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X Forns

Publications and source records attributed to X Forns.

At least 37 records · Page 2Linked to original sources
PubMed1999

Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases.

BACKGROUND/AIMS: A recently identified DNA virus, termed TT virus (TTV), has been associated with post-transfusional hepatitis, and a high prevalence of TTV infection in patients with acute or chronic liver disease of unknown etiology has been reported from Japan, but few data are available about TTV infection in other countries. METHODS: Using hemi-nested-PCR amplification to detect TTV-DNA sequences in serum, we investigated TTV infection in blood donors and in patients with liver diseases of varied etiology. RESULTS: The prevalence of TTV infection was 13.7% in blood donors (23/168), 18.6% in chronic hepatitis C (19/102), 28.6% in chronic hepatitis B (16/56), 29.9% in hepatocellular carcinoma (20/67), 9.1% in cryptogenic chronic liver disease (2/22) and 39.6% in fulminant hepatitis (19/48). The prevalence of TTV infection in patients with virus-induced or idiopathic fulminant hepatitis was similar. Comparison of TTV-infected and non-infected patients did not reveal significant differences concerning demographic, epidemiological or histopathological features. In patients with hepatitis C, response to interferon therapy was not related to TTV infection. Phylogenetic analysis of TTV isolates showed that at least three different types of TTV are present in Spain. CONCLUSIONS: Our data suggest that TTV infection is frequent among blood donors and patients with acute liver disease. However, pathogenic effects associated with TTV infection were not observed.

Acute Disease↗
PubMed1999

Quasispecies in viral persistence and pathogenesis of hepatitis C virus.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. This RNA virus circulates as a quasispecies and its genetic heterogeneity has been implicated in the lack of protective immunity against HCV and in its persistence following infection. HCV might escape from immune surveillance by developing mutations in proteins that are subject to immune pressure.

Animals↗
PubMed1999

The molecular biology of hepatitis C virus. Genotypes and quasispecies.

Hepatitis C virus (HCV) is an important cause of chronic liver disease worldwide. HCV is a positive-strand genotype RNA virus with extensive genetic heterogeneity; HCV isolates define 6 major genotypes, and HCV circulates within an infected individual as a number of closely related but distinct species, termed a quasispecies. This article reviews characteristic aspects of HCV molecular biology and their implications for treatment and vaccine development.

3' Untranslated Regions↗
PubMed1999

High prevalence of TT virus (TTV) infection in patients on maintenance hemodialysis: frequent mixed infections with different genotypes and lack of evidence of associated liver disease.

Recently, a novel DNA virus, TT virus (TTV), was identified in patients with post-transfusion non-A-G hepatitis. We analyzed the prevalence and clinical implications of TTV infection in a cohort of 96 Spanish patients on long-term hemodialysis. TTV DNA was detected by nested PCR in 51 (53%) of 96 patients, a prevalence significantly higher than that found in healthy blood donors. Persistent liver test abnormalities were found in only 2 (7.7%) of 26 patients infected with TTV alone, compared with 12 (75%) of 16 patients infected with hepatitis C or hepatitis B virus, or both (P < 0.01). Mixed infections with multiple strains of TTV, including different major genotypes, were common in patients on hemodialysis. These patients had received a significantly greater number of blood units (22.7 +/- 20) compared with patients apparently infected with a single strain of TTV (8.9 +/- 11) (P = 0.01). Phylogenetic analyses of TTV from infected patients identified strains of genotypes 1, 2, 3, and 4. In summary, TTV infection was common in patients on hemodialysis but was not associated with liver disease

Adult↗
PubMed1998

The prognostic relevance of the nonstructural 5A gene interferon sensitivity determining region is different in infections with genotype 1b and 3a isolates of hepatitis C virus.

