目的 探究白细胞介素-28B(IL-28B)基因多态性与慢性乙型肝炎病毒(HBV)感染相关肝硬化发生及预后的关联.方法 选取2021年10月-2022年12月于杭州市西溪医院就诊的慢性HBV感染相关肝硬化患者120例为肝硬化组,另招募同期性别、年龄匹配的体检健康人群120名为对照组,其中肝硬化患者根据疾病进展情况分为代偿期组和失代偿期组;检测血清IL-28B水平和肝功能标志物,并采用聚合酶链反应(PCR)法和直接测序法检测外周血IL-28B基因rs12979860、rs8099917位点多态性.结果 肝硬化组血清IL-28B水平低于对照组,肝功能指标丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)和总胆红素(TBIL)均高于对照组(P＜0.05);肝硬化组和对照组rs12979860位点、rs8099917位点基因型和等位基因差异有统计学意义(P＜0.05),其中rs12979860位点C等位基因、rs8099917位点T等位基因是HBV感染相关肝硬化的影响因素(P＜0.05);失代偿期组患者血清IL-28B低于代偿期组,ALT、AST及TBIL均高于代偿期组(P＜0.05).结论 IL-28B基因rs12979860、rs8099917位点多态性与HBV感染相关肝硬化发生和预后有关,可能通过影响血清IL-28B水平参与慢性HBV感染相关肝硬化发生发展.

目的 探讨慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的危险因素.方法 选取2018年1月至2020年6月在杭州市西溪医院诊断治疗的慢性乙型肝炎患者130例的临床资料进行回顾性分析,130例患者中35例发生慢加急性肝衰竭,为肝衰组,95例为非肝衰组.记录患者的一般资料及临床资料,单因素及多因素分析慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的危险因素.结果 单因素分析结果显示,HBV DNA≥107拷贝/L,有家族史,合并感染,肝功能分级C级的患者发生肝衰竭的发生率更高,差异有统计学意义(P<0.001);肝衰竭组TBiL更高,清蛋白水平更低,国际标准化比率更高,凝血酶原活动度更低,与非肝衰组比较,差异有统计学意义(P<0.001).多因素分析结果显示,HBV DNA≥107拷贝/L,感染,肝功能分级C级,TBiL≥171μmol/L,国际标准化比率≥1.5是慢性乙型病毒性肝炎发生慢加急性肝衰竭的独立危险因素,PTA>40％,清蛋白>20 g/L是保护因素(P<0.001).结论 慢加急性肝衰竭是慢性乙型病毒性肝炎严重的并发症,患者预后较差.影响慢性乙型病毒性肝炎患者发生慢加急性肝衰竭的因素较多,对于具有高危因素的患者,应积极预防慢加急性肝衰竭的发生.

目的 探讨外周血微小RNA(miR)-146基因多态性与乙型肝炎病毒感染患者肝硬化的易感性及其水平与病情严重程度的关系.方法 选择杭州市西溪医院肝病科2018年5月-2020年6月收治的乙型肝炎肝硬化患者100例纳入研究组,选择同期医院收治的乙型肝炎非肝硬化患者60例作为对照组.采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术检测两组miR-146a基因rs2910164位点基因型及表达水平,比较不同基因型患者乙型肝炎病毒载量、血清谷丙转氨酶(ALT)、谷草转氨酶(AST)及总胆固醇(TC)水平.结果 研究组miR-146a基因rs2910164位点CC基因型、C等位基因频率均高于对照组(P＜0.05);100例慢性乙型肝炎肝硬化患者根据病情程度分为Child-pugh(A、B、C)三组,Child-pugh C组CC基因型频率高于Child-pugh A组及Child-pugh B组(x2=18.291、11.431,P均＜0.001);miR-146a基因rs2910164位点CC基因型患者miR-146 mRNA、AST、ALT、TC水平高于TT/TC患者(P＜0.05),HBV-DNA水平比较差异无统计学意义.结论 miR-146a基因rs2910164位点多态性与HBV感染者发生肝硬化风险相关,miR-146 mRNA水平对肝硬化程度判断具有一定的价值.

