Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan / Recorrência do vírus da hepatite C após tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão

Although increased response rates concomitant in hepatitis C virus but relapse after treatment is threatened. Therefore, it is terrible requirement to evaluate the response of Pegylated interferon and direct acting antivirals in Punjab Pakistan. The study was conducted to find the rate of recurrence of HCV infection after treatment with Pegylated Interferon and Direct Acting Antivirals in Punjab Pakistan. This study was conducted at Department of Pathology, Nawaz Sharif Medical College Gujrat, while treatment effects monitored in different Government and Private Hospitals of Punjab, Pakistan. Total 973 patients who administered the recommended dose and divided in two groups (i) Interferon based therapy (ii) direct acting antivirals (DAAs).Other parameters like ALT and viral load studied. The rate of recurrence was higher in female infected with genotype 2b and in male with mixed genotype 3a/2b after six month of antiviral therapy. Genotype 3a showed significant response to therapy after three month. 32 among 374 (8.5%) were positive after 24 weeks of treatment with interferon, 29 (7.7%) patients have same genotype while 3 patients were re-infected with different HCV strains. With DAAs, only 27 (4.8%) patients were positive among 558 after 2 weeks and one patient re-infected with different genotype. Early and sustained virological response noted in DAAs. ALT and viral load decreased faster with DAAs that not achieved after 4 weeks with pegylated interferon. Sustained virological response appears in DAAs and recurrence rate is high in interferon therapy compared to DAAs. Therefore, reinfection has implications for correct treatment efficiency and to select strategies for retreatment cases.

Embora aumentem as taxas de resposta concomitantes no vírus da hepatite C (HCV), há risco de recidiva após o tratamento. Portanto, é um requisito terrível avaliar a resposta do interferon peguilado e antivirais de ação direta em Punjab, Paquistão. O estudo foi conduzido para encontrar a taxa de recorrência da infecção por HCV após o tratamento com interferon peguilado e antivirais de ação direta em Punjab, Paquistão. Este estudo foi conduzido no Departamento de Patologia Nawaz Sharif Medical College Gujrat, enquanto os efeitos do tratamento foram monitorados em diferentes hospitais públicos e privados de Punjab, Paquistão. Total de 973 pacientes que administraram a dose recomendada foram divididos em dois grupos: (i) Terapia baseada em interferon, (ii) antivirais de ação direta (DAAs). Outros parâmetros como ALT e carga viral foram estudados. A taxa de recorrência foi maior em mulheres infectadas com o genótipo 2b e em homens com genótipo misto 3a / 2b após seis meses de terapia antiviral. O genótipo 3a mostrou resposta significativa à terapia após três meses. 32 entre 374 (8,5%) foram positivos após 24 semanas de tratamento com interferon, 29 (7,7%) pacientes têm o mesmo genótipo, enquanto 3 pacientes foram reinfectados com diferentes cepas de HCV. Com DAAs, apenas 27 (4,8%) pacientes foram positivos entre 558 após duas semanas e um paciente reinfectado com genótipo diferente. Resposta virológica precoce e sustentada observada em DAAs. ALT e carga viral diminuíram mais rapidamente com DAAs, que não alcançou após 4 semanas com interferon peguilado. A resposta virológica sustentada aparece em DAAs, e a taxa de recorrência é alta na terapia com interferon em comparação com DAAs. Portanto, a reinfecção tem implicações para a eficiência do tratamento correto e para selecionar estratégias para casos de retratamento.

Clinical and epidemiological profile of HCV genotype 3 patients in southern Brazil

Introduction: Despite the emergence of new treatments for HCV genotype 3 (HCV G3), there is still a lack of data about this particular subgroup in Brazil. Our objective was to describe clinical and sociodemographic variables and treatment profile of HCV G3 Brazilian patients. Methods: This was a descriptive, retrospective study, performed in a specialized center for HCV treatment in the South Region of Brazil. Medical records of patients diagnosed with HCV G3 were reviewed to collect clinical, sociodemographic, and treatment information. Results: Participants included total of 564 patients, with a mean age of 59.3 years (SD = 10.5). Cirrhosis was present in 54.4% of patients. The most common coexisting conditions were systemic arterial hypertension (36.6%) and diabetes mellitus (30%). Regarding treatment, 25.2% of the patients were treatment-naïve and 74.8% were currently under treatment (11.6%) or had received a previous treatment (87%). The most frequent ongoing treatment was sofosbuvir + daclatasvir (± ribavirin) (87.8%). Of the 388 patients who had at least one previous treatment, 67% achieved sustained virologic response in the last treatment. Caucasian / white, non-obese, transplanted patients, those with longer time since diagnosis and with cirrhosis were more likely to receive treatment, according to multivariate analysis. Patients with hepatocellular carcinoma were 64.1% less likely to be on treatment during the study period than those without this condition; patients with chronic kidney disease were 2.91-fold more likely to have an interruption of treatment than those without this condition. Conclusion: This study describes a large sample of Brazilian patients with HCV G3. Treatment patterns were mainly influenced by the presence of HCV complications and comorbidities.(AU)

