Decompensated cirrhosis and liver transplantation negatively impact in DAA treatment response: Real-world experience from HCV-LALREAN cohort.

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

Disease burden of chronic hepatitis C in Brazil

Background: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective.Methods: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2).Results: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n= 325,900) and decompen- sated (n= 45,000) cirrhosis; hepatocellular carcinoma (n= 19,100); and liver-related deaths (n= 16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively.Conclusions: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Disease burden of chronic hepatitis C in Brazil.

BACKGROUND: Hepatitis C virus infection is a major cause of cirrhosis; hepatocellular carcinoma; and liver transplantation. The aim of this study was to estimate hepatitis C virus disease progression and the burden of disease from a nationwide perspective. METHODS: Using a model developed to forecast hepatitis C virus disease progression and the number of cases at each stage of liver disease; hepatitis C virus-infected population and associated disease progression in Brazil were quantified. The impact of two different strategies was compared: higher sustained virological response and treatment eligibility rates (1) or higher diagnosis and treatment rates associated with increased sustained virological response rates (2). RESULTS: The number of infected individuals is estimated to decline by 35% by 2030 (1,255,000 individuals); while the number of cases of compensated (n=325,900) and decompensated (n=45,000) cirrhosis; hepatocellular carcinoma (n=19,100); and liver-related deaths (n=16,700) is supposed to peak between 2028 and 2032. In strategy 2; treated cases increased over tenfold in 2020 (118,800 treated) as compared to 2013 (11,740 treated); with sustained virological response increased to 90% and treatment eligibility to 95%. Under this strategy; the number of infected individuals decreased by 90% between 2013 and 2030. Compared to the base case; liver-related deaths decreased by 70% by 2030; while hepatitis C virus-related liver cancer and decompensated cirrhosis decreased by 75 and 80%; respectively. CONCLUSIONS: While the incidence and prevalence of hepatitis C virus in Brazil are decreasing; cases of advanced liver disease continue to rise. Besides higher sustained virological response rates; new strategies focused on increasing the proportion of diagnosed patients and eligibility to treatment should be adopted in order to reduce the burden of hepatitis C virus infection in Brazil.

Effect of turbinate surgery in rhinoseptoplasty on quality-of-life and acoustic rhinometry outcomes: a randomized clinical trial.

OBJECTIVES/HYPOTHESIS: To evaluate the role of inferior turbinate reduction during rhinoseptoplasty in quality-of-life outcomes and nasal airway cross-sectional area. STUDY DESIGN: Randomized clinical trial. METHODS: Individuals over 16 years with nasal obstruction, candidates to functional and aesthetics primary rhinoseptoplasty, were evaluated from December 2010 though January 2012 at a tertiary University Hospital, Brazil. Eligible participants were randomly allocated to rhinoseptoplasty with or inferior turbinate reduction through submucosal diathermy. OUTCOMES: Relative changes ([postop-preop]/preop score) in specific (Nasal Obstruction Symptom Evaluation; NOSE) and general quality-of-life instruments (WHOQOL-bref), nasal obstruction visual analogue scale (NO-VAS) and nasal area measurements in acoustic rhinometry. OUTCOMES were blindly assessed 3 months postoperatively. Protocol was registered at ClinicalTrials.gov (NCT01457638). RESULTS: 50 patients were included, mainly Caucasians with moderate/severe allergic rhinitis symptoms. Mean age was 32 ± 12 yr and 58% were female. Rhinoseptoplasty improved specific and general quality-of-life scores irrespective of turbinate intervention (P < 0.001).There was no difference between subjects submitted or not to inferior turbinate reduction in NOSE score (-75% vs. -73%; P = 0.893); all WHOQOL-bref score domains (P > 0.05), NO-VAS (-88% vs. -81%; P = 0.89) and acoustic rhinometry recordings (P > 0.05).During follow-up less patients in the rhinoplasty with inferior turbinate reduction group were using topical corticosteroids (6[24%] vs. 13[54%]; P = 0.03). Multivariable analyses, adjusting for postoperative topical corticosteroid use and previous nasal fracture, had no effect on these results. CONCLUSIONS: Turbinate reduction through submucosal diathermy during primary rhinoseptoplasty did not improve short-term general and specific quality-of-life outcomes and acoustic rhinometry recordings. The role of turbinate reduction in sparing chronic corticosteroid use should be confirmed in long-term follow-up studies.

