studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 971A
1559
Genotype-Specific Prevalence and Importance of Naturally
Occurring Precore-, Basal Core Promoter- and
preS-Mutations in a Large European Study Cohort of
Patients Chronically Infected with Hepatitis B Virus
Lisa Sommer 1 , Kai-Henrik Peiffer 1 , Julia Dietz 1 , Simone Susser 1 ,
Joerg Petersen 2 , Peter Buggisch 2 , Markus Cornberg 3 , Stefan
Mauss 4 , Hartwig Klinker 5 , Martin F. Sprinzl 6 , Florian van Bömmel
7 , Eberhard Hildt 8 , Caterina Berkowski 1 , Dany Perner 1 , Sandra
Passmann 1 , Stefan Zeuzem 1 , Christoph Sarrazin 1 ; 1 Medical
Clinic 1, J. W. Goethe University Hospital, Frankfurt, Germany;
2 IFI-Institut an der Asklepiosklinik St. Georg, Hamburg, Germany;
3 Gastroenterology, Hepatology and Endocrinology, Hannover
Medical School, Hannover, Germany; 4 Center for HIV and Hepatogastroenterology,
Düsseldorf, Germany; 5 Internal Medicine II,
University of Wuerzburg Medical Center, Würzburg, Germany;
6 I. Medizinische Klinik und Poliklinik, Universitätsmedizin der
Johannes Gutenberg-Universität Mainz, Mainz, Germany; 7 University
Hospital Leipzig, Leipzig, Germany; 8 Paul-Ehrlich-Institut,
Langen, Germany
Background/Aims In several studies from Asia mutations in
HBV basal core promoter (BCP) and in the preS region are
associated with the development of liver fibrosis, cirrhosis and/
or hepatocellular carcinoma. For precore (PC) mutations data
are controversially discussed. In EU/US only limited data about
the significance of these mutations in chronically infected HBV
patients (pts.) is available. To establish prognostic markers
the genotype-specific prevalence of these mutations and their
importance for progression of disease were examined in a
large European study cohort of pts. infected with HBV genotypes
(gt) A to E. Methods In the prospective, longitudinal
ALBATROS study HBsAg carriers without antiviral therapy will
be followed for more than 10 years. In the present interim
analysis baseline (BL) sera of 340 pts. (gtA: 81, gtB: 28, gtC:
16, gtD: 192, gtE: 23) were examined. Progression of infection
was controlled up to 5 years follow-up (FU). BCP/PC and
preS regions were amplified via nested PCR and analyzed
by population-based sequencing. Results BCP double mutation
A1762T/G1764A was found frequently in our population
(203/340; 60%) with the highest prevalence in gtE (91%),
with moderate frequency (56-69%) in gtA, gtC and gtD and
with the lowest prevalence in gtB (29%). The PC G1896A
mutation was detected in 42% (142/340) with the highest
prevalence in gtB, gtC and gtD (71, 56 and 54%) and the
lowest prevalence in gtA and gtE (10 and 9%). In addition, the
PCG1896A/G1899A double mutation was found with moderate
frequency in gtD, gtB and gtC (27, 18 and 13%) but only
infrequently in gtA (3%) and was absent in gtE (0%). Deletions
in the preS region varying in length from 1aa to 41aa occurred
in 8% of investigated patients with the highest prevalence in
gtE (40%) and gtC (29%). Seven patients (gtA: 2; gtD: 4; gtE:
1) started antiviral therapy after 1-4 years of FU. BCP double
mutation was observed in 6/7 and PC double mutation in
1/7 patients at BL. Conclusion BCP and PC mutations were
found frequently in our study cohort in a HBV genotype-specific
pattern. Deletions in the preS region were found with a lower
prevalence but were observed predominantly in HBV gtE and
gtC. Interestingly, 6/7 HBsAg carriers who had to start treatment
during FU were positive for the BCP double mutation at
BL, whereas PC mutations were found only infrequently in these
patients. Therefore, BCP and PC mutations might be of clinical
interest as potential prognostic markers in HBsAg carriers.
