Combination of Virus and Host Factors Predict Virological Response to Pegylated Interferon plus Ribavirin for Chronic Hepatitis C

By Liz Highleyman

Research has revealed several factors associated with good response to interferon-based therapy for chronic hepatitis C, but experts continue to look for new ways to determine which patients will benefit most from treatment.

As described in the December 2008 issue of Hepatology, Japanese researchers evaluated a variety of viral and host factors for their ability to predict response to hepatitis C treatment, including analysis of the interferon sensitivity determining region (ISDR) of the HCV genome and the ratio of T-helper type 1 to type 2 immune response (Th1/Th2).

The study enrolled 120 chronic hepatitis C patients with HCV genotype 1 and a high baseline HCV RNA level -- both predictors of poor response -- who started 48-week combination therapy using pegylated interferon alpha-2b (PegIntron) plus ribavirin.

Results

54 of 120 patients (45) achieved sustained virological response (SVR), or continued undetectable HCV RNA 6 months after completing therapy.

In a logistic regression analysis, the pre-treatment factors significantly associated with SVR were:

ISDR mutation (odds ratio [OR] 86.0; P = 0.0008];

Th1 to Th2 ratio < 15.5 (OR 9.6; P = 0.0021);

Body weight of 59 kg;

Neutrophil count of 2300 cells/mL.

Employing a logistic regression model using these 4 factors to estimate SVR before starting therapy, patients fell into 3 groups when plotted according to estimated and actual SVR rates:

High sensitivity group: actual SVR rate 91% (32 of 35);

Intermediate sensitivity group: actual SVR rate 41% (15 of 37);

Low sensitivity group: actual SVR rate 15% (7 of 48).

Rapid or early virological responses were seen in 80% of high sensitivity patients who achieved SVR, but in only 40% of intermediate or low sensitivity patients

Null and very late virological responses were rare in the high sensitivity group.

In conclusion, the researchers wrote, "a logistic regression model that includes the sequence of ISDR of the HCV, Th1/Th2 ratio, body weight, and neutrophil count can be useful for accurately predicting actual SVR rate before combination therapy."

Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

1/27/09

Reference
H Shirakawa, A Matsumoto, S Joshita, and others. Pretreatment prediction of virological response to peginterferon plus ribavirin therapy in chronic hepatitis C patients using viral and host factors. Hepatology 48(6): 1753-1760. December 2008. (Abstract).