Biomedical subjects

Rafael Esteban

Publications and source records attributed to Rafael Esteban.

At least 19 recordsLinked to original sources

PubMed2006

Community-based seroepidemiological survey of hepatitis E virus infection in Catalonia, Spain.

The objective of the study was to investigate the prevalence of immunoglobulin G (IgG) antibodies to hepatitis E virus (HEV) infection in a population sample from Catalonia and to analyze the demographic and clinical variables associated with the presence of these antibodies. A total of 1,280 subjects between 15 and 74 years of age were selected randomly from urban and rural areas. Data for sociodemographic and clinical variables were collected by using a questionnaire. IgG antibodies to HEV were determined by an immunoenzymatic method. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated for studied variables. Multiple logistic regression analysis was used to determine which variables were independently associated with the prevalence of HEV infection. Anti-HEV antibodies were detected in 96 (7.3%) of the 1,280 samples analyzed. The prevalence of antibodies was greater among males (7.8%) than among women (7%) and increased with age for both sexes, from 3% among subjects 15 to 24 years of age to 12% among subjects >/=65 years of age. Bivariate analysis of the sociodemographic and clinical variables showed an association between the prevalence of hepatitis E virus infection and minor surgery (OR, 1.96; 95% CI, 1.24 to 3.11), abdominal surgery (OR, 1.74; 95% CI, 1.12 to 2.73), and, for women, being uniparous or multiparous (OR, 2.84; 95% CI, 1.19 to 6.79). The multivariate analysis showed an association with minor surgery only (OR, 1.68; 95% CI, 1.03 to 2.70). In conclusion, anti-HEV antibodies were detected in 7.3% of the Catalan population. The seroprevalence of anti-HEV antibodies increased with age and was associated with previous minor surgery.

Adolescent↗

PubMed2006

Hemodynamic response-guided therapy for prevention of variceal rebleeding: an uncontrolled pilot study.

The clinical usefulness of assessing hemodynamic response to drug therapy in the prophylaxis of variceal rebleeding is unknown. An open-labeled, uncontrolled pilot trial was performed to evaluate the feasibility and efficacy of using the hemodynamic response to pharmacological treatment to guide therapy in this setting. Fifty patients with acute variceal bleeding underwent a hepatic venous pressure gradient (HVPG) measurement 5 days after the episode. Nadolol and nitrates were initiated, and a second HVPG was measured 15 days later. Responder patients (> or =20% decrease in HVPG from baseline) were maintained on drugs, partial responders (> or =10% and <20%) had banding ligation added to the drugs, and nonresponders (<10%) received a transjugular intrahepatic portal-systemic shunt (TIPS). Mean follow-up was 22 months. Eight patients (16%) did not receive the second HVPG, 6 of them because of early variceal rebleeding. Of the other 42 patients, 24 were classified as responders (57%); 10 as partial responders (24%), who had banding added; and 8 as nonresponders (19%), who received a TIPS. Patients with cirrhosis of viral etiology compared to alcoholic cirrhosis tended to present more early rebleedings, less response to drugs and needed more TIPS. Variceal rebleeding occurred in 22% of all patients but only in 12% of patients whose hemodynamic response was assessed. The 3 therapeutic groups were not different. In conclusion, using hemodynamic response to pharmacological treatment to guide therapy in secondary prophylaxis to prevent variceal bleeding is feasible and effectively protects patients from rebleeding. In this context, viral cirrhosis seems to present a worse outcome than alcoholic cirrhosis.

Adrenergic beta-Antagonists↗

PubMed2006

Validity of the Spanish version of the Chronic Liver Disease Questionnaire (CLDQ) as a standard outcome for quality of life assessment.

