Search

Background: Chronic hepatitis B virus (HBV) remains a global concern, with current treatments achieving low rates of HBsAg seroclearance. VIR-2218 (elebsiran), a small interfering RNA agent against HBV transcripts, reduces HBsAg concentrations. We aimed to evaluate the safety and antiviral activity of VIR-2218 with and without pegylated interferon-alpha-2a treatment in participants with chronic HBV., Methods: This open-label, phase 2 study was conducted at 23 sites in six countries (New Zealand, Australia, Hong Kong, Thailand, South Korea, and Malaysia). Adults (aged 18-65 years) with chronic HBV infection without cirrhosis and with HBsAg more than 50 IU/mL and HBV DNA less than 90 IU/mL who were on continued nucleoside or nucleotide reverse transcriptase inhibitor (NRTI) therapy for 2 months or longer were eligible. Participants were enrolled into one of six cohorts to receive VIR-2218 200 mg subcutaneously every 4 weeks, with or without 180 μg subcutaneous pegylated interferon-alfa-2a once per week. Cohort 1 received six doses of VIR-2218 (total 20 weeks); cohort 2 received six doses of VIR-2218 starting at day 1, plus 12 doses of pegylated interferon-alfa-2a starting at week 12 (total 24 weeks); cohort 3 received six doses of VIR-2218 and 24 doses of pegylated interferon-alfa-2a (total 24 weeks); cohort 4 received six doses of VIR-2218 and up to 48 doses of pegylated interferon-alfa-2a (total 48 weeks); cohort 5 received up to 13 doses of VIR-2218 and up to 44 doses of pegylated interferon-alfa-2a (total 48 weeks); and cohort 6 received three doses of VIR-2218 and 12 doses of pegylated interferon-alfa-2a (total 12 weeks). The primary endpoints were the incidence of adverse events and clinical assessments (including results of laboratory tests). Secondary endpoints were the mean maximum reduction of serum HBsAg at any timepoint; the proportion of participants with serum HBsAg seroclearance at any timepoint and for more than 6 months after the end of treatment; and the proportion of participants with anti-HBs seroconversion at any timepoint. For patients who were HBeAg-positive, we also assessed the proportion with HBeAg seroclearance or anti-HBe seroconversion at any timepoint. This study is registered with ClinicalTrials.gov, NCT03672188, and is ongoing., Findings: Between July 2, 2020, and Nov 2, 2021, 124 individuals were screened for eligibility, 84 of whom were enrolled (15 in cohort 1, 15 in cohort 2, 18 in cohort 3, 18 in cohort 4, 13 in cohort 5, and five in cohort 6). Participants were predominantly HBeAg-negative, Asian, and male (66 [79%] participants were male and 18 [21%] were female). Most treatment emergent adverse events were grades 1-2. Three (20%) participants in cohort 1, four (27%) in cohort 2, eight (44%) in cohort 3, seven (39%) in cohort 4, six (46%) in cohort 5, and two (40%) in cohort 6 reported treatment-emergent adverse events related to VIR-2218. 12 (80%) participants in cohort 2, 12 (67%) in cohort 3, 14 (78%) in cohort 4, 13 (100%) in cohort 5, and three (60%) in cohort 6 reported treatment-emergent adverse events related to pegylated interferon-alfa-2a. Two (13%) participants in cohort 1 had elevations in alanine aminotransferase, compared with 13 (87%) participants in cohort 2, 15 (83%) in cohort 3, 17 (94%) in cohort 4, 11 (85%) in cohort 5, and three (60%) in cohort 6. The mean maximum change from baseline at any timepoint in HBsAg concentration was -2·0 log 10 IU/mL (95% CI -2·1 to -1·8) in cohort 1, -2·2 log 10 IU/mL (-2·5 to -1·8) in cohort 2, -2·5 log 10 IU/mL (-2·8 to -2·1) in cohort 3, -2·4 log 10 IU/mL (-3·1 to -1·8) in cohort 4, -3·0 log 10 IU/mL (-3·7 to -2·3) in cohort 5, and -1·7 log 10 IU/mL (-2·1 to -1·4) in cohort 6. 11 participants (one in cohort 2, one in cohort 3, five in cohort 4, and four in cohort 5) receiving VIR-2218 plus pegylated interferon-alfa-2a had HBsAg seroclearance at any timepoint. Of these, ten (91%; one in cohort 2, five in cohort 4, and four in cohort 5) had anti-HBs seropositivity. Six participants (one in cohort 2, three in cohort 4, and two in cohort 5) had sustained HBsAg seroclearance through to 24 weeks after the end of treatment. No participants receiving VIR-2218 monotherapy (cohort 1) or VIR-2218 plus pegylated interferon-alfa-2a 12-week regimen (cohort 6) had HBsAg seroclearance. 12 (42%) of 26 participants (one of four in cohort 1, two of six in cohort 2, four of seven in cohort 3, four of six in cohort 4, and one of three in cohort 5) who were HBeAg positive at baseline had HBeAg seroclearance or anti-HBe seroconversion., Interpretation: The results of this phase 2 study support further development of VIR-2218 as a potential therapy for patients with chronic HBV infection. Additional clinical trials of VIR-2218 with and without pegylated interferon-alfa-2a in combination with an HBsAg-targeting monoclonal antibody are ongoing., Funding: Vir Biotechnology., Competing Interests: Declaration of interests M-FY is a consultant for AbbVie, Arbutus Biopharma, Bristol Myers Squibb, ClearB Therapeutics, Dicerna Pharmaceuticals, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp & Dohme, Spring Bank Pharmaceuticals, Roche, and Vir Biotechnology, and has received grant support from Arrowhead Pharmaceuticals, Assembly Biosciences, Bristol Myers Squibb, Fujirebio Incorporation, Gilead Sciences, Merck Sharp & Dohme, Spring Bank Pharmaceuticals, and Sysmex Corporation. Y-SL has received grant support from Gilead Sciences, has received consultant fees from AbbVie, Assembly Biosciences, GlaxoSmithKline, Gilead Sciences, Janssen, Olix Pharmaceuticals, Roche, Vaccitech, and Vir Biotechnology, and has received honoraria from AbbVie, Gilead Sciences, and Vaccitech. JH has received grant support from Gilead Sciences and Roche, has received consultant fees from Roche and lecture fees from AbbVie Korea, Roche, Yuhan Korea, Oncolys, and Gilead, and is a member of an AstraZeneca steering committee. VT, SM, AA, ALC, SVG, and CH are employees of Vir Biotechnology. DC is a former employee of Vir Biotechnology. EG has served on scientific advisory boards for Gilead Sciences, ALIGOS, Janssen, Roche, and Assembly and has received unrestricted grant support from AbbVie. EG is an associate editor of the Journal of Hepatology and is a sponsored lecturer for the HCV Elimination Leaders Conference series for AbbVie. All other authors declare no competing interests., (© 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Aim: The definition of metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed. We aim to investigate the diagnostic efficacy of noninvasive fibrosis markers in predicting liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated fatty liver disease (MAFLD), and MASLD., Methods: This retrospective study involved 2843 patients diagnosed with steatotic liver disease at six tertiary hospitals in South Korea. Liver fibrosis was assessed using vibration-controlled transient elastography, and various noninvasive markers, including the aspartate aminotransferase-to-platelet ratio index (APRI), Fibrosis-4 index (FIB-4), NAFLD fibrosis score (NFS), and serum Mac-2-binding protein glycosylation isomer were analyzed., Results: Among 1106 patients, 79.9% met criteria for NAFLD, MAFLD, and MASLD. The APRI had area under the receiver operating characteristic curve (AUC) values of 0.819, 0.821, and 0.818 for liver fibrosis ≥F2, and 0.819, 0.824, and 0.884 for liver fibrosis ≥F3, and 0.890, 0.884, and 0.889 for fibrosis ≥F4 in NAFLD, MAFLD, and MASLD, respectively. The FIB-4 index showed AUC values of 0.776, 0.793, and 0.778 for fibrosis ≥F2, 0.788, 0.814, and 0.79 for fibrosis ≥F3, and 0.846, 0.859, and 0.856 for fibrosis ≥F4. The APRI consistently had the highest AUC values, except in individuals older than 64 years for fibrosis ≥F4., Conclusions: The APRI was the most effective noninvasive fibrosis marker across NAFLD, MAFLD, and MASLD, particularly in age-stratified analyses. Further research is needed to establish standardized cut-off values and enhance the clinical utility of these markers in managing liver fibrosis., (© 2024 Japan Society of Hepatology.)

