Association between HLA-DRB1* polymorphisms and hepatitis B infection in a brazilian population / Associação entre polimorfismos HLA-DRB1* e infecção por hepatite B em uma população brasileira

OBJECTIVE: The aim of the present study was to determine the genotype association for alleles of class II human leukocyte antigens (HLA) in the DRB1* locus among blood donors at the Fundação Hemope (Brazil) infected by or immunized for the hepatitis B virus (HBV). METHODS: A case-control study was performed, comprising a group of individuals infected by HBV and a control group of immunized individuals at a proportion of 1:4. Blood samples were taken for the HLA typing of the DRB1* locus. Univariate and multivariate analyses were performed for the assessment of associations between the categorical variables using the chi-squared test and Fisher's exact test. RESULTS: A total of 320 blood donors were analyzed (241 males [75%] and 79 females [25%] with a mean age of 39 years). The case group consisted of 64 HBV-infected donors and the control group was composed of 256 HBV-immunized donors. The multivariate analysis stratified by gender revealed that the DRB1*09 allele was associated with infected male donors (p = 0.016) and the DRB1*08 allele was associated with infected donors aged 39 years or younger (p = 0.031). CONCLUSION: The results of the present study reveal that younger blood donors and male blood donors who respectively exhibit the DRB1*08 and DRB1*09 alleles are more susceptible to intensification of HBV infection.

OBJETIVO: O objetivo do presente estudo foi determinar a associação genotípica dos alelos de classe II dos antígenos leucocitários humanos (HLA) presentes no locus DRB1* entre doadores de sangue da Fundação Hemope (Brasil), infectados pelo ou imunizados contra o vírus da hepatite B (HBV). MÉTODOS: Estudo caso-controle foi realizado com um grupo de indivíduos infectados pelo HBV e um grupo controle composto de indivíduos imunizados na proporção de 1:4. Amostras de sangue foram coletadas para a tipagem HLA do locus DRB1*. Análises univariada e multivariada foram realizadas para a avaliação de associações entre as variáveis categóricas pelo teste do qui-quadrado e teste exato de Fisher. RESULTADOS: Um total de 320 doadores de sangue foram analisados (241 homens [75%] e 79 do sexo feminino [25%], com idade média de 39 anos). O grupo de casos consistiu de 64 doadores infectados pelo HBV e o grupo controle foi composto de 256 doadores imunes ao HBV. A análise multivariada estratificada por sexo revelou que o alelo DRB1*09 foi associado com os doadores infectados do sexo masculino (p = 0,016) e do alelo DRB1*08 foi associado com os doadores infectados com idade entre 39 anos ou mais jovens (p = 0,031). CONCLUSÃO: Os resultados do presente estudo revelam que doadores de sangue mais jovens e doadores de sangue do sexo masculino que exibem, respectivamente, os alelos DRB1*08 e DRB1*09, são mais suscetíveis à cronificação da infecção pelo HBV.

Seroprevalencia de hepatitis viral B en estudiantes universitarios en Abancay, Perú / Seroprevalence of viral hepatitis B in university students in Abancay, Perú

Para determinar la prevalencia de marcadores serológicos de hepatitis viral B en estudiantes universitarios de la ciudad de Abancay, realizamos un estudio transversal en 240 estudiantes de tres universidades, entre enero a octubre de 2010. Previo consentimiento informado, se llenó, por cada estudiante, una ficha epidemiológica y se tomó una muestra sanguínea para determinar la presencia de HBsAg, anti-HBcAg total, anti-HBe, HBeAg e IgM anti-HBc por el método de ELISA. Se encontró una prevalencia de 2,5 por ciento (seis seropositivos) para el HBsAg y 28,3 por ciento (68 seropositivos) para los anticuerpos Anti-HBcAg. El sexo masculino estuvo asociado con la presencia del anti-HBcAg (OR = 2,0; IC 95 por ciento, 1,2- 3,6). No se encontró la presencia del HBeAg e IgM anti-HBc; los seis portadores del HBsAg fueron anti-HBe positivos. En conclusión, la infección por hepatitis B sigue siendo un problema de salud pública en Abancay, con una prevalencia importante en estudiantes universitarios.

