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.

Recurrence of hepatitis C virus after treatment with pegylated interferon and direct acting antivirals in Punjab Pakistan

Abstract 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.

RESUMO 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.

Suppression of HIV in the first 12 months of antiretroviral therapy: a comparative analysis of dolutegravir- and efavirenz-based regimens

ABSTRACT Objective To compare viral suppression in treatment-naïve adults starting antiretroviral therapy with dolutegravir (50mg)- and efavirenz (600mg)-based regimens. Methods We analyzed secondary data from Brazilian health information systems of people living with human immunodeficiency virus who started antiretroviral therapy between 2015 and 2017 in Minas Gerais, Brazil. The outcome was viral suppression, defined as the achievement of the first viral load <50 copies/mL within 12 months after initiating antiretroviral therapy. This outcome was also compared with viral load <1,000 copies/mL and analyzed in two scenarios: intention-to-treat versus per-protocol. Time to viral suppression and adjusted odds ratio accompanied by 95% confidence intervals were estimated. Results Of the 2,599 participants enrolled, 77.5% were men, and the median age was 34 years. In the intention-to-treat analysis, viral suppression was 58.1% for efavirenz and 76.7% for dolutegravir. People living with HIV on dolutegravir-based regimen were more likely to achieve viral suppression (aOR: 2.44; 95%CI: 2.01-2.95) and had a shorter median time to viral suppression (p<0.0001). Antiretroviral therapy initiation within <120 days, baseline CD4⁺T-cells ≥200 cells/mm3, and viral load <100,000 copies/mL had higher odds of viral suppression. According to the per-protocol analysis, viral suppression ≥90% was observed by considering viral load <1,000 copies/mL. Conclusion Our study demonstrated that viral suppression improved after introducing dolutegravir, although the proportion of patients with viral load <50 copies/mL was lower than expected. Improved access to routine viral load examinations and continuous surveillance of the effectiveness of antiretroviral therapy should be considered.

Hepatitis C-related membranoproliferative glomerulonephritis in the era of direct antiviral agents / Glomerulonefrite membranoproliferativa relacionada à hepatite C na era dos agentes antivirais diretos

Abstract Membranoproliferative glomerulonephritis (MPGN) is the most typical Hepatitis C virus (HCV)-associated glomerulopathy, and the available data about the utilization of direct-acting antivirals (DAA) in HCV-associated glomerulonephritis is inadequate. We evaluated the renal and viral response in two cases of HCV-related MPGN; the first caused by cryoglobulinemia while the second was cryoglobulin-negative. Both patients received immunosuppression besides DAA in different regimens. They achieved partial remission but remained immunosuppression-dependent for more than 6 months after DAA despite sustained virological response, which enabled safer but incomplete immunosuppression withdrawal. Both patients were tested for occult HCV in peripheral blood mononuclear cells and found to be negative. Hence, the treatment of HCV-related MPGN ought to be according to the clinical condition and the effects of drug therapy. It is important to consider that renal response can lag behind the virological response.

Resumo A glomerulonefrite membranoproliferativa (GNMP) é a glomerulopatia associada ao vírus mais típico da hepatite C (HCV), e os dados disponíveis sobre a utilização de antivirais de ação direta (AAD) na glomerulonefrite associada ao HCV são inadequados. Avaliamos a resposta renal e viral em dois casos de GNMP relacionados ao HCV; o primeiro causado por crioglobulinemia, enquanto o segundo era negativo para crioglobulina. Ambos os pacientes receberam imunossupressão além de AAD em diferentes esquemas terapêuticos. Eles alcançaram remissão parcial, mas permaneceram dependentes da imunossupressão por mais de 6 meses após os AAD, apesar da resposta virológica sustentada, que permitiu a retirada da imunossupressão mais segura, mas incompleta. Ambos os pacientes foram testados para HCV oculto em células mononucleares do sangue periférico e deram resultados negativos. Portanto, o tratamento do GNMP relacionado ao VHC deve ser de acordo com a condição clínica e os efeitos da terapia medicamentosa. É importante considerar que a resposta renal pode ficar aquém da resposta virológica.

