RESUMO
PURPOSE: A long-term follow-up study was carried out to evaluate the tolerability and efficacy of long-term therapy (1 to 3 years) with high doses (150 or 300 mg daily) of lamivudine for chronic hepatitis B. METHODS: Thirty-two patients were studied, including those who were seronegative for hepatitis B e antigen (HBeAg), as well as those with decompensated liver cirrhosis. Viral DNA clearance was monitored by using end-point dilution polymerase chain reaction (PCR), a highly sensitive method. Hepatitis B virus (HBV) polymerase gene mutations associated with resistance were determined by sequencing. RESULTS: Response to lamivudine in the sixth month was observed in 19/32 (59.4%) patients. With one exception, viral DNA results observed at this time were maintained. The YMDD mutation was detected in 12 nonresponder patients (9 YVDD, 2 YIDD, and 1 mixed population Y(V/I)DD), generally associated with the L528M mutation. Re-takeover by the wild type was observed 6 to 18 months after lamivudine withdrawal. Lamivudine response rates in noncirrhotic and cirrhotic patients were 9/18 (50%) and 10/14 (71.4%), respectively. HBeAg to anti-HBe seroconversion was found after different periods in all responder patients. Hepatitis B surface antigen (HBsAg) clearance and anti-HBs seroconversion were occasionally found. CONCLUSIONS: In nonresponder patients, resistant mutants appeared up to the second year of lamivudine therapy. In spite of the presence of resistant mutants, maintenance of therapy was usually associated with a lower viral load. In responder patients, maintenance of therapy was associated with continued absence of detectable HBV DNA in serum, as monitored by highly sensitive methods. No significant side effects caused by lamivudine were observed in our patients, even in those with liver cirrhosis.
Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Criança , DNA Viral/genética , Esquema de Medicação , Farmacorresistência Viral/genética , Feminino , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/enzimologia , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/uso terapêutico , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Viremia/tratamento farmacológico , Viremia/virologiaRESUMO
BACKGROUND: Lamivudine has been shown to be an efficient drug for chronic hepatitis B (CHB) treatment. AIM: To investigate predictive factors of response, using a quantitative method with high sensitivity. METHODS: We carried out a prospective trial of lamivudine in 35 patients with CHB and evidence for viral replication, regardless to their HBeAg status. Lamivudine was given for 12 months at 300 mg daily and 150 mg thereafter. Response was considered when DNA was undetectable by PCR after 6 months of treatment. Viral replication was monitored by end-point dilution PCR. Mutation associated with resistance to lamivudine was detected by DNA sequencing in non-responder patients. RESULTS: Response was observed in 23/35 patients (65.7%) but only in 5/15 (33.3%) HBeAg positive patients. Only three pre-treatment variables were associated to low response: HBeAg (p = 0.006), high viral load (DNA-VHB > 3 x 10(6) copies/ml) (p = 0.004) and liver HBcAg (p = 0. 0028). YMDD mutations were detected in 7/11 non-responder patients. CONCLUSIONS: HBeAg positive patients with high viral load show a high risk for developing drug resistance. On the other hand, HBeAg negative patients show a good response to lamivudine even with high viremia.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Lamivudina/uso terapêutico , Adolescente , Adulto , Idoso , Criança , Resistência a Medicamentos , Feminino , Hepatite B Crônica/genética , Hepatite B Crônica/imunologia , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Resultado do TratamentoRESUMO
Interferon is indicated in chronic infection by hepatitis C virus (HCV), however, cirrhosis has been reported as a bad response factor to the therapy. Fifteen cirrhotic patients with HCV, undergoing treatment with recombinant interferon-alpha, ribavirin and/or ursodeoxycholic acid were studied. They were followed-up and evaluated with dosages of alanine aminotransferase and HCV RNA investigation by PCR technique. Of the 15 cirrhotic patients, seven were negative for HCV RNA after antiviral treatment, however ALT was normal in only three of them. Of the eight patients who were not negative, two had normal ALT. Biochemical-virological discrepancy in the follow-up of the patients after antiviral treatment observed in this study has also been reported by other authors. These reports show that the criteria for response to the treatment is to be established.
Assuntos
Antivirais/uso terapêutico , Hepatite C/complicações , Hepatite C/terapia , Interferon-alfa/uso terapêutico , Cirrose Hepática/complicações , Ribavirina/uso terapêutico , Ácido Ursodesoxicólico/uso terapêutico , Doença Crônica , Feminino , Seguimentos , Hepacivirus/genética , Hepatite C/sangue , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangueRESUMO
T lymphocyte subsets were studied in 18 patients with chronic AgHBe positive hepatitis. The study was carried out before, during and after a ten week course of prednisone therapy. There was no statistically significant difference during and after prednisone therapy in patients with hepatitis as to the total lymphocyte number and T lymphocyte subsets. The CD4/CD8 ratio was significantly decreased when compared with that of the normal controls, as the result of a reduction in CD4 T lymphocyte population before the beginning of the therapy. The patients did not respond to prednisone therapy.
Assuntos
Relação CD4-CD8 , Hepatite B/tratamento farmacológico , Prednisona/uso terapêutico , Subpopulações de Linfócitos T , Método Duplo-Cego , Feminino , Hepatite B/imunologia , Antígenos E da Hepatite B/análise , Humanos , Masculino , Prednisona/administração & dosagemRESUMO
The detection of HBV-DNA in serum by molecular hybridization is the most sensitive and specific marker or replication and infectivity of hepatitis B virus and currently is proposed as a routine diagnostic technique in the follow-up of HBV-related diseases. Comparing different techniques already described, we found that direct spotting of serum samples on nitrocellulose membranes under vacuum filtration, followed by denaturing and neutralizing washes is more practical, simple, sensible and reproducible. DNA polymerase assay using phosphonoformic acid as specific viral inhibitor has shown 86.8% of concordance with HBV-DNA detection, and so, it is an useful alternative in the follow-up of hepatitis B chronic patients. We found 19.2% HBeAg positive samples with no other markers of viral replication and no anti-HBe positive sample had detectable HBV-DNA. Discordance between the 2 systems have been extensively described, and we confirm this for the first time in our country. Molecular biological techniques are essential to determine the replication status of chronic hepatitis B patients.
