Prevalence of TT virus in patients with hepatitis B,C and hepatitis of unknown etiology

Discovery of TT virus in 1997 gave raise to intensive subsequent studies to learn about its structure, features and, what is the most important, about its role in pathogenesis of liver disease. The aim of the work was to analyze prevalence of TTV DNA in patients with diagnosed hepatitis B, C, that of unknown etiology and in healthy blood donors as well. Additionally the divergence of TTV sequence was estimated in selected cases. TTV DNA was detected by PCR technique using specific oligonucleotide primers for coding regions. TT virus has been detected in 25.6% (32/125) HBsAg positive patients and in 23.9% (51/213) HCV infected patients. In healthy blood donors the frequency of TTV was 24.3% (34/140) similarly to that found in HCV and HBV infected patients. The frequency of TTV DNA among patients with hepatitis of unknown etiology was 9.1%. This result was statistically significant lower than in the other groups. When detected sequences have been compared to these from NCBI base the homology result was 71% to 95%, and among different patients and groups of patients identity was 46% to 73%. On the basis of the obtained results it can be concluded that it is very unlikely that TTV coinfection plays any significant role in HCV or HBV infection. The hypothetical role of TTV infection in the etiopathogenesis of cryptogenic chronic hepatitis has not been confirmed. The results obtained in the small group of patients with hepatitis of unknown etiology are not conclusive and should be taken with some precaution. The final conclusion is the TTV coinfection does not contribute to the liver pathology. The divergence of TTV sequences may explain the various frequency of TTV viremia reported by other authors.     

Hepatitis G virus (GBV-C) infection among Brazilian patients with chronic liver disease and blood donors

Background: The recently discovered hepatitis G virus (HGV) belongs, as hepatitis C virus (HCV), to the Flaviviridae family. HGV has been isolated from the serum of patients with non A-E hepatitis. However, the association of HGV with hepatitis is uncertain.Objective: To determine the HGV prevalence in blood donors and in patients with liver disease and to evaluate a possible correlation between HGV infection and liver disease.Study design: Sera from a total of 113 consecutive patients with chronic liver disease were submitted to a series of liver enzymes and function tests and analyzed for the presence of HBsAg, anti-HBs, anti-HBc, anti-HCV, HCV RNA and HGV RNA. Prevalence of HGV RNA was determined in a group of 87 blood donors.Results: Nine (10%) sera from blood donors and 15 (13%) sera from patients with chronic liver disease were HGV RNA positive. Some 28 (25%) patients were HCV RNA positive, with genotypes 1a, 1b and 3 present in 10, 12 and 5 patients, respectively. A total of 20 (18%) patients were HBsAg carriers. Five (4%) patients were double infected (one with HBV+HCV, one with HBV+HGV and three with HCV+HGV).Conclusion: The proportion (10%) of HGV-infected blood donors was very high when compared with other countries. The results did not allow to establish HGV as an etiologic agent for chronic liver disease. The parenteral route was the presumed means of HGV transmission for only one-third of the patients.     

Detection of HCV and GBV-CHGV RNA in peripheral blood mononuclear cells of patients with chronic type C hepatitis

Hepatitis C virus (HCV) and hepatitis G virus (HGV) viraemia were investigated by RT-PCR protocols in peripheral blood mononuclear cells (PBMC) of 22 patients with chronic type C hepatitis. Samplings were at basal and 4-8 months after a 12 month period of treatment with interferon-alpha. A plus strand of HCV in PBMC was detected in 8 of 21 patients (38%) (p <0.05; chi2 test) with a lack of response to therapy; a minus strand was detected in 10% of chronic type C hepatitis and 25% of the patients harboured HCV RNA in PBMC. The association with a response was nearly significant (p <0.1; chi2 test). GBV-C/HGV RNA was detected in the serum of 9 of 21 (43%) patients and in PBMC of 20% of the patients viraemic. Genomic sequences of GBVC/HGV in PBMC were found, but further investigation is needed to assess the findings reported for HCV.     