Risk factors for hepatocellular carcinoma after sustained virologic response in patients with chronic hepatitis C virus infection / 中华传染病杂志

Objective:To investigate the risk factors for hepatocellular carcinoma (HCC) after sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection.Methods:Patients with chronic HCV infection who were treated in Tianjin Second People′s Hospital from January 2012 to April 2019 were enrolled and the incidence of new HCC was retrospectively analyzed. Cox proportional hazards model was used to analyze the risk factors for HCC.Results:Among the 644 patients with chronic HCV infection, 421 cases (65.4%) had chronic hepatitis C(CHC), 223 cases (34.6%) had hepatitis C cirrhosis, and 34 cases had new HCC. No patient without cirrhosis developed HCC. Cox proportional hazards multivariate analysis showed that Child-Pugh grade B or above (hazard ratio ( HR)=6.050, 95% confidence interval ( CI) 2.658 to 13.771, P<0.001), drinking history ( HR=3.077, 95% CI 1.428 to 6.634, P=0.004), family history of cancer ( HR=2.376, 95% CI 1.155 to 4.888, P=0.019), age≥60 years old ( HR=3.301, 95% CI 1.563 to 6.974, P=0.002), controlled attenuation parameter>292 dB/m ( HR=3.842, 95% CI 1.543 to 9.565, P=0.004) were risk factors for HCC. Conclusions:Patients with CHC, especially cirrhosis, are still at risk of HCC post-SVR. HCC monitoring should be strengthened for individuals over 60 years of age, Child-Pugh grade B or above, with severe fatty liver disease, drinking history or family history of malignancy.

Long-term survival and clinical outcomes following direct-acting antiviral (DAA) treatment in HCV decompensated cirrhosis in Brazil: a real-world study

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.

Hepatitis crónica por virus C: evaluación de los pacientes tratados con antivirales de acción directa en el sistema público de Chile / Evaluation of patients with virus C hepatitis treated with direct-acting antivirals in the Chilean public system

Background Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of pa- tients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a signifi- cant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions These patients treated with DAAs presented SVR rates comparable with national and international data.

Virological response to direct-acting antiviral therapy and changes in liver fibrosis indices in chronic hepatitis C patients with different alanine aminotransferase and aspartate aminotransferase levels in a real-world setting / 临床肝胆病杂志

ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM ［6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043］ and APRI ［0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027］. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM ［89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047］ and APRI ［0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001］. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.

The cut off value of liver stiffness measurement needs to be lowered to predict liver fibrosis after sustained virologic response in chronic hepatitis C patients / 临床肝胆病杂志

Objective To further verify the ability of noninvasive diagnostic method for liver fibrosis in predicting liver fibrosis in chronic hepatitis C patients followed up after sustained virologic response (SVR) based on liver biopsy. Methods A prospective cohort study was performed for the chronic hepatitis C patients who attended Beijing YouAn Hospital, Capital Medical University, from October 2015 to December 2017, and all patients were followed up regularly after SVR and underwent liver biopsy. The diagnostic efficiency of the noninvasive diagnostic method for liver fibrosis was verified based on pathological results. The receiver operating characteristic (ROC) curve was used to evaluate the ability of LSM, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis-4 (FIB-4) in the diagnosis of liver fibrosis, and STATA and R language were used to compare the area under the ROC curve (AUC). Results A total of 96 patients were successfully enrolled. The LSM after SVR was significantly lower than that at baseline, and LSM had a significantly larger AUC than APRI (0.89 vs 0.67, P < 0.05) and FIB (0.89 vs 0.69, P < 0.05) in the diagnosis of liver cirrhosis after SVR. LSM at a cut-off value of 7.95 kPa, and based on the best specificity, the diagnosis of liver cirrhosis could be considered when LSM was greater than 9.15 kPa, with a positive likelihood ratio of 5.91%; progressive liver fibrosis could be excluded based on LSM < 6.85 kPa, with a negative predictive value of 0.98. Follow-up time and antiviral regimen had no influence on the diagnostic ability of LSM. Conclusion The cut off value of LSM needs to be lowered to predict liver fibrosis after SVR in chronic hepatitis C patients.

