External beam radiotherapy, transarterial chemoembolization and sorafenib are currently standard treatments for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. However, hepatic arterial infusion chemotherapy has been applied to advanced stage HCC with a view to improving the therapeutic effect. We experienced a case of advanced HCC with clinical complete response after hepatic artery infusion chemotherapy and radiation therapy and report that.
Carcinoma, Hepatocellular* ; Chemoradiotherapy ; Drug Therapy* ; Hepatic Artery* ; Portal Vein* ; Radiotherapy* ; Thrombosis* ; Venous Thrombosis

Recurrence of hepatocellular carcinoma (HCC) after hepatic resection is quite common. Peritoneal recurrence has been considered incurable status and related to poor prognosis. Although peritoneal metastasectomy is a therapeutic option for some selected patients with a few peritoneal metastasis, the indication and therapeutic effect has not been clear. We report a case of a 61-year-old man achieving complete remission of recurrent peritoneal metastasis after repeated surgical resection by a multidisciplinary approach. Peritoneal metastasectomy might be a therapeutic option for selected patients with localized oligonodular peritoneal metastasis.
Carcinoma, Hepatocellular* ; Hepatectomy* ; Humans ; Metastasectomy ; Middle Aged ; Neoplasm Metastasis* ; Prognosis ; Recurrence

BACKGROUND/AIMS: To retrospectively compare conventional and drug-eluting beads transarterial chemoembolization (C-TACE and DEB-TACE) for treatment of hepatocellular carcinoma (HCC) at very early and early stages. METHODS: We retrospectively compared patients treated with C-TACE (n=115) or DEB-TACE (n=103) from September 2009 to May 2016. All patients were in a very early (stage 0) or early stage (stage A) of the Barcelona Clinic Liver Cancer (BCLC) staging system, and all had Child–Pugh class A and ≤B7 liver status. Approval by the institutional review board was waived because the study was retrospective. The following parameters were evaluated: severe pain and bradycardia during TACE, post-embolization syndrome (PES), liver function change, complications, target tumor response, and conversion to another treatment modality. Numeric differences were assessed by the independent Student's t-test for continuous variables and by chi-square test for categorical variables. RESULTS: Severe intractable pain and bradycardia during the TACE procedure were significantly more frequent in the C-TACE group than in the DEB-TACE group (P<0.001). The incidence and duration of PES were significantly higher in the C-TACE group than in the DEB-TACE group (P<0.001). The increase in liver enzymes was significantly higher in the C-TACE group than in the DEB-TACE group (P<0.001). The deterioration of the Child-Pugh class was significantly higher in the C-TACE group than in the DEB-TACE group (P =0.006). There was no significant difference in serious complications except localized bile duct dilatation between the groups. There was no significant difference between the groups in tumor response at both immediate and 1-year assessment. The conversion rate to other treatment modalities was significantly higher in the DEB-TACE group than in the C-TACE group (P<0.001). CONCLUSIONS: DEB-TACE is better than C-TACE in terms of procedural safety as initial treatment in a very early or early stage of HCC.
Bile Ducts ; Bradycardia ; Carcinoma, Hepatocellular* ; Dilatation ; Ethics Committees, Research ; Humans ; Incidence ; Liver ; Liver Neoplasms ; Pain, Intractable ; Retrospective Studies

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.
Antiviral Agents ; Carcinoma, Hepatocellular ; Causality ; Cholangiocarcinoma ; Follow-Up Studies ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Incidence* ; Korea ; Liver Cirrhosis ; Liver Neoplasms* ; Liver* ; Mass Screening* ; Multivariate Analysis ; Quality Control ; Retrospective Studies ; Tertiary Care Centers ; Ultrasonography

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 HBx-transfected 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). pcDNA-HBx 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.
Apoptosis ; Apoptosis Regulatory Proteins ; Blotting, Western ; Carcinoma, Hepatocellular* ; Caspase 3 ; Caspase 8 ; Caspase 9 ; Caspases ; Cell Death ; Flow Cytometry ; Heat-Shock Proteins ; Hep G2 Cells ; Hepatitis B virus ; Hepatitis B* ; Hepatitis* ; Humans ; Transfection*