Lack of evidence for hepatitis G virus replication in the livers of patients coinfected with hepatitis C and G viruses.

The pathogenic implications of hepatitis G virus (HGV) infection are still unclear. We searched for the presence of HGV RNA and HCV RNA sequences in liver and serum samples from 10 patients with chronic liver disease, 9 of whom were coinfected with HCV. All livers were negative for the presence of the HGV RNA minus strand and only six were positive for the presence of the positive strand, albeit at low levels. In striking contrast, the HCV RNA positive strand was detectable in the liver samples from all nine HCV-positive patients in titers ranging from 10(2) to 10(8) genomic eq/microg of RNA, and the negative HCV RNA strand was present in all but two of these patients. However, the positive-strand RNA titers in serum for the two viruses had similar ranges. These findings imply that the liver is not the primary replication site for HGV, at least in the population of HCV/HGV-coinfected patients. Absence of replication in liver tissue may explain the reported lack of influence of HGV coinfection on the course of chronic hepatitis C.     

乙型肝炎病人重叠感染丙型肝炎的评价

应用ＥＬＩＳＡ和ＰＣＲ法检测５０２例乙肝病人血清,４０１例ＨＢｓＡｇ阳性血清中,有１１４例（２８．４％）抗－ＨＣＶ和ＨＣＶＲＮＡ双项阳性,２５例（６．２％）ＨＣＶＲＮＡ单项阳性;２１例（５．２％）抗－ＨＣＶ单项阳性。将ＨＢｓＡｇ乙肝病人分成ＨＢＶＤＮＡ,ＨＢｅＡｇ阳性组和ＨＢＶＤＮＡ,ＨＢｅＡｇ阴性组。前者抗－ＨＣＶ阳性率为１１．６％～２０．５％,ＨＣＶＲＮＡ阳性率为１６．２％～２０．５％。后者抗－ＨＣＶ阳性率为２０．２％～５５．６％,ＨＣＶＲＮＡ阳性率为２３％～６０．３％。结果说明长期携带ＨＢＶ者和慢性乙肝病人均可重叠ＨＣＶ感染。ＨＢＶＤＮＡ阳性组抗－ＨＣＶ和ＨＣＶＲＮＡ阳性率明显高于ＨＢＶＤＮＡ阳性组     

Dynamics of Persistent TT Virus Infection, as Determined in Patients Treated with Alpha Interferon for Concomitant Hepatitis C Virus Infection

TT virus (TTV) is a recently identified widespread DNA virus of humans that produces persistent viremia in the absence of overt clinical manifestations. In an attempt to shed light on the dynamics of chronic infection, we measured the levels of TTV in the plasma of 25 persistently infected patients during the first 3 months of alpha interferon (IFN-alpha) treatment for concomitant hepatitis C virus (HCV) infection. The first significant decline of TTV loads was observed at day 3 versus day 1 for HCV. Subsequently, the loads of TTV became progressively lower in most patients, but some initial responders relapsed before the end of the follow-up, suggesting that at least in some subjects the effects of IFN on TTV can be very short-lived. No correlation between the responses of TTV and HCV to therapy was found. Fitting the viremia data obtained during the first week of treatment into previously developed mathematical models showed that TTV sustains very active chronic infections, with over 90% of the virions in plasma cleared and replenished daily and a minimum of approximately 3.8 x 10(10) virions generated per day. Low levels of TTV were occasionally detected in the peripheral blood mononuclear cells of patients who had cleared plasma viremia, thus corroborating previous results showing that these cells may support TTV replication and/or persistence.     

