Status of clinical research in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts / 器官移植

Antiviral therapy for chronic hepatitis C virus (HCV) infection has entered the era of direct antiviral agent (DAA), and up to 95% of patients could be clinically cured. Under this circumstance, HCV infection has gradually changed from relative contraindication to surgical indication for kidney transplantation. However, at present, the number of kidney transplantation from HCV-infected donors or recipients has been rarely reported in China. The short-term follow-up data of HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts in other countries have confirmed that DAA yields high cure rate and safety in the treatment of HCV infection, and recipients could obtain favorable short-term survival and allograft outcome. However, the long-term safety of HCV-infected kidney transplantation remains to be validated by clinical trials with large sample size and long-term follow-up. In this article, the virological clearance, allograft outcome and safety of DAA use in HCV-negative recipients undergoing kidney transplantation from HCV-positive renal allografts under the intervention of DAA were investigated, aiming to evaluate clinical safety and efficacy of this pattern of kidney transplantation and deepen the understanding of safe use of HCV-positive organs.

Reinfección por virus de la hepatitis C: revisión de tema y presentación de un caso / Hepatitis C virus reinfection: A review of the topic and case report

Resumen La infección crónica por el virus de la hepatitis C (VHC) afecta a 58 millones de personas y es una importante causa de morbimortalidad alrededor del mundo. La reinfección por VHC es un problema creciente en personas con factores de riesgo como consumo pesado de alcohol, sexo anal, sexo grupal y compartir agujas y jeringas; este tipo de infección se define como un nuevo contagio de VHC con un genotipo viral diferente al de la primera infección en un paciente luego de lograr una respuesta viral sostenida (RVS). La reinfección se presenta, en parte, debido a la ausencia de estrategias de promoción y prevención. Teniendo en cuenta estos antecedentes, se han propuesto estrategias más pragmáticas para controlar la infección por VHC y evitar la reinfección, tales como la microeliminación. En el presente artículo se presenta un caso de un paciente que presenta alteración en los marcadores de la bioquímica hepática, por lo que se solicita una prueba diagnóstica de infección por VHC y luego genotipificación viral, y se evidenció una infección por VHC genotipo 1, subgenotipo 1A. Se inició el manejo con antivirales de acción directa y se documentó una adecuada RVS12. Tres meses después el paciente regresó a consulta y en los exámenes de control se evidenció una carga viral elevada de VHC, por lo que se solicitó genotipificación y se demostró una nueva infección por VHC genotipo 4.

Abstract Chronic hepatitis C (HCV) infection affects 58 million people and is a significant cause of morbidity and mortality worldwide. HCV reinfection is a growing problem in people with risk factors such as heavy alcohol use, anal sex, group sex, and sharing needles and syringes. This type of infection is defined as a new HCV infection with a different viral genotype than the first infection in a patient after achieving a sustained viral response (SVR). Reinfection occurs, in part, due to the absence of promotion and prevention strategies. Taking this background into account, more pragmatic approaches have been proposed to control HCV infection and avoid reinfection, such as micro elimination. This article reports the case of a patient with alterations in biochemical liver markers, for which a diagnostic test for HCV infection and then viral genotyping was requested. Infection by HCV genotype 1, subgenotype 1A, was evidenced. Management with direct-acting antivirals was started, and an adequate SVR12 was documented. Three months later, the patient returned, and the control tests showed a high HCV viral load, for which genotyping was requested, showing a new HCV genotype 4 infection.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: 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. Patients and methods: 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. Results: 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. Conclusion: 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.

Progress in the treatment of chronic hepatitis C virus genotype 3 infection / 中华临床感染病杂志

Hepatitis C virus genotype 3 (HCV G3) infection is the second most prevalent hepatitis C genotype globally, with higher rates of disease progression and mortality compared with other genotypes. After the advent of direct-acting antiviral drugs (DAAs), the efficacy of antiviral therapy for hepatitis C patients has been greatly improved, but the therapy for G3 type is less effective than that for other genotypes, so it is considered to be one of the most difficult subtypes to treat. This article reviews the available treatment options for HCV G3 patients and their sustained virological response rates to provide clinical reference.

