Liver fibrosis changes in HIV-HBV-coinfected patients: clinical, biochemical and histological effect of long-term tenofovir disoproxil fumarate use.
BACKGROUND
Data on liver fibrosis evolution in HIV-HBV-coinfected patients treated with tenofovir disoproxil fumarate (TDF) are scarce. The effect of TDF on liver fibrosis in 148 HIV-HBV-coinfected patients was prospectively evaluated using Fibrometer∆ scores and liver biopsies in a subset of patients.


METHODS
The mean change from baseline (Δ) in Fibrometer score was modelled using a generalized estimating equation. Homogeneous continuous-time Markov models were used to study risk factors for regression or progression of liver fibrosis.


RESULTS
Median follow-up of patients treated with TDF was 29.5 months (25th-75th percentile 20.9-38.1). The distribution of scored fibrosis at TDF initiation was F0-F1 n=65, F2 n=37 and F3-F4 n=46. In patients with a baseline fibrosis score of F3-F4, Fibrometer score decreased with a triphasic shape (Fibrometer Δ at 12, 24 and 36 months after TDF initiation was -0.079, -0.069 and -0.102, respectively). Despite duration on TDF, higher fibrosis scores were noted in F3-F4 patients with high HBV viral load and HDV coinfection, and in F0-F2 patients who had high HBV viral load and low CD4(+) T-cell count. Progression in fibrosis score over time was influenced by age, alcohol consumption, low CD4(+) T-cell count and HCV coinfection, whereas HDV coinfection and longer duration of HBV infection prevented fibrosis regression. No influence of antiretrovirals other than TDF was found.


CONCLUSIONS
The use of TDF in HIV-HBV-coinfected patients led to a decrease in liver fibrosis score in patients with advanced fibrosis or cirrhosis. Sustainability of its direct antiviral and indirect antifibrotic effects on the liver need to be studied further.
INSERM UMR-S707, Paris, France.
Anders
A
Boyd
Elisabeth
E
Lasnier
Jean Michel
JM
Molina
Caroline
C
Lascoux-Combe
Philippe
P
Bonnard
Patrick
P
Miailhes
Dominique
D
Wendum
Jean-Luc
JL
Meynard
Pierre-Marie
PM
Girard
Karine
K
Lacombe
D000225:Adenine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000378:metabolism / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004279:DNA, Viral / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000187:drug effects; D006515:Hepatitis B virus / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000150:complications / Q000188:drug therapy*; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy; D019701:Hepatitis D, Chronic / Q000150:complications / Q000188:drug therapy; D006801:Humans; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology / Q000821:virology; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000378:metabolism / Q000627:therapeutic use*; D000068698:Tenofovir; D019562:Viral Load
D019380:Anti-HIV Agents; D004279:DNA, Viral; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine