Abstract
The effectiveness of antiviral treatments of chronic hepatitis B has been poorly studied in Brazil. Here, hepatitis B virus (HBV) DNA positivity, drug resistance mutations and their association with HBV genotypes were evaluated in chronically HBV-infected patients under different drug regimens in Brazil. The study involved 129 patients under interferon or nucleos(t)ide analogue therapy for a median treatment time of 12 months. One hundred and five (81%) of these patients were treated with lamivudine (LAM), either in monotherapy or in combination with newer drugs, such as entecavir (ETV) or tenofovir (TDF). High (37.5-100%) rates of HBV DNA positivity were observed with all but one drug regimen (LAM + ETV). However, patients that were treated with ETV alone, TDF alone or with LAM combination therapies had a mean viral load that was 3-4 log lower than patients treated with LAM monotherapy. Of the patients treated with LAM, 47% developed resistance mutations. HBV genotypes A (59.1%), D (30.3%) and F (9.1%) were found. There was no association between the presence of LAM resistance mutations and genotypes, HBeAg status or treatment duration. Nevertheless, the rtM204V mutation was observed more frequently (12/13, 92%) in genotype A than in the others (p = 0.023). Six out of nine isolates that contained the rtM204I mutation belonged to genotype D and half of them displayed a single mutation. Genotype D isolates with the rtM204V variant preferentially displayed a triple mutation, while genotype A preferentially displayed a double mutation (p = 0.04).
Highlights
Hepatitis B virus (HBV) infection constitutes a major problem of public health
As the effectiveness of antiviral treatments against chronic hepatitis B in Brazil has been poorly studied, the aims of the present study were to evaluate the overall efficiency of each therapy in reducing hepatitis B virus (HBV) DNA levels, the frequency of drug-resistant isolates and to establish an association of the type of mutation with the HBV genotypes that are circulating in Brazil
Patients’ demographic, clinical and virological characteristics associated with the detection of hepatitis B virus (HBV) DNA
Summary
Hepatitis B virus (HBV) infection constitutes a major problem of public health. An estimated 350 million people worldwide are chronically infected with HBV and are exposed to a progressive disease that may lead to liver cirrhosis and hepatocellular carcinoma (HCC) (WHO 2008, Wiegand et al 2010). Advances in the antiviral therapy against chronic hepatitis B occurred during the last decade, as nucleos(t)ide analogue (NA) drugs were developed. These drugs provided a treatment option other than interferon-alpha (IFN-α). Available data indicate that the best treatment for patients with LAM resistance is to continue LAM and add on ADV or TDF (Zoulim & Locarnini 2009). The current protocol has established national guidelines for the treatment of chronic hepatitis B that incorporates ADV, ETV and TDF as antiviral drugs provided by the government in addition to IFN-α and LAM. Through a systematic review of the literature, the patterns of LAM resistance mutations associated with HBV genotypes, genotypes A-D, have been studied (Damerow et al 2010)
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