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1.
Ann Hepatol ; 30(2): 101582, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39276980

RESUMO

Hepatitis C virus (HCV) belongs to the Flaviviridae family, and is a single-stranded RNA virus with positive polarity. It is the primary cause of hepatocellular carcinoma (HCC) worldwide. The treatment of HCV has entered a new era with the advent of direct-acting antiviral drugs (DAAs) and is associated with cure rates of more than 95 %, making HCV the only curable viral disease. The successful treatment of chronic hepatitis C has greatly reduced, but not eliminated, the risk of HCC. Certain individuals, especially those with cirrhosis already present, remain vulnerable to HCC after achieving a sustained virological response (SVR). This article systematically reviews the recent studies on the risk and mechanisms of HCC development after HCV viral cure, the screening and predictive value of biological markers, and patient surveillance. Factors such as older age, diabetes, hepatic fat accumulation, alcohol use, and lack of fibrosis reversal are linked to increased HCC risk after HCV cure. The mechanism of HCC development after DAAs treatment remains unclear, but the possible mechanisms include immune cell dysfunction during HCV infection, cytokine network imbalance, epigenetic alterations, and host factors. Several biological markers and risk prediction models have been used to monitor the risk of HCC in CHC patients who have achieved SVR, but most still require validation and standardization. The implementation of risk-stratified surveillance programs is becoming urgent from a cost-effective point of view, but the availability of validated biomarkers to predict HCC in cured patients remains an unmet clinical need. Additionally, managing CHC patients who achieve SVR is becoming a growing challenge as an increasing number of HCV patients are cured.

2.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1529453

RESUMO

ABSTRACT Direct-acting antivirals are the gold-standard treatment for chronic HCV infections, but few studies have investigated their use on kidney and liver transplant recipients. We conducted a real-world study to evaluate the rates of sustained virological response with direct-acting antivirals in kidney and liver transplant recipients. Moreover, it also aimed to evaluate direct-acting antivirals (DAAs) interference with immunosuppressant levels and to describe the frequency of adverse events. As part of this retrospective observational cohort, we included adult patients that had undergone a kidney transplant (KT) or liver transplant (LT) at our center, had a chronic HCV infection, and were treated with DAAs from June 2016 to December 2021. A total of 165 patients were included in the analysis, divided in 108 KT and 57 LT recipients. HCV genotype 1 was more frequent in KT (58.4%), and genotype 3 was more prevalent in LT (57.9%) patients. Sustained virological response was achieved in 89.6% of patients. Adverse effects were reported by 36% of patients. There were significant interactions with immunosuppressants requiring dose adjustments. A total of three episodes of rejection were reported in KT recipients. In conclusion, DAA treatment resulted in high rates of SVR and was well tolerated in both kidney and liver transplant patients. Adverse events were frequent but not severe in most patients, with low treatment drop-out rates. Interactions with immunosuppressants need monitoring since dose adjustments may be required. Reporting real-life experiences is important to help build evidence for patient management in non-controlled environments.

3.
Braz J Infect Dis ; 26(5): 102697, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36037847

RESUMO

INTRODUCTION: The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. PATIENTS AND METHODS: This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. RESULTS: One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p < 0.001). CONCLUSIONS: Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Hipertensão Portal , Neoplasias Hepáticas , Idoso , Antivirais/uso terapêutico , Ascite/induzido quimicamente , Ascite/complicações , Ascite/tratamento farmacológico , Brasil/epidemiologia , Feminino , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Hipertensão Portal/induzido quimicamente , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
4.
Braz. j. infect. dis ; Braz. j. infect. dis;26(5): 102697, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1403888

