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Shu R, Tian S, Qu W, Yang J, Shi W, Li X, Zou T, Jiang C, Zhang Y, Yang Z, Tian H, Yang H, Fu J, She ZG, Li H, Zhang XJ. Hepatoprotective drug screening identifies daclatasvir a promising therapeutic candidate for MASLD by targeting PLIN2. J Lipid Res 2025:100835. [PMID: 40449734 DOI: 10.1016/j.jlr.2025.100835] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 05/22/2025] [Accepted: 05/27/2025] [Indexed: 06/03/2025] Open
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) has become global health challenges with limited therapeutic strategy. Here, the present study aims to identify promising drug candidates for MASH and to clarify their pharmacological mechanism. By an extensive screening of FDA-approved hepatoprotective medicines using a PA/OA-stimulated hepatocytes model, we identified daclatasvir showing potent anti-MASH capacity against hepatic steatosis deposition and inflammatory response. The hepatoprotective benefits of daclatasvir was further validated in MASH mouse models, induced by a high-fat high-cholesterol (HFHC) diet for 16 weeks or a methionine-choline-deficient (MCD) diet for 4 weeks, as supported by markedly improved histopathological characteristics, serum biochemical level, and transcriptomic analyses. Using the molecular docking assay followed by isothermal titration calorimetry confirmation, we identified that daclatasvir functions as a new perilipin-2 (PLIN2) inhibitor by interrupting its stability. In specific, PLIN2 subjected to MARCH6-mediated protein degradation in a K11-type ubiquitination. Daclatasvir can directly bind to PLIN2 and enhance its interaction with MARCH6, leading to markedly strengthened PLIN2 ubiquitinational degradation and the subsequent decline in lipid droplet disintegration and lipotoxicity. The specific mutation at the binding amino acid sites of PLIN2 with daclatasvir largely abolished the anti-MASH benefit of daclatasvir. In conclusion, the findings of our present study for the first time identified the anti-HCV drug daclatasvir as a novel and potent PLIN2 protein degradant for MASH protection.
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Affiliation(s)
- Rui Shu
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Song Tian
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Weiyi Qu
- Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jinjie Yang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; Qujing Medical College Basic Medical Department, Qujing, China
| | - Wei Shi
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Xinyan Li
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Toujun Zou
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Changjin Jiang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Yuxuan Zhang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China
| | - Zifeng Yang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Han Tian
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hailong Yang
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Jiajun Fu
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China
| | - Zhi-Gang She
- State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China
| | - Hongliang Li
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China; Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
| | - Xiao-Jing Zhang
- Wuhan University TaiKang Medical School (School of Basic Medical Sciences), Wuhan, China; State Key Laboratory of New Targets Discovery and Drug Development for Major Diseases, Gannan Innovation and Translational Medicine Research Institute; School of Pharmacy, Gannan Medical University, Ganzhou, China.
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Praguylertluck W, Kaewdech A, Chamroonkul N, Piratvisuth T, Sripongpun P. Effect of switching from prior Nucleos(t)ide Analogue(s) to Tenofovir alafenamide on lipid profile and cardiovascular risk in patients with Chronic Hepatitis B. PLoS One 2025; 20:e0324897. [PMID: 40424405 PMCID: PMC12112372 DOI: 10.1371/journal.pone.0324897] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Accepted: 05/04/2025] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION Tenofovir alafenamide (TAF) is recommended for chronic hepatitis B (CHB) treatment in international guidelines according to its efficacy and safety. However, in phase III study, an increased LDL-c was observed in those who were switched from Tenofovir disoproxil fumarate (TDF) to TAF. Limited data exists on whether lipid profiles change only in individuals who switched to TAF from TDF or from any nucleoside/nucleotide analogues (NUC). We investigated how switching to TAF affected lipid and cardiovascular outcomes in Thai CHB patients. MATERIALS AND METHODS We conducted a prospective observational study including CHB patients who had to switch from their prior NUC to TAF according to the national reimbursement policy in late 2022. All enrolled patients had lipid tests and transient elastography (TE) done at 0 and 48-week post-switch to TAF. Demographic data, prior NUC, liver biochemistry, controlled attenuated parameter (CAP) and liver stiffness (elastic modulus; E) data measured by TE were collected. The changes in lipid, Thai cardiovascular (CV) risk score, and TE results between 0 and 48-week were compared. RESULTS A total of 110 patients who were switched to TAF and completed 48-week follow-up were analyzed. The prior NUCs were as follows: 47 Lamivudine (LAM), 22 Entecavir (ETV), and 41 TDF-based. Baseline characteristics were similar between the three groups except for underlying hypertension was more frequent and baseline total cholesterol was lower in the TDF-based group. At 48-week post-switch, the median LDL-c changes were -2.45, -5.9 and +8.8 mg/dL (p<0.001), and total cholesterol changes were -4.5, -4 and +17 mg/dL (p<0.001), in the ETV, LAM, and TDF-based group, respectively. Whereas the changes in hepatic steatosis (measured by CAP), and liver stiffness (measured by E) as well as Thai CV risk score were not significantly different. No cardiovascular events occurred during follow-up. CONCLUSION Significant increase in LDL-c and total cholesterol after switching to TAF were observed only in patients with prior TDF, but not in those with prior ETV or LAM. Careful monitoring of lipids after the switch may not be universally needed. Data regarding long-term cardiovascular outcomes are warrant.
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Affiliation(s)
| | - Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Naichaya Chamroonkul
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
| | - Teerha Piratvisuth
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
- NKC Institute of Gastroenterology and Hepatology, Songklanagarind Hospital, Prince of Songkla University, Hat Yai, Thailand
| | - Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Thailand
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Kim LY, Kim JY, Yoo JJ, Kim SG, Kim YS. Tenofovir Disoproxil Fumarate Versus Entecavir: Effects on Lipid Profiles and Cardiovascular Outcomes in People Living With Chronic Hepatitis B. J Med Virol 2025; 97:e70187. [PMID: 39868849 DOI: 10.1002/jmv.70187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 01/02/2025] [Accepted: 01/13/2025] [Indexed: 01/28/2025]
Abstract
While entecavir (ETV) and tenofovir disoproxil fumarate (TDF) effectively manage chronic hepatitis B, their long-term effects on lipid metabolism and cardiovascular outcomes remain unclear. This study compares the impact of ETV, TDF, and treatment-naïve (control group) on hyperlipidemia and major adverse cardiac events (MACE) in people living with chronic hepatitis B (PLWHB). We used claim data from the South Korean National Health Insurance Service. Propensity score matching was used to account for confounding factors. The 5-year cumulative incidence of dyslipidemia was 7.10% for TDF, 12.17% for ETV, and 18.55% for the control group, with incidence rates per 1000 person-years of 14.5, 25.5, and 38.9, respectively. TDF showed a significantly lower risk of dyslipidemia compared to ETV (IRR: 0.56, p < 0.001) and the control group, which was confirmed in Cox regression analysis (HR: 0.392 vs. control, p < 0.001). For MACE, the 5-year cumulative incidence was 9.11% for TDF, 10.98% for ETV, and 12.32% for the control group, with incidence rates per 1000 person-years of 18.4, 22.5, and 24.8, respectively. TDF demonstrated a reduced risk compared to ETV (IRR: 0.817, p < 0.001), which was similarly supported by Cox regression analysis (HR: 0.728 vs. control, p < 0.001). In conclusion, TDF not only reduces the risk of hyperlipidemia but is also associated with a reduced risk of MACE compared to ETV or treatment-naive group in PLWHB.
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Affiliation(s)
- Log Young Kim
- Department of Big DATA Strategy, National Health Insurance Service, Wonju, Bucheon, South Korea
| | - Jae Young Kim
- Department of Internal Medicine, Soonchunhyang University School of Medicine, Asan, Bucheon, South Korea
| | - Jeong-Ju Yoo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Sang Gyune Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
| | - Young-Seok Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, South Korea
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Kong Q, Gao Q, Li W, Chen Z. Effect of tenofovir versus entecavir on the long-term prognosis in hepatocellular carcinoma patients with concurrent metabolic dysfunction-associated steatotic liver disease and hepatitis B. Asian J Surg 2024; 47:4725-4734. [PMID: 39289060 DOI: 10.1016/j.asjsur.2024.03.147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/08/2024] [Accepted: 03/22/2024] [Indexed: 09/19/2024] Open
Abstract
BACKGROUND Currently, there remains ongoing controversy about the selection of postoperative antiviral drugs for hepatocellular carcinoma (HCC) patients with concurrent metabolic dysfunction-associated steatotic liver disease (MASLD) and hepatitis B virus (HBV) infection (HPMH) who underwent hepatectomy. METHOD A multivariate Cox proportional hazards model and a propensity score matching (PSM) analysis were implemented to ensure equal baseline characteristics. The Kaplan‒Meier survival curves were employed for prognosis comparison between the two groups. RESULTS This study included 225 HPMH who all received post-hepatectomy antiviral therapy; with 107 in the tenofovir disoproxil fumarate (TDF) group and 118 in the entecavir (ETV) group. In the entire cohort, according to the multivariate analysis, patients in the TDF group showed better recurrence-free survival (RFS) (HR = 0.78; 95% CI, 0.55-0.95; p = 0.030) and overall survival (OS) (HR = 0.52; 95% CI, 0.30-0.97; p = 0.021) than those in the ETV group. After executing a PSM analysis, Kaplan‒Meier survival curve analysis disclosed significant differences for both RFS and OS between the two groups (p = 0.03 and p = 0.01, respectively). CONCLUSIONS In summary, our study suggests a more significant association of TDF in improving RFS and OS than ETV in HPMH who underwent hepatectomy through multivariate and PSM analysis. These findings indicate that the choice of antiviral drugs in HPHM holds crucial significance in guiding patient long-term prognosis.
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Affiliation(s)
- Qingyan Kong
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Qianqian Gao
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Wenjie Li
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China
| | - Zheyu Chen
- Division of Hepatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
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Cheng PN, Yu ML. Reply to correspondence on "Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide". Clin Mol Hepatol 2024; 30:1031-1032. [PMID: 38600870 PMCID: PMC11540407 DOI: 10.3350/cmh.2024.0228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 04/09/2024] [Indexed: 04/12/2024] Open
Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital; College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver, National Sun Yat-sen University, Kaohsiung, Taiwan
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Cao F, Fan T, Jiang X, Wang J, Liu Y, Zhu L, Xiong Y, Zhang S, Zhang Z, Pan Y, Li Y, Jiang C, Xia J, Yan X, Li J, Liu X, Zhu C, Huang R, Wu C. Effects of tenofovir alafenamide fumarate on serum lipid profiles in patients with chronic hepatitis B. Virol J 2024; 21:234. [PMID: 39342240 PMCID: PMC11439221 DOI: 10.1186/s12985-024-02515-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Accepted: 09/22/2024] [Indexed: 10/01/2024] Open
Abstract
BACKGROUND Concerns have been raised regarding changes in lipid profiles among patients with chronic hepatitis B (CHB) during tenofovir alafenamide fumarate (TAF) treatment. We aimed to evaluate the effect of TAF treatment on the lipid profiles of patients with CHB. METHODS A total of 430 patients with CHB from three hospitals were retrospectively included, including 158 patients treated with TAF and 272 patients treated with tenofovir disoproxil fumarate (TDF). RESULTS In this multicenter cohort, the cumulative incidence of dyslipidemia was notably higher in the TAF group than in the TDF group (P < 0.001). After TAF treatment, a significant elevation was observed in triglyceride (TG) levels (from 0.83 mmol/L to 1.02 mmol/L, P < 0.001) and total cholesterol (TC) levels (from 4.16 mmol/L to 4.32 mmol/L, P < 0.001). Similar changes in TG and TC levels were observed in the TAF group after propensity score matching (PSM). The TG levels (from 0.83 mmol/L to 1.04 mmol/L, P < 0.001) and TC levels (from 4.16 mmol/L to 4.38 mmol/L, P < 0.001) were both increased significantly compared to the baseline levels in the PSM cohort of patients treated with TAF. TAF treatment was independently associated with elevated TG levels (HR = 2.800, 95% CI: 1.334-5.876, P = 0.006) and TC levels (HR = 9.045, 95% CI: 3.836-21.328, P < 0.001). CONCLUSIONS Compared with TDF treatment, TAF treatment was associated with dyslipidemia in patients with CHB. Close monitoring of lipid profiles is needed in patients with CHB who received TAF treatment.
