Effect of IFN-γ and IL-12 expressions on intrauterine transmission in HBsAg-positive parturientsin late pregnancy / 中华流行病学杂志

Objective@#To investigate the influence of IFN-γ and IL-12 levels in prenatal peripheral blood of HBsAg-positive parturients on intrauterine transmission of hepatitis B virus (HBV).@*Methods@#A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B in peripheral blood of parturients. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of cytokines IFN-γ and IL-12 levels were conducted with liquid chip-based flow cytometry method. The serum levels of five serological markers of hepatitis B and HBV DNA in 285 newborns were detected within 24 hours after birth.@*Results@#The incidence of intrauterine dominant infection (DBI), occult infection (OBI) and intrauterine transmission of HBV in HBsAg positive parturients were 7.37% (21/285), 40.70% (116/285) and 48.07% (137/285), respectively. The level of IFN-γ in peripheral blood of HBsAg-negative parturients was significantly lower than those of HBsAg-positive parturients (t=-2.55, P=0.011), NBIT group (t=-2.54, P=0.012) and OBI group (t=-2.33, P=0.021). In HBV DNA load of 103-106 copies/ml group, the levels of IFN-γ in the DBI group were significantly lower than those in OBI group and NBIT group (P<0.01). The level of IFN-γ in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=6.40, P=0.041). In the antiviral treatment group, the level of IL-12 in maternal peripheral blood decreased significantly with the increased severity of intrauterine transmission of HBV (χ2=8.90, P=0.012). Multivariate analysis showed that there was a significant linear relationship between maternal IFN-γ level and maternal age, placenta previa and hepatitis B vaccine injection (P<0.05). The linear relationship between the level of maternal IL-12 and the mode of rupture and hepatitis B vaccine injection had statistical significance (P<0.05).@*Conclusions@#HBV can stimulate the expression of IFN-γ and inhibit the secretion of IL-12 in pregnant and lying-in women, but the expression of IFN-γ in HBsAg-positive parturients showed intra-group differentiation, and the maternal level of IFN-γ will decrease in HBeAg-positive and high-HBV DNA loadstatus. Increasing the levels of IFN-γ and IL-12 in HBsAg-positive parturients is beneficial to block intrauterine transmission of HBV, especially DBI.

Correlation study of IL-18 expression in HBsAg positive parturients in intrauterine transmission of HBV / 中华流行病学杂志

Objective@#To investigate the expression of IL-18 in peripheral blood of HBsAg positive parturients in intrauterine transmission of HBV.@*Methods@#A case-control study was conducted in 282 HBsAg positive parturients and 43 health parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B, real time PCR was used to detect HBV DNA, and flow liquid chip method was used to detect IL-18 levels in peripheral blood of parturients and newborns.@*Results@#The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 8.42% (24/285), 40.00% (114/285) and 48.42% (138/285), respectively. The level of IL-18 in peripheral blood of HBsAg-negative parturients were significantly lower than those of HBsAg-positive parturients (P=0.001), non-HBV intrauterine transmission (NBIT) group (P=0.001) and OBI group (P<0.001). The level of IL-18 in HBeAg negative group was significantly lower than that in HBeAg positive group (P=0.023). When HBV DNA load was ≥103 copies/ml, the level of IL-18 was significantly higher than that in HBsAg-negative group (P<0.01). With the increase of HBV DNA load in maternal blood, the level of IL-18 increased (P=0.024). When HBV DNA load was 103-106 copies/ml, the level of IL-18 in DBI group was significantly lower than that in NBIT group (P=0.022), and increased with the increase of HBV DNA load in maternal blood (P=0.016). With the increased severity of intrauterine transmission of HBV, the level of IL-18 in non-hepatitis B vaccine group decreased significantly (P=0.044). The level of IL-18 in non-hepatitis B vaccine group and immunoglobulin injection group was significantly higher than that in NBIT group (P<0.05). Multivariate analysis showed that the linear relationship between maternal HBeAg status and maternal IL-18 levels had statistical significance (P=0.01).@*Conclusions@#IL-18 is a higher level balance regulator of Th1/Th2 immune network. Monitoring the level of IL-18 in HBsAg-positive parturients can be used not only for predicting the probability of DBI and OBI, but also as an intervention mean, especially for those who are HBeAg-positive and had HBV DNA load ≥103 copies/ml, to improve maternal cellular immune function, which is conducive to interrupting intrauterine transmission and providing a theoretical basis for the prevention and control of HBV intrauterine transmission.

