Risk factors for progression to acute-on-chronic liver failure during severe acute exacerbation of chronic hepatitis B virus infection

BACKGROUND Acute exacerbation in patients with chronic hepatitis B virus(HBV) infection results in different severities of liver injury. The risk factors related to progression to hepatic decompensation(HD) and acute-on-chronic liver failure(ACLF) in patients with severe acute exacerbation(SAE) of chronic HBV infection remain unknown.AIM To identify risk factors related to progression to HD and ACLF in compensated patients with SAE of chronic HBV infection.METHODS The baseline characteristics of 164 patients with SAE of chronic HBV infection were retrospectively reviewed. Independent risk factors associated with progression to HD and ACLF were identified. The predictive values of our previously established prediction model in patients with acute exacerbation(AE model) and the model for end-stage liver disease(MELD) score in predicting the development of ACLF were evaluated.RESULTS Among 164 patients with SAE, 83(50.6%) had compensated liver cirrhosis(LC),43 had progression to HD without ACLF, and 29 had progression to ACLF within 28 d after admission. Independent risk factors associated with progression to HD were LC and low alanine aminotransferase. Independent risk factors for progression to ACLF were LC, high MELD score, high aspartate aminotransferase(AST) levels, and low prothrombin activity(PTA). The area under the receiver operating characteristic of the AE model [0.844, 95%confidence interval(CI): 0.779-0.896] was significantly higher than that of MELD score(0.690, 95%CI: 0.613-0.760, P < 0.05) in predicting the development of ACLF.CONCLUSION In patients with SAE of chronic HBV infection, LC is an independent risk factor for progression to both HD and ACLF. High MELD score, high AST, and low PTA are associated with progression to ACLF. The AE model is a better predictor of ACLF development in patients with SAE than MELD score.

Importance of adequate immunosuppressive therapy for the recovery of patients with "life-threatening" severe exacerbation of chronic hepatitis B

AIM: Hepatitis B virus (HBV) re-activation often occurs spontaneously or after withdrawal of immunosuppressive therapy in patients with chronic hepatitis B. Severe exacerbation, sometimes developing into fulminant hepatic failure, is at high risk of mortality. The efficacy of corticosteroid therapy in "clinically severe" exacerbation of chronic hepatitis B has not been well demonstrated. In this study we evaluated the efficacy of early introduction of high-dose corticosteroid therapy in patients with lifethreatening severe exacerbation of chronic hepatitis B.METHODS: Twenty-two patients, 14 men and 8 women,were defined as "severe" exacerbation of chronic hepatitis B using uniform criteria and enrolled in this study. Eleven patients were treated with corticosteroids at 60 mg or more daily with or without anti-viral drugs within 10 d after the diagnosis of severe disease ("early high-dose"group) and 11 patients were either treated more than 10 d or untreated with corticosteroids ("non-early high-dose"group).RESULTS: Mean age, male-to-female ratio, mean prothrombin time (PT) activity, alanine transaminase (ALT)level, total bilirubin level, positivity of HBeAg, mean IgMHBc titer, and mean HBV DNA polymerase activity did not differ between the two groups. Ten of 11 patients of the "early high-dose" group survived, while only 2 of 11 patients of the "non-early high-dose" group survived (P＜0.001). During the first 2 wk after the introduction of corticosteroids, improvements in PT activities and total bilirubin levels were observed in the "early high-dose"group. Both ALT levels and HBV DNA polymerase levels fell in both groups.CONCLUSION: The introduction of high-dose corticosteroid can reverse deterioration in patients with "clinically lifethreatening" severe exacerbation of chronic hepatitis B,when used in the early stage of illness.

Portalsystemic hemodynamic changes in chronic severe hepatitis B: An ultrasonographic study

