Identification and external validation of the optimal FIB‐4 and APRI thresholds for ruling in chronic hepatitis B related liver fibrosis in tertiary care settings

BackgroundWith the initially defined thresholds, the most widely used serum biomarkers for staging liver fibrosis (ie, APRI and FIB‐4 scores) proved to be ineffective among patients with chronic hepatitis B virus infection (CHB). Whether optimizing the FIB‐4 and APRI thresholds could improve their diagnostic accuracy requires further research.MethodsUsing data of treat‐naïve CHB patients from three tertiary hospitals, we explored the optimal FIB‐4 and APRI thresholds to rule in liver fibrosis accurately. Subsequently, we validated the applicability of the newly defined thresholds to the CHB patients from another two tertiary hospitals.ResultsThe fibrosis stages between discovery cohort (n = 433) and the external validation cohort (n = 568) were statistically different (P < .001). When ruling in significant fibrosis and advanced fibrosis by the newly defined FIB‐4 thresholds (2.25 and 3.00, respectively), 24.0% and 14.3% of patients, respectively, could be classified with excellent accuracy (PPVs of 91.3% and 80.6%, respectively; misdiagnosis rates of 6.0% and 5.4%, respectively), supported by the internal and external validation tests. Regrettably, the more accurate and robust thresholds of APRI score for ruling in significant fibrosis and advanced fibrosis could not be found. Besides, the FIB‐4 and APRI scores should not be recommended for ruling in cirrhosis because of poor clinical diagnostic performance.ConclusionThe newly defined FIB‐4 thresholds for ruling in significant fibrosis and advanced fibrosis showed superior and reproducible clinical diagnostic accuracy. The well‐validated threshold (≥2.25) of FIB‐4 score could aid in antiviral treatment decisions for treat‐naïve adult CHB patients by accurately ruling in significant fibrosis in tertiary care settings.     

The value of platelet parameters and related scoring system in predicting esophageal varices and collateral veins in patients with liver cirrhosis

ObjectiveTo explore the value of platelet parameters and related scoring system in predicting esophageal varices and collateral veins in patients with liver cirrhosis.MethodA total of 94 patients with liver cirrhosis diagnosed in our hospital from March 2017 to July 2018 were divided into without esophageal varices group (NEV) and esophageal varices group (EV) into mild, moderate, and severe subgroups according to the results of general gastroscopy. The differences of biological indexes among different degrees of esophageal varices and collateral veins were analyzed, and the related factors of esophageal varices and collateral veins were analyzed.ResultsPLT count and PCT decreased gradually with the increase of esophageal varices in EV group. There were significant differences in PLT count and PCT, which were negatively correlated with the degree of collateral vein in esophageal collateral vein group. The maximum cross‐sectional diameter and mean diameter of esophageal collateral veins in EV group were wider than those in NEV group. Further study showed that the maximum cross‐sectional total diameter and mean diameter of esophageal collateral veins in severe esophageal varices group were wider than those in NEV group and mild esophageal varices group. Sequential Logistic regression analysis showed that PCT could effectively predict the existence of esophageal varices. Platelet parameters had no significant diagnostic value in predicting peri‐ECV and Para‐ECV. For platelet‐related FI, APRI, FIB‐4, King, Lok, GUCI, and FibroQ scoring systems, multivariate Logistic regression showed that FI, FIB‐4, Lok and FibroQ scoring systems could effectively predict the presence of EV and Para‐ECV (P<0.05), and its Lok Index is better than other rating systems, with AUROC values of 0.773 and 0.747, respectively. There is no significant predictive value for above scoring systems of peri‐ECV.ConclusionsPCT and LOK index can effectively predict the existence of esophageal varices and para‐esophageal veins in patients with liver cirrhosis, and can be used as an effective filling method for common gastroscopy and endoscopic ultrasonography to detect EV and ECV in liver cirrhosis.     

Does the FT3-to-FT4 ratio easily predict the progression of NAFLD and NASH cirrhosis?

