替比夫定联合苦参素胶囊治疗慢性乙型性肝炎临床观察

慢性乙型肝炎（CHB）是严重危害人类健康的一种常见病，CHB的防治是全球性公共卫生问题。我国是病毒性肝炎的高发地区，平均年发病率为120／10万-140／10万，其中CHB尤为突出。目前在我国乙型肝炎病毒（HBV）感染仍相当严重，由此造成的肝炎后肝硬化患者居全球首位。CHB患者肝组织存在病毒复制活跃，就可使肝脏炎症坏死加重，发生肝硬化和肝癌的风险升高。我们应用替比夫定联合苦参素胶囊治疗CHB病例40例，取得了较好的疗效，现将有关资料报道如下：资料与方法一。

芍药汤灌肠对慢性乙型肝炎患者血清内毒素及瘤坏死因子-α水平的影响

目的:观察芍药汤灌肠对慢性乙型肝炎患者血清内毒素及瘤坏死因子-α(Tumor necrosis factor alpha,TNF-α)水平的影响,探讨其作用机制。方方法法:实验分阳性对照组、芍药汤灌肠组,各40例。观察患者肝功能状态、血清内毒素及TNF-α水平。结果:两组患者治疗前各项指标无明显差异(P>0.05)。治疗后,芍药汤肠能明显降低慢性乙型性肝炎患者血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST),明显降低血清内毒素及TNF-α水平(P<0.01),明显优于对照组(P<0.01或P<0.05)。结论:芍药汤肠能降低血清内毒素及肿瘤坏死因子α水平,从而减轻肝损伤,保护肝功能。其机制可能与其抑制、清除或减少肠道细菌,减少内毒素生成、吸收和减少肿瘤坏死因子α表达有关。

乙型病毒性肝炎T淋巴细胞亚群的测定及其意义

目的 :研究乙型病毒性肝炎患者在病毒复制状态下及重型肝炎患者的免疫功能紊乱情况。方法 :应用流式细胞仪检测T淋巴细胞亚群 ,ELISA法检测HBV m。结果 :乙型病毒性肝炎患者CD4+/CD8+值较正常对照组下降。在乙型肝炎病毒复制组为 0 .97± 0 .42 ,在重型肝炎组为 1 .0 9± 0 .2 8。结论 :乙型病毒性肝炎为免疫损伤所致 ,在重型肝炎及乙型肝炎病毒复制状态下存在严重免疫功能紊乱。

乙型肝炎肝硬化晚期并发肝性脊髓病2例

肝性脊髓病（hepatic myelopathy,HM）是由多种肝病引起的颈髓以下脊髓侧索脱髓鞘病变,呈现肢体缓慢进行性、对称性、痉挛性瘫痪。常见于肝硬化晚期,偶见于急慢性肝炎、重症肝炎、酒精性肝病及肝豆状核变性等肝病患者。现将我院近期收治的2例HM患者报告如下。

FibroScan在慢性乙型病毒性肝炎所致肝纤维化中的诊断价值研究进展

慢性乙型病毒性肝炎(CHB)可导致肝细胞的慢性炎症坏死,形成肝纤维化,最终导致肝硬化及多种并发症。CHB的发展及转归与肝脏纤维化的程度密切相关,准确判断肝纤维化分期对指导慢性肝脏疾病的治疗、评估预后、监测疾病进展有重要作用。肝组织病理活检虽是诊断肝纤维化的“金标准”,但因其是一种创伤性检查,患者接受度不高,不适于动态监测。而肝纤维化扫描仪(FibroScan)是一种无创评估肝纤维化的工具,重复性好,近年来被广泛认可。

退黄汤联合甘利欣治疗乙型黄疸性肝炎疗效观察

2003--2007年，笔者采用自拟退黄汤联合甘利欣治疗乙型黄疸性肝炎，并与单纯甘利欣治疗者对照，现总结报道如下。

中西医结合治疗慢性乙型黄疸性肝炎的临床研究

目的观察自拟退黄汤治疗乙型黄疸性肝炎的疗效。方法选取90名住院患者随机分为治疗组及对照组各45例,对照组给予常规西药治疗,治疗组在对照组基础上给予自拟退黄汤,疗程均为4周;观察治疗前及治疗后临床症状、肝功能的变化。结果治疗组对于症状改善、肝功能改善均优于对照组。结论自拟退黄汤治疗乙型黄疸性肝炎疗效确切。

