Occult and active hepatitis B virus detection in donated blood in São Paulo, Brazil.

BACKGROUND: The present study determined the HBV antigen, antibody, and DNA status in blood donations deemed to be HBV positive. Individuals with an occult HBV infection (OBI), defined as being positive for HBV DNA but negative for HBV surface antigen (HBsAg), as well as those with active infection (HBsAg-positive), were identified and characterized. STUDY DESIGN AND METHODS: From a total pool if 198,363 blood donations, we evaluated in a cross-sectional study, 1106 samples that were positive in screening tests for antibody to HBV core antigen (HBcAb), HBsAg, and/or HBV DNA by nucleic acid testing (NAT-HBV). The presence of genetic variants in the HBV pol/S gene in individuals with an active HBV infection was also determined. RESULTS: OBIs were detected in six of 976 samples (0.6%) that were positive only for HBcAb. The rate of HBV active infection was 0.024% (48/198,363) and there was a predominance of HBV sub-genotype A1 (62.2%, 28/45), followed by D3 (17.8%, 8/45). Mutations in the S gene were found in 57.8% (26/45) and immune escape mutations in 37.8% (17/45) of active HBV-infected donors. Among them, T123N, G145A, and D144G high-impact immune escape mutations were identified. CONCLUSION: Highly sensitive molecular tests improve the capacity to detect OBIs. When NAT is performed in pooled samples, HBcAb test has value in the detection of donors with OBI and improves transfusion safety. Mutations in the S gene are frequent in HBsAg-positive blood, including those associated with diagnostic failure and vaccine escape mutations.

Effects of chronic HBV infection on lipid metabolism in non-alcoholic fatty liver disease: A lipidomic analysis.

INTRODUCTION AND OBJECTIVES: Chronic hepatitis B virus (HBV) infection exerts an impact on lipid metabolism, but its interaction with dysmetabolism-based non-alcoholic fatty liver disease (NAFLD) remains uncertain. The purpose of the study was to investigate the effects of HBV infection on lipid metabolism, hepatic steatosis and related impairments of NAFLD patients. METHODS: Biopsy-proven Chinese NAFLD patients with (NAFLD-HBV group, n = 21) or without chronic HBV infection (NAFLD group, n = 41) were enrolled in the case-control study. Their serum lipidomics was subjected to individual investigation by ultra-performance liquid chromatography-tandem mass spectrometry. Steatosis, activity, and fibrosis (SAF) scoring revealed the NAFLD-specific pathological characteristics. RESULTS: Chronic HBV infection was associated with global alteration of serum lipidomics in NAFLD patients. Upregulation of phosphatidylcholine (PCs), choline plasmalogen (PC-Os) and downregulation of free fatty acids (FFAs), lysophosphatidylcholine (LPCs) dominated the HBV-related lipidomic characteristics. Compared to those of NAFLD group, the levels of serum hepatoxic lipids (FFA16:0, FFA16: 1, FFA18:1, FFA18:2) were significantly lowered in the NAFLD-HBV group. These low-level FFAs demonstrated correlation to statistical improvements in aspartate aminotransferase activity (FFA16:0, r = 0.33; FFA16:1, r = 0.37; FFA18:1, r = 0.32; FFA18:2, r = 0.42), hepatocyte steatosis (FFA16: 1, r = 0.39; FFA18:1, r = 0.39; FFA18:2, r = 0.32), and ballooning (FFA16:0, r = 0.30; FFA16:1, r = 0.45; FFA18:1, r = 0.36; FFA18:2, r = 0.30) (all P < 0.05). CONCLUSION: Chronic HBV infection may impact on the serum lipidomics and steatosis-related pathological characteristics of NAFLD.

Identification of mutations in the S gene of hepatitis B virus in HIV positive Mexican patients with occult hepatitis B virus infection.

