ObjectiveTo investigate the clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors. MethodsA total of 129 patients who were diagnosed with liver injury induced by anti-tuberculosis drugs in Shenzhen Third People’s Hospital from January 2017 to December 2018 were enrolled and divided into abnormal liver function group with 51 patients (39.53%) and drug-induced liver injury (DILI) group with 78 patients (60.47%), and among these 129 patients, 13 (10.08%) had liver failure. A retrospective analysis was performed for their laboratory markers as well as treatment and prognosis data. The chi-square test was used for comparison of categorical data between two groups; the independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariable logistic regression model was used to investigate the risk factors for DILI and liver failure. ResultsThere were significant differences between the DILI group and the abnormal liver function group in chronic HBV co-infection (χ2=5.616, P=0018), asymptomatic liver injury (χ2=9.451, P=0.002), liver failure (χ2=9.453, P=0.002), need to adjust anti-tuberculosis regimen (χ2=16.787, P＜0.001), time to identification of liver injury (Z=-4.001, P＜0.001), time to liver function recovery (Z=-1.735, P＜0.001), and hepatic encephalopathy (χ2=4.114, P=0.043). The multivariate logistic regression analysis showed that time to identification of liver injury ＞8 weeks (odds ratio ［OR］=3.94, 95% confidence interval ［CI］: 1.02-15.25, P=0.047) and asymptomatic liver injury (OR=7.64, 95% CI: 1.63-35.86, P=0.010) were independent risk factors for DILI; chronic HBV co-infection (OR=14.42, 95% CI: 2.66-78.09, P=0.002) and time to identification of liver injury ＞8 weeks (OR=11.97, 95% CI: 2.03-70.50, P=0.006) were independent risk factors for liver failure, while albumin ≥35 g/L (OR=0.07, 95% CI: 0.01-0.51, P=0.010) was a protective factor. ConclusionAnti-tuberculosis drugs may induce severe liver injury, and HBV co-infection, asymptomatic liver injury, long time to identification of liver injury, and low albumin level may increase the risk of severe liver injury. Regular follow-up, liver function monitoring, appropriate nutritional support, and HBV screening are important for reducing the risk of liver injury during anti-tuberculosis therapy.

肝脏作为人体的重要器官之一,具有去氧化以及储存肝糖原等主要功能,肝脏功能会受多种因素如饮酒以及病毒感染等影响.本文就长期饮酒、乙肝病毒(HBV)感染、两者相互作用对肝脏功能的影响及其作用机制等进行综述,旨为根据HBV携带者的饮酒行为及特点,制订有效措施进行必要的干预,从而改善他们的不良饮酒习惯,减少肝硬化以及肝癌的发生或减缓疾病的发展速度,提高HBV携带者的生活质量.

肝豆状核变性是一种罕见的铜代谢常染色体隐性遗传病.由于ATP-7B基因突变引起胆道排泄铜障碍导致肝脏、大脑基底节、肾脏和角膜组织中铜的异常蓄积.可导致重要器官,特别是肝脏、大脑的受损,如不恰当治疗将会致残甚至致死[1-2].肝豆状核变性起病临床症状及伴随疾病不一,本文报道1例肝豆状核变性伴多囊卵巢综合征患者. 1病例资料 患者女性,16岁,主因“闭经、双下肢浮肿1年余,加重10d”于2017年11月15日入本院治疗.患者1年前开始出现月经稀少、经期异常,后发展为闭经,外院查雄激素升高、附件彩超示卵巢体积增大,诊断为多囊卵巢综合征,于2017年7月开始服用“达英-35”治疗,后月经来潮.期间伴间断双下肢浮肿,休息后好转,未重视.10 d前出现双下肢浮肿加重,无泌乳、多毛,无行动失调、构语障碍,查Alb下降、PLT减少,至本院就诊.月经史:12岁初潮,12 ～ 14岁经期规律,经量正常.

炔诺酮是一种口服有效的孕激素( 19-去甲基睾酮衍生物),除作为避孕药外,还用于治疗功能性子宫出血、妇女不育症、痛经、闭经、子宫内膜异位症等. 常见的副作用有恶心、呕吐、乏力等类早孕反应及突破性出血、乳房肿胀、皮疹等,由其导致急性药物性肝损伤的报告相对少见.

