Fulminant hepatitis type B after chemotherapy in a serologically negative hepatitis B virus carrier with acute myelogenous leukemia

We report a case of a 41-year-old man with acute myelogenous leukemia who developed fulminant hepatitis from reactivation of trace hepatitis B virus (HBV) 2 months after complete remission. Although he became positive for HB surface antigen at the onset of fulminant hepatitis, he had been negative for HBV serum markers, and only HBV DNA was detected by polymerase chain reaction (PCR) amplification on admission. The original stocks of serum samples from all blood donors were tested again for HBV DNA by PCR, and all samples were negative. This case demonstrates that testing for HBV DNA by PCR is necessary before chemotherapy, because silent HBV carriers are rare and fulminant hepatitis may be induced by chemotherapy in patients with hematologic malignancies.     

Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in Japan

Genotypes of hepatitis B virus (HBV) were determined in 485 patients with acute hepatitis B from all over Japan. They were A in 92 (19%), Ba in 26 (5%), Bj in 32 (7%), C in 330 (68%) and D in 5 (1%). Sexual contacts were the main route of transmission in them. Overall, HBV persisted in only 5 of the 464 (1%) followed patients. Genotypes C accounted for more than 68% in northern as well as southern areas, contrasting with genotype A accounting for 34% in and around the Metropolitan areas. During 24 years from 1982 to 2005, genotype A increased from 5% to 33%, while genotype B gradually decreased from 26% to 8%. Fulminant hepatitis was significantly more frequent in infection with genotype Bj (41%) than those with the other genotypes (p < 0.01). The core-promoter double mutation (T1762/A1764) and precore stop-codon mutation (A1896) were more frequent in patients with fulminant than acute self-limited hepatitis (57% versus 15% and 58% versus 10%, respectively, p < 0.01 for both). In conclusion, genotype A distributes unevenly over Japan, prevails in younger patients through sexual transmission and has increased with years. Furthermore, fulminant outcome was more frequent in patients with genotype Bj than those with the other genotypes.     

重型乙型肝炎e抗原阴性患者前C变异株及其体外翻译

目的：探讨HBeAg阴性的慢性重型乙型肝炎患者HBV前C区变异及前C区T1862突变体对e抗原合成和分泌影响,方法：选取9例重型乙型重病毒性肝炎患者,用PCR方法扩增血清中HBV前C／C基因区,并克隆后测序和序列分析,构建HBV前C区T1862位点突变体表达质粒pGEMT,经体外翻译比较野毒株和变异株的表达产硪,结果：HBV前C区有3个位点异使氨其酸序列改变,A1896,A1899和T1862,A1899并不单独出现,前C区T1862突变并不阻止HBVe前体外合成,同时,有2例并未检测到前C区的变异,结论：部分重型肝炎HBeAg阳性原因降了T1896变异外,还存在T1862变异,前C1862突变对HBVe抗原前体蛋白合成并无影响,可能e抗原前在分泌过程中受阻。     

重型乙型肝炎患者肝组织和血清中乙型肝炎病毒前C区准种的比较

乙型肝炎病毒存在准种现象。为研究重型乙型肝炎患者血清和肝组织中乙型肝炎病毒（HBV）DNA前C区准种组成特点，本研究从3例重型乙型肝炎患者的血清和肝组织中提取HBV DNA，经巢式聚合酶链反应（PCR）扩增出HBV前C区，产物克隆后经单链构象多态性／异源双链分析（SSCP／HDA）筛选不同的克隆并测序，比较血清和肝组织中HBV前C区准种组成的异同。     

重型肝炎血清HBV前C区A83变异株比率的动态观察

目的 了解ＨＢＶ前区Ｃ区Ａ８３变异与重型肝炎的关系。方法 用套式错配ＰＣＲ限制片段长度多态性分析和凝胶光密度图象分析仪及定量ＰＣＲ,对９例重型肝炎患者血清ＨＢＶ变异株的比率和ＨＢＶ ＤＮＡ含量进行测定和动态观察。结果 Ａ８３变异株在６例阳性率中均与野生株呈混合感染,其比率〉５０．０％的仅２例,存活死亡各１例,〈３１．０％的４例均死亡,变异株的出现及其比率变化与ＨＢＣＶ ＤＮＡ含量的消长一致,但无统     

