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HCV Strains (hcv + strain)
Selected AbstractsRelapse of hepatitis C in a pegylated-interferon-,-2b plus ribavirin-treated sustained virological responderHEPATOLOGY RESEARCH, Issue 6 2010Hideki Fujii A 41-year-old woman with chronic hepatitis C was treated with pegylated-interferon (PEG-IFN)-,-2b plus ribavirin for 24 weeks. She had hepatitis C virus (HCV) genotype 2a (1600 KIU/mL), and her liver histology showed mild inflammation and fibrosis. Four weeks after the start of the therapy, she achieved a rapid virological response (RVR) and then a sustained virological response (SVR). Serum alanine aminotransferase (ALT) levels remained within normal ranges and HCV RNA continued to be negative. However, ALT levels flared with the re-emergence of HCV RNA in the serum 1.5 years after discontinuation of therapy. HCV RNA obtained from sera before therapy and after relapse shared a 98.6% homology with the E2 region, and phylogenetic analyses indicated that they were the same HCV strain. These results eliminated the possibility of a re-infection and strongly indicated a late relapse of the disease. Therefore, follow-up is necessary for chronic hepatitis C patients after SVR, even if they respond well to therapy, including RVR. [source] Analyses of amino acid sequences in hypervariable region-1 of hepatitis C virus (HCV) in sera from chimpanzees infected three times with the same HCV strainJOURNAL OF MEDICAL PRIMATOLOGY, Issue 1 2010M. Sugitani Abstract Background, To investigate whether or not the same strain of hepatitis C virus (HCV) can twice re-infect the same chimpanzee, we analyzed nucleic and amino acid sequences in HCV hypervariable region-1 (HVR1). Two chimpanzees were inoculated, three times each, with the same HCV strain during the 1983,1991. After each inoculation, chimpanzees developed acute hepatitis C, and then recovered. Methods, Using sera, HVR1 cloning and antibody to HVR1 major clone measurement were performed. Results, Clones from the first inoculum were divisible into major and minor types. Clones from the second and third inocula, as well as all post-inoculation sera, were essentially identical to the major type. Titers of antibody to HVR1 major clone were consistently low in pre- and post-inoculation sera. Conclusions, Both chimpanzees were re-infected twice with the same strain of HCV. The sequences from the second and third infections were similar to the major sequences in the first inoculum. [source] Phylogenetic analysis indicates transmission of hepatitis C virus from an infected orthopedic surgeon to a patientJOURNAL OF MEDICAL VIROLOGY, Issue 4 2002R. Stefan Ross Abstract During recent years, a controversial discussion has emerged in the medical community on the real number and possible public health implications of hepatitis C virus (HCV) transmissions from infected medical staff to susceptible patients. We report here on molecular virological and epidemiological analyses involving 229 patients who underwent exposure-prone operations by an HCV-infected orthopedic surgeon. Of the 229 individuals affected, 207 could be tested. Three were positive for HCV antibodies. Molecular and epidemiological investigation revealed that two of them were not infected by the surgeon. The third patient, a 50-year-old man, underwent complicated total hip arthroplasty with trochanteric osteotomy. He harbored an HCV 2b isolate that in phylogenetic analysis of the hypervariable region 1 (HVR 1) was closely related to the HCV strain recovered from the infected surgeon, indicating that HCV-provider-to-patient transmission occurred intraoperatively. To our knowledge, this is the first documented case of HCV transmission by an orthopedic surgeon. The recorded transmission rate of 0.48% (95% confidence interval: 0.09,2.68%) was within the same range reported previously for the spread of hepatitis B virus during orthopedic procedures. Since the result of our investigation sustains the notion that patients may contract HCV from infected health-care workers during exposure-prone procedures, a series of further retrospective exercises is needed to assess more precisely the risk of HCV provider-to-patient transmission and to delineate from these studies recommendations for the guidance and management of HCV-infected medical personnel. J. Med. Virol. 66:461,467, 2002. © 2002 Wiley-Liss, Inc. [source] A rapid real-time PCR assay for determination of hepatitis C virus genotypes 1, 2 and 3aJOURNAL OF VIRAL HEPATITIS, Issue 4 2006A. Moghaddam Summary., The genotypes of hepatitis C virus (HCV) in serum of patients have been described as independent predictors of success of antiviral therapy. Therefore, different antiviral regimens have been proposed depending on the infecting HCV genotype. HCV strain is usually determined by polymerase chain reaction (PCR) amplification of genome followed by sequencing or by line-probe assays. We report a new one step real-time PCR assay for genotyping of HCV strains that are prevalent in patients in Norway. HCV types 1, 2 and 3a were genotyped unambiguously in 37 patient serum samples with 100% correlation to genotyping by nucleotide sequence analysis and line-probe assays. Genotyping could also be