目的:分析湿热瘀黄证慢加急性肝衰竭患者肠道菌群分布特征,探讨其在预测慢加急性肝衰竭预后中的价值.方法:纳入湿热瘀黄证慢加急性肝衰竭患者37例,提取粪便肠道菌群DNA,进行16S rDNA高通量测序,以入组24周时状况或死亡为终点判断,分为好转组和无好转组,应用生物信息分析软件和统计学软件对测序结果进行分析.结果:好转组患者厚壁菌门、芽孢杆菌纲、丹毒丝菌纲、乳杆菌目、巴斯德菌科、十八梭菌属的相对丰度高于无好转组(P<0.05),而变形菌门、肠杆菌目的相对丰度低于无好转组(P<0.05);两组间Alpha多样性分析没有明显差异;好转组患者肠道菌群物种数量大于无好转组;Lefse分析显示两组患者肠道菌群在多个分类学水平都有比较大的差异(P<0.05).结论:湿热瘀黄证慢加急性肝衰竭患者病情进展与其肠道菌群有着密切联系,肠道菌群在预测病情转归及预后方面有着重要的价值.

自发性细菌性腹膜炎(spontaneous bacterial peritonitis,SBP)可加剧慢加急性肝衰竭并发肝功能损害,明显增加死亡风险,尽早诊断及预防SBP发生对降低慢加急性肝衰竭病死率有重要意义[1].越来越多的研究证实肠道菌群与肝脏疾病的发生发展存在密切联系,肠道微生态紊乱对肝衰竭病情进展也有一定影响,但尚待深入研究[2-4].本研究运用 16S rDNA高通量测序技术对慢加急性肝衰竭患者粪便菌群基因组进行分析,对比有无SBP患者肠道菌群在结构和功能上的异同,旨在探讨慢加急性肝衰竭患者并发SBP的肠道菌群特征,为提高SBP诊治能力并最终改善肝衰竭患者预后提供线索.

目的:探讨乙型肝炎病毒BCP区A1762T/G1764A变异与肝脏疾病进展的关系.方法:收集78例慢性乙型肝炎患者(CHB)和125例慢性重型乙型肝炎患者(CSHB)的血清及临床资料,并对所有入组患者进行随访,采用聚合酶链反应扩增HBV BCP区基因片段,产物纯化后直接测序,检测BCP区T1762/A1764位点变异.结果:CSHB组患者A1762T、G1764A及A1762T+ G1764A的变异频率分别为64.0％ (80/125)、60.0％ (75/125)、60.0％ (75/125),CHB患者3种变异的变异频率分别为30.8％(24/78)、28.2％ (22/78)、25.6％(20/78),CSHB组3种变异的变异频率均明显高于CHB组,差异有统计学意义(P ＜0.001).125例CSHB患者随访48周,死亡组A1762T/G1764A位点变异频率明显高于存活组,差异有统计学意义(x2=12.42,P＜0.001);A1762T/G1764A位点变异组的患者累积存活率明显低于未变异组(x2=9.742,P＜0.01).结论:HBV BCP区1762/1764位点变异可能会加重HBV感染后肝脏疾病病情,并且对慢性重型乙型肝炎的发病及预后可能起重要的作用.

Objective To investigate the efficacy of long-acting interferon (peginterferon alfa-2b, PEG-IFNα-2b) plus ribavirin for treating chronic hepatitis C(CHC) in comparison with that of conventional interferon alfa-2b (IFNα-2b) plus ribavirin. Methods A total of 96 consecutive, treatment-naive, HCV RNA-positive patients with chronic hepatitis were randomly assigned to once weekly PEG-IFNα-2b(Observational group, n=48) or every other day IFNα-2b(Control group, n=48) plus ribavirin for 48 weeks. The rates of early-, end of treatment-, and sustained- virological response (VR) to-gether with the safety and adverse-event profiles between the two groups were compared. Results More patients in obser-vational group than control group achieved an early VR (χ2=6.27,P<0.05), an end of treatment VR (χ2=4.17,P<0.05) and a sustained VR(χ2=4.44,P<0.05). The safety profile was similar between the two groups(χ2=0.12,P>0.05). Conclu-sions PEG-IFNα-2b plus ribavirin is more effective than IFNα-2b plus ribavirin for treating CHC, but its sustained VR rate needs further improvement.