INTRODUCTION AND AIM: Occult hepatitis B virus infection (OBI) is characterized by the presence of replication-competent hepatitis B virus (HBV) DNA in the liver and/or serum of patients with undetectable levels of the HBV surface antigen (HBsAg). Due to the shared infection routes HIV positive patients are at higher risk of developing OBI, thus, the aim of this study was to determine the frequency of OBI in Mexican HIV-infected patients and to identify mutations in the HBV S gene that could be associated to the development of OBI. MATERIALS AND METHODS: Plasma samples from 50 HIV-infected patients with undetectable levels of the HBsAg were obtained and analyzed. The Core, PreS and S genes were amplified by nested PCR and sequenced by the Sanger method. To analyze HBV diversity in the OBI-positive patients, ten sequences of 762bp from the HBV S gene were selected, cloned, and subsequently sequenced for mutational analyses. RESULTS: OBI infection was found with a frequency of 36% (18/50). All the HBV sequences corresponded to the H genotype. The most common mutations were: C19Y, Q129H, E164D, and I195M, with a frequency of 44%, 36%, 39% and 48% respectively. CONCLUSIONS: In this study, we report the presence of OBI in a cohort of Mexican HIV-infected patients with an overall prevalence of 36%. Mutational analyses revealed that four non-silent mutations were frequent in different regions of the HBsAg gene, suggesting that they might be associated to the development of OBI in this population, nevertheless, further studies are required to determine their role in the pathogenesis of OBI.

Occult hepatitis B virus infection in patients with leprosy.

Leprosy patients may present with immune system impairment and have a higher hepatitis B virus (HBV) seroprevalence, justifying the investigation of occult HBV infection in these individuals. The aim of this study was to verify the frequency and the clinical factors associated with occult HBV infection in leprosy patients. Between 2015 and 2016, leprosy patients from a reference center in Brazil were interviewed to assess clinical data. Blood samples were collected for the screening of HBV serological markers using enzyme-linked immunosorbent assay. Patients with negative hepatitis B surface antigen (HBsAg) that had positive anti-HBc and/or anti-HBs were selected for HBV DNA detection using real-time polymerase chain reaction. SPSS was used for data analysis. Among 114 selected patients, six were identified with occult infection (5.3%) and five of them with multibacillary leprosy. Three patients with occult infection had a history of a type 2 reaction (P = 0.072; OR, 4.97; 95% CI, 0.87-28.52). Only two patients with occult infection had isolated anti-HBc, while three had isolated anti-HBs, including those with the highest HBV DNA titers. In conclusion, in leprosy patients with negative HBsAg and positive anti-HBc and/or anti-HBs, occult HBV infection occurs in 5.3% and can be found even in patients with isolated anti-HBs.

Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan.

INTRODUCTION AND AIM: Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients. MATERIAL AND METHODS: DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalentlyclosed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI. RESULTS: HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies. CONCLUSIONS: OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.

Adherence and immune response to revaccination following hematopoietic stem cell transplantation at a pediatric onco-hematology reference center.

BACKGROUND: Revaccination after hematopoietic stem cell transplantation (HSCT) is necessary to compensate for the loss of immunological memory. The aims of this study were to evaluate the adherence to revaccination schedule and the humoral immune response to different vaccine antigens in HSCT pediatric and young adult patients. METHODS: Patients submitted to HSCT for over 3 years were recruited. After written informed consent, a questionnaire was filled in, the vaccination card was analyzed, a blood sample was collected and tested by ELISA for diphtheria, Haemophilus influenzae type b (Hib), hepatitis A, hepatitis B, tetanus, measles, rubella, and varicella antibodies. RESULTS: Sixty-three patients (mean age at HSCT, 10.7 years) were evaluated. Forty-one (65%) were male; 34 (54%) had allogeneic and 29 (46%), autologous HSCT. Complete adherence to diphtheria revaccination was found in 79.4% patients and seropositivity was found in 92% of those who completed the revaccination schedule; for Hib, 68.3% adherence and 95.3% seropositivity were observed; for hepatitis A, 63.5% adherence and 92.5% seropositivity; for 3 doses of hepatitis B, 86.8% adherence and 79.2% seropositivity; for tetanus, 79.4% adherence and 100% seropositivity; for measles and rubella, 17.5% adherence and 100% seropositivity; for varicella, 7.9% adherence and 100% seropositivity. The existence of a Vaccination Center for Special Immunobiologicals in patients' municipality was positively associated with completed vaccine schedule; on the other hand, chronic GVHD was negatively associated with revaccination adherence. CONCLUSION: Hematopoietic stem cell transplantation patients showed good seropositivity rates after complete vaccination schedule. However, a low coverage rate was observed for live attenuated antigens.