Perfil dos genótipos do HCV e subtipos de HIV em pacientes coinfectados no Sul do Brasil / Profile of hcv genotypes and hiv-subtypes among hiv-coinfected patients in southern brazil

ABSTRACT BACKGROUND: Hepatitis B and C virus (HBV and HCV) are the two most common infections among human immunodeficiency virus (HIV)-infected patients. OBJECTIVE: To identify the frequency of HIV subtypes and HCV genotypes in HIV-coinfected patients. METHODS: A cross-sectional and retrospective study was carried out into two reference centers in Southern Brazil between January 1, 2002 and June 30, 2016. The Abbott Real Time HCV Genotype II system was used for routine diagnostics to determine the HCV genotype based on dual-target real-time PCR. Proviral HIV-1 RNA was extracted from serum samples and fragments of the pol gene were generated by PCR. The HIV-1 PT and RT gene sequences were submitted to Maximum Likelihood Phylogenetic analysis by collecting reference sequences from the HIV-1 group M subtype of the Los Alamos database. RESULTS: During the study period, 3340 patients with HIV were diagnosed at both referral centers, of which 4.97% (166/3340) had HBV and/or HCV coinfection. Seroprevalence of HIV-HBV, HIV-HCV and HIV-HBV-HCV was 37.4%, 58.4%, and 4.2%, respectively. HIV-HCV-coinfected patients had a lower median nadir CD4+ T-cell count when compared to HIV-HBV-coinfected patients (P=0.01). Among those coinfected with HCV, HCV-1 (HCV-1) and HCV-3 (HCV-3) genotypes were the most prevalent, being detected in 73.8% and 21.4%, respectively. Among the HCV-1 coinfected patients, 79.3% and 20.1% had subtypes 1a and 1b, respectively. HIV subtype B was the most prevalent in HIV-coinfected patients. There was no significant difference regarding nadir CD4+ T-cell count and HIV viral load when compared to coinfected with HCV-1 with HCV-3, as well as those co-infected with HCV-1a with HCV-1b. CONCLUSION: In the present study, a higher frequency of subtype B of HIV and HCV-1 were found in HIV-coinfected patients. Further larger-scale and long-term studies are needed to better understand the effect of HCV genotypes in HIV-infected patients.

RESUMO CONTEXTO: Os vírus das hepatites B e C (VHB e VHC) são os causadores das duas infecções mais comuns entre os pacientes infectados pelo vírus da imunodeficiência humana (HIV). OBJETIVO: Identificar a frequência dos subtipos do HIV e genótipos de VHC em pacientes coinfectados com HIV. MÉTODOS: Estudo transversal e retrospectivo realizado em dois centros de referência do Sul do Brasil, entre 1º de janeiro de 2002 e 30 de junho de 2016. O sistema Abbott Real Time HCV Genótipo II foi utilizado para diagnósticos de rotina para determinar o genótipo do HCV com base na PCR em tempo real de duplo alvo. O RNA viral do HIV-1 foi extraído de amostras de soro e fragmentos do gene pol foram obtidos por PCR. As sequências do gene PT e RT do HIV-1 foram submetidas à análise filogenética por máxima verossimilhança através da coleta de sequências de referência do subtipo M do grupo HIV-1 da base de dados Los Alamos. RESULTADOS: Durante o período do estudo, 3340 pacientes foram diagnosticados com HIV em ambos os centros de referência, dos quais 4,97% (166/3340) possuíam coinfecção com HBV e/ou HCV. A soroprevalência de HIV-HBV, HIV-HCV e HIV-HBV-HCV foi de 37,4%, 58,4% e 4,2%, respectivamente. Pacientes HIV-VHC possuíam menor nadir de células T CD4+ quando comparados aos pacientes HIV-VHB (P=0,01). Entre os pacientes HIV-VHC, os genótipos VHC-1 e VHC-3 foram os mais prevalentes, sendo encontrados em 73,8% e 21,4%, respectivamente. Entre os coinfectados com VHC-1, 79,3% e 20,1% tinham subtipos 1a e 1b, respectivamente. O subtipo B do HIV foi o mais prevalente em pacientes coinfectados. Não houve diferença significativa em relação nadir de células T CD4+ e carga viral do HIV quando comparadas os coinfectados com o VHC-1 com o VHC-3, assim como, os coinfectados com HCV-1a quando comparados com o HCV-1b. CONCLUSÃO: No presente estudo, uma maior frequência do subtipo B do HIV e do VHC-1 foram encontrados em pacientes coinfectados com HIV. Outros estudos em larga escala e a longo prazo são necessários para entender melhor o efeito dos genótipos do HCV em pacientes infectados pelo HIV.

