Comparison of five point-of-care D-dimer assays with the standard laboratory method

Introduction: D‐dimer (DD) assays are effective for the exclusion of deep‐vein thrombosis (DVT), but point‐of‐care (POC) DD assays have not been fully evaluated. Methods: We have compared five POC DD assays (Pathfast, Cardiac, Vidas, Stratus and NycoCard) with our routine DD method (Tinaquant), testing 60 samples from patients with suspected DVT. Results: Using 0.5 μg/mL as a cut‐off value, four samples tested negative with Tinaquant were positive with Pathfast. There were no Tinaquant‐positive samples tested negative with Pathfast, while the overall agreement (k = 0.81) was very good. Four samples were discrepant between Tinaquant and Cardiac (cut‐off, 0.4 μg/mL), while k = 0.72. One of two Tinaquant‐negative samples was shown to be positive for either Vidas (cut‐off, 0.5 μg/mL) or Stratus (cut‐off, 0.4 μg/mL), respectively. The agreement with Tinaquant was excellent for both Vidas (k = 0.92) and Stratus (k = 0.94). Total CV was <10% for all four assays. Eight samples (of 27) were negative with NycoCard although they were positive with Tinaquant, while CV was 41%. Conclusion: Vidas cannot be considered a POC assay because the sample has to be centrifuged before testing. Our findings have also shown that the use of NycoCard is inappropriate. Stratus and Pathfast have a similar analytical profile in comparison with the Tinaquant method. Cardiac is potentially less sensitive but may still be acceptable for use. It seems that the employment of these three assays for rapid bed‐side analysis offers a possibility to adequately rule out DVT in outpatients within minutes after admission.     

The performance of STA-Liatest D-dimer assay in out-patients with suspected pulmonary embolism

Several studies have shown that d ‐dimer can reliably rule out pulmonary embolism (PE) in out‐patients. However, various assays have different sensitivities and specificities to detect thrombosis. Our aim was to evaluate the performance of STA‐Liatest D‐Di in out‐patients referred for suspected PE in a prospective outcome study. 495 consecutive patients referred to Østfold Hospital Trust‐Fredrikstad, Norway for suspected PE between February 2002 and December 2003, were recruited in a study evaluating a decision‐based algorithm combining clinical probability (CP), d ‐dimer, and multi‐slice computer tomography (MSCT). d ‐dimer was performed as a first step test. No further testing was carried out in patients with d ‐dimer ≤0·4 mg/l and low/intermediate CP. The remaining patients proceeded to MSCT. All patients were followed up for 3 months to assess the 3‐month thromboembolic risk. The final cohort consisted of 432 patients. PE was diagnosed in 102 (23%) patients. At a d ‐dimer cut‐off point of 0·4 mg/l the tests had the highest sensitivity (100%) and specificity (36%). It safely ruled out PE in 120 (28%) patients. Kappa‐coefficients for comparisons versus VIDAS and Asserachrom showed good concordance. STA‐Liatest is a reliable and effective assay that can safely rule out PE in out‐patients with a performance comparable with that of enzyme‐linked immunosorbent assay‐based d ‐dimer levels.     

Performance of a third‐generation TSH‐receptor antibody in a UK clinic

Background UK national guidelines recommend the measurement of TSH receptor antibodies (TRAb) in certain clinical scenarios. A commercial third‐generation TRAb autoantibody M22‐biotin ELISA assay was introduced in May 2008 in our centre. Objective To evaluate the diagnostic performance of a TRAb assay in a retrospective and subsequently a prospective cohort in a UK centre. Design A retrospective review of patients with thyroid disease followed by a prospective observational study in consecutive patients with newly found suppressed serum thyrotrophin (TSH). Patients and Measurements Medical records of 200 consecutive patients with thyroid disorders who had TRAb measured since the introduction of the assay. In a prospective study 44 patients with newly identified hyperthyroidism (TSH < 0·02 mIU/l) had sera assayed for TRAb prior to their clinic appointment at which a final diagnosis was sought. Results In the retrospective cohort, the manufacturer’s cut‐off point of TRAb ≥0·4 U/l resulted in a positive predictive value (PPV) of 95%, sensitivity 85%, specificity 94% and negative predictive value (NVP) 79% to diagnose Graves’ disease using defined criteria. Receiver operating characteristic (ROC) analysis determined an optimal cut‐off point of TRAb ≥3·5 U/l with a 100% specificity to exclude patients without Graves’ disease at the cost though of a lower sensitivity (43%). In the prospective study, the sensitivity, PPV, specificity and NPV were all 96% using the ≥0·4 U/l cut‐off. When combining hyperthyroid patients from both cohorts the assay sensitivity and specificity at ≥0·4 U/l cut‐off were 95% and 92% respectively. A positive TRAb result increased the probability of Graves’ disease for a particular patient by 25–35% and only six (2·5%) patients had a diagnosis of hyperthyroidism of uncertain aetiology after TRAb testing. Conclusions The assay studied specifically identifies patients with Graves’ disease. It is a reliable tool in the initial clinical assessment to determine the aetiology of hyperthyroidism and has the potential for cost‐savings.     

