Although the introduction of direct-acting antivirals (DAAs) transformed the treatment of hepatitis C virus (HCV), significant challenges in managing HCV infection in high-risk populations still remain.
A recent review article pointed out that “African Americans [AAs] in the US are twice as likely to be infected with HCV compared to the non-Hispanic-white US population (3% vs 1.5%).”1 AAs are also more likely to be infected with genotype 1 HCV, less likely to respond well to interferon-based therapies, and more likely to develop HCV-related complications such as hepatocellular carcinoma.1,2
A study examining HCV-associated all-cause mortality in the US population found that the mortality rate of Mexican Americans with chronic HCV was approximately 7 times higher than that in HCV-negative individuals.3 A different study conducted in a cohort on HCV-infected US veterans found that Hispanics with HCV had a significantly higher risk of developing cirrhosis and hepatocellular carcinoma than non-Hispanic whites.4
In an interview with Infectious Disease Advisor, Elana Rosenthal, MD, assistant professor of medicine at the Institute of Human Virology, University of Maryland School of Medicine in Baltimore, and Paul H. Naylor, PhD, adjunct associate professor at the Department of Internal Medicine/Gastroenterology, Wayne State University School of Medicine in Detroit, Michigan, discussed the latest insights on racial disparities in HCV incidence and treatment outcomes.
Infectious Disease Advisor: Which comorbidities increase the risk for mortality from HCV infection?
Elana Rosenthal, MD: Hepatitis C is an infection that can lead to chronic infection, cirrhosis, liver cancer, decompensated liver disease, and death; the natural history is such that this progression of liver disease occurs over decades, and not every patient develops morbidity and mortality associated with HCV. Mortality may be higher in patients whose progression of liver fibrosis is exacerbated by comorbidities such as HIV, HBV, diabetes, and obesity, as well as concomitant alcohol use; however, this progression can be interrupted by HCV eradication.
Infectious Disease Advisor: According to research to date, which group or groups of HCV-infected individuals are at highest risk for all-cause mortality resulting from HCV?
Dr Rosenthal: A recent study evaluated National Health and Nutrition Examination Survey data through 2011 and identified that Mexican-Americans with HCV had a significantly higher all-cause mortality compared with non-Hispanic blacks and non-Hispanic whites.3 It was postulated that this disparity may be related to higher risk for hepatocellular carcinoma in this population, or higher rates of lack of insurance. This highlights an important point: that in the era of direct-acting antivirals, the biggest risk for mortality lies in the inability to access curative therapy. In the United States, marginalized populations such as people who use drugs, incarcerated individuals, patients with limited insurance coverage, or those without medical insurance are most likely to suffer long-term consequences of hepatitis C, because they are the least likely to access HCV treatment.
Infectious Disease Advisor: What are some of the potential reasons for observed racial disparities in HCV treatment outcomes?
Dr Rosenthal: Historically, interferon-based therapy relied heavily on the host-immune response; therefore, AA patients were often less likely to achieve cure because of the underlying immune/genetic characteristics that were less effective at eradicating HCV. However, with the advent of DAAs, underlying immune characteristics and racial disparities in treatment efficacy are all but eliminated. There have been conflicting data regarding the efficacy of 8-week therapy with ledipasvir-sofosbuvir (LDV/SOF) in AA patients treated outside of clinical trials, leading the Infectious Diseases Society of America/the American Association of the Study of Liver Diseases to recommend against using LDV/SOF for 8 weeks in this patient population. However, given that AA patients are underrepresented in clinical trials, and real-world analyses often lack rigorous data on adherence and underlying host factors, it is hard to validate this finding or pinpoint a specific causation for this disparity.
Recently, Tang and coworkers5 reported high SVR among AA patients treated with 8 weeks of LDV/SOF in the Veterans Administration. Overall, data have overwhelmingly showed that race is no longer a factor in treatment outcomes, and that all patients achieve incredibly high rates of HCV cure as long as they complete the medication course.
Infectious Disease Advisor: How is the community of medical professionals and researchers addressing this problem?
