Seroprevalence of SARS-CoV-2 in Brazil: A systematic review and meta-analysis

Abstract Objectives To summarize the data on SARS-CoV-2 seroprevalence surveys conducted in Brazil before the introduction of vaccines Methods The authors conducted a systematic review and meta-analysis on the seroprevalence of SARS-CoV-2 infection in Brazil. The present review followed the PRISMA guidelines. The authors searched Medline, Embase, and LILACS databases for serologic surveys conducted in the Brazilian population, in the period from 01/10/2019 to 07/11/2021, without language restrictions. The authors included studies that presented data concerning SARS-CoV-2 antibodies seroprevalence in Brazil and had a sample size ≥50 individuals. Considering the expected heterogeneity between studies, all analyses were performed using the random effects model, and heterogeneity was assessed using the I2 statistic Results Of 586 publications identified in the initial searches, 54 were included in the review and meta-analysis, which contained the results of 135 surveys, with 336,620 participants. The estimated seroprevalence was 11.0%, ranging from 1.0% to 83.0%, with a substantial heterogeneity (I2= 99.55%). In subgroup analyses, the authors observed that the prevalence of SARS-CoV-2 antibodies was 13.0% in blood donors, 9.0% in the population-based surveys, 13% in schoolchildren, and 11.0% in healthcare workers. Conclusions Seroprevalence increases over time. Large differences were observed among the regions of the country. It was higher in the Northern region, decreasing towards the South. The present results may contribute to the analysis of the spread of SARS-CoV-2 infection in the Brazilian population before vaccination, one of the factors that may be influencing the clinical presentation of COVID-19 cases related to the new variants, as well as the effectiveness of the vaccination program.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Quantification of C4d deposition and hepatitis C virus RNA in tissue in cases of graft rejection and hepatitis C recurrence after liver transplantation

Histology is the gold standard for diagnosing acute rejection and hepatitis C recurrence after liver transplantation. However, differential diagnosis between the two can be difficult. We evaluated the role of C4d staining and quantification of hepatitis C virus (HCV) RNA levels in liver tissue. This was a retrospective study of 98 liver biopsy samples divided into four groups by histological diagnosis: acute rejection in patients undergoing liver transplant for hepatitis C (RejHCV+), HCV recurrence in patients undergoing liver transplant for hepatitis C (HCVTx+), acute rejection in patients undergoing liver transplant for reasons other than hepatitis C and chronic hepatitis C not transplanted (HCVTx-). All samples were submitted for immunohistochemical staining for C4d and HCV RNA quantification. Immunoexpression of C4d was observed in the portal vessels and was highest in the HCVTx- group. There was no difference in C4d expression between the RejHCV+ and HCVTx+ groups. However, tissue HCV RNA levels were higher in the HCVTx+ group samples than in the RejHCV+ group samples. Additionally, there was a significant correlation between tissue and serum levels of HCV RNA. The quantification of HCV RNA in liver tissue might prove to be an efficient diagnostic test for the recurrence of HCV infection.

Prevalence of hepatitis C virus in Brazil's inmate population: a systematic review / Prevalência do vírus da hepatite C na população carcerária do Brasil: revisão sistemática

OBJECTIVE To estimate the prevalence of hepatitis C virus infection in Brazil's inmate population.METHODS Systematic review on hepatitis C virus infection in the inmate population. Brazilian studies published from January 1, 1989 to February 20, 2014 were evaluated. The methodological quality of the studies was assessed using a scale of 0 to 8 points.RESULTS Eleven eligible studies were analyzed and provided data on hepatitis C virus infection among 4,375 inmates from seven states of Brazil, with a mean quality classification of 7.4. The overall hepatitis C virus prevalence among Brazilian inmates was 13.6% (ranging from 1.0% to 41.0%, depending on the study). The chances of inmates being seropositive for hepatitis C virus in the states of Minas Gerais (MG), Sergipe (SE), Mato Grosso do Sul (MS), Rio Grande do Sul (RS), Goiás (GO) and Espirito Santo (ES) were 84.0% (95%CI 0.06;0.45), 92.0% (95%CI 0.04;0.13), 88.0% (95%CI 0.09;0.18), 74.0% (95%CI 0.16;0.42), 84.0% (95%CI 0.08;0.31) and 89.0% (95%CI 0.01;0.05) respectively, lower than that observed in the Sao Paulo state (seroprevalence of 29.3%). The four studies conducted in the city of Sao Paulo revealed a lower prevalence in more recent studies compared to older ones.CONCLUSIONS The highest prevalence of hepatitis C virus infection in Brazil's inmate population was found in Sao Paulo, which may reflect the urban diversity of the country. Despite Brazilian studies having good methodological quality to evaluate the prevalence of the hepatitis C virus, they are scarce and lack data on risk factors associated with this infection, which could support decisions on prevention and implementation of public health policies for Brazilian prisons.

