A critique and systematic review of the clinical utility of hepatitis B core-related antigen.

BACKGROUND & AIMS: Hepatitis B core-related antigen (HBcrAg) is a new biomarker for chronic hepatitis B (CHB) whose performance has not been critically or systematically appraised. Herein, we performed a systematic review to determine its clinical utility. METHODS: We evaluated the biological pathway of HBcrAg and performed a systematic review of PubMed for clinical trials, cohort studies, and case-control studies that evaluated the clinical utility of HBcrAg. The effectiveness of HBcrAg in predicting HBV-specific clinical events (e.g. HBeAg seroconversion, phases of CHB, HBsAg loss, treatment response, and relapse after stopping therapy) was examined using receiver-operating characteristic curves. The correlation coefficients of HBcrAg with HBV DNA, quantitative HBsAg (qHBsAg), HBV RNA, and cccDNA were summarised from published studies. Median values were used as estimates. RESULTS: HBcrAg consists of three precore/core protein products: HBcAg, HBeAg, and a 22 kDa precore protein. HBcrAg assays have been associated with false-positive rates of 9.3% and false-negative rates of between 12-35% for CHB. The new iTACT-HBcrAg is more sensitive but does not reduce the false-positive rate. A PubMed search found 248 papers on HBcrAg, of which 59 were suitable for analysis. The clinical performance of HBcrAg was evaluated using AUROC analyses, with median AUROCs of 0.860 for HBeAg seroconversion, 0.867 for predicting HBeAg(-) hepatitis, 0.645 for HBsAg loss, 0.757 for treatment response, and 0.688 for relapse after stopping therapy. The median correlation coefficient (r) was 0.630 with HBV DNA, 0.414 with qHBsAg, 0.619 with HBV RNA and 0.550 with cccDNA. Correlation decreased during antiviral therapy, but combined biomarkers improved performance. CONCLUSIONS: HBcrAg has a mixed performance and has a poor correlation with HBsAg loss and antiviral therapy, hence HBcrAg results should be interpreted with caution. IMPACT AND IMPLICATIONS: Hepatitis B core-related antigen (HBcrAg) has been used to assess management of patients with chronic hepatitis B (CHB) without a systematic and critical Sreview of its performance. Our finding that HBcrAg had a false-positive rate of 9% and a false-negative rate of 12-35% raises concerns, although larger studies are needed for validation. A systematic review showed that the performance of HBcrAg was variable depending on the CHB endpoint; it was excellent at predicting HBeAg seroconversion and HBeAg-negative chronic hepatitis (vs. chronic infection), which should be its main use, but it was poor for relapse after stopping antiviral therapy and for HBsAg loss. HBcrAg results should be interpreted with considerable caution, particularly by physicians, researchers, guideline committees and agencies that approve diagnostic tests.

Controversies in Treating Chronic Hepatitis B virus: The Role of Hepatitis B Virus DNA and Surface Antigen Titer.

Controversial areas in chronic hepatitis B (CHB) are those where there is uncertainty, or differences of opinion in management, or where evidence may be insufficient. Areas of controversy include whether patients with high viral load but normal liver function tests should be treated to prevent hepatocellular carcinoma (HCC) or liver disease progression to cirrhosis. Another area is whether quantitative hepatitis B surface antigen (qHBsAg) can be used to better characterize phases of CHB and prognosticate. Finally, the utility of qHBsAg in the management of patients on antiviral therapy such as interferon and nucleoside analogues could improve management practices.

An Epidemiological Meta-Analysis on the Worldwide Prevalence, Resistance, and Outcomes of Spontaneous Bacterial Peritonitis in Cirrhosis.

