High prevalence of occult hepatitis B virus genotype H infection among children with clinical hepatitis in west Mexico

Studies on the prevalence of infection with hepatitis B virus (HBV) among children are scarce in Latin American countries, especially in Mexico. This study was aimed to investigate the prevalence of HBV infection, occult hepatitis B infection (OBI) and HBV genotypes among children with clinical hepatitis. In total, 215 children with clinical hepatitis were evaluated for HBV infection. HBV serological markers and HBV DNA were analysed. OBI diagnosis and HBV genotyping was performed. HBV infection was found in 11.2% of children with clinical hepatitis. Among these HBV DNA positive-infected children, OBI was identified in 87.5% (n = 21/24) of the cases and 12.5% (n = 3/24) were positive for both HBV DNA and hepatitis B surface antigen. OBI was more frequent among children who had not been vaccinated against hepatitis B (p < 0.05) than in those who had been vaccinated. HBV genotype H was prevalent in 71% of the children followed by genotype G (8%) and genotype A (4%). In conclusion, OBI is common among Mexican children with clinical hepatitis and is associated with HBV genotype H. The results show the importance of the molecular diagnosis of HBV infection in Mexican paediatric patients with clinical hepatitis and emphasise the necessity of reinforcing hepatitis B vaccination in children.

Is it necessary to delay antiviral therapy for 3-6 months to anticipate HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B in endemic areas of HBV genotype C?

BACKGROUND/AIMS: Spontaneous HBeAg seroconversion occurs frequently in the immune reactive phase in HBeAg-positive chronic hepatitis B (CHB). Therefore, observation for 3-6 months before commencing antiviral therapy is recommended in patients with alanine aminotransferase (ALT) levels that exceed twice the upper limit of normal (ULN). However, HBeAg seroconversion occurs infrequently in patients infected with hepatitis B virus (HBV) genotype C. The aim of the present study was to determine whether the waiting policy is necessary in endemic areas of HBV genotype C infection. METHODS: Ninety patients with HBeAg-positive CHB were followed prospectively without administering antiviral therapy for 6 months. Antiviral therapy was initiated promptly at any time if there was any evidence of biochemical (i.e., acute exacerbation of HBV infection or aggravation of jaundice) or symptomatic deterioration. After 6 months of observation, antiviral therapy was initiated according to the patient's ALT and HBV DNA levels. RESULTS: Only one patient (1.1%) achieved spontaneous HBeAg seroconversion. Biochemical and symptomatic deterioration occurred before 6 months in 17 patients (18.9%) and 5 patients, respectively. High ALT and HBV DNA levels were both independent risk factors for biochemical deterioration. Of 15 patients with HBV DNA > or =5.1x107 IU/mL and ALT > or =5xULN, biochemical deterioration occurred in 7 (46.7%), including 1 patient receiving liver transplantation due to liver failure. CONCLUSIONS: Spontaneous HBeAg seroconversion in patients with HBeAg-positive CHB is rare within 6 months. Biochemical deterioration was common and may lead to liver failure. Immediate antiviral therapy should be considered, especially in patients with high ALT and HBV DNA levels in endemic areas of genotype C infection.

Multiple cytokine expression profiles reveal immune-based differences in occult hepatitis B genotype H-infected Mexican Nahua patients

A high prevalence of occult hepatitis B (OHB) genotype H infections has been observed in the native Mexican Nahua population. In addition, a low incidence of hepatitis B virus (HBV)-associated hepatocellular carcinoma has been described in Mexico. The immune response to infection among OHB-infected patients has been poorly evaluated in vivo. Therefore, we assessed the expression profiles of 23 cytokines in OHB genotype H-infected Nahua patients. A total of 41 sera samples from natives of the Nahua community were retrospectively analysed. Based on their HBV antibody profiles, patients were stratified into two groups: OHB patients (n = 21) and patients that had recovered from HBV infection (n = 20). Herein, we report distinctive cytokines profiles in OHB-infected individuals. Compared to healthy controls (n = 20) and patients who resolved HBV infection, OHB-infected patients displayed an increase in interleukin (IL)-2 secretion in addition to a characteristic inflammation profile (decrease in IL-8 and tumour necrosis factor-alpha levels and increased levels of tumour growth factor-beta). IL-15 and interferon-gamma levels were reduced in OHB-infected individuals when compared to those patients who resolved HBV infection. In contrast, OHB patients showed an increase in monocyte chemoattractant protein (MCP)-1 and MCP-2 compared to healthy controls and patients who resolved HBV infection. These findings suggest that cytokine expression can influence the severity of OHB disease and could lead to new investigation into the treatment of liver and other infectious diseases.

