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Can Improved Nutritional Status of Patients Improve the Success Rate of Treatment with Interferon Alfa and Ribavirin?

Interferon (IFN) alfa-2b/ribavirin therapy is an effective antiviral therapy for the patients with hepatitis C virus (HCV) genotype 1. However, the response to this therapy is not satisfactory because only about 40-50% of the patients become sustained responders (SR). Further, patients receiving IFN alfa-2b/ribavirin therapy have frequently withdrawn from studies because of severe adverse effects.

The efficacy of IFN therapy is mediated by both genomic type and viral load and to immunological response of the hosts. Reportedly, some amino acids modulate the host's immunological response. In order to achieve a higher SR ratio after IFN alfa-2b/ribavirin therapy and to decrease the number of patients who withdraw, it seems important to improve the nutritional condition and to up-regurate potential immunological response by modifying the balance of amino acids.

In the present study, we investigated the dynamics of a panel of 41 amino acids during IFN alfa-2b/ribavirin therapy, and then analyzed the effects of nutrition on the clearance of HCV.

Seventy patients with chronic HCV infection were included after informed consent. Six million units of IFN alfa-2b in combination with ribavirin (600-800mg/day) were given over 6 months. During the first 2 weeks of the therapy, IFN alfa-2b was given daily. Blood samples were obtained after overnight fasting at 2weeks, 8 weeks, and 24 weeks of therapy and served as the analysis of amino acids. At the same time, peripheral blood mononuclear cells (PBMC) were collected and the numbers of IFNã- and IL4-producing cells were measured by FACS analysis. Th1/Th2 ratio was calculated as follows: Th1/Th2=IFNã-producing cells (%)/IL4-producing cells (%).Study Results

HCV RNA became undetectable in 22%, 52%, and 78% of the patients at weeks 2, 8, and 24 of therapy, respectively. Th1/Th2 ratio decreased gradually during therapy. Th1/Th2 ratio at the end of therapy (24 weeks) was significantly smaller than that at the beginning. (17.8±10.9 vs 13.5±8.0, p=0.011). However, there was no significant correlation of Th1/Th2 level with the rate of HCV eradication.

Total amino acids (TAAs) and branched chain amino acids (BCAAs) decreased gradually during therapy. Even at 8 weeks of therapy, there was a significant decrease in TAA and BCAA (p=0.017 and p<0.0001, respectively). Fischer ratio (FR) also showed dramatic change. It changed from 2.83 (at the beginning of the therapy) to 2.19 (at 8 weeks of therapy), indicating that the balance of amino acids rapidly changed to the condition similar to the patients with liver cirrhosis.

Of interest, the levels of TAA and BCAA at the beginning of the therapy were significantly higher in the HCV RNA-negative group than in the HCV RNA-positive group at the end of therapy (TAA: 3243±275 vs 2877±252 nmol/ml; p=0.004, BCAA: 470±92 vs 377±65 nmol/ml; p=0.024).

Although we could not find a significant difference, FR at the beginning of the therapy was larger in HCV RNA-negative group than in HCV RNA-positive group at the end of therapy (2.81±0.51 vs 2.47±0.68, p=0.15).

Analysis of each amino acids showed that there were significant differences in the concentration of citrulline and ornithine, both amino acids are involved in urea cycle, between HCV RNA-negative and HCV RNA-positive group at the end of therapy.Conclusions

Interferon alfa-2b/ribavirin therapy induces malnutrition in the early stage of therapy. Successful elimination of HCV RNA seemed to depend more on nutrition rather than on the ratio of Th1/Th2 during therapy, suggesting that a better response to interferon alfa-2b/ribavirin therapy might be possible by improving the nutritional status of the patients at the beginning of therapy. In addition, adequate nutrition support would contribute to the improvement of QOL of the patients, which would lead to a decrease in patient withdrawals during interferon alfa-2b/ribavirin therapy.

12/08/03

ReferenceA Okumura and others. NUTRITION IS MORE IMPORTANT THAN TH1-DOMINATED CONDITION FOR BETTER RESPONSE IN INTERFERON ALPHA-2B/RIBAVIRIN THERAPY. Abstract 323 (poster). Hepatology 38:4 (Suppl). October 2003. (54th Annual Meeting of the American Association for the Study of Liver Diseases. October 24-28, 2003. Boston, MA.)