Background and Aims: Spontaneous bacterial peritonitis (SBP) is a common and potentially fatal complication of liver cirrhosis. This study aims to analyze the prevalence of SBP among liver cirrhotic patients according to geographical location and income level, and risk factors and outcomes of SBP. Methods: A systematic search for articles describing prevalence, risk factors and outcomes of SBP was conducted. A single-arm meta-analysis was performed using generalized linear mix model (GLMM) with Clopper-Pearson intervals. Results: Ninety-Nine articles, comprising a total of 5,861,142 individuals with cirrhosis were included. Pooled prevalence of SBP was found to be 17.12% globally (CI: 13.63-21.30%), highest in Africa (68.20%; CI: 12.17-97.08%), and lowest in North America (10.81%; CI: 5.32-20.73%). Prevalence of community-acquired SBP was 6.05% (CI: 4.32-8.40%), and 11.11% (CI: 5.84-20.11%,) for healthcare-associated SBP. Antibiotic-resistant microorganisms were found in 11.77% (CI: 7.63-17.73%) of SBP patients. Of which, methicillin-resistant Staphylococcus aureus was most common (6.23%; CI: 3.83-9.97%), followed by extended-spectrum beta-lactamase producing organisms (6.19%; CI: 3.32-11.26%), and lastly vancomycin-resistant enterococci (1.91%; CI: 0.41-8.46%). Subgroup analysis comparing prevalence, antibiotic resistance, and outcomes between income groups was conducted to explore a link between socioeconomic status and SBP, which revealed decreased risk of SBP and negative outcomes in high-income countries. Conclusion: SBP remains a frequent complication of liver cirrhosis worldwide. The drawn link between income level and SBP in liver cirrhosis may enable further insight on actions necessary to tackle the disease on a global scale.

Factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic: a cross-sectional study in 12 Asian countries.

INTRODUCTION: Regardless of having effective vaccines against COVID-19, containment measures such as enhanced physical distancing and good practice of personal hygiene remain the mainstay of controlling the COVID-19 pandemic. Countries across Asia have imposed these containment measures to varying extents. However, residents in different countries would have a differing degree of compliance to these containment measures potentially due to differences in the level of awareness and motivation in the early phase of pandemic. OBJECTIVES: In our study, we aimed to describe and correlate the level of knowledge and attitude with the level of compliance with personal hygiene and physical distancing practices among Asian countries in the early phase of pandemic. METHODS: A multinational cross-sectional study was carried out using electronic surveys between May and June 2020 across 14 geographical areas. Subjects aged 21 years and above were invited to participate through social media, word of mouth and electronic mail. RESULTS: Among the 2574 responses obtained, 762 (29.6%) participants were from East Asia and 1812 (70.4%) were from Southeast Asia (SEA). A greater proportion of participants from SEA will practise physical distancing as long as it takes (72.8% vs 60.6%). Having safe distancing practices such as standing more than 1 or 2 m apart (AdjOR 5.09 95% CI (1.08 to 24.01)) or more than 3 or 4 m apart (AdjOR 7.05 95% CI (1.32 to 37.67)), wearing a mask when they had influenza-like symptoms before the COVID-19 pandemic, preferring online news channels such as online news websites/applications (AdjOR 1.73 95% CI (1.21 to 2.49)) and social media (AdjOR 1.68 95% CI (1.13 to 2.50) as sources of obtaining information about COVID-19 and high psychological well-being (AdjOR 1.39 95% CI (1.04 to 1.87)) were independent factors associated with high compliance. CONCLUSIONS: We found factors associated with high compliance behaviour against COVID-19 in the early phase of pandemic and it will be useful to consider them in risk assessment, communication and pandemic preparedness.

Multinational survey on the preferred approach to management of Barrett's esophagus in the Asia-Pacific region.

