RESUMO
UNLABELLED: Background and aim. Resistance-associated variants (RAVs) on the NS3 region of the hepatitis C virus (HCV) may be relevant for antiviral therapy, but data in human immunodeficiency virus (HIV) coinfected patients are scarce. We assessed frequencies of NS3 RAVs in patients infected with HCV genotype 1a with or without HIV coinfection. MATERIAL AND METHODS: HCV NS3 amino acids 1-181 were sequenced by the Sanger method and analyzed for RAVs. RAVs and their distribution between HCV genotype 1a clade I and II viruses were compared between HIV-infected versus HIV-uninfected patients. RESULTS: 148 samples were available (n = 68 HIV and n = 80 non-HIV). Relative frequency of clade I and clade II was significantly different between HIV (85% and 15%) and non-HIV groups (49% and 51%). Overall, HIV infected patients exhibited significantly lower prevalence of RAVs than HIV-uninfected patients (62% vs. 79%, p = 0.03). However, Q80K prevalence was significantly higher in HIV-infected subjects (50% vs. 24%, p = 0.001), whereas prevalence of S122D/G/N/S (2% vs. 16%, p = 0.002) and N174G/N/S (10% vs. 55%, p < 0.0001) polymorphisms were significantly lower. Q80K was found exclusively in clade I viruses. S122 (3% vs. 22%, p=0.001) and N174 (13% vs. 75%, p<0.0001) polymorphisms had significantly lower prevalence in clade I than clade II viruses. CONCLUSIONS: In the Netherlands, prevalence of clade I viruses and Q80K was significantly higher in HCV genotype 1a infected patients with HIV coinfection than in those without HIV coinfection. Prevalence of N174 and S122 polymorphisms was significantly higher in clade II than clade I viruses.
Assuntos
Coinfecção , Farmacorresistência Viral/genética , Infecções por HIV/epidemiologia , Hepacivirus/genética , Hepatite C Crônica/virologia , Polimorfismo Genético , Proteínas não Estruturais Virais/genética , Adulto , Idoso , Antivirais/uso terapêutico , Feminino , Frequência do Gene , Genótipo , Infecções por HIV/diagnóstico , Hepacivirus/efeitos dos fármacos , Hepacivirus/enzimologia , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Fenótipo , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND AND AIMS: Epidemiological data on autoimmune hepatitis (AIH) are scarce. In this study, we determined the clinical and epidemiological characteristics of AIH patients in the Netherlands (16.7 million inhabitants). METHODS: Clinical characteristics were collected from 1313 AIH patients (78% females) from 31 centers, including all eight academic centers in the Netherlands. Additional data on ethnicity, family history and symptoms were obtained by the use of a questionnaire. RESULTS: The prevalence of AIH was 18.3 (95% confidential interval [CI]: 17.3-19.4) per 100,000 with an annual incidence of 1.1 (95% CI: 0.5-2) in adults. An incidence peak was found in middle-aged women. At diagnosis, 56% of patients had fibrosis and 12% cirrhosis in liver biopsy. Overall, 1% of patients developed HCC and 3% of patients underwent liver transplantation. Overlap with primary biliary cirrhosis and primary sclerosing cholangitis was found in 9% and 6%, respectively. The clinical course did not differ between Caucasian and non-Caucasian patients. Other autoimmune diseases were found in 26% of patients. Half of the patients reported persistent AIH-related symptoms despite treatment with a median treatment period of 8 years (range 1-44 years). Familial occurrence was reported in three cases. CONCLUSION: This is the largest epidemiological study of AIH in a geographically defined region and demonstrates that the prevalence of AIH in the Netherlands is uncommon. Although familial occurrence of AIH is extremely rare, our twin data may point towards a genetic predisposition. The high percentage of patients with cirrhosis or fibrosis at diagnosis urges the need of more awareness for AIH.
Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatite Autoimune/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Anti-Inflamatórios/uso terapêutico , Anticorpos Antinucleares/sangue , Povo Asiático/estatística & dados numéricos , População Negra/estatística & dados numéricos , Criança , Pré-Escolar , Fadiga/etiologia , Feminino , Hepatite Autoimune/diagnóstico , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/genética , Humanos , Imunoglobulina G/sangue , Imunossupressores/uso terapêutico , Incidência , Icterícia/etiologia , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores Sexuais , América do Sul/etnologia , Inquéritos e Questionários , População Branca/estatística & dados numéricos , Adulto JovemRESUMO
INTRODUCTION: Poor adherence to treatment for various chronic diseases is a frequent phenomenon. Current guidelines for the treatment of chronic hepatitis B (HBV) and hepatitis C (HCV) recommend optimal adherence, since it has been suggested that poor adherence is associated with an increased risk of virological failure. We aimed to give an overview of studies exploring adherence to combination treatment (PEG-interferon plus ribavirin) for HCV and nucleos(t)ide analogues for HBV. Material and methods. A systematic review was conducted using the databases PubMed, Embase, Cochrane Library and Web of Knowledge. Search terms included "adherence" or "compliance" combined with "hepatitis B", "hepatitis C" or "viral hepatitis". RESULTS: The final selection included 19 studies (13 HCV, 6 HBV). Large differences in patient numbers and adherence assessment methods were found between the various studies. For HCV mean adherence varied from 27 to 97%, whereas the proportion of patients with ≥ 80% adherence varied from 27 to 96%. Mean adherence reported in HBV studies ranged from 81 to 99%, with 66 to 92% of patients being 100% adherent. For both HCV and HBV studies, the highest adherence rates were reported in studies using self-report whereas lower adherence rates were reported in studies using pharmacy claims. Poor adherence to treatment was associated with an increased risk of virological failure. CONCLUSION: Non-adherence to treatment in chronic viral hepatitis is not a frequent phenomenon. However, given the increased risk of virological failure in poorly adherent patients, clinicians should routinely address adherence issues in all patients treated for chronic viral hepatitis.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Adesão à Medicação , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Hepatite B Crônica/diagnóstico , Hepatite C Crônica/diagnóstico , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is important for early detection and therefore improvement of prognosis. Recently, two REVEAL-HBV studies from Taiwan have shown a positive correlation between viral load at any point in time and the development of cirrhosis and hepatocellular carcinoma. Due to differences in viral and host factors between Asians and other populations, it is unclear whether these results can be extrapolated to different populations. This manuscript will discuss viral predictors of hepatitis B related liver disease in relation to ethnic origin.
Assuntos
Carcinoma Hepatocelular/etnologia , Hepatite B/etnologia , Cirrose Hepática/etnologia , Neoplasias Hepáticas/etnologia , Carga Viral , Povo Asiático/etnologia , Carcinoma Hepatocelular/etiologia , Hepatite B/complicações , Antígenos E da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/etnologia , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Prognóstico , Fatores de Risco , TaiwanRESUMO
Patients with malignant tumors originating from the biliary tree have a poor prognosis, since only a minority of tumors can be resected and most palliative regimens have shown only limited success. We present two patients with unresectable tumors, who were treated with trans-arterial (90)yttrium radioembolization: a patient with an infiltrating gallbladder carcinoma and a patient with an extensive intrahepatic cholangiocarcinoma. In both cases the treatment was technically feasible, effective in controlling tumor growth, and without significant side effects. In conclusion, the presented cases demonstrate the potential of (90)yttrium radioembolization as a palliative treatment option for malignant tumors of the biliary tree.