Role of TLR 9 expression in maternal peripheral blood and placenta in intrauterine transmission of HBV / 中华流行病学杂志

Objective@#To explore the role of TLR 9 in intrauterine transmission of hepatitis B virus (HBV) through blood pathway and placenta.@*Methods@#Epidemiological investigation was carried out in 290 HBsAg positive parturients and 45 normal parturients (control group) in Northwest Women and Children Hospital of Shaanxi Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect five serological makers of hepatitis B and TLR 9 levels in peripheral blood of pregnant women and newborns. HBV DNA was detected by real-time fluorescence quantitative PCR. Detection of TLR 9 expression in placenta by immunohistochemical method. A case-control study was conducted to analyze the difference of TLR 9 levels in placenta and peripheral blood of HBsAg- positive pregnant women with intrauterine transmission of HBV.@*Results@#The incidence of dominant HBV infection (DBI), occult HBV infection (OBI) and intrauterine transmission of HBV were 9.28% (27/291), 40.21% (117/291) and 49.48% (144/291) respectively. (1) The level of TLR 9 in peripheral blood of HBsAg-positive parturients, non-HBV intrauterine transmission (NBIT) group and OBI group were significantly lower than that of control group (P<0.001). The level of TLR 9 in DBI group was significantly higher than those in NBIT group and OBI group (P=0.000). (2) The TLR 9 level in HBeAg-negative group was significantly lower than that in HBeAg-positive parturients in OBI group (P=0.01). (3) With the increased severity of intrauterine transmission of HBV in each HBV DNA load group, the TLR 9 level in maternal peripheral blood increased significantly (P<0.05). (4) With the increased severity of intrauterine transmission of HBV, the levels of TLR 9 increased significantly in antiviral therapy, immunoglobulin injection and non-hepatitis B vaccine groups (P<0.05). (5) The expression of TLR 9 in placenta tissues with DBI group was significantly higher than that in OBI group and NBIT group (P<0.05).@*Conclusions@#HBV can inhibit the secretion of TLR 9 in parturient to some extent, but HBeAg can stimulate the secretion of TLR 9. However, with the increased severity of intrauterine transmission of HBV, the level of TLR 9 in parturients is increased by intra-group cross-differentiation. Therefore, TLR 9 is not an independent marker for screening and grouping, but it can be used as an reference indicator for the monitoring and management of HBsAg-positive parturients.

Epidemiology study of intrauterine transmission of HBV in HBsAg-positive parturients in Xi’an / 中华流行病学杂志

