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.

Experiencia peruana en el tratamiento de hepatitis crónica C con las nuevas drogas antivirales de acción directa / Peruvian experience in the treatment of chronic hepatites C with the new direct acting antiviral drugs

Objetivos: La terapia ideal para la hepatitis crónica C consiste en el uso de drogas antivirales de acción directa (DAA). En el Perú la experiencia en vida real con DAA no se conoce, por lo que el objetivo del presente estudio es reportar la alta eficacia terapéutica con estos esquemas. Material y métodos: Mediante correo electrónico se invitó a participar a través de una encuesta a médicos hepatólogos a nivel nacional. Se incluyeron los datos de 4 médicos. Los resultados fueron analizados con estadística descriptiva. Resultados: Se incluyeron 63 pacientes, la edad promedio fue 59 años, varones fueron 49,21%, cirrosis estuvo presente en el 49,21% (31/63), 34,92% había sido no respondedor a terapia con PEGIFN/RBV. El Genotipo 1 estuvo presente en 93,65% de casos, siendo el 1a el predominante (58,73%). Solo hubo dos casos de genotipo 2 y uno de genotipo 3. Se utilizaron 10 esquemas de combinación con DAA, siendo los más eficaces, Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/ Ribavirina y Sofosbuvir/Simeprevir, en todos ellos se logró Respuesta Viral Sostenida (RVS) de 100%. Con los otros 7 esquemas la RVS fue menor a 90% o solo se había incluido uno o dos pacientes. La tolerancia a la terapia fue adecuada y todos los pacientes culminaron la terapia. Conclusiones: En vida real los esquemas de terapia antiviral para hepatitis C con DAA tienen alta eficacia y seguridad. Las mejores respuestas se obtuvieron con Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina y Sofosbuvir/Simeprevir. Esta data puede ser útil para considerar estrategias de tratamiento con el enfoque de salud pública.

Objective: The ideal therapy for chronic hepatitis C is the use of direct acting antivirals (DAA). In Peru there is no data in this aspect, in that sense it is necessary to report real life experience with these drugs. Material and methods: A digital survey was sent through e-mail to hepatologists, and the data of four is considered in this study. Statistical analysis was descriptive. Results: We included 63 patients, mean age was 59 years, 49.21% were male, cirrhosis was present in 49.21%, and 34.92% was non-responder to PEGIFN and Ribavirin. Genotype 1 was present in 93.65%, and subtype 1a was 58.73%, there were only 2 cases with Gt 2 and one with Gt 3. There were 10 different DAA combinations used, and the most effective were Sofosbuvir/ Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir, in all these cases the Sustained Viral Response (SVR) was 100%. The other combinations had SVR < 90% or only 1-2 patients included. All patients tolerated treatments and no serious adverse events occurred. Conclusions: In real life antiviral treatment for hepatitis C with AAD is effective and well tolerated. The best SVR was obtained with Sofosbuvir/Ledipasvir, Sofosbuvir/Ledipasvir/Ribavirina and Sofosbuvir/Simeprevir. This report may be useful to consider treatment strategies with focus in public health.

HPA-1a/1b could be considered a molecular predictor of poor prognosis in chronic hepatitis C

Abstract INTRODUCTION: HPA polymorphism has been associated with HCV presence and fibrosis progression in chronic hepatitis C. However, it is unknown if there is an association between HPA-1 polymorphism and hepatocellular carcinoma (HCC). Therefore, this study aimed to evaluate HPA-1 polymorphism in the presence of HCC. METHODS: PCR-SSP was used to perform HPA genotyping on 76 HCV-infected patients. RESULTS: There was no association between patients with and without HCC. There was significant difference in HPA-1 genotypic frequency distribution between HCC and F1/F2 fibrosis degree. CONCLUSIONS: The HPA-1a/1b polymorphism appears to be more associated with liver damage progression than with HCC presence.

Perfil dos pacientes com hepatite C crônica em um programa de saúde pública do sul do Brasil / Profile of patients with chronic hepatitis c in a public health program in southern brazil