Objective To investigate the hepatic expression of sterol regulatory element binding protein (SREBP)-1c in patients with non-alcoholic fatty liver disease (NAFLD) and its significance.Methods Twenty patients with NAFLD were included,and 20 age/sex matched asymptomatic HBV carriers (ASC) without steatosis evidenced by liver biopsy were used as control in the same time scale.Hepatic SREBP1c was detected using SP method of immunohistochemistry.An automatic biochemical analyzer (Hitachi 7060) was used to measure serum levels of lipids (TG,CHO),fasting blood glucose (FBG) and liver enzymes (AST,A LT,and GGT),and electrochemiluminescence was used to determine fasting insulin (FINS).Results Compared with the control group,NAFLD patients showed diffusely hepatic steatosis and a significantly higher expression of hepatic SREBP1c (P ＜ 0.05).Consistently,serum levels of ALT,AST,TG,CHO,FSG and FINS all increased than those of control group (P ＜ 0.05).Conclusions Hepatic expression of SREBP1c increased significantly in patients with NAFLD,and this over expression may be involve in fatty degeneration of the livers in human.

The present study aimed to compare the short-term prognostic performance of a series of model for end-stage liver disease (MELD) and respective delta (∆) scores scoring systems in a population with acute-on-chronic hepatitis B liver failure (ACHBLF), and to investigate the potential effects from antivirals. A total of 77 patients with ACHBLF of mean age 46 years, 82% male, with 58.4% receiving antivirals, were recruited for this study. The ∆ scores for MELDs were defined as the changes one week after admission. Thirty‑eight (49%) patients (22 treated with antivirals) died within three months. The mean MELD and ∆MELD scores of the survival group were 19.5 ± 4.4 and 0.2 ± 3.7 respectively, and those of the mortality group were 23.5 ± 5.5 and 7.9 ± 6, respectively. The area under the receiver operating characteristic curve (AUC) for MELD, integrated MELD (iMELD), MELD with the addition of serum sodium (MELD-Na), updated MELD (upMELD), MELD excluding the international normalized ratio (INR; MELD-XI), United Kingdom MELD (UKMELD) and their ∆ scores were 0.72, 0.81, 0.77, 0.69, 0.65, 0.77 and 0.86, 0.83, 0.83, 0.82, 0.79 and 0.79, respectively. iMELD and MELD-Na significantly improved the accuracy of MELD (P<0.05). A cut-off value of 41.5 for the iMELD score can prognose 71% of mortalities with a specificity of 85%. In each pair of models, the ∆ score was superior to its counterpart, particularly when applied to patients with MELD ≤ 30. Decreased accuracy was observed for all models in the subset of patients treated with antivirals, although their baseline characteristics were comparable to those of untreated patients, while iMELD, MELD-Na and respective ∆ models remained superior with regard to the predictability. The iMELD and MELD-Na models predicted three-month mortality more accurately, while the ∆ models were superior to their counterparts when MELD ≤ 30; however, their performance was altered by antivirals, and thus requires optimization.

OBJECTIVE:To explore the correlation of serum hepatitis B surface antigen (HBsAg) level and hepatic tissue pathological staging in the chronic hepatitis B infected persons.METHODS:Collect the clinical data of 272 cases who are HBsAg-positive more than 6 months and accepted hepatic biopsy in our hospital. Detect serum HBsAg quantification, ALT, HBV DNA, complete blood count, hepatic tissue pathological staging, grouping the cases according to the stage of inflammation and the fibrosis degree respectively. Observe serum HBsAg quantification, HBV DNA and the stage of inflammation and the fibrosis degree. Analyse the correlation between HBsAg quantification and HBV DNA.RESULTS:The correlation of serum HBsAg level and HBV DNA is notable. Serum HBsAg level is a variable affecting hepatic tissue pathological stage significantly.CONCLUSIONS:Serum HBsAg level is a marker having higher specificity and sensitivity to diagnose the hepatic fibrosis.