To determine the prevalence of serological markers of viral hepatitis B in university students of the city of Abancay, we performed a cross-sectional study on 240 students from three universities, from January to October 2010. Informed consent was requested to every student, an epidemiological record was filled, and a venous blood sample was drawn to determine the presence of HBsAg, total anti - HBcAg, anti - HBe, HBeAg and IgM Anti - HBc by ELISA. A prevalence of 2.5 percent (six positive samples) was found for HBsAg and of 28.3 percent (68 positive samples) for anti - HbcAg antibodies. The male sex was associated with the presence of anti - HBcAg (OR = 2.0, 95 percent CI, 1.2 to 3.6). We did not found HBeAg or IgM anti - HBc, however, the 6 HBsAg carriers were anti - HBe positive. In conclusion hepatitis B infection is still a public health problem in Abancay, with a significant prevalence in university students.

Non-association of IL-12 +1188 and IFN-gamma +874 polymorphisms with cytokines serum level in occult HBV infected patients

Occult hepatitis B infection [OBI] is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-gamma and +1188 of IL-12 with their serum level in patients suffering from OBI. In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen [HBsAg] and anti-HBc by ELISA. The HBsAg[-]/anti-HBc[+] samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-gamma. In addition, the serum levels of IL-12 and IFN-gamma were also determined by ELISA. Results of this study demonstrated that, 352 [9.5%] out of 3700 blood samples were HBsAg[-]/anti-HBc[+]and HBV-DNA was detected in 57/352 [16.1%] of HBsAg[-]/anti-HBc[+] samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-gamma were also not associated with serum level of cytokines. According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-gamma would not affect the expression of both cytokines at serum level in OBI patients

Situación actual de la hepatitis B en Chile / Present situation of hepatitis B in Chile

Background: Hepatitis B virus infection generates carriers and 8 percent will evolve to a chronic phase. Aim: To perform a compilation of studies on hepatitis B in Chile and other sources of information to estímate the impact of this disease in our country. Material and methods: Published and unpublished evidence about the infection, in the general population and risk groups in our country, was compiled and reviewed critically. Informal interviews to experts, revisión of the mandatory notification book of the Ministry of Health and collection of data from laboratories that study hepatitis B virus, were also carried out. Results: The seroprevalence of chronic carriers in blood donors is nearly O.3 percent. Among risk groups such as health care personnel, the figure is O.7 percent, among homosexuals 29 percent, among HIV positive patients 30 percent, among sexual workers 2 percent and among children with chronic hemodialysis, 9 percent. Prevalence rate according to notified cases in 2004 was 1.8 x 100,000 habitants. Detection of viral hepatitis B surface antigen in ¡aboratories occurs in 0.2 percent of donors and 1.396 of non donors. Conclusions: The seroprevalence of hepatitis B virus, the lack of notification, and the introduction of hepatitis B vaccine to our Regular Program of Immunizations, are arguments to develop in Chile a hepatitis B and C surveillance system.

Serological markers and risk factors for hepatitis B and C viruses in patients infected with human immunodeficiency virus

Both hepatitis B and hepatitis C viruses (HBV and HCV) infection are common in HIV-infected individuals as a result of shared risk factors for acquisition. A serological study for HBV and HCV was performed in 251 HIV-positive individuals from Medellín, Colombia. A qualitative RT-PCR for HCV was done in 90 patients with CD4+ T-cell count < 150 per mm³. Serological markers for HBV infection were present in 97 (38.6 percent) patients. Thirty six of them (37.1 percent) had isolated anti-HBc. A multivariate analysis indicated that the following risk factors were significantly associated with the presence of these markers: age (OR = 1.05, 95 percent CI: 1.01-1.08), pediculosis pubis (OR = 1.83, 95 percent CI: 1.01-3.33), men who have sex with men and women (OR = 3.23, 95 percent CI: 1.46-7.13) and men who have sex only with men (OR = 3.73, 95 percent CI: 1.58-8.78). The same analysis restricted to women showed syphilis as the only significant risk factor. Thus, HBV infection was considerably associated with high risk sexual behavior. HCV was present in only two (0.8 percent) of HIV patients. Both of them were positive by RT-PCR and anti-HCV. This low frequency of HIV/HCV coinfection was probably due to the uncommon intravenous drug abuse in this population. The frequent finding of isolated anti-HBc warrants molecular approaches to rule out the presence of cryptic HBV infection.

