RESUMO
Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT.
Assuntos
Hepatite Viral Humana/diagnóstico , Hepatite Viral Humana/terapia , Complicações Infecciosas na Gravidez , Doença Aguda , Doença Crônica , Gerenciamento Clínico , Feminino , Hepatite Viral Humana/complicações , Hepatite Viral Humana/patologia , Hepatite Viral Humana/virologia , Humanos , Transplante de Fígado , GravidezRESUMO
The role of innate immune response mediated by Toll-like receptors in HCV infection, is not yet well understood and there is a lack of data regarding liver tissue expression of these molecules in chronic hepatitis C (CHC). Our study is aimed to investigate ex vivo, liver expression of TLR2, TLR3 and TLR7, which are more involved in the immune-pathogenesis of CHC, and to explore possible correlations with features of disease. We obtained liver biopsies and collected peripheral blood mononuclear cells (PBMC) from 23 consecutive patients with CHC and from 6 patients of control, without liver disease, undergoing surgery for cholecystectomy. The levels of TLRs mRNA in the samples were determined using a real-time reverse transcription quantitative PCR (RT-qPCR). We found a significant high expression of TLR3 in the liver of CHC patients respect to controls (also higher than expression in the PBMC). Conversely no differences emerged in the TLR2 and TLR7 levels between cases and controls. Also we found a correlation of TLR2 and TLR7 levels with the grade of necro-inflammation in the liver. Furthermore TLR7 hepatic levels resulted related to a more advanced stage of liver fibrosis. Ours is the first study to provide data on tissue expression of TLRs during chronic hepatitis C and we believe that it could lead to a better understanding of the role of these molecules in the HCV-mediated liver damage.
Assuntos
Hepatite C Crônica/metabolismo , Fígado/metabolismo , Fígado/patologia , Receptores Toll-Like/metabolismo , Estudos de Casos e Controles , Feminino , Hepatite C Crônica/genética , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Receptores Toll-Like/genéticaRESUMO
There is a lack of updated nationwide records regarding hepatitis C virus (HCV) infection among drug addicts in Italy. The prevalence and characteristics of HCV infection in a national sample of drug addicts in Italy were determined. Five hundred forty-three drug addicts (mean age 35.3 years, 85.1% males), selected from 25 Italian Centers for Substance Dependence were enrolled to be evaluated for anti-HCV, HCV-RNA, HCV genotype, HBV markers, anti-HDV, and anti-HIV during the period of April-November 2009. Anti-HCV prevalence was 63.9%. HCV-RNA was detected in 68.3% of patients positive for anti-HCV. Genotypes 1 and 3 prevailed (49.3% and 39.7%, respectively). However, 9.3% of the subjects had genotype 4, a rate over threefold higher than the one observed in 1996 among drug addicts in central Italy. Needle sharing was the strongest independent predictor of the likelihood to contract an HCV infection (OR 8.9; 95% CI: 5.0-16.0). Only 19.3% of subjects received antiviral treatment for HCV. The prevalence of HBsAg and HIV positivity was 2.8% and 3.1%, respectively. The pattern of HBV markers showed that nearly one-third of subjects had been vaccinated, while 42.3% were negative for any marker of HCV. The prevalence of HCV infection is high among drug addicts in Italy. The incidence of Genotype 4 is increasing and this may lead to the spreading of the disease to the general population in the near future. Efforts should be made to improve the rate of antiviral treatment for drug addicts with HCV infection and vaccination against hepatitis B.
