Guilin Yang

Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome

Abstract Background. Severe acute respiratory syndrome (SARS) is a novel infectious disease. No information is currently available on host-specific immunity against the SARS coronavirus (CoV), and detailed characteristics of the epidemiology of SARS CoV infection have not been identified. Methods. ELISA was used to detect antibody to SARS CoV. Reverse-transcriptase polymerase chain reaction was used to detect SARS CoV RNA. T cells in peripheral blood of patients were quantified by flow cytometry. Results. Of 36 patients with probable SARS CoV infection, 30 (83.3%) were positive for IgG antibody to SARS CoV; in contrast, only 3 of 48 patients with suspected SARS CoV infection, 0 of 112 patients with fever but without SARS, and 0 of 96 healthy control individuals were positive for it. IgG antibody to SARS CoV was first detected between day 5 and day 47 after onset of illness (mean ± SD, 18.7±10.4). Conclusion. Detection of antibody to SARS CoV is useful in the diagnosis of SARS; however, at the incubation and initial phases of the illness, serological assay is of little value, because of late seroconversion in most patients.

Optimal linear combination of ARFI, transient elastography and APRI for the assessment of fibrosis in chronic hepatitis B

Accurate assessment of liver fibrosis in patients with chronic hepatitis B (CHB) is necessary not only to predict the long‐term clinical course but also to determine an appropriate antiviral therapy scheme. Several noninvasive approaches – serum markers and elastography – have been proposed as alternatives for the histopathological analysis of liver biopsies. The aim of this study was to evaluate two ultrasound elastography methods (ARFI and TE) and one biochemical test (APRI), as well as their optimal linear combination, in the assessment of liver fibrosis in CHB.

Elevated IL-6 Receptor Expression on CD4+ T Cells contributes to the increased Th17 Responses in patients with Chronic Hepatitis B

BackgroundIncreased numbers of Interleukin-17-producing CD4+ T cells (Th17) have been found in association with hepatitis B virus (HBV)-induced liver injury. However, the mechanism underlying the increase of Th17 responses in patients with HBV infection remains unclear. In this study, we investigate the possible regulatory mechanisms of increased Th17 responses in patients with chronic hepatitis B(CHB).MethodsTh17 response and IL-6R expression on CD4+ T cells in peripheral blood samples were determined by flow cytometry. Cytokines TGF-β, IL-1β, IL-6 and IL-17 in plasma and/or supernatant samples were determined by ELISA and the IL-17 and IL-6R mRNA levels were quantified by quantitative real-time reverse polymerase chain reaction.ResultsAll these data indicated that the frequency of periphery Th17 cells is significantly correlated with the percentage of CD4+ T cells expressing IL-6R in CHB patients. CD4+ T cells from patients with CHB, but not those from healthy donors, produced higher levels of IL-17 and had more IL-6R expression upon stimulation with the HBV core antigen (HBcAg) in vitro. The PMA/ionomycin and HBcAg -stimulated up-regulation of IL-17 production by CD4+ T cells could be reversed by a neutralizing antibody against IL-6R.Conclusionwe showed that enhancement of IL-6R expression on CD4+ T cells upon HBV infection contributes to increased Th17 response in patients with CHB.

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

AIM To investigate the combined diagnostic accuracy of acoustic radiation force impulse (ARFI), aspartate aminotransferase to platelet ratio index (APRI) and Forns index for a non-invasive assessment of liver fibrosis in patients with chronic hepatitis B (CHB). METHODS In this prospective study, 206 patients had CHB with liver fibrosis stages F0-F4 classified by METAVIR and 40 were healthy volunteers were measured by ARFI, APRI and Forns index separately or combined as indicated. RESULTS ARFI, APRI or Forns index demonstrated a significant correlation with the histological stage (all P < 0.001). According to the AUROC of ARFI and APRI for evaluating fibrotic stages more than F2, ARFI showed an enhanced diagnostic accuracy than APRI (P < 0.05). The combined measurement of ARFI and APRI exhibited better accuracy than ARFI alone when evaluating ≥ F2 fibrotic stage (Z = 2.77, P = 0.006). Combination of ARFI, APRI and Forns index did not obviously improve the diagnostic accuracy compared to the combination of ARFI and APRI (Z = 0.958, P = 0.338). CONCLUSION ARFI + APRI showed enhanced diagnostic accuracy than ARFI or APRI alone for significant liver fibrosis and ARFI + APRI + Forns index shows the same effect with ARFI + APRI.

