studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 271A
121
Objective Determination of Hepatitis B Phenotype using
Biochemical and Serological Markers: Immune Tolerant,
Immune Active, Inactive Carrier and Indeterminant Status
Adrian M. Di Bisceglie 1 , Manuel Lombardero 2 , Jeffrey Teckman 1 ,
Lewis R. Roberts 3 , Harry L. Janssen 4 , Steven H. Belle 2 , Jay H. Hoofnagle
5 ; 1 Saint Louis University, St. Louis, MO; 2 University of Pittsburgh,
Pittsburgh, PA; 3 Mayo Clinic, Rochester, MN; 4 University of
Toronto, Toronto, ON, Canada; 5 NIH, Bethesda, MD
Background: HBV infection is frequent world-wide and may
result in progressive liver disease or HCC. Effective therapies
are available but treatment is usually reserved for patients (pts)
with selected biochemical and serological profiles (phenotypes).
Currently, criteria for defining HBV phenotype are not
standardized and are based upon expert opinion rather than
medical evidence. Aim: To determine the distribution of phenotypes
in a large cohort of North American pts with chronic
HBV infection using standardized definitions and calculation.
Methods: Epidemiologic, demographic, biochemical and virologic
features of pts enrolled into the HBRN Cohort Study at 19
US and 1 Canadian site were analyzed, assigning pts into 1
of 4 phenotypes: immune tolerant (IT), chronic hepatitis B with
(CHB e+) or without HBeAg (CHB e-) or inactive carrier (IC)
based upon baseline HBV DNA and ALTs. Cut-off HBV DNA
values used to define phenotypes were 10 4 IU/ml for e-negative
and 10 5 for e-positive pts. ALT cut-offs were analyzed using
either fixed values (30 U/L for men, 20 U/L for women) or
using each local lab ULN. Pts not fitting into a phenotype were
designated “Indeterminant”. Independently, local investigators
assigned a phenotype at baseline based on available laboratory
values and clinical impression. Results: 1398 adults (51%
male, 71% Asian) had data needed to determine phenotype.
The table shows the distribution of phenotypes calculated by
two methods of assessing ALT and physician assessment. Only
moderate agreement was found between clinician-determined
and calculated phenotype using fixed ALTs (Kappa 0.39, 95%
CI 0.36-0.42). Of note, only 13% of pts were designated Indeterminant
by clinicians compared to 20-40% by computer calculation.
Using the Fixed ALT groups for comparison, IT was
most distinct, being generally younger, more frequently Asian
and female. The most frequent clinical phenotype identified
was Indeterminant, the majority of whom (83%) had elevated
ALT values despite low levels of HBV DNA, not apparently
associated with higher BMI, alcohol consumption or HBV genotype.
Clinician estimates often differed from the calculated
phenotype. Conclusions: The clinical significance of HBV phenotypes
using these standardized definitions requires further
study based on long term follow up of these patient cohorts but
there is clearly a need to re-examine categorization of pts with
chronic HBV infection to more accurately predict their outcomes
and need for therapy.
Disclosures:
Adrian M. Di Bisceglie - Advisory Committees or Review Panels: Gilead, AbbVie,
Novartis, Bayer, BTG; Grant/Research Support: Gilead, AbbVie
Jeffrey Teckman - Consulting: Dicerna, Isis Pharmaceuticals, Vertex, Proteostasis,
Genkyotex, The Alpha-1 Project, Retrophin, RxCelerate, Velgene; Grant/
Research Support: Alnylam, Arrowhead, Alpha-1 Foundation, Gilead
Lewis R. Roberts - Grant/Research Support: Bristol Myers Squibb, ARIAD Pharmaceuticals,
BTG, Wako Diagnostics, Inova Diagnostics, Gilead Sciences, Five
Prime Therapeutics
Harry L. Janssen - Consulting: AbbVie, Bristol Myers Squibb, GSK, Gilead Sciences,
Innogenetics, Merck, Medtronic, Novartis, Roche, Janssen, Medimmune,
ISIS Pharmaceuticals, Tekmira; Grant/Research Support: AbbVie, Bristol Myers
Squibb, Gilead Sciences, Innogenetics, Merck, Medtronic, Novartis, Roche,
Janssen, Medimmune
The following authors have nothing to disclose: Manuel Lombardero, Steven H.
Belle, Jay H. Hoofnagle
122
Length of antiviral therapy and cirrhosis are key factors
in the development of hepatocellular carcinoma among
U.S. veterans with chronic hepatitis B
Gina Choi, Marina Serper, David E. Kaplan, Kimberly A. Forde;
Gastroenterology, University of Pennsylvania, Philadelphia, PA
Background: The risk of hepatocellular carcinoma (HCC) and
the effect of anti-viral therapy in U.S. populations with chronic
hepatitis B (HBV) is poorly defined. Aim: To examine the incidence
and impact of anti-viral therapy on the development of
HCC among a national cohort of veterans with chronic HBV.
Methods: A retrospective cohort study using the VA Corporate
Data Warehouse was performed between 1999-2013. The
primary exposure variable was antiviral therapy, defined as
≥6 months of therapy with oral nucleosides. Additional covariates
such as demographics and clinical variables such as cirrhosis,
alcohol abuse, dyslipidemia, hepatitis C (HCV), and
HIV were obtained. Multivariable Cox proportional hazard
models were used to evaluate associations between exposures
and the primary outcome of HCC. Results: A total of 26,704
veterans had a HBsAg+ result; N=9001 were confirmed to
have chronic HBV. The median follow-up time was 7.6 years
(IQR 4.2–10.9). Patients were predominantly male (96%),
white (45%) and middle aged (M=51, SD 11). A total of 20%
had HCV, 7% had HIV, and 23% had alcohol abuse. The
prevalence of dyslipidemia was 52%; 13% had cirrhosis. The
overall incidence of HCC was 5.6 per 1000 person-years;
26 per 1000 person-years with cirrhosis and 1.9 per 1000
person-years without cirrhosis. The median exposure time of
antiviral therapy was 3.6 years (IQR 1.4-7.1). A total of 38%
(N=3333) received antiviral therapy for ≥6 months; 23%
received ≥3 years and 16% received therapy for ≥5 years.
In multivariable models adjusted for age, race, cirrhosis, alcohol
abuse, and dyslipidemia, antiviral therapy ≥5 years was
associated with decreased incidence of HCC (HR 0.77, 95%
CI 0.60-0.98, p=0.03), whereas ≥4 years of antiviral therapy
was not protective (HR 1.04, CI 1.03-1.05). Antiviral therapy
for ≥5years was associated with a decreased incidence of
HCC among cirrhotics (HR 0.56, CI 0.41-0.78, p