Assuntos
Usuários de Drogas , Hepatite C/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/complicações , Adolescente , Adulto , Coinfecção/epidemiologia , Estudos Transversais , Feminino , Genótipo , Anticorpos Anti-HIV/sangue , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/imunologia , Antígenos de Superfície da Hepatite B/sangue , Anticorpos Anti-Hepatite C/sangue , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , RNA Viral/sangue , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Treatment choice for chronic HBV infection is a continuously evolving issue, with a wide range of options. We aimed to evaluate the current practice of HBV therapies in the real world in Southern Italy. METHODS: A prospective study enrolling over a six month period (February-July 2010) all consecutive HBsAg positive subjects, never previously treated, referred to 16 liver units in two Southern Italy regions (Calabria and Sicily). RESULTS: Out of 247 subjects evaluated, 116 (46.9%) had HBV-DNA undetectable or lower than 2000 UI/ml. There were 108 (43.7%) inactive carriers, 103 (41.7%) chronic hepatitis, and 36 (14.6%) liver cirrhosis. Antiviral treatment was planned in 94 (38.0%) patients (26 cases with Interferon or Pegylated Interferon and 68 with nucleos(t)ides analogues). As many as 49.5% of subjects with chronic hepatitis did not receive antiviral treatment. DISCUSSION: The majority of chronic HBsAg carrier referring centres for evaluation were not considered suitable for antiviral treatment. Nucleos(t)ides analogues are the preferred first choice for therapy. A long-lasting period of observation may be needed to make appropriate therapeutic decisions in several cases.
Assuntos
Hepatite B Crônica/tratamento farmacológico , Adenina/análogos & derivados , Adenina/uso terapêutico , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Feminino , Guanina/análogos & derivados , Guanina/uso terapêutico , Antígenos E da Hepatite B/sangue , Humanos , Interferon-alfa/uso terapêutico , Itália , Lamivudina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Nucleosídeos/uso terapêutico , Organofosfonatos/uso terapêutico , Polietilenoglicóis/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Pirimidinonas/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Telbivudina , Tenofovir , Timidina/análogos & derivados , Adulto JovemRESUMO
BACKGROUND AND AIMS: Drug-induced liver injury (DILI) is the most common cause of death from acute liver failure, and accounts for approximately 13% of cases of acute liver failure in the United States. The clinical presentation of DILI covers a wide spectrum, from asymptomatic liver test abnormalities to symptomatic acute liver disease, prolonged jaundice and disability, or overt acute or subacute liver failure. The aim of our study was to evaluate the number of DILI cases admitted to our Unit and to identify the drugs responsible. Thus, we reviewed all clinical records of patients with DILI admitted to our Unit from 1996 to 2006. PATIENTS AND METHODS: A database was constructed, reporting demographic, clinical features at onset, laboratory results, suspected drugs and follow-up. Liver damage was defined as hepatocellular, cholestatic or mixed, according to clinical and laboratory data. RESULTS: Forty-six patients were admitted with a diagnosis of DILI. Presentation was jaundice in 22 patients and hepatic failure in 3 (all attributed to nimesulide). Liver damage was of a cytolytic pattern in 19 cases (41%), cholestatic in 15 (33%) and mixed in 12 (26%). Jaundice was found to be higher in nimesulide-induced liver damage compared to other drugs (p=0.007). Three out of 14 patients with nimesulide-induced DILI developed encephalopathy and/or ascites. Time of recovery in the nimesulide group was significantly lower than DILI from other drugs (p<0.001). CONCLUSION: Non-steroidal anti-inflammatory drugs, psychotropic drugs and antimicrobials are the most common causes of DILI. Nimesulide-induced DILI is usually reversible upon discontinuation of the drug, but occasionally progresses to liver failure.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Sulfonamidas/efeitos adversos , Adulto , Fatores Etários , Idoso , Anti-Infecciosos/efeitos adversos , Feminino , Humanos , Falência Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Psicotrópicos/efeitos adversos , Estudos Retrospectivos , Fatores SexuaisRESUMO