中西医结合治疗乙型黄疸性肝炎42例疗效观察

乙型肝炎为一种慢性难治性疾病，病程迁延，损害严重，病程中合并黄疸者治疗更为棘手。笔者于2008年在中西医结合基础上加用三七、水蛭治疗乙型黄疸性肝炎42例，并与未用三七、水蛭治疗的42例进行对比观察，取得了良好效果，现报道如下。

中西医结合治疗慢性乙型黄疸性肝炎的临床研究

目的:分析研究慢性乙型黄疸性肝炎的临床治疗方法及疗效。方法:选取48例患者随机分为治疗组及对照组各24例,对照组给予常规西药治疗,治疗组在对照组基础上给予自拟退黄汤,疗程均4周;观察治疗前及治疗后临床症状、肝功能的变化情况。结果:治疗组有效率87.50%,对照组有效率75.00%,两组比较差异有统计学意义(P<0.05)。结论:自拟退黄汤治疗乙型黄疸性肝炎疗效确切,且不良反应少。

恩替卡韦与阿德福韦酯治疗乙型病毒性肝炎失代偿性肝硬化的临床研究

目的分析恩替卡韦与阿德福韦酯治疗乙型病毒性肝炎失代偿性肝硬化患者临床疗效。方法选取温州市中心医院100例乙型病毒性肝炎失代偿性肝硬化患者为研究对象（2015年2月～2016年10月）,随机分为对照组和实验组,各50例。对照组给予阿德福韦酯治疗,实验组进行恩替卡韦与阿德福韦酯治疗。比较分析2组患者相关临床症状比较。结果治疗后,实验组ALT水平为（46.20±3.21）U/L,AST水平为（52.40±3.90）U/L。对照组ALT水平为（70.43±10.90）U/L,AST水平为（70.33±9.19）U/L,2组患者比较差异具有统计学意义（P〈0.05）。实验组患者HBV-DNA转阴率为76.0%显著高于对照组58.0%,差异具有统计学意义（P〈0.05）。2组患者HBeAg转阴率分别为22.0%与24.0%,差异无统计学意义。结论恩替卡韦与阿德福韦酯治疗乙型病毒性肝炎失代偿性肝硬化患者临床疗效较为理想,能够显著改善患者肝功能,改善临床症状,安全性高。

丁二磺酸腺苷蛋氨酸联合门冬氨酸钾镁、恩替卡韦治疗肝内胆汁淤积性乙型肝炎的效果分析

目的:探讨丁二磺酸腺苷蛋氨酸联合门冬氨酸钾镁、恩替卡韦治疗肝内胆汁淤积性乙型病毒性肝炎的临床效果。方法:108例肝内胆汁淤积性乙型病毒性肝炎患者随机分为两组。对照组54例,实施门冬氨酸钾镁、恩替卡韦治疗;研究组54例,在对照组基础上加用丁二磺酸腺苷蛋氨酸治疗。分析两组疗效,不良反应发生率,肝功能指标AST、ALT、TBIL和凝血功能指标PT、APTT、TT。结果:研究组治疗总有效率92.6%,高于对照组77.8%,差异有统计学意义(P<0.05);治疗后,研究组肝功能指标、凝血功能指标改善明显优于对照组(P<0.05);研究组不良反应发生率9.26%,与对照组5.56%比较,差异无统计学意义(P>0.05)。结论:丁二磺酸腺苷蛋氨酸、门冬氨酸钾镁、恩替卡韦联合治疗肝内胆汁淤积性乙型病毒性肝炎患者的效果明显提高。

自拟退黄汤联合甘利欣治疗乙型黄疸性肝炎75例疗效观察

目的:观察自拟退黄汤联合甘利欣治疗乙型黄疸性肝炎的疗效。方法:选取100名住院患者按3:1随机分为治疗组及对照组,治疗组给予甘利欣及自拟退黄汤,对照组给予甘利欣注射液,疗程均为4周;观察治疗前及治疗后临床症状、肝功能以及PCR-HBV-DNA的变化。结果:治疗组对于症状改善、肝功能改善以及PCR-HBV-DNA改善均优于对照组。结论:自拟退黄汤联合甘利欣治疗乙型黄疸性肝炎疗效确切。

中西医结合治疗慢性乙型黄疸性肝炎40例疗效观察

目的:观察退黄汤(自拟)治疗慢性乙型黄疸性肝炎的疗效。方法:选取80例患者随机分为两组各40例,对照组给予常规西药保肝治疗,治疗组在对照组基础上加服中药退黄汤。结果:治疗组对于症状及肝功能改善方面均优于对照组。结论:自拟退黄汤治疗乙型黄疸性肝炎疗效确切。

