Development and Pilot Testing of a Smartphone-Based Self-Care Program for Patients with Chronic Hepatitis B

The purpose of this study is to develop a smartphone-based self-care program (Hep B Care®) for patients with the chronic hepatitis B virus (HBV). To pilot test the feasibility of Hep B Care®, 63 participants with chronic HBV were recruited from an outpatient clinic at S hospital, Seoul, South Korea (experimental group [EG]: n = 30, control group [CG]: n = 33) between February and July 2016. Hep B Care® was developed based on the theory of self-care whilst having a chronic illness. During the 12-week intervention period, the application: (1) provided information about the disease, medication, nutrition, and exercise; (2) encouraged taking medication and exercise using alarms; and (3) enabled the exchange of messages between healthcare providers and patients. Salivary cortisol, fatigue, depression, anxiety, knowledge of the HBV, quality of life, and medication adherence were all measured as outcomes. Cortisol levels were significantly increased, knowledge of the HBV was improved, and the mean anxiety score was significantly decreased in the EG. Thus, Hep B Care ® partially improved health outcomes in the EG. We recommend that large trials be conducted among patients with the HBV. The smartphone-based self-care program for providing education and coaching is effective for improving knowledge and reducing anxiety among patients with the HBV.ope

RNA Interference Therapy With ARC-520 Results in Prolonged Hepatitis B Surface Antigen Response in Patients With Chronic Hepatitis B Infection

Background and aims: ARC-520, the first an RNA interference (RNAi) therapeutic, was designed to reduce all RNA transcripts derived from covalently closed circular DNA, leading to a reduction in viral antigens and hepatitis B virus (HBV) DNA. Approach and results: We aimed to evaluate the depth of hepatitis B surface antigen (HBsAg) decline in response to multiple doses of ARC-520 compared to placebo (PBO) in two randomized, multicenter studies in nucleoside/nucleotide analogue reverse-transcriptase inhibitor (NUC)-experienced patients with hepatitis B early antigen (HBeAg)-negative (E-neg) or HBeAg-positive (E-pos) disease. A total of 58 E-neg and 32 E-pos patients were enrolled and received four monthly doses of PBO (n = 20 E-neg, 11 E-pos), 1 mg/kg ARC-520 (n = 17 E-neg, 10 E-pos), or 2 mg/kg ARC-520 (n = 21 E-neg, 11 E-pos) concomitantly with NUC. HBsAg change from baseline to 30 days after the last ARC-520 dose were compared to PBO. Both E-neg and E-pos high-dose groups significantly reduced HBsAg compared to PBO, with mean reductions of 0.38 and 0.54 log IU/mL, respectively. HBsAg reductions persisted for approximately 85 days and >85 days after the last dose in E-neg and E-pos patients, respectively. The low-dose groups did not reach statistical significance in either study. E-pos patients showed a dose-dependent reduction in HBeAg from baseline. Mean maximum reduction was 0.23 and 0.69 log Paul Ehrlich IUs/mL in the low-dose and high dose ARC-520 groups respectively. ARC-520 was well tolerated, with only two serious adverse events of pyrexia possibly related to study drug observed. Conclusions: ARC-520 was active in both E-neg and E-pos, NUC-experienced HBV patients; but absolute HBsAg reductions were moderate, possibly due to expression of HBsAg from integrated HBV DNA, indicating the need for RNAi therapeutics that can target viral transcripts regardless of origin.ope

Downregulation of interleukin-18-mediated cell signaling and interferon gamma expression by the hepatitis B virus e antigen

The mechanisms by which hepatitis B virus (HBV) establishes and maintains chronic hepatitis B infection (CHB) are poorly defined. Innate immune responses play an important role in reducing HBV replication and pathogenesis. HBV has developed numerous mechanisms to escape these responses, including the production of the secreted hepatitis B e antigen (HBeAg), which has been shown to regulate antiviral toll-like receptor (TLR) and interleukin-1 (IL-1) signaling. IL-18 is a related cytokine that inhibits HBV replication in hepatoma cell lines and in the liver through the induction of gamma interferon (IFN-γ) by NK cells and T cells. We hypothesized that HBV or HBV proteins inhibit IFN-γ expression by NK cells as an accessory immunomodulatory function. We show that HBeAg protein inhibits the NF-κB pathway and thereby downregulates NK cell IFN-γ expression. Additionally, IFN-γ expression was significantly inhibited by exposure to serum from individuals with HBeAg-positive but not HBeAg-negative chronic HBV infection. Further, we show that the HBeAg protein suppresses IL-18-mediated NF-κB signaling in NK and hepatoma cells via modulation of the NF-κB pathway. Together, these findings show that the HBeAg inhibits IL-18 signaling and IFN-γ expression, which may play an important role in the establishment and/or maintenance of persistent HBV infection. Importance: It is becoming increasingly apparent that NK cells play a role in the establishment and/or maintenance of chronic hepatitis B infection. The secreted HBeAg is an important regulator of innate and adaptive immune responses. We now show that the HBeAg downregulates NK cell-mediated IFN-γ production and IL-18 signaling, which may contribute to the establishment of infection and/or viral persistence. Our findings build on previous studies showing that the HBeAg also suppresses the TLR and IL-1 signaling pathways, suggesting that this viral protein is a key regulator of antiviral innate immune responses.ope

