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Published in: BMC Gastroenterology 1/2020

Open Access 01-12-2020 | Hepatitis B | Research article

Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study

Authors: Yi-Cheng Chen, Wen-Juei Jeng, Chao-Wei Hsu, Chun-Yen Lin

Published in: BMC Gastroenterology | Issue 1/2020

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Abstract

Background

The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS.

Methods

We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed.

Results

A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (all p > 0.05).

Conclusions

HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.
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Literature
1.
go back to reference Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55.PubMedCrossRef Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015;386(10003):1546–55.PubMedCrossRef
2.
go back to reference Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.PubMedCrossRef Chalasani N, Younossi Z, Lavine JE, Charlton M, Cusi K, Rinella M, Harrison SA, Brunt EM, Sanyal AJ. The diagnosis and management of nonalcoholic fatty liver disease: practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018;67(1):328–57.PubMedCrossRef
3.
go back to reference European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402.CrossRef European Association for the Study of the L, European Association for the Study of D, European Association for the Study of O. EASL-EASD-EASO clinical practice guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388–402.CrossRef
4.
go back to reference Seto WK, Yuen MF. Nonalcoholic fatty liver disease in Asia: emerging perspectives. J Gastroenterol. 2017;52(2):164–74.PubMedCrossRef Seto WK, Yuen MF. Nonalcoholic fatty liver disease in Asia: emerging perspectives. J Gastroenterol. 2017;52(2):164–74.PubMedCrossRef
5.
go back to reference Fan JG, Chitturi S. Hepatitis B and fatty liver: causal or coincidental? J Gastroenterol Hepatol. 2008;23(5):679–81.PubMedCrossRef Fan JG, Chitturi S. Hepatitis B and fatty liver: causal or coincidental? J Gastroenterol Hepatol. 2008;23(5):679–81.PubMedCrossRef
6.
go back to reference Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol. 2011;26(9):1361–7.PubMed Machado MV, Oliveira AG, Cortez-Pinto H. Hepatic steatosis in hepatitis B virus infected patients: meta-analysis of risk factors and comparison with hepatitis C infected patients. J Gastroenterol Hepatol. 2011;26(9):1361–7.PubMed
7.
go back to reference Wong VW, Wong GL, Chu WC, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Chan HY, Woo J, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56(3):533–40.PubMedCrossRef Wong VW, Wong GL, Chu WC, Chim AM, Ong A, Yeung DK, Yiu KK, Chu SH, Chan HY, Woo J, et al. Hepatitis B virus infection and fatty liver in the general population. J Hepatol. 2012;56(3):533–40.PubMedCrossRef
8.
go back to reference Cheng YL, Wang YJ, Kao WY, Chen PH, Huo TI, Huang YH, Lan KH, Su CW, Chan WL, Lin HC, et al. Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up. PLoS One. 2013;8(8):e72049.PubMedPubMedCentralCrossRef Cheng YL, Wang YJ, Kao WY, Chen PH, Huo TI, Huang YH, Lan KH, Su CW, Chan WL, Lin HC, et al. Inverse association between hepatitis B virus infection and fatty liver disease: a large-scale study in populations seeking for check-up. PLoS One. 2013;8(8):e72049.PubMedPubMedCentralCrossRef
9.
go back to reference Joo EJ, Chang Y, Yeom JS, Ryu S. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: a cohort study. Hepatology. 2017;65(3):828–35.PubMedCrossRef Joo EJ, Chang Y, Yeom JS, Ryu S. Hepatitis B virus infection and decreased risk of nonalcoholic fatty liver disease: a cohort study. Hepatology. 2017;65(3):828–35.PubMedCrossRef
10.
