Skip to main content
Top
Published in: BMC Gastroenterology 1/2024

Open Access 01-12-2024 | Hepatitis B | Research

Successful therapy with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) does not guarantee amelioration of liver damage assessing by transient elastography. A retrospective - prospective multicenter study

Authors: Hariklia Kranidioti, Konstantinos Zisimopoulos, Theodora Oikonomou, Theodoros Voulgaris, Spyros Siakavellas, Polixeni Agorastou, Melanie Deutsch, Christos Triantos, Ioannis Goulis, George Papatheodoridis, Spilios Manolakopoulos

Published in: BMC Gastroenterology | Issue 1/2024

Login to get access

Abstract

Background

Preventing disease progression and viral suppression are the main goals of antiviral therapy in chronic hepatitis B (CHB). Liver stiffness measurement (LSM) by transient elastography is a reliable non-invasive method to assess liver fibrosis in patients with CHB. Our aim was to explore factors that may affect changes in LSMs during long term tenofovir (TDF) monotherapy in a well characterized cohort of patients with compensated CHB.

Methods

We analyzed serial LSMs in 103 adult patients with CHB who were on TDF monotherapy and had at least three LSMs over a period of 90 months.

Results

Twenty-five (24%) patients had advanced fibrosis at baseline. A significant decline in mean LSM between baseline and last visit (8.7 ± 6.2 kPa vs. 6.7 ± 3.3, p = 10− 3) was observed. Twenty-four (23%) patients had progression of liver fibrosis with mean increase in liver stiffness of 2.8 kPa (range: 0.2–10.2 kPa). Multivariate analysis showed that BMI ≥ 25 (OR, 0.014; 95% CI, 0.001–0.157; p = 0.001) and advanced fibrosis (OR, 5.169; 95% CI, 1.240–21.540; p = 0.024) were independently associated with a fibrosis regression of > 30% of liver stiffness compared to baseline value.

