慢性戊肝重叠急性乙肝患者一例报道并文献复习

目的:探讨慢性戊型病毒性肝炎合并急性乙型病毒性肝炎的发病机制、诊断、治疗及其预后。方法:回顾我院收治的一例慢性戊型病毒性肝炎合并急性乙型病毒性肝炎患者的临床资料,并结合文献探讨戊型病毒性肝炎及乙型病毒性肝炎的发病机制,总结其诊断及治疗经验,并评价其预后。结果:该患者戊肝抗体长期阳性,被诊断为慢性戊型病毒性肝炎,但合并急性乙型病毒性肝炎后,经治疗乙肝表面抗原转阴后戊肝抗体Ig M也阴转。结论:慢性戊型病毒性肝炎合并急性乙型病毒性肝炎患者经治疗后可同时出现乙肝表面抗原转阴,戊肝抗体阴转,预后可较好。     

应用血清学方法鉴别急性和慢性病毒性乙型肝炎

本文用ELISA间接法检测急性和慢性乙型肝炎病人血清特异性抗HBcIgG,用ELISA捕捉法检测特异性抗HBcIgM。11例急性乙肝病人急性期抗HBcIgM100％阳性,抗HBcIgG全部阴性;恢复期抗HBcIgM 81.8％阴转,抗HBcIgG则100％阳转。17例慢性乙肝病人抗HBcIgM82.35％阳性,抗HBcIgG 100％阳性。被检血清经密度梯度超速离心,证实抗HBcIgM和抗HBcIgG两类抗体反应在急性和慢性乙肝病人血清中具有不同的动态规律。     

急性病毒性肝炎的发病率慢性肝炎患病率和肝病死亡率的研究

1984～1987年,在黑龙江、河北、河南、湖南、上海五个省市城乡10.08855人口中进行急性肝炎发病率、慢性肝炎患病率、与病毒性肝炎有关的肝病死亡率的研究。急性肝炎标化发病率为152.19/10万,主要发生在20～50岁组人群;因无甲肝暴发流行,除上海外各点季节发病率分布均衡。慢性肝炎标化患病率为158.25/10万(诊断标准为6个月前有明确急性肝炎病史,现有明显的临床症状或体征,肝功能异常,故实际慢肝患病率要高于此数字);与病毒性肝炎有关的肝病死亡(包括肝癌)标化率为22.65/10万,其中肝病为 13.14/10万。男性死亡率显著高于女性。     

The natural course of chronic hepatitis C

Abstract: In 1988, investigators from the Chiron Company (USA) detected the non-A, non-B agent and named it hepatitis C virus (HCV). An anti-HCV antibody assay (ELISA) and subsequently confirmation tests (immunoblot and polymerase chain reaction) were developed. HCV exposure results in a chronic infection in a majority of cases. This chronic infection is associated with slowly progressive chronic liver disease. Chronic HCV infection is, like HBV, also associated with the development of hepatocellular carcinoma. Most HCV carriers are infected by parenteral routes. Intravenous drug users have the highest risk of becoming infected. Intrafamiliar spread is seen in certain parts of the world but sexual and perinatal transmission does not play an important role in spreading the infection. Antiviral therapy (alpha-interferon) in patients with chronic hepatitis C will normalize liver function tests in about 25% of the cases.     

急性病毒性肝炎患者外周血T 细胞亚群的检测和分析

目的:检测急性甲、乙型病毒性肝炎患者外周血T淋巴细胞亚群变化,探讨其对疗效和预后意义。方法:采用APAAP桥联酶标法检测115例急性甲、乙型病毒型肝炎患者外周血CD3+、CD4+、CD8+T细胞亚群比例,计算CD4+/CD8+值。并检测了34例患者治疗前后T淋巴细胞亚群变化。结果:115例急性甲、乙型病毒性肝炎患者外周血CD3+、CD4+T细胞比例及CD4+/CD8+值均低于正常对照组(P<0.05),而CD8+T细胞比例均高于正常对照组(P<0.01)。6例无明显疗效者,各亚群比例在治疗前后无显著差异(P>0.05)。28例有明显疗效者,治疗后各亚群比例恢复正常水平,与治疗前相比差别具有统计学意义(P<0.05)。结论:急性甲、乙型病毒性肝炎患者外周血CD4+/CD8+T细胞比值可在一定程度上反映疗效及预后。     