RESUMOOBJETIVO Estimar prevalência de infecção pelo vírus da hepatite C entre a população carcerária no Brasil.MÉTODOS Revisão sistemática sobre infecção pelo vírus da hepatite C em populações carcerárias. Foram avaliados estudos brasileiros publicados a partir de 1 de janeiro de 1989 até 20 de fevereiro de 2014. A qualidade metodológica dos estudos foi avaliada utilizando-se escala de zero a oito pontos.RESULTADOS Onze estudos elegíveis foram analisados, os quais forneceram dados sobre a infecção pelo vírus da hepatite C de 4.375 detentos de sete estados do Brasil, com classificação em média de qualidade de 7,4. A prevalência de infecção pelo vírus da hepatite C na população carcerária brasileira foi 13,6%, (variando de 1,0% a 41,0%, dependendo do estudo). As chances de os indivíduos serem soropositivos para o vírus da hepatite C nos estados de Minas Gerais, Sergipe, Mato Grosso do Sul, Rio Grande do Sul, Goiás e Espírito Santo foram 84,0% (IC95% 0,06;0,45), 92,0% (IC95% 0,04;0,13), 88,0% (IC95% 0,09;0,18), 74% (IC95% 0,16;0,42), 84,0% (IC95% 0,08;0,31) e 89,0% (IC95% 0,01;0,05), respectivamente, inferiores àquela observada no estado de São Paulo (soroprevalência de 29,3%). Os quatro estudos realizados na cidade de São Paulo mostraram menor prevalência em estudos mais recentes em comparação aos mais antigos.CONCLUSÕES A maior prevalência de infecção pelo vírus da hepatite C em população carcerária do Brasil foi encontrada em São Paulo, o que pode refletir a diversidade urbana do País. Apesar de os estudos brasileiros apresentarem boa qualidade metodológica para avaliação da prevalência do vírus da hepatite C, são escassos e faltam dados sobre fatores de risco associados a esta infecção, dados esses que poderiam auxiliar nas decisões de prevenção e implementação de políticas em saúde pública para as prisões brasileiras.

Hepatitis C virus: molecular and epidemiological evidence of male-to-female transmission

INTRODUCTION: There is general consensus that hepatitis C virus is efficiently transmitted by the parenteral route, whereas data on viral transmission by sexual or non-sexual intrafamilial contact are conflicting. OBJECTIVE AND METHOD: The aim of this study was to investigate the transmission of hepatitis C virus in nine heterosexual couples. RESULT: The mean age of the couples was 43.7 years. When interviewed, all of the women denied the presence of risk factors for acquisition of the infection, whereas the cause of infection in the nine husbands could be attributed to blood transfusions in two of them (22.2 percent), use of intravenous and inhaled drugs in six (66.7 percent), acupuncture in one (11.1 percent), and tattooing in one (11.1 percent). All men and none of the women reported sexual relations with sex professionals. The mean homology score (Non Structural 5b-hepatitis C virus) was 98.4 percent. Among the nine couples with matching subtypes, one (11.1 percent) was infected with subtype 1a, three (33.3 percent) with subtype 1b, and five (55.5 percent) with subtype 3a. Shared personal hygiene items showed a much higher correlation with the possible route of transmission and were better supported by the sequence homology data than the other associated risk factors. Three (33.3 percent) couples shared toothbrushes, seven (77.8 percent) shared razor blades, eight (88.8 percent) shared nail clippers, and six (66.7 percent) shared manicure cutters. CONCLUSION: Sharing of personal hygiene items was a confounding factor in the discussion of sexual hepatitis C virus transmission and the hypothesis of male-to-female transmission was supported in this study.

