Narrowing the Gap: Cause for Optimism for Racial Minorities with HCV in the US

Historically, racial minorities with HCV in the United States have fared worse than their white counterparts. Metrics ranging from screening rates to treatment outcomes were poorer in racial and ethnic minority patients compared with white patients. Of course it’s not just a black and white issue. The diversity of the U.S. population has presented the clinical community with a lifetime of challenges in sorting out the various causes and effects along the continuum of HCV care. Each race or ethnic group — blacks, Hispanics, Asians, Native Americans and other nonwhite groups — faces its own unique obstacles. Some of those groups experience lower rates of screening or diagnosis while others have difficulty acquiring health insurance coverage and, hence, treatment or achieving SVR. Moreover, determining where racial barriers end and socioeconomic barriers begin has confounded researchers for decades.

In spite of all these hurdles, there is a great deal of hope among clinicians who deal with HCV. And that hope can be summed up in three words: direct-acting antiviral.

“What we found was with the advent of these new agents, treatment outcomes have improved substantially, across the board,” Sammy Saab, MD, MPH, professor of Medicine and Surgery, assistant professor of nursing and head of Outcomes Research in Hepatology at the David Geffen School of Medicine at UCLA, told HCV Next in an interview. “These new agents have become a great equalizer in terms of efficacy rates. All groups are responding equally well. In many ways, there are no more special populations whose cure rates are low.”

But there are still obstacles, largely in the form of limited access to care and lack of adequate health insurance. Untangling the myriad factors and the places where the racial groups overlap is difficult, so perhaps it is best to break it down in terms of the challenges faced by each individual group.

Finally Looking Up for Black Patients

For Saab, the obstructions that confront black patients are something of a microcosm of the stumbling blocks faced by all groups. “One of the biggest problems in HCV care in general is simply knowing who is infected,” he said. “In that, blacks are at a disadvantage. One of the biggest hindrances to curing HCV is understanding who is infected.”

One of the reasons for this has to do with lower economic status, which, in turn, leads to lower rates of health insurance coverage. Patients who are not insured do not get screened, and, therefore, are not on the radar or in the system. “Lower socioeconomic status is related to poor screening rates,” Saab said.

An additional concern is that this lack of access to care can put these groups at risk for diabetes, hypertension and other chronic and nonchronic conditions. “As a result, HCV care frequently takes a back seat,” Saab said.

Robert J. Wong, MD, MS, director of Research and Education in the Division of Gastroenterology and Hepatology at Alameda Health System’s Highland Hospital and assistant clinical professor of medicine at the University of California, San Francisco, said that evidence has shown high rates of HCV recurrence among black patients. “It is not clear why we see higher rates of HCV recurrence after liver transplantation among black patients,” he said.

Knowledge of new HCV drugs — or lack thereof — is yet another concern, particularly among black patients who fared poorly on interferon-based regimens and may be reluctant to take another chance at treatment. But the DAA era may be changing all of that.

Anthony Michaels, MD, internal medicine specialist in gastroenterology, hepatology and nutrition at The Ohio State University Wexner Medical Center, addressed this shift. “SVR rates were lower among ethnic minorities because the response to interferon was lower, particularly among African-Americans,” he said. “That gap, as far as achieving SVR, has essentially closed.”

Wong agreed. “This is a very exciting time,” he said. “In clinical trials for these drugs, there doesn’t seem to be an ethnic disparity in response.”

Data from Saab and colleagues support this. They noted that despite slower progression to fibrosis, hepatocellular carcinoma and mortality are higher among black patients than other ethnic groups. Further evidence suggests that poor SVR rates could be attributed to both viral and host factors, and that this particular group has had low enrollment rates in clinical trials. “Nevertheless, the gap in SVR between African-Americans and Caucasians may be narrowing with the use of direct-acting agents,” they wrote. “Gastroenterologists, hepatologists, primary care physicians, and other health care providers need to address modifiable risk factors that affect the natural history, as well as treatment outcomes, for HCV among African-Americans. Efforts need to be made to improve awareness among health care providers to address the differences in screening and referral patterns for African-Americans.”

That said, there are still hurdles to clear. In a 2006 study, Merriman and colleagues investigated a VA cohort of 265 patients with HIV/HCV co-infection, 251 patients with HCV mono-infection and 227 patients with HIV mono-infection, to determine the impact of viral co-infections and race on HCV outcomes. HIV/HCV co-infection yielded increases in liver function abnormalities and death compared with mono-infection with HCV or HIV. In the co-infected group, black patients experienced significantly higher mortality than white patients, 31% vs. 15% (P = .011). However, no such racial disparity in mortality was observed for mono-infected patients. “We demonstrated a racial disparity in survival of HCV/HIV-coinfected patients that needs further investigation,” the researchers concluded. Further study is also needed to determine whether this disparity persists among co-infected black patients today.