Tendency and analysis of the epidemic situation in parenteral virus hepatitis B and C in the Russian Federation and a number of its regions

As revealed in the present survey, during the last 3 years, against a background of decreased number of registered cases of acute hepatitis B (HB) and acute hepatitis C (HC), an increase in the proportion of patients with the chronic forms of these diseases was observed. The incidence rate of carriership of hepatitis B (HBV) and hepatitis C viruses (HCV) is many times greater than morbidity rates in acute and chronic forms of the disease. Such differences could be due to imperfect laboratory and clinical diagnosis. The registered statistics on HBV and HCV carriership included newly detected HBsAg and anti-HCV in the absence of clinical manifestations, which did not reflect the true spread of HBV and HCV in a given territory. The group of HBV and HCV carriers was found to include a considerable proportion of patients with asymptomatic form of HB and HC. It was testing for HBsAg, anti-HCV only without determination of virus replication markers (anti-HBc IgM, HBV DNA, anti-HCV IgM, HCV RNA) that seemingly determined the category of carriers greatly exceeding the true incidence. To obtain reliable epidemiological information, the complex detection of HB and HC infection markers is necessary.     

Relationships between TT virus infection and hepatitis C virus response to interferon therapy in doubly infected patients

A group of 24 well-characterized patients doubly infected with hepatitis C virus (HCV) and TT virus (TTV) were studied to evaluate whether the loads and number or identity of the genogroups of TTV they carried could affect the response of HCV infection to interferon-alpha (IFN) treatment. The features of HCV infection in the study patients provided a fair representation of the variables that are usually found in considering patients for IFN treatment. The same was true for the features of TTV infection. In particular, plasma loads of TTV varied over a wide range in individual patients, and infection with multiple TTV genogroups was extremely frequent. TTV genogroups 1 and 3 were the most prevalent, followed by genogroups 4 and 5. The HCV response to IFN was evaluated by measuring plasma viraemia at 24 hours and 30 days after initiation of treatment. The results showed that the TTV parameters investigated had little or no impact on the response of HCV to therapy. Due to study design, these results do not exclude that the presence of a concomitant TTV infection can affect how HCV infection responds to treatment. However, they indicate that, should such effects exist, they would be independent on load and genetic features of the infecting TTV.     

延边地区丙型肝炎患者合并TT病毒感染的检测

检测丙型肝炎患者血清标本中的TT病毒 (transfusiontransmittedvirus,TTV) ,了解延边地区丙型肝炎患者合并TTV感染状况。采用ELISA检测抗TTVIgG和巢式PCR检测丙型肝炎病毒 (HCV)感染患者血清中TTVDNA。采用全自动生化分析仪检测患者血清谷氨酸氨基转移酶 (ALT)和谷氨酸草酰乙酸氨基转移酶 (AST)。 4 5例丙型肝炎患者抗TTVIgG阳性率为 37.8% (17/45 ) ,巢式PCR阳性率为 4 2 .2 % (19/45 )。延边地区HCV感染患者重叠感染TTV较常见。     

浙江省献血员HGV和TTV感染情况的调查

应用逆转录套式聚合酶链反应(RT-Nested PCR)和半套式聚合酶链反应(Semi-nested PCR)分别检测来自浙江省3个地区165例献血员血清标本中的庚型肝炎病毒(HGV)RNA和输血传播性病毒(TTV)DNA.14.6%(24/165)和12.7%(21/165)的血清标本分别检出HGV RNA和TTV DNA,其中3.6%的血清标本(6/165)可同时检出HGV RNA和TTV DNA.实验结果表明,浙江省献血员中HGV和TTV的感染率较高.     

血液透析患者输血传播肝相关病毒感染的调查

使用PCR结合微板杂交-ELtSA及DNA序列分析技术,分别研究了维持性血液透析患者输血传播性HBV、HCV、HDV、HGV、TTV感染状况,并对HBV、TTV进行基因分型、TTV基因变异状况进行分析。除HDV外,发现血液透析患者中存在多重感染。HBV基因型以C型为主,B型次之。TTV分离株中,G1型为主,G2型次之。TTV基因变异可达39．7％。     

Genomic variability of hepatitis G virus/GBV-C at the NS3 region: clinical implications