Background: Severe alcoholic hepatitis is a catastrophic disease with a mortality rate of up to 35-50% at 30 days. Bacterial infection is an important prognostic factor in patients with severe alcoholic hepatitis, but it is difficult to detect the presence of infection immediately. Procalcitonin (PCT) is a well-known inflammatory marker that can detect bacterial infections in various diseases early. Therefore, we aimed to evaluate the diagnostic accuracy of PCT for bacterial infection in severe alcoholic hepatitis., Methods: We prospectively enrolled patients with severe alcoholic hepatitis, defined as modified Maddrey's Discriminant Function ≥ 32, from 10 medical centers. At admission, we performed an initial evaluation including physical examination, laboratory test, radiology, blood and urine culture, PCT, and C-reactive protein (CRP). We compared the receiver operating characteristic (ROC) curves of PCT and CRP for bacterial infection, systemic inflammatory response syndrome (SIRS), and sepsis among total patients., Results: A total of 108 patients with severe alcoholic hepatitis were enrolled. The number of bacterial infections, SIRS, and sepsis were 31 (28.7%), 41 (38.0%), and 19 (17.6%), respectively. The patients with bacterial infection had significantly higher MELD scores (24.0 vs. 15.0), PCT levels (1.5 vs. 0.4 ng/mL), and CRP levels (4.9 vs. 2.5 mg/dL) compared to those without bacterial infection. The area under the ROC curve (AUROC) of PCT vs. CRP for bacterial infection was 0.752 and 0.655, respectively (P = 0.113). The AUROC of PCT vs. CRP for SIRS was 0.699 and 0.662, respectively (P = 0.490). The AUROC of PCT vs. CRP for sepsis was 0.780 and 0.630, respectively (P = 0.027)., Conclusions: Among patients with severe alcoholic hepatitis, PCT showed a trend of superior diagnostic performance in the early detection of bacterial infection and sepsis compared to CRP. Although PCT might have better potential to diagnose sepsis in the setting of severe alcoholic hepatitis, it is necessary to find more reliable diagnostic markers., Competing Interests: Declarations. Ethical approval and consent to participate: This study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This study protocol was approved by Institutional review boards of all ten participating medical centers; Inje University Haeundae Paik Hospital (Inje University Haeundae Paik Hospital Institutional Review Board), Inje University Busan Paik Hospital (Inje University Busan Paik Hospital Institutional Review Board), Dong-A University Hospital (Dong-A University Hospital Institutional Review Board), Pusan National University Yangsan Hospital (Pusan National University Yangsan Hospital Institutional Review Board), Kosin University Gospel Hospital (Kosin University Gospel Hospital Institutional Review Board), Gyeongsang National University Changwon Hospital (Gyeongsang National University Changwon Hospital Institutional Review Board), Daegu Catholic University Medical Center (Daegu Catholic University Medical Center Institutional Review Board), Kyungpook National University Hospital/Kyungpook National University Chilgok Hospital (Kyungpook National University Hospital Institutional Review Board), Keimyung University Dongsan Hospital (Keimyung University Dongsan Hosptial Institutional Review Board), Yeungnam University Medical Center (Yeungnam University Hospital Institutional Review Board). Consent for publication: Not applicable. Informed consent: was obtained from all individual participants included in the study. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

