Virological Markers Research Articles

Diversity of trends of viremia and T-cell markers in experimental acute feline immunodeficiency virus infection.

ObjectiveThe early events of human immunodeficiency virus infection seem critical for progression toward disease and antiretroviral therapy initiation. We wanted to clarify some still unknown prognostic relationships between inoculum size and changes in various immunological and virological markers. Feline immunodeficiency virus infection could be a helpful model.MethodsViremia and T-cell markers (number of CD4, CD8, CD8βlowCD62Lneg T-cells, CD4/CD8 ratio, and percentage of CD8βlowCD62Lneg cells among CD8 T-cells) were measured over 12 weeks in 102 cats infected with different feline immunodeficiency virus strains and doses. Viremia and T-cell markers trajectory groups were determined and the dose-response relationships between inoculum titres and trajectory groups investigated.ResultsCats given the same inoculum showed different patterns of changes in viremia and T-cell markers. A statistically significant positive dose-response relationship was observed between inoculum titre and i) viremia trajectory-groups (r = 0.80, p<0.01), ii) CD8βlowCD62Lneg cell-fraction trajectory-groups (r = 0.56, p<0.01). Significant correlations were also found between viremia and the CD4/CD8 ratio and between seven out of ten T-cell markers.ConclusionsIn cats, the infectious dose determines early kinetics of viremia and initial CD8+ T-cell activation. An expansion of the CD8βlowCD62Lneg T-cells might be an early predictor of progression toward disease. The same might be expected in humans but needs confirmation.

Severe hypovitaminosis D correlates with increased inflammatory markers in HIV infected patients

BackgroundEven though it has been suggested that antiretroviral therapy has an impact on severe hypovitaminosis D (SHD) in HIV infected patients, it could be speculated that the different levels of residual inflammation on HAART (Highly Active Anti Retroviral Therapy) could contribute to SHD and aggravate bone catabolism in these patients.MethodsA cross-sectional study was carried out in an unselected cohort of 263 HIV infected outpatients consulting during Spring 2010. Clinical examinations were performed and medical history, food habits, sun exposure and addictions were collected. Fasting blood samples were taken for immunological, virological, inflammation, endocrine and bone markers evaluations.ResultsNinety-five (36%) patients had SHD. In univariate analysis, a significant and positive association was found between SHD and IL6 (p = 0.001), hsCRP (p = 0.04), increased serum C-Telopeptides X (CTX) (p = 0.005) and Parathyroid Hormon (PTH) (p < 0.0001) levels. In multivariate analysis, SHD deficiency correlated significantly with increased IL-6, high serum CTX levels, lower mean daily exposure to the sun, current or past smoking, hepatitis C, and functional status (falls), but not with the time spent on the current HAART (by specific drug or overall).ConclusionsSHD is frequent and correlates with inflammation in HIV infected patients. Since SHD is also associated with falls and increased bone catabolism, it may be of interest to take into account not only the type of antiretroviral therapy but also the residual inflammation on HAART in order to assess functional and bone risks. This finding also suggests that vitamin D supplementation may be beneficial in these HIV-infected patients.

Diagnostikk av kronisk hepatitt B-infeksjon

Infection with the hepatitis B virus can lead to chronic liver inflammation with the risk of developing cirrhosis and cancer of the liver. Increased knowledge and improved treatment of chronic hepatitis B infection in recent years mean that virological tests are increasingly used to ascertain the course of illness, status and response to treatment by the individual patient. The purpose is therefore to provide an updated overview of available diagnostics. The article builds on a selection of original and review articles identified through a search in Medline, as well as experience of microbiological diagnostics from the national reference laboratory for the hepatitis virus in Norway. Detection of virus proteins and antibodies to these, as well as virus quantification and characterisation, form an important part of the assessment of hepatitis B infection, including confirmation of the chronic phase of the illness. Proper diagnosis is based on a broad selection of different serological and virological markers. Genotype and certain mutations may affect the course of illness and the response to treatment. To prevent further transmission and offer effective treatment, it is important to identify chronic carriers, but also persons who have previously been infected with hepatitis B virus with risk of reactivation.