Risk factors for infection with different hepatitis C virus genotypes in southern Brazil.

OBJECTIVES: To investigate the proportion of different genotypes in countryside microregions in southern Brazil, and their association with risk factors. METHODS: Cross-sectional study including a convenience sample of patients who tested positive for HCV-RNA and were referred to a regional health center for genotyping, from December 2003 to January 2008. Data were obtained through the National Disease Surveillance Data System, from laboratory registers and from patient charts. Identification of genotypes was carried out using the Restriction Fragment Length Polymorphism "in house" technique. Independent associations with genotypes were evaluated in multinomial logistic regression and prevalence rates of genotypes were estimated with modified Poisson regression. RESULTS: The sample consisted of 441 individuals, 41.1 ± 12.0 years old, 56.5% men. Genotype 1 was observed in 41.5% (95% CI 37.9-48.1) of patients, genotype 2 in 19.3% (95% CI 15.0-23.6), and genotype 3 in 39.2% (95% CI 35.6-43.0). HCV genotype was significantly associated with gender and age. Dental procedures were associated with higher proportion of genotype 2 independently of age, education, and patient treatment center. CONCLUSIONS: The hepatitis C virus genotype 1 was the most frequent. Genotype 2 was associated with female gender, age, and dental procedure exposition.

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.

Absence of occult hepatitis B among blood donors in southern Brazil.

BACKGROUND: Occult hepatitis B virus (HBV) infection is characterized by the detection of HBV DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). The reported prevalence of occult hepatitis B varies markedly among populations and according to the sensitivity of the HBV DNA assay. The aim of the present study was to describe the prevalence of occult hepatitis B among HCV-infected and non-infected blood donors in Porto Alegre, Southern Brazil, using a highly sensitive real time polymerase chain reaction (PCR) method. METHODOLOGY: Between 1995 and 1997 a sample of 178 blood donors with two positive anti-HCV ELISA tests were consecutively selected as cases, and 356 anti-HCV negative donors were selected as controls. Blood donors were randomly selected from eight blood centers in Porto Alegre, Southern Brazil, representative of the whole blood donor population. Blood samples were kept at 70ºC and defrosted for the first time for the analysis of this report. Tests previously performed in the laboratory using the same real time PCR for HBV DNA had sensitivity for detecting as low as 9 copies/mL. Among 158 blood samples from HBsAg-negative blood donors, five were anti-HBc positive, 53 tested positive for anti-HCV and 105 had anti-HCV negative. The samples analysis was performed in duplicate and all blood samples tested negative for HBV DNA. CONCLUSION: The result reflects a very low prevalence of occult hepatitis B in our setting.

Absence of occult hepatitis B among blood donors in southern Brazil

BACKGROUND: Occult hepatitis B virus (HBV) infection is characterized by the detection of HBV DNA in serum and/or in liver in the absence of detectable hepatitis B surface antigen (HBsAg). The reported prevalence of occult hepatitis B varies markedly among populations and according to the sensitivity of the HBV DNA assay. The aim of the present study was to describe the prevalence of occult hepatitis B among HCV-infected and non-infected blood donors in Porto Alegre, Southern Brazil, using a highly sensitive real time polymerase chain reaction (PCR) method. METHODOLOGY: Between 1995 and 1997 a sample of 178 blood donors with two positive anti-HCV ELISA tests were consecutively selected as cases, and 356 anti-HCV negative donors were selected as controls. Blood donors were randomly selected from eight blood centers in Porto Alegre, Southern Brazil, representative of the whole blood donor population. Blood samples were kept at 70ºC and defrosted for the first time for the analysis of this report. Tests previously performed in the laboratory using the same real time PCR for HBV DNA had sensitivity for detecting as low as 9 copies/mL. Among 158 blood samples from HBsAg-negative blood donors, five were anti-HBc positive, 53 tested positive for anti-HCV and 105 had anti-HCV negative. The samples analysis was performed in duplicate and all blood samples tested negative for HBV DNA. CONCLUSION: The result reflects a very low prevalence of occult hepatitis B in our setting.

