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.

A comparison between previous and present histologic assessments of chronic hepatitis C viral infections in humans

AIM To compare the previously employed classification of liver histology (minimal, chronic persistent hepatitis, chronic active hepatitis and cirrhosis) with a new classification recently described by Sheuer et al (activity grade and fibrosis stage) in percutaneous liver biopsies from patients with chronic hepatitis C viral infections.METHODS Liver biopsies from 79 untreated patients were reviewed. Anti-HCV testing had been performed by ELISA and confirmed by a recombinant immunoblot assay. With respect to the new classification, all the specimens were evaluated using the Knodell score for activity.RESULTS A good correlation was revealed between the previous and more recent histologic classifications in patients with abnormal liver enzyme tests. However, in 13/ 15 (87%) of patients with normal aminotransferase values, changes were consistent with chronic persistent hepatitis whereas normal activity and no fibrosis were demonstrated by the Sheuer classification.CONCLUSION The old classification is more often misleading but correlates well with the new classification and thereby permits comparisons between historically clinical studies.

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.

Association of human leukocyte antigen DQB1 and DRB1 alleles with chronic hepatitis B

AIM: To investigate the effect of human leukocyte antigen (HLA) DRB1 and DQB1 alleles on the inactive and advanced stages of chronic hepatitis B.

Expression of SOCS-1 in the liver tissues of chronic hepatitis B and its clinical significance

AIM： To study the expression of suppressor of cytokine signaling-1 （SOCS-1） in the liver tissues of chronic hepatitis 13 （CHB） and the clinical significance of this expression. METHODS： The expression of SOCS-1 in liver tissues of 45 cases of CHB was investigated by immunohistochemical staining, and its correlations with inflammation grades and fibrosis stage were analyzed by SPSS statistics software. RESULTS： The result showed SOCS-1 expressing could be observed in the liver tissue of CriB. The expression of SOCS-1 was mainly distributed near the portal area in the liver tissue of mild inflammation CriB group, and was diffusely distributed in the liver tissue of moderate and severe inflammation groups. SOCS-1 positive stains mainly appear in the hepatocytes, only a few of liver interstitial cells were involved. Inside the hepatocyte, SOCS-1 positive stains are mainly distributed in the plasma. Some of the staining was observed on the membrane. The inclusion bodies in the plasma of hepatocytes were observed occasionally. There were both obvious correlations between the expression of SOCS-1 and the inflammatory grade, and that between the expression of SOCS-1 and the fibrosis stage, CONCLUSION： The distribution of SOCS-1 in the liver tissue of CriB is variable. This expression was correlated with the inflammation grade and fibrosis stage.

Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV.METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV.RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA Ⅰ/Ⅱ restricted recognition epitopes reported by some investigators.CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Chronic hepatitis B:Enlarged perihepatic lymph nodes correlated with hepatic histopathology

AIM:To assess the value of enlarged perihepatic lymph nodes in determining hepatic histopathology for chronic hepatitis B(CHB) by magnetic resonance imaging(MRI).METHODS:Sixty-seven patients who were clinically and histologically diagnosed with CHB and 18 healthy subjects without history of liver disease underwent abdominal MRI.Histological diagnosis and hepatic inflammation(grade 0-4) and fibrosis(stage 0-4) were assessed by a simplified system for scoring in chronic viral hepatitis.The major imaging protocol included an axial breath-hold fat suppressed fast spoiled gradient echo T2-weighted imaging(T2WI),axial breath-trigger fat suppressed fast recovery fast spin echo T2WI,and axial and coronal fast imaging employing steady-state acquisition.Perihepatic lymph nodes larger than 5 mm in shortest diameter were noted.RESULTS:The numbers and size indexes of lymphnodes greater than 5 mm in shortest diameter in hepatic hilum suggested inflammatory activity for subjects with grade 2 or higher,with a high accuracy of diagnosis(the area under the curves > 0.9,P < 0.001).The numbers of lymph nodes were 2 or more with a sensitivity of 87.27%,a specificity of 90.00%,an accuracy of 88.24%,a positive predictive value of 94.12%,and a negative predictive value of 79.41% in patients with grade 2 or higher,and the size indexes were no less than 180 mm 2 with a sensitivity of 83.64%,a specificity of 100%,an accuracy of 89.41%,a positive predictive value of 100%,and a negative predictive value of 76.92%.The numbers and size indexes of lymph nodes were not correlated with hepatic fibrosis.The signal intensity indexes of lymph nodes were no significant correlation with histological grading or staging of liver.CONCLUSION:The numbers and size indexes of enlarged perihepatic lymph nodes for patients with CHB suggest inflammatory activity for subjects with grade 2 or higher.

