Impact of new direct-acting antiviral therapy on the prevalence and undiagnosed proportion of chronic hepatitis C infection.

BACKGROUND: Patients with chronic hepatitis C (CHC) can be cured with the new highly effective interferon-free combination treatments (DAA) that were approved in 2014. However, CHC is a largely silent disease, and many individuals are unaware of their infections until the late stages of the disease. The impact of wider access to effective treatments and improved awareness of the disease on the number of infections and the number of patients who remain undiagnosed is not known in Canada. Such evidence can guide the development of strategies and interventions to reduce the burden of CHC and meet World Health Organization's (WHO) 2030 elimination targets. The purpose of this study is to use a back-calculation framework informed by provincial population-level health administrative data to estimate the prevalence of CHC and the proportion of cases that remain undiagnosed in the three most populated provinces in Canada: British Columbia (BC), Ontario and Quebec. METHODS: We have conducted a population-based retrospective analysis of health administrative data for the three provinces to generate the annual incidence of newly diagnosed CHC cases, decompensated cirrhosis (DC), hepatocellular carcinoma (HCC) and HCV treatment initiations. For each province, the data were stratified in three birth cohorts: individuals born prior to 1945, individuals born between 1945 and 1965 and individuals born after 1965. We used a back-calculation modelling approach to estimate prevalence and the undiagnosed proportion of CHC. The historical prevalence of CHC was inferred through a calibration process based on a Bayesian Markov chain Monte Carlo (MCMC) algorithm. The algorithm constructs the historical prevalence of CHC for each cohort by comparing the model-generated outcomes of the annual incidence of the CHC-related health events against the data set of observed diagnosed cases generated in the retrospective analysis. RESULTS: The results show a decreasing trend in both CHC prevalence and undiagnosed proportion in BC, Ontario and Quebec. In 2018, CHC prevalence was estimated to be 1.23% (95% CI: .96%-1.62%), .91% (95% CI: .82%-1.04%) and .57% (95% CI: .51%-.64%) in BC, Ontario and Quebec respectively. The CHC undiagnosed proportion was assessed to be 35.44% (95% CI: 27.07%-45.83%), 34.28% (95% CI: 26.74%-41.62%) and 46.32% (95% CI: 37.85%-52.80%) in BC, Ontario and Quebec, respectively, in 2018. Also, since the introduction of new DAA treatment in 2014, CHC prevalence decreased from 1.39% to 1.23%, .97% to .91% and .65% to .57% in BC, Ontario and Quebec respectively. Similarly, the CHC undiagnosed proportion decreased from 38.78% to 35.44%, 38.70% to 34.28% and 47.54% to 46.32% in BC, Ontario and Quebec, respectively, from 2014 to 2018. CONCLUSIONS: We estimated that the CHC prevalence and undiagnosed proportion have declined for all three provinces since the new DAA treatment has been approved in 2014. Yet, our findings show that a significant proportion of HCV cases remain undiagnosed across all provinces highlighting the need to increase investment in screening. Our findings provide essential evidence to guide decisions about current and future HCV strategies and help achieve the WHO goal of eliminating hepatitis C in Canada by 2030.

High prevalence of hepatitis E virus antibodies in Sao Paulo, Southeastern Brazil: analysis of a group of blood donors representative of the general population

Abstract Brazil is a non-endemic country for hepatitis E virus (HEV) infection with seroprevalence from 1% to 4% in blood donors and the general population. However, data on seroprevalence of HEV in the country are still limited. This study evaluated the prevalence of past or present HEV infection in a group of blood donors representative of the general population of the city of Sao Paulo, Southeastern Brazil. Serum samples from 500 blood donors were tested from July to September 2014 by serological and molecular methods. Anti-HEV IgG antibodies were detected in 49 (9.8%) subjects and categorized age groups revealed an age-dependent increase of HEV seroprevalence. Among the anti-HEV IgG positive subjects, only 1 had anti-HEV IgM while none tested positive for HEV-RNA. The present data demonstrate a higher seroprevalence of anti-HEV IgG than previously reported in the region.

