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 C

The incidence and prevalence of hepatitis C virus (HCV) infection continue to decline, particularly among younger individuals. In the United States, the prevalence of HCV infection in the general population is 1.6% but varies among different age groups with adults 40–49 years of age now having the highest seroprevalence (4.3%). Elderly individuals aged 60–69 and 70 years or older have lower prevalence rates (0.9% and 1%, respectively).[56,57] Data from a European study show that the proportion of individuals infected with HCV genotype 1 increases with age: 57% in adults aged <65 years, 72% in those 65–80 years of age, and 84% in adults older than 80 years of age.[58] Risk factors for HCV infection in older individuals include blood product transfusions before 1992, military service, injection drug use, tattoos, hemodialysis, and employment as a health care worker.[59] The true prevalence of HCV infection among elderly adults residing in nursing homes is largely unknown; however, data from a prospective cohort study including residents of three different nursing homes in St Louis, MO, USA demonstrated that the seroprevalence of anti-HCV antibodies is surprisingly high in this population (4.5%).[60] Importantly, adults older than 65 years of age more often present with complications of cirrhosis particularly hepatic failure and HCC as initial manifestations of HCV infection compared with younger individuals.[58] Older age at the time of initial infection is an important factor associated with more advanced fibrosis score, even after adjusting for sex, alcohol consumption, body mass index, HIV status, and diabetes.[58] Furthermore, progression to fibrosis may be more rapid when initial HCV infection occurs in older individuals, regardless of duration of infection.[58,61,62] For example, the median time to development of cirrhosis from infection was 33 years in individuals infected with HCV between 21 and 30 years of age compared with 16 years in individuals older than 40 years of age.[63] Elderly individuals with HCV-RNA viremia are also more likely to have normal ALT levels than younger adults (46% vs. 10.6%, respectively; Table 1).[64] Similarly, the prevalence of elevated ALT levels is comparable in individuals older and younger than 65 years of age despite an apparent greater prevalence of fibrosis in the former group as determined by serological markers of fibrosis (Fibrotest-Fibrosure and Actitest).[58] Although the use of serological markers of fibrosis in patients older than 80 years of age has not been validated, preliminary investigations suggest that the characteristics of these tests are not affected by older age. The use of these non-invasive serological tests for assessment of fibrosis may potentially be valuable in older populations particularly when ALT levels are normal, as up to one third of elderly adults may have significant fibrosis despite elevation of the ALT.[58]

The National Institute of Health consensus conference on hepatitis C identified elderly patients with chronic HCV infection as a difficult-to-treat group. Although current practice guidelines do not establish an upper age limit for antiviral therapy, elderly individuals with HCV infection are more likely to have contraindications to antiviral therapy than younger adults.[65] Typically, major clinical trials have excluded individuals older than 65 years of age and, in general, adults over the age of 60 have a higher prevalence of co-morbidities compared with younger individuals (38% vs. 18%, respectively), particularly cardiovascular, renal, pulmonary, and hematological diseases that often preclude anti-HCV therapy in this population.[66] This was demonstrated on a study of 208 Japanese patients naïve to antiviral therapy (predominantly genotype 1) who underwent treatment with interferon-α-2b and ribavirin for a total of 24 weeks. Patients were stratified by age (<50, 50–59, and >60 years). A significantly higher prevalence of systemic hypertension, impaired renal function, anemia, thrombocytopenia, and leukopenia was noted at baseline in the elderly group. Discontinuation of therapy or dose reductions were twice more common in the elderly (77%) than in younger adults (38%). Importantly, patient age and systemic hypertension were found to be independently associated with adherence to therapy.[66] However, elderly individuals are less likely to have other barriers to anti-HCV therapy such as substance abuse and psychiatric disorders.[67]

Older age is an independent factor associated with a lower likelihood of being considered for antiviral therapy. For example, treatment eligibility based on accepted guidelines is lower in elderly individuals compared with younger adults (16% vs. 26%, respectively).[66] Older adults are also less likely to accept antiviral treatment and discontinuation of therapy and dose reductions are more frequently required in this age group compared with younger adults.[67] For example, data from an observational study of 220 patients treated with interferon-α-2b and ribavirin demonstrated that discontinuation rates of ribavirin were significantly more frequent in the elderly compared with younger adults. Reasons for discontinuation of therapy were similar in both age groups and consisted mainly of anemia, constitutional symptoms (fatigue and anorexia), and depression.[67] In clinical practice, <15% of adults treated with interferon and ribavirin discontinue therapy; however, discontinuation rates have been reported to be as high as 30% and dose reductions are required in >70% of individuals aged 60 years or older within the first 12 weeks of therapy.[61,66] Despite these limitations, sustained virological response rates following combination therapy with standard interferon and ribavirin are similar in individuals older than 60 years of age and those younger than 60 years of age.[66,67] Results of treatment with pegylated interferon and ribavirin in elderly individuals are scarce. A pilot study of 33 patients naïve to treatment (mean age of 70.2 years) suggested lower sustained virological response rates with a pegylated interferon-based regimen in the elderly compared with younger adults (46% vs. 69.7%).[68] The proportion of patients developing side effects that led to discontinuation of therapy was twofold higher in elderly compared with younger adults (24.2% vs. 12.2%, respectively).[68]

Current practice guidelines recommend not withholding antiviral therapy based purely on advanced age but suggested that special attention should be paid to co-morbid conditions and tolerance for potential side effects.[69,70] Adverse effects typically resolve spontaneously within 2–3 weeks of discontinuing treatment; however, depression may take longer to resolve in the elderly compared with younger adults and often requires continuing pharmacotherapy.[71] Although the recently licensed direct acting antiviral agents (boceprevir and telaprevir) significantly increase sustained virological response, there are no data assessing the efficacy and/or toxicity of these drugs in elderly populations.[72,73,74]

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