Lymphocyte-to-white blood cell ratio is associated with outcome in patients with hepatitis B virus-related acute-on-chronic liver failure

BACKGROUND The lymphocyte-to-white blood cell ratio(LWR)is a blood marker of the systemic inflammatory response.The prognostic value of LWR in patients with hepatitis B virus-associated acute-on-chronic liver failure(HBV-ACLF)remains unclear.AIM To explore whether LWR could stratify the risk of poor outcomes in HBV-ACLF patients.METHODS This study was conducted by recruiting 330 patients with HBV-ACLF at the Department of Gastroenterology in a large tertiary hospital.Patients were divided into survivor and non-survivor groups according to their 28-d prognosis.The independent risk factors for 28-d mortality were calculated by univariate and multivariate Cox regression analyses.Patients were divided into low-and high-LWR groups according to the cutoff values.Kaplan-Meier analysis was performed according to the level of LWR.RESULTS During the 28-d follow-up time,135 patients died,and the mortality rate was 40.90%.The LWR level in non-surviving patients was significantly decreased compared to that in surviving patients.A lower LWR level was an independent risk factor for poor 28-d outcomes(hazard ratio=0.052,95%confidence interval:0.005-0.535).The LWR level was significantly negatively correlated with the Child-Turcotte-Pugh,model for end-stage liver disease,and Chinese Group on the Study of Severe Hepatitis B-ACLF II scores.In addition,the 28-d mortality was higher for patients with LWR<0.11 than for those with LWR≥0.11.CONCLUSION LWR may serve as a simple and useful tool for stratifying the risk of poor 28-d outcomes in HBVACLF patients.

Value of gamma-glutamyltranspeptidase-to-platelet ratio in diagnosis of hepatic fibrosis in patients with chronic hepatitis B

AIM To investigate the value of the gamma-glutamyltraspeptidase(GGT)-to-platelet(PLT) ratio(GPR) in the diagnosis of hepatic fibrosis in patients with chronic hepatitis B(CHB). METHODS We included 390 untreated CHB patients in this study. The GPR, aspartate aminotransferase(AST)-to-PLT ratio index(APRI), and fibrosis-4(FIB-4) of all patients were analysed to determine if these parameter were correlated with age, gender, medical history, liver function [total bilirubin(TBil), alanine aminotransferase(ALT), and AST], GGT, PLT count, or hepatic fibrosis stage. The GPR, APRI, and FIB-4, as well as the combination of the GPR and APRI or the GPR and FIB-4 were assessed in different cirrhosis stages using receiver operating characteristic(ROC) curve analysis to evaluate their value in diagnosing hepatic fibrosis in CHB patients. RESULTS The GPR, APRI, and FIB-4 were not correlated withCHB patients' age, gender, or disease duration(P > 0.05), but all of these parameters were positively correlated with serum ALT, AST, GGT, and PLT count(P < 0.01). Additionally, the GPR, APRI, and FIB-4 were positively correlated with hepatic fibrosis(P < 0.01); the areas under the ROC curve for the GPR in F1, F2, F3, and F4 stages were 0.723, 0.741, 0.826, and 0.833, respectively, which were significantly higher than the respective values for the FIB-4 and APRI(F1: 0.581, 0.612; F2: 0.706, 0.711; F3: 0.73, 0.751; and F4: 0.799, 0.778). The respective diagnostic cut-off points for each stage were 0.402, 0.448, 0.548, and 0.833, respectively. The diagnostic sensitivity and specificity were, respectively, 88.8% and 87.5% in F1, 72.7% and 89.7% in F2, 81.3% and 98.6% in F3, and 80% and 97.4% in F4 when the GPR and APRI were connected in parallel; 86.6% and 90.2%, 78.4% and 96%, 78.6% and 97.4%, and 73.2% and 97.9%, respectively, when the GPR and APRI were connected in series; 80.2% and 89%, 65% and 89%, 70.3% and 98.5%, and 78.8% and 96.8%, respectively, when the GPR and FIB-4 were connected in parallel; and 83.6% and 87.9%, 76.8% and 96.6%, 72.7% and 98%, and 74.4% and 97.7%, respectively, when the GPR and FIB-4 were connected in series.CONCLUSION The GPR, as a serum diagnostic index of liver fibrosis, is more accurate, sensitive, and easy to use than the FIB-4 and APRI, and the GPR can significantly improve the sensitivity and specificity of hepatic fibrosis diagnosis in CHB when combined with the FIB-4 or APRI.