Objective:To investigate gene mutation in a inherited thrombophilia family.Methods:The levels of blood coagulation factor and coagulation study was measured,Whole exome sequencing was conducted use DNA samples of two affected members of this family.Candidate mutation was confirmed by Sanger sequencing.Results:Whole exome sequencing revealed an exonic missense mutation c.C494T:p.T165M in coagulation factor Ⅱ gene.Conclusion:We have identified and confirmed that the T165M mutation in F2 may have caused thrombophilia in a Chinese family,The technology for the whole genome exome sequencing can solve many problems of the traditional positional cloning,such as too few of the patients of the family members of this disease,sporadic cases,heterogeneity of the genetic locus,incomplete exon,too many candidate genes and so on,to provide new solutions of the prenatal diagnosis of this disease.

目的 分析以原发性胆汁性肝硬化患者使用熊去氧胆酸(优思弗)治疗的早期生化学指标改变预测其用药1年获得生化学应答的准确性.方法 回顾性分析2011-01-2014-12间深圳市第三人民医院44例原发性胆汁性肝硬化患者单一使用熊去氧胆酸治疗1月、3月及1年生化学指标的改变.分别按照巴塞罗那标准(ALP下降40%视为有效)及巴黎标准(ALP<3ULN为有效)评估其效果,并比较用药1个月与1年、3个月与1年治疗有效病例的一致性.结果 按照巴塞罗那标准,患者使用优思弗1个月与1年、3个月与1年获得生化学应答的病例一致性Kappa值分别为0.697及0.790;而按照巴黎标准,相应的Kappa值分别为0.686及0.722,均提示有可信度较好.结论 使用优思弗治疗原发性胆汁性肝硬化患者时,可用其用药3个月时的生化学应答情况预测其用药1年时能否生化学应答.

目的 分析乙肝相关性慢加急性肝衰竭(HBV-ACLF)患者治疗前后降钙素原(PCT)水平的差值(ΔPCT)与病情转归的相关性.方法 观察组为90例HBV-ACLF患者,空白对照组为30例乙肝肝硬化代偿期患者.观察组检测治疗前(基线水平)?治疗后的肝脏生化?凝血功能及PCT并计算MELD评分,将治疗2周时MELD评分下降≥3分患者记为好转,下降<3分记为无好转.空白对照组只检查上述指标1次作为基线水平的评估.分析观察组患者治疗前后PCT水平的变化及其差值(ΔPCT)与MELD评分?总胆红素?国际标准化比值?血肌酐的相关性.对观察组患者90 d死亡率作预测分析,比较PCT?ΔPCT?MELD评分及其联合应用的曲线下面积(AUC),评估上述指标的预测价值.结果 早期HBV-ACLF治疗好转组PCT的基线水平较治疗无好转组高[(1.08±0.82)mg/L vs(0.65±0.36)mg/L,P=0.007],且治疗好转组于2周时测PCT较基线水平明显下降,而治疗无好转组反而升高,ΔPCT分别为(-0.48±0.66)mg/L及(0.2±0.56)mg/L,组间比较差异有统计学意义(P<0.001).而中期HBV-ACLF患者治疗好转组及治疗无好转组的PCT基线水平无明显差异[(0.6±0.32)vs.(0.58±0.31)mg/L,P=0.980],两组患者治疗前后的PCT变化不明显,ΔPCT分别为(-0.07±0.37)mg/L及(0.01±0.39)mg/L,组间比较差异无统计学意义(P=0.959).观察组HBV-ACLF患者治疗前后的ΔPCT与ΔMELD分值?ΔTB呈中度相关(相关系数分别为0.430及0.528,P均<0.001),但与ΔCr及ΔINR无相关性.以受试者工作特征曲线(ROC)对观察组患者入院90 d死亡率作预测分析表明:在早期HBV-ACLF患者中,以ΔPCT联合MELD的AUC较单独使用MELD评分的要高,分别为0.80和0.69,P=0.054,处于临界值.结论 早期HBV-ACLF患者的PCT水平高者短期(2周)疗效好,其ΔPCT水平与其病情转归相关,以ΔPCT水平联合MELD评分对于患者的90 d死亡率有预测价值.

