Recent trends in hepatitis A incidence in Brazil.

Hepatitis A incidence has been decreasing in Brazil since child vaccination was implemented in 2014. This trend was interrupted by an outbreak among adult male in São Paulo in 2017. This study was outlined to estimate whether the increase of hepatitis A cases among adult men in Brazil was restricted to São Paulo. Cases reported to the national surveillance system from 14 large cities of all Brazilian regions were analyzed. Trends in time series from 2012 to 2018 were estimated by Prais-Winsten regression. The outbreak in São Paulo extended to 2018. In Rio de Janeiro, the number of cases rose again, achieving the same levels reported before the vaccination era. Three of six cities from South and Southeast regions showed an upward trend in the number of cases among adult men (P < .005). The large cities in the other three Brazilian macroregions showed a decrease or stabilization of cases without an increase among male adults. The increase of hepatitis A virus (HAV) cases in Brazil has happened not only in São Paulo, but also in other cities of South and Southeast regions. The northernmost cities were not affected. A change in the epidemiological pattern of HAV infection is emerging in Southern Brazil.

Detection of hepatitis B activity in HBeAg-negative carriers with normal aminotransferase levels in central Brazil.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Hepatitis B virus (HBV) chronic infection may follow a benign course with low risk of cirrhosis or liver cancer. As differentiation of inactive status from HBeAg-negative chronic hepatitis B is often challenging, monitoring of inactive HBV carriers is important to detect viral relapse or formerly undetected activity. The incidence of hepatitis activity in HBeAg-negative carriers with normal aminotransferases was examined by retrospective analysis of a cohort of carriers who had been followed-up at a hospital in Central Brazil. All patients had remained free of evidence of liver disease and maintained normal aminotransferase levels throughout the first year of follow-up. The incidence density of chronic HBV activity was determined and an incidence curve was constructed using the Kaplan-Meier method. Cox regression models were developed to identify for surrogate markers of activity. RESULTS: Among the 224 patients who comprised the cohort, chronic HBV activity was detected in 30 during followup. The incidence density of activity was 11.8 per 100 person-years (95% confidence interval: 8.3-16.9). The results of Cox regression analysis indicated that chronic HBV activity was associated with entrance in the latter years of the period examined (p = 0.001) and initial normal aspartate aminotransferase (AST) levels close to the upper-normal value (p = 0.022). CONCLUSION: Normal AST levels near the upper-normal value may be an indicator of relapse or previously undetected activity, and should thus be monitored closely in HBeAg-negative HBV carriers, in whom risk of relapse should remain an important managing consideration.

Clinical profile of hepatitis B virus chronic infection in patients of Brazilian liver reference units.

PURPOSE: To assess data about chronic forms of hepatitis B virus (HBV) infection in Brazilian reference units, the Brazilian Society of Hepatology (SBH) performed a survey, with its associates spread throughout the country. METHODS: SBH members were contacted by electronic mail. They were asked for data from their liver units regarding chronically infected HBV patients between January 2005 and September 2007. All subjects with HBV surface antigenemia lasting more than 6 months were eligible. Patients who died after January 2005 were also included. RESULTS: Data from 24 units of 17 cities (12 Brazilian states) were obtained. These corresponded to 3,913 patients. Mean age was 39 years, ranging from 1 to 84 years. The northern region had the lowest mean age (35 years) and the southern region the highest (43 years). Most of the sampled people were white; 1,448 of 3,614 patients had chronic hepatitis B. Most of them were HBeAg negative (1.4:1). There were 1,695 (46.9%) inactive carriers of 3,614 HBV-infected patients and other 69 (1.9%) were considered as having immune-tolerant status. Hepatitis D coinfection was common among the Amazonian sample (n = 369). CONCLUSIONS: This large sample study shows important tendencies of chronic hepatitis B infection in Brazilian reference units, such as HBeAg-negative chronic hepatitis B cases overwhelming wild-type strains infected cases. Besides, hepatitis D occurs only among the Amazonian patients.

Prevalence of hepatitis B virus and risk factors in Brazilian non-injecting drug users.

