As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

BACKGROUND/AIMS: Programmed death receptor 1 (PD-1) is a promising new target for treatment of patients with hepatocellular carcinoma (HCC). A high expression level of programmed death-ligand 1 (PD-L1) is a possible prognostic indicator for poor outcome in other malignancies. Here, we investigated the clinical significance of PD-1 and PD-L1 in patients with HCC. METHODS: We enrolled patients with HCC who underwent surgical resection at Severance Hospital between 2012 and 2017 and investigated the levels of PD-L1 in HCC tissues (tPD-L1) and PD-L1/PD-1 in serum (sPD-L1/sPD-1). We also aimed to determine whether expression levels correlated with clinical and histological features. RESULTS: A total of 72 patient samples were analyzed. The median sPD-L1 and sPD-1 levels were 25.72 and 341.44 pg/mL, respectively. A positive correlation was detected between tPD-L1 and sPD-1 levels (R²=0.426, P<0.001). The median sPD-1 level increased linearly with tPD-L1 score (P=0.002). During the follow-up period, HCC recurred in eight (11.1%) patients and liver-related mortality occurred in eight (11.1%) patients. Higher sPD-L1 levels (≥19.18 pg/mL) tended to be associated with liver-related mortality (hazard ratio 6.866; 95% confidence interval, 0.804–58.659, P=0.078). sPD-1 levels of patients treated with nivolumab as a second-line therapy changed serially, and a >50% reduction in sPD-1 levels was observed immediately after nivolumab administration. However, sPD-1 level was not associated directly with prognosis in patients with advanced HCC. CONCLUSIONS: The results demonstrated that PD-L1 and PD-1 levels changed according to the immunotherapy. However, no significant association with clinical outcome in patients with HCC was detected.
Carcinoma, Hepatocellular ; Follow-Up Studies ; Humans ; Immunotherapy ; Mortality ; Prognosis

BACKGROUND: Cell division cycle 6 (CDC6) is an essential regulator of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle. CDC6 has been associated with oncogenic activities in human cancers; however, the clinical significance of CDC6 in prostate cancer (PCa) remains unclear. Therefore, we investigated whether the CDC6 mRNA expression level is a diagnostic and prognostic marker in PCa. METHODS: The study subjects included 121 PCa patients and 66 age-matched benign prostatic hyperplasia (BPH) patients. CDC6 expression was evaluated using real-time polymerase chain reaction and immunohistochemical (IH) staining, and then compared according to the clinicopathological characteristics of PCa. RESULTS: CDC6 mRNA expression was significantly higher in PCa tissues than in BPH control tissues (P = 0.005). In addition, CDC6 expression was significantly higher in patients with elevated prostate-specific antigen (PSA) levels (> 20 ng/mL), a high Gleason score, and advanced stage than in those with low PSA levels, a low Gleason score, and earlier stage, respectively. Multivariate logistic regression analysis showed that high expression of CDC6 was significantly associated with advanced stage (≥ T3b) (odds ratio [OR], 3.005; confidence interval [CI], 1.212–7.450; P = 0.018) and metastasis (OR, 4.192; CI, 1.079–16.286; P = 0.038). Intense IH staining for CDC6 was significantly associated with a high Gleason score and advanced tumor stage including lymph node metastasis stage (linear-by-linear association, P = 0.044 and P = 0.003, respectively). CONCLUSION: CDC6 expression is associated with aggressive clinicopathological characteristics in PCa. CDC6 may be a potential diagnostic and prognostic marker in PCa patients.
Cell Cycle ; DNA Replication ; Gene Expression ; Humans ; Logistic Models ; Lymph Nodes ; Neoplasm Grading ; Neoplasm Metastasis ; Passive Cutaneous Anaphylaxis ; Prostate* ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Real-Time Polymerase Chain Reaction ; RNA, Messenger*

In this article, a part of fund and grant supports was omitted unintentionally.

PURPOSE: Previously, we reported the presence of virus-encoded microRNAs (miRNAs) in the urine of prostate cancer (CaP) patients. In this study, we investigated the expression of two herpes virus-encoded miRNAs in prostate tissue. METHODS: A total of 175 tissue samples from noncancerous benign prostatic hyperplasia (BPH), 248 tissue samples from patients with CaP and BPH, and 50 samples from noncancerous surrounding tissues from these same patients were analyzed for the expression of two herpes virus-encoded miRNAs by real-time polymerase chain reaction (PCR) and immunocytochemistry using nanoparticles as molecular beacons. RESULTS: Real-time reverse transcription-PCR results revealed significantly higher expression of hsv1-miR-H18 and hsv2-miRH9- 5p in surrounding noncancerous and CaP tissues than that in BPH tissue (each comparison, P<0.001). Of note, these miRNA were expressed equivalently in the CaP tissues and surrounding noncancerous tissues. Moreover, immunocytochemistry clearly demonstrated a significant enrichment of both hsv1-miR-H18 and hsv2-miR-H9 beacon-labeled cells in CaP and surrounding noncancerous tissue compared to that in BPH tissue (each comparison, P<0.05 for hsv1-miR-H18 and hsv2- miR-H9). CONCLUSIONS: These results suggest that increased expression of hsv1-miR-H18 and hsv2-miR-H95p might be associated with tumorigenesis in the prostate. Further studies will be required to elucidate the role of these miRNAs with respect to CaP and herpes viral infections.
Carcinogenesis ; Herpesviridae ; Humans ; Hyperplasia* ; Immunohistochemistry ; MicroRNAs ; Nanoparticles ; Prostate* ; Prostatic Hyperplasia ; Prostatic Neoplasms ; Real-Time Polymerase Chain Reaction