Hepatitis C virus (HCV) RNA serum concentration, quasispecies complexity, and sequence and phylogenetic analysis of the nonstructural 5A gene (NS5A) interferon sensitivity determining region (ISDR) were determined in pretreatment serum samples from 47 patients with chronic hepatitis C (36 infected by HCV genotype 1b and 11 by 3a). Among HCV genotype 1b-infected patients, virus load was lower (P = .003) and the number of NS5A-ISDR amino acid changes was higher (P = .001) in long-term responders than in non-long-term responders, but there were no differences in quasispecies complexity. Multivariate analysis showed a close association between response to interferon and NS5A-ISDR phenotype. Phylogenetic analysis showed that isolates from non-long-term responders clustered apart from the majority of isolates from long-term responders. There was no association between virologic features and therapeutic response in HCV genotype 3a-infected patients. In conclusion, low virus load and mutant NS5A-ISDR phenotype are closely associated with long-term response to interferon in HCV genotype 1b- but probably not in 3a-infected patients.

Adult↗
PubMed1998

Hepatitis G virus infection in chronic liver disease.

BACKGROUND: The hepatitis G virus (HGV), a recently identified member of the Flaviviridae family, can cause chronic infection in man but the role of this agent in chronic liver disease is poorly understood. AIMS: To evaluate the prevalence and meaning of HGV infection in a large series of patients with chronic liver disease. SUBJECTS: Two hundred volunteer blood donors, 179 patients with chronic hepatitis C, 111 with chronic hepatitis B, 104 with alcoholic liver disease, 136 with hepatocellular carcinoma, and 24 with cryptogenic chronic liver disease were studied. METHODS: HGV RNA was investigated in serum samples by reverse transcription and polymerase chain reaction amplification of the 5' non-coding region of HCV and hybridisation to a specific probe. The main features of HGV RNA seropositive and seronegative patients were compared. RESULTS: The prevalence of HGV infection was 3% in blood donors, 7% in chronic hepatitis C, 8% in chronic hepatitis B, 2% in alcoholic liver disease, 4% in hepatocellular carcinoma, and 8% in cryptogenic chronic liver disease. HGV infected patients tended to be younger than non-infected patients but no differences concerning sex, possible source of infection, clinical manifestations, biochemical and virological parameters, or severity of liver lesions were found. CONCLUSIONS: The prevalence of HGV infection in chronic liver disease seems to be relatively low in our area. Infection with HGV does not seem to play a significant pathogenic role in patients with chronic liver disease related to chronic HBV or HCV infection or to increased alcohol consumption, or in those with cryptogenic chronic liver disease.

Adult↗
PubMed1997

How Escherichia coli can bias the results of molecular cloning: preferential selection of defective genomes of hepatitis C virus during the cloning procedure.

Cloned PCR products containing hepatitis C virus (HCV) genomic fragments have been used for analyses of HCV genomic heterogeneity and protein expression. These studies assume that the clones derived are representative of the entire virus population and that subsets are not inadvertently selected. The aim of the present study was to express HCV structural proteins. However, we found that there was a strong cloning selection for defective genomes and that most clones generated initially were incapable of expressing the HCV proteins. The HCV structural region (C-E1-E2-p7) was directly amplified by long reverse transcription-PCR from the plasma of an HCV-infected patient or from a control plasmid containing a viable full-length cDNA of HCV derived from the same patient but cloned in a different vector. The PCR products were cloned into a mammalian expression vector, amplified in Escherichia coli, and tested for their ability to produce HCV structural proteins. Twenty randomly picked clones derived from the HCV-infected patient all contained nucleotide mutations leading to absence or truncation of the expected HCV products. Of 25 clones derived from the control plasmid, only 8% were fully functional for polyprotein synthesis. The insertion of extra nucleotides in the region just upstream of the start codon of the HCV insert led to a statistically significant increase in the number of fully functional clones derived from the patient (42%) and from the control plasmid (72-92%). Nonrandom selection of clones during the cloning procedure has enormous implications for the study of viral heterogeneity, because it can produce a false spectrum of genomic diversity. It can also be an impediment to the construction of infectious viral clones.

Animals↗
PubMed1997

Hepatitis C virus (HCV) genotypes in Spanish patients with HCV infection: relationship between HCV genotype 1b, cirrhosis and hepatocellular carcinoma.

