studies

1188A AASLD ABSTRACTS HEPATOLOGY, October, 2015
2011
The combination of IFN-Lambda-4 and HLA-DPB1 polymorphisms
accurately predict HBsAg loss in interferon
treated genotype D patients with HBeAg-negative
chronic hepatitis B
Pietro Lampertico 1 , Enrico Galmozzi 1 , Floriana Facchetti 1 , Cristina
Cheroni 2 , Federica Invernizzi 1 , Vincenza Valveri 2 , Roberta
Soffredini 1 , Mauro Viganò 3 , Sergio Abrignani 2 , Raffaele De Francesco
2 , Massimo Colombo 1 ; 1 Division of Gastroenterology and
Hepatology, Fondazione IRCCS Ca’ granda Ospedale Maggiore
policlinico, Università degli Studi di Milano, Milan, Italy; 2 INGM
- Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”,
Milan, Italy; 3 Division of Hepatology, Ospedale San
Giuseppe, Università degli Studi di Milano, Milan, Italy
Background. HLA-DP polymorphisms have recently been associated
to spontaneous hepatitis B virus (HBV) clearance in
Asians patients whereas polymorphisms mapping the interferon
lambda 3 and 4 (IFNL3 and 4) genes predicted the outcome
of IFN-based therapy of HCV infection. Whether the latter
applies also to HBsAg clearance in IFN treated difficult to cure
HBeAg-negative genotype D chronic hepatitis B Caucasian
patients, is unknown. Methods. 126 such patients with compensated
disease (46 years, 82% males, 90% genotype D,
HBV DNA 6.2 log cp/ml, ALT 132 IU/L, 40% with cirrhosis)
received (Peg)IFN alfa for 22 (6-48) months and were followed
for 11 (1-23) years with HBsAg clearance as a primary endpoint.
HLA-DPA1 (rs3077 A/G), HLA-DPB1 (rs9277534 A/G
and rs9277535 A/G), IFNL3 (rs8099917 T/G) and IFNL4
(rs12979860 C/T, rs368234815 TT/ΔG and rs117648444
C/T) polymorphisms were assessed by both TaqMan SNP
Genotyping Assays and Sanger sequencing. Results. Twenty-eight
patients ultimately cleared HBsAg with a 18-year
cumulative probability of 30%, with a preference for patients
with lower HBV DNA levels and higher ALT levels at baseline,
HLA-DPB1 AG/GG, HLA-DPA1 AG/GG, IFNL3 rs8099917
TT genotypes and the combination of IFNL4 rs368234815
TT/TT and rs117648444 CT/TT genotypes. At multivariate
analysis, HLA-DPB1 rs9277535 AG/GG genotype was the
strongest independent baseline predictor of HBsAg seroclearance
(HR: 6.61; 95%CI 2.6-16, p5 yrs
(mean follow-up:6.4, median:6.2). Results: HCCs have been
diagnosed in 90/1946 (4.6%) patients within the first 5 yrs
and 7/794 (0.9%) patients remaining at risk beyond the first 5
yrs of therapy. The 7 HCCs diagnosed after yr-5 (at 5.4-6.7 yrs
after ETV/TDF onset) developed in 4/531 (0.8%) non-cirrhotic
and 3/224 (1.3%) cirrhotic male patients [50-75 yrs old at
ETV (n=2) or TDF (n=5) onset] who had remained in on-therapy
virological remission since the first yr (the 75-yr old patient had
discontinued TDF at 5 yrs and had normal ALT and HBVDNA