Comparison Of The Effects Of The Antiviral Treatment Of Entecavir With Telbivudine On The Health-realted Quality Of Life In Patients With Chronic Hepatitis B

BackgroundPublic has thought no disease equals to health since the18th century, under the guide of traditional biomedical model, drug research, development and usage was only focused on efficiency and security. With the change of disease spectrum and the development of society, public know more about health. People become realize that the purpose of therapy is not only prolonging life but also improving patients’ quality of life. Health-related Quality of Life (HRQOL) should be paid more attention in clinical medical service.Nowerdays, HRQOL plays an important role in measurement of health items, and is used as the necessary part in the evaluation of clinical therapies.Chronic hepatitis B(CHB) is a globle common infection characterized by long course of disease, low cure rate and great individual difference,which becomes an enormous health burden. Approximately one third of general population in the world has serological evidence of present or past infection with hepatitis B virus(HB V) and more than350million people are chronic hepatitis B surface antigen (HBsAg) carriers. CHB is one of the serious problems of public health in our country, of which damage to people’s health can not be ignored, as it could develop into liver cirrhosis or even hepatocellular carcinoma. Because of the low cure rate, the toxicity and side effects of drugs, the huge economic burden, and the low acceptance from public, these all release CHB patients’ HRQOL. At home and abroad, some research on CHB patients’ HRQOL has been taken which reveal HBV carriers and CHB patients always have negative emotion such as depression, anxiety and so on, and their HRQOL are all at a low lever. Now, many guidelines point out that HRQOL should be an important aspect of the overall management of HBV infection as one goal of therapy for CHB and a new standard of efficacy assessment, only in this way can it present the comprehensiveness and integrity for therapy. Thus facilitating the establishment of more rational antiviral treatment scheme.The2009CHB guideline compiled by AASLD showed that lamivudine, adefovir, entecavir, telbivudine and tenofovir(not to sell in mainland China) could be chosen as the preferred drugs for therapy of CHB. Because the drug resistance rate of lamivudine monotherapy and adefovir monotherapy is high, enticavir and telbivudine become to the two widely used nucleoside analogues as antiviral treatment for CHB, and a number of studies have showed their respective predominance in efficacy, while the difference in increasing HRQOL is still not confirmed.A number of studies have shown impaired HRQOL in patients with CHB comparing with general population. Rational antivival treatment especially nucleoside analogues will not only suppress HBV replication and improve liver function, but also increase the patients’ HRQOL. while the difference in increasing HRQOL is still not confirmed.ObjectiveBy comparing effects of the antiviral treatment of entecavir with telbivudine on HRQOL in patients with CHB, the changes of patients of physical, psychological and social and the improvement on HRQOL can be measured. The assessment of clinical outcome will expand to the HRQOL, and it will help us to judge and formulate reasonable and economic treatment from different angles. Therefore, the Introduction of assessment of HRQOL is an important complement of evaluation of CHB antiviral treatment, it is also one of the selection basis of antiviral therapy drugs.MethodRefer to the guidelines of CHB therapy and the related literatures, the inclusion and exclusion criteria of the objects were made. This study used the36-item Short Form Health Survey (SF-36) developed by the institution of MOS in Boston, United States to measure the HRQOL of CHB patients, and the SF-36has good reliability and validity which tested by many reaserches. In accordance with the above standards and using the related measuring instruments in prospective cohort study and cross-sectional survey at the same time, fully compared the effects of entecavir with telbivudine on HRQOL in patients with CHB.1. Study population1.1Cross-sectional studyThe study was conducted from July2011to March2012at Nanfang hospital in Guangzhou. The patients rolled in were administrated with orally with0.5mg of entecavir(Squibb,0.5mg/tablet) monotherapy daily or orally600mg of telbivudine(Novartis,600mg/tablet) monotherapy daily respectively at that time.1.2Prospective cohort studyThe study was conducted from July2011to January2013at Nanfang hospital in Guangzhou. Those patients diagnosed as HBeAg-positive were proposed to be administered with orally with0.5mg of entecavir(Squibb,0.5mg/tablet) monotherapy daily or orally600mg of telbivudine (Novartis,600mg/tablet) monotherapy daily respectively, who did not accept any antiviral therapy.2. The inclusion criteriaAll subjects aged18to65years old who were diagnosed as HBeAg-positive CHB met the criterion of APSAL and Chinese guideline, and HBsAg-positive at least6months. Other inclusion criteria at screening were serum HBV DNA levels of51og10copies/ml or higher, the serum alanine aminotransferase (ALT) level of2to10the upper limit of normal (ULN). 