There is a lack of information on the characteristics of patients with chronic hepatitis C virus infection (HCV) who fail to respond to antiviral treatment. We studied HCV-positive subjects with chronic liver diseases treated with pegylated-interferon (PEG-IFN) and ribavirin (RBV) who failed to clear HCV in routine clinical practice. A total of 2150 consecutive adult patients treated with PEG-IFN plus RBV therapy in 46 Italian centres between 1 July 2004, and 30 June 2005, were studied. Of the 2150 patients, 923 (42.9%) (M/F 585/335, mean age 54.8 years) failed to achieve a serum HCV-RNA clearance. Of these 923 patients, 429 (46.5%) were nonresponders, 298 (32.3%) relapsers, 168 (18.2%) drop-outs for noncompliance or adverse events and 28 (3.0%) were lost during follow-up. Overall, 642 (70.6%) patients received adequate therapy (defined as more than 80% of the drug doses for >80% of the time). Genotypes 1-4 were observed in 76.9% of cases; genotypes 2-3 in 21.2% and mixed in 1.9%, respectively. Multiple logistic regression analysis identified genotypes 1 and 4 as the sole independent predictors of the likelihood of nonresponse to therapy compared with relapse (OR: 4.38; 95% CI = 2.28-8.4). Age older than 65 years was the sole independent factor associated with no adherence to therapy (OR: 2.22; 95% CI = 1.36-3.62). Patients who fail to respond to treatment are a nonhomogeneous population with different features, and the sole factor that discriminates nonresponse from relapse is the distribution of genotypes 1-4. Co-morbidities are unable to determine the type of treatment failure and inadequate adherence to therapy mostly affects patients older than 65 years of age.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , RNA Viral/sangue , Ribavirina/uso terapêutico , Adulto , Fatores Etários , Idoso , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Itália , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Proteínas Recombinantes , Estudos Retrospectivos , Fatores de Risco , Falha de TratamentoRESUMO
B-lymphocyte stimulator/B activating factor (BLyS/BAFF) is a tumour necrosis factor-family cytokine that plays a key role in generating and maintaining the mature B-cell pool. BLyS/BAFF expression by macrophages is stimulated by interferon-gamma and interleukin-10, and its serum levels are increased in chronic hepatitis C (CHC). The aim of this study was to assess serum levels of BLyS/BAFF in patients with acute hepatitis C (AHC) and correlate them with disease outcome. We studied 28 patients with AHC (14 males, mean age 59.3 +/- 15 years), followed for at least 7 months since onset, comparing them with 86 CHC patients and 25 healthy blood donors (HBD). BLyS/BAFF levels were assessed at baseline (within 4 weeks of onset) and during follow-up. BLyS/BAFF median levels were significantly higher in AHC (1485 pg/mL) than in CHC (1058 pg/mL) and in HBD (980 pg/mL) (P < 0.001). BLyS/BAFF levels were higher in AHC patients evolving to chronicity (1980 pg/mL) than in those with a self-limited course (1200 pg/mL), (P = 0.02). By logistic regression analysis, higher BLyS/BAFF levels were independently associated with persistence of HCV infection (OR 29.7; 95% CI: 1.73-508.20). High serum levels of BLyS/BAFF at onset of AHC can predict its evolution to chronic infection.
Assuntos
Fator Ativador de Células B/sangue , Hepatite C/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Feminino , Hepatite C Crônica/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.
RESUMO
UNLABELLED: Hepatitis C virus (HCV) infection is associated with a significant reduction of health related quality of life (QOL), the causes and mechanisms of which are still unknown. To explore whether treatment history could affect QOL, we examined patients with detectable HCV viraemia who had a different therapeutic background. Two hundred sixty-four consecutive subjects with chronic HCV infection and detectable viraemia were enrolled. Of these, 163 were untreated patients, 43 were relapsers, 58 were nonresponders (NR) to nonpegylated interferon (IFN) therapy. To assess QOL, three self-report instruments were employed: the Short Form-36 (SF-36), the Chronic Liver Disease Questionnaire (CLDQ-I) and the World Health Organization Quality of Life assessment (WHOQOL-BREF). Clinical and demographic data were collected, and the QOL scores of HCV-positive patients were compared with those of an Italian normative sample and healthy controls. Further antiviral treatment was offered to untreated and relapsed patients but not to NR. All patient groups displayed lower QOL scores compared with the normative sample and controls. NR displayed lower QOL scores in several areas compared with untreated patients and relapsers. In multivariate regression analyses, being NR and having a physical comorbidity were significantly associated with poorer QOL. CONCLUSIONS: Treatment history and expectations and physical comorbidity may affect QOL in HCV-positive patients. Untreated and relapsed patients have comparable levels of QOL and higher scores than NR.