Research progress of tenofovir dipivoxil in the treatment of hepatitis B

The application of tenofovir fumarate (TDF) in the field of hepatitis B treatment has always been of great concern In November 2018, the imported propofol tenofovir fumarate (TAF) tablet declared by giread was approved by China's CFDA for listing, thus opening a new chapter for the treatment of hepatitis B in China Due to the expiration of TDF's compound patent and crystal patent, and the uncertain prospect of TAF's core patent licensing, domestic enterprises have already set off a wave of imitation application for these two drugs (especially TDF) Based on PubMed's search and literature review, this paper reviews the clinical trials related to the treatment of hepatitis B by TDF and TAF published in 2018, in order to provide more information on the treatment of hepatitis B with tenofovir for domestic pharmaceutical and medical workers 1、 Overall effectiveness and / or safety study 1 Real world single center study to evaluate ETV and TDF in patients with chronic hepatitis B who have been treated or not treated [source] Saudi J castroenterol (influencing factor: 1.52) 2018 Nov Dec; 24 (6): 326-335 [Research Institute / first author unit] Kyunghee University of Korea [research type] real world retrospective study [basic information of subjects] all chronic hepatitis B patients treated with ETV or TDF from January 2007 to January 2017 [main results / Conclusion] both ETV and TDF can produce high complete virological response rate (94.2% vs 91.1%, P > 0.05) There was no difference in the annual incidence of HCC and other sclerosis related complications between the two groups 2 Evaluation of drug resistance of patients with chronic hepatitis B treated with TAF for 96 weeks [source] antimicrob agents chemother (influencing factor: 4.255) 2018 SEP 24; 62 (10) PII: e01064-18 [Research Institute / first author unit] randomized double-blind study [basic information of subjects] by giread science company [research type] 1298 HBeAg positive and negative chronic hepatitis B patients were randomly divided into fumaric acid TAF and TDF groups in a ratio of 2:1 [main results / Conclusion] after 96 weeks of treatment, the proportion of subjects who achieved case suppression in the two groups was similar (HBV DNA < 69 IU / ml), and no substitution related to drug resistance of fumaric acid TAF and TDF was detected 3 Compare the efficacy and safety of lamivudine combined with tenofovir and lamivudine alone in the treatment of HBV / HIV co infection; 15 (1): 139 Doi: 10.1186/s12985-018-1050-3 [Research Institute / first author unit] Chongqing Medical University and other [research type] meta-analysis [basic information of subjects] were included in 11 randomized controlled clinical trials [main results / Conclusion] the effect of lamivudine combined with TDF in the treatment of HBV / HIV co infection is significantly better than that of lamivudine alone 4 Study on Evaluation of 8-year survival of chronic hepatitis B patients treated with ETV or TDF [source] J Hepatol (influencing factor: 14.911) 2018 Jun; 68 (6): 1129-1136 Doi: 10.1016/j.jhep.2018.01.031 EPub 2018 Feb 8 [Research Institute / first author unit] cohort study of [research type] of School of medicine, University of Athens, national kapostria [basic information of subjects] 1951 adult Caucasian patients with chronic hepatitis B who had or did not have compensatory sclerosis and did not have hepatocytes, and had ETV or TDF treatment ≥ 12 months [main results / Conclusion] ETV or TDF treatment can bring excellent overall liver related 8-year survival effect for Caucasian patients with chronic hepatitis B, and its survival characteristics are similar to that of the whole population 5 Comparative study on the efficacy and safety of TAF and TDF in the treatment of HBV infection for 96 weeks [source] J hepatol.2018 Apr; 68 (4): 672-681 Doi: 10.1016/j.jhep.2017.11.039 EPub 2018 Jan 17 [Research Institute / first author's unit] two transnational, randomized and controlled studies [basic information of subjects] of King's College London [research type] [main results / Conclusion] after 96 weeks of treatment, the efficacy of TAF was similar to that of TDF, and its renal and skeletal safety was better than that of TDF 6 Study on Evaluation of HBsAg turning negative after 120 weeks' treatment with TDF and pegylated interferon α - 2A [source] dig dis SCI (influencing factor: 3.29) 2018 Dec; 63 (12): 3487-3497 Doi: 10.1007/s10620-018-5251-9 EPub 2018 Aug 22 [Research Institute / first author unit] Study on open label active drug control of [research type] school of medicine, Yonsei University, Seoul, Korea [basic information of subjects] 740 patients with chronic hepatitis B [main results / Conclusion] in addition, the published data further confirmed the earlier published results, that is, the rate of HBsAg turning negative after TDF combined with pegylated interferon α - 2A (PEG-IFN) treatment was higher than that of the two drugs alone 7 A comparative study of the effects of ETV and TDF on mortality, risk of liver transplantation and risk of liver complications in patients with chronic hepatitis B who have not been treated before [source] J viral hepat (influencing factor: 14.911) 2018 Dec; 25 (12): 1565-1575 Doi: 10.1111/jvh.12971 EPub 2018 Aug 14 [Research Institute / first author unit] school of medicine, Weishan University, South Korea [study type] observational study [basic information of subjects] 1325 patients with chronic hepatitis B whose cumulative compliance to ETV or TDF ≥ 80% [main results / Conclusion] during the 10-year study, there was no significant difference in mortality, incidence of liver transplantation events and incidence of liver complications between TDF group and ETV group 8 Study on the safety and efficacy of long-term treatment of ETV and TDF in hepatitis B patients who have not been treated with nucleoside