Trace elements in viral hepatitis

In this study, serum trace elements, including selenium (Se), zinc (Zn), copper (Cu), were determined by using Atomic Absorption Spectrophotometer (SpectrAA 250 Plus Zeeman, Varian, Australia) in sera of patients with viral hepatitis (A, B, C, D, E) cases (n = 102), and statistically compared with the controls (n = 52). In viral hepatitis, Cu levels were found as 3.23 ± 1.02 mg/L, and this value was significantly higher than the control group (1.13 ± 0.21) (p < 0.01). Both, Se and Zn levels found to be significantly low in viral hepatitis cases (p < 0.01). While Se level was 81.4 ± 26.01 μg/L in viral hepatitis (n = 101), it was found to be 166.15 ± 4.58 μg/L in healthy individuals. Meanwhile, Zn levels were 0.230 ± 0.081 mg/L and 0.748 ± 0.392 mg/L in hepatitis cases (n = 101) and the control group, respectively. There was no difference amongst viral hepatitis groups classified in regard with agents and clinical manifestation, such as A, acute hepatitis B, chronic hepatitis B, C, D and E. Previously, it was indicated that absorption disorders in gastrointestinal system, especially in chronic cases, were not main causes of decrease of trace elements by iron and several other parameters in sera of the cases. Therefore, we suggest that decrease in Zn and Se levels and elevation in Cu levels are probably resulted from defence strategies of organism and induced by the hormone-like substances.     

Insulin resistance is associated with DNA damage in peripheral blood cells in non-diabetic patients with genotype 1 chronic hepatitis C

Abstract

Background. In chronic liver diseases of different etiologies, including viral hepatitis, genotoxic effects of oxidative stress have been shown, both in clinical and in experimental conditions, suggesting that this mechanism may contribute to the evolution of the disease. Aim. To evaluate DNA damage in the peripheral blood of untreated non-diabetic patients with chronic hepatitis C and control subjects, and its correlation with demographic, anthropometric, biochemical, and histological parameters in the patient sample. Patients and methods. This study comprised 100 subjects of both genders, 60 of whom were treatment-naïve patients with positive serology for genotype 1 hepatitis C. The remaining 40 were blood donors with negative serology for hepatitis who were used as control subjects, and matched by gender, age, weight, and BMI. DNA damage was determined using the comet assay in the total peripheral blood. Results. The DNA damage evaluated by the comet assay revealed higher values in the group of patients with hepatitis compared with that in the control group. The relationships of the comet assay with the studied variables were assessed using multivariate analysis; significant correlations were only identified with insulin (r = 0.343, p = 0.008) and Homeostasis Model Assessment Insulin Resistance (HOMA-IR) (r = 0.331, p = 0.011). Conclusion. Patients with genotype 1 chronic hepatitis C have higher rates of DNA damage, as determined by comet assay and this alteration is correlated with the HOMA index of insulin resistance.     

I b 型慢性丙肝患者血清IL-10、IL-12 水平 与HCV-RNA 载量关系的研究*

目的:研究I b型慢性丙肝患者血清IL-10、IL-12水平与HCV-RNA载量的关系,探讨难治性丙肝的免疫发病机制。方法:选取HCV-RNA阳性的I b型慢性丙肝患者48例,依据病毒载量将其分为三个组,低病毒载量组(1.0*103IU/mL1.0*106IU/mL)13例,另选HCV-RNA阴性的慢性HCV感染者15例,健康献血员15例作为对照组;应用ELISA法检测所有研究对象的血清IL-10、IL-12水平。结果:慢性丙肝患者外周血IL-10水平显著高于健康献血员(P=0.003),IL-12水平低于健康献血员(P=0.045);随着HCV-RNA载量的升高,HCV-RNA阳性的I b型慢性患者外周血IL-10水平逐渐升高,组间比较差异具有统计学意义(F=18.65,P=0.000);血清HCV-RNA载量与血清IL-10水平呈正相关(相关系数r=0.71,P=0.000),与血清IL-12水平无相关性(P=0.479)。结论:慢性HCV感染者与患者的细胞免疫均倾向于TH2型;I b型慢性丙肝患者外周血IL-10水平与HCV-RNA病毒载量呈正相关。     

