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      Lamivudina por tempo prolongado no tratamento da hepatite B crônica no estado de Mato Grosso Translated title: Long-term use of lamivudine for treating chronic hepatitis B in the State of Mato Grosso

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          Abstract

          Para avaliar resultados do tratamento da hepatite B crônica com lamivudina, 100mg ou 150mg diários, foram acompanhados 34 pacientes em um serviço em Cuiabá, Mato Grosso. Entre os 34, 21 (62%), eram cirróticos e 24 (70%) HBeAg positivos. Genótipo viral foi determinado em 18, sendo predominante o genótipo A (12). O acompanhamento teve mediana de 27 meses (7 a 64). Do total, 23 (67%) apresentaram resposta bioquímica entre dois e 24 meses de tratamento. Dos 24 pacientes com positividade para o HBeAg, 13 (54%) apresentaram negativação do HBeAg durante o acompanhamento. Entre os anti-HBe positivos, 70% tiveram normalização das aminotransferases. Quatorze (41%) não apresentaram resposta bioquímica ou sorológica de início ou apresentaram breakthrough. Em seis dos que não responderam, foram encontradas as mutações L180M e M204V. Quatro pacientes faleceram após pelo menos 21 meses de lamivudina e três cirróticos desenvolveram hepatocarcinoma após 24 meses. A partir do terceiro ano surgiram complicações, como hepatocarcinoma ou hemorragia digestiva. Os presentes achados sugerem que resposta precoce ao tratamento com lamivudina pode estar associada a um melhor controle da hepatite B crônica.

          Translated abstract

          To assess the results from lamivudine treatment (100 mg or 150 mg) for chronic hepatitis B, 34 patients were followed at a clinic in Cuiabá, Mato Grosso, Central Brazil. Among them, 21 (62%) had liver cirrhosis and 24 (70%) were HBeAg-positive. The viral genotype was determined for 18 patients, among whom genotype A was the most prevalent (12). The median follow-up was 27 months (range from 7 to 64 months). Among the total, 23 (67%) presented a biochemical response after 2 to 24 months of treatment. Among the 24 HBeAg-positive subjects, 13 (54%) became HBeAg-negative during the follow-up. Among the anti-HBe-positive patients, 70% obtained normalization of aminotransferase levels. Fourteen (41%) did not present any initial biochemical or serological response or presented breakthrough. The L180M and M204V mutations were found in six of the non-responders. Four patients died after at least 21 months of lamivudine and three patients with liver cirrhosis developed liver cancer after 24 months. From the third year onwards, complications such as digestive system hemorrhage or liver cancer started to emerge. The present findings suggest that an early response to lamivudine treatment may be associated with better control over chronic hepatitis B.

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          Disease progression and hepatocellular carcinogenesis in patients with chronic viral hepatitis: a prospective observation of 2215 patients.

          The aim of this study was to elucidate the rate of development to cirrhosis and the rate of appearance of hepatocellular carcinoma in chronic viral hepatitis and to assess the risk factors for the development of disease in 2215 consecutive patients with viral hepatitis who were prospectively studied for a median observation period of 4.1 years. The rates of development to cirrhosis were 7.6%, 21.7%, and 32.2%, at the 5th, 10th, and 15th year, respectively. The carcinogenesis rates were 3.4%, 10.5%, and 22.4% at the 5th, 10th, and 15th year, respectively. The appearance rates of cancer in 645 patients with only hepatitis B surface antigen and in 1500 patients with only anti-hepatitis C virus antibodies were 2.1% and 4.8% at the 5th year, 4.9% and 13.6% at the 10th year, and 18.8% and 26.0% at the 15th year, respectively. The proportional hazard model identified that the amount of alcohol intake (p= 0.0002) and the indocyanine green retention rate (p= 0.022) were independently associated with carcinogenesis in hepatitis type B; and stage of hepatitis (p<0.0001), gamma-glutamyl transpeptidase (p= 0.0046), history of blood transfusion (p=0.0093), albumin (p=0.012), and amount of alcohol intake (p= 0.031) were independently associated with the carcinogenesis rate in hepatitis type C. Although the severity of portal fibrosis was closely correlated with the future disease development and carcinogenesis in chronic hepatitis C, it was not a good predictor in chronic hepatitis B. These epidemiological results suggest that there are some differences in the activity and modes of disease progression and cancer promotion between hepatitis B virus infection and hepatitis C virus infection.
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            A preliminary trial of lamivudine for chronic hepatitis B infection.