Neural network-based approach for the non-invasive diagnosis and classification of hepatotropic viral disease

A neural network-based method is presented for the diagnosis and classification of patients infected with hepatotropic viral disease. The non-invasive approach makes use of real-time pathological data in form of liver function tests and specific virological markers during training. The unknown patients, not included in the training set, are then processed through the trained neural network model. Experimental results demonstrate that the proposed method is able to effectively diagnose the disease and classifies its stage to be acute, chronic or cirrhosis. In addition, performance analysis is carried out for various supervised and unsupervised neural network models with optimal topologies. The topological architectures are chosen after experimenting with various training algorithms using diverse parameters such as different activation functions between layers, number of hidden layers, and number of neurons. It is concluded that the performance of the multilayered supervised feedforward neural network is the most accurate even with small data set. Whereas, the unsupervised Kohonen&apos;s self-organising maps do not perform well for the subject task under similar conditions.

Inflammation in HIV-Infected Patients: Impact of HIV, Lifestyle, Body Composition, and Demography – A Cross Sectional Cohort Study

ObjectivesTo examine mechanisms underlying the increased inflammatory state of HIV-infected patients, by investigating the association of HIV-related factors, demography, lifestyle, and body composition with the inflammatory marker soluble urokinase plasminogen activator receptor (suPAR).MethodssuPAR was measured in EDTA-plasma and associated with HIV-related factors (HIV-duration, combination antiretroviral treatment (cART), nadir CD4+ cell count, CD4+ cell count, and HIV RNA); demography; lifestyle; and body composition determined by Dual energy X-ray Absorptiometry (DXA) scan, in multiple linear regression analyses adjusted for biological relevant covariates, in a cross-sectional study of 1142 HIV-infected patients.ResultsIncreased suPAR levels were significantly associated with age, female sex, daily smoking, metabolic syndrome and waist circumference. cART was associated with 17% lower suPAR levels. In cART-treated patients 10-fold higher HIV RNA was associated with 21% higher suPAR, whereas there was no association in untreated patients. Patients with CD4+ cell count<350 cells/µL had 7% higher suPAR, but we found no association with nadir CD4+ cell count or with duration of HIV-infection. Finally, suPAR was not associated with adipose tissue distribution, but strongly associated with low muscle mass. In patients infected through intravenous drug use (IDU), CD4+ cell counts<350 cells/µL were associated with 27% lower suPAR (p = 0.03), and suPAR was 4% lower pr. year during treatment (p = 0.05); however, there was no association with HIV RNA, duration of HIV-infection, nor cART.ConclusionWe found elevated suPAR levels in untreated patients compared to patients on cART. Moreover, we observed a significant positive association between suPAR and HIV RNA levels in cART-treated patients. Age, HIV-transmission through IDU, metabolic syndrome, smoking, and low leg muscle mass were also significantly associated with suPAR levels. Our study therefore indicates, that also other aspects of living with HIV than virologic and immunologic markers add to the increased inflammation in HIV-infected patients.

Assessment of burden of virus agents in an urban sewage treatment plant in Rio de Janeiro, Brazil

Sewage discharge is considered to be the main source of virus contamination in aquatic environments. There is no correlation between the presence of viruses and the presence of fecal coliforms in water; therefore virological markers are needed when monitoring contamination. This study investigates DNA and RNA virus concentrations in wastewater and evaluates a potential virus marker of human contamination. Influent and effluent samples were collected twice a month throughout a 1-year period. Viruses were detected using quantitative polymerase chain reaction protocols; nucleotide sequencing was carried out for virus genotyping. Human adenovirus (HAdV) and polyomavirus JC (JCPyV) were the most prevalent viruses found in influent samples (100%) with a virus load that ranged from 10(6) to 10(5) genome copies per liter (gc l(-1)). Norovirus genogroup II (NoV GII) and human astrovirus (HAstV) were less prevalent, and ranged from 10(4) to 10(3)gc l(-1). Quantitative data on virus profiles in wastewaters stress the high level of rotavirus species A environmental dissemination and address the potential of HAdV as a useful virological marker of virus contamination in aquatic environments. This study corroborates other studies performed in developed countries on DNA viruses as good markers of human fecal contamination.