Hepatitis B virus genotyping among chronic hepatitis B patients with resistance to treatment with lamivudine in the City of Ribeirão Preto, State of São Paulo / Genotipagem do vírus da hepatite B de pacientes crônicos com resistência ao tratamento com lamivudina na Cidade de Ribeirão Preto, Estado de São Paulo

INTRODUCTION: Lamivudine is a nucleoside analogue that is used clinically for treating chronic hepatitis B infection. However, the main problem with prolonged use of lamivudine is the development of viral resistance to the treatment. Mutations in the YMDD motif of the hepatitis B virus DNA polymerase gene have been associated with resistance to drug therapy. So far, there have not been many studies in Brazil reporting on genotype-dependent development of resistance to lamivudine. Thus, the aim of the present study was to determine the possible correlation between a certain genotype and increased development of resistance to lamivudine among chronic hepatitis B patients. METHODS: HBV DNA in samples from 50 patients under lamivudine treatment was amplified by means of conventional PCR. Samples were collected at Hospital das Clínicas, FMRP-USP. The products were then sequenced and phylogenetic analysis was performed. RESULTS: Phylogenetic analysis revealed that 29 (58 percent) patients were infected with genotype D, 20 (40 percent) with genotype A and one (2 percent) with genotype F. Mutations in the YMDD motif occurred in 20 percent of the patients with genotype A and 27.6 percent of the patients with genotype D. CONCLUSIONS: Despite the small number of samples, our results indicated that mutations in the YMDD motif were 1.38 times more frequent in genotype D than in genotype A.

INTRODUÇÃO: Lamivudina é um análogo de nucleosídeo clinicamente utilizado para o tratamento da infecção crônica pela hepatite B. Entretanto, o principal problema do uso prolongado da lamivudina é o desenvolvimento de resistência viral ao tratamento. Mutações no motivo YMDD no gene da DNA polimerase do vírus da hepatite B estão associados com a resistência a terapia medicamentosa. Até o presente momento, não há muitos estudos no Brasil que descrevem o desenvolvimento genótipo-dependente da resistência à lamivudina. Assim, o intuito do trabalho aqui descrito foi determinar a possível correlação entre um determinado genótipo e o desenvolvimento aumentado da resistência à lamivudina em pacientes com hepatite B crônica. MÉTODOS: O HBV DNA foi amplificado por PCR convencional a partir de 50 amostras coletadas de pacientes submetidos ao tratamento com lamivudina no Hospital das Clínicas- FMRP- USP. Posteriormente, os produtos foram seqüenciados e a análise filogenética foi realizada. RESULTADOS: A análise filogenética mostrou que 29 (58 por cento) pacientes foram infectados com o genótipo D, 20 (40 por cento) com o genótipo A e 1 (2 por cento) com o genótipo F. Mutações no motivo YMDD ocorreu em 20 por cento dos pacientes com genótipo A e 27,6 por cento em pacientes do genótipo D. CONCLUSÕES: Apesar do baixo número de amostras, nossos resultados indicaram que mutações no motivo YMDD são 1,38 X mais frequentes no genótipo D em relação ao genótipo A.

Distribution of hepatitis B virus genotypes and viral load levels in Brazilian chronically infected patients in São Paulo city / Distribuição dos genótipos do vírus da hepatite B e níveis de carga viral em pacientes brasileiros cronicamente infectados na cidade de São Paulo

The objective of the present study was to evaluate the serum viral load in chronically infected Hepatitis B virus (HBV) patients and to investigate the distribution of HBV genotypes in São Paulo city. Quantitative HBV-DNA assays and HBV genotyping have gained importance for predicting HBV disease progression, have been employed for assessing infectivity, for treatment monitoring and for detecting the emergence of drug resistance. Twenty-nine Brazilian patients with suspected chronic hepatitis B were studied, using real time PCR for viral load determination and direct DNA sequencing for the genotyping. The serology revealed chronic HBV infection in 22 samples. The HBV-DNA was positive in 68 percent samples (15/22). The phylogenetic analysis disclosed that eleven patients were infected with HBV genotype A, two with genotype F and two with genotype D. Thus, the genotype A was the most prevalent in our study.