One-step real-time PCR assay for detection and quantification of RNA HCV to monitor patients under treatment in Brazil

ABSTRACT The Brazilian Public Health Service provides freely αPEG-IFN to treat patients infected with HCV. The primary goal of HCV therapy is the long-term elimination of HCV from the blood to reduce the risk of HCV associated complications and death. Patient viremia affects the treatment duration and response, thus influencing clinical decisions. We developed a high-throughput method to perform the quantification of RNA hepatitis C virus (HCV) virus load in plasma samples to monitor patients under treatment. The method is based on a duplex detection, in a one-step real-time RT-PCR assay and it has been validated according to the rules established by the official Brazilian regulatory agency (ANVISA). This new method was compared to a commercial kit (Cobas/Taqman HCV Test v2.0 - Roche), showing virus load results with significant correlation between them (p= 0,012) using commercial and clinical panels. In addition, 611 samples from patients treated with peguilated alfa-interferon (αPEG-IFN) from different regions of Brazil were analyzed. Our one-step real-time RT-PCR assay demonstrated good performance in viral load measurement and in treatment course monitoring, with acceptable sensitivity and specificity values.

Comportamiento virológico de pacientes con hepatitis C tratados con antivirales cubanos / Virological behavior of patients with hepatitis C treated with Cuban antivirals

Introducción: el seguimiento virológico de los pacientes con hepatitis C se realiza mediante la determinación cuantitativa del ácido ribonucleico viral por técnicas de biología molecular. Objetivos: evaluar el comportamiento virológico de los pacientes con hepatitis crónica C tratados con antivirales cubanos. Materiales y métodos: se realizó un estudio descriptivo, prospectivo en 45 pacientes con hepatitis crónica C atendidos en Consulta de Hepatología del Hospital Universitario Faustino Pérez, de Matanzas, en el período comprendido entre enero 2014 a diciembre 2017, tratados durante 48 semanas con PEG-heberon y ribavirina. De ellos se analizaron las características basales así como los diferentes tipos de respuesta al tratamiento según resultados virológicos. Resultados: predominaron los pacientes del sexo femenino, menores de 45 años, vírgenes de tratamiento y con cargas virales basales altas. Se alcanzó la respuesta virológica rápida en el 31,1%, la temprana total en el 19,4 %, al final del tratamiento en el 77,1% y la respuesta virológica sostenida en el 59,3%. Entre los respondedores predominaron los rápidos con respuesta virológica sostenida y entre los no respondedores, los nulos. Conclusiones: los estudios cuantitativos de ácido ribonucleico viral son esenciales para el seguimiento de los pacientes con hepatitis C ya que a través de sus determinaciones basales, durante el tratamiento y posterior a este, puede evaluarse la respuesta al tratamiento (AU).

Introduction: the virological follow-up of patients with hepatitis C is made through the quantitative determination of the viral ribonucleic acid using techniques of molecular biology. Objectives: to assess the virological behavior of patients with hepatitis C treated with Cuban antivirals. Materials and methods: a prospective, descriptive study was carried out in 45 patients with hepatitis C who attended the Consultation of Hepatology of the University Hospital "Faustino Pérez", of Matanzas, in the period from January 2014 to December 2017, treated with PEG-eberon and ribavirin for 48 weeks. Their basal characteristics were analyzed and also the different kinds of answer to the treatment according to the virological results. Results: female sex, patients aged less than 45 years old, non-treated before and with high viral loads. The fast virological answer was reached in 31 % of the patients, and the total early answer in 19.4 %; at the end of the treatment in 77.1 %, and the sustained virological answer in 59.3 % of the patients. Among the answering ones predominated the fast with sustained virological answer, and among the non-answering predominated the null ones. Conclusions: quantitative studies of viral ribonucleic acid are essential for the follow-up of patients with hepatitis C, because through their basal determinations, during and after the treatment, the answer to the treatment can be evaluated (AU).