3. The Exclusion criteriaExclusion criteria included co-infection with HCV, HIV or HDV, CHB patients who had already established decompensated cirrhosis, HCC or other severe organic diseases. Pregnant women and the patients with psychologic or psychotic disorders and immunopathy were excluded. Those patients who had bad compliance or lost to follow-up were excluded too.4. InstrumentsThe SF-36is a commonly used generic measurement of HRQOL with good reliability and validity. It measures eight scales including general health (GH), physical functioning (PF), role physical (RP), role-motional (RE), bodily pain (BP), social functioning (SF), vitality (VT) and mental health (MH). Each scale score is given by the summations of item scores of the same scale, which is transformed into a range from0to100, with higher scores indicating better HRQOL.5. Clinical indicatorsApart from SF-36, biochemistry (ALT), Virology indicators (HBV-DNA) and serology(HBsAg,HBeAg和HBeAb) were the important clinical indicators. When ALT<40u/L, HBV DNA≤1000copies/ml or less, and HBeAg-negative and HBeAb-positive imply immune responses.6. Survey methodSF-36questionares were completed by patients, the investigator could explain to some problems which is not clear, but did not put forward any revulsive questions. Clinical datas were obtained by patients’ medical records and relevant test results.Result1. Cross-sectional study1.1HRQOL of CHB patientsAt week12of antiviral treatment, there were not significant differences between the two agents groups on the scores of SF-36and all the scales(P>0.05). At week24, the group of entecavir was significant higher on the scores of SF-36, role physical, role emotional and bodily pain(P<0.05). At week48, the group of entecavir was significant higher on bodily pain and vitality (P<0.05).At week96, the group of entecavir was significant higher on physical functioning(P<0.05).1.2Clinical characteristicsThere were not significant differences in ALT normalization and Virological response during each compared group.1.3Adverse EventsThere were totally two adverse events happened in the group of entecavir(one in week12and other in week96) presented as fatigue and malaise, headache and chest distress, upper respiratory tract infection and abdominal pain. While there were totally thirteen adverse events happened in the group of telbivudine(one in week12, three in week24, six in week48and three in week96) presented as fatigue and malaise, muscular soreness, upper respiratory tract infection and nausea and vomiting. Among them, seven adverse events were muscular soreness with increased in blood levels of creating kinase. According to the statistical analysis, there was a significant difference between the two groups which the adverse events incidence of entecavir group was predominant lower than telbivudine group(P-value:0.003).2. Prospective cohort study2.1HRQOL of CHB patientsAt week12of antiviral treatment, there were not significant differences between the two agents groups on the scores of SF-36and all the scales(P>0.05). At week24, the group of entecavir was significant higher on the scores of SF-36, physical function, role physical, role emotional and bodily pain(P<0.05). At week48, the group of entecavir was significant higher on the scores of SF-36, bodily pain and vitality (P<0.05).2.2Clinical characteristicsThere were not significant differences in ALT normalization, Virological response and HBeAg seroconversion during each compared group, except the HBeAg seroconversion rate of the group of telbivudine which was substantial higher than entecavir at week48(P=0.045). 2.3Adverse EventsThere were totally three adverse events happened in the group of entecavir(two in week12and one in week24, respectively) presented as fatigue and malaise, headache and chest distress, and upper respiratory tract infection. While there were totally fifteen adverse events happened in the group of telbivudine(three in week12, four in week24, eight in week48) presented as fatigue and malaise, muscular soreness, nausea and vomiting, upper respiratory tract infection, and abdominal pain. Among them, seven adverse events were muscular soreness with increased in blood levels of creating kinase. According to the statistical analysis, there was a significant difference between the two groups which the adverse events incidence of entecavir group was predominant lower than telbivudine group(P-value:0.037).3. Control StudyThere were not differences among the groups of enteavir, telbivudine and the healthy control on HRQOL at week48, except the scale of bodily pain which were significant different among the three groups.ConclusionNucleoside analogues are the reasonable choice of a longtime therapy, for convenience, high adherence, good tolerance and curative effect, and are suitable for different stages of liver disease. Though, CHB patients’ HRQOL have increased which were still lower than healthy controls. It release that continuously long period of treatment and active, positive, health education and psychological tutoring can help those patients to improve their HRQOL. The comparison of HRQOL reveals entecavir can improve the HRQOL of patients with CHB better than telbivudine, and achieve the desired effect, which provides a basis for the reasonable selection of clinical treatment.The health-related quality of life and the evaluation of drugs were combined in this study which compared enticavir with telbivudine on HRQOL in the patients with CHB by SF-36. Evaluation of the effects of antiviral drugs from the perspective of HRQOL provides the basis for clinical rational drug selection. So the introduction of health related quality of life evaluation index is the important supplement of the assessment of CHB antiviral treatment, it is also one of the basis of antiviral therapy.