Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. Functional cure of CHB, defined as sustainable hepatitis B surface antigen (HBsAg) seroclearance, is associated with improved clinical outcomes. However, functional cure is rarely attainable by current treatment modalities. RNA interference (RNAi) by small-interfering RNA (siRNA) and anti-sense oligonucleotide (ASO) has been studied as a novel treatment strategy for CHB. RNAi targets post-transcriptional messenger RNAs and pregenomic RNAs to reduce hepatitis B virus (HBV) antigen production and viral replication. By reducing viral antigens, host immune reconstitution against HBV may also be attained. Phase I/II trials on siRNAs have demonstrated them to be safe and well-tolerated. siRNA is effective when given in monthly doses with different total number of doses according to different trial design, and can lead to sustainable dose-dependent mean HBsAg reduction by 2–2.5 log. Incidences of HBsAg seroclearance after siRNA therapy have also been reported. ASOs have also been studied in early phase trials, and a phase Ib study using frequent dosing regimen within 4 weeks could achieve similar HBsAg reduction of 2 log from baseline. Given the established efficacy and safety of nucleos(t) ide analogues (NAs), future RNAi regimens will likely include NA backbone. While the current evidence on RNAi appears promising, it remains undetermined whether the potent HBsAg reduction by RNAi can result in a high rate of HBsAg seroclearance with durability. Data on RNAi from phase IIb/III trials are keenly anticipated.

Asian Continental Ancestry Group ; genetics ; Carnitine Acyltransferases ; deficiency ; genetics ; China ; Founder Effect ; Humans ; Infant, Newborn ; Male ; Mutation ; Sudden Infant Death ; genetics

Background：In November 2012, an outbreak of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft tissue infections affecting students at a boarding school in Hong Kong Special Administrative Region (China) was detected.Methods：A case was defined as any student or staff notified with MRSA infection from 25 October 2012 to 5 July 2013 with the clinical isolate being of staphylococcal cassette chromosome mec type IV or V and positive for Panton-Valentine leukocidin gene. We conducted field investigations, advised on control measures and enhanced surveillance for skin and soft tissue infections at the school. Decolonization therapies were offered to all cases and contacts, and carrier screening was conducted.Results：There were five cases; two (40%) were hospitalized and three (60%) required surgical treatments. Initial screening comprised 240 students and 81 staff members. Overall, four cases (80%) plus eight other students (3.3%) were carriers, with eight of 12 (66.7%) from the same dormitory. All staff members screened negative. After intensified control measures, the number of students screened positive for CA-MRSA decreased from nine to one with no more cases identified in the school.Conclusion：Identification of carriers, decolonization therapy, monitoring of cases and contacts and strengthening of environmental and personal hygiene were control measures that helped contain this CA-MRSA outbreak in a boarding school in Hong Kong Special Administrative Region (China).

OBJECTIVETo report our experience of 200 endoscopic totally extraperitoneal inguinal hernioplasties utilizing reusable instruments.

METHODSBetween August 1999 and June 2000, 200 endoscopic totally extraperitoneal hernioplasties were performed on 163 patients. The mean age of the study population was 63 years with a male to female ratio of 157:6. Perioperative details and postoperative outcomes were prospectively evaluated and analyzed.

RESULTSA total of 196 (98%) endoscopic extraperitoneal inguinal hernioplasties were successfully performed. Conversion rates to transabdominal preperitoneal and open repairs were 1.5% (n = 3) and 0.5% (n = 1), respectively. There were no other intraoperative complications. Postoperative morbidity included retention of urine (n = 7), wound bruising (n = 2), atelectasis (n = 2) and gouty arthritis (n = 1). The mean visual analogue pain scores at rest were 2.3, 1.6 and 1.9 on postoperative days 0, 1 and 2, respectively. The mean length of hospital stay was 1.9 days. 113 patients (69%) returned to normal activities within one week. Of the 35 patients who experienced both open and laparoscopic repair, 80% expressed preference for endoscopic hernioplasty in the event of future recurrence.

CONCLUSIONSEndoscopic extraperitoneal inguinal hernioplasty can be safely performed utilizing reusable trocars. Substantial reduction of operative cost could be achieved by the elimination of disposable instruments. Deficiencies of the reusable metallic trocar, namely peri-cannula air-leak and sliding movements of the trocar, can be overcome by purse-string suture of the fascial opening.

Cost Control ; Endoscopy ; Female ; Follow-Up Studies ; Health Care Costs ; Hernia, Inguinal ; surgery ; Humans ; Male ; Postoperative Complications ; etiology ; Surgical Instruments

Chronic hepatitis B infection is a major public health challenge. With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for ≥6 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.