RESUMO

Abstract Introduction The outcomes regarding portal hypertension-related complications and infections after HCV cure in decompensated cirrhosis are scarcely reported. We aimed to identify the predictors of survival and to evaluate the frequency of decompensation events of cirrhosis, including hepatocellular carcinoma (HCC), portal hypertension complications and infections in a cohort of decompensated cirrhotic with sustained virological response (SVR) in a real-world scenario. Patients and methods This was a prospective study in consecutive HCV-infected patients with decompensated cirrhosis who achieved SVR after direct-acting antiviral (DAA) treatment. At baseline, clinical and laboratory data were recorded. Patients were followed until development of outcomes regarding further decompensation, death, or liver transplant. A Cox-regression analysis was performed and survival curves were constructed using the Kaplan Mayer method. Results One hundred and thirty patients (age 60 ± 9 years, 64% female, 70% genotype 1) were included and followed-up through three years. SVR was associated with a lower prevalence of ascites and an improvement in Child-Pugh and MELD scores. One and three-year probability of transplant-free survival was 93% and 66%, respectively. Variables related to three-years survival were MELD < 11 (HR 1.24, 95% CI 1.13-1.37) and absence of ascites (HR 2.03, 95% CI 0.99-4.13) after the end of treatment (91% versus 37% in patients with ascites and a higher MELD, p< 0.001). Conclusions Decompensated cirrhotics with SVR and a low MELD without ascites have an excellent long-term prognosis. On the contrary, those with higher MELD and ascites have a low probability of survival even in the short term and might be evaluated for liver transplantation.

5.
World J Hepatol ; 13(9): 1069-1078, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34630875

RESUMO

The hepatitis C virus has a high mutation capacity that leads to the emergence of resistance-associated substitutions (RAS). However, the consequence of resistance selection during new direct-acting antiviral drug (DAA) treatment is not necessarily the therapeutic failure. In fact, DAA treatment has shown a high rate (> 95%) of sustained virological response even when high baseline RAS prevalence has been reported. In the context of RAS emergence and high rates of sustained viral response, the clinical relevance of variants harboring RAS is still controversial. Therefore, in order to summarize the data available in international guidelines, we have reviewed the clinical utility of testing RAS in the era of new pangenotypic DAA drugs.

6.
J Viral Hepat ; 28(12): 1672-1682, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34320255

RESUMO

Direct-acting antivirals (DAAs) have been approved in recent years to treat patients infected by the Hepatitis C virus (HCV). The DAAs treatment is well tolerated and increases sustained virological responses, but there is no consensus about the neuropsychological functioning related to the treatment. This systematic review aims to provide an overview of the recent findings exploring the cognitive effects of DAAs treatment in patients with HCV. After a systematic search on PubMed, Embase, Scopus and LILACS, studies that assessed neuropsychological data related to DAAs treatment were included. We found nine articles, considering the inclusion and exclusion criteria. Three other manuscripts were included after searching for the references listed in the previously mentioned articles. We observed methodological heterogeneity in terms of neuropsychological tests used, cognitive domain explored and the sample characteristic presented between the studies. Studies presented data from HCV subjects monoinfected with or without cirrhosis, advanced liver disease and post-transplant patients; and HCV subjects coinfected with human immunodeficiency virus (HIV). Most results from the 12 studies that explored the effect of DAAs treatment in HCV subjects' neurocognitive functioning demonstrated cognitive improvement following treatment. In general, HCV and HCV/HIV subjects improved processing speed, verbal fluency and verbal/visual episodic memory. The DAAs treatment is effective for neurocognitive functioning in HCV monoinfected and coinfected subjects, with or without advanced liver disease, since neuropsychological scores increased after treatment. Further studies, however, are needed to confirm these findings.