ABSTRACT BACKGROUND: Chronic hepatitis C (CHC) can progress to cirrhosis and its complications as hepatocellular carcinoma, leading to morbidity and mortality. To know the profile of patients with CHC virus is fundamental to optimize management. OBJECTIVE: To describe the profile of patients with CHC in a public health program in Southern Brazil. METHODS: A retrospective study was carried out in patients with CHC who underwent treatment against hepatitis C virus in a dispensation and pharmaceutical assistance center of the Public Health Department of the State of Rio Grande do Sul, South Brazil. All medical records of patients attended between December/2015 and December/2016 were evaluated. RESULTS: A total of 1,431 records of patients with CHC were evaluated. Males were the most prevalent (802; 56%) patients. The mean age was 58.6±9.9 years, ranging from 18 to 89 years. Genotype 1 was the most frequent (866;60.5%) of the patients. Ninety (6.3%) patients were transplanted from a solid organ, and of these, 73 (5.1%) were transplanted from the liver. The fibrosis evaluation was performed in 1,300 (90.8%) patients. Of these, 566 (39.6%) were evaluated through liver biopsy. Regarding the degree of fibrosis, 779 (54.4%) presented fibrosis grade 4 (cirrhosis). The genotype 3 was the most associated with fibrosis grade 4, and genotype 1 was associated with high viral load. CONCLUSION: The present study made possible the evaluation of the characteristics of patients with CHC in a public health program in South Brazil. There was a predominance of CHC in males, and the mean age was 59 years. They presented a predominance of genotype 1, higher viral load in patients with genotype 1 and greater degree of fibrosis in patients with genotype 3.

RESUMO CONTEXTO: A hepatite crônica C (HCC) pode evoluir para cirrose e suas complicações como carcinoma hepatocelular, acarretando morbimortalidade. Conhecer o perfil dos pacientes portadores do vírus da HCC é fundamental para o melhor manejo do tratamento. OBJETIVO: Descrever o perfil dos pacientes portadores de HCC em um programa de saúde pública do sul do Brasil. MÉTODOS: Foi realizado um estudo retrospectivo onde foram incluídos os pacientes com HCC que realizaram o tratamento contra o vírus C em um polo de dispensação e assistência farmacêutica da Secretaria Estadual da Saúde do Estado do Rio Grande do Sul, Brasil. Foram avaliados todos os prontuários dos pacientes tratados entre dezembro/2015 e dezembro/2016. RESULTADOS: Foram avaliados 1.431 registros de pacientes portadores de HCC. O sexo masculino foi o mais prevalente (802; 56%) pacientes. A idade média dos pacientes foi de 58,6±9,9 anos, com variação de 18 a 89 anos. O genótipo 1 foi o mais frequente, em 866 (60,5%) dos pacientes. Noventa (6,3%) pacientes eram transplantados de órgão sólido, sendo que 73 (5,1%) eram transplantados de fígado. A avaliação de fibrose foi realizada em 1.300 (90,8%) pacientes. Dentre estes, 566 (39,6%) foram avaliados através de biópsia hepática. Em relação ao grau de fibrose, 779 (54,4%) apresentavam fibrose grau 4 (cirrose). Os genótipos foram analisados em relação aos diferentes graus de fibrose, sendo observado que o genótipo 3 está associado com o grau 4 de fibrose. O genótipo 1 está associado com alta carga viral. CONCLUSÃO: O presente estudo possibilitou a avaliação do perfil dos pacientes portadores de HCC em um programa de saúde pública do Brasil. Houve uma predominância de HCC no sexo masculino, e a média de idade foi de 59 anos. Apresentam um predomínio do genótipo 1, maior carga viral nos pacientes portadores do genótipo 1 e maior grau de fibrose nos portadores de genótipo 3.

First-wave protease inhibitors for hepatitis C genotype 1 treatment: a real-life experience in Brazilian patients

Abstract INTRODUCTION: Licensed for chronic hepatitis C treatment in 2011, the protease inhibitors (PIs) telaprevir (TVR) and boceprevir (BOC), which have high sustained viral responses (SVR), ushered a new era characterized by the development of direct-action drugs against the hepatitis C virus (HCV). The aim of this study was to analyze the effectiveness and safety of BOC and TVR administered with pegylated interferon and ribavirin and to share the experience of a Brazilian reference center. METHODS: A retrospective descriptive study was conducted in patients with HCV genotype 1 infection who started treatment between July 2013 and December 2015. Data were collected using a computerized system. RESULTS: A total of 115 subjects were included, of which 58 (50.4 %) had liver cirrhosis and 103 (89.6 %) used TVR. The overall SVR rate was 61.7 % (62.1 % for TVR and 58.3 % for BOC). The presence of cirrhosis was associated with a lower SVR rate, whereas patients who relapsed after prior therapy had a greater chance of showing SVR than did non-responders. The incidence of adverse drug reactions (ADRs) was high. Almost all patients (~100 %) presented with hematologic events. Furthermore, treatment had to be discontinued in 15 subjects (13 %) due to severe ADRs. CONCLUSIONS: In conclusion, the SVR rates in our study were lower than those reported in pre-marketing studies but were comparable to real-life data. ADRs, particularly hematological ADRs, were more common compared to those in previous studies and resulted in a high rate of treatment discontinuity.