Lamivudine treatment failure in preventing fatal outcome of de novo severe acute hepatitis B in patients with haematological diseases

BACKGROUND: Patients with malignant haematological diseases administered or no longer receiving immunosuppressive therapy are at high risk of reactivation or de novo hepatitis B infection and fulminant hepatitis. Despite promising results in the treatment of chronic hepatitis and its use in selected patients with acute hepatitis B, there is no consensus on lamivudine treatment in severe acute hepatitis portending a fatal clinical outcome. CASE REPORTS: Of the ten patients with malignant haematological disorders who became infected with the same strain of hepatitis B virus during hospitalisation in a haematology ward, five received lamivudine (and in some cases, ganciclovir and famciclovir). The other patients received only supportive therapy, since deteriorating clinical conditions hampered specific treatment efforts. Eight patients died from acute liver failure and one from a fatal course of the haematological disease; one had a favourable outcome from the therapy. There was no significant difference in terms of survival between the treated and untreated patients. CONCLUSIONS: Although lamivudine has proved promising in the therapy of chronic hepatitis B and of recurrent hepatitis after liver transplantation, its use in de novo severe acute hepatitis should be investigated further, particularly in immunocompromised patients.     

应用糖皮质激素治疗慢性乙型肝炎重度患者阻断坏死性肝炎的发生

目的暴发性肝衰竭的命名和诊断标准国内外一直存在争议。我国的慢性重型肝炎称谓在译成英文后,易与慢性肝炎重度混淆,且由于其潜在的基础肝病(乙型肝炎病毒携带者,慢性肝炎和肝硬化)不同,使其的治疗、预后也不同,并且由于在临床诊断要素方面的不确定性,使我们的研究论文很难被国外学者所承认。方法我们试探性修改并给出了乙型肝炎的临床分型标准。122例慢性乙型肝炎重度患者进入本研究。59例患者接受常规的护肝治疗措施;63例皮质激素治疗组在常规治疗的基础上给予氢化可的松琥珀酸钠150～200mg/d×7～10d;对无反应的患者,病情进展至坏死性或衰竭性肝炎时,加强支持治疗,皮质激素的剂量维持不变,待黄疸降至100μmol/L 以下时开始减量治疗至治愈停药(约3～5月)或死亡。结果在激素治疗组,22％(14/63)的患者发展至坏死性肝炎,显著低于常规治疗组的49％(x~2=8.54,P<0.01);在常规治疗组,55.2％(16/29)的坏死性肝炎患者死亡,而激素治疗组的病死率为28.6％(4/14,x~2=1.72,P>0.05)。尽管在皮质激素治疗组发生了一些能控制的严重感染,如白色念珠菌1例,糖尿病3例,带状疱疹和肺结核1例,两组的消化道出血、感染发生率无显著相差。结论结果提示,在基础治疗的支持下,皮质激素能阻断部分慢性乙型肝炎重度患者发展至坏死性肝炎,并能降低后者的病死率,值得进一步研究。     

Spontaneous regression of hepatitis B virus-associated cirrhosis developed in childhood

We reported two cases of hepatitis B virus infection-related cirrhosis developed during childhood and followed up for more than 20 years. Both the subjects remained untreated, and ultimately regression of cirrhosis was documented by clinical (including ultrasound) and histological examination. Recent studies have already suggested that hepatitis B virus-related cirrhosis may regress after treatment, but this is the first demonstration that hepatitis B virus-associated cirrhosis developed in childhood may be a spontaneously reversible process. Subsidence of virus replication and of necro-inflammatory process and the efficiency of liver regeneration and repair might contribute to this favourable outcome.     

YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines

AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect. METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM) and any other antivirus drugs within the last one year. Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination, HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed. RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes. HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations. CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations.     

急性乙型肝炎患者乙型肝炎病毒清除的临床观察

目的探讨急性乙型肝炎患者血清乙型肝炎病毒(HBV)清除及临床转归的机制。方法动态观察29例住院急性乙型肝炎患者肝功能、HBV DNA、HBV血清标志物的变化,检测其T细胞亚群并与慢性乙型肝炎患者进行比较。结果急性乙型肝炎早期患者HBV广泛抑制,两例患者HBV得到清除,随肝功能的恢复所有患者HBV DNA在较短时间内转阴、HBeAg与HBV DNA几乎同时转阴,肝功能恢复正常时有22例患者HBeAg发生血清学转换,11例患者HBsAg转阴,2例发生HBsAg血清学转换。急性乙型肝炎患者CD3 细胞、CD4 细胞高于慢性乙型肝炎患者,但差异无统计学意义,而CD8 细胞则显著高于慢性乙型肝炎患者(t=2.382,P<0.05)。结论非细胞毒机制在急性乙型肝炎早期HBV DNA的清除中具有重要作用,特异性细胞免疫反应对彻底清除HBV DNA、防止感染慢性化起更重要的作用。     

慢性乙型肝炎重叠HAV与HEV感染的临床分析

目的研究慢性乙型肝炎患者重叠甲型肝炎与重叠戊型肝炎病毒的临床特点及其对病情转归的影响。方法采用ELISA法检测甲、乙、丙、戊型肝炎病毒血清标记物,选择慢性乙型肝炎重叠甲型肝炎52例与慢性乙型肝炎重叠戊型肝炎267例进行对比分析。结果慢性乙型肝炎重叠戊型肝炎患者较慢性乙型肝炎重叠甲型肝炎患者总胆红素水平高、重型肝炎发生率高、病死率高,两组白蛋白水平和平均住院日无明显差异。结论慢性乙型肝炎患者重叠戊型肝炎病毒感染较重叠甲型肝炎病毒感染病情更重、预后差。     

Molecular analysis of hepatitis B virus isolates in Mexico： Predominant circulation of hepatitis B virus genotype H

INTRODUCTIONHepatitis B virus(HBV)is an important cause of morbidity and mortality worldwide.It is estimated that2billion people are infected with HBV and350million individuals suffer from chronic HBV infection in the world[1,2].Chronic HBV infection may …     

慢性乙型重型肝炎继发性感染的临床特点

目的研究慢性乙型重型肝炎继发性感染的临床特点。方法回顾性分析南方医科大学南方医院感染病内科收治的68例慢性乙型重型肝炎继发性感染的临床特点。结果68例病人中发生继发感染者61例(76.5%),其中33例出现2个以上部位感染。较常见的感染部位为腹腔、肺部和胆道,感染率分别为45.5%、38.2%和33.8%;其他感染部位有泌尿道、口腔、上呼吸道、肠道、败血症,感染率分别为7.4%、5.8%、4.4%、2.9%和2.9%。真菌感染20例,占所有感染的29.4%。继发感染病人体温可表现为高热、低热或体温正常;外周血白细胞和中性粒细胞比率可增高或正常。结论慢性乙型重型肝炎病人发生继发性感染比率高,表现复杂。     