Disclosures:
Joerg Petersen - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Gilead, Novartis, Merck, Bristol-Myers Squibb, Gilead, Novartis, Merck; Grant/
Research Support: Roche, GlaxoSmithKline, Roche, GlaxoSmithKline; Speaking
and Teaching: Abbott, Tibotec, Merck, Abbott, Tibotec, Merck
Peter Buggisch - Advisory Committees or Review Panels: Janssen, AbbVie, BMS;
Speaking and Teaching: Roche, MSD, Gilead, Merz Pharma
Markus Cornberg - Advisory Committees or Review Panels: Merck (MSD Germamny),
Roche, Gilead, Novartis, Abbvie, Janssen Cilag, BMS; Grant/Research
Support: Merck (MSD Germamny), Roche; Speaking and Teaching: Merck (MSD
Germamny), Roche, Gilead, BMS, Novartis, Falk, Abbvie
Stefan Mauss - Advisory Committees or Review Panels: BMS, AbbVie, Janssen,
ViiV, Gilead; Speaking and Teaching: BMS, AbbVie, Janssen, Gilead, MSD
Hartwig Klinker - Advisory Committees or Review Panels: Bristol-Myers Squibb,
Janssen, Hexal; Grant/Research Support: Gilead, Abbott, AbbVie, Janssen,
Novartis, Bristol-Myers Squibb; Speaking and Teaching: Gilead, Bristol-Myers
Squibb, Merck Sharp & Dohme
Martin F. Sprinzl - Grant/Research Support: GILEAD
Florian van Bömmel - Advisory Committees or Review Panels: Gilead Sciences
Inc., Roche Pharmaceutics; Grant/Research Support: Biopredictive; Speaking
and Teaching: Bristol-Myers Squibb, Janssen, Roche Pharmaceutics, Gilead Sciences
Inc., Abbvie
Stefan Zeuzem - Consulting: Abbvie, Bristol-Myers Squibb Co., Gilead, Merck
& Co., Janssen
Christoph Sarrazin - Advisory Committees or Review Panels: Bristol-Myers
Squibb, Janssen, Merck/MSD, Gilead, Roche, Abbvie, Janssen, Merck/MSD;
Consulting: Merck/MSD, Merck/MSD; Grant/Research Support: Abbott, Roche,
Merck/MSD, Gilead, Janssen, Abbott, Roche, Merck/MSD, Qiagen; Speaking
and Teaching: Gilead, Novartis, Abbott, Roche, Merck/MSD, Janssen, Siemens,
Falk, Abbvie, Bristol-Myers Squibb, Achillion, Abbott, Roche, Merck/MSD, Janssen
The following authors have nothing to disclose: Lisa Sommer, Kai-Henrik Peiffer,
Julia Dietz, Simone Susser, Eberhard Hildt, Caterina Berkowski, Dany Perner,
Sandra Passmann
1560
Individualizing Hepatitis B Prophylaxis in Liver Transplant
(LT) Recipients: Diminished Need for Hepatitis B
Immunoglobulin (HBIG)
Kavita Radhakrishnan 1 , Aileen Chi 2 , David J. Quan 2 , John P.
Roberts 3 , Norah Terrault 2 ; 1 Medicine, UCSF, San Francisco, CA;
2 Transplant Hepatology, UCSF, San Francisco, CA; 3 Transplant
Surgery, UCSF, San Francisco, CA
Background & Aims: HBIG has been central to the prevention
of hepatitis B virus (HBV) recurrence post-LT for two decades.
However, its high cost and need for IV or IM administration
have prompted HBIG minimization strategies. Elimination of
HBIG and use of antiviral therapy (AVT) alone is associated
with HBsAg recurrence in ~20% at 2 yrs (Fung, Gastroenterology.
2011). Achieving a higher rate of HBsAg negativity is
highly desirable. We report our experience with an individualized
protocol for HBIG prophylaxis. Methods: All HBsAg-positive
patients undergoing LT from 2009-2014 were included.
Patients at high risk for recurrence [defined as HBV DNA>100
IU/mL at time of LT (33%, 2 acute), prior AVT resistance (33%),
HDV+ (22%), or HIV+ (12%)] received HBIG 5K-10K U in anhepatic
phase & daily X 5 days, and every 4-12 wks to maintain
trough anti-HBs >100 U/L. In contrast, low risk patients [all
others] received HBIG 5K U in anhepatic phase & daily x 5
days only. Both groups received ATV therapy indefinitely. HBV
recurrence was defined as HBsAg positivity post-LT. Results: Of
79 LT recipients, 63% and 37% met criteria for high and low
risk protocols. Pre-LT characteristics and post-LT prophylaxis
are shown in Table. Median (IQR) follow-up was 2.9 (1.3-4.4)
years. The 1 and 3-yr cumulative incidences of HBsAg positivity
post-LT were 2.0% (CI 95
: 0.3 -13.4) and 5.4% (CI 95
: 1.3-
20.7) in the high risk vs. 0% (upper CI 95
: 11.9) in the low risk
groups (p=0.28). Only those who developed metastatic HCC
became HBsAg-positive (n=2). All patients were HBV DNA
negative post-LT, except one with recurrent HCC. Post-LT survival
was 91% and 84% at 3 and 5 years respectively, with no
difference between prophylaxis groups (p=0.55). Conclusion:
In patients without HIV and HDV who have HBV DNA levels