The Chronic Liver Disease Questionnaire (CLDQ) measures the impact on quality of life of chronic liver diseases, regardless of underlying etiology. The aim of this study was to develop a Spanish version of the CLDQ, and to assess its acceptability, reliability, validity, and sensitivity to change. The forward and back-translation method by bilingual translators, with expert panel and pilot testing on patients, was used for the adaptation. The final version was self-administered, together with the Short Form-36 Health Survey (SF-36), on 149 consecutive patients with chronic liver disease. Child-Turcotte-Pugh scores were evaluated by a physician. To assess reproducibility and responsiveness the CLDQ was readministered to a subsample of stable patients and to those who had received a liver transplant. Validity was evaluated via exploratory factor analysis, the CLDQ pattern across severity groups, and correlation coefficients with "itching" and SF-36 scores. Cronbach's alpha and Intraclass Correlation Coefficient for CLDQ global score were 0.93 and 0.90, respectively, demonstrating good reliability. Validity was supported by correlations of the CLDQ with SF-36 and "itching," and CLDQ severity gradient (global score means were 5.5, 5.2, 5.0, and 4.5 in patients with no cirrhosis, cirrhosis Child-Turcotte-Pugh A, B, and C, respectively; P = 0.012). Responsiveness was shown by a high CLDQ improvement in patients who had received liver transplant (mean change = -1.4; P < 0.001). In conclusion, the Spanish CLDQ is reliable, valid, responsive, and equivalent to the original. These findings support its use as a standard outcome for patients with chronic liver diseases within the whole severity range, from "no cirrhosis" to transplant recipients, both in Spanish and international studies.

Adaptation, Psychological↗

PubMed2005

Quality of life and cost-effectiveness of anti-HCV therapy in HIV-infected patients.

Quality of life studies in chronic hepatitis C using specific questionnaires have been performed in mono-infected patients; however, these studies have just begun in HIV-HCV co-infected patients. The questionnaires used in mono-infected patients are not well adapted for co-infected patients and need to be redesigned. Typically, co-infected patients have multiple symptoms that may be attributable to HIV, to HCV, to a combination of both diseases or even to side effects related to drug therapy. These patients usually need substitutive therapy to manage side effects related to HCV therapy, particularly anaemia, leukopenia and depression. There are no cost-effectiveness studies published on the current HCV standard therapy with pegylated interferon and ribavirin. However, there is some research on the old standard interferon and ribavirin, which shows that HCV therapy is cost-effective. Cost-effectiveness studies in co-infected patients will have to take into account variables that do not affect mono-infected patients, such as the different levels of CD4, the increase in the fibrosis progression rate and the use of other expensive drugs for the management of side effects. Currently, the literature does not provide adequate information on the effect of HCV infection on the quality of life of HIV-HCV co-infected patients or the most cost-effective HCV therapy.

Antiviral Agents↗

PubMed2005

Neuropsychological abnormalities in cirrhosis include learning impairment.

BACKGROUND/AIMS: Minimal hepatic encephalopathy is a neurocognitive disorder secondary to liver failure that is characterized by a pattern of subcortical impairment. The most conspicuous neuropsychological abnormalities are on attention and psychomotor tests; memory has been inconsistently implicated. We designed a study to assess the presence of memory abnormalities in cirrhotic patients and the effects of liver transplantation. METHODS: Ninety-seven cirrhotics without overt hepatic encephalopathy underwent neuropsychological assessment, including the Auditory Verbal Learning Memory Test. The results were compared to those of healthy controls (n=75) and the assessment was repeated at one year of follow-up (n=33) or after liver transplantation (n=23). RESULTS: Cirrhotic patients exhibited multiple neuropsychological abnormalities, including several disturbances of the Auditory Verbal Learning memory test: learning, long-term memory and recognition. Abnormalities of long-term memory and recognition were corrected after adjusting for learning impairment. Memory abnormalities correlated to attention impairment and to parameters of liver function. Neuropsychological indexes following liver transplantation did not differ from controls. Repeated testing did not have a major effect on neuropsychological tests in healthy subjects and in non-transplanted cirrhotics. CONCLUSIONS: Learning impairment is present in cirrhotic patients with neuropsychological abnormalities. This abnormality is consistent with attention deficit secondary to minimal hepatic encephalopathy.