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.

Effectiveness and safety of first-generation protease inhibitors in real-world patients with hepatitis C virus genotype 1 infection in Brazil: a multicenter study

OBJECTIVE: To evaluate the effectiveness and safety of first-generation protease inhibitors for the treatment of genotype 1 hepatitis C virus-infected patients at Brazilian reference centers. METHODS: This multicenter cross-sectional study included hepatitis C virus genotype 1 monoinfected patients treated with Peg-interferon, ribavirin, and either boceprevir (n=158) or telaprevir (n=557) between July 2013 and April 2014 at 15 reference centers in Brazil. Demographic, clinical, virological, and adverse events data were collected during treatment and follow-up. RESULTS: Of the 715 patients, 59% had cirrhosis and 67.1% were treatment-experienced. Based on intention-to-treat analysis, the overall sustained viral response was 56.6%, with similar effectiveness in both groups (51.9% for boceprevir and 58% for telaprevir, p=0.190). Serious adverse events occurred in 44.2% of patients, and six deaths (0.8%) were recorded. Cirrhotic patients had lower sustained viral response rates than non-cirrhotic patients (46.9% vs. 70.6%, p<0.001) and a higher incidence of serious adverse events (50.7% vs. 34.8%, p<0.001). Multivariate analysis revealed that sustained viral response was associated with the absence of cirrhosis, viral recurrence after previous treatment, pretreatment platelet count greater than 100,000/mm3, and achievement of a rapid viral response. Female gender, age>65 years, diagnosis of cirrhosis, and abnormal hemoglobin levels/platelet counts prior to treatment were associated with serious adverse events. CONCLUSION: Although serious adverse events rates were higher in this infected population, sustained viral response rates were similar to those reported for other patient cohorts.

Daclatasvir Plus Asunaprevir Dual Therapy for Chronic HCV Genotype 1b Infection: Results of Turkish Early Access Program

Abstract: Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. Aim. To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. Material and methods. Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. Results. Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. Conclusions. Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Predictors of early treatment discontinuation and severe anemia in a Brazilian cohort of hepatitis C patients treated with first-generation protease inhibitors

The aim of this study was to determine risk factors for adverse events (AE)-related treatment discontinuation and severe anemia among patients with chronic hepatitis C virus (HCV) genotype 1 infection, treated with first-generation protease inhibitor (PI)-based therapy. We included all patients who initiated treatment with PI-based therapy at a Brazilian university hospital between November 2013 and December 2014. We prospectively collected data from medical records using standardized questionnaires and used Epi Info 6.0 for analysis. Severe anemia was defined as hemoglobin ≤8.5 mg/dL. We included 203 patients: 132 treated with telaprevir (TVR) and 71 treated with boceprevir (BOC). AE-related treatment discontinuation rate was 19.2% and anemia was the main reason (38.5%). Risk factors for treatment discontinuation were higher comorbidity index (OR=1.85, CI=1.05-3.25) for BOC, and higher bilirubin count (OR=1.02, CI=1.01-1.04) and lower BMI (OR=0.98, CI=0.96-0.99) for TVR. Severe anemia occurred in 35 (17.2%) patients. Risk factors for this outcome were lower estimated glomerular filtration rate (eGFR; OR=0.95, CI=0.91-0.98) for patients treated with TVR, and higher comorbidity index (OR=2.21, CI=1.04-4.67) and ribavirin dosage (OR=0.84, CI=0.72-0.99) for those treated with BOC. Fifty-five (57.3%) patients treated with TVR and 15 (27.3%) patients treated with BOC achieved sustained virological response (SVR). Among patients who received TVR and interrupted treatment due to AE (n=19), only 26.3% (n=5) achieved SVR (P=0.003). Higher number of comorbidities, lower eGFR and advanced liver disease are associated with severe anemia and early treatment cessation, which may compromise SVR achievement.

