Abstract Background and Aim Plasma‐exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. Methods Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. Results ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS‐matched cohort (n = 208, [ALS‐119; PE‐94, FPSA‐25)], SMT‐89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42‐24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5‐11.1), and lower liver‐failure‐related deaths as compared to FPSA and SMT ( P < .05). PE cleared inflammatory cytokines, damage‐associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti‐inflammatory cytokine interleukin‐1 receptor antagonist (IL‐1RA) compared to non‐responders. PE was associated with lesser adverse effects as compared to FPSA. Conclusions PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma‐exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.
Summary Background Chronic hepatitis B patients ( CHB ) treated with adefovir were followed up to evaluate nephrotoxicity and its outcome. Aim To assess the incidence of renal dysfunction during adefovir therapy in Asian patients and factors associated with it, and evaluate strategies to improve adefovir‐related renal dysfunction and their impact on viral suppression. Methods Chronic hepatitis B clinic patients from a tertiary hospital on adefovir treatment, with their clinical and laboratory parameters were extracted from the hospital electronic clinical database in an observational study design. Patients were excluded if they had liver/renal transplant, baseline renal impairment or were on dialysis. Adefovir‐related renal dysfunction was defined as adefovir‐related abnormal serum creatinine (ARASC) > 125 μmol/L (males), >90 μmol/L (females); adefovir‐related abnormal GFR <60 mL/min; and adefovir‐related increased serum creatinine >0.5 mg/dL, without other known causes of nephrotoxicity. Results A total of 271/383 adefovir‐treated patients were suitable for analysis and 33(12%) patients developed abnormal serum creatinine. Cumulative increase in proportion of patients with ARASC was 33.8% and GFR ≤60 mL/min was 38.3% by 6 years, while serum creatinine increase ≥0.5 mg/dL was 21.48% by 5 years. Using multivariate analysis, the only independent baseline predictor of ARASC was GFR ≤76.1 mL/min. Patients who had ARASC had similar levels of viral suppression to those who did not have ARASC. Those who had ARASC either continued adefovir (24%), switched therapy (24%) or had adefovir dose reduction (52%). ARASC resolved and GFR normalised in almost all patients after either switching therapy or reducing adefovir dose, with no difference between the two strategies ( P = 0.737). Those with adefovir dose reduction had no significant increase in HBV DNA ( P = 0.170). Conclusions Adefovir‐related renal dysfunction occurred in a significant number of adefovir‐treated patients, but reduction of the dose led to renal improvement without compromising treatment efficacy.
Antiviral treatment is recommended to reduce the vertical transmission in women with high viral load for mother-to child-transmission (MTCT). However, most women decline treatment.
Objectives
We aimed to determine the knowledge and awareness of maternal chronic hepatitis B carriers to antiviral use.
Methods
A cross sectional study was carried out in a tertiary hospital in National University Hospital of Singapore. Maternal hepatitis B carriers with children less than 5 years old were surveyed on attitudes and knowledge on hepatitis B virus as well as what their reasons were for taking/not taking antivirals.
Results
Fifty-seven were surveyed; 50.9% had a degree, 64.9% worked full time, 47.4% had 1 child or more. Most were risk averse. Many, 78.9% were not aware of the role of antivirals to reduce MTCT. Only 21.1% knew the risk of vertical transmission with/without antiviral. Reasons for not taking antivirals were attributed to a lack of knowledge. Many, 87.7% are willing to take antiviral therapy during their pregnancy to reduce MTCT from 10% to 1% and 45.6% willing to pay at least S$2 to S$2.90 daily over 12 weeks for it.
Conclusions
It is the practitioner’s role to update and improve the quality of education programmes that target women of childbearing age about the benefits of antiviral use to reduce MTCT in mothers with high hepatitis B viral load. Additionally, from a health system perspective, providing subsidies for antiviral treatment to ease the financial concerns of parents, is likely to reduce long-term expenses generated by chronic hepatitis B virus complications, thus being more cost-effective.
