The Change Of Th1/Th2Cytokine Profile And Its Clinical Significance In The Process Of Antiviral Therapy

【Background and Objective】Hepatitis B is a worldwide disease caused by the hepatitis B virus, which More than7%of the Chinese population are infected with, of these approximately20million arechronic patients. At present, scientific and standardized antiviral therapy has still proved tobe a clinically effective strategy to control hepatitis B disease progression. Numerousstudies have demonstrated that antiviral therapy can relieve the inflammation, necrosis andfibrosis of the liver by lowering viral load and improving liver function, therebysignificantly reducing the incidence of hepatic decompensation, hepatocellular carcinomaand liver disease-related death.The accepted anti-HBV drugs include the nucleoside/nucleotide analogues (such aslamivudine, telbivudine, adefovir dipivoxil, entecavir Cabey, etc.) and the interferonagents(such as interferon-a, pegylated interferon, etc.). NAs exert their negative functionsby inhibiting the replication of HBV directly. While IFNs work against the hepatitis B virusby stimulating the function of the immune-system, in addition to its direct anti-viral effects.In detail, the two types of drugs have vastly different mechanisms. By interacting with their specific receptors, IFNs induce the cells to produce a largeamount of anti-viral proteins in response to new viral infections. Meanwhile, IFNs mayserve to active the cytolytic activity of NK cells, T cells and macrophages, leading to theup-regulation of an anti-viral immune response. Advantages of interferon include a lack ofdrug resistance, a finite and defined treatment course, and a higher rate of HBeAgseroconversion. But from the negative perspective, interferon-based therapy can be poorlytolerated, mainly because of the high incidence of flu-like symptoms, the need to give themedication as a subcutaneous injection, and a number of serious adverse effects(such asbone marrow suppression, psychiatric disturbances, etc.)Nucleos(t)ide analogues stop viral DNA Polymerase by working as chain terminators.Compared to IFNs, NAs have several important advantages: oral formulations, convenientonce-daily dosing, excellent tolerance, and low rate of adverse effects. However, the majordisadvantages of oral antiviral are the often prolonged and indeterminate duration oftherapy and the potential emergence of drug resistance.Although Factors affecting anti-viral treatment outcomes are complicated, a largenumber of studies have shown that the change of immune function during the anti-viraltreatment are essential to determine the drug efficacy and disease severity.CD4+helper T cells play an important role in regulating cellu-mediated immunity aswell as humoral immunity. Depending on the spectrum of cytokine secretion, there are twosubtypes of helper T cells known as Th1and Th2cells. Th1cells produce IL-2, IFN andTNF and other Th1type cytokines, promoting Cellular immune. While Th2cells secrete IL-4, IL-6, IL-10and other Th2type cytokines, stimulating humoral immunity. The mutualadjustments and balance between these two types of cells are required to provideour body with resistance to disease.Recent data have indicated that a Th1/Th2imbalance exists in patients withchronic HBV infection: the function of the Th1cell is inhibited, while that of the Th2cell is enhanced. But there are rare research reporting the relationship between the changes ofTh1/Th2cytokine balance the clinical efficacy on the patients with chronic hepatitis Bduring the course of antiviral therapyTraditionally, Enzyme-linked immunosorbent assay (ELISA) is a popular is methodfor the quantitative detection of cytokine levels. But it is not conducive to analysis thebody’s overall immune status, because each ELISA plate can measure only one cytokine ata time for a given sample. The innovative Cytometric Bead Array(CBA) technology allowsfor quantitative detection of multiple analyses in a single serum. Due to its high sensitivityand reproducibility compared to ELISA technique, CBA is developed suitably for thesystematic analysis of the immune status on patients.To gain more insight into the relationship between the Th1/Th2cytokine balance andantiviral efficacy during the telbivudine treatment of chronic hepatitis B patients, the goalof this study is dynamic monitoring into the levels of serum Th1/Th2cytokines using CBAtechnology, relied on a Clinical trials whose purpose is Evaluating the safety and efficacy oftelbivudine600mg tablets in Chinese patients with chronic hepatitis B.【Methods】In this study,48patients received telbivudine tablets600mg once-daily oral for48weeks and their serum samples were collected at baseline and during treatment.on12thweek,24th week,36th week and48th week.CBA technique was used to detect the level ofIL-2, IL-4, IL-6, IL-10, TNF and of IFN in serum. Then the data was grouped andanalyzed correlation with clinical data in the sense of virologic response and serologicalresponse at48th weeks respectively.【Result】1. Clinical efficacy: of the48patients after48weeks of telbivudine treatment,27cases achieved complete virological response,15cases did partial virologic responsewithout viral breakthrough,6cases occur viral breakthrough at48th week, and12patients had sustained HBeAg seroconversion.2. In the early period of antiviral treatment, the level of Th1type cytokines in serumhad no significant changes, while Th2cytokines is decreasing. The immune balance tendedto Th1side. Later, Th1cytokines showing a downward trend, the Th1/Th2cytokine balancegradually resorted to the pre-treatment state.3. In the sense of virological response, patients were classified into three groups:complete virological response, partial virologic response. In the group of complete response,there are no significant changes in Th1cytokine but gradual decline in Th2cytokines. Theimmune function of Th cell shifted to Th1side, especially in the early stage of the treatment.In partial virological response group, there are no significant changes in Th2cytokine butgradual decline in Th1cytokines.4.In the sense of serological response, there is no significant difference in Th1/Th2cytokine balance between different groups during treatment.【Conclusions】In this study, we made a dynamic detection of the serum Th1/Th2cytokines in48HBV patients who accepted telbivudine treatment for48weeks. Our results demonstratedthat there was a high correlation between the balance of Th1/Th2cytokines and the virusclearance ability. The Th1mode could help attack hepatitis B viruses; in contrast, the Th2mode did not. In addition, the trends of immune status on treatment at week12had apotential value to predict the long-term antiviral efficacy.