Cardiac Disorder in Chronic Hepatitis C

Chronic hepatitis C (CHC) has a high prevalence in the world. In addition to hepatic complications with cirrhosis in about 20% of patients and high risk for hepatocarcinoma, extrahepatic manifestations may also occur. Cardiac involvement in patients with CHC is associated with several factors, such as increased risk for coronary artery disease, primary cardiomyopathies, or hemodynamic and electrophysiological changes observed in liver cirrhosis. Furthermore, antiviral treatment may, in rare cases, causes cardiovascular adverse effects. Cardiac arrhythmias are the main form of clinical presentation, and, often, markers of poor prognosis in individuals with advanced liver disease. Although some mechanisms that justify these changes have already been reported, many questions remain unanswered, especially about the true involvement of the hepatitis C virus in the genesis of primary cardiac abnormalities, and the risk factors for cardiac-related complications of antiviral treatment

Hand-foot syndrome due to hepatitis C therapy

SUMMARY INTRODUCTION Direct-acting antivirals are new drugs for chronic hepatitis C treatment. They are usually safe and well tolerated, but can sometimes cause serious adverse effects and there is no consensus on how to treat or prevent them. We described a case of hand-foot syndrome due to hepatitis C virus interferon-free therapy. METHODS We report the case of a 49-year-old man with compensated liver cirrhosis due to chronic hepatitis C genotype 1, treatment-naïve, who started viral treatment with sofosbuvir, simeprevir and ribavirin for 12 weeks. RESULTS At the sixth week of treatment he had anemia, requiring a lower dose of ribavirin. At the tenth week, he had erythematous, pruritic, scaly and flaky lesions on hands and feet, which showed a partial response to oral antihistamines and topical corticosteroids. It was not necessary to discontinue antiviral treatment, but in the first week after the end of treatment, there was worsening of injuries, including signs of secondary infection, that required hospitalization, antibiotics and oral corticosteroid, with progressive improvement. Biopsy of the lesions was consistent with pharmacodermia. The patient had sustained a virological response, despite the side effect. He had a history of pharmacodermia one year ago attributed to the use of topiramate, responsive to oral corticosteroid. CONCLUSION Interferon-free therapies can rarely lead to severe adverse reactions, such as skin lesions. Patients receiving ribavirin combinations and those who had a history of pharmacodermia or skin disease may be more susceptible. There is no consensus on how to prevent skin reactions in these patients.

RESUMO INTRODUÇÃO Antivirais de ação direta são as novas drogas utilizadas no tratamento da hepatite C crônica. São geralmente seguros, com boa tolerância, mas eventualmente podem causar efeitos adversos graves, e não há consenso sobre como tratá-los ou preveni-los. Descrevemos um caso de síndrome mão-pé secundária à terapia livre de interferon para hepatite C crônica. Materiais e métodos Relatamos o caso de um paciente de 49 anos com cirrose hepática compensada secundária à hepatite C crônica, genótipo 1, virgem de tratamento, que iniciou terapia com sofosbuvir, simeprevir e ribavirina por 12 semanas. Resultados Na sexta semana de tratamento, apresentou anemia, sendo necessária redução de dose da ribavirina. Na 20a semana, apresentou lesões eritematosas e descamativas, com prurido em mãos e pés, que teve resposta parcial ao uso de anti-histamínico oral e corticoide tópico. Não foi necessário descontinuar os antivirais, mas na primeira semana após o término do tratamento, houve piora das lesões, com sinais de infecção secundária, sendo necessárias hospitalização e terapia com antibiótico e corticoide oral, com melhora progressiva. Biópsias das lesões foram compatíveis com farmacodermia. O paciente teve resposta virológica sustentada, apesar dos efeitos adversos. Tinha história de farmacodermia há um ano, atribuída ao uso de topiramato, responsiva a corticoterapia oral. Conclusão Os tratamentos livres de interferon raramente causam eventos adversos graves, como lesões cutâneas. Pacientes em uso de ribavirina e com história de farmacodermia ou doença cutânea prévia podem ser mais susceptíveis. Não existe consenso sobre como prevenir reações cutâneas nesses pacientes.

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.

Anthropometric changes caused by hepatitis C treatment with interferon and ribavirin: which patients and which measures are affected?