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Affiliation(s)
- Fei Cao
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Tao Fan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Xue Jiang
- Department of Clinical Laboratory, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Yilin Liu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Li Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Ye Xiong
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Shaoqiu Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Zhiyi Zhang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
| | - Yifan Pan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yuanyuan Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Chao Jiang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China
| | - Juan Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaomin Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China
| | - Xingxiang Liu
- Department of Clinical Laboratory, Huai'an No. 4 People's Hospital, Huai'an, Jiangsu, China
| | - Chuanwu Zhu
- Department of Infectious Diseases, The Affiliated Infectious Diseases Hospital of Soochow University, Suzhou, Jiangsu, China.
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, Jiangsu, China.
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, No. 321 Zhongshan Road, Nanjing, Jiangsu, 210008, China.
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
- Institute of Viruses and Infectious Diseases, Nanjing University, Nanjing, Jiangsu, China.
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China.
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Yoo J, Jung EA, Kim SG, Kim YS, Kim MJ. Risk of dyslipidaemia in people living with HIV who are taking tenofovir alafenamide: a systematic review and meta-analysis. J Int AIDS Soc 2024; 27:e26358. [PMID: 39301685 PMCID: PMC11413498 DOI: 10.1002/jia2.26358] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 09/02/2024] [Indexed: 09/22/2024] Open
Abstract
INTRODUCTION Among many antiretroviral drugs, tenofovir alafenamide is used extensively in combination regimens of tenofovir/emtricitabine or tenofovir/emtricitabine/bictegravir. However, concerns have arisen about the potential of tenofovir alafenamide to exacerbate hyperlipidaemia. This meta-analysis evaluates the relationship between tenofovir alafenamide use and lipid-profile alterations in people living with HIV. METHODS We searched PubMed, Ovid MEDLINE, EMBASE and the Cochrane Library to identify studies on changes in cholesterol levels (e.g. total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides) in people living with HIV who received treatment with a regimen containing tenofovir alafenamide (data collected 31 March 2023, review completed 30 July 2023). Potential risk factors for worsening lipid profile during treatment with tenofovir alafenamide were also evaluated. RESULTS Sixty-five studies involving 39,713 people living with HIV were selected. Significant increases in total cholesterol, low-density and high-density lipoprotein cholesterol, and triglycerides were observed after treatment with tenofovir alafenamide. Specifically, low-density lipoprotein cholesterol (+12.31 mg/dl) and total cholesterol (+18.86 mg/dl) increased markedly from the third month of tenofovir alafenamide use, with significant elevations observed across all time points up to 36 months. Comparatively, tenofovir alafenamide regimens resulted in higher lipid levels than tenofovir disoproxil fumarate regimens at 12 months of use. Notably, discontinuation of the tenofovir alafenamide regimen led to significant decreases in low-density lipoprotein cholesterol (-9.31 mg/dl) and total cholesterol (-8.91 mg/dl). Additionally, tenofovir alafenamide use was associated with increased bodyweight (+1.38 kg; 95% confidence interval: 0.92-1.84), which became more pronounced over time. Meta-regression analysis identified young age, male sex and low body mass index as risk factors for worsening cholesterol levels in individuals treated with tenofovir alafenamide. CONCLUSIONS Tenofovir alafenamide use in people living with HIV is associated with significant alterations in lipid profile.
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Affiliation(s)
- Jeong‐Ju Yoo
- Department of Internal MedicineSoonchunhyang University Bucheon HospitalSoonchunhyang University College of MedicineBucheonRepublic of Korea
| | - Eun Ae Jung
- Department of Medical LibrarySoonchunhyang University Bucheon HospitalSoonchunhyang University College of MedicineBucheonRepublic of Korea
| | - Sang Gyune Kim
- Department of Internal MedicineSoonchunhyang University Bucheon HospitalSoonchunhyang University College of MedicineBucheonRepublic of Korea
| | - Young Seok Kim
- Department of Internal MedicineSoonchunhyang University Bucheon HospitalSoonchunhyang University College of MedicineBucheonRepublic of Korea
| | - Min Jae Kim
- Department of Infectious DiseasesAsan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea
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Shin H, Lim GS, Yoon JW, Ko Y, Park Y, Park J, Hur MH, Park MK, Cho Y, Lee YB, Cho EJ, Kim BH, Lee JH, Yu SJ, Yoon JH, Kim YJ. Metabolic effects and cardiovascular disease risks of antiviral treatments in patients with chronic hepatitis B. J Med Virol 2024; 96:e29760. [PMID: 38940453 DOI: 10.1002/jmv.29760] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 05/13/2024] [Accepted: 06/11/2024] [Indexed: 06/29/2024]
Abstract
Different antiviral treatments for chronic hepatitis B (CHB) have been known to have different metabolic effects. This study aimed to reveal whether tenofovir alafenamide (TAF)-induced dyslipidemia and its associated outcomes are significant. This study utilized 15-year historical cohort including patients with CHB in Korea and consisted of two parts: the single-antiviral and switch-antiviral cohorts. In the single-antiviral cohort, patients were divided into four groups (entecavir [ETV]-only, tenofovir disoproxil fumarate [TDF]-only, TAF-only, and non-antiviral). Propensity score matching (PSM) and linear regression model were sequentially applied to compare metabolic profiles and estimated atherosclerotic cardiovascular disease (ASCVD) risks longitudinally. In the switch-antiviral cohort, pairwise analyses were conducted in patients who switched NAs to TAF or from TAF. In the single-antiviral cohort, body weight and statin use showed significant differences between groups before PSM, but well-balanced after PSM. Changes in total cholesterol were significantly different between groups (-2.57 mg/dL/year in the TDF-only group and +2.88 mg/dL/year in the TAF-only group; p = 0.002 and p = 0.02, respectively). In the TDF-only group, HDL cholesterol decreased as well (-0.55 mg/dL/year; p < 0.001). The TAF-only group had the greatest increase in ASCVD risk, followed by the TDF-only group and the non-antiviral group. In the switch-antiviral cohort, patients who switched from TDF to TAF had a higher total cholesterol after switching (+9.4 mg/dL/year) than before switching (-1.0 mg/dL/year; p = 0.047). Sensitivity analysis on data with an observation period set to a maximum of 3 years for NA treatment showed consistent results on total cholesterol (-2.96 mg/dL/year in the TDF-only group and +3.09 mg/dL/year in the TAF-only group; p = 0.001 and p = 0.005, respectively). Another sensitivity analysis conducted on statin-treated patients revealed no significant change in cholesterol and ASCVD risk. TAF was associated with increased total cholesterol, whereas TDF was associated with decreased total and HDL cholesterol. Both TAF and TDF were associated with increased ASCVD risks, and statin use might mitigate these risks.
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Affiliation(s)
- Hyunjae Shin
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Gyung Sun Lim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jae Woong Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yunmi Ko
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Youngsu Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jeayeon Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Min Kyung Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yuri Cho
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Yun Bin Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Eun Ju Cho
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Bo Hyun Kim
- Center for Liver and Pancreatobiliary Cancer, National Cancer Center, Goyang, South Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Su Jong Yu
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Jung-Hwan Yoon
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
| | - Yoon Jun Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, South Korea
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Hou J, Ning Q, Duan Z, Chen Y, Xie Q, Zhang L, Wu S, Tang H, Li J, Lin F, Yang Y, Gong G, Luo Y, Xie S, Wang H, Mateo R, Yazdi T, Abramov F, Yee LJ, Flaherty J, Chen C, Huang Y, Zhang M, Jia J. Five-year Treatment with Tenofovir Alafenamide Achieves High Rates of Viral Suppression, Alanine Aminotransferase Normalization, and Favorable Bone and Renal Safety in Chinese Chronic Hepatitis B Patients. J Clin Transl Hepatol 2024; 12:469-480. [PMID: 38779514 PMCID: PMC11106352 DOI: 10.14218/jcth.2023.00417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 01/14/2024] [Accepted: 02/02/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND AND AIMS After 3-years (144 week) of double-blind treatment in Chinese chronic hepatitis B patients in two ongoing phase 3 studies, tenofovir alafenamide (TAF) showed similar efficacy to tenofovir disoproxil fumarate (TDF), with improved renal and bone safety. In this study, we aimed to report the 5-year results from 2 years into the open-label TAF treatment phase. METHODS All participants completing the 144-week double-blind treatment were eligible to receive open-label TAF 25 mg once daily up to week 384. Serial analysis of viral suppression (hepatitis B virus DNA <29 IU/mL), alanine aminotransferase normalization, serological responses, and safety outcomes at year 5 (week 240) was performed. RESULTS The open-label phase included 93% (311/334) of the enrolled participants, which included 212 who switched from double-blind TAF to open-label TAF (TAF-TAF) and 99 who switched from double-blind TDF to open-label TAF (TDF-TAF). Baseline characteristics were comparable. Week 240 viral suppression rates were similar between groups [93.4% vs. 93.9%; difference: -1.5%, (95% CI: -6.4 to -3.5), p=0.857]. Alanine aminotransferase normalization and serological response rates were higher in the TAF-TAF group than in the TDF-TAF group. The frequencies of adverse events and laboratory abnormalities were low and similar between groups. Both groups had similar small numerical declines from baseline in estimated glomerular filtration rate at year 5 (week 240, -2.85 mL/min vs. -3.29 mL/min, p=0.910). The greater declines in renal and bone parameters in the TDF-TAF group through week 144 improved after switching to TAF. CONCLUSIONS The 5-year TAF treatment efficacy was high and similar to that of 3-year TDF followed by 2-year TAF in Chinese chronic hepatitis B patients. Favorable effects on bone and renal parameters were sustained with TAF treatment alone and were observed following the switch from TDF to TAF.
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Affiliation(s)
- Jinlin Hou
- Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Qin Ning
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhongping Duan
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Yu Chen
- Beijing YouAn Hospital, Capital Medical University, Beijing, China
| | - Qing Xie
- Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lunli Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shanming Wu
- Shanghai Public Health Clinical Center, Shanghai, China
| | - Hong Tang
- West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Jun Li
- The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Feng Lin
- Hainan General Hospital, Haikou, Hainan, China
| | - Yongfeng Yang
- The Second Hospital of Nanjing, Affiliated to Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Guozhong Gong
- The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | | | | | | | | | | | | | | | | | - Chengwei Chen
- The People’s Liberation Army No. 85 Hospital, Shanghai, China
| | - Yan Huang
- Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Mingxiang Zhang
- The Sixth People’s Hospital of Shenyang, Shenyang, Liaoning, China
| | - Jidong Jia
- Beijing Friendship Hospital, Capital Medical University, Beijing, China
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Tong K, Chen M, Wang D, Dai H, Peng J, Zhang J, Zhou J, Chang Y, Huang W. Effects of first-line nucleot(s)ide analogues on lipid profiles in patients with chronic hepatitis B: a network meta-analysis. Eur J Clin Pharmacol 2024; 80:335-354. [PMID: 38197944 DOI: 10.1007/s00228-023-03616-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 12/29/2023] [Indexed: 01/11/2024]
Abstract
INTRODUCTION Recent studies have found that lipid levels in patients with chronic hepatitis B (CHB) may change during antiviral therapy. OBJECTIVE To assess the effects of first-line nucleot(s)ide analogues (NAs) on lipid profiles in patients with CHB using network meta-analysis. METHODS Seven electronic databases (PubMed, Embase, Cochrane Library, and four Chinese databases) were searched for cohort studies on the effect of NA on lipids in patients with CHB up to August 1, 2023. The changes of serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were taken as outcomes. The mean difference (MD) of continuous variables and 95% confidence intervals (CI) were calculated using RevMan 5.4 and Stata 16.0 software, and network meta-analysis was based on a frequentist framework. RESULTS A total of 4194 patients were included in the study, including patients with CHB treated with entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), as well as patients not receiving antiviral therapy [patients with inactive CHB who were not receiving antiviral therapy (referred as inactive CHB patients) and non-HBV-infected patients]. TDF reduced TC levels compared to the non-antiviral group (TDF vs. inactive CHB patients: MD = - 17.27, 95% CI (- 30.03, - 4.47); TDF vs. non-HBV-infected individuals: MD = - 17.10, 95% CI (- 20.13, - 14.07)). TC changes in the TAF and ETV groups were not statistically different from the non-antiviral group (TAF vs. inactive CHB patients: MD = - 2.69, 95% CI (- 14.42, 9.04); TAF vs. non-HBV-infected individuals: MD = - 2.52, 95% CI (- 8.47, 3.43); ETV vs. inactive CHB patients: MD = - 4.24, 95% CI (- 17.12, 8.64); ETV vs. non-HBV-infected individuals: MD = - 4.07, 95% CI (- 9.90, 1.75)). The ranking of the effects for lowering TC is as follows: CHB patients treated with nucleotide analogues [with varying efficacy: TDF (SUCRA = 99.9) > ETV (SUCRA = 59.3) > TAF (SUCRA = 43.6)] > inactive CHB patients (SUCRA = 27.3) > non-HBV-infected individuals (SUCRA = 19.9). As for secondary outcomes, among the three antiviral drugs, TDF had the most significant effect on lowering TG, LDL-C, and HDL-C, but none of the three drugs was statistically different from the non-antiviral group. Subgroup analysis showed that the lipid-lowering effect of TDF was more pronounced in the elderly (≥ 50 years). CONCLUSION TDF was effective in lipid reduction, particularly pronounced in the older population. TAF and ETV had a neutral effect to TC, TG, LDL-C, and HDL-C. Despite a relative increase in lipids observed in patients transitioning from TDF to TAF or ETV, these changes remained within acceptable limits.
