Background/Aims Phosphatase and tensin homolog (PTEN) is a known tumor suppressor gene that is downregulated in hepatocellular carcinoma (HCC). Here, we investigated the association between single nucleotide polymorphisms (SNPs) of PTEN and HCC development in patients with hepatitis B virus (HBV) infection.
Methods Six SNPs of PTEN at positions rs1234221, rs1903860, rs1234220, rs1903858, rs2299941, and rs17431184 were analyzed in a development population (417 chronic HBV carriers without HCC and 281 chronic HBV carriers with HCC). PTEN rs1903858, rs1903860, and rs2299941 SNPs were further assessed for the development of HCC in a validation population of 200 patients with HBV-related liver cirrhosis.
Results In the development population, PTEN rs1903860 C allele, rs1903858 G allele, and rs2299941 G allele were associated with a low risk of HCC. The haplotype A-T-A-A-A was associated with an increased risk of HCC (recessive model; odds ratio=2.277, 95% confidence interval [CI] =1.144-4.532, P=0.019). In the validation population, PTEN rs2299941 G allele was the only significant protective genetic polymorphism related to HCC development after adjustment for age and sex (hazard ratio=0.582, 95% CI =0.353-0.962, P=0.035).
Conclusions These findings suggest that genetic polymorphisms in PTEN may affect HCC development in patients with chronic HBV infection.
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Appropriate prediction of hepatocellular carcinoma (HCC) development is of paramount importance in terms of decision on antiviral therapy and HCC surveillance. To date, many HCC risk prediction models had been derived based on well-known risk factors such as age, male gender, the degree of fibrosis, and serum hepatitis B virus (HBV)-DNA load. Overall, such models showed high negative predictive values of approximately >90%, excluding the possibility of HCC development in 3 to 10 years with considerable accuracy. On the other hands, on the basis that potent antiviral therapy can substantially reduce the risk of HCC, its indications are steadily getting expanded for prevention of disease progression. Since antiviral therapy is a very strong disease modifier, the uniform application of HCC risk scores developed before the era of potent antiviral therapy would overestimate the risk of HCC. Furthermore, the tools to assess the fibrotic burden have remarkably evolved, from subjective determination based upon clinical symptom sign and ultrasonographic finding to more objective and delicate non-invasive tests based upon imaging and/or serological methods. Therefore, in the current era of potent antiviral therapy, the clinical significance of recently developed HCC risk models for patients with chronic HBV infection should be reappraised further.
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Background/Aims Hepatitis B viral protein X (HBx) is implicated in the pathogenesis of
hepatocellular carcinoma (HCC) as well as the elevation of heat shock proteins (HSPs) after
hepatitis B virus (HBV) infection. We thus investigated the anticancer effects of an HSP90
inhibitor 17-Dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) in HBxtransfected
hepatocellular carcinoma cells.
Methods pcDNA-HBx was made by inserting the HBx gene derived from the HBV-infected
patient into pcDNA3.1 using the restriction enzymes (XbaI/HindIII). HBx-expressing HepG2
cells were then generated by transfecting HepG2 cells with pcDNA containing HBx gene. To
compare the anticancer effects of 17-DMAG between pcDNA-HBx transfected HepG2 cells and
the control cells (pcDNA-transfected HepG2 cells), we performed various molecular studies,
including Ez-cytox proliferation assay, Western blot analysis, and flow cytometry.
Results 17-DMAG inhibited the proliferation of pcDNA-HBx transfected HepG2 cells better
than control cells (P<0.05). After treating with a various concentration of 17-DMAG (50–1,000
nM), pcDNA-HBx transfected HepG2 cells exhibited higher expression of pro-apoptotic
proteins (c-caspase-3, c-caspase-8, and c-caspase-9) than did control cells (P<0.05). pcDNAHBx
transfected HepG2 cells showed higher activities of caspase-3, caspase-8, and caspase-9
than did control cells (P<0.05). Finally, we found that the expression of pro-apoptotic
proteins (PARP and c-caspase-3) was considerably decreased by the use of a caspase inhibitor
suggesting that 17-DMAG induces the cell death of HepG2 cells caspase-dependently.
Conclusions Our study strongly suggests that 17-DMAG has antiviral effects against HBV as
well as anticancer effects against HepG2 cells. Thus, the application of 17-DMAG appears to be
particularly advantageous to the HCC patients related with HBV infection.
The advent of oral antiviral agents has revolutionized hepatitis B treatment. It has led to
decreased incidence and mortality related to hepatocellular carcinoma. However, although
nucleos(t)ide analogs (NA) are fast and potent in inhibiting hepatitis B virus (HBV) polymerase
and reverse transcriptase activity, complete cure of the virus is not possible. The complete
eradication of HBV requires the covalently-closed-circular DNA (cccDNA) to be eliminated.
Novel gene editing methods, such as zing finger nucleases, transcription activator-like effector
nucleases, and the clustered regularly interspaced short palindromic repeats/Cas9 (CRISPR/
Cas9) system, designed to target specific DNA sequences has great potential for therapeutic
application. Among these, the CRISPR/Cas9 system may be the most feasible approach to
eradicate HBV cccDNA. Further studies are needed to develop a more efficient and safer
method of delivery using the CRISPR/Cas9 system to achieve complete cure of chronic
hepatitis B.
Advanced hepatocellular carcinoma with portal vein thrombosis has a poor prognosis. Concurrent
chemoradiation (CCRT) therapy achieved favorable results in advanced hepatocellular carcinoma with portal vein
thrombosis and can be considered as a treatment option for the management of advanced hepatocellular
carcinoma.2 But, exacerbation of liver function during concurrent chemoradiotherapy is a critical complication in
patients with hepatitis B virus (HBV) related HCC. Reactivation of HBV replication is a well-known complication
in cancer patients receiving chemotherapy. We report two cases with acute exacerbation of liver function. The one
result ed in hepatic decompensation after CCRT probably due to HCC progression and/or chemoradiotherapy and
the other is due to reactivation of HBV replication after CCRT, who recovered after lamivudine and corticosteroid
therapy.