Study on the Correlation of Plasma NO, ET-1 and ALT in the Patients with Chronic Hepatitis and Cirrhosis

The levels of plasma nitric oxide (NO), endothelin 1 (ET 1) and ALT in the patients with chronic hepatitis B and active cirrhosis and the correlation among them were observed and analyzed. NO 3 ˉ was restored by using cadmium column assay and NO 2 ˉ measured by heavy nitrogen assay. The primitive NO 3 ˉ and total restored NO 2 ˉ(NO 3 ˉ/ NO 2 ˉ) in plasma of the patients with chronic hepatitis and cirrhosis. Plasma ET 1 and ALT levels were determined by using radioimmunological assay and Lai's assay, respectively. Compared with normal control group, the plasma levels of NO 2 ˉ/NO 3 ˉ and ET 1 in the patients with chronic active hepatitis and active cirrhosis were significantly increased ( P <0.05-0.01). There was a positive correlation between NO and ALT, and ET 1 and ALT in the patients with chronic active hepatitis and active cirrhosis respectively. It was suggested that elevation of both NO and ET 1 levels were closely related with injury severity of liver function.

Expression of IL-4 and IFN-γ mRNA in PBMC of chronic hepatitis B individuals

Objective: To establish the relationship between hepatic inflammation activity and Th1/Th2 phenotype cytokines (IFN-γ, IL-4) and to investigate the fore of these cytokines as immunoregulator in inflammation activity of chronic hepatitis B. Methods: The expression of the mRNA of IL-4 and IFN-γin periphery blood monocytes (PBMC) in patients with chronic hepatitis B was determined by reverse transcription polymena chain reaction (RT-PCR) test. Results: mHNA of neither IL-4 nor IFN-γ was detected in quiescent stage, and the expression rate of IFN-γ mRNA was conspicuously higher in active stage than in convalescent stage (P < 0.05, 100% vs 50% ), while the reverse is true for the expression rate of IL-4 mrNA in convalescent stage (P < 0.05, 87% vs 13%; ). Conclusion: In patients with chronic hepatitis B, IFN-γand IL-2 serve as positive immunoregulatory cytokines, and IL-4 serves as a negative immunoregulator in HBV pathogenesis. These results indicate that Th1 phenotype cytokines up-regulate and Th2 phenotype cytokines down-regulate hepatic inflammation in chronic hepatitis B.

“Liverscore”is predictive of both liver fi brosis and activity in chronic hepatitis C

AIM:To formulate a noninvasive index predictive of se-verity of liver f ibrosis and activity in chronic hepatitis C.METHODS:This cross sectional study was conducted on polymerase chain reaction positive,treatment nave patients.Fibrosis was staged on a f ive point scale from F0-F4 and activity was graded on a four point scale from A0-A3,according to the METAVIR system.Patients were divided into two overall severity groups,minimal disease(< F2 and < A2)and signif icant disease(≥ F2 or ≥ A2).Eleven markers were measured in blood.Sta-tistically,the primary outcome variable was identif ica-tion of minimal and signif icant overall disease.Indices were formulated using β regression values of different combinations of nine statistically significant factors.Diagnostic performance of these indices was assessed through receiver-operating characteristic curve analysis.RESULTS:A total of 98 patients were included and of these 46 had an overall clinically significant disease.Our f inal six marker index,Liverscore for Hepatitis C,consisted of age,alanine transaminase,gamma-gluta-myl transpeptidase,apolipoprotein A-1,alpha-2 macro-globulin and hyaluronic acid.The area under the curve was found to be 0.813.On a 0-1 scale,negative predic-tive value at a cutoff level of ≤ 0.40 was 83%,while positive predictive value at ≥ 0.80 remained 89%.Al-together,61% of the patients had these discriminative scores.CONCLUSION:This index is discriminative of minimal and significant overall liver disease in a majority of chronic hepatitis C patients and can help in clinical de-cision making.

Epstein-Barr virus:Silent companion or causative agent of chronic liver disease?