Assuntos
Coinfecção , Infecções por HIV , Hepatite C Crônica , Hepatite C , Antivirais/efeitos adversos , Coinfecção/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Hepacivirus , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Resposta Viral Sustentada
7.
Ann Hepatol ; 23: 100268, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33059055

RESUMO

Patients with hepatitis C virus (HCV) genotype 3 (GT3) infection are resistant to direct-acting antiviral (DAA) treatments. This study aimed to analyze the effectiveness of sofosbuvir (SOF)+daclatasvir (DCV) ± ribavirin (RBV); SOF+velpatasvir (VEL)±RBV; SOF+VEL+voxilaprevir (VOX); and glecaprevir (GLE)+pibrentasvir (PIB) in the treatment of HCV GT3-infected patients in real-world studies. Articles were identified by searching the PubMed, EMBASE, and Cochrane Library databases from January 1, 2016 to September 10, 2019. The meta-analysis was conducted to determine the sustained virologic response (SVR) rate, using R 3.6.2 software. Thirty-four studies, conducted on a total of 7328 patients from 22 countries, met the inclusion criteria. The pooled SVR rate after 12/24 weeks of treatment was 92.07% (95% CI: 90.39-93.61%) for the evaluated regimens. Also, the SVR rate was 91.17% (95% CI: 89.23-92.94%) in patients treated with SOF+DCV±RBV; 95.08% (95% CI: 90.88-98.13%) in patients treated with SOF+VEL±RBV; 84.97% (95% CI: 73.32-93.91%) in patients treated with SOF+VEL+VOX; and 98.54% (95% CI: 96.40-99.82%) in patients treated with GLE+PIB. The pooled SVR rate of the four regimens was 95.24% (95% CI: 93.50-96.75%) in non-cirrhotic patients and 89.39% (95% CI: 86.07-92.33%) in cirrhotic patients. The pooled SVR rate was 94.41% (95% CI: 92.02-96.42%) in treatment-naive patients and 87.98% (95% CI: 84.31-91.25%) in treatment-experienced patients. The SVR rate of GLE+PIB was higher than other regimens. SOF+VEL+VOX can be used as a treatment regimen following DAA treatment failure.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Hepatite C/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Imidazóis/uso terapêutico , Compostos Macrocíclicos/uso terapêutico , Pirrolidinas/uso terapêutico , Quinoxalinas/uso terapêutico , Sofosbuvir/uso terapêutico , Sulfonamidas/uso terapêutico , Valina/análogos & derivados , Combinação de Medicamentos , Hepatite C/virologia , Humanos , Ribavirina/uso terapêutico , Valina/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-32659974

RESUMO

Hepatitis C (HCV) is a global pandemic. The World Health Organization has developed a strategic plan for HCV elimination that focuses on low- and middle-income countries (LMICs) and high-risk populations, including people who inject drugs (PWID). While direct-acting antiviral (DAA) therapies are highly effective at eliminating HCV infections and have few side effects, medical professionals and policymakers remain concerned about the risk of reinfection among PWID. This study is a systematic review of research measuring the rate of HCV reinfection among PWID in LMICs and identifies additional areas for further research. A systematic search strategy was used to identify studies documenting HCV reinfection after sustained virologic response in PWID in LMICs. We refined results to include studies where at least 50% of participants had DAA treatment for primary HCV infection. Pooled reinfection rate was calculated across all studies. Seven studies met eligibility criteria. Most studies were conducted in six upper middle-income countries (Mexico, Romania, Russia, Taiwan, Georgi, and Brazil) and one lower middle-income country (Bangladesh) with a total of 7665 participants. No study included information from PWID in low-income countries. Sample sizes ranged from 200 to 3004 individuals, with demographic data missing for most participants. Four studies used deep gene sequencing, and reflex genotyping procedures to differentiate reinfection (infection by a different HCV genotype/subtype) from virologic relapse (infection by the same strain). The follow-up time of people cured from primary chronic HCV infection ranged from 12 weeks to 6.6 years. The pooled reinfection rate of all seven studies was 2.8 (range: 0.02 to 10.5) cases per 100 person-years (PY). In the five studies that differentiated relapse from reinfection, the incidence of reinfection was 1.0 per 100 PY. To date, research on reinfection rates among PWID in LMICs remains limited. Research focused on PWID in low-income countries is particularly needed to inform clinical decision making and evidence-based programs. While rates of reinfection among PWID who complete DAA treatment in upper and lower middle-income countries were similar or lower than rates observed in PWID in high-income countries, the rates were highly variable and factors may influence the accuracy of these measurements. This systematic review identifies several areas for continued research. Policies concerning access to HCV testing and treatment should be comprehensive and not place restrictions on PWID in these settings.


