Background: /Aim: Abdominal ultrasonography (USG) is recommended as a surveillance test for high-risk groups for hepatocellular carcinoma (HCC). This study aimed to analyze the current status of the national cancer surveillance program for HCC in South Korea and investigate the effects of patient-, physician-, and machine-related factors on HCC detection sensitivity. Methods: This multicenter retrospective cohort study collected surveillance USG data from the high-risk group for HCC (liver cirrhosis or chronic hepatitis B or C >40 years of age) at eight South Korean tertiary hospitals in 2017. Results: In 2017, 45 experienced hepatologists or radiologists performed 8,512 USG examinations. The physicians had a mean 15.0±8.3 years of experience; more hepatologists (61.4%) than radiologists (38.6%) participated. Each USG scan took a mean 12.2±3.4 minutes. The HCC detection rate by surveillance USG was 0.3% (n=23). Over 27 months of follow-up, an additional 135 patients (0.7%) developed new HCC. The patients were classified into three groups based on timing of HCC diagnosis since the 1st surveillance USG, and no significant intergroup difference in HCC characteristics was noted. HCC detection was significantly associated with patient-related factors, such as old age and advanced fibrosis, but not with physician- or machine-related factors. Conclusions This is the first study of the current status of USG as a surveillance method for HCC at tertiary hospitals in South Korea. It is necessary to develop quality indicators and quality assessment procedures for USG to improve the detection rate of HCC.

Background/Aims: Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. Methods: The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. Results: The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. Conclusions The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Background/Aims: Sorafenib is the first approved systemic treatment for advanced hepatocellular carcinoma (HCC). However, its clinical utility is limited, especially in Asian countries. Several reports have suggested the survival benefits of hepatic arterial infusion chemotherapy (HAIC) for advanced HCC with main portal vein tumor thrombosis (PVTT). This study aimed to compare the efficacy of sorafenib-based therapy with that of HAIC-based therapy for advanced HCC with main PVTT. Methods: Advanced HCC patients with main PVTT treated with sorafenib or HAIC between 2008 and 2016 at Korea University Medical Center were included. We evaluated overall survival (OS), time-to-progression (TTP), and the disease control rate (DCR). Results: Seventy-three patients were treated with sorafenib (n=35) or HAIC (n=38). Baseline characteristics were not significantly different between groups, except the presence of solid organ metastasis (46% vs 5.3%, p<0.001). The median OS time was not significantly different between the groups (6.4 months vs 10.0 months, p=0.139). TTP was longer in the HAIC group than in the sorafenib group (2.1 months vs 6.2 months, p=0.006). The DCR was also better in the HAIC group than in the sorafenib group (37% vs 76%, p=0.001). Subgroup analysis, which excluded patients with extrahepatic solid organ metastasis, showed the same trends for the median OS time (8.8 months vs 11.1 months, p=0.097), TTP (1.9 months vs 6.0 months, p<0.001), and DCR (53% vs 81%, p=0.030). Conclusions HAIC-based therapy may be an alternative to sorafenib for advanced HCC with main PVTT by providing longer TTP and a better DCR.

Background: Prognosis of patients with diverse chronic diseases is reportedly associated with 25-hydroxyvitamin D levels. In this study, we investigated the potential role of 25-hydroxyvitamin D3 (25[OH]D3) levels in improving the predictive power of conventional prognostic models for patients with liver cirrhosis. Methods: We investigated clinical findings, including serum 25(OH)D3 levels at admission, of 155 patients with cirrhosis who were followed up for a median of 16.9 months. Results: Median 25(OH)D3 levels were significantly different among patients exhibiting Child-Pugh grades A, B, and C. Mortality, including urgent transplantation, was significantly associated with 25(OH)D3 levels in univariate analysis. Severe vitamin-D deficiency (serum 25[OH]D3 level < 5.0 ng/mL) was significantly related to increased mortality, even after adjusting for Child-Pugh and Model for End-stage Liver Disease (MELD) scores. In particular, the presence of severe vitamin D deficiency clearly defined a subgroup with significantly poorer survival among patients with Child-Pugh scores of 5–10 or MELD scores ≤ 20. A new combination model of MELD score and severe vitamin D deficiency showed significantly more accurate predictive power for short- and long-term mortality than MELD scores alone. Additionally, serum 25(OH)D3 levels and new model scores were significantly associated with the development of spontaneous bacterial peritonitis, overt encephalopathy, and acute kidney injury. Conclusion Serum 25(OH)D3 level is an independent prognostic factor for patients with liver cirrhosis and has a differential impact on disease outcomes according to MELD and Child-Pugh scores.

