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Antiviral Treatment (antiviral + treatment)
Selected AbstractsImpact of pegylated interferon and ribavirin on morbidity and mortality in patients with chronic hepatitis C and normal aminotransferases in France,HEPATOLOGY, Issue 5 2009Sylvie Deuffic-Burban Clinicians continue to raise questions concerning the necessity of treating chronic hepatitis C virus (HCV)-infected patients with normal alanine aminotransferase (N-ALT), in light of their slower progression to cirrhosis than patients with elevated alanine aminotraferase (E-ALT). This study was undertaken to predict the impact of pegylated interferon (IFN) and ribavirin on HCV-related morbidity and mortality in patients with N-ALT. A previous Markov model was adapted to separately simulate patients with N-ALT (30%) and those with E-ALT (70%). The model estimates fibrosis progression rates according to age, sex, and whether ALT levels are normal or elevated, assuming that patients with E-ALT have a 2.6 times higher progression than those with N-ALT. It takes into account improvement in HCV screening and treatment and competitive mortality. We assumed that N-ALT patients were treated 80% less frequently between 2002 and 2004 and 70% less frequently from 2005 on, as obtained in real life from three multicentric cohorts (Hepatys, Adequation, Persee). Antiviral treatment of HCV-infected populations might reduce 2008-2025 HCV-related morbidity and mortality by 34,200 cases of cirrhosis (36%, 33,000-35,000), 22,400 complications (28%, 21,000-23,000) and 17,500 deaths (25%, 17,000-18,000), including 3000 cases of cirrhosis (22%, 2000-5000), 1200 complications (15%, 1000-1700), and 1000 deaths (14%, 900-1300) in the N-ALT population, despite a probability of receiving treatment that is three to five times less in this population. If N-ALT patients are treated at the same proportions as those with E-ALT, morbidity and mortality could be further reduced by 1400 cases of cirrhosis (13%, 1200-2200), 600 complications (9%, 600-1000), and 500 deaths (9%, 500-800). Conclusion: Treatment of N-ALT patients would decrease HCV morbidity and mortality. These patients should be considered candidates for treatment just as others are. (HEPATOLOGY 2009.) [source] Future perspectives for hepatocellular carcinomaHPB, Issue 4 2003WY Lau Background Five facets of hepatocellular carcinoma (HCC) are identified that impact on future directions in the management of the disease: epidemiology, prevention, screening, diagnosis and therapy. Recent papers on HCC have been reviewed, and predictions have been made on developments in HCC over the next decade. Discussion It is predicted that hepatitis B-related HCC will decrease with vaccination, while hepatitis C-related HCC will become an increasing problem. Antiviral treatment and chemopreventive agents will prevent HCC development. Whole-population screening will not be an option, but screening is justified for individuals who can pay for it. There will be more emphasis on the use of tumour markers. Transabdominal ultrasound and triphasic spiral computed tomography will remain important radiological imaging techniques. The results of liver resection will not improve unless neoadjuvant/adjuvant therapy is proven to be effective. More patients with initially unresectable HCC will be down-staged to become resectable with improvements in local, regional and systemic therapies. Liver transplantation will be increasingly used. Local ablative therapy will improve the quality of survival but will have no impact on overall survival compared with surgical resection. The author hopes to review the accuracy of these predictions in 2013. [source] Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009F. SCHMIDT Summary Background, Antiviral treatment with interferon-alpha (IFN-,) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors. Aim, To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-,) on mental health in patients with psychiatric risk factors. Method, We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery,Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-, and ribavirin. Results, Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score ,5 (OR 14.21, 95% CI: 2.51,81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024,0.558), methadone substitution (OR = 0.20, 95% CI: 0.045,0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138,0.845) were significantly less likely to show a long-term worsening of depressive symptoms. Conclusions, Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-,. [source] In vivo immunization following virus suppression: a novel approach for inducing immune control in chronic hepatitis B,JOURNAL OF VIRAL HEPATITIS, Issue 1 2003D. Sprengers summary. Antiviral treatment of patients with active chronic hepatitis B may lead to significant reduction in morbidity and mortality. However, after stopping nucleoside therapy, relapse rates are high in those without acquired specific immunity. We have treated two chronic hepatitis B patients with in vivo immunization. In vivo immunization aims to optimize conditions for an effective immune response: following rapid and profound virus suppression by interferon-lamivudine combination therapy, lamivudine is withdrawn intermittently for 4 weeks during continued interferon therapy. In both patients with profound virus suppression a rapid rebound in viral replication was observed after lamivudine withdrawal; despite continued interferon. These periods of renewed viral replication were followed by rises in hepatitis activity. After re-introduction of lamivudine HBV DNA became undetectable by PCR followed by normalization of serum ALT. These observations are a stimulus to further explore the concept of in vivo immunization as a novel therapeutic approach for chronic hepatitis B. [source] Antiviral treatment of hepatitis B following solid organ transplantation in childrenPEDIATRIC TRANSPLANTATION, Issue 3 2006Stefan Wirth MD First page of article [source] Recurrent hepatitis