Rate Of Spontaneous Viral Clearance Research Articles

Present and future management of viral hepatitis B and C in children

Having a hepatitis B virus (HBV) or hepatitis C virus (HCV) infection places a child at higher risk for subsequent chronic hepatitis B (CHB) or chronic hepatitis C (CHC) infection. The risk of mother-to-child transmission is higher for HBV (20% to 90%) than for HCV (<5%). Perinatal HBV infection generally causes CHB infection while perinatal HCV infection has a certain rate of spontaneous viral clearance (around 20% to 30%). Of the two, only HBV infection can benefit from passive/active perinatal immunoprophylaxis. The risk of CHB in children with HBV horizontal transmission decreases with age, whereas HCV transmission among teenagers commonly results into a long-life infection and CHC infection. Children with CHB or CHC should be carefully assessed for the need for antiviral treatment. When treatment cannot be deferred, pediatric CHB infection has different first-line treatment options: standard interferon (for children aged≥1 year), pegylated interferon (for children aged≥3 years), and the oral nucleotide analogues entecavir (for children aged≥2 years) and tenofovir (for children aged≥12 years). The choice of treatment depends on the child's age, virus genotypes, previous treatment failure and presence of contraindications. Expected responsiveness rate is 25% of hepatitis B e-antigen clearance, with both standard interferon and nucleotide analogues. Direct antiviral agents are first-line treatment for CHC infection in children aged 3 years or older. Hepatitis C virus sustained virus response is as high as 97%. Therefore, if direct antiviral agents can be proven to be safe and well tolerated in very young children, HCV eradication could be planned after the first screening.

CD4+ and CD8+ T Cell Activation in Children with Hepatitis C

To assess if peripheral T cell populations in children with chronic hepatitis C virus (HCV) infection would show evidence of activation/exhaustion and an attenuated functional response. Compared with adults, children with HCV infection have a higher rate of spontaneous viral clearance. In adults, chronic HCV has been linked to T cell exhaustion. Little is known of the immune status of children with HCV. Peripheral blood mononuclear cells were isolated from 16 children with HCV (6 males, 10 females; mean age 8.6 years, range 2-17), 16 age- and sex-matched control children without HCV infection, and 20 adults with chronic HCV. Multiparameter flow cytometry was performed to characterize T cell differences across the 3 groups. Controls and children with HCV had similar levels of CD4(+), CD8(+), and γδ(+) T cells. Children with HCV demonstrated a decrease in naïve T cells compared with control children and increased activation/exhaustion marker expression on both CD8(+) and CD4(+) T cells. Transcription factor analysis suggested functional activation of T cells in children with HCV; however, only the CD4(+) subset had enhanced cytokine production (interferon gamma and interleukin-2) compared with control children. The HCV response in children is characterized by several changes in T cell phenotype. Many of these changes, such as increased T cell expression of programmed cell death-1, are similar to responses in adults. Of note, cytokine production by CD4(+) helper T cells is increased in children with HCV compared with age- and sex-matched control children, which may influence long-term prognosis in children with HCV.

Virus-Specific Cellular Response in Hepatitis C Virus Infection.

Studies performed on chimpanzees and humans have revealed that strong, multispecific and sustained CD4(+) and CD8(+) T cell immune responses is a major determinant of hepatitis C virus (HCV) clearance. However, spontaneous elimination of the virus occurs in minority of infected individuals and cellular response directed against HCV antigens is not persistent in individuals with chronic infection. This review presents characteristics of the HCV-specific T cell response in patients with different clinical course of infection, including acute and chronic infection, persons who spontaneously eliminated HCV and non-infected subjects exposed to HCV. Detection of HCV-specific response, especially in non-infected subjects exposed to HCV, may be indicative of HCV prevalence in population and rate of spontaneous viral clearance. Understanding the mechanisms and role of HCV-specific cellular immune response would contribute to better understanding of HCV epidemiology, immunopathogenesis and may help to design an effective vaccine.

