The diagnostic value of transient elastography combined with serum SAA and IL-6 in the degree of hepatitis B liver fibrosis

Objective:To investigat the diagnostic value of transient elastography combined with serum amyloid A and interleukin-6 in the degree of hepatitis B liver fibrosis.Methods:A total of 334 patients with chronic HBV infection that were admitted to the Department of Infectious Diseases of the First Affiliated Hospital of Hainan Medical College from January 2020 to May 2022 with informed consent and underwent liver biopsy puncture were selected.According to the pathological results,they were divided into no obvious fibrosis group,obvious fibrosis group and liver cirrhosis group.Comparison of liver stiffness measurement(LSM),serum amyloid A(SAA0,IL-6 levels between different groups.This study drawed was conducted draw the receiver operating characteristic(ROC)curve of each index to diagnose significant liver fibrosis and liver cirrhosis,and compared the area under the ROC curve(AUC)and diagnostic efficacy of each non-invasive fibrosis diagnostic model.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 In different degrees of liver fibrosis.Results:According to the degree of liver fibrosis,the levels of SAA,IL-6,and LSM in the no significant fibrosis group(n=140),the significant fibrosis group(n=134),and the cirrhosis group(n=60)were statistically significant difference(All P<0.001).SAA,IL-6 and LSM were significantly correlated with the degree of liver fibrosis(rs=0.456,rs=0.482,rs=0.602,All P<0.001).The AUC of SAA and IL-6 for the diagnosis of significant fibrosis in hepatitis B were 0.738 and 0.809,respectively.And the AUC for the diagnosis of liver cirrhosis were 0.813 and 0.823,respectively.The AUC for the combined diagnosis of significant fibrosis and cirrhosis were 0.930 and 0.964,respectively.The diagnostic performance of the combined assay was superior to that of APRI and FIB-4 in different degrees of liver fibrosis(All P<0.001).Conclusion:LSM combined with serum SAA and IL-6 has great diagnostic value for different degrees of hepatitis B liver fibrosis.

Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults:a Cross-sectional Study Based on the NHANES

Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

Morphological and serum hyaluronic acid, laminin and type Ⅳ collagen changes in dimethylnitrosamine-induced hepatic fibrosis of rats

AIM： To study the morphological and serum hyaluronic acid （HA）, laminin （LN）, and type IV collagen changes in hepatic fibrosis of rats induced by dimethylnitrosamine （DMN）.METHODS： The rat model of liver fibrosis was induced by DMN. Serum HA, type IV collagen, and LN were measured by ELISA. The liver/weight index and morphological changes were examined under electron microscope on d 7, 14, 21, and 28 by immunohistochemical alpha smooth muscle actin α-SMA staining as well as Sirius-red and HE staining.RESULTS： The levels of serum HA, type IV collagen and LN significantly increased from d 7 to d 28 （P = 0.043）. The liver/weight index increased on d 7 and decreased on d 28. In the model group, the rat liver stained with lie and Sirius-red showed evident hemorrhage and necrosis in the central vein of hepatic 10 Iobules on d 7. Thin fibrotic septa were formed joining central areas of the liver on d 14. The number of α-SMA positive cells was markedly increased in the model group. Transitional hepatic stellate cells were observed under electron microscope. All rats in the model group showed micronodular fibrosis in the hepatic parenchyma and a network of α-SMA positive cells. Typical myofibroblasts were embedded in the core of a fibrous septum. Compared to the control group, the area-density percentage of collagen fibrosis and pathologic grading were significantly different in the model group （P〈0.05） on different d （7, 14, and 28）. The area-density percentage of collagen fibrosis in hepatic tissue had a positive correlation with the levels of serum HA, LN, and type IV collagen.CONCLUSION： The morphological and serum HA, type IV collagen, and LN are changed in DMN-induced liver fibrosis in rats.

Real time shear wave elastography in chronic liver diseases:Accuracy for predicting liver fibrosis,in comparison with serum markers

AIM: To evaluate the correlation between liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) and liver fibrosis stage and the accuracy of LSM for predicting significant and advanced fibrosis, in comparison with serum markers.