C virus disease after liver transplantation and concurrent biliary tract complications: poor outcomeCLINICAL TRANSPLANTATION, Issue 4 2006Lior H. Katz Abstract:, Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post-liver transplantation setting, with rapid progression of liver fibrosis. Biliary complications remain a significant cause of morbidity following liver transplantation. Post-cholecystectomy biliary strictures are associated with advanced hepatic fibrosis. The aim of this retrospective study was to determine whether the presence of biliary complications affects survival in liver transplant recipients with recurrent HCV disease. The files of liver transplant recipients (53.7% male; mean age 52.7 ± 10.3 yr) were reviewed for incidence, type and treatment of biliary complications, and findings were compared between those who developed recurrent HCV disease (n = 47, 83.9%) and those who did not (n = 9). Twenty-one biliary complications developed in 12 patients with recurrent HCV (25.5%). Treatment with endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography with balloon dilatation and stent placement or surgical revision was successful in nine (75%). Three biliary complications developed in three patients with no recurrence (p = NS). There was no statistically significant association between recurrent HCV disease and biliary complications. However, among those with recurrent disease, the recurrence was severe in nine of 12 recipients with biliary complications (75%) but in only nine of 35 without biliary complications (26%) (p = 0.001). Death was documented in eight patients with severe recurrence (44.4%), including three (37.5%) with biliary complications and two (7%) with non-severe recurrence, neither of whom had biliary complications (p = 0.003). Antiviral treatment was successful in nine of 25 patients (36%) who received it. On multivariate analysis, biliary complications were a significant predictor of severe recurrence (OR 27.0, 95% confidence interval 2.07,351.4) (p = 0.012). Fibrosis stage in the second biopsy was significantly correlated with serum alanine aminotransferase (p = 0.01) and with duration of biliary obstruction (p = 0.07). In conclusion, biliary complications of liver transplantation strongly affect outcome in patients with recurrent HCV disease despite attempts to relieve the biliary obstruction and to treat the recurrent HCV disease. [source] Infantile spasms and cytomegalovirus infection: antiviral and antiepileptic treatmentDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 9 2007Dorota Dunin-Wasowicz MD PhD From 1 January 1995 to 31 December 2004, 22 patients (13 males, nine females; age range 2-12mo) with infantile spasms and cytomegalovirus (CMV) infection were treated with intravenous ganciclovir (GCV) and antiepileptic drugs. GCV was given for 3 to 12 weeks with a 1-month interval (one, two, or three courses). Epileptic spasms occurred before (group A: eight patients), simultaneously (group B: eight patients), and after (group C: six patients) a diagnosis of human CMV (HCMV) infection and antiviral treatment. In 11 patients, DNA HCMV was found in cerebrospinal fluid by nested-polymerase chain reaction method (neuroinfection). All infants excreted CMV in urine. DNA HCMV and specific immunoglobulin M and immunoglobulin G antibodies were present in blood. Ten patients, including four with neuroinfection, have been seizure-free for at least the past 18 months. In two patients with neuroinfection, vigabatrin monotherapy was withdrawn after a 2 year 6 month seizure-free period. Eighteen patients required antiepileptic drugs polytherapy, four of whom required additional adrenocorticotropic hormone (ACTH). Six patients on polytherapy were seizure-free on follow-up, two of whom were treated with ACTH, but no patient with hypsarrhythmia who required ACTH treatment was seizure-free on follow-up. In five patients, psychomotor development was normal, 16 had tetraplegia (Gross Motor Function Classification System [GMFCS] Level V), and one had diplegia (GMFCS Level III). Early antiviral and antiepileptic therapy could result in the long-term cessation of seizures. [source] Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatmentDRUG AND ALCOHOL REVIEW, Issue 3 2007BIANCA WATSON Abstract Amongst people on opioid maintenance treatment (OMT), chronic hepatitis C (HCV) is common but infrequently treated. Numerous barriers, including misuse of alcohol may limit efforts at anti-viral treatment. The aim of this study was to define barriers, including alcohol misuse, to the effective treatment of HCV amongst OMT recipients. Ninety-four OMT patients completed the 3-item Alcohol Use Disorders Identification Test (AUDIT-C). A semi-structured interview was used in 53 subjects to assess alcohol use in detail, psychological health, discrimination and access to HCV treatment. Feasibility of brief intervention for alcohol misuse was assessed. Of the screening participants, 73% reported they were HCV positive. Of the detailed interview participants, 26% reported no drinking in the past month, but 53% scored 8 or more on AUDIT and 42% exceeded NHMRC drinking guidelines. Twenty subjects received brief intervention and among 17 re-interviewed at one month, alcohol consumption fell by 3.1 g/day (p = 0.003). Severe or extremely severe depression, stress and anxiety were found in 57%, 51% and 40% of interviewees respectively. Episodic heavy drinking, mental health problems, perceived discrimination, limited knowledge concerning HCV were all common and uptake of HCV treatment was poor. Brief intervention for alcohol use problems was acceptable to OMT patients, and warrants further study. [source] Sustained virologic response prevents the development of esophageal varices in compensated, Child-Pugh class A hepatitis C virus,induced cirrhosis.HEPATOLOGY, Issue 6 2010A 12-year prospective follow-up study The incidence of de novo development of esophageal varices (EV) in patients with compensated liver cirrhosis has been determined by few studies