Chronic viral hepatitis and iron affect the plasma levels of LIGHT--a new member of the TNF superfamily in uraemic haemodialyzed patients

LIGHT (lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T cells) is a recently identified of the tumor necrosis factor alpha (TNF-alpha) ligand superfamily. We wanted to establish whether the presence of chronic viral hepatitis could be implicated in enhanced inflammation as well as the elevation of plasma LIGHT levels in haemodialyzed (HD) patients. The plasma levels of LIGHT, high sensitivity C-reactive protein (hs CRP) and TNF-alpha were measured in HD patients with hepatitis in comparison to subjects without hepatitis and to healthy volunteers. The values of hs CRP and TNF-alpha were significantly elevated in HD patients when compared to the controls. TNF-alpha levels were significantly higher in the hepatitis-positive relative to the hepatitis-negative group (p <0.01). LIGHT levels were significantly decreased in hepatitis-negative patients as compared to controls (p <0.001) and hepatitis-positive group (p < 0.01). Both LIGHT and TNF-alpha were directly associated with the presence of hepatitis. Multiple stepwise regression analysis identified increased iron levels as the only independent variable significantly associated with increased LIGHT (beta=0.475, p=0.003). These results suggest the presence of chronic viral hepatitis and iron levels are novel determinants of the increased LIGHT in the plasma of HD patients.     

丙型病毒性肝炎母婴传播的现状、进展及未来

丙型肝炎病毒(HCV)可引起急性和慢性病毒性肝炎,可发展成肝纤维化、肝硬化,甚至肝细胞癌。HCV经典的传播途径为经血液或血液制品传播,但1992年后献血员HCV的筛检已使输血后肝炎大为减少。在发达国家,HCV传播途径正在发生改变,儿童非血液制品的丙肝日渐增多。母婴间宫内、分娩时及产后感染已成为当前及今后的重要研究课题。研究证实,HCV可经胎盘引起胎儿感染,宫内感染是HCV传播的一条重要途径。尽管人们对HCV母婴传播中所涉及的风险因素逐渐明确,但到目前为止对具体的传播机制和传播时机仍知之甚少。我们就丙型病毒性肝炎母婴传播的现状、进展及未来做简要综述。     

Association between polymorphisms in OAS2 and CD209 genes and predisposition to chronic hepatitis C in Russian population

Chronic hepatitis C is a severe liver disease caused by positive-strand RNA virus. Previously, we reported an association between seven single nucleotide polymorphisms (SNPs) in four innate immunity genes (OAS2, OAS3, CD209, and TLR3) and human predisposition to tick-borne encephalitis, caused by a virus from the same Flaviviridae family, in a Russian population. Currently, genotype and allele frequencies for these SNPs were analyzed in 75 chronic hepatitis C patients and compared with the population control (269 Novosibirsk citizens). Data obtained suggest that the OAS2 rs1293762 and CD209 rs2287886 SNPs are associated with predisposition to chronic hepatitis C in Russian population.     

Increased serum oxysterol concentrations in patients with chronic hepatitis C virus infection

Oxidative stress and dysregulated cholesterol metabolism are characteristic features of chronic hepatitis C virus infection (CHC). Therefore, we analyzed serum oxysterol profiles in CHC patients and examined the significance of oxysterols in CHC. The concentrations of 7α-hydroxycholesterol, 4β-hydroxycholesterol and 25-hydroxycholesterol as determined by LC–ESI–MS/MS were significantly elevated by +236%, +29% and +44%, respectively, in CHC patients compared with controls. Moreover, the elevated levels were significantly decreased by anti-viral therapy using PEGylated-interferon and ribavirin for 3 months. In contrast, 24S-hydroxycholesterol, 27-hydroxycholesterol and 7α-hydroxy-4-cholesten-3-one concentrations were not affected by CHC or anti-viral treatment. These results suggest that some oxysterols that are elevated in CHC are produced by cholesterol autoxidation due to oxidative stress or inflammation in the liver. Oxysterols may represent novel targets for the inhibition of disease progression and the prevention of hepatocarcinogenesis in CHC patients.     

