RESUMO
Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 µg q4wk or Peg-IFNα-2a 180 µg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 µg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research.
Assuntos
Albuminas/efeitos adversos , Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/efeitos adversos , Doenças Pulmonares Intersticiais/induzido quimicamente , Pulmão/efeitos dos fármacos , Polietilenoglicóis/efeitos adversos , Ribavirina/efeitos adversos , Adulto , Albuminas/administração & dosagem , Antivirais/administração & dosagem , Feminino , Humanos , Interferon-alfa/administração & dosagem , Pulmão/diagnóstico por imagem , Pulmão/fisiologia , Doenças Pulmonares Intersticiais/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Capacidade de Difusão Pulmonar , Radiografia Torácica , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Ribavirina/administração & dosagem , EspirometriaRESUMO
Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)-α-2b, with â¼200-h half-life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open-label treatment groups: pegylated IFN (Peg-IFN)-α-2a 180 µg qwk or albIFN 900, 1200 or 1500 µg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 µg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 µg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm(3) occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 µg vs 1500 µg and Peg-IFNα-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg-IFNα-2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3.
Assuntos
Albuminas/administração & dosagem , Antivirais/administração & dosagem , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Interferon-alfa/administração & dosagem , Adulto , Albuminas/efeitos adversos , Antivirais/efeitos adversos , Feminino , Genótipo , Hepacivirus/isolamento & purificação , Humanos , Interferon-alfa/efeitos adversos , Interferons , Interleucinas/genética , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Resultado do Tratamento , Carga ViralRESUMO
International controlled trials have demonstrated increasing sustained virological response (SVR) rates to interferon-based therapies in hepatitis-C-treated patients. Response rates of 6-20% in the era of interferon monotherapy are compared with 42-82% with pegylated interferon plus ribavirin. The virological durability of the SVR is unknown and the optimal follow-up for these patients is unclear. The aim of our study was to determine SVR rates and the durability of the response to interferon-based therapies in the clinical setting. From our database of 1540 hepatitis C patients, 344 treatment courses of at least 12 weeks duration were identified, including interferon monotherapy (175 patients), interferon plus ribavirin (96 patients) and peginterferon plus ribavirin (73 patients). Interferon monotherapy was associated with an SVR rate of 5% in 103 genotype 1 patients and 25% in 72 genotype 2/3 patients. Response rates were higher (P < 0.001) with interferon plus ribavirin-41% in 34 genotype 1 patients and 73% in 62 genotype 2/3 patients-and with peginterferon plus ribavirin-47% in 47 genotype 1 patients and 79% in 26 genotype 2/3 patients. Of 147 patients with an SVR, 146 (>99%) remained hepatitis C virus PCR negative during a mean 2.3 years (range 0.3-10.3) of follow-up. In conclusion, with advances in therapies, we are achieving higher response rates in hepatitis C patients treated in the clinical setting. We can now expect an SVR in over half of the treated patients. Importantly, the response is durable and medium and long-term follow-up of these patients are of low yield and largely unnecessary.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adolescente , Adulto , Idoso , Ensaios Clínicos como Assunto , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Compostos Organometálicos , Peptídeos , Polietilenoglicóis , RNA Viral/sangue , Proteínas Recombinantes , Estudos RetrospectivosRESUMO