Serum ceruloplasmin can predict liver fibrosis in hepatitis B virusinfected patients

BACKGROUND The presence of significant liver fibrosis in hepatitis B virus(HBV)-infected individuals with persistently normal serum alanine aminotransferase(PNALT)levels is a strong indicator for initiating antiviral therapy.Serum ceruloplasmin(CP)is negatively correlated with liver fibrosis in HBV-infected individuals.AIM To examine the potential value of serum CP and develop a noninvasive index including CP to assess significant fibrosis among HBV-infected individuals with PNALT.METHODS Two hundred and seventy-five HBV-infected individuals with PNALT were retrospectively evaluated.The association between CP and fibrotic stages was statistically analyzed.A predictive index including CP[Ceruloplasmin hepatitis B virus(CPHBV)]was constructed to predict significant fibrosis and compared to previously reported models.RESULTS Serum CP had an inverse correlation with liver fibrosis(r=-0.600).Using CP,the areas under the curves(AUCs)to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.774,0.812,and 0.853,respectively.The CPHBV model was developed using CP,platelets(PLT),and HBsAg levels to predict significant fibrosis.The AUCs of this model to predict significant fibrosis,advanced fibrosis,and cirrhosis were 0.842,0.920,and 0.904,respectively.CPHBV was superior to previous models like the aspartate aminotransferase(AST)-to-PLT ratio index,Fibrosis-4 score,gamma-glutamyl transpeptidase-to-PLT ratio,Forn’s score,and S-index in predicting significant fibrosis in HBV-infected individuals with PNALT.CONCLUSION CPHBV could accurately predict liver fibrosis in HBV-infected individuals with PNALT.Therefore,CPHBV can be a valuable tool for antiviral treatment decisions.

The relationship between staging of hepatic fibrosis and the levels of serum biochemistry

Objective: To study the relationship between the de- gree of hepatic fibrosis and serum fibrosis markers. Methods: Liver biopsies were performed in 67 pa- tients with hepatitis. The sections were stained with hematoxylin eosin and immunohistochemical stain. Staging of hepatic fibrosis was made microscopically. The serum levels of hyaluronic acid (HA), type Ⅲ procollagen (PC-Ⅲ), laminin (LN), and type Ⅳ collagen (Ⅳ-C) were measured by radioimmunoas- say. Results: The serum levels of HA, PC-Ⅲ, LN and Ⅳ-C were elevated from S1 to S4 because of the in- crease of hepatic fibrosis. The serum concentrations of HA, PC-Ⅲ, LN and Ⅳ-C were increased with the progress of disease, with the highest concentration at the stage of cirrhosis. Conclusion: The stages of hepatic fibrosis are corre- lated with the serum levels of HA, PC-Ⅲ, LN and Ⅳ-C, which as markers may play a role in detecting the degree of hepatic fibrosis.

Matrix-derived serum markers in monitoring liver fibrosis in children with chronic hepatitis B treated with interferon alpha

To evaluate prospectively 4 selected serum fibrosis markers （tenascin, hyaluronan, collagen Ⅵ, TIMP-1） before, during and 12 mo after IFN treatment of children with chronic hepatitis B. METHODS： Forty-seven consecutive patients with chronic hepatitis B （range 4-16 years, mean 8 years） underwent IFN treatment （3 MU tiw for 20 wk）. Fibrosis stage and inflammation grade were assessed in a blinded fashion before and 12 mo after end of treatment. Serum fibrosis markers were determined using automated assays.RESULTS： IFN treatment improved histological inflammation but did not change fibrosis in the whole group or in subgroups. Only hyaluronan correlated significantly with histological fibrosis（r = 0.3383, P = 0.022）. Basal fibrosis markers did not differ between responders （42.5%） and nonresponders（57.5%）. During IFN treatment only serum tenascin decreased significantly in the whole group and in nonresponders. When pretreatment values were compared to values 12 mo after therapy, TIMP-1 increased in all patients and in nonresponders, and hyaluronan decreased in all patients and in responders.CONCLUSION： Tenascin reflects hepatic fibrogenesis and inflammation which decreases during IFN treatment of children with chronic hepatitis B. TIMP-1 correlates with nonresponse and hyaluronan with histological fibrosis.