老年下肢深静脉血栓患者D-二聚体的临界值研究

目的探讨老年患者血浆D-二聚体(DD)水平预测下肢深静脉血栓(DVT)的临界值。方法选择年龄≥60岁的住院患者394例,根据是否合并DVT,分为非DVT组235例和DVT组159例,DVT组60～79岁81例和≥80岁78例。住院期间,每隔1～2周进行血浆DD检查,对DD≥0.5mg/L的患者,即行下肢静脉血管超声检查,每隔3～5d进行超声复查,且DD检测时间缩短为每隔3～5d。结果与非DVT组比较,DVT组DD水平明显升高(P<0.01)。≥80岁患者DD水平较60～79岁患者明显升高(P<0.01);2个年龄段患者DD各临界值诊断下肢DVT的敏感性、特异性、阳性预测值及阴性预测值差异较大。结论将60～79岁患者预测下肢DVT的DD临界值定为0.5mg/L,≥80岁患者DD临界值定为2.0mg/L有临床指导意义。     

Diagnostic utility of an age‐specific cut‐off for d‐dimer for pulmonary embolism assessment when used with various pulmonary embolism risk scores

This retrospective cohort study compared the diagnostic utility (sensitivity, specificity and negative predictive value (NPV)) of the age‐times‐10 adjusted d‐dimer cut‐off used in combination with the original and simplified Well's pulmonary embolism (PE) scores and the original and simplified revised Geneva scores to identify patients in whom PE is classified as unlikely according to each score. The PE risk scores performed similarly with high sensitivity (97.6, 97.1, 96.9 and 97.1% respectively) and NPV (99.3, 99.3, 99.2 and 99.2% respectively). Each missed only one PE. The age‐times‐10 age‐adjusted d‐dimer assay cut‐off performed similarly with each of the clinical risk scores tested with high sensitivity and NPV.     

临床评分和D-二聚体检查在下肢深静脉血栓中的应用

目的 评价临床Wells评分和(或)D-二聚体检查能否安全、可靠地排除或诊断下肢深静脉血栓(DVT).方法 回顾性收集两家医院疑诊DVT的住院患者,所有患者均在48 h内进行临床评价、D-二聚体检查和双侧下肢静脉加压超声检查.比较单独应用临床评分或D-二聚体检查,以及临床评分结合D-二聚体检查诊断DVT的敏感性、特异性、阳性预测值和阴性预测值.描述性资料采用频数分析,组间比较采用卡方检验,以P<0.05为差异有统计学意义.结果 共有274例患者纳入研究.以低度可能性为阴性结果,中、高度可能性为阳性结果,临床Wells评分诊断DVT的敏感性、特异性、阳性预测值和阴性预测值分别为78.4%、66.1%、52.3%和86.6%;以D-二聚体≥500μg/L为阳性结果,D-二聚体检查诊断DVT的敏感性、特异性、阳性预测值和阴性预测值分别为73.9%、66.1%、50.8%和84.2%;以低度可能性同时D-二聚体<500μg/L为阴性结果,中、高度可能性同时D-二聚体≥500μg/L为阳性结果,临床Wells评分结合D-二聚体检查诊断DVT的敏感性、特异性、阳性预测值和阴性预测值分别为88.3%、76.8%、67.1%和92.5%.结论 针对临床疑诊DVT的患者,单独应用临床Wells评分或D-二聚体检查,以诊断或排除DVT是不准确的;联合应用临床Wells评分和D-二聚体检查,才能对患者是否患有DVT作出较为准确的判断.     