in the short term and never in the long term. The aims of the present study were to determine the incidence and the risk factors associated with the development of EV and to assess whether antiviral treatment and achievement of sustained virologic response (SVR) may prevent de novo EV development in patients with HCV-induced cirrhosis. We studied 218 patients with compensated EV-free, HCV-induced cirrhosis consecutively enrolled between 1989 and 1992 at three referral centers in Milan, Italy. Endoscopic surveillance was performed at 3-year intervals according to international guidelines. SVR was defined as undetectable serum HCV-RNA 24 weeks after treatment discontinuation. During a median follow-up of 11.4 years, 149/218 (68%) patients received antiviral treatment and 34 (22.8%) achieved SVR. None of the SVR patients developed EV compared with 22 (31.8%) of the 69 untreated subjects (P < 0.0001) and 45 (39.1%) of the 115 non-SVR patients (P < 0.0001). On multivariate analysis, HCV genotype 1b (hazard ratio [HR] 2.40; 95% confidence interval [CI] 1.17-4.90) and baseline model for end-stage liver disease (MELD) score (HR 1.20; 95% CI 1.07-1.35 for 1 point increase) were independent predictors of EV. Conclusion: In the long term, the achievement of SVR prevents the development of EV in patients with compensated HCV-induced cirrhosis. Therefore, in these patients, endoscopic surveillance can be safely delayed or avoided. Genotype 1b infection and MELD score identify the subset of patients at higher risk of EV development who need tailored endoscopic surveillance. Hepatology 2010 [source] CD81 expression in peripheral blood lymphocytes before and after treatment with interferon and ribavirin in HIV/HCV coinfected patientsHIV MEDICINE, Issue 3 2010D Micheloud Background CD81 is expressed on lymphocytes and confers HCV viral infectivity support. The aim of our study was to quantify CD81 expression in peripheral blood B- and T-cells of HCV/HIV-coinfected patients and healthy subjects to examine its association with several HCV virological characteristics and the therapeutic responsiveness to HCV antiviral treatment. Methods We carried out a cross-sectional study on 122 naďve patients. For a duration of 48 weeks, 24 out of 122 patients underwent HCV antiviral therapy with interferon (IFN)-, and ribavirin. T- and B-cell subsets were analysed by flow cytometry. Results We found that HIV/HCV coinfected patients with HCV-RNA ,850 000 IU/mL had lower values of %CD19+CD81-CD62L+ and %CD19+CD62L+; and higher values of CD19+CD81+CD62L, and CD19+CD81+ percentages and absolute counts than patients with HCV-RNA <850 000 IU/mL. Similarly, HIV/HCV coinfected patients with the genotype 1 had lower values of %CD19+CD81,CD62L+ and higher values of CD3+CD81+CD62L, and CD3+CD81+ percentages and absolute counts than patients without genotype 1. Moreover, we found that HIV/HCV coinfected patients had higher values of %CD19+HLA-DR+CD25+, %CD19+CD40+CD25+ and %CD19+CD25+ than healthy control patients. When we studied the B- and T-cell subset kinetics of 24 HIV/HCV coinfected patients on HCV antiviral therapy, we found a significant decrease in CD3+CD81+and CD3+CD81+CD62L, subsets and a significant increase in CD3+CD62L+ and CD3+CD81+CD62L+ percentages and absolute counts, but the variation in these markers disappeared several months after stopping the treatment. Conclusions We observed a different pattern of CD81 T-cell and B-cell levels in naďve HIV/HCV coinfected patients according to HCV virological status and their subsequent variations during HCV antiviral treatment. CD81 expression might influence HCV pathogenesis and response to HCV antiviral treatment. [source] Influenza-associated hospitalization in urban Thai childrenINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5-6 2007Piyarat Suntarattiwong Background, Studies in North America and Europe have shown that young children are at increased risk of serious complications and hospitalization from influenza infection. In Thailand, however, influenza is commonly considered a mild infection that rarely requires hospitalization. An improved understanding of the burden of serious complications from influenza infection in young children is needed to inform clinical treatment and vaccination guidelines. Methods, We conducted a prospective study of children 0,5 years of age with lower respiratory tract infection or influenza-like illness admitted to a pediatric tertiary-care hospital in Bangkok, Thailand during July 2004 to July 2005. All respiratory specimens were tested for influenza using a rapid antigen test and tissue cell culture. Results, Thirty-nine of 456 (8.6%) hospitalized children had culture-positive influenza. Eighty percent of hospitalized influenza patients had no underlying chronic illnesses. Nineteen (49%) influenza patients required hospital stays of 5 days or more and two patients required mechanical ventilation. Influenza activity demonstrated bimodal seasonal variation with peak activity from August to October and January to April. Cough was present in 38 (97%) cases and fever >38.5°C was significantly associated with influenza. Conclusion, Influenza is an important cause of hospitalization in children <5 years of age in Thailand. Children <5 years should be considered as a target group when establishing clinical guidelines for antiviral treatment and influenza vaccination. [source] Molecular, immunological and clinical properties of mutated hepatitis B virusesJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 1 2002C. Kreutz Abstract Hepatitis B virus (HBV) is at the origin of severe liver diseases like chronic active hepatitis, liver cirrhosis and hepatocellular carcinoma. There are some groups of patients with high risk of generation of HBV mutants: infected infants, immunosupressed individuals (including hemodialysis patients), patients treated with interferon and lamivudine for chronic HBV infection. These groups are the target for molecular investigations reviewed in this paper. The emergence of