            Better treatments for chronic hepatitis B are needed. Lamivudine, the (-)enantiomer of 3'-thiacytidine, is a potent inhibitor of hepatitis B virus (HBV). In a double-blind trial, we randomly assigned 32 patients with chronic hepatitis B (including 17 who had no response to earlier treatment with interferon) to receive 25, 100, or 300 mg of oral lamivudine daily for 12 weeks. The patients were then followed for 24 additional weeks. All the patients had hepatitis B antigen in serum. Levels of HBV DNA became undetectable (< or = 1.5 pg per milliliter) in 70 percent of the patients who received the 25-mg dose of lamivudine and 100 percent of those treated with the 100-mg or 300-mg dose. In most patients, HBV DNA reappeared after therapy was completed; however, six patients (19 percent), including five who had not responded to interferon, had sustained suppression of HBV DNA accompanied by normalization of alanine aminotransferase levels. Hepatitis B e antigen disappeared in four of these six patients (12 percent), three of whom had had no response to interferon. Levels of HBV DNA fell in all patients, including those who had had high levels at base line or normal alanine aminotransferase levels at base line, but sustained responses were more likely in patients with initially low HBV DNA levels and high alanine aminotransferase levels. During and after therapy, alanine aminotransferase levels at least doubled in five patients (50 percent) given the 25-mg dose and eight patients (36 percent) given the 100-mg or 300-mg dose. Minor adverse events occurred that were not related to the dose, as did transient, asymptomatic elevations of amylase, lipase, and creatine kinase levels. In a preliminary trial, 12 weeks of lamivudine therapy was well tolerated, and daily doses of 100 mg and 300 mg reduced HBV DNA to undetectable levels.
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              Effect of alpha-interferon treatment in patients with hepatitis B e antigen-positive chronic hepatitis B. A meta-analysis.

              To determine whether alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic hepatitis B virus (HBV) infection. Randomized controlled studies published in the English literature between January 1966 and June 1992 were identified through a MEDLINE computer search. Fifteen randomized controlled studies with a total of 837 adult chronic HBV carriers who were positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were identified. Studies were included if patients were treated for at least 3 months and followed for at least 6 months after cessation of therapy. Overall, the loss of HBsAg occurred 6% more often in interferon-treated patients than the natural seroconversion seen in controls (7.8% compared with 1.8%, P = 0.001), and the loss of viral replication occurred approximately 20% more often in treated patients than in controls (33% compared with 12% for loss of HBeAg and 37% compared with 17% for the loss of HBV DNA, P = 0.0001) if patients received interferon for 3 to 6 months and were followed for 6 to 12 months. Interferon also had a significant treatment effect on the development of antibodies to HBsAg (anti-HBs), antibodies to HBeAg (anti-HBe), and on the normalization of alanine aminotransferase levels. Alpha-interferon is effective in terminating viral replication and in eradicating the carrier state in patients with chronic HBV infection who are HBeAg positive when these patients are treated for 3 to 6 months and followed for 6 to 12 months after cessation of therapy. Follow-up studies are required to determine whether interferon reduces the risk for developing cirrhosis or hepatocellular carcinoma.
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                Author and article information

                Journal
                rsbmt
                Revista da Sociedade Brasileira de Medicina Tropical
                Rev. Soc. Bras. Med. Trop.
                Sociedade Brasileira de Medicina Tropical - SBMT (Uberaba, MG, Brazil )
                0037-8682
                1678-9849
                February 2007
                : 40
                : 1
                : 18-24
                Affiliations
                [01] Cuiabá MT orgnameUniversidade Federal de Mato Grosso orgdiv1Faculdade de Ciências Médicas orgdiv2Núcleo de Estudos de Doenças Infecciosas e Tropicais de Mato Grosso
                [02] RJ orgnameInstituto Oswaldo Cruz orgdiv1Departamento de Virologia orgdiv2Laboratório de Virologia Molecular
                Article
                S0037-86822007000100004 S0037-8682(07)04000104
                10.1590/S0037-86822007000100004
                18cae852-ec46-42dc-881a-908536a48bce

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 08 May 2006
                : 17 January 2007
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 31, Pages: 7
                Product

                SciELO Brazil

                Categories
                Artigos

                Vírus da hepatite B,Tratamento,Lamivudina,Agentes antivirais,Hepatitis B virus,Treatment,Lamivudine,Antiviral agents

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