Hepatitis B Surface Antigen Serum Level Is Correlated with Fibrosis Severity in Treatment-Naïve, Chronic Hepatitis B Patients in Côte d’Ivoire (West Africa)?

HBsAg serum level (quantification) may be useful for managing hepatitis B virus (HBV) infection patients. However few studies especially in Africa have evaluated the association between HBsAg serum level and liver fibrosis severity. The objective of this study was to estimate the correlation between HBsAg serum level and liver fibrosis severity with treatment naive chronic hepatitis B patients in Cote d’Ivoire. Methodology: It is a prospective study covering from February 1st, 2014 to April 30st, 2015 at Centre Hospitalier et Universitaire de Yopougon and a private medical office in Abidjan, Cote d’Ivoire. Inclusion criteria for patients were: HBsAg positive, known HBeAg status, serum HBsAg levels, serum HBV DNA levels, complex serum markers and absence of HCV, HDV, or HIV co-infection, drinking more than 30 g/day for men and 20 g/day in women over 10 years, metabolic disease and/or hepatic overload. Pearson’s Chi-square test (r2), Anova, Spearman, T-Student, Pearson’s (r) correlations and Mann Withney’s Test were carried out as appropriate. A p value < 0.05 was taken as significant. Results: We recruited, 105 patients (77 men) of whom the medium age was 39.01 ± 9.72 years. Predominant hepatitis B viral genotype was E (93%). Less than 10% patients had an inactive HBV in HBeAg-negative. Patients had an average high HBsAg serum level (mean 12111.2 ± 10617.4 IU/ml) as well as the one viral load (mean 4.4 e7 ± 7.5 e7). Serum ALAT levels averaged at the upper limit of normal value. The average liver fibrosis score was 0.34 ± 0.22 and the degree of viral activity was 0.19 ± 0.20. Half of our patients had no fibrosis (35.24%) or had mild fibrosis (20.95%). No significant association was observed between HBsAg serum level and patient age (p = 0.3994), genre (p = 0.8075) or serum ALT levels (p = 0, 0787). In multivariate analysis, there’s a significant correlation (r = 0.239, p = 0.014) between HBV DNA levels and HBsAg serum level. There’s a significant correlation (r = 0.923, p < 0.0001) between HBsAg serum level and the dosage of alpha-fetoprotein. HBsAg serum level was not associated with the fibrosis stage (p = 0.281). HBsAg levels average with patients without fibrosis or carry a slight fibrosis (F0, F1) was higher than patients with moderate to severe fibrosis (F2, F3, F4): 13679.2 UI/ml ± 1956.48 versus 10610.52 UI/ml ± 8998.99 (p = 0.29). There’s a negative correlation between HBsAg level and the liver fibrosis score was negative (r = -0.069, p = 0.48). No significant association between HBsAg level and the liver fibrosis patients that were normal (p = 0.7965) or elevated (p = 0.5845). HBV DNA level was significantly associated with fibrosis score (r = 0.30, p = 0.0018). Conclusion: This study shows that there’s a negative correlation between HBsAg serum level and liver fibrosis severity treatment naive with African chronic hepatitis B viral HBeAg-negative patients.

Baseline metabolites could predict responders with hepatitis B virus-related liver fibrosis for entecavir or combined with FuzhengHuayu tablet