lamivudine- or other antiviral-resistant variants, rises concern regarding long term use of these drugs. Infection or immunization with one HBV subtype confers immunity to all subtypes. However, reinfection or reactivation of latent HBV infection with HBV mutants have been reported in patients undergoing transplant and those infected with HIV. Mutations of the viral genome which are not replicative incompetent can be selected in further course of infection or under prolonged antiviral treatment and might maintain the liver disease. Four open reading frames (ORF) which are called S-gene, C-gene, X-gene and P-gene were identified within the HBV genome. Mutations may affect each of the ORFs. Mutated S-genes were described to be responsible for HBV-infections in successfully vaccinated persons, mutated C-genes were found to provoke severe chronic liver diseases, mutated X-genes could cause serious medical problemes in blood donors by escaping the conventional test systems and mutated P-genes were considered to be the reason for chemotherapeutic drug resistance. This paper reviews molecular, immunological and clinical aspects of the HBV mutants. [source] Prevention of hepatocellular carcinoma complicating chronic hepatitis CJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2009Yoshiyuki Ueno Abstract Chronic hepatitis C virus (HCV) infection accounts for most cases of hepatocellular carcinoma (HCC) in Japan and is the second major cause in many other countries. Development of HCC takes a considerable time after onset of HCV infection, between 20,40 years in most cases, and usually develops after cirrhosis is established. Although only a minority of HCV infections reach this stage, the high prevalence of chronic HCV infection in many countries (1,3%) is such that HCC related to HCV infection poses a significant public health issue 20,50 years after the onset of HCV epidemics. Due to advances in testing, and accessibility of clean, disposable medical apparatus including syringes and needles, and particularly screening of donor blood for anti-HCV and by nucleic acid testing, new cases of HCV infection have decreased in most countries, except for continued transmission by injection drug users (IDU). A key difference between HBV and HCV infection is that HCV can be eradicated by effective antiviral treatment. Sustained eradication of HCV reverses hepatic fibrosis, thereby preventing progression to cirrhosis and risk of HCC. Further, it has been well demonstrated that interferon-based antiviral therapy suppresses development of HCC in high-risk patients, particularly when sustained viral response (SVR) is obtained. In summary, the two key approaches to prevent development of HCV-related HCC are primary prevention of HCV infection (adequate programs to screen donor blood, universal precautions to stop medical transmission of blood-borne viruses, curbing transmission by IDU) and potent antiviral therapy of chronic HCV infection. [source] Development of real-time detection direct test for hepatitis B virus and comparison with two commercial tests using the WHO international standardJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 11 2003MOTOKAZU MUKAIDE Abstract Aims:, A highly reproducible and sensitive hepatitis B virus real-time detection direct (HBV RTD-direct) test using DNA extraction by magnetic beads coated with polyclonal anti-HBsAg, followed by the real-time detection polymerase chain reaction (PCR) method, was developed for the detection of HBV DNA. Methods:, The HBV DNA could be extracted from the HBsAg positive viral particles without resulting in viral DNA fragmentation. The HBV RTD-direct test was validated using a serial dilution panel of the WHO standard HBV DNA 97/746 I. Results:, The test had a dynamic range of 0.7,8.0 log10 international units (IU) per mL and the results were shown to be comparable to those obtained with two commercially available tests: the HBV DNA transcription-mediated amplification-hybridization protection assay and the Amplicor HBV Monitor test. In addition, the HBV RTD-direct test, based on magnetic extraction, successfully eliminated PCR inhibitors in clinical specimens. Conclusion:, We conclude that the HBV RTD-direct test is an excellent alternative for monitoring patients undergoing antiviral treatment or for screening various clinical specimens. [source] Circulating soluble cytochrome c in liver disease as a marker of apoptosisJOURNAL OF INTERNAL MEDICINE, Issue 2 2003Z. Ben-Ari Abstract. Ben-Ari Z, Schmilovotz-Weiss H, Belinki A, Pappo O, Sulkes J, Neuman MG, Kaganovsky E, Kfir B, Tur-Kaspa R, Klein T (Beilinson and Golda Campuses, Rabin Medical Center, Petah Tiqva and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel, and In Vitro Toxicology Laboratory, Sunnybrook Women's College, Toronto, Canada) Circulating soluble cytochrome c in liver disease as a marker of apoptosis. J Intern Med 2003; 254: 168,175. Objectives. To measure levels of soluble cytochrome c, a clinical marker of apoptosis in patients with liver disease; determine whether soluble cytochrome c is derived from the liver; and correlate soluble cytochrome c level with histology and disease activity. Design. Laboratory research study with comparison group. Setting. Liver Institute, at the Rabin Medical Center, Israel, and In Vitro Toxicology Laboratory, Canada. Subjects. A total of 108 patients with liver disease and 30 healthy controls. Interventions. Paired hepatic and portal vein samples were taken via the transjugular vein in patients after liver biopsy and transjugular intrahepatic portacaval shunt, and bile from patients with external biliary drainage. Soluble cytochrome c was measured with an enzyme-linked immunosorbent assay in peripheral blood. Apoptotic cells in liver tissue were identified by morphological criteria and quantitated with the dUTP nick-end-labelling (TUNEL) assay. Main outcome measures. Soluble cytochrome c level by type of liver disease by clinical and histological findings. Results. Soluble cytochrome c concentration (mean 