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Qualidade de Vida , Adulto , Idoso , Comorbidade , Feminino , Nível de Saúde , Hepatite C Crônica/virologia , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
We assessed the prevalence of gallbladder disease (i.e. gallstones plus cholecystectomy) among patients with liver disease and its association with the severity and aetiology of hepatic injury. Subjects, referred to 79 Italian hospitals, were enrolled in a 6-month period. The independent effect of the severity and aetiology of liver disease on gallstone disease prevalence was assessed by multiple logistic regression analysis. Overall, 4867 subjects tested anti-hepatitis C virus (HCV) positive alone, 839 were hepatitis B virus surface antigen (HBsAg) alone, and 652 had an excessive alcohol intake. The prevalence of gallstone disease was 23.3% in anti-HCV-positive patients, 12.4% in HBsAg positive and 24.2% in subjects reporting excessive alcohol intake, respectively. Gallstone disease prevalence increased by age in each aetiological category. The proportion of patients with gallstone disease who had a cholecystectomy was the highest in HCV+ subjects. After adjusting for the confounding effect of age and body mass index, compared with patients with less severe liver disease, subjects with HCV-related cirrhosis, but not those with alcohol-related cirrhosis, were more likely to have gallstone disease. Subjects with HCV-related cirrhosis (OR 2.13, 95% CI: 1.38-3.26) were more likely to have gallstone disease when compared with those with HBV-related cirrhosis. HCV infection is a risk factor for gallstone disease. In Italy, the high prevalence of HCV infection among cirrhotic patients has important implications, as cholecystectomy in these subjects is associated with high risk of morbidity and mortality.
Assuntos
Cálculos Biliares/epidemiologia , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Adulto , Idoso , Consumo de Bebidas Alcoólicas , Colecistectomia , Feminino , Cálculos Biliares/etiologia , Cálculos Biliares/virologia , Hepatite C Crônica/epidemiologia , Humanos , Itália/epidemiologia , Cirrose Hepática/epidemiologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
AIMS: To assess whether host metabolic factors influence the degree of hepatic steatosis and fibrosis in patients infected with hepatitis C virus, and to evaluate the impact of anti-viral therapy on insulin resistance and serum levels of adipocytokines. METHODS: Clinical and biochemical features, anthropometrical characteristics, and levels of fasting insulin, leptin, adiponectin and resistin were measured in 'naïve' patients with chronic hepatitis C, before, during and after therapy with Peg-Interferon-alpha 2a plus Ribavirin. RESULTS: Forty-eight patients were included (M/F 28/20; mean age 50.0 +/- 12.6 years; 62.5% genotype-1). Body mass index was 26.4 +/- 4.0 kg/m(2), and visceral obesity was present in 24 patients. At multivariate analysis (RR; 95% CI), steatosis was associated to older age (1.08; 1-1.18), necroinflammatory activity (17.67; 1.6-194.46), and raised insulin levels (1.39; 1.1-1.77). Fibrosis was related to necroinflammatory activity (25.73; 2.54-261.11), and steatosis (6.47; 1.09-38.29). Sustained viral response was achieved by 62.5% of patients and was associated with younger age (0.92; 0.85-0.99), genotype non-1 (10.61; 1.52-73.76) and absence of visceral obesity (13.78; 2.36-80.29). At the end of follow-up, insulin and the homeostasis model assessment for insulin resistance were reduced and adiponectin increased when compared with baseline, all unrelated to the outcome of treatment. CONCLUSIONS: Visceral obesity correlates with the degree of steatosis and fibrosis, and it negatively affects treatment response. Significant changes of insulin resistance and adipocytokines occur under treatment, irrespective of virological outcome.
