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      Randomised clinical trial: 48 weeks of treatment with tenofovir amibufenamide versus tenofovir disoproxil fumarate for patients with chronic hepatitis B

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          Summary

          Background

          Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF).

          Aim

          To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB).

          Methods

          We performed a randomised, double‐blind, non‐inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities.

          Results

          We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non‐inferiority criterion was met in all analysis sets. In the HBeAg‐positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAg‐negative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip ( P < 0.001) and spine ( P < 0.001), and a smaller increase in serum creatinine at week 48 ( P < 0.05). Other safety results were similar between groups.

          Conclusion

          TMF was non‐inferior to TDF in terms of anti‐HBV efficacy and showed better bone and renal safety. (NCT03903796).

          Abstract

          In a double‐blind, randomised placebo‐controlled trial, Tenofovir amibufenamide proved its non‐inferior anti‐HBV efficacy to tenofovir disoproxil fumarate and showed better bone and renal safety.

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          Most cited references44

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          EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection.

          Hepatitis B virus (HBV) infection remains a global public health problem with changing epidemiology due to several factors including vaccination policies and migration. This Clinical Practice Guideline presents updated recommendations for the optimal management of HBV infection. Chronic HBV infection can be classified into five phases: (I) HBeAg-positive chronic infection, (II) HBeAg-positive chronic hepatitis, (III) HBeAg-negative chronic infection, (IV) HBeAg-negative chronic hepatitis and (V) HBsAg-negative phase. All patients with chronic HBV infection are at increased risk of progression to cirrhosis and hepatocellular carcinoma (HCC), depending on host and viral factors. The main goal of therapy is to improve survival and quality of life by preventing disease progression, and consequently HCC development. The induction of long-term suppression of HBV replication represents the main endpoint of current treatment strategies, while HBsAg loss is an optimal endpoint. The typical indication for treatment requires HBV DNA >2,000IU/ml, elevated ALT and/or at least moderate histological lesions, while all cirrhotic patients with detectable HBV DNA should be treated. Additional indications include the prevention of mother to child transmission in pregnant women with high viremia and prevention of HBV reactivation in patients requiring immunosuppression or chemotherapy. The long-term administration of a potent nucleos(t)ide analogue with high barrier to resistance, i.e., entecavir, tenofovir disoproxil or tenofovir alafenamide, represents the treatment of choice. Pegylated interferon-alfa treatment can also be considered in mild to moderate chronic hepatitis B patients. Combination therapies are not generally recommended. All treated and untreated patients should be monitored for treatment response and adherence, and the risk of progression and development of complications. HCC remains the major concern for treated chronic hepatitis B patients. Several subgroups of patients with HBV infection require specific focus. Future treatment strategies to achieve 'cure' of disease and new biomarkers are discussed.
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            Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance.

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              The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level : Results From the Global Burden of Disease Study 2015