Poorer Outcomes in Hispanic Populations

Hashem B. El-Serag, MD, MPH, professor of medicine, chief of gastroenterology and hepatology at the Houston VA Medical Center and Baylor College of Medicine, and colleagues gathered data from the national VA HCV Clinical Case Registry to determine the impact of race on cirrhosis and HCC risk. They accounted for demographic, clinical and virological factors among patients identified between 2000 and 2009. The study included 149,407 eligible patients with at least 1 year of follow-up with the VA.

The cohort was 56.3% non-Hispanic white, 36.1% black, 6% Hispanic and 1.6% in other racial groups. The analysis included 13,099 patients with cirrhosis and 3,551 with HCC. The highest rates of cirrhosis were among Hispanic patients, at 28.8%. Hispanic patients also had the highest rates of HCC, at 7.8%. The lowest rates of these two complications were reported among black patients. Hispanic patients had the highest rate of HIV co-infection, followed by non-Hispanic white patients and black patients. Obesity was more frequent in the Hispanic group, while both black and Hispanic patients had nearly double the rate of diabetes reported in white patients. An absence of antiviral therapy was most likely to be reported among black patients, at 89.6%.

Adjusted analysis results indicated that the likelihood of cirrhosis persisted among Hispanic patients compared with non-Hispanic white patients (adjusted HR = 1.28; 95% CI, 1.21-1.37), as did the risk for HCC (HR = 1.61; 95% CI, 1.44-1.80). Conversely, black patients were less likely to have cirrhosis (HR = 0.58; 95% CI, 0.55-0.60) and HCC (HR = 0.77; 95% CI, 0.71-0.83) compared with non-Hispanic white patients, according to the results.

“Some of the possible reasons Hispanics experienced these outcomes include higher likelihood of abdominal obesity and greater risk of insulin resistance and diabetes,” El-Serag said. “All are risk factors for liver disease.”

El-Serag added that it is possible that alcohol use is higher among Hispanics. “There may also be genetic differences, similar to what was found in the case of fatty liver disease, where Hispanics are more likely to carry the unfavorable gene form of PNPLA3,” he said.

That said, he noted that white patients tend to have higher abdominal obesity, pound for pound, than black patients. “Abdominal obesity is associated with hepatic steatosis,” he said. “It is noteworthy that similar findings were reported for fatty liver disease-related damage which was lower in blacks than whites.”

Saab added that the language barrier may be a hindrance to Hispanic patients, from knowledge of the disease to treatment adherence, while Wong stressed that lower rates of insurance coverage in this group are also a contributing factor.

Disparities Among Asian, Native American Populations

In a study published in Clinical Medicine Insights: Gastroenterology, Lee and colleagues suggested that Vietnamese Americans are at an increased risk for HCV. Vietnamese American men, in particular, carry a high risk for associated liver cancer. The researchers aimed to determine whether an education intervention could improve knowledge about HCV among Vietnamese Americans. The study included 306 participants assessed with a test about HCV knowledge during 2010 and 2011.

The average pretest score was 3.32 out of 10, compared with a post-test score of 5.88. Adjusted analysis results indicated that age and higher education were positively associated with a higher pretest score. However, participants with a physician who spoke English or Vietnamese carried a negative association with higher pretest scores. Household income, education level and having a family member with HCV were significantly associated with increased knowledge of the disease.

“Promotion and development of HCV educational programs can increase HCV knowledge among race and ethnic groups, such as Vietnamese Americans,” the researchers concluded. “Giving timely information to at-risk groups provides the opportunity to correct misconceptions, decrease HCV risk behaviors and encourage testing that might improve timely HCV diagnosis and treatment.”

“We see a lot of genotype 6 disease among patients from Southeast Asia,” Wong said. “Of course there are still disparities in these groups, but the good news is that we are seeing good, consistent responses across ethnic groups and genotypes with the new DAAs. They are leveling the playing field.”

Unfortunately, this may not be true for all population groups. Hossain and colleagues investigated challenges to HCV treatment in a population of Native Americans treated at two facilities in North Dakota. They wrote that HCV prevalence is higher in indigenous populations than in nonindigenous populations, and that HCV is an important cause of chronic liver disease in American Indians or Alaska Natives. In the current retrospective study, they aimed to compare outcomes for indigenous patients with a cohort of white patients.

