RESUMO
Efficacy of chronic hepatitis C (CHC) treatment with Peg-IFN and Ribavirin (RBV) is superior for genotypes 2/3 (GT-2/3) than for genotype 1 (GT-1) patients. Efficacy of treatment in Latinos infected with GT-2/3 is unknown. The purpose of the study was to examine efficacy of Peg-IFN/RBV in Latinos and factors that predict sustained viral response (SVR). This was a retrospective study of GT-2/3 patients treated with Peg-IFN alfa-2a and RBV for 24 weeks. Multiple baseline characteristics were evaluated. SVR and relapse rates were calculated, as well as multiple regression models performed to examine factors that predict SVR and relapse, as genotype, HVL, weight, steatosis at liver biopsy, total cholesterol triglyceride and diabetes. Thirty five consecutive patients were included in the study; [26] GT-2 and [9] GT-3. Baseline characteristics were similar between both genotypes. SVR was (18/26) or 69.2% for GT-2 and (8/9) or 88.9% for GT-3 for combined SVR of (26/35), 74.3%. Relapse rates were 28.0% for GT-2 and 11.1% for GT-3 patients for a combined relapse rate of 23.5%. Patients heavier than 75 kg had relapse rates twofold higher than leaner patients, (6/21) or 28.6% versus (2/14) or 14.3% (P = 0.088). Weight increase in kg was the only predictor for risk of relapse, P = 0.043 (SD 0.0445 95% CI 1.0026-1.1772). In conclusion, Latinos heavier than 75 kg with GT-2/3 HCV infection achieve lower SVR than those who weight less than 75 kg, because a higher relapse rate. More research in ethnic and racial minorities is needed to further establish optimal treatment in this population.
Assuntos
Antivirais/uso terapêutico , Peso Corporal , Hepacivirus/genética , Hepatite C Crônica/epidemiologia , Hepatite C Crônica/virologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Feminino , Genótipo , Hepacivirus/classificação , Hepatite C Crônica/tratamento farmacológico , Hispânico ou Latino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Recidiva , Estudos Retrospectivos , Ribavirina/administração & dosagem , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND: Thyroid dysfunction (TD) is associated to chronic hepatitis C (HCV) and interferon (IFN) therapy. The prevalence of TD at baseline and during IFN therapy among stages of hepatic fibrosis is unknown. GOALS: To examine the frequency of TD at baseline and during Peg-IFN therapy among patients with severe and mild fibrosis. STUDY: 100 patients were treated with Peg-IFN and divided in 2 groups (50 each), according to liver histology; Metavir 0-2 (mild fibrosis) and Metavir 3-4 (severe fibrosis). Baseline TD was defined as history of TD, or abnormal thyroid stimulating hormone (TSH) or antiperoxidase thyroid auto-antibodies (TPO -Ab). Frequency of TD during therapy was defined as TD that required treatment. RESULTS: 20% in the severe fibrosis group and 10% in the mild fibrosis group, had TD at baseline. Most of the cases, 31.4% were female as compared to 6.25% males. During therapy, 24% of patients in the severe fibrosis group, compared to 12% in the mild fibrosis, had TD. Most patients had biochemical hypothyroidism, and 66% were female, compared to 33.33 % male. TPO-Ab predicted TD during therapy in 50% of cases while those negative only had 16.6% TD during IFN therapy. CONCLUSIONS: Patients with severe fibrosis have more TD events at baseline and during treatment with Peg IFN alfa-2a. Patients with more hepatic fibrosis require careful attention to diagnose and manage TD. More research in the immune mechanisms of hepatic fibrosis progression and autoimmune complications is needed.
Assuntos
Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Tireoidite Autoimune/virologia , Antivirais/efeitos adversos , Biomarcadores , Feminino , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/epidemiologia , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/efeitos adversos , Prevalência , Proteínas Recombinantes , Índice de Gravidade de Doença , Distribuição por Sexo , Tireoidite Autoimune/epidemiologia , Tireoidite Autoimune/imunologiaRESUMO
BACKGROUND/AIMS: Patients with hepatitis C and human immunodeficiency virus coinfection have rapid fibrosis progression. The effect on fibrosis progression rate and time to cirrhosis of HCV treatment has not been extensively studied. First aim of the study was to assess changes in FPR and TTC and staging after HCV therapy vs. no treatment. Secondary aim was to study changes in FPR/staging of sustained viral responders and non-responders to Peg-IFN alfa-2a and RBV. METHODS: Seventy-four (74) co-infected patients were grouped in three according to HCV treatment, Group 1 - None (n=9), Group 2 - IFN (n=30), Group 3-Peg-IFN alfa-2a (n=35). Paired liver biopsies were analyzed and FPR/TTC calculated for each biopsy. RESULTS: Baseline characteristics, duration of treatment and time between biopsies were similar among groups. HCV therapy, improved grading, but only Peg-IFN alfa-2a therapy resulted in staging decrease. Group 2 had significant staging increase and Group 1 had doubling of FPR and (TTC) reduction from 22.7 to 9.09 years. Peg-IFN alfa-2a treated patients had negative change in FPR and stabilization in TTC. SVR and NR with Peg-IFN alfa-2a/RBV had same FPR and staging. CONCLUSIONS: In patients with HIV/HCV co-infection Peg-IFN alfa 2a based treatment produced regression or stable fibrosis in contrast to accelerated progression in those without treatment.
Assuntos
Antivirais/uso terapêutico , Infecções por HIV/complicações , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Cirrose Hepática/patologia , Fígado/patologia , Polietilenoglicóis/uso terapêutico , Adulto , Antivirais/administração & dosagem , Progressão da Doença , Esquema de Medicação , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferons/uso terapêutico , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Proteínas Recombinantes , Resultado do TratamentoRESUMO
BACKGROUND: Interferon (IFN) regimens for HCV treatment are less effective in HCV/HIV-coinfected patients. There are no effective treatments for patients who fail IFN therapies. We examined the safety and efficacy of peginterferon alfa-2a (peg-IFNalpha-2a) plus ribavirin (RBV) in 41HCV/HIV-coinfected patients non-responsive to prior IFN treatment. METHODS: Patients received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks (n=41). At week 24, patients with non-detectable HCV RNA or > or =2-log decrease from baseline, received peg-IFNalpha-2a (180mg/week) plus RBV (800mg/day) for 24 weeks further. Patients not responding to treatment at week 24 were discontinued. RESULTS: Intent to treat (ITT) sustained viral response (SVR) was 21.9%. Patients who received at least 24 weeks of peg-IFNalpha-2a plus RBV treatment (n=35), SVR rates were 25.7%. SVR was associated with significant improvements in liver histology grade (p=0.02), stage (p=0.02), and fibrosis progression rate (FPR) (p=0.03). Patients that failed to achieve SVR had statistically significant decreases in grade (p=0.09) and FPR (p=0.01). CONCLUSION: peg-IFNalpha-2a plus RBV is effective and safe to achieve SVR in HCV/HIV coinfected patients non-responsive to prior IFN treatment. Patients that achieve SVR have significant improvements in liver histology parameters. In patients that do not achieve SVR there are histological benefits beyond virological response that suggest that peg-IFNalpha-2a+RBV therapy may decrease risk of progression to end stage liver disease.
Assuntos
Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Ribavirina/uso terapêutico , Doença Aguda , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/virologia , Humanos , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Interferons/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Resultado do Tratamento , Carga ViralRESUMO
BACKGROUND: Hepatitis C virus (HCV) infection is prevalent in Latinos. There is some evidence that progression to cirrhosis is more rapid. END POINTS: To calculate time of cirrhosis from time of HCV infection in a large Latino population. Other end points were to assess variables that predict cirrhosis and the effect of gender, alcohol, and human immunodeficiency virus (HIV) infection status on time to cirrhosis. METHODS: Four hundred sixty-nine Latino patients evaluated at a referral center in Puerto Rico were included. Several demographic parameters, such as risk factors, estimated duration of HCV infection, alcohol use, HIV status, and findings from the usual HCV and HIV laboratory tests were noted. All patients had liver biopsy specimens assessed by Ishak score. RESULTS: Monoinfected and coinfected latinos have a median cumulative risk/hazard for cirrhosis of 42.0 vs. 32.0 years after infection (P = 0.0016). The median age of cirrhotic patients is 53.0 years in monoinfections and 42.0 years in coinfection. Among coinfected patients there is no gender-associated difference in time to onset of cirrhosis (P = 0.785). Among monoinfected patients, males have a shorter median risk/hazard to cirrhosis than females (11.0-year difference; P = 0.05) and have a shorter time until onset of cirrhosis by fibrosis progression rate (FPR) (33.33 vs. 41.66 years; P = 0.021). There is no difference between male patients with regard to HIV status (P = 0.199). Alcohol use is significant in monoinfected males (59.2 g/day) vs. females (11.4 g/day; P = 0.001). Variables that predict cirrhosis are male sex, age, and Ishak grade in monoinfected patients and alanine aminotransferase value in coinfected patients. CONCLUSIONS: Puerto Ricans with HCV have a median risk/hazard time to cirrhosis at younger age than other populations. Males who are HIV/HCV-coinfected have the same median risk/hazard and time to cirrhosis than those monoinfected with HCV. Special attention for early diagnosis and treatment is mandatory.