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Affiliation(s)
- Kexin Tong
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mingjing Chen
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Danni Wang
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Haifeng Dai
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jiayi Peng
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jia Zhang
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Jiao Zhou
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yujiao Chang
- Department of Infectious Diseases, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wenxiang Huang
- Department of Geriatrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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11
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Sun YT, Chen QQ. Review on article of effects of tenofovir alafenamide and entecavir in chronic hepatitis B virus patients. World J Hepatol 2024; 16:109-111. [PMID: 38313247 PMCID: PMC10835485 DOI: 10.4254/wjh.v16.i1.109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 12/04/2023] [Accepted: 01/12/2024] [Indexed: 01/23/2024] Open
Abstract
This letter comments on the article which reported that tenofovir alafenamide may increase blood lipid levels compared with entecavir in patients with chronic hepatitis B published on World J Hepatol 2023 August 27. We review the related research content, topic selection, methodology, conclusions, strengths and weaknesses of this article. And evaluate it in relation to other published relevant articles.
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Affiliation(s)
- Yu-Tong Sun
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100193, China
| | - Qian-Qian Chen
- Department of Gastroenterology, The First Medical Center of Chinese PLA General Hospital, Beijing 100193, China.
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Fernandez CJ, Alkhalifah M, Afsar H, Pappachan JM. Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Viral Hepatitis: The Interlink. Pathogens 2024; 13:68. [PMID: 38251375 PMCID: PMC10821334 DOI: 10.3390/pathogens13010068] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 01/05/2024] [Accepted: 01/07/2024] [Indexed: 01/23/2024] Open
Abstract
Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one-third of the global population and has become the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) remain significant challenges to liver health even in the 21st century. The co-existence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. A thorough understanding of the pathobiological interactions between MAFLD and these two chronic viral infections is crucial for appropriately managing these patients. In this comprehensive clinical review, we discuss the various mechanisms of chronic viral hepatitis-mediated metabolic dysfunction and the impact of MAFLD on the progression of liver disease.
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Affiliation(s)
- Cornelius J. Fernandez
- Department of Endocrinology and Metabolism, Pilgrim Hospital, United Lincolnshire Hospitals NHS Trust, Boston PE21 9QS, UK;
| | - Mohammed Alkhalifah
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Department of Family Medicine and Polyclinics, King Faisal Specialist Hospital & Research Centre, Riyadh 11211, Saudi Arabia
- University Diabetes Center, King Saud University Medical City, King Saud University, Riyadh 11411, Saudi Arabia
| | - Hafsa Afsar
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
| | - Joseph M. Pappachan
- Department of Endocrinology and Metabolism, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane, Preston PR2 9HT, UK; (M.A.); (H.A.)
- Faculty of Science, Manchester Metropolitan University, Manchester M15 6BH, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PL, UK
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Cheng PN, Liu CJ. Editorial: Tenofovir disoproxil fumarate more than an antiviral drug-Another piece of the puzzle. Authors' reply. Aliment Pharmacol Ther 2024; 59:289-290. [PMID: 38153280 DOI: 10.1111/apt.17807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2023]
Abstract
LINKED CONTENTThis article is linked to Cheng et al papers. To view these articles, visit https://doi.org/10.1111/apt.17765 and https://doi.org/10.1111/apt.17793
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Affiliation(s)
- Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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14
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Yang L, Lu Z, Bian J, Li F, Zou H. Association between chronic viral infection-related hospitalization and risk of cardiovascular disease: A population-based cohort study. J Med Virol 2024; 96:e29350. [PMID: 38180233 DOI: 10.1002/jmv.29350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Revised: 12/12/2023] [Accepted: 12/15/2023] [Indexed: 01/06/2024]
Abstract
Chronic viral infection induces immunosenescence and systemic low-grade inflammation, leading to worsened long-term outcomes. We sought to explore the short- and long-term effects of chronic viral infection on cardiovascular disease (CVD). Based on UK Biobank data, exposed group was identified as individuals who had chronic virus infection-related hospitalization (IRH). Unexposed group was randomly selected, matched by 5-year age interval, sex, and Charlson comorbidity index at a ratio up to 1:10. Restricted cubic splines were used to model time-varying effects of IRH in nonproportional Cox models. A cut-off value of 5 years was recorded and used in piecewise Cox proportional hazards models as we estimated short- and long-term effects of IRH on CVD. A total of 2826 exposed participants and 28 212 matched unexposed participants were included. Chronic viral IRH was associated with increased risk of CVD (0-5 years: hazard ratio, 1.57 [95% confidence interval: 1.32, 1.87] and 5+ years: 1.31 [1.06, 1.61]). Elevated risk of stroke was only observed within the initial 5-year follow-up (0-5 years: 1.91 [1.30, 2.81]). The short- and long-term associations were observed in herpes or hepatitis virus IRH with risk of CVD (all p < 0.05). Subgroup analysis revealed long-term association between chronic viral IRH and CVD among female (5+ years: 1.68 [1.27, 2.22]) but not among male. The association between chronic viral infection and elevated CVD risk appeared to be stronger among individuals who did not take cholesterol-lowering medication, antithrombotic medication, or certain antihypertensive medications (all p for interaction < 0.05). The risk of CVD event remained persistently higher within and over 5 years following chronic viral IRH, especially in individuals infected with herpes and hepatitis virus.
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Affiliation(s)
- Luoyao Yang
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Zhen Lu
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Junye Bian
- School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, People's Republic of China
| | - Feng Li
- Department of Cardiac and Vascular Surgery, The 1st Affiliated Hospital of AnHui Medical University, Hefei, China
| | - Huachun Zou
- School of Public Health, Fudan University, Shanghai, China
- School of Public Health, Southwest Medical University, Luzhou, China
- Kirby Institute, University of New South Wales, Sydney, Australia
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15
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Yeh ML, Huang JF, Yu ML. Fatty liver and viral hepatitis: Prevalence, risk factors, natural course, pathogenesis, and management. METABOLIC STEATOTIC LIVER DISEASE 2024:261-275. [DOI: 10.1016/b978-0-323-99649-5.00008-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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16
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Hong H, Choi WM, Lee D, Shim JH, Kim KM, Lim YS, Lee HC, Choi J. Cardiovascular risk in chronic hepatitis B patients treated with tenofovir disoproxil fumarate or tenofovir alafenamide. Clin Mol Hepatol 2024; 30:49-63. [PMID: 37981763 PMCID: PMC10776286 DOI: 10.3350/cmh.2023.0328] [Citation(s) in RCA: 10] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 11/19/2023] [Accepted: 11/19/2023] [Indexed: 11/21/2023] Open
Abstract
BACKGROUND/AIMS Tenofovir disoproxil fumarate (TDF) is known to have a lipid-lowering effect. This is in contrast to tenofovir alafenamide (TAF), which has a lipid-neutral effect. Therefore, concerns have been raised as to whether these differences affect long-term cardiovascular risk. Here, we aimed to evaluate the long-term risk of cardiovascular events in chronic hepatitis B (CHB) patients treated with TAF or TDF. METHODS We retrospectively analyzed 4,124 treatment-naïve CHB patients treated with TDF (n=3,186) or TAF (n=938) between 2012 and 2022. The primary outcome was a composite endpoint of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, and hospitalization for unstable angina or heart failure. Serial changes in lipid profiles between two treatments were also explored. RESULTS The median age of the patients was 50.6 years, and 60.6% of the patients were male. At baseline, 486 (11.8%) and 637 (15.4%) of the patients had dyslipidemia and fatty liver, respectively. A total of 42 MACE occurred, with an annual incidence of 0.2%/100 person-years (PYs). At 1, 3, and 5 years, the cumulative risk of MACE was 0.4%, 0.8%, and 1.2% in patients treated with TDF, and 0.2%, 0.7%, and 0.7% in patients treated with TAF, respectively (p=0.538). No significant differences in the risk of MACE were observed between TDF and TAF. A multivariable analysis found that current smoker and a history of cardiovascular events were risk factors associated with an increased risk of MACE. CONCLUSION Patients treated with TAF had comparable risks of cardiovascular outcomes, defined as MACE, as patients treated with TDF.
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Affiliation(s)
- Hyeyeon Hong
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Won-Mook Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Danbi Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ju Hyun Shim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kang Mo Kim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young-Suk Lim
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Han Chu Lee
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Jonggi Choi
- Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Congly SE, Syed A, Haylock-Jacobs S, Israelson H, Pinto J, Williams S, Lee SS, Coffin CS. A real-world retrospective single-centre study of the cost-effectiveness and long-term outcomes of pegylated interferon for chronic hepatitis B. CANADIAN LIVER JOURNAL 2023; 6:305-313. [PMID: 38020196 PMCID: PMC10652987 DOI: 10.3138/canlivj-2022-0043] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2022] [Accepted: 11/20/2022] [Indexed: 12/01/2023]
Abstract
Background Pegylated interferon (Peg-IFN) is recommended as first-line therapy for chronic hepatitis B (CHB) but has significant side effects and is rarely used compared to oral nucleos(t)ide analogues (NA). There are limited recent clinical efficacy or economic analysis data comparing approved CHB therapy in North America. Methods This retrospective study examined clinical outcomes, off-treatment durability, and cost-effectiveness of Peg-IFN versus NA for CHB. Demographic (age, sex, ethnicity), clinical data (i.e., liver tests, hepatitis B virus DNA, serology, transient elastography) and documented side effects were collected by retrospective chart review of patients followed in the University of Calgary Liver Unit who received Peg-IFN therapy from January 2007 to December 2020. The cost-effectiveness of Peg-IFN versus NA therapy was modelled over a 10-year time horizon. Results Sixty-eight CHB patients were treated with Peg-IFN (median age 45.65, 74% male, 84% Asian); 50/68 (74%) completed 48 weeks of treatment with a median follow-up of 6.54 years (interquartile range 5.07). At the last known follow-up, 23/68 (34%) have not required NA treatment and one had HBsAg loss; 27 have been started on NA. Predictors of obtaining a sustained virological response included being hepatitis B e antigen-negative at treatment end and a quantitative hepatitis B surface antigen <1000 IU/mL. Economic modelling showed that finite Peg-IFN was not cost-effective versus NA at a 10-year time horizon. Conclusions PEG-IFN remains a potential treatment for CHB although there is a significant intolerance/failure rate. Using PEG-IFN based on patient preference is reasonable and optimal patient selection may improve treatment cost-effectiveness.
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Affiliation(s)
- Stephen E Congly
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- O’Brien Institute of Public Health, University of Calgary, Calgary, Alberta, Canada
| | - Ahsan Syed
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Sarah Haylock-Jacobs
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Heidi Israelson
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Jacqueline Pinto
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Sarah Williams
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Samuel S Lee
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Carla S Coffin
- Division of Gastroenterology and Hepatology, Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
- Department of Microbiology, Immunology and Infectious Diseases, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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Su JY, Wu YL, Wu XL, Liu ZX, Wang YY, Li ZH, Luo JX, Wu KJ, Zhong JH. Letter: Entecavir versus tenofovir on serum lipoprotein levels of hepatitis B virus-related hepatocellular carcinoma after curative hepatectomy. Aliment Pharmacol Ther 2023; 58:842-844. [PMID: 37768294 DOI: 10.1111/apt.17668] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 09/29/2023]
Abstract
LINKED CONTENTThis article is linked to Ogawa et al papers. To view these articles, visit https://doi.org/10.1111/apt.17107 and https://doi.org/10.1111/apt.17693.