HCV-RNA和抗-HCV的联合检测在丙型肝炎确诊中的临床意义

目的:探讨抗-HCV和HCV-RNA的联合检测在丙型肝炎确诊中的临床意义。方法:采用ELISA法检测抗-HCV及实时荧光定量PCR检测HCV-RNA。结果:在急性丙型肝炎组中抗-HCV和HCV-RNA同时阳性所占百分率(29.8%)显著低于慢性丙型肝炎患者(62.3%)(P<0.05);抗-HCV阴性和HCV-RNA阳性在急性丙型肝炎组所占百分率(58.3%)显著高于慢性丙型肝炎患者(24.6%)(P<0.05);经相关性分析,ALT含量与HCV-RNA含量呈正相关性(r=0.725,P<0.05)。结论:临床抗-HCV和HCV-RNA的联合检测有助于丙型肝炎的早期明确诊断。     

Small rodent models of hepatitis B and C virus replication and pathogenesis

The narrow host range of infection supporting the long-term propagation of hepatitis B and C viruses is a major limitation that has prevented a more thorough understanding of persistent infection and t...     

A viral mechanism in acute exacerbations of chronic type B hepatitis: Hepatitis B virus reinfection and subsequent reactivation of two viral strains

Chronic hepatitis B virus (HBV) infections are frequently associated with exacerbations of hepatitis of which the majority are due to reactivation of viral activity. Variation in a viral genome during persistent infection has been shown to be a possible cause for reactivation. In this study, we have found another possible mechanism. HBV in a patient with repeated exacerbations was isolated at six different times during follow-up and was characterized by polymerase chain reaction and DNA sequencing. The first episode of exacerbation was accompanied with increased replication of an HBV strain. The second episode, however, was associated with the sudden appearance of an HBV strain that displayed enough sequence variations to warrant the designation as a separate strain. The results suggested a reinfection event by another independent HBV. Subsequent exacerbations were then related to coactivation of both viral stains. These observations provide significant information toward understanding the acute exacerbations of chronic type B hepatitis.     

Plasma Superoxide Dismutase Measurement in Children with Viral Hepatitis

Seventy-seven blood samples from normal controls aged 0–8 years and 93 blood samples from children of similar ages with various viral hepatitis were investigated by measuring plasma superoxide dismutase (EC 1.15.1.1) using chemiluminescence immunoassay (CLIA). Total and Cu,Zn-SOD activities of normal controls of group 2(1–8 years old) were significantly higher than that of normal controls of group 1 (0–1 year old) (P < 0.01. P < 0.01), while there were no differences of Mn-SOD activities between the two groups. Total. Cu,Zn-and Mn-SOD activities significantly increased in the acute phase (0–4 weeks after onset) and dropped to the normal levels in the restoration phase (4th week later) for 29 children with cytomegalovirus hepatitis (CMVH), in comparison with group 1. Only Mn-SOD activities were significantly increased in the acute phase (with increased ALT levels) and restoration phase (with normal ALT levels) for 18 children with hepatitis A (HA). Total and Cu,Zn-SOD activities significantly decreased and Mn-SOD activities significantly increased in both the active (with increased ALT levels) and the inactive phases (with normal ALT levels) for 36 children with chronic persistent hepatitis (CPH). Only Cu,Zn-SOD activities fell significantly in both active and inactive phases for 10 children with chronic active hepatitis (CAH).     