Assuntos
Antivirais , Hepatite C Crônica , Hepatite C , Abuso de Substâncias por Via Intravenosa , Antivirais/uso terapêutico , Bangladesh , Brasil , Hepatite C/tratamento farmacológico , Hepatite C/epidemiologia , Humanos , México , Recidiva , Romênia , Federação Russa , Abuso de Substâncias por Via Intravenosa/tratamento farmacológico , Abuso de Substâncias por Via Intravenosa/epidemiologia , Taiwan
9.
Ann Hepatol ; 19(4): 367-372, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32444247

RESUMO

INTRODUCTION AND OBJECTIVES: We examined whether Mac-2-binding protein glycosylation isomer (M2BPGi) levels could be a predictive marker for the presence of esophagogastric varices (EGV) in cirrhotic patients after hepatitis C virus (HCV) eradication with direct-acting antivirals (DAAs). PATIENTS AND METHODS: A total of 102 cirrhotic patients with HCV infection treated with DAAs were enrolled. Esophagogastroduodenoscopy was performed in 84 of the patients before treatment (Cohort A), in 66 after treatment (Cohort B), and in 48 at both time points (Cohort C). We examined factors associated with EGV before and after DAA treatment. RESULTS: In Cohort A, M2BPGi levels and liver stiffness were significantly higher in the EGV-positive group than the EGV-negative group (p=0.034, and p=0.042, respectively). The proportion of EGV-positive patients with before-treatment levels of M2BPGi ≧ 7.3 C.O.I. was significantly higher than in patients with M2BPGi levels<7.3 C.O.I. (p=0.015). In Cohort B, M2BPGi levels were significantly higher in the EGV-positive group than EGV-negative group (p=0.003). The proportion of EGV-positive patients with after-treatment levels of M2BPGi ≧ 3.4 C.O.I. was significantly higher than in patients with M2BPGi levels<3.4C.O.I. (p=0.001). In Cohort C, M2BPGi levels decreased during DAA treatment regardless of EGV development, but there was no significant difference in the reduction of M2BPGi among the EGV-improvement, EGV-invariant, and EGV-exacerbation groups (p=0.659). CONCLUSIONS: M2BPGi levels may be a novel serum marker for the presence of EGV before and after DAA treatment.


Assuntos
Antígenos de Neoplasias/metabolismo , Antivirais/uso terapêutico , Biomarcadores Tumorais/metabolismo , Varizes Esofágicas e Gástricas/metabolismo , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/metabolismo , Idoso , Idoso de 80 Anos ou mais , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/etiologia , Feminino , Glicosilação , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Resposta Viral Sustentada , Resultado do Tratamento
11.
J Pediatr ; 219: 106-110, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32008767

