studies

1026A AASLD ABSTRACTS HEPATOLOGY, October, 2015
1676
Noninvasive markers of liver fibrosis remain stable in
the majority of hepatitis B virus and human immunodeficiency
virus co-infected patients undergoing tenofovir-containing
antiretroviral therapy
Anders Boyd 1 , Karine Lacombe 1,2 , Pierre-Marie Girard 1,2 , Caroline
Lascoux-combe 3 , Patrick Miailhes 4 , Hayette Rougier 2 , Lawrence
Serfaty 2 ; 1 Inserm UMR_S1136, Paris, France; 2 Hôpital
Saint-Antoine, Paris, France; 3 Hôpital Saint-Louis, Paris, France;
4 Hôpital Croix-Rousse, Lyon, France
Long-term tenofovir (TDF) use has been associated with significant
regression of liver fibrosis during hepatitis B virus (HBV)
monoinfection. However, there are few data in TDF-treated
patients infected with both HBV and the human immunodeficiency
virus (HIV), in whom HIV-associated immunosuppression
could affect liver repair. In this prospective study, 168 HIV-HBV
co-infected patients enrolled in the French HIV-HBV cohort were
included if they initiated TDF-containing antiretroviral therapy
and had liver fibrosis measurements at baseline and ≥1 during
treatment. Patients with hepatitis C of D virus were not included.
Fibrosis was assessed at baseline and every 6-12 months and
≥F3 fibrosis determined from two noninvasive measures: biochemical
score (≥0.59, FibroTest®) and/or transient elastography
(≥7.6kPa, FibroScan). Determinants for fibrosis regression
or progression were evaluated using Cox proportional hazards
regression. Patients were predominately male (86.3%) with
a median age of 41 years (IQR=36-48). At baseline, HBV-
DNA was detectable in 134 (80.2%) patients with a median
HBV-DNA viral load of 5.02 IU/mL (IQR=2.95-7.15) and 104
(61.9%) had HBeAg-positive serology. After a median follow-up
of 59.3 months (IQR=36.1-92.7), 140 (83.3%) patients
were able to maintain or achieve undetectable HBV-DNA viral
loads. Among patients with F3-F4 baseline liver fibrosis, 24/53
(45.3%) remained at the same level of fibrosis during treatment
and 29/53 (54.7%) regressed to F0-F1-F2 fibrosis after
a median 16.9 months (IQR=8.6-32.8). Of the latter group,
10/29 (34.5%) maintained F0-F1-F2 fibrosis until the end of
follow-up. Liver fibrosis regression was significantly associated
with CD4+ cell count ≥500/mm 3 (HR=2.09, 95%CI=1.13-
3.88) in multivariable analysis. Among patients with F0-F1-F2
baseline liver fibrosis, 70/115 (60.9%) remained at the same
level of fibrosis and 45/115 (39.1%) progressed to F3-F4
fibrosis after a median 29.0 months (IQR=18.0-47.4). Of the
latter group, 28/45 (59.6%) maintained F3-F4 fibrosis. Liver
fibrosis progression was significantly associated with higher
age (HR/year=1.10, 95%CI=1.06-1.14), alanine aminotransferase
>2X ULN (HR=2.10-9.28), and tended to be associated
with an AIDS-defining event (HR=1.79, 0.98-3.27) in
multivariable analysis. In conclusion, liver fibrosis levels are
stable for the majority of HIV-HBV co-infected patients undergoing
TDF-containing ART, despite extensive control of HBV
replication. Immunosuppression plays a strong role in reducing
fibrosis levels, supporting the need for earlier ART-initiation in
this patient population.
Disclosures:
Lawrence Serfaty - Advisory Committees or Review Panels: MSD, Janssen, Roche,
Gilead, BMS, Abbvie; Speaking and Teaching: Aptalis
The following authors have nothing to disclose: Anders Boyd, Karine Lacombe,
Pierre-Marie Girard, Caroline Lascoux-combe, Patrick Miailhes, Hayette Rougier
1677
Factors associated with decreases in estimated glomular
filtration rates for patients co-infected with hepatitis B
virus and human immunodeficiency virus undergoing
tenofovir-containing antiretroviral therapy
Anders Boyd 1 , Karine Lacombe 2,1 , Patrick Miailhes 3 , Caroline
Lascoux-combe 4 , Hayette Rougier 2 , Julie Bottero 2,1 , Pierre-Marie
Girard 2,1 ; 1 Inserm UMR_S1136, Paris, France; 2 Hôpital Saint-Antoine,
Paris, France; 3 Hospices Civils de Lyon, Lyon, France; 4 Hôpital
Saint-Louis, Paris, France
Renal toxicity remains one of the more common tolerance
issues encountered during prolonged treatment with tenofovir
(TDF). Although determinants for renal impairment during TDF
have been well established among patients infected with hepatitis
B virus (HBV) or human immunodeficiency virus (HIV), little
is known how these specific factors influence renal function in
HIV-HBV co-infected patients. In this prospective study, 175
HIV-HBV co-infected patients enrolled in the French HIV-HBV
cohort were included if they initiated TDF-containing antiretroviral
therapy (ART) and had creatinine levels available at
baseline and ≥1 during treatment. Patients with hepatitis C
or D virus were not included. Estimated glomular filtration
rates (eGRF) were calculated using the CKD-EPI equation
from creatinine values obtained at baseline and every 6-12
months. Mixed-effect linear regression models were used to
evaluate differences in eGRF changes from baseline (ΔeGFR)
between certain risk-factors. Determinants towards impaired
renal function (90 (p=0.002), males (p=0.04), an AIDS-defining illness
(p=0.03), shorter duration of ART at baseline (p=0.01), concomitant
therapy with a protease inhibitor (p=0.005), and
baseline liver cirrhosis (p=0.03). Among patients with normal
baseline renal function, 51/114 (44.7%) maintained eGFR
levels >90 mL/min/1.73m 2 , while 63/114 (55.3%) developed
either mild (60-89 mL/min/1.73m 2 , n=59) or moderate
(30-59 mL/min/1.73m 2 , n=4) renal impairment after 15.0
months (IQR=7.1-35.8). In multivariable analysis, higher age
(HR/year=1.05, 95%CI=1.01-1.10) and AIDS-defining illness
(HR=1.68, 95%CI=1.05-2.69) were associated with developing
renal impairment, whereas undetectable HBV-DNA was
significantly protective (HR=0.41, 95%CI=0.23-0.76). In conclusion,
liver fibrosis and AIDS-defining illnesses negatively
and independently affect renal function in HIV-HBV co-infected
patients undergoing long-term TDF. Controlled HBV-infection
prevents further progression towards renal impairment, stressing
the need for effective therapy in this population.
Disclosures:
The following authors have nothing to disclose: Anders Boyd, Karine Lacombe,
Patrick Miailhes, Caroline Lascoux-combe, Hayette Rougier, Julie Bottero,
Pierre-Marie Girard