BackgroundFactors causing progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis (NASH) and liver cirrhosis remain relatively unknown. We aimed to evaluate the power and effectiveness of the free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio to predict non-alcoholic fatty liver disease (NAFLD)/liver fibrosis and NASH cirrhosis severity.MethodsPatients (n = 436) with NASH-associated liver cirrhosis (n = 68), patients with liver biopsy-proven NAFLD (n = 226), or healthy participants (n = 142) were enrolled between January 2010 and January 2020. The aspartate aminotransferase-to-thrombocyte ratio (APRI), NAFLD fibrosis score, albumin–bilirubin score (ALBI), aspartate aminotransferase (AST)-to-alanine aminotransferase (ALT) ratio, FT3-to-FT4 ratio, and Fibrosis-4 (FIB-4) were calculated and evaluated.ResultsAll parameters were significantly higher in NASH cirrhosis than in the healthy group. Body mass index, ALT, fasting insulin, homeostatic model assessment for insulin resistance, and triglyceride levels were significantly higher in liver biopsy-proven NAFLD than in the healthy group. The APRI, NAFLD fibrosis score, ALBI, AST-to-ALT ratio, FT3-to-FT4 ratio, and FIB-4 were significantly higher in the NASH cirrhosis group than in the healthy group. In patients with biopsy-proven NAFLD, the FT3-to-FT4 ratio was significantly lower than in the healthy group.ConclusionThe FT3-to-FT4 ratio is an effective and useful indicator to predict NAFLD/liver fibrosis and NASH cirrhosis severity.     

Non-invasive Assessment of Liver Fibrosis with ElastPQ: Comparison with Transient Elastography and Serologic Fibrosis Marker Tests,and Correlation with Liver Pathology Results

We investigated the feasibility of using ultrasound shear wave elastography point quantification (ElastPQ) for liver fibrosis staging and compared it with other non-invasive tools with respect to efficacy in liver stiffness measurement. A total of 106 patients who underwent liver stiffness measurements, using ElastPQ and biochemical investigations, before parenchymal liver biopsy or surgery were included. Among these, 51 also underwent transient elastography (TE). Correlations of ElastPQ, TE and aspartate aminotransferase-to-platelet ratio index (APRI) with histopathological findings (as the reference standard) were determined using Spearman's correlation coefficient. The diagnostic performance of ElastPQ, TE and APRI was evaluated using receiver operating characteristic (ROC) curve analysis. ElastPQ had good diagnostic accuracy in identifying each liver fibrosis stage, with an area under the ROC curve (AUC) of 0.810 to 0.864. Stiffness values obtained using ElastPQ, TE and APRI were significantly positively correlated (r = 0.686, r = 0.732 and r = 0.454, respectively) with histologic fibrosis staging (p < 0.001). According to the AUC for the diagnosis of significant fibrosis (≥F2) and cirrhosis (=F4), ElastPQ had better diagnostic accuracy (AUC = 0.929 and 0.834, respectively) than APRI (AUC = 0.656 and 0.618, respectively) (p < 0.05), and was similar to TE (AUC = 0.915 and 0.879, respectively). ElastPQ is a promising ultrasound-based imaging technique for evaluation of liver fibrosis, with a diagnostic accuracy comparable to that of TE.     

Risk of severe illness of COVID‐19 patients with NAFLD and increased NAFLD fibrosis scores

BackgroundThere is still little knowledge about the association of liver fibrosis with the clinical outcomes of COVID‐19 patients with non‐alcoholic fatty liver disease (NAFLD). The aim of the study was to determine the association of NAFLD fibrosis score (NFS)–determined liver fibrosis with clinical outcomes of COVID‐19 patients with NAFLD.MethodsThe NAFLD was diagnosed by the Hepatic Steatosis Index (HSI) in the absence of other causes of chronic liver diseases. NFS was used to evaluate the severity of liver fibrosis.ResultsA total of 86 COVID‐19 patients with NAFLD were included. The median age was 43.5 years, and 58.1% of patients were male. Thirty‐eight (44.2%) patients had advanced liver fibrosis according to the NFS. Multivariate analysis indicated that concurrent diabetes (odds ratio [OR] 8.264, 95% confidence interval [CI] 1.202–56.830, p = 0.032) and advanced liver fibrosis (OR 11.057, 95% CI 1.193–102.439, p = 0.034) were independent risk factors of severe illness in COVID‐19 patients with NAFLD.ConclusionNAFLD patients with NFS‐determined advanced liver fibrosis are at higher risk of severe COVID‐19.     

Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening

OBJECTIVEAssess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).RESEARCH DESIGN AND METHODSA total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m²; and HbA_1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.RESULTSThe prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3–4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).CONCLUSIONSModerate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.     

Validation of the hepatocellular carcinoma early detection screening algorithm Doylestown and aMAP in a cohort of Chinese with cirrhosis

BackgroundPrevious studies have developed some blood‐based biomarker algorithms such as the Doylestown algorithm and aMAP score to improve the detection of Hepatocellular carcinoma (HCC). However, no one has studied the application of the Doylestown algorithm in the Chinese. Meanwhile, which of these two screening models is more suitable for people with liver cirrhosis remains to be investigated.MethodsIn this study, HCC surveillance was performed by radiographic imaging and testing for tumor markers every 6 months from August 21, 2018, to January 12, 2021. We conducted a retrospective study of 742 liver cirrhosis patients, and among them, 20 developed HCC during follow‐up. Samples from these patients at three follow‐up time points were tested to evaluate alpha‐fetoprotein (AFP), the Doylestown algorithm, and aMAP score.ResultsOverall, 521 liver cirrhosis patients underwent semiannual longitudinal follow‐up three times. Five patients were diagnosed with HCC within 0–6 months of the third follow‐up. We found that for these liver cirrhosis patients, the Doylestown algorithm had the highest accuracy for HCC detection, with areas under the receiver operating characteristic curve (AUCs) of 0.763, 0.801, and 0.867 for follow‐ups 1–3, respectively. Compared with AFP at 20 ng/ml, the Doylestown algorithm increased biomarker performance by 7.4%, 21%, and 13% for follow‐ups 1–3, respectively.ConclusionsOur findings show that the Doylestown algorithm performance appeared to be optimal for HCC early screening in the Chinese cirrhotic population when compared with the aMAP score and AFP at 20 ng/ml.     

Combination of C‐reactive protein,procalcitonin, IL‐6, IL‐8, and IL‐10 for early diagnosis of hyperinflammatory state and organ dysfunction in pediatric sepsis

BackgroundAlthough early diagnosis and management are critical for prognosis of pediatric sepsis, there are no specific diagnostic biomarkers for the hyperinflammatory state and organ dysfunction, important stages of sepsis.MethodsWe enrolled 129 children with infection into three groups: non‐sepsis infection (33), Sepsis 1.0 (hyperinflammatory state, 67), and Sepsis 3.0 (organ dysfunction, 29). Another 32 children with no infections were included as controls. Serum C‐reactive protein (CRP), procalcitonin (PCT), interleukin (IL)‐1β, IL‐2, IL‐4, IL‐5, IL‐6, IL‐8, IL‐10, IL‐12p70, IL‐17, tumor necrosis factor (TNF)‐α, interferon (IFN)‐α, and IFN‐γ were assessed to diagnose the two stages, and their diagnostic capacities were evaluated using receiver operating characteristic (ROC) curves. We also examined whether combining biomarkers improved diagnostic efficiency.ResultsSignificantly higher CRP, PCT, and IL‐6 levels were detected in the Sepsis 1.0 than the non‐sepsis infection group (p < 0.001). The areas under the curve (AUCs) for diagnosing Sepsis 1.0 were 0.974 (CRP), 0.913 (PCT) and 0.919 (IL‐6). A combination of any two biomarkers increased diagnostic sensitivity to ≥92.54% and specificity to 100.00%. Significantly higher PCT, IL‐8, and IL‐10 levels were found in the Sepsis 3.0 than the Sepsis 1.0 group (p ≤ 0.01), with AUCs for diagnosing Sepsis 3.0 0.807 (PCT), 0.711 (IL‐8), and 0.860 (IL‐10). Combining these three biomarkers increased diagnostic sensitivity to 96.55% and specificity to 94.03%.ConclusionIn pediatric sepsis, combining any two of CRP, PCT, and IL‐6 can accurately diagnose the hyperinflammatory state and increase diagnostic specificity. Early diagnosis of organ dysfunction requires a combination of PCT, IL‐8, and IL‐10.     