Female↗

PubMed2005

Combined treatment with pegylated interferon (alpha-2b) and ribavirin in the acute phase of hepatitis C virus recurrence after liver transplantation.

BACKGROUND/AIMS: The efficacy and safety of treatment with pegylated interferon alpha-2b (Peg-Intron, 1.5 microg/kg) and ribavirin (400-800 mg) in the acute phase of recurrent HCV after LT is presented. METHODS: Twenty-four patients (17 men) transplanted for HCV-associated cirrhosis (genotype 1b) were treated for at least 6 months and compared with 24 consecutive transplant patients (16 men) without antiviral therapy (controls). RESULTS: At completion of treatment, 14/24 treated patients (58%) achieved HCV-RNA negativity, compared to none of controls (P<0.0001). Sustained virological response (SVR) occurred in 8/23 treated patients (34.7%) who reached week 24 after treatment and none of controls (P<0.005). At 12 weeks after treatment, 15/24 patients (62.5%) had an early virological response (EVR) (seven tested HCV-RNA negative). SVR was associated with absence of corticosteroid bolus administration (P=0.01), presence of EVR (P=0.002) and absence of cytomegalovirus infection (P=0.001). Haematological adverse effects included anaemia, 17/24 cases (71%) and leukopenia, 23/24 cases (96%). One patient presented mild acute rejection that resolved by adjusting immunosuppressive dose. CONCLUSIONS: Treatment with pegylated interferon alpha-2b plus ribavirin in the acute phase of HCV reinfection yielded an EVR of 62.5% and a SVR of 34.7%. The combination was safe, with a low rate of therapy withdrawal.

Aged↗

PubMed2005

Cardiac alterations in cirrhosis: reversibility after liver transplantation.

BACKGROUND/AIMS: Liver cirrhosis induces cardiac alterations. We aimed to define these alterations and assess their reversibility after transplantation. METHODS: Cirrhotic patients (n = 40) and controls (n = 15) underwent echocardiography and stress ventriculography. Fifteen cirrhotics were reevaluated 6-12 months after transplantation. RESULTS: Cirrhotics had higher left ventricular wall thickness (9.6+/-1.2 vs. 8.8+/-1.2 mm; P < 0.05) and ejection fraction (73+/-6 vs. 65+/-4%, P < 0.001) than controls. Basal diastolic function was similar. During stress, cirrhotics presented lower increases of heart rate, left ventricular ejection fraction, stroke volume and cardiac index (P < 0.05 for all), and diastolic dysfunction with lower ventricular peak filling rate (P = 0.001). Exercise capacity was reduced (48+/-21 vs. 76+/-24 W; P < 0.001). Ascitic patients exhibited more diastolic dysfunction at rest and during stress compared to non-ascitic patients. Liver transplantation caused regression of ventricular wall thickness (10.2+/-1.3 vs. 9.5+/-1.2 mm; P < 0.05), improvement of diastolic function, and normalization of systolic response and exercise capacity during stress (significant increases in heart rate, ventricular ejection fraction, stroke volume and cardiac index; P < 0.05 for all). CONCLUSIONS: Cardiac alterations in cirrhosis present with mild increases in ventricular wall thickness, diastolic dysfunction that worsens with ascites and physical stress, and abnormal systolic response to stress limiting exercise capacity. Liver transplantation reverses these alterations.

Adult↗

PubMed2005

Extended lamivudine treatment in patients with HBeAg-negative chronic hepatitis B.