Association between age at diagnosis and degree of liver injury in hepatitis C

Introduction: A population-based survey conducted in Brazilian capital cities found that only 16% of the population had ever been tested for hepatitis C. These data suggest that much of the Brazilian population with HCV infection remains undiagnosed. The distribution of age ranges at diagnosis and its association with the degree of hepatitis C are still unknown in Brazilian patients. Material and methods: Patients with HCV infection, diagnosed by HCV RNA (Amplicor-HCV, Roche), were included in the study. Patients with HBV or HIV coinfection, autoimmune diseases, or alcohol intake > 20 g/day were excluded. HCV genotyping was performed by sequence analysis, and viral load by quantitative RT-PCR (Amplicor, Roche). The METAVIR classification was used to assess structural liver injury. The Chi-square (χ2) test and student's t-test were used for between-group comparisons. Spearman's rank correlation coefficient were used for analysing the correlation between parameters. Results: A total of 525 charts were reviewed. Of the patients included, 49.5% were male, only 10% of the patients were aged less than 30 years; peak prevalence of HCV infection occurred in the 51-to-60 years age range. Genotype 1 accounted for 65.4% of the cases. Information on HCV subtype was obtained in 227 patients; 105 had subtype 1a and 122 had 1b. According to the degree of structural liver injury, 8.3% had F0, 23.4% F1, 19.8% F2, 11.9% F3, and 36.5% F4. Age at diagnosis of hepatitis correlated significantly with fibrosis (rs = 0.307, p < 0.001). The degree of fibrosis increased with advancing age. Only age at diagnosis and fasting blood glucose were independently associated with disease stage. Those patients with subtype 1a had higher prevalence of F2–F4 than those with subtype 1b. Conclusion: In Brazil, diagnosis of hepatitis C is more commonly established in older patients (age 45–60 years) with more advanced disease. Reassessment of strategies ...

Do differences exist between chronic hepatitis C genotypes 2 and 3?

Introduction Six genotypes of the hepatitis C virus (HCV) have been identified thus far, and their distribution is well defined. Genotype 1, which is the most prevalent worldwide, is always compared to genotypes 2 and 3, particularly in terms of treatment response. However, little is known about the differences between genotypes 2 and 3 because these genotypes are analyzed together in most studies. Therefore, the aim of this study was to evaluate differences in the clinical, epidemiological, laboratory, and histological parameters between HCV-2 and HCV-3. Methods Patients with chronic hepatitis C infected with genotypes 2 and 3 were studied retrospectively and compared according to clinical, laboratory, and histological aspects. Hepatitis C virus-ribonucleic acid (HCV-RNA) was analyzed quantitatively by TaqMan® real-time PCR, and the HCV genotype was determined by sequencing the 5′-untranslated region. Results A total of 306 patients with chronic HCV-2 (n=50) and HCV-3 (n = 256) were studied. Subtype 2b (n=17/50) and subtype 3a (n=244/256) were the most prevalent among patients infected with HCV-2 and HCV-3, respectively. The mean age was 47 ± 10 years, and there was a predominance of men in the group studied (61%). Comparative analysis between HCV-2 and HCV-3 showed a younger age (p=0.002), less prevalence of arterial hypertension (p=0.03), higher serum albumin levels (p=0.01), more advanced stage of liver fibrosis (p=0.03), and higher frequency of steatosis in patients with HCV-3 (p=0.001). After multivariate regression analysis, all the variables, except serum albumin, remained as variables associated with HCV-3 in the final model. Conclusions Clinical and histological differences exist between HCV-2 and HVC-3, which suggests the need for separate analyses of these genotypes. .

Peginterferon plus ribavirin and sustained virological response rate in HCV-related advanced fibrosis: a real life study

Background: Tolerance and response to antiviral HCV treatment is poor in advanced fibrosis. The aim of this study was to assess SVR rate and its predictive factors in HCV advanced fibrosis patients treated in real life with full dose PEG-IFN plus RBV and to evaluate the adverse events related to treatment. Methods: A multicentric, retrospective study was conducted at six university hospitals. METAVIR F3 and F4 HCV monoinfected patients who were treated with PEG-IFN and RBV had their data analyzed. A stepwise logistic regression analysis was performed to identify the variables independently related to SVR. Adverse events were recorded during treatment. Results: 308 patients were included, 75% genotype 1 and 23% genotype 3. METAVIR F3 was present in 39% and F4 in 61% of patients. The median Child Pugh score for F4 patients was 5 (5–9). The global SVR rate was 34%, 11% were relapsers and 55% were nonresponders. SVR rates were similar between patients treated with PEG-IFN alfa 2a or alfa 2b (p = 0.24). SVR rates according to Child–Pugh score were 26% (Child A) and 18% (Child B). The independent factors related to SVR in F4 patients were genotype 3, RVR and fewer Child Pugh score points. Treatment interruption occurred in 31% patients and death occurred in 1.9%, all with liver cirrhosis. Conclusion: Treatment of HCV in patients with advanced fibrosis should not be postponed. However, a very careful evaluation of cirrhotic patients must be performed before treatment is indicated and careful monitoring is required during treatment. .