Of 124 American Indian/Alaska Native patients in the study, only 18% were treated. Lack of access to specialists was the main reason for lack of treatment, along with concomitant or decompensated liver disease, alcohol and drug abuse and cost of therapy, according to the findings. White patients and American Indian/Alaska Native patients had similar baseline characteristics and predictors of SVR. “Most [American Indian/Alaska Native] patients with HCV infection do not receive treatment despite comparable treatment response rates to Caucasians,” the researchers concluded. “Further population-based studies addressing access to specialized hepatitis C treatment and public health concerns are warranted, as it is crucial to treat chronic HCV infection to decrease the burden of disease in the [American Indian/Alaska Native] community.”

Insurance Coverage

In general terms, health insurance coverage is lower across ethnic minorities than in white patients. “The majority of the minority patients that we see have insurance,” Michaels said. “But over half usually have a government-assisted program. We see a fair proportion of African-American patients covered with government programs.”

Most experts lament that the biggest challenge in HCV today is not treating the patients, but securing insurance coverage of the medications. “So many of our patients have dotted their i’s and crossed their t’s and followed up with us, but patients can still be denied coverage,” Michaels said. “We have a pharmacy clinic in-house, and this helps us get the drugs approved. We state our case with insurance companies, but it takes time and effort.”

An additional concern, from a public health perspective, is that Medicare and Medicaid do not allow clinicians to treat early disease. “If the patient doesn’t have late-stage disease, we state our case,” Michaels said. “We look for assistance programs like the one Gilead was offering, but that’s closed now. With Abbvie and other companies in play, we are hoping that there will be more access, but that remains to be seen.”

The good news is that prices have come down, and likely will come down further, albeit slowly. “Eventually insurance companies are going to have to accept earlier-stage patients,” Michaels said.

El-Serag stressed that rates of treatment were significantly lower in Hispanic and black patients in the pre-DAA era. “It is known that patients with HCV are more likely to be un- or underinsured than patients without HCV,” he said. “This is likely to translate to lower receipt of expensive DAAs. However, in health care systems such as the VA, one would expect equal opportunity for treatment. Nevertheless, early DAA data demonstrate that similar racial discrepancy exists.”

Saab put the issue of health insurance coverage into more general terms. “Most Medicare and Medicaid patients are indigent,” he said. “If we think about the type of insurance as a surrogate marker for ethnicity, then there is clearly a racial disparity.”

From Screening to Adherence

For El-Serag, the recommendation for universal screening among the baby boomer birth cohort has the potential to accomplish the dual goals of raising awareness and bringing patients into care. “The difcult question, though, is how birth cohort screening should be implemented,” he said. “Several strategies have met variable success; these include electronic health record reminders, testing in hospitalized patients, and those who come to the emergency department.”

Identifying the disease, however, is of little utility unless patients are then linked to a provider who can appropriately evaluate and treat HCV infection, according to El-Serag. “There, racial disparities still exist,” he said. “It is too early to tell whether universal testing has resulted in change in outcomes, given its recent introduction and very spotty application. In general, insured patients tend to be screened more, as do patients in integrated health care systems such as the VA.”

Michaels acknowledged that there is considerably more awareness of HCV, across the board. “Many of our patients are fairly well educated now,” he said. “The recommendations have contributed to this, as have the advertisements for Harvoni on TV. They come to us knowing what they want. There are, of course, patients who don’t know much about the disease or therapies, but the patients in that category may be black or white.”

There are also few disparities in terms of patient adherence, at least as far as Michaels has experienced. “When we consider someone for treatment, we try to assess compliance,” he said. “We never start treatment the first day. We have a pharmacy clinic that the patients attend that helps us with drug approval. Once they demonstrate that they are going to be compliant with our process, then we tend to see high compliance rates while on antiviral therapy.”

In the Transplant Setting

Wong and Ahmed investigated and aimed to assess race- and ethnicity-specific and etiology-specific factors contributing to survival outcomes among black patients undergoing liver transplantation in the U.S. They suggested that HCV recurrence occurs more frequently in black patients, along with lower response rates to interferon-containing regimens, and these factors may be associated with poor transplantation outcomes.

The study included data from the United Network for Organ Sharing registry from 2002 through 2012. Patients had HCV, HCC, alcoholic liver disease, nonalcoholic steatohepatitis and cryptogenic cirrhosis. During the study period, HCV was the leading indication for transplantation, according to the results.