Influence of virologic response on disease progression in patients with compensated hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the effect of sustained virologic response on disease progression and the development of hepatocellular carcinoma (HCC) in patients with compensated hepatitis B cirrhosis receiving antiviral therapy with nucleos(t)ide analogues (NAs). MethodsA total of 542 patients with compensated hepatitis B cirrhosis who attended Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 1 to December 31, 2013, received antiviral therapy, and were followed up for more than 5 years were enrolled, and according to the status of virologic response during follow-up, they were divided into a sustained virologic response cohort with 496 cases and a non-sustained virologic response cohort with 46 cases. With disease progression as the outcome event, general information and examination data were collected during the 5-year follow-up period. The t-test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test was used for comparison of categorical data between groups. A multivariate logistic regression analysis was performed; relative risk and 95% confidence interval (CI) were used to investigate the degree of correlation of factors measured with the progression of liver cirrhosis. The life-table method was used to calculate the 1-, 3-, and 5-year progression-free survival rates, and the Kaplan-Meier method was used to plot survival curves; the log-rank test was used for univariate analysis, and the Cox regression model was used for multivariate regression analysis. ResultsFor the 542 patients, the mean progression-free survival time was 62.50 months (95% CI: 61.01-63.92), and the 1-, 3-, and 5-year progression-free survival rates were 94%, 82%, and 71%, respectively. The sustained virologic response cohort had a significantly longer mean progression-free survival time than the non-sustained virologic response cohort ［63.10 months (95% CI: 61.65-64.55) vs 55.95 months (95% CI: 50.19-61.71), χ2=12.058, P=0.001］. Compared with the non-sustained virologic response cohort, the sustained virologic response cohort had significantly lower 5-year cumulative incidence rate of HCC than (20.6% vs 34.8%, χ2=5.759, P=0.016) and 5-year cumulative incidence rate of decompensated cirrhosis (5.0% vs 15.2%, χ2=8.239, P=0.004). Virologic response was an independent risk factor for disease progression (hazard ratio=232, 95% CI: 1.45-3.72). ConclusionSustained virologic response can reduce the incidence rates of complications and HCC, improve long-term prognosis, and prolong survival time in patients with compensated hepatitis B cirrhosis.

Virologic success under antiretroviral therapy among people living with HIV/AIDS in the state of Paraná, Brazil / Avaliação do sucesso virológico da terapia antirretroviral em pessoas vivendo com HIV/AIDS no estado do Paraná, Brasil

ABSTRACT Objective: To characterize the sociodemographic profile of the population undergoing antiretroviral treatment in the state of Paraná, Brazil, to investigate the proportion of people undergoing treatment among all those diagnosed, and to analyze the proportion of patients with suppressed viral load in different regions of the state. Methods: Observational descriptive and analytical study carried out with information referring to the period from January 2018 to January 2019. Data were obtained from the Sistema Informatizado de Monitoramento Clínico das Pessoas Vivendo com HIV/AIDS [Computerized System for Clinical Monitoring of People Living with HIV/AIDS] and Sistema de Controle Logístico de Medicamentos[Drug Supply Control System]. The proportion of people on antiretroviral treatment in the state and the proportion of patients with viral load ≤1,000 copies/mL and ≤50 copies/mL were calculated. The results were compared with the corresponding parameters of the World Health Organization goal 90-90-90. Results: The state of Paraná managed to reach the second and third parameters of the 90-90-90 goal of the World Health Organization. Among those diagnosed, 93.12% were on antiretroviral treatment, and 90.0% of them had a viral load below 50 copies of viral RNA/mL of blood, indicating virologic success. Conclusion: The health policy aimed at the population living with HIV/AIDS, and the health services available in Paraná have been successful in parameters relevant to the control of the epidemic. However, it is necessary to ensure the diagnosis of people infected with HIV in the population.

RESUMO Objetivo: Caracterizar o perfil sociodemográfico da população em tratamento antirretroviral no estado do Paraná, investigar a proporção de pessoas em tratamento entre todos os diagnosticados e analisar a proporção de pacientes com carga viral suprimida nas diferentes regiões do estado. Métodos: Estudo observacional descritivo e analítico realizado com informações referentes ao período de janeiro de 2018 a janeiro de 2019. Os dados foram obtidos do Sistema Informatizado de Monitoramento Clínico das Pessoas Vivendo com HIV/AIDS e do Sistema de Controle Logístico de Medicamentos. Foram calculadas as proporções de pessoas em tratamento antirretroviral no estado e de pacientes com carga viral ≤1.000 cópias/mL e ≤50 cópias/mL. Os resultados foram comparados com os parâmetros correspondentes da meta 90-90-90 da Organização Mundial da Saúde. Resultados: O estado do Paraná alcançou o segundo e o terceiro parâmetros da meta 90-90-90 da Organização Mundial da Saúde. Entre os diagnosticados, 93,12% encontravam-se em tratamento antirretroviral, e 90,0% destes apresentavam carga viral abaixo 50 cópias do RNA viral/mL de sangue, indicando sucesso virológico. Conclusão: A política de saúde voltada à população vivendo com HIV/AIDS e os serviços de saúde disponibilizados no Paraná têm obtido êxito em parâmetros relevantes para o controle da epidemia. Entretanto, é necessário assegurar o diagnóstico das pessoas infectadas por HIV na população.

