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      Influência da infecção pregressa pelo vírus da hepatite B na fibrose hepática em portadores de hepatite C crônica: avaliação retrospectiva de uma série de casos Translated title: Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation

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          Abstract

          INTRODUCÃO: A hepatite C é uma das principais causas de doença hepática em todo mundo. Apresenta um curso evolutivo dinâmico e influenciável por diversos co-fatores. Dentre eles, a infecção pregressa pelo vírus B (anti-HBcAg [+] e HBsAg [-]) tem se associado a pior prognóstico histológico e terapêutico. Este trabalho teve como objetivo analisar a associação entre a infecção pregressa pelo vírus B e fibrose hepática em portadores de hepatite C crônica, de maneira independente. MÉTODOS: Foram revistos retrospectivamente prontuários médicos de pacientes infectados cronicamente pelo vírus C, atendidos consecutivamente durante um ano no ambulatório de Doenças Infecciosas e Parasitárias - HC FMUSP, quanto aos dados epidemiológicos, clínicos, laboratoriais e histológicos. A análise de independência do impacto da infecção pregressa pelo vírus B foi realizada através de modelo estatístico de regressão logística multivariado, considerando a detecção do anti-HBcAg como variável de exposição, sendo o desfecho a alteração estrutural histopatológica graus 3 e 4 (septos com formação de nódulos e cirrose).0 RESULTADOS: 145 indivíduos foram avaliados pelo estudo, 47.2% com anti-HBcAg (+). O fator de risco mais comumente relatado foi transfusão de sangue e hemoderivados (35,9%). Embora necrose em saca-bocado tenha sido encontrada com maior frequência no grupo de infecção pregressa, a sorologia anti-HBcAg (+) não se associou à fibrose hepática avançada. CONCLUSÕES: A infecção pregressa pelo vírus B não parece acentuar a lesão estrutural desencadeada pela hepatite C crônica, após controle estatístico para outros co-fatores sabidamente capazes de influenciar a história natural desta infecção.

          Translated abstract

          INTRODUCTION: Hepatitis C is a major cause of liver disease worldwide. Its evolutionary course is dynamics and may be influenced by several cofactors. Among them, previous hepatitis B virus infection (anti-HBcAg [+] and HBsAg [-]) has been associated with worse histological and therapeutic prognosis. This study had the objective of independently assessing the relationship between previous hepatitis B infection and liver fibrosis in patients with chronic hepatitis C. METHODS: The medical records of patients chronically infected with the hepatitis C virus who had been seen consecutively during a one-year period at the infectious and parasitic diseases outpatient clinic of HC FMUSP were retrospectively reviewed in relation to epidemiological, clinical and histological data. Analysis on the independence of the previous hepatitis B infection was performed using the statistical model of multivariate logistic regression. Detection of anti-HBcAg was taken to be the independent variable. The outcome was taken to be grade 3 and 4 histopathological abnormality (septa with nodule formation and cirrhosis). RESULTS: 145 subjects were evaluated in this study. 47.2% of them were anti-HBcAg (+). The main risk factor for infection was blood and blood derivative transfusion (35.9%). Findings of anti-HBcAg (+) were not related to advanced liver fibrosis, although piecemeal necrosis has been found frequently in patients with this serological marker. CONCLUSIONS: Previous hepatitis B infection does not seem to increase the structural liver damage triggered by chronic hepatitis C virus infection, after statistical control for other co-factors capable to impact the natural history of this infection.

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          Most cited references26

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          Statistics review 14: Logistic regression

          This review introduces logistic regression, which is a method for modelling the dependence of a binary response variable on one or more explanatory variables. Continuous and categorical explanatory variables are considered.
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            Intrahepatic levels and replicative activity of covalently closed circular hepatitis B virus DNA in chronically infected patients.

            Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence in the natural course of chronic HBV infection and during prolonged antiviral therapy and serves as the template for the production of HBV pregenomic RNA (pgRNA), the primary step in HBV replication. In this study, we have developed and applied sensitive and specific quantitative real-time polymerase chain reaction (PCR) assays for the measurement of intrahepatic concentration, pgRNA production, and replicative activity of cccDNA in liver biopsy samples from 34 non-treated patients with chronic hepatitis B (CHB); 12 hepatitis B e antigen (HBeAg)(+) and 22 HBeAg(-). Median copy number for cccDNA was 1.5 per cell and for pgRNA significantly higher, 6.5 copies per cell, with a good correlation between cccDNA and pgRNA levels in all samples. In HBeAg(-) patients, median values of cccDNA and pgRNA levels were 10-fold and 200-fold lower than in HBeAg(+), respectively, reflecting the differences in viral activity and clinical characteristics of the two groups. Furthermore, the replicative activity of intrahepatic cccDNA was significantly lower in HBeAg(-) patients harboring mutant HBV strains than in HBeAg(+) patients: median 3.5 versus 101 pgRNA copies per cccDNA molecule. In conclusion, the levels of both HBV cccDNA, a marker of HBV persistence, and pgRNA, an indicator of viral replication, in the liver of chronically infected patients correlate with viral activity and the phase of HBV infection. The combined measurement of cccDNA and pgRNA levels provides valuable information on the presence and replicative activity of intrahepatic HBV cccDNA.
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              The hepatitis B virus persists for decades after patients' recovery from acute viral hepatitis despite active maintenance of a cytotoxic T-lymphocyte response.

              It is widely believed that the hepatitis B virus (HBV) is completely cleared by antiviral antibodies and specific cytotoxic T lymphocytes (CTLs) during acute viral hepatitis. We now demonstrate that traces of HBV are often detectable in the blood for many years after clinical recovery from acute hepatitis, despite the presence of serum antibodies and HBV-specific CTLs, which can be present at acute-stage levels. The strength of the CTL response to HBV following clinical recovery correlates with persistence of HBV DNA. It is of particular interest that HBV-specific CTLs from patients studied up to 23 years after clinical and serological recovery expressed activation markers (HLA-DR, CD69) indicating recent contact with antigen. These results suggest that sterilizing immunity to HBV frequently fails to occur after recovery from acute hepatitis and that traces of virus can maintain the CTL response for decades following clinical recovery, apparently creating a negative feedback loop that keeps the virus under control, perhaps for life.
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                Author and article information

                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba, MG, Brazil )
                0037-8682
                1678-9849
                August 2010
                : 43
                : 4
                : 416-420
                Affiliations
                [01] São Paulo SP orgnameUniversidade de São Paulo orgdiv1Faculdade de Medicina orgdiv2Hospital das Clínicas
                Article
                S0037-86822010000400016 S0037-8682(10)04300416
                afba2710-ea29-4a96-9e3f-37423429f900

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 26 December 2009
                : 25 May 2010
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 27, Pages: 5
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                SciELO Brazil

                Self URI: Texto completo somente em PDF (PT)
                Categories
                Artigos

                Hepatite C crônica,Hepatite B oculta,Anticorpos anti-hepatite B,Occult hepatitis B,Hepatitis B antibodies,Chronic hepatitis C

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