Coagulation and inflammation biomarkers may help predict the severity of community‐acquired pneumonia

Background and objective: There are limited data on the relationship between the severity of community‐acquired pneumonia (CAP) and biomarkers of inflammation and coagulation. The aim of this study was to evaluate the association between the severity of CAP and serum levels of antithrombin III (AT‐III), protein C (P‐C), D‐dimers (D‐D) and CRP, at hospital admission. Methods: This was a prospective observational study in 77 adults (62.3% men), who were hospitalized for CAP. The severity of CAP was assessed using the confusion, uraemia, respiratory rate ≥30 breaths/min, low blood pressure, age ≥65 years (CURB‐65) score. Results: Forty patients (52%) had severe CAP (CURB‐65 score 3–5). Serum levels of AT‐III were lower and levels of D‐D and CRP were higher in patients with severe CAP than in patients with mild CAP (CURB‐65 score 0–2) (P < 0.001 for all comparisons). Levels of P‐C were lower in patients with severe CAP compared with those with mild CAP, but the difference was not significant (P = 0.459). At a cut‐off point of 85%, AT‐III showed a sensitivity of 80% and a specificity of 75%, as a determinant of the need for hospitalization. At a cut‐off point of 600 ng/mL, D‐D showed a sensitivity of 90% and a specificity of 75% and at a cut‐off point of 110 mg/L, CRP showed a sensitivity of 83% and a specificity of 79%, as determinants of the need for hospitalization. Conclusions: Serum levels of AT‐III, D‐D and CRP at admission appear to be useful biomarkers for assessing the severity of CAP.     

Validity of D-dimer tests in the diagnosis of deep vein thrombosis: a prospective comparative study of three quantitative assays

OBJECTIVES: To assess the diagnostic reliability of a new quantitative D-dimer assay (VIDAS New) and an established quick test (Nycocard D-dimer assay) in the diagnosis of deep vein thrombosis (DVT) compared with ultrasonography. A third assay (Auto Dimer) became available during sample collection and has been included in the final assessment. The diagnostic performance of the Auto Dimer assay was evaluated on three different coagulation analysers. DESIGN: A clinical prospective study of patients admitted to hospital for evaluation of DVT. Setting. The admission ward at Aalborg Hospital. Subjects. A total of 113 outpatients with suspected DVT. Main outcome measures. Compression ultrasonography was used as the reference method for a diagnosis of DVT and compared with different D-dimer assays. The results were expressed as sensitivity, specificity, positive predictive value and negative predictive value (NPV). RESULTS: Deep vein thrombosis was established in 49 patients (43%). Two D-dimer assays (VIDAS New and Auto Dimer) showed sensitivities of 90 and 88%, specificities of 42 and 44%, and NPV's of 85 and 83%, respectively. The Nycocard D-dimer assay showed a sensitivity of 63%, specificity of 67% and NPV of 71%. CONCLUSIONS: The diagnostic performance of VIDAS New and the Auto Dimer D-dimer assays is almost identical, but this study suggests that neither of the D-dimer assays is suitable as the only screening method for DVT, in a situation with a high pretest probability of DVT. This call for a differential strategy that distinguishes between cases of low and high clinical probability using either a D-dimer test or ultrasonography. Abbreviations DVT, deep venous thrombosis, NPV, negative predictive value, PPV, positive predictive value     

联合应用慢性乙型肝炎肝纤维化非创伤性诊断模型与血清透明质酸的诊断价值

背景：肝活检组织病理学检查是肝纤维化诊断的金标准,但其临床应用有一定局限性。目的：联合应用慢性乙型肝炎（CHB）肝纤维化非创伤性诊断模型Fibromodel与血清肝纤维化指标透明质酸（HA）,评价其诊断价值。方法：选取130例CHB患者,行肝活检病理分期,以≥S2为显著肝纤维化的分界点,以S4为早期肝硬化的分界点;同时检测相关实验室指标。以接受者操作特征（ROC）曲线分析Fibromodel和血清HA的诊断价值;根据阳性预测值（PPV）和阴性预测值（NPV）评估两者联合应用的诊断价值。结果：Fibromodel对≥S2的曲线下面积（AUC）为0.792,以0.15为界定值排除显著肝纤维化的敏感性、特异性和NPV分别为81.1%、62.4%和87.5%;以0.5为界定值诊断显著肝纤维化的敏感性、特异性和PPV分别为68.1%、76.9%和64.2%。只对Fibromodel介于0.15～0.5之间者行肝活检,可避免46.2%的肝活检,准确性为76.7%。血清HA对≥S2的AUC为0.789,诊断界值为60ng/ml时,敏感性、特异性和NPV分别为76.8%、78.2%和82.9%;对S4的AUC为0.801,诊断界值为140ng/ml时,敏感性、特异性和PPV分别为85.5%、81.6%和82.1%。进一步应用血清HA评价未被Fibromodel确定的患者,可避免60.0%的肝活检,准确性为83.3%。结论：Fibromodel与血清HA联合应用可提高无创评估CHB肝纤维化的诊断效率,在一定程度上可替代肝活检。     