Association between histological findings, aminotransferase levels and viral genotype in chronic hepatitis C infection

Introduction: The genomic heterogeneity of hepatitis C virus (HCV) influences liver disorders. This study aimed to determine the prevalence of HCV genotypes and to investigate the influence of these genotypes on disease progression. Methods: Blood samples and liver biopsies were collected from HCV-seropositive patients for serological analysis, biochemical marker measurements, HCV genotyping and histopathological evaluation. Results: Hepatitis C virus-ribonucleic acid (HCV-RNA) was detected in 107 patients (90.6% with genotype 1 and 9.4% with genotype 3). Patients infected with genotype 1 exhibited higher mean necroinflammatory activity and fibrosis. Conclusions: HCV genotype 1 was the most prevalent and was associated with greater liver dysfunction. .

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

A single-nucleotide polymorphism (SNP) upstream of interleukin (IL)28B was recently identified as an important predictor of the outcome of chronic hepatitis C patients treated with pegylated interferon plus ribavirin (PEG-IFN/RBV). The aim of this study was to investigate the association between the IL28B gene polymorphism (rs12979860) and virological response in chronic hepatitis C patients. Brazilian patients (n = 263) who were infected with hepatitis C virus (HCV) genotype 1 and were receiving PEG-IFN/RBV were genotyped. Early virological response (EVR) (12 weeks), end-of-treatment response (EOTR) (48 weeks), sustained virological response (SVR) (72 weeks) and relapse were evaluated using conventional and quantitative polymerase chain reaction (PCR) assays. The frequency of the C allele in the population was 39%. Overall, 43% of patients experienced SVR. The IL28B CC genotype was significantly associated with higher treatment response rates and a lower relapse rate compared to the other genotypes [84% vs. 58% EVR, 92% vs. 63% EOTR, 76% vs. 38% SVR and 17% vs. 40% relapse rate in CC vs. other genotypes (CT and TT), respectively]. Thus, the IL28B genotype appears to be a strong predictor of SVR following PEG-IFN/RBV therapy in treatment-naïve Brazilian patients infected with HCV genotype 1. This study, together with similar research examining other SNPs, should help to define adequate protocols for the treatment of patients infected with HCV genotype 1, especially those with a poor prognosis.

Effectiveness of alpha interferon (+ ribavirin) in the treatment of chronic viral hepatitis C genotypes 2 and 3 in a brazilian sample / Efetividade da alfainterferona (+ribavirina) no tratamento da hepatite viral crônica C genótipos 2 e 3 em amostra brasileira

CONTEXT: Pharmacovigilance studies aim to detect, assess, understand and prevent risks of adverse effects of medications or any other possible drug related problem. Alpha interferon is being produced by Bio-Manguinhos/Fiocruz, Rio de Janeiro, RJ, Brazil and used in the treatment of chronic hepatitis C at Brazilian National Health System. OBJECTIVE: To study the safety profile and effectiveness of alpha interferon in a sample of Brazilian patients with chronic hepatitis C genotypes 2 and 3, in Porto Alegre, RS, Brazil. METHOD: We followed a cohort of chronic hepatitis C genotypes 2 and 3 patients treated with alpha interferon plus ribavirin in a specialized outpatient clinic in southern Brazil. Adverse events were collected and classified according to severity in monthly structured interviews. To measure effectiveness, hepatitis C viral load was evaluated before, at the end and 24 weeks after the treatment. RESULTS: We followed 141 patients during the study period, of which 52.5% were female with mean age of 52 years. The most frequent adverse events were fatigue (84%), headache (79%) and myalgia (75%). There were 13 treatment interruptions due to adverse events, 9 of those considered serious adverse events. Virological response at end of treatment was 54.6% and after 24 weeks 39.7%, considering all patients who started treatment. CONCLUSION: The product produced by Bio-Manguinhos has similar efficacy and adverse event and sustained virological response profiles comparable to those found in the literature. This is the first study of pharmacovigilance performed with the Brazilian product. These data will be useful for planning and management of this disease in Brazil.