肿瘤抑制基因P53在乙型肝炎病毒相关肝细胞癌的发生中起着关键作用。研究乙型肝炎病毒基因组编码蛋白对P53基因网络的调控作用,有助于阐明两者在肝细胞癌发病中的作用机制。本文重点对P53基因网络的调控、P53基因突变、凋亡调节异常及乙型肝炎病毒X蛋白对P53基因网络调控的影响进行了综述。

Objective:To observe the relationship of Yin deficiency and hepatic pathology and genotyping of HLA-DRB1 HLA DQA1 alleles in chronic asymptomatic HBV carrier,and discuss the effect of constitution factor on degrees of inflammatory activity and fibrosis.To improve inflammatory activity and fibrosis by adjusting pathological.Method:According to the diagnostic criteria,105 cases of chronic HBV carriers were selected,then divided into two groups:Yin deficiency(47 cases)and non-Yin deficiency(58 cases).The general condition such as age,gender and family history were recorded.The bioptic liver specimens from 105 cases of patients with chronic asymptomatic HBV carrier were analyzed.The examine of pathogeny,hepatic function and genotyping of HLA-DRB1 HLA DQA1 alleles were tested.Results:Through statistical analysis,there was no significant difference of pathogen indicators(HBsAg,HBV-DNA,HBeAg)and liver functional indices(TBiL,DBiL,ALT,AST,AlB,GLB)between the two groups(P>0.05).The difference was not statistically significant on inflammatory activity between the two groups(P>0.05).The incidence of fibrosis in patients of Yin deficiency was significantly higher than that in non-Yin deficiency group(P<0.05).There was no statistical significance on HLA-DRB1,HLA-DQA1 allele frequency among the degrees of liver pathologic histology in chronic asymptomatic HBV carrier(P>0.05).Conclusion:Most chronic asymptomatic HBV carriers had mild liver pathologic histology,but some were moderate and severe hepatitis.The incidence of fibrosis in patients of Yin deficiency was significantly higher than that in non-Yin deficiency group.Yin deficiency has susceptibility to liver fiberosis,further progress to be liver cirrhosis namely.

Objective:To explore the relationship between prognosis and TCM syndrome differentiation of severe chronic hepatitis B.Methods:Prospective studies were used to investigate 97 hospitalized cases of severe chronic hepatitis B in our hospital from March 2009 to June 2010.All patients were typed by the symptom differentiation and follow-up visited until death or for at least 24 weeks.Results:The 12-week fatality rates of qi-deficiency related stagnant jaundice and yin-deficiency related stagnant jaundice were much higher than that of heat-stagnant jaundice syndrome(P0.05),The 12-week fatality rate of qi-deficiency related stagnant jaundice was also higher than that of damp-heat jaundice syndrome(P=0.020);there was significant deviation among different groups' cumulative survival rates,the 24-week cumulative survival rates of patients with qi-deficiency or yin-deficiency were obviously lower than other three syndromes(P=0.022).Conclusions:There is some relation between prognosis and TCM syndrome differentiation of severe chronic hepatitis B.

OBJECTIVE:To evaluate the prognostic value of the model for end-stage liver disease (MELD) and deltaMELD in liver failure patients infected with hepatitis B virus. METHODS:Based on prospective study design, 98 hospitalized cases were studied and followed up for 24 weeks. The clinical data were recorded. We calculated the score of MELD and deltaMELD, and also compare the score between the survival group and death group. Using ROC curve plotting obtained the better decisive threshold. The case fatality rate were compared at different time points which the patients were classified by the best critical value of MELD and deltaMELD. We draw the Kaplan-Meier survival curve of different group and analyse the change of survival rate by log-rank analysis. RESULTS:52 of 97 patients died and 46 survive during 24 weeks of followup. There was significant difference between the two groups for MELD and deltaMELD (P < 0.01). The case fatality rate in group which MELD > or = 23 was obviously higher than in that MELD < 23. The rate in group which deltaMELD > 4.5 was obviously higher than in that deltaMELD < 4.5 (P < 0.001). The area under curve (AUC) for the twelfth and 24th week's prognosis judgment of deltaMELD (0.823, 0.815) was larger than that of MELD (0.680, 0.684) (P < 0.05). Survival analyses (Kaplan-Meier) indicated that there were significant differences in cumulative survival rates among the groups which were grouped by optimization critical value ( P = 0. 000). CONCLUSIONS:The scoring system of MELD also applied to the forecasting of prognosis for severe hepatitis B patients in China. The accuracy of deltaMELD to predict the prognosis was higher than that of MELD. The combination of MELD and deltaMELD showed good clinical practical value.