187.1 ± 219.5 ng mL,1) was significantly higher in patients with liver disease than in controls (39.8 ± 35.1 ng mL,1; P = 0.0001), with highest levels in the primary sclerosing cholangitis group (mean 1041.0 ± 2844.8 ng mL,1; P = 0.001). Cytochrome c levels were correlated with serum bilirubin, alkaline phosphatase, creatinine levels, necroinflammatory score and apoptotic index, but not with serum alanine aminotransferase and synthetic liver function tests. In the 16 paired samples, soluble cytochrome c level was higher in the hepatic (mean 267.9 ± 297.0 ng mL,1) than the portal vein (mean 169.2 ± 143.3 ng mL,1), and it was highly detectable in bile (mean 2288.0 ±4596.0 ng mL,1) (P = 0.001). Untreated patients with chronic viral hepatitis (B and C) had significantly higher levels (mean 282.8 ±304.3 ng mL,1) than treated patients (77.9 ± 35.8 ng mL,1; P = 0.001). Conclusions. Soluble cytochrome c levels are increased in different types of liver disease. Soluble cytochrome c is probably derived from the liver and secreted into the bile. Levels correlate with the apoptotic index and are affected by antiviral treatment. Soluble cytochrome c may serve as a serum marker of apoptosis. [source] Early and reliable detection of herpes simplex virus type 1 and varicella zoster virus DNAs in oral fluid of patients with idiopathic peripheral facial nerve palsy: Decision support regarding antiviral treatment?JOURNAL OF MEDICAL VIROLOGY, Issue 9 2010Andreas Lackner Abstract Idiopathic peripheral facial nerve palsy has been associated with the reactivation of herpes simplex virus type 1 (HSV-1) or varicella zoster virus (VZV). In recent studies, detection rates were found to vary strongly which may be caused by the use of different oral fluid collection devices in combination with molecular assays lacking standardization. In this single-center pilot study, liquid phase-based and absorption-based oral fluid collection was compared. Samples were collected with both systems from 10 patients with acute idiopathic peripheral facial nerve palsy, 10 with herpes labialis or with Ramsay Hunt syndrome, and 10 healthy controls. Commercially available IVD/CE-labeled molecular assays based on fully automated DNA extraction and real-time PCR were employed. With the liquid phase-based oral fluid collection system, three patients with idiopathic peripheral facial nerve palsy tested positive for HSV-1 DNA and another two tested positive for VZV DNA. All patients with herpes labialis tested positive for HSV-1 DNA and all patients with Ramsay Hunt syndrome tested positive for VZV DNA. With the absorption-based oral fluid collection system, detections rates and viral loads were found to be significantly lower when compared to those obtained with the liquid phase-based collection system. Collection of oral fluid with a liquid phase-based system and the use of automated and standardized molecular methods allow early and reliable detection of HSV-1 and VZV DNAs in patients with acute idiopathic peripheral facial nerve palsy and may provide a valuable decision support regarding start of antiviral treatment at the first clinical visit. J. Med. Virol. 82:1582,1585, 2010. © 2010 Wiley-Liss, Inc. [source] Role of long-term lamivudine treatment of hepatitis B virus recurrence after liver transplantationJOURNAL OF MEDICAL VIROLOGY, Issue 11 2008Hyun Young Woo Abstract In this study, the long-term (>3 years) efficacy of combination therapy for hepatitis B virus (HBV) recurrence and the associated factors were investigated. One hundred and sixty-five consecutive HBsAg-positive patients (92 with liver cirrhosis, 73 with hepatocellular carcinoma; HCC) who underwent liver transplantation were assessed with a median follow-up time of 40 months. One hundred and twenty-one patients (121/165, 73.3%) were treated with lamivudine before transplantation for a mean of 8.4 months (range 0.1,72 months). The post-transplantation treatment protocol consisted of a high dose intravenous hepatitis B immunoglobulin (HBIg) followed by a low dose intramuscular HBIg and lamivudine combination therapy. Seven (4.2%, 7/165) recipients experienced HBV recurrence at a median time of 19 months (range 5,36 months) following transplantation. Six of seven cases of HBV recurrence were treated with lamivudine before transplantation for a median period of 15 months (range 0.6,30 months). Eighteen (24.6%, 18/73) patients had HCC recurrences after transplantation. Of the four patients with both HCC and HBV recurrence, three experienced HBV recurrence after recurrence of HCC. The clinical factor associated with HBV recurrence in the total cohort (n,=,165) was the duration of antiviral treatment (over 6 months) before transplantation (P,=,0.004). In the HCC group, HCC recurrence after transplantation (P,=,0.002), tumor burden before transplantation (P,=,0.005), and postoperative adjuvant chemotherapy (P,=,0.002), were additional factors for HBV recurrence. Combination therapy of HBIg and antiviral drugs was effective over 3 years regardless of the pretransplantation viral load. However, the possible recurrence of HBV needs to be monitored cautiously in patients treated with long-term (over 6 months) lamivudine. J. Med. Virol. 80:1891,1899, 2008. © 2008 Wiley-Liss, Inc. [source] Virus load dynamics of individual CMV-genotypes in lung transplant recipients with mixed-genotype infectionsJOURNAL OF MEDICAL VIROLOGY, Issue 8 2008Irene Görzer Abstract Human cytomegalovirus (CMV) is a major cause of disease and transplant dysfunction in lung transplant recipients. Simultaneous emergence of more than one CMV-genotype can occur, and appears to be disadvantageous for the patient. In this study, the dynamics of individual CMV-genotypes in blood and lung was assessed within mixed CMV-genotype populations emerging after lung transplantation. In 69 plasma and 76 bronchoalveolar lavage samples of 16 lung transplant recipients with mixed CMV-genotype infections within the first year posttransplantation each of the major glycoprotein B (gB) and glycoprotein H (gH) genotypes was selectively quantified by genotype-specific quantitative TaqMan assays. The data obtained revealed that individually different genotype dynamics occurred for the individual patients and that the relative levels of the genotypes to each other may change over time. The quantitative development was independent of the specific gB,gH-genotype. In 10 of the 16 lung recipients the patient's individual genotype composition was the same in blood and lung. Genotype development during the follow-up was influenced by antiviral treatment. These data show for the first time that the CMV load used as diagnostic tool after transplantation is not always a constant entity but reflects the sum of the individual CMV-genotype dynamics developing over time. J. Med. Virol. 