BACKGROUND: Chronic hepatitis C causes chronic hepatic inflammation, which can lead to cirrhosis, terminal liver failure, and hepatocellular carcinoma. The treatment aims to achieve viral clearance, but the usage of pegylated interferon and ribavirin is linked to side effects such as severe weight loss, which can lead to complications and treatment discontinuation. The aim of this study was to investigate which anthropometric measures were more affected in patients with chronic hepatitis C during 24 weeks of treatment with pegy lated interferon and ribavirin. Then, the influence of age, sex, hepatic fibrosis stage, and ribavirin doses on each measure was also evaluated. METHODS: Seventy-six patients were included and their weight, triceps skin fold thickness, arm circumference, middle-arm muscle circumference, and corrected arm muscle area were measured before and after 24 weeks of treatment. Epidemiological data and liver biopsy findings were obtained from patients' records. The sample was divided into two groups: one with advanced hepatic fibrosis and another group with mild to moderate fibrosis. Comparisons into each group were made using Wilcoxon or paired tests. After that, a linear regression model was applied to estimate the anthropometric changes during the treatment according to age, sex, hepatic fibrosis stage, and ribavirin doses. RESULTS: The subjects suffered reductions of important anthropometric measures, mainly related to fat mass (p<0.001).Some decrease of fat-free mass was also observed in subjects with advanced fibrosis. The statistic model showed that age and sex were more associated with the anthropometric changes observed. CONCLUSIONS: In conclusion, the antiviral treatment caused loss of relevant anthropometric measures, and the model proposed was able to estimate some of them

High Prevalence of ITPA Alleles Associated with Ribavirin-Induced Hemolytic Anemia Among Mexican Population

ABSTRACT Background. The prevalence of two functional polymorphisms (rs1127354 and rs7270101) of the inosine triphosphatase (ITPA) gene associated with ribavirin-induced hemolytic anemia (RIHA) during antiviral therapy for hepatitis C virus (HCV) infection varies by ethnicity. In Mexico, the distribution of these polymorphisms among Native Amerindians (NA) and admixed population (Mestizos) is unknown. This study aimed to determine the prevalence of the ITPA polymorphisms among healthy NA and Mestizos, as well as in HCV patients from West Mexico. Material and methods. In a cross-sectional study, 600 unrelated subjects (322 Mestizos, 100 NA, and 178 treatment-naïve, HCV-infected Mestizos patients) were enrolled. A medical history was registered. ITPA genotype was determined by Real-Time PCR. Fst-values and genetic relatedness between study and reference populations were assessed. Results. The frequency of the risk genotypes rs1127354CC and rs7270101AA was higher among NA (98-100%) than in Mestizos (87-92.9%), (p < 0.05). The NA presented the highest prevalence of the rs1127354CC genotype reported worldwide. The Fst-values revealed a genetic relatedness among Mexican NA, South Americans and African populations (p > 0.05). The frequency of the predicted risk for RIHA was higher among NA (98%) than in Mestizos (80.5%) and HCV-infected patients (81.5%) (p < 0 .01). The CC/AA alleles were associated with lower values of total bilirubin, aspartate/alanine aminotransferases, and aspartate-to-platelet-ratio-index score among HCV-patients. Conclusion. A high prevalence of the ITPA polymorphisms associated with RIHA was found in Mexican NA. These polymorphisms could be a useful tool for evaluating potential adverse effects and the risk or benefit of antiviral therapy in Mexicans and other admixed populations.

Hematologic adverse effects and efficacy monitoring in chronic Hepatitis C patients treated with interferon and ribavirin combination therapy

180 million people are affected by chronic Hepatitis C Virus infection globally and more than 50 million in South East Asia. Combination of Interferon and Ribavirin is the current anti-HCV therapy in practice and is associated with certain hematologic adverse effects. In this concurrent observational study the incidence rate of major hematologic adverse effects and efficacy outcomes of Interferon and Ribavirin combination therapy was evaluated in 288 chronic hepatitis C patients at Lahore General Hospital. Levels of Hb, TLC, and Platelets counts were monitored for hematologic adverse effects monitoring, whereas, ALT, AST and bilirubin levels were monitored for efficacy. PCR was done at week 4, 12 and 36 for therapeutic success evaluation. A significant reduction in Hb levels [p<0.05] was observed after week 4, 8 and 12 of therapy. Frequency of anemia increased in both genders with body weight <65kg and platelet count <150,000/mm3. End Treatment Response [ETR] was achieved in 64.5%. Anemia was the major side effect of the combination therapy particularly in the males. Higher ETR was observed in patients who achieved RVR and were <50 years of age

sustained virologic response and adverse effects of peg interferon alfa and ribavirin in the treatment of patients with chronic hepatitis c: a study from Iran