Objective@#To investigate the current status and influence factors of HBV intrauterine transmission (BIT) in HBsAg-positive parturients and understand the outcome of HBV transmission and response to hepatitis B vaccine immunization in children in Xi’an.@*Methods@#An epidemiological survey was conducted in 341 HBsAg-positive parturients who gave birth in Northwest Women and Children Hospital of Shaanxi Province from January 2015 to January 2018. Serological tests were performed by using venous blood from 344 newborns within 24 hours after birth and at the age of 1 year old. A nested case-control study was conducted to analyze the infection rates of intrauterine dominate HBV infection (DBI) and intrauterine occult HBV infection (OBI) in BIT and their influencing factors in newborns. The epidemiological survey was conducted to collect the information about the outcome of HBV transmission and the positive rate of HBsAb in children at high-risk from August 2016 to October 2018.@*Results@#The BIT rate was 46.51%(160/344) in HBsAg-positive parturients, the DBI rate was 8.14% (28/344), the OBI rate was 38.37% (132/344), and the odds ratio of DBI and BIT in neonates of HBeAg-positive parturients were respectively 2.60 (95%CI: 1.19-5.70) and 2.21 (95%CI: 1.36-3.61) times higher than that of HBeAg-negative parturients. The odds ratio of BIT in neonates with maternal peripheral blood HBV DNA load ≥200, ≥103 and>106 copies/ml were 1.99 (95%CI: 1.29-3.08), 1.73 (95%CI: 1.11-2.69) and 2.33 (95%CI: 1.33-4.10) times higher than those in neonates with maternal peripheral blood HBV DNA<200,<103, and ≤106 copies/ml respectively. The incidence of DBI in neonates of parturients with placenta previa was 14.07 times higher than that of parturients without placenta previa (95%CI: 1.23-160.76). The incidence of BIT in neonates of parturients who received no hepatitis B immunoglobulin during pregnancy was 1.60 times higher than that in neonates of those who received hepatitis B immunoglobulin (95%CI: 1.02-2.53). Follow-up results showed that HBsAg negative conversion was found in 9 of 14 children with DBI, and 24.17%(22/91) of children had OBI. The overall rate of immune response to hepatitis B vaccine was 69.23%(63/91). The immune response rate in children with OBI was only 59.09%(13/22).@*Conclusion@#Newborns of HBsAg-positive parturients had high rate of OBI and lower rate of immune response to hepatitis B vaccine detected in follow-up, indicating a gap in hepatitis B prevention and control. HBV monitoring and intervention in HBsAg-positive women of childbearing age and hepatitis B antibody monitoring in children at high-risk are important measures to control infection source and protect susceptible population.

Important role of study on intrauterine transmission of HBV in prevention and control of hepatitis B / 中华流行病学杂志

The new research of intrauterine transmission of HBV includes intrauterine dominant infection and occult infection. Intrauterine dominant infection of HBV is the traditional intrauterine infection. Although intrauterine infection of HBV has been studied for decades, the intervention effects on HBV infection are very limited. As a result, mother to child transmission has become the main route of the transmission of HBV. With the development of science and technology, people’s understand of intrauterine occult infection of HBV has been deepened, and the definition of intrauterine transmission of HBV has been further completed and expanded. The study of intrauterine occult infection of HBV will play an important role in prevention and control of hepatitis B in China through filling in a gap in the field of prevention and control of vertical transmission of HBV, exploring new research perspective and providing guideline for related decision-making.

Re-recognition of occult hepatitis B virus infection / 中华预防医学杂志

Hepatitis B virus (HBV) infection remains to be a serious public health problem in China. There used to be a high prevalence of HBV infection in China, which resulted in a large number of HBV susceptible and post-infected population. Single anti-HBc positive usually indicates post HBV infection and its prevalence is particularly high among people over 40 years old, some of whom may be occult hepatitis B virus infection (OBI). The clinical diagnosis of OBI is difficult and easily missed. Since OBI may cause chronic liver disease progression and even lead to cirrhosis and hepatocellular carcinoma eventually, and more importantly, patients with OBI may leed to HBV reactivation when the immune function decreases or immunosuppressive therapy is performed, the accurate identify of OBI is of particular importance. Moreover, OBI is the potential source of HBV infection, which may transmit through blood transfusion, organ transplantation and mother-to-child transmission. In view of this situation, we reviewed the mechanism, prevalence and definition of OBI, and proposed a determination system for replication-competent HBV DNA based on our understanding of the updated OBI definition. It is expected to be beneficial for OBI diagnosis, treatment and management.