Decompensation with ascites portends a poor prognosis in cirrhosis. The aim of this study was to compare the outcomes of patients with nonalcoholic steatohepatitis (NASH) with hepatitis B virus (HBV) cirrhosis after decompensation with ascites.We conducted a retrospective study to evaluate the outcomes of patients with NASH and HBV cirrhosis who were admitted to hospital for first-onset ascites from January 1, 2004, to June 30, 2015. They were followed up until death, liver transplantation, or loss to follow up.Patients with NASH had lower median (interquartile range) Model for End-Stage Liver Disease score (11 [9-14] vs 14 [11-17], P < 0.001). Over 60 months, patients with NASH cirrhosis had higher cumulative incidence of dilutional hyponatremia (P < 0.001) and refractory ascites (P = 0.028). They also had higher cumulative incidence of cirrhosis-related deaths and liver transplantation compared with HBV cirrhosis (65.7%; [95% confidence interval (CI) 53.6-75.4] vs 42.5% [95% CI 32.4-55.2], P = 0.008). Multivariable competing risk analysis showed that NASH (subdistribution hazard ratio [sHR] 1.88 [95% CI 1.14-3.11], P = 0.014), non-Chinese ethnicity (sHR 1.63 [95% CI 1.06-2.50], P = 0.027), history of hepatocellular carcinoma (sHR 1.76 [95% CI 1.05-2.95], P = 0.033), estimated glomerular filtration rate <60 mL/min/1.73 m2 (sHR 1.70 [95% CI 1.09-2.65], P = 0.020), and Model for End-Stage Liver Disease score ≥15 (sHR 3.26 [95% CI 2.11-5.05], P < 0.001) were independent predictors of poor transplant-free survival.Patients with decompensated cirrhosis due to NASH had much poorer prognosis compared with HBV with more complications and greater healthcare resource utilization. Greater awareness is necessary for early diagnosis of NASH before decompensation.
INTRODUCTION: Acute-on-chronic liver failure (ACLF) is a clinical syndrome associated with high short-term mortality. Numerous models have been proposed to predict outcomes in ACLF patients, including novel ones by Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC), but their utility in a heterogeneous population of ACLF patients remains inconclusive. The study aims to assess the performance of established and newer models for predicting mortality of ACLF patients. METHODS: A retrospective study of 96 patients fulfilling either APASL or European Association for the Study of the Liver (EASL) criteria for ACLF admitted to a tertiary hospital in Singapore between 2004 and 2018 was performed. Child-Turcotte-Pugh (CTP) score, Model for End-Stage Liver Disease (MELD)-Na, Chronic Liver Failure Consortium (CLIF)-SOFA, CLIF-C ACLF and AARC prognostic scores (MELD-lactate, AARC-ACLF) were calculated on days 1, 4, 7 of hospital admission and days 1, 4 of ICU admission. Outcomes assessed were survival to discharge without transplant, 30-day survival and 90-day survival. The scores were evaluated by measuring area under receiver operating characteristic (AUROC) curve at each time point and compared. RESULTS: 28 patients (29.2%) survived to discharge without transplant, 21 patients (21.9%) underwent urgent transplant and 47 patients (49%) died before discharge. 30-day transplant-free survival was 21.9% and 90-day survival was 19.8%. CTP, MELD-Na, MELD-lactate, CLIF-C ACLF and AARC-ACLF scores had high accuracy in predicting hospital mortality on day 4 admission (CTP D1 AUROC 0.642, D4 0.715; MELD-Na D1 0.607, D4 0.721; MELD-lactate D1 0.664, D4 0.861; CLIF-C ACLF D1 0.559, D4 0.697; AARC-ACLF D1 0.571, D4 0.747). CTP, MELD-Na and MELD-lactate scores also had good predictive utility on day 7 admission (CTP D7 0.684; MELD-Na 0.67; MELD-lactate 0.848). This held true regardless of whether APASL or EASL criteria was applied. In addition, the sequential change in CLIF-SOFA and CLIF-C ACLF scores from day 1 to day 4 was significantly associated with need for urgent transplant or death before discharge. CONCLUSION: CTP, MELD-Na and MELD-lactate scores are superior at prognosticating outcomes on day 4 and 7 of admission in our multi-ethnic Asian population. The trend of CLIF-SOFA and CLIF-C ACLF scores from day 1 to day 4 of admission may also contribute valuable information to our assessment of ACLF patients.