Background: Hepatitis C infection is a worldwide problem. In Iran, hepatitis C virus [HCV] infection prevalence is about 1-2%. A combination therapy of pegylated interferon alfa-2a and ribavirin [PEG-IFNalpha/RBV] is a standard treatment, but our aim was to determine the efficacy and safety of dual PEG-IFNalpha/RBV therapy in treating patients infected with HCV in Iranian context

Materials and Methods: This study is a cross sectional conducted among 98 HCV infected patients who were admitted to Labbafinezhad Hospital [Tehran, Iran] for treatment from April 2014 to September 2016. Patients were medicated with Peg Interferon Alfa [INFalpha] and Ribavirin [RBV]. Lab tests were monitored through the study and dose modification was done. We also assessed treatment responses at the defined time points. The incidences of adverse events were determined either. We investigated independent predictors of sustained virologic response [SVR] in the participants. Finally, data were gathered and statistical analysis was completed

Results: Eighty-eight percent of patients were male and 11.2% were female. Mean age was 43.44 years. Patients were mostly male, single, with nongovernmental business and low level of education. Risk factors were known to be addiction with non-injectable substances and phlebotomy. Myalgia, fatigue and malaises were the most common complications and suicide intention was the least one. SVR was estimated 76.7%. AST and ALT were significantly reduced in treatment period

Conclusion: Peg INFa and RBV are effective in treating HCV infection

Hematological and dermatological adverse events during hepatitis C treatment with peg-interferon and ribavirin / Eventos adversos hematológicos e dermatológicos durante o tratamento da hepatite C com interferon peguilado e ribavirina

Objective: To evaluate frequency and impact of adverse events, mainly the hematological and dermatological ones, on sustained virological response, and compliance to hepatitis C treatment. Methods: Patients were treated according to the guidelines of the Brazilian Ministry of Health. Variables associated with hematological and dermatological adverse events were: age, gender, stage of fibrosis, type of Pegylated interferon, dose reductions, temporary discontinuation and early interruption of treatment. Results: Two hundred and twenty two patients were studied (58% females; age 49±11 years). Dose reductions, temporary interruptions, and early discontinuations were observed in 21%, 8% and 9.5% of patients, respectively. The main adverse events were hematological (anemia, neutropenia and thrombocytopenia) and dermatological (pruritus and alopecia). Anemia (Hemoglobin <10g/dL) was associated with female gender (p<0.001), advanced fibrosis (p=0.047) and dose reductions (p<0.001); neutropenia with advanced fibrosis (p=0.003) and temporary discontinuation (p=0.002); thrombocytopenia with advanced fibrosis (p<0.001) and pegylated interferon α2a (p=0.05). Pruritus and alopecia were associated to female gender (p=0.008 and p=0.02) and treatment interruption (p=0.029 and p=0.02).Conclusion: Hematological and dermatological adverse events are frequent in hepatitis C patients treated with pegylated interferon and ribavirin. However, despite frequent dose reductions and interruptions, these adverse events did not affect the sustained virological response.

