RESUMO Objetivo Identificar estudos que realizaram rastreio para hepatite C e que também avaliaram a prevalência do vírus em usuários de unidades de urgência e emergência. Método Revisão sistemática ...realizada nas bases de dados LILACS, MEDLINE via PubMed, SciELO e Biblioteca Virtual em Saúde. Resultados Após criteriosa busca e análise, fizeram parte dos resultados 19 publicações, essas em conformidades com os critérios pré-definidos. As datas de publicação se concentraram entre 1992 e 2018. A principal revista a publicar tais artigos foi a Annals of Emergency Medicine (26,31%). Em relação à origem das publicações, destacam-se: Estados Unidos (63,15%), Europa (31,57%) e Ásia (5,28%). Em relação à prevalência, nos Estados Unidos, se observou uma variação entre 1,4% e 18%. Por sua vez, na Europa, a prevalência variou de 0 a 5%. No estudo asiático, a prevalência foi de 1,8%. Conclusão O rastreio realizado em unidades de urgência e emergência se mostrou eficiente na identificação de novos casos, especialmente quando associado ao fator idade, que demonstra ser superior à estratégia baseada apenas em fatores de risco. Assim, para maior efetividade, recomenda-se a associação das três estratégias: local do rastreio, faixa etária e fatores de risco.
RESUMEN Objetivo Identificar los estudios que realizaron pruebas de detección de hepatitis C y que también evaluaron la prevalencia del vírus en usuarios de unidades de urgencia y emergencia. Método revisión sistemática realizada en bases de datos LILACS, MEDLINE a través de PubMed, SciELO y la Biblioteca Virtual en Salud. Resultados Después de una cuidadosa búsqueda y análisis, 19 publicaciones fueron parte de los resultados, estos cumplieron con los criterios predefinidos. Las fechas de publicación se concentraron entre 1992 y 2018. La revista principal para publicar dichos artículos fue el Annals of Emergency Medicine (26,31%). En cuanto al origen de las publicaciones, destacan las siguientes: Estados Unidos (63,15%), Europa (31,57%) y Asia (5,28%). Con respecto a la prevalencia, en los Estados Unidos, se observó una variación entre 1.4% y 18%. En Europa, a su vez, la prevalencia varió de 0 a 5%. En el estudio asiático, la prevalencia fue de 1,8%. Conclusión La evaluación realizada en las unidades de urgencias y emergencias demostró ser eficiente en la identificación de nuevos casos, especialmente cuando se asocia con el factor de edad, que demuestra ser superior a la estrategia basada solo en factores de riesgo. Por lo tanto, para una mayor efectividad, se recomienda la asociación de las tres estrategias: ubicación del examen, grupo de edad y factores de riesgo.
ABSTRACT Objective Identifying studies that performed screening for hepatitis C and that also assessed the virus prevalence in urgency and emergency unit users. Method A systematic review performed on the LILACS, MEDLINE databases via PubMed, SciELO and Virtual Health Library. Results After careful search and analysis, 19 publications were part of the results, in compliance with the pre-defined criteria. Publication dates were concentrated between 1992 and 2018. The main journal to publish such articles was the Annals of Emergency Medicine (26.31%). Regarding the origin of publications, the following stand out: United States (63.15%), Europe (31.57%), and Asia (5.28%). Regarding prevalence, in the United States, a variation between 1.4% to 18% was observed. In Europe, in turn, the prevalence ranged from 0 to 5%. In the Asian study, the prevalence was 1.8%. Conclusion The screening performed in urgent and emergency units proved to be efficient in identifying new cases, especially when associated with the age factor, which proves to be superior to the strategy based only on risk factors. Thus, for greater effectiveness, the association of three strategies is recommended: screening location, age group, and risk factors.
Acute pancreatitis associated with boceprevir: a case report Bilar, Juliana Miguel; Carvalho-Filho, Roberto José; Mota, Carolina Frade Magalhães Girardin Pimentel ...
