ABSTRACT
Nucleos(t)ide analogues (NAs), which are widely used as the first-line anti-hepatitis B virus (HBV) drugs in clinical practice, can effectively inhibit the replication of HBV DNA, significantly slow down disease progression in chronic hepatitis B (CHB) patients, and reduce the development of end-stage liver diseases such as liver failure and liver cancer. However, for some CHB patients receiving first-line NAs for 48 weeks or longer, serum HBV DNA is still persistently or intermittently higher than the lower detection of limit of sensitive nucleic acid detection reagents. After discussion by the authors, low-level viremia (LLV) is defined as follows: persistent LLV refers to the condition in which CHB patients, who receive entecavir, tenofovir disoproxil fumarate, or tenofovir alafenamide fumarate for ≥48 weeks, test positive for HBV DNA by two consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml; intermittent LLV refers to the condition in which patients test positive for HBV DNA intermittently by at least three consecutive detections with sensitive quantitative PCR, with an interval of 3-6 months, but have an HBV DNA level of ＜2000 IU/ml. For the diagnosis of LLV, the issues of poor compliance and drug-resistant mutations should be excluded. LLV might be associated with the increased risk of progression to liver fibrosis or hepatocellular carcinoma in patients with liver cirrhosis under NA treatment, but there are still controversies over whether the original treatment regimen with NAs should be changed after the onset of LLV. This article summarizes the incidence rate of LLV under NA treatment and the influence of LLV on prognosis and analyzes the possible mechanisms of the osnet of LLV, so as to provide a reference for the management of LLV in patients treated with NAs.
ABSTRACT
In order to investigate the effect of anti-hepato-cellular carcinoma of HSV-tk suicide gene system, we constructed the HSV - tk recombinant retroviral vector pLXT. SMMC - 7721 hepatocellular carconoma cells more transfected with pLXT by lipofectin were obtained by subsequent G418 screen. 3H-TdR incorparation assay showed that HSV - tk/ACV had strong cytotoxic effect on HSV - tk gene transfected tumor cells. Lipofectin pLXT complex was directly injected into murine H22 hepatoma tissue, followed by delivery of ACV prodrup, and it was found that the tumor growth masses more greatly reduced. Animals treated with Liptk + ACV and tk + ACV had an apparent reduction of tumor size as compared with the animals in other six groups ( P