恩替卡韦与阿德福韦酯治疗乙型病毒性肝炎失代偿性肝硬化患者的临床研究

目的观察恩替卡韦与阿德福韦酯对乙型病毒性肝炎失代偿性肝硬化患者甲状腺功能和肝功能的影响。方法 183例乙型病毒性肝炎失代偿性肝硬化患者随机分为试验组92例与对照组91例。对照组口服阿德福韦酯,每日1次,每次10 mg;试验组口服恩替卡韦,每日1次,每次0.5 mg。2组治疗均持续48周。比较2组治疗前后甲状腺功能及肝功能变化情况。结果治疗12,24,48周后,试验组乙型病毒性肝炎病毒(HBV)DNA阴转率分别为4.35%(4/92例),8.69%(8/92例),26.09%(24/92例),对照组分别为7.69%(7/91例),9.89%(9/91例),28.57%(26/91例),(P<0.05)。治疗后,试验组谷丙转氨酶(ALT)复常和HBV e抗原(HBe Ag)转阴率分别为91.30%(84/92例),26.09%(24/92例),对照组分别为97.80%(89/91例),28.57%(26/91例),差异无统计学意义(P>0.05)。治疗后,试验组的ALT为(46.37±3.86)U·L^(-1),谷草转氨酶(AST)为(52.13±3.86)U·L^(-1),对照组的ALT为(70.36±12.69)U·L^(-1),AST为(70.31±11.26)U·L^(-1)(P<0.05)。试验组总胆红素(TBIL)为(31.91±5.40)μmol·L^(-1),Child-pugh评分为(6.04±0.39),对照组的TBIL为(60.37±5.20)μmol·L^(-1),Child-pugh评分为(6.47±0.38),差异有统计学意义(P<0.05)。治疗后,试验组三碘甲状腺原氨酸(T3)为(1.52±0.40)nmol·L^(-1),甲状腺素(T4)为(96.37±37.05)nmol·L^(-1),对照组的T3为(1.02±0.41)nmol·L^(-1),T4为(78.26±28.34)nmol·L^(-1),差异有统计学意义(P<0.05)。试验组游离三碘甲状腺原氨酸(FT3)为(4.23±1.25)pmol·L^(-1),游离甲状腺素(FT4)为(11.97±2.40)pmol·L^(-1),对照组FT3为(3.16±1.84)pmol·L^(-1),FT4为(9.61±2.23)pmol·L^(-1),2组差异有统计学意义(P<0.05)。试验组促甲状腺素(TSH)水平为(2.27±1.14)μU·m L^(-1),对照组的为(3.60±1.21)μU·m L^(-1)(P<0.05)。2组死亡原因主要为消化道出血、肝性脑病、细菌感染,试验组死亡率为8.69%(8/92例),对照组死亡率为7.69%(7/91例,P>0.05)。2组治疗期间均未见耐药、明显药物不良反应及肾功能变化。结论与阿德福韦酯相比,恩替卡韦对乙型肝炎失代偿性肝硬化患者甲状腺功能及肝功能有更佳的改善作用。

Integrating proteomics and targeted metabolomics to reveal the material basis of liver-gallbladder damp-heat syndrome in chronic hepatitis B