Diabetes influences liver stiffness in chronic hepatitis C patients with and without virological cure: A longitudinal study

OBJECTIVES: The aim was to prospectively assess the variation in liver stiffness (LS) and the associated factors for LS progression in a cohort of naïve, non-responder (NR), and sustained virological response (SVR) chronic hepatitis C (CHC) patients. METHODS: This was a longitudinal study on CHC patients prospectively followed with serial elastography (Fibroscan®). The LS progression rate was determined, and the associated factors for progression were assessed using multiple linear regression analysis. RESULTS: A total of 406 patients were followed up for 44 (35-53) months [naïve (29%), NR (24%), and SVR (47%)]. At the end of the follow-up period, the SVR group had a significant decrease in LS [11.8 (9.2) vs. 8.8 (8.4) kPa (p<0.001)], the NR group had a significant increase in LS [6.6 (5.2) vs. 7.1 (4.5) kPa (p=0.069)], and the naïve group had no change in LS [6.3 (3.0) vs. 6.0 (3.8) kPa (p=0.22)]. The related factors for LS progression were lack of SVR (p=0.002) and diabetes (p=0.05). In the non-diabetic SVR group, a negative rate of progression (-0.047 kPa/month) was observed, whereas in the diabetic SVR group, a positive rate of progression (+0.037 kPa/month) was observed. The highest rate of progression was observed in NR with diabetes at the rate of +0.044 kPa/month. CONCLUSION: LS in diabetes patients progresses despite SVR, suggesting the need for a close follow-up of this group post-treatment considering the risk of progression of liver disease even after SVR.

Polimorfismos del gen de interleucina 10 y respuesta virológica sostenida en pacientes cubanos coinfectados con virus de hepatitis C y virus de inmunodeficiencia humana / Interleukin-10 gene polymorphisms and sustained virological response in Cuban patients coinfected with hepatitis C virus and human immunodeficiency virus

Introducción: En pacientes infectados con el virus de la hepatitis C se demostró que los polimorfismos de un simple nucleótido del gen de la interleucina 10 (IL10), influyen en la respuesta virológica sostenida al tratamiento con interferón y ribavirina, y en la inmunopatogénesis de la enfermedad. Objetivo: Determinar la frecuencia de los polimorfismos de un simple nucleótido de la región promotora del gen de la interleucina 10, según respuesta virológica sostenida y grado de lesión hepática. Métodos: Se realizó un estudio descriptivo, de corte transversal y se determinó la carga del virus de la hepatitis C por RT-PCR en tiempo real. Se estudiaron 25 pacientes cubanos con virus de inmunodeficiencia humana coinfectados con VHC, 24 semanas después del tratamiento con interferón y ribavirina. Para evaluar la variabilidad genética de la interleucina 10, los polimorfismos de un simple nucleótido se identificaron por secuenciación nucleotídica, -592 (A>C) y -819 (T>C). El grado de fibrosis hepática se calculó por el índice aspartato aminotransferasa/plaquetas. Resultados: El 44,0 por ciento (11/25) de los pacientes lograron respuesta virológica sostenida, y en el 56,0 por ciento (14/25) restante no se obtuvo esta. En los individuos en que se dio la respuesta predominaron los genotipos bajos productores de la interleucina 10, -592AA (36,3 por ciento vs. 21,4 por ciento) y -819TT (54,5 por ciento vs. 21,4 por ciento). En estos casos, el análisis de la frecuencia alélica mostró mayor frecuencia del alelo T para el SNP -819 (p= 0,0470). El índice aspartato aminotransferasa/plaquetas fue compatible con fibrosis hepática sin cirrosis en pacientes sin respuesta virológica sostenida, mientras que en los coinfectados que tuvieron respuesta indicó ausencia de lesión hepática. Conclusiones: Los resultados sugieren que las variantes de los polimorfismos de un simple nucleótido del gen de la interleucina 10 evaluados, podrían estar relacionados con la respuesta virológica sostenida y la patogénesis de la hepatitis C en los pacientes estudiados(AU)