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)

Background and aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. Results: Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1-3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9-38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3-163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.ope

Clinical Outcome of Pulmonary Resections in Patients with Pulmonary Metastasis of Hepatocellular Carcinoma

Background/Aims: Although the lung is the most common site of extrahepatic spread from hepatocellular carcinoma (HCC), the role of surgery for pulmonary metastasis remains unclear. The aim of this study was to evaluate the efficacy of pulmonary resection in patients with pulmonary metastasis from HCC. Methods: Between July 2000 and July 2004, a total of 6 patients with pulmonary metastasis from HCC underwent curative pulmonary resections. The patients were divided into two groups (Surgery group and Non-surgery group) according to the primary treatment modality of HCC. Medical records, imaging studies, and pathologic reports of the surgical specimens were reviewed. Results: Three patients in the surgery group underwent pulmonary resections for a solitary metastasis after hepatectomy for HCC, and they are all still alive. One of the 3 patients developed a tumor recurrence in the chest wall after pulmonary resection. The survival time after diagnosis of HCC were 79, 122, and 54 months, respectively. The survival time after pulmonary metastatectomy were 49, 39, and 20 months in the three patients. Another 3 patients in the non-surgery group, received a pulmonary metastatectomy; they had either a complete response HCC or partial radiologic response. These 3 patients developed recurrent disease in the liver. One of 3 patients died. The survival time after diagnosis of HCC were 153, 83, 12 months. The survival time after pulmonary metastatectomy were 51, 4, 2 months. Conclusions: The surgical resections of a solitary pulmonary metastasis from HCC in highly selected patients might be an effective treatment modalities for prolonged survival. (Korean J Hepatol 2005;11:350-358)ope

Serum Wisteria floribunda agglutinin-positive human Mac-2 binding protein level predicts recurrence of hepatitis B virus-related hepatocellular carcinoma after curative resection

BACKGROUND/AIMS: To investigate whether serum Wisteria floribunda agglutinin-positive human Mac-2-binding protein (WFA+-M2BP) can predict the recurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after curative resection. METHODS: Patients with chronic hepatitis B (CHB) who underwent curative resection for HCC between 2004 and 2015 were eligible for the study. Recurrence was sub-classified as early (<2 years) or late (≥2 years). RESULTS: A total of 170 patients with CHB were selected. During the follow-up period (median, 22.6 months), 64 (37.6%) patients developed recurrence. In multivariate analyses, WFA+-M2BP level was an independent predictor of overall (hazard ratio [HR]=1.490), early (HR=1.667), and late recurrence (HR=1.416), together with male sex, des-gamma carboxyprothrombin level, maximal tumor size, portal vein invasion, and satellite nodules (all P2.14 experienced recurrence more frequently than those with a WFA+-M2BP level ≤2.14 (P=0.011 by log-rank test), and had poorer postoperative outcomes than those with a WFA+-M2BP level ≤2.14 in terms of overall recurrence (56.0 vs. 34.5%, P=0.047) and early recurrence (52.0 vs. 20.7%, P=0.001). CONCLUSION: WFA+-M2BP level is an independent predictive factor of HBV-related HCC recurrence after curative resection. Further studies should investigate incorporation of WFA+-M2BP level into tailored postoperative surveillance strategies for patients with CHB.ope

External Finance and Productivity Growth in Korea:Firm Level Evidence Before and After the Financial Crisis

This paper empirically investigates the finance-growth linkage in Korea by utilizing firm-level data of manufacturing industries before and after the 1997 financial crisis. We find that, first, an increase in external finance is associated with a faster sI. Introduction II. Literature Review III. Corporate Investment and Financing Patterns Beforeand After the 1997 Financial Crisis IV. TFP Growth and Credit Allocation in KoreanManufacturing Industriesn V. Regression Analyses and Empirical Results VI

Management of patients with liver derangement during the COVID-19 pandemic: an Asia-Pacific position statement