Drainage of pseudocyst and walled-off pancreatic necrosis has traditionally been achieved by surgical means. Recently, there has been a progressive shift in paradigm to performing endoscopic drainage for these conditions. Endoscopic ultrasound (EUS)-guided drainage is the preferred approach for drainage of pancreatic pseudocyst. However, many controversies still exist on the optimal management and wide variations in techniques exist. There is a pressing need for establishment of a consensus for safe practices in EUS-guided pseudocyst drainage.
Asian Continental Ancestry Group* ; Consensus* ; Drainage* ; Humans ; Necrosis ; Pancreatic Pseudocyst* ; Ultrasonography

Background/Aims: Studies of hepatic steatosis (HS) effect on COVID-19 vaccine immunogenicity are lacking. We aimed to compare immunogenicity of BNT162b2 and CoronaVac among moderate/severe HS and control subjects. Methods: Two hundred ninety-five subjects who received BNT162b2 or CoronaVac vaccines from five vaccination centers were categorized into moderate/severe HS (controlled attenuation parameter ≥268 dB/m on transient elastography) (n=74) or control (n=221) groups. Primary outcomes were seroconversion rates of neutralising antibody by live virus Microneutralization (vMN) assay (titer ≥10) at day21 (BNT162b2) or day28 (CoronaVac) and day56 (both). Secondary outcome was highest-tier titer response (top 25% of vMN titer; cutoff: 160 [BNT162b2] and 20 [CoronaVac]) at day 56. Results: For BNT162b2 (n=228, 77.3%), there was no statistical differences in seroconversion rates (day21: 71.7% vs. 76.6%; day56: 100% vs. 100%) or vMN geometric mean titer (GMT) (day21: 13.2 vs. 13.3; day56: 91.9 vs. 101.4) among moderate/severe HS and control groups respectively. However, lower proportion of moderate/severe HS patients had highest-tier response (day56: 5.0% vs. 15.5%; P=0.037). For CoronaVac (n=67, 22.7%), there was no statistical differences in seroconversion rates (day21: 7.1% vs. 15.1%; day56: 64.3% vs. 83.0%) or vMN GMT (5.3 vs. 5.8,) at day28. However, moderate/severe HS patients had lower vMN GMT (9.1 vs. 14.8, P=0.021) at day 56 with lower proportion having highest-tier response (21.4% vs. 52.8%, P=0.036). Conclusions While there was no difference in seroconversion rate between moderate/severe HS and control groups after two doses of vaccine, a lower proportion of moderate/severe HS patients achieved highest-tier response for either BNT162b2 or CoronaVac.

Background: In non-alcoholic fatty liver disease (NAFLD), transient elastography (TE) is an accurate non-invasive method to identify patients at risk of advanced fibrosis (AF). We developed a diabetes-specific, non-invasive liver fibrosis score based on TE to facilitate AF risk stratification, especially for use in diabetes clinics where TE is not readily available. Methods: Seven hundred sixty-six adults with type 2 diabetes and NAFLD were recruited and randomly divided into a training set (n=534) for the development of diabetes fibrosis score (DFS), and a testing set (n=232) for internal validation. DFS identified patients with AF on TE, defined as liver stiffness (LS) ≥9.6 kPa, based on a clinical model comprising significant determinants of LS with the lowest Akaike information criteria. The performance of DFS was compared with conventional liver fibrosis scores (NFS, FIB-4, and APRI), using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values (NPV). Results: DFS comprised body mass index, platelet, aspartate aminotransferase, high-density lipoprotein cholesterol, and albuminuria, five routine measurements in standard diabetes care. Derived low and high DFS cut-offs were 0.1 and 0.3, with 90% sensitivity and 90% specificity, respectively. Both cut-offs provided better NPVs of >90% than conventional fibrosis scores. The AUROC of DFS for AF on TE was also higher (P<0.01) than the conventional fibrosis scores, being 0.85 and 0.81 in the training and testing sets, respectively. Conclusion Compared to conventional fibrosis scores, DFS, with a high NPV, more accurately identified diabetes patients at-risk of AF, who need further evaluation by hepatologists.

Hepatocellular carcinoma (HCC) is a major public health burden in Hong Kong, and chronic hepatitis B is the most common HCC etiology in our region. With the high case load, extensive local expertise on HCC has been accumulated. This article summarized local guidelines and real-life practice on HCC management in Hong Kong. For HCC surveillance, liver ultrasound and serum alpha-fetoprotein for periodic screening is recommended in viral hepatitis or cirrhotic patients, and this is adhered to in clinical practice. HCC diagnosis is not covered in local guidelines, yet our practice is in-line with regional guidelines, where diagnosis is usually achieved by cross-sectional imaging and without the need for histology. Our guidelines recommend using the Hong Kong Liver Cancer Staging for pre-treatment staging, yet we routinely use other widely-adopted systems such as the Barcelona Clinic Liver Cancer Staging and the Tumor-Node-Metastasis Staging as well. Our local guidelines have provided clear treatment algorithms for the whole range of HCC therapies, including resection, ablation, transplant, transarterial chemoembolization, transarterial radioembolization, stereotactic body radiation therapy, targeted therapy, and immunotherapy. Real-life treatment choices are largely in line with the guidelines, although treatment protocols are individualized, and availability of specific therapies can vary between centers. Overall, HCC guidelines in Hong Kong are tailored based on local expertise and our unique patient population. The guidelines are up-to-date and provide practical pathways to assist our routine practice. Regular updates of local guidelines are warranted to account for the rapidly evolving paradigm of HCC management.

Adolescent ; Death, Sudden, Cardiac ; etiology ; Female ; Humans ; Ion Channels ; physiology ; Mutation ; Ryanodine Receptor Calcium Release Channel ; genetics ; Syncope ; etiology ; Tachycardia, Ventricular ; genetics