Objetivo: Avaliar a frequência e o impacto de eventos adversos, principalmente hematológicos e dermatológicos, na resposta virológica sustentada e na aderência ao tratamento para hepatite C. Métodos: Os pacientes foram tratados de acordo com diretriz do Ministério da Saúde. Variáveis associadas com eventos adversos hematológicos e dermatológicos foram: idade, sexo, grau de fibrose, tipo de interferon peguilado, reduções de dose, descontinuação temporária e interrupção precoce do tratamento. Resultados: Foram estudados 232 pacientes (58% mulheres; idade 49±11 anos). Reduções de dose, interrupções temporárias e descontinuações precoces foram observadas em 21%, 8% e 9,5% dos pacientes, respectivamente. Os principais eventos adversos foram hematológicos (anemia, neutropenia e plaquetopenia) e dermatológicos (prurido e alopecia). Anemia (hemoglobina <10g/dL) se associou a sexo feminino (p<0,001), fibrose avançada (p=0,047) e reduções de doses (p<0,001); neutropenia com fibrose avançada (p=0,003) e interrupção temporária (p=0,002); plaquetopenia com fibrose avançada (p<0,001) e interferon peguilado α2a (p=0,05). Prurido e alopecia se associaram ao sexo feminino (p=0,008 e p=0,02) e interrupção do tratamento (p=0,029 e p=0,02). Conclusão: Eventos adversos hematológicos e dermatológicos foram frequentes em pacientes tratados com interferon peguilado e ribavirina. Entretanto, a despeito de frequentes reduções de dose e interrupções, estes eventos adversos não afetaram a resposta virológica sustentada.

Depressive episode incidence in patients with chronic hepatitis c treated with pegylated interferon and ribavirin

ABSTRACT Background The effectiveness of antiviral therapy with pegylated interferon and ribavirin for chronic hepatitis C is far from ideal and presents several adverse events. Among such events, there is the depressive episode that can even lead to treatment discontinuity Objective Analyze the incidence of depressive episodes in patients with chronic hepatitis C treated with pegylated interferon (IFN-PEG) and ribavirin, as well as the possible factors associated with its occurrence and its impact on patients' sustained virological response. Methods People with chronic hepatitis C undergoing antiviral therapy were interviewed at the baseline, at the 4th, 12th, 24th and 48th treatment weeks and 4 weeks after the end of it, using the HADS scale for tracking the depressive episode. Patients with HADS ≥9 were subjected to Beck Depression Inventory (BDI-II) to grade the episode. Clinical, sociodemographic, laboratorial and histological variables were obtained to identify factors related to the onset of depression. The sustained virological response rate (negative HCV-RNA 6 months after end of therapy) was compared among patients with and without depressive symptoms. Results The study comprised 32 patients, most men (59%) with mean age of 54±11.13 years old. Genotype non-1 was prevalent (56%) and 81% of the patients were non-cirrhotic. The depressive episode was diagnosed in 25% of the patients and the peak incidence was found in the 12th treatment week. The depressive episode was moderate in 87% of the patients and only one patient abandoned the treatment. None of the analyzed factors was associated with depressive episode onset. A trend was observed in female patients ( P=0.08). The sustained virological response rate was of 75% and 67% in patients with and without depressive episode, respectively (P =0.66). Conclusion The incidence of depressive episodes in patients with chronic hepatitis C undergoing antiviral therapy was of 25% and the 12th treatment week was the most critical one. The presence of depressive episode did not affect the sustained virological response rate.

RESUMO Contexto A terapia antiviral para a hepatite C crônica com interferon peguilado e ribavirina tem eficácia longe do ideal e é repleta de eventos adversos. Entre estes, destaca-se o transtorno depressivo que pode inclusive levar a interrupção do tratamento. Objetivos Em pacientes com hepatite C crônica tratados com interferon peguilado (IFN-PEG) e ribavirina, verificar a incidência de episódio depressivo, os possíveis fatores associados ao seu surgimento e o impacto deste sobre a resposta virológica sustentada. Métodos Portadores de hepatite C crônica submetidos à terapia antiviral foram entrevistados no Baseline, nas semanas 4, 12, 24, 48 de tratamento e quatro semanas após o término do mesmo utilizando a escala HADS para rastreamento do episódio depressivo e naqueles com HADS ≥9 o Inventário de Depressão de Beck (BDI-II) para graduação do episódio. Variáveis clínicas, sociodemográficas, laboratoriais e histológicas foram obtidas com o objetivo de identificar os fatores relacionados ao surgimento da depressão. A taxa de resposta virológica sustentada (HCV-RNA negativo seis meses após a interrupção da terapia) foi comparada entre os pacientes com e sem sintomas depressivos. Resultados Foram incluídos 32 pacientes, a maioria do sexo masculino (59%) e com média de idade de 54±11,13 anos. Prevaleceu o genótipo não 1 (56%) e 81% dos pacientes foram não cirróticos. Episódio depressivo foi diagnosticado em 25% dos pacientes sendo o pico de incidência observado na semana 12 de tratamento. O episódio depressivo foi moderado em 87% dos pacientes e motivou a interrupção em somente 1 deles. Nenhum dos fatores analisados foi associado ao surgimento de episódio depressivo observando-se uma tendência com relação ao sexo feminino ( P =0,08). A taxa de resposta virológica sustentada foi 75% e 67% nos pacientes com e sem episódio depressivo, respectivamente ( P =0,66). Conclusão A incidência de episódio depressivo em pacientes com hepatite C crônica submetidos à terapia antiviral foi de 25% e a semana 12 é a mais crítica. A presença de episódio depressivo não interferiu na taxa de resposta virológica sustentada.

HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT / Carcinoma hepatocelular em paciente não cirrótico com resposta virológica sustentada após tratamento para hepatite C

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.

A infecção crônica pelo vírus da hepatite C é um dos principais fatores de risco para o desenvolvimento de cirrose hepática e carcinoma hepatocelular. Entretanto, o surgimento do carcinoma hepatocelular em pacientes portadores de hepatite C na ausência de cirrose, especialmente após o tratamento e a obtenção de resposta virológica sustentada, é um evento incomum. Recentemente tem sido sugerido que o genótipo 3 do vírus da hepatite C possa ter um mecanismo oncogênico particular, mas todos os fatores envolvidos nestes casos, assim como o perfil destes pacientes, ainda não estão totalmente esclarecidos. Deste modo, apresentamos o caso de um paciente masculino de 50 anos de idade, com infecção pelo vírus da hepatite C genótipo 3a, não cirrótico, que desenvolveu carcinoma hepatocelular dois anos após ter atingido resposta virológica sustentada com o tratamento com interferon peguilado e ribavirina.

Inosine triphosphatase allele frequency and association with ribavirin-induced anaemia in Brazilian patients receiving antiviral therapy for chronic hepatitis C

Inosine triphosphatase (ITPA) single nucleotide polymorphisms (SNPs) are strongly associated with protection against ribavirin (RBV)-induced anaemia in European, American and Asian patients; however, there is a paucity of data for Brazilian patients. The aim of this study was to evaluate the ITPA SNP (rs7270101/rs1127354) frequency in healthy and hepatitis C virus (HCV)-infected patients from Brazil and the association with the development of severe anaemia during antiviral therapy. ITPA SNPs were determined in 200 HCV infected patients and 100 healthy individuals by sequencing. Biochemical parameters and haemoglobin (Hb) levels were analysed in 97 patients who underwent antiviral therapy. A combination of AArs7270101+CCrs1127354 (100% ITPase activity) was observed in 236/300 individuals. Anaemia was observed in 87.5% and 86.2% of treated patients with AA (rs7270101) and CC genotypes (rs1127354), respectively. Men with AA (rs7270101) showed a considerable reduction in Hb at week 12 compared to those with AC/CC (p = 0.1475). In women, there was no influence of genotype (p = 0.5295). For rs1127354, men with the CC genotype also showed a sudden reduction in Hb compared to those with AC. Allelic distribution of rs7270101 and rs1127354 shows high rates of the genotypes AA and CC, respectively, suggesting that the study population had a great propensity for developing RBV-induced anaemia. A progressive Hb reduction during treatment was observed; however, this reduction was greater in men at week 12 than in women.

TRIPLE THERAPY IN CHRONIC HEPATITIS C: initial series in a public health program in the South of Brazil / Terapia tripla em pacientes com hepatite C: experiência inicial em um pólo de aplicação do Sul do Brasil