Unsatisfactory long-term virological suppression in human immunodeficiency virus-infected children in the Amazonas State, Brazil

Abstract INTRODUCTION: Achieving viral suppression (VS) in children is challenging despite the exponential increase in access to antiretroviral therapy (ART). We evaluated VS in children >1 year of age and adolescents 5 years after they had begun ART, in Manaus, Amazonas state, Brazil. METHODS: HIV-infected, ART-naive children >1 year of age between 1999 and 2016 were eligible. Analysis was stratified by age at ART initiation: 1-5 y, >5-10 y, and >10-19 y. CD4+ T-cell count and viral load were assessed on arrival at the clinic, on ART initiation, and at 6 months, 1 year, 2 years, and 5 years after ART initiation. The primary outcome was a viral load <50 copies/mL 5 years after ART initiation. RESULTS: Ultimately, 121 patients were included. The mean age at diagnosis was 4.8 years (SD 3.5), mean CD4% was 17.9 (SD 9.8), and mean viral load was 4.6 log10 copies/ml (SD 0.8). Five years after ART initiation, the overall VS rate was 46.9%. VS by patient age group was as follows: 36.6% for 1-5 y, 53.3% for >5-10 y, and 30% for >10-19 y. Almost all children (90,4%) showed an increase in CD4%+ T cell count. There were no statistically significant predictors for detecting children who do not achieve VS with treatment. VS remained below 65% in all the evaluated periods. CONCLUSIONS: Considerable immunological improvement is seen in children after ART initiation. Further efforts are needed to maintain adequate long-term VS levels and improve the survival of this vulnerable population.

Influence of different virologic responses on the prognosis of patients with decompensated hepatitis B cirrhosis / 临床肝胆病杂志

ObjectiveTo investigate the influence of different virologic responses on long-term survival rate and incidence rate of liver cancer in patients with decompensated hepatitis B cirrhosis. MethodsA total of 378 patients with decompensated hepatitis B cirrhosis who were admitted to The Affiliated Hospital of Xuzhou Medical University from September 2010 to September 2016 were enrolled, and according to whether HBV DNA was continuously undetectable during antiviral therapy, they were divided into sustained virologic response group with 243 patients and non-sustained virologic response group with 135 patients. The patients were stratified according to the application of different antiviral drugs. Baseline data were recorded and the patients were followed up to the occurrence of end events or study endpoint to record death and hepatocellular carcinoma (HCC). The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method was used to plot survival curves, and the log-rank test was used to compare survival rates between groups. ResultsCompared with the non-sustained virologic response group, the sustained virologic response group had a significantly lower 5-year cumulative incidence rate of HCC (7.4% vs 19.3%, χ2=10.627, P=0.001) and a significantly higher 5-year transplant-free survival rate (93.4% vs 80.7%, χ2=12.594, P＜0.001). For the sustained virologic response group, there were no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate (94.7% vs 90.2%, χ2=1.122, P=0.290) and the 5-year cumulative incidence rate of liver cancer (6.4 % vs 9.7%, χ2=0.552, P=0.458). For the non-sustained viral response group, there were also no significant differences between the entecavir group and the non-entecavir group in the 5-year transplant-free survival rate (78.4% vs 82.8%, χ2=1.526, P=0.217) and the 5-year cumulative incidence rate of liver cancer (21.5% vs 17.1%, χ2=1.844, P=0.174). ConclusionAntiviral therapy can improve the prognosis of patients with decompensated hepatitis B cirrhosis, and sustained virologic response can reduce the incidence rate of liver cancer and prolong survival time.

Tratamiento actual de la hepatitis C en Colombia / Current treatment for hepatitis C in Colombia

La infección por el virus de hepatitis C (VHC) es una epidemia global que afecta a 71 millones de personas. El diagnóstico inicial se hace mediante la detección de anticuerpos contra el VHC, que luego requiere una prueba confirmatoria molecular, debido a que la determinación de anticuerpos no diferencia los individuos que tienen una infección activa, de aquellos con una infección resuelta y sin viremia. El objetivo del tratamiento de la infección crónica por VHC es curar la enfermedad, lo que se determina cuando se logra una respuesta viral sostenida; es decir, cuando no se detecta carga viral 12 semanas o más después de terminada la terapia. Para un tratamiento óptimo de la infección y alcanzar la curación, se recomienda evaluar previamente de manera no invasiva el estadio de fibrosis, y garantizar la adherencia durante todo el tiempo de tratamiento. En la presente revisión se incluyen las recomendaciones para el tratamiento de la infección crónica por VHC, según el genotipo viral, basadas en los medicamentos disponibles en nuestro medio y en los que próximamente estarán llegando al país.