Objective:To study the correlation between the IL-28 B gene polymorphism and Traditional Chinese Medicine syudrome,liver biochemical characteristics and APRI in patients with chronic hepatitis C.Methods:Pyrosequencing method was used to test genotype IL28B gene rs12979860 SNP and completed the liver biochemistry test,blood routine test,ultrasound examinatio in 105 cases of naive chronic HCVpatients visited our hospital.Then the TCM syndrome types were classified and the distribution of TCM Syndromes and their correlation with biochemical characteristics and APRI score were compared.Results:There were 90 cases CC type of IL28B gene in 105 chronic HCV patients visited our hospital.,the liver and kidney yin deficiency was the most common TCM syndrome in these patients(37 cases,41.1％),AST and APRI score in this TCM syndrome were significantly higher than other syndromes,and the percentage of liver cirrhosis was the highest in this syndrome.(P ＜ 0.05).Conclusion:The liver biochemical abnormalities and APRI score are most obvious in the liver and kidney Yin deficiency syndrome of IL28B allele for CC in patients with chroinc HCV,so the patients in liver and kidney Yin deficiency syndrome has the higher potential risk to cirrhosis.

[Objective]To analyze the changes of biochemical and immune indexes in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) superinfection.[Methods]The subjects of this study included: 30 cases with HIV infection (HIV group), 32 cases with HBV infection (HBV group), and 20 cases with both HIV and HBV superinfection(C group).The liver function, immune function, and routine blood biochemical indexes were compared between the three groups.[Results]①CD3+, CD4+ and CD4+/CD8+ in the HBV group were higher than those in the HIV group and C group (P<0.05), there was no significant difference in these values between the HIV group and C group (P>0.05).②AST, ALT, and TBiL in the HBV group were higher than those in the HIV group and C group (P<0.05).There was no significant difference between the HIV group and C group (P>0.05);③ The viral loads of HIV RNA and HBV DNA in the C group were higher than those in the HIV group (P<0.05).④Compared to the HIV and C group, the Hb levels were higher while the levels of PLT and RBC were lower in the HBV group (P<0.05).There were no significant differences in the Hb, PLT and RBC levels between the HIV group and C group (P>0.05).[Conclusion]A HIV / HBV superinfection may cause the body's immune function to decrease further and their condition to exacerbate, but it may actually reduce liver inflammatory injury in patients with HBV.It has no significant effect on HIV-induced anemia.

Objective To investigate the difference of the blood,child Pugh classification,liver function and HBV - DNA in patients with HBeAg negative and HBeAg positive hepatitis B cirrhosis,and analysis the relationship between disease progression in patients with HBeAg negative and HBeAg positive hepatitis B and liver cirrhosis. Methods From February 2013 to February 2015 in our hospital,215 cases with liver cirrhosis were divided into two groups according to HBeAg detection results,HBeAg negative group(137 cases)and HBeAg positive group(78 cases). Routine blood indexes of white cell count(WBC),platelet count(PLT),hemoglobin(HB),and liver function index of alanine amino transferase(ALT),serum total bilirubin(TBIL),albumin(ALB),and prealbumin(PA),prothrombin activity(PTA),and HBV - DNA by fluorescent quantitative PCR were detected;then record the gender,age,course of disease and child Pugh classification of the two groups. The difference in gender,age,course of disease,the hemogram,liver function,child Pugh classification of patients in the two groups were compared. Results There was no significant difference between the two groups in gender and disease course( P > 0. 05);the age of HBeAg negative group was significantly higher than the positive group,the difference was statistically significant( P < 0. 05). In HBeAg negative group,WBC and PLT were significantly lower than that in the positive group,the difference was statistically significant( P < 0. 05). HBeAg negative group ALT of liver function index was significantly lower than that of the positive group,the difference was statistically significant( P < 0. 05);in child Pugh classifi-cation,the proportion of patients with HBeAg negative group B was significantly lower than that of positive group,and the proportion of patients with grade C was significantly higher than that of the positive group,differences were statistically significant( P < 0. 05);the positive rate of HBeAg negative group,HBV - DNA fluorescence quantitative detection was significantly lower than that of the positive group,the differences were statistically significant( P < 0. 05). Conclusion Compared with HBeAg positive liver cirrhosis patients,HBeAg negative patients with liver cir-rhosis and inflammatory reaction are more serious,and the liver reserve function is poor,but HBeAg positive patients should be actively cooperate with the treatment,to prevent the generation of HBV mutant strain,and the increase of liver cirrhosis and into the development of liver cancer.