BACKGROUND After receiving entecavir or combined with FuzhengHuayu tablet(FZHY)treatment,some sufferers with hepatitis B virus(HBV)-related liver fibrosis could achieve a histological improvement while the others may fail to improve even worsen.Serum metabolomics at baseline in these patients who were effective in treatment remain unclear.AIM To explore baseline serum metabolites characteristics in responders.METHODS A total of 132 patients with HBV-related liver fibrosis and 18 volunteers as healthy controls were recruited.First,all subjects were divided into training set and validation set.Second,the included patients were subdivided into entecavir responders(E-R),entecavir no-responders(E-N),FZHY+entecavir responders(FR),and FZHY+entecavir no-responders(F-N)following the pathological histological changes after 48 wk’treatments.Then,Serum samples of all subjects before treatment were tested by high performance liquid chromatographytandem mass spectrometry(LC-MS)high-performance LC-MS.Data processing was conducted using multivariate principal component analysis and orthogonal partial least squares discriminant analysis.Diagnostic tests of selected differential metabolites were used for Boruta analyses and logistic regression.RESULTS As for the intersection about differential metabolic pathways between the groups E-R vs E-N and F-R vs F-N,results showed that 4 pathways including linoleic acid metabolism,aminoacyl-tRNA biosynthesis,cyanoamino acid metabolism,alanine,aspartate and glutamate metabolism were screened out.As for the differential metabolites,these 7 intersected metabolites including hydroxypropionic acid,tyrosine,citric acid,taurochenodeoxycholic acid,benzoic acid,2-Furoic acid,and propionic acid were selected.CONCLUSION Our findings showed that 4 metabolic pathways and 7 differential metabolites had potential usefulness in clinical prediction of the response of entecavir or combined with FZHY on HBV fibrotic liver.

Serum biomarkers in evaluation and management of idiopathic pulmonary fibrosis

Despite there has greater understanding of the pathophysiology in idiopathic pulmonary fibrosis,idiopathic pulmonary fibrosis still remains a challenge in clinical practice and translational research due to its heterogeneity.Improvements in molecular techniques have identified potential pathways and targets for diagnosis and therapeutic intervention.Several types of idiopathic pulmonary fibrosis biomarkers such as KL-6,SP-A,SP-D,MMP7 and other potential ones have been studied extensively.In addition,many studies have confirmed that levels of some tumor markers such as CA 19-9,CA 15-3,CEA,CA 125,CYFRA 21-1 are useful for idiopathic pulmonary fibrosis.The present study focuses on serum biomarkers including tumor markers to provide an overview on the current roles of these biomarkers in the setting of diagnosis,prediction as well as response to therapy in idiopathic pulmonary fibrosis.

肝纤维化患者血清核心岩藻糖基化低分子量激肽原和α-半乳糖基化抗体的表达及预测价值

目的:肝纤维化是许多慢性肝脏疾病的共同病理基础,可进展至肝硬化,是肝脏疾病的主要致死因素,而早期识别并逆转肝纤维化进程是慢性肝病治疗的关键,本研究旨在比较血清核心岩藻糖标志物低分子量激肽原(core fucosylated low molecular weight kininogen,LMWK-Fc)和α-半乳糖基化(alpha-galactosidase,α-Gal)抗体在不同阶段肝纤维化患者体内的表达情况,评估其诊断肝纤维化的效能。方法:回顾性纳入2022年6月至2023年3月在中南大学湘雅二医院感染科就诊的275例慢性肝病患者,其中115例患者接受了肝活检。根据病理结果显示的肝组织内胶原沉积对肝结构破坏范围、程度和肝微循环影响的大小将115例完善肝活检的患者分为0~4期:S0,肝组织内无明显胶原沉积,肝结构和肝微循环正常;S1,肝组织内有轻度胶原沉积,部分破坏肝小叶结构,但肝微循环基本正常;S2,肝组织内中度胶原沉积,部分破坏肝小叶结构和肝微循环;S3,肝组织内广泛胶原沉积,大量破坏肝小叶结构和肝微循环;S4,发展为肝硬化,肝组织内高度胶原沉积,肝小叶结构完全破坏,肝微循环严重受损。并根据分期标准分为无肝纤维化组(S0)、肝纤维化组(S1~S2)、显著纤维化组(S3~S4)。160例未完善肝活检的患者则按照肝硬度值(liverstiffness measurement,LSM)分为无肝纤维化组(F0:LSM<7.3k Pa)、肝纤维化组(F1~F2:LSM为7.3~12.4 kPa)、明显肝纤维化组(F3~F4:LSM>12.4 kPa)。采集患者的年龄、性别等基本人口学资料以及丙氨酸转氨酶、天冬氨酸转氨酶、γ-谷氨酰转肽酶、碱性磷酸酶、甲胎蛋白、血小板计数等实验室指标,计算肝纤维化-4指数(fibrosis-4 index,FIB-4)、天冬氨酸转氨酶/血小板比值指数(aspartate aminotransferase-to-platelet ratio index,APRI),并对各项指标进行差异性分析;对入组的患者分别行血清LMWK-Fc和α-Gal抗体检测,比较各组间LMWK-Fc、α-Gal抗体及其他肝纤维化指标的表达情况;分析LMWK-Fc、α-Gal抗体表达水平与肝纤维化程度的相关性;采用受试者操作特征(receiver operating characteristic,ROC)曲线分析血清LMWK-Fc、α-Gal抗体水平预测肝纤维化的价值。结果:在未完善肝活检的160例患者中,血清α-Gal抗体及LMWK-Fc的表达水平在无肝纤维化组、肝纤维化组、明显肝纤维化组依次递增,差异有统计学意义(P<0.05)。在完善肝活检的115例患者中,血清LMWK-Fc水平在无纤维化组、肝纤维化组、显著肝纤维化组间依次增高,血清α-Gal抗体表达水平在显著肝纤维化组中高于无纤维化组、肝纤维化组,差异有统计学意义(P<0.001,P=0.032)。单变量和多元线性回归分析结果显示肝纤维化与性别、LMWKFc水平均有相关性(均P<0.05),与年龄、α-Gal抗体水平、FIB-4和APRI均无相关性(均P>0.05)。结论:血清LMWK-Fc和α-Gal抗体在不同分级肝纤维化患者血清中的表达水平存在差异,可能与肝纤维化进展有一定的相关性,LMWK-Fc水平对肝纤维化诊断具有一定的预测价值。

