Implementation of a re-linkage to care strategy in patients with chronic hepatitis C who were lost to follow-up in Latin America.

To achieve WHO's goal of eliminating hepatitis C virus (HCV), innovative strategies must be designed to diagnose and treat more patients. Therefore, we aimed to describe an implementation strategy to identify patients with HCV who were lost to follow-up (LTFU) and offer them re-linkage to HCV care. We conducted an implementation study utilizing a strategy to contact patients with HCV who were not under regular follow-up in 13 countries from Latin America. Patients with HCV were identified by the international classification of diseases (ICD-9/10) or equivalent. Medical records were then reviewed to confirm the diagnosis of chronic HCV infection defined by anti-HCV+ and detectable HCV-RNA. Identified patients who were not under follow-up by a liver specialist were contacted by telephone or email, and offered a medical reevaluation. A total of 10,364 patients were classified to have HCV. After reviewing their medical charts, 1349 (13%) had undetectable HCV-RNA or were wrongly coded. Overall, 9015 (86.9%) individuals were identified with chronic HCV infection. A total of 5096 (56.5%) patients were under routine HCV care and 3919 (43.5%) had been LTFU. We were able to contact 1617 (41.3%) of the 3919 patients who were LTFU at the primary medical institution, of which 427 (26.4%) were cured at a different institutions or were dead. Of the remaining patients, 906 (76.1%) were candidates for retrieval. In our cohort, about one out of four patients with chronic HCV who were LTFU were candidates to receive treatment. This strategy has the potential to be effective, accessible and significantly impacts on the HCV care cascade.

B.A.R.C.O.S. (Brazilian Argentine Hepatitis C Collaborative Observational Study): Effectiveness and clinical outcomes of HCV treatment with daclatasvir and sofosbuvir with or without ribavirin.

Real-world data evaluating the effectiveness of direct-acting antivirals (DAAs) in hepatitis C virus (HCV) treatment have been reported from different regions. Our aim was to evaluate the effectiveness and clinical outcomes of daclatasvir (DCV) and sofosbuvir (SOF) ± ribavirin (RBV) in a prospective multicentre cohort study including patients from Argentina and Brazil who received DCV/SOF ± RBV for 12 or 24 weeks from 2015 to 2018. Multivariable logistic regression models were carried out to identify factors associated with failure to achieve sustained virologic response (SVR) as a primary end point, and to death, decompensation, hepatocellular carcinoma (HCC) or liver transplantation (LT) as a composite secondary end point. From a total of 1517 patients treated with DCV/SOF, 906 completed 12 weeks post-treatment evaluation and were included in the analysis. Overall SVR12 rate was 96.1% (95% CI: 94.6%-97.2%), and 95% (95% CI: 92.8%-96.6%) in patients with cirrhosis. LT recipients and presence of cirrhosis were independently associated with failure to achieve SVR. During post-SVR12 follow-up, cumulative incidence of the secondary end point was 2.4% (95% CI: 1.5%-3.6%); two patients died from nonliver-related causes and two from HCC, five underwent LT, 12 developed HCC and 17 patients developed hepatic decompensation. Independent variables associated with these composite secondary end points were prior to HCV treatment and presence of cirrhosis. In conclusion, although the high pangenotypic effectiveness of DCV/SOF ± RBV was confirmed in our real-life cohort, patients with compensated and decompensated cirrhosis showed higher risk of non-SVR and complication appearance during treatment or after achieving SVR.

Treatment of Chronic HCV Infection with the New Direct Acting Antivirals (DAA): First Report of a Real World Experience in Southern Brazil.