High frequency of hepatitis E virus infection in swine from South Brazil and close similarity to human HEV isolates

Abstract Hepatitis E virus is responsible for acute and chronic liver infections worldwide. Swine hepatitis E virus has been isolated in Brazil, and a probable zoonotic transmission has been described, although data are still scarce. The aim of this study was to investigate the frequency of hepatitis E virus infection in pigs from a small-scale farm in the rural area of Paraná State, South Brazil. Fecal samples were collected from 170 pigs and screened for hepatitis E virus RNA using a duplex real-time RT-PCR targeting a highly conserved 70 nt long sequence within overlapping parts of ORF2 and ORF3 as well as a 113 nt sequence of ORF2. Positive samples with high viral loads were subjected to direct sequencing and phylogenetic analysis. hepatitis E virus RNA was detected in 34 (20.0%) of the 170 pigs following positive results in at least one set of screening real-time RT-PCR primers and probes. The swine hepatitis E virus strains clustered with the genotype hepatitis E virus-3b reference sequences in the phylogenetic analysis and showed close similarity to human hepatitis E virus isolates previously reported in Brazil.

Hepatitis E virus seroprevalence among schistosomiasis patients in Northeastern Brazil

Abstract Background Hepatitis E virus (HEV) can cause chronic infection with rapid progression to liver cirrhosis in immunocompromised patients. HEV seroprevalence in patients with Schistosoma mansoni in Brazil is unknown. We evaluated the prevalence of past or present HEV infection in schistosomiasis patients in Recife, Pernambuco, Brazil. A total of 80 patients with Schistosoma mansoni were consecutively enrolled in a cross-sectional study. Serum samples were tested for the presence of anti-HEV IgG antibodies by enzyme immunoassay (Wantai anti-HEV IgG, Beijing, China) and for the presence of HEV RNA using real time reverse transcriptase-polymerase chain reaction with primers targeting the HEV ORF2 and ORF3. Clinical and laboratory tests as well as abdominal ultrasound were performed at the same day of blood collection. Results Anti-HEV IgG was positive in 18.8% (15/80) of patients with SM. None of the samples tested positive for anti-HEV IgM or HEV-RNA. Patients with anti-HEV IgG positive presented higher levels of alanine aminotranferase (p = 0.048) and gama-glutamil transferase (p = 0.022) when compared to patients without anti-HEV IgG antibodies. Conclusion This study demonstrates that the seroprevalence of HEV is high in patients with Schistosoma mansoni in Northeastern of Brazil. Past HEV infection is associated with higher frequency of liver enzymes abnormalities. HEV infection and its role on the severity of liver disease should be further investigated among patients with Schistosoma mansoni.

Serum lipidomic profiling as a useful tool for screening potential biomarkers of hepatitis B-related hepatocellular carcinoma by ultraperformance liquid chromatography-mass spectrometry.

BACKGROUND: Chronic hepatitis B (CHB) virus infection is a major cause of hepatocellular carcinoma (HCC), as late diagnosis is the main factor for the poor survival of patients. There is an urgent need for accurate biomarkers for early diagnosis of HCC. The aim of the study was to explore the serum lipidome profiles of hepatitis B-related HCC to identify potential diagnostic biomarkers. METHODS: An ultraperformance liquid chromatography mass spectrometry (UPLC-MS) lipidomic method was used to characterize serum profiles from HCC (n = 32), liver cirrhosis (LC) (n = 30), CHB (n = 25), and healthy subjects (n = 34). Patients were diagnosed by clinical laboratory and imaging evidence and all presented with CHB while healthy controls had normal liver function and no infectious diseases. RESULTS: The UPLC-MS-based serum lipidomic profile provided more accurate diagnosis for LC patients than conventional alpha-fetoprotein (AFP) detection. HCC patients were discriminated from LC with 78 % sensitivity and 64 % specificity. In comparison, AFP showed sensitivity and specificity of 38 % and 93 %, respectively. HCC was differentiated from CHB with 100 % sensitivity and specificity using the UPLC-MS approach. Identified lipids comprised glycerophosphocolines, glycerophosphoserines and glycerophosphoinositols. CONCLUSIONS: UPLC-MS lipid profiling proved to be an efficient and convenient tool for diagnosis and screening of HCC in a high-risk population.

