Until recently, the only generally approved treatment for chronic hepatitis B was alpha-interferon; however, it gives only moderate efficacy in terms of sustained response (biochemical, virological and histological). In fact, only 20% to 40% of treated patients respond to therapy, with lower percentages (~ 10%) among patients infected with precore-mutant strains of HBV (HBeAb HBV-DNA positive). The FDA of the USA approved the use of lamivudine in adult patients affected by chronic hepatitis B in 1998. In this review, we focused on the pharmacokinetic and pharmacodynamic properties and efficacy and tolerability of lamivudine in the treatment of chronic hepatitis B cases that are both HBeAg and anti-HBe-positive.
Visceral leishmaniasis (VL) or kala-azar is an infection disease caused by hemiflagellate protozoan parasites (Leishmania donovani) and transmitted to humans by the phlebotomine sandfly. Leishmaniasis is distributed worldwide and 13 million people are estimated to be infected, with about 1.8 million new cases each year. All antileishmanial drugs are toxic and most have to be used parenterally for prolonged period. The therapy has been further complicated by large number of infected children and declining effectiveness of pentavalent antimonial compounds. Although the lipid formulations of amphotericin B are an important advance in therapy, their high cost precludes their use. Miltefosine, a phosphocholine analogue originally developed as antimalignant drug, has been found to be highly active against Leishmania in vitro and in animal model. Based on these experiences this drug was tried against human visceral leishmaniasis and found to be highly effective in children. The aim of this review is to evidence the pharmacodymamic and pharmacokinetic characteristics and the safety, tolerance and efficacy of this drug for treatment of visceral leishmaniasis in children.
This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBVgenotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7%) resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37) and 12 (85.7 %) came from Brazil, while 2 (14.3%) came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312) and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648). Genotype distribution was as follow: genotype D, 9 (64.2%), genotype A, 5 (35.8%). All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.
BACKGROUND: The genetic heterogeneity of the HBV genome has been established and eight genotypes can be classified according to the criterion of >8% differences in the complete nucleotide sequence of the viral genome. AIMS: To evaluate the prevalence of HBV-infection in a population of immigrants and to determine in patients with detectable serum HBV-DNA the HBV-genotypes. METHODS: Between January 2005 and December 2005 a total of 556 immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV) were evaluated. In patients with detectable serum HBV DNA, the HBV-genotype was determined by INNOLiPA. RESULTS: Among the 556 subjects tested, 60 (10.7%) resulted HBsAg positive. All were men, and 42 (70%) come from Africa, 10 (16.6%) from Asia and 9 (14.4%) from East-Europe. 28/60 (46.6%) patients presented normal ALT levels (<40 IU/L) and undetectable serum HBV DNA (<100 copies/mL in real-time PCR), while 32 (53.4%) patients had ALT levels above laboratory normal values and detectable serum HBV DNA. Genotype distribution was as follow: genotype E, 16 (50%), genotype D, 9 (28.1%), genotype A, 7 (21.9%). CONCLUSION: Our study evidences a moderate prevalence of HBV-infection in immigrants, particularly in sub-Saharan African people, and the potentiality of migratory flow in the introduction of genotype non-D hepatitis B virus, potentially characterized by a different natural history and, possibly, a different response to antiviral treatment.
RACIONAL: A heterogeneidade do genoma do vírus da hepatite B (VHB) foi estabelecida e oito genótipos podem ser classificados de acordo com o critério de diferenças de percentagem maior ou igual a 8 na seqüência completa do nucleotídeo do genoma vira!. OBJETIVOS: Verificar a prevalência da infecção pelo vírus da hepatite B (VHB) em uma população de imigrantes na Itália e determinar os genótipos do VHB em pacientes com níveis séricos detectáveis do VHB-DNA. MÉTODOS: Entre janeiro e dezembro de 2005, o total de 556 imigrantes foram testados para o HbsAg. Se positivos, a atividade bioquímica e viral da infecção e a possível presença de co-infecções (HVC, HVD e HIV) foram examinadas. Nos pacientes positivos para o VHB-DNA, o genótipo do VHB foi determinado pelo método INNOLiPA. RESULTADOS: Entre os 556 pacientes, 60 (10,7%) tinham HbsAg positivo. Todos eram do sexo masculino e 42 (70%), provenientes da África, 10 (16,6%) da Ásia e 9 (14,4%) do Leste Europeu. 28/60 (46,6%) apresentaram níveis de ALT normais (<40 UI/L) e soro negativo ou indetectável para o VHB-DNA (<100 copies/mL PCR "real-time"), enquanto 32 (53,4%) tinham níveis mais elevados de ALT e soro positivo para VHB-DNA. A distribuição do genótipo foi a seguinte: genótipo E, 16 (50%), genótipo D, 9 (28,1%), genótipo A, 7 (21,1%). CONCLUSÃO: O estudo evidencia a prevalência moderada do HVB em imigrantes, particularmente na população africana, sub-Sahara e o potencial fluxo migratório na introdução da hepatite B, genótipo não-D, potencialmente caracterizada pela história natural e possivelmente levar à diferença no tratamento anti-viral.