Non-injecting drug users are at high-risk for acquiring hepatitis B virus (HBV), although the factors contributing to this increased risk are not known. In the present study, the overall and occult HBV infection prevalence rates were determined in a large population of non-injecting drug users in the Central-West region of Brazil. HBV genotypes and predictors of infection were also identified. A total of 852 individuals in 34 drug treatment centers were interviewed, and their serum samples were tested for the presence of HBV markers by ELISA. HBsAg and anti-HBc-positive samples were tested for HBV DNA by PCR. Samples with HBV DNA were genotyped by restriction fragment length polymorphism (RFLP). The overall prevalence of HBV infection was 14% (95% CI: 11.7-16.5). A multivariate analysis of risk factors showed that age >30 years, non-white race/ethnicity, duration of drug use >10 years, lifetime number of sexual partners >10, non-use of condoms, and HCV and HIV status were associated significantly with HBV infection. Of the 9 (1%) HBsAg-reactive samples, HBV DNA was present in 2/2 of HBeAg-positive and in 5/7 anti-HBe-positive samples. An occult HBV infection rate of 2.7% (3/110) was found among anti-HBc-positive individuals. All HBV DNA-positive samples were genotyped: seven were genotype A, two were genotype D, and one was genotype F. Finally, few individuals (8%) had serological evidence of a previous HBV vaccination. These findings indicate that preventive interventions are needed for both sexual and drug-related high-risk behavior. Additionally, non-injecting drug users should be targeted for HBV vaccination.

Hepatitis B virus genotypes and resistance mutations in patients under long term lamivudine therapy: characterization of genotype G in Brazil.

BACKGROUND: Lamivudine is an oral nucleoside analogue widely used for the treatment of chronic hepatitis B. The main limitation of lamivudine use is the selection of resistant mutations that increases with time of utilization. Hepatitis B virus (HBV) isolates have been classified into eight genotypes (A to H) with distinct geographical distributions. HBV genotypes may also influence pathogenic properties and therapeutic features. Here, we analyzed the HBV genotype distribution and the nature and frequency of lamivudine resistant mutations among 36 patients submitted to lamivudine treatment for 12 to 84 months. RESULTS: Half of the patients were homosexual men. Only 4/36 (11%) patients were HBV DNA negative. As expected for a Brazilian group, genotypes A (24/32 positive individuals, 75%), D (3/32, 9.3%) and F (1/32, 3%) were present. One sample was from genotype C, which is a genotype rarely found in Brazil. Three samples were from genotype G, which had not been previously detected in Brazil. Lamivudine resistance mutations were identified in 20/32 (62%) HBV DNA positive samples. Mean HBV loads of patients with and without lamivudine resistance mutations were not very different (2.7 x 107 and 6.9 x 107 copies/mL, respectively). Fifteen patients showed the L180M/M204V lamivudine resistant double mutation. The triple mutant rt173V/180M/204V, which acts as a vaccine escape mutant, was found in two individuals. The three isolates of genotype G were entirely sequenced. All three showed the double mutation L180M/M204V and displayed a large genetic divergence when compared with other full-length genotype G isolates. CONCLUSION: A high (55%) proportion of patients submitted to long term lamivudine therapy displayed resistant mutations, with elevated viral load. The potential of transmission of such HBV mutants should be monitored. The identification of genotypes C and G, rarely detected in South America, seems to indicate a genotype distribution different to that observed in non treated patients. Disparities in routes of transmission (genotype G seems to be linked to homosexual behavior) and in pathogenic properties (genotype C is very aggressive) among HBV genotypes may explain the presence of rare genotypes in the present work.

Hepatitis B virus genotypes circulating in Brazil: molecular characterization of genotype F isolates.

BACKGROUND: Hepatitis B virus (HBV) isolates have been classified in eight genotypes, A to H, which exhibit distinct geographical distributions. Genotypes A, D and F are predominant in Brazil, a country formed by a miscegenated population, where the proportion of individuals from Caucasian, Amerindian and African origins varies by region. Genotype F, which is the most divergent, is considered indigenous to the Americas. A systematic molecular characterization of HBV isolates from different parts of the world would be invaluable in establishing HBV evolutionary origins and dispersion patterns. A large-scale study is needed to map the region-by-region distribution of the HBV genotypes in Brazil. RESULTS: Genotyping by PCR-RFLP of 303 HBV isolates from HBsAg-positive blood donors showed that at least two of the three genotypes, A, D, and F, co-circulate in each of the five geographic regions of Brazil. No other genotypes were identified. Overall, genotype A was most prevalent (48.5%), and most of these isolates were classified as subgenotype A1 (138/153; 90.2%). Genotype D was the most common genotype in the South (84.2%) and Central (47.6%) regions. The prevalence of genotype F was low (13%) countrywide. Nucleotide sequencing of the S gene and a phylogenetic analysis of 32 HBV genotype F isolates showed that a great majority (28/32; 87.5%) belonged to subgenotype F2, cluster II. The deduced serotype of 31 of 32 F isolates was adw4. The remaining isolate showed a leucine-to-isoleucine substitution at position 127. CONCLUSION: The presence of genotypes A, D and F, and the absence of other genotypes in a large cohort of HBV infected individuals may reflect the ethnic origins of the Brazilian population. The high prevalence of isolates from subgenotype A1 (of African origin) indicates that the African influx during the colonial slavery period had a major impact on the circulation of HBV genotype A currently found in Brazil. Although most genotype F isolates belonged to cluster II, the presence of some isolates belonging to clusters I (subgroup Ib) and IV suggests the existence of two or more founder viral populations of genotype F in Brazil.