BACKGROUND: Major societies provide differing guidance on management of Barrett's esophagus (BE), making standardization challenging. AIM: To evaluate the preferred diagnosis and management practices of BE among Asian endoscopists. METHODS: Endoscopists from across Asia were invited to participate in an online questionnaire comprising eleven questions regarding diagnosis, surveillance and management of BE. RESULTS: Five hundred sixty-nine of 1016 (56.0%) respondents completed the survey, with most respondents from Japan (n = 310, 54.5%) and China (n = 129, 22.7%). Overall, the preferred endoscopic landmark of the esophagogastric junction was squamo-columnar junction (42.0%). Distal palisade vessels was preferred in Japan (59.0% vs 10.0%, P < 0.001) while outside Japan, squamo-columnar junction was preferred (59.5% vs 27.4%, P < 0.001). Only 16.3% of respondents used Prague C and M criteria all the time. It was never used by 46.1% of Japanese, whereas 84.2% outside Japan, endoscopists used it to varying extents (P < 0.001). Most Asian endoscopists (70.8%) would survey long-segment BE without dysplasia every two years. Adherence to Seattle protocol was poor with only 6.3% always performing it. 73.2% of Japanese never did it, compared to 19.3% outside Japan (P < 0.001). The most preferred (74.0%) treatment of non-dysplastic BE was proton pump inhibitor only when the patient was symptomatic or had esophagitis. For BE with low-grade dysplasia, 6-monthly surveillance was preferred in 61.9% within Japan vs 47.9% outside Japan (P < 0.001). CONCLUSION: Diagnosis and management of BE varied within Asia, with stark contrast between Japan and outside Japan. Most Asian endoscopists chose squamo-columnar junction to be the landmark for esophagogastric junction, which is incorrect. Most also did not consistently use Prague criteria, and Seattle protocol. Lack of standardization, education and research are possible reasons.

Novel albumin, bilirubin and platelet criteria for the exclusion of high-risk varices in compensated advanced chronic liver disease: A validation study.

BACKGROUND AND AIMS: Availability of transient elastography (TE) limits the application of Baveno-VI criteria. In a derivation study, the ABP criteria (Albumin >40 g/l, Bilirubin <22 µmol/l and Platelet >114,000/µl) had been shown to perform well in identifying compensated advanced chronic liver disease (cACLD) patients without high-risk varices (HRV). We aim to externally validate this novel ABP criteria for the exclusion of HRVs among cACLD patients. METHODS: Data was retrospectively collected from consecutive cACLD patients with paired TE and esophagogastroduodenoscopy (EGD) performed between 2011 and 2017 in Changi General Hospital, Singapore. We estimate the discriminative ability of ABP criteria in validation cohort using AUROC and calibration-in-the-large. We subsequently compare the performance between ABP and Baveno-VI criteria in the validation cohort. RESULTS: Among 314 patients included in our validation cohort, 32 (10.2%) had HRV on screening EGD. Application of ABP criteria within this validation cohort has increased discriminative ability than the derivation cohort. The AUROC of validation and derivation cohort were 0.68 (0.60-0.76) and 0.66 (0.60-0.76), respectively. The mean and standard error for calibration-in-the-large and calibration slope were -0.08 (0.22) and 0.93 (0.26) respectively. The ABP criteria had excellent performance in excluding HRV and will spare more screening EGDs than the Baveno-VI criteria (39.2% vs 27.4%, p < 0.001), without missing more HRVs. CONCLUSION: We validated the performance of ABP criteria for the exclusion of HRVs in cACLD patients. ABP criteria is superior to Baveno-VI criteria by sparing more screening EGD without the need of TE.

Impact of the coronavirus disease 2019 pandemic on irritable bowel syndrome.

BACKGROUND AND AIM: Gastrointestinal manifestations of the coronavirus disease 2019 (COVID-19) pandemic may mimic irritable bowel syndrome (IBS), and social distancing measures may affect IBS patients negatively. We aimed to study the impact of COVID-19 on respondents with self-reported IBS. METHODS: We conducted an anonymized survey from May to June 2020 in 33 countries. Knowledge, attitudes, and practices on personal hygiene and social distancing as well as psychological impact of COVID-19 were assessed. Statistical analysis was performed to determine differences in well-being and compliance to social distancing measures between respondents with and without self-reported IBS. Factors associated with improvement or worsening of IBS symptoms were evaluated. RESULTS: Out of 2704 respondents, 2024 (74.9%) did not have IBS, 305 (11.3%) had self-reported IBS, and 374 (13.8%) did not know what IBS was. Self-reported IBS respondents reported significantly worse emotional, social, and psychological well-being compared with non-IBS respondents and were less compliant to social distancing measures (28.2% vs 35.3%, P = 0.029); 61.6% reported no change, 26.6% reported improvement, and 11.8% reported worsening IBS symptoms. Higher proportion of respondents with no change in IBS symptoms were willing to practice social distancing indefinitely versus those who deteriorated (74.9% vs 51.4%, P = 0.016). In multivariate analysis, willingness to continue social distancing for another 2-3 weeks (vs longer period) was significantly associated with higher odds of worsening IBS. CONCLUSION: Our study showed that self-reported IBS respondents had worse well-being and compliance to social distancing measures than non-IBS respondents. Future research will focus on occupational stress and dietary changes during COVID-19 that may influence IBS.