Objective To elucidate the biological basis of liver-gallbladder damp-heat syndrome(LGDHS)within the framework of traditional Chinese medicine(TCM)as a complementary diagnostic and therapeutic approach in chronic hepatitis B(CHB).Methods CHB patients and healthy volunteers were enrolled from Shuguang Hospital Affili-ated to Shanghai University of Traditional Chinese Medicine between August 21,2018 and December 31,2020.They were divided into three groups:healthy group,LGDHS group,and latent syndrome(LP)group.Proteomic analysis using isobaric tags for relative and absolute quantitation(iTRAQ)was performed to identify differentially expressed proteins(DEPs).Metabolomic profiling via ultra-performance liquid chromatography-tandem mass spec-trometry(UPLC-MS/MS)was applied to serum samples to detect differentially regulated metabolites(DMs).Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment were employed to explore dysregulated pathways.Principal component analysis(PCA)and orthogonal partial least squares discriminant analysis(OPLS-DA)were utilized to visualize group separation and identify key metabolites and proteins contributing to LGDHS differentiation.Receiver operating characteristic(ROC)curve analysis evaluated the diagnostic performance of key biomarkers,while logistic regression models assessed their predictive accuracy.P values were corrected for multiple tests using the Benjamini-Hochberg method to control the false discovery rate(FDR).Validation of potential biomarkers was con-ducted using independent microarray data and real-time quantitative polymerase chain reac-tion(RT-qPCR).Results A total of 150 participants were enrolled,including healthy group(n=45),LGDHS group(n=60),and LP group(n=45).254 DEPs from proteomics data and 72 DMs from metabolomic profiling were identified by PCA and OPLS-DA.DEPs were mainly enriched in immune and complement pathways,while DMs involved in amino acid and energy metabolism.The integrated analysis identified seven key biomarkers:α1-acid glycoprotein(ORM1),asparagine synthetase(ASNS),solute carrier family 27 member 5(SLC27A5),glu-cosidase II alpha subunit(GANAB),hexokinase 2(HK2),5-methyltetrahydrofolate-homocys-teine methyltransferase(MTR),and maltase-glucoamylase(MGAM).Microarray validation confirmed the diagnostic potential of these genes,with area under the curve(AUC)values for ROC analysis ranging from 0.536 to 0.759.Among these,ORM1,ASNS,and SLC27A5 showed significant differential ability in differentiating LGDHS patients(P=0.016,P=0.035,and P<0.001,respectively),with corresponding AUC of 0.749,0.743,and 0.759,respectively.A logis-tic regression model incorporating these three genes demonstrated an AUC of 0.939,indicat-ing a high discriminatory power for LGDHS.RT-qPCR further validated the differential ex-pression of ORM1 and SLC27A5 between LGDHS and LP groups(P=0.011 and P=0.034,re-spectively),with ASNS showing a consistent trend in expression(P=0.928).Conclusion This study integrates multi-omics approaches to uncover the molecular mecha-nisms underlying LGDHS in CHB.The identification of biomarkers ORM1,ASNS,and SLC27A5 offers a solid basis for the objective diagnosis of LGDHS,contributing to the stan-dardization and modernization of TCM diagnostic practices.

Role of Antivirus Therapy in Treatment of Hepatocellular Carcinoma with Chronic Hepatitis B Infection

Objective： To observe the recurrence and prognosis of hepatocellular carcinoma （HCC） patients coexisting with chronic hepatitis B infection with active virus replication after receiving antivirus therapy using lamivudine and thymosin α1 （Tα1） postoperatively. Methods： From Jan. 2000 to Dec. 2003, 70 patients with HCC coexisting chronic hepatitis B infection with active virus replication were prospectively divided into two groups： control group （n=35） received hepatectomy only; treatment group （n=35） received hepatectomy and lamivudine plus Tα1 therapy postoperatively. The suppression of HBV-DNA, HBeAg seroconverted rate, tumor recurrent rate and the median survival for the two groups were observed and calculated. Results： In treatment group and control group, the 2-year HBV-DNA suppression rate was 100% vs. 4% （P=0.0000）; HBeAg seroconverted rate was 73.0% vs. 7.5% （P〈0.05）; the recurrent rate was 10.0 vs 6.5 months （P=0.0032）; the median survival time was 12.5 vs. 6.0 months （P=0.0023）, respectively. Conclusion： Antivirus therapy using lamivudine and Tα1 postoperatively may suppress the HBV reaction, delay the recurrent time and prolong the survival for HCC patients coexisting chronic HBV infection with active virus replication.

Reduced bone mineral density and altered bone turnover markers in patients with non-cirrhotic chronic hepatitis B or C infection

AIM: Previous studies suggest that loss of bone mineral density (BMD) frequently occurs in patients with chronic viral liver disease, presenting with histologically proven liver cirrhosis. However, little is known about the occurrence of bone disease in non-cirrhotic patients with chronic hepatitis B or C. Therefore, it was the aim of this study to evaluate this particular population for BMD and bone turnover markers. METHODS: Biochemical markers of bone turnover and BMD were measured in 43 consecutive patients with HCV (n = 30) or HBV (n = 13) infection without histological evidence for liver cirrhosis. Mean age was 49 years (range 26-77 years). BMD was measured by dual X-ray absorptiometry in the femoral neck (FN) and the lumbar spine (LS) region. In addition, bone metabolism markers were measured. RESULTS: BMD was lowered in 25 (58%) of the patients with chronic hepatitis B or C (FN; 0.76 (0.53-0.99); LS: 0.96 (0.62-1.23) g/cm2). Eight (32%) osteopenic patients were diagnosed with osteoporosis. Bone-specific alkaline phosphatase (P= 0.005) and intact parathyroid hormone (iPTH) (P = 0.001) were significantly elevated in the more advanced stages of fibrosis. Mean T-score value was lower in patients with chronic hepatitis C as compared to patients suffering from chronic hepatitis B; however, the difference was not statistically significant (P= 0.09). CONCLUSION: There was a significantly reduced BMD in non-cirrhotic patients with chronic hepatitis B or C infection. Alterations of bone metabolism already occurred in advanced liver fibrosis without cirrhosis. According to our results, these secondary effects of chronic viral hepatitis should be further investigated.