The prognostic values of serum markers in hepatocellular carcinoma after invasive therapies based on real‐world data

Background and aimsHepatocellular carcinoma (HCC) is one of the most common malignancy with poor prognosis, and the mortality rate remains high. More than 70% of HCC patients have recurrence within 5 years after treatment. The purpose of this study is to evaluate the prognostic values of serum markers with retrospective data.MethodsWe applied real‐world data (RWD) to analyze the prognostic values of six serum markers for HCC patients after treatment, including α‐fetoprotein (AFP), α‐fetoprotein‐L3 (AFP‐L3), Golgi protein73 (GP73), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin (TBil). A total of 268 cases were enrolled to analyze recurrence‐free survival (RFS), and 104 cases were used to analyze overall survival (OS).ResultsOur results demonstrated that patients with higher AFP and AFP‐L3 had shorter RFS (p = 0.016 and 0.004), while higher GP73, ALT, and TBil experienced longer RFS (p = 0.000, 0.020, and 0.019). Patients with high‐level GP73, ALT, TBil, and low‐level ALB had significantly higher mortality rate (p=0.035, 0.008, 0.010, and 0.005). Multivariate analysis revealed that GP73 (HR = 1.548, p = 0.001) and ALT (HR = 1.316, p = 0.046) were identified as independent prognostic factors for RFS, ALB (HR = 0.127, p = 0.007), and ALT (HR = 0.237, p = 0.01) were identified as independent prognostic factors for OS. Subgroups analysis showed that GP73 had better prognostic values than other serum markers in early‐stage HCC (p = 0.023).ConclusionsOur study demonstrates that AFP, AFP‐L3, and GP73 can be used as prognostic indicators for predicting the recurrence of HCC, while liver function tests have better survival prediction values. GP73 can act as a promising prognostic marker for early‐stage HCC.     

Real-time elastography (RTE): a valuable sonography-based non-invasive method for the assessment of liver fibrosis in chronic hepatitis B

Purpose

To investigate the diagnostic usefulness of real-time elastography (RTE) for liver fibrosis in chronic hepatitis B (CHB).

Methods

89 CHB patients were enrolled in the cross-sectional study. Ultrasound-guided percutaneous liver biopsies, RTE, and blood testing were performed in all patients. Areas under receiver operating characteristic curves (AUROC) were used to examine the diagnostic performance of liver fibrosis index (LFI) for the assessment of liver fibrosis.

Results

LFI differed significantly across histologic fibrosis stages (P < 0.05), except the comparison between S0 and S1 (P = 0.298). There was a strong positive correlation between LFI and histologic liver fibrosis stage (Spearman r = 0.831, P < 0.001). The cutoff LFI value of >2.74 indicated a sensitivity of 0.766 and a specificity of 0.872 for predicting significant liver fibrosis (S ≥ 2), and the cutoff LFI value of >3.61 indicated a sensitivity of 0.833 and a specificity of 0.878 for predicting early liver cirrhosis (S = 4). LFI showed higher AUROC for discriminating significant liver fibrosis (0.873 vs. 0.614) and early liver cirrhosis (0.923 vs. 0.769) than aspartate aminotransferase-to-platelet ratio index (APRI).

Conclusions

RTE is a valuable sonography-based non-invasive method for assessment of liver fibrosis and has better discrimination power for significant liver fibrosis and early liver cirrhosis than APRI in CHB.

     