Diagnostic value of FIB-4, aspartate aminotransferaseto-platelet ratio index and liver stiffness measurement in hepatitis B virus-infected patients with persistently normal alanine aminotransferase

AIM To assess the diagnostic value of FIB-4, aspartate aminotransferase-to-platelet ratio index(APRI), and liver stiffness measurement(LSM) in patients with hepatitis B virus infection who have persistently normal alanine transaminase(PNALT).METHODS We enrolled 245 patients with chronic hepatitis B: 95 in PNALT group, 86 in intermittently elevated alanine transaminase(PIALT1) group [alanine transaminase(ALT) within 1-2 × upper limit of normal value(ULN)], and 64 in PIALT2 group(ALT > 2 × ULN). All the patients received a percutaneous liver biopsy guided by ultrasonography. LSM, biochemical tests, and complete blood cell counts were performed.RESULTS The pathological examination revealed moderate inflammatory necrosis ratios of 16.81%(16/95), 32.56%(28/86), and 45.31%(28/64), and moderate liverfibrosis of 24.2%(23/95), 33.72%(29/86), and 43.75%(28/64) in the PNALT, PIALT1, and PIALT2 groups, respectively. The degrees of inflammation and liver fibrosis were significantly higher in the PIALT groups than in the PNALT group(P < 0.05). No significant difference was found in the areas under the curve(AUCs) between APRI and FIB-4 in the PNALT group; however, significant differences were found between APRI and LSM, and between FIB-4 and LSM in the PNALT group(P < 0.05 for both). In the PIALT1 and PIALT2 groups, no significant difference(P > 0.05) was found in AUCs for all comparisons(P > 0.05 for all). In the overall patients, a significant difference in the AUCs was found only between LSM and APRI(P < 0.05).CONCLUSION APRI and FIB-4 are not the ideal noninvasive hepatic fibrosis markers for PNALT patients. LSM is superior to APRI and FIB-4 in PNALT patients because of the influence of liver inflammation and necrosis.

Total cholesterol to high-density lipoprotein ratio and nonalcoholic fatty liver disease in a population with chronic hepatitis B

BACKGROUND Nonalcoholic fatty liver disease(NAFLD)is characterized by hypertriglyceridemia,increased low-density lipoprotein cholesterol levels,and reduced highdensity lipoprotein cholesterol(HDL-C)particles.Previous studies have shown that the total cholesterol to high-density lipoprotein cholesterol ratio(TC/HDL-C)was superior to other lipid metabolism biomarkers for predicting NAFLD risk and could be a new indicator of NAFLD.However,the association between TC/HDL-C and NAFLD in patients with hepatitis B virus(HBV)has not yet been determined.AIM To investigate the association between TC/HDL-C and NAFLD in a population with chronic hepatitis B(CHB).METHODS In this study,183 HBV-infected patients were enrolled.All participants underwent blood chemistry examinations and abdominal ultrasound.Univariate and multivariate logistic regression models,curve fitting analysis,and threshold calculation were used to assess the relationship between TC/HDL-C and NAFLD.RESULTS The overall prevalence of NAFLD was 17.49%(n=32)in the 183 CHB participants.The TC/HDL-C of non-NAFLD and NAFLD patients were 3.83±0.75 and 4.44±0.77,respectively(P<0.01).Logistic regression analysis showed that TC/HDL-C was not associated with NAFLD after adjusting for other pertinent clinical variables.However,at an optimal cutoff point of 4.9,a non-linear correlation between TC/HDL-C and NAFLD was detected.The effect size of the left and right sides of the inflection point were 5.4(95%confidence interval:2.3-12.6,P<0.01)and 0.5(95%confidence interval:0.1-2.2,P=0.39),respectively.On the left side of the inflection point,TC/HDL-C was positively associated with NAFLD.However,no significant association was observed on the right side of the inflection point.CONCLUSION This study demonstrated a non-linear correlation between TC/HDL-C and NAFLD in a population with CHB.TC/HDL-C was positively associated with NAFLD when TC/HDL-C was less than 4.9 but not when TC/HDL-C was more than 4.9.

