HCV in Older Adults: Effects of Prolonged Infection, Aging-Related Mechanisms, and Treatment

More than 4 million people have been exposed to hepatitis C virus (HCV) in the United States.¹ Although the rate of new HCV infections has decreased in recent decades because of improved blood screening measures and other efforts, the number of HCV-infected older adults with long-term infection has increased.

Approximately three-fourths of US adults with chronic HCV infection “were born between 1945 and 1964, and most were infected between 1970 and 1990 when the incidence of new HCV infections peaked,” according the authors of a paper published in Infectious Disease Clinics of North America.² The estimated prevalence of HCV antibody in this “baby boomer” cohort is 3.25% (95% CI, 2.8%0-3.76%), or more than twice that of the general US population.³

Effects of Prolonged Infection

As the duration of infection has increased in this patient group, the incidence of HCV-associated liver disease and its sequalae has also increased. Although treatment has vastly improved since the introduction of direct-acting antiviral (DAA) agents in 2011, there is a dearth of information pertaining to treatment effects and other outcomes in older patients with HCV. Reid et al reviewed the available literature regarding HCV infection and treatment in this population.

In a retrospective cohort study published in 2016 (n = 161,744), HCV-infected US veterans older than 65 years were compared with those aged 20 to 49 years.⁴ After adjusting for various metabolic factors, the older group showed a greater risk for hepatocellular carcinoma, cirrhosis, and death from all causes (2.44, 1.14, and 2.09, respectively). The increased risk in older patients is likely primarily the result of a longer duration of infection, which has been linked to elevated risk for hepatocellular carcinoma and predicts more rapid progression to cirrhosis.^5,6

Aging-Related Mechanisms

However, other findings suggest that “older age independent of duration of HCV infection may also play a role in the progression of HCV-associated liver disease,” Reid et al noted. “Aging-related mechanisms that have been postulated to increase the risk of liver disease outcomes in the setting of HCV infection include a greater vulnerability to environmental factors, such as oxidative stress, with increasing age; reduction in the rate of hepatic flow; reduced mitochondrial capacity; impaired immunity; and increased carcinogenic potential caused by a reduced ability to repair DNA.”^7,8 In a study of patients who acquired infection during transfusion, those aged 50 years or older at the time of infection developed hepatocellular carcinoma in 15 years (mean) vs 32 years among those who were younger than 50 years at the time of infection.⁶

Reid et al stated that, “HCV infection is a chronic inflammatory process leading to not only hepatic inflammation but also persistent systemic inflammation, which has been associated with extrahepatic outcomes that are also common with aging.” In addition to a greater risk for liver cancers, a study of adults ≥65 years linked HCV infection to increased risk for intrahepatic (adjusted odds ratio [aOR], 3.40) and extrahepatic (aOR, 1.90) bile duct cancer, anal cancer (aOR, 1.97), myelodysplastic syndrome (aOR, 1.56), pancreatic cancer (aOR, 1.23), nonmelanoma nonepithelial skin cancer (aOR, 1.53), and diffuse large B-cell lymphoma (aOR, 1.57).⁹ Other research indicates an increased risk for diabetes, kidney disease, cardiovascular disease, and neuropsychological and neurocognitive impairment among older HCV-infected adults.

Reid et al also examined results of the limited studies that have investigated outcomes of DAAs in older patients, and they concluded that efficacy and safety are generally similar between older and younger patients.^10,11

For additional insight into this topic, Infectious Disease Advisor interviewed 1 of the coauthors of the review, Phyllis Tien, MD, a professor of medicine in the Division of Infectious Diseases at the University of California, San Francisco, and a staff physician at the San Francisco Veterans Affairs Medical Center, as well as Morgan Katz, MD, MHS, an assistant professor of medicine in the Division of Infectious Diseases at The Johns Hopkins University School of Medicine in Baltimore, Maryland.

Infectious Disease Advisor: Why is HCV infection of particular concern in older adults?

Dr Tien: The association of HCV infection with the development of liver disease has been the primary focus of HCV care, but HCV is also associated with clinical outcomes that are outside the liver, such as cardiovascular disease, kidney injury, diabetes, and loss of bone mineral density. These clinical outcomes are more common as we age, and the presence of HCV infection may further accelerate their development.