La infección por los virus de la hepatitis B y hepatitis C (VHB y VHC) es frecuente en individuos infectados por el VIH como resultado de compartir factores de riesgo para su contagio. Se realizó un estudio serológico para el VHB y VHC en 251 individuos VIH positivos de la ciudad de Medellín, Colombia. En 90 pacientes con un recuento de linfocitos T < 150 células por mm³ se hizo una PCR-RT cualitativa para el VHC. Se encontraron marcadores serológicos para la infección por el VHB en 97 (38.6 por ciento) pacientes. Treinta y seis de 97 (37.1 por ciento) tuvieron un anti-HBc aislado. El análisis multivariado indicó que los factores de riesgo significativos asociados a la presencia de estos marcadores fueron: edad (OR = 1.05, 95 por ciento IC: 1.01-1.08), pediculosis púbica (OR = 1.83, 95 por ciento IC: 1.01-3.33), hombres que tienen sexo con hombres y mujeres (OR = 3.23, 95 por ciento IC: 1.46-7.13) y hombres que tienen sexo solo con hombres (OR = 3.73, 95 por ciento IC: 1.58-8.78). El mismo análisis restringido a mujeres mostró que la sífilis fue el único factor de riesgo significativo. Por lo tanto, la infección por el VHB fue considerablemente asociada a conductas sexuales de alto riesgo. El VHC se presentó en solo 2 (0.8 por ciento) de los pacientes VIH. Ambos pacientes fueron positivos por la PCR-RT y los anti-VHC. La baja frecuencia de la coinfección VIH/VHC fue probablemente debido al bajo uso de drogas intravenosas en esta población. El hallazgo frecuente de anti-HBc como marcador aislado asegura estudios moleculares para descartar la presencia de infección críptica por el VHB.

An economic evaluation of universal infant vaccination strategies against hepatitis B in Thailand: an analytic decision approach to cost-effectiveness.

To evaluate the cost-effectiveness of four infant vaccination strategies aimed at protecting the Thai population against hepatitis B virus (HBV) infection, vaccination and giving hepatitis B immunoglobulin (HBIg) to high-risk infants were compared with universal vaccination of infants and no vaccination. An analytic decision model was used to estimate the clinical and economic consequences of HBV for a hypothetical cohort of newborns for each of the immunization strategies. The model focused on the numbers and the costs of cases prevented. The decision model examined four different HBV management strategies: 1. screening for HBsAg, and vaccination; 2. screening for HBsAg, then HBeAg, and vaccination; 3. universal vaccination of all neonates; and 4. no vaccination. The cost-effectiveness per case prevented for Strategy 1 was 292.79 baht; for Strategy 2, 264.34 baht; for Strategy 3, 151.05 baht; and for Strategy 4, 0 baht. The incremental cost comparing Strategy 3 to Strategy 4 was 6,521 baht; comparing Strategy 2 to Strategy 3, 20,000 baht; and comparing Strategy 1 to Strategy 2, 95,000 baht. There is no socially acceptable threshold value for cost per case prevented to guide decisions on funding health care interventions. Strategy 3 should certainly be continued. Nevertheless, based on these results, Strategy 2 may be considered, despite the incremental cost being about 2 times that of Strategy 3, as it might represent a worthwhile investment of public funds.

Occult hepatitis B virus infection as a cause of cirrhosis of liver in a region with intermediate endemicity.