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Affiliation(s)
- Jia-Yong Su
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Ying-Ling Wu
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Xuan-Lin Wu
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhen-Xiu Liu
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Yi-Yang Wang
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Zhong-Hai Li
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jia-Xin Luo
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Kun-Jun Wu
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
| | - Jian-Hong Zhong
- Hepatobiliary Surgery Department, Guangxi Medical University Cancer Hospital, Nanning, China
- Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor (Guangxi Medical University), Ministry of Education, Nanning, China
- Guangxi Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Nanning, China
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19
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Lai RM, Lin S, Wang MM, Li N, Zhou JH, Lin XY, Chen TB, Zhu YY, Zheng Q. Tenofovir alafenamide significantly increased serum lipid levels compared with entecavir therapy in chronic hepatitis B virus patients. World J Hepatol 2023; 15:964-972. [PMID: 37701915 PMCID: PMC10494560 DOI: 10.4254/wjh.v15.i8.964] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 05/26/2023] [Accepted: 08/03/2023] [Indexed: 08/22/2023] Open
Abstract
BACKGROUND Tenofovir alafenamide (TAF) has a serum lipid-raising effect in patients with HIV; however, its effect on serum lipids and nonalcoholic fatty liver disease (NAFLD) risk in patients with chronic hepatitis B (CHB) is unclear. AIM To compare the effects of TAF and entecavir (ETV) on serum lipid levels in patients with CHB. METHODS In this retrospective cohort study, the data including the clinical features, serum lipids, and metabolic factors of patients with CHB at baseline and approximately 1 year after TAF or ETV treatment were collected and analyzed. We used propensity score-matched models to assess the effects on high-density lipoprotein, low-density lipoprotein, triglycerides, and total cholesterol (TCHO). RESULTS A total of 336 patients (75.60% male) were included; 63.69% received TAF and 36.31% received ETV. Compared with the ETV group, the TAF group had significantly higher TCHO levels after treatment (4.67 ± 0.90 vs 4.36 ± 1.05, P = 0.006). In a propensity score-matched model for body mass index, age, sex, smoking, drinking, presence of comorbidities such as NAFLD, cirrhosis, diabetes mellitus, and hypertension, TAF-treated patients had significantly increased TCHO levels compared to that at baseline (P = 0.019). There was no difference for the ETV group. Body mass index, sex, hypertension, baseline TCHO, and creatine kinase-MB isoenzyme levels were significantly associated with elevated TCHO levels in logistic regression analysis. However, 1-year TAF treatment did not increase the incidence of NAFLD. CONCLUSION A greater increase in TCHO was observed in patients with CHB receiving TAF compared to those receiving ETV. However, TAF-induced dyslipidemia did not increase the incidence of NAFLD.
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Affiliation(s)
- Rui-Min Lai
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China
| | - Shan Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Miao-Miao Wang
- Department of Endocrinology, The 910th Hospital of The Joint Service Support Force, Quanzhou 362000, Fujian Province, China
| | - Na Li
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Jia-Hui Zhou
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Xiao-Yu Lin
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Tian-Bin Chen
- Department of Laboratory Medicine, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian Province, China
| | - Yue-Yong Zhu
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
| | - Qi Zheng
- Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fujian Clinical Research Center for Hepatopathy and Intestinal Diseases, Fuzhou 350005, Fujian Province, China
- Department of Hepatology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, Fujian Province, China.
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20
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Maggi P, Ricci ED, Cicalini S, Pellicanò GF, Celesia BM, Vichi F, Cascio A, Sarchi E, Orofino G, Squillace N, Madeddu G, De Socio GV, Bargiacchi O, Molteni C, Masiello A, Saracino A, Menzaghi B, Falasca K, Taramasso L, Di Biagio A, Bonfanti P. Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens. BMC Infect Dis 2023; 23:227. [PMID: 37059996 PMCID: PMC10103465 DOI: 10.1186/s12879-023-08191-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Accepted: 03/22/2023] [Indexed: 04/16/2023] Open
Abstract
BACKGROUND Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. METHODS We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. RESULTS In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. CONCLUSIONS PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.
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Affiliation(s)
- Paolo Maggi
- Infectious Diseases Unit, AORN Sant'Anna e San Sebastiano, Caserta, Italy
| | | | - Stefania Cicalini
- National Institute for Infectious Diseases Lazzaro Spallanzani Institute for Hospitalization and Care Scientific, Roma, Lazio, Italy
| | - Giovanni Francesco Pellicanò
- Unit of Infectious Diseases, Department of Human Pathology of the Adult and the Developmental Age 'G. Barresi', University of Messina, Messina, Italy
| | | | - Francesca Vichi
- Unit of Infectious Diseases, USLCENTRO FIRENZE, Santa Maria Annunziata Hospital, Florence, Italy
| | - Antonio Cascio
- Unit of Infectious Diseases, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy
| | - Eleonora Sarchi
- Infectious Diseases Unit, S.Antonio e Biagio e Cesare Arrigo Hospital, Alessandria, Italy
| | - Giancarlo Orofino
- Division I of Infectious and Tropical Diseases, ASL Città di Torino, Torino, Italy
| | - Nicola Squillace
- Infectious Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy
| | - Giordano Madeddu
- Unit of Infectious Diseases, Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
| | | | - Olivia Bargiacchi
- Unit of Infectious Diseases, Ospedale Maggiore della Carità, Novara, Italy
| | - Chiara Molteni
- Unit of Infectious Diseases, A. Manzoni Hospital, Lecco, Italy
| | | | - Annalisa Saracino
- Department of Biomedical Sciences and Human Oncology, Clinic of Infectious Diseases, University of Bari Aldo Moro, Bari, Italy
| | - Barbara Menzaghi
- Unit of Infectious Diseases, ASST della Valle Olona - Busto Arsizio (VA), Busto Arsizio VA, Italy
| | - Katia Falasca
- Clinic of Infectious Diseases, Department of Medicine and Science of Aging, G. D'Annunzio University, Chieti-Pescara, Chieti, Italy
| | - Lucia Taramasso
- Infectious Diseases, San Martino Hospital Genoa, University of Genoa, Genoa, Italy
| | - Antonio Di Biagio
- Infectious Diseases, San Martino Hospital Genoa, University of Genoa, Genoa, Italy
| | - Paolo Bonfanti
- Infectious Disease Unit, Fondazione IRCCS San Gerardo dei Tintori, Monza - University of Milano-Bicocca, Monza, Italy
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21
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Cao X, Hu Q, Xu W, Li Q, Zhang J, Chen L, Huang Y, Qi X. Kinetics changes in total cholesterol predict HBeAg seroconversion in chronic hepatitis B patients treated with pegylated interferon-alfa. J Viral Hepat 2023; 30:310-318. [PMID: 36529685 DOI: 10.1111/jvh.13787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 11/24/2022] [Accepted: 12/10/2022] [Indexed: 01/07/2023]
Abstract
There is no satisfactory standard for predicting HBeAg seroconversion during Pegylated interferon alpha (PegIFNα) treatment. Studies have shown that IFNα therapy in chronic hepatitis C patients could alter serum lipid profiles. However, there have been no studies on lipid changes that predict the outcome of PegIFNα monotherapy in treated-naive chronic hepatitis B (CHB) patients. This retrospective study included 130 treated-naive HBeAg-positive CHB patients receiving PegIFNα monotherapy. The relationship between serum lipid changes and HBeAg seroconversion was analysed. The TC-ALT-HBsAg-HBeAg-Genotype-Age (CASEGA) model was established to predict HBeAg seroconversion after PegIFN-α monotherapy. Among 130 patients, 33 achieved HBeAg seroconversion (SR) and 97 did not achieve HBeAg seroconversion (NR). The decrease in serum total cholesterol (TC) in the NR group was significantly higher than in the SR group at Week 24 (-9.59% vs. -0.31%, p < 0.001). Multivariate logistic regression analysis showed that the change in TC at Week 24 (odds ratio = 1.065, p = 0.009) was an independent predictor of HBeAg seroconversion. The area under the receiver operating characteristic curve for the CASEGA model was 0.883. The model score at the maximum Youden index was 90, and the specificity, sensitivity, positive predictive value and negative predictive value were 0.727, 0.794, 0.546 and 0.895, respectively. The HBeAg seroconversion rate at Week 72 in patients with scores >90 was significantly higher than that in patients with scores <90 (54.55% vs. 10.47%, p < 0.001). This study indicated that the change in the TC level at 24 weeks in CHB patients treated with PegIFNα was associated with HBeAg seroconversion. The CASEGA prediction model based on the TC change rate of 24 weeks has good predictive efficiency for HBeAg seroconversion.
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Affiliation(s)
- Xiongyue Cao
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiankun Hu
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Wei Xu
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Qiang Li
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Jiming Zhang
- Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Liang Chen
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
| | - Yuxian Huang
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.,Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China
| | - Xun Qi
- Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
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22
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Lu R, Liu Y, Hong T. Epidemiological characteristics and management of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis in China: A narrative review. Diabetes Obes Metab 2023; 25 Suppl 1:13-26. [PMID: 36775938 DOI: 10.1111/dom.15014] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/27/2023] [Accepted: 02/08/2023] [Indexed: 02/14/2023]
Abstract
AIM With industrialization and spread of the westernized lifestyle, the number of people affected by non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is growing rapidly in China; this has become a major public health concern. To better understand the burden and characteristics of NAFLD/NASH in China, we aim to perform a narrative review of the literature published in this field. MATERIALS AND METHODS We carried out a comprehensive electronic search of five English-language and three Chinese-language databases, to identify studies regarding NAFLD or NASH published from inception to November 30, 2022. Epidemiological studies of NAFLD/NASH in China were particularly noticed and summarized. We also searched the www. CLINICALTRIALS gov and www.chictr.org.cn websites for the registered trials on the treatment of the disease led by Chinese investigators or located in China. RESULTS The increasing rate of NAFLD prevalence in China is strikingly high, reaching more than twice that in western countries. The prevalence of NAFLD is nearly 30% of the general Chinese population, making it the leading cause of chronic liver diseases. The prevalence of NAFLD/NASH varies between provinces/regions, age groups, sexes, and individuals with different metabolic profiles. NAFLD co-exists in many Chinese patients with chronic hepatitis B. Since 2020, more Chinese studies have used the term metabolic-associated fatty liver disease (MAFLD), emphasizing the underlying metabolic disorders that occur concurrently with this disease. Several clinical trials involving lifestyle interventions, antidiabetic drugs, or traditional Chinese medicines, registered by Chinese investigators, have been completed or are ongoing. Moreover, several innovative targeted therapies developed in China are revolutionizing the treatment of NAFLD/NASH. CONCLUSIONS NAFLD has cast a heavy burden on the Chinese healthcare system. Chinese scholars are making efforts to achieve the optimal management of this disease.
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Affiliation(s)
- Ran Lu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Ye Liu
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
| | - Tianpei Hong
- Department of Endocrinology and Metabolism, Peking University Third Hospital, Beijing, China
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23
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Martínez-Sanz J, Serrano-Villar S, Muriel A, García Fraile LJ, Orviz E, Mena de Cea Á, Campins AA, Moreno S. Metabolic-Related Outcomes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in Adults With Human Immunodeficiency Virus (HIV): A Multicenter Prospective Cohort Study. Clin Infect Dis 2023; 76:e652-e660. [PMID: 35903910 DOI: 10.1093/cid/ciac621] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 07/14/2022] [Accepted: 07/26/2022] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Tenofovir alafenamide (TAF) has replaced tenofovir disoproxil fumarate (TDF) in many clinical settings. However, concerns remain about potential metabolic complications of TAF. We aimed to evaluate changes in weight, laboratory markers, and metabolic-related clinical events after replacing TDF with TAF. METHODS Multicenter prospective cohort study in the Spanish CoRIS cohort. We included virologically suppressed adults with human immunodeficiency virus (HIV) receiving TDF for more than 12 months who either switched to TAF or maintained TDF, with no changes in the core agent. Participants were matched by propensity score. We fitted generalized equation models to assess changes in weight, blood lipids, and hepatic steatosis index, and to compare the incidence of diabetes, hypertension, and lipid-lowering drug use after 144 weeks. RESULTS In total, 1446 participants were matched in each group. Median age was 38 years, 85% were male, mean weight at baseline was 73 kg. Participants who switched to TAF had a mean weight increase of +0.5 kg at 144 weeks over those who maintained TDF, with no difference in the occurrence of overweight or obesity. Individuals who switched to TAF had a significant increase in total cholesterol (+7.9 mg/dL) and triglycerides (+11.2 mg/dL), with no differences in the total cholesterol-high-density lipoprotein (HDL) ratio. However, no increased incidence of diabetes, hypertension, or lipid-lowering drug use was observed after the follow-up period. CONCLUSIONS Switching from TDF to TAF is associated with modest weight gain and increases in total cholesterol and triglycerides, without an impact on the incidence of obesity or metabolic-related clinical events, in this Spanish cohort with a majority White male population.
