Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

Abstract

According to the World Health Organization, hepatitis B virus (HBV) carriers account for 5% of the world population. These potential infection transmitter individuals can evolve from the asymptomatic condition to a severe hepatic damage and even hepatocellular carcinoma. A similar HBV epidemiological distribution is observed for hepatitis D virus (HDV) that shares the obligatory association to HBV for its replication (Smedile et al. 1981). Frequently related to HBV chronic carriers and less frequently to the acute disease forms (Colombo et al. 1983, Rizzetto et al. 1983, HDV antigen was identified by immunohistochemical assays in liver cell nuclei of patients with chronic persistent or chronic active hepatitis, hepatitis B surface antigens (HBsAg-positive) (Rizzetto et al. 1977). In South America HDV infection was first observed in Venezuela as a severe and fulminant attack among Yucpa indians (Purcell & Gerin 1983) and in Colombia where 60% of the individuals studied were simultaneously HBV and HDV reactive (Ljunggren et al. 1984). In Brazil, the Amazon Region endemicity for both viruses is well known (Figueiredo Mendes et al. 1984, Fonseca et al. 1986, Simonetti et al. 1986 showing high prevalence pattern compared to the other parts of the world (Purcell & Gerin 1983, Nordenfelt et al. 1983, Fonseca et al. 1988). This region is also endemic for yellow fever and it is thought whether another human hepatitis viruses had been introduced in this area by human serum present in vaccines against yellow fever, since there are observations on the occurrence of icterus in England and in Brazil, following vaccination against yellow fever in the 1930s and 1940s decades (Findlay & Mac Callum 1937, 1938, Soper & Smith 1938, Fox et al. 1942 dengue virus antigen research in this study, once the same pathological liver findings are observed in yellow fever and haemorrhagic dengue, such as hepatomegaly, focal visceral haemorrhages, focal necrosis, sinusoidal acidophilic bodies, Kupffer cell hypertrophy and portal tract mononuclear cell infiltration.To observe the simultaneous HBV and HDV antigen frequency and to detect yellow fever and dengue viral antigens in histological sections we studied 79 hepatic samples by immunohistochemical assays. Hepatic viscerotomy samples belong to the Yellow Fever Collection (Department of Pathology, Instituto Oswaldo Cruz, Brazil) created in the 1930s decade from an agreement between Brazilian Government and the Rockefeller Foundation International Division to study yellow fever in Brazil. MATERIALS AND METHODSMaterial -Seventy-nine paraffin-embedded hepatic samples collected from 1934 to 1967 were analyzed. Sixtynine samples were from the Labrea Region, State of Amazonas and ten random samples were from other different localities in the same state. The cases were diagnosed at that time as viral hepatitis, yellow fever, focal necrosis or hepatic atrophy according to clinical aspects and histopathological findings.Methods -Four or five micra thick paraffin-embedded histological sections were ...

Transaminase Elevations during Treatment of Chronic Hepatitis B Infection: Safety Considerations and Role in Achieving Functional Cure

“…In chronic HBV infection, numerous studies have confirmed the heterogenous pattern of infected hepatocytes in chronic HBV infection ( Figure 1 ) where infection is spread intermittently throughout the liver in patches comprised entirely of infected cells [ 21 , 23 , 24 , 25 , 26 , 27 , 28 ] or in sparsely infected regions [ 21 , 24 , 25 , 27 , 29 , 30 ]. In many instances, HBsAg expression is detected in cells devoid of HBV DNA or HBcAg [ 26 , 28 , 31 , 32 , 33 ] ( Figure 1 ), which signals the presence of cells containing integrated HBV DNA, producing HBsAg efficiently (as SVP) but not HBV pgRNA (and HBV DNA) or other viral antigens [ 11 ].…”

Hepatopatias fulminantes/febres hemorrágicas na Amazônia: revisão histórica, padrões de lesão hepática e diagnóstico etiológico

“…Observamos, em nossa casuística, a presença associada do antígeno de superfície do VHB em três casos com achados morfológicos de FA.Adicionalmente, em dois casos com características morfológicas de HL e expressão de AgHBs e/ou AgHD, houve a expressão do antígeno da FA em hepatócitos, dado ainda não referido nos trabalhos por nós estudados.Ricaurte et al (1983) referem, em trabalho de avaliação da utilização do método imuno-histoquímico para a detecção do antígeno da FA em tecido hepático, a negatividade para este antígeno em quatro casos-controle de pacientes com co-infecção por VHB e VHD. No mesmo sentido,Simonetti et al (2002), ao estudarem amostras de viscerotomias hepáticas com expressão imuno-histoquímica do AgHBs provenientes da Amazônia, a maior parte deles da região de Lábrea, pertencentes à coleção de febre amarela da Fundação Instituto Oswaldo Cruz, Rio de Janeiro, não detectam a expressão de antígeno da FA nos casos estudados por método de imuno-fluorescência, cuja sensibilidade para a detecção deste antígeno, segundo eles, é mais baixa que a da imuno-histoquímica.O encontro de expressão imuno-histoquímica de antígenos dos vírus da FA e das hepatites B e/ou Delta em um mesmo paciente nos parece interessante e viável, face à alta endemicidade destas doenças encontrada na Amazônia( Quaresma, 2003;Bensabath et al, 1987a Bensabath et al, e 1987b, principalmente se considerarmos que nossos casos são provenientes de materiais coletados em localidades próximas à floresta amazônica, onde os vetores da FA mantêm o ciclo silvestre desta doença e, o período do qual provêm estes casos, entre os anos de 1936 e 1972 precedeu, em parte, a implantação dos programas nacionais de vacinação.6.4 FibroseAté onde pudemos levantar, a avaliação de fibrose com a tipificação de fibras colágenas, presença de depósitos portais de fibras elásticas e evidências de ativação de células estreladas ainda não foram previamente estudadas nas hepatites fulminantes da Amazônia. Embora, nos casos de FA, não tenhamos detectado significativa fibrose portal, cerca de metade dos nossos casos de HL a apresentaram, predominantemente sob a forma de fibras colágenas do tipo I e de fibras elásticas.…”