The effect of occult HBV infection on carcinogenesis of cryptogenic hepatocellular carcinoma / 中华肝胆外科杂志

Objective To investigate the effect of occult HBV infection (OBI) on carcinogenesis of cryptogenic hepatocellular carcinoma.Methods Samples of hepatocellular carcinoma (HCC) and pericarcinomatous tissues obtained after hepatectomy from January 2011 to November 2013 at the Third Affiliated Hospital of Sun Yat-Sen University were collected.They were divided into two groups:the cryptogenic HCC group (the CH group,n =26) and the HBV related HCC group (the HH group,n =40).These samples were compared with the normal liver tissues obtained in 30 patients.HBV DNA was identified by the nested polymerase chain reaction and the immunohistochemical method was taken to examine the hepatitis B virus X protein (HBx) and Yes-associated protein (YAP) expressions.Results OBI was identified in 20 (77.8％) cryptogenic HCC patients and 8 (26.7％) in the control group.There was a significant difference between the two groups (x2 =14.072,P ＜ 0.05).HBV DNA was detected in all the HBV-related HCC patients.The HBx protein expression was mainly located in the cytoplasm of liver cells and liver cancer cells,but YAP was expressed in the nucleus.Both of them showed diffuse brown or tan particles.In the HH group and the CH group,the positive expression rates of HBx protein in the tumorous tissues were 80.0％ and 90.0％,respectively,and 85.0％ and 82.5％ in the nontumorous tissues,but only in 40.0％ in the control group.The positive expression rates of YAP in the tumorous tissues were 65.0％ and 67.5％,respectively,15.0％ and 20.0％ in the nontumorous tissues,respectively,but only in 12.5％ in the control group.The HBx expression in the cancerous tissues and para-cancerous tissues of the HH group and the CH group showed no significant difference (P ＞ 0.05),but the YAP expression in the tumor tissues was significantly higher than that in the nontumorous tissues (P ＜ 0.05).The HBx and YAP expressions in the HH group were comparable to the CH group (P ＞ 0.05).However,their expressions in the cancerous tissue of the HH group and the CH group were significantly higher than in the normal liver tissues (P ＜ 0.05).Conclusion A high prevalence of HBV infection was observed in HBsAg-negative HCC and the high expressions of HBx and YAP might be involved in the process of cryptogenic hepatocellular carcinoma.

Role of occult hepatitis B virus infection in the pathogenesis of mul-tiple myeloma / 中国肿瘤临床

Objective:To explore the relationship between hepatitis B virus (HBV) infection and the pathogenesis of multiple my-eloma (MM), in order to provide an epidemiological evidence for the prevention and treatment of MM. Methods:Clinical and epidemi-ological data of 185 MM patients and 182 non-tumorous patients were collected. Subjects were randomly selected from in-patients who were homeochronously admitted to the same five grade-III A hospitals, including Xi'an Central Hospital, Shaanxi People's Hospital, Xi'an Jiaotong University Xibei Hospital, and so on. MM patients were selected in terms of age and gender. Peripheral blood HBsAg was assayed by ELISA. If HBsAg was negative, the S and C-gene fragments of HBV DNA were tested using nested PCR . Fisher's ex-act test orχ2 test (SPSS statistical software) was used to compare the differences between the groups. Logistic regression was employed to examine the association between the pathogenesis of MM and HBV infection. Results:In MM patients, the HBsAg positive rate was 8.11% (15/185), the occult HBV infection (OBI) positive rate was 3.53% (6/170), and the total HBV infection rate was 11.35% (21/185). For the control group, the HBsAg positive rate was 4.40%(8/182), the OBI positive rate was 0.57%(1/174), and the total HBV in-fection rate was 4.95%(9/182). No statistical difference in HBsAg or OBI positive rate was found between the two groups (P>0.05). However, MM patients showed significantly higher total HBV infection rate than that of the controls [χ2=5.02, P<0.05;OR was 2.46 (95%CI:1.10-5.53, P<0.05)]. Additionally, the proportion of ISS stage III was significantly higher in MM patients with HBV infection than in uninfected MM patients (85.71%vs. 60.37%,χ2=5.15, P<0.05). Patients with HBV infection showed reduced albumin level (χ2=5.60, P<0.05) and aκ/λlight chain ratio (P<0.05) compared with uninfected patients. Conclusion:The risk of MM pathogenesis after HBV infection is significantly increased as OBI is included in the analyses. Furthermore, MM patients with HBV infection will develop more severe liver damage, indicating that OBI in MM patients with negative HBsAg should be screened before chemotherapy to pre-vent HBV reactivation.