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Affiliation(s)
- Javier Martínez-Sanz
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.,CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Sergio Serrano-Villar
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.,CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain
| | - Alfonso Muriel
- Clinical Biostatistic Unit, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.,CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.,University of Alcalá, Madrid, Spain
| | - Lucio J García Fraile
- CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.,Department of Internal Medicine, Hospital Universitario de La Princesa, Madrid, Spain
| | - Eva Orviz
- Centro Sanitario Sandoval, Hospital Clínico San Carlos, IdISSC, Madrid, Spain
| | - Álvaro Mena de Cea
- Infectious Diseases Unit, Complejo Hospitalario Universitario a Coruña (CHUAC), Madrid, Spain
| | - Antoni A Campins
- Department of Internal Medicine - Infectious Diseases, Hospital Universitario Son Espases, Palma, Spain
| | - Santiago Moreno
- Department of Infectious Diseases, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, Spain.,CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.,University of Alcalá, Madrid, Spain
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24
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Hepatitis B virus infection combined with nonalcoholic fatty liver disease: Interaction and prognosis. Heliyon 2023; 9:e13113. [PMID: 36747946 PMCID: PMC9898750 DOI: 10.1016/j.heliyon.2023.e13113] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 01/07/2023] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
Hepatitis B virus (HBV) infection is still one kind of the infectious diseases that seriously threaten human health. Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. HBV infection complicated with NAFLD is increasingly common. This review mainly describes the interaction between HBV infection and NAFLD, the interaction between steatosis and antiviral drugs, and the prognosis of HBV infection complicated with NAFLD. Most studies suggest that HBV infection may reduce the incidence of NAFLD. NAFLD can promote the spontaneous clearance of hepatitis B surface antigen (HBsAg), but whether it affects antiviral efficacy has been reported inconsistently. HBV infection combined with NAFLD can promote the progression of liver fibrosis, especially in patients with severe steatosis. The outcome of HBV infection combined with NAFLD predisposing to the progression of HCC remains controversial.
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Key Words
- AVT, antiviral therapy
- Antiviral efficacy
- BMI, body mass index
- CHB, chronic hepatitis B
- CI, confidence interval
- ETV, entecavir
- HBV infection
- HBV, hepatitis B virus
- HBeAg, hepatitis B e antigen
- HBsAg, hepatitis B surface antigen
- HCC, hepatocellular carcinoma
- HDL, high-density lipoprotein
- HDL-C, high-density lipoprotein-cholesterol
- HR, hazard ratio
- HS, hepatis steatosis
- Hepatocellular carcinoma
- LDL-C, low-density lipoprotein cholesterol
- Liver fibrosis
- NA, nucleos(t)ide analogue
- NAFLD, nonalcoholic fatty liver disease
- NASH, nonalcoholic steatohepatitis
- NR, not reported
- Nonalcoholic fatty liver disease
- OR, odds ratio
- PEG-IFN, pegylated interferon
- TAF, tenofovir alafenamide
- TDF, tenofovir
- TLR4, Toll-Like Receptor 4
- aHR, adjusted hazard ratio
- non-HDL-C, non-high-density lipoprotein-cholesterol
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25
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Liu SQ, Zhang XJ, Xue Y, Huang R, Wang J, Wu C, He YS, Pan YR, Liu LG. Dynamic changes of estimated glomerular filtration rate are conversely related to triglyceride in non-overweight patients. World J Clin Cases 2022; 10:11371-11380. [PMID: 36387799 PMCID: PMC9649538 DOI: 10.12998/wjcc.v10.i31.11371] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Revised: 08/30/2022] [Accepted: 09/23/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Correlation between Triglyceride (TG) and estimated glomerular filtration rate (eGFR) remains largely unknown in overweight and non-overweight patients.
AIM To investigated the dynamic changes of eGFR and lipid profiles during 3-year tenofovir disoproxil fumarate (TDF) treatment in patients with chronic hepatitis B (CHB) and overweight.
METHODS A total of 202 CHB patients who received TDF treatment at the Third People's Hospital of Changzhou (Changzhou, China) and Nanjing Drum Tower Hospital (Nanjing, China) between January 2016 and May 2018 were retrospectively enrolled. According to the body mass index (BMI) at the initiation of TDF treatment, CHB patients were divided into overweight (BMI ≥ 25 kg/m2) and non-overweight (BMI < 25 kg/m2) groups. Logistic regression was applied for the analysis of risk factors for eGFR < 90 mL/(min·1.73 m2).
RESULTS There is no significant difference in hepatitis B virus DNA (HBV DNA) negativity and hepatitis Be antigen (HBeAg) loss between patients with overweight and non-overweight (both P > 0.05). More patients in non-overweight group achieved alanine aminotransferase normalization compared with those in overweight group (χ2 = 11.036, P < 0.01). In non-overweight patients, the eGFR significantly declined in the 1st year (P < 0.01), then remained at a relatively lower level. TG significantly declined in the 2nd year (P = 0.02) and increased in the 3rd year. Moreover, TG was negatively correlated with GFR at the four-time points (P = 0.002, 0.030, 0.007, 0.008, respectively). In overweight patients, eGFR and TG remained relatively stable during the 3-year treatment, and eGFR showed no significant relationship with TG. Moreover, multivariate analysis showed that age [P < 0.01, 95%CI (0.97-1.005)] and baseline eGFR [P < 0.01, 95%CI (5.056-33.668)] were independent risk factors for eGFR < 90 mL/(min·1.73 m2) at the 3rd year.
CONCLUSION Dynamic changes in renal function were conversely related to TG during TDF treatment in patients with CHB and normal BMI, but not with overweight.
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Affiliation(s)
- Si-Qi Liu
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Xiu-Jun Zhang
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
| | - Yuan Xue
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Jian Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing 210008, Jiangsu Province, China
| | - Yi-Shan He
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Ya-Ru Pan
- Changzhou Clinical Medical College, Nanjing Medical University, Changzhou 213000, Jiangsu Province, China
| | - Long-Gen Liu
- Institute of Hepatology, The Third People’s Hospital of Changzhou, Changzhou 213000, Jiangsu Province, China
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26
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Zhang Q, Liang J, Yin J, Jiang Y, Yu N, Liao X, Zhao S, Wu L, Fan R. Real-life impact of tenofovir disoproxil fumarate and entecavir therapy on lipid profile, glucose, and uric acid in chronic hepatitis B patients. J Med Virol 2022; 94:5465-5474. [PMID: 35794065 DOI: 10.1002/jmv.27977] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 06/16/2022] [Accepted: 07/05/2022] [Indexed: 12/15/2022]
Abstract
The impact of long-term nucleos(t)ide analogs treatment on host metabolism is a concern. Hence, we conducted this study to compare the effect of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on metabolic parameters among chronic hepatitis B (CHB) patients. In this real-life retrospective study, 2030 CHB outpatients treated with ETV or TDF at Nanfang Hospital, China, were included. For treatment-naïve patients, pretreatment and semiannual metabolic parameters were collected. For treatment-experienced patients, metabolic parameters were collected at the first visit. Propensity score matching (PSM) was used to balance the effects of potential confounding factors. Among 122 treatment-naïve patients and 1908 treatment-experienced patients, ETV-treated patients were older with a higher percentage of metabolic syndrome. After PSM, the characteristics were comparable between the two groups. For treatment-naïve patients, four lipid parameters, including total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein, and triglyceride levels showed a decreasing trend during the 42-month TDF treatment, while they remained relatively stable or increased during ETV treatment. At Month 30, the levels of TC and LDL among TDF-treated patients were significantly lower than those among ETV-treated patients (TC: 4.7 mmol/L vs. 3.9 mmol/L, p = 0.004; LDL: 3.0 mmol/L vs. 2.4 mmol/L, p = 0.009). For treatment-experienced patients, we also observed lower levels of lipid parameters in patients with different durations of TDF treatment. The levels of glucose and uric acid were similar among ETV- and TDF-treated patients. TDF has a lipid-lowering effect in CHB patients, which provides a basis for the selection of antiviral drugs for aging CHB patients.
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Affiliation(s)
- Qi Zhang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Jinlin Liang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Junhua Yin
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yiyue Jiang
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ning Yu
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Xingmei Liao
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Siru Zhao
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Leyuan Wu
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Rong Fan
- Department of Infectious Diseases and Hepatology Unit, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital, Southern Medical University, Guangzhou, China
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DURAK S, COŞAR AM. Evaluation of the safety and antiviral efficacy of the tenofovir alafenamide fumarate molecule in immunosuppressed patients. JOURNAL OF HEALTH SCIENCES AND MEDICINE 2022. [DOI: 10.32322/jhsm.1179106] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Aim: Patients with chronic or prior hepatitis B virus (HBV) infection may experience HBV reactivation during immunosuppressive therapy. The objective of this study was to evaluate the safety and antiviral efficacy of tenofovir alafenamide fumarate (TAF) for prophylaxis of HBV reactivation in patients on immunosuppressive therapy.
Material and Method: This study included patients who were started on immunosuppressive treatment due to hematologic/solid malignancy, autoimmune disease, or inflammatory disease and were treated with TAF for at least six months due to HBsAg and/or total anti-HBc positivity at Karadeniz Technical University Farabi Hospital between January 2018 and February 2021. Electronic medical records were retrospectively reviewed and the adverse event profile was analyzed.
Results: Of the 94 patients enrolled in the study, 70.2% (n=66) were male. The mean age of the patients was 60.37±14.56 years. The reasons for initiation of immunosuppressive drug treatment were hematologic malignancies in 48.9% (n=46), solid tumors in 27.7% (n=26), and other causes (autoimmune/inflammatory) in 23.4% (n=22). There was no statistically significant difference in creatinine, phosphorus, glucose, and LDL profile between baseline and 6-12 months of TAF treatment (p=0.861, p=0.136, p=0.323, p=0.304, respectively). All patients in whom HBV DNA was detectable at baseline became negative at the last follow-up visit. None of the patients developed HBV reactivation and there was no need to discontinue antiviral/immunosuppressive treatment due to side effects.
Conclusion: TAF is a safe and effective short-term option to prevent HBV reactivation in patients receiving immunosuppressive therapy.
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Affiliation(s)
- Serdar DURAK
- Kanuni Training and Research Hospital, Department of Gastroenterology
| | - Arif Mansur COŞAR
- KARADENIZ TECHNICAL UNIVERSITY, SCHOOL OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, GASTROENTEROLOGY
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Changes in blood lipids in patients with chronic hepatitis B after 48 weeks of tenofovir alafenamide treatment: A prospective real-world clinical study. Antivir Ther 2022. [DOI: 10.1177/13596535221082399] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Background Tenofovir alafenamide (TAF) is a new anti-hepatitis B virus nucleotide analogue that can cause dyslipidaemia in AIDS patients, but the effect of TAF on blood lipids in patients with chronic hepatitis B (CHB) is unknown. This study aimed to evaluate the effect of TAF on blood lipid levels in patients with CHB. Methods One hundred and twenty-one CHB patients were recruited as TAF group, including 69 treatment-naïve patients and 52 patients with nucleoside/nucleotide analogue experience before TAF treatment. All patients were followed up regularly for 48 weeks. Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels and the incidence of dyslipidaemia before and after TAF treatment were compared. Results After 48 weeks of TAF treatment, the levels of TC, TGs and LDL-C in TAF group were significantly higher than those in control group. In TAF group, the TC and TG levels were significantly higher than that at baseline. Baseline TC and TGs levels had a significant effect on the incidence of abnormal TC and TG levels after 48 weeks treatment. The LDL-C decreased slightly but not significantly. The proportion of patients with TC abnormalities increased from 20.7% at baseline to 26.3% at week 48, LDL-C abnormalities decreased from 50.4% to 42.5% and TG abnormalities increased from 14.2% to 22.5%. There were no significant differences compared with control group, as well as compared with baseline. Conclusions Tenofovir alafenamide treatment mainly affects the TC and TG level in patients with CHB but has little effect on LDL-C.
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Wang X, Xie Q. Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) and Viral Hepatitis. J Clin Transl Hepatol 2022; 10:128-133. [PMID: 35233381 PMCID: PMC8845159 DOI: 10.14218/jcth.2021.00200] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 12/04/2022] Open
Abstract
A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed in 2020. The change from nonalcoholic fatty liver disease (NAFLD) to MAFLD highlights the metabolic abnormalities that accompany fatty liver. The diagnosis of MAFLD does not require exclusion of secondary causes of liver diseases and alcohol consumption. Thus, MAFLD may coexist with other types of liver diseases, such as viral hepatitis, a disease that remains the most common cause of liver disease-related death. With the increasing prevalence of MAFLD, patients with coincidental MAFLD and viral hepatitis are frequently encountered in clinical practice. In this review, we mainly summarize the mutual relationship between hepatitis B/C and systematic metabolism dysfunction related to MAFLD. We discuss the impact of MAFLD on progression of viral hepatitis and the therapies. Some unaddressed clinical problems related to concomitant MAFLD and viral hepatitis are also identified.