go back to reference Hui RWH, Seto WK, Cheung KS, Mak LY, Liu KSH, Fung J, Wong DK, Lai CL, Yuen MF. Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study. J Viral Hepat. 2018;25(1):97–104.PubMedCrossRef Hui RWH, Seto WK, Cheung KS, Mak LY, Liu KSH, Fung J, Wong DK, Lai CL, Yuen MF. Inverse relationship between hepatic steatosis and hepatitis B viremia: results of a large case-control study. J Viral Hepat. 2018;25(1):97–104.PubMedCrossRef
11.
go back to reference Rastogi A, Sakhuja P, Kumar A, Hissar S, Jain A, Gondal R, Sarin SK. Steatosis in chronic hepatitis B: prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol. 2011;54(3):454–9.PubMedCrossRef Rastogi A, Sakhuja P, Kumar A, Hissar S, Jain A, Gondal R, Sarin SK. Steatosis in chronic hepatitis B: prevalence and correlation with biochemical, histologic, viral, and metabolic parameters. Indian J Pathol Microbiol. 2011;54(3):454–9.PubMedCrossRef
12.
go back to reference Zhang Z, Pan Q, Duan XY, Liu Q, Mo GY, Rao GR, Fan JG. Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic mice model. J Gastroenterol Hepatol. 2012;27(12):1858–64.PubMedCrossRef Zhang Z, Pan Q, Duan XY, Liu Q, Mo GY, Rao GR, Fan JG. Fatty liver reduces hepatitis B virus replication in a genotype B hepatitis B virus transgenic mice model. J Gastroenterol Hepatol. 2012;27(12):1858–64.PubMedCrossRef
13.
go back to reference Hu D, Wang H, Wang H, Wang Y, Wan X, Yan W, Luo X, Ning Q. Non-alcoholic hepatic steatosis attenuates hepatitis B virus replication in an HBV-immunocompetent mouse model. Hepatol Int. 2018. Hu D, Wang H, Wang H, Wang Y, Wan X, Yan W, Luo X, Ning Q. Non-alcoholic hepatic steatosis attenuates hepatitis B virus replication in an HBV-immunocompetent mouse model. Hepatol Int. 2018.
14.
go back to reference Chu CM, Lin DY, Liaw YF. Does increased body mass index with hepatic steatosis contribute to seroclearance of hepatitis B virus (HBV) surface antigen in chronic HBV infection? Int J Obes. 2007;31(5):871–5.CrossRef Chu CM, Lin DY, Liaw YF. Does increased body mass index with hepatic steatosis contribute to seroclearance of hepatitis B virus (HBV) surface antigen in chronic HBV infection? Int J Obes. 2007;31(5):871–5.CrossRef
15.
go back to reference Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Wang LY, You SL, Iloeje UH, Chen CJ, Group R-HS. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology. 2010;139(2):474–82.PubMedCrossRef Liu J, Yang HI, Lee MH, Lu SN, Jen CL, Wang LY, You SL, Iloeje UH, Chen CJ, Group R-HS. Incidence and determinants of spontaneous hepatitis B surface antigen seroclearance: a community-based follow-up study. Gastroenterology. 2010;139(2):474–82.PubMedCrossRef
16.
go back to reference Cindoruk M, Karakan T, Unal S. Hepatic steatosis has no impact on the outcome of treatment in patients with chronic hepatitis B infection. J Clin Gastroenterol. 2007;41(5):513–7.PubMedCrossRef Cindoruk M, Karakan T, Unal S. Hepatic steatosis has no impact on the outcome of treatment in patients with chronic hepatitis B infection. J Clin Gastroenterol. 2007;41(5):513–7.PubMedCrossRef
17.
go back to reference Ates F, Yalniz M, Alan S. Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B. World J Gastroenterol. 2011;17(40):4517–22.PubMedPubMedCentralCrossRef Ates F, Yalniz M, Alan S. Impact of liver steatosis on response to pegylated interferon therapy in patients with chronic hepatitis B. World J Gastroenterol. 2011;17(40):4517–22.PubMedPubMedCentralCrossRef
18.
go back to reference Gong L, Liu J, Wang J, Lou GQ, Shi JP. Hepatic Steatosis as a predictive factor of antiviral effect of Pegylated interferon therapy in patients with hepatitis B. Transplant Proc. 2015;47(10):2886–91.PubMedCrossRef Gong L, Liu J, Wang J, Lou GQ, Shi JP. Hepatic Steatosis as a predictive factor of antiviral effect of Pegylated interferon therapy in patients with hepatitis B. Transplant Proc. 2015;47(10):2886–91.PubMedCrossRef