Infection by the hepatitis C virus in chronic renal failure patients undergoing hemodialysis in Mato Grosso state, central Brazil: a cohort study.

BACKGROUND: Hepatitis C virus (HCV) is a significant problem for patients undergoing hemodialysis therapy. This situation has never been studied in Mato Grosso state, central Brazil. This study was conducted aiming to estimate the prevalence of the anti-HCV and the incidence of seroconversion in the main metropolitan region of the state. METHODS: 433 patients from the six hemodialysis units were interviewed and anti-HCV was tested by a third-generation enzyme immunoassay. An open cohort of patients who tested negative for anti-HCV at the entry of the study was created and seroconversions was assessed monthly. The staff responsible for the units were interviewed to assess whether the infection control measures were being followed. Logistic and Cox regression analysis were performed in order to assess risk factor to HCV. RESULTS: The entry on the study took place between January 2002 and June 2005. 73 out of 433 (16.9%, CI 95%: 13.3-20.8) was found to be anti-HCV reactive. The multivariate analysis indicated as risk factors associated to anti-HCV the duration of the hemodialysis treatment, the number of transfusions received, and the unit of treatment. An open cohort of 360 patients who tested negative for anti-HCV was created, with a following average of 24 (+/- 15) months. Forty seroconversions were recorded corresponding to an incidence density of 4.6/1000 patient-months, ranges 0 to 30 among the units. Cox regression indicated the time of hemodialysis (RR = 2.2; CI 95%: 1.1-4.6; p < 0.05) and the unit where treatment was performed (RR = 42.4; CI 95%: 9.9-180.5; p < 0.05) as risk factors for seroconversion. The three units with highest anti-HCV prevalence and incidence were identified as those that more frequently failed to apply control measures. CONCLUSION: The study demonstrated high prevalence and incidence of anti-HCV in some of the hemodialysis units. Time on hemodialysis therapy was an independent factor associated to HCV. Blood transfusion was associated with anti-HCV in initial survey but was not important in incident cases. Failure of applying control measures was more evident in units with the highest HCV prevalence and incidence. The results suggest that nosocomial transmission was the main spread factor of HCV in the studied population.

Distribution of hepatitis C virus genotypes among blood donors from mid-west region of Brazil.

In order to investigate the hepatitis C virus (HCV) genotypes in mid-west region of Brazil, 250 anti-HCV positive blood donors were studied. Among them, the anti-HCV serological status was confirmed in 205 (82%). HCV RNA was detected in 165 samples, which were genotyped. HCV types 1, 2 and 3 were found in 67.9%, 3% and 29.1% of the donors, respectively. In Goiás state, subtype 1a (50%) was the most prevalent, followed by subtypes 3a (30.9%) and 1b (16.7%). In Mato Grosso state, subtype 1a was also predominant (41%), followed by subtypes 1b (29.5%) and 3a (25%). In Mato Grosso do Sul state, subtypes 1a and 1b were detected equally (36.8%), followed by 3a (21.1%). Subtype 2b was rare (2.4%, 4.5% and 5.3%, respectively). In Distrito Federal, subtype 3a (39%) was more frequent than 1a (31.7%) and the remaining (29.3%) belonged to subtype 1b.

Distribution of hepatitis C virus genotypes among blood donors from mid-west region of Brazil

Com objetivo de determinar os genótipos do vírus da hepatite C (HCV) circulantes na Região Centro-Oeste do Brasil, 250 doadores de sangue anti-HCV positivos foram estudados. Dentre eles, a positividade para anti-HCV foi confirmada em 205 (82%). O RNA-HCV foi detectado em 165 amostras, as quais foram genotipadas. Os tipos 1, 2 e 3 do HCV foram encontrados em 67,9%, 3% e 29,1% dos doadores, respectivamente. No Estado de Goiás, o subtipo 1a (50%) foi o mais prevalente, seguido pelos subtipos 3a (30,9%) e 1b (16,7%). No Estado de Mato Grosso, o subtipo 1a (41%) foi também predominante, seguido pelos subtipos 1b (29,5%) e 3a (25%). No Estado de Mato Grosso do Sul, os subtipos 1a e 1b foram igualmente detectados (36,8%), seguidos por 3a (21,1%). O subtipo 2b foi raro (2,4%, 4,5% e 5,3%, respectivamente). No Distrito Federal, o subtipo 3a (39%) foi mais freqüente que 1a (31,7%), sendo o restante (29,3%) identificado como subtipo 1b.