Profiles of liver fibrosis evolution during long-term tenofovir treatment in HIV-positive patients coinfected with hepatitis B.
group-based trajectory models
hepatic fibrosis
hepatitis B virus
human immunodeficiency virus
Journal
Liver international : official journal of the International Association for the Study of the Liver
ISSN: 1478-3231
Titre abrégé: Liver Int
Pays: United States
ID NLM: 101160857
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
11
07
2021
received:
05
05
2021
accepted:
19
07
2021
pubmed:
24
7
2021
medline:
4
3
2022
entrez:
23
7
2021
Statut:
ppublish
Résumé
Data on liver fibrosis evolution and its involvement in liver-related morbidity are scarce in individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection during treatment. We identified profiles of liver fibrosis evolution in coinfected patients undergoing tenofovir (TDF). We included 169 HIV-HBV-coinfected patients on TDF-based antiretroviral therapy. Virological and clinical data were obtained at TDF-initiation and every 6-12 months. From data on non-invasive liver fibrosis assessments collected yearly (FibroTest®), we established clusters of individuals with similar liver fibrosis evolution using group-based trajectory models. Four profiles of liver fibrosis evolution were established from a median follow-up of 7.6 years (IQR = 3.1-13.1): low fibrosis with no progression (29.6%, profile A), low fibrosis with progression (22.5%, profile B), moderate fibrosis with high fluctuation (39.6%, profile C), and cirrhosis with no regression (8.3%, profile D). When compared to profile A, baseline HBeAg-positive status was associated with profiles B (P = .007) and C (P = .004), older age with profiles C (P < .001) and D (P = .001), exposure to second-generation protease inhibitors with profile C (P = .004), and CD4 TDF-treated HIV-HBV coinfected individuals do not seem to benefit from comparable levels of liver fibrosis regression as in HBV mono-infection. Liver-related morbidity occurs mainly in those with fluctuating or consistently high fibrosis levels.
Sections du résumé
BACKGROUND & AIMS
Data on liver fibrosis evolution and its involvement in liver-related morbidity are scarce in individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection during treatment. We identified profiles of liver fibrosis evolution in coinfected patients undergoing tenofovir (TDF).
METHODS
We included 169 HIV-HBV-coinfected patients on TDF-based antiretroviral therapy. Virological and clinical data were obtained at TDF-initiation and every 6-12 months. From data on non-invasive liver fibrosis assessments collected yearly (FibroTest®), we established clusters of individuals with similar liver fibrosis evolution using group-based trajectory models.
RESULTS
Four profiles of liver fibrosis evolution were established from a median follow-up of 7.6 years (IQR = 3.1-13.1): low fibrosis with no progression (29.6%, profile A), low fibrosis with progression (22.5%, profile B), moderate fibrosis with high fluctuation (39.6%, profile C), and cirrhosis with no regression (8.3%, profile D). When compared to profile A, baseline HBeAg-positive status was associated with profiles B (P = .007) and C (P = .004), older age with profiles C (P < .001) and D (P = .001), exposure to second-generation protease inhibitors with profile C (P = .004), and CD4
CONCLUSIONS
TDF-treated HIV-HBV coinfected individuals do not seem to benefit from comparable levels of liver fibrosis regression as in HBV mono-infection. Liver-related morbidity occurs mainly in those with fluctuating or consistently high fibrosis levels.
Substances chimiques
DNA, Viral
0
Tenofovir
99YXE507IL
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2874-2884Informations de copyright
© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Références
Leumi S, Bigna JJ, Amougou MA, Ngouo A, Nyaga UF, Noubiap JJ. Global burden of hepatitis B infection in people living with human immunodeficiency virus: a systematic review and meta-analysis. Clin Infect Dis. 2020;71:2799-2806.
Singh KP, Crane M, Audsley J, Avihingsanon A, Sasadeusz J, Lewin SR. HIV-hepatitis B virus coinfection: epidemiology, pathogenesis, and treatment. AIDS. 2017;31:2035-2052.
Chen C-J, Yang H-I, Iloeje UH, The REVEAL-HBV study group. Hepatitis B virus DNA levels and outcomes in chronic hepatitis B. Hepatology. 2009;49:S72-S84.
Piroth L, Pol S, Miailhes P, et al. Therapeutic management and evolution of chronic hepatitis B: does HIV still have an impact? The EPIB 2012 study. Liver Int. 2015;35:1950-1958.