Introduction: The study of patients infected with hepatitis C virus revealed that polymorphisms of a single nucleotide of the interleukin-10 (IL10) gene influence the sustained virological response to the treatment with interferon and ribavirin, and the immunopathogenesis of the disease. Objective: Determine the frequency of single-nucleotide polymorphisms from the interleukin-10 gene promoter region according to the sustained virological response and the degree of liver injury. Methods: A descriptive cross-sectional study was conducted and hepatitis C viral load was determined by RT-PCR. A sample of 25 Cuban HIV/HCV coinfected patients were studied 24 weeks after treatment with interferon and ribavirin. To evaluate the genetic variability of interleukin 10, the single-nucleotide polymorphisms were identified by nucleotide sequencing, -592 (A>C) and -819 (T>C). The degree of liver fibrosis was estimated by the aspartate aminotransferase / platelet index. Results: Of the patients studied, 44.0 percent (11/25) achieved a sustained virological response and 56.0 percent (14/25) did not. In individuals displaying the response, a predominance was found of low interleukin-10 producing genotypes, -592AA (36.3 percent vs. 21.4 percent) and -819TT (54.5 percent vs. 21.4 percent). In those cases, allele frequency analysis showed a greater allele T frequency for SNP -819 (p= 0.0470). The aspartate aminotransferase / platelet index was compatible with kidney fibrosis without cirrhosis in patients without a sustained virological response, and indicated an absence of liver injury in coinfected patients displaying a response. Conclusions: Results suggest that the variants evaluated of single-nucleotide polymorphisms of the interleukin-10 gene could be related to the sustained virological response and the pathogenesis of hepatitis C in the patients studied(AU)

Perfil epidemiológico e resposta virológica sustentada de pacientes com hepatite C crônica em resposta ao tratamento com os novos antivirais de ação direta em dois serviços de referência do extremo sul catarinense / Epidemiological profile and sustained virological response of patients with chronic hepatitis C in response to treatment with the new direct action antivirals in two reference services of the extreme south of santa catarina

A hepatite C, causada pelo vírus da hepatite C, acomete aproximadamente 80 a 150 milhões da população mundial e 2 a 3 milhões da população brasileira. Dos pacientes infectados, 60 a 70% irão evoluir para doença hepática crônica, e seu tratamento atual é realizado com os novos antivirais de ação direta de segunda geração (sofosbuvir, simeprevir e daclatasvir). Este estudo objetivou verificar o perfil epidemiológico e a resposta virológica sustentada dos pacientes com hepatite C crônica submetidos a tratamento nas cidades de Criciúma - Santa Catarina e Araranguá - Santa Catarina, no período de outubro de 2015 a fevereiro de 2017. É um estudo observacional, quantitativo com delineamento retrospectivo. A amostra foi composta por 172 prontuários de pacientes portadores do vírus da hepatite C crônica. A análise dos dados foi feita com o auxílio do software IBM Statistical Package for the Social Sciences (SPSS) versão 22.0 e nível de significância α = 0,05. Dos pacientes tratados, 69,2% eram do sexo masculino, 45,9% estavam entre a faixa etária de 51 a 60 anos, 60,5% possuíam genótipo tipo 1, 5,2% eram transplantados hepáticos, 19,2% eram coinfectados pelo vírus da imunodeficiência humana adquirida, 52,9% realizaram outro tratamento prévio e a resposta virológica sustentada da amostra foi de 94,2%. Dessa forma, o estudo sugere eficácia do tratamento instituído quando comparado a dados nacionais, em vista de sua elevada taxa de resposta virológica sustentada.

Hepatitis C, caused by the hepatitis C virus, affects approximately 80 to 150 million of the world's population and 2 to 3 million of the Brazilian population. Among the infected patients, 60 to 70% will progress to chronic liver disease, and their current treatment is with the new second generation direct acting antivirals (sofosbuvir, simeprevir and daclatasvir). This study aimed to verify the epidemiological profile and sustained virological response of patients with chronic hepatitis C undergoing treatment in the cities of Criciúma - Santa Catarina and Araranguá - Santa Catarina, from October 2015 to February 2017. It is an observational study, quantitative study with a retrospective design. The sample consisted of 172 medical records of patients with chronic hepatitis C virus. Data analysis was performed with the aid of the IBM Statistical Package for Social Sciences (SPSS) version 22.0 and significance level α = 0.05. About the patients treated, 69,2% were male, 45,9% were between 51 and 60 years old, 60,5% had type 1 genotype, 5,2% were hepatic transplants, 19,2% were coinfected with the acquired human immunodeficiency virus, 52.9% had undergone another previous treatment and the sustained virological response of the sample was 94,2%. Therefore, the research performed suggests the effectiveness of the treatment instituted when compared to national data.