A case of hepatitis B reactivation due to the hepatitis B virus escape mutant in a patient undergoing chemotherapy

A 62-year-old man had chronic hepatitis B virus (HBV) infection and was diagnosed with liver cirrhosis. At the time of diagnosis the patient's virologic markers were positive for hepatitis B surface antigen (HBsAg), antibody to hepatitis B e antigen (anti-HBe) and antibody to hepatitis B core antigen (anti-HBc), while antibody to hepatitis B surface antigen (anti-HBs) and HBV DNA were negative. Later the patient received chemotherapy for malignancy. However, this was interrupted due to elevated liver enzymes. At the same time HBV DNA became positive. Lamivudine (LMV) therapy was administered immediately. However, the levels of serum aminotransferase and total bilirubin (TB) were still rising. Finally the patient died of fulminant hepatic failure. A sequence revealed HBV genotype C (HBsAg subtype adw) with immune escape mutations, F8L, S34L, F41S, G44V, F93C, V96G, L110I, C149Y and F161Y. The high morbidity and mortality of this complication is one of the major obstacles to completing the standard treatment for malignancy in HBV carriers. Therefore, the relative risk of antiviral prophylactic failure should be further assessed and the optimal strategy for antiviral prophylaxis in HBsAg-positive patients with oncologic and hematologic malignancies undergoing chemotherapy should be revised.

Prevalence and Follow-Up of Occult HCV Infection in an Italian Population Free of Clinically Detectable Infectious Liver Disease

BackgroundOccult hepatitis C virus infection (OCI) is a recently described phenomenon characterized by undetectable levels of HCV-RNA in serum/plasma by current laboratory assays, with identifiable levels in peripheral blood mononuclear cells (PBMCs) and/or liver tissue by molecular tests with enhanced sensitivity. Previous results from our group showed an OCI prevalence of 3.3% in a population unselected for hepatic disease. The present study aimed to evaluate OCI prevalence in a larger cohort of infectious liver disease-free (ILDF) subjects. Clinical follow-up of OCI subjects was performed to investigate the natural history of the infection.Methods and Findings439 subjects referred to a Turin Blood Bank for phlebotomy therapy were recruited. They included 314 ILDF subjects, 40 HCV-positive subjects and 85 HBV-positive subjects, of whom 7 were active HBV carriers. Six subjects (4/314 ILDF subjects [1.27%] and 2/7 active HBV carriers [28%]) were positive for HCV-RNA in PBMCs, but negative for serological and virological markers of HCV, indicating OCI. HCV genotypes were determined in the PBMCs of 3/6 OCI subjects two had type 1b; the other had type 2a/2c. OCI subjects were followed up for at least 2 years. After 12 months only one OCI persisted, showing a low HCV viral load (3.73×101 UI/ml). By the end of follow-up all OCI subjects were negative for HCV. No seroconversion, alteration of liver enzyme levels, or reduction of liver synthesis occurred during follow-up.ConclusionsThis study demonstrated the existence of OCI in ILDF subjects, and suggested a high OCI prevalence among active HBV carriers. Follow-up suggested that OCI could be transient, with a trend toward the decrease of HCV viral load to levels undetectable by conventional methods after 12–18 months. Confirmation studies with a longer follow-up period are needed for identification of the OCI clearance or recurrence rates, and to characterize the viruses involved.

A Randomized, Double-Blind Placebo Controlled Trial of Balapiravir, a Polymerase Inhibitor, in Adult Dengue Patients

Background. Dengue is the most common arboviral infection of humans. There are currently no specific treatments for dengue. Balapiravir is a prodrug of a nucleoside analogue (called R1479) and an inhibitor of hepatitis C virus replication in vivo.Methods. We conducted in vitro experiments to determine the potency of balapiravir against dengue viruses and then an exploratory, dose-escalating, randomized placebo-controlled trial in adult male patients with dengue with <48 hours of fever.Results. The clinical and laboratory adverse event profile in patients receiving balapiravir at doses of 1500 mg (n = 10) or 3000 mg (n = 22) orally for 5 days was similar to that of patients receiving placebo (n = 32), indicating balapiravir was well tolerated. However, twice daily assessment of viremia and daily assessment of NS1 antigenemia indicated balapiravir did not measurably alter the kinetics of these virological markers, nor did it reduce the fever clearance time. The kinetics of plasma cytokine concentrations and the whole blood transcriptional profile were also not attenuated by balapiravir treatment.Conclusions. Although this trial, the first of its kind in dengue, does not support balapiravir as a candidate drug, it does establish a framework for antiviral treatment trials in dengue and provides the field with a clinically evaluated benchmark molecule.Clinical Trials Registration. NCT01096576.

