infection, the prevalence of HBeAg is inversely related to the patient's age. For example, adults older than 60 years of age have a fourfold higher prevalence of HBeAg compared with younger individuals aged 30–39 years.[34] No correlation was found between patient age and HBV precore mutant/total HBV ratio in one study including individuals aged 18–52 years.[35] With respect to HBV-DNA levels in patients naïve to treatment, age older than 40 years was associated with a 2.5 higher odds of serum HBV-DNA levels >108 copies/ml in a multicenter cross-sectional study from the United States (mainly HBV genotypes A, B, C, and a small proportion of genotypes D, E, F, and G). Patients with wild-type and variant precore/core promoter sequences were comparable in age.[36] However, data from a large Asian cohort show that adults older than 60 years of age infected with HBV genotypes B and C have lower HBV-DNA levels compared with individuals aged 30–59 years (HBeAg positive and negative). This difference persisted when only HBeAg-negative younger and elderly individuals were compared.[31] Additional data from the same Asian cohort demonstrate that progression to cirrhosis is mainly correlated with HBV-DNA levels but older age and male sex are also important risk factors.[37]

Therapeutic options for HBV have greatly expanded since the mid-1990s with the introduction of oral therapies. Clinical trials showed equivalent therapeutic efficacy of standard and pegylated interferons in the elderly compared with younger adults.[38] Lamivudine was also equally effective in individuals younger and older than 60 years of age as evidenced by response to therapy, loss of HBV-DNA, and development of viral resistance.[39] Unfortunately, the use of lamivudine is limited by the high rate of development of resistant mutants. Anti-HBV therapy with newer nucleoside or nucleotide analogs (tenofovir, entecavir, and adefovir) is associated with high rates of recurrence after treatment is stopped; therefore, most individuals require long-term therapy with these drugs.[40] Interferon-based therapy may also be effective; however, virologic relapse is more frequent in the elderly (defined as reappearance of HBV-DNA and/or HBeAg).[41]

Vaccination against HBV is recommended in elderly individuals at risk for infection, including all nursing home residents because of the higher risk of transmission of HBV in these facilities.[42] Nursing home residence is associated with an increased risk for HBV infection due to breaches in standard precautions and cross-contamination with blood and other body fluids. Therefore, HBV immunization should also be recommended for care providers at these institutions.[42] The prevalence of HBsAg has been reported to be higher in nursing home residents compared with non-institutionalized populations in the same geographic area.[42] Normal aging is associated with a decline in immune function; therefore, elderly individuals have an attenuated immune response to HBV vaccination compared with younger adults (70% vs. 98%, respectively).[43] The major factor implicated is T-cell dysfunction in elderly adults. Supporting this hypothesis, in vitro studies have demonstrated that production of antibodies against HBsAg is normal when T cells from young individuals are added to serum from older adults.[43] Furthermore, aging is also associated with a decreased number of T cells. In an attempt to overcome this disadvantage, particularly the quantitative deficiency of T cells, growth factors (i.e., granulocyte-monocyte colony stimulating factor) have been used as an adjuvant to enhance vaccine-induced seroprotection in elderly individuals.[44] However, a pilot trial evaluating this intervention did not show a clinically significant effect on immune response in healthy elderly individuals following HBV immunization.[45]

HCC is a major complication of chronic HBV infection. Older age is a predictor for development of HCC in patients with chronic hepatitis B by increasing the risk of this neoplasm by a 2.7 increment with every decade of life.[46,47] Therefore, age is a factor in determining initiation of surveillance for HCC in patients with chronic HBV infection but current guidelines only provide age-specific recommendations for HCC surveillance in hepatitis B carriers of Asian ethnicity (men >40 years of age and women >50 years of age).[48] Spontaneous annual seroclearance rates of HBsAg are higher in older adults compared with younger individuals; however, HBsAg seroclearance (either spontaneous or as a result of antiviral therapy) does not eliminate the risk of HCC.[32,49] Furthermore, recent data suggest that HBsAg seroclearance after 45–50 years of age is associated with higher incidence of HCC compared with seroclearance at a younger age. The increased incidence of HCC in patients with "late" HBsAg seroclearance may reflect the oncogenic nature of HBV.[50]

Reactivation of HBV infection with elevated HBV-DNA and ALT levels may occur in up to 50% of HBV-infected individuals following immunosuppressive chemotherapy.[48] Although the majority of cases of HBV reactivation in this setting are asymptomatic, fatal hepatic decompensation is well recognized.[51] Reactivation of HBV in patients receiving antineoplastic chemotherapy typically results in interruption of treatment with reduced antineoplastic efficacy.[52] However, data from prospective studies suggest that older adults receiving antineoplastic chemotherapy are at lower risk for HBV reactivation compared with younger individuals.[51,53] Rituximab and systemic corticosteroids, two key agents in the treatment of lymphoid neoplasms, which occur more commonly in younger adults, have been associated with a higher risk of HBV reactivation.[54,55] Current recommendations for testing for HBsAg and anti-hepatitis B-core in individuals at risk for HBV infection before initiation of immunosuppressive chemotherapy are not different for younger and elderly adults.[48] Prophylactic use of antiviral agents in HBV carriers regardless of age is indicated if immunosuppressive therapy is to be initiated: lamivudine or telbivudine if the anticipated duration of treatment is ≤12 months, and tenofovir or entecavir if longer treatment is anticipated.[48]

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