An electron transport layer (ETL) for highly efficient perovskite solar cells (PSCs) should exhibit superior electrical transport properties and have its band levels aligned with interfacing layers to ensure efficient extraction of photo-generated carriers. Nitrogen-doped TiO 2 (TiO 2 :N) is considered a promising ETL because it offers higher electrical conductivity compared to conventional ETLs made from spray-pyrolyzed TiO 2 . However, the application of highly doped TiO 2 :N in PSCs is often limited by the misalignment of energy band levels with adjacent layers and reduced optical transparency. In this study, a novel approach is introduced to enhance the charge transport characteristics and accurately align the electronic band alignment of TiO 2 :N layer through nanoscale doping level grading, achieved through the pulsed laser deposition (PLD) technique. The TiO 2 :N ETL with a graded doping profile can combine characteristics of both highly doped and lightly doped phases on each side. Furthermore, a nanoscale doping gradation, employing an ultrathin sub-layer structure with graded doping levels, creates a smoothly cascading band-level alignment that bridges the adjacent layers, enhancing the transport of photo-generated carriers. Consequently, this method leads to a substantial increase in the power conversion efficiency (PCE), exceeding 22%, which represents a relative improvement of 11% compared to traditional spray-pyrolyzed TiO 2 -based PSCs., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background: It is unclear whether direct-acting antivirals (DAAs) treatment improves the disease burden in hepatitis C virus (HCV) infection. This study aimed to investigate the effect of DAA treatment on the reduction of disease burden in patients with HCV infection using individual participant data., Methods: This nationwide multicentre retrospective cohort study recruited patients with HCV infection from 29 tertiary institutions in South Korea. The data collection was done from medical records in each institution. The study included the untreated patients and the DAAs-treated patients and excluded those with a history of interferon-based treatments. Disease burden was the primary outcome, as represented by disability-adjusted life years (DALYs). Improvement in fibrosis after DAA treatment was assessed using APRI, FIB-4 index, and liver stiffness (LS) as assessed by transient elastography. Clinical outcomes were hepatocellular carcinoma (HCC), decompensation, and mortality., Findings: Between January 1, 2007, and February 17, 2022, data from 11,725 patients with HCV infection, 8464 (72%) of whom were treated with DAAs, were analysed. DAA treatment significantly improved APRI- (median 0.64 [interquartile range (IQR), 0.35-1.31]-0.33 [0.23-0.52], p < 0.0001), FIB-4- (median 2.42 [IQR, 1.48-4.40]-1.93 [1.31-2.97], p < 0.0001), and liver LS-based fibrosis (median 7.4 [IQR, 5.3-12.3]-6.2 [4.6-10.2] kPa, p < 0.0001). During the median follow-up period of 27.5 months (IQR, 10.6-52.4), 469 patients died (4.0%), 586 (5.0%) developed HCC, and 580 (4.9%) developed decompensation. The APRI-based DALY estimate was significantly lower in the DAA group than in the untreated group (median 4.55 vs. 5.14 years, p < 0.0001), as was the FIB-4-based DALY estimate (median 5.43 [IQR, 3.00-6.44] vs. 5.79 [3.85-8.07] years, p < 0.0001). The differences between the untreated and DAA groups were greatest in patients aged 40-60 years. In multivariable analyses, the DAA group had a significantly reduced risk of HCC, decompensation, and mortality compared with the untreated group (hazard ratios: 0.41 [95% confidence interval (CI), 0.34-0.48], 0.31 [95% CI, 0.30-0.38], and 0.22 [95% CI, 0.17-0.27], respectively; p < 0.0001)., Interpretation: Our findings suggest that DAA treatment is associated with the improvement of liver-related outcomes and a reduction of liver fibrosis-based disease burden in patients with HCV infection. However, further studies using liver biopsy are needed to clarify the effect of DAA treatment on the reduction in the exact fibrosis-based disease burden beyond noninvasive tests., Funding: The Korea Disease Control and Prevention Agency., Competing Interests: All authors declare no financial or non-financial competing interests., (© 2024 The Authors. Published by Elsevier Ltd.)