BACKGROUND: Serological tests may fail to identify hepatitis B virus (HBV) infection as a cause of liver cirrhosis in a proportion of patients. The frequency of such occult infection in regions with intermediate HBV endemicity is not known. Such cases may be diagnosed by incremental testing for IgG anti-HBc, serum HBV DNA, and HBV DNA in liver tissue. METHODS: We tested sera of 111 patients with cirrhosis, including 39 with history of significant alcohol ingestion, for HBsAg, anti-HBc and serum HBV DNA. In addition, in a subset of 14 patients, HBV DNA was looked for in liver tissue. RESULTS: On HBsAg and anti-HBc testing, 66 patients had HBV infection. Serum HBV DNA testing identified HBV infection in 13 additional cases. Of 18 patients labeled as 'cryptogenic' on serological testing, HBV DNA was detected in the serum in 7 patients. Of 14 patients in whom paired liver tissue and serum specimens were tested, 4 additional patients with HBV infection were detected after liver biopsy analysis. CONCLUSIONS: Serological tests for HBsAg and anti-HBc antibody are insensitive in identifying HBV infection in patients with liver cirrhosis. HBV DNA testing in serum and liver can help in establishing HBV infection as etiology, either alone or in addition to another cause.

Niveles séricos de la molécula CD30 soluble en la infección por el virus de hepatitis B / Serum levels of soluble CD30 molecule in hepatitis B virus infection

Background: The release of CD30 molecule in the soluble form (sCD30) is considered a feature of Th2 activation and proliferation of the cellular phenotype Th2. Aim: To analyze the immunoregulatory role of sCD30 in the evolution of hepatitis B virus (HBV) infection. Patients and methods: Three study groups were formed: 15 patients with acute infection by HBV who remitted toward the resolution of the infection; 15 patients who evolved to the carrier state and 15 subjects without clinical history of infection by this or other viruses. The determination of serological markers for the HBV was done by the Microparticles Enzymatic Immunoanalysis techniques (MEIA). The method of double antibody by ELISA was used For sCD30 determination. Results: A significant sCD30 increase (p < 0.05) was observed in patients with acute infection, during the acute phase (135.7 ñ 36.7). These values decreased to 16.2 ñ 2.5 during the convalescent phase. Patients that evolved to the carrier state, did not experience a rise in sCD30 values (40.2 ñ 6.7, 38 ñ 9.2 and 36.1 ñ 8.3 during the acute phase, at 120 and 240 days respectively). The value in the control group was 34.8 ñ 6.7. Conclusions: The group that evolved towards remission experienced a higher activation of the Th2 cellular phenotype, promoting humoral immune response. An inactivity of sCD30 values was observed in the group that evolved to the carrier state

Ten-year serological follow up of hepatitis B vaccine recipients.

AIM: To determine long-term persistence of antibodies to hepatitis B surface antigen (anti-HBs) after vaccination against hepatitis B. METHODS: Thirty-four laboratory workers received hepatitis B vaccine in 1989 in a 0-1-6 month vaccination schedule. Group A (n = 16) received a booster at 3 years after vaccination whereas Group B (n = 18) did not. Anti-HBs was quantitated at 1 month and 1, 2, 3, 5, 6 and 8 years post-vaccination. RESULTS: At eight-year follow up, 10 of 15 subjects in Group A and 3 of 16 in Group B had protective levels of anti-HBs; in addition, two and four subjects, respectively, had detectable anti-HBs though below protective levels. At ten years, 9/15 and 3/16 were anti-HBs positive in Groups A and B, respectively. One subject in each group had rise in anti-HBs titer at 6-year follow up but both of them tested negative for IgG antibodies to hepatitis B core antigen (anti-HBc). A booster dose at 10 years to anti-HBs negative subjects led to an anamestic response in 3/4 and 8/10 persons in Groups A and B, respectively. CONCLUSION: Immunological memory after vaccination against hepatitis B is maintained for at least 10 years.

Hepatitis B and C virus markers among new entrant medical students.

