Advertisement

Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2792–2799 | Cite as

Effect of Metabolic Syndrome on the Clinical Outcomes of Chronic Hepatitis B Patients with Nucleos(t)ide Analogues Treatment

  • Nam Hee Kim
  • Yong Kyun Cho
  • Byung Ik Kim
  • Hong Joo Kim
Original Article
  • 113 Downloads

Abstract

Background

No data are available about the effect of MS on oral nucleos(t)ide analogues (NUCs) treatment and clinical outcomes in chronic hepatitis B (CHB) patients.

Aims

We aimed to elucidate whether coexistence of MS and CHB affects the long-term prognosis of CHB patients with oral NUCs treatment.

Methods

We performed a retrospective data analysis for a total of 587 CHB patients who started oral NUCs treatment for the first time in our institution from January 2006 to March 2016.

Results

Among the 587 patients, 70 (11.9%) had MS, but 517 (88.1%) had no evidence of MS when oral NUCs treatment was initiated. Cumulative occurrence rates of viral breakthrough, genotypic resistance, HCC, disease progression (PD), and overall adverse outcomes (OAO) were significantly higher in CHB patients with MS than in those without MS, although HBV-DNA suppression and cumulative occurrence rates of HBeAg negative conversion and seroconversion were not significantly different between the two groups. The overall survival (OS) was also significantly shorter in CHB patients with MS than in those without MS. Multivariate analysis indicated that the MS was an independent, poor prognostic factor for occurrence of genotypic resistance (adjusted hazard ratio [aHR], 22.3; 95% confidence interval [CI] 6.61–75.02; P < 0.001), HCC (aHR, 3.98; 95% CI 2.07–7.66; P < 0.001), PD (aHR, 6.18; 95% CI 3.43–11.14; P < 0.001), OAO (aHR, 8.10; 95% CI 4.68–14.02; P < 0.001), and OS (aHR, 12.29; 95% CI 2.25–67.24; P < 0.001).

Conclusions

MS is an independent determinant of poor prognosis in CHB patients receiving oral NUCs treatment.

Keywords

Metabolic syndrome Nucleos(t)ide analogue Hepatocellular carcinoma Disease progression Survival 

Notes

Compliance with ethical standards

Conflict of interest

All authors declare that they have no competing conflicts of interests.

Supplementary material

10620_2018_5165_MOESM1_ESM.tif (1.7 mb)
Supplementary Fig. 1 (A) CR rate (P < 0.198) and (B) ALT normalization rate (p < 0.001) in CHB patients with vs. without metabolic syndrome (TIFF 1726 kb)
10620_2018_5165_MOESM2_ESM.tif (1003 kb)
Supplementary Fig. 2 (A) Cumulative occurrence rates of HBeAg negative conversion (P = 0.434) and (B) seroconversion (P = 0.119) in CHB patients with vs. without metabolic syndrome (TIFF 1003 kb)

