Chronic Hepatitis С in African Americans: DISCUSSION

Chronic Hepatitis С in African Americans DISCUSSION

Treatment of HCV using pegylated interferon and has clearly improved upon SVR rates compared to the older formulations. However, differences in racial responsiveness to therapy continue to be reported. There have been several trials that have attempted to address the question of discordant response to treatment among different races. Historically, Reddy et al. first noted that African Americans had a significantly lower response to interferon monotherapy compared with other racial groups (SVR rates 2% versus 12%), but this study only had a small cohort of African Americans compared with Caucasians. McHutchison et al. initially studied this question utilizing standard interferon monotherapy versus combination therapy. Their study concluded that the seemingly impaired responsiveness of African Americans compared to Caucasians could be overcome with the advent of combination therapy, and they reported that SVR rates were similar for African Americans and non-African Americans with genotype l. However, subsequent studies did not match this equality in responsiveness.

In our study, it is noted that the majority of African Americans were genotype 1, as compared with a greater variability of genotypes among non-African Americans. In some studies, as the proportion of patients who are nongenotype 1 in a population increases, the overall SVR for that population also increases, accounting for higher overall SVR rates in non-African-American patients of all genotypes. However, in our subgroup analysis by genotype, we noted that genotype-1 patients also have a lower rate of SVR compared to nongenotype-1 patients, regardless of race. Interestingly, there was no significant difference between SVR rates in African-American compared to non-African-American genotype-1 patients. Our results suggest that the lower response rates of African-American patients can be accounted for by the predominance of genotype 1 in the population, but genotype 1 in other racial groups is also associated with a proportionately lower SVR.

The SVR rates among genotype-1 African Americans in our study are on par with those studied by Daniel and Jeffers et al. in non-HIV, coinfected patients; and by Muir et al. and Chung et al. in patients with HCV and HIV (is used for treating HIV infection) coinfection.

Our data also corroborate the conclusions of McHutchison et al., who found that the disparity in treatment response with nonpegylated interferon correlated with a higher incidence of genotype 1 in their patients. In their study, the SVR for African Americans as well as for Caucasians was in the range of 20-23%. While Muir et al. reported that African-American patients had an SVR of 19% with a pegylated interferon regimen, which is identical to our SVR rate, they found that this was a significantly lower SVR compared to that of the Caucasians in their study (52%)—a finding that cannot be explained by viral genotype alone.

Proposed mechanisms to account for differences in racial responsiveness to treatment include disparate viral kinetics, which prevent inhibition of viral production in African Americans; the presence of the HLA-DQB1*0301 allele in African Americans that is associated with lower rate of viral clearance; and dysregulation of CD4 T-cell function in African Americans with HCV infection. In the study by Muir et al, African Americans also had a significantly higher incidence of obesity, hypertension and diabetes, all of which are components of the metabolic syndrome that have also been implicated in a lower response to interferon-based therapy. Higher body weight has been identified in previous trials as an independent factor to explain decreased response to interferon. Finally, recent reports suggest that there is a correlation between the number of mutations in the interferon-sensitive region of the HCV protein and genotype lb. Accelerated drug resistance in the setting of genotype lb (which is less common in areas where Caucasian populations predominate, such as Northern Europe), also may help to explain the differences in racial response rates.

Differences in racial responsiveness are not unique to therapies; similar treatment-related disparities are seen in many other common diseases, including diabetes, hypertension and end-stage renal disease. African Americans have been less responsive to treatment of hypertension with ACE inhibitors and angiotensin receptor blockers. Furthermore, studies in anesthesia demonstrate that there are also ethnic differences in response to certain anesthetics, including propofol and fentanyl.

Our results also highlight two interesting findings that heretofore have not been the subject of much attention. The first centers around the fact that only about one-third of eligible patients (without medical or other contraindications to receiving pegylated interferon and ribavirin therapy) actually decided to undergo treatment. The majority of those who opted for expectant management most often cited the perceived low efficacy coupled with a high risk of side effects associated with treatment for genotype 1 as the major reasons why they chose to be followed. The demographics of these patients were quite similar to those who were treated. The second phenomenon we observed was the delayed relapse after achieving SVR by the traditional six-month definition in three of our genotype-1 patients. This raises the possibility that the current definition of SVR may not always apply, especially in genotype-1 and/or African-American patients.

In conclusion, we found that both African-American and non- African-American patients with genotype-1 chronic HCV infections have a lower SVR rate to pegylated interferon and ribavirin therapy compared to nongenotype-1 patients of all races. Although the African-American population has the highest percentage of genotype-1 infections, our results suggest that the lower SVR rates for all genotype-1 patients may not be simply due to racial factors but that viral factors may be equally as important. Therefore, in the current therapeutic environment, we consider genotype to be more important than racial factors when discussing treatment options with HCV patients. We also recognize that many patients with genotype-1 infections who have clinically mild (often silent) disease are choosing to be followed expectantly until newer, more efficacious and better tolerated therapies are developed. While they remain untreated, such groups represent an opportunity to help define the truly long-term natural history of chronic hepatitis C.

What This Study Adds
• The SVR-to-pegylated-interferon-based regimens with canadian ribavirin in African Americans and non-African Americans chronically infected with HCV genotype 1 are similarly low.
• The predominance of genotype 1 among African-American patients likely accounts for the lower overall SVR rate in this population, but genotype in other racial groups may also be associated with a proportionately lower SVR rate.
• A substantial number of asymptomatic HCV genotype-1 patients with clinically mild disease opt to be followed expectantly rather than receive any of the currently available treatment regimens.
• HCV genotype 1 may also be associated with a higher risk for delayed relapse after achieving SVR. This suggests that we need to reexamine the length of optimal treatment in difficult-to-treat populations, including genotype-1 and African-American patients.
• Newer treatment options must be pursued for relatively resistant populations for whom pegylated-interferon-based regimens have failed.

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