AIM:To evaluate portalsystemic hemodynamic changes in chronic severe hepatitis B. METHODS:Hemodynamic parameters included portal vein diameter (PVD), portal vein peak velocity (PVPV), portal vein volume (PVV), spleen length (SPL), spleen vein diameter (SPVD), spleen vein volume (SPVV) and umbilical vein recanalization. They were measured by Color Doppler ultrasonography in 36 patients with chronic severe hepatitis B, compared with 51 normal controls, 61 patients with chronic hepatitis B, 46 patients with compensable cirrhosis, and 36 patients with decompensable cirrhosis. RESULTS:In the group of chronic severe hepatitis B, PVD (12.38 ± 1.23 mm) was significantly different from the normal control, compensable cirrhosis and decompensable cirrhosis groups (P = 0.000-0.026), but not significantly different from the chronic hepatitis group. PVPV (16.15 ± 3.82 cm/s) dropped more significantly in the chronic severe hepatitis B group than the normal control, chronic hepatitis B and compensable cirrhosis groups (P = 0.000-0.011). PVV (667.53 ± 192.83 mL/min) dropped significantly as compared with the four comparison groups (P = 0.000-0.004). SPL (120.42 ± 18.36 mm) and SPVD (7.52 ± 1.52 mm) were longer in the normal control and chronic hepatitis B groups (P = 0.000-0.009), yet they were significantly shorter than those in the decompensable cirrhosis group (P = 0.000). SPVV (242.51 ± 137.70 mL/min) was also lower than the decompensable cirrhosis group (P = 0.000). The umbilical vein recanalization rate (75%) was higher than the chronic hepatitis B and compensable cirrhosis groups. In the course of progression from chronic hepatitis to decompensable cirrhosis, PVD, SPL and SPVD gradually increased and showed significant differences between every two groups (P = 0.000-0.002). CONCLUSION:Patients with chronic severe hepatitis B have a tendency to develop acute portal hypertension, resulting in significantly reduced portal vein perfusion. Observation of the portalsystemic hemodynamic changes may be contributed to the disease progression of chronic liver disease.

Combined human growth hormone and lactulose for prevention and treatment of multiple organ dysfunction in patients with severe chronic hepatitis B

AIM: To evaluate the efficiency and safety of combined recombinant human growth hormone (rhGH) and lactulose for treatment and/or prevention of multiple organ dysfunction in patients with chronic severe hepatitis B. METHODS: Forty-eight inpatients with chronic severe hepatitis B were randomly divided into rhGH group (n = 28)and control group (n = 20). In rhGH group, 4-4.5 IU of rhGH was injected intramuscularly once daily for 2-4 wk,and 100 mL of enema containing 30 mL of lactulose, 2 g of metronidazole and 0.9% saline was administered every 2 d for 2-4 wk. Their symptoms and complications were noted. Liver and kidney functions were analyzed by an Olympus analyzer. Serum GH, IGF-1, IGFBP1 and IGFBP3 were measured by ELISA.RESULTS: Clinical symptoms of 90% of these patients in rhGH group were obviously improved. The total effectiveness in rhGH group was better than that in control group (75% vs40%, P＜0.05). After 2- and 4-wk treatment of rhGH respectively, serum albumin (26.1±4.1 vs 30.2±5.3,31.9±5.1 g/L), prealbumin (79.6±28.0 vs 106.6±54.4,108.4±55.0 g/L), cholesterol (76.3±16.7 vs 85.6±32.3,96.1±38.7 mg/dL), and IGFBP1 (56.8±47.2 vs 89.7±50.3ng/mL after 2 wk) were significantly increased compared to control group (P＜0.05). However, serum GH was decreased. The increase of serum IGF1 and IGFBP3 after rhGH treatment was also observed.CONCLUSION: rhGH in combination with lactulose may be beneficial to the prevention and treatment of multiple organ dysfunction in patients with chronic severe hepatitis.

DETECTION OF PLASMA SOLUBLE INTERLEUKIN－2 RECEPTOR IN PATIENTS WITH SEVERE AND CHRONIC ACTIVE HEPATITIS B

Plasma levels of soluble interleukin-2 receptor (sIL-2R) in patients with chronic active hepatitis B (CAHB) or severe hepatitis B (SHB) were measured quantitatively by 'sandwich' ELISA with monoclonal antibodies in order to explore the change of sIL-2R levels, its clinical significance,and its relation to liver damage. The results showed that the plasma sIL-2R levels in patients with CAHB and SHB were much higher than those in normal controls (P < 0. 01 ), and the level ofplasma sIL-2R in patients with SHB was greatly higher than that in patients with CAHB. These results suggest that there is close relation between plasma level of sIL-2R, the clinical types of hepatitis B,and the severity of liver damage. In addition, there is no significant difference in plasma levels of sIL-2R between acute severe hepatitis B (ASHB), subacute severe hepatitis B (SASHB), and chronic severe hepatitis B (CSHB). No relation was found between sIL-2R level and hepatitis B virusreplication activity.