Objective: To observe the therapeutic effect of TCM syndrome differentiation and treatment on novel H1N1 influenza A.Methods: 120 cases of novel H1N1 influenza A were randomly divided into TCM group and western medicine group(n=60).The patients of western medicine group received oseltamivir phosphate capsules,and the patients of TCM group were given Sangjuyin Decoction plus or minus,or Yinqiao Powder plus Baihu Decoction plus or minus.The improvement of the symptom and physical sign of patients were observed,the subsets of T-lymphocyte was analyzed before and after treatment.Results: There was no difference between two groups in influenza symptoms of the patients before the treatment.The clinical score of influenza symptoms in TCM group was 1.40±0.85 and in western medicine group was 2.90±1.35 after treatment,which showed significant difference(P0.01).The mean fever duration was(3.67±1.13)d in TCM group and(3.83±1.81)d in western medicine group,the difference was not significant.Compared with before treatment,the counts of CD3,CD4 and CD8 cells were significantly improved both in TCM group and western medicine group,while there were no difference between the two groups after treatment.Conclusion: TCM syndrome differentiation and treatment has a similar efficacy in shorten duration of fever to western medicine,with better efficacy in improvement of influenza symptom.TCM syndrome differentiation and treatment affected the count of peripheral blood T-lymphocyte subsets as well as western medicine.

OBJECTIVE:To investigate the effect of extract of ginkgo biloba leaf (EGb) during the formation of HBV-related hepatocellular carcinoma (HCC).METHODS:99 HBV transgenic mice were randomly divided into control group, high-dose group, low-dose group. High-dose group and low-dose group were intraperitoneal injected 35mg/(kg x d) and 17.5 mg/(kg x d) of the shuxuening injection. Control group without special treatment. The serological markers and immunohistochemical markers in liver tissue will be done at the first 12 months and 18 months.RESULTS:(1) HBV transgenic mice can be found HCC at the 18 months. The incidence of HCC was lower in high-dose group and low-dose group, there was statistically different among the three groups. (2) The semi-quantitative scoring of liver HBx expression was highest in the control group at the 12 months. The semi-quantitative scoring of liver HBx, p53 and Bcl-2 expression was highest in the control group at the 18 months. They all appeared statistically different among the three groups. (3) Spearman correlation analysis showed that HCC incidence and liver tissue HBx, p53, Bcl-2 expression was a certain degree of positive correlation, r was 0.536, 0.487 and 0.403, P < 0.05.CONCLUSION:EGb can reduced the incidence of the HCC with HBV transgenic mice. The reason may be that the EGb can reduce liver HBx, p53, Bcl-2 protein expression in the HBV transgenic mice.

OBJECTIVE:To observe p53 expression in liver tissue of patients with chronic hepatitis B and its influencing factors.METHODS:17 cases HBeAg-negative chronic hepatitis B patients and 31 cases HBeAg-positive chronic hepatitis B patients were divided into 2 groups.RESULTS:(1) HBeAg-negative chronic hepatitis B patients were older, mostly male and HBV DNA lower. These three indicators between two groups patients appeared statistical difference. Serum markers were no statistical difference between two groups patients except Glo. (2) Pathological inflammation and fibrosis Staging were no statistical difference between two groups patients. p53 expression positive rate and p53 expression semi-quantitative scoring in liver tissue were no statistical difference between the two groups. (3) Logistic regression analysis showed that only liver fibrosis staging (S) is a risk factor for p53 expression. Compared with the S0-1, p53 expression increased by 3.9 times the rate of positive in S > or = 2.CONCLUSION:Liver fibrosis staging in patients with chronic hepatitis B is a risk factor for p53 positive expression in liver.