19.
go back to reference Charatcharoenwitthaya P, Pongpaibul A, Kaosombatwattana U, Bhanthumkomol P, Bandidniyamanon W, Pausawasdi N, Tanwandee T. The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response. Liver Int. 2017;37(4):542–51.PubMedCrossRef Charatcharoenwitthaya P, Pongpaibul A, Kaosombatwattana U, Bhanthumkomol P, Bandidniyamanon W, Pausawasdi N, Tanwandee T. The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response. Liver Int. 2017;37(4):542–51.PubMedCrossRef
20.
go back to reference Chung WG, Kim HJ, Choe YG, Seok HS, Chon CW, Cho YK, Kim BI, Koh YY. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naive patients with chronic hepatitis B infection. Clin Mol Hepatol. 2012;18(2):195–202.PubMedPubMedCentralCrossRef Chung WG, Kim HJ, Choe YG, Seok HS, Chon CW, Cho YK, Kim BI, Koh YY. Clinical impacts of hazardous alcohol use and obesity on the outcome of entecavir therapy in treatment-naive patients with chronic hepatitis B infection. Clin Mol Hepatol. 2012;18(2):195–202.PubMedPubMedCentralCrossRef
21.
go back to reference Hsiang JC, Wong GL, Chan HL, Chan AW, Chim AM, Wong VW. Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B. Aliment Pharmacol Ther. 2014;40(6):716–26.PubMedCrossRef Hsiang JC, Wong GL, Chan HL, Chan AW, Chim AM, Wong VW. Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B. Aliment Pharmacol Ther. 2014;40(6):716–26.PubMedCrossRef
22.
go back to reference Jin X, Chen YP, Yang YD, Li YM, Zheng L, Xu CQ. Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B. PLoS One. 2012;7(3):e34198.PubMedPubMedCentralCrossRef Jin X, Chen YP, Yang YD, Li YM, Zheng L, Xu CQ. Association between hepatic steatosis and entecavir treatment failure in Chinese patients with chronic hepatitis B. PLoS One. 2012;7(3):e34198.PubMedPubMedCentralCrossRef
23.
go back to reference Kim DS, Jeon MY, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, Kim SU. Influence of hepatic steatosis on the outcomes of patients with chronic hepatitis B treated with entecavir and tenofovir. Clin Mol Hepatol. 2019;25(3):283-93. Kim DS, Jeon MY, Lee HW, Kim BK, Park JY, Kim DY, Ahn SH, Han KH, Kim SU. Influence of hepatic steatosis on the outcomes of patients with chronic hepatitis B treated with entecavir and tenofovir. Clin Mol Hepatol. 2019;25(3):283-93.
24.
go back to reference Chen YC, Jeng WJ, Chien RN, Chu CM, Liaw YF. Clinical outcomes after spontaneous and nucleos(t)ide analogue-treated HBsAg seroclearance in chronic HBV infection. Aliment Pharmacol Ther. 2016;43(12):1311–8.PubMedCrossRef Chen YC, Jeng WJ, Chien RN, Chu CM, Liaw YF. Clinical outcomes after spontaneous and nucleos(t)ide analogue-treated HBsAg seroclearance in chronic HBV infection. Aliment Pharmacol Ther. 2016;43(12):1311–8.PubMedCrossRef
25.
go back to reference Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32(1):3–13.PubMedCrossRef Kleiner DE, Brunt EM. Nonalcoholic fatty liver disease: pathologic patterns and biopsy evaluation in clinical research. Semin Liver Dis. 2012;32(1):3–13.PubMedCrossRef
26.
go back to reference Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.PubMedCrossRef Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.PubMedCrossRef
27.
go back to reference Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.PubMedCrossRef Desmet VJ, Gerber M, Hoofnagle JH, Manns M, Scheuer PJ. Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology. 1994;19:1513–20.PubMedCrossRef
28.
go back to reference Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696–9.PubMedCrossRef Ishak K, Baptista A, Bianchi L, Callea F, De Groote J, Gudat F, Denk H, Desmet V, Korb G, MacSween RN. Histological grading and staging of chronic hepatitis. J Hepatol. 1995;22(6):696–9.PubMedCrossRef
29.