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 / Influence of previous hepatitis B virus infection on liver fibrosis in patients with chronic hepatitis C: a retrospective case series evaluation

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 por cento com anti-HBcAg (+). O fator de risco mais comumente relatado foi transfusão de sangue e hemoderivados (35,9 por cento). 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.

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 percent of them were anti-HBcAg (+). The main risk factor for infection was blood and blood derivative transfusion (35.9 percent). 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.

Hepatitis C: sexual or intrafamilial transmission? Epidemiological and phylogenetic analysis of hepatitis C virus in 24 infected couples / Hepatite C: transmissão sexual ou intrafamiliar? Análise epidemiológica e filogenética do vírus da hepatite C em 24 casais infectados

The role of sexual or intrafamilial transmission of hepatitis C is controversial. A phylogenetic analysis was performed on the non-structural region 5B of the hepatitis C virus (NS5B-HCV). High percentages of homology (mean of 98.3 percent) were shown between the couples. Twenty (83.3 percent) of the 24 men but only two of the women (8.3 percent) reported having had sexually transmitted diseases during their lives. The risk factors for HCV acquisition were blood transfusion (10 couples), use of illegal injected drugs (17), use of inhalants (15), acupuncture (5) and tattoos (5). The shared use of personal hygiene items included toothbrushes between six couples (25 percent), razor blades between 16 (66.7 percent), nail clippers between 21 (87.5 percent) and manicure pliers between 14 (58.3 percent). The high degree of similarity of the hepatitis C virus genome supports the hypothesis of hepatitis C virus transmission between these couples. The shared use of personal hygiene items suggests the possibility of intrafamilial transmission of infection.

O papel da transmissão sexual ou intrafamiliar da hepatite C é controverso. Foi feita análise filogenética, região não estrutural 5B do vírus da hepatite C (NS5B-HCV). Altas percentagens de homologia com média de 98,3 por cento foi revelada entre os casais. Vinte (83,3 por cento) de 24 homens, contra apenas duas (8,3 por cento) mulheres reportaram doença sexualmente transmisível durante suas vidas. Os fatores de risco para aquisição da doença foram: transfusão de sangue para 10 casais, uso de drogas ilícitas injetáveis para 17, inalatórias para 15, acupuntura em 5 e tatuagens para 5. O compartilhamento de utensílios de higiene pessoal incluem: escova de dente para seis (25 por cento) dos casais, lâmina de barbear para 16 (66,7 por cento), cortador de unhas para 21 (87,5 por cento) e alicate de manicure para 14 (58,3 por cento). O alto grau de similaridade genômica entre os vírus da hepatite C suporta a hipótese de transmissão entre os casais. O uso compartilhado de utensílios de higiene pessoal sugere a possibilidade de transmissão intrafamiliar.

Detection of HCV by PCR in serum and PBMC of patients with hepatitis C after treatment

Although hepatitis C is mainly hepatotropic, some studies suggest that hepatitis C virus (HCV) infects peripheral blood mononuclear cells (PBMC), using them as a reservoir, which might contribute to the development of resistance to treatment. Fifty-four hepatitis-C patients, who had been submitted to treatment, were selected. Blood samples were collected on the same day for the detection of HCV RNA in serum and PBMC by PCR, using the Amplicor HCV 2.0 assay (Roche Diagnostics). HCV genotyping was performed using the INNO-LiPA HCV kit (Versant, Bayer Diagnostics). HCV RNA was detected in both serum and PBMC in 35 (64 percent) patients and no RNA in 16 (29.6 percent). Disagreement between the serum and PBMC results was observed for three patients (5.6 percent), with HCV RNA being detected in PBMC but not in serum. Four months later, new serum and PBMC samples were collected from one of these patients and HCV RNA was detected in both samples, showing that PBMC can reveal signs of a lack of response to treatment. We conclude that the absence of HCV in the serum of patients with chronic hepatitis C by the end of treatment does not mean that there is no circulating virus. HCV in mononuclear cells may be an indicator of the persisting infection.