Objective To explore the clinical application of hepatitis B virus (HBV) gene mutation analysis in the individualized diagnosis of patients with hepatitis B.Methods A total 120 cases of peripheral blood samples from hepatitis B patients without any drugs and pathologic specimens from liver cancer patients after operations which were collected in our hospital form August 2011 to August 2014 were divided into group A and group B respectively.The relationship between HBV gene mutation in the BCP-PreC/C segment and clinical diagnosis was studied, and the DNA gene sequences were compared and analyzed by the HBV drug guide software.Results Results indicated that, there was a positive correlation between liver injury and gene mutation in the 1762/1764 segment,and there was a negative correlation between HBeAg and gene mutation in the 1896/1899 segment.Conclusion This paper provides a clinical reference for the individualized diagnosis of hepatitis B patients based on hepatitis B virus gene mutation analysis.

目的:本项目采用焦磷酸测序法对慢性丙型肝炎（CHC）患者的IL-28B基因SNP进行分型,明确CHC患者中IL-28B等位基因频率与其中医证候、肝纤维化的分布特征,借以比较肝纤维化在不同IL-28B等位基因及中医证候患者中的发生率,并指导今后针对CHC患者尤其是可能进展为肝硬化的高危患者的治疗。方法:采用焦磷酸测序法对在我院门诊及住院的105例CHC初治患者的IL-28B基因rs12979860 SNP位点的基因型进行检测,完善其血生化、病理学等检查,再对其进行中医辨证分型,比较不同等位基因中的中医证候的分布及不同证候中肝纤维化患者所占的比例。结果:采用焦磷酸测序法测得我院CHC患者的IL-28B基因分型为CC型（90例）及CT型（15例）。在等位基因为CC型的CHC患者中,中医证候为肝肾阴虚的患者比例最多[41.3%（37/90）],而CC型患者中肝纤维化的比例为53.3%（48/90）,CT型为20%（3/15）,差异有显著性意义（＜0.05）,其中CC型患者中医证候为肝肾阴虚的发生肝纤维化的相对危险度RR值为4.1,95%CI为1.6~10.2。结论:IL-28B等位基因为CC型的CHC患者主要中医证候为肝肾阴虚,CC型比CT型更容易发生肝纤维化,CC型中肝肾阴虚患者发生肝纤维化的概率最高,我们应加强对IL-28B等位基因为CC型患者的治疗与监测。

<正>他汀类也称3-羟基-3-甲戊二酰辅酶A还原酶抑制剂,具有竞争性抑制细胞内胆固醇合成早期过程中限速酶的活性,常用于治疗高血脂症,能显著降低总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C),也可降低甘油三酯(TG)水平和轻度升高高密度脂蛋白胆固醇(HDL-C)。大量循证医学证据表明,他汀类药物可以显著减少急性冠状动脉综合征及冠心病高危患者的主要心血管事件如死亡、心肌梗死、卒中

<正>【据Hepatology 2011年11月报道】题:HBV基因型B型或C型采用PEG-IFNα-2a治疗的疗程和剂量与HBeAg血清转换率相关(作者Liaw YF等)我国台湾地区长庚纪念医院肝病研究中心Liaw等进行了一项临床试验,旨在对使用聚乙二醇干扰素a-2a(PEG-IFNα-2a)90μg/周或180μg/周治疗24或48周疗程的疗效及安全性进行比较。HBeAg阳性患者544人(B、C基因型各占34%、51%)随机分组接受90μg/周或180μg/周PEG-IFN-2a 24或48周治疗,通过符合方案集分析方法进行2×2析因分析。该临床试验为非劣效性研究,主要疗效终点是治疗6个月后HBeAg血清学转换率。预先设定的OR非劣效性检验界值为1.88,单侧显著性差异水平为0.025。治疗6个月后HBeAg

