High body mass index hinders fibrosis improvement in patients receiving long-term tenofovir therapy in hepatitis B virus-related cirrhosis
Young Eun Chon
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorKyu Sik Jung
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorYeonjung Ha
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorMi Na Kim
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorJoo Ho Lee
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorSeong Gyu Hwang
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorSang Hoon Ahn
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorDo Young Kim
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorKwang-Hyub Han
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jun Yong Park
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Correspondence
Jun Yong Park, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul 03722, South Korea.
Email: [email protected]
Search for more papers by this authorYoung Eun Chon
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorKyu Sik Jung
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorYeonjung Ha
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorMi Na Kim
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorJoo Ho Lee
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorSeong Gyu Hwang
Department of Internal Medicine, Institute of Gastroenterology, CHA Bundang Medical Center, CHA University, Seongnam, Korea
CHA Bundang Liver Center, CHA Bundang Hospital, Seongnam, Korea
Search for more papers by this authorSang Hoon Ahn
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorDo Young Kim
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorKwang-Hyub Han
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Search for more papers by this authorCorresponding Author
Jun Yong Park
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
Yonsei Liver Center, Severance Hospital, Seoul, Korea
Correspondence
Jun Yong Park, Department of Internal Medicine, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun–gu, Seoul 03722, South Korea.
Email: [email protected]
Search for more papers by this authorAbstract
Long-term suppression of hepatitis B virus with tenofovir (TDF) induces fibrosis regression, and repeated liver stiffness (LS) measurement can indicate the improvement of fibrosis. We aimed to investigate predictors for LS improvement assessed by changes in patients receiving long-term TDF therapy in chronic hepatitis B (CHB) with liver cirrhosis. CHB patients with histologically proven liver cirrhosis who received TDF as the first-line therapy from 2012 to 2015 were recruited. LS and controlled attenuation parameter (CAP) measurements were repeated at baseline and 3 years after therapy. Liver stiffness improvement was defined as a drop of LS value ≥30% from the baseline. A total of 131 patients were enrolled (mean age 51.4% and male 64.9%). After 3 years of TDF therapy, the mean LS value significantly improved (from 14.7 to 8.6 kPa, P < .001), and 96 (73.3%) patients have achieved LS improvement. Predictors associated with improvement of LS were low body mass index (BMI), HBeAg positivity, and low CAP value at baseline. In multivariate analysis, low BMI was a single factor independently associated with LS improvement (odds ratio 0.680, 95% CI 0.560-0.825, P < .001). Patients with BMI < 23.5, had a 1.96 times more chance of achieving LS improvement compared to those with BMI ≥ 23.5 (90.1% vs. 46.0%, P = .001). High BMI was a single significant factor hindering the fibrosis improvement in patients receiving long-term TDF therapy in CHB with liver cirrhosis. Life style modification and BMI reduction should be encouraged to enhance fibrosis improvement.
REFERENCES
- 1Yim HJ, Lok AS. Natural history of chronic hepatitis B virus infection: what we knew in 1981 and what we know in 2005. Hepatology. 2006; 43(2 Suppl 1): S173-S181.
- 2Iloeje UH, Yang HI, Su J, Jen CL, You SL, Chen CJ. Predicting cirrhosis risk based on the level of circulating hepatitis B viral load. Gastroenterology. 2006; 130(3): 678-686.
- 3 Korean Association for the Study of the Liver (KASL). Korean Association for the Study of the Liver (KASL). KASL clinical practice guidelines for management of chronic hepatitis B. Clin Mol Hepatol. 2019; 25(2): 93-159.
- 4Dienstag JL, Goldin RD, Heathcote EJ, et al. Histological outcome during long-term lamivudine therapy. Gastroenterology. 2003; 124(1): 105-117.
- 5Marcellin P, Chang T-T, Lim SGL, et al. Long-term efficacy and safety of adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2008; 48(3): 750-758.
- 6Chang T-T, Liaw Y-F, Wu S-S, et al. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology. 2010; 52(3): 886-893.
- 7Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet. 2013; 381(9865): 468-475.
- 8Regev A, Berho M, Jeffers LJ, et al. Sampling error and intraobserver variation in liver biopsy in patients with chronic HCV infection. Am J Gastroenterol. 2002; 97(10): 2614-2618.
- 9Zhang X, Wong GL, Wong VW. Applications of transient elastography in nonalcoholic fatty liver disease. Clin Mol Hepatol. 2020; 26(2): 128-141.
- 10Kim JH, Kim MN, Han KH, Kim SU. Clinical application of transient elastography in patients with chronic viral hepatitis receiving antiviral treatment. Liver Int. 2015; 35(4): 1103-1115.
- 11Fung J, Lai CL, Wong DK, Seto WK, Hung I, Yuen MF. Significant changes in liver stiffness measurements in patients with chronic hepatitis B: 3-year follow-up study. J Viral Hepat. 2011; 18(7): e200-e205.
- 12Wong G-H, Wong V-S, Choi P-L, et al. On-treatment monitoring of liver fibrosis with transient elastography in chronic hepatitis B patients. Antivir Ther. 2011; 16(2): 165-172.