BACKGROUND: The optimal treatment for hepatitis C patients unresponsive to interferon is unclear. High-dose induction interferon may enhance early viral clearance, whilst ribavirin reduces relapse; in combination, they may improve sustained virological response rates. AIM: To compare the efficacy and safety of re-treatment with interferon induction, with or without ribavirin, in interferon non-responders. METHODS: We randomized 218 biochemical interferon non-responders to 10 MU interferon alpha 2b daily for 4 weeks, followed by 5 MU thrice weekly for 48 weeks plus ribavirin (II + R), or to the same interferon regimen plus placebo (II + P). All patients were viraemic at entry. RESULTS: The sustained virological response in the II + R group was 39%[95% confidence interval (CI), 30-48%], compared with 16% (95% CI, 9-23%) in the II + P group (P < 0.002). The study drug was discontinued for intolerable symptoms during induction in 9% of the II + R group and in 5% of the II + P group. By logistic regression, a sustained virological response was more likely following II + R treatment (odds ratio, 4.4; 95% CI, 2.1-9.7) and less likely in patients with genotype 1 or 4 (odds ratio, 0.16; 95% CI, 0.07-0.36). CONCLUSION: High-dose induction interferon plus ribavirin is well tolerated and effective for patients unresponsive to interferon alone.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Adolescente , Adulto , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Ribavirina/efeitos adversos , Resultado do TratamentoRESUMO
The response to antiviral therapy and the rate of fibrosis progression in chronic hepatitis C virus (HCV) infection are related to common factors, including age and gender. The aim of this study was to evaluate the relationship between the rate of fibrosis progression and the sustained virologic response (SVR) to interferon (IFN)-based treatment. A total of 332 patients treated for chronic HCV infection were evaluated. Using multivariate logistic regression analysis, the impact of the rate of fibrosis progression (defined as the stage of liver fibrosis according to the Metavir system/duration of infection) on the rate of SVR (negative HCV RNA at least 6 months following the end of treatment), was determined. The median age of the patients was 44 (range 25-77) years, 64% were male, and 66% were infected with genotypes 1, 4, 5 or 6. The median rate of fibrosis progression was 0.083 (range 0-2) Metavir units/year; 158 patients (48%) had F2-F4 fibrosis. After a median of 48 (range 2-126) weeks of therapy (IFN, n=190; IFN and ribavirin, n=96; pegylated IFN, n=20; pegylated IFN and ribavirin, n=26), 93 patients (28%) achieved an SVR. In univariate analysis, the rate of SVR was higher in slow [< 0.083 Metavir units/year (n=162)] than rapid progressors [> or = 0.083 Metavir units/year (n=170)] (35%vs 22%, P=0.01). After controlling for age, gender, genotype, viral load, and treatment regimen and duration, the rate of fibrosis progression remained an independent predictor of SVR (slow vs rapid progressors, OR 2.74; 95% CI 1.27-5.92; P=0.01). Hence the rate of fibrosis progression is an independent predictor of SVR to IFN-based therapy in patients with chronic hepatitis C. This additional factor should be considered in economic models evaluating this condition.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Cirrose Hepática/etiologia , Adulto , Idoso , Estudos de Coortes , Progressão da Doença , Quimioterapia Combinada , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , RNA Viral/análise , Resultado do Tratamento , Carga ViralRESUMO
The hepatitis C virus (HCV) is a major cause of liver disease and the complications of cirrhosis. Liver biopsies, performed prior to the development of liver cirrhosis, characteristically show an inflammatory cell infiltrate with varying degrees of fibrosis. Precisely how HCV infection induces hepatic fibrogenesis is unknown. Recent studies suggest the release of oxidants, cytokines and proteases from the host immune system are key to the development of fibrosis. Macrophages and neutrophils, cells heavily represented in the inflammatory cell response, contain the oxidant generating enzyme myeloperoxidase (MPO). Cellular levels of MPO can be influenced by a functional promotor polymorphism, -463G/A, which precedes the MPO gene. We examined the relationship between this MPO promotor genotype and the degree of fibrosis in 166 patients with chronic HCV infection. All patients had previously participated in clinical drug trials for the treatment of chronic HCV infection. The MPO genotype was determined from cryo-preserved lymphocytes obtained from patients prior to treatment. The degree of fibrosis was estimated from liver biopsy specimens obtained prior to treatment. We found that patients with the MPO GA/AA genotype were more likely to have advanced fibrosis scores compared with those with the GG genotype: Of the patients with GG genotype, 78% (79 of 102 cases) had lower Knodell Fibrosis scores of 0 or 1, compared to 56% (37 of 64 cases) of patients with GA/AA genotype (P < 0.05). The mechanism(s) by which MPO contributes to fibrosis progression remains to be determined.