confirmed against an HCV genotype panel from the National Institute for Biological Standards and Control. This assay does not require manipulation of amplified PCR products, it involves very little hands on and analysis time. This assay can be used for rapid genotyping of HCV-RNA in infected patients to aid physicians decide suitability of patients for treatment and subsequent length of treatment. [source] NS5A mutations predict biochemical but not virological response to interferon-, treatment of sporadic hepatitis C virus infection in European patientsJOURNAL OF VIRAL HEPATITIS, Issue 4 2001I. Stratidaki The NS5A region of the hepatitis C virus (HCV) genome has been reported by Japanese but not European investigators to be a significant factor in predicting interferon (IFN) response patients with HCV of genotype 1. We correlated the NS5A region with treatment outcome in patients with sporadic HCV infection. Twenty-eight patients (10 men, 18 women, mean age 60 ± 2 years) with histologically proven HCV chronic hepatitis, genotype 1b, were treated with 6 MU IFN-, for 6 months. The 6954,7073 area of the NS5A region was directly sequenced for nucleotide and amino acids mutations and the results were related to biochemical and virological response. None of the patients had a strain with nucleotide sequence identical to the Japanese HCV-J. However, in five strains the nucleotide mutations led to synonymous amino acids and the amino acid sequences were identical to the prototype Japanese strain. Only 2/28 patients had four or more amino acid mutations (mutant strains) while 21 demonstrated an intermediate type and five belonged to the wild-type. The most frequent non-synonymous substitution was at position 6982 (A,G) corresponding to an amino acid change at codon 2218 (His,Arg). All patients with the wild-type were biochemical nonresponders while the two patients with the mutant strains had a sustained biochemical response. Twenty-three percent of the intermediate type had a sustained biochemical response. NS5A mutations predict the biochemical but not the virological response of patients. Virological response was poor and unrelated to the type of HCV strain. Biochemical responders had significantly lower amino acid mutations (1.14 ± 0.19) compared with nonresponders (2.57 ± 1.4, P < 0.003) as well as lower aminotransferase values (P < 0.01). Hence, mutational analysis of the NS5A region showed that our patients have a mutational profile similar to the European studies with a wild-type that is slightly different from the Japanese HCV-J sequence. The biochemical, but not the virological response to IFN-, is similar to the Japanese studies, with no response of the patients with wild-type sequence, a good response in the limited number of patients with mutant strains and 23% response rate in the patients with intermediate type sequences. [source] Hepatitis C virus quasispecies in the natural course of HCV-related disease in patients with haemophiliaHAEMOPHILIA, Issue 1 2004G. Tagariello Summary., Patients with haemophilia show high prevalence of hepatitis C infection but low rate of progressive liver disease when they are not co-infected with HIV. The balance between host immune system and hepatitis C virus (HCV) variability seems to play a major role in the evolution of the HCV-related disease. To address this point we have studied, in a group of selected patients with haemophilia, the composition and in some cases the evolution, of the highest variable envelope gene within the hypervariable region 1 (HVR1) of the HCV, which is the region more directly exposed to the host immune response. Five of 12 patients show a very high homogeneity of the HVR1 and four of those had severe progressive liver disease. These results seem to confirm the major role of the immunity in driving the variability of the HCV rather than the high degree of different HCV strains to which haemophiliacs have been in touch with, during their long-term replacement therapy. Our results seem in keeping with other studies on different type of patients, where a low degree of quasispecies variability has been demonstrated in relationship with the progression and the severity of their liver disease. [source] Hepatocyte NAD(P)H oxidases as an endogenous source of reactive oxygen species during hepatitis C virus infection,HEPATOLOGY, Issue 1 2010Nabora Soledad Reyes de Mochel Oxidative stress has been identified as a key mechanism of hepatitis C virus (HCV),induced pathogenesis. Studies have suggested that HCV increases the generation of hydroxyl radical and peroxynitrite close to the cell nucleus, inflicting DNA damage, but the source of reactive oxygen species (ROS) remains incompletely characterized. We hypothesized that HCV increases the generation of superoxide and hydrogen peroxide close to the hepatocyte nucleus and that this source of ROS is reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase 4 (Nox4). Huh7 human hepatoma cells and telomerase-reconstituted primary human hepatocytes, transfected or infected with virus-producing HCV strains of genotypes 2a and 1b, were examined for messenger RNA (mRNA), protein, and subcellular localization of Nox proteins along with the human liver. We found that