BACKGROUND/AIMS: The influence of the infecting virus genotype on the progression of the underlying liver disease in patients with chronic hepatitis C virus (HCV) infection remains controversial. The aim of this study was to investigate the prevalence of HCV genotypes in Spanish patients with chronic HCV infection and to elucidate the relationship between the infecting genotype and the severity of the disease. METHODS: A cross-sectional, retrospective analysis of frequency distribution of HCV genotypes was carried out in 414 Spanish patients with chronic HCV infection, including 243 patients with asymptomatic or minimally symptomatic chronic hepatitis, 112 patients with cirrhosis and hepatocellular carcinoma and 59 patients with decompensated cirrhosis. HCV genotype was determined by restriction fragment length polymorphisms of the 5' non-coding region. RESULTS: Infection with HCV genotype 1b was found in 72% of patients with chronic hepatitis and in more than 90% of patients with cirrhosis, with or without hepatocellular carcinoma. Older age, infection with genotype 1b and absence of overt parenteral exposure as a possible source of infection were associated with cirrhosis and hepatocellular carcinoma by univariate analysis and this association was confirmed by regression analysis. CONCLUSIONS: HCV genotype 1b is associated with advanced liver disease in our geographical area. However, this may be related to a cohort-effect caused by over-representation of genotype 1b in older patients with more advanced disease, because, in our country, this HCV genotype appeared earlier in time and is therefore associated with more prolonged periods of infection.

Adult↗
PubMed1997

Hepatitis G virus infection in chronic hepatitis C: frequency, features and response to interferon therapy.

BACKGROUND/AIMS: The pathogenic relevance of the hepatitis G virus (HGV) and its sensitivity to interferon are currently under investigation. This study aimed to investigate the prevalence of HGV infection in patients with chronic hepatitis C and to elucidate if HGV co-infection modifies the clinical course and the response to interferon therapy in this disease. METHODS: HGV-RNA was investigated by reverse transcription-polymerase chain reaction in serum from 143 consecutive patients who received interferon alpha-2b (3 MU t.i.w.) for 24 weeks. Baseline features and response to therapy in HGV-infected and non-infected patients were compared. To assess the antiviral effect of interferon, serial quantitative measurement of HCV-RNA and HGV-RNA in serum was performed in patients co-infected with HCV and HGV. RESULTS: Eight patients (5.6%) presented HGV-RNA sequences in serum. No significant differences were found between HGV-infected and non-infected patients in relation to age, sex, source of infection, liver function tests, liver histology and HCV genotype, nor in the biochemical response to interferon, which was sustained in 12% and 15%, transient in 37% and 30% and absent in 50% and 55% of HGV-infected and non-infected patients, respectively. HGV-RNA became negative in all treated patients, but sustained viral inhibition was observed only in those with low viral load. CONCLUSIONS: The prevalence of HGV infection in HCV-infected patients is relatively low in our geographical area. HGV co-infection does not appear to modify the clinical presentation nor the response to interferon in chronic hepatitis C. HGV is sensitive to interferon, particularly if pre-treatment viral load is low.

Adult↗
PubMed1997

Incidence and risk factors of hepatitis C virus infection in a haemodialysis unit.

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on maintenance haemodialysis. The aim of this study was to prospectively investigate the incidence of de novo hepatitis C virus (HCV) infection in a haemodialysis unit and to identify factors currently involved in HCV transmission to haemodialysis patients. METHODS: One hundred and fourteen anti-HCV negative and HCV-RNA negative patients who started long-term haemodialysis were followed for a mean period of 36 months (range 18-56). Liver tests and anti-HCV were performed at 6-month intervals. Factors that might be implicated in HCV transmission, such as blood transfusions, sexual habits, surgery and other invasive procedures, were recorded. HCV markers were re-examined in transfused blood and the HCV genotype was investigated in seroconverters to anti-HCV and in patients with previous HCV infection who were treated in the vicinity of those who seroconverted. RESULTS: Eight patients (7%) seroconverted to anti-HCV and seven of them became HCV-RNA positive. HCV markers, including HCV-RNA, were negative in the blood transfused to seroconverters. No differences between seroconverters and non-seroconverters. No differences found in other risk factors not directly related to haemodialysis. The investigation of HCV genotype suggested that HCV transmission was not restricted to patients treated in the vicinity of previously HCV infected patients. Occasional failure to observe strict measures of asepsis was detected in the haemodialysis unit and this was the only factor that might be incriminating. CONCLUSIONS: HCV acquisition in patients on haemodialysis is currently not related to blood transfusion, and nosocomial transmission within the haemodialysis unit seems to be the main mechanism of HCV infection. Extremely careful observation of preventive measures seems essential to eradicate HCV transmission in haemodialysis units.