BACKGROUND/AIMS: The histological and clinical outcome of lamivudine 100mg/day was assessed in 76 HBeAg-negative chronic hepatitis B patients previously randomised to a double-blind comparison study of lamivudine and placebo. METHODS: Paired liver biopsies were available before 1 year of randomised lamivudine treatment and after 2 years of further open-label treatment for 48 patients. Serum samples were analysed for hepatitis B markers and ALT levels (n=74). RESULTS: The histological activity index improved, remained unchanged and worsened in 64, 32 and 5%, respectively, for patients without YMDD-variant HBV compared to 15, 54 and 31% with the variant. None of the 42/48 patients without cirrhosis at baseline progressed to cirrhosis. Of 24/48 patients without bridging fibrosis at pre-treatment, 83% (20/24) did not progress to bridging fibrosis. Median HBV DNA remained below the lower limit of detection and ALT < or =1 times the ULN for patients without the variant whereas levels gradually increased to 11.3Meq/ml (bDNA assay) and 2 times the upper limit of normal by month 24 for patients with variant. CONCLUSIONS: The clinical benefit of lamivudine is greatest for patients without YMDD variants over 2 years of extended treatment. Additional therapies should be considered for patients with YMDD variants.

DNA, Viral↗

PubMed2005

Estimating the impact of hepatitis C virus therapy on future liver-related morbidity, mortality and costs related to chronic hepatitis C.

BACKGROUND/AIMS: Chronic Hepatitis C virus (HCV) infection is common and often produces a progressive disease. Some studies suggest that HCV related complications will increase in the future. Our aim was to estimate the future morbidity, mortality and costs of chronic HCV infection in a cohort of patients infected by HCV and to evaluate the impact of HCV therapy. METHODS: A mathematical model was used to project over the next 30 years, the HCV related complications and costs in a cohort of 419,895 infected patients representing the HCV infected population in Spain. The impact of HCV therapy with peginterferon and ribavirin in this population was also projected. RESULTS: A gradual decline in the infected population is expected in the future, however, the proportion of patients with cirrhosis will increase by up to 14% and morbidity associated with HCV infection by up to 10% by the year 2030 with a subsequent increment in HCV related costs. However, treating from 10 to 50% of the HCV population will result in a reduction of 6 and 26% in morbidity and 4 and 20% in mortality, respectively. The cost per year of life gained ranges from 6078 for a 29-year-old patient to 8911 for a 59-year-old patient. CONCLUSIONS: In the future, HCV infection mortality, morbidity and associated costs will increase. Treatment of the chronic HCV infected population can eradicate the infection, increase patients' survival and reduce the need for liver transplantation, making this a cost-effective strategy.

Adolescent↗

PubMed2005

Hepatitis B virus genome variability and disease progression: the impact of pre-core mutants and HBV genotypes.

The hepatitis B virus (HBV), a member of the Hepadnaviridae family, is prone to mutations due to its asymmetric replication via reverse transcription of an RNA intermediate. The estimated mutation rate of the hepadnavirus genome is 2 x 10(4) base substitutions/site/year. This mutation rate is approximately 100 times higher than that of other DNA viruses but between 100 and 1000 times lower than that of RNA viruses. Analyses of both naturally occurring viral variants and in vitro mutagenesis studies have identified some mutations that have a role in viral latency, pathogenesis of liver disease, immune escape, and resistance to antiviral therapy.

Animals↗

PubMed2005

Effect of bottlenecking on evolution of the nonstructural protein 3 gene of hepatitis C virus during sexually transmitted acute resolving infection.

Sexual partners of patients infected with the hepatitis C virus (HCV) often have detectable HCV-specific T-cell responses in the absence of seroconversion, suggesting unapparent, spontaneously resolving infection. To determine whether differences in the evolutionary potential of bottlenecked inoculum may explain the low rate of HCV persistence after sexual exposure, we have investigated changes in the entire HCV nonstructural 3 (NS3) gene over time in a chronic carrier and compared his viral quasispecies with that of the acute-phase isolate of his sexual partner, who developed acute resolving hepatitis C. The overall rate of accumulation of mutations, estimated by regression analysis of six consecutive consensus NS3 sequences over 8 years, was 1.5 x 10(-3) mutations per site per year, with small intersample fluctuations related to changes in environmental conditions. Comparison of quasispecies parameters in one isolate of the chronic carrier with those of the acute-phase isolate of the infected partner revealed a higher heterogeneity and lower proportion of nonsynonymous mutations in the former. All NS3 sequences from the acute-phase isolate clustered with a single sequence from the chronic isolate, despite complete HLA mismatch between the patients, suggesting bottlenecking during transmission. The low risk of viral persistence after sexual exposure to HCV may be related to the selection of a limited number of viral particles carrying a particular combination of mutations which may further limit the potential of a relatively homogeneous quasispecies to rapidly diversify and overcome the immune response of the exposed host.