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of shortened 8-week regimen of ledipasvir/sofosbuvir (LED/SOF) combination therapy in treatment-naïve children without cirrhosis aged 4-10 years of age with chronic hepatitis C virus (HCV) infection. STUDY DESIGN: This observational single arm prospective study included 30 treatment-naïve children (20 males) with proved chronic HCV fulfilling inclusion criteria. Their body weights ranged from 17 to 26 kg. Four patients were excluded from the study. All the included children received a single oral dose of LED/SOF 45/200 mg for 8 weeks. Body weight, HCV-RNA, complete blood count, and liver function tests were monitored at 0, 2, 4, and 8 weeks and sustained virologic response was evaluated after 12 weeks after treatment (SVR12). The emergence of any side effects was also monitored. RESULTS: The most common risk factor (53.3%) was an parent or sibling with HCV infection. Twenty-nine patients (96.7%) were negative for HCV-RNA by week 2 of treatment and 1 patient became negative by week 4. The end of treatment response and SVR12 were 100%. Transaminases levels declined and returned to normal levels by week 2. Major side effects were fatigue in 90% (27/30) and headache in 76.7% (23/30). Side effects were minimal, tolerable, and did not interfere with daily activity or necessitate treatment discontinuation. CONCLUSIONS: A shortened 8-week regimen of LED/SOF (45/200 mg) is safe and effective with 100% SVR12 in treatment-naïve children with cirrhosis aged 4-10 years with chronic HCV infection genotype 4.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Uridina Monofosfato/análogos & derivados , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Criança , Pré-Escolar , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Masculino , Estudos Prospectivos , Sofosbuvir , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos
12.
Braz. j. infect. dis ; Braz. j. infect. dis;24(1): 25-29, Feb. 2020. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1089328

RESUMO

ABSTRACT Background: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). Methods: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. Results: Thirty-five patients were treated. The mean age was 52.1 ± 10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8 ± 28.6 and 63.7 ± 28.3 ml/min pre- and post-treatment respectively (p > 0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. Conclusion: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sofosbuvir/uso terapêutico , Índice de Gravidade de Doença , Reprodutibilidade dos Testes , Estudos Retrospectivos , Análise de Variância , Transplante de Rim , Resultado do Tratamento , Estatísticas não Paramétricas , Creatinina/sangue , Insuficiência Renal Crônica/terapia , Resposta Viral Sustentada , Taxa de Filtração Glomerular , Imidazóis/uso terapêutico , Imunossupressores/uso terapêutico
13.
Braz J Infect Dis ; 24(1): 25-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31760038

RESUMO

BACKGROUND: To analyze the effectiveness and the safety of Sofosbuvir-based regimens to treat patients with chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD). METHODS: A retrospective, observational study in patients with chronic HCV infection and CKD treated with Sofosbuvir-based regimens was performed. Liver fibrosis, comorbidities, HCV genotype and sustained virological resposnse (SVR) at 12th week post-treatment were evaluated. Kidney function was accessed by serum creatinine and glomerular filtration rate (GFR). The assumed level of significance was 5 %. RESULTS: Thirty-five patients were treated. The mean age was 52.1±10.9 years, 19 (54.3 %) were women, 32 (91.4 %) were already kidney transplanted and 3 (8.6 %) were on hemodialysis. The SVR by intention to treat was 88.6 %. The mean GFR was 65.8±28.6 and 63.7±28.3ml/min pre- and post-treatment respectively (p>0.05). Treatment was interrupted in 1 (2.85 %) patient due to anemia and in 2 (5.7 %) due to loss of kidney function. CONCLUSION: Sofosbuvir-based regimens are effective to treat HCV in patients with CKD. In patients with mild CKD this type of therapy seems to be safe.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Sofosbuvir/uso terapêutico , Adulto , Idoso , Análise de Variância , Carbamatos , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Imidazóis/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Insuficiência Renal Crônica/terapia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resposta Viral Sustentada , Resultado do Tratamento , Valina/análogos & derivados
14.
Virus Res ; 274: 197778, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31618615

RESUMO

NS3 is an important therapeutic target for direct-acting antiviral (DAA) drugs. However, many patients treated with DAAs have unsustained virologic response (UVR) due to the high mutation rate of HCV. The aim of this work was to shed some light on the puzzling molecular mechanisms of the virus's of patients who showed high viral loads even under treatment with DAA. Bioinformatics tools, molecular modelling analyses were employed to identify mutations associated with HCV resistance to boceprevir and possible structural features related to this phenomenon. We identified two mutations of NS3 that may be associated with HCV resistance: D168N and L153I. The substitution D168N was previously reported in the literature as related with drug failure. Additionally, we identified that its molecular resistance mechanism can be explained by the destabilization of receptor-ligand hydrogen bonds. For the L153I mutation, the resistance mechanism is different from previous models reported in the literature. The L153I substitution decreases the S139 deprotonation susceptibility, and consequently, this mutation impairs the covalent binding between the residue S139 from NS3 and the electrophilic trap on boceprevir, which can induce drug failure. These results were supported by the time course analysis of the mutations of the NS3 protease, which showed that boceprevir was designed for enzymes with an L residue at position 153; however, the sequences with I153 are predominant nowadays. The results presented here could be used to infer about resistance in others DAA, mainly protease inhibitors.