Arthritis Prediction of Advanced Hepatic Fibrosis in HFE Hemochromatosis

ObjectiveTo evaluate whether arthritis predicts the likelihood of advanced hepatic fibrosis in HFE hemochromatosis.Patients and MethodsWe conducted a retrospective, cross-sectional analysis of 112 well-characterized patients with HFE hemochromatosis and liver biopsy–validated fibrosis staging recruited between January 1, 1983, and December 31, 2013. Complete clinical, biochemical, hematologic, and noninvasive serum biochemical indices (aspartate aminotransferase to platelet ratio index [APRI] and fibrosis 4 index [FIB4]) were available. Scheuer fibrosis stages 3 and 4, APRI greater than 0.44, or FIB4 greater than 1.1 were used to define advanced hepatic fibrosis. Comparisons between groups were performed using categorical analysis, unpaired or paired t test.ResultsMale (n=76) and female (n=36) patients were similar in age. Nineteen patients had advanced hepatic fibrosis, and 47 had hemochromatosis arthritis. Arthritis was significantly associated with the presence of advanced hepatic fibrosis as determined by liver biopsy (sensitivity, 84%, [95% CI, 62% to 95%]; negative predictive value, 95% [95% CI, 87% to 99%]; relative risk, 7.4 [95% CI, 2.5 to 23]; P<.001), APRI (sensitivity, 75% [95% CI, 55% to 88%]; negative predictive value, 91% [95% CI, 81% to 96%]; relative risk, 4.5 [95% CI, 2.0 to 10.2]; P<.001), or FIB4 (sensitivity, 61% [95% CI, 41% to 78%]; negative predictive value, 67% [95% CI, 68% to 90%]; relative risk, 2.2 [95% CI, 1.1 to 4.6]; P=.03). Mean cell volume values were significantly higher pretreatment in patients with F3-4 fibrosis (96.7±1.1 fL) compared with F0-2 fibrosis (93.4±0.5 fL; P=.004) and declined following treatment (F3-4, 93.2±0.9 fL, P=.01; F0-2, 91.7±0.6 fL, P=.01).ConclusionAdvanced hepatic fibrosis is strongly associated with arthritis in HFE hemochromatosis. The absence of arthritis predicts a low likelihood of advanced hepatic fibrosis, supporting its use as a clinical marker for advanced hepatic fibrosis in HFE hemochromatosis.     

Comparison of Acoustic Structure Quantification,Transient Elastography (FibroScan) and Histology in Patients with Chronic Hepatitis B and without Moderate to Severe Hepatic Steatosis

The purpose of this study was to compare acoustic structure quantification (ASQ) with transient elastography for staging liver fibrosis. One hundred eighty-two patients with chronic hepatitis B and without moderate to severe hepatic steatosis scheduled for liver biopsy underwent ASQ and transient elastography examinations. All ASQ parameters, including total mode, total average, red mode, red average, red standard deviation, blue mode, blue average, blue standard deviation and focal disturbance (FD) ratio and liver stiffness obtained via transient elastography were found to correlate with fibrosis stage (Spearman's r?=?0.783, 0.791, 0.750, 0.771, 0.544, 0.718, 0.691, 0.439, 0.815 and 0.814, respectively; all p values < 0.001). Among the ASQ parameters, the FD ratio had the highest correlation with the stage of fibrosis. The areas under the receiver operating characteristic curves (AUCs) of FD ratio and liver stiffness were 0.911 and 0.906 for F ≥ F1, 0.918 and 0.882 for F ≥ F2, 0.911 and 0.914 for F ≥ F3 and 0.926 and 0.978 for F?=?F4, respectively. There was no significant difference in AUCs between FD ratio and liver stiffness in predicting different stages of fibrosis (p?=?0.062–0.912). ASQ is a promising technique for assessing liver fibrosis in the absence of moderate to severe hepatic steatosis.     

Clinical impact of antibodies to Sp100 on a bacterial infection in patients with primary biliary cholangitis

BackgroundA specific antinuclear antibody for primary biliary cholangitis (PBC) is anti‐Sp100, which was recognized as a serological marker of concurrent urinary tract infection. We sought to determine the clinical characteristics of PBC patients who had anti‐Sp100.Patients and MethodsFifty‐one patients with PBC and 10 healthy controls (HCs) were enrolled. Anti‐Sp100 were determined with an ELISA method. Lipopolysaccharide‐binding protein (LBP) was measured as a serological hallmark for bacterial infection. The correlations of anti‐Sp100 with demographic, laboratory, and pathological parameters were investigated.ResultsSix of the 51 (11.8%) PBC patients had anti‐Sp100, whereas none of the HCs did. There was no significant difference in the frequency of antimitochondrial antibodies (AMAs) between PBC patients with and without anti‐Sp100 (67% vs. 82%, p = 0.5839). Biochemical and immunological parameters were not associated with the emergence of anti‐Sp100 in these patients. The clinical stage by Scheuer classification was not correlated with the existence of anti‐Sp100. No significant difference in the serum LBP levels was found between PBC patients with and without anti‐Sp‐100, although serum LBP levels were significantly higher in PBC patients with anti‐Sp100 than in HCs (8.30 ± 2.24 ng/ml, vs. 5.12 ± 2.48 ng/ml, p = 0.0022). The frequency of granuloma formation was higher in the liver specimens of PBC patients with anti‐Sp100 than in those without anti‐Sp100 (67% vs 29%, p = 0.0710).Conclusionanti‐Sp100 does not become a complementary serological marker for PBC in AMA‐negative patients. A bacterial infection may trigger the production of anti‐Sp100. Another factor is required to initiate the autoantibody production.     