The Brazilian journal of infectious diseases,
07/2014, Volume:
18, Issue:
4
Journal Article
Peer reviewed
Open access
Approximately 170 million people are infected with hepatitis C, and the sustained virological response rate to treatment with pegylated interferon and ribavirin is 30–50%. In an attempt to improve ...the chances of cure, boceprevir is being added to therapy, but it is associated with an increased incidence of adverse events. We herein report a case of acute pancreatitis developed during treatment with pegylated interferon, ribavirin and boceprevir. Boceprevir was the most likely cause of drug-associated pancreatitis after the most common causes were ruled out, since this adverse event had not occurred when the patient had previously been exposed to pegylated interferon and ribavirin and there was no recurrence of the episode of pancreatitis when these two drugs were reintroduced. Acute pancreatitis is a rare adverse event associated with boceprevir therapy, but a potentially fatal event. Sequential determination of pancreatic enzymes should be considered during hepatitis C treatment with boceprevir.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Direct-acting antivirals have revolutionized hepatitis C treatment, also for patients with chronic kidney disease (CKD), but some controversy exists regarding the use of sofosbuvir (SOF) in patients ...with glomerular filtration rate (GFR) <30 mL/min.
To evaluate the efficacy and safety of these regimens for hepatitis C treatment of patients with CKD and after renal transplantation, as well as the impact of SOF on renal function in non-dialysis patients.
All patients with hepatitis C and CKD or renal transplant treated with direct-acting antivirals at a referral center in Brazil between January 2016 and August 2017 were included. Efficacy was evaluated based on viral load (HCV RNA) and a sustained virological response (SVR) consisting of undetectable RNA 12 and/or 24 weeks after the end of treatment (SVR12 and SVR24) was defined as cure. Safety was determined by adverse events and ribavirin, when combined, was administered in escalating doses to all patients with GFR <60 mL/min. The impact of SOF on renal function was determined by the measurement of baseline creatinine during and after the end of treatment and its increase was evaluated using the Acute Kidney Injury Network (AKIN) classification.
A total of 241 patients (52.7% females) with a mean age of 60.72±10.47 years were included. The combination of SOF+daclatasvir was the predominant regimen in 75.6% of cases and anemia was present in 28% of patients who used ribavirin (P=0.04). The SVR12 and SVR24 rates were 99.3% and 97.1%, respectively. The treatment was well tolerated and there were no major clinically relevant adverse events, with the most prevalent being asthenia (57.7%), itching (41.1%), headache (40.7%), and irritability (40.2%). Among conservatively treated and renal transplant patients, oscillations of creatinine levels (AKIN I) were observed in 12.5% of cases during treatment and persisted in only 8.5% after the end of treatment. Of these, 2.0% had an initial GFR <30 mL/min and this percentage decreased to 1.1% after SOF use. Only 0.5% and 1.6% of the patients progressed to AKIN II and AKIN III elevation, respectively.
The direct-acting antivirals were safe and efficacious in CKD patients treated with SOF-containing regimens, with the observation of high SVR rates, good tolerability and few severe adverse events. The combination with ribavirin increased the risk of anemia and the administration of escalating doses seems to be useful in patients with GFR <60 mL/min. In patients with GFR <30 mL/min, SOF had no significant renal impact, with serum creatinine returning to levels close to baseline after treatment.
AbstractBackground. HBV/HCV coinfection is a common finding among hemodialysis patients. However, there is scarce information concerning the impact of HBV coinfection on the response to treatment of ...HCV-infected patients on hemodialysis. Aim. We aimed to compare the rate of sustained virologic response (SVR) to treatment with interferon-alfa (IFN) between hemodialysis patients with HBV/HCV coinfection and those with HCV-monoinfection. Material and methods. HCV-infected patients on hemodialysis treated with IFN were included. Patients coinfected by HBV/HCV were compared to HCV-monoinfected patients, regarding clinical and biochemical features and rates of SVR. Results. One hundred and eleven patients were treated. HBV/HCV coinfection was observed in 18/111 patients (16%). Coinfected patients were younger (p = 002), had more time on dialysis (p = 0.05) and showed a tendency to present a higher prevalence of septal fibrosis (p = 0.06). The analysis by intention to treat showed SVR of 56% among coinfected patients and 18% in HCV-monoinfected patients (p = 0.004). Conclusion. In conclusion, end-stage renal disease patients with HBV/HCV coinfection exhibit higher rate of SVR to HCV treatment than HCV-monoinfected patients. It is possible that factors related to the host immune response and viral interaction could explain the better response observed among coinfected patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
There is scarce information regarding clinical evolution of HBV infection in renal transplant patients.
To evaluate the prevalence of acute exacerbation in HBV-infected renal transplant patients and ...its association with the time after transplantation, presence of viral replication, clinical evolution, and use of antiviral prophylaxis.
HBV infected renal transplant patients who underwent regular follow-up visits at 6-month intervals were included in the study. The criteria adopted to characterize exacerbation were: ALT >5× ULN and/or >3× baseline level. Predictive factors of exacerbation evaluated were age, gender, time on dialysis, type of donor, post-transplant time, ALT, HBeAg, HBV-DNA, HCV-RNA, immunosuppressive therapy, and use of antiviral prophylaxis.