Background/aims: Noninvasive methods have become increasingly critical in the diagnosis of fibrosis in chronic liver diseases. Herein, we compared the diagnostic performance of serum Mac2 binding protein glycosylation isomer (M2BPGi) and other serological panels for fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) and proposed an improved two-step diagnostic algorithm for advanced fibrosis., Methods: We enrolled 231 patients diagnosed with NAFLD who underwent a liver biopsy. We subsequently evaluated the diagnostic performance of serological panels, including serum M2BPGi, a fibrosis index based on four factors (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI), and NAFLD fibrosis score (NFS), in predicting the stage of liver fibrosis. We then constructed a two-step algorithm to better differentiate advanced fibrosis., Results: The areas under the receiver operating characteristic curves of serum M2BPGi, FIB-4, APRI, and NFS for advanced fibrosis (≥F3) were 0.823, 0.858, 0.779, and 0.827, respectively. To reduce the performance of unnecessary liver biopsy, we propose a two-step algorithm using FIB-4 as an initial diagnostic tool and serum M2BPGi (≥0.6) as an additional diagnostic method for patients classified as intermediate (23%). Using the proposed algorithm, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.812, 0.814, 0.814, 0.600, and 0.927, respectively., Conclusions: Serum M2BPGi is a simple and effective test for advanced fibrosis in patients with NAFLD. Application of the two-step algorithm based on FIB-4 and M2BPGi proposed here can improve diagnostic performance and reduce unnecessary tests, making diagnosis easily accessible, especially in primary medical centers.

A novel approach to producing high-color-purity blue-light-emitting diodes based on single-crystalline Ruddlesden-Popper perovskites (RPPs) is reported. The utilization of a pure bromide composition eliminates any possibility of halide segregation, which can otherwise lead to undesired shifts in the emission wavelength or irreversible degradation of the spectral line width. Phase-pure PEA 2 MAPb 2 Br 7 single crystals with a lateral size exceeding 1 cm 2 can be synthesized using the inverse temperature crystallization method. To prepare RPP layers with a thickness of less than 50 nm, we employ a thinning process of the initially thick bulk crystals, followed by a dry-transfer process to place them onto a hole transport layer and an indium-tin-oxide-coated glass substrate. By utilizing polydimethylsiloxane as a handling layer, deformations of the bulk RPP crystal and exfoliated RPP layer, as well as the formation of defects such as pinholes, can be effectively suppressed. Subsequent depositions of an electron transport layer and a metal contact complete the fabrication of electroluminescence (EL) devices. The EL devices utilizing the single-crystalline RPP demonstrate excellent spectral stability across a broad range of the applied bias voltage spanning from 4.5 to 10 V, exhibiting a significantly narrow line width of 14 nm at an emission wavelength of 440 nm that can potentially cover 99.3% of the Rec. 2020 color gamut. The sharp EL emission spectrum can be effectively preserved, avoiding any broadening of the line width, by suppressing Joule heating throughout the device operation, in addition to the intrinsic stability of single-crystalline RPPs.

Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea. Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea. Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration ( p  < 0.001). Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea. Clinical trial registration: ClinicalTrials.gov NCT05225207.

Work-related musculoskeletal disorders represent a major occupational disability issue, and 53.4% of these disorders occur in the back or shoulders. Various types of passive shoulder exoskeletons have been introduced to support the weight of the upper arm and work tools during overhead work, thereby preventing injuries and improving the work environment. The general passive shoulder exoskeleton is constructed with rigid links and joints to implement shoulder rotation, but there exists a challenge to align with the flexible joint movements of the human shoulder. Also, a force-generating part using mechanical springs require additional mechanical components to generate torque similar to the shoulder joint, resulting in increased overall volume and inertia to the upper arm. In this study, we propose a new type of passive shoulder exoskeleton that uses magnetic spring joint and link chain. The redundant degrees of freedom in the link chains enables to follow the shoulder joint movement in the horizontal direction, and the magnetic spring joint generates torque without additional parts in a compact form. Conventional exoskeletons experience a loss in the assisting torque when the center of shoulder rotation changed during arm elevation. Our exoskeleton minimizes the torque loss by customizing the installation height and initial angle of the magnetic spring joint. The performances of the proposed exoskeleton were verified by an electromyographic evaluation of shoulder-related muscles in overhead work and box lifting task.

Background: Life-threatening bleeding following endoscopic variceal ligation (EVL) in patients with cirrhosis rarely can occur. The present study aimed to evaluate the performance of computed tomography (CT) in predicting the risk of early bleeding following EVL in cirrhotic patients., Methods: We retrospectively investigated 285 cirrhotic patients who had undergone EVL. EVL was performed for prophylaxis or acute variceal bleeding. The patients were classified into 2 groups: early bleeding (< 14 days after EVL) and non-early bleeding. We compared baseline characteristics including CT findings between the patient groups., Results: Among the 285 patients who underwent EVL treatment, 19 patients (6.7%) experienced early bleeding. On average, these bleeding occurred 9.3 ± 3.5 days after the EVL, with a range of 3 to 13 days. Patients who experience early bleeding had a higher six-week bleeding-related mortality rate compared to those in the non-early bleeding group (31.6% vs. 10.2%; p = 0.014). There was a correlation between the grade of esophageal varix observed during endoscopy and the diameter of esophageal varix observed on CT (p < 0.001). The diameter of esophageal varix on CT was identified as the only significant predictive factor for early bleeding (p = 0.005)., Conclusion: A larger esophageal varix diameter observed on CT is associated with an increased risk of early bleeding after EVL treatment. Early identification of this high-risk group can provide a change of treatment strategies to improve patient outcomes., (© 2023. The Author(s).)

Purpose: To evaluate the incidence, risk factors, and prognosis associated with peritoneal seeding after percutaneous radiofrequency ablation (RFA) for HCC, focusing on viable tumors after previous locoregional treatment, including TACE and RFA., Methods: Exactly 290 patients (mean age, 67.9 years ± 9.74; 223 men) with 383 HCCs (mean size, 15.9 mm ± 5.49) who underwent RFA between June 2012 and December 2019 were included in this retrospective study. Among them, 158 had history of previous treatment (mean number, 1.3 ± 1.8) with 109 viable HCCs. Cumulative seeding after RFA was estimated using the Kaplan-Meier method. Independent factors affecting seeding were investigated using multivariable Cox proportional hazards regression analysis., Results: Median follow-up was 1175 days (range: 28-4116). Seeding incidence was 4.1 (12/290) and 4.7% (17/383) per patient and tumor, respectively. The median time interval between RFA and detection of seeding was 785 days (range: 81-1961). Independent risk factors for seeding included subcapsular tumor location (hazard ratio [HR] 4.2; 95% confidence interval [CI] 1.4, 13.0; p = 0.012) and RFA for viable HCC after previous locoregional treatment (HR 4.5; 95% CI 1.7, 12.3; p = 0.003). Subgroup analysis for viable tumors, revealed no significant difference in cumulative seeding rates between the TACE and RFA groups (p = 0.078). Cumulative overall survival rates differed significantly between patients with and without seeding metastases (p < 0.001)., Conclusion: Peritoneal seeding after RFA is a rare, delayed complication. Subcapsular-located and viable HCC after previous locoregional treatment are potential risk factors for seeding. Seeding metastases could affect the prognosis of patients who cannot receive local therapy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: This study aimed to investigate the prevalence rate of hepatitis C virus (HCV) infection and identify the demographic, and sociological characteristics and changes in awareness of HCV infection by participating the study for North Korean defectors residing in South Korea., Methods: This study prospectively enrolled participants. Demographic, sociological and clinical data, and questionnaire surveys focused on awareness of HCV infection were collected., Results: In total, 211 North Korean defectors participated in this study from September 2020 until June 2021. There were 174 women (82.5%), and the overall mean age was 48.9 years (range, 20 to 80 years). Of these participants, 112 (53.1%) had immigrated to South Korea since 2011. The overall prevalence of anti-HCV antibody among North Korean defectors was 1.9%. Thirty participants (14.2%) had hepatitis B surface antigens. A huge lack of awareness regarding HCV infection has been observed among North Korean defectors., Conclusion: This is the first prospective study to investigate the prevalence rate of HCV infection among North Korean defectors residing in South Korea. As North Korean defectors are a vulnerable group concerning HCV infection, they may benefit from HCV screening policies and educational interventions for HCV infection., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Background/aims: Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir for 12 weeks in HCV-infected Korean adults., Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir-velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir-velpatasvir-voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment., Results: Of 53 participants receiving sofosbuvir-velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir-velpatasvir-voxilaprevir achieved SVR 12. Overall, sofosbuvir-velpatasvir and sofosbuvir-velpatasvir-voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported., Conclusion: Treatment with sofosbuvir-velpatasvir or sofosbuvir-velpatasvir-voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