Adaptive evolution in the S gene of hepatitis B virus from patients with occult HBV infection / 中华微生物学和免疫学杂志

Objective To detect the positively selected sites in the surface ( S) gene of hepatitis B viruses ( HBVs) from patients with occult HBV infection and to study the molecular mechanism of occult HBV infection.Methods The sequence of S gene from patients with occult HBV infection and reference strains of eight HBV genotypes ( A through H) were downloaded from GenBank and then alignment analysis were performed by using Clustal W software .Phylogenetic trees were constructed by using MEGA 5.05 soft-ware package.PAML4.7 was used to analyze positively selected sites .Results A total of 1286 HBV se-quences from patients with occult infection were searched in GenBank .One hundred and seventy-four com-plete gene sequences encoding surface S protein were screened after alignment analysis and confirmation , of which 13 sequences with nonsense mutation were removed .The likelihood ratio test showed that for both the 161 remained sequences and the 31 reference sequences , the selection models of M2, M3 and M8 were sig-nificantly better than the neutral models of M0, M1 and M7 (2△lnL<55.12, P<0.001).By using Bayes Empirical Bayes (BEB) analysis, 14 positively selected sites (including codon 3, 8, 40, 45, 46, 47, 49, 68, 126, 127, 164, 184, 207 and 210) were detected in the surface gene of HBVs from patients with occult HBV infection, eight of which were located at the immune epitope of HBsAg .However, only 2 positively se-lected sites were identified in reference sequences .Conclusion The long-lasting persistence of HBV in pa-tients with occult HBV infection might be caused by the adaptive evolution of their surface gene in a form of escape mutant under immune suppressive condition .

Infección oculta por el virus de la hepatitis B Aspectos clínicos epidemiológicos y moleculares / Occult hepatitis B virus infection Clinical epidemiological and molecular aspects

Resumen Propósito: La infección oculta por el virus de la hepatitis B se caracteriza por la presencia del genoma viral en muestras de suero y/o tejido hepático pero sin detección de antígeno de superficie. Los mecanismos de patogénesis no se conocen completamente. El propósito del presente artículo es discutir y describir los aspectos clínicos, epidemiológicos y moleculares más importantes de este tipo de infección. Metodología: Se realizó una búsqueda de literatura en la base de datos PUBMED, de trabajos originales y revisiones de tema publicados entre 1979 y 2012. La búsqueda se realizó utilizando las palabras claves "Occult HBV infection, Epidemiology, clinical implications, mechamisms y outcome". Artículos relevantes citados en las publicaciones seleccionadas también fueron consultados. Conclusiones: La identificación de casos de infección oculta por el virus de la hepatitis B y la descripción de la prevalencia es de importancia para la prevención de la transmisión de la infección y del desarrollo de hepatopatías terminales. La disponibilidad de métodos sensibles y específicos para la detección del genoma viral ha permitido explorar la epidemiologia. No obstante, aún son materia de estudio los mecanismos de patogénesis. (Acta Médica Colombiana 2013; 38: 143-153).