Abstract Infection with hepatitis C virus (HCV) is a global epidemic that affects 71 million people. Initial diagnosis is made by detecting antibodies against HCV, which then requires a confirmatory molecular assay in order to discriminate individuals who have an active infection from those with a resolved infection and without active viremia. The goal of treating chronic HCV infection is to cure the disease, which is determined when a sustained virological response is achieved; that is, when viral load is not detected 12 weeks or more after completing treatment. For an optimal treatment of the infection and to achieve a cure, it is recommended to previously and non-invasively evaluate the fibrosis stage, and to guarantee adherence throughout the treatment period. This review includes some guidelines for the treatment of chronic HCV infection, according to the viral genotype, and based on the drugs available and soon to be available in our country.

Response to direct-acting antiviral agents in chronic hepatitis C patients with end-stage renal disease: a clinical experience

SUMMARY OBJECTIVE The recent development of direct-acting antiviral agents (DAAs) has dramatically changed the treatment of chronic hepatitis C, and interferon-based regimes have become a poor treatment choice in clinical practice. Today DAAs offer shorter, well-tolerated, highly effective curative therapies. This study aimed to evaluate the effectiveness and safety of DAAs in patients with end-stage renal disease and HCV genotype 1 infection in real clinical practice. METHODS Thirty-six patients who attended our clinic, were diagnosed with chronic hepatitis C (CHC), undergoing hemodialysis, and fulfilled the criteria of age >18 years, genotype 1 infection, with a detectable HCV RNA level were considered for the study. Patients with GT1a infection received OBV/PTV/r plus DSV plus RBV for 12 weeks; GT1b infected patients received this regimen without RBV for 12 weeks. RESULTS The study was conducted on 33 patients. The mean age was 52.30 ±13.77 years, and 70 % of them were male. By the fourth week of treatment, HCV RNA levels decreased below 15 IU/ml in all patients. Sustained virologic response (SVR) 12 rate was 100%. Nine patients had side effects during treatment. Of the patients with side effects, 89.9% were in group 1a and 11.1% in group 1b. CONCLUSION In this study, treatment with OBV/PTV/r and DSV with or without RBV resulted in high rates of sustained virologic response in HCV GT1-infected patients with end-stage renal disease (ESRD). SVR was achieved in all patients with few side effects.

RESUMO O recente desenvolvimento de agentes antivirais de ação direta (DAAs) mudou drasticamente o tratamento da hepatite C crônica, e os regimes livres de interferon tornaram-se pobres escolhas para tratamento na prática clínica. Hoje os DAAs oferecem terapias curativas mais curtas, bem toleradas e altamente eficazes. O objetivo deste estudo foi avaliar a eficácia e segurança dos DAAs em pacientes com doença renal em estágio terminal e infecção pelo genótipo 1 do HCV na prática clínica real. MÉTODOS Trinta e seis pacientes, que se inscreveram em nossa clínica com diagnóstico de hepatite C crônica (CHC), inclusive no programa de hemodiálise, e preencheram os critérios de idade >18 anos, foram considerados para infecção pelo genótipo 1 com nível detectável de RNA do HCV. Os pacientes com infecção por GT1a receberam OBV/PTV/r mais DSV mais RBV por 12 semanas. Os pacientes infectados com GT1b receberam este regime sem RBV por 12 semanas. RESULTADOS O estudo foi realizado em 33 pacientes. A idade média foi de 52,30±13,77 anos e 70% deles eram do sexo masculino. Na semana 4 do tratamento, os níveis de ARN do VHC diminuíram para menos de 15 UI/ml em todos os pacientes. A taxa de resposta virológica sustentada (RVS) 12 foi de 100%. Nove pacientes apresentaram efeitos colaterais durante o tratamento. Dos pacientes com efeitos colaterais, 89,9% estavam no grupo 1a e 11,1% no grupo 1b. CONCLUSÃO Neste estudo, o tratamento com OBV/PTV/r e DSV com ou sem RBV resultou em altas taxas de resposta virológica sustentada em pacientes infectados pelo VGC GT1 com doença renal em estágio final (ESRD). A RVS foi alcançada em todos os pacientes com poucos efeitos colaterais.