Background Chronic hepatitis C has great impact on world’s health. Current therapy for genotype 1 hepatitis C virus includes protease inhibitors boceprevir and telaprevir, associated to standard therapy - peginterferon alfa + ribavirin. There are no published data in Brazil on the results of this new therapy, and it is interesting an evaluation of what was accomplished up to this moment. Objectives To evaluate virologic response to triple therapy, as well as the safety profile and tolerability. Method This study is a clinical series of patients receiving triple therapy for C hepatitis in a single center of a Public Health System of South Brasil. Out of the 121 patients that initiated the triple therapy, the first patients that finished the treatment and evaluated the sustained virological response (24 weeks after the end of treatment) were included. Results Twenty four genotype 1 chronic hepatitis C monoinfected patients were included. Nineteen (79.2%) patients had been previously treated. Thirteen (54.2%) patients were cirrhotic. Nineteen (79.2%) patients completed the planned therapy. By the end of the treatment, 14 (58.3%) out of 24 patients had undetectable viral load. Sustained virologic response occurred in 12 (50.0%) out of 24 patients, 07 (58.3%) in telaprevir group and 05 (41.7%) in boceprevir group. Out of 24 patients under triple therapy, 58% (n=14) presented anemia. Conclusions In conclusion, despite the small number of patients treated with triple therapy evaluated in the current study, it possibly reflects the population under this therapy in real-life. .

Contexto A hepatite crônica pelo vírus C tem grande impacto na saúde mundial. A terapia atual do genótipo 1 inclui os inibidores de protease (IP) boceprevir e telaprevir, associados à terapia padrão - alfapeginterferona + ribavirina (PR). No Brasil ainda não há estudos publicados sobre os resultados dessa nova terapia, sendo de interesse uma avaliação do que foi realizado até o momento. Objetivos Avaliar a resposta virológica ao tratamento triplo, bem como o perfil de segurança e tolerabilidade. Métodos O estudo consta de série de casos dos pacientes em uso de terapia tripla para o tratamento da hepatite C em um polo de tratamento da Secretaria Estadual da Saúde do Estado do Rio Grande do Sul, Brasil. Dentre os 121 pacientes que estão em uso de terapia tripla (PR e IP) foram apresentados os dados referentes aos primeiros que finalizaram o tratamento e realizaram avaliação da resposta virológica sustentada na semana 24 pós-tratamento. Resultados Foram incluídos 24 pacientes monoinfectados por hepatite C crônica genótipo 1. Dezenove (79%) pacientes eram previamente experimentados. Treze (54,2%) pacientes apresentavam cirrose. Dezenove (79,2%) pacientes completaram o tratamento planejado. Ao final do tratamento, 14 (58,3%) dos 24 pacientes apresentaram carga viral indetectável. Resposta virológica sustentada ocorreu em 12 (50%) dos 24 pacientes, sendo 07 (58,3%) no grupo telaprevir e 05 (41,7%) no grupo boceprevir. Dos 24 pacientes submetidos à terapia tripla, 58% (n=14) apresentaram anemia. Conclusões Embora o presente estudo tenha avaliado um pequeno número de casos, possivelmente reflete a população submetida à terapia tripla na vida real, despida das restrições dos estudos de registro. .

The clinical effectiveness of pegylated interferon and ribavirin for the treatment of chronic hepatitis C in HIV-infected patients in Brazil: a multicentric study

Introduction: in Brazil, chronic hepatitis C in patients coinfected with the human immunodeficiency virus (HIV) is treated with pegylated interferon (Peg-IFN) and ribavirin (RBV). However, few studies have evaluated the effectiveness of this treatment in this particular population. The identification of the factors that predict sustained virological response (SVR) under current clinical practice would enable clinicians to more accurately estimate the probability of achieving an SVR and therefore utilize the appropriate therapeutics, especially in the era of direct-acting antiviral (DAA) agents. Aims: the primary aim of our study was to determine the SVR rate under current clinical practice. The secondary aims were as follows: (1) to determine the factors before and during treatment that predict SVR; and (2) to identify the causes of treatment interruption. Methods: within a cohort of HIV/hepatitis C virus (HCV)-coinfected patients in Brazil, we performed a retrospective analysis of those individuals treated with Peg-IFN and RBV. Results: among the 382 analyzed patients, SVR was observed in 118 [30.9% (95% confidence interval (CI): 26.3-35.8)], which included 25.9% (75/289) of the patients with genotypes 1 and 4 and 48.2% (41/85) of those with genotypes 2 and 3. After multivariate analyses the independent positive predictors for SVR after treatment for chronic hepatitis C with PegIFN and RBV were: absence of an AIDS-defining illness (p = 0.001), HCV viral load lower than 600,000 IU/mL at the onset of treatment (p = 0.003), higher liver enzyme levels (p = 0.039) at baseline, infection with genotypes 2 or 3 (p = 0.003), and no transient treatment interruption (p = 0.001). The treatment was interrupted in 25.6% (98/382) of the patients because of adverse events (11.3%, 43/382), virologic failure (7.8%, 30/382), and dropout (6.5%, 43/382). The main adverse events were cytopenia and psychiatric disorders. Conclusions: ...