              Importance Liver cancer is among the leading causes of cancer deaths globally. The most common causes for liver cancer include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection and alcohol use. Objective To report results of the Global Burden of Disease (GBD) 2015 study on primary liver cancer incidence, mortality, and disability-adjusted life-years (DALYs) for 195 countries or territories from 1990 to 2015, and present global, regional, and national estimates on the burden of liver cancer attributable to HBV, HCV, alcohol, and an “other” group that encompasses residual causes. Design, Settings, and Participants Mortality was estimated using vital registration and cancer registry data in an ensemble modeling approach. Single-cause mortality estimates were adjusted for all-cause mortality. Incidence was derived from mortality estimates and the mortality-to-incidence ratio. Through a systematic literature review, data on the proportions of liver cancer due to HBV, HCV, alcohol, and other causes were identified. Years of life lost were calculated by multiplying each death by a standard life expectancy. Prevalence was estimated using mortality-to-incidence ratio as surrogate for survival. Total prevalence was divided into 4 sequelae that were multiplied by disability weights to derive years lived with disability (YLDs). DALYs were the sum of years of life lost and YLDs. Main Outcomes and Measures Liver cancer mortality, incidence, YLDs, years of life lost, DALYs by etiology, age, sex, country, and year. Results There were 854 000 incident cases of liver cancer and 810 000 deaths globally in 2015, contributing to 20 578 000 DALYs. Cases of incident liver cancer increased by 75% between 1990 and 2015, of which 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, HBV accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), HCV for 167 000 (21%), and other causes for 133 000 (16%) deaths, with substantial variation between countries in the underlying etiologies. Conclusions and Relevance Liver cancer is among the leading causes of cancer deaths in many countries. Causes of liver cancer differ widely among populations. Our results show that most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use. In line with the Sustainable Development Goals, the identification and elimination of risk factors for liver cancer will be required to achieve a sustained reduction in liver cancer burden. The GBD study can be used to guide these prevention efforts. This data analysis of the Global Burden of Disease 2015 study on primary liver cancer reports incidence, mortality, and disability-adjusted life-years for 195 countries or territories from 1990 to 2015, and presents global, regional, and national estimates on the burden of liver cancer. Question What is the burden of liver cancer globally, what are the major risk factors for liver cancer across countries, regions, and at the global level and how did these change between 1990 and 2015? Findings There were 854 000 incident liver cancer cases and 810 000 deaths globally in 2015, contributing to 20 578 000 disability-adjusted life-years. Hepatitis B virus infection accounted for 265 000 liver cancer deaths (33%), alcohol for 245 000 (30%), hepatitis C virus infection for 167 000 (21%), and other causes for 133 000 (16%) deaths. Meaning Most cases of liver cancer can be prevented through vaccination, antiviral treatment, safe blood transfusion and injection practices, as well as interventions to reduce excessive alcohol use.
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                Author and article information

                Contributors
                junqiniu@aliyun.com
                jlhousmu@163.com
                Journal
                Aliment Pharmacol Ther
                Aliment Pharmacol Ther
                10.1111/(ISSN)1365-2036
                APT
                Alimentary Pharmacology & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0269-2813
                1365-2036
                29 September 2021
                November 2021
                : 54
                : 9 ( doiID: 10.1111/apt.v54.9 )
                : 1134-1149
                Affiliations
                [ 1 ] Guangzhou China
                [ 2 ] Changchun China
                [ 3 ] Urumchi China
                [ 4 ] Changsha China
                [ 5 ] Chongqing China
                [ 6 ] Fuzhou China
                [ 7 ] Liuzhou China
                [ 8 ] Guangzhou China
                [ 9 ] Changsha China
                [ 10 ] Xinxiang China
                [ 11 ] Chengdu China
                [ 12 ] Chongqing China
                [ 13 ] Zunyi China
                [ 14 ] Zhengzhou China
                [ 15 ] Changsha China
                [ 16 ] Harbin China
                [ 17 ] Hefei China
                [ 18 ] Tianjin China
                [ 19 ] Chongqing China
                [ 20 ] Lianyungang China
                Author notes
                [*] [* ] Correspondence

                Jinlin Hou, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.

                Email: jlhousmu@ 123456163.com

                Junqi Niu, Department of Hepatobiliary and Pancreatology of The First Hospital of Jilin University, Jilin, China; No. 71, Xinmin Street, Zhaoyang District, Changchun City, Jilin Province, China.

                Email: junqiniu@ 123456aliyun.com

                Author information
                https://orcid.org/0000-0003-1142-3589
                https://orcid.org/0000-0002-8523-1689
                https://orcid.org/0000-0001-8803-4069
                https://orcid.org/0000-0001-8481-0841
                https://orcid.org/0000-0002-9857-6520
                https://orcid.org/0000-0001-8230-8583
                Article
                APT16611
                10.1111/apt.16611
                9292801
                34587302
                ec6d3362-9f5d-43b1-bcaa-45672bbc56af
                © 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 10 June 2021
                : 04 June 2021
                : 07 September 2021
                Page count
                Figures: 5, Tables: 5, Pages: 16, Words: 11268
                Funding
                Funded by: Hansoh Pharmacy Co.
                Categories
                Superfast
                Randomised Clinical Trials
                Custom metadata
                2.0
                November 2021
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.1.7 mode:remove_FC converted:18.07.2022

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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