Dr Rosenthal: To address racial disparities in HCV treatment, it is critical that efforts are made to improve access to approved therapies for marginalized populations; this includes continued development of short course treatments, which may be cheaper and easier to administer to high-risk populations such as people who inject drugs and incarcerated individuals. Medical professionals should participate in ongoing efforts to reinforce the need for universal access to HCV treatment and overturn nonevidence-based insurance restrictions, which often deny treatment to those with early fibrosis, people who use drugs or alcohol, and those without access to specialist providers. Last, to better understand and address disparities in treatment outcomes, it is imperative that clinical trials include minorities and women in early-phase studies. AA men are disproportionately affected by the HCV epidemic; however, they make up only a small minority of patients studied with DAAs. Embedding clinical trials in community-based settings can help facilitate this process.
Infectious Disease Advisor: In a review paper published recently in Hepatic Medicine: Evidence and Research, you analyzed data from published studies and medical records reporting treatment response of HCV-infected AA patients to a combination of LDV/SOF. What did you find?
Paul H. Naylor, PhD: We were excited to confirm in a real-world setting that AA patients treated with the new DAAs (eg, LDV/SOF) have a similar high response rate as non-AA patients. In view of the previous racial disparity in interferon-based treatment and the considerable adverse effects, these observations should provide an incentive for AA patients to seek treatment.
Infectious Disease Advisor: What are some of the reasons why interferon-based therapy is less effective in HCV-infected AAs than combination therapy with DAAs?
Dr Naylor: Although it is not completely understood why interferon-based therapies were less effective in HCV-infected AAs, it is most likely that different mechanisms of action account for the disparity. Interferon required the host immune response to act in concert with the antiviral activity, and genetic differences in the host immune response were most likely the reason for the lack of effectiveness in AA patients. The DAAs act directly on the virus and prevent its replication, thus stemming its growth directly. They do not rely on the immune response for their effectiveness, and thus, genetic differences between individuals are not likely to be relevant to virus clearance.
Infectious Disease Advisor: What types of studies still need to be conducted to learn more about racial disparities in HCV treatment outcomes and ways to address them?
Dr Naylor: The most pressing issues with respect to racial disparities reside in the medical system, rather than the patient. AA patients are less likely than Caucasians in the United States to be aware of new treatment opportunities and are also more likely to be seen in economically restricted medical treatment systems. For example, in many states, Medicare patients who are predominately AA were, and to varying extent still are, restricted in their access to DAA treatment. Also, as HCV is often described as a silent virus because its manifestation of disease often occurs when liver disease is acute, patients need to be screened and identified before significant disease development. Again, AA patients who are less likely to have access to medical care may not be screened. This is especially important because recent reports indicate that fewer than 15% of US patients in the recommended screening population (adults born between the years of 1946 and 1945) have been tested to determine their hepatitis C status.
- Naylor PH, Mutchnick M. Decreasing racial disparity with the combination of ledipasvir-sofosbuvir for the treatment of chronic hepatitis C. Hepat Med. 2017;9:13-16.
- Devhare PB, Steele R, Di Bisceglie AM, et al. Differential expression of microRNAs in hepatitis C virus-mediated liver disease between African Americans and Caucasians: Implications for racial health disparities. Gene Expr. 2017;17:89-98.
- Emmanuel B, Shardell MD, Tracy L, et al. Racial disparity in all-cause mortality among hepatitis C virus-infected individuals in a general US population, NHANES III. J Viral Hepat. 2017;24:380-388.
- El-Serag HB, Kramer J, Duan Z, Kanwal F. Racial differences in the progression to cirrhosis and hepatocellular carcinoma in HCV-infected veterans. Am J Gastroenterol. 2014;109:1427-1435.
- Tang L, Parker A, Flores Y, et al. Treatment of hepatitis C with 8 weeks of ledipasvir/sofosbuvir: Highly effective in a predominantly black male patient population [published online October 30, 2017]. J Viral Hepat. doi:10.1111/jvh.12796.