HBeAg‐positive hepatitis delta: virological patterns and clinical long‐term outcome

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.

PMO-178 The significance of viral and serological markers in predicting liver disease severity in e-Ag negative hepatitis b virus infection

IntroductionIn hepatitis B virus (HBV) infection, seroconversion to HBeAg negative/eAb positive accompanied by low serum HBV-DNA (persistently ≤2000 IU/ml) and low quantitative HBsAg (qHBsAg) signifies transition to an inactive carrier...

Core antigen tests for hepatitis C virus: a meta-analysis

Diagnosis and monitoring of hepatitis C virus (HCV) infection relies mainly on the detection of HCV antibodies and HCV RNA. HCV antibody test has a longer window period and is not applicable in the immunosuppressed population. Although HCV RNA test reduces the window period, it is still not widely recommended because of its high cost and requirement of specific equipment. HCV core antigen is another direct virological marker which has been investigated in recent years. HCV core antigen assay is as simple as the HCV antibodies assay and can detect HCV infection only 1 day delay compared to the HCV RNA assay. In order to evaluate the application of HCV core antigen test in HCV diagnosis and management, we performed this meta-analysis. Twenty five articles were finally included in meta-analysis. All statistical analyses were performed with MetaDisc 1.4 and Stata 11.0. The pooled sensitivity of HCV core antigen assay was 0.84 (95 % CI, 0.83-0.85), and the pooled specificity was 0.98 (95 % CI, 0.97-0.98). HCV core antigen assays may not displace HCV RNA assays to be a definitive diagnosis of HCV infection until now. Considering the higher sensitivity (0.926) and specificity (0.991) of subgroup, HCV-cAg detection is a promising method as a confirmatory test for HCV antibody positive, therapy-naive individuals. Explored by meta-regression and subgroup analysis, possible sources of heterogeneity of specificity was found, while the heterogeneity of sensitivity was still significant.

Epidemiological Aspects and Clinicopathological Findings in Cats Naturally Infected with Feline Leukemia Virus (FeLV) and/or Feline Immunodeficiency Virus (FIV)

Infections produced by feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV), two of the most prevalent pathogens in cats, range from passing unnoticed to presenting a wide variety of clinical signs. Different epidemiological, clinical, hematological and virological parameters were analyzed in 78 FIV- and/or FeLV-infected cats. FeLV-infected (FeLV+) cats were considerably younger than FIV-infected (FIV+) cats, and in general were seen to have a more severe disease than FIV+ cats. Around one third of the cats presented anemia, and neutropenia was also frequently observed. Though a higher percentage of FIV+ than FeLV+ cats had altered leukocyte counts, FeLV+ cats had altered counts of both neutrophils and lymphocytes more frequently than FIV+, which usually presented only either altered neutrophils or lymphocyte counts. Virological markers were only detected in FeLV+cats, either as mono- or dual-infection, and correlated with the severity of the disease, but not in FIV+ cats. In conclusion, these results suggest that FeLV affects more blood cell types and provokes death of affected animals at a much earlier age than FIV and that the severity of the disease seemed to depend on the viral status of the cat.

Prediction of early HBeAg seroconversion by decreased titers of HBeAg in the serum combined with increased grades of lobular inflammation in the liver

SummaryBackgroundHepatitis B e antigen (HBeAg) seroconversion is an important hallmark in the natural course of chronic hepatitis B. This study was designed to predict early HBeAg seroconversion within 1 year, by not only biochemical and virological markers, but also pathological parameters in patients with chronic hepatitis B.Material/MethodsIn a retrospective cohort study, 234 patients with HBeAg were reviewed for demographic, biochemical, virological and pathological data at the time of liver biopsy. Then, the patients who accomplished HBeAg seroconversion within 1 year thereafter were compared with those who did not, for sorting out factors predictive of early HBeAg seroconversion.ResultsEarly HBeAg seroconversion occurred in 58 (24.8%) patients. In univariate analysis, factors predictive of early HBeAg seroconversion were: alanine aminotransferase (ALT) (p=0.002), IP-10 (p=0.029), HBsAg (p=0.003), HBeAg (p<0.001), HBV DNA (p=0.001), HBcrAg (p=0.001), core-promoter mutations (p=0.040), fibrosis (p=0.033) and lobular inflammation (p=0.002). In multivariate analysis, only serum HBeAg levels <100 Paul Ehrlich Institute (PEI) U/ml and grades of lobular inflammation ≥2 were independent factors for early HBeAg seroconversion (odds ratio 8.430 [95% confidence interval 4.173–17.032], p<0.001; and 4.330 [2.009–9.331], p<0.001; respectively).ConclusionsHBeAg levels < 100 PEIU/ml combined with grades of lobular inflammation ≥2 are useful for predicting early HBeAg seroconversion. In patients without liver biopsies, high ALT levels (≥200 IU/L) can substitute for lobular inflammation (grades ≥2).

