studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 1099A
1825
Hepatitis C Virus (HCV) Eradication in Patients with
Varying Severity of Cirrhosis: Impact on Portal Hypertensive
Complications, Liver Transplant (LT) and Death
Varun Saxena 1 , Lisa M. Nyberg 2 , Aditi Dasgupta 1 , Stephanie Straley
1 , Lisa Catalli 1 , Anders H. Nyberg 2 , Norah Terrault 1 ; 1 Gastroenterology,
University of California San Francisco, San Francisco,
CA; 2 Kaiser Permanente Southern California, San Diego, CA
Background: Recent all-oral antiviral therapy for HCV results in
high rates of sustained virologic response (SVR) among patients
with varying severity of cirrhosis. The impact of SVR on longer-term
hepatic outcomes (beyond SVR12) in patients with
cirrhosis, especially those who are Child-Pugh (CP) B/C, is
currently unknown. Aims: We aimed to compare the liver-related
events in a cohort of HCV-infected patients with varying
severity of cirrhosis who achieved SVR with all oral antiviral
therapy vs. those not achieving SVR / untreated matched controls.
Methods: Adults with HCV genotype 1 cirrhosis treated
with simeprevir (SMV) + sofosbuvir (SOF) ± ribavirin (RBV)
were followed for a median of 0.80 yrs (IQR: 0.65-0.93) after
treatment discontinuation. Randomly selected, untreated controls
(1-3/pt) matched on site, age ± 5yrs, CP (A vs. B/C) and
model for end-stage liver disease (MELD) score ± 2 were followed
for a similar duration. Safety outcomes included change
in MELD and CP scores, number of emergency room (ER) visits
and hospitalizations, presence of portal hypertensive complications
(new/worsening ascites, varices, encephalopathy and/or
spontaneous bacterial peritonitis), need for LT and death. Survival
from treatment discontinuation was compared in treated
patients and matched controls over equivalent timeframe.
Results: Of 371 patients, 93 were treated with SMV+SOF±RBV
and 278 were matched, untreated controls. Cohort median
age was 62yrs (IQR: 58-68), 32% female, 25% Hispanic, 5%
Black, 24% diabetes, median (range) platelet count 133K/
mm 3 (20-341), albumin 3.5g/dL (2.3-4.7), MELD 8 (6-18),
35% CP-B/C, 22% ascites, 22% encephalopathy, 8% varices.
Of the SMV+SOF±RBV treated patients, 78 (84%) achieved
SVR12. Liver-related outcomes between groups are shown in
the Table. In bivariate Cox survival analysis, achievement of
SVR vs. non-SVR/untreated (HR 0.15, 95% CI 0.02-0.97) and
CP-A vs. CP-B/C (HR: 0.57, 95% CI 0.28-0.96) protected from
LT/death. Conclusions: Achieving HCV cure among patients
with compensated and decompensated cirrhosis significantly
reduced the frequency of liver-related outcomes including portal
hypertensive complications and LT/death.
Liver-Related Outcomes in Patients Achieving SVR vs. Non-SVR/
Untreated Matched Controls
*unadjusted log-rank
Disclosures:
Lisa M. Nyberg - Grant/Research Support: Merck, Gilead, Abbvie
Lisa Catalli - Advisory Committees or Review Panels: Gilead, Kadmon
Norah Terrault - Advisory Committees or Review Panels: Eisai, Biotest; Consulting:
BMS, Merck, Achillion; Grant/Research Support: Eisai, Biotest, Vertex,
Gilead, AbbVie, Novartis, Merck
The following authors have nothing to disclose: Varun Saxena, Aditi Dasgupta,
Stephanie Straley, Anders H. Nyberg
1826
Can HCV Antigen Testing Replace HCV RNA PCR Analysis,
for Diagnosis and Monitoring of Treatment for
Hepatitis C?