Computerised risk scores to guide recognition and diagnosis in patients with possible heparin‐induced thrombocytopenia

The heparin‐induced thrombocytopenia computerised risk (HIT‐CR) score is designed to aid in the diagnosis of HIT. We sought to evaluate its potential clinical utility. In this retrospective cohort study, we collected HIT‐CR scores on all inpatients receiving heparin over a 4‐month period and performed chart reviews on the subset who independently underwent clinical diagnostic testing for HIT to identify patients with HIT. In all, 34 342 patients received heparin, 1744 had high‐risk HIT‐CR scores of ≥3 and 220 had the maximal risk score of 4. Only 6% of high‐risk and 10% of maximal‐risk patients underwent testing for HIT. Conversely, among all 317 patients who underwent independent testing for HIT, 67% had low‐risk HIT‐CR scores (<3). Among patients independently tested, the positive predictive value (PPV) was 6·6% [95% confidence interval (CI) 4·9–8·8%] and the negative predictive value (NPV) was 99·5% (95% CI 97·1–99·9%) at a HIT‐CR score cut‐off of 3, and the PPV was 22·7% (95% CI 12·7–37·4%) and NPV was 99·0% (95% CI 97·6–99·6%) at a cut‐off of 4. This study suggests clinicians fail to test most high‐risk patients and unnecessarily test many low‐risk patients for HIT. A reasonable approach to clinical application of HIT‐CR scores would be recommending no testing for patients with a score of <3 and recommend testing for patients with a score of 4.     

Diagnostic value of d-dimer in patients with a moderate pretest probability of deep venous thrombosis

The negative predictive value (NPV) of d-dimer (DD) for the exclusion of venous thromboembolism is, overall, high and tends to increase as clinical pretest probability decreases. We have assessed the accuracy of a diagnostic protocol including clinical evaluation and DD in 134 outpatients presenting with a moderate pretest probability of proximal deep venous thrombosis (DVT). In these patients, a negative DD value safely excluded DVT (NPV 100%, 95% CI 85-100) In our experience, these results are equivalent to those found for low-pretest probability patients and therefore the same diagnostic strategy can be used for both risk groups.     

Accuracy of glycated haemoglobin in screening for pre‐diabetes in Asian Indians—a community survey: the Chandigarh Urban Diabetes Study (CUDS)

Aim To compare American Diabetes Association and International Expert Committee recommended cut‐off values of HbA_1c for detecting the presence of pre‐diabetes against plasma glucose values obtained from oral glucose tolerance tests in Asian Indians. Methods A cross‐sectional randomly sampled population survey involving 2368 adults, aged ≥ 20 years. HbA_1c was measured on a Bio‐Rad 10 system in 1972 subjects. Results Of the 1972 subjects studied, 329 were detected to have pre‐diabetes based on isolated impaired fasting glucose in 125 subjects (6.3%), isolated impaired glucose tolerance in 141 subjects (7.1%) and the presence of both in 63 subjects (3.2%). The HbA_1c cut‐off of 34 mmol/mol (5.7%), as recommended by the American Diabetes Association for detecting the presence of pre‐diabetes, showed sensitivity of 62%, specificity 77%, with a positive predictive value of 34.7%, a negative predictive value of 89.5% and accuracy of 67.8%; whereas the HbA_1c cut‐off recommended by the International Expert Committee of 42 mmol/mol (6%) had a sensitivity of 36%, specificity of 90%, positive predictive value of 42.7%, negative predictive of 85.4% and an accuracy of 77%. However, both these HbA_1c cut‐offs underdiagnosed the presence of pre‐diabetes in 38 and 64% of these subjects, respectively. Conclusions The American Diabetes Association and the International Expert Committee recommended HbA_1c cut‐off values and oral glucose tolerance tests identify different pre‐diabetes cohorts. Long‐term prospective studies are required to define the usefulness of one over the other.     