CONTEXTO: Estudos de farmacovigilância têm por objeto a detecção, avaliação, compreensão e prevenção dos riscos dos efeitos adversos dos medicamentos ou qualquer outro possível problema relacionado com medicamento. A alfainterferona (IFN) está sendo produzida por Bio-Manguinhos/Fiocruz e utilizada no tratamento da hepatite C crônica no âmbito do Sistema Único de Saúde (SUS). OBJETIVO: Conhecer o perfil de segurança e efetividade deste IFN em uma amostra de pacientes brasileiros com hepatite crônica pelo vírus C genótipos 2 e 3, em Porto Alegre, RS, Brasil. MÉTODO: Trata-se de uma coorte de pacientes com hepatite crônica pelo vírus C genótipos 2 e 3 tratados com IFN e ribavirina e acompanhados em um serviço ambulatorial especializado no sul do Brasil. Os eventos adversos foram coletados e classificados de acordo com a gravidade em entrevistas mensais estruturadas. Para medida de eficácia foi avaliada a carga viral do HCV antes, ao final e 24 semanas após o término do tratamento. RESULTADOS: Foram acompanhados 141 pacientes no período do estudo, sendo 52,5% do sexo feminino com média de idade de 52 anos. Os eventos adversos mais frequentes foram fadiga (84%), cefaleia (79%) e mialgia (75%). Ocorreram 13 interrupções de tratamento por eventos adversos, sendo nove destes considerados eventos adversos graves. A resposta virológica ao final do tratamento foi de 54,6% e 24 semanas após de 39,7%, considerando todos os pacientes que iniciaram o tratamento. CONCLUSÃO: O produto produzido por Bio-Manguinhos possui eficácia e um perfil de eventos adversos e de resposta virológica sustentada comparáveis aos encontrados na literatura. Este é o primeiro estudo de farmacovigilância realizado com o produto brasileiro. Estes dados serão úteis para planejamento e gestão do tratamento desta doença no Brasil.

Assessment of the treatment of chronic hepatitis C in the state of Mato Grosso, central Brazil

In Brazil, the treatment of hepatitis C virus (HCV) infection is funded by the national public health system (SUS). To evaluate treatment results in the state of Mato Grosso, central Brazil, we have consulted the files of the office of the State Department of Health responsible for supplying such medications. We obtained information on 232 treatments of 201 patients who underwent treatment in or prior to 2008. The study was conducted by reviewing medical records, making telephone calls and interviewing the assistant physicians. Thirty-nine patients (19.4 percent) had cirrhosis and HCV genotype 1 predominated (64.3 percent). Excluding patients with comorbidities or treatment without ribavirin we analysed 175 treatments (sustained virologic response occurred in 32.6 percent of cases). Twenty-six of these 175 were retreatments and the sustained virological response (SVR) rate among them was 30.8 percent; the SVR rate was 32.9 percent among those receiving treatment for the first time. The SVR rate of genotype 1 patients was 27.8 percent, whereas it was 37.5 percent in non-1 genotype patients. The adjusted multivariate analysis showed association of SVR with the absence of cirrhosis [odds ratio (OR): 7.7; confidence interval (CI) 95 percent: 2.5, 33.3], the use of pegylated interferon (OR: 5.8; CI 95 percent: 1.5, 21.4), non-1 genotype (OR: 5.3; CI 95 percent: 1.7, 16.7) and uninterrupted treatment (OR: 9.0; CI 95 percent: 3.3, 45.4). The SVR rates were similar to those found in other Brazilian studies about HCV, but lower than those found in national and international clinical trials. These data suggest that the treatments of chronic hepatitis C that are made available by SUS does not, under normal conditions, work as well as the original controlled studies indicated.

Analysis of the sustained virological response in patients with chronic hepatitis C and liver steatosis / Análise da resposta virológica sustentada em pacientes com hepatite crônica pelo vírus da hepatite C e esteatose hepática

CONTEXT: Chronic hepatitis C as well as non-alcoholic fatty liver disease are recognized as the main cause of liver disease in Western countries. It is common to see the concomitance of the diseases and the influence of steatosis in the sustained virological response of patients with hepatitis C virus. OBJECTIVE: Assess the sustained virological response in chronic hepatitis C patients according to the presence of liver steatosis. METHODS: One hundred sixty patients with chronic hepatitis C were retrospectively evaluated. Demographic data such as gender, age, body mass index, presence of diabetes mellitus and systemic arterial hypertension, virus genotype and use of pegylated interferon were analyzed, as was the staging of fibrosis and the presence of steatosis at histology. RESULTS: Most patients were male (57.5 percent), with a mean age of 48 ± 9.7 years. The most frequent genotype observed was 3 (56.9 percent) and, in the histological evaluation, steatosis was observed in 65 percent of the patients (104/160). Sustained virological response in patients with steatosis occurred in 38.5 percent, and in 32.1 percent in patients without steatosis (P = 0.54). When we analyzed possible factors associated with the presence of steatosis, only body mass index and systemic arterial hypertension revealed a significant association. When the factors that influenced sustained virological response were evaluated in a logistic regression, genotype and use of pegylated interferon proved to be independent factors associated to the response. CONCLUSION: In the evaluated patients the presence of liver steatosis did not influence the sustained virological response of patients with chronic hepatitis C treated with interferon and ribavirin.

