African Americans and Hepatitis C Virus Infection

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African Americans and Hepatitis C Virus Infection

As the most common cause of liver-related deaths, hepatitis C virus

(HCV) is now regarded as a major health problem in the US. HCV is

thought to cause approximately 10,000 deaths annually in the US. [1]

Unfortunately, that number is expected to increase threefold by 2020.

[2]

In the US, people of all races are adversely affected by HCV

infection. However, for reasons that are not yet understood, African

Americans have disparate clinical features (e.g., response to

therapy) and more complications from HCV infection than Caucasians.

The source of the present summary text is a Review Article by

Pearlman, MD, " Hepatitis C Virus Infection in African Americans, "

published in the January 1, 2006 issue of Clinical Infectious

Diseases. Dr Pearlman is affiliated with the Center for Hepatitis C,

Atlanta Medical Center, Medical College of Georgia, and Emory

University School of Medicine, Atlanta, Georgia.

" The aim of this review is to highlight the discrepancies in HCV

infection characteristics and treatment responses between African

American and white persons in the United States, " writes Dr.

Pearlman.

Epidemiology, Genotype, and Natural History

The most recent US census data records that 12% of the population is

African American, whereas 75% is white [3]. HCV infection is more

prevalent in the African American population than in any other racial

group in the United States. Although African Americans represent only

12% of the US population, they represent approximately 22% of the

estimated Americans with chronic HCV infection [1].

The mode of transmission of HCV appears to be similar for white and

African American individuals. In a large, prospective, controlled

trial involving >400 patients, injection drug use was identified as

the primary transmission route among both whites and African

Americans. [4]

While 70% of all HCV-infected individuals in the US have genotype 1,

African Americans have the highest prevalence of genotype 1 than any

other racial group. The reason for this is not known.

In addition, it is well recognized that the chronic HCV infection

rate is higher among African American than among white individuals.

Despite higher rates of chronic infection, HCV positive African

American persons may have a slower rate of fibrosis progression,

compared to whites. [5] Results of several studies

suggest that histologic progression of HCV infection occurs less

rapidly among African American patients than among white patients.

The mechanism for these and other possible discrepancies in the

natural history of hepatitis C in African Americans is unknown. The

answer may lie in the differing HCV-specific CD4 T cell responses

between African American and white persons.

Although African Americans may experience slower progression of

fibrosis, their rate of progression to hepatocellular carcinoma is

faster. In addition, the rate of progression to hepatocellular

carcinoma among African American persons is 2-fold higher than among

white persons [6]. The rate of deaths from liver cancer is 23 times

higher among African American patients than among whites [7]. More

recent data confirm that the risk of hepatocellular carcinoma is

twice as high among African American men as it is among white men [8].

Treatment

African Americans are usually underrepresented in clinical trials of

treatment for acute and chronic HCV infection, even though their

prevalence of chronic HCV infection is higher than among whites. Also

concerning is the fact that despite the improved benefits from the

pegylated interferons, the rates of sustained virologic response

(SVR) among African Americans is significantly lower than in whites.

In the registration trials of treatment with pegylated IFN and

ribavirin, too few African American subjects were enrolled to make

outcome assessments. Fortunately, two recent prospective trials have

examined the effect of pegylated IFN treatment in a large number of

African Americans.

The first trial [9] compared a group of 100 African American patients

with a control group of 100 non-Hispanic white patients, both of

which were treated with pegylated IFN alfa-2b (PegIntron) 1.5 mcg/kg

per week and ribavirin (1000 mg per day for 3 months, followed by 800

mg per day until week 48). Both groups were equally matched with

regard to age, HCV viral load, genotype, and other attributes.

Treatment was well tolerated in both groups; 81% of African American

and 79% of white patients completed therapy. Rates of adherence to

treatment and of adverse events were also similar in both groups, and

depression was the most common reason for discontinuation of therapy,

regardless of ethnicity.