go back to reference Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Schall RA, 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):468–75.PubMedCrossRef Marcellin P, Gane E, Buti M, Afdhal N, Sievert W, Jacobson IM, Washington MK, Germanidis G, Flaherty JF, Schall RA, 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):468–75.PubMedCrossRef
30.
go back to reference Liaw YF. Clinical utility of hepatitis B surface antigen quantitation in patients with chronic hepatitis B: a review. Hepatology. 2011;54(2):E1–9.PubMedCrossRef Liaw YF. Clinical utility of hepatitis B surface antigen quantitation in patients with chronic hepatitis B: a review. Hepatology. 2011;54(2):E1–9.PubMedCrossRef
31.
go back to reference Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, Chan HY, Chan FK, Sung JJ, Chan HL. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58(1):111–7.PubMedCrossRef Wong GL, Wong VW, Choi PC, Chan AW, Chim AM, Yiu KK, Chan HY, Chan FK, Sung JJ, Chan HL. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58(1):111–7.PubMedCrossRef
32.
go back to reference Wong GL, Chan HL, Yu Z, Chan AW, Choi PC, Chim AM, Chan HY, Tse CH, Wong VW. Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B--a prospective cohort study with paired transient elastography examinations. Aliment Pharmacol Ther. 2014;39(8):883–93.PubMedCrossRef Wong GL, Chan HL, Yu Z, Chan AW, Choi PC, Chim AM, Chan HY, Tse CH, Wong VW. Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B--a prospective cohort study with paired transient elastography examinations. Aliment Pharmacol Ther. 2014;39(8):883–93.PubMedCrossRef
33.
go back to reference Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354(10):1001–10.PubMedCrossRef Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, et al. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006;354(10):1001–10.PubMedCrossRef
34.
go back to reference Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, Heathcote EJ, Manns M, Bzowej N, Niu J, et al. 2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136(2):486–95.PubMedCrossRef Liaw YF, Gane E, Leung N, Zeuzem S, Wang Y, Lai CL, Heathcote EJ, Manns M, Bzowej N, Niu J, et al. 2-year GLOBE trial results: telbivudine is superior to lamivudine in patients with chronic hepatitis B. Gastroenterology. 2009;136(2):486–95.PubMedCrossRef
35.
go back to reference Ceylan B, Arslan F, Batirel A, Fincanci M, Yardimci C, Fersan E, Pasaoglu E, Yilmaz M, Mert A. Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir. Turk J Gastroenterol. 2016;27(1):42–6.PubMedCrossRef Ceylan B, Arslan F, Batirel A, Fincanci M, Yardimci C, Fersan E, Pasaoglu E, Yilmaz M, Mert A. Impact of fatty liver on hepatitis B virus replication and virologic response to tenofovir and entecavir. Turk J Gastroenterol. 2016;27(1):42–6.PubMedCrossRef
36.
go back to reference Lau E, Carvalho D, Freitas P. Gut microbiota: association with NAFLD and metabolic disturbances. Biomed Res Int. 2015;2015:979515.PubMedPubMedCentral Lau E, Carvalho D, Freitas P. Gut microbiota: association with NAFLD and metabolic disturbances. Biomed Res Int. 2015;2015:979515.PubMedPubMedCentral
37.
go back to reference Kim NH, Cho YK, Kim BI, Kim HJ. Effect of metabolic syndrome on the clinical outcomes of chronic hepatitis B patients with Nucleos(t)ide analogues treatment. Dig Dis Sci. 2018;63(10):2792–9.PubMedCrossRef Kim NH, Cho YK, Kim BI, Kim HJ. Effect of metabolic syndrome on the clinical outcomes of chronic hepatitis B patients with Nucleos(t)ide analogues treatment. Dig Dis Sci. 2018;63(10):2792–9.PubMedCrossRef
Metadata
Title
Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study
Authors
Yi-Cheng Chen
Wen-Juei Jeng
Chao-Wei Hsu
Chun-Yen Lin
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Gastroenterology / Issue 1/2020
Electronic ISSN: 1471-230X
DOI
https://doi.org/10.1186/s12876-020-01289-w

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