CONTEXTO: Tanto a hepatite crônica pelo vírus C quanto a doença hepática gordurosa não-alcoólica são reconhecidas como causas frequentes de doença hepática nos países ocidentais. É comum observar a concomitância das duas doenças e a influência da esteatose na resposta virológica sustentada dos pacientes com hepatite crônica pelo vírus C. OBJETIVO: Avaliar a resposta virológica sustentada nos pacientes com hepatite crônica pelo vírus C de acordo com a presença de esteatose. MÉTODOS: Foram avaliados, retrospectivamente, 160 pacientes com hepatite crônica C. Dados demográficos, como sexo, idade, índice de massa corpórea, presença de diabetes mellitus e hipertensão arterial sistêmica, genótipo do vírus e uso de interferon peguilado foram analisados, bem como o estadiamento e a presença de esteatose, quando da histologia. RESULTADOS: A maioria dos pacientes era masculina (57,5 por cento), com média de idade de 48 anos ± 9,7. O genótipo mais frequente foi o 3 (56,9 por cento) e, na avaliação histológica, foi observada esteatose em 65 por cento dos pacientes (104/160). A resposta virológica sustentada nos pacientes com esteatose foi de 38,5 por cento, sendo de 32,1 por cento nos pacientes sem esteatose (P = 0,54). Quando se analisaram possíveis fatores associados à presença de esteatose, somente índice de massa corpórea e hipertensão arterial sistêmica estiveram associados de forma significativa. Quando se avaliaram em regressão logística os fatores que influenciaram a resposta virológica sustentada, genótipo e uso de interferon peguilado mostraram-se fatores independentes associados à resposta. CONCLUSÃO: A presença de esteatose hepática não influenciou a resposta virológica sustentada de pacientes com hepatite crônica pelo vírus C tratados com interferon e ribavirina.

Resultados del tratamiento con peginterferón alfa-2a y ribavirina en pacientes con hepatitis crónica C / Results of treatment with peginterferon plus ribavirin in patients with chronic hepatitis C

Background: The current treatment recommendation for chronic hepatitis C virus infection is the combination of peginterferon and ribavirin for 24 or 48 weeks, depending on the viral genotype. The aim of the therapy is to obtain a sustained virological response. Aim: To report our experience in the treatment of chronic hepatitis C. Material and Methods: Analysis of 52 patients treated between September 2000 and June 2009. Patients with genotype 1 or 5 were treated with peginterferon alpha 2a (180 ug/week) and ribavirin (1000 mg/day for those weighing less than 75 kg and 1200 mg/day for those weighing more than 75 kg) during 48 weeks. Patients with genotypes 2 and 3 were treated for 24 weeks with the same dose of peginterferon and ribavirin 800 mg /day. Results: Viral genotypes 1, 2, 3 and 5 were present in 81, 4, 11 and 4 percent of patients, respectively. Twenty four patients (46 percent), 18 with genotype 1, achieved a sustained viral response. Age was the only variable that infl uenced the response to treatment. Conclusions: Approximately half of the patients with chronic hepatitis C, achieve a sustained viral response with peginterferon and ribavirin.

Should active injecting drug users receive treatment for chronic hepatitis C? / Usuários ativos de drogas injetáveis devem receber tratamento para hepatite crônica tipo C?

CONTEXT: Accumulating data propose that active injecting drug users might not differ from the general population in terms of sustained virological response when adherent to therapy for chronic hepatitis C. However, current guidelines contain restrictive recommendations for therapy in this group of patients. OBJECTIVE: Therefore, we evaluated a cohort of chronic hepatitis C patients regarding the potent influence of active drug using on initial informed consent, compliance and sustained virological response to treatment. METHOD: For that purpose, 162 consecutive patients (of which 62 active injecting drug users), who had been evaluated during the last 6 years in our center for chronic hepatitis C and proposed to receive treatment with pegylated interferon alpha and ribavirin, were enrolled. Initial informed consent, compliance, and sustained virological response as well as data regarding age, gender, body mass index, genotype, viral load, coinfection with HBV/HDV/HIV, administered interferon alpha (2a or 2b), liver function tests, liver histology, urban residence, ethnicity, and concomitant use of alcohol were collected and analyzed in respect with injecting drug using. RESULTS: Injecting drug using was positively correlated with male gender (P<0.001), young age (P<0.001), native origin (P = 0.043), and concomitant use of alcohol (P<0.001). Comparable initial informed consent (P = 0.836), compliance (P = 0.879), and sustained virological response (P = 0.132) were observed between injecting drug users and non- injecting drug users. The results were confirmed using a multiple regression model. CONCLUSION: Our data further support that active injecting drug users do not constitute a distinct chronic hepatitis C patient group in terms of initial informed consent, compliance, or sustained virological response. Therefore, injecting drug using should not be a major determinant influencing the decision for treatment of chronic hepatitis C in eligible patients.