Abstract Objective: occult hepatitis B virus infection is characterized by the presence of the viral genome in serum and / or liver tissue samples but without surface antigen detection. The mechanisms of pathogenesis are not fully known. The purpose of this article is to discuss and describe the most important clinical, epidemiological and molecular aspects of this type of infection. Methods: we performed a literature search in PUBMED database of original works and reviews of the subject published between 1979 and 2012. The search was performed using the keywords "occult HBV infection, epidemiology, clinical implications, mechanisms and outcome". Relevant articles cited in the selected publications were also consulted. Conclusions: the identification of cases of occult hepatitis B virus infection and the description of its prevalence is important in preventing transmission of the infection and the development of terminal hepatic diseases. The availability of sensitive and specific methods for the detection of viral genome has allowed us to explore the epidemiology. However, the mechanisms of pathogenesis are still under examination. (Acta Médica Colombiana 2013; 38: 143-153).

Occult hepatitis B virus infection among injecting drug users in the Central-West Region of Brazil

The prevalence of occult hepatitis B virus (HBV) infection was investigated in 149 hepatitis B surface antigen (HBsAg) negative injecting drug users (IDUs) in the Central-West Region of Brazil. Of these individuals, 19 were positive for HBV DNA, resulting in an occult HBV infection prevalence of 12.7% (19/149); six of these 19 individuals had anti-HBV core and/or anti-HBV surface antibodies and 13 were negative for HBV markers. All IDUs with occult hepatitis B reported sexual and/or parenteral risk behaviours. All HBV DNA-positive samples were successfully genotyped. Genotype D was the most common (17/19), followed by genotype A (2/19). These findings reveal a high prevalence of occult HBV infection and the predominance of genotype D among IDUs in Brazil's Central-West Region.

Occult Hepatitis B Virus Infection: Transmission and Reactivation / 대한소화기학회지

Occult HBV infection (OBI) is defined as presence of HBV DNA in the liver tissue in patients with serologically undetectable HBsAg. There are differences in virologic and serological profiles of OBI. Majority of OBI are positive for anti-HBs and/or anti-HBc and minor portion are negative for all HBV markers. However, there are no HBV mutations in the surface and its regulatory regions. HBV infection persists by the presence of covalently closed circular DNA (cccDNA) within the infected hepatocytes, which serves as a reservoir for future infection. OBI increases the risk of HBV transmission through transfusion, hemodialysis, and organ transplantation. Therefore effective measures should be employed to screen OBI. Antiviral therapy is needed in HBsAg-negative transplant patients who are anti-HBc positive to prevent the recurrence of HBV infection. Since HBV replication is strongly suppressed by immune surveillance system in OBI patients, immunosuppression results in massive HBV replication. This leads to acute hepatitis and sometimes mortality when immune surveillance is recovered after stopping immunosuppressive drugs/anticancer chemotherapy. Therefore, narrow surveillance is required to recognize the viral reactivation and start antiviral agents during immunosuppressive therapy/anticancer chemotherapy in patients with OBI.

Occult Hepatitis B Virus Infection in Chronic Hepatitis C / 대한소화기학회지

Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.

Occult hepatitis B virus infection in hemodialysis patients in Recife, State of Pernambuco, Brazil / Infecção oculta para o vírus da hepatite B em pacientes hemodialisados de Recife, Estado de Pernambuco, Brasil