Black patients comprised 9.5% of indications for liver transplantation in the study. However, they had the lowest overall and etiology-specific rates of survival 5 years after transplantation. Multivariate analysis results indicated that black patients had significantly lower survival after transplantation compared with non-Hispanic white patients with HCV (HR = 1.3; 95% CI, 1.19-1.41), HCC (HR = 1.49; 95% CI, 1.25-1.79) and alcoholic liver disease (HR = 1.52; 95% CI, 1.19-1.94).

“Race/ethnicity and the etiology of chronic liver disease were observed to have a combined detrimental effect, leading to lower survival following [liver transplantation] in African-Americans,” the researchers concluded.

“Even when we corrected for the etiology of the disease, and even just looking at HCV, blacks had higher post-transplant mortality by almost 30%,” Wong said. “It was difficult to specifically pull out reasons why they had such poor survival rates.”

Based on other prior literature and similar studies conducted by Wong, there may be a few potential reasons for this difference in outcomes. “One, several studies show that blacks are referred for transplantation much later than white patients,” Wong said. “In this case, these patients will have more advanced liver disease and potentially more complications when they arrive, which, in turn, contributes to higher rates of peri-operative and postoperative complications.”

Another potential reason is that there is a much higher rate of HCV recurrence among black patients, according to Wong. “That factor, in and of itself, may contribute to higher rates of post-transplantation mortality among blacks with HCV,” he said. “Post-transplant HCV recurrence can lead to more aggressive disease progression.”

Further reason for the disparity in transplantation outcomes goes back to the days of interferon-based therapies. “Traditionally, those therapies were less effective in black patients,” Wong said. “They fared poorly in the pre- and post-transplant setting because of interferon, but the current era of DAAs hold great promise in limiting ethnicity-specific disparities in HCV treatment response.”

A final reason is that immunosuppression following transplantation may not be as effective in black patients, according to Wong. “They may require more aggressive immunosuppressive regimens, which can lead to complications and higher rates of rejection of the organ,” he said. “The metabolism of immunosuppression may vary by ethnicity.”

“But these are all just theories,” he added. “We need more research and education, across the board, to clarify all of these potential explanations.”

HCV Prevalence in MSM

Kara Chew, MD, assistant clinical professor of medicine in the Division of Infectious Diseases and based at the Center for Clinical AIDS Research and Education (CARE) at the David Geffen School of Medicine at UCLA, and colleagues looked at a group of 185 men who have sex with men who had recently been diagnosed with HIV. Their aim was to characterize prevalence and risk factors for HCV, along with patterns of transmission of the two diseases. Sixty-five percent of the cohort was of a minority race or ethnicity. Despite a high rate of reported unprotected receptive anal intercourse (74.6%) and group sex (33.3%), HCV RNA was detectable in only 1.6% of the cohort. “Prevalence of HCV co-infection was low and there was no evidence of HIV-HCV co-transmission in this cohort of relatively young, predominantly minority, newly HIV-diagnosed MSM, most with early HIV infection, with high rates of high-risk sexual behaviors, [sexually transmitted infection] and non-[injection drug use],” the researchers concluded. “The low HCV prevalence in a group with high-risk behaviors for non-IDU HCV acquisition suggests an opportune time for targeted HCV prevention measures.”

“I believe the low prevalence primarily relates to the young age of the individuals in our cohort,” Chew said in an interview. The average age was 28 years in their cohort, compared with around 40 years in other cohorts. “Thus, they likely had fewer total encounters and exposures to HCV to date,” she added.

Michaels stressed that there has been a rise in heroin and IV drug use in recent years. “However, this is seen a lot more in younger patients, in their 20s and 30s, and typically these patients are white,” he said.

“We found high rates of risk behaviors/risk factors that in other studies have been associated with risk for non-IDU HCV infection in HIV-infected MSM,” Chew said. “This does suggest that while not currently infected, this population is at high risk for future HCV infection. This would be an opportune time — at HIV diagnosis, prior to HCV infection — for an intervention, such as an educational or behavioral intervention, to reduce risk for incident HCV infection. This is particularly important given HIV-infected persons are less likely to clear HCV infection spontaneously, or in other words, more likely to develop chronic HCV infection, with its attendant complications.”

In a 2004 study, Piasecki and colleagues looked at spontaneous HCV clearance during primary infection. Univariate analysis results indicated that alcohol use disorder (OR = 0.52; 95% CI, 0.31-0.85) and black race (OR = 0.65; 95% CI, 0.44-0.96) were the two main factors that decreased the likelihood of spontaneously clearing the disease. The association between alcohol use disorder and spontaneous clearance remained in multivariate analysis, but the association with black race did not.