CONTEXTO: Dados acumulados demonstram que usuários ativos de drogas injetáveis podem não diferir da população em geral em termos de resposta virológica sustentada quando aderentes à terapia para a hepatite crônica C. No entanto, as atuais orientações publicadas contêm recomendações restritivas para a terapia nesse grupo de pacientes. OBJETIVO: Com este propósito, avaliou-se uma coorte de pacientes com hepatite crônica C após consentimento informado inicial, no que diz respeito à influência da droga ativa na adesão e na resposta virológica sustentada ao tratamento. MÉTODOS: Para o efeito, foram convidados 162 pacientes (dos quais 62 ativos usuários de drogas injetáveis), que foram avaliados durante os últimos 6 anos em um centro de referência para a hepatite crônica C e se propuseram a receber tratamento com interferon alfa peguilado e ribavirina. O consentimento inicial, a adesão ao tratamento e a resposta virológica sustentada, bem como dados sobre idade, sexo, índice de massa corporal, genótipo, carga viral, com coinfecção HBV/HDV/HIV, tipo de interferon alfa administrado (2a ou 2b), testes de função hepática, histologia hepática, residência urbana, etnia e uso concomitante de álcool foram coletados e analisados em relação com o uso de drogas injetáveis. RESULTADOS: O uso de drogas injetáveis teve correlação positiva com o sexo masculino (P<0,001), idade (P<0,001), de origem nativa (P = 0,043) e uso concomitante de álcool (P<0,001). Foram observados entre usuários de drogas injetáveis e usuários de drogas não-injetáveis dados comparáveis em relação ao consentimento informado inicial (P = 0,836), adesão (P = 0,879) e resposta virológica sustentada (P = 0,132). Os resultados foram confirmados através de um modelo de regressão múltipla. CONCLUSÃO: Os dados confirmam ainda que usuários ativos de drogas injetáveis não constituem um grupo distinto de paciente com hepatite crônica C em termos de consentimento inicial, adesão, ou a resposta virológica sustentada. Assim, o uso de drogas injetáveis não deve ser um dos principais determinantes que influenciam a decisão para o tratamento da hepatite C crônica em pacientes elegíveis.

Long-term follow-up of patients with chronic hepatitis C with sustained virologic response to interferon

BACKGROUND AND AIM: The durability of the sustained virologic response (SVR) in patients with chronic hepatitis C after treatment and the ideal follow-up time for these patients remains undefined. The objective of the study was to evaluate the durability of the virologic response in patients with chronic hepatitis C followed up for at least 12 months after SVR at HCFMRP-USP. METHODS: The study was conducted on 174 patients with chronic hepatitis C treated with different antiviral regimens who had achieved SVR. Qualitative serum HCV-RNA was determined by the commercial kit (COBAS AMPLICOR HCV, v2.0). RESULTS: There was predominance of male (73 percent) with a mean age of 45.6 ± 10 years. Liver cirrhosis was present in 16.1 percent of the study subjects. Mean follow-up time after SVR was 47 months (12-156 months). Twenty-two patients received monotherapy with interferon; 94 received interferon plus ribavirin, and 58 received pegylated interferon plus ribavirin. A total of 134 patients (77.0 percent) received one treatment course, 29 (16.7 percent) received two courses, and 11 (6.3 percent) received three courses. The distribution of HCV genotypes was: genotype 1 (40.2 percent), genotype 3 (40.8 percent) and genotype 2 (10.3 percent). Genotype was undetermined in 8.7 percent of cases. None of the 174 patients had recurrence of HCV infection. Two cirrhotic patients developed hepatocellular carcinoma (HCC) during follow-up. CONCLUSIONS: Among patients with SVR there was no recurrence of HCV infection or evidence of liver disease progression in any patient followed up for a mean of 47 months after SVR, except for patients with advanced hepatic disease before treatment, who may develop HCC despite SVR. Therefore, one can assume that SVR is associated with long term good prognosis.