References

  1. 1.
    Chan HL, Sung JJ. Hepatocellular carcinoma and hepatitis B virus. Semin Liver Dis. 2006;26:153–161.CrossRefGoogle Scholar
  2. 2.
    Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003;362:2089–2094.CrossRefGoogle Scholar
  3. 3.
    Tran TT, Martin P. Hepatitis B: epidemiology and natural history. Clin Liver Dis. 2004;8:255–266.CrossRefGoogle Scholar
  4. 4.
    Welzel TM, Graubard BI, Zeuzem S, El-Serag HB, Davila JA, McGlynn KA. Metabolic syndrome increases the risk of primary liver cancer in the United States: a study in the SEER-Medicare database. Hepatology. 2011;54:463–471.CrossRefGoogle Scholar
  5. 5.
    Nderitu P, Bosco C, Garmo H, et al. The association between individual metabolic syndrome components, primary liver cancer and cirrhosis: a study in the Swedish AMORIS cohort. Int J Cancer. 2017;141:1148–1160.CrossRefGoogle Scholar
  6. 6.
    Alberti KG, Zimmet P, Shaw J. Metabolic syndrome—a new world-wide definition. A Consensus Statement from the International Diabetes Federation. Diabet Med. 2006;23:469–480.CrossRefGoogle Scholar
  7. 7.
    Chen CL, Yang HI, Yang WS, et al. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology. 2008;135:111–121.CrossRefGoogle Scholar
  8. 8.
    Wong GL, Wong VW, Choi PC, et al. Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B. Gut. 2009;58:111–117.CrossRefGoogle Scholar
  9. 9.
    Wang CC, Tseng TC, Kao JH. Hepatitis B virus infection and metabolic syndrome: fact or fiction? J Gastroenterol Hepatol. 2015;30:14–20.CrossRefGoogle Scholar
  10. 10.
    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;40:716–726.CrossRefGoogle Scholar
  11. 11.
    Mena A, Pedreira JD, Castro A, Lopez S, Vazquez P, Poveda E. Metabolic syndrome association with fibrosis development in chronic hepatitis B virus inactive carriers. J Gastroenterol Hepatol. 2014;29:173–178.CrossRefGoogle Scholar
  12. 12.
    Huang YW, Wang TC, Lin SC, et al. Increased risk of cirrhosis and its decompensation in chronic hepatitis B patients with newly diagnosed diabetes: a nationwide cohort study. Clin Infect Dis. 2013;57:1695–1702.CrossRefGoogle Scholar
  13. 13.
    Yu MW, Shih WL, Lin CL, et al. Body-mass index and progression of hepatitis B: a population-based cohort study in men. J Clin Oncol. 2008;26:5576–5582.CrossRefGoogle Scholar
  14. 14.
    Yu MW, Lin CL, Liu CJ, Yang SH, Tseng YL, Wu CF. Influence of metabolic risk factors on risk of hepatocellular carcinoma and liver-related death in men with chronic hepatitis B: a large cohort study. Gastroenterology. 2017;153:e1005.Google Scholar
  15. 15.
    Wen CP, David Cheng TY, Tsai SP, et al. Are Asians at greater mortality risks for being overweight than Caucasians? Redefining obesity for Asians. Public Health Nutr. 2009;12:497–506.CrossRefGoogle Scholar
  16. 16.
    Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008;371:838–851.CrossRefGoogle Scholar
  17. 17.
    Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology. 2011;53:1020–1022.CrossRefGoogle Scholar
  18. 18.
    Fisher B, Anderson S, Fisher ER, et al. Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet. 1991;338:327–331.CrossRefGoogle Scholar
  19. 19.
    Wong GL, Chan HL, Yu Z, et al. 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;39:883–893.CrossRefGoogle Scholar
  20. 20.
    Jarcuska P, Drazilova S, Fedacko J, Pella D, Janicko M. Association between hepatitis B and metabolic syndrome: current state of the art. World J Gastroenterol. 2016;22:155–164.CrossRefGoogle Scholar
  21. 21.
    Yoon H, Lee JG, Yoo JH, et al. Effects of metabolic syndrome on fibrosis in chronic viral hepatitis. Gut Liver. 2013;7:469–474.CrossRefGoogle Scholar
  22. 22.
    Paradis V, Perlemuter G, Bonvoust F, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology. 2001;34:738–744.CrossRefGoogle Scholar
  23. 23.
    Chettouh H, Lequoy M, Fartoux L, Vigouroux C, Desbois-Mouthon C. Hyperinsulinaemia and insulin signalling in the pathogenesis and the clinical course of hepatocellular carcinoma. Liver Int. 2015;35:2203–2217.CrossRefGoogle Scholar
  24. 24.
    Asselah T, Rubbia-Brandt L, Marcellin P, Negro F. Steatosis in chronic hepatitis C: why does it really matter? Gut. 2006;55:123–130.CrossRefGoogle Scholar
  25. 25.
    Lonardo A, Adinolfi LE, Loria P, Carulli N, Ruggiero G, Day CP. Steatosis and hepatitis C virus: mechanisms and significance for hepatic and extrahepatic disease. Gastroenterology. 2004;126:586–597.CrossRefGoogle Scholar
  26. 26.
    Chung WG, Kim HJ, Choe YG, et al. 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;18:195–202.CrossRefGoogle Scholar
  27. 27.
    Marcellin 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;381:468–475.CrossRefGoogle Scholar
  28. 28.
    Varbobitis I, Papatheodoridis GV. The assessment of hepatocellular carcinoma risk in patients with chronic hepatitis B under antiviral therapy. Clin Mol Hepatol. 2016;22:319–326.CrossRefGoogle Scholar
  29. 29.
    Sohn W, Cho JY, Kim JH, et al. Risk score model for the development of hepatocellular carcinoma in treatment-naive patients receiving oral antiviral treatment for chronic hepatitis B. Clin Mol Hepatol. 2017;23:170–178.CrossRefGoogle Scholar
  30. 30.
    Nestel P, Lyu R, Low LP, et al. Metabolic syndrome: recent prevalence in East and Southeast Asian populations. Asia Pac J Clin Nutr. 2007;16:362–367.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Preventive Healthcare Center, Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulKorea
  2. 2.Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung HospitalSungkyunkwan University School of MedicineSeoulKorea

Personalised recommendations