“Real-Life” comparison of pegylated-interferon 2a versus 2b combination therapy of chronic hepatitis C virus


  • Potential conflict of interest: Nothing to report.

“Real-Life” Comparison of Pegylated-Interferon 2a Versus 2b Combination Therapy of Chronic Hepatitis C Virus

To the Editor:

With great interest, we read the recent meta-analysis published in HEPATOLOGY, which compared peginterferon (PEG-IFN) alpha 2a and PEG-IFN alpha 2b for treatment of chronic HCV infection.1 The results of this meta-analysis and the entire topic are still controversially discussed and methodologic concerns have been raised about the recent study.2, 3 Awad et al. conclude in their study, in contrast to the results of the largest, well-controlled single trial published in 2009,4 that according to their analysis of pooled data from eight studies, PEG-IFN alpha 2a is associated with significantly higher SVR rates than PEG-IFN alpha 2b.

Here, we present the treatment results of a large, retrospective unsponsored, single center study of a northern German cohort of HIV-negative patients with chronic HCV infection. We analyzed a total of 486 treatment-naïve, monoinfected patients with chronic hepatitis C (genotype 1-3) who were treated at the University of Hamburg after January 2002 until June 2008 with standard combination treatment regimen with either PEG-IFN alpha 2a (Group A) or PEG-IFN alpha 2b (Group B) for 48 weeks (genotype 1) or 24 weeks (genotypes 2 and 3) with weight adapted ribavirin doses of 800-1400 mg, respectively. There were no significant differences of the demographics or severity of the liver disease in the two groups with the exception of slightly higher baseline viral loads in group B (Table 1).

Table 1. Baseline Clinical and Virological Characteristics of the Cohort and Virological Response at the End of Treatment and Follow-Up by Intention-to-Treat Analysis
CharacteristicGroup A (PEG-IFN Alpha 2a + Ribavirin)Group B (PEG-IFN Alpha 2b + Ribavirin)P Value
  1. ns, not significant.

Patients, n304182 
Mean age (minimum/maximum)43 (15/76)41 (19/68)ns
Sex, male/female (%)182/122 (60/40)110/72 (60/40)ns
Liver biopsy, n (%)180 (59)103 (57)ns
Fibrosis F3-F4, n (%)33 (18)15 (15)ns
HCV RNA, mean (minimum/maximum)649,197 (308/13,154,000)1,342,536 (269/20,000,000)0.02
Alanine aminotransferase mean (minimum/maximum)104 (11/422)93 (7/906)ns
Genotype, n (%)   
 1147 (48)88 (48)ns
 240 (13)18 (10)ns
 3117 (38)76 (42)ns
Rapid virologic response141/304 (46%)80/182 (44%)ns
Complete early virologic response111/304 (37%)72/182 (40%)ns
End-of-treatment response268/304 (88%)156/182 (86%)ns
SVR185/304 (60,9%)109/182 (59.9%)ns
Relapse31/304 (10%)18/182 (10%)ns
Nonresponse23/304 (8%)16/182 (9%)ns
Breakthrough3/304 (1%)4/182 (2%)ns
Lost to follow-up62/304 (20%)35/182 (19%)ns
SVR by genotype   
 179/147 (53.7%)47/88 (53.4%)ns
 229/40 (72.5%)13/18 (72.2%)ns
 377/117(65.8%)49/76 (64.5%)ns
Patients with side effects294/304 (97%)179/182 (98%)ns

Both groups received comparable ribavirin doses during the treatment period. Primary endpoint of the study was defined as sustained viral response (SVR) by intention to treat analysis. Overall, SVR rates were comparable for both regimens (group A: 185/304 [60.9%]/group B: 109/182 [59.9%] P = ns) (Table 1). There were also no differences detected for any of the genotypes (GT) 1 through 3 (GT1: 79/147 [53.7%] versus 47/88 [53.4%], GT2 29/40 [72.5%] versus 13/18 (72.2%), GT3 77/117 [65.8%] versus 49/76 [64.5%]). Notably, we neither observed any significant differences of the early virologic response rates, the relapse rates nor differences of the rate of side effects in either group (Table 1). We conclude that the efficacy and safety of standard combination treatment regimens for chronic hepatitis C infection with PEG-IFN alpha 2a versus PEG-IFN alpha 2b are comparable in real-life treatment settings in a large northern German university-based study center.

One issue that has not been addressed thoroughly in recent discussions is the difficult handling of the PEG-IFN alpha 2b syringes which might have simply lead to a lower exposure to the interferon because of faulty handling of the syringes in a subset of patients. We specifically addressed and trained the handling of the PEG-interferon alpha 2b syringe with the patients. Thus it is intriguing to speculate that one of the reasons for the relative high SVR rate and much lower drop-out rate of patients treated with PEG-interferon alpha 2b in our cohort than found in the study published by Ascione et al. and Witthoeft et al.5, 6 might be due to this training. In our view, it is time to end this “pseudo-debate”: it can only be reiterated that equally high SVR rates can be achieved using either PEG-IFN and many other factors like optimal dosing of ribavirin, individualized tailoring of the length of the therapy, patient counseling about the proper handling of the syringes and the importance of adherence,7 or treatment of the side-effects have a much greater impact on “real life” treatment outcome than the actual choice of the interferon.8


We thank the patients who participated in this study. This work was supported by the German Research Agency (SFB841). JSzW, AWL, SL, PB have received speaker's fees from Roche and Essex Pharma in the past.

Julian Schulze zur Wiesch*, Neele Pudelski*, Lena Hoepner*, Michael Supplieth*, Peter Buggisch*, Ansgar W. Lohse*, Stefan Lüth*, * University Medical Center Hamburg–Eppendorf, Hamburg, Germany.