Acute Disease↗

PubMed2005

Improved attachment of natural HCV isolate to Daudi cells upon elimination of immune complexes and close pH control.

OBJECTIVES: To study the viral requirements for attachment, entry and infection using natural isolates of HCV (infectious plasma of a patient infected with HCV from genotype 1b) and a cell line which has previously been shown to support HCV replication (Daudi cells). METHODS: We studied attachment of HCV to Daudi cells, a human B-cell line. Quantification was done by real-time RT-PCR. RESULTS: The best attachment levels were obtained using plasma depleted of immunocomplexes. Results of kinetics of HCV attachment to Daudi cells show that attachment is maximum at pH 7.0, and that it decreased drastically at any other pH studied (5.5, 6.0, 6.5, 7.5 and 8.0). CONCLUSIONS: Depletion of immunocomplexes and pH control during infection are important parameters to improve attachment of HCV to Daudi cells using plasma as a natural source of virus.

Antigen-Antibody Complex↗

PubMed2005

Drugs in development for hepatitis B.

The management of chronic hepatitis B (CHB) has improved dramatically over the last decade with the development of new drugs such as lamivudine and adefovir dipivoxil, in addition to the now standard interferon (IFN)-alpha therapy. These new drugs can achieve a significant reduction or inhibit replication of hepatitis B virus (HBV) DNA during therapy. However, in the majority of patients, particularly in those who are hepatitis B e antigen (HBeAg)-negative, the sustained off-therapy suppression of HBV DNA is rare. For this reason, several new antiviral and immunomodulatory agents are currently being evaluated. Among the immunomodulatory agents, pegylated IFNalpha (peginterferon-alpha) has been shown to be more effective for HBeAg-positive CHB than either lamivudine or standard IFNalpha monotherapy, particularly in those patients infected by HBV genotypes A and B. The new antivirals entecavir, tenofovir disoproxil fumarate and telbivudine exhibit a more potent viral inhibitory effect than the currently approved drugs (IFNs, lamivudine and adefovir dipivoxil). However, the emergence of viral resistance has been witnessed and this could be one of the major limitations to the clinical use of these new drugs, particularly during prolonged therapy. In HBeAg-negative patients it is more and more common for oral antiviral therapy to be administered for prolonged periods, as the sustained off-therapy response rates of short-term therapy are very low. Different studies are currently evaluating combination therapy, using lamivudine with adefovir dipivoxil or peginterferon-alpha with lamivudine; the preliminary results show virological responses no better than those achieved by monotherapy. However, as combination therapy is associated with a low likelihood of developing HBV drug resistance, this could result in a higher virological response during prolonged therapy. In the near future the most realistic therapeutic option for the majority of patients with CHB will be long-term use of these new, more potent antiviral drugs, if they can achieve good safety profiles while maintaining low resistance rates at affordable costs.

Adenine↗

PubMed2005

Financial impact of two different ways of evaluating early virological response to peginterferon-alpha-2b plus ribavirin therapy in treatment-naive patients with chronic hepatitis C virus genotype 1.