Lieveld FI, Smit C, Richter C, et al. Liver decompensation in HIV/hepatitis B coinfection in the combination antiretroviral therapy era does not seem increased compared to hepatitis B mono-infection. Liver Int. 2019;39:470-483.
Dezanet LNC, Kassime R, Miailhes P, et al. Effect of viral replication and liver fibrosis on all-cause mortality in HIV/HBV coinfected patients: a retrospective analysis of a 15-year longitudinal cohort. Clin Infect Dis. 2021;ciab594. https://doi.org/10.1093/cid/ciab594
Boyd A, Lacombe K, Lavocat F, et al. Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients. J Hepatol. 2016;65:683-691.
Marcellin P, Gane E, Buti M, 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;381:468-475.
Boyd A, Miailhes P, Lascoux-Combe C, et al. Renal outcomes after up to eight years of tenofovir exposure in HIV-HBV-coinfected patients. Antivir Ther. 2016;22:31-42.
Stockdale AJ, Phillips RO, Beloukas A, et al. Liver fibrosis by transient elastography and virologic outcomes after introduction of tenofovir in lamivudine-experienced adults with HIV and hepatitis B virus coinfection in Ghana. Clin Infect Dis. 2015;61:883-891.
Boyd A, Lacombe K. More long-term assessment of transient elastography is needed for HIV/hepatitis B virus-coinfected patients undergoing treatment with tenofovir. Clin Infect Dis. 2016;62:128-130.
Vinikoor MJ, Sinkala E, Chilengi R, et al. Impact of antiretroviral therapy on liver fibrosis among human immunodeficiency virus-infected adults with and without HBV coinfection in Zambia. Clin Infect Dis. 2017;64:1343-1349.
Boyd A, Bottero J, Miailhes P, et al. Liver fibrosis regression and progression during controlled hepatitis B virus infection among HIV-HBV patients treated with tenofovir disoproxil fumarate in France: a prospective cohort study. J Int AIDS Society. 2017;20:21426.
Sterling RK, Wahed AS, King WC, et al. Spectrum of liver disease in hepatitis B virus (HBV) patients co-infected with human immunodeficiency virus (HIV): results of the HBV-HIV cohort study. Am J Gastroenterol. 2019;114:746-757.
Audsley J, Robson C, Aitchison S, et al. Liver fibrosis regression measured by transient elastography in human immunodeficiency virus (HIV)-hepatitis B virus (HBV)-coinfected individuals on long-term HBV-active combination antiretroviral therapy. Open Forum Infect Dis. 2016;3:ofw035.
Boyd A, Dezanet LNC, Kassime R, et al. Subclinical and clinical outcomes in patients coinfected with HIV and chronic hepatitis B virus from clinical outpatient centers in France: protocol for an ambispective, longitudinal cohort study. JMIR Res Protoc. 2021;10:e24731.
Boyd A, Gozlan J, Miailhes P, et al. Rates and determinants of hepatitis B ‘e’ antigen and hepatitis B surface antigen seroclearance during long-term follow-up of patients coinfected with HIV and hepatitis B virus. AIDS. 2015;29:1963-1973.
Poynard T, Ngo Y, Munteanu M, Thabut D, Ratziu V. Noninvasive markers of hepatic fibrosis in chronic hepatitis B. Curr Hepat Rep. 2011;10:87-97.
Bottero J, Lacombe K, Guéchot J, et al. Performance of 11 biomarkers for liver fibrosis assessment in HIV/HBV co-infected patients. J Hepatol. 2009;50:1074-1083.
Nagin DS. Analyzing developmental trajectories: a semiparametric, group-based approach. Psychol Methods. 1999;4:139-157.
Boyd A, Maylin S, Gozlan J, et al. Use of hepatitis B surface and “e” antigen quantification during extensive treatment with tenofovir in patients co-infected with HIV-HBV. Liver Int. 2015;35:795-804.
Chen C, Lee W, Yang H, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology. 2011;141:1240-1248.e2.
Elmer J, Jones BL, Nagin DS. Using the beta distribution in group-based trajectory models. BMC Med Res Methodol. 2018;18:152.
Sun Y, Wu X, Zhou J, et al. Persistent low level of hepatitis B virus promotes fibrosis progression during therapy. Clin Gastroenterol Hepatol. 2020;18:2582-2591.e6.