Quantitative Computerized Tomography (QCT) versus Dual X-Ray Absorptiometry (DXA) in the Assessment of Bone Mineral Density of HIV-1 Infected Children

Bone studies of HIV-infected children using dual X-ray absorptiometry (DXA) suggest bone mineral density (BMD) abnormalities. Pediatric studies are often performed using DXA instead of computed tomography (CT), which accounts for 3-dimensional differences in bone size of growing children. We evaluated whether CT would match DXA measurements in this population. For this purpose, the BMD of 16 perinatally HIV-infected patients, ages 6 to 22 was assessed. Subjects were matched by age, gender, and race to controls. BMD was assessed via DXA and QCT. Clinical anthropometric data, body mass index, immunologic and virologic parameters and laboratory markers for osteoblastic and osteoclastic activity were performed. No statistically significant differences in age and anthropometric parameters between subjects and controls were found. Individual CT and DXA z-scores were significantly different when subjects were evaluated as a group (p = 0.0002) or when males and females were analyzed independently (p = 0.001 and 0.03). DXA z-scores were below 1 SD, while CT z-scores were above the mean. 31% of subjects were identified as having poor bone mineralization by DXA while none had osteopenia/osteoporosis by CT. There was no correlation between immunologic/virologic parameters and BMD by either method. Increased osteoclastic activity was noted in 10 patients receiving tenofovir. In summary, decreased BMD diagnosed by DXA in pediatric HIV-infected subjects was not confirmed by CT. Increased bone turnover in patients on tenofovir was suggested by laboratory markers. Prospective studies using CT as the imaging standard are needed for evaluation of bone mineral changes in HIV-infected children.

Laboratory Evaluation of Three Regimens of Treatment of Chronic Hepatitis B: Tenofovir, Entecavir and Combination of Lamivudine and Adefovir

Background:Chronic hepatitis B is a disease of concern due to its life-threatening complications like cirrhosis, and hepatocellular carcinoma (HCC) in 20-40% of patients. There are about 400 million people affected worldwide with HBV, and over 300,000 die every year from HBV-related diseases. Oral antivirals like lamivudine, adefovir, entecavir, and tenofovir are commonly used to treat chronic hepatitis B. In this study, we tried to evaluate the comparative efficacy of these drugs alone and in combination.Materials and Methods:Chronic hepatitis B patients with HBV-DNA more than 104 Copies/mL irrespective of their HBeAg status (n = 60) were enrolled in a prospective study. 21, 20, and 19 patients were treated with lamivudine (100 mg/day) plus adefovir (10 mg/day) combination entecavir monotherapy (0.5 mg/day) and tenofovir monotherapy (300 mg/day), respectively and were followed up for 24 weeks with their virological, serological, and biochemical markers measured at 12 and 24 weeks.Results:After 24 weeks of treatment, there was no significant difference between the 3 groups in suppressing HBV-DNA to undetectable levels. The median decrease in HBV-DNA levels from baseline was better with tenofovir and entecavir monotherapies than lamivudine and adefovir combination, which was statistically significant. There was no significant difference between the 3 groups in HBsAg and HBeAg seroconversion and normalization of biochemical parameters.Conclusion:Entecavir and tenofovir monotherapy were found to be more effective than lamivudine plus adefovir combination in reducing the HBV-DNA levels. However, lamivudine plus adefovir combination was not too inferior, especially when cost of treatment was taken into consideration.

Why the Use of Adenoviruses as Water Quality Virologic Marker?

Adenovirus is the virus that contains the highest amount of features favorable to its use as a virologic marker for water quality. Those pathogens are resistant on the environment, abundant, easily detected by molecular methods and are of great importance in public health.