HCV F protein amplifies the predictions of IL-28B and CTLA-4 polymorphisms about the susceptibility and outcomes of HCV infection in Southeast China

Cytotoxic T lymphocyte associated antigen-4(CTLA-4) is an inhibitory receptor with great value in the progression of hepatitis C virus (HCV) infection related diseases. To determine the potential associations of IL-28B rs12979860 and CTLA-4 rs231775, rs3087243 and rs5742909 polymorphisms with the generation of HCV F protein, susceptibility and outcomes of HCV infection, a total of 375 healthy controls, 219 HCV spontaneous recovered patients and 600 chronic HCV patients from Southeast China were recruited and genotyped in this study. And the relative mRNA levels of CTLA-4 in T cells were detected. Logistic regression analysis showed that rs231775 A allele was associated with significantly higher rate of spontaneous viral clearance in anti-HCV F antibody negative patients (adjusted OR=0.512, P=0.008), but allele A was related to higher mRNA level of CTLA-4 with the generation of HCV F protein. And rs5742909 T allele added up to the risk of HCV infection chronicity significantly in patients with the presence of HCV F protein (adjusted OR=2.698, P=0.003). Also, the rs5742909 CC genotype, along with the presence of HCV F protein, indicated a significantly higher CTLA-4 level than that in anti-HCV F antibody negative patients. The AG+AA genotype of rs3087243 significantly increased the susceptibility to HCV infection in subjects over 56years old (adjusted OR=1.595, P=0.011). Genotype–genotype interaction between IL-28B rs12979860 and CTLA-4 rs3087243 was found to be significantly associated with increased susceptibility to HCV infection (adjusted OR=1.509, P=0.005). Haplotype analysis in CTLA-4 also showed significant association with the generation of HCV F protein. All these results indicated the importance of IL-28B and CTLA-4 polymorphisms and their associations with HCV F protein in the risk and chronicity of HCV infection in Chinese Han population in Southeast China.

Natural history of vertically acquired HCV infection and associated autoimmune phenomena

The natural history of vertically acquired HCV infection is ill defined. The aim of this study was to outline the natural course of vertical HCV infection in a cohort of untreated children, including rate of spontaneous viral clearance, frequency and features of HCV-related autoimmune disorders. Children with vertical HCV infection were prospectively followed from the first month of life with regular clinical and laboratory assessments. Statistical analysis was performed using Prism 5.0. Forty-five children (median age 12years, interquartile range 6.9-15.5) were studied. Genotype 1 was predominant (53.3%). Spontaneous viral clearance was achieved by 12 patients (26.7%) and associated with genotype 3. Alanine-amino-transferase levels were increased in most children in the first 2years of life with higher values in those who later cleared the infection. All children were asymptomatic for liver disease. Transient elastography (32 patients) showed mild or moderate fibrosis in nine and two cases, respectively. Non-organ-specific autoantibodies were detected in 24 children (53.3%) independently of viremia; of these, one developed type-1 diabetes. Cryoglobulinemia was associated with genotype 1 infection and found in 15 subjects (33.3%): two had low C4 levels and persistent proteinuria. Vertically acquired HCV infection may result in spontaneous clearance in up to 27% of children. Resolution of infection is higher with genotype 3, usually occurs in preschool age and persists over time. Chronic infection is generally asymptomatic, although hepatomegaly and mild fibrosis may develop. Autoantibodies and cryoglobulins are frequent, whereas the associated clinical manifestations are rare.