Infección oculta por el virus de la hepatitis B en pacientes hemodializados cubanos / Occult hepatitis B virus infection in hemodialysis patients

Introducción: la infección oculta por el virus de la hepatitis B se caracteriza por la presencia en suero o plasma del genoma viral y anticuerpos contra la proteína de la cápsida (anti-HBc) en ausencia del marcador de infección.Objetivos: detectar la IOB en los pacientes hemodializados e identificar la posible relación de la IOB con la infección por el virus de la hepatitis C y variables sociodemográficas y epidemiológicas.Métodos: se estudiaron 709 muestras de pacientes provenientes de 18 unidades de hemodiálisis de Cuba. Se determinaron marcadores de infección, exposición e inmunidad al virus de la hepatitis B. Las muestras con HBsAg negativo, anti-HBc positivo y niveles de anti-HBs < 50 UI/L se les analizó la detección de ADN del virus de la hepatitis B y marcadores de lvirus de la hepatitis C.Resultados: las prevalencias de la infección y la exposición al virus de la hepatitis B fueron de 6,9 por ciento y 28,6 por ciento, respectivamente. El 4,3 por ciento de las muestras tuvieron criterio de infección oculta por el virus de la hepatitis B ; esta se detectó en el 58,1 por ciento (18/31) de los casos, con cargas virales menores de 105 UI/mL. La prevalencia global de infección oculta por el virus de la hepatitis B fue de 2,5 por ciento (18/709). No se encontró asociación significativa entre las variables analizadas.Conclusiones: la infección oculta por el virus de la hepatitis B fue frecuente en pacientes hemodializados con bajos niveles de anti-HBs, principalmente en aquellos con concentraciones no protectoras. Este estudio ratifica la necesidad de mantener la estrategia de prevención contra las hepatitis virales de transmisión parenteral en las unidades de diálisis(AU)

Introduction: occult hepatitis B virus infection is characterized by the presence of the viral genome and antibodies to the capside protein in serum or plasma (anti-HBc) that test negative for the infection marker.Objectives: to detect the occult hepatitis B virus in hemodialysis patients and to identify the possible relationship between occult hepatitis B infection and hepatitis C virus infection and the epidemiological and demographic variables.Methods: seventy thousand and nine serum samples from patients treated in 18 hemodialysis units were included. Serological markers for HBV infection, exposure and immunity were tested. Samples with negative HBsAg , positive anti-HBc and anti-HBs titers <50 IU/L were tested for detection of HBV-DNA and HCV markers.Results: the prevalence of HBV infection and exposure were 6.9 percent and 28.6 percent respectively. In the group, 4.3 percent of samples met occult hepatitis B infection criteria, the HBV-DNA was detected in 58.1 percent (18/31) of the samples, with viral loads below 105 IU/mL. Overall occult hepatitis B infection prevalence was 2.5 percent (18/709). There was no significant association among the analyzed variables.Conclusions: occult hepatitis B infection was frequent in hemodialysis patients with low levels of anti-HBs mainly in those with non protected titers. This study supports the need of keeping the prevention strategies against parenterally transmitted viral hepatitis in dialysis units(AU)

Infección oculta por el virus de la hepatitis B en pacientes hemodializados cubanos / Occult hepatitis B virus infection in hemodialysis patients

Introducción: la infección oculta por el virus de la hepatitis B se caracteriza por la presencia en suero o plasma del genoma viral y anticuerpos contra la proteína de la cápsida (anti-HBc) en ausencia del marcador de infección.Objetivos: detectar la IOB en los pacientes hemodializados e identificar la posible relación de la IOB con la infección por el virus de la hepatitis C y variables sociodemográficas y epidemiológicas.Métodos: se estudiaron 709 muestras de pacientes provenientes de 18 unidades de hemodiálisis de Cuba. Se determinaron marcadores de infección, exposición e inmunidad al virus de la hepatitis B. Las muestras con HBsAg negativo, anti-HBc positivo y niveles de anti-HBs < 50 UI/L se les analizó la detección de ADN del virus de la hepatitis B y marcadores de lvirus de la hepatitis C.Resultados: las prevalencias de la infección y la exposición al virus de la hepatitis B fueron de 6,9 por ciento y 28,6 por ciento, respectivamente. El 4,3 por ciento de las muestras tuvieron criterio de infección oculta por el virus de la hepatitis B ; esta se detectó en el 58,1 por ciento (18/31) de los casos, con cargas virales menores de 105 UI/mL. La prevalencia global de infección oculta por el virus de la hepatitis B fue de 2,5 por ciento (18/709). No se encontró asociación significativa entre las variables analizadas.Conclusiones: la infección oculta por el virus de la hepatitis B fue frecuente en pacientes hemodializados con bajos niveles de anti-HBs, principalmente en aquellos con concentraciones no protectoras. Este estudio ratifica la necesidad de mantener la estrategia de prevención contra las hepatitis virales de transmisión parenteral en las unidades de diálisis(AU)