INTRODUCTION: Persistence of the hepatitis B virus (HBV) genome in individuals negative for the HBV surface antigen (HBsAg) reflects occult infection. The aim of this study was to identify occult HBV infection among hemodialysis patients at 5 clinics in Recife, State of Pernambuco, Brazil, between August 2006 and August 2007. METHODS: Serum samples underwent enzyme-linked immunosorbent assay to investigate total antibodies against HBcAg (anti-HBc), HBsAg, and antibodies against HBsAg (anti-HBs). Samples that were HBsAg-negative were tested for total anti-HBc, and those that were positive for total anti-HBc were tested for anti-HBs. HBV DNA was investigated with an in-house PCR technique to identify samples positive for total anti-HBc. Subsequently, the samples positive for HBV DNA were sequenced to identify the genotype and mutations. RESULTS: The study population (n = 752) had a mean age of 50 15.1 years and included both sexes. All samples analyzed were negative for HBsAg. The seroprevalence of total anti-HBc was 26.7% (201/752), while that of anti-HBs was 67.2% (135/201). Total anti-HBc alone was detected in 5.7% of the patients. Occult infection was found in 1.5%, comprising genotypes A (33.3%, 1/3) and D (66.7%, 2/3). No mutations were found. CONCLUSIONS: The study detected occult hepatitis B virus infection in hemodialysis patients. Molecular studies on HBV are of fundamental importance because they identify patients that had been considered virus-negative but who, in reality, host the virus and have the ability to transmit it to other patients and staff.

INTRODUÇÃO: A persistência do genoma do vírus da hepatite B (HBV) em indivíduos com o antígeno de superfície para o HBV (HBsAg) negativo, caracteriza-se como infecção oculta. O objetivo desse trabalho foi identificar infecção oculta pelo HBV em hemodialisados provenientes de cinco clínicas de Recife, Estado de Pernambuco, Brasil, de agosto de 2006 a agosto de 2007. MÉTODOS: Os soros foram submetidos à pesquisa do HBsAg, anticorpos totais para o AgHBc (anti-HBc total) e para os anticorpos contra o antígeno de superfície do HBV (anti-HBs) pelo ensaio imunoenzimático (ELISA). As amostras negativas para o HBsAg foram testadas para o anti-HBc total e os soros reativos, foram testados para o anti-HBs. O DNA-HBV foi analisado pela reação em cadeia da polimerase (PCR) in house nas amostras anti-HBc total reagentes. As amostras DNA-HBV positivas foram sequenciadas para a identificação do genótipo e pesquisa de mutação. RESULTADOS: A população estudada foi de 752 hemodialisados, com média de idade de 50±15,1 e ambos os sexos. Todos os soros analisados foram HBsAg negativos. A soroprevalência para o anti-HBc total e anti-HBs foi de 26,7% (201/752) e 67,2% (135/201), respectivamente. O anti-HBc total foi encontrado em 5,7% dos pacientes. A infecção oculta foi identificada em 1,5% (3/201) das amostras, sendo 33,3% com o genótipo A e 66,7% com o D. Nenhuma mutação foi observada. CONCLUSÕES: O estudo encontrou infecção oculta na amostra analisada. A infecção oculta encontrada mostra a importância de estudos moleculares, pois pacientes HBsAg negativos podem albergar o vírus disseminando-o para os demais pacientes.

Occult Hepatitis B Virus Infection in Patients with Chronic Hepatitis C: Innocent Bystander or Not? / 대한내과학회지

Occult hepatitis B virus (HBV) infection is defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in serum) for individuals testing HBV surface antigen negative. Until recently, the clinical implication of occult HBV infection was unclear. Several studies suggest a high prevalence of occult HBV infection among patients with chronic liver disease. Occult HBV infection is a complex entity comprising many conditions and situations that may be widely different from the biological point of view and clinical consequences. Data regarding natural course and therapy in chronic hepatitis C patients with occult HBV are limited and based on small case numbers. These considerations imply the need for a critical re-evaluation of this field to define better strategies to diagnose and treat this infection.