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Affiliation(s)
- Xiaolin Wang
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qing Xie
- Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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30
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Lin HY, Tseng TC. Dyslipidemia in CHB patients on TAF: Facts and Puzzles. Clin Mol Hepatol 2022; 28:181-182. [PMID: 35184513 PMCID: PMC9013606 DOI: 10.3350/cmh.2022.0028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 02/18/2022] [Indexed: 11/07/2022] Open
Affiliation(s)
- Hung-Yao Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.,Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
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31
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Suzuki K, Suda G, Yamamoto Y, Abiko S, Kinoshita K, Miyamoto S, Sugiura R, Kimura M, Maehara O, Yamada R, Kitagataya T, Shigesawa T, Ohara M, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Sakamoto N. Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B. PLoS One 2022; 17:e0261760. [PMID: 35051189 PMCID: PMC8775237 DOI: 10.1371/journal.pone.0261760] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 12/09/2021] [Indexed: 12/22/2022] Open
Abstract
For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.
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Affiliation(s)
- Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
- * E-mail:
| | - Yoshiya Yamamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Satoshi Abiko
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Kenji Kinoshita
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Shuichi Miyamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Ryo Sugiura
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Osamu Maehara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, Hokkaido, Japan
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Hosaka T, Suzuki F, Kobayashi M, Fujiyama S, Kawamura Y, Sezaki H, Akuta N, Suzuki Y, Saitoh S, Arase Y, Ikeda K, Kobayashi M, Kumada H. Renal safety and biochemical changes for 2 years after switching to tenofovir alafenamide from long-term other nucleotide analog treatment in patients with chronic hepatitis B. Hepatol Res 2022; 52:153-164. [PMID: 34687121 DOI: 10.1111/hepr.13726] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 09/24/2021] [Accepted: 10/20/2021] [Indexed: 02/08/2023]
Abstract
BACKGROUND Long-term use of nucleotide analogs such as adefovir (ADV) or tenofovir disoproxil fumarate (TDF) may cause renal impairment. Tenofovir alafenamide (TAF) has less systemic exposure than TDF did. The aims were to examine longitudinal changes in renal function and biochemical parameters for 2 years after switching from long-term ADV and TDF to TAF, and to explore factors associated with improved renal function after TAF in patients with chronic hepatitis B. METHODS The prospective observational cohort study included 306 patients with chronic hepatitis B who underwent switching from long-term TDF or ADV to TAF. The primary outcome was the changes in estimated glomerular filtration rate (eGFR) after TAF. RESULTS Among 306 patients, 190 (65.3%) and 106 (34.7%) had chronic kidney disease (CKD) stages 1-2 and 3a-4 at baseline. In patients with CKD stages 3a-4, the mean eGFR significantly increased until week 12 and plateaued from week 12 to year 2 (adjusted slope using linear mixed effect models: +9.01 ml/min/1.73 m2 /year until week 12; p < 0.001). In contrast, the mean eGFR plateaued from baseline to year 2 in the CKD stages 1-2 subgroup. Multivariate logistic regression showed that baseline CKD stage ≥3a, steeper decline in eGFR 1 year before TAF, and shorter duration of any nucleotide analog use was significantly associated with ≥10% improvement in eGFR in year 1. CONCLUSIONS Switching from TDF or ADV to TAF resulted in favorable renal safety for 2 years. In CKD stage 3a-4 subgroup, eGFR after TAF was recovered in the first 12 weeks and subsequently stabilized.
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Affiliation(s)
- Tetsuya Hosaka
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | | | | | | | - Hitomi Sezaki
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Norio Akuta
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | | | - Satoshi Saitoh
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Yasuji Arase
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Kenji Ikeda
- Department of Hepatology, Toranomon Hospital, Tokyo, Japan
| | - Mariko Kobayashi
- Research Institute for Hepatology, Toranomon Hospital, Tokyo, Japan
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Mallon PWG, Brunet L, Fusco JS, Prajapati G, Beyer A, Fusco GP, Wohlfeiler MB. Lipid Changes After Switch From TDF to TAF in the OPERA Cohort: LDL Cholesterol and Triglycerides. Open Forum Infect Dis 2022; 9:ofab621. [PMID: 35028335 PMCID: PMC8753026 DOI: 10.1093/ofid/ofab621] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 12/07/2021] [Indexed: 12/22/2022] Open
Abstract
Background Increases in lipids have been observed in people with HIV (PWH) switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). We assessed changes in low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) following a switch from TDF to TAF. Methods Adults with ≥1 lipid measure before and after switch from TDF to TAF were identified in the OPERA cohort. Multivariable linear regression using generalized estimating equations was used to estimate predicted changes in lipids over time on TAF, modeled flexibly with linear splines. Results A total of 6451 PWH switched from TDF to TAF, of whom 4328 maintained all other agents. LDL-C increased significantly by 1.40 mg/dL/mo over the first 3 months on TAF, by 0.33 mg/dL/mo between 3 and 9 months and then plateauing beyond 9 months. TG increased significantly by 3.52 mg/dL/mo over the first 3 months of TAF, by 0.91 mg/mL/mo between 3 and 9 months and by 0.72 mg/mL/mo between 9 and 16 months, but decreased thereafter. Similar patterns were observed in analyses restricted to PWH who switched from TDF to TAF but maintained all other agents. Conclusions TDF-to-TAF switch was associated with LDL-C and TG increases over the first 9 to 16 months on TAF. The dynamic patterns observed cannot be attributed to changes in other agents.
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Affiliation(s)
- Patrick W G Mallon
- Centre for Experimental Pathogen Host Research, School of Medicine, University College Dublin, Dublin, Ireland
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Comparison of Tenofovir Alafenamide and Entecavir Therapy in Patients with Chronic Hepatitis B Initially Treated with Tenofovir Disoproxil: A Retrospective Observational Survey. HEPATITIS MONTHLY 2022. [DOI: 10.5812/hepatmon.118721] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/13/2023]
Abstract
Background: In chronic hepatitis B patients with or exposed to the risk of osteoporosis or renal dysfunction, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) or entecavir (ETV) may be the right choice. Objectives: This study aimed to present real-life data in terms of the efficacy and safety of a TAF/ETV treatment change while receiving TDF. Methods: This retrospective study was conducted on 344 adult patients from 10 centers. The data of patients who had changed to ETV (n = 107) and TAF (n = 237) while receiving TDF were analyzed. The data collected at 0 and 6 months of treatment were analyzed. The virological response was assessed based on undetected hepatitis B virus (HBV) DNA. Serum alanine aminotransferase (ALT) values were used to evaluate the biochemical response. For renal function, serum creatinine and phosphorus, as well as estimated glomerular filtration rate (eGFR), were recorded. Moreover, lumbar spine and hip T-scores along with the serum lipid profile were evaluated. Results: The mean age of patients was 41.14 ± 13.46 years, and 224 (65.1%) of the participants were male. The treatment arms were not significantly different in terms of demographic characteristics, comorbid diseases, infection duration, family history of HBV infection, blood platelet count, serum biomarkers, such as ALT, phosphorus, creatinine, total bilirubin, albumin, lipid profile, and HBV DNA levels at the beginning. No statistically significant difference was found between the proportion of undetectable HBV DNA of the two treatment groups after 6 months (P = 0.221). The ALT normalization in the ETV and TAF groups at the sixth month compared to the baseline levels was not significantly different (P = 0.853, P = 0.330, respectively). There was no statistically significant difference between the two treatment arms regarding changes in eGFR, creatinine, phosphorus, hip, and spine T-scores from baseline to 6 months (P = 0.296, P = 0.78, P = 0.141, P = 0.832, P = 0.947, respectively). In those who switched to TAF or ETV, low-density lipoproteins cholesterol were observed to be significantly higher after 6 months compared to baseline values (P = 0.002, P = 0.049, respectively). The TC increased significantly in the TAF group (P = 0.035). Conclusions: Our study showed that switching to ETV and TAF sustained the viral suppression and biochemical response achieved by TDF therapy. The treatment switch to TAF of ETV can control renal dysfunction and reduce bone mineral density caused by TDF.
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Liu Z, Liu Z, Xiao L, Niu J, Hou J. Editorial: the three tenors in HBV-TDF, TAF and now TMF. Authors' reply. Aliment Pharmacol Ther 2022; 55:121. [PMID: 34907550 DOI: 10.1111/apt.16692] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Zhihong Liu
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ziyang Liu
- Jiangsu Hansoh Pharmaceutical Co Ltd, Lianyungang, China
| | - Ling Xiao
- Jiangsu Hansoh Pharmaceutical Co Ltd, Lianyungang, China
| | - Junqi Niu
- Department of Hepatobiliary and Pancreatology of The First Hospital of Jilin University, Changchun, China
| | - Jinlin Hou
- Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China
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Jeong J, Shin JW, Jung SW, Park EJ, Park NH. Tenofovir alafenamide treatment may not worsen the lipid profile of chronic hepatitis B patients: a propensity score-matched analysis. Clin Mol Hepatol 2021; 28:254-264. [PMID: 34959261 PMCID: PMC9013607 DOI: 10.3350/cmh.2021.0314] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2021] [Accepted: 12/25/2021] [Indexed: 11/10/2022] Open
Abstract
Background/Aims Tenofovir alafenamide (TAF) has shown less favorable effect on lipids compared to tenofovir disoproxil fumarate (TDF) in clinical trials. However, data regarding these outcomes in patients with chronic hepatitis B (CHB) are scarce. Therefore, this study aimed to evaluate the effect of TAF on the lipid in patients with CHB. Methods A total of 237 TAF-treated CHB patients compared with TDF, inactive CHB, and non-hepatitis B virus (HBV)-infected control groups using propensity score matching (PSM). Results Following PSM, each analysis was conducted on cohorts via the matching of 70:140 (TAF:TDF), 89:89 (TAF:inactive CHB), 140:560 (TAF:non-HBV infected control), and 368:1,472 (TDF:non-HBV-infected control). A significant decrease in the total cholesterol (TC) level was noted at 48 weeks in the TDF group compared to the TAF group (176.3±32.9 vs. 156.7±27.7, P<0.001) and the non-HBV-infected control group (175.0±29.5 vs. 156.2±28.3, P<0.001). However, no significant change in TC was observed in the TAF group and inactive CHB or non-HBV-infected control groups at 48 weeks. For the subgroup analyses of TAF vs. non-HBV-infected control subjects and inactive CHB patients whose detailed lipid profile information were available, no between-group differences in TC, low-density lipoprotein (LDL)-cholesterol, highdensity lipoprotein (HDL)-cholesterol, TC/HDL ratio, and LDL/HDL ratio were observed at 48 weeks. Conclusions TDF seems to have a lipid-lowering effect compared to the non-HBV-infected control and TAF-treated groups. However, in real practice, TAF might not worsen the lipid profiles of subjects compared to non-HBV-infected controls and patients with inactive CHB.
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Affiliation(s)
- Joonho Jeong
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Jung Woo Shin
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Seok Won Jung
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Eun Ji Park
- Big-data Center, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
| | - Neung Hwa Park
- Department of Internal Medicine, University of Ulsan College of Medicine, Ulsan University Hospital, Ulsan, Republic of Korea
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Brunet L, Mallon P, Fusco JS, Wohlfeiler MB, Prajapati G, Beyer A, Fusco GP. Switch from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living with HIV: Lipid Changes and Statin Underutilization. Clin Drug Investig 2021; 41:955-965. [PMID: 34546533 PMCID: PMC8556204 DOI: 10.1007/s40261-021-01081-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/02/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND OBJECTIVE Many people living with HIV (PLWH) on stable tenofovir disoproxil fumarate (TDF)-containing regimens have switched to tenofovir alafenamide (TAF), despite the potential lipid-lowering effect of TDF. We aimed to assess the impact of switching from TDF to TAF on lipids in real-world clinical practice. METHODS PLWH prescribed TDF for ≥ 4 weeks who switched to TAF were identified in the OPERA cohort. Patterns of dyslipidemia were compared before and after switch based on NCEP ATPIII guidelines. Elevated 10-year risk of atherosclerotic cardiovascular disease (ASCVD ≥ 7.5%) and statin use were assessed. RESULTS Among 6423 PLWH switched from TDF to TAF, the proportion with dyslipidemia/severe dyslipidemia observed after switch from TDF to TAF increased statistically significantly (p < 0.0001) with total cholesterol (5-10%), low-density lipoprotein cholesterol (16-23%), and triglycerides (21-27%), but decreased statistically significantly with high-density lipoprotein cholesterol (35-30%, p < 0.0001). These patterns of dyslipidemia persisted in sensitivity analyses restricted to PLWH who maintained all other antiretrovirals (N = 4328) or stratified by pharmaco-enhancer use before and after switch. An elevated ASCVD risk was detected in 29% before and 31% after switch. As many as 59% of PLWH with an elevated ASCVD risk were not prescribed a statin after switch from TDF to TAF. CONCLUSIONS In this large, diverse population of PLWH in the USA, the switch from TDF to TAF was associated with development of less favorable lipid profiles, regardless of pharmaco-enhancers or third-agent use. Statins remained underutilized after a switch from TDF to TAF.