Assuntos
Hepatite C Crônica/genética , Cirrose Hepática/genética , Peroxidase/genética , Feminino , Hepatite C Crônica/fisiopatologia , Humanos , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-IdadeRESUMO
Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C virus (HCV) infection is associated with advanced liver disease, including cirrhosis. The aims of this study were to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in HCV-infected patients and to determine the role of Fas in HCV-mediated apoptosis. Liver tissue from 44 HCV-infected patients with variable alcohol consumption, and 10 normal control subjects who did not consume alcohol was examined for hepatocyte apoptosis, proliferation and Fas expression. Alcohol consumption was assessed using the 'Lifetime Drinking History' alcohol questionnaire. HCV RNA, alanine aminotransferase (ALT) and ferritin were also assessed in addition to demographic data. Hepatocyte apoptosis was significantly greater in HCV-infected patients compared to controls. Expression of Fas (CD95) was found in HCV patients but not in controls. The degree of Fas expression correlated with hepatocyte apoptosis as detected by terminal UTP nick end labelling (TUNEL). Active ethanol consumption led to a significant increase in hepatocyte apoptosis. Fas expression correlated with fibrosis in HCV-infected patients who were not actively drinking ethanol. In summary, HCV leads to increased apoptotic cell death in hepatocytes. Programmed cell death can be further up-regulated by active ethanol consumption. The correlation between Fas expression and TUNEL supports the hypothesis that the Fas-Fas ligand interaction is the major mechanism for HCV-induced hepatocyte apoptosis.
Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Apoptose , Hepatite C Crônica/patologia , Hepatócitos/patologia , Cirrose Hepática/etiologia , Fígado/patologia , Receptor fas/metabolismo , Adulto , Idoso , Feminino , Genes bcl-2/genética , Hepatite C Crônica/complicações , Humanos , Fígado/imunologia , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND/AIMS: Interferon plus ribavirin is the most effective therapy for chronic hepatitis C. The aim of this study was to evaluate the effect of chronic hepatitis C and therapy on health-related quality of life and work functioning. METHODS: Nine hundred and twelve patients with hepatitis C infection were randomized in a controlled trial of Interferon alpha 2b 3 MU tiw for 24 or 48 weeks plus ribavirin 1000-1200 mg or placebo. Questionnaire-based assessments of health-related quality of life and work functioning were performed before, during, and after treatment. Outcome measures included the SF-36 Health Survey and additional generic and specific scales. Work functioning was assessed as missed days, shorter hours or less productivity at work. RESULTS: Pre-treatment, patients had significant impairment in five of eight SF-36 concepts compared to matched population norms. Sustained responders had a return to normal for four of these five concepts. Quality of life did not improve in non-responders. Improvements in histology, viral load or ALT values predicted improvements in quality of life. Sustained responders also had improvements in work functioning and productivity. CONCLUSIONS: Hepatitis C patients had impaired quality of life. After combination therapy, sustained virologic responders achieved benefits in their quality of life and work functioning.