Blood T‐helper 17 cells and interleukin‐17A correlate with the elevated risk of postpartum depression and anxiety

BackgroundT‐helper (Th) cells regulate inflammation and immunity, which is implicated in psychological disorders. The current study aimed to explore the clinical role of blood Th1, Th2, and Th17 cells and their main secreted cytokines in postpartum depression (PPD) and postpartum anxiety (PPA).MethodsA total of 226 postpartum women were included. At 6 weeks postpartum, Edinburgh Postnatal Depression Scale (EPDS) and State Trait Anxiety Inventory 6 item version (STAI6) scores were assessed; meanwhile, blood Th1, Th2, and Th17 cells were detected by flow cytometry, serum interferon‐gamma (IFN‐γ), interleukin‐4 (IL‐4), and IL‐17A were detected by enzyme‐linked immunosorbent assay.ResultsThe incidence of PPD and PPA were 24.3% and 27.9%, respectively. Th17 cells and IL‐17A were positively correlated with EPDS score and STAI6 score (all p < 0.001). Besides, Th17 cells (p < 0.001) and IL‐17A (p = 0.002) were increased in PPD cases vs. non‐PPD cases, and they were also elevated in PPA cases vs. non‐PPA cases (both p < 0.05). However, Th1 cells, Th2 cells, IFN‐γ, and IL‐4 were not linked with EPDS score or STAI6 score (all p > 0.05); besides, they did not vary in PPD cases vs. non‐PPD cases or in PPA cases vs. non‐PPA cases (all p > 0.05). Multivariate logistic regression model analysis showed that Th17 cells were independently associated with an elevated risk of PPD (odds ratio [OR] = 1.600, p = 0.001) and PPA (OR = 1.371, p = 0.022).ConclusionBlood Th17 cells and IL‐17A are positively linked with the risk of PPD and PPA, indicating which may be involved in the development of PPD and PPA.     

FibroTouch联合FIB-4、APRI及GPRI评估肝纤维化

目的 评估肝脏瞬时弹性成像技术（FibroTouch）联合天冬氨酸氨基转移酶（aspartate transaminase,AST）/血小板（platelet,PLT）比值（APRI）、age AST PLT 丙氨酸氨基转移酶（alanine transaminase,ALT）相关的比值（FIB 4）及谷氨酰胺转肽酶（glutamyl transferase,GGT）/PLT比值（GPRI）诊断肝纤维化的临床价值。方法 选择2014年1月至2017年4月就诊于河北医科大学第三医院经肝组织病理学证实的慢性肝病患者337例,采用FibroTouch检测肝脏硬度值（liver stiffness measurement,LSM）,同步检测ALT、AST、GGT、总胆红素（total bilirubin,TBIL）及PLT,计算FIB 4、APRI及GPRI。应用受试者工作特征（receiver operating characteristic,ROC）曲线对比分析FibroTouch及3种血清学模型的诊断效能,Spearman秩相关检验分析其与影响因素的相关性,验后概率对比分析FibroTouch联合多参数模型的诊断准确度。结果 肝组织病理学结果：显著肝纤维化（≥S2）169例,进展期肝纤维化（≥S3）86例,肝硬化（S4）42例。LSM诊断纤维化分期S≥2、S≥3、S=4 的ROC曲线下面积依次为0.826、0.882、0.920,明显高于FIB 4（0.734、0.711、0.739）、APRI（0.662、0.669、0.719）和GPRI（0.621、0.674、0.720）,P值均<0.01。相关因素分析显示年龄、肝脏炎症程度、ALT、AST及TBIL水平可影响LSM、FIB 4、APRI及GPRI诊断肝纤维化。计算验后概率示,FibroTouch诊断纤维化分期S≥2、S≥3、S=4与肝组织病理学的符合率分别为72.44%、80.52%、84.21%;LSM联合FIB 4诊断肝纤维化的符合率优于LSM联合APRI或GPRI,S≥2、S≥3、S=4分别为85.88%、92.38%、95.83%;进一步联合其余模型的诊断准确率进一步提高,四者联合诊断肝纤维化分期S≥2、S≥3、S=4的符合率分别为95.71%、98.6%、99.08%。结论 FibroTouch联合FIB 4评估慢性肝病肝纤维化程度的准确度高,进一步联合APRI及GPRI可在一定程度上减少肝穿活检的需求,为肝纤维化的无创诊断、动态监测及疗效评估提供可靠依据。     