BACKGROUND: Patients infected with chronic hepatitis C virus (HCV) genotype 1 are the least responsive to peginterferon (pegIFN) and ribavirin therapy. The monitoring of early virological response (EVR) is therefore an important tool for quickly identifying non-responders, permitting therapy discontinuation and avoiding adverse effects and costs. OBJECTIVE: To analyse the financial impact, in treatment-naive patients infected with HCV genotype 1, of two different measurement techniques for evaluating the EVR during pegIFN-alpha-2b plus ribavirin therapy, and to compare the results of a 48-week standard course of therapy with pegIFN-alpha-2b plus ribavirin without measuring EVR. METHODS: A budget impact model was constructed using a decision-tree analysis. EVR was defined as a >2 log decline in HCV RNA levels at week 12 either tested with two quantitative HCV RNA tests or undetectable HCV core antigen (HCV core Ag) protein levels at week 12 (one HCV core Ag test). Clinical data were taken from multicentre trials and costs from the published literature (euro, 2003 values). The analysis was carried out from the perspective of the Spanish healthcare system and therefore only direct costs were considered. The base-case scenario assumed that a potential study population of 18,504 people in Spain with chronic HCV genotype 1 would be eligible for treatment with pegIFN-alpha-2b plus ribavirin. RESULTS: In the base case, the most effective strategy was testing EVR by HCV core Ag. This resulted in 12,745 patients reaching a sustained virological response (SVR) at an overall cost of 243.98 million euro (19,142 euro per SVR). Conversely, quantitative HCV RNA testing resulted in 11,776 patients with an SVR at a cost of 232.73 million euro ( 19,763 euro per SVR). The incremental cost per successfully treated patient with HCV core Ag testing versus quantitative HCV RNA testing was 11,597 euro. One-way sensitivity analyses demonstrated that changes in the study parameters did not modify the outcomes, except when increasing the EVR or SVR of strategy 2 or when decreasing the EVR or SVR of strategy 3. CONCLUSION: This model suggests, with its underlying assumptions and data, that the assessment of EVR at week 12 by HCV core Ag testing in chronic HCV patients infected with genotype 1 permits identification of those patients expected to achieve an SVR with pegIFN-alpha-2b and ribavirin, resulting in a lower overall cost to the Spanish healthcare system than HCV RNA testing or no testing at all.

Antiviral Agents↗

PubMed2004

Structural analysis of hepatitis C RNA genome using DNA microarrays.

Many studies have tried to identify specific nucleotide sequences in the quasispecies of hepatitis C virus (HCV) that determine resistance or sensitivity to interferon (IFN) therapy, unfortunately without conclusive results. Although viral proteins represent the most evident phenotype of the virus, genomic RNA sequences determine secondary and tertiary structures which are also part of the viral phenotype and can be involved in important biological roles. In this work, a method of RNA structure analysis has been developed based on the hybridization of labelled HCV transcripts to microarrays of complementary DNA oligonucleotides. Hybridizations were carried out at non-denaturing conditions, using appropriate temperature and buffer composition to allow binding to the immobilized probes of the RNA transcript without disturbing its secondary/tertiary structural motifs. Oligonucleotides printed onto the microarray covered the entire 5' non-coding region (5'NCR), the first three-quarters of the core region, the E2-NS2 junction and the first 400 nt of the NS3 region. We document the use of this methodology to analyse the structural degree of a large region of HCV genomic RNA in two genotypes associated with different responses to IFN treatment. The results reported here show different structural degree along the genome regions analysed, and differential hybridization patterns for distinct genotypes in NS2 and NS3 HCV regions.

Conserved Sequence↗

PubMed2004

Usefulness of dried blood samples for quantification and molecular characterization of HBV-DNA.