Assuntos
Adipócitos/efeitos dos fármacos , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Resistência à Insulina/fisiologia , Cirrose Hepática/virologia , Obesidade/complicações , Adulto , Antivirais/metabolismo , Fígado Gorduroso/virologia , Feminino , Hepatite C Crônica/complicações , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Gordura Intra-Abdominal/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Proteínas Recombinantes , Ribavirina/uso terapêuticoRESUMO
OBJECTIVES: To evaluate the clinical efficacy and the effects on the quality of life of iloprost, a prostacyclin analogue, used according to a new protocol in patients with Raynaud's phenomenon secondary to systemic sclerosis. METHODS: In this randomized study, we treated 30 patients with iloprost, given by intravenous infusion, at progressively increasing doses (from 0.5 to 2 ng/kg/min) over a period of 6 h each day for 10 days in two consecutive weeks, with repeated cycles at regular intervals of 3 months for 18 months. The results were compared with those obtained in 30 other patients who received the same drug but with different dosing schemes. RESULTS: The total average daily duration of the attacks, the average duration of a single attack and the average daily frequency of the attacks were reduced significantly in all treatment groups, but the comparison between the groups demonstrated significant differences between patients treated with the new protocol and the others at later times (12 and 18 months). The effects on the quality of life in the group treated with the new protocol, evaluated with the Short Form-36, demonstrated a marked improvement regarding both the scale relating to the physical aspect of the illness and, especially, the scale relating to the mental aspect. CONCLUSIONS: In patients with systemic sclerosis, cyclic intravenous iloprost infusion is efficacious in the treatment of Raynaud's phenomenon. The protocol that we used, compared with others, not only has favourable clinical effects but also leads to a marked improvement in the quality of life.
Assuntos
Iloprosta/uso terapêutico , Qualidade de Vida , Doença de Raynaud/tratamento farmacológico , Escleroderma Sistêmico/complicações , Vasodilatadores/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doença de Raynaud/etiologia , Doença de Raynaud/psicologia , Escleroderma Sistêmico/psicologia , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
Hepatitis C virus is not cleared after primary infection in 50-85% of subjects exposed to hepatitis C virus. Anti-viral treatment during the early phase of infection significantly enhances the likelihood of a sustained clearance of hepatitis C virus. Although, a variety of autoimmune-related side effects have been observed during interferon therapy for chronic hepatitis, immuno-mediated adverse reactions have not been reported during treatment of acute hepatitis C. We describe the case of a patient who developed acute hepatitis C virus infection and, while receiving pegylated interferon alpha-2b monotherapy, developed a severe polymyositis. This case illustrates the potential risk of autoimmunity by interferon, also for acute hepatitis, and underlines the importance of a prompt diagnosis and a rapid discontinuation of interferon treatment for an improvement of clinical outcomes.
Assuntos
Antivirais/efeitos adversos , Hepatite C/tratamento farmacológico , Interferon-alfa/efeitos adversos , Polietilenoglicóis/efeitos adversos , Polimiosite/induzido quimicamente , Doença Aguda , Antivirais/farmacologia , Antivirais/uso terapêutico , Autoimunidade/efeitos dos fármacos , Creatina Quinase/sangue , Portadores de Fármacos , Hepacivirus , Hepatite C/imunologia , Humanos , Interferon alfa-2 , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , RNA Viral/análise , Proteínas RecombinantesRESUMO
PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.
Assuntos
Apomorfina/administração & dosagem , Agonistas de Dopamina/administração & dosagem , Disfunção Erétil/tratamento farmacológico , Inibidores de Fosfodiesterase/administração & dosagem , Piperazinas/administração & dosagem , Administração Oral , Administração Sublingual , Adulto , Idoso , Estudos Cross-Over , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Purinas , Citrato de Sildenafila , SulfonasAssuntos
Dor Abdominal/etiologia , Doenças do Ceco , Doenças do Ceco/diagnóstico , Doenças do Íleo/diagnóstico , Tuberculose Gastrointestinal/diagnóstico , Adulto , Antituberculosos/administração & dosagem , Antituberculosos/uso terapêutico , Doenças do Ceco/complicações , Doenças do Ceco/diagnóstico por imagem , Doenças do Ceco/tratamento farmacológico , Doenças do Ceco/cirurgia , Doença de Crohn/diagnóstico , Diagnóstico Diferencial , Quimioterapia Combinada , Etambutol/administração & dosagem , Etambutol/uso terapêutico , Feminino , Humanos , Doenças do Íleo/complicações , Doenças do Íleo/diagnóstico por imagem , Doenças do Íleo/tratamento farmacológico , Doenças do Íleo/cirurgia , Obstrução Intestinal/diagnóstico , Obstrução Intestinal/cirurgia , Isoniazida/administração & dosagem , Isoniazida/uso terapêutico , Pirazinamida/administração & dosagem , Pirazinamida/uso terapêutico , Radiografia , Fatores de Tempo , Resultado do Tratamento , Tuberculose Gastrointestinal/diagnóstico por imagem , Tuberculose Gastrointestinal/tratamento farmacológicoRESUMO