Objects: To investigate the association between TCM constitution type and chronic severe hepatitis B(CSH) in Chinese Han population.Methods: A total of 80 consecutive subjects with CSH and 100 patients with biopsy-proven hepatitis B virus infection(60 patients with chronic hepatitis B and 40 patients with asymptomatic HBV carrier) were studied.The constitution type was determined by Wangqi'classification.Rerults: ①There was no significant differences about frequencies of constitution type between CSH group and chronic hepatitis B group.②The frequency of dampness-heat constitution and yin-deficiency in CSH group were significant higher(45%vs7.5%;25%vs5%),the frequency of harmony constitution,qi-deficiency and yang-deficiency were significant lower(6.2%vs42.5%;3.8%vs22.5%;2.5%vs15%,respectively),than those in asymptomatic HBV carrier group(P0.01).Conclusion: TCM constitution type may play an important role in the development of CSH.Dampness-heat constitution and yin-deficiency constitution could facilitate the development of CSH in asymptomatic HBV carrier.

目的 分析、总结重症手足口病病例的临床表现、流行病学特征,帮助及早发现重型病例.方法 回顾性分析杭州市第六人民医院2010年4～8月收住院的116例重症手足口病的临床表现、流行病学特征.结果 发病年龄以3岁以下为主,发热发生率为100%,出现肢体抖动、肢体无力或肌阵挛症状的占92.24%,反复或持续发热发生率为58.62%,病原学检查肠道病毒71型(EV71)核酸阳性74.51%;死亡4例,占3.45%.结论 肢体抖动、肌阵挛、发热持续时间对早期发现重型病例有重要的提示意义.

Objective:To explore the distribution and characteristics of TCM syndromes of chronic severe hepatitis B(CSHB),in order to provide dialectical evidence for future clinics.Methods:Collect the general conditions,four diagnostic information of TCM and related laboratory tests of patients with CSHB in Hangzhou Sixth Hospital between May 2009 to January 2010.Zheng differentiation-classification relied on the major science and technology projects of National 11th five-year plan-the TCM syndromes characteristics and conbined therapy of traditional Chinese medicine and western medicine of chronic severe hepatitis B,to analyze the relationship between the characteristics of TCM syndromes and the clinical feature.Results:(1)In total of 99 CSHB patients were included,which encompassed of 80(80.08%) cases with acute-on-chronic liver failure.Our objects were 15 to 72 years old(mean age 44.48 12.26),74(74.75%) cases were male.(2)In terms of TCM syndromes,there were 27(27.27%) cases with heat-stagnant jaundice syndrome,26(26.26%) cases with qi-deficiency related stagnant jaundice,21(21.21%) cases with damp-heat jaundice syndrome,16(16.16%) cases with yin deficiency related stagnant jaundice and 9(9.09%) cases with yang deficiency related stagnant jaundice.(3)No differences were found among the TCM sydromes(P0.05).(4)In the 80 patients with acute-on-chronic liver failure,the distribution of TCM syndromes in the three clinical stages had statistically difference(P0.05),the predominant sydrome in early-,mid-,and end stage were qi-deficiency related stagnant jaundice(43.6%),heat-stagnant(27.3%) and damp-heat jaundice syndrome(22.7%),yin deficiency related stagnant jaundice(27.8%),in turn.(5)In terms of laboratory results,none of the markers related to TCM sydromes except for the international normalized ratio(INR),the INR level in yin deficiency related stagnant jaundice was higher than that in qi-deficiency related stagnant jaundice(P0.05).Conclusion: Heat-stagnant jaundice syndrome,qi-deficiency related stagnant jaundice and damp-heat jaundice syndrome were the predominant types of TCM sydromes in CSHB in Zhejiang province.For the acute-on-chronic liver failure,the predominant sydrome in early-,mid-,and end stage were qi-deficiency related stagnant jaundice,heat-stagnant and damp-heat jaundice syndrome,yin deficiency related stagnant jaundice,in turn.The coagulation function in yin deficiency related stagnant jaundice worsen than that in qi-deficiency related stagnant jaundice,but it is difficult to differentiate the TCM sydromes relying on the routine laboratory markers in CSHB.