140 HBV-infected renal transplant patients were included (71% males; age 46±10 years; post-renal transplant time 8±5 years). During follow-up, 25% (35/140) of the patients presented exacerbation within 3.4±3 years after renal transplant. Viral replication was observed in all patients with exacerbation. Clinical and/or laboratory signs of hepatic insufficiency were present in 17% (6/35) of the patients. Three patients died as a consequence of liver failure. In univariate analysis variables associated with exacerbation were less frequent use of prophylactic/preemptive lamivudine and of mycophenolate mofetil. Lamivudine use was the only variable independently associated with exacerbation, with a protective effect.
Acute exacerbation was a frequent and severe event in HBV-infected renal transplant patients. Prophylactic/preemptive therapy with antiviral drugs should be indicated for all HBsAg-positive renal transplant patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done ...according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs.
Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included.
As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions.
The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes ...2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3.
Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5'-untranslated region.
A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model.
Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes.
Autoantibodies to inosine monophosphate dehydrogenase-2 (IMPDH2), an enzyme involved in de novo biosynthesis of guanine nucleotides, are observed in a subset of hepatitis C virus (HCV) patients ...receiving interferon alpha (IFN-α) plus ribavirin. Anti-IMPDH2 antibodies display a peculiar cytoplasmic “rod/ring” (RR) pattern in IIF-HEp-2. We examined the dynamics of anti-RR autoimmune response with respect to immunoglobulin isotypes, titer, avidity, and protein targets in 80 sequential samples from 15 HCV patients (plus 12 randomly selected anti-RR-positive, totalizing 92 samples) collected over an 18-month period, including samples collected before, during, and after IFN-α + ribavirin treatment. Immunoprecipitation showed reactivity with the 55 kDa IMPDH2 protein in 12/15 patients (80 %) and 11/15 (73 %) reacted with IMPDH2 in a sandwich ELISA. During treatment, anti-IMPDH2 autoantibodies hit their highest levels after 6–12 months of treatment and decreased post-treatment, while anti-HCV antibodies levels were stable over time. Anti-IMPDH2 IgM levels increased up until the sixth month of treatment and remained stable thereafter, while IgG levels increased steadily up to the twelfth month. Both IgG and IgM decreased during the post-treatment period. IgG avidity increased steadily up to the twelfth month of treatment. In conclusion, this study showed that the temporal kinetics of IFN-α + ribavirin-induced humoral autoimmune response to IMPDH2 exhibited a considerably delayed pace of increase in antibody levels and avidity as well as in isotype class switch in comparison with a conventional humoral response to infectious agents. These unique findings uncover intriguing differences between the autoimmune response and the immune response to exogenous agents in humans.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
New direct‐acting antiviral (DAA) agents are in development or already approved for the treatment of chronic hepatitis C virus (HCV) infection. The effectiveness of these drugs is related to the ...previous existence of resistant variants. Certain clinical conditions can allow changes in immunological characteristics of the host and even modify genetic features of viral populations. The aim of this study was to perform HCV molecular characterization from samples of end‐stage renal disease patients on hemodialysis (ESRD‐HD). Nested PCR and Sanger sequencing were used to obtain genetic information from the NS5B partial region of a cohort composed by 86 treatment‐naïve patients. Genomic sequences from the Los Alamos databank were employed for comparative analysis. Bioinformatics methodologies such as phylogenetic reconstructions, informational entropy, and mutation analysis were used to analyze datasets separated by geographical location, HCV genotype, and renal function status. ESRD‐HD patients presented HCV genotypes 1a (n = 18), 1b (n = 16), 2a (n = 2), 2b (n = 2), and 3a (n = 4). Control subjects were infected with genotypes 1a (n = 11), 1b (n = 21), 2b (n = 4), and 3a (n = 8). Dataset phylogenetic reconstruction separated HCV subtype 1a into two distinct clades. The entropy analysis from the ESRD‐HD group revealed two amino acid positions related to an epitope for cytotoxic T lymphocytes and T helper cells. Genotype 1a was found to be more diverse than subtype 1b. Also, genotype 1a ERSD‐HD patients had a higher mean of amino acids changes in comparison to control group patients. The identification of specific mutations on epitopes and high genetic diversity within the NS5B HCV partial protein in hemodialysis patients can relate to host immunological features and geographical distribution patterns. This genetic diversity can affect directly the new DAA's resistance mechanisms.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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