AIM: Chronic hepatitis C is a progressive disease that leads to liver cirrhosis and hepatocellular carcinoma in a period ranging from 10 to 30 y. Many factors have been related to disease progression and, among them, persistent HCV replication has been advocated as one of the major determinant of hepatic deterioration. With this respect any treatment of chronic hepatitis C is mainly aimed to reduce necro-inflammation by suppressing viral activity in the long-term. We evaluated the persistence of HCV clearance after interferon therapy during follow-up in patients considered as long-term responders. Secondly, we analyzed the rate of progression from hepatitis to cirrhosis and hepatocellular carcinoma in patients with persistent viral elimination as compared to those who did not respond to treatment. METHODS: We performed a systematic review of published data as full papers on treatment of chronic hepatitis that reported data on long-term follow-up of patients with persistent HCV suppression and the rate of cirrhosis and hepatocellular carcinoma in long-term responders as compared to non-responders. Data were pooled to obtain a combined estimate of the reduced relative risk using the random effect model. RESULTS: In patients achieving a sustained virological response a relapse was observed in about 13% (range 0-86%). In subjects with a sustained viral response progression to cirrhosis is uncommon. When compared to relapsers or non-responders the calculated risk reduction in this group was -0.22 (95% C.I. - 0.36/-0.08). The calculated estimates of risk reduction of developing hepatocellular carcinoma in patients achieved sustained response were -0.097 (95% C.I. -0.13/-0.07). CONCLUSION: There is a high chance that patients in remission during the first 6 mo after antiviral treatment will remain so for the rest of their life. Cumulative data from literature showed a significant reduction in the rate of progression to cirrhosis and development of hepatocellular carcinoma in sustained viral responders as compared to non-responders or relapsers. However, since factors predictive of sustained response to interferon are independently associated with less frequent and/or later development of decompensation or HCC, the beneficial effects of antiviral therapy may be probably overestimated.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Carcinoma Hepatocelular/etiologia , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Prognóstico , Fatores de Risco , Replicação Viral/efeitos dos fármacosRESUMO
BACKGROUND: Occult HBV infection in subjects with chronic hepatitis C is related to more severe disease outcome. It has been suggested that it might reduce sensitivity to antiviral treatment. AIMS: To assess in HBsAg negative subjects with chronic hepatitis C any effect of the presence of HBV genomes in the liver on the early kinetics of HCV-RNA under PEG-IFN plus ribavirin. PATIENTS AND METHODS: Twenty-two anti-HCV and HCV-RNA positive subjects, with biopsy-proven chronic hepatitis C (M/F 15/7; 50 +/- 8.6 years, 16 genotype 1b) were given PEG-IFN alpha 2b 1.0 microg qw plus ribavirin (800 to 1,200 mg daily according to body weight) for an intended 52 week period. Early virological response was assessed over the first 4 weeks of therapy by quantifying HCV-RNA. Occult HBV infection was assessed by testing for HBV-DNA in the liver before therapy. RESULTS: HBV genomes were found in the liver of 7 of 22 (31.4%) patients, unrelated to anti-HBc status. Kinetics of HCV-RNA during the first 4 weeks of antiviral treatment was unaffected by occult HBV infection, both in terms of absolute reduction of viral load and of number of cases with a reduction of > or = 2 log10 on treatment. CONCLUSIONS: Occult HBV infection does not affect the early phase of response to combination therapy. Further follow-up of patients into the maintenance phase of antiviral treatment and after stopping it will clarify if and when occult HBV has a role in reducing sustained virological response.
Assuntos
Hepacivirus/efeitos dos fármacos , Hepatite B/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Polietilenoglicóis , Ribavirina/uso terapêutico , Replicação Viral/efeitos dos fármacos , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , Biópsia , DNA Viral/análise , DNA Viral/isolamento & purificação , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite B/diagnóstico , Anticorpos Anti-Hepatite B/sangue , Vírus da Hepatite B/genética , Anticorpos Anti-Hepatite C/sangue , Hepatite C Crônica/complicações , Humanos , Interferon alfa-2 , Fígado/química , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/efeitos dos fármacos , Proteínas Recombinantes , Resultado do Tratamento , Carga Viral/métodosRESUMO
BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.