BACKGROUND/AIMS: In addition to the globally endorsed Barcelona Clinic Liver Cancer (BCLC) staging system, other algorithms or staging systems have been developed, including the Hong Kong Liver Cancer (HKLC) staging system. This study aimed to validate the HKLC staging system relative to the BCLC staging system for predicting survival for hepatocellular carcinoma (HCC) patients in Korea. METHODS: From 2004 to 2013, 2,571 patients newly diagnosed with HCC were consecutively enrolled at three Korea University medical centers. RESULTS: Both staging systems differentiated survival well (p < 0.001). However, 1-year and 3-year survival were predicted better using the HKLC system than the BCLC system (area under the receiver operating characteristic curve: 0.869 vs 0.856 for 1 year, p=0.002; 0.841 vs 0.827 for 3 years, p=0.010). In hypothetical survival curves, the HKLC system exhibited better median overall survival than the BCLC system (33.1 months vs 19.2 months). In evaluations of prognosis according to either BCLC or HKLC treatment guidelines, risk of death was reduced in the group following only HKLC guidelines compared with the group following only BCLC guidelines (hazard ratio, 0.601; 95% confidence interval, 0.443 to 0.816; p=0.001). CONCLUSIONS: Although both staging systems predicted and discriminated HCC prognoses well, the HKLC system showed more encouraging survival benefits than the BCLC system.
Academic Medical Centers ; Carcinoma, Hepatocellular ; Hong Kong ; Humans ; Korea ; Liver Neoplasms ; Liver ; Neoplasm Staging ; Prognosis ; ROC Curve

BACKGROUND/AIMS: Data are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB. METHODS: Patients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment. RESULTS: Of the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p<0.0001) and showed the greatest reduction of HBV DNA levels from baseline compared to all other groups (p=0.004) at week 48. HBV DNA was undetectable (<70 IU/mL) in 0%, 57.1%, 21.2%, and 27.5% (p=0.003) of the patients in each group, respectively, at week 48. At the end of the study, the mean alanine transaminase (ALT) level, rate of ALT normalization, and rate of hepatitis B envelope antigen loss or seroconversion did not differ between groups. CONCLUSIONS: CLV+ADV combination therapy in patients with CLV-resistant CHB more effectively suppresses HBV replication than ETV, ADV, or LAM+ADV therapy.
Alanine Transaminase ; Cohort Studies* ; DNA ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Lamivudine ; Seroconversion

Since sorafenib was introduced in 2007 for treating advanced hepatocellular carcinoma (HCC), 15 patients have achieved a complete response (CR) in advanced HCC. However, only four of these reports can be regarded as real CRs involving adequate assessments including imaging, serum tumor markers, and histologic examinations of completely resected specimens. A 54-year-old man with hepatitis C virus (HCV)-related liver cirrhosis (LC) presented to our unit. A CT scan demonstrated a 3.8-cm arterial hypervascular/portal-washout mass in the right lobe and invasion in the right portal vein. Twelve weeks after beginning sorafenib therapy, the AFP level was normalized and a CT scan showed a prominent decrease in the hepatic mass and a significant decrease in the volume of portal vein thrombosis (PVT). The patient received a right liver hemihepatectomy after 12 months. No viable tumor cells were found in the resected specimen, and there was no thrombotic obstruction of the portal vein. Twelve months later the patient showed no clinical evidence of HCC recurrence. This is the first case of CR in HCC treatment following sorafenib with histologically confirmed HCV-related HCC without LC evidence, HCC with PVT, and a follow-up of longer than 12 months. This case seems to be an extremely unusual clinical outcome in advanced HCC.
Biomarkers, Tumor ; Carcinoma, Hepatocellular* ; Follow-Up Studies ; Hepacivirus ; Hepatitis C ; Humans ; Liver ; Liver Cirrhosis ; Middle Aged ; Portal Vein ; Recurrence ; Response Evaluation Criteria in Solid Tumors ; Tomography, X-Ray Computed ; Venous Thrombosis