肝硬化腹水患者血清与腹水中LDH、ADA、SAAG联合检测的临床意义

目的探讨联合检测肝硬化腹水患者腹水／血清LDH、ADA、SAAG的临床意义。方法以117例肝硬化腹水患者为研究对象，设立两组对照：肝癌腹水组36例，结核性腹膜炎组26例，分别对3组腹水中的LDH、ADA、SAAG及其对应血清中的LDH、ADA、SAAG进行测定，对其结果比较分析。结果肝硬化腹水组SAAG与肝癌腹水组的SAAG比较差异无统计学意义（P〉0．05）；肝硬化腹水组SAAG与结核性腹膜炎组sAAG比较，以及肝癌性腹水SAAG与结核性腹膜炎组sAAG比较差异均有统计学意义（P〈0．05）。肝硬化腹水组LDH、肝癌腹水组LDH与结核性腹膜炎组三组中两两比较差异均有统计学意义（P〈O．05）。肝硬化腹水组ADA与肝癌腹水组ADA比较差异无统计学意义（P〉0．05）；肝硬化腹水组ADA与结核性腹膜炎组ADA比较以及肝癌腹水组ADA与结核性腹膜炎组ADA比较差异均有统计学意义（P〈0．05）。结论腹水中的LDH、ADA、sAAG及其对应血清中LDH、ADA、sAAG指标联合检测并计算其比值，对临床肝硬化腹水诊断有一定的实用价值，值得推广。

