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Pioglitazone decreases hepatitis C viral load in overweight, treatment naïve, genotype 4 infected-patients: a pilot
Mario Chojkier1, Hisham Elkhayat, Dina Sabry
1Department of Medicine, San Diego VA Healthcare System, San Diego, California, United States of America. mchojkier@ucsd.edu
Background:
Insulin resistance (IR) is induced by chronic hepatitis C virus (HCV) genotypes 1 and 4 infections. It is not known whether drugs that affect IR such as Pioglitazone and Prednisone also affect serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment. The primary aim was to assess whether Pioglitazone by improving IR and/or inflammation decreases HCV viral load independently of standard of care HCV treatment. A secondary aim was to assess whether Prednisone, a drug that induces insulin resistance and stimulates HCV viral entry and replication in replicon culture systems, increases HCV viral load in this population.
Methodology/Principal Findings:
We designed a two-arm, parallel Pilot Study of overweight, treatment naïve genotype 4 HCV-infected patients at a public referral Liver Clinic in Giza, Egypt. The subjects received Pioglitazone (30 mg/day for 14 days) or Prednisone (40 mg/day for 4 days) in a randomized fashion, but the two arms can be considered independent pilot studies. Only changes from baseline within each arm were assessed and no contrasts of the interventions were made, as this was not an aim of the study. Among 105 consecutive HCV genotype 4 patients, 39 were enrolled based on the optimal sample size and power analysis according to the CONSORT statement; 20 to the Pioglitazone group and 19 to the Prednisone group. Pioglitazone was effective in decreasing serum HCV RNA at day-14 (n = 10; difference of means = 205,618 IU/ml; 95% CI 26,600 to 384,600; P<0.001). Although Prednisone did increase serum HCV RNA at day-4 (n = 10; change from baseline = -42,786 IU/ml; 95% CI -85,500 to -15,700; P = 0.049), the log(10) HCV RNA titers were statistically not different from baseline day-0.
Conclusion/Significance:
This is the first documentation that Pioglitazone decreases the serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment. The novel findings of our Study provide the foundation for basic and clinical investigations on the molecular mechanisms responsible for the Pioglitazone-induced decrease in HCV genotype 4 RNA titers.
Trial Registration:
ClinicalTrials.gov NCT01157975.
Insights
Pioglitazone significantly decreased Hepatitis C Virus (HCV) RNA titers in patients with genotype 4 infection. This study suggests Pioglitazone may offer a novel therapeutic approach for HCV treatment.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Insulin resistance (IR) is associated with chronic Hepatitis C Virus (HCV) genotypes 1 and 4 infections.
- The independent effect of IR-modulating drugs like Pioglitazone and Prednisone on HCV RNA titers is not well understood.
- This study investigated the impact of Pioglitazone and Prednisone on HCV viral load, independent of standard antiviral therapy.
Purpose of the Study:
- To determine if Pioglitazone improves insulin resistance and/or inflammation, leading to a decrease in HCV viral load.
- To assess whether Prednisone, known to induce insulin resistance and promote HCV replication, increases HCV viral load.
Main Methods:
- A randomized, two-arm pilot study was conducted with treatment-naive, overweight patients infected with HCV genotype 4.
- Participants received either Pioglitazone (30 mg/day for 14 days) or Prednisone (40 mg/day for 4 days).
- Changes in serum HCV RNA titers from baseline were assessed within each treatment arm.
Main Results:
- Pioglitazone treatment resulted in a significant decrease in serum HCV RNA at day 14 (mean difference of 205,618 IU/ml, P<0.001).
- Prednisone treatment showed a trend towards increasing serum HCV RNA at day 4, but log(10) HCV RNA titers were not statistically different from baseline.
- The study enrolled 39 patients (20 in Pioglitazone group, 19 in Prednisone group) based on sample size calculations.
Conclusions:
- This is the first study to demonstrate that Pioglitazone decreases serum HCV RNA titers independently of PEG-Interferon-α2/ribavirin treatment.
- The findings suggest a potential new therapeutic avenue for managing HCV genotype 4.
- Further research is warranted to elucidate the molecular mechanisms behind Pioglitazone's antiviral effects in HCV.
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