Hematological adverse effects in HCV patients treated with pegylated interferon and ribavirin in a Tertiary Care Hospital Peshawar

To know the frequency of common hematological adverse effects during treatment of HCV. Comparative study. This study was carried out OPD of gastroenterology unit HMC Peshawar from November 2013 to August 2014. This study comprising of 42 patients. Patient age more than 17 years, both genders, previously treatment experienced patients with normal hematologic and radiological parameters were included in the study. Patients age more than 70 years, patients with uncontrolled depressive illness, pregnant ladies, treatment naive patients and decompensated cirrhotics were excluded from the study. Patients were evaluated for treatment with pegylated and ribavirin by history, clinical examination, routine laboratory investigations, ultrasound abdomen, HCV genotyping and upper GI endoscopy where considered necessary. Patient's who fulfilled the inclusion criteria were included in the study. Total of 42 patients, 24 [57.14%] male and 18 [42.85%] female were included in this study. The mean age was 39.05 +/- 8.54 with minimum age of 18 years and maximum age of 55 years. Genotype 3 was the most frequent genotype, present in 26 [61.90%] patients followed by untypeable genotype, present in 12 [28.57%] patients. Anemia was present in 18 [42.85%], thrombocytopenia in 10 [23.80%] patients. Leucopenia was present in 6 [12.28%] patients. Haematological abnormalities are common during treatment for HCV, so patients should be regularly followed to diagnose and treat the cytopenias in time

Highly effective peginterferon alpha-2a plus ribavirin combination therapy for chronic hepatitis C in hemophilia in Korea

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.

Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.

Association between IPTA Gene Polymorphisms and Hematological Abnormalities in Hepatitis C Virus-Infected Patients Receiving Combination Therapy

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.

Incidence of and risk factors for thyroid dysfunction during peginterferon alpha and ribavirin treatment in patients with chronic hepatitis C

BACKGROUND/AIMS: Thyroid dysfunction (TD) is more likely to occur in patients with chronic hepatitis C (CHC) and is particularly associated with interferon (IFN) treatment. The purpose of this study was to investigate the incidence, outcomes, and risk factors for TD during pegylated interferon (PEG-IFN) and ribavirin (RBV) combined therapy in patients with CHC. METHODS: A total of 242 euthyroid patients with CHC treated with PEG-IFN/RBV were included. Thyroid function and autoantibodies were measured at baseline, and virologic response and thyroid function were assessed every 3 months during therapy. RESULTS: TD developed in 67 patients (27.7%) during the PEG-IFN/RBV treatment. The types of TD were subclinical hypothyroidism (50.7%), hypothyroidism (14.9%), thyroiditis (11.9%), subclinical hyperthyroidism (10.4%), and hyperthyroidism (10.4%). Most of the patients with TD recovered spontaneously; however, seven patients (10.4%) needed thyroid treatment. The sustained virological response rate was higher in patients with TD than those without (65.7% vs. 49.1%, p = 0.02). Baseline thyroid stimulating hormone (TSH) concentrations (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.96 to 8.77; p < 0.001), presence of the thyroid peroxidase antibody (OR, 8.81; 95% CI, 1.74 to 44.6; p = 0.009), and PEG-IFNalpha-2b (OR, 3.01; 95% CI, 1.43 to 6.39; p = 0.004) were independent risk factors for the development of TD. CONCLUSIONS: TD developed in 27.7% of patients with CHC during PEG-IFN/RBV treatment, and 10.4% of these patients needed thyroid treatment. TD is associated with a favorable virologic response to PEG-IFN/RBV. Assessment of TSH and thyroid autoantibodies at baseline and close monitoring of thyroid function during PEG-IFN/RBV therapy are necessary for early detection and management of IFN-induced TD.