80:1405,1414, 2008. © 2008 Wiley-Liss, Inc. [source] Another cause of bloody diarrhoea in infancy: Cytomegalovirus colitis in an immunocompetent childJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 9-10 2004R Hinds Abstract: Although a ubiquitous pathogen, cytomegalovirus (CMV) is very rarely thought to be the cause of significant gastrointestinal infection in the immunocompetent child. We report the case of a 2-month-old infant who presented with bloody diarrhoea and severe dehydration, which was subsequently diagnosed as CMV enterocolitis and resolved spontaneously without antiviral treatment. [source] Oseltamivir Treatment Prevents the Increased Influenza Virus Disease Severity and Lethality Occurring in Chronic Ethanol Consuming MiceALCOHOLISM, Issue 8 2010Ryan A. Langlois Background:, Chronic consumption of ethanol (EtOH) is well recognized to lead to defective innate and adaptive immune responses and increase the severity of pulmonary infections. Our own studies have demonstrated that chronic EtOH consumption decreases CD8 T-cell immunity to influenza virus infections (IAV) leading to severe infections and mortality. Interestingly, antiviral treatment of IAVs has been shown to be compromised in mice and humans that are immuno-deficient. It is known that EtOH can alter the pharmacokinetics of antivirals. Therefore, the effectiveness of influenza antiviral therapy during chronic ethanol consumption remains in question. Methods:, BALB/c mice were placed on 18% (w/v) EtOH in their drinking water for 8 weeks. Chronic EtOH consuming and water controls were then treated with 10 mg/kg oseltamivir orally and infected intranasally with influenza virus 4 hours post-oseltamivir treatment. The mice were then treated with oseltamivir twice daily until day 7 postinfection. Influenza disease severity was measured by morbidity and mortality, pulmonary viral titers, and histology. Results:, Chronic EtOH consuming mice infected with IAV and treated with oseltamivir have decreased morbidity and mortality, pulmonary viral titers, and pulmonary pathology compared to untreated EtOH mice. Conclusions:, Despite the severe immune defect seen in chronic EtOH mice as well as the potential for EtOH to inhibit the conversion of oseltamivir into an active form, treatment with oseltamivir reduces viral shedding as well as disease severity. These data suggest that the combination of a limited adaptive immune response plus the anti-IAV drug oseltamivir is sufficient to curb high mortality and mediate resolution of IAVs in mice chronically consuming ethanol. [source] Meta-analysis: ribavirin plus interferon vs. interferon monotherapy for chronic hepatitic C , an updated Cochrane reviewALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2010J. Brok Aliment Pharmacol Ther 2010; 32: 840,850 Summary Background, Multiple randomized trials have been published on antiviral treatment for chronic hepatitis C. Aim, To meta-analyse the effect of adding ribavirin to interferon for chronic hepatitis C. Methods, The results of randomized trials were combined in cumulative meta-analyses. Trial sequential analyses were used to adjust for spurious results because of random errors and multiplicity. The outcome measures were undetectable hepatitis C virus RNA in serum (sustained virological response) and liver-related morbidity plus all-cause mortality. Results, We included 82 randomized trials with 12 615 patients. Trial sequential analysis established clear beneficial effect of interferon plus ribavirin vs. interferon on the sustained virological response in 1998 after nine trials (RR: 0.74; 95% CI: 0.64,0.85, P < 0.0001, 1734 patients). Subsequently, additional 73 trials were published just narrowing the confidence interval and decreasing the P -value. By contrast, trial sequential analysis found that additional evidence is needed to convincingly detect a beneficial effect of interferon plus ribavirin vs. interferon monotherapy on clinical outcomes. Conclusions, The rationale behind several recent trials on adding ribavirin to interferon for chronic hepatitis C is debatable as the effect on virological response is established. More evidence is needed to assess if adding ribavirin to interferon improves clinical outcomes. [source] Factors influencing long-term changes in mental health after interferon-alpha treatment of chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2009F. SCHMIDT Summary Background, Antiviral treatment with interferon-alpha (IFN-,) is associated with several acute psychiatric side effects. Little is known about long-term effects on mental health after treatment independent from viral response and the influence of pre-existing psychiatric risk-factors. Aim, To evaluate long-term effects of antiviral treatment with interferon-alpha (IFN-,) on mental health in patients with psychiatric risk factors. Method, We prospectively investigated long-term mental health changes in 81 hepatitis C virus-infected patients. Psychiatric outcome was measured with the Montgomery,Asberg Depression Scale (MADRS), Brief Psychiatric Rating Scale, the Global Social Functioning Scale and the Global Clinical Impression Scale 6 months after the end of antiviral treatment with IFN-, and ribavirin. Results, Six months after antiviral