Kim MN, Kim SU, Kim BK, et al. Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir. Liver Int. 2014;34:1216-1223.
Sterling RK, King WC, Khalili M, et al. A prospective study evaluating changes in histology, clinical and virologic outcomes in HBV-HIV co-infected adults in North America. Hepatology. 2021. https://doi.org/10.1002/hep.31823
Iser DM, Lewin SR. The pathogenesis of liver disease in the setting of HIV-hepatitis B virus coinfection. Antivir Ther. 2009;14:155-164.
Sarmati L, Malagnino V. HBV infection in HIV-driven immune suppression. Viruses. 2019;11:1077.
Singh KP, Zerbato JM, Zhao W, et al. Intrahepatic CXCL10 is strongly associated with liver fibrosis in HIV-hepatitis B co-infection. PLoS Pathog. 2020;16:e1008744.
Loko M-A, Bani-Sadr F, Winnock M, et al. Impact of HAART exposure and associated lipodystrophy on advanced liver fibrosis in HIV/HCV-coinfected patients. J Viral Hepat. 2011;18:e307-e314.
Blanco F, Barreiro P, Ryan P, et al. Risk factors for advanced liver fibrosis in HIV-infected individuals: role of antiretroviral drugs and insulin resistance: predictors of advanced liver fibrosis in HIV-infected patients. J Viral Hepat. 2011;18:11-16.
Klein MB, Althoff KN, Jing Y, et al. Risk of end-stage liver disease in HIV-viral hepatitis coinfected persons in North America from the early to modern antiretroviral therapy eras. Clin Infect Dis. 2016;63:1160-1167.
Carr A. Toxicity of antiretroviral therapy and implications for drug development. Nat Rev Drug Discov. 2003;2:624-634.
Sulkowski MS. Drug-induced liver injury associated with antiretroviral therapy that includes HIV-1 protease inhibitors. Clin Infect Dis. 2004;38:S90-S97.
Boyd A, Bottero J, Miailhes P, et al. Liver fibrosis regression and progression during controlled hepatitis B virus infection among HIV-HBV patients treated with tenofovir disoproxil fumarate in France: a prospective cohort study. J Int AIDS Soc. 2017;20:21426.
Surgers L, Lacombe K. Hepatoxicity of new antiretrovirals: a systematic review. Clin Res Hepatol Gastroenterol. 2013;37:126-133.
Núñez M. Clinical syndromes and consequences of antiretroviral-related hepatotoxicity. Hepatology. 2010;52:1143-1155.
McMahon BJ. The natural history of chronic hepatitis B virus infection. Hepatology. 2009;49:S45-S55.
Poynard T, Munteanu M, Deckmyn O, et al. Validation of liver fibrosis biomarker (FibroTest) for assessing liver fibrosis progression: proof of concept and first application in a large population. J Hepatol. 2012;57:541-548.
de Lédinghen V, Vergniol J, Barthe C, et al. Non-invasive tests for fibrosis and liver stiffness predict 5-year survival of patients chronically infected with hepatitis B virus. Aliment Pharmacol Ther. 2013;37:979-988.
Terrault NA, Lok ASF, McMahon BJ, et al. Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance. Hepatology. 2018;67:1560-1599.
World Health Organization. WHO guidelines for the prevention, care and treatment of persons with chronic hepatitis B virus infection. [Internet]. World Health Organization Stylus Publishing, LLC. https://www.ncbi.nlm.nih.gov/books/NBK305553. Accessed April 22, 2021
European AIDS Clinical Society. European AIDS Clinical Society guidelines, version 10.1. [Internet]. October 2020. https://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html. Accessed April 22, 2021
Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. [Internet]. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines. Accessed July 11, 2021
Miailhes P, Pradat P, Chevallier M, et al. Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients: elastometry in HIV-HBV patients. J Viral Hepat. 2011;18:61-69.
Sterling RK, King WC, Wahed AS, et al. Evaluating noninvasive markers to identify advanced fibrosis by liver biopsy in HBV/HIV co-infected adults. Hepatology. 2020;71:411-421.
Béguelin C, Moradpour D, Sahli R, et al. Hepatitis delta-associated mortality in HIV/HBV-coinfected patients. J Hepatol. 2017;66:297-303.