Assuntos
Infecções por HIV/epidemiologia , Hepatite C Crônica/epidemiologia , Hispânico ou Latino , Cirrose Hepática/epidemiologia , Adulto , Comorbidade , Estudos Transversais , Progressão da Doença , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/etnologia , Humanos , Cirrose Hepática/etnologia , Cirrose Hepática/etiologia , Cirrose Hepática/virologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Porto Rico/etnologia , Fatores Sexuais , Fatores de TempoRESUMO
Chronic diarrhea and colitis are common in patients positive for human immunodeficiency virus (HIV) under highly active antiretroviral treatment (HAART). This prospective double-blind study explores the effect of mesalamine vs. placebo in HIV-positive patients. Thirteen HIV-infected patients with noninfectious chronic diarrhea and > 250 CD4+ cells/mm(3) were randomized to mesalamine (2.4 g/day; n = 9) or placebo (n = 4) for 6 weeks. Colonoscopy was performed at baseline and week 6, and biopsies were obtained to calculate the Biopsy Activity Index (BAI). Diarrhea was assessed at baseline and end of treatment using the Disease Activity Index (DAI). Patients and clinicians completed Patient Global Improvement index (PGI) and Clinical Global Improvement index (CGI) at weeks 2 and 6. Comparisons at week 6 were statistically significant between mesalamine and placebo groups for BAI (P = 0.03), DAI (P = 0.007), PGI (P = 0.008), and CGI (P = 0.008). Furthermore, major improvements were documented in the mesalamine group at week 6 compared to baseline for all variables, whereas the placebo group did not have any. Mesalamine was effective for treatment of chronic diarrhea and moderate nonspecific colitis in HIV patients.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Colite/tratamento farmacológico , Diarreia/tratamento farmacológico , Infecções por HIV/complicações , Hospedeiro Imunocomprometido , Mesalamina/uso terapêutico , Adulto , Biópsia , Doença Crônica , Colite/complicações , Colite/patologia , Colonoscopia , Diarreia/complicações , Diarreia/patologia , Método Duplo-Cego , Feminino , Seguimentos , HIV/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/imunologia , Humanos , Masculino , Projetos Piloto , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
H. pylori eradication is a challenge in patients allergic to penicillin, both first-line and failures of prior therapy. We aimed to assess the eradication rate of H. pylori in patients allergic to penicillin, first-line and failures of prior therapy, the efficacy of healing of active duodenal ulcer disease (DUD) and erosive gastritis, and the safety and tolerability of the combination. Twenty patients with documented allergy to penicillin, DUD, and H. pylori infection, 17 (85%) for first-line treatment and 3 (15%) prior therapy failures, were given a 10-day regimen of esomeprazole, 40 mg qid, tetracycline, 500 mg qid, and metronidazole, 500 mg qid. Baseline and follow-up panendoscopy > or =30 days after end of treatment was performed for rapid urease test (Clotest), and four site biopsies for H. pylori, and to document endoscopic peptic ulcer disease. All adverse events during treatment were documented. Eradication rates by intention to treat (ITT) were 85% for first-line treatment and 100% for failures. Seventy percent of all cases had a normal endoscopy at follow-up, and 85 and 100% of patients had healed erosive gastritis and DUD, respectively, from baseline. There were histological improvements in most patients. A high eradication rate was obtained even in patients who had a shorter duration of treatment. The combination was well tolerated. A combination of esomeprazole, tetracycline, and metronidazole is effective for eradication of H. pylori in patients allergic to penicillin, for both first-line treatment and failures of prior treatment.