Taxa de resposta viral sustentada em pacientes de hepatite C crônica tratados com antivirais de ação direta / Sustained virologic response rate in chronic hepatitis c patients through direct-acting antivirals therapy

ABSTRACT BACKGROUND: In recent years the management of hepatitis C virus infection and the possibility of its eradication have been researched due to the importance that they represent in the health of the world population. Obtaining data that help to cope with this pathology improves the quality of life of those affected by it. The present study evaluated the effectiveness of direct-acting antiviral therapies provided by the Brazilian Ministry of Health in accordance to the Clinical Protocol and Therapeutic Guidelines of 2015. OBJECTIVE: To evaluate the epidemiological profile of patients with chronic hepatitis C and the rate of sustained virologic response using direct-acting antivirals of all individuals that attended the referral service for the treatment of chronic hepatitis C at the Hospital of the Federal University of Rio Grande. METHODS: This was an observational, retrospective/prospective study with all patients with chronic hepatitis C who had their treatments available from December 2015 to August 2017 according to the criteria of the Clinical Protocol and Therapeutic Guidelines of 2015. In the first phase, the clinical and demographic variables of all individuals enrolled in a treatment for hepatitis C were selected and collected from the Reference Service database. In the second phase, treatment data were collected. The outcome variable, sustained virologic response, was defined as an undetectable viral load on the blood test three months after the end of treatment. The descriptive and bivariate analyzes were performed with Pearson's chi-square and Fisher's Exact test, adopting a P value ≤0.05 in the SPSS 20 software. RESULTS: Of the 252 participants in the study, 228 (90.5%) had a sustained virologic response, 55.2% were male with an average age of 58.6 years (SD±9.1). Genotype 1 was the most prevalent, observed in 54.4% of the participants, and 87.4% of the patients had moderate/advanced hepatic fibrosis. After the statistical analysis, it was observed that the individuals with genotype 3 and moderate/advanced hepatic fibrosis had lower sustained virologic response rate (P=0.05 and P=0.04, respectively). CONCLUSION: It was observed that the use of direct-acting antivirals, in comparison to previous therapeutic regimens, increases the sustained virologic response, reaching all patients with mild fibrosis. This study provides information that helps in the hepatitis C treatment by showing that prescribing early treatment for patients without hepatic fibrosis and/or genotype 3 virus could increase therapeutic effectiveness.

RESUMO CONTEXTO: O manejo e a possibilidade de erradicação da infecção pelo vírus da hepatite C têm sido muito pesquisados nos últimos anos pela importância que representam na saúde pública para a população mundial. A obtenção de dados que auxiliem o enfrentamento dessa patologia resulta na melhor qualidade de vida dos seus portadores. O presente estudo avaliou a efetividade da terapêutica com os antivirais de ação direta, fornecida pelo Ministério da Saúde, através do Protocolo Clínico e Diretrizes Terapêuticas de 2015. OBJETIVO: Avaliar o perfil epidemiológico dos portadores de hepatite C crônica e a taxa de resposta viral sustentada com o uso dos antivirais de ação direta em todos os indivíduos atendidos no Centro de Referência no tratamento da hepatite C crônica do Hospital Universitário da Universidade Federal do Rio Grande. MÉTODOS: Estudo observacional retrospectivo/prospectivo com todos os portadores de hepatite C crônica que tiveram seus tratamentos disponibilizados no período de dezembro de 2015 a agosto de 2017 segundo os critérios do Protocolo Clínico e Diretrizes Terapêuticas de 2015. Na primeira fase foram selecionadas e coletadas as variáveis demográficas e clínicas, no banco de dados do centro de referência de todos os indivíduos cadastrados para tratamento para hepatite C e na segunda fase foram coletados dados referentes ao tratamento. A variável desfecho, resposta viral sustentada, foi definida pela carga viral indetectável no exame sanguíneo três meses após o término do tratamento. Foram realizadas as análises descritivas e bivariadas com cálculo do qui quadrado de Pearson e Exato de Fisher, adotando um valor P≤0,05, no programa SPSS 20. RESULTADOS: Dos 252 participantes do estudo 228 (90,5%) obtiveram resposta viral sustentada, sendo 55,2% do sexo masculino com média de idade de 58,6 anos (DP±9,1). O genótipo 1 foi o mais prevalente, presente em 54,4% dos participantes, 87,4% dos estudados apresentavam grau de fibrose hepática moderada/avançada. Após a análise estatística observou-se que os indivíduos com genótipo 3 e fibrose hepática moderada/avançada, tiveram menor taxa de resposta viral sustentada (P=0,05 e P=0,04 respectivamente). CONCLUSÃO: Observou-se que com o uso dos antivirais de ação direta as taxas de resposta viral sustentada foram altas, em relação aos esquemas terapêuticos anteriores, podendo chegar à totalidade nos pacientes com fibrose leve. Este estudo mostra que a realização do tratamento precoce, ou seja, de forma antecipada em pacientes sem fibrose hepática e genótipo 3 pode aumentar a taxa de sucesso.