Viral and host causes of fatty liver in chronic hepatitis B

AIM: To investigate the viral and host causes of fatty liver in chronic hepatitis B patients and the role of fat deposits in liver damage.METHODS: A total of 164 patients (113 males and 51 females, average age 35±11.3 years, and range 10-62 years) with previously untreated chronic hepatitis B were included in the study. The patients were divided into two groups depending on the result of liver biopsy: group without steatosis (100 patients with ＜5% hepatosteatosis) and group with steatosis (64 patients with ＞5% hepatosteatosis). The groups were compared in terms of gender, body mass index (BMI), liver enzymes (ALT, AST, ALP, GGT), cholesterol, triglyceride, HBeAg, viral load, and histological findings. In the group with steatosis, the patients were subdivided depending on the degree of steatosis into mild group (45 patients with 5-24% steatosis), and severe group (19 patients with ＞25% steatosis). RESULTS: In the group of chronic hepatitis B with steatosis, the mean age, BMI, cholesterol, and triglyceride levels were significantly higher than those in the group without steatosis (P＜0.05). Steatosis was found in 53 (46.9%) of male patients and 11 (22%) of female patients (P＜0.05). No significant difference was found in the positivity of ALT, AST, ALP, GGT, HBeAg, viral load, histological activity index (HAI) and stage between the two groups (P＞0.05). In the group with severe steatosis, the BMI was significantly higher than that in the group with mild steatosis (P＜0.05). No significant difference was found in the other parameters between the groups (P＞0.05). CONCLUSION: Steatosis in chronic hepatitis B appears to be a result of metabolic factors of the host rather than the effect of viruses. Steatosis is unrelated to the HAI and degree of fibrosis, which are considered as the histological indicators of liver damage.

Relationship of human leukocyte antigen class II genes with the susceptibility to hepatitis B virus infection and the response to interferon in HBV-infected patients

AIM： To study the relationship of human leukocyte antigen （HLA）-DRB1 and -DQB1 alleles with the genetic susceptibility to HBV infection and the response to interferon （IFN） in HBV-infected patients. METHODS： Low-resolution DNA typing kit was used to determine HLA-DR-1 and -DQB1 genes in 72 patients with chronic hepatitis B （CHB） and HLA-DRB1 in 200 healthy people ready to donate their bone marrow in Shanghai. Among CHB patients, 35 were treated with IFNα-1b for 24 wk. RESULTS： The frequencies of HLA-DRBI＊06, DRBI＊08 and DRB1＊16 alleles in 72 patients were higher than in 200 healthy people （2.08% vs0%, OR = 3.837, P= 0.018; 11.11% vs5.50%, OR = 2.148, P= 0.034; and 6.94% vs 3.00%, OR = 0.625, P = 0.049, respectively）; whereas that of DRBI＊07 allele was lower （2.78% vs 7.75%, OR = 0.340, P= 0.046）. The frequency of HLA-DRBI＊ 14 allele was higher in 11 responders to IFN compared with 24 non-responders （18.18% vs2.08%, OR = 10.444, P = 0.031）, whereas that of DQBI＊07 allele was inverse （9.09% vs37.50%, OR = 0.167, P= 0.021）. CONCLUSION： The polymorphism of HLA class II may influence the susceptibility to HBV infection and the response to IFN in studied CHB patients. Compared with other HLA-DRB1 alleles, HLA-DRBI＊06, DRBI＊08, and DRB1＊16 may be associated with chronicity of HBV infection, HLA-DRBI＊07 with protection against HBV infection, and HLA-DRB1＊14 allele may be associated with a high rate of the response of CHB patients to IFN treatment. Compared with other HLA-DQB1 alleles, HLA-DQBI＊07 may be associated with low response rate to IFN. 2005 The WJG Press and Elsevier Inc. All rights reserved