Randomized Clinical Trial
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. May 18, 2016; 8(14): 625-631
Published online May 18, 2016. doi: 10.4254/wjh.v8.i14.625
Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial
Zaigham Abbas, Mohammad Sadik Memon, Muhammad Amir Umer, Minaam Abbas, Lubna Shazi
Zaigham Abbas, Department of Gastroenterology, Ziauddin University Hospital, Karachi 74400, Pakistan
Zaigham Abbas, Muhammad Amir Umer, Department of Medicine, Orthopedic and Medical Institute, Karachi 74400, Pakistan
Zaigham Abbas, Minaam Abbas, Lubna Shazi, Liver Stomach Clinic Zamzama, Karachi 75500, Pakistan
Mohammad Sadik Memon, Asian Institute of Medical Sciences, Hyderabad 71000, Pakistan
Author contributions: Abbas Z was responsible for the study conception and design, data analysis and interpretation, and manuscript drafting; Abbas Z and Memon MS recruited patients for the study; Umer MA, Abbas M and Shazi L coordinated study related activities and helped in manuscript drafting; all authors reviewed and approved the final version to be submitted for publication.
Institutional review board statement: The study was approved by Independent Ethics Review Board and Institutional Review Board.
Clinical trial registration statement: This investigator initiated trial was registered with the Roche (ML25746).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Authors do not have any conflict of interest to declare.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Zaigham Abbas, FCPS, FRCP, Department of Gastroenterology, Ziauddin University Hospital, Shahrah-e-Ghalib, Karachi 74400, Pakistan. drzabbas@gmail.com
Telephone: +92-21-35862939 Fax: +92-21-35862940
Received: January 25, 2016
Peer-review started: January 27, 2016
First decision: March 9, 2016
Revised: March 30, 2016
Accepted: April 14, 2016
Article in press: April 18, 2016
Published online: May 18, 2016

AIM: To investigate the efficacy of pegylated interferon alfa (PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D.

METHODS: Forty hepatitis D virus (HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily (n = 21) or PEG-IFNα alone (n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed.

RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9 (43%) patients receiving combination therapy and 12 (63%) patients receiving PEG-IFNα alone (P = 0.199). Decline in hepatitis B surface antigen (HBsAg) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients (38%) receiving combination therapy and 10 patients (53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7 (33%) and 8 (42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBsAg and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance.

CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.

Keywords: Hepatitis D, Entecavir, Hepatitis B surface antigen, Pegylated interferon, Hepatitis D virus RNA, Treatment

Core tip: Chronic hepatitis D is a difficult to treat infection. Six months post treatment response is seen only in one quarter of the patients treated with pegylated interferon alfa (PEG-IFNα). In an attempt to improve the response of PEG-IFN, we combined entecavir. This is the first study to evaluate the efficacy of PEG-IFN with entecavir compared to PEG-IFN alone for the treatment of hepatitis D infection. Our study showed that the combination treatment did not have any additional benefit in terms of hepatitis D virus RNA suppression and hepatitis B surface antigen reduction as compared to PEG-IFN alone.