O objetivo do presente estudo foi avaliar a carga viral no soro de pacientes cronicamente infectados pelo vírus da Hepatite B (HBV) e investigar a distribuição de genótipos HBV na cidade de São Paulo. PCR quantitativo do HBV e genotipagem ganharam importância para a previsão de progressão da doença, empregada para avaliar a infectividade, para tratamento e acompanhamento e para detectar o aparecimento de resistência aos anti-retrovirais. Vinte e nove pacientes brasileiros com suspeita de hepatite B crônica foram estudados, utilizando PCR em tempo real para a determinação da carga viral e seqüenciamento direto para determinação do genótipo. A sorologia revelou que 22 estavam, de fato, cronicamente infectados pelo HBV. O HBV-DNA foi positivo em 68 por cento das amostras (15/22). Em sete casos, HBV-DNA foi indetectável por PCR quantitativo. A análise filogenética mostra que onze pacientes foram infectados com hepatite B genótipo A, dois com genótipo F e dois com genótipo D. Desta forma, o genótipo A foi o mais prevalente em nosso estudo.

Hepatitis B virus genotype E detected in Brazil in an African patient who is a frequent traveler

Genotype E of hepatitis B virus (HBV) has not been described in Brazil and is found mainly in Africa. Genotype A is the most prevalent in Brazil, and genotypes B, C, D, and F have already been reported. We report here an HBV genotype E-infected patient and some characterization of surface (S) protein, DNA polymerase (P) and precore/core (preC/C) coding regions based on the viral genome. The patient is a 31-year-old black man with chronic hepatitis B who was born and raised in Angola. He has been followed by a hepatologist in São Paulo, Brazil, since November 2003, and he is a frequent traveler to Latin America, Africa, and Europe. In 2003, he was diagnosed with HBV infection and started treatment with lamivudine with the later addition of adefovir dipivoxil. No known risk factor was identified. Serologically, he is HBsAg and anti-HBe positive, but HBeAg and anti-HBs negative. DNA sequence analysis of the S/P region confirmed that this patient is infected with genotype E, subtype ayw4. The preC/C region showed G1896A and G1899A mutations but no mutations in the basal core promoter. Nucleotide substitutions common in genotype E were also observed (C1772, T1858 and A1757). Although this is not an autochthonous case and there is no evidence of further spread, the description of this case in Brazil highlights the current risk of viral genotypes spreading with unprecedented speed due to constant travel around the world.

Distribution of Hepatitis B Virus Genotypes according to the Clinical Outcomes in Patients with Chronic Hepatitis B Virus Infection in Jeju Island / 대한소화기학회지

BACKGROUND/AIMS: The genotype of hepatitis B virus (HBV) has been suggested to correlate with the clinical outcome of HBV infection. We analyzed the distribution of HBV genotypes according to the clinical outcomes of HBV infection in Jeju island. METHODS: A total of 145 HBsAg-positive samples were enrolled. To identify specific patterns of HBV genotypes, we performed restriction fragment length polymorphism (RFLP). In the case that typical restriction pattern of RFLP was not determined, phylogenetic analysis was performed. RESULTS: RFLP analysis was possible in 65 patients. Clinical diagnoses of the 65 patients with chronic liver disease were as follows: HBeAg-positive healthy carrier (HBeAg+, anti-HBe, HBV DNA+, transaminase normal; n=20); Inactive HBsAg carrier (n=12); chronic hepatitis B (n=14); liver cirrhosis (n=9); hepatocellular carcinoma (n=10). Sixty-two patients showed a typical restriction pattern by HinfI. However, 3 patients showed a unique restriction pattern by HinfI, which were not reported in the literature. When phylogenetic analysis was performed to classify the genotype of these 3 patients, they were also genotype C. However, all 65 patients showed typical restriction patterns by Tsp509I, which were reported in genotype C. CONCLUSIONS: All chronic HBV infections are genotype C in Jeju island regardless of clinical outcomes.