AIM: To investigate the presence of hepatitis B and C virus markers in new entrant medical students at the Faculty of Medicine, University of Kelaniya. METHOD: 456 students (mean age 24 years, SD 3.5, 257 men) were investigated before they were exposed to clinical work, using a questionnaire to assess sociodemographic factors and possible risk factors for contracting hepatitis B or C. Blood samples were tested for HBs Ag and anti HBs (n = 456), and anti-HCV (n = 162 randomly selected samples) with a third generation sandwich radioimmunoassay technique. RESULTS: The students were from 20 of the 25 districts in the country, although their distribution was not inform. A past history of hepatitis or jaundice was obtained from 24 (5.3%) and 6 (1.3%) students respectively. None of them had been vaccinated against hepatitis B. At least one risk factor for hepatitis B or C was present in 32 (7%) of them. None of the samples were positive for HBsAg or anti-HCV, and only two (0.44%) were positive for anti-HBs. CONCLUSION: Our results support the view that exposure to hepatitis B and C seems to be uncommon in this country, at least up to young adulthood. As most new entrant medical students are not immune to these infections there is a strong case to vaccinate them against hepatitis B before they are exposed to clinical work.

Tamizaje de marcadores para hepatitis B pre y post-vacunación en el hospital de C. del Uruguay, Argentina / Screening of the hepatitis B markers before and after vaccination at the C. del Uruguay's hospital, Argentina

Se estudió entre 1993 y 1995 la prevalencia para tres marcadores de hapatitis B (antiHBs, AgHBs y antiHBc) en 382 de 402 (95 por ciento) empleados del hospital público de C. del Uruguay, por presunción de unaincidencia elevada y la necesidad de identificar subgrupos de mayor riesgo, con un muestreo único transversal. Se utilizó la prueba de inmunosorción enzimática (ELISA), y se siguió la respuesta inmune a la vacuna por DNA-recombinante para un mínimo de tres y hasta cuatro dosis, mediante el dosaje de anti HBs. Los resultados muestran una prevalencia general prevacunación para al menos algún marcador de 5,6 por ciento (de 2,9 a 16,7 por ciento según profesiones) y para sólo el anti HBc de 4,2 por ciento. La seroprevalencia positiva del personal fue significativamente mayor en los servicios de odontología, laboratorio, pediatría, cirugía y guardia, en ese orden, que entre el personal de los servicios (p < 0,05). No se encontró asociación con el sexo, edad, antigüedad en el servicio, condición familiar, intervenciones quirúrgicas, transfusiones ni enfermedades crónicas, pero sí con las aplicaciones endovenosas de medicamentos recibidas. El 70 por ciento de los seropositivos eran médicos, personal de enfermería, de laboratorio e instrumentadores, y el resto personal administrativo de servicios y auxiliares. La asociación con la frecuencia de contacto sanguíneo o de mucosas expuestas resultó significativa (p < 0,05). Con respecto a la respuesta inmune frente a la vacunación, el 93,4 por ciento respondieron satisfactoriamente luego de la tercera dosis, y el 100 por ciento luego de la cuarta. El 80 por ciento del personal que requiriera una cuarta dosis, tenían una antigüedad media de 15,5 ñ 2,3 años en el servicio de radiología, en ausencia de otros factores, lo que sugiere la posibilidad de un grupo con depresión inmunológica. En la población estudiada la magnitud de la respuesta inmune o el retardo en la misma no aparece asociada con la edad, el sexo, los otros lugares de desempeño, el hábito de fumar, enfermedades crónicas o la obesidad

Hepatitis B and C virus infection prevalence among women in Manila, the Philippines.