Objective To investigate the incidence of gastric cancer (GC) attributed to gastric intestinal metaplasia (IM), and validate the Operative Link on Gastric Intestinal Metaplasia (OLGIM) for targeted endoscopic surveillance in regions with low-intermediate incidence of GC. Methods A prospective, longitudinal and multicentre study was carried out in Singapore. The study participants comprised 2980 patients undergoing screening gastroscopy with standardised gastric mucosal sampling, from January 2004 and December 2010, with scheduled surveillance endoscopies at year 3 and 5. Participants were also matched against the National Registry of Diseases Office for missed diagnoses of early gastric neoplasia (EGN). Results There were 21 participants diagnosed with EGN. IM was a significant risk factor for EGN (adjusted-HR 5.36; 95% CI 1.51 to 19.0; p<0.01). The age-adjusted EGN incidence rates for patients with and without IM were 133.9 and 12.5 per 100 000 person-years. Participants with OLGIM stages III–IV were at greatest risk (adjusted-HR 20.7; 95% CI 5.04 to 85.6; p<0.01). More than half of the EGNs (n=4/7) attributed to baseline OLGIM III–IV developed within 2 years (range: 12.7–44.8 months). Serum trefoil factor 3 distinguishes (Area Under the Receiver Operating Characteristics 0.749) patients with OLGIM III–IV if they are negative for H. pylori . Participants with OLGIM II were also at significant risk of EGN (adjusted-HR 7.34; 95% CI 1.60 to 33.7; p=0.02). A significant smoking history further increases the risk of EGN among patients with OLGIM stages II–IV. Conclusions We suggest a risk-stratified approach and recommend that high-risk patients (OLGIM III–IV) have endoscopic surveillance in 2 years, intermediate-risk patients (OLGIM II) in 5 years.
The relationship between ammonia and liver-related complications (LRCs) in acute-on-chronic liver failure (ACLF) patients is not clearly established. This study aimed to evaluate the association between ammonia levels and LRCs in patients with ACLF. The study also evaluated the ability of ammonia in predicting mortality and progression of LRCs. The study prospectively recruited ACLF patients based on the APASL definition from the ACLF Research Consortium (AARC) from 2009 to 2019. LRCs were a composite endpoint of bacterial infection, overt hepatic encephalopathy (HE), and ascites. A total of 3871 cases were screened. Of these, 701 ACLF patients were enrolled. Patients with LRCs had significantly higher ammonia levels than those without. Ammonia was significantly higher in patients with overt HE and ascites, but not in those with bacterial infection. Multivariate analysis found that ammonia was associated with LRCs. Additionally, baseline arterial ammonia was an independent predictor of 30-day mortality, but it was not associated with the development of new LRCs within 30 days. In summary, baseline arterial ammonia levels are associated with 30-day mortality and LRCs, mainly overt HE and ascites in ACLF patients.
The advent and utility of new endoscopic imaging modalities for predicting the histology of Barrett's esophagus (BE) in real time with high accuracy appear promising and could potentially obviate the need to perform random biopsies where guidelines are poorly adhered to. We embarked on evaluating the performance characteristics of white-light endoscopy with magnification (WLE-z), narrow-band imaging with magnification (NBI-z) and a combination of both modalities.This was a prospective online study with 28 endoscopists from 11 countries (Asia-Pacific region) participating as assessors. In total, 35 patients with BE were assessed using 150 slides from WLE-z and NBI-z randomly arranged using a simple classification with corresponding histology. The overall Accuracy (Acc), Sensitivity (Sn), Specificity (Sp), Positive Predictive Value (PPV), and Negative Predictive Value (NPV) of WLE-z, NBI-z and a combination of both were calculated.The overall Acc for WLE-z and NBI-z images was 87.1 % and 88.7 %, respectively. When images from the two modalities were placed side by side, the Acc increased to 90.3 %. The Sn, Sp, PPV, and NPV of WLE-z were 48 %, 92 %, 45 %, and 93 % while with NBI-z, these improved to 89 %, 89 %, 56 %, and 98 %, respectively. When both imaging modalities were viewed together, they improved further to 93 %, 90 %, 61 %, and 99 %.The high NPV (99 %) when both WLE-z and NBI-z were used simultaneously indicates that areas with regular appearance that are diagnosed with confidence can effectively be left alone and not biopsied when performed at a skilled resourced center. This approach could potentially lead to a paradigm shift of how patients with BE are assessed.
As the human cost of the pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still being witnessed worldwide, the development of broad-spectrum antiviral agents against emerging and re-emerging viruses is seen as a necessity to hamper the spread of infections. Various targets during the viral life-cycle can be considered to inhibit viral infection, from viral attachment to viral fusion or replication. Macromolecules represent a particularly attractive class of therapeutics due to their multivalency and versatility. Although several antiviral macromolecules hold great promise in clinical applications, the emergence of resistance after prolonged exposure urges the need for improved solutions. In the present article, the recent advancement in the discovery of antiviral peptides and polymers with diverse structural features and antiviral mechanisms is reviewed. Future perspectives, such as, the development of virucidal peptides/polymers and their coatings against SARS-CoV-2 infection, standardization of antiviral testing protocols, and use of artificial intelligence or machine learning as a tool to accelerate the discovery of antiviral macromolecules, are discussed.
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