Preliminary study of combination therapy with interferon-α and zinc in chronic hepatitis C patients with genotype 1b

We have evaluated the efficacy of interferon-α (IFN-α) plus zinc therapy in hepatitis C patients with genotype 1b, poor responders for IFN alone. Ten patients were injected with 10 MU of IFN-α every day for 4 wk, followed by three times a week for 20 wk (control group). Nine patients took 300 mg of zinc sulfate a day orally during IFN-α therapy (zinc sulfate group), and 15 patients took IFN-α and 150 mg of polaprezinc (polaprezinc group). On the d 8 of IFN therapy, circadian zinc levels in serum elevated significantly in the polaprezinc group compared to the zinc sulfate group or control group. Serum ALT levels normalized in 73.3% of the polaprezinc group, 55.6% of the zinc sulfate group, and 40.0% of the control group at 6 mo after the end of IFN therapy. Sustained eradication for the hepatitis C virus RNA judged at the end of the 6-mo follow-up period was higher in the polaprezinc group than in the zinc sulfate group (53.3% vs 11.1%, p<0.05) or the control group (20.0%). No clinical side effects of zinc were observed at the dose used. The data suggest that polaprezinc is expected to increase the therapeutic response of IFN-α for chronic hepatitis C with genotype 1b.     

慢性乙型肝炎患者肝组织和外周血白细胞中钠离子依赖性维生素C转运体的表达

用免疫组化和Western blot技术检测SVCT1和SVCT2蛋白在慢性乙型肝炎患者及正常人外周血白细胞中的表达.免疫组化结果显示：在慢性乙型肝炎患者肝组织中SVCT1和SVCT2蛋白的阳性表达率和阳性表达强度显著低于正常肝组织（P〈0.01）;Western-blot检测显示,慢性乙型肝炎患者外周血白细胞中SVCT1表达缺失,SVCT2蛋白表达强度为0.481&#177;0.056,均显著低于正常人（分别为0.325&#177;0.085和0.971&#177;0.140）（P〈0.01）.提示慢性乙型肝炎患者体内肝细胞和外周血白细胞存在SVCT1和SVCT2蛋白表达低下或缺失;SVCT1和SVCT2蛋白表达低下或缺失可能是乙型肝炎病毒易感性的主要原因之一.     

Single nucleotide polymorphism rs1800872 in the promoter region of the IL10 gene is associated with predisposition to chronic hepatitis C in Russian population

Previously, we studied an association of two IL28B gene single nucleotide polymorphisms (SNPs) and three IL10 gene SNPs with predisposition to tick-borne encephalitis in a Russian population. In this study, a possible involvement of these SNPs in the development of predisposition to chronic hepatitis C (caused by structurally similar, related virus from the Flaviviridae family) was investigated in the same population. Only the IL10 promoter rs1800872 SNP was associated with predisposition to chronic hepatitis C. This SNP seems to be a common genetic marker of predisposition to two diseases caused by hepatitis C and tick-borne encephalitis viruses in Russian population.     

Interferon therapy in chronic hepatitis C virus infection

Abstract: Antiviral treatment of chronic hepatitis C with interferon is reviewed. Alpha-interferon, both recombinant alpha-2a, -2b and human lymphoblastoid interferon given at a dose of ≥3MU t.i.w. for 6–12 months will result in normalisation of ALT levels complete response) in some 50–60% of treated patients with chronic hepatitis C virus (HCV) infection. Approximately half of the complete responders to interferon will relapse within 6 months once treatment is withdrawn (non-sustained response). Longer treatment schedules (6 vs. 12 months) seem to diminish the relapse rate and increase the percentage of sustained response. In patients with sustained response to interferon treatment with continuously normal ALT levels ≥6 months after treatment stop a concomitant eradication of the viraemia is usually seen, whereas a non-sustained or non-response to interferon usually will indicate a continuous viraemia. Factors predictive of a favourable response are low pretreatment HCV RNA levels in serum, genotypes other than type II according to Okamoto, short disease duration, female gender and less pronounced liver damage, whereas high serum HCV RNA levels, having genotype II and cirrhosis, are predictive of a less favourable response. Patients with a sustained response and eradication of the viraemia will also improve their liver inflammation with diminishing scores for portal inflammation, piecemeal necrosis, lobular inflammation and also fibrosis after treatment. For non-responders and non-sustained responders to interferon, ribavirin especially in combination with interferon will offer some hope for the future.