Adult↗
PubMed1997

Hepatitis G virus infection in a haemodialysis unit: prevalence and clinical implications.

BACKGROUND: Hepatitis viruses have become one of the main infectious problems in patients on long-term haemodialysis. A new RNA virus, designated hepatitis G virus (HGV) has been recently identified. The pathogenic relevance of this virus is currently under investigation. The aim of this study was to analyse the prevalence and clinical implications of hepatitis G virus infection in patients on haemodialysis. METHODS: The presence of HGV-RNA was investigated in 96 patients on maintenance haemodialysis. Hepatitis viral markers (HBsAg, anti-HCV, HGV-RNA) and liver tests were assessed in all these patients, as well as the risk factors for hepatitis viruses acquisition. As a control group, 200 blood donors were tested for the presence of HGV-RNA. RESULTS: HGV-RNA was detected in 25 of 96 patients on haemodialysis (26%) and in six of 200 blood donors (3%) (P < 0.001). Thirteen of 25 HGV infected patients (52%) were coinfected with other hepatitis viruses (HBV and/or HCV). Evidences of chronic liver disease were more frequent in patients infected by HBV and/or HCV (61%) than in patients infected by HGV alone (17%) (P = 0.01). Although 80% of HGV infected patients had received blood products, the transfusion rate was not different from non HGV-infected patients. Time on haemodialysis was significantly shorter in patients infected with HGV alone (3.1 +/- 3.5 years) compared to patients infected with HBV and/or HCV (7.6 +/- 5.8 years) (P = 0.04). CONCLUSIONS: Patients on maintenance haemodialysis are at increased risk for HGV infection. HGV infection itself does not seem to be a frequent cause of chronic liver disease in these patients. Since the prevalence of HGV infection in blood donors is high, blood transfusion could be one of the main factors implicated in HGV transmission in patients on haemodialysis.

Adolescent↗
PubMed1997

Evaluation of commercially available and in-house reverse transcription-PCR assays for detection of hepatitis G virus or GB virus C.

Serum samples from 96 Spanish hemodialysis patients, as well as serial dilutions of RNA extracted from a reference strain of hepatitis G virus (HGV), were tested for HGV or GB virus C (GBV-C) RNA. Two different reverse transcription (RT)-PCR-based methods of detection were compared for the ability to detect RNA extracted from the samples: an RT-nested PCR assay with primers derived from the 5' noncoding region (5'NC) or nonstructural region 3 (NS3) sequences and a commercially available RT-PCR assay with primers derived from the 5'NC or NS5A sequences. When RT-nested PCR was performed on 10-fold serial dilutions of RNA from the HGV reference strain, the last positive dilution was 10(-7) to 10(-8). With the commercial RT-PCR assay, the last positive dilution was 10(-6) to 10(-7). When equal amounts of RNA extracted from serum samples from 96 hemodialysis patients were tested for HGV or GBV-C RNA, 25 patients (26%) were positive by the RT-nested PCR. However, only 21 (84%) of these 25 positive patients were positive for HGV or GBV-C by the commercial RT-PCR assay. Analysis of the 5'NC and NS3 sequences amplified by RT-nested PCR demonstrated that all but two positive patients had unique HGV or GBV-C sequences. In summary, RT-nested PCR and a commercially available RT-PCR assay for HGV or GBV-C gave concordant results for 96% of the patients tested.

Base Sequence↗
PubMed1997

Hepatitis G virus infection in fulminant hepatic failure.