Background: Hyperdynamic circulation in portal hypertension (PHT) depends on central neural activation. However, the initiating mechanism that signals PHT to the central neural cardiovascular-regulatory centers remains unclear. We aimed to test the hypothesis that oxidative stress in the gut initiates the signal that activates central cardiovascular nuclei in portal hypertensive rats., Methods: Two groups of rats were used. One had portal hypertension produced by partial portal vein ligation, while controls underwent sham operation. Hemodynamics including portal pressure, cardiac output, mean arterial pressure (MAP) and peripheral vascular resistance were measured. Activation of central cardiovascular nuclei was determined by immunohistochemical Fos expression in the paraventricular nucleus (PVN) of the hypothalamus. Myeloperoxidase activity, an oxidative stress marker, was measured in the jejunum. Hydrogen peroxide, the antioxidant N-acetyl-cysteine (NAC) or saline controls were administered for 12-14 days by gavage or osmotic minipumps placed in the peritoneal cavity., Results: Compared with controls, PHT rats showed increased cardiac output (54.2 ± 9.5 vs 33.6 ± 2.4 ml/min/100 g BW, p < 0.01), decreased MAP (96.2 ± 6.4 mmHg vs 103.2 ± 7.8, p < 0.01) and systemic vascular resistance (1.84 ± 0.28 vs 3.14 ± 0.19 mmHg/min/ml/100 g BW, p < 0.01). PHT rats had increased jejunal myeloperoxidase and PVN Fos expression. NAC treatment eliminated the hyperdynamic circulation, decreased jejunal myeloperoxidase and PVN Fos expression in PHT rats, but had no effect on sham controls. H 2 O 2 significantly increased PVN Fos expression and decreased MAP., Conclusion: These results indicate that in PHT, mesenteric oxidative stress is the initial signal that activates chemoreceptors and triggers hyperdynamic circulation by central neural cardiovascular-regulatory centers., (© 2023. Asian Pacific Association for the Study of the Liver.)