Dr Katz: Older adults make up the majority of the population with hepatitis C in the United States today. The Infectious Diseases Society of America now recommends 1-time screening for all adults born between 1945 and 1965. The leading edge of this baby boomer cohort are now in their late 60s and early 70s, so older adults are our target population for treatment.

Older adults are particularly at risk of suffering from more severe chronic effects of hepatitis C. They are not only more likely to develop advanced cirrhosis and hepatocellular carcinoma than their younger counterparts but also have been found to suffer worse extrahepatic manifestations of the disease, including depression and fatigue.

Infectious Disease Advisor: What are some top takeaways regarding treatment of this population?

Dr Tien: HCV is often asymptomatic at the time of infection, and people are not diagnosed until years later, when elevated liver enzymes on routine labs prompt checking HCV serologies. So, the first key point, as per recent CDC guidelines, is that patients who do not have risk factors for HCV infection, such as current or past injection drug use, blood transfusion, or organ transplant recipient, and who were born in the baby boomer years (1945-1965), should be tested for HCV antibodies. 

Second, if a person is found to have chronic HCV infection, there are now treatments that can cure HCV in the majority of people with chronic infection who complete a course of HCV treatment. The current medications to treat HCV are pills that are taken by mouth, unlike old regimens that required a weekly injection plus pills, for as short as 8 weeks, depending on the type of HCV infection and the severity of HCV-related liver disease.

Dr Katz: Given the high (nearly 100%) clinical response rates and relatively low adverse effect profile of new drug therapies for HCV, older adults should be evaluated for treatment, and this should be pursued unless there is a significant reason not to treat, such as severe comorbid disease or significant drug-drug interactions, or if their anticipated life span is less than 1 year.

We need to start the conversation and define more clear guidelines about who will benefit from treatment, as limited resources and high costs of therapy are going to make universal treatment very challenging. This will be an issue particularly in long-term care facilities, as most of these facilities are under capitation plans, which include total drug costs. Under these plans, there will be considerable pressure to decline therapy to residents who may actually warrant treatment.

Infectious Disease Advisor: What should be the focus of future research in this area?

Dr Tien: Future studies should focus on whether HCV cure also improves clinical outcomes such as cardiovascular disease, diabetes, kidney injury, and bone mineral density loss.

Dr Katz: Research specifically addressing the cost-effectiveness of treatment with new DAA therapy for the older population is going to be very important. Most of the current research testing DAA outcomes is focused on younger individuals with few comorbidities, which is not our target population. We have been extrapolating outcomes for older adults using subgroup analyses of these studies, but dedicated research in this field is necessary to help clinicians decide whether it is beneficial to pursue therapy in patients who may have a more limited life expectancy.

References

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2. Reid M, Price JC, Tien PC. Hepatitis C virus infection in the older patient. Infect Dis Clin North Am. 2017;31:827-838.
3. Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rep. 2012;61(RR-4):1-32.
4. El-Serag HB, Kramer J, Duan Z, Kanwal F. Epidemiology and outcomes of hepatitis C infection in elderly US Veterans. J Viral Hepat. 2016;23:687-696.
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7. Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J. Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol. 2001;34:730-739.
8. Horiike N, Masumoto T, Nakanishi K, et al. Interferon therapy for patients more than 60 years of age with chronic hepatitis C. J Gastroenterol Hepatol. 1995;10:246-249.
9. Mahale P, Torres HA, Kramer JR, et al. Hepatitis C virus infection and the risk of cancer among elderly US adults: a registry-based case-control study. Cancer. 2017;123:1202-1211.
10. Saab S, Park SH, Mizokami M, et al. Safety and efficacy of ledipasvir/sofosbuvir for the treatment of genotype 1 hepatitis C in subjects aged 65 years or older. Hepatology. 2016; 63:1112-1119.
11. Su F, Beste LA, Green PK, Berry K, Ioannou GN. Direct-acting antivirals are effective for chronic hepatitis C treatment in elderly patients: a real-world study of 17 487 patients. Eur J Gastroenterol Hepatol. 2017;29:686-693.