Assuntos
Antivirais/farmacologia , Farmacorresistência Viral/genética , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Proteínas não Estruturais Virais/genética , Antivirais/química , Farmacorresistência Viral/efeitos dos fármacos , Hepatite C Crônica/virologia , Humanos , Modelos Moleculares , Mutação , Prolina/análogos & derivados , Prolina/química , Prolina/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Proteínas não Estruturais Virais/química
15.
J Med Virol ; 91(11): 1970-1978, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31273794

RESUMO

Direct acting antiviral (DAA) therapy against hepatitis C virus (HCV) increases sustained virologic response rates. Nevertheless, drug resistance has occasionally been associated with failure to DAA. However, the information about the prevalence of NS5A and NS5B resistance-associated substitutions (RASs) in Argentina is very scarce. In this study, we determine the prevalence of NS5A and NS5B resistances to treatment in Argentinean DAA treatment-naïve patients chronically infected with genotype 1 (HCV-1). In this retrospective cross-sectional study, 108 HCV-1-infected patients were studied. RASs in NS5A and NS5B were analyzed by Sanger at baseline and phylogenetic analysis was performed. NS5A and NS5B RASs were detected in 25.8% and 6.3% of the analyzed sequences, respectively. The most frequent primary RASs for NS5A were L31M (7.5%) and Y93H (3.2%) and for NS5B was L159F (3.8%). No association between the presence of RASs and the outcome of DAA treatment was found in this study. Additionally, most of the Argentinean samples were randomly distributed among sequences around the world in the phylogenetic analysis. Only one significant Argentinean cluster was observed in both regions but without any particular RASs pattern. Baseline RASs in NS5A and NS5B were frequently observed in HCV-1-infected patients from Buenos Aires, Argentina but not related to treatment outcome. No clusters related to RASs transmission were observed in the phylogenetic analysis. The frequency of RASs detected in this study supports the need for more molecular epidemiology studies on RASs to adjust local treatment guidelines with the incorporation of autochthonous data.


Assuntos
Substituição de Aminoácidos , Antivirais/uso terapêutico , Farmacorresistência Viral/genética , Hepacivirus/genética , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Argentina/epidemiologia , Estudos Transversais , Feminino , Genótipo , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Estudos Retrospectivos
16.
Arq. bras. oftalmol ; Arq. bras. oftalmol;82(2): 161-167, Mar.-Apr. 2019.
Artigo em Inglês | LILACS | ID: biblio-989396

RESUMO

ABSTRACT This review aims to caution ophthalmologists about the ocular consequences leading to the diagnosis of hepatitis C virus infection. In addition, in this context, the effects of old and new drugs are discussed in the ophthalmological setting. The importance of early diagnosis and the curative treatment of the disease has been reported in the national and international literature, demonstrating that its progression has important implications for daily clinical and surgical ophthalmological practice. Despite the scarcity of studies on new direct-acting antiviral drugs, fewer side effects of these drugs have been shown when compared with conventional interferon treatment with or without ribavirin. The ophthalmologist's risk of becoming infected, as demonstrated by the presence of the virus in ocular structures, and the possibility of contamination, is also discussed.


