American Gastroenterological Association
by Andrea E. Reid, MD. MPH
Since its discovery in 1989, hepatitis C virus (HCV) has emerged as one of the leading causes of chronic liver disease. Racial and ethnic disparities in HCV prevalence have been appreciated since its discovery. In the third National Health and Nutrition Examination survey (NHANES III), the prevalence of HCV in African Americans was 3.2 percent, compared to 2.1 percent in Mexican Americans and 1.5 percent in non-Hispanic whites.1 Almost 10 percent of African American males age 40 to 49 years had HCV. NHANES data from 1999 to 2002 showed smaller disparities in HCV prevalence. However, the HCV prevalence rate among African American men age 40 to 49 years and Mexican-American men age 50 to 59 years remained high at 13.4 percent and 10 percent, respectively.2 African-American women also had higher HCV prevalence than non-Hispanic white and Mexican-American women.
HCV prevalence in other Hispanic populations has not been investigated adequately, but evidence suggests that they may have higher HCV prevalence than non-Hispanic whites, and may progress to fibrosis and cirrhosis faster.3 Chronic liver disease, due predominately to HCV and/or alcohol, is the seventh leading cause of death among Hispanics, while it is the twelfth leading cause of death in other groups. The impact of this disparity on the health-care system is significant since Hispanics are the fastest-growing demographic in the U.S.
Native American/Alaskan Natives (NA/AN) are burdened disproportionately by chronic liver disease, however HCV prevalence in NA/AN is unknown. One study documented anti-HCV antibody in 28/243 (11.5 percent) of NA patients at a large urban clinic,4 while a study of pregnant NA women documented HCV infection in 3.1 percent. The actual prevalence of HCV in NA/AN probably lies between these numbers. HCV incidence is declining for all racial/ethnic groups, however, persistent racial and ethnic differences in chronic HCV, especially among people > 40 years, illuminate an important cohort effect that will persist as infected people age.
High HCV prevalence among African Americans and Hispanics translates into a substantial risk of HCV-associated cirrhosis, end-stage liver disease and hepatocellular carcinoma (HCC). A recent study documented a two- to three-fold higher incidence of HCC among African Americans and Hispanics compared to non-Hispanic whites. Much of the burden of HCC in minority populations is attributable to HCV.5
In order to prevent HCV-associated complications, we need treatment against HCV that is well tolerated and effective in most patients. Unfortunately, standard treatment for HCV — peginterferon and ribavirin — is neither. Treatment is effective in only 50 percent of patients infected with genotype 1 HCV, and African Americans and Hispanics may respond less to antiviral treatment than non-Hispanic whites. Furthermore, there are virtually no treatment data for NA/AN, as they are poorly represented in clinical trials. The Virahep-C study, a large study of African Americans and whites with genotype 1 HCV treated with peg-interferon α-2a and ribavirin, demonstrated a significantly lower sustained virologic response (SVR) rate in African Americans compared to whites (28 percent versus 52 percent).6 Inferior treatment response in African Americans has also been demonstrated with peg-interferon α-2b, and in patients with HCV genotypes two and three.
A recent study of white Hispanics with HCV suggests that they may not respond as well to antiviral treatment as non-Hispanic whites. The LATINO study demonstrated lower SVR to peginterferon and ribavirin in white Hispanics with genotype one HCV compared to non-Hispanic whites (34 percent versus 49 percent).7 However, the inclusion/exclusion criteria for this study were very narrow, and the study did not measure insulin resistance, which is prevalent in Hispanics and is associated with lower response to HCV treatment. Therefore, the LATINO study results may not apply to most HCV-infected Hispanics. Studies have shown that Hispanics are more likely than other groups to refuse treatment or to discontinue treatment prematurely. This impacts SVR and may increase the risk of HCV progression in Hispanics.
The big question remains: why don’t African Americans, and possibly Hispanics, respond to HCV treatment as well as whites? There are many theories but few answers. Racial and ethnic differences in intrinsic interferon signaling, HCV-specific T cell responses, viral kinetic response or cytokine production may play a role. Differences in body mass index, insulin resistance, steatosis, fibrosis and medication adherence have been examined, and racial and ethnic differences in these factors are insufficient to explain the inferior treatment response among African Americans and some Hispanic groups.
I am most intrigued by the recent identification of a genetic polymorphism near the IL28B gene, which encodes interferon-λ-3 and is associated with a two- to three-fold difference in treatment response among whites, African Americans and Hispanics.8 Investigators estimate that half the difference in SVR between populations can be explained by variable frequency of the CC genotype of IL28B. This genotype is found in higher frequency among whites and East Asians (groups that respond best to anti-HCV therapy) than among African Americans and Hispanics. This is a groundbreaking discovery that has the potential to change practice once a commercial test for IL28B is available. Such a test may identify patients who will respond best to antiviral therapy, and may help to identify novel targets for anti-HCV treatments.
We are on the cusp of elucidating the role(s) of race and ethnicity in HCV infection. Progress will be enhanced by well-designed clinical trials that recruit adequate numbers of racial and ethnic minorities. In the meantime, we should tell our minority patients that treatment for HCV is available, tolerable and sometimes successful; encourage their participation in clinical trials; educate our patients about the risk of HCV progression; and aggressively screen appropriate patients for HCC.
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2.Armstrong GL, Wasley A, Simard EP, et al. The Prevalence of Hepatitis C Virus Infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705-14.
3.Verma S, Bonacini M, Govindarajan S, et al. More advanced hepatic fibrosis in Hispanics with chronic hepatitis C infection: role of patient demographics, hepatic necroinflammation, and steatosis. Am J Gastroenterol 2006;101:1817-23.
4.Neumeister AS, Pilcher LE, Erickson JM, et al. Hepatitis-C prevalence in an urban Native-American clinic: a prospective screening study. J Natl Med Assoc 2007 Apr;99: 389-92.
5.Wong R, Corley DA. Racial and ethnic variations in hepatocellular carcinoma incidence within the United States. Am J Med 2008;121:525-31.
6.Conjeevaram HS, Fried MW, Jeffers LJ, et al. Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1. Gastroenterology 2006;131:470-7.
7.Rodriguez-Torres M, Jeffers LJ, Sheikh MY, et al. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med 2009; 360:257-67.
8.Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009;461:399-401.