Background/Aims Because hepatitis B virus (HBV) replication has been known to play an
important role in cancer recurrence after curative treatment of HBV-related hepatocellular
carcinoma (HCC), we examined whether treatment based on nucleos(t)ide analogues (NAs)
might decrease the recurrence rate and improve patient survival.
Methods The retrospective cohort study enrolled 73 patients with chronic hepatitis B who
were treated with transarterial chemoembolization (TACE) and radiofrequency ablation (RFA)
with curative intent for HCC. Among those, 30 and 43 patients were treated with tenofovir
disoproxil fumarate (TDF) and entecavir (ETV), respectively.
Results Of the 73 patients, 51 experienced HCC recurrence, and 14 patients were dead
during a follow-up of 73±34 months. Multivariate analyses showed that tumor size (hazard
ratio [HR], 1.590; 95% confidence-interval [CI], 1.106-2.285; P=0.012) and Child-Pugh class B
(vs. class A/non cirrhosis; HR, 5.794; 95% CI, 2.311-14.523; P=0.001) was significantly associated
with HCC recurrence, and Child-Pugh class B (HR, 7.357; 95% CI, 2.100-25.777; P=0.002) was an
independent unfavorable prognostic factor for survival. During NAs therapy, TDF was superior
to ETV for complete viral response at 1 year after the date of combination of TACE and RFA
(P=0.016). However, the risks of HCC recurrence and survival were not significantly different
between those treated with TDF versus ETV.
Conclusions TDF was superior to ETV for achieving complete viral response. However, the
recurrence and mortality after TACE and RFA for HBV-related HCC were not significantly
different between patients treated with TDF versus ETV.
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J Liver Cancer. 2021;21(1):58-68. Published online March 31, 2021
Background/Aims Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related death in Korea. This study evaluated the characteristics of Korean patients newly diagnosed with HCC in 2015.
Methods Data from the Korean Primary Liver Cancer Registry (KPLCR), a representative sample of patients newly diagnosed with HCC in Korea, were analyzed. A total of 1,558 patients with HCC registered in the KPLCR in 2015 were investigated.
Results The median age was 61.0 years (interquartile range, 54.0-70.0 years), and men accounted for 79.7% of the subjects. Hepatitis B virus infection was the most common underlying liver disease (58.1%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stage 0, A, B, C, and D HCCs accounted for 14.2%, 31.5%, 7.6%, 39.0%, and 7.8% of patients, respectively. Transarterial therapy (32.1%) was the most commonly performed initial treatment, followed by surgical resection (23.2%), best supportive care (20.2%), and local ablation therapy (10.7%). Overall, 34.5% of patients were treated in accordance with the BCLC guidelines: 59.2% in stage 0/A, 48.4% in stage B, 18.1% in stage C, and 71.6% in stage D. The 1-, 3-, and 5-year OS rates were 67.1%, 50.9%, and 27.0%, respectively.
Conclusions In 2015, approximately 45% of Korean HCC cases were diagnosed at a very early or early stage, and 35% of patients underwent potentially curative initial treatment. BCLC guidance was followed in 34.5% of patients; in patients with stage B or C disease, there was relatively low adherence.
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J Liver Cancer. 2020;20(2):135-147. Published online September 30, 2020
Background/Aims Considering the high prevalence and mortality of hepatocellular carcinoma (HCC) in Korea, accurate statistics for HCC are important. We evaluated the characteristics of Korean patients with newly diagnosed HCC.
Methods We retrospectively evaluated data from the Korean Primary Liver Cancer Registry (KPLCR). The baseline characteristics, treatment modalities, and overall survival (OS) of 4,572 patients with HCC registered in the KPLCR between 2012 and 2014 were investigated.
Results At the time of HCC diagnosis, the median age was 60.0 years, with male predominance (79.6%). Hepatitis B virus infection was the most common etiology (59.1%). The rates of Barcelona Clinic Liver Cancer (BCLC) stages 0, A, B, C, and D at diagnosis were 3.9%, 36.9%, 12.5%, 39.4%, and 7.3%, respectively. The proportion of very early or early stage HCC at diagnosis (BCLC stage 0 or A) in the 2012-2014 cohort was significantly lower than that in the 2008-2011 cohort (40.8% vs. 48.3%, P<0.001). Transarterial therapy (37.5%) was the most commonly performed initial treatment, followed by surgical resection (19.8%), best supportive care (19.1%), and local ablation (10.6%). The median OS was 2.9 years, and the 1-, 3-, and 5-year OS rates were 67.7%, 49.3% and 41.9%, respectively. The OS rate of the 2012-2014 cohort was significantly higher than that of the 2008-2011 cohort (log-rank, P<0.001).