Assuntos
Antivirais/administração & dosagem , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/administração & dosagem , Qualidade de Vida , Ribavirina/administração & dosagem , Adulto , Alanina Transaminase/sangue , Quimioterapia Combinada , Feminino , Hepatite C Crônica/psicologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , RecidivaRESUMO
BACKGROUND & AIMS: Black patients with chronic hepatitis C have lower response rates than white patients to interferon monotherapy. The factors responsible for these differences are unknown, as is the impact of combination antiviral therapy on responsiveness among ethnic groups. We evaluated the impact of race on response to therapy in these patients. METHODS: A total of 1744 patients with chronic hepatitis C were randomized in 2 recent clinical trials to receive 24 or 48 weeks of interferon monotherapy or interferon-ribavirin combination therapy. RESULTS: Sustained virologic responses occurred in 27% of 1600 whites, 11% of 53 blacks (P = 0.01 vs. white), 44% of 32 Asians, and 16% of 27 Hispanics. No black patient had a sustained virologic response to interferon monotherapy, but 20% and 23% had sustained responses to 24 and 48 weeks, respectively, of combination therapy. Among black patients, 96% had hepatitis C genotype 1 compared with 65% of white subjects (P < 0.0001). Sustained response rates were similar for black and white patients with genotype 1 infection (23% vs. 22%, respectively). Compared with whites, black patients were older, weighed more, and had higher median Histologic Activity Index scores but did not differ in sex, baseline alanine aminotransferase or hepatitis C virus (HCV)-RNA levels, degree of fibrosis or percentage with cirrhosis, or other demographic variables. White subjects had a significantly greater reduction in HCV-RNA levels than blacks at weeks 4, 12, 24, and 48 of therapy, but only for black patients treated with interferon monotherapy. The decreased reduction of HCV-RNA reduction among blacks was eliminated by combination therapy. CONCLUSIONS: These observations suggest that the impaired responsiveness of black patients to interferon monotherapy can be overcome partially by combination interferon-ribavirin therapy.
Assuntos
Antivirais/uso terapêutico , População Negra , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/etnologia , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Combinação de Medicamentos , Feminino , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , RNA Viral/sangue , Proteínas RecombinantesRESUMO
BACKGROUND: Epidemiological studies have established that heavy alcohol consumption in persons with chronic hepatitis C infection is associated with advanced liver disease, including cirrhosis. The cellular mechanisms underlying this process, which appear to occur over decades, are unknown. Increased hepatocyte apoptosis has been observed in association with hepatitis C infection. The aim of this study was to evaluate the relationship between alcohol consumption and hepatocyte apoptosis in hepatitis C-infected patients. METHODS: Liver tissue from 20 hepatitis C-infected patients with variable alcohol consumption, and 10 normal control subjects was examined for hepatocyte apoptosis, proliferation and bcl-2 expression. RESULTS: Hepatocyte apoptosis was significantly greater in hepatitis C-infected patients than in controls. In hepatitis C-infected patients, significantly more hepatocyte apoptosis was seen in those consuming at least 30 g per day of alcohol compared with those drinking less than 10 g daily. Bcl-2, an inhibitor of apoptosis, was not detected in liver tissue from patients with the highest ethanol intake and rate of hepatocyte apoptosis. In contrast, patients drinking lesser amounts of ethanol had lower rates of hepatocyte apoptosis and more frequent bcl-2 expression. CONCLUSIONS: This study confirms that both hepatitis C infection and ethanol consumption induce hepatocyte apoptosis in humans. Ethanol-induced hepatocyte apoptosis has previously been shown only in animal models of alcohol-related liver injury. The precise role of apoptosis in the pathogenesis of hepatitis C-related liver injury remains unclear, but its induction may be related to downregulation of bcl-2 expression associated with ethanol consumption.