Identifying Patients With Cirrhosis Who Might Avoid Screening Endoscopy Based on Serum Albumin and Bilirubin and Platelet Counts.

The presence of gastroesophageal varices is a major complication of portal hypertension associated with significant morbidity and mortality.1 The Baveno VI criteria state that patients with liver stiffness measurement (LSM) <20 kPa by transient elastography (TE) and platelet count >150,000/µL can avoid screening endoscopy for high-risk varix (HRV).2 However, because TE is not widely available, the Baveno VI criteria could not be applied in many clinical settings. As such, we aim to determine a concise clinical criterion as an alternative noninvasive tool to predict absence of HRV among patients with compensated cirrhosis to avoid screening esophagogastroduodenoscopy (EGD).

Strategies to Improve Persistent Adherence in Colorectal Cancer Screening.

Colorectal cancer is a major cause of morbidity and mortality, and screening has been shown to reduce morbidity and mortality. This review highlights pertinent aspects of adherence to screening including the various options available and key concepts to consider in any systematic program. Persistent adherence, which is key to an efficacious screening program, is the compliance with repeated screening tests over a period of time. A "chain of survival" mindset emphasizes the stepwise, sequential and persistent approach to screening and is a helpful concept to drive the message of persistent adherence. A framework for the patient and physician interactions that support screening intervention is examined, and various factors that impact both patient and physician adoption and screening modality recommendations are reviewed. While systems-based approaches to screening have great utility in automation and monitoring in a surveillance program, some emerging data suggests that the human touch is still an essential driver for active participation in these programs. Finally, the proportion of time concept is discussed as a useful index for monitoring persistent adherence in both individuals and populations.

Poor adherence to anticoagulation guidelines in patients with non-valvular atrial fibrillation treated in a tertiary cardiology unit.

INTRODUCTION: Atrial fibrillation (AF) is a well-known cause of strokes and all major society guidelines recommend oral anticoagulants (OAC) such as vitamin K antagonists (VKA) for patients with concomitant risk factors to prevent them. However, compliance with these guidelines is historically poor. This study aims to evaluate the adherence to CHADS2 (congestive heart failure, hypertension,age ≥75 years, diabetes mellitus and prior stroke or transient ischaemic attack) guidelines, explore reasons and evaluate outcomes for non-adherence in a tertiary cardiology unit. MATERIALS AND METHODS: A retrospective study of patients admitted into a tertiary cardiology unit from January to March 2010. RESULTS: Of 1826 unique cardiac patients screened, 163 (8.9%) of them had non-valvular AF or atrial flutter. Their mean age was 69.8 years and 58.9% were men. Of the 54 patients on warfarin with documented international normalised ratio (INR), only 22 (40.7%) of them had an INR within the therapeutic range (INR less than two in 22 (40.7%) and greater than three in 10 (18.5%)). Of the 119 patients with CHADS2 greater than or equal to two, only 46 (38.7%) were discharged with warfarin. Among the remaining 73 (61.3%) patients, the most common reasons for not prescribing warfarin include history of bleeding (n=24, 32.9%), no reason documented (n=17, 23.3%) and patient preference (n=12, 19.2%). On follow-up, patients on warfarin were found to have better survival outcomes (mean 1522±41 days) as compared with (mean 1255±63 days) in patients not on OAC (p value=0.001). CONCLUSIONS: Few patients who require anticoagulation receive it in accordance with the guidelines even in a tertiary cardiology unit. There are many impediments to the effective use of VKA for stroke prevention among patients with AF.