急性心肌梗死合并收缩功能障碍患者血清miR-125b与依普利酮抗纤维化反应的关系

目的探讨血清miR-125b对依普利酮抗纤维化治疗反应评估的价值。方法前瞻性纳入2020年8月9日—2021年4月1日在太原市急救中心心内科接受依普利酮治疗的89例急性心肌梗死(AMI)伴或不伴ST段抬高且伴有左心室收缩功能障碍患者。采集受试者依普利酮治疗前和治疗6个月后的外周血浆样本。二维超声心动和多普勒超声心动图评估心脏收缩功能。采用实时荧光定量PCR法检测血浆中循环miR-125b表达水平;采用放射免疫测定法和酶联免疫吸附法分别检测血清Ⅲ型胶原氨基末端前肽(PⅢNP)和Ⅰ型胶原羧基末端前肽(PⅠCP)水平,计算基线至第6个月血清PⅢNP(?PⅢNP)和PⅠCP(?PⅠCP)水平变化。并记录依普利酮治疗6个月期间患者的主要不良心血管事件(MACEs)。结果依普利酮治疗6个月后,AMI患者收缩压与超声心动图参数较基线值显著改善(P<0.05),收缩压、血清PⅢNP和PⅠCP水平降低(P<0.05),但同时血钾和血钠浓度有所升高(P<0.05)。其中50例患者第6个月时血清PⅢNP水平值较基线值绝对减少,纳入PⅢNP降低亚组,其他39例患者?PⅢNP≤0,被纳入PⅢNP稳定/增加亚组。Logistic回归分析显示,女性、经皮冠状动脉介入治疗、血清miR-125b是PⅢNP降低的独立预测因子(P<0.05)。Spearman等级相关系数分析显示,PⅢNP降低的患者基线血清miR-125b与?PⅢNP(rs=-0.566,P<0.001)和?PⅠCP(rs=-0.524,P<0.001)存在负相关关系。进一步校正危险因素后,基线血清miR-125b仍是影响血清PⅢNP和PⅠCP降低程度的独立负相关因素(P<0.05)。此外,在AMI患者中,PⅢNP降低的患者累积MACEs发生率更低(调整后HR=0.431,95%CI:0.129~1.440,P=0.171),同样血清miR-125b水平>2.23患者无MACEs事件累积生存率更低(Log rank=32.568,P<0.001)。结论血清miR-125b高表达水平有助于识别依普利酮抗纤维化作用更显著的AMI患者。

Fibrotouch联合血清标志物评估慢性乙型肝炎肝纤维化的价值

目的分析瞬时弹性成像技术(Fibrotouch)评估联合血清标志物在慢性乙型肝炎肝纤维化程度评估中的价值。方法选择厦门市第三医院2019年3月—2021年9月收治的180例慢性乙型肝炎患者作为研究对象。依病理结果分为无纤维化组72例、早期纤维化组68例和进展性纤维化组40例。所有患者均接受Fibrotouch检测肝脏硬度值(liver stiffness measurement,LSM)、血清透明质酸(hyaluronic acid,HA)、黏连蛋白(laminin,LN)、Ⅳ型胶原(collage typeⅣ,CⅣ)和Ⅲ型前胶原(precollagen typeⅢ,PCⅢ)水平。Spearman相关性分析LSM、HA、LN、CⅣ、PCⅢ水平与肝纤维化程度的相关性。受试者工作特征(receiver operating characteristic,ROC)曲线分析上述指标联合检测诊断肝纤维化的价值。结果不同肝纤维程度患者LSM、HA、LN、CⅣ、PCⅢ比较,差异有统计学意义(P<0.05);且进展性纤维化组各指标均高于早期纤维化组、无纤维化组,早期纤维化组各指标均高于无纤维化组(P<0.05);LSM、HA、LN、CⅣ、PCⅢ均与肝纤维化程度呈正相关,相关系数分别为0.949、0.912、0.898、0.867、0.893(P<0.05);ROC曲线分析显示,LSM、HA、LN、CⅣ、PCⅢ、联合检测肝纤维化曲线下面积(area under curve,AUC)分别为0.790、0.839、0.623、0.863、0.804、0.968,联合检测预测效果最好,且联合检测敏感度高于其他各项单独检测指标(P<0.05)。结论慢性乙型肝炎患者LSM、HA、LN、CⅣ、PCⅢ均与肝纤维化程度呈正相关,上述指标联合检查效果最好,敏感度最高,临床可联合检测上述指标诊断肝纤维化。