ORIGINAL ARTICLE: Comparison of a point of care device against current laboratory methodology using citrated and EDTA samples for the determination of D-dimers in the exclusion of proximal deep vein thrombosis

D-dimer estimation is a routine part of diagnostic algorithms for the exclusion of venous thromboembolism (VTE). We evaluated a point of care device, Biosite Triage (Inverness Medical UK, Cheshire, UK) for the estimation of D-dimers in both samples taken into citrate and EDTA against our routine laboratory D-dimer (Liatest D-dimer, Diagnostica Stago, Reading, UK) performed on the STA-R Evolution. With informed consent, 102 consecutive patients presenting with possible deep vein thrombosis (DVT) were enrolled and D-dimers along with Wells scores and compression ultrasonography (CUS) were recorded. Using the manufacturers’ recommended cut offs of 500 μg/l fibrinogen equivalent units and 400 μg/l for the Stago and Triage, respectively, sensitivity, specificity, positive and negative predictive values were calculated. These were 1.00, 0.42, 0.17, and 1.00 for the Triage machine using citrate samples, 1.00, 0.32, 0.14, and 1.00 using EDTA samples and 1.00, 0.29, 0.16, and 1.00 for the Stago Liatest assay, respectively. Three patients had significantly higher results for the Stago Liatest D-dimer assay compared with the Biosite Triage device although ultrasound scans were negative. Conclusion: The Biosite Triage D-dimer assay performed on either citrate or EDTA samples is comparable with the Stago Liatest laboratory D-dimer assay when used in conjunction with clinical pretest probability scoring and CUS for the exclusion of DVT.     

Diagnostic value of D-dimer in outpatients with suspected deep venous thrombosis receiving oral anticoagulation.

D-dimer has proved a useful diagnostic tool for the exclusion of deep venous thrombosis (DVT). The objective of this paper was to evaluate the diagnostic performance of a diagnostic algorithm combining clinical probability and D-dimer in outpatients receiving oral anticoagulant treatment (OAT) similar to those regularly applied to nonanticoagulated individuals. We enrolled 70 outpatients on OAT who presented with clinically suspected DVT; a standard diagnostic algorithm including clinical evaluation using the modified Wells score and a quantitative immunoturbidimetric D-dimer assay (STA Liatest D-Di; Diagnostica Stago, Asniéres sur Seine, France) was used. A 3-month follow-up period was applied for those patients in whom DVT was initially excluded. The prevalence of DVT was 18.5% (13/70); four of the diagnoses were made during the 3-month follow-up period. The sensitivity, specificity and negative predictive value of D-dimer were 69.2% (95 confidence interval, 42.4-87.3), 47.4% (95% confidence interval, 35.0-60.1) and 87.1% (95% confidence interval, 71.1-94.9), respectively. In conclusion, D-dimer is of limited value in outpatients on OAT presenting with clinically suspected DVT and should be omitted in such individuals; these patients should always undergo compression venous ultrasound, and repeat ultrasonography within 1 week might be warranted in cases with an initial negative examination.     

An evaluation of rapid D-dimer assays for the exclusion of deep vein thrombosis

We evaluated the performance of eight d-assays for the exclusion of deep vein thrombosis (DVT); Biopool AutoDimer, Biopool MiniQuant, bioMèrieux MDA D-Dimer, VIDAS, Dade Behring D-Dimer Plus, Trinity Biotech AMAX, NycoCard D-dimer and IL Test D-Dimer. The assays were evaluated both as stand-alone tests, and in combination with pretest probability (PTP). D-dimer assays and PTP assessment were performed on 410 patients presenting to the emergency department with suspected acute DVT. DVT was diagnosed in 76 of 410 patients (18.5%) by compression ultrasound or other imaging techniques, as required. Receiver operator characteristics analysis established optimum cut-off values and these were compared with manufacturer's cut-off values where provided. As stand-alone tests, the assays varied immensely regarding cut-off value, negative predictive value (NPV 93-100%) and specificity (0-67%). At least one patient with confirmed DVT had a low d-dimer level by each method: to achieve 100% sensitivity it would be necessary to reduce cut-off values to levels below clinical usefulness. When low d-dimer was used in combination with PTP, six of eight methods achieved > or =98% NPV, with a diagnosis of DVT excluded in 16-44% of patients without the requirement for diagnostic imaging. The highly variable diagnostic performance of these d-dimer assays means that some assays are unsuitable for certain diagnostic strategies. However, our data suggest that the combination of sensitive D-dimer assays with an assessment of PTP may be used to exclude a diagnosis of DVT.     