Background & Aims: Loss-of-function HSD17β13 mutations protect against the development of chronic liver disease. HSD17β13 inhibition represents a potential approach to treat liver diseases, such as non-alcoholic steatohepatitis (NASH). ARO-HSD is an RNA interference (RNAi) therapeutic designed to selectively reduce expression of HSD17β13 mRNA in hepatocytes. In this study, we evaluated the effects of ARO-HSD in normal healthy volunteers (NHVs) and patients with confirmed or clinically suspected NASH., Methods: The safety, tolerability, and pharmacodynamics of ARO-HSD were evaluated in 32 NHVs and 18 patients with confirmed/clinically suspected NASH. Double-blind NHV cohorts received single escalating doses of ARO-HSD (25, 50, 100, or 200 mg) or placebo subcutaneously on Day 1. Open-label patient cohorts received ARO-HSD (25, 100, or 200 mg) subcutaneously on Days 1 and 29. Liver biopsy was performed pre-dose and on Day 71 to evaluate expression levels of HSD17β13 mRNA and protein., Results: ARO-HSD treatment was well tolerated with no treatment-related serious adverse events or drug discontinuations. The most frequently reported treatment-emergent adverse events were mild injection site reactions, which were short in duration. Mean changes in hepatic HSD17β13 mRNA from baseline to Day 71 were: -56.9% (25 mg), -85.5% (100 mg), and -93.4% (200 mg). The mean HSD17β13 mRNA reduction was 78.6% (p <0.0001) across pooled cohorts. Hepatic HSD17β13 protein levels were similarly reduced across doses. In patients, mean changes in alanine aminotransferase from baseline to Day 71 were -7.7% (25 mg), -39.3% (100 mg), and -42.3% (200 mg) (p <0.001 for pooled cohorts)., Conclusions: ARO-HSD was well tolerated at doses ≤200 mg. This proof-of-concept study demonstrated that short-term treatment with ARO-HSD reduces hepatic HSD17β13 mRNA and protein expression, which is accompanied by reductions in alanine aminotransferase., Gov Number: NCT04202354., Impacts and Implications: There is an unmet medical need for new therapies to treat alcohol-related and non-alcoholic liver disease. ARO-HSD is a small-interfering RNA designed to silence HSD17β13 expression and hence to phenocopy the protective effect seen in individuals with HSD17β13 loss-of-function. The reductions in HSD17β13 expression and in transaminases seen with ARO-HSD administration represent an initial step towards clinical validation of HSD17β13, a drug target with substantial genetic validation, as an important modulator of human liver disease., (Copyright © 2022 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: The bowel-cleansing efficacy and safety of 2 L polyethylene glycol (PEG) with ascorbic acid (2L PEG + Asc) has rarely been studied in the elderly population. In this randomized trial, we compared the bowel cleanliness, safety, and tolerability of 2L PEG + Asc with those of 4 L PEG in an elderly population aged 60-79., Methods: Study participants were randomized either to 2L PEG + Asc or 4L PEG. The primary endpoint was the success rate of bowel preparation, using the Boston Bowel Preparation Scale. Before colonoscopy, all participants were questioned about adverse events and tolerability regarding purgative ingestion., Results: A total of 347 individuals were enrolled (2L PEG + Asc, 174; 4L PEG, 173). Mean age in the 2L PEG + Asc and the 4L PEG was 69.3 ± 5.6 and 69.3 ± 5.0, respectively (P = 0.917). The rate for successful bowel cleansing was comparable between the 2L PEG + Asc (92%) and the 4L PEG (96%, P = 0.118). Total ingested liquid including purgative and water was lower in the 2L PEG + Asc group (2.9 L) than in the 4L PEG group (4.2 L, P < 0.001). The tolerability of purgative was superior in the 2L PEG + Asc (overall satisfaction, P < 0.001; willingness to reuse, P < 0.001). There were no serious adverse events during the trial., Conclusions: The bowel-cleansing efficacy of 2L PEG + Asc was comparable to that of 4L PEG. Tolerability was superior in the 2L PEG + Asc group. For older people, 2L PEG + Asc is an efficacious and safe bowel cleanser. (Clinical trial registration number: KCT0004123)., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alphaviruses are single stranded, positive sense RNA viruses that are often transmitted through mosquito vectors. With the increasing spread of mosquito populations throughout the world, these arboviruses represent a significant global health concern. Viruses such as Sindbis Virus (SINV), Chikungunya Virus (CHIKV) and Equine Encephalitis Viruses (EEV) are all alphaviruses. As viruses, these pathogens are dependent on the host cell environment for successful viral replication. It has been observed that viruses manipulate cellular metabolism and mitochondrial shape, activity, and dynamics to favor viral infection. This report looked to understand the metabolic changes present during Sindbis virus infection of hamster and human kidney cells. Cells were infected with increasing levels of SINV and at 24 hours post infection the mitochondria morphology was assessed with staining and mitochondrial activity was measured with a real-time Seahorse Bioanalyzer. The relative amount of mitochondrial staining intensity decreased with Sindbis virus infected cells. Both oxygen consumption rate and ATP production were decreased during SINV infection while non-mitochondrial respiration and extracellular acidification rate increased during infection. Collectively, the data indicates that SINV primarily utilizes non-mitochondrial metabolism to support viral infection within the first 24 hours. This understanding of viral preference for host cell metabolism may provide critical targets for antiviral therapies and help further define the nature of alphavirus infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rodriguez, Costlow, Sheedy, Yoon, Gabaldón and Steel.)

In the natural course of chronic hepatitis B, the immune tolerance phase is characterized by HBeAg positivity, very high levels of HBV DNA, and persistent normal alanine aminotransferase. The international guideline recommendation for patients in this phase is observation without antiviral treatment because of the low risk of disease progression and the lack of effective antiviral agents. However, recent retrospective studies have shown that progression to hepatic fibrosis and hepatocellular carcinoma may occur in patients who are in the immune tolerance phase. Despite the conceptual definition and clinical diagnostic criteria for this phase, it is difficult to accurately diagnose the true immune tolerance phase. Therefore, we should pay attention to the clinical evaluation and interpretation of the immune tolerance phase and understand the clinical situations in which antiviral treatments should be considered.