Antiviral therapy with nucleos(t)ide analogues for severe chronic hepatitis B

To the Editor:I read the paper by Chen et al[1]with great interest.The authors performed a retrospective study to evaluate the short-term efficacy of antiviral therapy with

Score model for predicting acute-on-chronic liver failure risk in chronic hepatitis B

AIM: To establish a clinical scoring model to predict risk of acute-on-chronic liver failure(ACLF) in chronic hepatitis B(CHB) patients.METHODS: This was a retrospective study of 1457 patients hospitalized for CHB between October 2008 and October 2013 at the Beijing Ditan Hospital, Capital Medical University, China. The patients were divided into two groups: severe acute exacerbation(SAE) group(n = 382) and non-SAE group(n = 1075). The SAE group was classified as the high-risk group based on the higher incidence of ACLF in this group than in the non-SAE group(13.6% vs 0.4%). Two-thirds of SAE patients were randomly assigned to risk-model derivation and the other one-third to model validation. Univariate risk factors associated with the outcome were entered into a multivariate logistic regression model for screening independent risk factors. Each variable was assigned an integer value based on the regression coefficients, and the final score was the sum of these values in the derivation set. Model discrimination and calibration were assessed using area under the receiver operating characteristic curve and the Hosmer-Lemeshow test. RESULTS: The risk prediction scoring model includedthe following four factors: age ≥ 40 years, total bilirubin ≥ 171 μmol/L, prothrombin activity 40%-60%, and hepatitis B virus DNA > 107 copies/m L. The sum risk score ranged from 0 to 7; 0-3 identified patients with lower risk of ACLF, whereas 4-7 identified patients with higher risk. The Kaplan-Meier analysis showed the cumulative risk for ACLF and ACLF-related death in the two risk groups(0-3 and 4-7 scores) of the primary cohort over 56 d, and log-rank test revealed a significant difference(2.0% vs 33.8% and 0.8% vs 9.4%, respectively; both P < 0.0001). In the derivation and validation data sets, the model had good discrimination(C index = 0.857, 95% confidence interval: 0.800-0.913 and C index = 0.889, 95% confidence interval: 0.820-0.957, respectively) and calibration demonstrated by the Hosmer-Lemeshow test(χ2 = 4.516, P = 0.808 and χ2 = 1.959, P = 0.923, respectively).CONCLUSION: Using the scoring model, clinicians can easily identify patients(total score ≥ 4) at high risk of ACLF and ACLF-related death early during SAE.

Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure

AIM:To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure(ACLF)patients with chronic hepatitis B virus(HBV)infection as the single etiology.METHODS:Full length and caspase cleaved cytokeratin 18(detected as M65 and M30 antigens)represent circulating indicators of necrosis and apoptosis.M65and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls(n=33),patients with chronic hepatitis B(CHB,n=55)and patients with ACLF(n=81).According to the 3-mo survival period,ACLF patients were defined as having spontaneous recovery(n=33)and non-spontaneous recovery which included deceased patients and those who required liver transplantation(n=48).RESULTS:Both biomarker levels significantly increased gradually as liver disease progressed(for M65:P<0.001 for all;for M30:control vs CHB,P=0.072;others:P<0.001 for all).In contrast,the M30/M65 ratio was significantly higher in controls compared with CHB patients(P=0.010)or ACLF patients(P<0.001).In addition,the area under receiver operating characteristic curve(AUC)analysis demonstrated that both biomarkers had diagnostic value(AUC≥0.80)in identifying ACLF from CHB patients.Interestingly,it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients(P=0.032).The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease(MELD)and Child-Pugh scores at the 3-mo survival period,the AUC of the M30/M65ratio was 0.66 with a sensitivity of 52.9%and the highest specificity of 92.6%(MELD:AUC=0.71;sensitivity,79.4%;specificity,63.0%;Child-Pugh:AUC=0.77;sensitivity,61.8%;specificity,88.9%).CONCLUSION:M65 and M30 are strongly associated with liver disease severity.The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF.