BACKGROUND: RNA sequences of the recently identified hepatitis GB virus C (HGBV-C), also named hepatitis G virus (HGV), have been detected in patients with idiopathic fulminant hepatic failure (FHF) but the role of this agent in the disease remains controversial. AIMS: To investigate the presence and implications of HGV infection in a large series of Spanish patients with FHF. PATIENTS: Sixty eight patients with FHF, including 19 with idiopathic disease, were studied. In 28 cases, studies were performed before and after liver transplantation. For comparison 200 volunteer blood donors and 22 patients transplanted for chronic liver disease were also studied. METHODS: HGV RNA was measured in serum by reverse transcriptase polymerase chain reaction of the 5' non-coding region. RESULTS: Evidence of HGV infection was found in 3% (6/200) of blood donors and in 19% (13/68) of patients with FHF. HGV infection was more frequent in patients with hepatitis B (24%, 6/25) or hepatitis D (42%, 5/12), than in patients with idiopathic disease (11%, 2/19). Half of the patients with HGV infection used illicit intravenous drugs. Specific clinical features associated with HGV infection were not identified. A very high rate of infection with HGV was observed in patients who underwent liver transplantation, either for FHF (60%, 15/24) or chronic liver disease (45%, 9/20). CONCLUSIONS: In our geographical area, HGV infection is relatively frequent in FHF, but it does not seem to play a major role in idiopathic cases.

Adult↗
PubMed1996

Quality of life, major medical complications and hospital service utilization in patients with primary biliary cirrhosis after liver transplantation.

AIMS/METHODS: Major medical complications, hospital service utilization and quality of life were investigated in 26 out of 29 consecutive primary biliary cirrhosis transplanted patients who survived at least 2 years after the procedure (90% survival rate). RESULTS: Before liver transplant, the most relevant clinical data were jaundice (96%), pruritus (92%), ascites (50%), gastrointestinal bleeding (19%), hepatic encephalopathy (12%) and bone pain (12%). During the first postoperative year, the most significant complications were bone pain (58%) and fractures (31%), arterial hypertension (50%), and mild/moderate renal failure (46%). The frequency of these complications remained similar during the second year, but there was a significant reduction in the incidence of bone fractures. Bone pain was the only postoperative complication which correlated with an increased number of unscheduled outpatient and emergency visits. Quality of life was measured cross-sectionally either at or after the second postoperative year. The Karnofsky index was 90 in 69% of the patients and 76% were able to perform usual daily activities. Self-assessed health perception was good or very good in almost all the patients. However, the Nottingham Health Profile showed that approximately 70% of the patients gave a positive response to some questions in areas of pain, sleep, emotional reactions and physical activities. CONCLUSIONS: The results of the present study confirm that patients with primary biliary cirrhosis have a high survival rate after liver transplantation and that bone pain and fractures are important postoperative complications. Good self-perceived health and return to daily activities evidenced in most PBC patients should be balanced with problems identified by more specific tools, which could have an impact on the health service utilization and quality of life.

Adult↗
PubMed1996

Permanent response to alpha-interferon therapy in chronic hepatitis C is preceded by rapid clearance of HCV-RNA from serum.

BACKGROUND/AIMS: Prediction of response to interferon therapy is important in the management of chronic hepatitis C. Pre-therapy data are valuable but they may be inaccurate in some cases. Our aim was to investigate whether the biochemical and virological events that occur early during interferon therapy in chronic hepatitis C may predict the final result of the treatment. METHODS: ALT and serum HCV-RNA were serially measured in 53 HCV-RNA-positive patients who received a standard 6-month course of interferon therapy. Eleven patients with a sustained response, 23 who responded but subsequently relapsed and 19 who did not respond were studied. HCV-RNA was measured with a commercial kit (Amplicor HCV). RESULTS: After 4 weeks of treatment, HCV-RNA became negative in 73% of sustained responders, in 26% of transient responders (p = 0.02) and in none of the non-responders. Corresponding figures after 8 weeks of therapy were 82% in sustained responders, 61% in transient responders and 9% in non-responders. The difference between sustained and transient responders at this time was not significant. After 4 weeks of therapy, 82% of sustained responders, 52% of transient responders and none of the non-responders presented normalization of alanine transferase. The difference between sustained and transient responders was not significant. Corresponding figures for normalization of alanine transferase at 8 weeks were 82%, 96% and 0% respectively. At the end of treatment, all sustained responders, 70% of transient responders and none of the non-responders had cleared HCV-RNA from serum. CONCLUSIONS: A rapid normalization of alanine transferase induced by interferon therapy is associated with response, but does not differentiate between transient and permanent response. In contrast, clearance of HCV-RNA after 4 weeks of treatment, but not after 8 weeks, is significatively associated with sustained response. Testing for HCV-RNA early during interferon administration may be valuable for further decisions concerning therapy in patients with chronic hepatitis C.

