Prognostic Factors for Transplant-Free Survival and Validation of Prognostic Models in Chinese Patients with Primary Biliary Cholangitis Receiving Ursodeoxycholic Acid

OBJECTIVES: We aimed to validate the prognostic models for primary biliary cholangitis (PBC) in Chinese patients receiving ursodeoxycholic acid (UCDA), and to compare their performances in predicting the long-term survival. METHODS: Chinese patients with PBC from a tertiary center were identified via electronic search of hospital medical registry. Risk factors associated with adverse events (liver transplantation or death from liver-related causes including hepatocellular carcinoma (HCC) and liver decompensation) were determined. Transplant-free survival was defined as survival free of liver-related death or transplantation. RESULTS: Of the 144 patients, 41 (28.5%) had baseline cirrhosis. The median age at diagnosis was 57.8 years. During a median follow-up of 7.0 years, 40 patients died (21 liver-related; 19 non-liver-related), 12 developed HCC, and 10 underwent transplantations. The 5-, 10-, and 15-year transplant-free survival probabilities were 91.0%, 78.1%, and 58.9%, respectively. Independent risk factors for adverse events were increasing age (hazard ratio (HR) 1.05), cirrhosis (HR 8.53), and suboptimal treatment response (HR 3.06). Aspartate aminotransferase/platelet ratio index at 1 year (APRI-r1) in combination with treatment response optimized the risk stratification. The performances of the GLOBE, UK-PBC scores, Rotterdam criteria, and APRI-r1 were comparable in predicting adverse events. The area under receiver operating curves within 5, 10, and 15 years were as follows-GLOBE score: 0.83, 0.85, and 0.85, respectively; UK-PBC score: 0.89, 0.83, and 0.79, respectively; Rotterdam criteria: 0.82, 0.76, and 0.80, respectively; APRI-r1: 0.80, 0.83, and 0.77, respectively. CONCLUSIONS: The UK-PBC, GLOBE scores, Rotterdam criteria, and APRI-r1 had good and comparable prognostic prediction values for Chinese PBC patients receiving UCDA.published_or_final_versio

Epidemiology and Natural History of Primary Biliary Cholangitis in the Chinese: A Territory-Based Study in Hong Kong between 2000 and 2015

OBJECTIVES: Studies on the epidemiology of primary biliary cholangitis (PBC) in the Chinese population are lacking. We aimed to determine the epidemiology of PBC in Hong Kong (HK) with a population of 7.3 million. METHODS: We retrieved data from the electronic database of the HK Hospital Authority, the only public healthcare provider in Hong Kong. PBC cases between 2000 and 2015 were identified by International Classification of Diseases (ICD)-9 code. We estimated the age-/sex-adjusted incidence rate and prevalence of PBC, and analyzed the adverse outcomes (hepatocellular carcinoma (HCC), liver transplantation, and death). RESULTS: One thousand and sixteen PBC patients aged >/=20 years were identified (female-to-male ratio 4:1; median age 60.6 years, interquartile range (IQR) 51.8-72.6 years; median follow-up 5.6 years, IQR 1.6-8.7 years). The average age/sex-adjusted annual incidence rate and prevalence were 8.4 per million person-years and 56.4 per million, respectively. Between 2000 and 2015, the age/sex-adjusted annual incidence rate increased from 6.7 to 8.1 per million person-years (Poisson P=0.002), while age/sex-adjusted prevalence increased from 31.1 to 82.3 per million (Poisson P<0.001). Fifty patients developed HCC, and 49 underwent liver transplantation. Case fatality risk decreased from 10.8 to 6.4% (Poisson P=0.003). The 5- and 10-year overall survival rates were 81.5 and 78.3%, whereas the transplant-free survival rates were 78.0% and 74.3%, respectively. Increasing age, cirrhosis and being treatment-naive were associated with lower transplant-free survival. CONCLUSIONS: There is a considerable increase in the incidence and prevalence of PBC in the Chinese population over the past 16 years, with significant morbidity and mortality.published_or_final_versio

Development of human single-chain antibodies against SARS-associated coronavirus.

