感染HBV或HCV的肝病患者血清半胱氨酸蛋白酶抑制剂C的改变

目的探讨血清半胱氨酸蛋白酶抑制剂C（Cystatin C）在感染HBV或HCV肝病患者中的临床应用。方法测定了207例HBV或者HCV感染的肝病患者和32名健康对照组（H组）中Cystatin C和金属蛋白酶组织抑制剂（TIMPs）浓度。肝病患者被分成肝硬化组（A组，67例）、慢性乙肝组（B组，73例）、慢性丙肝组（C组，39例）和肝癌组（D组，28例）。结果受试者Cystatin C、TIMP-1和TIMP-2在各组间差异均有统计学意义（F值分别为28．234、128．091、196．549，P值均〈0．001）。Cystatin C与TIMPs在各肝病组中的变化一致：肝病组均显著高于健康对照组，A组和D组均显著高于B组与C组，A组与D组、B组与C组间均差异无统计学意义。Pearson相关分析显示Cystatin C与TIMP-1在各肝病组中均呈明显正相关，且有显著性差异；但Cystatin C与TIMP-2的相关性仅A组（r=0．269，P〈0．05）和D组（r=0．398，P〈0．05）呈正相关，有显著性差异，而B组（r=-0．102，P〈0．05）和C组（r=-0．107，P〈0．05）则呈负相关，且差异无统计学意义。结论血清胱抑素C可能是监测肝脏功能的有用指标。     

Phylogenetic analysis of hepatitis GB virus type C/hepatitis G virus in Spanish patients with chronic hepatitis B or C virus infection.

The nucleotide sequence of hepatitis GB virus type C (HGBV-C)/hepatitis G virus (HGV) NS3/helicase and 5'-untranslated regions from 23 Spanish patients were analyzed to assign the HGV isolates one of the proposed HGBV-C/HGV genotypes. The analysis of the evolutionary distance frequency showed that the distances among all sequences in NS3/helicase region were distributed around a single peak of 0.20, suggesting that all included sequences belonged to the same HGBV-C/HGV genotype. By contrast, in the 5'-untranslated region, all the distances corresponding to our sequences and those of the HGBV-C/HGV types 2 and 3 were distributed around a major peak of 0.03. The remaining distances corresponding to the HGBV-C/HGV type 1 sequences were distributed around a minor peak of 0.11. The phylogenetic tree and pairwise comparison of evolutionary distances among the 5'-untranslated region of the infected patients and each HGBV-C/HGV genotype demonstrated that our HGBV-C/HGV isolates belonged to subtype 2a (17/23; 78%) and 2b (5/23; 22%). No relation was found between HGBV-C/HGV subtype and hepatitis B or C virus infection.     

病毒性肝炎患者中柯萨奇B组病毒的感染情况调查

目的了解柯萨奇B组病毒(coxackie virus B, CVB)在病毒性肝炎中的感染情况.方法用免疫酶法对203例各型肝炎组进行CVB 1至6型免疫球蛋白G(IgG)检测,并与105例病毒性心肌炎组及正常对照组进行分析.结果肝炎组阳性率(39.9%)高于正常对照组(13.4%),P<0.005,而低于心肌炎组(53.3%),P<0.025,B1～6型都有一定的检出率,且以各型交叉感染为主.结论病毒性肝炎患者对CVB各型普遍易感,其致病性应引起重视与探讨.     

不同类型乙型肝炎患者HBV基因型的分布

目的 探讨乙型肝炎病毒（HBV）各种基因型在不同类型乙型肝炎患者中的分布.方法 用PCR结合限制性片段长度多态性（PCR-RFLP）方法检测56例HBV感染的肝癌、58例肝硬化、60例慢性乙型肝炎患者以及60例HBV无症状携带者血清HBV基因型.结果 无症状携带者中B基因型为46.7%（28/60）,C基因型为33.3%（20/60）,D基因型为20.0%（12/60）;慢性乙型肝炎组B基因型为41.7%（25/60）,C基因型为36.7%（22/60）,D基因型为21.7%（13/60）;肝癌患者中B基因型为33.9%（19/56）、C基因型为60.7%（34/56）、D基因型为5.4%（3/56）;肝硬化患者中B基因型为31.0%（18/58）、C基因型为63.8%（37/58）,D基因型为3.5%（2/58）.结论 在慢性乙型肝炎和无症状携带者中以B基因型为优势感染毒株,而肝硬化和肝癌患者则以C基因型为优势感染毒株.     