therapy, 49% of the patients showed a worsening and 27.2% an improvement of depression scores. The most important predictor for a long-term improvement of depression scores was a pre-treatment MADRS score ,5 (OR 14.21, 95% CI: 2.51,81.30). Patients with pre-existing psychiatric disorders (OR = 0.117, 95% CI: 0.024,0.558), methadone substitution (OR = 0.20, 95% CI: 0.045,0.887) or genotype 2/3 (OR = 0.341, 95% CI: 0.138,0.845) were significantly less likely to show a long-term worsening of depressive symptoms. Conclusions, Pre-existing psychiatric risk factors increase the chance for a long-term improvement and reduce the risk for a long-term worsening of mental health after antiviral treatment of chronic hepatitis C with IFN-,. [source] Specialty care and education associated with greater disease-specific knowledge but not satisfaction with care for chronic hepatitis CALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 3 2009L. A. BESTE Summary Background, Little is known about differences among hepatitis C virus (HCV) patients managed by generalists vs. specialists with respect to patient-centred outcomes, such as disease-specific knowledge, health-related quality of life (HRQoL) and satisfaction with care. Aim, To examine selected patient-centred outcomes of HCV-related care provided in primary care, specialty care or both. Methods, A total of 629 chronic HCV patients completed a survey including an HCV knowledge assessment and validated instruments for satisfaction and HRQoL. Multivariable linear regression was used to compare outcomes between groups. Results, Adjusted total HCV knowledge score was lower among patients who did not attend specialty care (P < 0.01). Primary care and specialty patients did not differ in adjusted general HRQoL or satisfaction. Sixty percent of specialty patients underwent formal HCV education, which was associated with 5% higher knowledge score (P = 0.01). General HRQoL and patient satisfaction did not differ between primary care and specialty groups. Disease-specific knowledge and care satisfaction were independent of mental illness, substance abuse, socio-economic variables, history of antiviral treatment, formal HCV education and duration of time between last visit and survey completion. Conclusions, Primary care patients with chronic HCV have lower adjusted disease-specific knowledge than specialty patients, but no difference in general HRQoL or patient satisfaction. [source] Epidemiological characteristics and response to peginterferon plus ribavirin treatment of hepatitis C virus genotype 4 infectionJOURNAL OF VIRAL HEPATITIS, Issue 7 2007D. Roulot Summary., Hepatitis C virus genotype 4 (HCV-4) infection is progressing in Europe, where epidemiology and sustained virological response (SVR) seem to be different than in the Middle East. We analysed epidemiological features and SVR rates in a retrospective study of 1532 HCV-4-infected patients, including 1056 patients infected in France, 227 immigrants infected in Egypt and 249 in sub-Saharan Africa. SVR rates were assessed in 242 naive patients of the 1532, who received peginterferon plus ribavirin for 48 weeks. HCV subtype 4a or 4d was the most common among patients infected in France, where the predominant route of transmission was intravenous drug abuse. The 4a subtype was largely predominant (93%) among patients infected in Egypt, where transmission was mostly because of parenteral treatment for schistosomiasis. More than seven different subtypes and no predominant route of infection were found in patients infected in sub-Saharan Africa. Liver fibrosis was significantly less severe in patients infected in France and Africa than in patients infected in Egypt. SVR rates were higher in patients infected in Egypt, compared with those infected in France or Africa (54.9%, 40.3% and 32.4%, respectively, P < 0.05). An overall better response was observed in patients infected with the 4a subtype. In multivariate analysis, two factors were associated independently with SVR: the Egyptian origin of transmission and the absence of severe fibrosis. In conclusion, the distribution of HCV-4 subtypes varies with the geographical origin of transmission and affects the SVR following antiviral treatment. [source] Longitudinal evaluation of a fibrosis index combining MMP-1 and PIIINP compared with MMP-9, TIMP-1 and hyaluronic acid in patients with chronic hepatitis C treated by interferon-alpha and ribavirinJOURNAL OF VIRAL HEPATITIS, Issue 10 2006C. Trocme Summary., We have recently described a fibrosis index combining serum procollagen type III N-terminal peptide (PIIINP) and matrix metalloproteinase 1 (MMP-1) concentrations for evaluating the amount of liver fibrosis in chronic hepatitis C patients. The aims of the present study were to validate this score in another cohort of patients and to assess its variations along those of TIMP-1, hyaluronic acid (HA) and MMP-9 during antiviral treatment. Seventy-nine patients treated by interferon-alpha and ribavirin for 24 or 48 weeks were included. A liver biopsy was performed within the 6 months before the start of treatment. Serum markers were measured in serum collected the day of the liver biopsy, at start of treatment, and every 3 months during treatment and a 6-month follow-up period. The PIIINP/MMP-1 index was significantly correlated to the METAVIR fibrosis (r = 0.68, P < 0.001). Its overall diagnostic value defined by the area under the receiver operating characteristics curves was 0.77 for discriminating F1 vs F2F3F4, and 0.81 for discriminating F1F2 vs F3F4, and was better than that observed for HA and TIMP-1. At the end of follow-up, the PIIINP/MMP-1 index significantly decreased in responders and remained stable in nonresponder patients. This decrease occurred early and continued regularly during the treatment period. This variation was because of both a decrease of PIIINP and an increase of MMP-1 concentrations. HA and TIMP-1 serum concentrations were also significantly lower at the end of follow-up in responder patients, but early changes were minimal and not influenced by the response to treatment. Our study shows that a noninvasive index combining PIIINP and MMP-1 is a useful tool to follow-up fibrosis change during and after antiviral therapy chronic hepatitis C patients. [source] Is the management of hepatitis C patients appropriate?ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 8 2005A population-based study Summary Background :,In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. Aim :,To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. Methods :,Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. Results :,Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. Conclusion :,In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population. [source] How to use virological tools for optimal management of chronic hepatitis CLIVER INTERNATIONAL, Issue 2009Stéphane Chevaliez Abstract Chronic hepatitis C is a global health problem that may cause cirrhosis and progression to hepatocellular carcinoma. Currently available antiviral treatments are moderately effective. Several virological assays are available to help diagnose and manage patients infected with the hepatitis C virus (HCV). These include the anti-HCV antibody assays, measurement of HCV RNA viral load and HCV genotyping. HCV RNA can be assayed by two types of molecular biology-based techniques: target amplification as in polymerase chain reaction methods and signal amplification such as the branched DNA assay. Monitoring of viral kinetics during the early phases of antiviral treatment is crucial in making treatment decisions such as early stopping rules and also in optimizing the length of treatment. The HCV genotype can be determined by several methods. Whatever the method, pretreatment determination allows treatment length and ribavirin dose to be optimized and also offers prognostic information on treatment outcomes as certain genotypes respond more favourably to treatment. Thus, virological assays are indispensable in the diagnosis and management of individuals infected with the HCV. [source] Long-term antiviral therapy for recurrent hepatitis C after liver transplantation in nonresponders: Biochemical, virological, and histological impactLIVER TRANSPLANTATION, Issue 1 2009Thomas Walter More than 50% of patients with a recurrent posttransplant hepatitis C virus infection fail to respond to antiviral treatment. The aim of this study was to evaluate the interest of a long-term antiviral treatment maintained for more than 48 weeks. Seventy treated patients, with a histological follow-up > 1 year, were enrolled in this observational, retrospective study. The duration of antiviral treatment, tolerance, and occurrence of virological, biochemical, and histological responses were recorded. Thirty-two patients were nonresponders after 48 weeks of treatment. Combined antiviral therapy was maintained for >12 months in 26 and for >18 months in 21. Twelve patients had to discontinue their treatment. At 48 weeks, the rates of virological response and sustained virological response were 37% and 24.3%, respectively; at the end of the follow-up, they were 48.5% and 35.7%. Virological response was significantly associated with a higher incidence of biochemical and histological response, regardless of its time of occurrence (before or after 6 months). Even in the absence of virological response, the rate of progression of fibrosis was significantly slowed in patients treated for more than 6 months. Our results show the feasibility, safety, and efficacy of long-term antiviral therapy in nonresponder patients with a recurrent posttransplant hepatitis C virus infection. Liver Transpl 15:54,63, 2009. © 2008 AASLD. [source] Detection of HCV antigens in liver graft: Relevance to the management of recurrent post-liver transplant hepatitis CLIVER TRANSPLANTATION, Issue 11 2006Alberto Grassi The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes ,50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with ,-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment. Liver Transpl, 2006. © 2006 AASLD. [source] Analysis of a successful HCV-specific CD8+ T cell response in patients with recurrent HCV-infection after orthotopic liver transplantation,,LIVER TRANSPLANTATION, Issue 12 2004Norbert Hubert Gruener Virus-specific CD8+ T cells play a major role in antiviral immune defenses; their significance in the transplant setting, however, is unclear. In the present study, we asked whether hepatitis C virus (HCV)-specific CD8+ T cells were detectable in the presence of an immunosuppressive treatment and whether the HCV-specific CD8+ T cell response correlates with treatment outcome in patients who receive interferon (IFN)-, / ribavirin therapy after orthotopic liver transplantation (OLTx). Liver- and blood-derived T cell lines of 21 patients after OLTx were studied before, at the end of, and after antiviral treatment. Virus-specific IFN-, production in response to a panel of previously identified HCV-specific epitopes restricted by the human leukocyte antigen (HLA) class I molecules A2, A3, B7, B35, and B44 of structural and nonstructural HCV protein was determined by enzyme-linked immunospot (ELISPOT) assay. Before treatment, only low numbers of HCV-specific CD8+ T cells were detectable. In 6 patients with a sustained virological response, a significant, multispecific, and sustained CD8+ T cell response was detectable, which was mainly found in the peripheral blood. Nonresponders and transient responders showed undetectable, weak, or transient HCV-specific CD8+ T cell responses. (Sustained responders vs. transient and nonresponders: Wilcoxon rank-signed test; P < .01). In conclusion, our data indicate that despite immunosuppression, HCV-specific CD8+ T cells are detectable in patients with recurrent HCV infection after OLTx and that a significant, multispecific, and long-lasting HCV-specific CD8+ T cell response contributes to viral elimination. (Liver Transpl 2004;10:1487,1496.) [source] | |||||||||||||||||||||||||||||||||||||