Efficacy and Safety of Daclatasvir and Asunaprevir in Patients with Hepatitis C Virus Genotype 1b Infection on Hemodialysis

BACKGROUND/AIMS: We evaluated the efficacy and safety of daclatasvir (DCV) and asunaprevir (ASV) in patients with chronic hepatitis C virus (HCV) infection on hemodialysis. METHODS: We performed a single-arm, multicenter prospective study. Twenty-one chronic hemodialysis patients with HCV infection were prospectively enrolled from February 2016 to April 2017. We evaluated the virological responses at weeks 4, 12, and 24 (end of treatment [EOT]) and the sustained virological response at 12 weeks after the EOT (SVR12). The tolerability and safety of the drugs were also assessed. RESULTS: None of the 20 patients had the NS5A resistance-associated variant (NS5A RAV), and one patient was indeterminate for the NS5A RAV. Seventeen patients (80%) completed the 24 weeks of treatment with DCV and ASV. Four patients discontinued the study prior to week 12. In an intention-to-treat analysis, the SVR12 was 76.1%. In a per-protocol analysis, patients who completed DCV and ASV treatment achieved an SVR12 of 100%. DCV and ASV were well tolerated by the majority of patients. Three patients discontinued treatment due to adverse events (AEs) including dizziness, dyspnea, and neutropenia. The patient with indeterminate NS5A RAV showed viral breakthrough and discontinued treatment. CONCLUSIONS: DCV and ASV combination therapy in chronic hemodialysis patients with HCV infection achieved a high SVR12 rate with few AEs. To maximize the SVR12 rate, it is important to identify candidates by baseline RAV testing. Close monitoring of the safety and tolerability of DCV and ASV may be necessary in HCV-infected patients on hemodialysis. (ClinicalTrials.gov ID NCT02580474)

Efficacy and safety of yimitasvir phospha combined with sofosbuvir in patients with chronic hepatitis C virus infection / 中华传染病杂志

Objective To assess the efficacy and safety of 100 mg or 200 mg yimitasvir phosphate combined with sofosbuvir in patients with non-cirrhotic chronic hepatitis C virus ( HCV) genotype 1 infection who were treatment-na?ve or had a virologic failure to prior interferon-based treatment.Methods A multicenter, randomized, open-label, phase 2 clinical trial was conducted.The patients were randomly assigned to yimitasvir phosphate 100 mg+sofosbuvir 400 mg group (Group 100 mg) and yimitasvir phosphate 200 mg+sofosbuvir 400 mg group ( Group 200 mg) in a 1∶1 ratio with the stratified factors of " treatment-naive" or"treatment-experienced" for 12 weeks and followed up for 24 weeks after the end of treatment.During the clinical trial, HCV RNA was tested in all patients.Resistance of virus in patients who didn′t achieved sustained virological response (SVR) was monitored.Safety and tolerability were assessed by monitoring adverse events , physical examination , laboratory examination, electrocardiogram, and vital signs during the study.The primary end point was SVR12 after the end of therapy.Descriptive statistics were used for categorical variables and eight descriptive statistics were used for continuous variables.Descriptive statistics were used and summarized according to HCV genotypes and treatment groups.Safety data were presented using descriptive statistics and summarized according to treatment groups.Results A total of 174 subjects were screened from July 31, 2017 to September 26, 2018.One hundred and twenty-nine patients were successfully enrolled and received treatment , and 127 completed the study.There were 64 patients and 65 patients assigned to Group 100 mg and Group 200 mg, respectively.Among the 129 patients who underwent randomization and were treated , 18.6% were treatment-experienced and: 100%were HCV genotype 1b infection.The total SVR rate was 98.4%(127／129), with 98.4%(63／64, 95%confidence interval [CI]: 91.60%-99.96%) in the Group 100 mg, and 98.50%(64／65, 95%CI: 91.72%-99.96%) in the Group 200 mg.There was no significant difference between the two groups (χ2 ＝0.000 2, P＝0.989 2).The SVR rates in treatment-naive group and treatment-experienced group were 98.10%(95%CI: 93.29%-99.77%) and 100.00%(24／24, 95%CI: 85.75%-100.00%), respectively.Virological failure during treatment ( including breakthrough , rebound and poor efficacy) and relapse after treatment did not occur during the trial.By Sanger sequencing , 11.6%(15／129) patients had baseline NS5A Y93H／Y or Y93H resistance-associated substitutions ( RAS), 1.6%( 2／129) patients had baseline NS5A L31M RAS.No mutation was observed in NS5B S282 at baseline.There was no S282 mutation in HCV NS5B.A total of 100 (77.5%) subjects had adverse events.No adverse events ≥Grade 3 or severe adverse events related to the study treatment.No patient prematurely discontinued study treatment owing to an adverse event.No life-threatening adverse event was reported.Conclusion Twelve weeks of yimitasvir phosphate 100 mg or 200 mg combined with sofosbuvir 400 mg daily is a highly effective and safe regimen for patients without cirrhosis with HCV genotype 1b infection who had not been treated previously or had a virologic failure to prior interferon-based treatment.