Fatores associados às formas evolutivas graves da infecção crônica pelo vírus da hepatite C / Factors associated with severe evolutive forms of chronic infection with hepatitis c virus

Com o objetivo de descrever os fatores epidemiológicos e clínicos-laboratoriais e avaliar os fatores associados ao desenvolvimento de fibrose moderada e grave, realizou-se a revisão de 426 prontuários médicos de pacientes com infecção crônica pelo vírus da hepatite C, atendidos na Clínica de Moléstias Infecciosas e Parasitárias da Faculdade de Medicina da Universidade de São Paulo, no período de 01/01 a 31/12/2000. Dos pacientes incluídos no estudo, 56,3 por cento eram do sexo masculino e 43,7 por cento do sexo feminino. A idade deles variou de 18 a 69 anos. A hemotransfusão foi a forma mais freqüente de transmissão do vírus da hepatite C, encontrada em 128 (30 por cento) dos casos e em 187 (43,9 por cento) pacientes não foi encontrado nenhum fator de risco. A distribuição dos pacientes quanto à alteração arquitetural visto na biópsia hepática foi: grau 0 (14,1 por cento), grau 1 (51,2 por cento), grau 2 (20,6 por cento), grau 3 (8 por cento) e grau 4 (6,1 por cento). Na análise multivariada, encontramos associação positiva entre intensidade da fibrose e idade maior que 40 anos na data da biópsia hepática, níveis séricos de albumina abaixo do limite inferior normal, gama-glutamiltransferase maior ou igual a duas vezes o limite superior da normalidade, plaquetas em número menor que 150.000/mm³ e alta atividade necro-inflamatória. Os dados foram inconclusivos para testar a associação entre gravidade da fibrose e alcoolismo.

To assess the factors associated with the development of moderate and severe fibrosis, the medical records of 426 patients with chronic hepatitis C virus infection attended at the Infectious and Parasitic Diseases Clinic of the University of São Paulo Faculty of Medicine from January 1 to December 31, 2000 were reviewed. Of the patients included in the study, 56.3 percent were male and 43.7 percent, female. Patient age ranged from 18 to 69 years. Blood transfusion was the most frequent form of hepatitis C virus transmission, detected in 128 (30 percent) cases, and no risk factor was detected in 187 (43.9 percent) patients. Patient distribution regarding architectural changes observed in a liver biopsy was: grade 0 (14.1 percent); grade 1 (51.2 percent); grade 2 (20.6 percent); grade 3 (8 percent); grade 4 (6.1 percent). Multivariate analysis revealed a positive correlation between fibrosis severity and age greater than 40 years at the time of the liver biopsy, serum albumin levels below normal lower limits, gamma-glutamyltransferase levels equal to or higher than twice upper normal limits, platelet numbers less than 150,000/mm³ and high necroinflammatory activity. The data obtained were inconclusive regarding a possible correlation between severity of fibrosis and alcoholism.