Introduction: occult hepatitis B virus infection is characterized by the presence of the viral genome and antibodies to the capside protein in serum or plasma (anti-HBc) that test negative for the infection marker.Objectives: to detect the occult hepatitis B virus in hemodialysis patients and to identify the possible relationship between occult hepatitis B infection and hepatitis C virus infection and the epidemiological and demographic variables.Methods: seventy thousand and nine serum samples from patients treated in 18 hemodialysis units were included. Serological markers for HBV infection, exposure and immunity were tested. Samples with negative HBsAg , positive anti-HBc and anti-HBs titers <50 IU/L were tested for detection of HBV-DNA and HCV markers.Results: the prevalence of HBV infection and exposure were 6.9 percent and 28.6 percent respectively. In the group, 4.3 percent of samples met occult hepatitis B infection criteria, the HBV-DNA was detected in 58.1 percent (18/31) of the samples, with viral loads below 105 IU/mL. Overall occult hepatitis B infection prevalence was 2.5 percent (18/709). There was no significant association among the analyzed variables.Conclusions: occult hepatitis B infection was frequent in hemodialysis patients with low levels of anti-HBs mainly in those with non protected titers. This study supports the need of keeping the prevention strategies against parenterally transmitted viral hepatitis in dialysis units(AU)

Occult hepatitis B virus infection in liver transplant patients in a Brazilian referral center

Estimates of occult hepatitis B virus (HBV) infection prevalence varies among different studies depending on the prevalence of HBV infection in the study population and on the sensitivity of the assay used to detect HBV DNA. We investigated the prevalence of occult HBV infection in cirrhotic patients undergoing liver transplantation in a Brazilian referral center. Frozen liver samples from 68 adults were analyzed using a nested polymerase chain reaction assay for HBV DNA. The specificity of the amplified HBV sequences was confirmed by direct sequencing of the amplicons. The patient population comprised 49 (72.1%) males and 19 (27.9%) females with a median age of 53 years (range=18-67 years). Occult HBV infection was diagnosed in three (4.4%) patients. The etiologies of the underlying chronic liver disease in these cases were alcohol abuse, HBV infection, and cryptogenic cirrhosis. Two of the patients with cryptic HBV infection also presented hepatocellular carcinoma. Markers of previous HBV infection were available in two patients with occult HBV infection and were negative in both. In conclusion, using a sensitive nested polymerase chain reaction assay to detect HBV DNA in frozen liver tissue, we found a low prevalence of occult HBV infection in cirrhotic patients undergoing liver transplant, probably due to the low prevalence of HBV infection in our population.

Occult hepatitis B virus infection among Mexican human immunodeficiency virus-1-infected patients.

AIM: To determine the frequency of occult hepatitis B infection (OHBI) in a group of human immunodeficiency virus (HIV)-1+/ hepatitis B surface antigen negative (HBsAg)- patients from Mexico. METHODS: We investigated the presence of OHBI in 49 HIV-1+/HBsAg- patients. Hepatitis B virus (HBV) DNA was analyzed using nested PCR to amplify the Core (C) region and by real-time PCR to amplify a region of the S and X genes. The possible associations between the variables and OHBI were investigated using Pearson's χ(2) and/or Fisher's exact test. RESULTS: We found that the frequency of OHBI was 49% among the group of 49 HIV-1+/HBsAg- patients studied. The presence of OHBI was significantly associated with the HIV-1 RNA viral load [odds ratio (OR) = 8.75; P = 0.001; 95%CI: 2.26-33.79] and with HIV-antiretroviral treatment with drugs that interfere with HBV replication (lamivudine, tenofovir or emtricitabine) (OR = 0.25; P = 0.05; 95%CI: 0.08-1.05). CONCLUSION: The OHBI frequency is high among 49 Mexican HIV-1+/HBsAg- patients and it was more frequent in patients with detectable HIV RNA, and less frequent in patients who are undergoing HIV-ARV treatment with drugs active against HBV.