Is the neutrophil to lymphocyte ratio associated with liver fibrosis in patients with chronic hepatitis B?

AIM: To determine the association between the neutrophil to lymphocyte(N/L) ratio and the degree of liver fibrosis in patients with chronic hepatitis B(CHB) infection. METHODS: Between December 2011 and February 2013, 129 consecutive CHB patients who were admitted to the study hospitals for histological evaluation of chronic hepatitis B-related liver fibrosis were included in this retrospective study. The patients were divided into two groups based on the fibrosis score: individuals with a fibrosis score of F0 or F1 were included in the "no/minimal liver fibrosis" group, whereas patients with a fibrosis score of F2, F3, or F4 were included in the "advanced liver fibrosis" group. The Statistical Package for Social Sciences 18.0 for Windows was used to analyze the data. A P value of < 0.05 was accepted as statistically significant.RESULTS: Three experienced and blinded pathologists evaluated the fibrotic status and inflammatory activity of 129 liver biopsy samples from the CHB patients. Following histopathological examination, the "no/minimal fibrosis" group included 79 individuals, while the "advanced fibrosis" group included 50 individuals. Mean(N/L) ratio levels were notably lower in patients with advanced fibrosis when compared with patients with no/minimal fibrosis. The mean value of the aspartate aminotransferase-platelet ratio index was markedly higher in cases with advanced fibrosis compared to those with no/minimal fibrosis.CONCLUSION: Reduced levels of the peripheral blood N/L ratio were found to give high sensitivity, specificity and predictive values in CHB patients with significant fibrosis. The prominent finding of our research suggests that the N/L ratio can be used as a novel noninvasive marker of fibrosis in patients with CHB.

Noninvasive assessment of liver fibrosis with combined serum aminotransferase/platelet ratio index and hyaluronic acid in patients with chronic hepatitis B

AIM:To construct a noninvasive assessment model consisting of routine laboratory data to predict significant fibrosis and cirrhosis in patients with chronic hepatitis B (CHB). METHODS: A total of 137 consecutive patients with CHB who underwent percutaneous liver biopsy were retrospectively analyzed. These patients were divided into two groups according to their aminotransferase (ALT) level. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), the likelihood ratio (LR) of aminotransferase/platelet ratio index (APRI)≥1.5 or <1.5 in combination with different hyaluronic acid (HA) cut-off points were calculated for the presence of moderate to severe fibrosis/cirrhosis (fibrosis stages 2 and 4) and no to mild fibrosis/cirrhosis (fibrosis stages 0 and 1). RESULTS: The APRI correlated with fibrosis stage in CHB patients. The APRI≥1.5 in combination with a cut-off HA cut-off point >300 ng/mL could detect moderate to severe fibrosis (stages 2-4) in CHB patients. The PPV was 93.7%, the specificity was 98.9%. The APRI <1.5 in combination with different HA cut-off points could not detect no to mild fibrosis in CHB patients. CONCLUSION: The APRI≥ 1.5 in combination with a HA cut-off point >300ng/mL can detect moderate to severe fibrosis (stages 2-4) in CHB patients.

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.

Difference in incidence of developing hepatocellular carcinoma between hepatitis B virus-and hepatitis C virus-infected patients