genotype 2a HCV induced persistent elevations of Nox1 and Nox4 mRNA and proteins in Huh7 cells. HCV genotype 1b likewise elevated the levels of Nox1 and Nox4 in telomerase-reconstituted primary human hepatocytes. Furthermore, Nox1 and Nox4 proteins were increased in HCV-infected human liver versus uninfected liver samples. Unlike Nox1, Nox4 was prominent in the nuclear compartment of these cells as well as the human liver, particularly in the presence of HCV. HCV-induced ROS and nuclear nitrotyrosine could be decreased with small interfering RNAs to Nox1 and Nox4. Finally, HCV increased the level of transforming growth factor beta 1 (TGF,1). TGF,1 could elevate Nox4 expression in the presence of infectious HCV, and HCV increased Nox4 at least in part through TGF,1. Conclusion: HCV induced a persistent elevation of Nox1 and Nox4 and increased nuclear localization of Nox4 in hepatocytes in vitro and in the human liver. Hepatocyte Nox proteins are likely to act as a persistent, endogenous source of ROS during HCV-induced pathogenesis. Hepatology 2010 [source] Primary hepatocyte culture supports hepatitis C virus replication: A model for infection-associated hepatocarcinogenesis,HEPATOLOGY, Issue 6 2010Krishna Banaudha Analysis of progressive changes in hepatic gene expression that underlie hepatocarcinogenesis following hepatitis C virus (HCV) infection require examination of long-term cultures of normally differentiating primary human hepatocytes. We report a culture system of primary hepatocytes that support productive replication of infectious HCV. Hepatic functions were analyzed by reverse-transcription polymerase chain reaction amplification of total cell RNA from cultures maintained in serum-free defined medium for up to 190 days. Sustained hepatic function was assessed by expression of albumin, alpha-fetoprotein, cytochrome P4502E1, cytokeratin-18, type-1 collagen, transforming growth factor-beta 1, matrix metalloproteinase-2 (MMP-2), MMP-13, and interferon alpha-receptors 1 and 2. Normally differentiated human primary hepatocytes supported productive replication of infectious clones of HCV genotypes 1a, 1b, and 2a; virus infection was inhibited by antibodies against CD81 virus entry factor. Virus released into the culture media of HCV-infected primary hepatocytes repeatedly passage to naïve hepatocytes. Replication of the three HCV genotypes shows interferon sensitivity observed in natural infections. Conclusion: Sustained cultures of physiologic host cells for the propagation of infectious HCV strains should accelerate studies of host response to HCV infection and progressive liver disease. Hepatology 2010;51:1922,1932 [source] Strain-dependent viral dynamics and virus-cell interactions in a novel in vitro system supporting the life cycle of blood-borne hepatitis C virus,HEPATOLOGY, Issue 3 2009Hussein Hassan Aly We developed an in vitro system that can be used for the study of the life cycle of a wide variety of blood-borne hepatitis C viruses (HCV) from various patients using a three-dimensional hollow fiber culture system and an immortalized primary human hepatocyte (HuS-E/2) cell line. Unlike the conventional two-dimensional culture, this system not only enhanced the infectivity of blood-borne HCV but also supported its long-term proliferation and the production of infectious virus particles. Both sucrose gradient fractionation and electron microscopy examination showed that the produced virus-like particles are within a similar fraction and size range to those previously reported. Infection with different HCV strains showed strain-dependent different patterns of HCV proliferation and particle production. Fluctuation of virus proliferation and particle production was found during prolonged culture and was found to be associated with change in the major replicating virus strain. Induction of cellular apoptosis was only found when strains of HCV-2a genotype were used for infection. Interferon-alpha stimulation also varied among different strains of HCV-1b genotypes tested in this study. Conclusion: These results suggest that this in vitro infection system can reproduce strain-dependent events reflecting viral dynamics and virus-cell interactions at the early phase of blood-borne HCV infection, and that this system can allow the development of new anti-HCV strategies specific to various HCV strains. (HEPATOLOGY 2009.) [source] HCV genotypes in Sicily: Is there any evidence of a shift?JOURNAL OF MEDICAL VIROLOGY, Issue 6 2009Paola Pizzillo Abstract The distribution of HCV strains in any area is characterized by a relative prevalence of one genotype, and a number of less prevalent types. In some Western countries a change from the prevalent HCV genotype 1 to genotypes 3 and 4 has been reported in the last decade. In order to assess possible variations of the distribution of HCV genotypes in Sicily, a southern region of Italy, a hospital-based cohort, collected prospectively, of 3,209 subjects with chronic HCV infection was surveyed, comparing the distribution of HCV genotypes during two consecutive periods, from 1997 to 2002 and from 2003 to 2007, according to age and gender. The results show that genotype 1b, which has been historically the most prevalent in Sicily, is still predominant, followed more distantly by genotypes 2 and 3a. However, a cohort effect for these genotypes was seen when comparing the two time periods. Genotype 1b decreased slowly over the last decade, due to the death of the people infected, leading to a proportional increase of the other genotypes. No evidence was found in support of a major increase in the prevalence of other genotypes, such as genotype 4, in relation to migration patterns. J. Med. Virol. 