Assuntos
Neoplasias dos Ductos Biliares/terapia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/terapia , Embolização Terapêutica/métodos , Neoplasias da Vesícula Biliar/terapia , Radioisótopos de Ítrio/administração & dosagem , Idoso , Neoplasias dos Ductos Biliares/diagnóstico , Colangiocarcinoma/diagnóstico , Progressão da Doença , Evolução Fatal , Neoplasias da Vesícula Biliar/diagnóstico , Humanos , Injeções Intra-Arteriais , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos , Resultado do TratamentoRESUMO
BACKGROUND AND RATIONALE: Anemia is a major side effect of combination therapy for chronic hepatitis C. In this study, severity, potential risk factors for and potential underlying mechanisms of anemia were evaluated. PATIENTS AND METHODS: 44 chronic hepatitis C patients on interferon-ribavirin treatment were included. Anemia-related parameters were measured before and during treatment. Potential changes in membrane phospholipids composition of erythrocytes of patients on anti-viral treatment and potentially increased erythrocyte susceptibility to osmotic or bile salt induced stress were explored. RESULTS: Anemia was almost universal during treatment, with evidence of hemolysis. Decrease of Hb after six months of therapy was 2.1 +/- 0.1 mmol/L (range -0.6-4.1). Higher pre-treatment Hb, highest ribavirin dose (15-17.5 mg/kg) and lower pre-treatment platelet level were independent risk factors for decrease of Hb. Serum erythropoietin levels increased during treatment with negative correlation to Hb levels at week 12 (r = -0.70, p = 0.002) and 24 (r = -0.72, p = 0.002). Erythrocyte membrane phospholipid composition did not differ between anemic patients and healthy controls. Also, resistance to osmotic or bile salt induced stress was normal in anemic patients. Phosphatidylserine exposure at the outer membrane leaflet did not change upon 24 hrs ex vivo incubation with pharmacological ribavirin concentration. CONCLUSIONS: Anemia is almost universal during anti-HCV treatment. The extent of anemia correlates with pre-treatment levels of thrombocytes and Hb and with high ribavirin dosing. Although we found hemolysis as contributing factor, our data do not indicate that altered membrane phospholipids composition is an important factor in pathogenesis of anemia.
Assuntos
Anemia/sangue , Anemia/induzido quimicamente , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Adulto , Idoso , Amantadina/efeitos adversos , Amantadina/uso terapêutico , Ácidos e Sais Biliares/metabolismo , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Membrana Eritrocítica/metabolismo , Eritropoetina/metabolismo , Feminino , Seguimentos , Hemoglobinas/metabolismo , Hepatite C/sangue , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fosfolipídeos/metabolismo , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes , Ribavirina/efeitos adversos , Ribavirina/uso terapêuticoRESUMO
Since impaired gallbladder emptying contributes to gallstone formation, the evaluation of gallbladder motility requires accurate methodology. Recently developed 3-dimensional ultrasonography may take into account various gallbladder shapes more accurately than conventional 2-dimensional ultrasonography. Therefore, volumes of water-filled balloons of various sizes were determined in vitro by 2-dimensional ultrasonography with the sum of cylinders method and by 3-dimensional ultrasonography. Also, in 15 gallstone patients and 6 healthy volunteers, fasting gallbladder volumes and postprandial motility were determined by both methods. Volumes of water-filled balloons as measured by both methods correlated strongly with true volumes (R= 0.93 for 2-dimensional and R = 0.98 for 3- dimensional ultrasonography). Gallbladder volumes measured by both methods were also correlated (R = 0.66, P <0.001). In gallstone patients, 3-dimensional ultrasonography yielded smaller gallbladder volumes than 2-dimensional ultrasonography (P = 0.007), but not in healthy subjects. With both methods, gallstone patients exhibited decreased postprandial gallbladder motility compared to healthy subjects. In conclusion, gallbladder volume measurements by 3-dimensional and 2-dimensional ultrasonography are strongly correlated.Nevertheless, in gallstone patients, gallbladder volumes by 3-dimensional ultrasonography tend to be smaller than by 2-dimensional ultrasonography, possibly due to interference of gallstones with the volume measurement.
Assuntos
Esvaziamento da Vesícula Biliar/fisiologia , Vesícula Biliar/diagnóstico por imagem , Vesícula Biliar/fisiologia , Ultrassonografia/métodos , Adulto , Feminino , Cálculos Biliares/fisiopatologia , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Microlithiasis is the underlying cause in a significant proportion of patients with "idiopathic" acute pancreatitis. The mechanism appears to be a relative deficiency of phosphatidylcholine in bile, with fast and extensive cholesterol crystallization as a result. Diagnosis of microlithiasis by microscopic detection of cholesterol crystals in bile is important and should lead to appropriate therapy (cholecystectomy, endoscopic sphincterotomy or ursodeoxycholic acid maintenance therapy).