Sofosbuvir-based regimens combined with ribavirin for recipients with genotype 1 hepatitis C after liver transplantation: a Meta-analysis / 器官移植

Objective To evaluate whether sofosbuvir (SOF)-based direct-acting antiviral agents (DAAs) combined with ribavirin (RBV) (combined RBV) can yield benefits to the recipients infected with hepatitis C virus (HCV) genotype 1 (GT1) after liver transplantation through systematic evaluation and Meta-analysis. Methods Multiple databases at home and abroad were systematically searched, the literature screening was conducted according to relevant standards, the quality of literatures was evaluated and data extraction was performed. The literature was divided into two groups according to the recipients with HCV-GT1 hepatitis after liver transplantation who received the treatment combined RBV or SOF-based DAAs alone without RBV (not combined RBV). Meta-analysis of the data was carried out using Rev Man 5.3 and R3.4.3 software. The incidence of sustained virological response 12 weeks (SVR12) after therapy was evaluated. Results A total of 2 195 articles were retrieved, and 6 articles published in English were eventually included according to the inclusion criteria. The Meta-analysis results demonstrated that the incidence of SVR12 did not significantly differ between the combined RBV and not combined RBV groups (P=0.28). However, the incidence of anemia in the combined RBV group was significantly higher than that in the other group (P < 0.01). Both combined RBV and not combined RBV therapies were efficacious in treating HCV-GT1a and HCV-GT1b subtypes after liver transplantation with similar clinical efficacy (P=0.33). The incidence of SVR in HCV-GT1 recipients did not significantly differ after receiving 12- and 24-weeks therapy after liver transplantation (P=0.95). Conclusions When SOF-based DAAs regimen is adopted to treat HCV-GT1 in recipients after liver transplantation, combination with RBV not only fails to improve the virus clearance rate and bring clinical benefits, but also increases the risk of anemia in the recipients.

Clinical effect and safety of sofosbuvir-ledipasvir regimen in treatment of patients with HCV genotype 6a chronic hepatitis C / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of sofosbuvir (SOF)-ledipasvir (LDV) in the treatment of patients with HCV genotype 6a chronic hepatitis C (CHC). MethodsA total of 63 patients with HCV genotype 6a CHC who visited Department of Infectious Diseases, Henan Provincial People’s Hospital and Nanfang Hospital, from October 2014 to December 2016 were enrolled in this prospective observational study. They were divided into SOF-LDV group (treated with SOF-LDV for 12 weeks) and PR group (treated with pegylated interferon combined with ribavirin for 24 weeks). HCV RNA was measured during treatment and follow-up, and virologic response was evaluated. The chi-square test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of continuous data between two groups. ResultsThere were no significant differences between the PR group and the SOF-LDV group in rapid virologic response rate (85.3% vs 100%, P＞0.05) and virologic response rate at the end of treatment (94.1% vs 100%, P＞005). The SOF-LDV group had a significantly higher sustained virologic response rate than the PR group (96.4% vs 73.5%, χ2=438, P=0.036). The PR group had a significantly higher incidence rate of adverse events than the SOF-LDV group(χ2=754,P=0006). During follow-up, one patient with liver cirrhosis in the SOF-LDV group developed small hepatocellular carcinoma, while no patient in the PR group developed liver cancer at the end of follow-up. ConclusionSOF-LDV for 12 weeks is safe and effective in the treatment of HCV genotype 6a CHC, but liver cancer should be closely monitored in patients with liver cirrhosis.