- 13Facciorusso A, Garcia Perdomo HA, Muscatiello N, Buccino RV, Wong VW, Singh S. Systematic review with meta-analysis: change in liver stiffness during anti-viral therapy in patients with hepatitis B. Dig Liver Dis. 2018; 50(8): 787-794.
- 14Ogawa E, Furusyo N, Murata M, et al. Longitudinal assessment of liver stiffness by transient elastography for chronic hepatitis B patients treated with nucleoside analog. Hepatol Res. 2011; 41(12): 1178-1188.
- 15Osakabe K, Ichino N, Nishikawa T, et al. Reduction of liver stiffness by antiviral therapy in chronic hepatitis B. J Gastroenterol. 2011; 46(11): 1324-1334.
- 16Kim MN, Kim SU, Kim BK, et al. Long-term changes of liver stiffness values assessed using transient elastography in patients with chronic hepatitis B receiving entecavir. Liver Int. 2014; 34(8): 1216-1223.
- 17Chon YE, Park JY, Myoung S-M, et al. Improvement of liver fibrosis after long-term antiviral therapy assessed by fibroscan in chronic hepatitis B patients with advanced fibrosis. Am J Gastroenterol. 2017; 112(6): 882-891.
- 18Stasi C, Salomoni E, Arena U, et al. Non-invasive assessment of liver fibrosis in patients with HBV-related chronic liver disease undergoing antiviral treatment: a preliminary study. Eur J Pharmacol. 2017; 806: 105-109.
- 19Wang HM, Hung CH, Lee CM, et al. Three-year efficacy and safety of tenofovir in nucleos(t)ide analog-naive and nucleos(t)ide analog-experienced chronic hepatitis B patients. J Gastroenterol Hepatol. 2016; 31(7): 1307-1314.
- 20Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. The METAVIR Cooperative Study Group. Hepatology. 1996; 24(2): 289-293.
- 21de Ledinghen V, Vergniol J, Capdepont M, et al. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations. J Hepatol. 2014; 60(5): 1026-1031.
- 22Castera L, Foucher J, Bernard PH, et al. Pitfalls of liver stiffness measurement: a 5-year prospective study of 13,369 examinations. Hepatology. 2010; 51(3): 828-835.
- 23Wong VW, Petta S, Hiriart JB, et al. Validity criteria for the diagnosis of fatty liver by M probe-based controlled attenuation parameter. J Hepatol. 2017; 67(3): 577-584.
- 24Chon YE, Jung KS, Kim SU, et al. Controlled attenuation parameter (CAP) for detection of hepatic steatosis in patients with chronic liver diseases: a prospective study of a native Korean population. Liver Int. 2014; 34(1): 102-109.
- 25 The World Health Organization Western Pacific Region TIAftSoO, and The International Obesity Task Force. The Asia-Pacific Perspective: Redefining Obesity and its Treatment. Sydney: Health Communications Australia Pty Limited; 2000.
- 26Yao FY, Bass NM. Lamivudine treatment in patients with severely decompensated cirrhosis due to replicating hepatitis B infection. J Hepatol. 2000; 33(2): 301-307.
- 27Lee HW, Yoo EJ, Kim BK, et al. Prediction of development of liver-related events by transient elastography in hepatitis B patients with complete virological response on antiviral therapy. Am J Gastroenterol. 2014; 109(8): 1241-1249.
- 28Kim MN, Kim SU, Park JY, et al. Risk assessment of liver-related events using transient elastography in patients with chronic hepatitis B receiving entecavir. J Clin Gastroenterol. 2014; 48(3): 272-278.
- 29Wong GL, Chan HL, Chan HY, et al. Accuracy of risk scores for patients with chronic hepatitis B receiving entecavir treatment. Gastroenterology. 2013; 144(5): 933-944.
- 30Kim BK, Fung J, Yuen MF, Kim SU. Clinical application of liver stiffness measurement using transient elastography in chronic liver disease from longitudinal perspectives. World J Gastroenterol. 2013; 19(12): 1890-1900.
- 31Seto W-K, Fung J, Cheung K-S, et al. Body-mass index is associated with fibrosis regression during long-term nucleoside analogue therapy in chronic hepatitis B. Aliment Pharmacol Therapeut. 2016; 44(10): 1071-1079.
- 32Marra F, Navari N, Vivoli E, Galastri S, Provenzano A. Modulation of liver fibrosis by adipokines. Dig Dis. 2011; 29(4): 371-376.
- 33Boutari C, Perakakis N, Mantzoros CS. Association of adipokines with development and progression of nonalcoholic fatty liver disease. Endocrinol Metab (Seoul). 2018; 33(1): 33-43.
- 34Saxena NK, Anania FA. Adipocytokines and hepatic fibrosis. Trends Endocrinol Metab. 2015; 26(3): 153-161.
- 35Wong GL, Chan HL, Choi PC, et al. Association between anthropometric parameters and measurements of liver stiffness by transient elastography. Clin Gastroenterol Hepatol. 2013; 11(3): 295-302.e3.
- 36Chan Hl-y, Wong Gl-h, Choi Pc-l, et al. Alanine aminotransferase-based algorithms of liver stiffness measurement by transient elastography (Fibroscan) for liver fibrosis in chronic hepatitis B. J Viral Hepat. 2009; 16(1): 36-44.
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