基于血清代谢组学研究佛手柑内酯治疗肝纤维化的作用机制

目的 基于血清代谢组学技术研究佛手柑内酯(BP)治疗肝纤维化的作用及机制。方法 将40只小鼠分为正常对照组(0.5%羧甲基纤维素钠溶液)、模型组(0.5%羧甲基纤维素钠溶液)和BP低、高剂量组(50、100 mg/kg),每组10只。除正常对照组外其余3组小鼠均采用四氯化碳诱导肝纤维化模型。同时,各组小鼠灌胃相应药物/溶剂,每日1次,连续8周。末次给药后,检测小鼠血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,观察小鼠肝组织病理形态学变化,检测小鼠肝组织中α-平滑肌肌动蛋白(α-SMA)、Ⅰ型胶原蛋白(CollagenⅠ)表达,同时对小鼠血清进行代谢组学分析。结果 与模型组比较,BP低、高剂量组小鼠血清中ALT、AST水平和肝组织中α-SMA、CollagenⅠ蛋白表达水平均显著降低(P<0.05),肝组织的纤维化程度显著改善。代谢组学结果显示,BP高剂量组和模型组共有175个血清差异代谢物,其中18个物质上调、157个物质下调,涉及的主要代谢途径有嘧啶代谢、丁酸盐代谢、脂肪酸合成、酪氨酸代谢、β-丙氨酸代谢、烟酸和烟酰胺代谢以及谷胱甘肽代谢等。结论 BP可能通过调节肝纤维化小鼠血清中嘧啶代谢、丁酸盐代谢和谷胱甘肽代谢等途径达到治疗肝纤维化的作用。

血清ADA水平和T-spot.TB联合检测在肺结核诊断中的应用

目的探讨分析肺结核诊断中联合应用血清腺苷脱氨酶(ADA)以及结核感染T细胞斑点试验(T-spot.TB)检测的临床价值。方法随机选取该院2015年1月—2016年10月收治的140例拟诊为肺结核患者分为治疗组(肺结核患者,70例)和对照组(非肺结核健康者,70例),对比两组ADA水平以及T-spot.TB阳性率以及联合检测的灵敏度、特异性等情况。结果治疗组患者ADA水平显著高于对照组(P<0.05),治疗组患者ADA检测阳性率(55.7%)、T-spot.TB阳性率(88.6%)显著高于对照组(15.7%、17.1%)。血清ADA、T-spot.TB平行联合检测可提高对肺结核诊断灵敏度(91.6%)及阴性预测值(93.6%),但阳性预测值、特异性明显下降,系列联合检测可提高对肺结核诊断的特异性(94.9%)、阳性预测值(86.2%),但是灵敏度、阴性预测值较低。结论肺结核患者采用血清ADA水平以及T-spot.TB斑点数联合检测的临床价值较高,值得推荐。

Metabolomics in liver diseases: A novel alternative for liver biopsy?

Hepatitis C virus(HCV)remains a significant public health problem as it can cause acute and chronic hepatitis.Chronic HCV infection is a major cause of liver fibrosis,and evaluation of liver fibrosis is essential because the prognosis of patients with chronic HCV infection is closely related to the stage of fibrosis.Liver fibrosis is traditionally evaluated based on pathological analysis of biopsy specimens,which is considered the gold standard.Nevertheless,liver biopsy is invasive and susceptible to sampling error and inter-and intraobserver variation in pathological interpretation;it is also costly.Therefore,noninvasive diagnostic investigations have been developed,including the use of fibrotic markers,scoring systems based on routine blood tests,and transient elastography with magnetic resonance imaging or ultrasonography.Recently,metabolomics,an emerging technology,has been used to detect the fibrosis stage.In this editorial,I comment on the article titled“Metabolomics in chronic hepatitis C:Decoding fibrosis grading and underlying pathways”by Ferrasi et al published in the recent issue of the World Journal of Hepatology.I discuss previous studies on the use of metabolome analysis for the diagnosis of HCV-related liver fibrosis and the potential development of biopsy-free diagnostic techniques.

聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗HBeAg阳性慢性乙肝的临床效果

目的观察聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗乙肝e抗原(HBeAg)阳性慢性乙肝的临床效果。方法选取2019年1月—2023年1月厦门市第三医院收治的HBeAg阳性慢性乙肝患者80例,按随机数字表法分为联合组(n=40)和单药组(n=40)。单药组予替诺福韦二吡呋酯治疗,联合组在单药组基础上予聚乙二醇干扰素α-2b治疗,2组均持续治疗6个月。比较2组HBeAg及乙肝病毒脱氧核糖核酸(HBV-DNA)转阴率,治疗前后肝功能指标[天冬氨酸氨基转移酶(AST)、丙氨酸氨基转移酶(ALT)、总胆红素(TBil)]、血清炎性因子[肿瘤坏死因子-α(TNF-α)、白介素(IL)-6、IL-10]、肝纤维化指标[透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层粘连蛋白(LN)]及不良反应。结果与单药组比较,联合组HBeAg及HBV-DNA转阴率均更高(χ^(2)=10.208,P=0.001;χ^(2)=4.507,P=0.034);与治疗前比较,治疗6个月后,2组AST、ALT、TBil、TNF-α、IL-6、IL-10、HA、PCⅢ、LN水平均降低,且联合组低于单药组(P<0.01)。联合组与单药组不良反应总发生率比较差异不明显(12.50%vs.7.50%,χ^(2)=0.139,P=0.709)。结论HBeAg阳性慢性乙肝患者应用聚乙二醇干扰素α-2b联合替诺福韦二吡呋酯治疗效果确切,有助于提高HBeAg、HBV-DNA转阴率,改善肝功能,减轻炎性反应及肝纤维化程度,且安全性较高。