Interferon lambda 3 rs12979860 polymorphism in patients with haemophilia and HCV infection: a predictor of spontaneous viral clearance and sustained virological response

Chronic hepatitis C is the main cause of morbidity and mortality in adult haemophilic patients who received non-virally inactivated plasma-derived clotting factor concentrates. Overall, spontaneous viral clearance rate is 10-25% and the only approach that can halt disease progression is hepatitis C virus (HCV) eradication by means of antiviral therapy. In non-haemophilic patients a single nucleotide polymorphism located upstream the gene of interferon lambda 3 (IFNλ3) has been associated with both spontaneous viral clearance and sustained virological response after antiviral treatment. The aim of this study was to assess whether the rs12979860 polymorphism was a predictor of spontaneous viral clearance and of sustained virological response after antiviral therapy in a large cohort of haemophilic patients with HCV infection. The rs12979860 polymorphism, defined as CC genotype or T allele, was tested in a cohort of 342 haemophilic patients and evaluated as predictor of spontaneous clearance or response to antiviral therapy. By multivariate regression analysis the IFNλ3 CC genotype was an independent predictor of spontaneous viral clearance (odds ratio: 3.7, 95% confidence interval: 2.0-6.8). Sustained virological response rates were doubled in patients with the CC genotype than in those with the T allele (78% vs 44%; p<0.001), especially in patients with HCV type 1 (67% vs 32%; p<0.001) and higher sustained response rates were observed in patients with the CC genotype who did not achieve rapid virological response (61% vs 30% in T allele patients; p=0.006).

Vitamin D-binding protein gene polymorphisms may contribute to the racial disparity in genotype 1 chronic hepatitis C treatment outcome

We read with great interest the study by Falleti et al. in which the authors report that the rs7041 G>T and rs4588 C>A single nucleotide polymorphisms (SNPs) of the vitamin D-binding protein gene are predictors of the treatment outcome of patients with chronic hepatitis C.1 The authors found that patients with any combination of three or more rs7041 G and rs4588 C alleles (wild type [WT+]) achieve a sustained virologic response (SVR) at a greater rate than patients with other genotypes (WT−). Additionally, they found that the relative frequency of the rs7041 T allele was increased significantly among the patients when compared with its frequency among healthy controls, raising the possibility that rs7041 T alleles are associated with increased susceptibility to infection or a lower rate of spontaneous viral clearance. Importantly, there is biologic plausibility for these findings in that each of the protein isoforms encoded by the variants of the vitamin D-binding protein gene studied by Falleti et al. differentially affect certain components of the immune response.2 In light of these findings, we sought to determine if there are racial differences in the distribution of the alleles of these SNPs among patients with chronic hepatitis C that could potentially contribute to the racial disparity in treatment outcome. We genotyped the rs7041 G>T and rs4588 C>A SNPs in 48 Caucasian and 95 African American genotype 1 chronic hepatitis C patients. Most notable were our findings concerning the rs7041 G>T SNP. The frequency of the rs7041 G>T alleles among the Caucasians was G = 0.542 and T = 0.458. This is similar to the frequency among the patients studied by Falleti et al., all of whom were Caucasian, of G = 0.553 and T = 0.447. However, the rs7041 G>T allele frequency among the African Americans we studied was G = 0.147 and T = 0.853, which is significantly different than that of the Caucasians we studied (P < 0.0001) and the patients studied by Falleti et al. (P < 0.0001). We then grouped our patients into the WT+ and WT− categories as defined by Falleti et al. (Table 1). Of the Caucasian patients we studied, 26/48 (54.2%) were WT+. This is similar to the finding by Falleti et al. that 100/206 (48.5%) of their patients were WT+. In contrast, however, only 25/95 (26.3%) of the African American patients in our study were WT+, which is significantly less than the frequency of the WT+ genotype in both our group of Caucasian patients (P = 0.0016) and the patients examined by Falleti et al. (P = 0.0003). Although our study was not sufficiently powered to confirm that vitamin D-binding protein genotype predicts antiviral treatment outcome independently of race, when considered with the findings of Falleti et al. our findings raise the possibility that racial variations in distribution of vitamin D-binding protein gene SNP alleles contribute to the racial disparity in treatment outcome in patients with chronic hepatitis C. Further studies are warranted. Acknowledgment: Supported by a grant from the Washington University School of Medicine Institute for Clinical and Translational Studies (to S.J.W.), the NIH (grants AI048216, AI066316, RR00211; to J.F.F., T.N.M., and M.A.M.) and the University of Tennessee Health Science Center Clinical and Translational Science Institute (to J.F.F., T.N.M., and M.A.M.). The Institute for Clinical and Translational Studies is supported by the NIH (grant RR024992). The University of Tennessee Cooperative Hepatitis C Center is a National Institute of Allergy and Infectious Diseases-sponsored cooperative center. Steven J. Weintraub, M.D.1,2Jaquelyn F. Fleckenstein, M.D.3,4Tony N. Marion, Ph.D.4,5Margaret A. Madey, B.S., R.N.6 1Department of Medicine Saint Louis Veterans Affairs Medical Center John Cochran Division St. Louis, MO2Department of Medicine Washington University School of Medicine St. Louis, MO3Division of Gastroenterology Department of Medicine Washington University School of Medicine St. Louis, MO4Hepatitis C Cooperative Research CenterUniversity of Tennessee Health Science Center Memphis, TN5Department of Molecular SciencesUniversity of Tennessee Health Science Center Memphis, TN6Department of Radiological Sciences St. Jude Children's Research Hospital Memphis, TN