BACKGROUND It is generally accepted that the incidence of hepatocellular carcinoma(HCC)in hepatitis C virus(HCV)-associated patients is higher than that in hepatitis B virus(HBV)-associated patients.The reason why this difference in the incidence of HCC occurs in patients with HBV and HCV infections remains unclear.We report the possibility that the contributing power of inflammation,which is the main risk factor for developing HCC,may be different with HBV and HCV infections.AIM To investigate this,we surveyed the hazard ratio of inflammation for HCC development which was identified by serum alanine aminotransferase(ALT)levels between patients with HBV and HCV infections.METHODS The PubMed database was searched(2001-2021)for studies published in English regarding the incidence of HCC identifying 8924 HBV-and 7376 HCV-infected patients.From these studies,interferon-treated patients with both HBV and HCV infections were excluded.Furthermore,in HBV patients,those administered nucleos(t)ide analogues were excluded,and in HCV patients,those administered direct acting antivirals were also excluded.Studies citing hazard ratios of HCC regarding inflammation(serum elevated alanine aminotransferase levels)were selected.Finally,there were 14 studies of HBV-infected patients and 8 studies of HCV-infected patients.We calculated the hazard ratio in patients in an inflammatory state(serum ALT levels were above the normal range).RESULTS In the 14 studies of HBV patients,the average hazard ratio(HR)of elevated ALT for developing HCC was 2.74[1.98-3.77]and that in the 8 studies of HCV-infected patients was 5.51[3.08-9.83].The HR of inflammation for HCC development in HCV-associated liver diseases is about twice that in HBV-associated liver diseases.HR in HCV-infected patients was significantly(P=0.0391)higher than that in HBV-infected patients.In hepatitis B patients,the abnormal range adopted was 28-45 IU/L,and in hepatitis C patients,it was 20-50 IU/L.It was demonstrated that the abnormal ALT levels adopted in hepatitis B and C patients were very similar in this series.CONCLUSION The difference in the incidence of HCC development between HBV and HCV patients may depend on the difference in the hazard risk of ALT between HBV and HCV infections.

Serum angiotensin-converting enzyme level for evaluating significant fibrosis in chronic hepatitis B

AIM To evaluate the diagnostic performance of angiotensinconverting enzyme(ACE)on significant liver fibrosis in patients with chronic hepatitis B(CHB). METHODS In total,100 patients with CHB who underwent liver biopsy in our hospital were enrolled,and 70 patients except for 30 patients with hypertension,fatty liver or habitual alcoholic consumption were analyzed.We compared histological liver fibrosis and serum ACE levels and evaluated the predictive potential to diagnose significant liver fibrosis by comparison with several biochemical marker-based indexes such as the aspartate aminotransferase(AST)-to-platelet ratio index(APRI),the fibrosis index based on four factors(FIB-4),the Mac-2 binding protein glycosylation isomer(M2BPGi)level and the number of platelets(Plt). RESULTS Serum ACE levels showed moderately positive correlation with liver fibrotic stages(R2=0.181).Patients with significant,advanced fibrosis and cirrhosis(F2-4)had significantly higher serum ACE levels than those with early-stage fibrosis and cirrhosis(F0-1).For significant fibrosis(≥F2),the 12.8 U/L cut-off value of ACE showed 91.7%sensitivity and 75.0%specificity.The receiver-operating characteristic(ROC)curves analysis revealed that the area under the curve(AUC)value of ACE was 0.871,which was higher than that of APRI,FIB-4,M2BPGi and Plt. CONCLUSION The serum ACE level could be a novel noninvasive,easy,accurate,and inexpensive marker of significant fibrosis stage in patients with CHB.

Non-invasive diagnosis of hepatitis B virus-related cirrhosis

Chronic hepatitis B(CHB)infection is a major public health problem associated with significant morbidity and mortality worldwide.Twenty-three percent of patients with CHB progress naturally to liver cirrhosis,which was earlier thought to be irreversible.However,it is now known that cirrhosis can in fact be reversed by treatment with oral anti-nucleotide drugs.Thus,early and accurate diagnosis of cirrhosis is important to allow an appropriate treatment strategy to be chosen and to predict the prognosis of patients with CHB.Liver biopsy is the reference standard for assessment of liver fibrosis.However,the method is invasive,and is associated with pain and complications that can be fatal.In addition,intra-and inter-observer variability compromises the accuracy of liver biopsy data.Only small tissue samples are obtained and fibrosis is heterogeneous in such samples.This confounds the two types of observer variability mentioned above.Such limitations have encouraged development of non-invasive methods for assessment of fibrosis.These include measurements of serum biomarkers of fibrosis;and assessment of liver stiffness via transient elastography,acoustic radiation force impulse imaging,real-time elastography,or magnetic resonance elastography.Although significant advances have been made,most work to date has addressed the diagnostic utility of these techniques in the context of cirrhosis caused by chronic hepatitis C infection.In the present review,we examine the advantages afforded by use of non-invasive methods to diagnose cirrhosis in patients with CHB infections and the utility of such methods in clinical practice.