Usefulness of Gd-EOB-DTPA-enhanced MRI for evaluating the potential for early development of hepatocellular carcinoma after HCV eradication by direct-acting antiviral treatment / Journal of Rural Medicine

Objective: The development of hepatocellular carcinoma (HCC) is not uncommon in patients who achieve eradication of the hepatitis C virus through direct-acting antiviral (DAA) treatment. The aim of this study was to identify the patients at high risk for novel HCC development after a sustained virologic response (SVR) by DAA treatment.Patients and Methods: A total of 518 patients with no history of HCC treatment and who achieved SVR by DAA treatment were evaluated retrospectively. The correlations between HCC development and the patients’ characteristics were evaluated. For patients who underwent gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) or dynamic contrast-enhanced computed tomography, the relationship between the imaging findings and subsequent HCC development was also assessed.Results: HCC developed newly in 22 patients, and the 1-year and 3-year cumulative HCC rates were 2.0% and 8.5%, respectively. In multivariate analysis, a FIB-4 index >4.0 and a post-treatment α-fetoprotein >4.0 ng/ml were significant risk factors for HCC. In 26 of 118 patients who underwent an MRI before DAA treatment, a non-hypervascular hypo-intense nodule was seen in the hepatobiliary phase, and in 6 of 182 patients who underwent a CT, a non-hypervascular hypo-enhanced nodule was seen in the delayed phase. The sensitivity and specificity of the MRI-positive findings for the subsequent development of HCC were 0.92 and 0.87, respectively, and those of the CT were 0.40 and 0.99, respectively. In multivariate analysis of patients who underwent an MRI, a non-hypervascular hypo-intense nodule was the only factor that was significantly related to HCC development (HR 32.4, p = 0.001).Conclusion: Gd-EOB-DTPA-enhanced MRI was found to be reliable for risk evaluation of subsequent HCC development in patients after SVR by DAA treatment. Patients with a non-hypervascular hypo-intense nodule need more careful observation for incident HCC.

An integrated analysis of elbasvir/grazoprevir in Korean patients with hepatitis C virus genotype 1b infection

BACKGROUND/AIMS: In the Republic of Korea, an estimated 231,000 individuals have chronic hepatitis C virus (HCV) infection. The aim of the present analysis was to evaluate the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) administered for 12 weeks in Korean patients who were enrolled in international clinical trial phase 3 studies.METHODS: This was a retrospective, integrated analysis of data from patients with HCV genotype (GT) 1b infection enrolled at Korean study sites in four EBR/GZR phase 3 clinical trials. Patients were treatment-naive or had previously failed interferon-based HCV therapy, and included those with human immunodeficiency virus coinfection or Child-Pugh class A cirrhosis. All patients received EBR 50 mg/GZR 100 mg once daily for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after completion of therapy (SVR12, HCV RNA <15 IU/mL).RESULTS: SVR12 was achieved by 73 of 74 (98.6%) patients. No patients had virologic failure and one discontinued from the study after withdrawing consent. SVR12 rates were uniformly high across all patient subgroups. A total of 16 patients had nonstructural protein 5A resistance-associated substitutions at baseline (16/73, 22%), all of whom achieved SVR12. Adverse events (AEs) reported in >5% of patients were fatigue (6.8%), upper respiratory tract infection (5.4%), headache (5.4%), and nausea (5.4%). Thirteen patients (17.6%) reported drug-related AEs, two serious AEs occurred, and two patients discontinued treatment owing to an AEs.CONCLUSIONS: In this retrospective analysis, EBR/GZR administered for 12 weeks was well-tolerated and highly effective in Korean patients with HCV GT1b infection.