The Epstein-Barr virus(EBV)has an important and multifaceted role in liver pathology.As a member of the herpes virus family,EBV establishes a persistent infection in more than 90%of adults.Besides acute hepatitis during primary infection,many clinical syndromes of interest for the hepatologist are associated with EBV infection.The role of EBV in the evolution of chronic hepatitis from hepatotropic viruses is considered.Chronic EBVassociated hepatitis is suspected in immunocompetent adults with compatible serology,suggestive histology and detection of the viral genome in the liver and/or increase of specific circulating cytotoxic T-lymphocytes.EBV is the main cause of post-transplant lymphoproliferative disorders which occur in up to 30%of cases.EBV-driven lymphoproliferative diseases are also recognized in non-immunocompromised patients and liver is involved in up to a third of the cases.Directly implicated in the pathogenesis of different tumors,EBV has a disputable role in hepatocellular carcinoma carcinogenesis.Further research is required in order to establish or reject the role of EBV in human liver cancer.This paper attempts to discuss the range of EBV-associated chronic liver diseases in immunocompetent patients,from mild,self-limiting mononuclear hepatitis to liver cancer.

血清preS1水平与慢性乙型肝炎患者肝纤维化的关系及对癌变的诊断价值

目的分析血清乙型肝炎病毒(hepatitis B virus,HBV)前S1蛋白(precursor S1 protein,preS1)与慢性乙型肝炎(chronic hepatitis B,CHB)肝纤维化及癌变进展的相关性。方法对2019年10月—2021年10月期间在青海红十字医院接受检查的228例乙肝表面抗原(hepatitis B surface antigen,HBsAg)阳性慢性HBV感染者进行回顾性分析,其中CHB患者75例、肝硬化(liver cirrhosis,LC)患者93例(LC组)、肝细胞癌(hepatocellular carcinoma,HCC)患者60例(HCC组)。根据LC和HCC组肝组织活检分析肝脏炎症活动及肝纤维化程度。结果HCC组血清preS1水平[496.32(457.63,988.0)ng/mL]和LC组[338.72(247.93,554.61)ng/mL]血清preS1水平均显著高于CHB组[113.69(87.09,177.40)ng/mL],且差异具有统计学意义(P均<0.05)。HCC组血清preS1水平亦高于LC组(P=0.002)。经受试者工作特征曲线分析,血清preS1水平鉴别诊断CHB与LC的曲线下面积(area under the curve,AUC)是0.881(95%CI:0.830~0.932),鉴别诊断CHB/LC与HCC的AUC是0.861(95%CI:0.815~0.908)。3组患者的血清preS1水平与HBsAg(rs=0.799,P<0.001)呈强正相关和Log HBV DNA(rs=0.262,P<0.001)呈弱正相关。此外LC组和HCC组血清preS1水平与肝脏炎症活动分级(rs=0.201,P=0.009)及肝纤维化分期也呈弱正相关性(rs=0.295,P<0.001)。结论血清preS1水平与血清HBsAg、HBV DNA水平和肝脏炎症和纤维化进展呈正相关,有可能成为鉴别诊断HBV相关慢性肝病肝硬化或癌变的候选标志物。

HBeAg诱导的免疫激活和免疫抑制在慢性乙型肝炎中的作用

HBV感染诱导的慢性乙型肝炎是导致肝硬化和肝癌的重要危险因素。半个世纪前,HBeAg在HBV感染者血清中首次被发现,尽管HBeAg并不参与HBV在肝细胞中的感染或复制,但其已被证实可干扰宿主先天性和适应性免疫反应,在慢性HBV感染的过程中发挥着重要的免疫激活和免疫抑制作用。HBV对于感染的肝细胞并没有细胞毒性,免疫应答介导的抗病毒作用和炎症反应决定HBV是否被清除或者诱导肝脏炎症相关疾病。因此,本文对HBeAg的形成及其在慢性HBV感染中引起的免疫激活和免疫抑制机制进行综述,重点论述HBeAg对先天免疫和适应性免疫细胞所引起的不同免疫效应,阐述了其诱导免疫反应的两面性,并探讨HBeAg在慢性HBV感染不同阶段间的转换作用。

Fas/FasL and Complement Activation are Associated with Chronic Active Epstein-Barr Virus Hepatitis