Aumento dos lípides durante tratamento para VHC: ação do vírus ou da medicação? / Increase of lipids during hcv treatment: virus action or medication?

ABSTRACT BACKGROUND: The interaction between serum lipids and C virus infection is well known, as are serum lipid levels in the Peg-IFN / RBV-based treatment. However, with direct action antivirals (DAAs) this behavior is still unclear. OBJECTIVE: To compare serum lipids levels between patients treated with Peg-IFN/RBV and DAAs and to evaluate lipids in sustained virological response (SVR) with DAAs. METHODS: Retro prospective study comparing the behavior of total cholesterol (TC), low-density lipoprotein (LDL) and triglycerides (TG) serum levels during treatment with DAAs (G-DAAs) and a control historic group Peg-IFN/RBV (G-PR). Coorte, prospective study, to study the behavior of lipids in the SVR with DAAs. Data were collected at the beginning of treatment (baseline: t-base) and at week 12 of treatment (t-12) for G-DAAs and at week 24 (t-24) for G-PR, groups. In the cohort evaluation, the samples at t-base and at week 12 after the end of treatment (t-SVR). Delta lipids: difference between lipids in t-12 / t-24 minus t-base for comparison between G-PR and G-AADs groups and t-SVR minus t-base for lipid analysis in SVR. Analysis with Kruskal Wallis and Wilcoxon tests to compare the delta lipids of the groups. The P value was 0.05. RESULTS: In the assessment between G-PR and G-DAAs groups, we included 63 and 121 patients, respectively. The groups did not differ one from the other (BMI, sex, genotype, fibrosis, total cholesterol, LDL, and TG) except by age (50.38±10.44 vs 56±9.69, P=0.0006). We observed a decrease in levels of TC and LDL and an increase in TG, in G-PR, and in G-DAAs the opposite (Δ TC -13.9±34.5 vs 4.12±34.3 P=0.0005, Δ LDL -7.16±32 vs 10.13±29.92, P=0.003, Δ TG 4.51±53.7 vs -8.24±49.93, P=0.0025). In the coorte analysis, we included 102 patients, 70% men and 56% F4, 95 of them reached SVR. We observed an increase of TC and LDL and a decrease of TG in both groups (SVR and non SVR), with no statistical difference (Δ TC P=0.68; Δ LDL P=0.69; Δ TG P=0.43). We did not find significant difference in delta evaluation by genotype 1 and 3 (Δ TC +29.7±40.2 vs +13.4±30.3, P=0.06; Δ LDL +21.4±28.6 vs +16.6±31.3, P=0.41; Δ TG -3.6±60.6 vs -0.7±40, P=0.91). CONCLUSION: Serum lipids level differed during treatment with Peg-IFN and DAAs. Treatment with DAAs was associated with an increase of TC and LDL and a decrease of TG, independently of SVR.

RESUMO CONTEXTO: A interação entre lípides séricos e infecção pelo vírus C já é bem conhecida, assim como o comportamento dos níveis séricos daqueles durante o tratamento com Peg-IFN/RBV. No entanto, com antivirais de ação direta (AADs) este comportamento ainda não está claro. OBJETIVO: Comparar os níveis séricos de lípides entre pacientes tratados com Peg-IFN/RBV e AADs e avaliar os lípides na resposta virológica sustentada (RVS) com AADs. MÉTODOS: Estudo retro prospectivo comparando o comportamento dos níveis séricos de colesterol total (CT), lipoproteínas de baixa densidade (LDL) e triglicérides (TG) durante o tratamento com AADs (G-AADs) e um grupo histórico de controle Peg-IFN/RBV (G-PR). Coorte, estudo prospectivo, para estudar o comportamento dos lípides na RVS com AADs. Os dados foram coletados no início do tratamento (baseline: t-base) e na décima segunda semana de tratamento (t-12) para G-AADs e na vigésima quarta semana de tratamento (t-24) para G-PR para a análise comparativa entre os dois grupos. Na avaliação de coorte, as amostras foram coletadas no t-base e na décima segunda semana após o término do tratamento (t-RVS). Delta lípides: diferença entre lípides em t-12/t-24 menos t-base para comparação entre os grupos G-PR e G-AADs e t-RVS menos t-base para análise de lípides na RVS. A análise estatística descritiva, os testes não paramétricos de Kruskal Wallis e Wilcoxon foram utilizados para comparar o delta lípides dos grupos. O valor de P considerado foi de 0,05. RESULTADOS: Na avaliação entre os grupos G-PR e G-AADs, incluímos 63 e 121 pacientes, respectivamente. Os grupos não diferiram um do outro (IMC, sexo, genótipo, fibrose, colesterol total, LDL e TG), exceto por idade (50,38±10,44 vs 56±9,69, P=0,0006). Observamos uma diminuição nos níveis de CT e LDL e um aumento de TG no G-PR, no G-AADs ocorreu o oposto (Δ CT -13,9±34,5 vs 4,12±34,3 P=0,0005, Δ LDL -7,16±32 vs 10,13±29,92, P=0,003, Δ TG 4,51±53,7 vs -8,24±49,93, P=0,0025). Na análise de coorte, foram incluídos 102 pacientes, 70% homens e 56% F4. Noventa e cinco deles atingiram a RVS. Observamos um aumento de CT e LDL e uma diminuição de TG em ambos os grupos (RVS e não RVS), sem diferença estatística (Δ CT P=0,68; Δ LDL P=0,69; Δ TG P=0,43). Não encontramos diferença significativa na avaliação dos deltas pelos genótipos 1 e 3 (Δ CT +29,7±40,2 vs +13,4±30,3, P=0,06; Δ LDL + 21,4±28,6 vs +16,6±31,3, P=0,41; Δ TG -3,6±60,6 vs -0,7±40, P=0,91). CONCLUSÃO: O nível de lípides séricos diferiu durante o tratamento com Peg-IFN/RBV e AADs. O tratamento com AADs foi associado a um aumento de CT e LDL e uma diminuição de TG, independentemente da RVS.