入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与CHB肝纤维化严重程度的相关性及对疾病预后的预测价值

目的探讨入院时血清转化生长因子-β1(TGF-β1)、Smad同源蛋白2(Smad2)、Smad同源蛋白3(Smad3)及透明质酸(HA)、Ⅲ型前胶原(PCⅢ)、层黏连蛋白(LN)、Ⅳ型胶原(CⅣ)水平与慢性乙型肝炎(CHB)肝纤维化严重程度的相关性及联合检测对疾病预后的预测价值。方法选取河南省中医院2021年3月至2022年3月收治的78例CHB肝纤维化患者作为研究组,选择同期78名健康体检者作为对照组。比较研究组和对照组及不同肝纤维化分期、不同炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平与肝纤维化分期、炎症活动分级的相关性。CHB肝纤维化患者治疗3个月后,根据患者预后分为预后良好和预后不良亚组,比较预后良好和预后不良患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平;分析入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平联合检测对CHB肝纤维化患者预后不良的预测价值。结果研究组入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ高于对照组(P<0.05);不同肝纤维化分期、炎症活动分级CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ比较:S1<S2<S3<S4、G1<G2<G3<G4,差异有统计学意义(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平与肝纤维化分期、炎症活动分级均呈正相关(P<0.05)。预后良好患者入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平均低于预后不良患者(P<0.05);入院时血清TGF-β1、Smad2、Smad3、HA、LN、PCⅢ、CⅣ水平联合预测肝纤维化患者预后不良的曲线下面积(AUC)优于各指标单一检测(P<0.05)。结论CHB肝纤维化患者入院时血清TGF-β1、Smad2、Smad3、HA、PCⅢ、LN、CⅣ水平均呈现高表达,且与肝纤维化分期、炎症活动分级密切相关,其联合检测对CHB肝纤维化患者预后有较高的预测价值,可用于评估CHB肝纤维化患者病情严重程度和预后,为制定针对性治疗措施提供参考。

Model for end-stage liver disease-sodium predicts prognosis in patients with chronic severe hepatitis B

Background Serum sodium predicts prognosis in chronic severe hepatitis B and may improve the prognostic accuracy of the model for end-stage liver disease （MELD） score, but the available information is limited. The present study was undertaken to study the clinical use of the serum sodium incorporated MELD （MELD-Na） and assess its validity by the concordance （c）-statistics in predicting the prognosis of the patient with chronic severe hepatitis B.Methods A total of 426 adult patients with a diagnosis of chronic severe hepatitis B between January 1, 2007, and December 31, 2007 at a single center were studied. The scores of serum sodium, MELD, MELD-Na, and ΔMELD-Na （ΔMELD-Na=MELD-Na at 14 days after medical treatment -MELD-Na score on admission） of the patients with chronic severe hepatitis B were calculated. The 3-month mortality in the patients was measured, and the validity of the models was determined by means of the concordance （c） statistics.Results The average MELD, MELD-Na scores of survival group were 25.70±5.08 and 26.60±6.90, and those of dead group were 35.60±6.78 and 42.80±9.57 on admission. There was a significant difference in MELD and MELD-Na between the survival and dead groups （P 〈0.01）. The average △MELD-Na score of the survival group was -0.97±3.51, and that of the dead group was 3.45±2.38 at 2 weeks after the treatment. There was a significant difference in △MELD-Na between the survival and dead groups （P 〈0.01）. The areas under the receiver-operating characteristic curves of Na, MELD and MELD-Na for the occurrence of death in 3 months were 0.742, 0.875 and 0.922. The 3-month mortality of the MELD-Na scores group 〈25, 25-30, 31-34, 35-40 and 〉40 were 2.0%, 5.4%, 35.4%, 53.8 % and 86.9%, respectively. There was a significant difference in the 3-month mortality between the five groups （P 〈0.05）. The 3-month mortality of the △MELD-Na〉0 group was 65.9%, and that of the △MELD-Na ≤0 group was 15.8%; there was a significant difference in the 3-month mortality between the two groups （P 〈0.05）.Conclusions MELD-Na score is a valid model to predict the 3-month mortality in patients with chronic severe hepatitis B. △MELD-Na is a clinically useful parameter for predicting the therapeutic effect of chronic severe hepatitis B.