The outbreak of severe acute respiratory syndrome (SARS), caused by a distinct coronavirus, in 2003 greatly threatened public health in China, Southeast Asia as well as North America. Over 1,000 patients died of the SARS virus, representing 10% of infected people. Like other coronaviruses, the SARS virus also utilizes a surface glycoprotein, namely the spike protein, to infect host cells. The spike protein of SARS virus consists of 1,255 amino acid residues and can be divided into two sub-domains, S1 and S2. The S1 domain mediates the binding of the virus to its receptor angiotensin-converting enzyme 2, which is abundantly distributed on the surface of human lung cells. The S2 domain mediates membrane fusion between the virus and the host cell. Hence two strategies can be used to block the infection of the SARS virus, either by interfering with the binding of the S1 domain to the receptor or by blocking the fusion of the virus with the cell membrane mediated by the S2 domain. Several antibodies against the S1 domain have been generated and all of them are able to neutralize the virus in vitro and in vivo using animal models. Unfortunately, point mutations have been identified in the S1 domain, so that the virus isolated in the future may not be recognized by these antibodies. As no mutation has been found in the S2 domain indicating that this region is more conserved than the S1 domain, it may be a better target for antibody binding. After predicting the immunogenicity of the epitopes of the S2 domain, we chemically synthesized two peptides and also expressed one of them using a recombinant DNA method. We screened a phage displaying library of human single-chain antibodies (ScFv) against the predicted epitopes and obtained a human ScFv which can recognize the SARS virus in vitro

The use of an HEPA respirator in combating SARS

published_or_final_versio

Middle East respiratory syndrome coronavirus M protein suppresses type I interferon expression through the inhibition of TBK1-dependent phosphorylation of IRF3

published_or_final_versio

High recurrence rate supports need for secondary prophylaxis in non-HIV patients with disseminated mycobacterium avium complex infection: a multi-center observational study

© 2016 Sridhar et al.Background: Long-term outcomes in non-HIV immunocompromised patients with disseminated Mycobacterium avium complex (dMAC) infections are unknown and the need for post-treatment secondary prophylaxis against MAC is uncertain in this setting. The objective of this study was to determine the need of continuing secondary anti-MAC prophylaxis in non-HIV patients after completing treatment of the primary dMAC episode. Methods: We conducted a ten-year multi-center analysis of non-HIV immunosuppressed patients with dMAC infections in Hong Kong. Results: We observed sixteen patients with dMAC during the study period of which five (31 %) were non-HIV immunosuppressed patients. In the non-HIV immunosuppressed group, three patients completed a treatment course without secondary prophylaxis, one patient received azithromycin-based secondary prophylaxis and one patient was still receiving therapy for the first dMAC episode. All the three patients who completed treatment without being given secondary prophylaxis developed recurrent dMAC infection requiring retreatment. Conclusions: In view of the high rate of dMAC infection recurrence in non-HIV immunocompromised patients following treatment completion, our data support long-term anti-MAC suppression therapy after treatment of the first dMAC infection episode in immunocompromised non-HIV patients, as is recommended for patients with advanced HIV. Tests of cell mediated immune function need to be evaluated to guide prophylaxis discontinuation in non-HIV patients.published_or_final_versio

Recalculation of 11‐year total ozone of Brewer spectrophotometer 115

Author name used in this publication: K. S. Lam2007-2008 > Academic research: refereed > Publication in refereed journalVersion of RecordPublishe

Suppression of type I and type III interferon signalling by NSs protein of severe fever-with-thrombocytopenia syndrome virus through inhibition of STAT1 phosphorylation and activation

Severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging tick-borne pathogen causing significant morbidity and mortality in Asia. NSs protein of SFTSV is known to perturb type I IFN induction and signalling, but the mechanism remains to be fully understood. Here, we showed the suppression of both type I and type III IFN signalling by SFTSV NSs protein is mediated through inhibition of STAT1 phosphorylation and activation. Infection with live SFTSV or expression of NSs potently suppressed IFN-stimulated genes but not NFκB activation. NSs was capable of counteracting the activity of IFN-α1, IFN-β, IFN-λ1 and IFN-λ2. Mechanistically, NSs associated with STAT1 and STAT2, mitigated IFN-β-induced phosphorylation of STAT1 at S727, and reduced the expression and activity of STAT1 protein in IFN-β-treated cells, resulting in the inhibition of STAT1 and STAT2 recruitment to IFN-stimulated promoters. Taken together, SFTSV NSs protein is an IFN antagonist that suppresses phosphorylation and activation of STAT1.postprin

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

published_or_final_versio