<正>我国毒蕈(毒蘑菇)有200多种,广东则有100多种[1]。部分毒蕈及食用蕈的外观无明显区别,误食毒蘑菇中毒事件时有发生,每种毒蕈均有数个毒性肽,引起的临床表现也各异[2,3]。本文报道一起食用自采野生蕈(致命白毒伞,广东常见的剧毒蕈类)后发生6例中毒,其中4例为胃肠

Objective To analyze the clinical features and correlative factors of anti-tuberculosis drug-induced liver failure(DILF).Methods Thirty-four cases of anti-tuberculosis DILF were retrospectively analyzed.The patients were divided into the young group(<35 years old),middle-aged group(36-55 years old) and aged group(>56 years old). Statistical analysis was performed by using SPSS 13.0.Results In the 34 cases,the ratio between male and female was 0.8:1.The median age was 38.2(ranging 14-68) years old and the total mortality was 67.6%(23/34).There were 2 cases of hyper-acute liver failure and 8 cases of acute liver failure.The incidence was higher in young women(7 out of 10).The mortality was 80%.All of the aged were sub-acute liver failure.The mortality in aged group was higher than that in the young and middle aged groups(81.8%vs.33.3%,P<0.01).All patients initially received the anti-tuberculosis regimen of isoniazid,pyrazinamide and rifampin.The period from the initial treatment to drug-withdrawal in the occurrence of DILF ranged from 5 to 56 days(average 23 days).Ratio of serum HBsAg positive was 23.5%before treatment. In 3 cases with HBeAg negative,1 case developed into HBeAg positive and 2 cases with HBV DNA below the limit of detection developed into HBV DNA positive after the treatment with glucocorticoid.The mortality of HBsAg carriers was higher than that of non-carriers(75%vs 65.4%;P<0.05).Conclusion Hyper-acute liver failure or acute liver failure caused by anti-tuberculosis drugs was likely to be related to genetic polymorphism and human immune state.Subacute liver failure was likely related to the changes of liver pharmacokinetics in the old age.Glucocorticoid may enhanced HBV replication,which was related to the prognosis of liver failure.

Objective:To study HBV covalently closed circular DNA (cccDNA) in the distribution of peripheral blood and liver tissue content in the patients of chronic HBV infections,investigate the impact of anti-viral treatment on serum HBV covalently closed circular DNA(cccDNA)of patients with chronic hepatitis B.Methods:Randomly selected a total of 125 cases with HBV DNA positive chronic hepatitis B,cirrhosis,severe hepatitis patients,using real-time fluorescence quantitative PCR for the detection of serum cccDNA.DNA were extracted from serum and liver biopsy samples of 36 patients with chronic hepatitis B,and were measured by the real-time fluorescence quantitative PCR assay.Sixty cases of chronic hepatitis B patients were randomly assigned to receive lamivudine or interferon treatment in a ratio of 1:1.Serum HBV cccDNA and HBV DNA levels were detected with real-time PCR at the time of 0,8,12,24 weeks.Results:The cccDNA-positive rate was 71.2% in 125 patients,to the lowest positive rate in patients with cirrhosis.The positive rate of HBV cccDNA had significant difference between patients with cirrhosis and chronic hepatitis B patients or severe hepatitis patients(P<0.05).There was a significant correlation between intra-hepatic cccDNA,intra-hepatic total HBV DNA and serum HBV DNA(P<0.05).Mean-while,the positive rate had significant difference between HBeAg-positive group and HBeAg-negative group(P<0.05).After receiving antiretroviral therapy,level of serum HBV DNA and HBV cccDNA was decreased.Conclusion:Positive rate of serum HBV cccDNA in patients with cirrhosis is low.Viral replication in HBeAg(+) group is more active than in HBeAg(-) group.Anti-viral therapy has inhibition on serum HBV cccDNA;serum HBV cccDNA can be used as an important anti-viral treatment indicators for monitoring.