Hepatocellular carcinoma (HCC) is one of the most common life-threatening cancers worldwide. Recently, many patients with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have progressed to HCC even in the absence of cirrhosis. As the morbidity of metabolic syndrome increases, the proportion of HCC associated with NAFLD is expected to increase gradually. A new mechanism for the development of HCC in NAFLD has been identified; Diabetes mellitus, insulin resistance, obesity, lipotoxicity, gut dysbiosis are risk factors. Inflammatory cytokines such as adipokines, leptin, tumor necrosis factor-α, interlukin-8, nuclear factor-κB constitute dysplasia-carcinoma sequence. At the time of diagnosis, NAFLD/NASH related HCC tend to progress to larger and in advanced tumor-node-metastasis stages compared to viral hepatitis related HCC. But there are no guidelines for early detection of NAFLD-related HCC. So, it is essential to study the screening program for the early detection of NAFLD-related HCC and precise methods for NAFLD.
Adipokines ; Carcinoma, Hepatocellular* ; Cytokines ; Diabetes Mellitus ; Diagnosis ; Dysbiosis ; Fatty Liver ; Fibrosis ; Hepatitis ; Humans ; Insulin Resistance ; Leptin ; Mass Screening ; Metabolic Syndrome X ; Necrosis ; Non-alcoholic Fatty Liver Disease* ; Obesity ; Risk Factors

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.
Antiviral Agents ; Base Sequence ; Carcinoma, Hepatocellular ; Clustered Regularly Interspaced Short Palindromic Repeats ; DNA ; DNA, Circular ; Fingers ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis B, Chronic ; Hepatitis* ; Incidence ; Methods ; Mortality ; RNA-Directed DNA Polymerase

Liver cancer is one of the leading causes of cancer-related death in Korea. Liver cancer imposes a considerable societal burden due to its high incidence and high mortality rate in younger patients, as compared to other cancers. However, interest in liver cancer among researchers and health-policy makers is low. In this review, recent trends in the number of published articles on liver cancer in Korea and internationally were analyzed. The key finding is that the rate of growth in the number of published articles on liver cancer is slowly decreasing and financial investment for research into liver cancer is very limited, despite the increasing research and development investment budget in Korea. Meanwhile, the rate of growth of research into liver cancer in China has recently increased markedly. Therefore, the scale and rate of growth of research into liver cancer in Korea should be enhanced.
Budgets ; Carcinoma, Hepatocellular ; China ; Humans ; Incidence ; Investments ; Korea* ; Liver Neoplasms* ; Liver* ; Mortality

Transarterial chemoembolization (TACE) is recommended as the first line treatment option for the patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC), however, treatment strategy and evaluation of effects after TACE has not been fully established. Recently, sub-stage of BCLC stage B has been proposed and validated, but it should be validated including a large number of the patients and its refinement should be discussed. We have validated the sub-stage of BCLC stage B (B1-B4) by comparing overall survival after TACE, and there was no statistically significant difference in overall survival after TACE between B1 and B2. After excluding the patients with Child-Pugh point 7 from B1, the overall survival was significantly better than that of B2. Therefore, up-to-seven criteria is shown to be a reliable tool for the treatment strategy in the patients with intermediate stage of HCC. Refinement of sub-stage of BCLC stage B has been proposed by some other institutes, and it is important to establish novel treatment strategy for the patients with BCLC stage B after TACE to improve the prognosis of the patients after TACE, and to define the best timing for conversion to sorafenib or liver transplantation should be discussed.
Academies and Institutes ; Carcinoma, Hepatocellular ; Humans ; Liver Neoplasms* ; Liver Transplantation ; Liver* ; Prognosis

Sorafenib is the standard treatment for advanced hepatocellular carcinoma according to the Barcelona Clinic Liver Cancer staging system. However, because of its unsatisfactory efficacy, adverse effects, and high cost, the use of sorafenib is limited, and other treatment modalities are required. Recent studies reported that treatment modalities other than sorafenib, such as hepatic arterial infusion chemotherapy and transarterial radioembolization, showed comparable or better response rates and survival rates than sorafenib. In this review, treatment modalities that could be used as alternatives to sorafenib will be discussed.
Carcinoma, Hepatocellular* ; Drug Therapy ; Humans ; Liver Neoplasms ; Survival Rate