Compared with non-Hispanic white subjects, African American subjects

had substantially poorer rates of sustained virologic response (19%

vs. 52%; P < .001). The only predictor of sustained virologic

response in multivariate analysis was race.

Also analyzed was the predictive value of an early virologic

response, defined as a >/= 2-log10 reduction in HCV RNA level at week

12 of therapy. None of the subjects who did not achieve an early

virologic response at week 12 reached a sustained virologic response,

irrespective of ethnicity. Thus, the negative predictive value of

early virologic response was 100%.

Study limitations included differences in sex, body weight, and

diabetes status, some of which may have impacted response rates.

Furthermore, alcohol use and abstinence were not documented in the

study. Because alcohol affects response to IFN-based therapy [10],

discrepancies in the 2 groups' rates of alcohol consumption may have

influenced results.

The second study [11] enrolled 78 African American subjects and 28

white subjects who were infected with HCV genotype 1 and were

treatment-naive. All subjects received pegylated IFN alfa-2a

(Pegasys) 180 mcg per week and ribavirin (10001200 mg per day, dosed

on the basis of weight) for 48 weeks. Unlike the study mentioned

above, this trial allowed the use of growth factors.

Patient characteristics were similar in the 2 groups. Rates of

adverse events were higher among white patients. Thirty-nine percent

of white subjects discontinued therapy, compared with 23% of African

American subjects. At week 72, in the African American group, the

rate of sustained virologic response was 26%, significantly lower

than the 39% rate for the white group.

Interestingly, of the 36 African American patients who did not

achieve sustained virologic response and who underwent both liver

biopsies, 22% achieved fibrosis improvement. These data may support

the concept that some patients may achieve reversal in fibrosis,

irrespective of whether they achieve a sustained virologic response.

Like the previous study, this study did not indicate differences in

alcohol use between patient groups.

Despite the fact that early virologic response had an inferior

positive predictive value for African American patients, patients of

both ethnicities should be treated for 48 weeks if early virologic

response is achieved.

WIN-R Trial

Preliminary findings from the weight-based dosing of Peg-Intron and

Rebetrol (WIN-R) trial demonstrate that weight-based dosing of

ribavirin confers a significant advantage in the treatment of African

American persons infected with genotype 1, compared with fixed dosing

of ribavirin [12]. WIN-R is a prospective trial of 5000 treatment-

naive HCV-infected patients from >200 US study centers designed to

study weight-based versus fixed-dose ribavirin therapy.

Three hundred eight-seven genotype 1infected African American

patients were among those treated. Of the 362 African American

subjects who weighed >/= 65 kg, those who received weight-based

ribavirin dosing had better end-of-treatment and sustained virologic

response rates than did those who received flat dosing. VR rates were

more than doubled (sustained virologic response rate, 21% vs. 10%; P

= .004). However, even though African American patients achieved

higher response rates with weight-based doses of ribavirin, rates of

sustained virologic response were still inferior to the rates for

white patients.

Of the 3 recent large trials that have focused on HCV treatment in

HCV-HIV coinfected persons, only 2 enrolled a significant percentage

of African American subjects. However, race was not predictive for

sustained response [13,14].

Conclusions

With few exceptions, African Americans have been significantly

Under-represented in clinical trials of HCV infection. More clinical

studies are needed that seek answers for why African Americans have

much lower treatment responses than whites, particularly those

studies that investigate the mechanisms for different treatment

responses in African Americans compared to whites.

In 2006, final results are expected from a multicenter trial, the

Viral Resistance to Antiviral Therapy for Chronic Hepatitis C

(VIRAHEP-C) Study. Approximately 200 African American subjects and

200 white subjects in this study are receiving treatment with

pegylated IFN and ribavirin. The objectives are to assess response

rates to therapy, and to analyze both viral factors and host factors,

including genetic and immunologic variables, that may influence

treatment results.