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Affiliation(s)
- Laurence Brunet
- Epividian, Inc., 4819 Emperor Blvd., Suite 400, Durham, NC, 27703, USA.
| | - Patrick Mallon
- Centre for Experimental Pathogen Host Research, University College Dublin, Dublin, Ireland
| | - Jennifer S Fusco
- Epividian, Inc., 4819 Emperor Blvd., Suite 400, Durham, NC, 27703, USA
| | | | | | | | - Gregory P Fusco
- Epividian, Inc., 4819 Emperor Blvd., Suite 400, Durham, NC, 27703, USA
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Chang XJ, Shi YW, Wang J, Liu HB, Chen Y, Zhu XN, Chen YP, Yu ZJ, Shang QH, Tan L, Li Q, Jiang L, Xiao GM, Chen L, Lu W, Hu XY, Long QH, An LJ, Zou ZY, Wong VWS, Yang YP, Fan JG. Influence of weight management on the prognosis of steatohepatitis in chronic hepatitis B patients during antiviral treatment. Hepatobiliary Pancreat Dis Int 2021; 20:416-425. [PMID: 34275749 DOI: 10.1016/j.hbpd.2021.06.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Accepted: 06/25/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Although concomitant nonalcoholic steatohepatitis (NASH) is common in chronic hepatitis B (CHB), the impact of viral factors on NASH and the outcome of CHB patients concomitant with NASH remain unclear. We aimed to investigate the outcomes of NASH in CHB patients receiving antiviral treatment. METHODS In the post-hoc analysis of a multicenter trial, naïve CHB patients receiving 72-week entecavir treatment were enrolled. We evaluated the biochemical, viral and histopathological responses of these patients. The histopathological features of NASH were also evaluated, using paired liver biopsies at baseline and week 72. RESULTS A total of 1000 CHB patients were finally enrolled for analysis, with 18.2% of whom fulfilling the criteria of NASH. A total of 727 patients completed entecavir antiviral treatment and received the second biopsy. Serum HBeAg loss, HBeAg seroconversion and HBV-DNA undetectable rates were similar between patients with or without NASH (P > 0.05). Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up (all P < 0.001), 46% (63/136) achieved NASH resolution. Patients with baseline body mass index (BMI) ≥ 23 kg/m2 (Asian criteria) [odds ratio (OR): 0.414; 95% confidence interval (95% CI): 0.190-0.899; P = 0.012] and weight gain (OR: 0.187; 95% CI: 0.050-0.693; P = 0.026) were less likely to have NASH resolution. Among patients without NASH at baseline, 22 (3.7%) developed NASH. Baseline BMI ≥ 23 kg/m2 (OR: 12.506; 95% CI: 2.813-55.606; P = 0.001) and weight gain (OR: 5.126; 95% CI: 1.674-15.694; P = 0.005) were predictors of incident NASH. CONCLUSIONS Lower BMI and weight reduction but not virologic factors determine NASH resolution in CHB. The value of weight management in CHB patients during antiviral treatment deserves further evaluation.
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Affiliation(s)
- Xiu-Juan Chang
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Yi-Wen Shi
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Jing Wang
- Department of Liver Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 610072, China
| | - Hua-Bao Liu
- Department of Liver Diseases, Traditional Chinese Medicine Hospital of Chongqing, Chongqing 400038, China
| | - Yan Chen
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Xiao-Ning Zhu
- Department of Liver Disease, Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou 610072, China
| | - Yong-Ping Chen
- Department of Infectious and Liver Diseases, Liver Research Center, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
| | - Zu-Jiang Yu
- Department of Infectious Disease, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
| | - Qing-Hua Shang
- Center of Therapeutic Liver Disease, the 960th Hospital of Chinese PLA, Taian 271000, China
| | - Lin Tan
- Liver Disease Department, Fuyang 2nd People's Hospital, Fuyang 236015, China
| | - Qin Li
- Department of Liver Diseases, Fuzhou Infectious Diseases Hospital, Fuzhou 350025, China
| | - Li Jiang
- Department of Infectious Diseases, Southwest Hospital, Army Military Medical University, Chongqing 400038, China
| | - Guang-Ming Xiao
- Department of Infectious Diseases, Guangzhou 8th People's Hospital, Guangzhou 510060, China
| | - Liang Chen
- Department of Hepatic Diseases, Shanghai Public Health Clinical Center, Shanghai 201508, China
| | - Wei Lu
- Department of Liver Diseases, Tianjin Second People's Hospital, Tianjin Institute of Hepatology, Tianjin 300192, China
| | - Xiao-Yu Hu
- National Integrative Medicine Clinical Base for Infectious Diseases and Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610000, China
| | - Qing-Hua Long
- Department of Infection and Liver Disease, Yichun People's Hospital, Yichun 336028, China
| | - Lin-Jing An
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China
| | - Zi-Yuan Zou
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
| | - Yong-Ping Yang
- Department of Liver Disease, Chinese PLA General Hospital, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China.
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Shi YW, Yang RX, Fan JG. Chronic hepatitis B infection with concomitant hepatic steatosis: Current evidence and opinion. World J Gastroenterol 2021; 27:3971-3983. [PMID: 34326608 PMCID: PMC8311534 DOI: 10.3748/wjg.v27.i26.3971] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2021] [Revised: 04/28/2021] [Accepted: 05/27/2021] [Indexed: 02/06/2023] Open
Abstract
With the increasing incidence of obesity and metabolic syndrome worldwide, concomitant nonalcoholic fatty liver disease (NAFLD) in patients with chronic hepatitis B (CHB) has become highly prevalent. The risk of dual etiologies, outcome, and mechanism of CHB with concomitant NAFLD have not been fully characterized. In this review, we assessed the overlapping prevalence of metabolic disorders and CHB, assessed the risk of advanced fibrosis/hepatocellular carcinoma in CHB patients concomitant with NAFLD, and discussed the remaining clinical issues to be addressed in the outcome of such patients. We also explored the possible roles of hepatitis B virus in the development of steatosis and discussed difficultiesof histological evaluation. For CHB patients, it is important to address concomitant NAFLD through lifestyle management and disease screening to achieve better prognoses. The assessment of progressive changes and novel therapies for CHB patients concomitant with NAFLD deserve further research.
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Affiliation(s)
- Yi-Wen Shi
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Rui-Xu Yang
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
| | - Jian-Gao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China
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Suzuki K, Suda G, Yamamoto Y, Furuya K, Baba M, Nakamura A, Miyoshi H, Kimura M, Maehara O, Yamada R, Kitagataya T, Yamamoto K, Shigesawa T, Nakamura A, Ohara M, Kawagishi N, Nakai M, Sho T, Natsuizaka M, Morikawa K, Ogawa K, Ohnishi S, Sakamoto N. Tenofovir-disoproxil-fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection. J Gastroenterol 2021; 56:168-180. [PMID: 33211179 DOI: 10.1007/s00535-020-01750-3] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Accepted: 11/02/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND Entecavir and tenofovir-disoproxil-fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism. METHODS A retrospective study was performed on HBV patients administered entecavir or tenofovir-disoproxil-fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6-12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir-disoproxil-fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism. RESULTS Administration of tenofovir-disoproxil-fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir-disoproxil-fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir-disoproxil-fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir-disoproxil-fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir-disoproxil-fumarate on CD36. CONCLUSIONS Tenofovir-disoproxil-fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA.
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Affiliation(s)
- Kazuharu Suzuki
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Goki Suda
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
| | - Yoshiya Yamamoto
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Ken Furuya
- Department of Gastroenterology, JCHO Hokkaido Hospital, Hokkaido, Japan
| | - Masaru Baba
- Department of Gastroenterology, JCHO Hokkaido Hospital, Hokkaido, Japan
| | - Akinobu Nakamura
- Department of Rheumatology, Endocrinology and Nephrology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Graduate School of Medicine, Hokkaido, Japan
| | - Hideaki Miyoshi
- Division of Diabetes and Obesity, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
| | - Megumi Kimura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Osamu Maehara
- Department of Gastroenterology, Hakodate Municipal Hospital, Hokkaido, Japan
| | - Ren Yamada
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takashi Kitagataya
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Koji Yamamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Taku Shigesawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Akihisa Nakamura
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Masatsugu Ohara
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Naoki Kawagishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Masato Nakai
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Takuya Sho
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Mitsuteru Natsuizaka
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Kenichi Morikawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Koji Ogawa
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Shunsuke Ohnishi
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
| | - Naoya Sakamoto
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Hokkaido University, North 15, West 7, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan
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Con D, Goodwin T, Majeed A, Roberts S, Kemp W. Comparison of 48-week efficacy of tenofovir vs entecavir for patients with chronic hepatitis B: A network meta-analysis. J Viral Hepat 2021; 28:40-50. [PMID: 32893921 DOI: 10.1111/jvh.13400] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 08/15/2020] [Accepted: 08/17/2020] [Indexed: 02/06/2023]
Abstract
Both tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are accepted as first-line treatments for chronic hepatitis B (CHB). However, there are few randomized studies comparing their efficacy. The primary aim of this study was to compare the efficacy of TDF and ETV using a network meta-analysis of randomized trials. The secondary aim was to additionally include propensity-matched cohort studies in a conventional meta-analysis. We systematically searched PubMed, EMBASE, Cochrane Library and Web of Science for published English-language randomized and propensity-matched studies between 1/1/2000 and 4/2/2020. Outcomes included undetectable HBV DNA, ALT normalization and HBeAg seroconversion at 48 weeks. We excluded patients who had co-infection or significant prior treatment with antivirals. 13 517 participants from 16 studies (11 RCTs, n = 2675; five propensity-matched cohort studies, n = 10 842) were included. Virological response at 48 weeks was higher in patients receiving TDF compared to ETV using both the network meta-analytic approach (OR 1.69, P < .001) and the conventional meta-analysis including propensity-matched cohort studies (OR 1.40, P < .001). On subgroup analysis, this difference was only significant in HBeAg-positive patients (OR 1.81, P = .037). There was limited evidence to suggest a higher rate of ALT normalization with ETV (OR 0.74, P = .07). There was no difference in rates of HBeAg seroconversion between the two antivirals. TDF is more likely than ETV to induce virological response at 48 weeks in treatment-naïve CHB patients. Future studies should focus on elucidating associations between early and sustained virological response with adverse patient outcomes including development of HCC or cirrhosis.
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Affiliation(s)
- Danny Con
- Department of General Medicine, Eastern Health, Melbourne, Victoria, Australia
| | - Thomas Goodwin
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
| | - Ammar Majeed
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - Stuart Roberts
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
| | - William Kemp
- Department of Gastroenterology, Alfred Health, Melbourne, Victoria, Australia
- Central Clinical School, Faculty of Medicine Nursing & Health Sciences, Monash University, Melbourne, Victoria, Australia
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Amponsah-Dacosta E, Tchuem CT, Anderson M. Chronic hepatitis B-associated liver disease in the context of human immunodeficiency virus co-infection and underlying metabolic syndrome. World J Virol 2020; 9:54-66. [PMID: 33362998 PMCID: PMC7747023 DOI: 10.5501/wjv.v9.i5.54] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 09/24/2020] [Accepted: 10/12/2020] [Indexed: 02/06/2023] Open
Abstract
Globally, a shift in the epidemiology of chronic liver disease has been observed. This has been mainly driven by a marked decline in the prevalence of chronic hepatitis B virus infection (CHB), with the greatest burden restricted to the Western Pacific and sub-Saharan African regions. Amidst this is a growing burden of metabolic syndrome (MetS) worldwide. A disproportionate co-burden of human immunodeficiency virus (HIV) infection is also reported in sub-Saharan Africa, which poses a further risk of liver-related morbidity and mortality in the region. We reviewed the existing evidence base to improve current understanding of the effect of underlying MetS on the development and progression of chronic liver disease during CHB and HIV co-infection. While the mechanistic association between CHB and MetS remains poorly resolved, the evidence suggests that MetS may have an additive effect on the liver damage caused by CHB. Among HIV infected individuals, MetS-associated liver disease is emerging as an important cause of non-AIDS related morbidity and mortality despite antiretroviral therapy (ART). It is plausible that underlying MetS may lead to adverse outcomes among those with concomitant CHB and HIV co-infection. However, this remains to be explored through rigorous longitudinal studies, especially in sub-Saharan Africa. Ultimately, there is a need for a comprehensive package of care that integrates ART programs with routine screening for MetS and promotion of lifestyle modification to ensure an improved quality of life among CHB and HIV co-infected individuals.