Prevalence of human immunodeficiency virus testing in patients with hepatitis B and C infection

OBJECTIVES: To determine the proportion of patients with hepatitis B virus (HBV) and hepatitis C virus (HCV) who are adequately assessed for human immunodeficiency virus (HIV) and to identify variables associated with absence of HIV testing. PATIENTS AND METHODS: We retrospectively reviewed the medical records of patients who had positive serologic test results for reactive HBV and/or HCV between January 1999 and December 1999 and were followed up at a general internal medicine clinic in East Harlem, NY. Data were collected on patient demographics, HIV risk factors, and other variables that might influence the physician's decision to test the patient for HIV. Primary outcomes were HIV tests performed and documented discussions of at-risk HIV behavior. RESULTS: The HIV tests were performed in 40% (95% confidence interval [CI], 32%-49%) of the 141 patients with reactive HBV and/or HCV serologic test results. Predictors of HIV testing on multivariate logistic regression were age younger than 50 years (odds ratio [OR], 25; 95% CI, 13-3.8), male sex (OR, 1.6; 95% CI, 1.1-2.2), and having an established primary care provider (OR, 2.3; 95% CI, 1.2-3.9). Injection drug use was not significantly associated with HIV testing. CONCLUSIONS: Although HBV and HCV have clear epidemiological links with HIV, this study shows that a high percentage of these patients are not being tested. Although some of the factors associated with lack of testing were identified, further studies on the barriers to HIV testing are needed to reveal potential approaches to increase rates of HIV testing in this high-risk population.     

病毒性肝炎患者中柯萨奇B组病毒的感染情况

目的：了解柯萨奇B组病毒（coxackie virus B,CVB)在病毒性肝炎中的感染情况。方法：用免疫酶法对203例各型肝炎组进行CVB1至6型免疫球蛋白G（IgG)检测，并与105例病毒性心肌炎组及正常对照组进行分析。结果：肝炎组阳性率（39．9％）高于正常对照组（13．4％），P＜0．005，而低于心肌炎组（53．3％），P＜0．025，B1－6型都有一定的检出率，且以各型交叉感染为主。结论：病毒性肝炎患者对CVB各型普遍易感，其致病性应引起重视与探讨。     

乙型肝炎病毒感染者血清抗核抗体的研究

目的探讨乙型肝炎(简称乙肝)病毒(HBV)感染者血清抗核抗体(ANA)特征及其与临床的相关性。方法收集慢性乙肝(CHB)、乙肝后肝硬化(LC)、肝癌(HCC)患者共376例,采用酶联免疫吸附试验检测ANA。结果 (1)376例患者中ANA阳性99例(26.3%),其中CHB组58例,占21.0%(58/276),LC组20例,占38.5%(20/52),HCC组21例,占43.7%(21/48);健康对照组ANA阳性2例,占3.0%(2/66)。3组均明显高于健康对照组;LC、HCC与CHB组比较,差异有统计学意义(P<0.01);LC组与HCC组比较,差异无统计学意义(P>0.05)。(2)CHB、LC和HCC组ANA以低滴度(1/100)为主,分别为72.4%(42/58)、65.0%(13/20)和71.4%(15/21)。(3)ANA滴度1/100和大于或等于1/320的丙氨酸氨基转移酶、天门冬氨酸氨基转移酶、HBV-DNA各指标比较,差异无统计学意义(P>0.05)。结论 HBV感染者出现的自身抗体以ANA为主,HCC组阳性率最高。70.7%的HBV感染者ANA为低滴度阳性,对其滴度的高低与肝细胞损伤及HBV-DNA复制率无明显相关。     

Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection

Surface gene mutants of hepatitis B virus (HBV) have been reported in a variety of patient groups. Because of limited data regarding these mutations in patients with occult HBV infections; we aimed to determine these mutations among high-risk patients with occult HBV infection. The presence of HBV-DNA was determined in patients with isolated anti-HBc by real-time polymerase chain reaction (PCR). Then, surface gene region was amplified by nested PCR and mutations were analyzed after sequencing. The mutations that resulted in nonfunctional hepatitis B surface antigen (HBsAg) were insertion of single nucleotide in 2 cases, which causes frameshift and single-nucleotide replacement, and premature stop codons at Leu15 and Gly10 in the other 2 cases. Amino acid substitution at amino acid position 207(S207N) was found in the other isolates. Our study suggested that “a” region mutations did not play a major role in HBsAg detection, and other genetic and nongenetic factors may be responsible for failure to detect HBsAg by routine laboratory tests.     

Diagnostic significance of hepatitis B viral antigens in patients with glomerulonephritis-associated hepatitis B virus infection

Hepatitis B viral infection can lead to hepatitis B virus-associated glomerulonephritis, a clinically significant subtype of secondary nephritis. In the present study, we examined the presence of PreS1/S2 antigen in renal tissues by use of immunohistochemistry and investigated the use of PreS1/S2 and 2 HBV serum antigens, HBe-Ag and HBs-Ag, in the diagnosis. We assessed the presence of these 3 antigens in patients with confirmed hepatitis B virus-associated glomerulonephritis (n = 22) and patients without this disease (n = 19). Our results indicate that the combined use of PreS1/S2-Ag and serum HBe-Ag in the diagnosis of hepatitis B virus-associated glomerulonephritis had good positive predictive value (0.89), modest negative predictive value (0.77), and substantial agreement based on Cohen's kappa coefficient (κ = 0.660, P < 0.001). We suggest that our results be considered in the development of more definitive diagnostic criteria for hepatitis B virus-associated glomerulonephritis.     

Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus

The standard antiviral therapy for dialysis patients infected with hepatitis C virus (HCV) is (pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents (DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure (CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients.     

丙型肝炎病毒感染者17种自身抗体的检测及其临床意义

目的：观察丙型肝炎病毒（HCV）感染者的自身抗体情况,了解 HCV 感染后疾病严重程度与抗核抗体（ANA）谱阳性率的关系。方法收集123例 HCV感染患者的血清标本作为 HCV组,根据病毒感染的严重程度将其分为3组：A组,急性丙型肝炎17例;B组,慢性丙型肝炎64例;C组,肝硬化42例。将排除病毒感染和自身免疫性疾病的健康者52例作为对照组。采用间接酶联免疫吸附测定法检测抗 HCV 抗体,线性免疫印迹法检测123例 HCV 感染者血清中抗 dsDNA、核小体、组蛋白、SmD1、增殖细胞核抗原（PCNA）、P0、SSA/Ro60kD、SSA/Ro52kD、SSB/La、CENP-B、Scl70、U1-snRNP、AMA-M2、Jo-1、PM-Scl、Mi-2和Ku 抗体。结果47．2％（58/123）HCV 感染者至少1种自身抗体阳性,明显高于对照组的9．6％,差异有统计学意义（P＜0．01）。ANA谱17种自身抗体阳性率由高到低依次为：抗SSA/Ro52kD抗体（23．6％）、抗SSB/La抗体（6．5％）、抗 Mi-2抗体（5．7％）、抗PCNA抗体（4．9％）、抗核小体抗体（3．3％）、抗 Ku 抗体（3．3％）,抗 dsDNA、SmD1、AMA-M2、PM-Scl 抗体均为1．6％,抗组蛋白、P0、SSA/Ro60kD、CENP-B、U1-snRNP、Jo-1抗体均为0．8％,未发现抗Scl-70抗体。ANA谱阳性率与 HCV感染者的性别和年龄无关（P＞0．05）。急性丙型肝炎患者、慢性丙型肝炎患者与肝硬化患者的 ANA 谱阳性率分别为47．1％、40．6％和57．1％,差异无统计学意义（P＝0．25）。结论 HCV感染者可检测到多种自身免疫性疾病的特异度抗体,其ANA谱阳性率与性别、年龄及 HCV感染疾病的严重程度均无关。     