Assuntos
Anticorpos Anti-Hepatite A/sangue , Vírus da Hepatite A Humana/imunologia , Hepatite A/epidemiologia , Hepatite B Crônica/complicações , Hepatite C Crônica/complicações , Adolescente , Adulto , Idoso , Feminino , Hepatite A/complicações , Hepatite A/imunologia , Hepatite B Crônica/imunologia , Hepatite C Crônica/imunologia , Humanos , Incidência , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Therapy of chronic hepatitis C non- responders to interferon monotherapy with standard doses of interferon plus ribavirin is usually ineffective. AIM: To evaluate the efficacy and tolerability of high-dose prolonged combination retreatment in non- responder patients. METHODS: Patients were retreated for 6 months with 6 MU alphaIFN on alternate days and 1000 or 1200 mg/day ribavirin. HCV-RNA negative patients continued therapy for an additional 6 months. RESULTS: Forty patients (29 males, mean age 49.7 years, 34 genotype 1b, 11 with F3 fibrosis) were treated. At 6 months, 20 (50%) patients were HCV-RNA negative but six of them discontinued therapy because of adverse events. A sustained response was achieved in 28% of patients (11/40). A sustained response was more frequent among patients with genotype non-1b than in those with genotype 1b (67 vs. 21%, P=0.005) and clearance of HCV-RNA in the first 3 months had a high predictive value for sustained response (100% of sustained responders vs. 24% of non-responders, P=0.0001). CONCLUSIONS: High-dose prolonged combination therapy in non-responders to IFN monotherapy leads to a higher rate of sustained response than the standard combination regimen. Tolerability may be a rate-limiting factor. Maximal effectiveness can be predicted in patients with non-1b genotype and in those who clear HCV-RNA soon after starting retreatment.
Assuntos
Antivirais/farmacologia , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/farmacologia , Ribavirina/farmacologia , Adulto , Antivirais/administração & dosagem , Antivirais/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Resistência a Medicamentos , Quimioterapia Combinada , Feminino , Fibrose , Genótipo , Hepatite C Crônica/patologia , Humanos , Interferon-alfa/administração & dosagem , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Ribavirina/administração & dosagem , Ribavirina/uso terapêutico , Resultado do TratamentoRESUMO
AIM: To establish the efficacy of combination therapy with ursodeoxycholic acid (UDCA) and colchicine in patients with symptomatic primary biliary cirrhosis (PBC), defined by the presence of liver cirrhosis, pruritus or bilirubin exceeding 2 mg/mL. METHODS: A total of 90 patients were randomly assigned to ursodeoxycholic acid 500 mg/daily plus placebo (UDCA group, n=44), or ursodeoxycholic acid at the same dosage plus colchicine, 1 mg/daily (UDCA/C group, n=46). The two groups were comparable for age, sex, stage of disease, severity of pruritus, bilirubin, and Mayo score. All patients underwent clinical, ultrasonographic, and biochemical examinations at entry and then every 6 months up to 3 years of follow-up. Patients with cirrhosis underwent endoscopy every 12 months. In a sub-group of patients without cirrhosis, who consented, liver biopsy was repeated at the end of the study. RESULTS: The number of treatment failures (i.e. dead, orthotopic liver transplantation (OLT), complications of cirrhosis, doubling of bilirubin, untreatable pruritus) was 11 (25%) in the UDCA group and four (9%) in the UDCA/C group (P < 0.05). No significant differences were observed in terms of improvement of liver enzymes related to cholestasis and cytolysis and of amelioration of pruritus. The Mayo score values increased less above the baseline values at 24 and 36 month-intervals in the UDCA/C group than in the UDCA group. Histological evaluation at baseline and at the end of the study was available for 15 patients with pre-cirrhotic stage. A significant reduction in histological grading score was observed in patients from the UDCA/C group, whereas no changes in these histological scores were observed in the UDCA group. CONCLUSIONS: The addition of colchicine to ursodeoxycholic acid in patients with symptomatic primary biliary cirrhosis results in a small but significant reduction of disease progress.