Clinical effect and safety of sofosbuvir-ledipasvir regimen in treatment of patients with HCV genotype 6a chronic hepatitis C / 临床肝胆病杂志

ObjectiveTo investigate the clinical effect and safety of sofosbuvir (SOF)-ledipasvir (LDV) in the treatment of patients with HCV genotype 6a chronic hepatitis C (CHC). MethodsA total of 63 patients with HCV genotype 6a CHC who visited Department of Infectious Diseases, Henan Provincial People’s Hospital and Nanfang Hospital, from October 2014 to December 2016 were enrolled in this prospective observational study. They were divided into SOF-LDV group (treated with SOF-LDV for 12 weeks) and PR group (treated with pegylated interferon combined with ribavirin for 24 weeks). HCV RNA was measured during treatment and follow-up, and virologic response was evaluated. The chi-square test was used for comparison of categorical data between two groups, and the Mann-Whitney U test was used for comparison of continuous data between two groups. ResultsThere were no significant differences between the PR group and the SOF-LDV group in rapid virologic response rate (85.3% vs 100%, P＞0.05) and virologic response rate at the end of treatment (94.1% vs 100%, P＞005). The SOF-LDV group had a significantly higher sustained virologic response rate than the PR group (96.4% vs 73.5%, χ2=438, P=0.036). The PR group had a significantly higher incidence rate of adverse events than the SOF-LDV group(χ2=754,P=0006). During follow-up, one patient with liver cirrhosis in the SOF-LDV group developed small hepatocellular carcinoma, while no patient in the PR group developed liver cancer at the end of follow-up. ConclusionSOF-LDV for 12 weeks is safe and effective in the treatment of HCV genotype 6a CHC, but liver cancer should be closely monitored in patients with liver cirrhosis.

A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection / 中华肝脏病杂志

Objective@#To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection.@*Methods@#Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval.@*Results@#132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death.@*Conclusion@#Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India

Background & objectives: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. Methods: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon ?-2a 180 ?g per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). Results: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). Interpretation & conclusions: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

Effectiveness of chronic hepatitis C treatment with direct-acting antivirals in the Public Health System in Brazil

ABSTRACT Introduction Chronic hepatitis C virus infection is one of the major causes of cirrhosis, hepatocellular carcinoma and liver transplantation. Treatment using direct-acting antivirals has revolutionized the treatment of hepatitis C virus, increasing long-term prognosis after cure. The goal of the present study was to evaluate the effectiveness of direct-acting antivirals in a Public Health System in southern Brazil. Methods A retrospective study evaluated all patients with chronic hepatitis C virus infection who underwent treatment at one center of the Public Health Department of the State of Rio Grande do Sul - Brazil, according to the Brazilian Clinical Protocol and Therapeutic Guidelines. The effectiveness was assessed in terms sustained virological response 12 weeks after the end of treatment. Results A total of 1002 patients who were treated for chronic hepatitis C virus infection were evaluated. The mean age was 58.6 years, 557 patients (55.6%) were male and 550 (54.9%) were cirrhotic. Overall sustained virological response was observed in 936 (93.4%) patients. There was a difference in sustained virological response rate varied according to sex, 91.6% in men and 95.7% in women (p= 0.009), length of treatment in genotype 1, 92.7% with 12 weeks and 99.1 with 24 weeks (p= 0.040), and genotype, 94.7% in genotype 1, 91.7% in genotype 2, and 91.4% in genotype 3 (p= 0.047). Conclusion The treatment of chronic hepatitis C virus infection for genotypes 1, 2 or 3 with the therapeutic regimens established by the Brazilian guidelines showed high rates of SVR, even in cirrhotic patients.

Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Abstract INTRODUCTION: In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated. METHODS: Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant. RESULTS: Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia. CONCLUSIONS: The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.

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.