Adult↗
PubMed1996

Comparative study of three methods for genotyping hepatitis C virus strains in samples from Spanish patients.

Hepatitis C virus (HCV) genotypes may be investigated by a variety of laboratory methods that target different parts of the HCV genome and have various degrees of technical difficulty. Since the choice of a particular method is difficult, we compared the performance of (i) a type-specific PCR with type-specific primers from the core region, (ii) molecular hybridization of the PCR-amplified 5' noncoding region to type-specific probes, and (iii) identification of type-specific antibodies against epitopes of nonstructural region 4 by enzyme-linked immunosorbent assay (ELISA). One hundred fifty-one patients with biopsy-proved chronic hepatitis and HCV RNA in serum were investigated. The HCV genotype was identified in 99%, 100%, and 85% of the cases by type-specific PCR, probe hybridization, and ELISA, respectively. The type-specific PCR disclosed infection with type 1a in 3%, type 1b in 74%, and type 3a in 4% of the cases and suggested infection with two or more HCV types, including 2a/2c and 2b, in the remaining 18%. Apparently mixed infections were more prevalent in patients with past intravenous drug use (P < 0.001), but cloning and sequencing of PCR products did not confirm a mixed infection in any of the four cases investigated. Concordant results were obtained by the three procedures with virtually all of the samples in which the type-specific PCR revealed a single HCV genotype. Type-specific hybridization and ELISA usually recognized the genotype producing the strongest DNA band in samples in which type-specific PCR suggested a mixed infection. In conclusion, the three procedures evaluated in this study are reliable for investigation of HCV genotype. Type-specific PCR provides information about HCV subtypes, but a mixed infection detected with this method should be interpreted with caution.

Enzyme-Linked Immunosorbent Assay↗
PubMed1996

Low dose alpha interferon therapy can be effective in chronic active hepatitis C. Results of a multicentre, randomised trial.

BACKGROUND: There is some controversy concerning the efficacy of low dose alpha interferon therapy in chronic hepatitis C. AIMS: To evaluate the effectiveness of treatment with low doses of alpha interferon in chronic hepatitis C. PATIENTS: One hundred and forty one patients with anti-HCV positive chronic active hepatitis C from six hospitals were enrolled in the study. METHODS: Patients were randomised to treatment with 5 MU (group A) or 1.5 MU (group B) injections. The dose was reduced in responders from group A or increased in non-responders from group B to maintain treatment with the minimal effective dose. Patients were treated for 48 weeks and followed up for 24 additional weeks with no treatment. Normalisation of alanine aminotransferase (ALT) was used to evaluate response. RESULTS: A sustained response was seen in eight patients from group A (12%) and in 15 (21%) from group B. This difference was not statistically significant. Increasing the dose of interferon led to sustained response in only five of 58 patients (9%) from group B who did not respond to 1.5 MU injections. In contrast, 15 of 21 patients (71%) in whom ALT remained normal with 1.5 MU injections developed a sustained response. By multivariate analysis sustained response seemed associated with young age and was more frequent in patients with genotype 3 HCV infection. Sustained response was preceded by a rapid normalisation of ALT and was inversely related to the amount of alpha interferon necessary to maintain ALT at low values during treatment. CONCLUSIONS: Some patients with chronic hepatitis C are very sensitive to alpha interferon and can be successfully treated with low doses. Treatment with higher doses may be effective in a minority of patients who do not respond to low doses.

Alanine Transaminase↗