Acute Hepatitis C in an HIV-Infected patient: A Case Report and Review of Literature

With the decrease in transmission via transfusions and injection drug use, acute symptomatic hepatitis C is infrequently seen in developed countries. We report a case of a human immunodeficiency virus (HIV)-infected adult who presented with abdominal pain. His alanine aminotransferase was greater than sixty times the upper limit of normal without any evidence on examination of fulminant hepatic failure. His workup revealed an elevated hepatitis C viral level with a negative hepatitis C antibody. He was discharged once his liver function tests improved. As an outpatient, he had a recurrent bout of symptoms with an elevation of his alanine aminotransferase and hepatitis C viral levels that promoted anti-hepatitis C virus treatment. This case illustrates the importance of considering acute hepatitis C as a cause of acute hepatitis in HIV-infected men who have sex with men. While patients with acute symptomatic hepatitis C generally have a higher rate of spontaneous viral clearance compared to those with an insidious acute infection, most still progress to chronic hepatitis C infection, and patients with HIV coinfection carry a higher risk of progression to chronic disease.

Prevalence of hepatitis C virus infection and human immunodeficiency virus in a cohort of Egyptian hemophiliac children

BACKGROUND AND OBJECTIVEThe risk of blood-borne infections, especially hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infection still remains in developing countries among children receiving blood products as hemophiliacs, but the risk is not known in Egypt. The objective of this study was to detect the prevalence of HCV and HIV infection among hemophiliac children to know the magnitude of the problem and determine potential risk factors.PATIENTS AND METHODSThis was a cross-sectional study conducted on 100 hemophiliac children that assessed the liver clinically and by laboratory tests. All children were screened for HCV and HIV antibodies by enzyme-linked immunosorbent assay. Those with positive HCV antibody titre were tested by polymerase chain reaction (HCV-PCR).RESULTSForty were positive for HCV antibodies with 19 children (47.5%) HCV-PCR positive as well. The mean age, average frequency of bleeds/year, dose of replacement therapy/year and alanine aminotransferase (ALT) levels were significantly high in HCV-antibody and PCR positive patients as compared to HCV antibody and PCR negative ones. None of our patients had clinical evidence of hepatic involvement or was co-infected with HIV.CONCLUSIONHIV infection does not appear to be a current health problem in Egyptian hemophiliac children though the prevalence of HCV infection is still high.

Female Sex and IL28B, a Synergism for Spontaneous Viral Clearance in Hepatitis C Virus (HCV) Seroconverters from a Community-Based Cohort

Background & AimsSince acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort.MethodsSubjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance.ResultsThe spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2–42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjustedOR 6.62, 95% 2.69–26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance.ConclusionsThis study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.