Assessment of liver fibrosis in chronic hepatitis B via multimodal data

Abstract Assessing liver fibrosis with chronic hepatitis B (CHB) in patients is quite important. Some non-invasive approaches for evaluating liver fibrosis include blood tests and ultrasound elastography. How to effectively combine multiple methods to improve the diagnostic performance remains a challenging problem. The main goal of this paper is to assess and stage liver fibrosis in CHB using feature selection and machine learning methods based on multimodal data. Popular machine learning approaches (e.g., support vector machine (SVM)) and feature selection (FS) were explored to stage the CHB. 16 volunteers and 92 patients with CHB were investigated for liver fibrosis staging based on transient elastography (TE) and acoustical radiation force impulse imaging (ARFI) data. The accuracy of the staging result using FS and a SVM classifier was an accuracy of 90.68% for significant fibrosis (≥F2) and an accuracy of 93.52% for cirrhosis (F4), respectively. The proposed method also increased the sensitivity, specificity, and area under curve (AUC) values for both significant fibrosis and cirrhosis diagnosis, which is very promising for staging liver fibrosis from multimodal information. It outperforms any single method and their linear combination and also achieves a state-of-the-art performance.

The Relationship between Intrahepatic Distribution of Hepatitis B Virus Core Antigen and Serum ALT, HBV DNA Levels and HBeAg Status

Abstract Objective The clinical significance of differential distribution of hepatitis B virus (HBV) nucleocapsid antigen in hepatocytes remains unknown. The goal of this study is to determine the relationship between distinct HBV core antigen distribution pattern and alanine transaminase (ALT), liver histological inflammatory activity grades, serum HBeAg status and HBV DNA level. Methods Total of 958 cases with chronic hepatitis B were recruited into this study. Liver function tests, serum HBV DNA level, serological HBV markers and liver immunohistochemistry were examined according to the conventional instructions. Chi Square tests were performed to analyze the differences among these groups. Results It was found that 552 (58%) cases were tested positive for HBV core antigen by immunohistochemical staining. Cytoplasmic hepatitis B core antigen (HBcAg) expression correlated with ALT level and serum HBV DNA and liver inflammatory activity scores, however, nuclear HBcAg expression in hepatocytes was associated with normal ALT level, lower liver inflammatory activity score and higher serum HBV DNA level and rate of HBeAg positivity. Both nuclear and cytoplasmic HBcAg expression in hepatocytes associated with a middle ALT level and liver inflammatory activity score, higher rate of serum detectable HBeAg and a higher HBV DNA level. However, undetectable core antigen was related to a lower ALT level and histological inflammatory activity grade, lower positive HBeAg rate and HBV DNA level. Conclusions Undetectable liver HBcAg is associated with HBV clearance, ALT normalization and hepatitis B e antigen (HBeAg) seroconversion, and cytoplasmic HBcAg expression associated with higher hepatic inflammatory activity. However, nuclear HBcAg expression correlates with immune tolerance characterized with normal ALT and lower liver inflammatory activity, higher HBV replication level and higher rate of HBeAg positivity.

Implementing targeted region capture sequencing for the clinical detection of Alagille syndrome: An efficient and cost‑effective method

Alagille syndrome (AGS) is a highly variable, autosomal dominant disease that affects multiple structures including the liver, heart, eyes, bones and face. Targeted region capture sequencing focuses on a panel of known pathogenic genes and provides a rapid, cost‑effective and accurate method for molecular diagnosis. In a Chinese family, this method was used on the proband and Sanger sequencing was applied to validate the candidate mutation. A de novo heterozygous mutation (c.3254_3255insT p.Leu1085PhefsX24) of the jagged 1 gene was identified as the potential disease‑causing gene mutation. In conclusion, the present study suggested that target region capture sequencing is an efficient, reliable and accurate approach for the clinical diagnosis of AGS. Furthermore, these results expand on the understanding of the pathogenesis of AGS.

Investigation on Factors Associated with Severe Hand, Foot and Mouth Disease

Abstract Objective To analyze the clinical and laboratory features of patients with mild and severe HFMD to identify early predictive or diagnostic markers for severe cases. Methods Samples of feces, nasopharyngeal-swab specimens, peripheral blood, serum and cerebral spinal fluid were collected. Postmortem pathological examination was conducted on 2 dead patients with complication due to neurogenic pulmonary edema. Reverse transcription-polymerase chain-reaction (RT-PCR), culture and isolation of enterovirus 71 (EV71) were performed to detect EV71 infection. Both univariate and multivariate logistic analysis were used to identify factors associated with severe cases. Results EV71 was mainly responsible for HFMD. In this study, 5 isolated EV71 strains belonged to C4 gene subtype. Compared with mild patients, EV71-RNA detection rate was higher and CoxA16 detection rate was lower among severe patients (P < 0.01). Inflammatory cell infiltration in the lung, cardiac and liver tissues were mild by postmortem pathological examination. It was found that body temperature, vomitting, limb tremor, neutrophil, blood glucose and EV71 infection were significantly related to the severe cases by univariate logistic analysis. However, after multivariate logistic regression analysis, only vomiting (OR 16.1, CI 2.3-110.5, P < 0.01) and limb tremor (OR 117.6, CI 13.8-1004.5, P < 0.01) were significantly and independently correlated with the severe cases. Conclusions EV71 was mainly responsible for HFMD, particularly for severe cases. Vomiting and limb tremor were predictive markers for severe cases.

Reply to Tso et al

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