Patients with chronic hepatitis C and normal transaminases

Hepatite C é uma doença de evolução progressiva. A maioria dos pacientes tem nível de ALT elevada e 25% apresentam níveis normais. Os com ALT normal geralmente são do gênero feminino e sem associação entre genótipo e gravidade de lesão hepática. O exame histopatológico mostra geralmente ausência de ou leve fibrose (cerca de 20% tem fibrose), embora cirrose já tenha sido relatada. Visando estimar a prevalência, características demográficas, genotípicas e anatomopatológicas em pacientes com ALT normal, realizamos um estudo de série com 68 casos com diagnóstico de hepatite C crônica. Os pacientes foram selecionados de janeiro de 1977 a abril de 2002. Encontrou-se uma prevalência de 13,8% (45,6% masculinos). A média de idade foi 39 +/- 13 anos. Predomínio de genótipo 1 (84,8%), seguido pelo 3 (8,5%) e 2 (6,7%). Encontramos fígado reacional em 52,9% das biópsias, atividade periportal de 0-1 em 85,3% e atividade periportal de 2-4 em 14,7%. Apresentaram atividade estrutural de 0 a 1 73,5% e 26,5% com atividade estrutural de 2 a 4, sendo que 29% da amostra apresentou APP > 2 e AE > 1; 73,5% não apresentaram esteatose. Nossos dados reforçam a necessidade de biópsia em pacientes com hepatite C e níveis de ALT normais.

Are anti-interferon antibodies the cause of failure in: chronic HCV hepatitis treatment?

A follow-up study was made of 94 chronic hepatitis C patients at a hepatitis clinic in Brazil, after interferon alpha (IFN-alpha) therapy, to determine the influence of anti-interferon antibodies on treatment outcome. Patients diagnosed as having chronic hepatitis C, confirmed by PCR (HCV RNA) and liver biopsy, were treated with interferon alpha 2a or 2b for at least six months, and were followed up for 24 weeks after termination of treatment in order to assess biochemical, virological and clinical pathology responses. Only 6 percent of the 94 patients developed anti-IFN antibodies, 70 percent presented a biochemical response and 23 percent maintained a sustained virological response. Clinical evaluation revealed that in only 2 patients was there progression of fibrosis; the necro-inflammatory score indicated that 72 percent maintained the same activity, 12 percent had worsening necro-inflammatory activity, and the remaining 16 percent had decreased activity. There was no significant correlation of demographic and laboratory variables with levels of anti-interferon antibodies. Similarly, biochemical and virological responses were not influenced by anti-interferon antibodies. Multivariate analysis by logistic regression revealed that clinical pathological parameters, staging and necro-inflammatory activity did not influence the response to the virus.

Sexual transmission of hepatitis C virus

In order to contribute to a better understanding of the forms of acquisition of hepatitis C virus (HCV) in Brazil, with special emphasis on sexual transmission, we determined the presence of HCV infection in regular partners and in non-sexual home communicants of blood donors seen at Fundaçäo Pró-Sangue Hemocentro de Säo Paulo from January 1992 to July 1996. Of 154 blood donors with HCV infection (index cases), 111 had had regular partners for at least 6 months. Sixty-eight of 111 partners were evaluated for HCV infection. Of these, 8 (11.76 percent) were considered to have current or previous HCV infection; a history of sexually transmissible diseases and index cases with a positive HCV-RNA test were more prevalent among partners with HCV infection. Of the 68 index cases whose partners were studied, 56 had non-sexual home communicants. Of the total of 81 home communicants, 66 accepted to be evaluated for HCV infection. None of them was HCV-positive, suggesting that the high prevalence of HCV infection among partners may be attributed at least partially to sexual transmission

Prevalence of hepatitis B and C in the sera of patients with HIV infection in São Paulo, Brazil

The objective of this study was to evaluate the prevalence of hepatitis B and C viruses in a group of HIV infected patients, followed at a single institution since 1996. 1,693 HIV positive patients (1,162 male, 531 female) were tested for HBV infection. Virological markers for HBV included HBsAg and total anti-HBc by ELISA. 1,457 patients (1,009 male, 448 female) were tested for HCV infection. Detection of HCV antibodies was carried out by ELISA. A sample of HCV antibody positive patients was tested for HCV by PCR to confirm infection. Of 1,693 patients tested for HBV, 654 (38.6 per cent) and 96 (5.7 per cent) were anti-HBc and HBsAg positive, respectively. Of 1,457 patients tested for HCV, 258 (17.7 per cent) were anti-HCV positive. 82 of these patients were also tested by PCR and 81 were positive (98 per cent). Of 1,411 patients tested for HBV and HCV 26 (1.8 per cent) were positive for both viruses.