基于HBV感染自然病程的慢性乙型肝炎患者外周血白细胞 介素-35表达水平及与病毒载量和转氨酶的相关性

目的探究白细胞介素-35(IL-35)在慢性HBV感染自然病程中的表达及与病毒载量和肝脏生化指标的相关性,评估其在HBV慢性感染管理中的作用,为动态监测慢性乙型肝炎(简称乙肝)病程并降低重症化提供证据。方法选取2015年1月至2020年11月上海长海医院感染科就诊的慢性HBV感染者83例,依据慢性HBV感染的自然病程分为免疫耐受期22例、免疫清除期29例及重型肝炎32例。选取健康对照20例。空腹采取患者静脉血,应用酶联免疫吸附试验(ELISA)检测外周血IL-35表达水平,同时检测HBV DNA及转氨酶水平。统计学方法采用两组间Mann-Whitney U检验、多组间Kruskal-Wallis H检验以及相关性分析。结果慢性HBV感染者与健康对照者的IL-35分别为51.75(9.9,96.5)pg/ml和7.33(3.35,8.76)pg/ml,差异有统计学意义(Z=-5.69,P<0.01)。慢性HBV感染后各自然病程中IL-35表达水平均高于健康对照组,其中在重型肝炎患者中表达最高,为121.46(68.98,213.44)pg/ml。IL-35指标变化与HBV DNA无明显相关性(r分别为0.385、0.392、-0.168,P均>0.05)。重型肝炎患者的IL-35与ALT呈正相关(ρ=0.543,P=0.045),慢性HBV感染后整体IL-35与ALT和AST均呈较好的正相关(ALT:r=0.684,P=0.001;AST:r=0.618,P=0.001)。血清IL-35每增加1个单位,进展至重型肝炎的可能性增加7.2%。血清IL-35水平的ROC曲线显示AUC为0.9491(95%CI:0.9078~0.9905,P<0.01),cut off值<50.95pg/ml。结论①HBV慢性感染病程中外周血高表达IL-35,IL-35水平同肝脏炎症程度呈正相关;②IL-35在临床评估乙肝患者病情方面有重要应用价值,可动态监测外周血IL-35水平辅助评估患者免疫状态,及早抗病毒治疗以降低重型肝炎的发生率。

慢性乙型肝炎PBMC凋亡及淋巴细胞亚群的检测

目的 :了解慢性 /慢性重型乙型肝炎外周血淋巴细胞激活诱导细胞死亡 (AICD)现象的存在情况、各免疫细胞的状况、AICD与淋巴细胞状况的关系 ,以探讨乙型肝炎慢性化和重型化的机制。方法 :利用慢性、慢性重型乙型肝炎病人和健康献血员外周血单个核细胞 (PBMC)在PHA P刺激下培养 72h ,通过流式细胞仪检测PBMC的凋亡情况 ;采用流式细胞仪结合全自动血液分析仪对慢性、慢性重型乙型肝炎病人及正常对照组外周血各淋巴细胞亚群进行检测。结果 :慢性乙型肝炎组PBMC凋亡率高于慢性重型乙型肝炎组 ( P<0 0 1) ,高于正常对照组 ( P <0 0 1)。慢性乙型肝炎组总淋巴细胞百分率高于慢性重型乙型肝炎组 (P <0 0 1) ,慢性重型乙型肝炎组淋巴细胞数低于正常对照组 (P <0 0 1) ;CD3 +、CD3 +CD4 +细胞数低于正常对照组 (P <0 0 1) ,低于慢性乙型肝炎组 (P <0 0 5 ) ;CD3 +CD8+细胞数低于正常对照组 (P <0 0 5 ) ,低于慢性乙型肝炎组 (P <0 0 5 )。单核细胞百分率高于正常对照组 (P <0 0 1) ,高于慢性乙型肝炎组 (P <0 0 5 )。结论 :慢性乙型肝炎患者外周血淋巴细胞活化与凋亡共存 ,慢性重型乙型肝炎患者外周血淋巴细胞消耗严重 ,AICD参与乙型肝炎慢性化、重型化的发生机理。

不同临床类型HBV感染者外周血T细胞亚群的差异

目的:观察不同临床类型HBV感染者外周血T淋巴细胞亚群的差异.方法:收集2006-9/2009-03贵阳医学院附属医院门诊及住院部慢性HBV携带者30例、慢性乙型肝炎患者47例、重型乙型肝炎患者26例以及非乙型肝炎且无影响T细胞亚群疾患者34例(高血压15例,冠心病9例,非甾体药物相关性消化性溃疡10例)的外周血,用流式细胞技术检测T细胞亚群.结果:慢性HBV携带者组、慢性乙型肝炎患者组及重型乙型肝炎患者组外周血中CD3+、CD4+、CD8+T细胞计数及CD3+、CD4+T细胞百分数及CD4+/CD8+(计数与百分数比)均较正常对照组明显降低(P<0.05或0.01),CD8+T细胞百分数明显升高(P<0.05或0.01),以上改变有统计学意义,且不同组间对比也有不同程度的统计学差异(P<0.05或0.01).结论:不同临床类型的慢性HBV感染者均存在不同程度的细胞免疫功能低下及免疫调节紊乱,紊乱的程度与病情的进展有关.