analogues before [source] Clin res Hepatol castroenterol (influencing factor: 2.62) 2018 Feb; 42 (1): 40-47 Doi: 10.1016/j.clinre.2017.06.008 EPub 2017 Jul 27 [Research Institute / first author unit] University of irdinbayaz, Turkey [study type] a multicenter retrospective study [basic information of subjects] 252 patients with chronic hepatitis B who had not received nucleoside analogue treatment before [main results / Conclusion] in the first year of treatment, the time of HBV DNA reduction in ETV group was earlier than that in TDF group, but the effect of virological suppression in TDF group was better than that in ETV group 9 In summary, there are about 240 million people suffering from chronic hepatitis B in the world The prevalence of chronic hepatitis B varies greatly in different regions, with Africa and Asia having the highest prevalence At present, international guidelines recommend the injection of pegylated interferon (PEG-IFN) or long-term oral administration of third generation nucleoside antiviral drugs such as entecavir (TTV) or tenofovir fumarate (TDF) to control the progress of HBV related liver disease However, the application of PEG-IFN is limited because of many adverse reactions In addition, PEG-IFN has many contraindications (for example, it is forbidden to be used in patients with compensatory disorder HBV associated sclerosis, patients with autoimmune diseases, etc.) In the treatment of chronic hepatitis B, TDF and ETV have a stronger effect of virus inhibition than other antiviral drugs, and the probability of HBV mutation is lower than the latter TDF and ETV can be used in most patients with chronic hepatitis B with good compliance, and have good safety characteristics 2、 Study on the risk of HBV recurrence after discontinuation of drug 1 Study on the comparison of HBV recurrence rate between ETV and tenofovir after discontinuation of drug [source] aliment pharmacolher (influencing factor: 7.36) 2018 Nov 28 Doi: 10.1111/apt.15053 [ePub ahead of print] [Research Institute / first author unit] Changgeng Memorial Hospital, Kaohsiung, Taiwan, China [study type] Retrospective prospective study [basic information of subjects] 342 chronic hepatitis B patients treated with ETV or TDF [main results / Conclusion] the recurrence time of HBV after TDF discontinuation was earlier than that after ETV discontinuation, and its severity was also higher than that of the latter 2 A study to evaluate the effect of hepatitis B surface on the recurrence of hepatitis B virus in patients receiving chemotherapy after prevention with ETV or TDF [source] J gastroenterol Hepatol (influencing factor: 15.04) 2018 Oct; 33 (10): 1766-1772 Doi: 10.1111/jgh.14142 EPub 2018 APR 17 [Research Institute / first author unit] 122 HBeAg positive cancer patients receiving chemotherapy and using ETV or TDF for antiviral prevention in the observational study [study type] of Changgeng Memorial Hospital in Kaohsiung, Taiwan [basic information of subjects] [main results / Conclusion] baseline HBV-DNA level and HBsAg level at the end of treatment can be used to prevent the possibility of virological recurrence after ETV or TDF is used for prevention 3 A 5-year follow-up study to evaluate the effect of ETV or tenofovir alone on the prevention of HBV recurrence in liver transplant recipients [source] dig liver dis (influencing factor: 3.29) 2018 Sep; 50 (9): 944-953 [Research Institute / first author unit] a cohort study [study type] at King's College Hospital in London [basic information of subjects] liver transplantation patients with HBV single infection (group A, n = 69) and HBV / HDV co infection (group B, n = 8) and discontinuation of HBV immunoglobulin ± non nucleoside analogues [main results / Conclusion] during the 5-year follow-up period, 6 (9%) of the patients in group A were re positive for HBsAg after the median 18 months, while no one in group B relapsed Therefore, the patients with HBsAg positive liver transplantation can stop HBV immunoglobulin and switch to ETV or TDF 4 Study on the evaluation of the effect of stopping effective ETV or TDF treatment in non sclerotic HBeAg negative chronic hepatitis B patients before HBsAg turning negative [source] antivirther (influencing factor: 2.15) 2018 Jul 25 Doi: 10.3851/imp3256 [ePub ahead of print] [Research Institute / first author] National School of medicine, University of Athens, kapostria [study type] prospective study [basic information of subjects] 57 hepatitis B patients who stopped treatment after virological rehabilitation (median time 5.3 years) [main results / Conclusion] patients with non sclerotic HBeAg positive chronic hepatitis B who have been treated with ETV or TDF for more than 4 years can stop the corresponding treatment and will not bring safety problems After 6 months, the recurrence rate decreased Although virologic recurrence is common, most patients, especially those with mild to moderate pre-treatment fibrosis, can achieve HBsAg turning negative, and eventually become inactive carriers, so they do not need to be treated again 5 Study to evaluate the probability and predictors of HBV recurrence in patients with chronic hepatitis B after TDF discontinuation [source] J viral hepat (influencing factor: 14.911) may 2018; 25 (5): 590-597 Doi: 10.1111/jvh.12851 EPub 2018 Mar 1 [Research Institute / first author unit] retrospective study of [research type] in the Memorial Hospital of Changgeng, Kaohsiung, Taiwan, China [basic information of subjects] 143 chronic hepatitis B patients without sclerosis who have been treated with TDF before [main results / conclusions] 104 relapses after discontinuation are shown in the table below For HBeAg positive and negative patients, the recurrence probability of HBV can be predicted according to the level of HBsAg at the end of treatment 6 Summary: people with chronic HBV infection may not show any symptoms for several years, so their infection situation and