INTRODUCTION AND AIM: There is almost no data regarding the efficacy of direct acting antivirals (DAAs) therapy in Brazil. The aim of this historical cohort study is to describe the sustained virologic response (SVR) rate among real-world compensated chronic hepatitis C patients in three hepatology centers from Southern Brazil. MATERIALS AND METHODS: Patients were included if they had at least 12 weeks follow-up after the end of therapy. Patients that were lost to follow-up or had treatment prematurely interrupted for any reason were considered treatment failure in this intention to treat analysis. RESULTS: 219 patients were analyzed. Mean age was 57.4 ± 10.9 years and 142/219 (64.8%) were male. Genotype 1 was present in 166 patients (75.8%; 1a 29.2%, 1b 46.6%); Genotypes 2, 3 and 4 in 8 (3.7%), 43 (19.6%) and 2 (0.9%), respectively. 96 (43.8%) were cirrhotic. 134 (59.5%) were treatment experienced. DAA therapies were: sofosbuvir (SOF) + ribavirin (RBV) in 10 patients; SOF + simeprevir (SMV) ± RBV in 73; SOF + pegylated interferon (PEG-IFN) + RBV in 6; SOF + daclatasvir (DCV) ± RBV in 51, SOF + ledipasvir (LDV) ± RBV in 61, and paritaprevir/ ritonavir + ombitasvir + dasabuvir (PTVr/OBV/DSV) ± RBV in 18 patients. SVR-12 was achieved in 208/219 (95%). Ten patients had virologic failure: 6 cirrhotic, 7 treatment experienced, and 6 either genotype 3 or 1a. No adverse event was attributed to the DAA therapy. CONCLUSIONS: Real world experience with DAA therapy in Southern Brazil showed a high rate of SVR and excellent tolerability. Failure to achieve SVR was mainly observed among patients with at least one negative predictor of response: cirrhosis and/or genotypes 1a or 3.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin.

CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

Effect of HFE gene polymorphism on sustained virological response in patients with chronic hepatitis C and elevated serum ferritin / Efeito do polimorfismo do gene HFE sobre a resposta viral sustentada em portadores de hepatite crônica C com ferritina sérica elevada

CONTEXT: Abnormal serum ferritin levels are found in approximately 20%-30% of the patients with chronic hepatitis C and are associated with a lower response rate to interferon therapy. OBJECTIVE: To determine if the presence of HFE gene mutations had any effect on the sustained virological response rate to interferon based therapy in chronic hepatitis C patients with elevated serum ferritin. METHODS: A total of 44 treatment naÏve patients with histologically demonstrated chronic hepatitis C, all infected with hepatitis C virus genotype non-1 (38 genotype 3; 6 genotype 2) and serum ferritin above 500 ng/mL were treated with interferon (3 MU, 3 times a week) and ribavirin (1.000 mg, daily) for 24 weeks. RESULTS: Sustained virological response was defined as negative qualitative HCV-RNA more than 24 weeks after the end of treatment. Serum HCV-RNA was measured by qualitative in house polymerase chain reaction with a limit of detection of 200 IU/mL. HFE gene mutation was detected using restriction-enzyme digestion with RsaI (C282Y mutation analysis) and BclI (H63D mutation analysis) in 16 (37%) patients, all heterozygous (11 H63D, 2 C282Y and 3 both). Sustained virological response was achieved in 0 of 16 patients with HFE gene mutations and 11 (41%) of 27 patients without HFE gene mutations (P = 0.002; exact Fisher test). CONCLUSION: Heterozigozity for H63D and/or C282Y HFE gene mutation predicts absence of sustained virological response to combination treatment with interferon and ribavirin in patients with chronic hepatitis C, non-1 genotype and serum ferritin levels above 500 ng/mL.

CONTEXTO: Níveis séricos anormais de ferritina são encontrados em aproximadamente 20%-30% dos pacientes com hepatite crônica C e estão associadas a uma baixa taxa de resposta à terapia com interferon. OBJETIVO: Avaliar a associação entre a presença de mutações do gene HFE e a taxa de resposta virológica sustentada ao interferon em pacientes portadores de hepatite crônica C com ferritina sérica elevada. MÉTODOS: Um total de 44 pacientes, virgem de tratamento, infectado pelo vírus da hepatite C de genótipos não-1 (38 genótipo 3; 6 genótipo 2) e ferritina sérica acima de 500 ng/mL foi tratado com interferon (3 MU, três vezes por semana) e ribavirina (1000 mg/dia) por 24 semanas. Resposta virológica sustentada foi definida como HCV-RNA indetectável 24 semanas após o fim do tratamento. Foi utilizado técnica de reação em cadeia da polimerase em tempo-real com limite de detecção de 200 UI /mL. RESULTADOS: Mutações do gene HFE foram detectadas por "restriction-enzyme digestion" com RsaI (análise de mutação C282Y) e BclI (análise de mutação H63D) em 16 pacientes (37%), todos heterozigotos (11 H63D, 2 C282Y e 3 ambos). Resposta virológica sustentada foi alcançada em 0 de 16 pacientes com mutações do gene HFE e 11 (41%) dos 27 pacientes sem mutações do gene HFE (P = 0,002; teste exato de Fisher). CONCLUSÃO: A heterozigose para os genes H63D e/ou C282Y HFE está associada à redução significativa da taxa de resposta virológica sustentada ao tratamento com interferon e ribavirina em pacientes com hepatite crônica C, genótipo não-1 e com níveis séricos de ferritina acima de 500 ng/mL.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55 percent) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3 percent) vs. 8 (17 percent) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Effect of sustained virologic response on the incidence of hepatocellular carcinoma in patients with HCV cirrhosis.