EFFECTS OF ACUPUNCTURE ON THE IMMUNOLOGICAL FUNCTIONS IN HEPATITIS B VIRUS CARRIERS

A contrast study on the effects of manual acupuncture and electroacupuncture wasconducted in 60 cases of chronic hepatitis B carriers.The results demonstrated that theimmunological functions,both cellular and humoral,were markedly regulated asevidenced by the negative turnover rates of HBsAg,HBeAg,anti-HBc and HBcAg,as wellas the positive turnover rate of anti-HBe.

Optimal use of red cell volume distribution width-to-platelet ratio to exclude cirrhosis in patients with chronic hepatitis B

Background and aims:Hepatitis B virus(HBV)infection is a major public health issue worldwide as it may cause serious liver diseases such as cirrhosis and hepatocellular carcinoma(HCC).Ruling out cirrhosis is important when treating chronic hepatitis B(CHB).The aim of this study was to compare the performance of the aspartate aminotransferase-to-platelet ratio index(APRI),fibrosis score based on four factors(FIB-4),and red cell volume distribution width-to-platelet ratio(RPR)in diagnosing liver fibrosis stages and to identify new cut-off values to rule out cirrhosis.Methods:Between 2005 and 2020,2182 eligible individuals who underwent liver biopsy were randomly assigned to derivation and validation cohorts in a 6:4 ratio.A grid search was applied to identify optimal cut-off values with a sensitivity of>90% and a negative predictive value(NPV)of at least 95%.Results:Overall,1309 individuals(175 patients with cirrhosis)were included in the derivation dataset,and 873(117 patients with cirrhosis)were included in the validation cohort.The area under the receiver operating characteristic curve of RPR for diagnosing cirrhosis was 0.821,which was comparable to that of APRI(0.818,P=0.7905)and FIB-4(0.803,P=0.2395).When applying an RPR of 0.06,cirrhosis was correctly identified with a sensitivity of 93.1% and an NPV of 97.1%,while it misclassified 12 of 175(6.9%)patients in the derivation cohort.In the validation cohort,RPR had a sensitivity and NPV of 97.4% and 99.0%,respectively,and only misclassified 3 of 117(2.6%)patients.Subgroup analysis indicated that the new RPR cut-off value performed more consistently than that of APRI and FIB-4 in all subgroups.Conclusion:A recently established cut-off value for RPR(≤0.06)was validated and was more effective than APRI and FIB-4 in excluding patients with cirrhosis due to a higher sensitivity and NPV and a lower misclassification rate.This simple and dependable test could have significant clinical implications in identifying patients who require monitoring for portal hypertension-associated complications and screening for HCC,particularly in middle and primary healthcare settings.

Combined Hangzhou criteria with neutrophillymphocyte ratio is superior to other criteria in selecting liver transplantation candidates with HBV-related hepatocellular carcinoma

BACKGROUND： The elevation of neutrophil-lymphocyte ratio （NLR） has adverse effects on the prognosis of patients with hepatocellular carcinoma （HCC） who have received liver transplantation （LT）. The Hangzhou criteria are set for selecting HCC patients for LT. The present study aimed to establish a set of new criteria combining the NLR and Hangzhou crite- ria for selecting HCC patients for LT.

