Response to Interferon-based Therapy in Hispanic Patients with Chronic Hepatitis C

By Liz Highleyman

It is well known that people of African descent typically do not respond as well as Caucasians to interferon-based therapy for chronic hepatitis C. But response rates in people of other racial/ethnic groups, including Latinos and Asians, have been less extensively investigated.

Two such studies were presented at the Digestive Disease Week (DDW) 2008 conference taking place this week in San Diego.

Study 1

In the first study, Stanley Yu and colleagues compared responses of Hispanic and non-Hispanic white patients treated with pegylated interferon plus ribavirin. They conducted a retrospective review of all treatment-naive Hispanic and white patients with chronic hepatitis C treated at the University of New Mexico or the Albuquerque Veterans Affairs Medical Center between October 2001 and January 2007.

The analysis included 179 Hispanic and 217 white patients. Baseline characteristics of the 2 groups were not significantly different. In accordance with current guidelines, individuals with HCV genotype 1 received pegylated interferon plus ribavirin for 48 weeks, while those with genotypes 2 or 3 were treated for 24 weeks.

Results

• Of the 179 Hispanic patients, 64% had genotype 1 and 36% had genotypes 2/3.

• Of the 217 white patients, 61% had genotype 1 and 39% had genotypes 2/3.

• More Hispanics than whites prematurely discontinued therapy (35% vs 20%; P < 0.001).

• Among genotype 1 patients, early virological response (EVR) at week 12, end-of-treatment response (ETR), and sustained virological response (SVR) 24 weeks after completion of therapy did not significantly differ between the Hispanic and white groups.

• Differences were observed, however, among genotype 2/3 patients:

• Intent-to-treat results, Hispanic vs white:

- EVR: 81% vs 88% (P = non-significant);
- ETR: 64% vs 83% (P < 0.05);
- SVR: 45% vs 75% (P < 0.0005);

• As-treated results, after adjusting for premature treatment discontinuation, Hispanic vs white:

- EVR: 98% vs 97% (P = non-significant);
- ETR: 88% vs 94% (P = non-significant);
- SVR: 66% vs 87% (P < 0.05).
- Relapse after ETR: 25% vs 7% (P < 0.05).

"Hispanics with genotype 2/3 hepatitis C infection are less likely to achieve ETR and SVR with pegylated interferon and ribavirin therapy compared to non-Hispanic whites," the investigators concluded.

"After correcting for premature treatment discontinuation," they continued, "SVR in genotype 2/3 Hispanics continued to be lower due to increased relapse and a diminished ability to maintain viral clearance after treatment completion."

Study 2

In the second study, Maribel Rodriguez-Torres and colleagues with the multicenter, open-label LATINO Study prospectively compared responses of previously untreated Latino and non-Latino Caucasian patients (equivalent to Hispanics and non-Hispanic whites, respectively, in the previous study).

Unlike Yu's study, this one included only participants with HCV genotype 1. The intent-to-treat population consisted of 269 Latino and 300 non-Latino Caucasian patients. Higher percentages of the Latino group were age 40 or younger (28% vs 16%), had a body mass index (BMI) greater than 27 kg/m2 (65% vs 51%) or greater than 30 kg/m2 (40% vs 25%), had ALT more than 3 x the upper limit of normal (ULN) (25% vs 17%), and had cirrhosis (13% vs 10%). Other baseline characteristics were similar.

All patients were treated with 180 mcg/week pegylated interferon alfa-2a (Pegasys) plus 1000-1200 mg/day ribavirin for 48 weeks. At the outset, the investigators hypothesized that the SVR rate would be at least 15% lower among Latinos than non-Latinos. They performed multiple logistic regression analysis to determine the effect on SVR of baseline factors including ethnicity, sex, age (over or under 40 years), baseline ALT (? vs > 3 x ULN), HCV RNA level (< vs > 400,000 IU/mL), and presence or absence of cirrhosis.

Results

• The overall SVR rate was significantly higher for non-Latinos Caucasians than for Latino patients (49% vs 33%; P < 0.0001).

• SVR rates differed significantly by sex for non-Latinos, but not for Latinos:

• Latinos: men 32.8% vs women 34.9%;
• Non-Latinos: men 53.1% vs women 42.6%.

• Latinos with lower ALT had a higher SVR rate, while among non-Latinos, those with higher ALT were more likely to achieve SVR:

• Latinos: ALT < 3 x ULN 36.5% vs > 3 x ULN 24.2%;

• Non-Latinos: ALT < 3 x ULN 46.0% vs > 3 x ULN 66.0%.

• For Latinos, by multiple logistic regression, the following were significant predictors of SVR:

• Baseline ALT < 3 x ULN (OR 1.7; P = 0.0797);
• Baseline HCV RNA < 400,000 IU/mL (OR 2.62; P = 0.008);
• Absence of cirrhosis (OR 2.13; P = 0.0959).

• For non-Latino Caucasians, the following factors significantly predicted SVR:

• Male sex (OR 1.60; P = 0.0664);
• ALT > 3 x ULN (OR 2.33; P = 0.0126);
• Baseline HCV RNA < 400,000 IU/mL (OR 3.11; 95% P = 0.0016).

Based on these findings, the investigators concluded, "Virologic response rates to 48 weeks of treatment with [Pegasys]/ribavirin were lower in HCV genotype-1 infected Latino[s] than in non-Latino Caucasians."

"The predictors of SVR were different for Latinos and non-Latinos," they added, "indicating the need for further study in Latinos."

5/20/08

References

S Yu, J Douglass, C Qualls, and others. Response to therapy with pegylated interferon and ribavirin in Hispanics with hepatitis C compared to non-Hispanic whites. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract S1003.

M Rodriguez-Torres, L Jeffers, M Sheikh, and others. Virologic responses to pegIFN-2a/ribavirin in treatment-naive Latino vs non-Latino Caucasians infected with HCV genotype 1: the LATINO study. Digestive Disease Week (DDW) 2008. San Diego, CA. May 17-22, 2008. Abstract 161.