The silkworm extract powder contain 1-deoxynojirimycin (DNJ), a potent alpha-glycosidase inhibitor, has therapeutic potency against diabetes mellitus. Therefore, natural products containing DNJ from mulberry leaves and silkworm are consumed as health functional food. The present study was performed to evaluate the safety of the silkworm extract powder, a health food which containing the DNJ. The repeated toxicity studies and gentic toxicity studies of the silkworm extract powder were performed to obtain the data for new functional food approval in MFDS. The safety was evaluated by a single-dose oral toxicity study and a 90 day repeated-dose oral toxicity study in Sprague-Dawley rats. The silkworm extract powder was also evaluated for its mutagenic potential in a battery of genetic toxicity test: in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay. The results of the genetic toxicology assays were negative in all of the assays. The approximate lethal dose in single oral dose toxicity study was considered to be higher than 5000 mg/kg in rats. In the 90 day study, the dose levels were wet at 0, 500, 1000, 2000 mg/kg/day, and 10 animals/sex/dose were treated with oral gavage. The parameters that were monitored were clinical signs, body weights, food and water consumptions, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weights, and histopathological examination. No adverse effects were observed after the 90 day administration of the silkworm extract powder. The No-Observed-Adverse-Effect-Level (NOAEL) of silkworm extract powder in the 90 day study was 2000 mg/kg/day in both sexes, and no target organ was identified.
1-Deoxynojirimycin ; Animals ; Biochemistry ; Biological Agents ; Body Weight ; Bombyx* ; Bone Marrow ; Chromosome Aberrations ; Diabetes Mellitus ; Functional Food ; Food, Organic ; Hematology ; Mice ; Micronucleus Tests ; Morus ; Mutagenicity Tests ; Organ Size ; Rats ; Rats, Sprague-Dawley ; Toxicology ; Urinalysis ; Drinking

No abstract available.
Antiviral Agents/therapeutic use ; Ascites/diagnosis/prevention & control/therapy ; Cholagogues and Choleretics/therapeutic use ; Fatty Liver/diagnosis/diet therapy ; Fatty Liver, Alcoholic/diagnosis/drug therapy ; Hemorrhage/prevention & control/therapy ; Hepatic Encephalopathy/diagnosis/prevention & control/therapy ; Hepatitis B, Chronic/diagnosis/drug therapy ; Hepatitis C, Chronic/diagnosis/drug therapy ; Humans ; Liver Cirrhosis/*diagnosis/drug therapy/pathology/*therapy ; Liver Cirrhosis, Biliary/drug therapy ; Vasodilator Agents/therapeutic use

BACKGROUND: Heart rate is tightly controlled by brain. If activity of brain and electroencephalograph (EEG) are changed by anesthetics, electrocardiograph (ECG) might be changed. We investigated whether there is a correlation between EEG and ECG, ECG could replace EEG as a monitor for depth of anesthesia. METHODS: We recruited 50 patients, aged 2-8 years. Inspired and expired end-tidal sevoflurane concentrations were held constant at 1.0 or 2.5 vol%, after which ECG and EEG were obtained for 15 minutes. Total power (TP), low-frequency power (LFP), high-frequency power (HFP), approximate entropy (ApEn), and Hurst exponent (H) were calculated from the ECG. The relationship between EEG and ECG indices at the two sevoflurane concentrations was measured by Pearson's correlation coefficient. RESULTS: As anesthesia deepened, ApEn, H of ECG and beta wave decreased and those of delta and theta increased in 4 channels. In FP2, changes of beta and theta wave were negatively correlated with ApEn and H of ECG (P < 0.05), and changes of delta wave was positively correlated with ApEn (P < 0.05) and H (P < 0.01). In F8, changes of beta and theta wave were negatively correlated with ApEn (P < 0.05) and only theta wave was negatively correlated with H (P < 0.05). In C4, change of delta wave was positively correlated with ApEn (P < 0.001) and H (P < 0.05). CONCLUSIONS: EEG and ECG indices are correlated during sevoflurane anesthesia in children, and ECG-derived indices could possibly be used to monitor depth of anesthesia.
Aged ; Anesthesia ; Anesthetics ; Brain ; Child ; Electrocardiography ; Electroencephalography ; Entropy ; Heart Rate ; Humans ; Methyl Ethers ; Organothiophosphorus Compounds