Is transient elastography valuable for high‐risk esophageal varices prediction in patients with hepatitis‐B‐related cirrhosis?

Background and Aim: The aim of this study was to evaluate the clinical value of transient elastography (TE) for high‐risk esophageal varices (HREV) prediction in hepatitis‐B‐related cirrhosis patients. Methods: A total of 238 patients with hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area under ROC curve (AUROC), predictive value and likelihood ratio. Results: The size of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236 overall and 0.425 in patients with ALT ≥ 5 × upper limit of normal (ULN). The AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66–0.80) overall and 0.92 (0.82–1.01) for patients with ALT ≥ 5 × ULN. In patients with ALT ≥ 5 × ULN, cut‐off 36.1 kPa predicted HREV with a 100% negative predictive value (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV‐predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77–0.90) in the training set and 0.85 (0.76–0.94) in the validating set. Cut‐off 3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut‐off 5.98 determined HREV with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid endoscopic screening. The model's predictive values were maintained at similar accuracy in the validation set. Differences of AUROC in USLS, liver stiffness/spleen diameter to platelet ratio score and ultrasonic score were not significant. Conclusions: TE may predict HREV in patients with ALT ≥ 5 × ULN. Overall, the clinical values of TE and USLS for HREV prediction should be evaluated by further studies.     

Relationship between HBsAg,HBcrAg and hepatocellular carcinoma in patients with undetectable HBV DNA under nucleos(t)ide therapy

We examined the relationship between hepatitis B surface and core‐related antigens (HBsAg, HBcrAg) and hepatocellular carcinoma (HCC) development in patients with undetectable serum HBV DNA receiving nucleos(t)ide analogue (NA). Seventy‐six HBV carriers with undetectable HBV DNA (<20 IU/mL) who subsequently developed HCC were compared with 152 matched controls. Clinical and laboratory parameters (including novel assays to measure linearized HBsAg [HQ‐HBsAg] and HBcrAg) were analysed. There were no significant differences in HBsAg/HQ‐HBsAg levels between the two groups. There was a significant difference in the median values of both pre‐ and post‐NA HBcrAg levels between the HCC and control groups (pre‐treatment: 279.0 vs 35.4 kU/mL, P=.005; post‐treatment: 10.2 vs 1.7 kU/mL, P=.005, respectively). For the whole HCC group, a cut‐off value of post‐treatment HBcrAg level ≥7.8 kU/mL yielded an area under receiver operating curve (AUROC) of 0.61 with a negative predictive value (NPV) of 77.0%. The OR of HCC development was 3.27. For noncirrhotic patients, the median values of post‐treatment HBcrAg level of HCC group and controls were 10.2 and 1.0 kU/mL, respectively (P=.001). A cut‐off value of HBcrAg level ≥7.9 kU/mL yielded an AUROC of 0.70 with a NPV of 80.6%. The OR of HCC development was 5.95. A higher pre‐ and post‐NA treatment HBcrAg level (but not HBsAg) was associated with an increased risk of HCC development in patients achieving undetectable serum HBV DNA while on NA therapy. HBcrAg may serve as a novel risk marker for HCC in this group of patients.     

Vibration‐controlled transient elastography for the detection of cirrhosis in chronic hepatitis D infection