Hepatitis C viral load in HCV-monoinfected and HCV/HIV-1-, HCV/HTLV-1/-2-, and HCV/HIV/HTLV-1/-2-co-infected patients from São Paulo, Brazil

ABSTRACT Co-infections of hepatitis C virus (HCV) and either human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type 1 (HTLV-1) or type 2 (HTLV-2) have been described as having an impact on HCV viremia and subsequent disease progression. HCV load in serum samples from 622 patients (343 males, 279 females; median age 50.8 years) from São Paulo/southeast Brazil was analyzed using the Abbott Real Time HCV assay (Abbott Molecular Inc., IL, USA). Samples were obtained from HCV-monoinfected (n = 548), HCV/HIV-1- (n = 41), HCV/HTLV-1- (n = 16), HCV/HTLV-2- (n = 8), HCV/HIV/HTLV-1- (n = 4), and HCV/HIV/HTLV-2-co-infected (n = 5) patients, and results were compared among the groups and according to sex. The median HCV load in HCV-monoinfected patients was 5.23 log10 IU/mL and 0.31 log10 higher in men than in women. Increases in viral load of 0.51 log10, 0.54 log10, and 1.43 log10 IU/mL were detected in HCV/HIV-1-, HCV/HTLV-1- and HCV/HIV/HTLV-1-co-infected individuals, respectively, compared with HCV-monoinfected counterparts. In contrast, compared to HCV/HIV co-infected patients, HCV/HTLV-2-co-infected patients had an HCV load of 5.0 log10 IU/mL, whereas HCV/HIV/HTLV-2-co-infected patients had a median load 0.37 log10 IU/mL lower. Significant differences in HCV loads were detected, with males and HCV/HIV-1- and HCV/HIV/HTLV-1-co-infected patients presenting the highest values. Conversely, females and HCV/HTLV-2-co-infected patients exhibited lower HCV loads. Overall, HCV viremia is increased in HIV and/or HTLV-1-co-infection and decreased in HTLV-2 co-infection.

Transient Elastography vs Aspartate Aminotransferase to Platelet Ratio Index in Hepatitis C: A Meta-Analysis

ABSTRACT Background and rationale. Many different non-invasive methods have been studied with the purpose of staging liver fibrosis. The objective of this study was verifying if transient elastography is superior to aspartate aminotransferase to platelet ratio index for staging fibrosis in patients with chronic hepatitis C. Material and methods. A systematic review with meta-analysis of studies which evaluated both non-invasive tests and used biopsy as the reference standard was performed. A random-effects model was used, anticipating heterogeneity among studies. Diagnostic odds ratio was the main effect measure, and summary receiver operating characteristic curves were created. A sensitivity analysis was planned, in which the meta-analysis would be repeated excluding each study at a time. Results. Eight studies were included in the meta-analysis. Regarding the prediction of significant fibrosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 11.70 (95% confidence interval = 7.13-19.21) and 8.56 (95% confidence interval = 4.90-14.94) respectively. Concerning the prediction of cirrhosis, transient elastography and aspartate aminotransferase to platelet ratio index had diagnostic odds ratios of 66.49 (95% confidence interval = 23.71- 186.48) and 7.47 (95% confidence interval = 4.88-11.43) respectively. Conclusion. In conclusion, there was no evidence of significant superiority of transient elastography over aspartate aminotransferase to platelet ratio index regarding the prediction of significant fibrosis, but the former proved to be better than the latter concerning prediction of cirrhosis.

