studies

HEPATOLOGY, VOLUME 62, NUMBER 1 (SUPPL) AASLD ABSTRACTS 439A
456
Impact of Hepatic p62 Overexpression on Survival of
Patients with Hepatocellular Carcinoma
Yasuji Komorizono 1 , Masaki Kitazono 2 , Sadao Tanaka 3 , Kazuhisa
Nakashima 1 , Toshihiko Shibatou 1 , Katsumi Sako 1 ; 1 Hepatology,
Nanpuh Hospital, Kagoshima, Japan; 2 Digestive Surgery, Nanpuh
Hospital, Kagoshima, Japan; 3 Pathology, Nanpuh Hospital,
Kagoshima, Japan
Purpose: p62 is an adaptor or a scaffolding substrate between
the ubiquitin–proteasome and the autophagy–lysosome pathways.
p62 overexpression has been demonstrated to play a
critical role in tumorigenesis of various malignancies, including
hepatocellular carcinoma (HCC); however, the association
between p62 overexpression and survival in HCC is currently
unknown. Our purpose was to clarify whether overexpression
of p62 impacts survival of patients with HCC. Methods:
Between May 2003 and July 2013, we retrospectively identified
78 patients with primary HCC (51 men and 27 women
aged 34 to 81 years; mean, 68.4 years) who had undergone
surgical resection and enrolled them in this study. We performed
immunohistochemical analyses of their p62 expression
and correlated the findings with annotated clinicopathologic
data. Fifty-four patients (69%) were positive for hepatitis virus C
antibody and 11 (14%) for hepatitis B antigen; the remaining
13 patients (17%) were negative for both markers. We performed
immunohistochemical analyses with antibody against
p62 on surgically resected specimens and compared the overall
survival of the p62-positive and -negative groups using the
Kaplan–Meier method. We assessed differences between these
two groups using the log-rank test. A Cox proportional hazards
model was used to evaluate the interactions between the baseline
characteristics and the impact of p62 overexpression on
overall survival. Results:We detected p62 overexpression in 54
patients (69%). Overall, 38 deaths (49%) occurred during follow-up
(26 in the p62-positive and 12 in the -negative group).
In the baseline characteristics, there was significant difference
in the histological differentiation (poorly versus well and moderately)
between the p62 positive group and the p62 negative
group (p = 0.047). The overall survival rates at 5, 7, and 10
years were 56%, 45%, and 23 % in the p62 positive group
and 86%,58%, and 46% in the p62 negative group, respectively.
The log-rank test revealed that the overall survival was
significantly shorter in the p62 positive group than in the p62
negative group (p = 0.046). Multivariate analyses showed that
only p62 overexpression (HR, 2.29; 95% CI, 1.03–5.12; P =
0.043) and main tumor size (HR, 1.17; 95% CI, 1.0–1.35; p
= 0.044) were independently associated with overall survival.
Conclusion: The results of the current study indicated that overexpression
of p62 was closely associated with overall survival
in patients with HCC. P62 could be used as a prognostic biomarker
in patients with HCC.
Disclosures:
The following authors have nothing to disclose: Yasuji Komorizono, Masaki Kitazono,
Sadao Tanaka, Kazuhisa Nakashima, Toshihiko Shibatou, Katsumi Sako
457
Improved Survival of Hepatocellular Carcinoma (HCC)
in HIV/Hepatitis B Virus (HBV)-Coinfected Patients Who
Are Diagnosed Through HCC Screening
Maaz B. Badshah 1 , Meritxell Ventura-Cots 2 , Caitlin C. Citti 3 , Luciana
Kikuchi 4 , Sonja Marcus 5 , Beatriz Minguez 6 , Ting-Yi Chen 7 ,
Maria D. Hernandez 8 , Judith Aberg 3 , Myron E. Schwartz 9 , Douglas
Dieterich 3 , Norbert Bräu 5,3 ; 1 Indiana University School of
Medicine, Indianapolis, IN; 2 Hospital Universitari Vall ‘Hebron,
Barcelona, Spain; 3 Dept. of Medicine, Icahn School of Medicine
at Mount Sinai, New York, NY; 4 Universidade de São Paulo, São
Paulo-SP, Brazil; 5 James J. Peters VA Medical Center, Bronx, NY;
6 Hospital Universitari Vall d’Hebron, Barcelona, Spain; 7 University
of Texas Southwestern Medical Center, Dallas, TX; 8 University of
Miami School of Medicine, Miami, FL; 9 Dept. of Surgery, Icahn
School of Medicine at Mount Sinai, New York, NY
BACKGROUND: Current recommendations for HCC screening
in patients chronically infected with the hepatitis B virus
(HBV) are based on a randomized controlled trial from China.
However, no data are available on the effectiveness of HCC
screening in HIV/HBV-coinfected patients. METHODS: HIV/
HBV-coinfected patients with HCC were retrospectively identified
from 1992-2013 in 38 centers in 8 countries. Patients
were considered screened if they presented with an abnormal
alpha-fetoprotein level or imaging study, and not screened
if they presented with symptoms. RESULTS: Among 74 HIV/
HBV-coinfected patients with HCC, 40 (60%) were screened.
Compared to 34 unscreened patients, screened patients had
similar mean age (49.4 vs. 50.7 years). However, screened
patients had a lower mean Child-Pugh score (5.8 vs. 7.4,
p=0.002), had a smaller median tumor size (3.6 vs. 8.7 cm,
p=0.001), had a lower median alpha-fetoprotein level (107
vs. 1,422 ng/ml, p=0.010), and more commonly met Milan
criteria for liver transplantation (44% vs. 7%, p=0.001). They
presented less frequently with portal vein thrombosis (23% vs.
47%, p=0.031) and with advanced Barcelona-Clinic-Liver-Cancer
stages C+D (36% vs. 78%, p=0.001), and more often
received effective HCC therapy (80% vs. 27%, p< 0.001). With
adjustment for lead time of 10.2 months, screened patients had
a longer median survival (89 vs. 3.7 months, p=0.010, log
rank). The actuarial 1-year survival rate was 70% in screened
patients and 27% in unscreened patients. In multi-variable Cox
proportional hazard analysis, screening was an independent
predictor of survival (hazard ratio for death, 0.42; 95% confidence
interval, 0.19 – 0.93; p=0.033), together with effective
HCC therapy and Child-Pugh score. CONCLUSIONS: In
HIV/HBV-coinfected patients with HCC, a diagnosis through
screening was associated with earlier HCC stages, more HCC
therapy, and independently predicted better survival.