Noninvasive detection of cirrhosis via vibration‐controlled transient elastography (VCTE) has revolutionized the management of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. However, VCTE has not been studied in chronic hepatitis D virus (HDV) infection and accuracy remains in question due to the significant hepatic inflammation associated with this infection. Consecutive HBV, HCV and HDV patients who underwent VCTE (2006‐2019) were evaluated. Diagnosis of cirrhosis was made via liver biopsy or clinical findings. VCTE was compared with other noninvasive serum fibrosis tests using AUROC curves. The performance of VCTE in HBV/HCV/HDV was also compared. We evaluated 319 patients (HBV‐112; HCV‐132; HDV‐75), 278(87%) patients had histology for evaluation. HDV patients had evidence of higher hepatic inflammation as evidence by aspartate aminotransferase, alanine aminotransferase and histology activity index. Cirrhotic HDV patients had higher mean liver stiffness measurements compared with noncirrhotic patients (29.0 vs 8.3 kPa, P < .0001). VCTE demonstrated excellent diagnostic accuracy for the detection of cirrhosis with an AUROC of 0.90 compared with APRI (0.83), FIB‐4 (0.88), AAR (0.73) and RPR (0.85). Performance of VCTE in HDV was comparable with HBV (0.93) and HCV (0.94). At the optimized cut‐off value of ≥14.0 kPa for determining cirrhosis in HDV, VCTE had a sensitivity of 0.78, specificity of 0.86, NPV of 0.93 and PPV of 0.64. Hence, VCTE is a useful noninvasive test in HDV for determining cirrhosis despite the presence of significant hepatic inflammation.     

Performance of HbA1c for detecting newly diagnosed diabetes and pre‐diabetes in Chinese communities living in Beijing

Aim To determine the performance of glycated haemoglobin (HbA_1c) as a screening tool for detecting newly diagnosed diabetes (NDM) and pre‐diabetes. Methods A diabetes survey was conducted in Beijing among community dwellers who were willing to participate in the survey. Included in the survey were 903 individuals aged 21–79 years without previously diagnosed diabetes and in whom HbA_1c and other required covariates had been measured. NDM and pre‐diabetes (impaired glucose tolerance + impaired fasting glucose) were defined according to the World Health Organization 1999 criteria based on 75‐g oral glucose tolerance test. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA_1c. Results The prevalence of NDM and pre‐diabetes was 11.1% and 22.4%, respectively. At an optimal HbA_1c cut‐off point of ≥ 6.0%, the test gave a sensitivity of 80.0% and a specificity of 89.8% for diagnosing NDM; at an optimal cut‐off point of ≥ 5.7%, the sensitivity was 59.4% and specificity 73.9% for diagnosing pre‐diabetes. Individuals with HbA_1c≥ 6.0% tended to be more obese than those with HbA_1c < 6.0%, but blood pressure and lipid profiles did not differ between the two groups. Conclusions HbA_1c as a single screening test is adequate to detect newly diagnosed diabetes but is not able to identify pre‐diabetes in this obese Chinese population.     

Combined use of aspartate aminotransferase,platelet count and matrix metalloproteinase 2 measurements to predict liver fibrosis in HIV/hepatitis C virus‐coinfected patients

Objective Noninvasive tests that can be used in place of liver biopsy to diagnose fibrosis have major limitations. They either leave a significant proportion of patients without a definitive diagnosis or produce inaccurate results. Moreover, the performance of these tests is lower in HIV/hepatitis C virus (HCV) coinfection. Against this background, we examined the utility of serum matrix metalloproteinase 2 (MMP‐2) and tissue inhibitor of metalloproteinase 1 (TIMP‐1) measurements in combination with routine clinical data to predict fibrosis in HIV/HCV‐coinfected patients. Methods Patients with a liver biopsy who had not received anti‐HCV therapy were included in the study. A model including variables independently associated with fibrosis was constructed. Diagnostic accuracy was determined by measuring the area under the receiver operating characteristic curve (AUROC). Positive (PPV) and negative (NPV) predictive values were calculated. Results Ninety patients were included in the study. Aspartate aminotransferase (AST), platelet count and MMP‐2 were predictors of significant fibrosis (F≥2) and cirrhosis (F4). A score constructed using these variables yielded an AUROC of 0.76 for F≥2 and 0.88 for F4. Score cut‐offs detected (value ≥3.5) and excluded (value ≤1.5) F≥2 with a PPV of 87% and an NPV of 88%. Thirty‐one patients (34%) were correctly diagnosed using these cut‐offs, with four (13%) incorrect classifications. Cirrhosis was excluded with a certainty of 98% and diagnosed with a probability of 83%. Two (17%) of 12 patients were misclassified as having cirrhosis. The AST to platelet count index and MMP‐2 levels were sequentially applied to detect F≥2. Forty‐one patients (46%) were identified with this approach, with six (15%) misclassifications. Conclusion MMP‐2 levels can be used in combination with AST and platelet count to aid the diagnosis of liver fibrosis in HIV/HCV‐coinfected patients.