Cytomegalovirus infection in pregnancy / Infecção pelo citomegalovírus na gestação

ABSTRACTCongenital cytomegalovirus (CMV) infection is the leading cause of infectious congenital defects and disabilities. Its transmission can occur in primary and non-primary infections; however the transmission rate is considerably higher in primary infections. The diagnosis of congenital infection is complex, and there is a discussion concerning serological evaluation during pregnancy. This article aims to review the literature concerning CMV infection, its diagnosis and epidemiology.

RESUMOA infecção congênita pelo citomegalovírus (CMV) é a principal causa de deficiências congênitas infecciosas. Sua transmissão pode ocorrer em infecções primárias (cuja taxa de transmissão é consideravelmente mais alta) e não primárias. O diagnóstico da infecção congênita é complexo e existe controvérsia sobre a avaliação sorológica durante a gravidez. Este artigo tem como objetivo revisar a literatura acerca da infecção por CMV, seu diagnóstico e sua epidemiologia.

Hepatitis E virus infection in Brazil: results of laboratory-based surveillance from 1998 to 2013

Data on hepatitis E virus (HEV) in Brazil are limited. We analyzed 15 years of HEV surveillance data in a major clinical laboratory in São Paulo, Brazil.

Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation.

Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

Optimisation of a quantitative polymerase chain reaction-based strategy for the detection and quantification of human herpesvirus 6 DNA in patients undergoing allogeneic haematopoietic stem cell transplantation

Human herpesvirus 6 (HHV-6) may cause severe complications after haematopoietic stem cell transplantation (HSCT). Monitoring this virus and providing precise, rapid and early diagnosis of related clinical diseases, constitute essential measures to improve outcomes. A prospective survey on the incidence and clinical features of HHV-6 infections after HSCT has not yet been conducted in Brazilian patients and the impact of this infection on HSCT outcome remains unclear. A rapid test based on real-time quantitative polymerase chain reaction (qPCR) has been optimised to screen and quantify clinical samples for HHV-6. The detection step was based on reaction with TaqMan® hydrolysis probes. A set of previously described primers and probes have been tested to evaluate efficiency, sensitivity and reproducibility. The target efficiency range was 91.4% with linearity ranging from 10-106 copies/reaction and a limit of detection of five copies/reaction or 250 copies/mL of plasma. The qPCR assay developed in the present study was simple, rapid and sensitive, allowing the detection of a wide range of HHV-6 loads. In conclusion, this test may be useful as a practical tool to help elucidate the clinical relevance of HHV-6 infection and reactivation in different scenarios and to determine the need for surveillance.

Plasma lipidomic fingerprinting to distinguish among hepatitis C-related hepatocellular carcinoma, liver cirrhosis, and chronic hepatitis C using MALDI-TOF mass spectrometry: a pilot study.

BACKGROUND AND AIMS: Hepatitis C (HC) is a major cause of hepatocellular carcinoma (HCC), and a late diagnosis is the main factor for the poor survival of patients. There is an urgent need for identifying sensitive and specific biomarkers for HCC diagnosis. In the present study, plasma lipid patterns of patients with HC-HCC, HC-liver cirrhosis (LC), and chronic HC (CHC) were assessed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). METHODS: Plasma samples of 25 patients with HC-HCC, 15 patients with HC-LC, and 25 patients with CHC were evaluated by MALDI-MS using a Q-ToF premier (Synapt) mass spectrometer (Waters, Manchester, UK) equipped with a 200-Hz solid-state laser in the mass range between m/z (mass-to-charge ratio) of 700-1200. RESULTS: A total of 2205 ions were initially obtained and 7 ions (m/z) were highlighted as corresponding to the most important lipids to differentiate HCC patients from LC and CHC patients. The specific lipidomic expression signature generated resulted in an overall predictive accuracy of 93% of HC-HCC and HC-LC, and 100% of HC-HCC and CHC. The 7-peak algorithm distinguished HCC from LC with a sensitivity of 96% and a specificity of 87%, and HCC from CHC with both sensitivity and specificity of 100%. CONCLUSION: MALDI-MS-specific signature peaks accurately distinguished patients with HC-HCC from those with HC-LC and CHC. The results indicate the potential of MALDI-MS and the selected peaks to improve HCC surveillance in patients with viral C cirrhosis and chronic hepatitis C.