Conclusions

In CHB patients TDF monotherapy resulted in liver fibrosis regression, especially in patients with advanced fibrosis. Despite the successful antiviral effect of TDF, 1 out of 4 patients had liver fibrosis progression. Obesity and advanced fibrosis at baseline were independently associated with significant liver fibrosis regression.
Literature
1.
go back to reference Progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies, 2016–2021. World Health Organization; 2019. Progress report on HIV, viral hepatitis and sexually transmitted infections. Accountability for the global health sector strategies, 2016–2021. World Health Organization; 2019.
2.
go back to reference Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–86.CrossRefPubMed Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ, et al. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006;130(3):678–86.CrossRefPubMed
4.
go back to reference European Association for the Study of the Liver. Electronic address eee, European Association for the study of the L. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.CrossRef European Association for the Study of the Liver. Electronic address eee, European Association for the study of the L. EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67(2):370–98.CrossRef
5.
go back to reference Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12(8):1295–303.CrossRefPubMed Yuen MF, Seto WK, Chow DH, Tsui K, Wong DK, Ngai VW, et al. Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease. Antivir Ther. 2007;12(8):1295–303.CrossRefPubMed
6.
go back to reference Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75.CrossRefPubMed Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013;381(9865):468–75.CrossRefPubMed
7.
go back to reference Manolakopoulos S, Triantos C, Theodoropoulos J, Vlachogiannakos J, Kougioumtzan A, Papatheodoridis G, et al. Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension. J Hepatol. 2009;51(3):468–74.CrossRefPubMed Manolakopoulos S, Triantos C, Theodoropoulos J, Vlachogiannakos J, Kougioumtzan A, Papatheodoridis G, et al. Antiviral therapy reduces portal pressure in patients with cirrhosis due to HBeAg-negative chronic hepatitis B and significant portal hypertension. J Hepatol. 2009;51(3):468–74.CrossRefPubMed
8.
go back to reference Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53(2):348–56.CrossRefPubMed Papatheodoridis GV, Lampertico P, Manolakopoulos S, Lok A. Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy: a systematic review. J Hepatol. 2010;53(2):348–56.CrossRefPubMed
9.
go back to reference Bedossa P. Reversibility of hepatitis B virus cirrhosis after therapy: who and why? Liver Int. 2015;35(Suppl 1):78–81.CrossRefPubMed Bedossa P. Reversibility of hepatitis B virus cirrhosis after therapy: who and why? Liver Int. 2015;35(Suppl 1):78–81.CrossRefPubMed
11.
go back to reference Chon YE, Choi EH, Song KJ, Park JY, Kim DY, Han KH, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS ONE. 2012;7(9):e44930.CrossRefPubMedPubMedCentral Chon YE, Choi EH, Song KJ, Park JY, Kim DY, Han KH, et al. Performance of transient elastography for the staging of liver fibrosis in patients with chronic hepatitis B: a meta-analysis. PLoS ONE. 2012;7(9):e44930.CrossRefPubMedPubMedCentral
12.
go back to reference Papatheodoridis GV, Manolakopoulos S, Margariti A, Papageorgiou MV, Kranidioti H, Katoglou A, et al. The usefulness of transient elastography in the assessment of patients with HBeAg-negative chronic hepatitis B virus infection. J Viral Hepat. 2014;21(7):517–24.CrossRefPubMed Papatheodoridis GV, Manolakopoulos S, Margariti A, Papageorgiou MV, Kranidioti H, Katoglou A, et al. The usefulness of transient elastography in the assessment of patients with HBeAg-negative chronic hepatitis B virus infection. J Viral Hepat. 2014;21(7):517–24.CrossRefPubMed
13.
go back to reference Kim MN, Kim SU, Kim BK, Park JY, Kim DY, Ahn SH, et al. Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir. Liver Int. 2014;34(8):1216–23.CrossRefPubMed Kim MN, Kim SU, Kim BK, Park JY, Kim DY, Ahn SH, et al. Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir. Liver Int. 2014;34(8):1216–23.CrossRefPubMed
14.
go back to reference Fung J, Lai CL, Wong DK, Seto WK, Hung I, Yuen MF. Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study. J Viral Hepat. 2011;18(7):e200–5.CrossRefPubMed Fung J, Lai CL, Wong DK, Seto WK, Hung I, Yuen MF. Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study. J Viral Hepat. 2011;18(7):e200–5.CrossRefPubMed
15.
go back to reference Facciorusso A, Garcia Perdomo HA, Muscatiello N, Buccino RV, Wong VW, Singh S. Systematic review with meta-analysis: change in liver stiffness during anti-viral therapy in patients with hepatitis B. Dig Liver Dis. 2018;50(8):787–94.CrossRefPubMed Facciorusso A, Garcia Perdomo HA, Muscatiello N, Buccino RV, Wong VW, Singh S. Systematic review with meta-analysis: change in liver stiffness during anti-viral therapy in patients with hepatitis B. Dig Liver Dis. 2018;50(8):787–94.CrossRefPubMed
16.
go back to reference Ji D, Chen Y, Shang Q, Liu H, Tan L, Wang J, et al. Unreliable estimation of Fibrosis Regression during treatment by liver stiffness measurement in patients with chronic Hepatitis B. Am J Gastroenterol. 2021;116(8):1676–85.CrossRefPubMedPubMedCentral Ji D, Chen Y, Shang Q, Liu H, Tan L, Wang J, et al. Unreliable estimation of Fibrosis Regression during treatment by liver stiffness measurement in patients with chronic Hepatitis B. Am J Gastroenterol. 2021;116(8):1676–85.CrossRefPubMedPubMedCentral