A new hepatitis virus, named GBV-C or hepatitis G virus (HGV), closely related to the hepatitis C virus (HCV), was identified in 1994. The existence of quasispecies in HCV is very important. In this work polymerase chain reaction amplification of the NS3 region of the genome of GBV-C/HGV and heteroduplex mobility assay (HMA) were combined to investigate the presence of quasispecies in patients with chronic infection by GBV-C/HGV. Patients with chronic infection by HCV were used to validate the method. The HMA was also used to investigate the similarity between the cited genomic region of GBV-C/HGV in different infected patients. A high degree of heterogeneity was found for HGV existing as quasispecies and as differences between samples. This is of extreme importance because of the intrinsic clinical and pathogenic implications of quasispecies of a virus capable of producing disease, and is in accord with other studies which report on the genomic variability of the NS3 region.     

丙型肝炎患者血浆和外周血单个核细胞同步检测HCV—RNA和HGV—RNA

庚型肝炎和丙型肝炎传播途径是一致的 ,主要通过血制品和注射途径 ,有可能同时或重叠感染 ,尽管ＨＧＶ感染能否导致肝损害仍有争论 ,由于国外近年做了许多研究 ,而国内仅有血清检测丙肝和庚肝重叠感染的个别报道 ,但对外周血单个核细胞和血浆未作同步检测。我们对此进行了探讨 ,现将结果报道如下。1　方法观察组 72例患者均为我院住院治疗或门诊追踪观察病例 ,所有病例通过血清学检查排除甲、乙、丁、戊型肝炎。 70 %有输血史 ,肝功能反复异常 ,抗ＨＣＶ阳性 ,临床诊断为慢性或急性丙型肝炎 ,以 2 0例健康献血员作阴性对照 ,用比重 1.0 77的…     

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.     

Nanomedicines in the treatment of patients with hepatitis C co-infected with HIV--focus on pegylated interferon-alpha

In immuno-competent individuals, the natural course of chronic hepatitis C virus (HCV) infection is highly variable and 5%-30% of patients develop cirrhosis over 20 years. Co-infection with HCV and human immunodeficiency virus (HIV) is an important prognostic factor and associated with more frequent and accelerated progression to cirrhosis. Until recently HIV/AIDS-related complications were life limiting in patients co-infected with HCV; the introduction of highly active antiretroviral treatment (HAART) and the better prognosis of HIV infection has made HCV-related complications an emerging health problem in HCV/HIV coinfected individuals. Treatment of chronic HCV infection has also evolved since the introduction of interferon-alpha. Recently, introduction of pegylated interferon-alpha (peginterferon-alpha) has resulted in an increase in sustained virus clearance rates of up to 80% in selected genotypes and patient populations. The safety and efficacy of modern anti HCV treatment regimens - based on peginterferon-alpha in combination with ribavirin - was evaluated in 4 controlled trials. Sustained clearance of hepatitis C virus can be achieved in up to 35% of patients with HIV/HCV co-infection, and novel HCV treatment regimens based on peginterferon-alpha have no negative effect on the control of HIV disease. In conclusion, if HIV infection is well controlled and CD4+ cell counts >100/mm3, treatment of chronic hepatitis C with peginterferon in combination with ribavirin is safe and should be given for 48 weeks regardless of the HCV genotype. Introduction of peginterferon-alpha has significantly improved adherence to treatment and treatment efficacy; in particular sustained virologic response in patients with HCV genotype 1 or 4 infection improved, but sustained viral clearance in only 7%-38% of patients infected with genotype I and 4 cannot be the final step in development of effective treatments in patients with HCV/HIV co-infection.     