Author’s Reply; Nucleic Acid Testing for the Detection of HBV DNA

: Dear Editor, First, we agree with Seto et al. regarding the impacts of the sensitivity of the detection methods of OBI (occult hepatitis B infection) prevalence but disagree regarding their idea on the lack of usefulness of anti-HBc screens. They have referred to Seo et al., who reported that the prevalence of anti-HBc positivity in Korea was 13.5%, whereas the prevalence of OBI was 0.016% (1). Anti-HBc is the first antibody that is produced against HBV and is the most stable antibody (2); hence, the presence of the antibody in individuals demonstrates introduction of HBV to the immune system via several mechanisms, including transfusion (3, 4). Therefore, it seems that the rate of OBI among anti-HBc-positive persons is more than the anti-HBc-negative blood donors (5). During blood screening programs, hepatitis B surface antigen (HBsAg) testing, followed by polymerase chain reaction (PCR) assays, will be the most accurate approach of identifying OBI, but some blood transfusion services are unable to use PCR (based on high costs). We have proposed applying anti-HBc as a screening test for blood transfusion services that are unable to use PCR to reduce the risk of PTH via OBI-infected blood and its components. Second, Seto et al. have presented a nice mechanism for the possible cause for cryptogenic HCC in endemic chronic hepatitis B regions. They have described a good, probable mechanism of undetectable virological HBV markers in tumor histology. These mechanisms should be examined in future studies.

Author’s Reply; Nucleic Acid Testing for the Detection of HBV DNA

Dear Editor, First, we agree with Seto et al. regarding the impacts of the sensitivity of the detection methods of OBI (occult hepatitis B infection) prevalence but disagree regarding their idea on the lack of usefulness of anti-HBc screens. They have referred to Seo et al., who reported that the prevalence of anti-HBc positivity in Korea was 13.5%, whereas the prevalence of OBI was 0.016% [1]. Anti-HBc is the first antibody that is produced against HBV and is the most stable antibody [2]; hence, the presence of the antibody in individuals demonstrates introduction of HBV to the immune system via several mechanisms, including transfusion [3],[4]. Therefore, it seems that the rate of OBI among anti-HBc-positive persons is more than the anti-HBc-negative blood donors [5]. During blood screening programs, hepatitis B surface antigen (HBsAg) testing, followed by polymerase chain reaction (PCR) assays, will be the most accurate approach of identifying OBI, but some blood transfusion services are unable to use PCR (based on high costs). We have proposed applying anti-HBc as a screening test for blood transfusion services that are unable to use PCR to reduce the risk of PTH via OBI-infected blood and its components. Second, Seto et al. have presented a nice mechanism for the possible cause for cryptogenic HCC in endemic chronic hepatitis B regions. They have described a good, probable mechanism of undetectable virological HBV markers in tumor histology. These mechanisms should be examined in future studies.

Author’s Reply; Nucleic Acid Testing for the Detection of HBV DNA

: Dear Editor, First, we agree with Seto et al. regarding the impacts of the sensitivity of the detection methods of OBI (occult hepatitis B infection) prevalence but disagree regarding their idea on the lack of usefulness of anti-HBc screens. They have referred to Seo et al., who reported that the prevalence of anti-HBc positivity in Korea was 13.5%, whereas the prevalence of OBI was 0.016% (1). Anti-HBc is the first antibody that is produced against HBV and is the most stable antibody (2); hence, the presence of the antibody in individuals demonstrates introduction of HBV to the immune system via several mechanisms, including transfusion (3, 4). Therefore, it seems that the rate of OBI among anti-HBc-positive persons is more than the anti-HBc-negative blood donors (5). During blood screening programs, hepatitis B surface antigen (HBsAg) testing, followed by polymerase chain reaction (PCR) assays, will be the most accurate approach of identifying OBI, but some blood transfusion services are unable to use PCR (based on high costs). We have proposed applying anti-HBc as a screening test for blood transfusion services that are unable to use PCR to reduce the risk of PTH via OBI-infected blood and its components. Second, Seto et al. have presented a nice mechanism for the possible cause for cryptogenic HCC in endemic chronic hepatitis B regions. They have described a good, probable mechanism of undetectable virological HBV markers in tumor histology. These mechanisms should be examined in future studies.