急性乙型肝炎与慢性乙型肝炎急性发作的临床特征比较

目的探讨鉴别急性乙型肝炎(AHB)和慢性乙型肝炎(CHB)急性发作的临床特征。方法回顾性分析2014年6月~(-1)2月在复旦大学附属公共卫生临床中心就诊的96例AHB和124例CHB急性发作患者的临床资料。计量资料组间比较采用MannWhitney U检验,计数资料组间比较采用χ~2检验。结果 AHB和CHB急性发作在发病年龄和性别方面差异无统计学意义,男性发病率高于女性。AHB以性接触和医源性传播为主,而CHB急性发作以母婴垂直传播为主。基线ALT水平≥1072 U/L诊断AHB的敏感性和特异性分别为78.6%和79.2%;抗-HBc-Ig M滴度≥13.6 S/CO诊断AHB的敏感性和特异性分别为94.5%和89.3%。入院2周时AHB组HBs Ag、HBe Ag和HBV DNA较基线的下降值均显著高于CHB急性发作组且差异有统计学意义(P值均0.05)。入院第8周时AHB患者HBs Ag阴转率、抗-HBs阳转率、HBe Ag阴转率、抗-HBe阳转率和HBV DNA阴转率均显著高于CHB急性发作患者(P值均0.05)。结论明确传播途径、基线高ALT水平和抗-HBc-Ig M水平、快速HBV DNA阴转和HBV血清学标志物转换均有助于AHB和CHB急性发作的鉴别诊断。     

Differentiation of acute and chronic hepatitis B in IgM antiHBc positive patients

AIM: To identify the factors that differentiate acute hepatitis B(AHB) from chronic hepatitis B with acute exacerbation(CHB-AE).METHODS: From 2004 to 2013, a total of 82 patients(male n = 52, 63.4%; female n = 30, 36.6%) with clinical features of acute hepatitis with immunoglobulin M antibodies to the hepatitis B core antigen(Ig M antiHBc) were retrospectively enrolled and divided into two groups; AHB(n = 53) and CHB-AE(n = 29). The AHB group was defined as patients without a history of hepatitis B virus(HBV) infection before the episode and with loss of hepatitis B surface antigen within 6 mo after onset of acute hepatitis. Biochemical and virological profiles and the sample/cutoff(S/CO) ratio of Ig M anti-HBc were compared to determine the differential diagnostic factors.RESULTS: The multivariate analysis demonstrated that, the S/CO ratio of Ig M anti-HBc and HBV DNA levels were meaningful factors. The S/CO ratio of Ig M anti-HBc was significantly higher in the AHB group, while the HBV DNA level was significantly higher in the CHB-AE group. The optimal cutoff values of Ig M anti-HBc and HBV DNA levels for differentiating the two conditions were 8 S/CO ratio and 5.5 log10 IU/m L, respectively. The sensitivity and specificity were 96.2% and 89.7% for the S/CO ratio of Ig M anti-HBc and 81.1% and 72.4% for HBV DNA levels, respectively. The area under receiver operating characteristic curves of both the S/CO ratio of Ig M anti-HBc and HBV DNA levels were not significantly different(0.933 vs 0.844, P = 0.105). When combining Ig M anti-HBc and HBV DNA, the diagnostic power significantly improved compared to HBV DNA alone(P = 0.0056). The combination of these factors yielded a sensitivity and specificity of 98.1% and 86.2%, respectively.CONCLUSION: The combination of the S/CO ratio of Ig M anti-HBc and HBV DNA levels was a useful tool for differentiating AHB from CHB-AE in patients with positive Ig M anti-HBc.     

慢性乙型肝炎急性发作患者血清病毒准种动力学研究

目的揭示慢性乙型肝炎急性发作及重型化过程中血清乙型肝炎病毒(HBV)基因组前C／C 及基本核心启动子(BCP)区准种的动态变化规律。方法选取1例慢性乙型肝炎两次急性发作伴重型化患者病程中5份血清样本,采用聚合酶链反应-TA克隆-构象敏感凝胶电泳-测序的方法,研究慢性乙型肝炎重型化过程中血清HBV准种的动态变化。结果血清HBV准种复杂性在慢性乙型肝炎急性发作时为10～ 12,在好转时为14～17(t=3．133,P<0．05),且随时间推移有逐渐升高的趋势;在此过程中优势准种组成及比例亦发生了变化(t=3．295,P相似文献   