LMR/LDH对弥漫大B细胞淋巴瘤合并乙型病毒性肝炎患者预后的价值

目的探讨外周血淋巴细胞/单核细胞比值(LMR)与乳酸脱氢酶(LDH)的比值(LMR/LDH)对弥漫大B细胞淋巴瘤(DLBCL)合并乙型病毒性肝炎患者预后的价值。方法选取DLBCL合并乙型病毒性肝炎患者77例为研究对象,收集患者的临床资料[性别、年龄、临床分期、B症状、美国东部肿瘤协作组(ECOG)评分、淋巴结外受累数量、国际预后指数(IPI)分级等];抽取治疗前空腹抗凝全血及静脉血,采用电阻抗、高频电导及激光散射联合检测法检测淋巴细胞绝对值和单核细胞绝对值并计算LMR,采用紫外分光光度法和免疫比浊法检测血清乳酸脱氢酶(LDH)和β2-微球蛋白(β2-MG);所有患者出院后随访36个月,记录患者的总生存期(OS)及无进展生存期(PFS);采用患者工作特征(ROC)曲线确定LMR/LDH的临界值,分析LMR/LDH高低对患者OS及PFS的影响;采用COX回归模型分析LMR/LDH与患者临床特征的关系。结果ROC曲线分析显示,LMR/LDH的临界值为0.008,敏感度和特异度分别为0.6607和0.7619,曲线下面积(AUC)为0.7054(95%CI为0.5491~0.8937,P=0.0057);LMR/LDH与临床分期、ECOG评分、淋巴结外受累数量、IPI、LDH、β2-MG相关(P<0.05);单因素分析显示,LMR/LDH、临床分期、ECOG≥2分、淋巴结外受累数量≥2个、IPI、LDH及β2-MG对患者OS及PFS均有影响(P<0.05);多因素分析显示,LMR/LDH是影响DLBCL合并乙型病毒性肝炎患者OS及PFS的独立危险因素(P<0.05);高LMR/LDH组的OS与PFS高于低LMR/LDH组。结论LMR/LDH对DLBCL合并乙型病毒性肝炎患者的预后有一定的临床预测价值。

血常规衍生指标与HBV-DNA载量及ALT关系的研究

目的:选择中性粒细胞淋巴细胞比值(NLR)、血小板淋巴细胞比值(PLR)和血清谷丙转氨酶(ALT)、HBV-DNA作为研究指标,通过分析HBV感染者外周血NLR、PLR的表达与疾病进程及HBV-DNA载量和ALT的关系,探讨NLR和PLR在慢性乙型肝炎患者病情发展的临床意义。方法:收集慢性乙型肝炎患者475例外周血标本,检测血常规、肝功能和乙肝DNA水平,按照HBV-DNA载量水平不同分为阴性组(作为对照组)、低拷贝组、中拷贝组、高拷贝组,分别比较HBV-DNA升高组与阴性组外周血NLR、PLR水平,分析其差异性;同时按照ALT升高水平分为轻、中、重度三个观察组和正常对照组,分别比较观察组与正常组对应的外周血NLR、PLR水平,查找规律;对HBV-DNA阳性的患者在进行药物治疗过程中,监测血NLR、PLR水平变化。结果:NLR与疾病的进展有一定的相关性,其中中拷贝组和高拷贝组与阴性组比较,差异有统计学意义(P均<0.05);而PLR与HBV-DNA未发现有显著相关性,但三个升高组与阴性组比较,PLR数值差异有统计学意义(P均<0.05);随着ALT的逐步升高,NLR也随着升高,轻度和中度升高组,NLR变化不大,但重度升高组与正常组比较,差异有统计学意义(P<0.05);而PLR与ALT的关系不大,差异无统计学意义(P均>0.05);在抗病毒治疗的早期,由于淋巴细胞数量的减少,NLR和PLR会一时性升高。结论:NLR和PLR具有评估慢性HBV感染患者肝脏炎症活动度的临床应用价值,持续动态检测这两个指标的变化对慢性乙肝患者的病情预判有一定的指导作用。

AARC-ACLF评分联合NLR对HBV相关慢加急性肝衰竭短期预后的评估价值

目的探究亚太肝脏研究协会ACLF(AARC-ACLF)评分联合中性粒细胞与淋巴细胞比值(NLR)对HBV相关慢加急性肝衰竭(ACLF)短期预后的预测价值。方法选择94例HBV相关ACLF患者作为研究对象,于入组24 h内检测NLR,计算AARC-ACLF评分。根据临床疗效及生存情况,分为转归良好组及不佳组。分析HBV相关ACLF患者病情转归的影响因素。评估AARC-ACLF评分和血清NLR水平对HBV相关ACLF预后的预测效能。结果94例受试者中,转归良好58例,转归不佳36例。转归不佳组凝血酶原时间(PT)、总胆红素(TBil)、白细胞(WBC)、NLR及AARC-ACLF评分分别为(26.68±6.91)s、(330.2±126.4)μmol/L、(6.67±2.06)×10^(9)/L、6.45±2.76、(10.14±1.29)分,转归良好组为(20.32±4.20)s、(180.1±83.7)μmol/L、(5.06±1.97)×10^(9)/L、2.85±1.67、(8.03±1.09)分,差异有统计学意义(P<0.05)。NLR及AARC-ACLF评分偏高均为HBV相关ACLF患者病情转归不佳的影响因素(P<0.05);血清NLR、AARC-ACLF评分、NLR联合AARC-ACLF评分预测HBV相关ACLF患者预后的AUC分别为0.878、0.892、0.943。结论HBV相关ACLF患者的血清NLR及AARC-ACLF评分均较高,对该病的短期预后具有一定的临床预测价值,且两者联合预测效能更高。