Andrew M. Hill 1 , Teri Roberts 2 , Valerianna Amorosa 3 , Kamron
Pourmand 3 , Gail Matthews 4 , Graham Cooke 5 , Harun Khan 5 ,
Janice Main 5 , Ashley Brown 5 , Joy A. Peter 9 , David R. Nelson 6 ,
Michael W. Fried 7 , Jennifer Cohn 8 , Camilla S. Graham 10 ; 1 Pharmacology
and Therapeutics, Liverpool University, Liverpool, United
Kingdom; 2 Treatment Access Campaign, Medecins Sans Frontieres,
Geneva, Switzerland; 3 Philadelphia VAMC, University of
Pennsylvania, PA; 4 University of New South Wales, Kirby Institute,
Sydney, NSW, Australia; 5 Faculty of Medicine, Imperial College,
London, United Kingdom; 6 Clinical and Translational Science Institute,
University of Florida, Gainesville, FL; 7 Liver Center, University
of North Carolina, Chapel Hill, NC; 8 Division of Infectious Diseases,
University of Pennsylvania, Philadelphia, PA; 9 Hepatology
Research, University of Florida, Gainsville, FL; 10 Beth Israel Deaconess
Medical Centre, Boston, MA
Background: Simplified systems of diagnostic testing for hepatitis
C virus (HCV) could make widespread implementation of
Direct Acting Antiviral (DAA) based treatment more feasible in
low and middle income countries. HCV core antigen tests (e.g.
Abbott Architect assay) are cheaper and simpler to perform,
but have lower limits of detection in the range of 1000 IU/mL.
More expensive, complex HCV RNA nucleic acid assays (e.g.
Roche TAQMAN) can detect HCV virus at levels of 15-25 IU/
mL. Methods: A systematic review identified studies testing samples
in duplicate for HCV antigen and HCV RNA. Clinical data
from 4 cohort studies evaluating patients relapsing on PEG-
IFN or DAA based treatment for acute and chronic HCV were
reviewed to determine the percentage of relapsing patients
with HCV RNA levels above 1000 IU/mL before treatment and
at End of Treatment (EOT)+12-48 week time points. Results: In
24 studies evaluating 8142 samples tested in parallel by the
Abbott Architect antigen and HCV RNA assays, 46 samples
(0.6%) were HCV antigen positive but HCV RNA undetectable.
There were 280 samples (3.5%) HCV antigen negative but
HCV RNA detectable: these samples generally showed HCV
RNA results 1000 IU/mL in 31 (100%) before treatment, 28 (87%) at
EOT+12, 29 (94%) at EOT+24, and 31 (100%) at EOT+48.
In a Philadelphia chronic HCV treatment cohort, among 90
relapsing patients HCV RNA levels were >1000 IU/mL in
90 (100%) before treatment, and 89 (99%) at EOT+. In an
Australian acute/early chronic HCV treatment cohort, among
13 relapsing patients, HCV RNA levels were >1000 IU/ml in
12 (92%) before treatment, and 9 (69%) at EOT+12 (n=11)
or EOT+24 (n=2). In the HIV-TARGET observational cphprt
study, all 232 relapsing patients had HCV RNA levels >1000
IU/mL before treatment. There were 92 relapser patients with
HCV RNA data available at least 10 weeks after EOT: 89/92
(97%) had HCV RNA >1000 IU/mL at first relapse. Summary:
In the 4 cohort studies, 365/366 patients (99.7%) had HCV
RNA levels >1000 IU/mL before treatment; 214/224 relapsing
patients (96%) had HCV RNA levels above 1000 IU/mL
12 weeks after EOT, and so could have been detected by the
Abbott Architect assay. A minority of patients relapsed with
HCV RNA>1000 IU/mL 24-48 weeks after EOT. Antigen testing
before and after treatment could potentially replace HCV
RNA PCR analysis, but further validation studies are required in
acute and chronic infection. New, low-cost Point-of-Care HCV
antigen assays are needed for use in low income countries,
with lower detection limits in the range of 1000 IU/mL.