81:1040,1046, 2009. © 2009 Wiley-Liss, Inc. [source] Genetic characterization of hepatitis C virus strains in Estonia: Fluctuations in the predominating subtype with timeJOURNAL OF MEDICAL VIROLOGY, Issue 4 2007Tatjana Tallo Abstract During the last decade, there has been a dramatic increase in intravenous drug use in young adults in Estonia with an increased incidence of both hepatitis B and C as a consequence. Since genetic data are limited regarding hepatitis C virus (HCV) strains in Estonia, the aim of the study was to characterize HCV strains in different risk groups to determine their relatedness to strains from other geographical regions. Three hundred fifty-three anti-HCV positive sera collected during 1994,2004 from hospitalized patients, blood donors and health care workers were used as source of HCV RNA. Two hundred nine (59%) of the sera were positive for HCV RNA by PCR directed to the 5,-UTR region. For 174 strains the HCV subtype was determined by analyses of the NS5B and/or the 5,UTR-core regions. 1b (71%) was the most common subtype followed by 3a (24%), 2c (2%), 1a (1%), and 2a (1%). The 1b and 3a strains were similar to strains from other regions of the former USSR. Within genotype 1b there were several HCV lineages. However, for 3a there seemed to be two separate introductions into Estonia. There was a relative shift from subtype 1b to 3a in 1999,2000 with a further replacement of 3a with 1b in intravenous drug users in 2001 and onwards (P,<,0.05). However, both subtypes were found to co-circulate in the community independent of risk factors. One patient was infected with the 2k/1b recombinant presumed to originate from St. Petersburg being the first isolate of this recombinant recovered outside Russia. J. Med. Virol. 79:374,382, 2007. © 2007 Wiley-Liss, Inc. [source] A rapid real-time PCR assay for determination of hepatitis C virus genotypes 1, 2 and 3aJOURNAL OF VIRAL HEPATITIS, Issue 4 2006A. Moghaddam Summary., The genotypes of hepatitis C virus (HCV) in serum of patients have been described as independent predictors of success of antiviral therapy. Therefore, different antiviral regimens have been proposed depending on the infecting HCV genotype. HCV strain is usually determined by polymerase chain reaction (PCR) amplification of genome followed by sequencing or by line-probe assays. We report a new one step real-time PCR assay for genotyping of HCV strains that are prevalent in patients in Norway. HCV types 1, 2 and 3a were genotyped unambiguously in 37 patient serum samples with 100% correlation to genotyping by nucleotide sequence analysis and line-probe assays. Genotyping could also be confirmed against an HCV genotype panel from the National Institute for Biological Standards and Control. This assay does not require manipulation of amplified PCR products, it involves very little hands on and analysis time. This assay can be used for rapid genotyping of HCV-RNA in infected patients to aid physicians decide suitability of patients for treatment and subsequent length of treatment. [source] Genotype diversity of hepatitis C virus (HCV) in HCV-associated liver disease patients in IndonesiaLIVER INTERNATIONAL, Issue 8 2010Andi Utama Abstract Background: Hepatitis C virus (HCV) genotype distribution in Indonesia has been reported. However, the identification of HCV genotype was based on 5,-UTR or NS5B sequence. Aims: This study was aimed to observe HCV core sequence variation among HCV-associated liver disease patients in Jakarta, and to analyse the HCV genotype diversity based on the core sequence. Methods: Sixty-eight chronic hepatitis (CH), 48 liver cirrhosis (LC) and 34 hepatocellular carcinoma (HCC) were included in this study. HCV core variation was analysed by direct sequencing. Results: Alignment of HCV core sequences demonstrated that the core sequence was relatively varied among the genotype. Indeed, 237 bases of the core sequence could classify the HCV subtype; however, 236 bases failed to differentiate several subtypes. Based on 237 bases of the core sequences, the HCV strains were classified into genotypes 1 (subtypes 1a, 1b and 1c), 2 (subtypes 2a, 2e and 2f) and 3 (subtypes 3a and 3k). The HCV 1b (47.3%) was the most prevalent, followed by subtypes 1c (18.7%), 3k (10.7%), 2a (10.0%), 1a (6.7%), 2e (5.3%), 2f (0.7%) and 3a (0.7%). HCV 1b was the most common in all patients, and the prevalence increased with the severity of liver disease (36.8% in CH, 54.2% in LC and 58.8% in HCC). These results were similar to a previous report based on NS5B sequence analysis. Conclusion: Hepatitis C virus core sequence (237 bases) could identify the HCV subtype and the prevalence of HCV subtype based on core sequence was similar to those based on the NS5B region. [source] | ||||||||||