RESUMO Esta revisão objetiva alertar os oftalmologistas sobre as consequências oculares que levam ao diagnóstico da infecção pelo vírus da Hepatite C. Além disso, neste contexto, os efeitos de drogas antigas e novas são discutidos no cenário oftalmológico. A importância do diagnóstico precoce e do tratamento curativo da doença tem sido relatada na literatura nacional e internacional, demonstrando que sua progressão tem implicações importantes para a prática oftalmológica diária. Apesar da escassez de estudos sobre novos medicamentos antivirais de ação direta, foram demonstrados menos efeitos colaterais desses medicamentos quando comparados ao tratamento convencional com interferon, com ou sem ribavirina associado ou não à rivabirina. O risco do oftalmologista de se infectar, como demonstrado pela presença do vírus nas estruturas oculares, e a possibilidade de contaminação, também é discutido.


Assuntos
Humanos , Infecções Oculares Virais/virologia , Hepatite C/complicações , Antivirais/uso terapêutico , Ribavirina/uso terapêutico , Infecções Oculares Virais/patologia , Fatores de Risco , Interferons/uso terapêutico , Hepatite C/patologia , Hepatite C/tratamento farmacológico
17.
Gac Med Mex ; 155(1): 80-89, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-30799461

RESUMO

La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.


Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.


Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/epidemiologia , Fatores Etários , Antivirais/efeitos adversos , Criança , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , Humanos , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , México/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Prevalência
18.
Gac. méd. Méx ; Gac. méd. Méx;155(1): 80-89, Jan.-Feb. 2019. tab
Artigo em Inglês, Espanhol | LILACS | ID: biblio-1286463

RESUMO

Resumen La infección por el virus de hepatitis C es un problema global de salud pública; en México aproximadamente 2 % de la población se encuentra infectada. En niños, los datos de prevalencia son variables según la edad, pero se estima que 0.1 a 2 % de los niños presenta infección crónica por virus de hepatitis C, cuya principal vía de transmisión es la perinatal. Actualmente existen antivirales de acción directa aprobados en adultos con una tasa de respuesta viral sostenida superior a 95 %; sin embargo, en niños aún son pocos los estudios que confirman su seguridad y efectividad. Aunque todavía estamos lejos de la meta, avanzamos rápidamente hacia un tratamiento óptimo de curación también para pacientes pediátricos.


Abstract Infection with hepatitis C virus is a global health problem; in Mexico, approximately 2% of the population is infected. In children, data on prevalence are variable according to the age group, but 0.1-2% of children are estimated to have chronic infection with hepatitis C virus, the main way of transmission of which is perinatal. Currently, there are direct-acting antiviral agents approved in adults that offer a sustained viral response rate higher than 95%; however, in children there are still only few studies confirming their safety and effectiveness. Although we are still far from the goal, we are rapidly advancing towards an optimal curative treatment also for pediatric patients.


Assuntos
Humanos , Feminino , Gravidez , Criança , Antivirais/administração & dosagem , Hepatite C Crônica/epidemiologia , Antivirais/efeitos adversos , Complicações Infecciosas na Gravidez/virologia , Prevalência , Fatores Etários , Transmissão Vertical de Doenças Infecciosas/estatística & dados numéricos , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/transmissão , México/epidemiologia
19.
Ann Hepatol ; 17(5): 815-821, 2018 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-30145562