Viral Outcome in Patients with Occult HBV Infection or HCV-Ab Positivity Treated for Lymphoma

ABSTRACT HBV and HCV reactivation has been widely reported in patients undergoing immunosuppressive therapy for oncohaematological diseases. We aimed to evaluate the HBV and HCV reactivation events in patients with non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) underwent cytotoxic chemotherapy containing or not rituximab. This is a retrospective observational study, including all patients with NHL and HL attending an Italian tertiary referral hospital, the University of Naples "Federico II". A total of 322 patients were enrolled. We evaluated serum HBV and HCV markers. A total of 47 (38%) patients with occult HBV infection were enrolled. Seven/47 were treated with therapeutic cytotoxic schedule containing rituximab. Of them, 6/7 received prophylaxis with lamivudine. HBV reactivation was observed in two patients treated with rituximab. A reactivation was observed in the only patient (HBcAb+/HBsAb+) not receiving lamivudine prophylaxis, and the other one was observed in 1 patient with isolated HBcAb positivity during lamivudine prophylaxis. Moreover, 8 patients with HCV-Ab positivity were enrolled. No viral reactivation was observed in these patients. In conclusion, patients with occult HBV infection receiving chemotherapy containing rituximab for lymphoma without antiviral prophylaxis are at risk of viral reactivation. On the contrary, there is no risk of reactivation in patients undergoing rituximab-free schedule. Our findings suggest that there is also very low risk of HCV reactivation. This preliminary report underlines the concept that HBV reactivation is strongly related to the type of immunosuppressive therapy administered and that antiviral prophylaxis needs to be tailored.

Combination of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C Virus Genotype 1 Infection: Systematic Review and Meta-Analysis

ABSTRACT Background and aim. The combination of Sofosbuvir (SOF) and Ledipasvir (LDV) has been lead to considerable enhancement of treatment of hepatitis C virus (HCV) genotype 1 infection. A meta-analysis of the currently available studies was undertaken with the aim to evaluate the antiviral efficacy of SOF/LDV therapy for 12 or 24 weeks with or without Ribavirin (RBV) in patients with HCV genotype 1 infection. Material and methods. In this meta-analysis, we searched databases including PubMed, Scopus, Science Direct and Web of Science using appropriate keywords. All papers which evaluated the efficacy of combination therapy of SOF/LDV with or without RBV for 12 or 24 weeks among patients with HCV genotype 1 infection were included. Results. The 20 published articles were assessed for eligibility and finally 10 articles pooling 2248 participants were included in this meta-analysis. Pooled SVR12 for four SOF/LDV regimens were 95% (95%CI = 93%-97%) for 12 weeks of treatment with SOF/LDV, 97% (95%CI = 95%-98%) for 24 weeks of treatment with SOF/LDV, 96% (95%CI = 94%-97%) for 12 weeks of treatment with SOF/ LDV/RBV and 98% (95%CI = 97%-99%) for 24 weeks of treatment with SOF/LDV/RBV. Only in treatment regimen of SOF/LDV for 12 weeks, cirrhosis had a significant effect on the SVR12 (OR = 0.21, 95%CI = 0.07-0.66). Furthermore, NS5A resistance-associated substitutions at baseline were associated with decrease in the rate of SVR (OR = 0.31, 95%CI = 0.2-0.5). Conclusions. The Interferon-free regimen of SOF/LDV for 12 or 24 weeks with or without RBV is highly effective for treatment of patients with HCV genotype 1 infection.

Sofosbuvir and Daclatasvir in Mono-and HIV-coinfected Patients with Recurrent Hepatitis C After Liver Transplant