Advances in treatment and prevention of hepatitis B

Chronic hepatitis B(CHB) continues to contribute to worldwide morbidity and mortality significantly. Scientists, clinicians, pharmaceutical companies, and health organizations have dedicated substantial Intellectual and monetary resources to finding a cure, increasing immunization rates, and reducing the global burden of CHB. National and international health-related organizations including the center for disease control, the national institute of health, the American Association for the study of liver disease(AASLD), The European association for the study of the Liver(EASL), The Asia Pacific association for the study of the Liver(APASL) and the world health organization release periodic recommendations for disease prevention and treatment. Our review of the most recent guidelines by EASL, AASLD, APASL, and Taiwan Association for the Study of the Liver revealed that an overwhelming majority of cited studies were published before 2018. We reviewed Hepatitis B-related literature published 2018 onwards to identify recent developments and current barriers that will likely direct future efforts towards eradicating hepatitis B. The breakthrough in our understanding of the hepatitis B virus life cycle and resulting drug development is encouraging with significant room for further progress. Data from high-risk populations, most vulnerable to the devastating effects of hepatitis B infection and reactivation remain sparse. Utilization of systems approach, optimization of experimental models, identification and validation of next-generation biomarkers, and precise modulation of the human immune response will be critical for future innovation. Within the foreseeable future, new treatments will likely complement conventional therapies rather than replace them. Most Importantly, pragmatic management of CHB related population health challenges must be prioritized to produce real-world results.     

Epidemiology of acute and chronic hepatitis B and delta over the last 5 decades in Italy

The spread of hepatitis B virus (HBV) infection has gradually decreased in Italy in the last 5 decades as shown by the steady reduction in the incidence rates of acute hepatitis B, from 10/100000 inhabitants in 1984 to 0.85/100000 in 2012, and by the reduced prevalence of hepatitis B surface antigen (HBsAg)-positive cases among chronic hepatitis patients with different etiologies, from 60% in 1975 to about 10% in 2001. The prevalence of HBsAg chronic carriers in the general population also decreased from nearly 3% in the 1980s to 1% in 2010. Linked to HBV by its characteristics of defective virus, the hepatitis delta virus (HDV) has shown a similar epidemiological impact on the Italian population over time. The incidence of acute HDV infection decreased from 3.2/100000 inhabitants in 1987 to 0.8/100000 in 2010 and the prevalence of HDV infection in HBsAg chronic carriers decreased from 24% in 1990 to 8.5% in 2006. Before the beneficial effects of HBV mass vaccination introduced in 1991, the decreased endemicity of HBV and HDV infection in Italy paralleled the improvement in screening blood donations, the higher standard of living and impressive reduction in the birth rate associated with a marked reduction in the family size. A further contribution to the decline in HBV and HDV infections most probably came from the media campaigns to prevent the spread of human immunodeficiency virus infection by focusing the attention of the general population on the same routes of transmission of viral infections such as unsafe sexual intercourse and parenteral exposures of different kinds.     

Different natural courses of chronic hepatitis B with genotypes B and C after the fourth decade of life

AIM To investigate the different impact of genotypes B and C on the development of liver cirrhosis (LC) among different age groups of patients with chronic hepatitis B (CH-B).METHODS We examined the outcome of 121 patients with CH-B, divided by age and genotype. Univariate analyses were used to compare different groups. The Cox proportional hazard model was employed to evaluate factors affecting the development of LC.RESULTS In patients ＜ 30 years old, there were no significant predictors for development of LC. However,in patients ≥ 30 years old, genotype C was the only significant predictor. In the genotype C group, 8 of 12patients who progressed to LC were 30-49 years old at initial diagnosis of chronic hepatitis (7 patients were positive for HBeAg). In the genotype B group, 4 of 8patients who developed LC were ≥ 50 years old at initial diagnosis and were HBeAg-negative.CONCLUSION The rate of development of LC was comparable in patients infected with genotypes B and C when CH-B occurred at ＜ 30 years old. However,CH-B patients infected with genotype C showed poor prognosis if they were 30-49 years old and were positive for HBeAg. Age-specific natural course of CH-B should be considered when patients with CH-B are treated with antiviral drugs.