Chronic hepatitis C in children - review of natural history at a National Centre

The natural history of hepatitis C virus (HCV) infection in adults has been established, but less is known about outcome in children. We conducted a retrospective review of patients referred to Birmingham Children's Hospital Liver Unit, from 1991 till 2008, with the diagnosis of HCV was undertaken. Only children with documented positive HCV RNA and a minimum duration of follow-up of 6 months were included. One hundred and thirty-three children were identified. The route of transmission was transfusion acquired in 47%, vertically acquired in 49% and transplantation in 2%. Since 2000, most children were infected vertically. The overall rate of spontaneous viral clearance was 17.5% with higher clearance (27%) in the transfusion group compared to the vertically acquired group (9%). Seventy-six had a liver biopsy at diagnosis. There was no evidence of fibrosis in 46%, mild fibrosis in 50% and moderate to severe fibrosis in 4%. None had cirrhosis. There was a statistically significant relationship between fibrosis score and older age at the time of biopsy (P = 0.02) and longer duration of infection (P = 0.05). Eighty children received treatment for HCV. Sustained viral response (SVR) was influenced by viral genotypes, with significantly increased response rates in genotypes (G) 2 and 3 compared to G 1 and 4. Vertical infection is now the major route of HCV infection in children in the UK. Histological changes were mild at diagnosis, but the severity of fibrosis progressed with age. Consideration should be given to improve detection and diagnosis to refer children to specialist centres for management and antiviral therapy before developing fibrosis.

Protektiver Effekt von HLA-B27 auf den Verlauf der HIV- und Hepatitis-C-Virus-Infektion

The human leukocyte antigen (HLA) B27 has been linked to rheumatic diseases such as ankylosing spondylitis nearly 40 years ago, but its role in pathogenesis remains unclear. Apart from this association, HLA-B27 has a positive effect in two of the most threatening human viral infections: in HIV infection, HLA-B27 positive patients have low viral loads, CD4+ T cell counts decline slowly and AIDS progresses slowly. In acute hepatitis C virus (HCV) infection, HLA-B27 is associated with a very high rate of spontaneous viral clearance. The mechanisms of protection by HLA-B27 in HIV and HCV infection have been characterized in the recent years and will be discussed in this article.

Prospective Follow‐Up of Patients with Acute Hepatitis C Virus Infection in Brazil

The natural outcome of infection with hepatitis C virus (HCV) varies substantially among individuals. However, little is known about host and viral factors associated with a self-limiting or chronic evolution of HCV infection. From 1 January 2001 through 31 December 2008, a consecutive series of 65 patients from Rio de Janeiro, Brazil, with a well-documented diagnosis of acute HCV infection, acquired via various routes, were enrolled in this study. Patients were prospectively followed up for a median of 40 months after the estimated date of HCV infection with serial measurements of serum alanine aminotransferase, HCV RNA, and anti-HCV antibodies. Spontaneous viral clearance (SVC) was defined as undetectable levels of HCV RNA in serum, in the absence of treatment, for 3 consecutive HCV polymerase chain reaction tests within the first 6 months of follow-up. Cox proportional hazards regression was used to identify host and viral predictors of SVC. The cumulative rate of SVC was 44.6% (95% confidence interval, 32.3%-57.5%). Compared with chronic HCV evolution, patients with self-limiting disease had significantly lower peak levels of anti-HCV antibodies (median, 109.0 vs 86.7 optical density-to-cutoff ratio [od/co]; P<.02), experienced disease symptoms more frequently (69.4% vs 100%; P<.001), and had lower viral load at first clinical presentation (median, 4.3 vs 0.0 log copies; P=.01). In multivariate analyses, low peak anti-HCV level (<93.5 od/co) was the only independent predictor for SVC; the hazard ratio compared with high anti-HCV levels (> or =93.5 od/co) was 2.62 (95% confidence interval, 1.11-6.19; P=.03). Our data suggest that low levels of anti-HCV antibodies during the acute phase of HCV infection are independently related to spontaneous viral clearance.

Low viraemia at enrollment in children with chronic hepatitis C favours spontaneous viral clearance

The significance of hepatitis C viral (HCV)-RNA levels in long-term clinical outcomes of children with chronic HCV infection is not well understood. We conducted a long-term follow-up study of 42 children with chronic HCV infection that included clinical evaluation, biochemical tests, HCV genotyping and repeated quantitative HCV-RNA detection. Patients were divided into low and high viraemia groups according to RNA levels at enrollment (below/above 4.5 x 10(4) IU/mL), and clinical, biochemical and virological factors were evaluated. Overall, 14.3% (6/42) of patients developed spontaneous viral clearance during a median 10.1 years of follow-up. HCV-RNA levels at enrollment and mean RNA levels during follow-up for each patient were significantly correlated (R = 0.9018, 95% CI: 0.6637-0.9038, P < or = 0.001). HCV-RNA level fluctuation was within two log units in 76% of patients. Cumulative viraemia probability during follow-up could be predicted by viraemia levels at enrollment (P = 0.0092). Chronic HCV-infected children, with an RNA level below 4.5 x 10(4) IU/mL at enrollment, have a higher spontaneous viral clearance rate.

Symptomatic Acute Hepatitis C in Egypt: Diagnosis, Spontaneous Viral Clearance, and Delayed Treatment with 12 Weeks of Pegylated Interferon Alfa-2a

Background and ObjectivesThe aim of this study was to estimate the proportion of spontaneous viral clearance (SVC) after symptomatic acute hepatitis C and to evaluate the efficacy of 12 weeks of pegylated interferon alfa-2a in patients who did not clear the virus spontaneously.MethodsPatients with symptomatic acute hepatitis C were recruited from two “fever hospitals” in Cairo, Egypt. Patients still viremic three months after the onset of symptoms were considered for treatment with 12 weeks of pegylated interferon alfa-2a (180 µg/week).ResultsBetween May 2002 and February 2006, 2243 adult patients with acute hepatitis were enrolled in the study. The SVC rate among 117 patients with acute hepatitis C was 33.8% (95%CI [25.9%–43.2%]) at three months and 41.5% (95%CI [33.0%–51.2%]) at six months. The sustained virological response (SVR) rate among the 17 patients who started treatment 4–6 months after onset of symptoms was 15/17 = 88.2% (95%CI [63.6%–98.5%]).ConclusionSpontaneous viral clearance was high (41.5% six months after the onset of symptoms) in this population with symptomatic acute hepatitis C. Allowing time for spontaneous clearance should be considered before treatment is initiated for symptomatic acute hepatitis C.

Acute Hepatitis C in a Contemporary US Cohort: Modes of Acquisition and Factors Influencing Viral Clearance

Acute hepatitis C virus (HCV) infection is often asymptomatic; thus, its epidemiology and natural history are difficult to define. Acute HCV infection was identified on the basis of HCV seroconversion within 1 year (n=45), new anti-HCV seropositivity with clinical acute hepatitis (n=21), or HCV strain sequencing after an iatrogenic exposure (n=1). Risk factors were assessed with a baseline questionnaire, and participants were followed up prospectively with serial measurement of viral loads. Of 67 persons with acute HCV infection, most were asymptomatic (64%) and injection drug users (66%). Thirteen had an unknown mode of transmission; of these, 11 reported high-risk sexual behavior. Ten acquired acute HCV infection within 3 months of an iatrogenic exposure; 3 had confirmed iatrogenic infection, and 4 had no other risk factors identified. The spontaneous viral clearance rate after 6 months of infection was 18% (95% confidence interval, 11%-31%). The rate of viral clearance varied significantly by sex (34% vs. 3% for women vs. men; P<.001). High-risk sexual or iatrogenic exposures may be important contemporary risk factors for HCV infection. The spontaneous viral clearance rate (18%) in this contemporary study was similar to that reported for past studies of transfusion-associated HCV infection. Women were more likely to clear acute HCV infection than men.

P.217 High rate of spontaneous viral clearance in patients with symptomatic acute hepatitis C

To evaluate the effects of the Toll/interleukin-1 receptor domain-containing adaptor-inducing interferon-beta (TRIF) on immune responses induced by DNA vaccines, mice were immunized with the eukaryotic expression plasmid pcDNA/E2 encoding classical swine fever virus (CSFV) E2 alone or in combination with the TRIF genetic adjuvant. Immune responses were examined in immunized mice. Our data demonstrates that co-delivery of the DNA vaccine pcDNA/E2 with the TRIF adjuvant augmented specific humoral and cellular immune responses in a mouse model. Vaccination of pigs confirmed that the pcDNA/E2 in combination with TRIF conferred total protection against lethal challenge with highly virulent CSFV. We conclude that TRIF enhances the effects of the DNA vaccine against CSFV infection and could be used as a potential genetic adjuvant for DNA vaccines in large animal species.

Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies

A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow-up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post-transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero-incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4-67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22-0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.

Complications of β-thalassemia major in North America

AbstractTreatment of patients with β-thalassemia major has improved dramatically during the past 40 years; however, the current clinical status of these patients remains poorly characterized. We performed a cross-sectional study of 342 patients in the Registry of the National Institutes of Health-sponsored Thalassemia Clinical Research Network. Evidence of hepatitis C exposure was present in 35% of tested patients, was associated with age, and had a rate of spontaneous viral clearance of 33%. Ferritin levels ranged from 147 to 11 010 ng/mL (median, 1696 ng/mL). Median hepatic iron content was 7.8 mg/g dry weight and 23% of patients had values of 15 mg/g dry weight or higher. No patients 15 years or younger and 5% of patients aged 16 to 24 years had heart disease requiring medication. Ten percent had cirrhosis on biopsy. Endocrinologic complications were common among adults. Seventy-four (22%) patients had recent implantable central venous access devices (CVADs) placed. Among 80 episodes of bacteremia in 38 patients, 90% were attributable to the CVAD. Among 330 patients who had received deferoxamine chelation therapy, 224 (68%) reported no complications. We conclude that hepatitis C, iron-related organ dysfunction, and complications of iron chelation therapy are strongly age-dependent in North American patients with β-thalassemia.

Acute hepatitis C: high rate of both spontaneous and treatment-induced viral clearance

Background & Aims: Acute hepatitis C virus infection accounts for approximately 20% of cases of acute hepatitis today. The aim of this study was to define the natural course of the disease and to contribute to the development of treatment strategies for acute hepatitis C virus. Methods: The diagnosis of acute hepatitis C virus in 60 patients was based on seroconversion to anti-hepatitis C virus antibodies or clinical and biochemical criteria and on the presence of hepatitis C virus RNA in the first serum sample. Results: Fifty-one of 60 (85%) patients presented with symptomatic acute hepatitis C virus. In the natural (untreated) course of acute symptomatic hepatitis C (n = 46), spontaneous clearance was observed in 24 patients (52%), usually within 12 weeks after the onset of symptoms, whereas all asymptomatic patients (n = 9) developed chronic hepatitis C. The start of antiviral therapy (interferon-α with or without ribavirin) beyond 3 months after the onset of acute hepatitis induced sustained viral clearance in 80% of treated patients. Conclusions: The management of acute hepatitis C has to take into account the high rate of spontaneous viral clearance within 12 weeks after the onset of symptomatic disease. Treatment of only those patients who remain hepatitis C virus RNA positive for more than 3 months after the onset of disease led to an overall viral clearance (self-limited and treatment induced) in 91% of patients, and unnecessary treatment was avoided in those with spontaneous viral clearance. Patients with asymptomatic acute hepatitis C virus infection are unlikely to clear the infection spontaneously and should be treated as early as possible.