Survival benefits of interferon-based therapy in patients with recurrent hepatitis C after orthotopic liver transplantation

Recurrent hepatitis C after orthotopic liver transplantation (OLT) is universal and can lead to graft failure and, consequently, reduced survival. Hepatitis C treatment can be used to prevent these detrimental outcomes. The aim of this study was to describe rates of hepatitis C recurrence and sustained virological response (SVR) to interferon-based treatment after OLT and its relationship to survival and progression of liver disease through retrospective analysis of medical records of 127 patients who underwent OLT due to cirrhosis or hepatocellular carcinoma secondary to chronic hepatitis C between January 2002 and December 2013. Fifty-six patients were diagnosed with recurrent disease, 42 started interferon-based therapy and 37 completed treatment. Demographic, treatment- and outcome-related variables were compared between SVR and non-responders (non-SVR). There was an overall 54.1% SVR rate with interferon-based therapies. SVR was associated with longer follow-up after treatment (median 66.5 vs 37 months for non-SVR, P=0.03) and after OLT (median 105 vs 72 months, P=0.074), and lower rates of disease progression (15 vs 64.7%, P=0.0028) and death (5 vs 35.3%, P=0.033). Regardless of the result of therapy (SVR or non-SVR), there was a significant difference between treated and untreated patients regarding the occurrence of death (P<0.001) and months of survival (P<0.001). Even with suboptimal interferon-based therapies (compared to the new direct-acting antivirals) there is a 54.1% SVR rate to treatment. SVR is associated with improved survival and reduced risks of clinical decompensation, loss of the liver graft and death.

Treatment research progress of cirrhosis of the liver decompensation period, the splenic function and thrombocytopenia after hepatitis C / 中国综合临床

HCV-related decompensated cirrhos,hypersplenism,thrombocytopenia,which not only affect the standard antiviral therapy,fail to achieve the sustained virological response(SVR),but also increase the risk of infection and bleeding.The only successful option is liver transplantation (LT),but the recurrence of HCV after LT remains to be resolved.The patients of HCV genotype 2 are suitable for splenectomy and antiviral therapy following splenectomy,which can achieved a higher SVR and reversed cirrhosis.As an effective alternative to splenectomy,the partial splenic embolization (PSE) can improve the changes of portal hemodynamics and reduce the sequelae of portal hypertension.The appearance of direct antiviral drugs (DAAs)has bring hope for those with decompensated cirrhos and whom IFN is contraindicated or tolerated poorly,those who are waiting for LT or with recurrence of hepatitis C after LT.The treatment of patients with decompensated cirrhos is as follows.

The clinical features and treatment outcome of chronic hepatitis C with pegylated interferon and ribavirin in routine care

Aim: To describe the clinical characteristic of hepatitis C (HCV) patients and the results of pegylated interferon and ribavirin (PegIFN/RBV) therapy in a routine clinical practice. Methods: A retrospective review of consecutive HCV patients treated with PegIFN/RBV in 2004 to 2012. Results: A total of 273 patients received treatment. The mean age was 44.16 ± 10.5 years and 76% were male. The top 2 self-reported risks were blood or blood product transfusion before 1994 and injection drug use, found in 57.1% of patients. The predominant HCV genotype (GT) was 3 at 60.6%, second was GT1 at 36.1% and other GTs were uncommon at about 1% or less. About half of our patients have high baseline viral load (>800,000 iu/ml), 18.3% had liver cirrhosis and 22.3% had HIV co-infection. Co-morbid illness was found in 42.9%, hypertension and type 2 diabetes were the two most common. The overall sustained virological response (SVR) by intention-to-treat analysis were 54.9% (n=150/273), 41.2% (40/97) for GT1, 100% (5/5) for GT2 and 62% (101/163) for GT3. Subgroup analysis for HCV monoinfected, treatment naïve showed SVR of 49.2% (31/63) for GT1, 100% (5/5) for GT2 and 67% (69/103) for GT3. In HCV mono-infected and treatment experienced (n=29), the SVR was 28.6% (4/14) for GT1, 21.4% (69/103) for GT3. In the HIV/HCV co-infected, treatment naïve (n=56), the SVR was 28.6% (4/14) for GT1 and 64.3% (27/42) for GT3. Treatment naïve GT3 mono-infected patients had a statistically significant higher SVR compared to treatment experienced patients (P=0.001). In GT3 patients who achieved rapid virological response, the SVR was significantly higher at 85.2% (P< 0.001). The SVR for cirrhotics were low especially for GT1 at 21% (4/19) and 31% (4/13) based on all patients and treatment naïve HCV monoinfected respectively. In GT3 cirrhotics the corresponding SVR were 57.1% (16/28) and 60.9% (14/23). Premature discontinuation rate was 21.2% with the majority due to intolerable adverse events at 12.1%. Conclusions: In our routine clinical practice, the HCV patients we treated were young, predominantly of GT3 and many had difficult-to-treat clinical characteristics. The SVR of our patients were below those reported in Asian clinical trials but in keeping with some “real world” data.