Clinical Characteristics of Occult HBV Infection and Impact on Treatment Response in Patients with Chronic Hepatitis C / 대한내과학회지

BACKGROUND/AIMS: The prevalence of occult HBV infection (OBI) in patients with chronic hepatitis C (CHC) in Korea has not been reported. Additionally, it is unclear whether OBI influences treatment outcome in CHC patients. We investigated the prevalence of OBI and its impact on treatment outcome in patients with CHC. METHODS: Seventy-six patients with CHC were enrolled and treated with pegylated or conventional interferon and ribavirin. Hepatitis B virus (HBV) DNA was detected by nested polymerase chain reaction. RESULTS: Among the 68 patients who completed treatment and follow-up, HBV DNA was detected in serum from nine (13.2%) patients, liver tissue from 10 (14.7%), and serum or liver tissue from 15 (22.1%). OBI was diagnosed in nine (12.7%) control subjects. No difference in the prevalence of OBI between patients with CHC and controls was observed (13.2 vs. 12.0%; p = 0.92). No significant differences in age, sex, genotype 1 frequency, amount of hepatitis C virus RNA, anti-hepatitis B surface antigen/anti-hepatitis B core-IgG seropositivity, staging, or histology grading were observed in patients with or without HBV DNA. Sustained virological response was achieved in 73.3% of patients with OBI and 83.0% without OBI (p = 0.46). CONCLUSIONS: These results demonstrate that a significant proportion of patients with CHC have occult HBV infection and that OBI does not affect treatment outcome in patients with CHC.

Clinical significance of occult hepatitis B virus infection in chronic hepatitis C patients / 대한간학회지

BACKGROUND/AIMS: We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. METHODS: Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. RESULTS: Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. CONCLUSIONS: Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.

Prevalence of occult HBV infection in alcholic and non-alcoholic subjects lacking the hepatitis B surface antigen / 대한내과학회지

BACKGROUNDS/AIMS: Hepatitis B virus (HBV) infection and chronic alcoholism are major risk factors for chronic liver disease in Korea. METHODS: We investigated the prevalence of occult HBV infection in 198 non-alcoholic (group I) and 85 chronic alcoholic subjects (group II), none of whom showed the hepatitis B surface antigen (HBsAg). Among chronic alcoholics, 25 patients showed cirrhosis. Using serum samples stored at -70 degrees C, liver enzymes, anti-Hbs, and IgG anti-HBc were measured via EIA and serum HBV DNA was quantified via real time PCR. RESULTS: IgG anti-HBc seropositivity, an indicator of past infection, was higher in group II (64.7%) than in group I (43.4%; p<0.01). Eleven of 283 patients (3.2%) were seropositive for HBV DNA, indicating occult infection, but this value did not differ between groups (group I: 3.5%, 7/198; group II: 4.7%, 4/85; p=0.64). In group II, HBV DNA seropositivity was higher in cirrhotic patients (12%, 3/25) than in non-cirrhotic alcoholic liver disease (1.7%, 1/60; p=0.074). CONCLUSIONS: Past HBV infection was more prevalent in alcoholics than non-alcoholics, but the prevalence of occult HBV infection did not differ between groups. However, alcoholics with cirrhosis tended to show a higher prevalence of occult HBV infection.

The preliminary report of occult HBV infection in Vietnamese

Background: Vietnam is located in the endemic region of hepatitis B virus (HBV) infection, but no data of occult HBV infection was reported at present. Objectives: To investigate the prevalence of occult HBV infection in different ethnics of people and generations. Subjects and method: 80 voluteers with HbsAg negative from five different ethnics: Kinh, Tay, Mong, Giay and Dao in a Chino \ufffd?Vietnamses border province (Lao Cai) were enrolled in the study. After HBV-DNA was extracted, nested PCR of S gene and of Core-promoter/Pre-core region were used to detect HBV-DNA. Specifying nucleotide sequence was confirmed by direct sequencing. Results:The prevalence of occult HBV infection in population study was very high 73/80 (91,3%) by nested PCR of Core-promoter/Pre-core, significantly more sensitive than nested PCR of S gene (26,3%) (p<0,0001). The prevalence of occult HBV infection was notdifferent between ethnics of people or between children, adults. Conclusion: Occult HBV infection in Vietnamese is very common; however, nationwide further studies should be carried out to confirm this preliminary results and evaluate the impact of occult HBV infection in Vietnam.