Abstract: Background and aims. Pegylated interferon (Peg-INF) and ribavirin (RBV) based therapy is suboptimal and poorly tolerated. We evaluated the safety, tolerability and efficacy of a 24-week course of sofosbuvir plus daclatasvir without ribavirin for the treatment of hepatitis C virus (HCV) recurrence after liver transplantation (LT) in both HCV-monoinfected and human immunodeficiency virus (HIV)-HCV coinfected patients. Material and methods. We retrospectively evaluated 22 consecutive adult LT recipients (16 monoinfected and 6 coinfected with HIV) who received a 24-week course of sofosbuvir plus daclatasvir treatment under an international compassionate access program. Results. Most patients were male (86%), with a median age of 58 years (r:58-81y). Median time from LT to treatment onset was 70 months (r: 20-116 m). HCV genotype 1b was the most frequent (45%), 55% had not responded to previous treatment with Peg-INF and RBV and 14% to regiments including first generation protease inhibitors. Fifty-six percent of the patients had histologically proven cirrhosis and 6 had ascites at baseline. All patients completed the 24-week treatment course without significant side effects except for one episode of severe bradicardya, with only minor adjustments in immunosuppressive treatment in some cases. Viral suppression was very rapid with undetectable HCV-RNA in all patients at 12 weeks. All 22 patients achieved a sustained virological response 12 weeks after treatment completion. Conclusion. The combination of sofosbuvir plus daclatasvir without ribavirin is a safe and effective treatment of HCV recurrence after LT in both monoinfected and HIV-coinfected patients, including those with decompensated cirrhosis.

Association of genotypes with viral load and biochemical markers in HCV-infected Sindhi patients

Abstract The presented study had two objectives. The first was to examine distributions of Hepatitis C Virus (HCV) genotypes in Sindh, Pakistan, where HCV is prevalent. The other was to explore clinically relevant relationships between the genotypes, viral load (measured by real-time polymerase chain reaction assays) and biochemical markers. For this, 1471 HCV-infected patients in six cities in Sindh were recruited and sampled. HCV genotype distributions varied among the cities, but genotype 3a was most prevalent, followed by 3b, 1a and 1b (detected in 51.5, 22.7. 9.25 and 3.2% of the cases, respectively). No type-specific sequences were detected in serum samples from 189 (12.8%) of the 1471 patients. Frequencies of low (<200,000 IU/mL serum), intermediate (200,000-600,000 IU/mL serum) and high (>600,000 IU/mL serum) viral loads were respectively 45.4, 16.5 and 38.1% for patients infected with genotype 3, and 16.9, 36.9 and 46.2%, respectively, for patients with other genotypes. Infection with genotype 1a was associated with significantly higher (p < 0.005) alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase titers than infection with genotype 3a. The results will help in the formulation of treatment strategies.

In-house quantitative real-time PCR for the diagnosis of hepatitis B virus and hepatitis C virus infections

Abstract The quantification of viral nucleic acids in serum by real-time PCR plays an important role in diagnosing hepatitis B virus and hepatitis C virus infection. In this study, we developed an assay using specific primers and probes to quantify hepatitis B virus DNA or hepatitis C virus RNA in serum from infected patients. For standardization and validation of the assay, an international panel of hepatitis B virus/hepatitis C virus and standard plasmids was used. A correlation coefficient of 0.983 and 0.963 for hepatitis B virus and hepatitis C virus, respectively, was obtained based on cycle threshold values and concentrations of DNA or RNA. The standard curve showed a linear relationship from 19 IU/mL to 1.9 × 109 IU/mL of serum, with a coefficient of determination (r2) of 0.99. In sera from patients infected with hepatitis B virus or hepatitis C virus viral loads (19 IU/mL and 1.9 × 109 IU/mL), we quantified viral loads with a detection limit of 1.9 × 102 IU/mL. The real-time quantitative PCR assay developed in this study provides an ideal system for routine diagnosis and confirmation of indeterminate serological results, especially in immunosuppressed patients.

An original method for producing acetaldehyde and diacetyl by yeast fermentation

Abstract In this study a natural culture medium that mimics the synthetic yeast peptone glucose medium used for yeast fermentations was designed to screen and select yeasts capable of producing high levels of diacetyl and acetaldehyde. The presence of whey powder and sodium citrate in the medium along with manganese and magnesium sulfate enhanced both biomass and aroma development. A total of 52 yeasts strains were cultivated in two different culture media, namely, yeast peptone glucose medium and yeast acetaldehyde-diacetyl medium. The initial screening of the strains was based on the qualitative reaction of the acetaldehyde with Schiff's reagent (violet color) and diacetyl with Brady's reagent (yellow precipitate). The fermented culture media of 10 yeast strains were subsequently analyzed by gas chromatography to quantify the concentration of acetaldehyde and diacetyl synthesized. Total titratable acidity values indicated that a total titratable acidity of 5.5 °SH, implying culture medium at basic pH, was more favorable for the acetaldehyde biosynthesis using strain D15 (Candida lipolytica; 96.05 mg L-1 acetaldehyde) while a total titratable acidity value of 7 °SH facilitated diacetyl flavor synthesis by strain D38 (Candida globosa; 3.58 mg L-1 diacetyl). Importantly, the results presented here suggest that this can be potentially used in the baking industry.