Alinity hq platelet count is not impacted by severe microcytosis

BackgroundImpedance technology has been shown to overestimate platelet (PLT) count in samples with microcytes, while the optical‐fluorescence PLT count (PLT‐F) by Sysmex has been suggested to be unaffected by microcytosis. The Abbott Alinity hq analyzer employs multi‐dimensional optical PLT counting. Our goal was to assess the accuracy of this technology in microcytic samples.MethodsPlatelet measurements were performed by Alinity hq and the impedance (PLT‐I) and PLT‐F methods on a Sysmex XN‐3000 analyzer on 464 samples. PLT concentration range was 6.56–947 × 10⁹/L and mean cell volume (MCV) 40.9–123.0 fL. Samples were categorized into normocytic (MCV > 80 fL), microcytic (MCV 65–80 fL), and severely microcytic (MCV < 65 fL) groups.ResultsAlinity hq PLT count showed excellent agreement with PLT‐F (r = 1.00). Sysmex PLT‐I data showed somewhat weaker correlation with both PLT‐F and Alinity hq (r = 0.98). Increasing bias between Sysmex PLT‐I and PLT‐F was seen with decreasing MCV values, with mean bias of 35.2 × 10⁹/L in severe microcytosis. An inverse relationship was demonstrated between the PLT‐I versus PLT‐F bias and MCV (p < 0.0001). Consistent mean bias was observed between Alinity hq and PLT‐F across all MCV ranges.Mean platelet volume was suppressed or flagged by Sysmex XN in 50% of the samples in the severely microcytic group, and markedly higher red cell distribution width (RDW) was reported compared to Alinity hq (18.1% vs 13.7%, p < 0.0001).ConclusionThe Sysmex PLT‐I method overestimated the PLT count in samples with severe microcytosis. Alinity hq provided PLT counts and PLT and RBC indices that were not impacted by microcytosis.     

Combined procalcitonin and hemogram parameters contribute to early differential diagnosis of Gram‐negative/Gram‐positive bloodstream infections

BackgroundHemogram parameters and procalcitonin (PCT) play auxiliary roles in the diagnosis and outcome of sepsis. However, it is not clear whether these indicators can quickly distinguish bacterial classification or guide the choice of empirical antibiotics.MethodsWe retrospectively enrolled 381 patients with bloodstream infections (BSI), divided into Gram‐positive bloodstream infections (GP‐BSI) and Gram‐negative bloodstream infections (GN‐BSI). Demographic parameters, hemogram parameters, and PCT were recorded and compared between the two groups.ResultsThe mean platelet volume (MPV), platelet distribution width (PDW), and PCT in the GN‐BSI group were significantly higher than those in the GP‐BSI group, while the platelet count (PLT), plateletcrit, platelet count‐to‐white blood cell count ratio (PWR), platelet count‐to‐neutrophil count ratio (PNR), platelet count‐to‐PCT ratio (PLT/PCT), and mean platelet volume‐to‐PCT ratio (MPV/PCT) were significantly lower in the GN‐BSI group. Multivariate stepwise logistic regression analysis revealed that the independent predictors of GN‐BSI were MPV, PWR, and PCT. The areas under the curve (AUC) for this prediction model was 0.79, with sensitivity =0.75 and specificity =0.71.ConclusionsThere were significant differences in terms of PCT, platelet parameters, and platelet‐related index‐PCT ratio between GN‐BSI and GP‐BSI. Combined PCT and hemogram parameters are more conducive to the early differential diagnosis of bacterial classification of BSI.     