Background and Aims:Chronic active Epstein-Barr virus hepatitis(CAEBVH)is a rare and highly lethal disease char-acterized by hepatitis and hepatomegaly.This study aimed to investigate the clinicopathological features and pathogenic mechanisms of CAEBVH.Methods:Ten patients with con-firmed Epstein-Barr virus hepatitis infection were enrolled.The clinicopathological characteristics of these patients were summarized and analyzed.Flow cytometry was utilized to detect peripheral blood immune cell phenotypes and whole exome sequencing was used to explore pathogenic genetic mechanisms.Lastly,immunohistochemical staining was em-ployed to verify pathogenic mechanisms.Results:Clinical features observed in all Epstein-Barr virus hepatitis patients included fever(7/10),splenomegaly(10/10),hepatomeg-aly(9/10),abnormal liver function(8/10),and CD8+T cell lymphopenia(6/7).Hematoxylin and eosin staining revealed lymphocytic infiltration in the liver.Positive Epstein-Barr vi-rus-encoded small RNA in-situ hybridization(EBER-ISH)of lymphocytes of liver tissues was noted.Whole exome se-quencing indicated that cytotoxic T lymphocytes and the complement system were involved.The expression of CD8,Fas,FasL,and Caspase-8 expression as well as apoptotic markers was enhanced in the Epstein-Barr virus hepatitis group relative to the controls(p<0.05).Lastly,Complement 1q and complement 3d expression,were higher in CAEBVH patients relative to controls(p<0.05).Conclusions:CAE-BVH patients developed fever,hepatosplenomegaly,and lymphadenopathy.Histopathological changes were a diffuse lymphocytic sinusoidal infiltrate with EBER-ISH positivity.Fas/FasL and complement activation were involved in CAE-BVH patients.

Efficacy observation of Yiguanjian decoction combined adefovir Dipivoxil tablet in treating HBeAg negative chronic viral hepatitis B active compensated liver cirrhosis patients

Objective To explore clinical efficacy of Yiguanjian Decoction(YD)combined Adefovir Dipivoxil Tablet(ADT)in treating HBe Ag negative chronic viral hepatitis B(CVHB)active compensated liver cirrhosis(LC)patients.Methods Totally 68 HBe Ag negative CVHB active compensated LC patients initially treated were assigned to the treatment group and the control group

血清HCY与肝功能指标联合检测在肝病诊断中的应用研究

目的：探讨各种肝病患者血清同型半胱氨酸（HCY）水平变化，研究其对不同肝病的发生、发展和治疗的影响。方法选择陕西省人民医院消化内科已经确诊不同肝病的住院病人123例（男性79例，女性44例），其中慢性活动性肝炎39例、肝硬化52例和肝癌32例。另选取门诊体检中心健康体检者90例作为对照组。于罗氏 MODUALR 全自动生化分析仪上采用酶循环速率法测定上述血清 HCY水平，同时检测血清总胆红素（TBIL）、丙氨酸氨基转移酶（ALT）、γ-谷氨酰转肽酶（GGT）和总胆汁酸（TBA）等肝功能指标，并进行统计学分析。结果慢性活动性肝炎、肝硬化和肝癌组血清 HCY （μmol/L）分别为16.25±3.98，20.89±4.26和22.92±6.08，均显著高于正常对照组（8.16±4.03），二者差异有统计学意义（t＝5.352-9.021，P均＜0.01）。肝病组之间，肝硬化组和原发性肝癌组比慢性活动性肝炎组高（P＜0.05）。三组肝病经治疗后血清 HCY明显低于治疗前水平（P＜0.05）。阳性率也以 HCY为高，且与肝功能其他指标存在显著性差异（P＜0.05）。结论血浆同型半胱氨酸可能作为肝损害的一个重要指标，同时联合其他肝功能指标检测可对肝病诊断、鉴别诊断、疗效观察及预后等具有重要的临床价值。