PT和γ-GT/Alb比值对慢性乙型肝炎患者肝纤维化分期的预测价值

目的:评估凝血酶原时间(PT)、γ-谷氨酰转肽酶/白蛋白(γ-GT/Alb)比值对慢性乙型肝炎(CHB)患者肝纤维化分期的预测价值,并与经典无创模型天冬氨酸氨基转移酶/血小板比值指数(APRI)评分、4因子模型(FIB-4)进行对比。方法:收集2020年4月至2021年5月北京中医药大学东方医院收治的108例CHB肝纤维化患者病例资料作回顾性分析,根据肝活检病理结果将患者分为无或轻度肝纤维化组(S0~S1期,68例)、显著肝纤维化组(≥S2期,40例)。收集患者的血清学指标、APRI、FIB-4等数据,运用单因素分析、多因素logitstic回归分析筛选出独立预测指标并建立综合预测模型,同时采用受试者工作特征曲线(ROC)评价综合模型的预测准确性。结果:单因素分析结果显示,两组患者在γ-GT、Alb、γ-GT/Alb、PT、LN、PLT方面比较,差异具有统计学意义(均P<0.05);多因素logitstic回归分析结果显示,PT和γ-GT/Alb是显著肝纤维化的独立预测指标(P<0.05)。依据logistic回归分析结果建立综合预测模型[logit(P)=-4.926+0.048×γ-GT/Alb+0.147×PT],其ROC曲线下面积(AUC)为0.839,截断值为0.469时,敏感度为78.04%,特异度为97.09%。预测肝纤维化的准确性明显优于APRI及FIB-4,差异有统计学意义(P<0.05)。结论:PT和γ-GT/Alb的综合预测模型对预测CHB导致的显著肝纤维化(≥S2)具有优势,其预测准确性均高于APRI、FIB-4两项指标。

Restoring the Treg cell to Th17 cell ratio may alleviate HBV-related acute-on-chronic liver failure

AIM: To investigate the role of T helper 17 cells (Th17) and regulatory T cells (Treg) in hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).METHODS: We enrolled 79 patients with HBV infection into the study, 50 patients with HBV-related ACLF and 29 patients with chronic hepatitis B (CHB), from the First Affiliated Hospital of Medical College from January 2009 to June 2012. The ACLF patients were diagnosed according to the criteria recommended by The 19th Conference of the Asian Pacific Association for the Study of the Liver in 2009. Twenty healthy individuals with a similar gender and age structures to the two patient groups were also included as the normal controls (NC). Of the 50 ACLF patients, 28 were subsequently classified as non-survivors: 19 patients died from multiorgan failure, 3 underwent liver transplantation, and 6 discontinued therapy during follow-up because of financial reasons. The remaining 22 ACLF patients whose liver and anticoagulation function recovered to nearly normal levels within the next 6 mo were classified as survivors. The number of circulating Treg and Th17 cells was determined upon diagnosis and during the 8th week of follow-up through flow cytometry. RESULTS: The percentage of circulating Treg cells in the ACLF group was significantly higher than that in the CHB group (5.50% ± 1.15% vs 3.30% ± 1.13%, P < 0.01). The percentages of circulating Th17 cells in the ACLF and the CHB groups were significantly higher than that in the NC group (6.32% ± 2.22% vs 1.56% ± 0.44%, P < 0.01; 3.53% ± 1.65% vs 1.56% ± 0.44%, P < 0.01). No significant difference in Treg cell to Th17 cell ratio was observed between the ACLF group and the CHB group (0.98 ± 0.44 vs 1.12 ± 0.64, P = 0.991), whereas those in the two HBV infection groups were significantly lower than that in the NC group (1.85 ± 1.22; both P < 0.01). The percentage of Treg cells in the survivors during the 8th week of follow-up was significantly lower than that during peak ACLF severity [total bilirubin (TBIL) peak] (3.45% ± 0.97% vs 5.18% ± 1.02%, P < 0.01). The percentage of Th17 cells in survivors during the 8th week of follow-up was significantly lower than that during the peak TBIL (2.89% ±0.60% vs 5.24% ± 1.46%; P < 0.01). The Treg cell to Th17 cell ratio during the 8 th week of follow-up was significantly higher than that during the TBIL peak (1.22 ± 0.36 vs 1.10 ± 0.54; P < 0.05). CONCLUSION: Restoring the Treg cell to Th17 cell ratio during the follow-up phase of ACLF could maintain the immune system at a steady state, which favours good prognosis.

