Ann Lab Med.  2016 Sep;36(5):469-474. 10.3343/alm.2016.36.5.469.

Adeno-Associated Virus 2-Mediated Hepatocellular Carcinoma is Very Rare in Korean Patients

Affiliations
  • 1Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, Korea. kimjw@skku.edu
  • 2Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 3Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
  • 4Department of Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Abstract

BACKGROUND
The incidence and etiology of hepatocellular carcinoma (HCC) vary widely according to race and geographic regions. The insertional mutagenesis of adeno-associated virus 2 (AAV2) has recently been considered a new viral etiology of HCC. The aim of this study was to investigate the frequency and clinical characteristics of AAV2 in Korean patients with HCC.
METHODS
A total of 289 unrelated Korean patients with HCC, including 159 Hepatitis-B-related cases, 16 Hepatitis-C-related cases, and 114 viral serology-negative cases, who underwent surgery at the Samsung Medical Center in Korea from 2009 to 2014 were enrolled in this study. The presence of AAV2 in fresh-frozen tumor tissues was investigated by DNA PCR and Sanger sequencing. The clinical and pathological characteristics of AAV2-associated HCC in these patients were compared with previous findings in French patients.
RESULTS
The AAV2 detection rate in Korean patients (2/289) was very low compared with that in French patients (11/193). Similar to the French patients, the Korean patients with AAV2-related HCC showed no signs of liver cirrhosis. The Korean patients were younger than the French patients with the same AAV2-associated HCC; the ages at diagnosis of the two Korean patients were 47 and 39 yr, while the median age of the 11 French patients was 55 yr (range 43-90 yr).
CONCLUSIONS
AAV2-associated HCC was very rare in Korean patients with HCC. Despite a limited number of cases, this study is the first to report the clinical characteristics of Korean patients with AAV2-associated HCC. These findings suggest epidemiologic differences in viral hepatocarcinogenesis between Korean and European patients.

Keyword

Adeno-associated virus 2; Epidemiology; Hepatocellular carcinoma; Korean

MeSH Terms

Adult
Asian Continental Ancestry Group
Capsid Proteins/genetics
Carcinoma, Hepatocellular/etiology/*pathology/virology
DNA, Viral/chemistry/genetics/metabolism
DNA-Binding Proteins/genetics
Dependovirus/*genetics/isolation & purification/pathogenicity
Female
Humans
Incidence
Inverted Repeat Sequences/genetics
Liver Neoplasms/etiology/*pathology/virology
Male
Middle Aged
Parvoviridae Infections/complications/epidemiology
Polymerase Chain Reaction
Republic of Korea
Sequence Analysis, DNA
Viral Proteins/genetics
Capsid Proteins
DNA, Viral
DNA-Binding Proteins
Viral Proteins

Figure

  • Fig. 1 Genomic sequences of the adeno-associated virus 2 (AAV2) and the viral fragments that were identified in the Korean patients with hepatocellular carcinoma. The reference genome of AAV2 is AF043303.1.Abbreviations: ORF, open reading frame; ITR, inverse tandem repeat; Rep, replication protein; VP, viral capsid protein.


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