Conclusions The OS of HCC patients registered in the KPLCR between 2012 and 2014 significantly improved. Nevertheless, as about half of the HCC patients were diagnosed at an advanced stage, vigorous and optimized HCC screening strategies should be implemented.
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Backgrounds/Aims Backgrounds/Aims: In Korea, hepatocellular carcinoma (HCC) is the sixth most common cancer and results in the second-highest cancer death rate among all cancers. We aimed to describe the characteristics of patients who were newly diagnosed with HCC in Korea between 2008 and 2011.
Methods The Korean Primary Liver Cancer Registry (KPLCR) is a random sample consisting of approximately 15% of patients with newly diagnosed primary liver cancer registered in the Korean Central Cancer Registry. We investigated the baseline characteristics, treatment modalities, and overall survival (OS) of patients with HCC registered in the KPLCR between 2008 and 2011.
Results A total of 6,083 patients were histologically or radiologically diagnosed with HCC. The hepatitis B virus was the predominant HCC etiology (72.0%). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, stages 0, A, B, C, and D accounted for 8.6%, 39.7%, 11.5%, 33.8%, and 6.9%, respectively. Transarterial therapy (41.7%) was the most commonly performed initial treatment, followed by best supportive care (21.7%), surgical resection (16.7%), and local ablation therapies (10.6%). The overall rate of adherence to the BCLC treatment guideline was only 37.7%. The 1-, 3-, and 5-year OS rates were 65.6%, 46.2%, and 36.8%, respectively.
Conclusions Between 2008 and 2011, approximately half of patients with HCC (48.3%) were candidates for curative treatment (BCLC stage 0 or A), but one-third of patients (33.8%) had advanced HCC (BCLC stage C). Transarterial therapy was the most commonly conducted initial treatment and the 5-year OS rate was 36.8% in this period.
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Background/Aims Tenofovir disoproxil fumarate (TDF) is potentially nephrotoxic in chronic hepatitis B patients. Hepatocellular carcinoma (HCC) patients treated using transarterial chemoembolization (TACE) are at an increased risk of renal injury. The aim of this study was to determine whether TDF is associated with more renal adverse events than entecavir (ETV) in HCC patients treated with TACE.
Methods In this retrospective single-center study, we selected 53 HCC patients who were treated with TDF from January 2012 to July 2013 and had their first TACE procedure in the same period. These patients were matched by age and sex to patients treated with ETV.
Results There were no significant differences in baseline characteristics, including HCC factors, and nephrotoxic drug use, between the two groups. The median follow-up period was 17.0 and 20.0 months for the TDF and ETV groups, respectively. There was no difference during the follow-up period between the TDF and ETV groups in the increase in creatinine over 0.5 mg/dL (17.0% and 17.0%, P=1.00, respectively) and the decrease in eGFR over 25% (43.4% and 41.5%, P=0.84, respectively). Multivariate analysis revealed that Child-Pugh class over B (hazard ratio [HR], 7.30; 95% confidence interval [CI] 2.79-19.10; P<0.01) was associated with increase in creatinine, and Child-Pugh class over B (HR, 82.74; 95% CI 12.31-555.83; P<0.01) and Barcelona-Clinic Liver Cancer stage over B (HR, 14.93; 95% CI 1.60-139.51; P=0.02) were associated with decrease in eGFR.
Conclusions TDF has comparable safety to that of ETV for HCC patients undergoing TACE.
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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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Background/Aims The National Liver Cancer Screening Program (NLCSP) has been implemented for the past 15 years in Korea. However, the actual clinical experience in Korea is inconsistent with the expectations of the hepatocellular carcinoma (HCC) surveillance program. To evaluate the actual clinical situation of HCC diagnoses, we investigated disease severity in patients with HCC and the diagnostic environment.
Methods From January 2011 to December 2015, all patients who were diagnosed with HCC in a single secondary hospital in Daejeon city were retrospectively enrolled in this study. Severity of HCC was evaluated according to the Barcelona Clinic Liver Cancer (BCLC) staging system.
Results Over the course of 5 years, 298 participants were enrolled. The mean age of participants was 64.0 years. Positive hepatitis B surface antigen was confirmed in 134 patients (45.0%), 35 patients (11.7%) tested positive for anti-hepatitis C virus antibody, and 93 patients (32.2%) had more than 40 g/day of alcohol consumption. The proportions of patients according to BCLC stages were as follows: BCLC-0, 28 patients (9.4%); BCLC-A, 42 patients (14.1%); BCLC-B, 26 patients (8.7%); BCLC-C, 134 patients (45.0%); and BCLC-D, 68 patients (22.8%). The diagnostic environments were as follows: 19 patients were in the NLCSP group (6.4%), 114 in the group with presenting signs (38.3%), 110 in the regular outpatient care group (36.9%), and 55 patients in the incidental diagnosis group (18.5%).