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Affiliation(s)
- Edina Amponsah-Dacosta
- Vaccines for Africa Initiative, School of Public Health and Family Medicine, University of Cape Town, Cape Town 7925, Western Cape, South Africa
| | - Cynthia Tamandjou Tchuem
- Health Economics Unit, School of Public Health and Family Medicine, University of Cape Town, Cape Town 7925, Western Cape, South Africa
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Yang J, Chen J, Ji Y, Tang Q, Zhang R, Liu L, Shen Y, Xun J, Song W, Tang Y, Wang Z, Qi T, Lu H. Lipid profile and renal safety of tenofovir disoproxil fumarate-based anti-retroviral therapy in HIV-infected Chinese patients. Int J Infect Dis 2019; 83:64-71. [PMID: 30951879 DOI: 10.1016/j.ijid.2019.03.034] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2019] [Revised: 03/27/2019] [Accepted: 03/28/2019] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Tenofovir disoproxil fumarate (TDF) is an important component of antiretroviral therapy (ART) that has been widely used. The aim of this study was to observe the long-term impact of TDF-based ART on lipid metabolism profiles and renal functions in Chinese patients. METHODS 414 and 124 HIV-infected, ART-naïve patients who initiated TDF-based regimens and non-TDF regimens respectively were retrospectively included. Demographic characteristics and clinical information of each patient was collected. Changes of lipid profiles and renal function, as well as the risk factors of hyperlipidemia and renal dysfunction were analyzed. RESULTS After 96 weeks of ART, HIV viral loads were undetectable in 97.34% (403/414) of patients exposed to TDF. The plasma total cholesterol (TCH) increased from 3.97 ± 0.83 mmol/L to 4.53 ± 0.87 mmol/L (P < 0.001), which did not show a significant difference comparing with non-TDF exposed group. By contrast, the plasma triglyceride (TG) levels increased, but were still lower than that in the non-TDF exposed group (0.26 ± 1.24 vs. 0.89 ± 1.78, P < 0.001). The mean estimated glomerular filtration rate (eGFR) decreased from 127.29 ± 24.04ml∙min-1∙1.73 m-2 at baseline to 118.84 ± 22.74 ml∙min-1∙1.73 m-2(P < 0.001) in the TDF exposed group, while it increased in the non-TDF exposed group. In the TDF group, high body mass index (BMI) (OR = 1.13, P = 0.01), high baseline TG (OR = 2.33, P<0.001) and receiving protease inhibitors (PIs) (OR = 7.58, P < 0.001) were associated with hypertriglyceridemia after ART, while high baseline TCH predicted hypercholesterolemia (OR = 3.58, P < 0.001). MSM (OR = 0.22, P = 0.02) and baseline eGFR (OR = 0.90, P < 0.001) was associated with renal dysfunction after ART. CONCLUSIONS TDF-based regimens are of good therapeutic effect among Chinese people. These regimens showed a better plasma lipid profile but mild renal dysfunction as compared to non-TDF based regimens. Patients with high BMI, high baseline TG, high baseline TCH and low baseline eGFR should be closely monitored when using TDF-based ART.
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Affiliation(s)
- Junyang Yang
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Wenzhou Medical University, Wenzhou, Zhejiang, China.
| | - Jun Chen
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Yongjia Ji
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Qi Tang
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Renfang Zhang
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Li Liu
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Yinzhong Shen
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Jingna Xun
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Wei Song
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Yang Tang
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Zhenyan Wang
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Tangkai Qi
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
| | - Hongzhou Lu
- Department of Infectious and Immune Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China; Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University, Shanghai, China; Department of Internal Medicine, Shanghai Medical College, Fudan University, Shanghai, China.
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Zhao Y, Xing H, Wang X, Ou W, Zhao H, Li B, Li Y, Duan Y, Zhuang L, Li W, Cheng D, Quan M, Zhang Y, Ji S. Management of Diabetes Mellitus in Patients with Chronic Liver Diseases. J Diabetes Res 2019; 2019:6430486. [PMID: 31915709 PMCID: PMC6931017 DOI: 10.1155/2019/6430486] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Accepted: 11/09/2019] [Indexed: 02/06/2023] Open
Abstract
Diabetes mellitus (DM) is a common chronic disease affecting humans globally. During the last few years, the incidence of diabetes has increased and has received more attention. In addition to growing DM populations, DM complications are involving injuries to more organs, such as the heart and cerebral vessel damage. DM complications can reduce quality of life and shorten life spans and eventually also impede social and economic development. Therefore, effective measures to curb the occurrence and development of diabetes assist in improving patients' quality of life, delay the progression of DM in the population, and ease a social burden. The liver is regarded as an important link in the management and control of DM, including the alleviation of glucose metabolism and lipid metabolism and others via glucose storage and endogenous glucose generation from glycogen stored in the liver. Liver cirrhosis is a very common chronic disease, which often lowers the quality of life and decreases life expectancy. According to a growing body of research, diabetes shows a close correlation with hepatitis, liver cirrhosis, and liver cancer. Moreover, coexistence of liver complications would accelerate the deterioration of patients with diabetes. Liver cirrhosis and diabetes influence each other. Thus, in addition to pharmacological treatments and lifestyle interventions, effective control of cirrhosis might assist in a better management of diabetes. When it comes to different etiologies of liver cirrhosis, different therapeutic methods, such as antiviral treatment, may be more effective. Effective control of cirrhosis might be a strategy for better management of diabetes.
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Affiliation(s)
- Yingying Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Huichun Xing
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Xiaomei Wang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Weini Ou
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Hong Zhao
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Ben Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Yue Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Ying Duan
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Liwei Zhuang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Wei Li
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Danying Cheng
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Min Quan
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Yu Zhang
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
| | - Shibo Ji
- Department of Hepatology, Division 3, Beijing Ditan Hospital, Capital Medical University and Teaching Hospital of Peking University, 8 Jingshundong Street, Beijing 100015, China
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Effect of entecavir and adefovir dipivoxil on thyroid function and liver function in patients with decompensated hepatitis B cirrhosis. Shijie Huaren Xiaohua Zazhi 2018; 26:311-317. [DOI: 10.11569/wcjd.v26.i5.311] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the effect of entecavir and adefovir dipivoxil on thyroid function and liver function in patients with decompensated hepatitis B cirrhosis.
METHODS One hundred and twenty patients with decompensated hepatitis B cirrhosis treated from September 2014 to September 2016 at our hospital were randomly divided into an observation group (n = 60) and a control group (n = 60). Both groups received conventional treatment. The control group was additionally given adefovir dipivoxil, and the observation group was given entecavir. At 3, 6, and 12 mo after treatment, hepatitis B virus (HBV) DNA negative rate, HBeAg negative rate, Child-Pugh score, liver function, thyroid function, the incidence of complications, mortality, and the incidence of adverse drug reactions were observed.
RESULTS At 3, 6, and 12 mo after treatment, HBV DNA negative rates were significantly higher in the observation group than in the control group (P < 0.05), although there was no significant difference in hepatitis B e antigen negative rates (P > 0.05); the Child-Pugh scores and serum levels of alanine transaminase, aspartate transaminase, and total bilirubin were significantly lower in the observation group than in the control group (P < 0.05). After treatment for 1 year, the levels of T3, T4, FT3, and FT4 were significantly higher and that of TSH was significantly lower in the observation group than in the control group (P < 0.05). There was no significant difference in the incidence of complications or mortality (P > 0.05), and no severe adverse reactions were observed in either group.
CONCLUSION Entecavir is significantly effective in patients with decompensated hepatitis B cirrhosis and can improve liver function and thyroid function with good safety.
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Aspinall AI, Shaheen AA, Kochaksaraei GS, Haslam B, Lee SS, Macphail G, Kapler J, Larios OE, Burak KW, Swain MG, Borman MA, Coffin CS. Real-world treatment of hepatitis C with second-generation direct-acting antivirals: initial results from a multicentre Canadian retrospective cohort of diverse patients. CMAJ Open 2018; 6:E12-E18. [PMID: 29305405 PMCID: PMC5963434 DOI: 10.9778/cmajo.20170059] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND High hepatitis C cure rates have been observed in registration trials with second-generation direct-acting antivirals. Real-world data also indicate high sustained viral response (SVR) rates. Our objective was to determine real-world SVR rates for patients infected with hepatitis C virus (HCV) who were treated with second-generation direct-acting antivirals in the first 18 months of their availability in Canada. METHODS Four centres in Calgary contributed their treatment data for a diverse patient population including those who had or had not undergone liver transplantation, those coinfected with HIV and vulnerable populations. We included all patients documented to have started hepatitis C treatment with direct-acting antivirals between October 2014 and April 2016, with follow-up through October 2016. We used multivariate analysis to determine independent predictors of treatment failure. RESULTS Outcome data were available for 351 patients, of whom 326 (92.9%) achieved an SVR (193/206 [93.7%], 57/59 [96.6%] and 44/51 [86.3%] for genotypes 1a, 1b and 3, respectively, p = 0.2). Independent predictors of not achieving SVR were older age (adjusted odds ratio [OR] 0.95 [95% confidence interval (CI) 0.90-1.00]), male sex (adjusted OR 0.30 [95% CI 0.10-0.89]) and, in patients with genotype 1a infection, history of hepatocellular carcinoma (adjusted OR 0.13 [95% CI 0.03-0.53]). In the entire cohort, the presence of cirrhosis, genotype and hepatocellular carcinoma were not associated with a lower SVR rate. There were no differences in SVR rate according to treatment centre, HIV coinfection or liver transplantation. Among patients with genotype 3 infection, a significantly lower SVR rate was observed for those treated outside of standard of care than for those treated within standard of care (33.3% v. 89.6%, p = 0.04). De novo hepatocellular carcinoma developed in 12 patients (3.4%) despite successful direct-acting antiviral therapy. INTERPRETATION We report high SVR rates in a real-world diverse cohort of HCV-infected patients treated with second-generation direct-acting antivirals. The results highlight the importance of conducting real-world analyses to elucidate clinical factors associated with poorer outcomes that may not be identified in registration trials.
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Affiliation(s)
- Alex I Aspinall
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Abdel A Shaheen
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Golasa S Kochaksaraei
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Breean Haslam
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Samuel S Lee
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Gisela Macphail
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Jeff Kapler
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Oscar E Larios
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Kelly W Burak
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Mark G Swain
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Meredith A Borman
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
| | - Carla S Coffin
- Affiliations: Calgary Liver Unit (Aspinall, Shaheen, Kochaksaraei, Haslam, Lee, Burak, Swain, Borman, Coffin), Division of Gastroenterology and Hepatology, Department of Medicine, University of Calgary; Calgary Urban Project Society (Macphail); Southern Alberta Clinic (Kapler, Larios, Coffin), Alberta Health Services, Calgary, Alta
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Huang R, Wang J, Xia J, Yan X, Wu C. Letter: lipid-lowering effect of tenofovir disoproxil fumarate in chronic hepatitis B-more evidence is needed. Aliment Pharmacol Ther 2017; 46:769-770. [PMID: 28901572 DOI: 10.1111/apt.14266] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- R Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - J Wang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Jiangsu, China
| | - J Xia
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - X Yan
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
| | - C Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Jiangsu, China
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Shaheen AA, Al-Mattooq M, Yazdanfar S, Burak KW, Swain MG, Congly SE, Borman MA, Lee SS, Myers RP, Coffin CS. Letter: lipid-lowering effect of tenofovir disoproxil fumarate in chronic hepatitis B-more evidence is needed. Authors' reply. Aliment Pharmacol Ther 2017; 46:770-771. [PMID: 28901569 DOI: 10.1111/apt.14282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/08/2022]
Affiliation(s)
- A A Shaheen
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - M Al-Mattooq
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - S Yazdanfar
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - K W Burak
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - M G Swain
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - S E Congly
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - M A Borman
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - S S Lee
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - R P Myers
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - C S Coffin
- Calgary Liver Unit, Division of Gastroenterology and Hepatology, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada
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