Assuntos
Consumo de Bebidas Alcoólicas , Apoptose , Genes bcl-2/genética , Hepatite C Crônica/patologia , Hepatócitos/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Doença Aguda , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Quimioterapia Combinada , Humanos , Interferon alfa-2 , Proteínas Recombinantes , Recidiva , Ribavirina/administração & dosagem , Ribavirina/efeitos adversosAssuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Amantadina/administração & dosagem , Antivirais/administração & dosagem , Quimioterapia Combinada , Humanos , Interferon-alfa/administração & dosagem , Ribavirina/administração & dosagem , Falha de TratamentoRESUMO
The Th1/Th2 cytokine balance is important in persistence of infection and liver injury in chronic hepatitis C. The aim of this study was to administer the anti-inflammatory cytokine, recombinant human interleukin-10 (rHuIL-10), for 28 days in patients with chronic hepatitis C and to assess the safety and measure the effect on alanine aminotransferase (ALT, a marker of hepatic inflammation) levels and serum hepatitis C virus (HCV) RNA values. Three treatment-naive and 13 interferon (IFN) nonresponder patients (total 16 patients) with compensated chronic HCV infection were enrolled in this study. Patients were randomized to receive rHuIL-10 at a dose of 4 or 8 microg/kg/day as a single daily subcutaneous injection for 28 days. ALT values and serum HCV RNA were measured at days 0, 1, 3, 8, 15, 22, and 28 during therapy and at follow-up 2 and 4 weeks after cessation of the 4-week treatment period. ALT values normalized in 9 of 16 patients during therapy and remained normal until the end of treatment in 8 patients. The decreases in ALT values occurred in both the 4 microg and 8 microg dosage groups and were seen in both IFN naive and nonresponder patients. Mean ALT values fell significantly during the study period but usually returned to pretreatment levels by the end of the 4-week follow-up period (p < 0.05). HCV RNA concentrations did not vary significantly during or after therapy. (No patient had either an increase or a decrease in HCV RNA levels of > or =1.5 log during the study.) The drug was well tolerated, with no adverse symptoms noted. Platelet counts fell transiently to 73,000 and 63,000 in 2 patients. No other toxicity was observed, and no patients discontinued therapy. In chronic hepatitis C, short-term therapy with IL-10 was well tolerated and caused transient normalization of ALT values in 50% of patients, which returned to pretreatment levels on cessation of treatment. There were no significant changes observed in serum HCV RNA concentrations during the study. These immunomodulatory effects are similar to those observed with ribavirin monotherapy in chronic hepatitis C. Further study of rHuIL-10 alone or in combination with antiviral agents in chronic hepatitis C is warranted.
Assuntos
Hepatite C Crônica/tratamento farmacológico , Interleucina-10/uso terapêutico , Alanina Transaminase/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Interleucina-10/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêuticoRESUMO
BACKGROUND: There are persuasive arguments for treating all patients with Helicobacter pylori-associated peptic ulcer disease. However, the choice of therapeutic regimen remains problematical. Bismuth triple therapy produces greater than 80% cure of H. pylori infection, whereas omeprazole and bismuth quadruple therapy has produced cure rates in excess of 90%. Colloidal bismuth is not available in many countries, hence limiting the use of bismuth-based therapeutic regimens. We substituted widely available sucralfate for bismuth in a quadruple-therapy regimen. METHOD: We studied 223 consecutive patients with gastritis or peptic ulcer disease in whom H. pyori infection was confirmed by CLOtest (Delta West Ltd., Bentley, WA, Australia) or histological assessment. Successful therapy was validated by the 14C urea breath test 4 to 6 weeks after therapy. Omeprazole, 20 mg was given twice daily for 10 days. After 3 days of omeprazole sucralfate (1 gm qid), tetracycline (500 mg qid) and metronidazole (400 mg tid) were added for 7 days. RESULTS: Therapy was successful in 194 of 223 patients (87%). Compliance was excellent, with only two patients being unable to tolerate therapy. Side effects were minimal and included nausea, vomiting, headache, and vaginal moniliasis. At 6 months' follow-up, 10 of 210 patients (5%) who were previously documented as "cured" had a positive breath test. CONCLUSIONS: The wide availability of sucralfate in many countries makes it a possible alternative to bismuth for use in proton pump quadruple-therapy regimens, achieving a reasonable cure rate for H. pylori infection.
Assuntos
Antiulcerosos/uso terapêutico , Bismuto/uso terapêutico , Gastrite/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori , Úlcera Péptica/tratamento farmacológico , Sucralfato/uso terapêutico , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Gastrite/microbiologia , Humanos , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Úlcera Péptica/microbiologia , Tetraciclina/uso terapêuticoRESUMO
The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.