“In my experience, the vast majority of patients are infected via substance abuse,” Saab said. “Whether rates of alcoholism are higher in black patients vs. whites or Hispanics is unclear. It is difficult to say that one group is more likely to use alcohol over another.”

In New York, Breskin and colleagues investigated a cohort of 41,303 MSM with HIV who were not injection drug users. The study was conducted using data from 2000 through 2010. The cohort included 2,016 patients who were diagnosed with HCV after HIV diagnosis. Adjusted analysis results indicated that non-Hispanic black patients were at an increased risk for HCV diagnosis than non-Hispanic white patients (RR = 1.6; 95% CI, 1.4-1.8). “With curative HCV treatment available, emphasis should be placed on adherence to guidelines recommending annual HCV screening for HIV-infected MSM, and education and outreach to MSM to prevent sexually transmitted HCV infections,” the researchers concluded.

Moving Forward

“I’m optimistic,” Michaels said. “The current therapies are working well in most racial groups, and more will be hitting the market. There is still some disparity among patients depending on their insurance coverage. Patients with government-assisted insurance programs have typically been at a disadvantage when we have tried to obtain coverage for their HCV medications. But once we can secure coverage for more and more of these patients, I’m confident that we will be able to cure them.”

Saab and his colleagues are currently treating more than 600 patients. “Screening rates are always lower among patients with lower socioeconomic status, which includes a lot of minorities,” he said. “If clinicians can continue to follow screening recommendations, we’d see improvement in all populations, not just minority groups.”

For Wong, there is no magic bullet. “The reasons for racial disparity in all facets of HCV are complicated and multifactorial,” he said. “There are ethnic disparities, socioeconomic disparities, access disparities. Many of our poorer patients, who are disproportionately ethnic minorities, don’t have adequate social support. This deserves greater attention.”

Much of this will depend on how things play out with DAAs, which is largely out of the hands of both clinicians and patients. So in the end, for Wong, ongoing and frank discussion always has the potential to lead to answers. “Highlighting issues of race and disparities in access when discussing the state of affairs of HCV will be especially important,” he said. - by Rob Volansky

• References:
• Breskin A, et al. Sex Transm Dis. 2015;doi:10.1097/OLQ.0000000000000293.
• Chew KW, et al. BMC Infect Dis. 2015;doi:10.1186/s12879-015-1279-z.
• El-Serag HB, et al. Am J Gastroenterol. 2014;doi:10.1038/ajg.2014.214.
• Hossain S, et al. Rural Remote Health. 2014;14:2982.
• Lee S, et al. Clin Med Insights Gastroenterol. 2015;doi:10.4137/CGast.S24737.
• Merriman NA, et al. Am J Gastroenterol. 2006;101:760-767.
• Piasecki BA, et al. Hepatology. 2004;40:892-899.
• Saab S, et al. Am J Gastroenterol. 2014;doi:10.1038/ajg.2014.243.
• Wong RJ, Ahmed A. Clin Transplant. 2014;doi:10.1111/ctr.12374.

• For more information:
• Kara Chew, MD, can be reached at UCLA CARE Center, 11075 Santa Monica Blvd, Suite 100, Los Angeles, CA 90025; email: KChew@mednet.ucla.edu.
• Hashem B. El-Serag, MD, MPH, can be reached at 7200 Cambridge St., Houston, TX, 77030; email: hasheme@bcm.edu.
• Anthony Michaels, MD, can be reached at Public Affairs & Media Relations, 650 Ackerman Rd., Suite 135, Columbus, OH 43202; email: Marti.Leitch@osumc.edu.
• Sammy Saab, MD, MPH, can be reached at Pfleger Liver Institute, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095; email: ssaab@mednet.ucla.edu.
• Robert J. Wong, MD, MS, can be reached at 1411 East 31st Street, Highland Hospital, Highland Care Pavilion - 5th Floor Endoscopy Unit, Division of Gastroenterology and Hepatology, Oakland, CA 94602; email: rowong@alamedahealthsystem.org.

Disclosures: Chew reports receiving grant funding for investigator-initiated research from Merck. El-Serag reports receiving research funding from Gilead Sciences and Wako. Michaels reports being a speaker for Gilead Sciences and being on the advisory board of Gilead Sciences and Janssen in the last 12 months. Saab reports being a speaker and a consultant for AbbVie, BMS, Gilead Sciences, Janssen and Merck. Wong reports receiving research support from Gilead Sciences.