African American Patients with Hepatitis C Struggle with SVR

Jihane N. Benhammou, MD

African-American patients with hepatitis C (HCV) were significantly less likely to achieve sustained virologic response (SVR) after treatment with direct-acting antiviral (DAA) drugs than white patients, an analysis of data from a US Veterans Affairs healthcare center has found.

The findings indicate that these patients may need to be followed more closely post therapy, first author Jihane N. Benhammou, MD, told MD Magazine.

The odds of reaching SVR-12, or undetectable HCV RNA 12 weeks after therapy ends, were 57% less for African-Americans in the retrospective study, the researchers reported. Advanced fibrosis was also an important predictor of failure to achieve SVR.

“The study findings highlight the importance of ethnic and racial diversity when designing and conducting clinical trials, which has lacked in prospective direct-acting antiviral trials,’’ Benhammou said.

Benhammou and a team from the University of California, Los Angeles, set out to compare the SVR rates among HCV patients treated with DAAs in 5 racial/ethnic categories: non-Hispanic white, non-Hispanic black (African-Americans), Hispanic, Asian, and unknown/other.

“Historically, race has played a major role in chronic hepatitis C rates and treatment responses, with African-Americans being disproportionately affected,’’ the researchers wrote.

That has been due in part to differences in immune responses, previous studies have suggested. African-Americans are more likely to harbor the non-CC interleukin IL28B genotype. This affected their response to pegylated interferon, the therapy widely used before the advent of DAAs, the researchers wrote.

To determine whether race or ethnicity would be factors in the DAA era, the team reviewed data on 1068 mostly male patients treated at the VA Greater Los Angeles Healthcare System from 2014 to 2016.

White people and African-Americans were equally represented at 37.8% of the population. Among all of the patients studied, 35.4% had advanced liver disease. The majority — 79.5% — were treatment naïve at the time DAAs were administered.

The most common therapy was a regimen of sofosbuvir/ledipasvir (Harvoni) with and without ribavirin. Almost half (47.8%) received this treatment. Older antiviral regimens such as sofosbuvir/simeprevir (Sovaldi; Olysio); sofosbuvir/simeprevir with and without ribavirin; and sofosbuvir/ribavirin were also tracked.

The results were adjusted for age, HCV genotype, human immunodeficiency virus (HIV) status, body mass and other factors.

“In our cohort, the lower SVR rates observed in African-Americans relative to white people is persistent despite at least 12 weeks of therapy, even when only using current ‘optimal’ therapies,’ researchers wrote.

Benhammou noted potential differences in how a patient metabolizes medications may be the reason for the disparity.

“Drug metabolism through the liver is driven by the cytochrome P450 enzyme,’’ she said. “Differences in the function of these enzymes could affect how DAAs are metabolized and therefore how available the drug is to kill the virus.’’

To determine if African-Americans have different ways of metabolizing medications, the patients’ genes would need to be studied as would drug levels in their blood. Other factors that might cause differences include whether the genotype of the virus being studied affect how the DAAs work and whether a patient is taking the medication as prescribed.

Benhammou said her team considered the Medical Procession Ratio (MPR), which is used in pharmacology research to control for adherence.

“Adherence is not a concern in well-designed clinical trials and adherence trends are generally identified in real world effectiveness data,’’ she said.

Though adherence seemed to attenuate some of the SVR12 differences, researchers continued to see a lower rate based on the adjusted odds ratios, indicating a possible underlying biological etiology.

Benhammou said the team had 2 main goals for this study and future investigations.

“We hope to not only bring awareness to clinicians taking care of similar patient populations, but also stimulate research on why this is occurring,” she said.

The study, "Race affects SVR12 in a large and ethnically diverse hepatitis C‐infected patient population following treatment with direct‐acting antivirals: Analysis of a single‐center Department of Veterans Affairs cohort," was published online in the British Journal of Pharmacology last month.