Cardiac dysfunction associated with cirrhosis in the absence of preexisting heart disease is a condition known as cirrhotic cardiomyopathy (CCM). Cardiac abnormalities consist of enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM may contribute to cardiovascular morbidity and mortality after liver transplantation and other major surgeries, and also to the pathogenesis of hepatorenal syndrome. The underlying mechanisms of CCM are poorly understood and as such medical therapy is an area of unmet medical need. The present review focuses on the pathogenic mechanisms responsible for development of CCM. The two major concurrent mechanistic pathways are the inflammatory phenotype due to portal hypertension, and protein/lipid synthetic/metabolic defects due to cirrhosis and liver insufficiency. The inflammatory phenotype arises from intestinal congestion due to portal hypertension, resulting in bacteria/endotoxin translocation into the systemic circulation. The cytokine storm associated with inflammation, particularly TNFα acting via NFκB depresses cardiac function. They also stimulate two evanescent gases, nitric oxide and carbon monoxide which produce cardiodepression by cGMP. Inflammation also stimulates the endocannabinoid CB-1 pathway. These systems inhibit the stimulatory beta-adrenergic contractile pathway. The liver insufficiency of cirrhosis is associated with defective synthesis or metabolism of several substances including proteins and lipids/lipoproteins. The protein defects including titin and collagen contribute to diastolic dysfunction. Other protein abnormalities such as a switch of myosin heavy chain isoforms result in systolic dysfunction. Lipid biochemical changes at the cardiac sarcolemmal plasma membrane result in increased cholesterol:phospholipid ratio and decreased membrane fluidity. Final common pathway changes involve abnormal cardiomyocyte intracellular ion kinetics, particularly calcium. In conclusion, cirrhotic cardiomyopathy is caused by two pathways of cellular and molecular dysfunction/damage due to hepatic insufficiency and portal hypertension., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Nguyen, Yoon and Lee.)

Background/aims: Galectin-3 plays a key pathogenic role in cardiac hypertrophy and heart failure. The present study aimed to investigate the effects of galectin-3 on cardiomyopathy - related factors and cardiac contractility in a rat model of cirrhotic cardiomyopathy., Methods: Rats were divided into two sets, one for a functional study, the other for cardiac contractile-related protein evaluation. There were four groups in each set: sham operated and sham plus N-acetyllactosamine (N-Lac, a galectin-3 inhibitor; 5 mg/kg); bile duct ligated (BDL) and BDL plus N-Lac. Four weeks after surgery, ventricular level of galectin-3, collagen I and III ratio, tumor necrosis factor alpha (TNFα), and brain natriuretic peptide (BNP) were measured either by Western blots or immunohistochemistry or enzyme-linked immunosorbent assay. Blood pressure was measured by polygraph recorder. Cardiomyocyte contractility was measured by inverted microscopy., Results: Galectin-3 and collagen I/III ratio were significantly increased in cirrhotic hearts. TNFα and BNP were significantly increased in BDL serum and heart compared with sham controls. Galectin-3 inhibitor significantly decreased galectin-3, TNFα, and BNP in cirrhotic hearts but not in sham controls. N-Lac also significantly improved the blood pressure, and systolic and diastolic cardiomyocyte contractility in cirrhotic rats but had no effect on sham controls., Conclusion: Increased galectin-3 in the cirrhotic heart significantly inhibited contractility via TNFα. Inhibition of galectin-3 decreased the cardiac content of TNFα and BNP and reversed the decreased blood pressure and depressed contractility in the cirrhotic heart. Galectin-3 appears to play a pathogenic role in cirrhotic cardiomyopathy.

Rationale: Most gastric varices at the fundus drain into the left renal vein via the gastrorenal shunt (80-85% of cases) or the inferior vena cava via the gastrocaval shunt (10-15%). Therefore, plug-assisted retrograde transvenous obliteration (PARTO) is usually performed via a gastrorenal shunt. Here, we report a case of gastric varix treated with PARTO via a gastrocaval shunt., Patient Concerns: A 46-year-old woman with hepatitis B virus and liver cirrhosis visited the emergency room in our hospital with the main symptom of hematemesis and hematochezia., Diagnoses: Endoscopy and computed tomography (CT) revealed a gastric varix and thrombotic-occluded transjugular intrahepatic portosystemic shunt (TIPS) stent., Interventions: The patient underwent PARTO via a gastrocaval shunt to manage gastric variceal bleeding after failed TIPS revision., Outcomes: On CT, the gastric varix completely disappeared. The patient did not experience any additional bleeding events., Lessons: PARTO via a gastrocaval shunt is safe and effective., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)