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

Anders Boyd (1) , Julie Bottero (2) , Patrick Miailhes (3) , Caroline Lascoux-Combe (4) , Hayette Rougier (5) , Pierre-Marie Girard (1, 2) , Lawrence Serfaty (2) , Karine Lacombe (1, 2)

1 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
2 CHU Saint-Antoine [AP-HP]
3 Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL]
4 Service des Maladies Infectieuses et Tropicales [CHU Saint Louis]
5 IMEA - Institut de Médecine et d'Epidémiologie Appliquées

Introduction: Long-term tenofovir disoproxil fumarate (TDF) use has been associated with significant regression of liver fibrosis during hepatitis B virus (HBV) mono-infection, yet little is known during HIV–HBV coinfection. The aim of this study was to evaluate the evolution of liver fibrosis and its determinants in TDF-treated coinfected patients. Methods: In this prospective cohort study, 167 HIV–HBV-infected patients initiating TDF-containing antiretroviral therapy were included. Fibrosis was assessed using the FibroTest® at baseline and every six to twelve months. Risk factors for fibrosis progression (F0–F1–F2 to F3–F4) and regression (F3–F4 to F0–F1–F2) were evaluated. Results: At baseline, 134 (80.2%) patients had detectable HBV-DNA (median = 4.93 log 10 IU/mL, IQR = 2.94–7.15) and 104 (62.3%) had hepatitis B " e " antigen-positive serology. Median follow-up was sixty months (IQR = 36–93). In the 47 (28.1%) patients with F3–F4 baseline fibrosis, 7/47 (14.9%) regressed to F0–F1–F2 at last follow-up visit. Fibrosis regression was significantly associated with higher CD4+ cell counts (P = 0.009) and lower fasting triglyceride levels (P = 0.007) at TDF-initiation. In the 120 (71.9%) patients with F0–F1–F2-baseline fibrosis, 20/120 (16.7%) progressed to F3–F4 at last follow-up visit. Fibrosis progression was associated with male gender (P = 0.01), older age (P = 0.001), from low/moderate HBV-endemic country (P = 0.007), lower nadir CD4+ cell count (P = 0.03), higher fasting glycaemia (P = 0.03) and anaemia (P = 0.004) at TDF-initiation. Control of HBV replication at end of follow-up was extensive (88.1%), while no HBV-related factors emerged as predictors of progression/regression. Incidence of severe liver-related events was low (n = 4, rate = 0.5/100 person-years). Conclusions: Liver fibrosis levels are stable for most coinfected patients undergoing TDF, despite control of HBV replication. Nevertheless, a concerning amount of liver fibrosis progression did occur, which could be partly explained by metabolic abnormalities and past severe immunosuppression and requires further evaluation.

Mots clés: noninvasive markers; liver fibrosis; liver cirrhosis; hepatocellular carcinoma; immunosuppression

Domaines: Maladies infectieuses; Hépatologie et Gastroentérologie

Anders Boyd, Julie Bottero, Patrick Miailhes, Caroline Lascoux-Combe, Hayette Rougier, 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. Journal of the International AIDS Society, 2017, 20 (1), pp.21426. ⟨10.7448/IAS.20.1.21426⟩. ⟨hal-01502149⟩