Nuevas perspectivas en el tratamiento farmacológico de la Hepatitis C / New perspectives in the pharmacological treatment of Hepatitis C

Introducción: La infección por el virus de la hepatitis C (VHC) es una de las principales causas de enfermedad hepática a nivel mundial. Alrededor de 60-80 por ciento de los infectados sufren una infección crónica pudiendo desarrollar otras patologías hepáticas como cirrosis y hepatocarcinoma. El tratamiento contra el VHC ha experimentado un enorme avance en la última década, cuya culminación ha llegado con la aparición de los Agentes Antivirales Directos (AAD) que han conseguido obtener tasas de curación superiores a 90 por ciento. Objetivo: Describir los diferentes mecanismos de acción de los AAD, además de contrastar los principales ensayos clínicos que están actualmente en desarrollo, hacer recomendaciones acerca de las opciones de tratamiento disponibles y perfilar los cambios que van a tener lugar en el tratamiento farmacológico de la Hepatitis C. Material y Métodos: Se realizaron varias búsquedas sistemáticas en la base de datos Pubmed, en los artículos expuestos en el Congreso The liver meeting en noviembre de 2014 de la AASLD (American Association for the Study of Liver Diseases), así como en la guía de la EASL (European Association for the Study of the Liver). Desarrollo: La llegada de nuevos fármacos con nuevas estrategias terapéuticas están incrementando la complejidad de la terapia, por ello es necesario conocer estos nuevos fármacos y sus posibles combinaciones. Conclusiones: Los excelentes resultados de la terapia con AAD han producido un intenso cambio en las recomendaciones terapéuticas, al permitir terapias de menor duración, mejor toleradas y de mayor seguridad(AU)

Introduction: The infection by the Hepatitis C virus (HCV) is one of the most common causes of liver's disease worldwide. Approximately between 60-80% of infected people, infection becomes chronic, and can lead in the long-term to the development of other liver's diseases such as cirrhosis and the hepatocellular carcinoma. Treatment of HCV has progressed enormously in the last decade, concluding with the development of Direct-acting Antiviral Agents (DAA), which has achieved cure rates over 90 percent. Objective: To know the different available treatments options as well as which will be available in a near future. Materials and methods: Several systematic searches were made in the PubMed database; in the articles from the liver meeting congress of AASLD (American Association for the Study of Liver Diseases) in November 2014 and in the EASL (European Association for the Study of Liver) guide. Development: The arrivals of new drugs with new therapeutic strategies have made this therapy more complex, and for that reason it is necessary to have knowledge of these drugs and their possible combinations. Conclusions: The excellent results of the therapy with AAD have made a huge change in therapeutic recommendations, making possible shorter therapies, better tolerated by patients and safer for health(AU)

Association between the IL28B rs12979860 POLYMORPHISM and therapy response in patients infected with genotype 1 of hepatitis c virus in central Brazil

Single nucleotide polymorphisms (SNPs) upstream of the IL28B gene have been associated with the spontaneous clearance of hepatitis C virus (HCV) and with a sustained virological response (SVR) to HCV infection treatment. This study aimed to investigate the association between IL28B SNP rs12979860 and SVR in patients with hepatitis C in Central Brazil. A total of 101 HCV genotype 1 mono-infected chronic patients treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were studied in the City of Goiânia, Central Brazil. Analysis of rs12979860 showed that the most prevalent genotype was CT (57.4%), followed by CC (23.8%) and TT (18.8%). An overall SVR rate of 28.7% (95% CI: 20.4-38.7) was found in the study population. In a multivariate analysis, only IL28B rs12979860 CC genotype (OR: 3.77; 95% CI: 1.13-12.60; p = 0.031) was associated with SVR. These findings show that IL28B SNP rs12979860 is a strong predictor of SVR in the PEG-IFN/RBV treatment in patients infected with genotype 1 of HCV in Central Brazil