17.
go back to reference The 68th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2017. Hepatology. 2017;66(S1):1–1185. The 68th Annual Meeting of the American Association for the Study of Liver Diseases: The Liver Meeting 2017. Hepatology. 2017;66(S1):1–1185.
18.
go back to reference Abstracts of the 27th Annual Conference of APASL, March 14-18, 2018, New Delhi, India. Hepatol Int. 2018:181–661. Abstracts of the 27th Annual Conference of APASL, March 14-18, 2018, New Delhi, India. Hepatol Int. 2018:181–661.
19.
go back to reference European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline P, Chair, representative EGB, Panel m. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol. 2021;75(3):659–89. European Association for the Study of the Liver. Electronic address eee, Clinical Practice Guideline P, Chair, representative EGB, Panel m. EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update. J Hepatol. 2021;75(3):659–89.
20.
go back to reference Xu W, Hu Q, Chen C, Li W, Li Q, Chen L. Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic Hepatitis B: A Retrospective Cohort Study. Infect Dis Ther. 2023;12(2):487–98. Xu W, Hu Q, Chen C, Li W, Li Q, Chen L. Non-invasive Assessment of Liver Fibrosis Regression in Patients with Chronic Hepatitis B: A Retrospective Cohort Study. Infect Dis Ther. 2023;12(2):487–98.
21.
go back to reference de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VIIF. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–74. de Franchis R, Bosch J, Garcia-Tsao G, Reiberger T, Ripoll C, Baveno VIIF. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–74.
22.
go back to reference Chon YE, Park JY, Myoung SM, Jung KS, Kim BK, Kim SU, et al. Improvement of Liver Fibrosis after Long-Term Antiviral Therapy Assessed by Fibroscan in Chronic Hepatitis B Patients With Advanced Fibrosis. Am J Gastroenterol. 2017;112(6):882–91. Chon YE, Park JY, Myoung SM, Jung KS, Kim BK, Kim SU, et al. Improvement of Liver Fibrosis after Long-Term Antiviral Therapy Assessed by Fibroscan in Chronic Hepatitis B Patients With Advanced Fibrosis. Am J Gastroenterol. 2017;112(6):882–91.
23.
go back to reference Cho H, Lee YB, Ha Y, Chon YE, Kim MN, Lee JH, et al. Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study. BMC Gastroenterol. 2023;23(1):210. Cho H, Lee YB, Ha Y, Chon YE, Kim MN, Lee JH, et al. Changes in liver stiffness values assessed using transient elastography in chronic hepatitis B patients treated with tenofovir disoproxil fumarate: a prospective observational study. BMC Gastroenterol. 2023;23(1):210.
24.
go back to reference Chon YE, Jung KS, Ha Y, Kim MN, Lee JH, Hwang SG, et al. High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis. J Viral Hepat. 2020;27(11):1119–26. Chon YE, Jung KS, Ha Y, Kim MN, Lee JH, Hwang SG, et al. High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis. J Viral Hepat. 2020;27(11):1119–26.
25.
go back to reference Seto WK, Fung J, Cheung KS, Mak LY, Hui RW, Liu KS, et al. Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2016;44(10):1071-9. Seto WK, Fung J, Cheung KS, Mak LY, Hui RW, Liu KS, et al. Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B. Aliment Pharmacol Ther. 2016;44(10):1071-9.
26.
go back to reference Shen F, Mi YQ, Xu L, Liu YG, Wang XY, Pan Q, et al. Moderate to severe hepatic steatosis leads to overestimation of liver stiffness measurement in chronic hepatitis B patients without significant fibrosis. Aliment Pharmacol Ther. 2019;50(1):93–102. Shen F, Mi YQ, Xu L, Liu YG, Wang XY, Pan Q, et al. Moderate to severe hepatic steatosis leads to overestimation of liver stiffness measurement in chronic hepatitis B patients without significant fibrosis. Aliment Pharmacol Ther. 2019;50(1):93–102.
27.
go back to reference Liu J, Ma Y, Han P, Wang J, Liu YG, Shi RF, et al. Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients. Clin Res Hepatol Gastroenterol. 2022;46(8):101957. Liu J, Ma Y, Han P, Wang J, Liu YG, Shi RF, et al. Hepatic steatosis leads to overestimation of liver stiffness measurement in both chronic hepatitis B and metabolic-associated fatty liver disease patients. Clin Res Hepatol Gastroenterol. 2022;46(8):101957.
28.
go back to reference Kim WR, Berg T, Asselah T, Flisiak R, Fung S, Gordon SC, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. J Hepatol. 2016;64(4):773–80. Kim WR, Berg T, Asselah T, Flisiak R, Fung S, Gordon SC, et al. Evaluation of APRI and FIB-4 scoring systems for non-invasive assessment of hepatic fibrosis in chronic hepatitis B patients. J Hepatol. 2016;64(4):773–80.
Metadata
Title
Successful therapy with tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) does not guarantee amelioration of liver damage assessing by transient elastography. A retrospective - prospective multicenter study
Authors
Hariklia Kranidioti
Konstantinos Zisimopoulos
Theodora Oikonomou
Theodoros Voulgaris
Spyros Siakavellas
Polixeni Agorastou
Melanie Deutsch
Christos Triantos
Ioannis Goulis
George Papatheodoridis
Spilios Manolakopoulos
Publication date
01-12-2024
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2024
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-024-03200-3

Other articles of this Issue 1/2024

BMC Gastroenterology 1/2024 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine