Regina Raupach

Hannover Medical School, Hanover, Lower Saxony, Germany

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Publications (22)57.67 Total impact

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    ABSTRACT: Immigrant populations are believed to be more frequently infected with hepatitis viruses. However, limited unbiased data are available on immigrants outside of academic centres. Therefore, the aim of this study was to perform large-scale screening for hepatitis markers in primary care centres treating mainly individuals with a migrational background in Germany.
    European journal of gastroenterology & hepatology. 07/2014;
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    ABSTRACT: Abstract Anti-HCV testing is the first step to diagnose hepatitis C. Although anti-HCV assay performance improved during the last 2 decades, very high sensitivity required for screening may lead to limitations in specificity. Thus, there remains an uncertainty how to interpret anti-HCV test results with a borderline signal-to-cut-off ratio. Comparison was made of concordance and performance of four licensed anti-HCV assays in samples with borderline signal-to-cut-off ratios. Out of 12,090 consecutive samples tested for anti-HCV with the Abbott Architect Anti-HCV assay over a period of 29 months, 95 plasma samples with a signal-to-cut-off ratio between 0.5 and 2 were selected for this study. All samples were re-tested with the Enzygnost Anti-HCV version 4.0, the Ortho anti-HCV version 3.0, and the Monolisa anti-HCV-Plus version 2 assays. Discordant samples were classified by additional immunoblot testing. Overall, only 52% of the Architect borderline samples gave similar results in all four assays. Inter-assay concordance ranged between 58% and 80%. The highest discordance was observed between the Architect and the Monolisa assay (42%). In contrast, a high level of concordance was found between the Enzygnost and Ortho assays (80%). The Monolisa was best to identify negative samples (100%), while the Enzygnost correctly classified most of the positive samples (96%). Anti-HCV antibody assays show significant variation in classifying samples with low signal-to-cut-off ratios. Different performances may have cost and management implications, as false-positive results are not infrequent. However, sensitivities were good for all assays if indeterminate results are not considered as negative.
    Viral immunology 02/2014; 27(1):7-13. · 1.78 Impact Factor
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    ABSTRACT: Hepatitis E virus (HEV) infection takes a clinically silent, self-limited course in the far majority of cases. Chronic hepatitis E has been reported in some cohorts of immunocompromised individuals. The role of HEV infections in patients with autoimmune hepatitis (AIH) is unknown. 969 individuals were tested for anti-HEV antibodies (MP-diagnostics) including 208 patients with AIH, 537 healthy controls, 114 patients with another autoimmune disease, rheumatoid arthritis (RA), and 109 patients with chronic HCV- or HBV-infection (HBV/HCV). Patients with AIH, RA and HBV/HCV were tested for HEV RNA. HEV-specific proliferative T cell responses were investigated using CFSE staining and in vitro stimulation of PBMC with overlapping HEV peptides. HEV-antibodies tested more frequently positive in patients with AIH (n = 16; 7.7%) than in healthy controls (n = 11; 2.0%; p = 0.0002), patients with RA (n = 4; 3.5%; p = 0.13) or patients with HBV/HCV infection (n = 2; 2.8%; p = 0.03). HEV-specific T cell responses could be detected in all anti-HEV-positive AIH patients. One AIH patient receiving immunosuppression with cyclosporin and prednisolone and elevated ALT levels had acute hepatitis E but HEV viremia resolved after reducing immunosuppressive medication. None of the RA or HBV/HCV patients tested HEV RNA positive. Patients with autoimmune hepatitis but not RA or HBV/HCV patients are more likely to test anti-HEV positive. HEV infection should been ruled out before the diagnosis of AIH is made. Testing for HEV RNA is also recommended in AIH patients not responding to immunosuppressive therapy.
    PLoS ONE 01/2014; 9(1):e85330. · 3.53 Impact Factor
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    ABSTRACT: HCV RNA levels correlate with the long-term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra- and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real-world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.
    Journal of Viral Hepatitis 11/2013; · 3.08 Impact Factor
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    ABSTRACT: Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were prospectively screened for HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. In addition, 137 patients undergoing cardiac surgery (non-HTR) and 537 healthy subjects were studied cross-sectionally. The anti-HEV-IgG seroprevalence was 11% in HTR, 7% in non-HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non-HTR vs. healthy controls p<0.01). Anti-HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV-PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined.
    American Journal of Transplantation 07/2012; · 6.19 Impact Factor
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    ABSTRACT: The presence of the hepatitis B virus (HBV)-eAg in patients with hepatitis B is associated with higher HBV replication and with an increased risk to develop liver-related clinical endpoints defined as liver related death, liver transplantation, development of hepatocellular carcinoma and hepatic decompensation. The aim of this study was to investigate the role of HBeAg in patients co-infected with the hepatitis D virus (HDV). We studied virological markers of HBV and HDV infection and as well as biochemical and clinical features of liver disease in a cohort of 534 anti-HDV-positive patients. In addition, we compared the clinical long-term outcome of HBeAg-positive HDV-infected patients with HBeAg-negative control patients matched for age, gender and baseline-MELD score. HBeAg-positive hepatitis delta was detected in 71 of 534 patients (13.3%). HBeAg positivity was associated with a higher biochemical disease activity and higher HBsAg levels in HDV co-infected patients. Sixty one per cent of the HBeAg-positive HDV-infected patients presented with HBV DNA levels below 2000 IU/ml, at least once during follow-up. Both HBeAg-positive and -negative patients showed a similar severe clinical long-term course with about half of the patients developing a liver-related clinical complication after a median follow-up period of 51 months (range: 9-193 months). HBV DNA levels are low in both HBeAg-negative and HBeAg-positive patients suggesting suppressive effects of HDV on HBV irrespective of the phase of HBV infection. The clinical long-term outcome of HBeAg-positive patients is not different to HBeAg-negative patients infected with the HDV.
    Liver international: official journal of the International Association for the Study of the Liver 06/2012; 32(9):1415-25. · 3.87 Impact Factor
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    ABSTRACT: Cases of chronic or prolonged hepatitis E virus (HEV) infections have been described in solid organ transplant recipients, HIV infected patients and in patients with malignancies or idiopathic CD4(+) T lymphopenia. It is unknown if HEV infection also takes chronic courses in patients with common variable immunodeficiency (CVID). We studied a cohort of 73 CVID patients recruited in a low endemic Central European country. None of the subjects tested positive for HEV RNA or anti-HEV IgG. Immunoglobulin transfusions (n=10) tested negative for HEV RNA but all were anti-HEV positive. To verify that such pooled blood products contain anti-HEV protective antibodies we measured the anti-HEV IgG optical density (OD) values in patients before and after transfusion. Anti-HEV OD values increased after infusion but did not reach the cut-off considered as positive. Thus, chronic HEV infections seem to be rare events in CVID patients in Germany. Commercially available immunoglobulin infusions contain anti HEV antibodies and may contribute to protection from HEV infection.
    Infectious disease reports 04/2012; 4(2):e28.
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    ABSTRACT: Chronic courses of hepatitis E virus (HEV) infections have been described in immunosuppressed patients. We aimed to study the role of HEV infections in heart transplant recipients (HTR). 274 HTR were prospectively screened for HEV infection using an anti-HEV-IgG ELISA and HEV-PCR. In addition, 137 patients undergoing cardiac surgery (non-HTR) and 537 healthy subjects were studied cross-sectionally. The anti-HEV-IgG seroprevalence was 11% in HTR, 7% in non-HTR and 2% in healthy controls (HTR vs. healthy controls p<0.0001; non-HTR vs. healthy controls p<0.01). Anti-HEV tested positive in 4.0% in control cohorts of other immunocompromised patients (n = 474). Four HTR (1.5%) were chronically infected with HEV as shown by HEV-PCR and all four patients had liver transaminases of >200 IU/L and histological or clinical evidence of advanced liver disease. In three patients ribavirin treatment was successful with a sustained biochemical and virological response while treatment failed in one cirrhotic patient after ribavirin dose reduction. Heart transplant recipients and patients undergoing cardiac surgery have an increased risk for HEV infections. Chronic hepatitis E may explain elevated liver enzymes in heart transplant recipients. Treatment of HEV infection with ribavirin is effective but the optimal dose and duration of ribavirin therapy remains to be determined.
    American Journal of Transplantation 01/2012; · 6.19 Impact Factor
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    ABSTRACT: Cases of chronic hepatitis E have been described in patients after kidney and liver transplantation. In addition, hepatitis E virus (HEV) reactivation was reported after hematopoietic stem cell transplantation (HSCT). We here evaluated if HEV infection might explain elevated liver enzymes in a well selected cohort of allogeneic HSCT patients with biochemical evidence of hepatitis (n = 52). Of note, none of the subjects tested positive for HEV RNA, including 2 HSCT patients who had been infected with HEV already before transplantation. Thus, both chronic courses of HEV infections and HEV reactivations seem to be rather rare events in HSCT patients in a non-endemic country.
    Transplant Infectious Disease 12/2011; 14(1):103-6. · 1.98 Impact Factor
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    ABSTRACT: A quantitative HCV core antigen (HCVcoreAg) immunoassay has been developed for the confirmation of viremia in patients with hepatitis C. We evaluated the correlation of HCV RNA and HCVcoreAg in different patient populations without HCV-specific treatment: HIV/HCV-coinfection, HBV/HCV-coinfection, and patients with end-stage renal disease. HCVcoreAg was quantified by a fully-automated immunoassay. Correlation of HCVcoreAg with HCV RNA was studied cross-sectionally in HIV/HCV- and HBV/HCV-coinfected patients, as well as before and after hemodialysis in patients with end-stage renal disease. A concordant positive or negative test result for both HCV RNA and HCVcoreAg was observed in 68 of 71 (96%), 55 of 57 (96%), and in 109 of 109 (100%) samples of patients with HIV- or HBV/HCV-coinfection, and patients undergoing hemodialysis, respectively. HCVcoreAg showed high correlation with HCV RNA in samples from HIV/HCV-coinfected patients and HCV-infected patients undergoing hemodialysis (r=0.97 and r=0.94, p<0.001). There was no overall correlation between HCVcoreAg and HCV RNA in HBV/HCV-coinfected individuals (r=0.04, p=0.822). Excluding patients with HCV RNA to HCVcoreAg ratios below 100 and above 10,000kIU/fmol led to improved correlation (r=0.53; p=0.02), but remained worse than for the other cohorts. Overall, HCV RNA to HCVcoreAg ratios did not differ significantly between the different patient populations, though variation tended to be higher in HBV/HCV-coinfected patients. Patients with lower HCV RNA levels tend to have lower HCV RNA/HCVcoreAg ratios. HCVcoreAg represents a reliable marker of viral replication showing a good correlation with HCV RNA in various patient populations, with some limitations in HBV/HCV-coinfection.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 12/2011; 53(2):110-5. · 3.12 Impact Factor
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    ABSTRACT: Increased frequencies of HEV infections have been reported in several industrialized countries. We suggest that this finding might be explained by a better awareness of the disease and not by an increased incidence. Although reported HEV infections increased more than 6-fold in Germany in recent years, the seroprevalence remained unchanged (2 %).
    Zeitschrift für Gastroenterologie 09/2011; 49(9):1255-7. · 1.41 Impact Factor
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    ABSTRACT: Hepatitis C virus (HCV) and hepatitis B virus (HBV) infections are common in haemodialysis units. Moreover, some studies reported seronegative cases of viral hepatitis. We and others have previously shown an HCV RNA decline during haemodialysis; however, limited data on HBV viraemia during haemodialysis are available. A total of 142 haemodialysis patients participated in this study, 11 were anti-HCV positive and 7 were HBsAg positive. HCV RNA and HBV DNA were determined in all patients irrespective of hepatitis serology. HBV DNA, HCV RNA, HBsAg and HCV core antigen (HCVcoreAg) were quantified repeatedly in anti-HCV- and HBsAg-positive patients before and after haemodialysis. No case of seronegative viral hepatitis could be identified. HCV RNA was detected in 9 of the 11 anti-HCV-positive patients, while HBV DNA tested positive in all 7 HBsAg-positive patients. A decrease of HCVcoreAg was observed during four dialysis sessions in 8/9 patients (-24.4 ± 22.7%, P < 0.001) parallelled by HCV RNA decline in most individuals (-10.1 ± 48.6%, P = 0.22). In contrast, HBV DNA and HBsAg declined only in 1/7 patients during all four independent measurements. The remaining six patients showed heterogeneous patterns of HBV DNA and HBsAg before and after haemodialysis without a significant change in mean HBV DNA and HBsAg levels (+14 ± 60.6% and -0.2 ± 25.3%, P > 0.05, respectively). HCVcoreAg correlated strongly with HCV RNA (r = 0.937; P < 0.001, n = 72), while there was no correlation between HBV DNA and HBsAg (r = -0.234; P = 0.131, n = 43). Seronegative viral hepatitis is rare in German maintenance haemodialysis patients. HCV RNA and HCVcoreAg decline during haemodialysis indicating a potential beneficial effect of haemodialysis during antiviral therapy of hepatitis C, which does not apply to HBV infection.
    Nephrology Dialysis Transplantation 01/2011; 26(8):2648-56. · 3.37 Impact Factor
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    ABSTRACT: Hepatitis B surface antigen (HBsAg) clearance during chronic hepatitis B (CHB) infection is associated with improved long-term clinical outcome, so is considered an important therapeutic goal in CHB. Studies have shown that serum HBsAg quantification during, and at end of, treatment may predict long-term HBsAg loss. Performance comparison of the qualitative Elecsys HBsAg II assay using a quantitative research protocol and an established quantitative HBsAg assay. A dilution algorithm was developed for the Elecsys HBsAg II assay to allow quantification of HBsAg levels; this was used to measure HBsAg levels in a range of samples including sera from patients infected with different HBV genotypes, HBV mutants, and longitudinal samples from patients undergoing antiviral treatment. Results were compared with those from the quantitative Architect HBsAg assay. There was significant overall correlation between Elecsys and Architect assays (correlation coefficient [r]=0.97; p<0.001). HBsAg levels measured with both assays correlated well in all phases of infection (r=0.80-0.96), across all genotypes tested (HBV genotype A, r=0.89; HBV genotype D, r=0.97), and in samples with lamivudine-resistant mutations (r=0.94). Bland-Altman analysis showed only minor discordance between assays in different phases of chronic HBV-infection (3.8-5.1%). This strong correlation was also present for sera with lower HBsAg concentrations. On-treatment HBsAg levels were similar when measured with either assay. Using a simple dilution algorithm, the quantitative Elecsys HBsAg II assay reliably determined serum HBsAg levels in a wide range of samples, and showed very high correlation with the Architect HBsAg assay.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2011; 50(4):292-6. · 3.12 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2011; 54.
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    ABSTRACT: The quantifiable level of HBsAg has been suggested as a predictor of treatment response in chronic hepatitis B. However, there is limited information on HBsAg levels considering the dynamic natural course of HBV-infection. This study aimed to determine HBsAg levels in the different phases of HBV-infection in European HBsAg-positive patients. 226 HBV-monoinfected patients, not undergoing antiviral therapy, were analyzed in a cross-sectional study. Patients were categorized according to the phase of HBV-infection: HBeAg(+) immune tolerance phase (IT, n=30), immune clearance phase (IC, n=48), HBeAg(-) low-replicative phase (LR, n=68), HBeAg(-) hepatitis (ENH, n=68), and acute hepatitis B (n=12). HBsAg was quantified and correlated with HBV-DNA, HBV-genotypes and clinical parameters. In addition, 30 LR-patients were followed longitudinally. HBsAg levels were higher in IT-patients and IC-patients compared to LR-patients and ENH-patients (4.96/4.37/3.09/3.87-log(10)IU/ml, p<0.001). HBsAg showed a strong correlation with HBV-DNA during acute hepatitis B (R=0.79, p<0.01). Correlation of HBsAg and HBV-DNA was weak or missing when analyzing different phases of persistent HBV-infection separately. However, associations between HBsAg and HBV-DNA were observed in patients infected with HBV-genotype D but not with HBV-genotype A. LR-patients with HBV-reactivation during follow-up (increase of HBV-DNA >2000IU/ml) showed >3-fold higher baseline HBsAg levels with a NPV of 95% for an HBsAg cut-off of 3500IU/ml. HBsAg levels show significant differences during the natural course of HBV-infection and between HBV-genotypes. These findings may have important implications for understanding the natural history of HBV-infection and for using quantitative HBsAg as a diagnostic tool, i.e. as a marker for predicting HBV-reactivation.
    Journal of Hepatology 02/2010; 52(4):514-22. · 9.86 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2010; 52.
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    ABSTRACT: Hepatitis E virus (HEV) infection induces self-limiting liver disease in immunocompetent individuals. Cases of chronic hepatitis E have recently been identified in organ transplant recipients. We questioned if chronic hepatitis E plays a role in graft hepatitis after liver transplantation in a low endemic area. Two hundred twenty-six liver transplant recipients, 129 nontransplanted patients with chronic liver disease, and 108 healthy controls were tested for HEV antibodies. HEV RNA was investigated in all sera from transplanted patients. HEV antibodies were detected in 1 healthy control (1%), 4 patients with chronic liver disease (3%), and 10 liver transplant recipients (4%). Three liver transplant patients also tested positive for HEV RNA. Two of them developed persistent viremia with HEV genotype 3. The patients were anti-HEV immunoglobulin G-negative and HEV RNA-negative before transplantation and had an episode of acute hepatitis 5 or 7 months after transplantation, which led to advanced liver fibrosis after 22 months in 1 patient. Seroconversion to anti-HEV occurred not before 4 months after the first detection of HEV RNA. The possibility of reverse zoonotic transmission was experimentally confirmed by the infection of 5 pigs with a patient's serum. The pigs showed histological inflammation in the liver, and HEV RNA was detectable in different organs, including muscle. In conclusion, the prevalence of HEV infection in Central European liver transplant recipients is low; however, chronic hepatitis E may occur and needs to be considered in the differential diagnosis of graft hepatitis. The diagnosis of HEV infection should be based on HEV RNA determination in immunosuppressed patients. We suggest that immunocompromised individuals should avoid eating uncooked meat and contact with possibly HEV-infected animals.
    Liver Transplantation 10/2009; 16(1):74-82. · 3.94 Impact Factor
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    ABSTRACT: Hepatitis D virus (HDV) or delta hepatitis has mainly been studied in Asian and Mediterranean cohorts, but data on virological and clinical characteristics of HDV-infected Central and Northern European patients are limited. We investigated virological patterns, as well as biochemical and clinical features of liver disease in 258 HDV infected patients recruited over a period of 15 years at Hannover Medical School. Virological parameters were compared to 2083 anti-HDV negative hepatitis B surface antigen (HBsAg) positive individuals. In this cohort, (i) HDV infection was associated with both suppressed hepatitis B virus (HBV) and hepatitis C virus (HCV) replication, (ii) the suppression of HBV-DNA and HCV-RNA was not related to HDV-RNA replication, (iii) mean HBsAg levels did not significantly differ between HBV-monoinfected patients and individuals with delta hepatitis, (iv) HCV coinfection was rather frequent as about one third of our delta hepatitis patients tested anti-HCV positive, however, without being associated with more advanced liver disease, (v) delta hepatitis patients presented in a high frequency with an advanced stage of liver disease, and (vi) the course of delta hepatitis did not differ between Turkish-born, Eastern European (EE)-born and German-born patients. In summary, in this cohort of patients which is the largest so far Central European single centre group of delta hepatitis patients, we confirm the presence of frequently severe disease and describe novel virological profiles which require consideration in the management of this difficult to treat group of patients.
    Journal of Viral Hepatitis 07/2009; 16(12):883-94. · 3.08 Impact Factor
  • Journal of Hepatology - J HEPATOL. 01/2009; 50.
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    ABSTRACT: BackgroundRecently, a novel quantitative HCVcoreAg immunoassay developed for commercialisation by Abbott has become available in Europe and Asia.ObjectivesWe evaluated the correlation of HCV-RNA and HCVcoreAg and investigated the stability of HCVcoreAg and HCV-RNA.Study designHCVcoreAg was quantified by a novel fully automated immunoassay (Architect HCVAg, Abbott, Germany). HCV-RNA quantification was performed either using the Cobas-TaqMan assay or Amplicor-HCV-Monitor (Roche-Diagnostics, Germany). Correlation of HCVcoreAg with HCV-RNA was studied cross-sectionally and longitudinally in untreated patients followed for up to 8 years. Stability of HCVcoreAg and HCV-RNA was evaluated in plasma and whole blood stored for up to 96 h at different conditions.ResultsHCVcoreAg showed good correlation with HCV-RNA in all 118 cross-sectional tested samples irrespective of the HCV genotype (r = 0.75). In the majority but not all of the 10 longitudinally studied patients HCVcoreAg also demonstrated a good correlation with HCV-RNA. HCVcoreAg was stable in plasma at 4, 20, and 37 °C for up to 96 h, whereas HCV-RNA significantly declined at 37 °C. In whole blood, HCVcoreAg and HCV-RNA levels declined at all conditions with exception of HCVcoreAg at 37 °C. HCVcoreAg was stable after 1–5 freezing/thawing cycles and not light-sensitive.ConclusionsHCVcoreAg represents a stable and reliable marker of viral replication showing a good correlation with HCV-RNA irrespective of the HCV genotype. HCVcoreAg determination can be used to confirm viral replication and monitor viral load or acquisition of HCV over time.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 01/2009; · 3.12 Impact Factor