A seroepidemiological survey of HBsAg, HBeAg, anti-HBs, anti-HBc, anti-HBe and anti-HCV positivities was conducted in 1997 in Manila, The Philippines. Adult women (21 to 59 years of age) were invited to donate peripheral blood for the study, and 50 people volunteered. They were nonsmokers, nonhabitual drinkers, and mostly married; none of them was a professional blood donor. The serum assay showed that all subjects were negative for HBsAg and HBeAg. Overall, a half (50%) of the study subjects were positive for any one of the HBV infection markers (i.e. HBV+). The older group (25 women at 36-59 years of age) showed significantly higher prevalence than the younger group (25 women at 21-35 years of age) of positivity to all three HBV antibody markers and therefore HBV positivity also. None of the study subjects was positive for anti-HCV. Comparison of the present findings with the results reported in the literature for the 1980s suggests that the risk of HBV infection and most probably that of HCV infection also has decreased in this 10-year period in the Philippines.

Soroepidemiologia para o vírus da hepatite B (VHB) em gestantes/parturientes e sua transmissäo para recém-nascidos em Goiânia-GO / Soroepidemiology for hepatitis B virus (HBV) in pregnant/parturients and its transmission to new-born babies in Goiânia, GO

In order to detect hepatitis B virus (HBV), 1459 serum samples from pregnant/parturient women were collected at two public hospitals in Goiânia, GO. These samples were tested by enzyme linked immunosorbent assay for HBsAg and anti-HBs. 109 (7.5 per cent) serum samples were positive. Eight (0.5 per cent) sera were positive for HBsAg and 101 (7.0 per cent) for anti-HBs. Viral positivity for both HBsAg and anti-HBs were observed in women which age ranged from 15 to 30 years. Four newborns from HBsAg positive mothers were submitted to the treatment with HBV vaccine (Engerix B) and with hyperimmune gammaglobulin (HBIG, Abbott Laboratories, Brazil). Cord blood from one of the newborns was positive for HBsAg. A positive association was found between hepatitis B and sexually transmitted infections and blood transfusion. These results emphasize the need for prenatal screening for HBV in pregnant women and treatment of the newborns from AgHBs-positive mothers.

Infeccion por virus de hepatitis y respuesta a vacuna anti-hepatitis B en hemodializados / Viral hepatitis infection and response to the anti B-hepatitis vaccine in hemodialyzed patients

La infección por virus de hepatitis B (HBC) y C (HCV) en hemodializados es elevada, y genera problemas epidemiológicos, aumento de la morbilidad y menores expectativas de éxito para el transplante renal; de hecho, la vacunación anti HBV es una indicación racional para este grupo de pacientes, aunque su respuesta es variable. En esta comunciación se analiza el impacto de esta problemática en nuestro medio. Se presentan 219 pacientes (132 del sexo masculino) hemodializados en nuestro hospital y unidades privadas de nuestra ciudad, con edad media de 46,9 años (R=14-85); la media de permanencia en diálisis fue de 20 meses, y la de transfusiones de 5 por ciento/años. En todos los casos se investigó por enzimo-inmunoanálisis (EIA) la presencia en suero de HBs Ag, anti HBs y anti HBc, y en 73 pacientes anti HCV por EIA II; en los casos HBs Ag positivos confirmados se determinó HBe Ag y HBe, y los anti HCV reactivos fueron confirmados por immunobloting de Péptidos Sintéticos LIA-TEK Organon Teknika. Recibieron 40 mcg de vacuna anti HBC recombinante intra deltoidea a 0,1 y 6 meses, 81 pacientes sin marcadores HBC en suero; la respuesta anti HBstitulada dos meses depués de la última dosis fue considerada protectora con títulos superiores a 10µ/ml. La prevalencia de anti HBc y anti HBs fue de 38 por ciento y la de HBs Ag de 21 por ciento; 78 por ciento de los evaluados resultaron reactivos a HBe Ag. La reactividad anti HCV se presentó en 35.6 por ciento, confirmada por LIA (9,7 por ciento en nuestro hospital y 54,8 por unidades privadas con p=0.007). Se halló niveles superiores a 10 mu/ml de anti HBs en 49 por ciento vacunados en los que se tituló el mismo. Los 12 casos restantes (14,8 por ciento) experimentaron hepatitis aguda B durante el período de vacunación...