不同活血化瘀法分阶段辨证干预乙肝肝纤维化的临床疗效研究

目的观察不同活血化瘀法分阶段辨证干预乙肝肝纤维化的临床疗效。方法选取2008年7月—2011年12月期间在中国中医科学院西苑医院肝病科门诊就诊的正虚血瘀型乙肝肝纤维化患者100例,随机分为治疗组和对照组,每组50例。治疗组根据其病情轻、中、重的阶段不同,分别给予自拟方活血养血、活血化瘀、活血软坚3组汤药治疗,对照组则予中成药复方鳖甲软肝片治疗,统计两组治疗前后的中医证候积分、肝功能[主要为ALT、白蛋白/球蛋白(A/G)]、肝脏超声检查(主要包括肝脏回声、脾脏厚度、门静脉宽度)以及血清肝纤维化四项指标[包括血清透明质酸(HA)、层黏蛋白(LN)、Ⅳ型胶原(Ⅳ-C)、Ⅲ型前胶原蛋白肽(P-Ⅲ-P)]。疗程6个月。结果与本组治疗前比较,两组治疗后证候积分均降低,治疗组脾脏厚度较治疗前明显下降,差异有统计学意义(P<0.05)。与对照组同期比较,治疗组治疗后证候积分及脾脏厚度改善更明显,差异有统计学意义(P<0.05)。与治疗前比较,两组治疗后ALT、HA、LN显著下降,A/G显著升高,差异有统计学意义(P<0.05)。与对照组同期比较,治疗组治疗后A/G、HA、LN改善更为明显,差异有统计学意义(P<0.05)。治疗后治疗组与对照组疾病疗效总有效率分别为76%、46%,治疗组明显高于对照组(P<0.05)。结论不同活血化瘀法分阶段辨证干预乙肝肝纤维化的疗效优于复方鳖甲软肝片,其对乙肝肝纤维化的临床症状及血清生化指标有良好的改善作用。

慢性活动性乙型肝炎患者细胞免疫功能检测及其临床意义

测定了例慢性活动性乙型肝炎患者外周血单个核细胞（ＰＢＭＣ）产生的白细胞介素２（ＩＬ－２）活性。其中部分病人检测了血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）水平，膜白细胞介素２受体（ｍＩＬ－２Ｒ）表达，ＬＡＫ活性及外周血Ｔ淋巴细胞亚群，并分析了它们之间的相关性，结果表明：ＩＬ－２活性、ｍＩＬ－２Ｒ表达，ＬＡＫ活性，ＣＤ４￣＋／ＣＤ８￣＋比值显著低于正常对照组（Ｐ＜０．００１），而ｓＩＬ－２Ｒ水平、ＣＤ８￣＋细胞显著高于正常对照组（Ｐ＜０．００１）。提示慢活肝患者细胞免疫功能低下，为临床过继免疫治疗提供了依据。

抗HBV治疗性疫苗治疗HBV携带者的临床实验研究

目的 进一步验证抗HBV治疗性疫苗治疗HBV携带者的临床疗效。方法 将确诊为HBV携带者的 6 0 0例患者随机分为两组 ,一组为抗HBV治疗性疫苗实验组 ,30 0例 ,用抗HBV治疗性疫苗治疗 ,每月 1次 ,皮下注射 ,同时服用维生素C 5 0 0mg/d,疗程为1 2个月 ;另一组为对照组 ,30 0例 ,用生理盐水 2ml,皮下注射 ,每月 1次 ,同时服用维生素C 5 0 0mg/d,1 2个月为 1疗程。两组在年龄、性别、病程、HBV标记物状况方面均有良好的可比性。治疗过程中第 1 2、2 4、4 8周复诊 1次。治疗前及每次复诊时检测血清HBsAg、HBeAg、HBVDNA、抗 HBe、抗 HBs及ALT。上述指标第 4 8周的检验结果作为评价疗效的依据。疗程期满停止治疗后 ,对实验组 2 0 8例与对照组 1 96例进行为期 1 2个月的随访。随访期内第 1 2个月做上述HBV标记物检测 ,以评价终止治疗 1 2个月内HBV标记物的改变。结果 抗HBV治疗性疫苗实验组的HBsAg、HBeAg、HBVDNA的阴转率及抗 HBe与抗 HBs的阳转率分别为 1 4 7%、32 0 %、37 3%、2 0 0 %和 7 1 % ;对照组分别为 2 0 %、6 0 %、6 7%、1 3%和 0 % ,两组相比差异有统计学意义 (P <0 0 5 )。实验组停止治疗后随访 1年 ,复发率为 5 9%。

活血祛风法治疗慢性活动性乙型肝炎临床观察

用活血祛风法治疗反复发作的慢性活动性乙型肝炎70例,总有效率为95.7%,对照组65例用健脾清热利湿法治疗,总有效率为78.5%(P<0.05)。治疗组抗 LSP、LMA、抗核抗体、类风湿因子阴转率、HBeAg、抗 HBcIgM、HBV-DNA 阴转率、抗 HBe 阳转率均优于对照组(P<0.001)。