RESUMO

INTRODUCTION AND AIM: Approximately 10%-15% of patients with hepatitis C genotype 1 (HCV GT1) experience virological relapse after all-oral antiviral regimen using simeprevir (SMV) and sofosbuvir (SOF). The efficacy and safety of treating such relapsers using ledipasvir/sofosbuvir (LDV/SOF) with/without ribavirin (RBV) has been limited. OBJECTIVE: Report the virological response and safety of LDV/SOF with/without RBV for 12-24 weeks in treating HCV GT1 relapsers after SMV + SOF. MATERIAL AND METHODS: Patients treated with standardized clinical protocol utilizing LDV/SOF with/without RBV at three transplant centers were retrospectively reviewed. RESULTS: Forty-five patients (29% post-LT, 82% male, 13% non-white, 73% subtype 1a, 86% IL28B CT/TT, 78% F3-4) started LDV/SOF with/without RBV at a median of 22 weeks (range 7-55 weeks) after the last dose of SMV+SOF treatment. Thirty-seven patients received LDV/SOF for 24 weeks (24/37 patients with RBV) and eight patients received LDV/SOF for 12 weeks (5/8 patients with RBV). RBV dose was adjusted for renal function. Sixteen patients who were RBV-ineligible received LDV/SOF without RBV for 12 or 24 weeks. SVR 12 was achieved in 96% (43/45) of patients. Baseline viral load, RBV use, or GT1 subtype did not impact SVR 12. Minimal adverse events were reported in those without RBV; 45% of patients who received RBV developed significant anemia requiring RBV dose reduction and/or discontinuation. In LT recipients, minimal immunosuppression dose adjustments were required and no biopsy-proven acute rejection occurred. CONCLUSIONS: Treatment with LDV/SOF with/without RBV for 12-24 weeks was very well tolerated and resulted in high SVR 12 rates (96%) in HCV GT1 relapsers to SMV + SOF treatment.


Assuntos
Antivirais/uso terapêutico , Benzimidazóis/uso terapêutico , Fluorenos/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Ribavirina/uso terapêutico , Simeprevir/uso terapêutico , Sofosbuvir/uso terapêutico , Uridina Monofosfato/análogos & derivados , Idoso , Antivirais/efeitos adversos , Benzimidazóis/efeitos adversos , Quimioterapia Combinada , Feminino , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C/diagnóstico , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Ribavirina/efeitos adversos , Simeprevir/efeitos adversos , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/uso terapêutico , Carga Viral
20.
Clin Biochem ; 60: 17-23, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30030979

RESUMO

BACKGROUND: Hepatitis C virus is known to be highly dependent of lipid metabolism to infect new cells and replicate. AIMS: To investigate lipid and apolipoprotein profile in chronic HCV patients according to treatment response. METHODS: Patients recruited from the Hepatitis Treatment Center at Niteroi (Brazil) who received interferon (IFN)-based therapies were separated into two groups, those who achieved sustained virological response (SVR) or not (non-SVR). Another group of patients treated with IFN-free direct-acting antiviral (DAA) therapies was followed from before starting the treatment until one year after therapy. Triglycerides, total cholesterol and fractions were determined by colorimetric and/or electrophoresis techniques. Lecithin cholesterol acyltransferase (LCAT) activity and serum levels of apolipoproteins A1, A2, B, C2, C3 and E were assessed by enzymatic and multiplex assays, respectively. RESULTS: We studied 114 patients, and SVR was reached in 28 (39.4%) patients treated with IFN-therapy and in all (100%) patients who received DAA. Non-SVR patients (n = 43) presented altered liver parameters post-treatment. Levels of total cholesterol, LDL-C, VLDL-C and triglycerides were significant higher in SVR group. In contrast, LCAT activity and HDL-C levels were elevated in non-SVR patients. Only apolipoproteins B, C2 and C3 levels were increased in SVR group. The follow-up of SVR-DAA patients (n = 43) revealed a significant and progressive increase in serum levels of total cholesterol, LDL-C, VLDL-C and triglycerides. CONCLUSIONS: After a successful treatment, chronic hepatitis C patients experienced a reestablishment of lipid metabolism. Our results suggest that the monitoring of serum lipids could be a practical and routine laboratory tool to be applied during the treatment follow-up.


Assuntos
Antivirais/uso terapêutico , Apolipoproteínas/sangue , Hepatite C Crônica/sangue , Lipídeos/sangue , Idoso , Eletroforese em Gel de Poliacrilamida , Feminino , Hepatite C Crônica/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilcolina-Esterol O-Aciltransferase/sangue , Estudos Prospectivos , Resultado do Tratamento
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