Presente y futuro de la terapia contra la hepatitis C / Present and future of therapy against hepatitis C

Un 3% de la población mundial está infectado por el virus de la hepatitis C (VHC). Un 70-80% de los individuos infectados desarrollan una infección crónica. No se dispone de una vacuna contra la hepatitis C y aproximadamente 50% de los pacientes infectados no responden a la terapia estándar basada en la combinación de interferón-alfa (IFN-α) y ribavirina. Recientemente se han hecho disponibles drogas antivirales de acción directa contra el VHC, que representan una mejora significativa en el éxito terapéutico. En el 2014, la agencia reguladora de drogas y alimentos de Estados Unidos (de sus siglas en inglés FDA), aprobó el uso de ledipasvir más sofosbuvir para el tratamiento crónico de la infección, siendo el primer régimen aprobado que no requiere la administración de IFN-α ó ribavirina. Estos avances hacen esperar la erradicación de esta enfermedad, si no fuera por los altos costos asociados al tratamiento. Una alternativa emergente es la terapia enfocada a la inhibición de blancos celulares que intervienen en la infección por el VHC. Esta terapia podría aumentar tanto el número de opciones para la terapia como la barrera genética para la selección de variantes virales resistentes. El tratamiento de la hepatitis C podría llevar al uso de la terapia enfocada en blancos celulares en combinación con la terapia tradicional, esperando un posible efecto sinérgico.

Around 3% of the human population is infected with hepatitis C virus (HCV) and 70-80% of these individuals develop a chronic infection. There is no vaccine available against HCV and up to 50% of the infected patients do not respond to standard therapy, based on the combination of interferon-alpha (IFN-α) and ribavirin. Recently, direct acting antiviral drugs against HCV have been made available for treatment, leading to a significant improvement in therapeutic success. In 2014, the U.S. Food and Drug Administration approved ledipasvir plus sofosbuvir to treat the chronic infection, the first IFN- and ribavirin-free approved treatment. With such treatment, the eradication of the disease would be feasible, although drug costs are high. Host target therapy represents an emerging alternative, based on the understanding of host factors involved in the HCV infection. This therapy might show at least two theoretical benefits, increasing the number of options for therapy and raising the genetic barrier for selection of resistant variants. New treatment regimens may consist of classical therapy combined with host target-based therapy, hopefully in a synergistic manner.

Phylogenetic analysis of the emergence of main hepatitis C virus subtypes in São Paulo, Brazil

ABSTRACTBACKGROUND: It is recognized that hepatitis C virus subtypes (1a, 1b, 2a, 2b, 2c and 3a) originated in Africa and Asia and spread worldwide exponentially during the Second World War (1940) through the transfusion of contaminated blood products, invasive medical and dental procedures, and intravenous drug use. The entry of hepatitis C virus subtypes into different regions occurred at distinct times, presenting exponential growth rates of larger or smaller spread. Our study estimated the growth and spread of the most prevalent subtypes currently circulating in São Paulo.METHODS:A total of 465 non-structural region 5B sequences of hepatitis C virus covering a 14-year time-span were used to reconstruct the population history and estimate the population dynamics and Time to Most Recent Common Ancestor of genotypes using the Bayesian Markov Chain Monte Carlo approach implemented in BEAST (Bayesian evolutionary analysis by sampling tree software/program).RESULTS:Evolutionary analysis demonstrated that the different hepatitis C virus subtypes had distinct growth patterns. The introduction of hepatitis C virus-1a and -3a were estimated to be circa 1979 and 1967, respectively, whereas hepatitis C virus-1b appears to have a more ancient entry, circa 1923. Hepatitis C virus-1b phylogenies suggest that different lineages circulate in São Paulo, and four well-supported groups (i.e., G1, G2, G3 and G4) were identified. Hepatitis C virus-1a presented the highest growth rate (r = 0.4), but its spread became less marked after the 2000s. Hepatitis C virus-3a grew exponentially until the 1990s and had an intermediate growth rate (r = 0.32). An evident exponential growth (r = 0.26) was found for hepatitis C virus-1b between 1980 and the mid-1990s.CONCLUSIONS:After an initial period of exponential growth, the expansion of the three main subtypes began to decrease. Hepatitis C virus-1b presented inflated genetic diversity, and its transmission may have been sustained by different generations and transmission routes other than blood transfusion. Hepatitis C virus-1a and -3a showed no group stratification, most likely due to their recent entry.