Assuntos
DNA Viral/sangue , Genes Virais , Vírus da Hepatite B/genética , Hepatite B/sangue , DNA Polimerase Dirigida por DNA/sangue , Antígenos E da Hepatite B/análise , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Replicação ViralRESUMO
Few data on chronic hepatitis B (CHB) have been published in our country, despite the fact that it is responsible for more than 50% of all types of chronic hepatitis. From 1968 to 1988, 164 patients were attended with the diagnosis of CHB, from whom 136 (82.9%) were male. Only 11 (8.1%) admitted homosexual behavior. Twenty six out of 39 (66.7%) health professionals were medical doctors; among them 12 (46.2%) were surgeons. The mode of transmission was unknown in 55% of the cases, but vertical and sexual transmissions were also frequent. Commercial gammaglobulin, used with prophylactic purpose, was probably responsible for eight cases between 1972 and 1975. The most frequent forms of CH were chronic active hepatitis (CAH) and liver cirrhosis (LC): 72 or 43.9% and 53 or 32.3%, respectively. The predominance of HBeAg (66.4%) was observed in all forms of CHB. Repeated biopsies showed that chronic lobular hepatitis (CLH) and chronic persistent hepatitis (CPH) may occasionally progress to CAH. This form may persist as such for some years or progress to cirrhosis. In a few cases the evolution to CPH was observed. In the long term follow-up of our patients, the appearance of hepatocellular carcinoma was observed in 8 (4.9%).
Assuntos
Hepatite B , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/etiologia , Criança , Pré-Escolar , Doença Crônica , Feminino , Hepatite B/complicações , Hepatite B/imunologia , Hepatite B/patologia , Hepatite B/transmissão , Hepatite Crônica/etiologia , Homossexualidade , Humanos , Lactente , Cirrose Hepática/etiologia , Neoplasias Hepáticas/etiologia , Masculino , Pessoa de Meia-Idade , Recursos Humanos em Hospital , Estudos RetrospectivosRESUMO
Recombinant alpha-interferon (IFN-R) was given to 17 patients with non-A, non-B chronic hepatitis (NANB-CH) and to 11 patients with B chronic hepatitis (B-CH). Fever (100.4 to 102.2 Fahrenheit) was observed in every patient during the early phase of treatment. Other side-effects included rigors, myalgia, headache and laboratory changes such as leucopenia, neutropenia and, in some cases, thrombocytopenia. However, the tolerance was considered acceptable and treatment had to be interrupted in only one patient presenting generalized mucosal lesions attributed to a hypersensitivity reaction. The response to IFN-R in NANB-CH was considered positive when serum aminotransferase levels became normal or below two times the upper normal limit. Out of eight patients who completed the treatment, four were considered as responders but one of them, treated during five months, showed a relapse after three months. On the other hand, in one patient treated for twelve months, a persistent normalization of serum amino-transferases was observed: a liver biopsy showed a striking decrease of the inflammatory changes. As to the B-CH. 3 out of 8 patients who completed the treatment showed a disappearance of HBeAg and DNA-polymerase and were considered as responders. These preliminary results show that IFN-R is a promising drug but only multicenter controlled trials will establish its value in the treatment of viral chronic hepatitis.
Assuntos
Hepatite B/terapia , Hepatite C/terapia , Hepatite Viral Humana/terapia , Interferon Tipo I/uso terapêutico , Adolescente , Adulto , Criança , DNA Polimerase Dirigida por DNA/sangue , Feminino , Hepatite B/sangue , Antígenos E da Hepatite B/análise , Hepatite C/sangue , Humanos , Interferon Tipo I/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Transaminases/sangueRESUMO
Few data on chronic non-A, non-B hepatitis (NANB-CH) have been published so far in our country. We have studied 85 patients classified into four groups: I. post-transfusional (PT), 35 patients (41.2%); II. risk group (GR), including health professionals and drug addicts, 11 (12.9%); III. sporadic with a well defined beginning (EBD), 19 (22.4%) and IV. sporadic with ill-defined beginning (END), 20 (23.5%). The mean age in group I was significantly higher than in groups II and III. A polyphasic pattern of serum aminotransferases and severe histological forms were observed in all groups. It is concluded that the way of infection has probably no prognostic importance.
Assuntos
Hepatite C , Hepatite Viral Humana , Adolescente , Adulto , Idoso , Criança , Doença Crônica , Feminino , Hepatite C/enzimologia , Hepatite C/etiologia , Hepatite C/patologia , Hepatite Viral Humana/enzimologia , Hepatite Viral Humana/etiologia , Hepatite Viral Humana/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transaminases/sangueRESUMO
Schedule for vaccination against HBV infection has usually been based on three separate injections of 20 mcg of the vaccine by intramuscular route. One of the main shortcomings to its use in large scale programs has been its high cost. Ninety out of 300 health workers were submitted to three injections of 2 mcg of plasma-derived vaccine (PDV) by intradermal (ID) route on days 0, 30, and 180. Anti-HBs was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third dose, a non-significant difference. However, levels above 10 times the cut-off were observed in 29 (32.2%) and 77 (85.5%), respectively (p less than 0.001). The results showed that a low-dose schedule is effective when used in health workers and should be tried with other risk groups.