The COVID-19 pandemic has spread rapidly worldwide. It is common to encounter patients with COVID-19 with abnormal liver function, either in the form of hepatitis, cholestasis, or both. The clinical implications of liver derangement might be variable in different clinical scenarios. With growing evidence of its clinical significance, it would be clinically helpful to provide practice recommendations for various common clinical scenarios of liver derangement during the COVID-19 pandemic. The Asia-Pacific Working Group for Liver Derangement during the COVID-19 Pandemic was formed to systematically review the literature with special focus on the clinical management of patients who have been or who are at risk of developing liver derangement during this pandemic. Clinical scenarios covering the use of pharmacological treatment for COVID-19 in the case of liver derangement, and assessment and management of patients with chronic hepatitis B or hepatitis C, non-alcoholic fatty liver disease, liver cirrhosis, and liver transplantation during the pandemic are discussed.ope

Probability of HBsAg loss after nucleo(s)tide analogue withdrawal depends on HBV genotype and viral antigen levels

Background & aims: Nucleo(s)tide analogue (NUC) withdrawal may result in HBsAg clearance in a subset of patients. However, predictors of HBsAg loss after NUC withdrawal remain ill-defined. Methods: We studied predictors of HBsAg loss in a global cohort of HBeAg-negative patients with undetectable HBV DNA who discontinued long-term NUC therapy. Patients requiring retreatment after treatment cessation were considered non-responders. Results: We enrolled 1,216 patients (991 with genotype data); 98 (8.1%) achieved HBsAg loss. The probability of HBsAg loss was higher in non-Asian patients (adjusted hazard ratio [aHR] 8.26, p 100 IU/ml) and HBcrAg (100 IU/ml with detectable HBcrAg. HBsAg loss rates also varied with HBV genotype; the highest rates were observed for genotypes A and D, and none of the patients with HBV genotype E experienced HBsAg loss (p <0.001 for the overall comparison across genotypes; p <0.001 for genotypes A/D vs. genotypes B/C). HBV genotype C was independently associated with a higher probability of HBsAg loss when compared to genotype B among Asian patients (aHR 2.494; 95% CI 1.490-4.174, p = 0.001). Conclusions: The probability of HBsAg loss after NUC cessation varies according to patient ethnicity, HBV genotype and end-of-treatment viral antigen levels. Patients with low HBsAg (<100 IU/ml) and/or undetectable HBcrAg levels, particularly if non-Asian or infected with HBV genotype C, appear to be the best candidates for treatment withdrawal. Lay summary: A subset of patients may achieve clearance of hepatitis B surface antigen (HBsAg) - so-called functional cure - after withdrawal of nucleo(s)tide analogue therapy. In this multicentre study of 1,216 patients who discontinued antiviral therapy, we identified non-Asian ethnicity, HBV genotype C, and low hepatitis B surface antigen and hepatitis B core-related antigen levels as factors associated with an increased chance of HBsAg loss.ope

Laparoscopic double tract proximal gastrectomy for proximal early gastric cancer

학위논문 (석사)-- 서울대학교 대학원 : 의학과 외과학 전공, 2013. 2. 김형호.Background: LAPG is not routinely performed because it is associated with increased reflux symptoms and anastomotic strictures. The purpose of this study is to describe a novel method of laparoscopy-assisted proximal gastrectomy (LAPG) with double tract reconstruction (DTR) for proximal early gastric cancer (EGC), and to evaluate the technical feasibility, safety, and short-term surgical outcomes, especially reflux symptoms, after LAPG. Methods: Retrospective review of the prospective cohort data of 43 patients who presented to a single tertiary hospital from June 2009 through April 2012 and underwent LAPG with DTR for proximal EGC. The data of this prospective cohort were analyzed, and the reflux symptoms, clinicopathologic characteristics, surgical outcomes, postoperative morbidities and mortalities, and follow-up findings were analyzed. Results: The mean surgical time was 180.7 minutesmean estimated blood loss, 120.4 mLmean length of the proximal resection margin, 4.13 cmmean number of retrieved lymph nodes, 41.2and mean postoperative hospital stay, 7.1 days. Early complication rate was 11.6% (n = 5)major complication (grade higher than Clavien-Dindo IIIa) occurred in 1 patient (2.3%). Late complication rate was 11.6% (n = 5): 2 patients had esophagojejunostomy stenosis, which was successfully treated with fluoroscopic balloon dilatations1, chylous ascitesand 2 had Visick grade II reflux symptoms (4.6%), managed by medication during the mean follow-up period of 21.6 months. Conclusion: DTR after LAPG is a feasible, simple, and novel reconstruction method with excellent postoperative outcomes in terms of preventing reflux symptoms. Its clinical applicability must be validated by prospective randomized trials.Contents Abstract-----------------------------------------i List of Tables---------------------------------------- iii List of Figures----------------------------------------iv Contents--------------------------------------------v Introduction------------------------------------------1 Materials and Methods------------------------------------2 Results--------------------------------------------13 Discussion------------------------------------------29 References------------------------------------------35Maste