Copyright
©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue
Alnoor Ramji, Karen Doucette, Curtis Cooper, Gerald Yosel Minuk, Mang Ma, Alexander Wong, David Wong, Edward Tam, Brian Conway, David Truong, Philip Wong, Lisa Barrett, Hin Hin Ko, Sarah Haylock-Jacobs, Nishi Patel, Gilaad G Kaplan, Scott Fung, Carla S Coffin
Alnoor Ramji, Hin Hin Ko, Department of Medicine, University of British Columbia, Vancouver V6T 1Z3, Canada
Karen Doucette, Mang Ma, Department of Medicine, University of Alberta, Edmonton T6G 2R7, Canada
Curtis Cooper, Department of Medicine, The Ottawa Hospital Research Institute, University of Ottawa, Ottawa ON K1H 8L6, Canada
Gerald Yosel Minuk, Department of Medicine, University of Manitoba, Winnipeg R3E 3J7, Canada
Alexander Wong, Department of Medicine, University of Saskatchewan, Saskatoon S7N 5E5, Canada
David Wong, Scott Fung, Department of Medicine,University Health Network, Toronto M5G 2C4, Canada
Edward Tam, Pacific Gastroenterology Associates, Vancouver V6Z 2K5, Canada
Brian Conway, David Truong, Vancouver Infectious Disease Centre, Vancouver V6Z 2C7, Canada
Philip Wong, Department of Medicine, McGill University, Montreal H3A 0G4, Canada
Lisa Barrett, Department of Microbiology and Immunology, Dalhousie University, Halifax B3H 4R2, Canada
Sarah Haylock-Jacobs, Nishi Patel, Gilaad G Kaplan, Carla S Coffin, Cumming School of Medicine, University of Calgary, Calgary T2N 1N4, Canada
Author contributions: Ramji A contributed to study design, data contribution, and manuscript draft; Coffin CS contributed to manuscript draft, data contribution, data analysis, and resource support; Haylock-Jacobs S contributed to data analysis and manuscript draft; Patel N and Kaplan GG contributed to data analysis; all other authors contributed to data contribution, manuscript review and feedback.
Institutional review board statement: The study was reviewed and approved by the Conjoint Health Research Ethics Board, No. REB17-2321_REN4.
Conflict-of-interest statement: Dr. Alnoor Ramji and Dr. Carla S Coffin didn’t receive at any time payment from a third party for any aspect for the submitted work; there are no relevant conflict of interest; there are no patents related to this work; Dr. Alnoor Ramji and Dr. Carla S Coffin have nothing to disclosure.
Data sharing statement: No data sharing is approved by the institutional ethics board.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Alnoor Ramji, MD, Associate Professor, Department of Medicine, University of British Columbia, 2775 Laurel Str, Gordon and Leslie Diamond Health Care, Vancouver V6T 1Z3, Canada. ramji_a@hotmail.com
Received: April 22, 2022
Peer-review started: April 22, 2022
First decision: May 9, 2022
Revised: May 22, 2022
Accepted: July 25, 2022
Article in press: July 25, 2022
Published online: August 21, 2022
ARTICLE HIGHLIGHTS
Research background
Therapy of hepatitis B virus (HBV) with nucleos(t)ide analogues (NA) can be associated with fibrosis regression. There are both low and high potency agents approved for therapy and access to these therapies maybe variable. There is limited real-world data comparing these agents on their effect to result in fibrosis regression and long term outcomes.
Research motivation
Although high-potency agents are considered the standard of care, there has been variable access to these agents and indeed ongoing use of these agents in 1st world countries to include Canada. It is thus important to provide evidence in outcomes to include fibrosis regression between the high and low potency NA’s. This study may impact the use of these agents in the future, and allow consideration for switching from low to high potency agents if possible.
Research objectives
To assess HBV viral response, biochemical remission, liver fibrosis regression and hepatitis B surface antigen (HBsAg) sero-clearance after treatment with either a 1st or 2nd line NA therapy. These objectives were realized and the future impact would be the consideration of utilizing 1st vs 2nd line NA’s. Further, other outcome measure to include HBsAg loss and development of hepatocellular carcinoma (HCC) may be considered.
Research methods
We performed a retrospective observational cohort study utilizing a National network in HBV. Novel aspects that allowed this study is the utilization of a National Network which was able to capture differences in NA utilization based on regional differences of reimbursement. The strength of this study lies in the diversity that the Canadian HBV Network provides. The utilization of liver stiffness by transient elastography in a North American cohort for this objective is also unique.
Research results
As per differences in utilization, a larger proportion of patients with advanced fibrosis were initiated with tenofovir disoproxil fumarate (TDF) compared to LAM. At the end of the study period there were similar stages of fibrosis between the 2 groups. There was an increased fibrosis regression in those treated with a high potency compared to a low-potency NA. More patients in the TDF group also achieved virological suppression, though alanine amino transferase (ALT) normalization was similar.
Research conclusions
In this diverse cohort treatment with low and high potency NA’s achieves high rates of viral suppression, ALT normalization and a large proportion achieve fibrosis regression. The strength of national collaboration within a network is exemplified in this study in particular taking advantages of diversity within an overall similar medical system. These differences within a Network can be a powerful tool to answer research questions and can reduce a number of biases inherent when comparing populations/studies between countries or regions.
Research perspectives
The future direction would include potential for long-term outcomes with differential NA usage to include HBsAg loss or seroconversion and any differences in development of HCC albeit in a population with differences in stage of fibrosis at baseline. This study population and Network provides a unique perspective to answer this question.