HBV DNA对不同临床分期慢性乙型重型肝炎预后的影响

目的探讨慢性乙型重症肝炎早、中、晚期患者HBV DNA对预后的影响。方法统计我院2004～2008年197例不同时期慢性乙型重型肝炎HBV DNA阳性情况,并统计早、中、晚期HBV DNA阳性与阴性组的3个月死亡率,入院2周终末期肝病模型(MELD)分值变化情况。结果早期HBV DNA阳性及阴性组3个月死亡率分别为34%、7.4%(P<0.01);中期分别为48.8%、44.4%(P>0.05);晚期分别为80.0%、76.9%(P>0.05)。早期HBV DNA阳性及阴性组入院2周△MELD值分别为3.6±4.8、0.8±4.1(P=0.01);中期分别为1.5±4.2、1.1±6.5(P>0.05);晚期分别为-1.6±7.3、-1.1±5.8(P>0.05)。结论慢性乙型重型肝炎早期HBV DNA阳性对预后有影响,但中、晚期HBV DNA阳性对预后无影响。

慢性重型乙型肝炎患者HBV DNA前C/BCP区突变基因分析

目的分析慢性重型乙型肝炎(慢重乙肝)患者HBV DNA前C区和基本核心启动子(前C/BCP)区突变特点与意义。方法收集87例慢重乙肝和196例慢性乙型肝炎(慢乙肝)患者血清,提取HBV DNA,用巢式PCR扩增HBV DNA前C/BCP区基因,PCR产物进行DNA测序,用NBI软件比对结果,重点分析G1896、G1862、G1899、A1762、G1764、T17536个位点突变。结果慢重乙肝组和慢乙肝组6个位点突变全阴率分别为3.4%和28.1%(P<0.01);慢重乙肝组在其中5个位点上的突变检出率显著高于慢乙肝组。此外,慢重乙肝组和慢乙肝组≥三联突变检出率分别为56.3%和35.2%(P<0.01),≥四联突变检出率分别为25.3%和8.7%(P<0.01),插入/缺失突变检出率分别为10.3%和1.0%(P<0.01)。结论HBV DNA前C/BCP区基因突变发生频率的增加与慢乙肝发生重症化相关,结合临床资料分析突变的意义将有助于认识慢乙肝重症化的发生机制。

HBV DNA阳性慢性重型乙型肝炎的抗病毒疗效分析

目的:探讨核苷类抗病毒药治疗对HBV DNA阳性慢性重型乙型肝炎患者短期生存率的影响及不同药物的疗效差异。方法:将入院时432例HBV DNA阳性的慢性重型乙型肝炎患者分为两组:230例为抗病毒组(根据服用不同抗病毒药又分为3组),202例为对照组。比较两组患者治疗12周的生存率及总胆红素(TBil)、凝血酶原活动度(PTA)、HBV DNA转阴率的差异,同时比较不同抗病毒药物治疗12周的生存率差异和生化指标及HBV DNA阴转的差异。结果:①治疗12周生存率抗病毒组为70.70%,对照组为58.50%,两组比较差异有显著性意义(P<0.05)。②治疗12周HBV DNA阴转率,抗病毒组为69.06%(96/139),对照组为32.29%(31/96),两组比较差异有显著性意义(P<0.01)。③不同抗病毒药物中12周生存率,恩替卡韦组为73.30%,拉米夫定组70.50%,替比夫定组67.70%,3种药物比较差异无显著性意义(P>0.05)。④治疗12周时患者TBil、PTA、HBV DNA转阴率拉米夫定组分别为(83.63±99.47)μmol/L、(58.57±16.69)%、65.08%,替比夫定组分别为(102.33±113.58)μmol/L、(55.61±15.98)%、69.23%,恩替卡韦组分别为(70.66±108.86)μmol/L、(57.46±17.12)%、74.00%。3组比较差异均无显著性意义(P>0.05)。结论:抗病毒治疗可以改善慢性重型乙型肝炎的预后及肝功能,常用的3种核苷类药物疗效的差异无统计学意义。