血清铁蛋白可识别肠衰竭相关性肝病

目的:探讨血清铁蛋白在肠衰竭相关性肝病中的诊断价值。方法:回顾性分析2019年1月至2022年12月在南京大学附属金陵医院普通外科收治的成人短肠综合征病人的临床资料,通过线性回归确定血清铁蛋白和肝脏酶谱的相关性,通过多因素Logistic回归分析筛选肝损伤的潜在危险因素,并建立肝纤维化预测模型。同时计算曲线下面积以评估模型的准确性。结果:共纳入106例短肠综合征病人,其中血清铁蛋白(SF)升高的有55例(51.9%)。线性回归分析显示血清铁蛋白和ALT(r=0.427,P<0.001)、ALP(r=0.365,P<0.001)以及γ-GT(r=0.423,P<0.001)呈正相关,单因素Logistic回归分析显示血清铁蛋白水平越高,差异越明显[SF>ULN(血清铁蛋白正常值上限),P=0.033;SF>1.5×ULN,P=0.018;SF>2.5×ULN,P=0.006]。多因素Logistic回归分析显示:PN依赖(OR=3.366,P=0.017)、血清铁蛋白>2.5 ULN(OR=3.292,P=0.014)是肠衰竭相关性肝病—肝纤维化的独立危险因素,受试者工作曲线(ROC)显示曲线下面积为74.8%,95%CI:0.652~0.844。结论:血清铁蛋白可作为一个可靠的临床生物标志物,帮助识别肠衰竭相关性肝病。

血清病毒学、肝纤维化分级对慢性乙型肝炎患者合并肝脂肪变性的预测效能及相关性

目的:探索慢性乙型肝炎患者血清病毒学、肝纤维化分级对慢性乙型肝炎合并肝脂肪变性的预测效能及相关性。方法:选择2021年6月至2023年6月150例行肝穿刺活组织检查的慢性乙型肝炎患者作为观察对象,根据肝脏病理中脂肪变性是否≥5%,分为脂肪变性组(脂肪变性≥5%,n=54)和非脂肪变性组(脂肪变性<5%,n=96),回顾性分析两组患者各项临床指标,研究肝脂肪变性与AST、ALT、HBeAg、HBsAg、HBV DNA、肝纤维化分级相关性;进一步分析影响慢性乙型肝炎患者肝脂肪变性的独立因素。结果:两组患者AST、ALT、HBeAg、HBsAg、HBV DNA、肝纤维化分级差异具有统计学意义(P<0.05)。二元Logistic回归分析结果显示,HBeAg、HBsAg、HBV DNA、肝纤维化分级是导致患者肝脂肪变性的危险因素,AST、ALT属于保护因子。Spearman法分析结果显示,肝脂肪变性与AST、ALT呈负相关,与HBeAg、HBsAg、HBV DNA、肝纤维化分级呈正相关(P<0.05)。经ROC曲线分析,AST、ALT、HBeAg、HBsAg、HBV DNA、肝纤维化分级预测肝脂肪变性的AUC分别为0.928、0.802、0.925、0.903、0.917、0.813。结论:慢性乙型肝炎患者HBeAg、HBsAg、HBV DNA水平及肝纤维化分级与肝脂肪变性存在一定关联,且通过重点监测血清病毒学指标以及肝纤维化分级,能够更好预测患者肝脂肪变性情况。