Luteolin enhances the antitumor efficacy of oncolytic vaccinia virus that harbors IL‐24 gene in liver cancer cells

BackgroundInterleukin 24 (IL‐24) is an IL‐10 family member and a secreted cytokine characterized by cancer‐targeted toxicity and can activate apoptosis by sensitizing cancer cells to chemotherapy. Cytotoxic effects of luteolin on different types of cancer cells suppress their growth by acting on the components of the apoptosis signaling cascade. Therefore, our study aimed to prove whether oncolytic vaccinia virus (VV) that harbors IL‐24 (VV‐IL‐24) combine with luteolin exerts a synergistic inhibitory effect in liver cancer cells.MethodsImpacts on cell viability of VV‐IL‐24 and luteolin were assessed by MTT in various liver cancer cell lines. Then, liver cancer cell apoptosis was analyzed via flow cytometry and Western blotting. Besides, the MHCC97‐H xenograft mouse model was employed as a means of assessing in vivo antitumor efficacy.ResultsMTT assay confirmed that the combination treatment decreased liver cancer cells viability to a greater degree than treatment with VV‐IL‐24 or luteolin alone. Flow cytometry and Western blot assay proved that VV‐IL‐24 plus luteolin induced more liver cancer cells apoptosis than single treatment. Furthermore, in the MHCC97‐H xenograft model, 15 days of treatment with VV‐IL‐24 plus luteolin inhibited tumor growth significantly more than single treatment.ConclusionThese data confirm that the synergistic mechanism of VV‐IL‐24 and luteolin elicits a stronger tumor growth inhibition than any single therapy. Thus, the combination of VV‐IL‐24 and luteolin could provide the basis for preclinical research in the treatment of liver cancer.     

Levels of SERPIN family proteins in peri‐implant crevicular fluid in patients with peri‐implantitis

PurposeSerine protease inhibitors (SERPINs) family has been discovered in many disorders with proteolysis mechanisms. Our study determined the SERPINBs protein expression via public‐based GEO databases and further validated by peri‐implant crevicular fluid (PICF) of peri‐implantitis patients and healthy recruiters.MethodsThis study is a retrospective analysis. A total of 123 participants of Fujian Medical University Fujian Stomatological Hospital, consisting of 58 cases of peri‐implantitis and 65 samples of healthy control were retrospectively analyzed by ELISA assays and explored the gene enrichment pathways and clinical significance of SERPINBs expression accompanied by two different cytokines (IL‐6 and TNF‐α). Moreover, the clinical significance of SERPINBs was evaluated in peri‐implantitis patients with PICF samples by the receiver operating curve (ROC) using the area under the curve (AUC).ResultsKEGG database showed that Starch and sucrose metabolism, Retrograde endocannabinoid signaling, Prion diseases, Pentose phosphate pathways, and Olfactory pathways are up‐regulated; GO database showed that synapse organization, synapse assembly, sequestering of triglyceride, sensory perception of smell, and regulation of synapse organization pathways are up‐regulated. SERPINBs were overexpressed in peri‐implant tissues and peri‐implantitis patients with PICF. SERPINBs was positively correlated to IL‐6 and TNF‐α in peri‐implantitis patients with PICF. The ROC‐AUCs of SERPINBs achieved a significantly higher range from 0.895 to 0.939 in peri‐implantitis patients with PICF. Therefore, certain SERPINBs expressions were not only perceived through PICF and peri‐implant tissues but also showed potential significance in peri‐implantitis.ConclusionSERPINBs play an influential role in the pathogenesis of peri‐implantitis via binding with other inflammatory cytokines.     

Assessment of liver fibrosis progression in patients with chronic hepatitis C and normal alanine aminotransferase values: the role of AST to the platelet ratio index

OBJECTIVES: To verify the value of indirect serum markers in the non-invasive assessment of liver fibrosis in patients with persistently normal or near normal alanine aminotransferases levels (NALT). DESIGN AND METHODS: Forty HCV RNA positive, untreated patients with NALT (30 non-drinkers) underwent two liver biopsies, with a median interval of 78.5 months. The AST/ALT ratio, age-platelet index, AST to platelet ratio index (APRI), Forns fibrosis index and Bonacini's discriminant score were simultaneously determined. RESULTS: In 19 patients, worsening of fibrosis was observed at the second biopsy in comparison to the index biopsy. Among non-drinkers, an APRI >0.4 had a 100% sensitivity in identifying subjects with significant liver fibrosis (Ishak staging score >2) and an APRI < or =0.4 had a 100% negative predictive value in excluding significant liver fibrosis. CONCLUSIONS: APRI performs better, in comparison to all other markers, in correctly classifying patients with NALT with no progression to significant liver fibrosis.