Genotype and subtype analyses of hepatitis B virus (HBV) and possible co-infection of HBV and hepatitis C virus (HCV) or hepatitis D virus (HDV) in blood donors, patients with chronic liver disease and patients on hemodialysis in Surabaya, Indonesia

Four subtypes (adw, adr, ayw, and ayr ) and eight genotypes (A to H) of the hepatitis B virus (HBV) have been identified. They appear to be associated with particular geographic distribution, ethnicity, and possibly clinical outcomes. In this study, hepatitis B surface antigen (HBsAg) subtyping and HBV genotyping were carried out on sera obtained from HBsAg-positive HBV carriers, including healthy blood donors; patients with acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma; and patients on hemodialysis all located in Surabaya, Indonesia. We report here that all HBV isolates tested in Surabaya belonged to genotype B, with more than 90% of them being classified into subtype adw. Our results also revealed that prevalence of hepatitis C virus (HCV) co-infection among HBV carriers in Surabaya was approximately 10% for healthy blood donors and patients with chronic liver disease, and approximately 60% for patients on maintenance hemodialysis. Interestingly, HBsAg titers were lower in HBV carriers with HCV co-infection than in those without HCV co-infection. We also found that prevalence of hepatitis D virus (HDV) co-infection was < 0.5% among HBV carriers in Surabaya.     

Advances in therapy for hepatitis C infection

The first approved therapy for chronic hepatitis C virus (HCV) infection was recombinant interferon. Subsequently, controlled studies demonstrated that the combination of interferon-alpha and ribavirin leads to significantly higher virologic sustained responses in patients with chronic hepatitis C. A novel modification of the interferon molecule resulted in the formulation of pegylated interferons, which have a longer half-life than standard interferon. Two recent trials have established the superiority of pegylated interferons compared with interferon-alpha in inducing sustained virologic responses in patients with chronic HCV infection, with or without cirrhosis. Presumably, pegylated interferons will replace standard interferon in treating HCV infection. Phase 3 trials of pegylated interferons in combination with ribavirin are currently under way. Noninterferon-based therapies for the treatment of HCV infection are also in the developmental and experimental phases. Our aims in this review are to present the currently available therapeutic options for HCV infection and the evidence supporting their use in typical patients with chronic hepatitis C or in patients with special circumstances. We also briefly review novel therapeutic approaches, including noninterferon-based therapies.     

Prevalence, genotypes and risk factors associated with hepatitis C virus infection in hemodialysis patients in Campo Grande, MS, Brazil

A survey was conducted among the hemodialysis units of the city of Campo Grande, located in the state of Mato Grosso do Sul in the Mid-west region of Brazil, with the aim of investigating the prevalence, risk factors, and genotypes of hepatitis C virus (HCV) infection. A total of 163 patients were interviewed in five dialysis units. Serum samples were screened for anti-HCV. Positive samples were tested for HCV RNA and genotyped. The prevalence of anti-HCV was 11% (95% CI: 6.8-17.1). A history of transfusion with blood that was not screened for anti-HCV and length of time on hemodialysis were associated with HCV infection. HCV RNA was detected in 12 samples: ten were of genotype 1, subtypes 1a (75%) and 1b (8.3%), and two were of genotype 3, subtype 3a (16.7%).     

Prospective study of hepatitis C virus infection in hemodialysis patients by monthly analysis of HCV RNA and antibodies

The aims of this study were to (i) evaluate the prevalence and the incidence of hepatitis C virus (HCV) infection in hemodialysis patients in two different centers in S?o Paulo (Brazil), (ii) determine the time required to detect HCV infection among these patients by serology or PCR, (iii) establish the importance of alanine aminotransferase determination as a marker of HCV infection, and (iv) identify the HCV genotypes in this population. Serum samples were collected monthly for 1 year from 281 patients admitted to hospital for hemodialysis. Out of 281 patients, 41 patients (14.6%) were HCV positive; six patients seroconverted during this study (incidence = 3.1/1000 person-month). In 1.8% (5/281) of cases, RNA was detected before the appearance of antibodies (up to 5 months), and in 1.1% (3/281) of cases, RNA was the unique marker of HCV infection. The genotypes found were 1a, 1b, 3a, and 4a. The presence of genotype 4a is noteworthy, since it is a rare genotype in Brazil. These data pointed out the high prevalence and incidence of HCV infection at hemodialysis centers in Brazil and showed that routine PCR is fundamental for improving the detection of HCV carriers among patients undergoing hemodialysis.