Incidence of hepatitis B virus infection in patients with blood disease

AIM: To define incidence of HBV infection in patients with blood diseases caused by blood components transfusion; correlation between infection rate and blood disease nosological entity, intensity of hemoreplacement therapy, time of hepatitis B incubation period in patients with hematological malignancies after the diagnosis and initiation of polychemotherapy (PCT). MATERIAL AND METHODS: In 2000-2007 a prospective clinicoepidemiological trial was made to detect markers of HBV infection among 303 patients 15 to 76 years of age treated in the department of acute leukemia chemotherapy of N.N. Burdenko Military Hospital for acute lymphoid and myeloblastic leukemia, chronic myeloid leukemia in a blastic crisis, myelodysplastic syndrome in blast transformation, lymphoproliferative diseases with bone marrow affection. Statistic processing was performed with standard methods. RESULTS: HBV infection markers were detected in 30 (9.9%) of 303 examinees. Among the infected patients there were 16 (53.4%) patients with different variants of acute myeloblastic leukemia, 12 (40.0%) with different immunophenotypes of acute lymphoblastic leukemia, 1 (3.3%) patient with acute biphenotypical leukemia and 1 (3.3%) with lymphoma/leukemia. HBV infection was registered in patients 2 to 32 months after the beginning of the treatment. Most of the patients - 23 (74%) of 30 - were infected with HBV within the first year after hematological diagnosis and PCT induction course. HBV was diagnosed within treatment year two in 5 (16%) patients and within year three after PCT in 3 (10%). CONCLUSION: High incidence of HBV infection in patients with hematological malignancies points to a high epidemiological risk of hemoreplacement therapy, unsatisfactory quality of donor blood testing and necessity of updating methods of donor infection detection. To lower the risk of HBV infection in patients with hematological malignancies it is necessary to perform vaccine prophylaxis of hepatitis B before PCT.     

Role of hepatitis B virus infection in alcoholic patients

Summary The aim of this study was to determine the incidence of HBV markers in patients with alcoholic liver disease and to compare the results with those of patients with non-alcoholic liver disease and control subjects. We tried to determine whether the association between alcohol intake and HBV infection increases the risk of developing severe liver disease. The results showed an increased incidence of HBsAg in alcoholic patients when compared with controls as well as an increased incidence of severe chronic liver disease in HBV-positive groups when compared with HBV-negative groups. We conclude that HBV infection is an important additional risk factor for the development of severe liver disease in alcoholic patients.     

血液透析患者HCV感染不同筛查指标的比较研究

测方法相比,HCV Ag/抗-HCV联合检测可提高血液透析人群HCV感染的检出率.     

Anti-TNF drugs in patients with hepatitis B or C virus infection: safety and clinical management

INTRODUCTION: Drugs targeting TNF-α biological activity are increasingly used for the treatment of immune-mediated diseases, like rheumatoid arthritis, inflammatory bowel diseases and psoriasis. Since TNF-α is a mediator of the immune response against viral infections, use of TNF-α inhibitors in patients with concurrent HBV or HCV infection can promote viral reactivation and potentially fatal liver failure. AREAS COVERED: This paper reviews TNF mechanisms of action in viral hepatitis B and C, recommendations for managing HBV and HCV-infected patients receiving treatment with anti-TNF drugs, safety and anti-TNF hepatotoxicity. EXPERT OPINION: In hepatitis B surface antigen (HBsAg) carriers undergoing anti-TNF therapy, either anti-HBV treatment or prophylaxis is mandatory to prevent hepatitis reactivation, whereas HBsAg-negative antibody to hepatitis B core antigen (anti-HBc) seropositive patients require watchful monitoring, only. Conversely, in HCV-infected patients, TNF-α inhibition by specific drugs is safe and could be even beneficial, as TNF-α pathways are involved in perpetuating liver inflammation and fibrosis progression in HCV. HBV- or HCV-infected patients should be referred to a hepatologist for expert clinical management whenever antiviral therapy is deemed necessary or hepatitis reactivation occurs.