Ophthalmologic findings in hepatitis C patients treated with pegylated interferon α-2b and ribavirin / Achados oftalmológicos nos pacientes portadores de hepatite C em tratamento com interferon peguilado α-2b e ribavirina

Purpose: To identify the effect of pegylated interferon α-2b and ribavirin treatment in the ocular fundus examination, visual acuity, and visual field. Methods: Prospective observational study was performed at the Hepatology Clinic of São José Regional Hospital and at the Vitreoretinal Department at the Sadalla Amin Ghanem Eye Hospital in patients with chronic hepatitis C before and during treatment with pegylated interferon α-2b together with ribavirin. Results: Six (37.5%) of 16 patients developed retinopathy during the treatment, two of which (12.5%) presented retinal hemorrhage, and four patients (6 eyes) presented cotton-wool spots (25%) that regressed during the treatment. One patient (6.25%) presented transient decrease in visual acuity during the treatment and recovered spontaneously without specific therapy. Conclusion: Recommended treatment methods for hepatitis C may cause transient retinopathy, commonly without any damage to visual function in most patients. Although ocular involvement is rare, follow-up with an ophthalmologist is recommended during the course of the hepatitis C medication. .

Objetivo: Identificar possíveis mudanças no exame de fundo de olho após o início do tratamento, bem como alterações na acuidade visual e campo visual. Métodos: Estudo observacional prospectivo realizado na Clínica de Hepatologia do Hospital Regional de São José e no Departamento de Vítreo e Retina do Hospital de Olhos Sadalla Amin Ghanem, em pacientes com hepatite C crônica antes e durante o tratamento com interferon peguilado α-2b associado à ribavirina. Resultados: Six (37,5%) dos 16 participantes desenvolveram retinopatia durante o tratamento, dois dos quais (12,5%) apresentaram hemorragia retiniana unilateral, e quatro pacientes com exsudatos algodonosos (25%), seis olhos, que regrediu durante o tratamento. Um participante (6,25%) apresentou diminuição transitória da acuidade visual durante o tratamento com recuperação espontaneamente sem tratamento específico. Conclusão: O tratamento recomendado para a hepatite C pode estar associado com o desenvolvimento de retinopatia transitória, geralmente sem dano à função visual na maioria dos pacientes. Embora o envolvimento ocular seja raro, o acompanhamento com o médico oftalmologista é recomendado durante todo o uso da medicação. .

Anti-hepatitis C virus treatment may prevent the progression of liver fibrosis in non-responder human immunodeficiency virus/hepatitis C virus coinfected patients

AIM: To evaluate changes in liver histology in patients with human immunodeficiency virus/hepatitis C virus coinfection non-responders to a suboptimal Interferon+Ribavirine regimen. MATERIALS AND METHODS: We investigated 49 patients with two sequential liver biopsies: 18 were non-responders to Interferon+Ribavirine treatment (Group hepatitis C virus Rx) administered after the 1st liver biopsy who underwent a 2nd liver biopsy after a median period of 3.92 year and 31 were patients who remained untreated for hepatitis C virus disease (Group hepatitis C virus untreated) after the 1st liver biopsy because of refusal and underwent a 2nd liver biopsy after a median period of 5.05-years. Most patients in both groups were under highly active antiretroviral therapy. At the time of 1st liver biopsy similar degrees of necro-inflammation, fibrosis and steatosis were observed in both groups. Changes in liver lesions between 1st and 2nd liver biopsys were adjusted for different intervals between liver biopsys by a mathematic formula. RESULTS: Liver fibrosis did not change in 88.9% of patients in Group hepatitis C virus Rx and in 77.4% in Group hepatitis C virus untreated. A marked deterioration in liver fibrosis was observed in 5 (16%) patients in Group hepatitis C virus untreated and in none in Group hepatitis C virus treated. Necro-inflammation and steatosis remained substantially unchanged in both groups. CONCLUSION: Liver histology remained substantially unchanged in human immunodeficiency virus/hepatitis C virus patients non-responder to anti-hepatitis C virus therapy over 4 years observation, suggesting an effective anti-hepatitis C virus early treatment for all hepatitis C virus/human immunodeficiency virus coinfected patients who can reasonably tolerate therapy. .