Objective To understand the virology test characteristics of hepatitis B virus (HBV) for discuss the relation of HBV genotype and HBeAg, anti-HBc-IgM, HBV DNA and disease progression. Methods Two hundred cases of hepatitis B were detected by the ELJSA assay with two pairs of semi-markers (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc) and anti-HBc-IgM, using fluorescence quantitative polymerase chain reaction (FQ-PCR) for detecting HBV DNA, using monoclonal antibody ELISA method (mAbs ELISA) for HBV genotyping and analysis of test results. Results In 200 patients with hepatitis B, the HBV genotype detected in 179 cases (89.5%), B-type 121 cases(60.5%), C-type 58 cases (29.0% ). There had no relationship with HBeAg, anti-HBc-IgM, HBV DNA and genotype. B-type HBV prevalent in asymptomatic carriers (ASC) and chronic hepatitis B (mild);C-type common in patients with liver cirrhosis (LC) and chronic hepatitis B (severe). Conclusions HBV genotype in Shenzhen mainly is B-type, C-type second;mAbs ELISA assay with HBV genotype is specific, sensitive, simple and practical features, HBV replication strength has nothing to do with the virus genotype. HBV genotype and HBeAg, anti-HBc-IgM, HBV DNA testing may complement each other, with the clinical application value.

Objective To compare the clinical efficacy and safety of pegylated interferon α-2a (Peg IFN α-2a) or adefovir dipivoxil(ADV) monotherapy and their combination therapy in HBeAg positive chronic hepatitis B (CHB) patients. Methods An open randomized controlled multicenter clinical trial was performed. One hundred and twenty cases with CHB were divided into 3 groups: Peg IFN α-2a monotherapy (group A), ADV monotherapy (group B) and Peg IFN α-2a plus ADV combination therapy (group C). The virological response (VR), serological response (HBeAg, HBsAg clearance and seroconversion), biochemical response (BR) and sustained response (SR) were tested at week 24 and 48 of therapy and week 48 of follow-up after end of treatment (EOT) for'evaluation of therapeutic effects, safety and drug resistance. The efficacy was compared using X2 test. Results At week 48 of treatment, the VR (HBV DNA ≤500 copy/mL) rates were 36. 8%(14/38), 37. 5%(15/40) and 62. 9% (22/35), respectively in groups A, B and C; that in group C was higher than those in groups A and B (X2 = 4. 933, 4. 801, respectively; both P < 0. 05); HBeAg seroconversion rates in three groups were 44. 7% (17/38), 17. 5% (7/40) and 51. 4% (18/35), respectively. At week 48 of follow-up,SR rates in three groups were 34. 2%(13/38), 15. 0%(6/40) and 48. 6% (17/35), respectively; those in groups C and A were higher than that in group B (X2 = 9. 894,P<0. 01;X2 =3. 903, P<0. 05, respectively). Conclusions VRs at week 24 and 48 of Peg IFN α-2a plus ADV combination therapy are better than Peg IFN α-2a or ADV monotherapy. SRs at week 48 of follow-up after Peg IFN α-2a monotherapy and combination therapy are both better than ADV monotherapy.

OBJECTIVE:To explore the association between HBV genotyping and clinical characteristics and expression of TH1/TH2 cytokines. METHODS:The expression of IL-4 and IFN-gamma was detected with flow cytometry for 102 HBV infections and 48 healthy controls. 50 CHB patients were randomly selected for HBV genotyping with real-time fluorescence PCR assay. RESULTS:Higher expression of IL-4 in peripheral blood was detected in patients with HBV infection than healthy controls (P < 0.001); No significant differences on expression of Th1/Th2 cytokines were observed in CHB patients with different HBV DNA levels or HBeAg status (P > 0.05). There were 34 (68%) patients with genotype B infection and 16 (32%) with genotype C infection. Compared to patients with genotype B infection, the patients with genotype C infection showed higher levels of IL-4 (P = 0.018), and Th1/Th2 ratio decreased,but the difference was not statistically significant (P = 0.2262). CONCLUSION:The different expression of TH1/TH2 cytokines may elucidate cellular immune response and clinical outcome difference between patients with genotype B infection and genotype C infection.