Neutrophil-lymphocyte ratio predicts the prognosis of patients with hepatocellular carcinoma after liver transplantation

AIM:To determine whether an elevated neutrophillymphocyte ratio(NLR)is negatively associated with tumor recurrence in patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)after liver transplantation(LT),and to determine the optimal predictive NLR cut-off value.METHODS:The data of HCC patients who had undergone LT came from the China Liver Transplant Registry database.We collected data from 326 liver cancer patients who had undergone LT at our medical center.We divided the patients into groups based on their NLRs(3,4 or 5).We then compared the clinicopathological data and long-time survival between these groups.Meanwhile,we used receiver operating characteristic analysis to determine the optimal NLR cut-off.RESULTS:Of 280 HCC patients included in this study,263 were HBV positive.Patients with an NLR<3 and patients with an NLR≥3 but<4 showed no significant differences in overall survival(OS)(P=0.212)or disease-free survival(DFS)(P=0.601).Patients with an NLR≥4 but<5 and patients with an NLR≥5also showed no significant differences in OS(P=0.208)or DFS(P=0.618).The 1-,3-and 5-year OS rates of patients with an NLR<4 vs an NLR≥4 were 87.8%,63.8%and 61.5%vs 73.9%,36.7%and 30.3%,respectively(P<0.001).The 1-,3-and 5-year DFS rates of patients with an NLR<4 vs NLR≥4 were 83.9%,62.9%and 60.7%vs 64.9%,30.1%and 30.1%,respectively(P<0.001).Univariate and multivariate analyses demonstrated that three factors,including NLR≥4(P=0.002),were significant predictors of tumor recurrence in HCC patients after LT.CONCLUSION:A preoperative elevated NLR significantly increased the risk for tumor recurrence in HCC patients after LT.

APRI评分对HBV相关肝细胞癌切除术患者预后的预测价值

目的:评估天冬氨酸转氨酶与血小板计数比值指数(APRI)对HBV相关肝细胞癌(HCC)切除术患者术后总生存率(OS)的预测价值。方法:采用回顾性队列研究方法,收集2012年1月至2016年12月期间在广西医科大学附属肿瘤医院行切除术治疗的1 031例HBV相关HCC患者的术前临床资料。通过Kaplan-Meier生存曲线确定APRI评分的cutoff值。采用Kaplan-Meier法绘制不同APRI组患者的生存曲线,并通过Log-rank检验评估两组人群的生存差异。运用逐步多因素Cox回归筛选患者OS独立影响因素。采用限制性立方条图(RCS)评价患者APRI与死亡风险的相关性。建立列线图模型评估APRI对OS的预测能力并内部验证。结果:RCS显示APRI与死亡风险呈非线性关联(非线性P<0.001)。多因素Cox回归结果显示:APRI、BCLC分期、AFP、性别和肿瘤大小是OS独立影响因素,高APRI组死亡风险是低APRI组2.1倍。患者OS的列线图显示APRI对OS的预测能力仅次于BCLC分期。在建模组和验证组中预测OS列线图的C-in-dex分别为0.71(95%CI:0.68~0.74)、0.69(95%CI:0.64~0.75);1和5年OS校正曲线显示列线图具有良好的校准度;临床决策曲线(DCA)显示模型具有良好的临床应用价值。结论:APRI是HBV相关HCC切除术患者OS独立影响因素,基于APRI对患者预后进行分层,有利于进行个体化治疗和随访。