肝细胞凋亡及凋亡相关基因Caspase-3、Bcl-2在慢性乙型重型肝炎中的作用

目的探讨肝细胞凋亡及凋亡相关基因Caspase-3、Bcl-2在慢性乙型重型肝炎(慢重肝)发生发展机制中的作用。方法选择慢重肝肝组织标本68例(慢重肝组),正常肝组织标本20例(对照组)。采用原位末端转移酶标记技术(terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling,TUNEL)技术和免疫组织化学法检测2组肝组织中Cas-pase-3和Bcl-2的表达及肝细胞凋亡情况。结果慢重肝组凋亡指数的平均值为41.6±4.9,而在正常对照组肝组织中,未见到TUNEL阳性表达的肝细胞,2组差异有统计学意义。慢重肝组的肝组织中Caspase-3蛋白阳性表达程度明显高于对照组(P<0.05),而Bcl-2蛋白阳性表达程度明显低于对照组。Spearman相关分析发现,慢重肝组的肝组织中肝细胞凋亡指数与Caspase-3表达之间呈正相关(r=0.592,P<0.01),与Bcl-2表达之间呈负相关(r=-0.461,P<0.05)。结论肝细胞凋亡在慢重肝的发生过程中起重要作用,而Caspase-3和Bcl-2均参与了慢重肝的肝细胞凋亡过程。

141例慢性重度乙型肝炎患者凝血功能与HBV标志物模式HBV-DNA载量相关性研究

目的:研究慢性重度乙型肝炎患者HBV标志物模式(HBV-M)、病毒载量(HBV-DNA)与凝血功能的关系。方法:测定141例慢性重度乙型肝炎患者血清凝血功能、HBV-M及HBV-DNA载量,运用SPSS17.0统计软件对结果进行统计学分析。结果:141例慢性重度乙型肝炎患者中,HBV-DNA阳性率为85.8%,依HBV-M及HBV-DNA载量分组的各组凝血功能四项指标与对照组比较,差异有统计学意义(P<0.05),并且慢性重度乙型病毒性肝炎患者的凝血功能与HBV-M及HBV-DNA载量变化具有相关性,凝血酶原时间(PT)、活化部分凝血酶时间(APTT)、凝血酶时间(TT)与HBV-M和HBV-DNA呈正相关性;纤维蛋白原(FIB)与HBV-M和HBV-DNA呈负相关性。结论:慢性重度乙型肝炎患者的凝血功能变化与其HBV-M及HBV-DNA载量有关,该三项指标的变化对此类患者的治疗及治疗效果的判定有重要意义。

慢性乙型重型肝炎HBV基因型和核苷酸多态性分析

目的探讨无锡地区慢性乙型重型肝炎HBV基因型和核苷酸多态性分布的特点。方法套式PCR扩增HBVDNAS基因后作序列分析。结果50例慢性乙型重型肝炎患者B基因型1例(2%),C基因型43例(86%),BC混合基因型6例(12%);各基因型死亡率无显著差异,P>0.05。B、BC混合基因型S基因第139位、140位、146位、167位、170位、176位、191位、248位、254位、328位、337位、377位核苷酸与C基因型S基因第145位、157位、203位核苷酸各有聚集性改变,其中139与140位、145与146位有联合改变,并导致相应氨基酸的置换。结论无锡地区慢性乙型重型肝炎多见于C、BC混合基因型,C、B、BC基因型核苷酸呈多态性改变。

慢性重型肝炎患者血中LPS、LBP和sCD14的水平及其临床意义

探讨LBP、sCD14水平在慢性重型肝炎 (慢重肝 )患者伴肠源性内毒素血症中的作用。应用基质显色法和ELISA双抗体夹心法 ,检测 2 4例慢重肝患者血中LPS、LBP和sCD14的水平 ,并以 10名献血员和 16例慢性乙型肝炎患者作为对照。结果慢重肝患者在早期、中期、晚期 ,其血中LPS、LBP和sCD14的水平均明显高于慢乙肝患者及献血员 ;慢重肝死亡者其LPS、LBP和sCD14的水平也显著高于存活者。提示慢重肝患者伴肠源性内毒素血症时 ,血清中LBP和sCD14的水平 ,可显著提高机体对内毒素的敏感性。在内毒素浓度较低时 ,仍可诱导Kupffer细胞释放TNF α,从而加剧肝细胞损伤。