Impact of sustained virologic response on glucose parameters among patients with chronic hepatitis C treated with direct-acting antivirals

ABSTRACT Objective: The aim of this study was to evaluate the glycated hemoglobin (HbA1c) levels before and after sustained virologic response (SVR) and investigate the baseline characteristics associated with improved glycemic control in patients with chronic hepatitis C (CHC) achieving SVR after direct-acting antivirals (DAA) therapy. Materials and methods: Consecutive adult patients with CHC who achieved SVR after DAA treatment between January 2016 and December 2017 at Hospital de Clínicas de Porto Alegre (RS, Brazil) were prospectively included. Levels of HbA1c were measured up to 24 weeks before DAA therapy and 12 weeks after SVR. Exclusion criteria were decompensated cirrhosis, HIV and/or hepatitis B virus, liver disease of other etiologies, and/or modification of prediabetes/type 2 diabetes mellitus (PDM/T2DM) management. The primary outcome was a comparison of HbA1c levels before and after SVR. Secondary outcomes were the baseline variables associated with improved glycemic control. Results: The study included 207 patients with a mean age of 60.6±10.7 years, of whom 51.7% were women, 56% had cirrhosis, 37.7% had HCV genotype 3, and 54.5% had baseline T2DM or PDM. The median HbA1c level reduced significantly after SVR (5.5%, interquartile range [IQR] 4.9%-6.3%) compared with baseline (5.7%, IQR 5.3­%-6.7%; p = 0.01). The baseline characteristics associated with improved HbA1c after SVR were cirrhosis, genotype 3, and age ≤ 60 years. Conclusion: Among patients with CHC, SVR after DAA was associated with HbA1c reduction, particularly in those with cirrhosis, genotype 3, and age ≤ 60 years.

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.

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.

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.

Low-dose adrenocorticotropin test in patients with the Acquired Immunodeficiency Syndrome

Adrenocortical insufficiency is a serious complication of AIDS. Usually, integrity of the hypothalamo-pituitary-adrenal (HPA) axis in AIDS patients is assessed by measuring basal cortisol levels and cortisol response to 250 µg of ACTH. Recent studies suggest that a lower ACTH dose increases the sensitivity of the procedure. In the present study, we investigated the prevalence of adrenal hypofunction in AIDS patients using a low-dose ACTH test (1 µg), evaluated the clinical characteristics that might suggeest this diagnosis, and the diseases and/or drugs that could be associated with it. We prospectively evaluated 63 very ill AIDS patients and 16 normal controls. A standard examination assessed the presence of signs and symptoms of adrenal insufficiency. Blood samples were colleted before and 30 and 40 minutes after an injection of 1 µg 1-24 ACTH. No opportunistic disease, signs, symptoms or drugs were associated with an abnormal cortisol response to ACTH. The lowest stimulated cortisol level in the contol group was 18.5 µg/dL; cortisol level (greather or equal) 18 µg/dL were taken to indicate a normal HPA axis. Test results revealed that 12/63 AIDS patients (19 percent) had an abnormal HPA axis. With these data in mind, we suggest a prospective adrenal function evaluation of all severely ill AIDS patients.

Clinical and endoscopic aspects in the evolution of patients with bleeding peptic ulcer: a cohort study

BACKGROUND: Bleeding ulcers are a major problem in public health and represent approximately half of all the cases of upper gastrointestinal hemorrhage in the United States. This study aims to determine the prognostic value of factors such as clinical history, laboratory and endoscopic findings in the occurrence of new episodes of bleeding in patients who have upper gastrointestinal hemorrhage caused by gastric or duodenal peptic ulcer. METHODS: A cohort study with 94 patients was designed to investigate prognostic factors to the occurrence of new episodes of bleeding. RESULTS: From the 94 patients studied, 88 did not present a new bleeding episode in the 7 days following hospital admission. The incidence of rebleeding was significantly higher in those patients with hemoglobin < 6 g/dL at the admission (P = 0.03, RR = 6.2). The localization of the ulcers in bulb was positively associated to rebleeding (P = 0.003). The rebleeding group needed a greater number of units transfunded (P = 0.03) and the time of hospitalization was longer than the time of the hemostasia group (P = 0.0349). CONCLUSIONS: The identification of patients with risk of death by bleeding peptic ulcer remains as a challenge, once few factors are capable of predicting the severity of the evolution. The identification of such factors will alow the choice of the better therapeutic conduct improving the diagnosis and decreasing the rate of rebleeding and the mortality

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.

Infarto agudo do miocárdio: análise de 84 casos / Acute myocardial infarction: 84 cases analysis

Os autores realizaram o levantamento de 84 casos de infarto agudo do miocárdio (IAM) em pacientes internados na Unidade de Terapia Intensiva (UTI) e na Clínica Médica do Hospital Universitário São Francicso (HUSF), de janeiro de 1994 a fevereiro de 1996, baseado nos prontuários com diagnósticos comprovados pela história clínica e alterações eletrocardiiográficas. É proposto um protocolo de atendimento e evolução dos pacientes com infarto do miocárdio para se iniciar um estudo prospectivo de maiior valor clínico e epidemiológico.