The purpose of this study was to assess the use of dried blood spot (DBS) samples for hepatitis B virus (HBV) DNA quantification, HBV genotyping, and detection of G1896A precore mutants and variants in the YMDD polymerase motif. We studied DBS and serum samples from 82 patients with chronic HBV infection (23 hepatitis B e antigen [HBeAg]-positive and 39 HBeAg-negative), 20 HBeAg-inactive carriers, and 15 HBeAg-negative patients under lamivudine therapy (selected from chronic HBV patients). DBS samples consisted of approximately 20 microL of blood applied to 5-mm paper disks. HBV DNA quantification and HBV precore mutant detection were done using real-time polymerase chain reaction, HBV genotyping using restriction fragment length polymorphism, and YMDD variant detection by Inno-lipa assay. DBS and serum results were compared. HBV DNA was detected in a range of 10(2)-10(8) copies/mL, with low intra-assay and inter-assay variation (<10%). Median DBS HBV DNA (copies/mL) was: 3.7 x 10(6) in HBeAg-positive, 6.2 x 10(5) in HBeAg-negative, and 5.5 x 10(2) in inactive carriers (P <.05). HBV DNA was positive in serum (median 5 x 10(3) copies/mL) but negative in DBS for five inactive carriers. The correlation coefficient between HBV DNA concentration in DBS versus serum samples was r(2) = 0.96 (P <.001). The sensitivity of HBV DNA detection in DBS samples was 1 log(10) lower than in serum samples. Concordance between DBS and serum for HBV genotyping, and for precore mutant and YMDD variant detection was optimal. DBS storage for 7 days at room temperature and 21 days at -20 degrees C revealed no decrease in HBV DNA levels or integrity. In conclusion, the DBS sample is useful for HBV DNA quantification, genotyping, and detection of precore mutant and YMDD variants. All four determinations can be completed with a single drop of dried blood.

Blood↗

PubMed2004

Mutations in the basic core promoter region of hepatitis B virus. Relationship with precore variants and HBV genotypes in a Spanish population of HBV carriers.

BACKGROUND/AIMS: To determine the prevalence and significance of hepatitis B virus (HBV) basic core promoter (BCP) mutations and to establish their relationship with precore (preC) mutations, HBV genotypes and HBV-DNA levels. METHODS: BCP and preC mutations and genotypes were determined by sequencing. RESULTS: Genomic analysis was performed in 129 (71%) of 182 patients. BCP mutations were detected in 83% of 18 HBeAg-negative (e-) chronic hepatitis B (CHB) patients with fluctuating ALT levels, and in 76% of 58 e- CHB with elevated ALT. The prevalence was lower and similar, 55% in 30 HBeAg-positive CHB (e+ CHB) with elevated ALT and in 23 e- inactive carriers. Frequency of preC mutations was higher in e- CHB (80%) than in e- inactive carriers (65%). Among e- CHB, patients with elevated ALT and preC mutations at nt 1896 showed highest HBV-DNA, regardless of BCP mutations. BCP mutations were similar in genotypes A and D, while preC mutations were most common in genotype D (82 vs. 40%). Simultaneous presence of the main BCP (1762, 1764) and preC (1896, 1899) mutations was associated with the degree of histological injury. CONCLUSIONS: Combined BCP and preC mutational and genotype analysis provides clinically relevant information in the study of HBV infection.

Adult↗

PubMed2004

Hepatitis C virus Core Antigen as a predictor of non-response in genotype 1 chronic hepatitis C patients treated with peginterferon alpha-2b plus ribavirin.

BACKGROUND/AIMS: Chronic hepatitis C patients infected by genotype 1 are the least responsive to combination therapy and therefore monitoring response is important in identifying non-responders quickly, permitting therapy discontinuation and avoiding side effects and costs. We examined the usefulness of measuring total HCV Core Ag in early treatment with peginterferon alpha-2b and ribavirin in genotype 1 patients in the prediction of response and compared the results with those from HCV RNA quantification. METHODS: Two hundred and sixty-eight serum samples from 46 genotype 1 patients receiving combination therapy were examined for HCV Core Ag and quantitative HCV RNA. RESULTS: At baseline, mean HCV RNA and HCV Core Ag concentrations were significantly lower in sustained virologic responders than in non-responders. The negative predictive value of HCV Core Ag testing in predicting non-response at week 12 is 100%, and for a 2 log drop in HCV RNA, using two quantitative tests, it is 88%. CONCLUSIONS: HCV Core Ag determination allows the identification of non-responders with only one test at week 12 and permits stopping therapy in these patients. HCV Core Antigen testing is cheaper and easier to perform than HCV RNA quantification.

Antiviral Agents↗