PURPOSE: MicroRNAs (miRNAs) in biological fluids are potential biomarkers for the diagnosis and assessment of urological diseases such as benign prostatic hyperplasia (BPH) and prostate cancer (PCa). The aim of the study was to identify and validate urinary cell-free miRNAs that can segregate patients with PCa from those with BPH. METHODS: In total, 1,052 urine, 150 serum, and 150 prostate tissue samples from patients with PCa or BPH were used in the study. A urine-based miRNA microarray analysis suggested the presence of differentially expressed urinary miRNAs in patients with PCa, and these were further validated in three independent PCa cohorts, using a quantitative reverse transcriptionpolymerase chain reaction analysis. RESULTS: The expression levels of hsa-miR-615-3p, hsv1-miR-H18, hsv2-miR-H9-5p, and hsa-miR-4316 were significantly higher in urine samples of patients with PCa than in those of BPH controls. In particular, herpes simplex virus (hsv)-derived hsv1-miR-H18 and hsv2-miR-H9-5p showed better diagnostic performance than did the serum prostate-specific antigen (PSA) test for patients in the PSA gray zone. Furthermore, a combination of urinary hsv2-miR-H9-5p with serum PSA showed high sensitivity and specificity, providing a potential clinical benefit by reducing unnecessary biopsies. CONCLUSIONS: Our findings showed that hsv-encoded hsv1-miR-H18 and hsv2-miR-H9-5p are significantly associated with PCa and can facilitate early diagnosis of PCa for patients within the serum PSA gray zone.
Biomarkers ; Biopsy ; Cohort Studies ; Diagnosis ; Early Diagnosis ; Herpes Simplex ; Humans ; Microarray Analysis ; MicroRNAs* ; Passive Cutaneous Anaphylaxis ; Prostate ; Prostate-Specific Antigen ; Prostatic Hyperplasia ; Prostatic Neoplasms* ; Sensitivity and Specificity ; Simplexvirus ; Urologic Diseases

In this study, 23 oleanane-type triterpenoid saponins were isolated from a methanol extract of the roots of Pulsatilla koreana. The NF-kappaB inhibitory activity of the isolated compounds was measured in TNFalpha-treated HepG2 cells using a luciferase reporter system. Compounds 19-23 inhibited TNFalpha-stimulated NF-kappaB activation in a dose-dependent manner, with IC50 values ranging from 0.75-8.30 microM. Compounds 19 and 20 also inhibited the TNFalpha-induced expression of iNOS and ICAM-1 mRNA. Moreover, effect of the isolated compounds on PPARs transcriptional activity was assessed. Compounds 7-11 and 19-23 activated PPARs the transcriptional activity significantly in a dose-dependent manner, with EC50 values ranging from 0.9-10.8 microM. These results suggest the presence of potent anti-inflammatory components in P. koreana, and will facilitate the development of novel anti-inflammatory agents.
Anti-Inflammatory Agents ; Hep G2 Cells ; Inhibitory Concentration 50 ; Intercellular Adhesion Molecule-1 ; Luciferases ; Methanol ; NF-kappa B ; Peroxisome Proliferator-Activated Receptors* ; Pulsatilla* ; RNA, Messenger ; Saponins* ; Tumor Necrosis Factor-alpha

There have been numerous reports on the relationship between eosinophilia and toxocariasis. The present study investigated seropositive rates of toxocariasis among healthy people with or without eosinophilia in urban and rural areas, and assessed risk factors for positive antibody test. A total of 610 healthy people, who visited health check-up (Medicheck(R), Korea Association of Health Promotion), 310 from Seoul and 300 from Gyeongsangnam-do, were subjected for this study. Their serum samples were tested by ELISA with the crude antigen of Toxocara canis larvae. Cross-reactions with other tissue invading helminth antigens were also investigated. Total antibody positive rate of toxocariasis was 8.7% of the 610 subjects. When the subjects were grouped into 3 by their eosinophil counts, the antibody positive rates significantly differed by the groups; 5.9% (18/306) in the group<350/microL, 10.0% (11/110) in the group 350-500/microL, and 12.4% (24/194) in the group>500/microL (P=0.028). A total of 22 serum samples cross-reacted with other tissue-invading helminth antigens. A questionnaire analysis recognized drinking alcohol and smoking as significant risk factors of toxocariasis. In conclusion, toxocariasis antibody positive rate is correlated with eosinophil counts. It is recommended that healthy subjects with eosinophilia by routine health examination and risk factors undergo Toxocara serology by multiantigen ELISA to investigate etiology.
Age Distribution ; Comorbidity ; Eosinophilia/*diagnosis/*epidemiology ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Reference Values ; Republic of Korea/epidemiology ; Risk Factors ; Rural Population/*statistics & numerical data ; Serologic Tests/statistics & numerical data ; Sex Distribution ; Toxocariasis/*diagnosis/*epidemiology ; Urban Population/*statistics & numerical data