Serum Anti-Interferon Alpha Antibodies in Chronic Hepatitis C Patients Treated with Pegylated Interferon Alpha Containing Therapy

Special Article - Pegylated Interferon and Ribavirin Treatment for Hepatitis

J Hepat Res. 2015; 2(3): 1030.

Serum Anti-Interferon Alpha Antibodies in Chronic Hepatitis C Patients Treated with Pegylated Interferon Alpha Containing Therapy

Loggi E¹#, Vukotic R¹#, Cursaro C¹, Scuteri A¹, Martello Panno A¹, Grandini E¹, Margotti M¹, Lorenzini S1,2, Brillanti S¹, Bernardi M¹ and Andreone P¹*

¹Department of Medical and Surgical Sciences, University of Bologna and Azienda Ospedaliero-Universitaria Policlinico Sant’Orsola-Malpighi, Italy

²Emergency Department, Azienda ASL Ravenna, Ospedale Santa Maria delle Croci, Italy #Both authors contributed equally to this work

*Corresponding author: Andreone P, Department of Medical and Surgical Sciences - OU Medical Semiotics, Via Massarenti 9, 40138 Bologna, Italy

Received: August 27, 2015; Accepted: December 23, 2015; Published: December 31, 2015


The development of anti-IFNα antibodies is an occurrence described in chronic hepatitis C patients during treatment with Interferonα/PEG-Interferonα. However, its relevance, especially in difficult-to treat patients, has not been defined.

We retrospectively measured the serum levels of anti-IFNα antibodies (baseline and week 12) and IFNα levels (week 12) by ELISA in 76 previous nonresponders, and in 14 naïve patients treated with Pegylated-IFNα and Ribavirin. A group of 57 Healthy Donors (HD) was also assessed as control. Positivity to anti-IFNα antibodies was established on the values of HD.

Baseline anti-IFNα antibodies were detected in 15.5% of patients and in 7% of HD, with significantly higher concentrations in patients than HD (181.5±389.9 vs 95.9±143.0 ng/mL, p=0.0023). All positive patients were IFNα-experienced. At week 12, the prevalence of positivity increased to 22.3 and 28.5% in experienced and naïve patients, respectively, and the levels of anti-IFNα antibodies did not differ between the two groups (391±792.3 vs 384.7±662.6 ng/mL, respectively). IFNα concentrations were significantly lower in antibody-positive patients than in antibody-negatives (988.2±1402 vs 3462±830.8 pg/mL, p≤0.0001) and the levels of antibodies and IFNα were inversely correlated (r=-0.405, p=0.0001). The antibody-positive population clustered in null responders (67%) and 19/21 patients (90%) did not achieve SVR.

In Conclusion, the development of anti-IFNα antibodies is a non-negligible occurrence in patients treated with PEG-IFNα, is stable over time, and has a relevant clinical impact when associated with low levels of circulating PEG-IFNα. It should be considered in patients undergoing treatments including PEG-IFNα.

Keywords: Chronic Hepatitis C; Interferon alpha antibodies; Interferon alpha; Treatment; Antiviral therapy; Non-response


HCV: Hepatitis C Virus; CHC: Chronic HCV Infection; PEGIFNα: Pegylated Interferon alpha; RBV: Ribavirin; DAAs: Direct Acting Antivirals; anti-IFNα-Ab: anti-IFN alpha Antibodies; IFNα: Interferon-alpha; EVR: Early Virological Response; EOT: End of Treatment response; SVR: Sustained Virological Response; NR: Null Response; PR: Partial Response; RR: Relapser; SD: Standard Deviation; PCR: Polymerase Chain Reaction; SNPs: Single Nucleotide Polymorphisms; HD: Healthy Donor


The primary goal of Hepatitis C Virus (HCV) treatment is to achieve a sustained virological response, defined as persisting undetectable HCV-RNA after treatment withdrawal leading to the resolution of liver disease, at least in patients without cirrhosis [1].

The treatment of hepatitis C has dramatically improved over the past decade, so much that a significant proportion of chronic patients can now be cured.

Until recently, the standard of care for Chronic HCV Infection (CHC) has been based on the antiviral and immunomodulatory effect of Pegylated Interferon alpha (PEG-IFNα) and Ribavirin (RBV) [2]. Current schedules take advantage of direct acting antiviral (DAAs), agents able to interfere with HCV enzymes essential for viral replication. The “new era” of HCV treatment has started with the approval of two drugs against the NS3/4A serine protease for genotype 1 infections [3-6], and since then, several DAAs with other viral targets have been approved or are in the pipeline [7]. These drugs promise to lead to viral eradication with simplified regimens, very low toxicity, and without the use of interferon. However, the “first generation” (telaprevir and boceprevir) and the most recent secondwave DAAs (simeprevir, sofosbuvir and daclatasvir) will continue to include PEG-IFNα plus RBV, even if with shorter schedules [1].

Due to the important limitations of this therapy, such as the suboptimal response rates, severe side effects and high costs, its efficacy also depends on an appropriate selection of patients. Selection should include a careful evaluation of the well-described host and viral factors associated with therapeutic failure [8].

Among these factors, the development of serum anti-IFN alpha antibodies (anti-IFNα-Ab) that able to both bind and neutralise the biologic activity of IFNα, has been proposed as a mechanism against non-response in patients treated with recombinant IFNα [9-11], while others did not arrive at the same conclusions [12,13]. More recently, the role of anti-IFNα-Ab in combination with the pegylated form of IFN has been evaluated, providing controversial results [14-17].

In addition, the “natural” production of anti-IFNα-Ab has been reported in patients with various autoimmune disorders [18-20], and auto antibodies anti-cytokines have also been detected in healthy donors, with unknown significance [21].

Thus, this phenomenon could be more complex than it appears, and its clinical impact remains elusive. In particular, its role should be addressed in difficult to treat patients, who remain the clinical category less prone to benefit from advancements in HCV therapy, and for whom there is the urgent need of optimising the costeffectiveness of new treatment schedules containing both interferon and antiviral.

On the basis of these remarks, we performed a retrospective study on stored serum samples from CHC patients with the following purposes: