Pioglitazone improves virological response to peginterferon alpha-2b/ribavirin combination therapy in hepatitis C genotype 4 patients with insulin resistance.
OBJECTIVE
Insulin resistance (IR) affects sustained virological response (SVR). The use of insulin-sensitizing agents has been proposed to improve therapy outcome. The safety and efficacy of pioglitazone on insulin sensitivity and SVR in treatment-naïve patients with chronic hepatitis C (CHC) genotype 4 with IR receiving standard antiviral therapy were evaluated in a randomized-controlled study.


METHODS
Ninety-seven previously untreated patients with CHC and IR [homeostasis model assessment (HOMA>2)] were randomly assigned into two arms; (arm A; n=48) were given pioglitazone 30 mg/day combined with peginterferon (Peg-IFN)-alpha-2b/ribavirin (RBV) for 48 weeks, and (arm B; n=49) were given standard of care (Peg-IFN-alpha-2b/RBV for 48 weeks); HOMA index and hepatitis C virus RNA (HCV RNA) levels were measured at baseline, during therapy and follow-up. Treatment was stopped in patients without an early virological response or those who were HCV RNA positive at 24 weeks.


RESULTS
Baseline data of both groups were comparable, with no significant statistical differences. The percentages of rapid virological response (RVR) and SVR were significantly higher in patients given triple therapy compared with standard of care (27.08 vs. 6.1%; P=0.006 and 60.4 vs. 38.7%; P=0.04 respectively); patients in arm A showed a greater decrease in the HOMA index than those in arm B (-1.8 +/- 0.3, -2.1 +/- 0.3 vs. -1.1 +/- 0.6, -1.3 +/- 0.7) at week 24 and at the end of follow-up (P=0.001 at both time points). The triple therapy was well tolerated.


CONCLUSIONS
A combination of pioglitazone, Peg-IFN-alpha-2b and ribavirin increased RVR, SVR and decreased IR, compared with patients given Peg-IFN plus ribavirin without an increase in adverse events.
Khattab
Mahmoud
M
Department of Internal Medicine, Minya University, Minya, Egypt. mkhattabmed@hotmail.com
Emad
Mohammed
M
Abdelaleem
Asharf
A
Eslam
Mohammed
M
Atef
Rabab
R
Shaker
Yehia
Y
Hamdy
Lamia
L
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage*; D055815:Young Adult
D000998:Antiviral Agents; D007004:Hypoglycemic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; D000077205:Pioglitazone