Controlled study of the frequency of anti-HSP 70 with the ELISA and the Western Blot methods in patients with Ménière Disease.

OBJECTIVES: To establish the frequency of auto-antibodies anti-HSP 70 using ELISA and Western Blot (WB) methods and to compare the results of each method among patients with the Ménière's Disease (MD) and internal ear diseases (IED) who do not fulfill criteria for MD. Sensibility, specificity and predictive values of anti-HSP70 test in diagnosis of MD were calculated. STUDY: Prospective, case-control. METHODS: Blood samples were collected from 31 patients with MD and 78 patients with non Ménière IED. Data regarding cochlear and vestibular symptoms were obtained and blood sample was tested. RESULTS: ELISA tests results were positive in 4(13%) patients and results of WB were positive in 8(26%) patients. Among patients with positive ELISA results, 1 patient presented active disease and in the remaining 3 patients the disease was inactive. Among the 8 WB positive patients, only 2 patients presented active disease. Statistical analyses did not establish any association between serologic findings and clinical factors of MD. CONCLUSION: The presence of anti-HSP70 using the ELISA and the WB methods did not demonstrate clinical value for the diagnosis of MD. We did not find association between idiopathic MD nor unspecific etiology MD and the presence of anti-HSP70 auto-antibodies.

Estudo de 100 pacientes com clínica sugestiva de hipoglicemia e manifestaçöes de vertigem, surdez e zumbido / Study of 100 patients with suggestive clinics of hypoglycemia and manifestations of vertigo, deafness and tinnitus

O estudo avaliou a sensibilidade da história clínica para detectar alterações metabólicas em pacientes com hipoacusia e/ou zumbido e/ou vertigem associados à clínica sugestiva de hipoglicemia. Para tanto, 100 pacientes com este quadro foram submetidos a teste de tolerância à glicose de 5h com dosagem simultânea de insulina (hipoglicemia = glicose < ou = 55 mg/dL em qualquer momento da curva glicêmica). Curvas glicêmicas alteradas foram observadas em 59 pacientes (44 hipoglicêmicas). A hipoglicemia foi detectada apenas após a terceira hora do exame em 38 pacientes. As curvas insulinêmicas foram compatíveis com hiperinsulinismo em 73 pacientes. Apenas quatro pacientes apresentaram ambas as curvas dentro da normalidade. O valor preditivo positivo para detecção de anormalidades no metabolismo glicídico pela história clínica foi de 96 por cento. Este fato sugere a implantação de um teste terapêutico, com dieta específica, como parte da avaliação de pacientes com clínica sugestiva de hipoglicemia e manifestações de vertigem, surdez e zumbido.

Prevalência de adenocarcinoma do esôfago e da junçäo esofagogástrica durante 10 anos nun centro de referência para câncer no Sul do Brasil / Prevalence of adenocarcinoma of the esophagus and esophagogastric junction during a 10 year period in a cancer referral center in Southern Brazil

A incidência do adenocarcinoma do esôfago e junção esofagogástrica tem aumentado dramaticamente nos EUA e na Europa, mas dados epidemiológicos no Brasil são escassos. Objetivo e métodos - Foram revisados os casos de câncer envolvendo o esôfago e confirmados, histologicamente, num período de 10 anos (1987-1996) obtidos por biopsia durante endoscopia digestiva alta, para determinar a prevalência desse tumor em um centro médico de referência para câncer, no Sul do Brasil. Os casos de câncer foram classificados em três categorias: adenocarcinoma, carcinoma epidermóide e outros. Resultados - Entre 349 casos de câncer; encontrou-se adenocarcinoma em 53 (15,2 por cento), carcinoma epidermóide em 283 (81,1 por cento) e outras neoplasias em 13 (3,7 por cento). Conclusões - A prevalência encontrada de adenocarcinoma na população estudada foi de 15 por cento.