Retrospective Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Aug 21, 2022; 28(31): 4390-4398
Published online Aug 21, 2022. doi: 10.3748/wjg.v28.i31.4390
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
Processing time: 115 Days and 17.5 Hours
Abstract
BACKGROUND

Hepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF).

AIM

To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (i.e., FibroScan®).

METHODS

Retrospective, observational cohort study from the Canadian HBV Network. Data collected included demographics, NA, HBV DNA, alanine aminotransferase (ALT), and LSM. Patients were HBV monoinfected patients, treatment naïve, and received 1 NA with minimum 1 year follow-up.

RESULTS

In 465 (median 49 years, 37% female, 35% hepatitis B e antigen+ at baseline, 84% Asian, 6% White, and 9% Black). Percentage of 64 (n = 299) received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years, respectively. The mean baseline LSM was 11.2 kPa (TDF) vs 8.3 kPa (LAM) (P = 0.003). At 5-year follow-up, the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM (P = 0.83). There was a significant difference in fibrosis regression between groups (i.e., mean -4.2 kPa change in TDF and -1.6 kPa in LAM, P < 0.05). The last available data on treatment showed that all had normal ALT, but more TDF patients were virologically suppressed (< 10 IU/mL) (n = 170/190, 89%) vs LAM-treated (n = 35/58, 60%) (P < 0.05). None cleared HBsAg.

CONCLUSION

In this real-world North American study, approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

Keywords: Nucleos(t)ide analog therapy; Functional cure; Hepatitis B virus surface antigen loss; Fibrosis regression; Liver stiffness measurement; Transient elastography

Core Tip: In summary in this real-world diverse cohort study of chronic hepatitis B patients in Canada, long-term nucleo(s)ide analog (either 1st or 2nd generation) therapy suppresses hepatitis B virus DNA and improves hepatic inflammation and liver fibrosis, as determined by non-invasive testing (i.e., transient elastography). In patients treated for up to 5 years, none achieved hepatitis B surface antigen loss (functional cure), highlighting the need for improved therapeutic strategies to reduce the life-long burden of antiviral therapy.