BACKGROUND AND OBJECTIVES: Evidence suggests that sustained virologic response to interferon treatment decreases incidence of hepatocellular carcinoma in patients with hepatitis C virus cirrhosis. This study was designed to compare the incidence of hepatocellular carcinoma among cirrhotic patients exposed to interferon based treatment with or without achieving a sustained virological response, in order to evaluate the role of interferon itself in the prevention hepatocellular carcinoma. METHODS: A cohort of 85 patients with compensated hepatitis C cirrhosis was followed after treatment with interferon and ribavirin. Sustained virological response was defined as negative polymerase chain reaction assay 24 weeks after the end of treatment. Patients were followed every 6 months with ultrasound and alpha-fetoprotein. Hepatocellular carcinoma was diagnosed by the finding of a focal liver lesion greater than 2 cm with arterial hypervascularization on two imaging techniques and/or by liver biopsy. RESULTS: The mean follow-up time was 32.1 ± 20 months for patients who achieved a sustained virological response and 28.2 ± 18 months among 47 patients (55%) without SVR. Hepatocellular carcinoma was diagnosed in 1 (3%) vs. 8 (17%) responders and non responders respectively (p = 0.02). CONCLUSION: Patients with cirrhosis due to hepatitis C virus who achieved sustained virological response had significantly lower incidence of hepatocellular carcinoma when compared to those without treatment response. Interferon treatment without achieving sustained virological response does not seem to protect against hepatocellular carcinoma.

Resposta sustentada após 1 ano de interferon isolado ou associado a ribavirina em pacientes com cirrose pelo vírus C / Sustained response after one-year treatment with interferon, exclusively or in association with ribavirin in positive hepatitis c virus cirrhotic patients

O trabalho teve por objetivo avaliar a taxa de resposta completa ao final do tratamento e de resposta sustentada em pacientes com cirrose pelo vírus da hepatite C tratados com interferon isolado ou combinado com ribavirina. Um total de 33 pacientes cirróticos ambulatoriais, VHC positivos, sem outras causas identificáveis de doença hepática, compensados e classificados como Child-Pugh A, foram divididos em dois grupos, de forma não randomizada...

Prevalência de diabetes mellitus em pacientes com hepatite C / Prevalence of diabetes mellitus in patients with chronic hepatitis C

O vírus da hepatite C pode cursar com manifestações extra-hepáticas relacionadas a distúrbio imunológico. Este trabalho objetivou verificar a prevalência de Diabetes mellitus em pacientes com hepatite crônica C. Entre novembro de 1992 e dezembro de 1997 foram avaliados prospectivamente 140 pacientes ambulatoriais e consecutivos, com anti-VHC (ELISA-2) e PCR positivos...

Mecanismos de açäo dos interferons: uma revisäo / Pharmacodynamics of interferons: a review

Os autores realizam uma revisäo sobre os principais aspectos farmacodinâmicos e farmacocinéticos dos interferons humanos. Atualmente classificados no grupo das citocinas, estes agentes säo secretados por diversas células do organismo em resposta à infecçäo viral e a diversos outros estímulos, sendo divididos em alfa, beta e gama...

Colangite esclerosante primária associada à anemia hemolítica auto-imune / Primary sclerosing cholangitis associated to autoimmune hemolytic anemia

Colangite esclerosante primária (CEP) é doença de etiologia desconhecida caracterizada por inflamaçao e fibrose envolvendo a árvore biliar intra e/ou extra-hepática, levando à dilataçao e estenose dos ductos biliares. Estudos recentes têm demonstrado importante papel dos falores imunológicos e genético na patogênese desta condiçao. A anemia hemolítica auto-imune (AHA) caraacteriza-se por anticorpos antieritrocitários que parecem surgir como resultado de distúrbio funcional específico do linfócito T supressor. A oportunidade que tivemos de diagnosticar e tratar dois pacientes com CEP associada à AHA motiva o presente estudo. De nosso conhecimento, existem apenas dois relatos prévios desta associaçao publicados na literatura.