Conclusions Most patients (67.8%) had advanced stage HCC at diagnosis, and curative treatment was not indicated due to the severity disease. Thus, the actual situation is far worse than the theoretical expectation of HCC surveillance, suggesting that many high-risk patients for HCC are missed in surveillance.
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Background/Aims To optimize efficacy of National Liver Cancer Screening Program (NLCSP)
for subjects with chronic hepatitis B (CHB), it is needed to know the incidence of liver cancer
and its predisposing factors in the program.
Methods From January 2010 to December 2014, all the hepatitis B surface antigen (HBsAg)
positive participants who received at least two or more abdominal ultrasonography under
NLCSP were retrospectively enrolled in a single tertiary hospital. Annual incidence of primary
liver cancer was calculated and related clinical factors were investigated.
Results During 5 years, 541 subjects were enrolled. Mean age was 53 years old and 292
subjects (54%) were receiving antiviral agents. Liver cirrhosis (LC) was diagnosed in 212 (39.2%).
Mean follow-up time was 2.36 years and 15 hepatocellular carcinoma and 1 intrahepatic
cholangiocarcinoma were diagnosed. Annual incidence of primary liver cancer was 9.8
per 1,000 patient year. Cumulative incidence at 1, 3, and 5 year was 0.6%, 2.6%, and 6.4%,
respectively. In multivariate analyses, LC (hazard ratio [HR] 8.74, 95% confidence interval [CI]
1.97–38.71, P=0.024), age (HR 1.08, 95% CI 1.01–1.15, P=0.024) were significantly associated
with cancer development.
Conclusions Despite of high rate of oral antiviral therapy, incidence of primary liver cancer
is not low in CHB patients in Korea. Old age and presence of LC are independently associated
with higher risk of cancer development during surveillance. This study could be used as
baseline data for quality control of NLCSP.
Citations
Citations to this article as recorded by
Effectiveness of Hepatocellular Carcinoma Surveillance and an Optimal Surveillance Interval: Nationwide Cohort of Korea Heejin Bae, Sang Ah Lee, Jong Won Choi, Shin Hye Hwang, Sumi Park, Mi-Suk Park Yonsei Medical Journal.2021; 62(8): 758. CrossRef
A Survey of Liver Cancer Specialists’ Views on the National Liver Cancer Screening Program in Korea Won Sohn, Young-Sun Lee, Jae Geun Lee, Jihyun An, Eun Sun Jang, Dong Ho Lee, Dong Hyun Sinn Journal of Liver Cancer.2020; 20(1): 53. CrossRef
Discrepancy between the Actual Clinical Status of Patients with Hepatocellular Carcinoma and Expectations from Hepatocellular Carcinoma Surveillance: a Single-Center Study Nak Min Kim, Young Seok Doh, Ji Woong Jang, Seok-Hwan Kim, Hyuk Soo Eun, Jae Hyuck Jun, Sae Hee Kim, Il Hyun Baek, Sung Hee Jung Journal of Liver Cancer.2019; 19(1): 30. CrossRef
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.
Background/Aims Hepatocellular carcinoma (HCC) is common cause of liver related death in Korea, and the importance of alcohol as an etiology of chronic liver disease including cirrhosis is emphasized recently. We investigated the epidemiologic changes of HCC during last 10 years in single tertiary center in Gangneung, Korea.
Methods We retrospectively reviewed the medical records of admitted patients diagnosed as HCC in year 2002 and 2012 respectively, and their clinical characteristics were compared.
Results A total of 214 patients were enrolled. Mean age was 60.1 years and 179 (83.6%) was male. Number of patient with cirrhosis was 160 (74.8%) and with viral hepatitis was 164 (74.8%). Chronic hepatitis B (CHB) was the most common cause of HCC patients with liver cirrhosis (61.9%), and alcohol was 14.4%. The possible curative group (by BCLC stage 0 or A) was only 36.4% (n=78), and had not decreased during the study periods (36.3 % vs. 36.6%, P=0.144), and other clinical variables also had no statistical differences.
Conclusions The clinical characteristics of HCC including clinical stage at the time of diagnosis were not changed over the last 10 year period, and CHB was still the most common etiology of HCC in Gangneung, Korea.
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.