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Liver Cirrhosis, Not Antiviral Therapy, Predicts Clinical Outcome in Cohorts with Heterogeneous Hepatitis B Viral Status

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Background/Aims: Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status. Methods: A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development. Results: The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p<0.05). Cirrhosis significantly predicted the risk of HCC development in subgroups with and without ongoing AVT at enrollment, regardless of adjustment. Conclusions: Our study showed that cirrhosis, not AVT and HBV-related variables, was associated with HCC development in a cohort of patients with heterogeneous HBV status. Our results may help clinicians apply individualized surveillance strategies according to fibrotic status in patients with CHB.

Abstract

Background/Aims: Antiviral therapy (AVT) reduces the risk of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB). This multicenter retrospective study investigated the effects of AVT and hepatitis B virus (HBV)-related factors on the risk of HCC development in a cohort with heterogeneous HBV status. Methods: A total of 1,843 patients with CHB from two institutions were included in this study. Ultrasound and laboratory tests, including the α-fetoprotein test, were conducted regularly to detect HCC development. Results: The mean age of our study population (1,063 men and 780 women) was 49.4 years. Cirrhosis was identified in 617 patients (33.5%). During follow-up (median, 42.5 months), 81 patients developed HCC (1.39% per person-year). A total of 645 patients (35.0%) received ongoing AVT at enrollment. Ongoing AVT was not significantly associated with the risk of HCC development (all p>0.05). HBV-related variables (HBV DNA level, hepatitis B e antigen status, and alanine aminotransferase level) were also not significantly associated with the risk of HCC development (all p>0.05). In contrast, cirrhosis was significantly associated with the risk of HCC development, regardless of adjustment (adjusted hazard ratio=4.098 to 7.020; all p<0.05). Cirrhosis significantly predicted the risk of HCC development in subgroups with and without ongoing AVT at enrollment, regardless of adjustment. Conclusions: Our study showed that cirrhosis, not AVT and HBV-related variables, was associated with HCC development in a cohort of patients with heterogeneous HBV status. Our results may help clinicians apply individualized surveillance strategies according to fibrotic status in patients with CHB.

참고문헌 (38)

  1. Iloeje UH, "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load", Gastroenterology, 130, pp.678~686 (2006)
  2. European Association for the Study of the Liver, "Electronic address:easloffice@easloffice.eu; European Association for the Study of the Liver. EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
  3. Liaw YF, "Asian-Pacific consensus statement on the management of chronic hepatitis B : a 2012 update", Hepatol Int, 6, pp.531~561 (2012)
  4. Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
  5. Papatheodoridis GV, "Risk of hepatocellular carcinoma in chronic hepatitis B : assessment and modification with current antiviral therapy", J Hepatol, 62, pp.956~967 (2015)
  6. Papatheodoridis GV, "Incidence of hepatocellular carcinoma in chronic hepatitis B patients receiving nucleos(t)ide therapy : a systematic review", J Hepatol, 53, pp.348~356 (2010)
  7. Wong GL, "Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis", Hepatology, 58, pp.1537~1547 (2013)
  8. Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
  9. Yasunaka T, "Entecavir reduces hepatocarcinogenesis in chronic hepatitis B patients", Acta Med Okayama, 70, pp.1~12 (2016)
  10. Kumada T, "Effect of nucleos(t)ide analogue therapy on hepatocarcinogenesis in chronic hepatitis B patients : a propensity score analysis", J Hepatol, 58, pp.427~433 (2013)
  11. Cho JY, "Patients with chronic hepatitis B treated with oral antiviral therapy retain a higher risk for HCC compared with patients with inactive stage disease", Gut, 63, pp.1943~1950 (2014)
  12. Park YE, "Gamma-glutamyl transpeptidaseto-platelet ratio is an independent predictor of hepatitis B virusrelated liver cancer", J Gastroenterol Hepatol, 32, pp.1221~1229 (2017)
  13. Korean Association for the Study of the Liver, "KASL clinical practice guidelines : management of chronic hepatitis B", Clin Mol Hepatol, 22, pp.18~75 (2016)
  14. Ahn J, "Lower observed hepatocellular carcinoma incidence in chronic hepatitis B patients treated with entecavir : results of the ENUMERATE study", Am J Gastroenterol, 111, pp.1297~1304 (2016)
  15. Bruix J, "Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)
  16. Yuen MF, "Long-term lamivudine therapy reduces the risk of long-term complications of chronic hepatitis B infection even in patients without advanced disease", Antivir Ther, 12, pp.1295~1303 (2007)
  17. Matsumoto A, "Efficacy of lamivudine for preventing hepatocellular carcinoma in chronic hepatitis B : a multicenter retrospective study of 2795 patients", Hepatol Res, 32, pp.173~184 (2005)
  18. Eun JR, "Risk assessment for the development of hepatocellular carcinoma : according to on-treatment viral response during long-term lamivudine therapy in hepatitis B virus-related liver disease", J Hepatol, 53, pp.118~125 (2010)
  19. Papatheodoridis GV, "Virological suppression does not prevent the development of hepatocellular carcinoma in HBeAg-negative chronic hepatitis B patients with cirrhosis receiving oral antiviral(s) starting with lamivudine monotherapy: results of the nationwide HEPNET. Greece cohort study", Gut, 60, pp.1109~1116 (2011)
  20. Kurokawa M, "Long-term effect of lamivudine treatment on the incidence of hepatocellular carcinoma in patients with hepatitis B virus infection", J Gastroenterol, 47, pp.577~585 (2012)
  21. Kim DY, "Transient elastography-based risk estimation of hepatitis B virus-related occurrence of hepatocellular carcinoma : development and validation of a predictive model", Onco Targets Ther, 6, pp.1463~1469 (2013)
  22. Lok AS, "Chronic hepatitis B : update 2009", Hepatology, 50, pp.661~662 (2009)
  23. Lee KS, "Management of chronic hepatitis B", Korean J Hepatol, 13, pp.447~488 (2007)
  24. Chu CM, "Incidence and risk factors of progression to cirrhosis in inactive carriers of hepatitis B virus", Am J Gastroenterol, 104, pp.1693~1699 (2009)
  25. Chen JD, "Carriers of inactive hepatitis B virus are still at risk for hepatocellular carcinoma and liver-related death", Gastroenterology, 138, pp.1747~1754 (2010)
  26. Kim GA, "High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B", Gut, 67, pp.945~952 (2018)
  27. Wang JP, "Nucleos(t)ide analogues associated with a reduced risk of hepatocellular carcinoma in hepatitis B patients : a population-based cohort study", Cancer, 121, pp.1446~1455 (2015)
  28. Orito E, "Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside", nucleotide analog therapy, 2015, pp.45, 872~879
  29. Papatheodoridis GV, "Incidence and predictors of hepatocellular carcinoma in Caucasian chronic hepatitis B patients receiving entecavir or tenofovir", J Hepatol, 62, pp.363~370 (2015)
  30. Singal AK, "Meta-analysis : the impact of oral anti-viral agents on the incidence of hepatocellular carcinoma in chronic hepatitis B", Aliment Pharmacol Ther, 38, pp.98~106 (2013)
  31. Wong GL, "Personalized management of cirrhosis by non-invasive tests of liver fibrosis", Clin Mol Hepatol, 21, pp.200~211 (2015)
  32. Martin J, "Accuracy of ultrasound and noninvasive markers of fibrosis to identify patients with cirrhosis", Dig Dis Sci, 60, pp.1841~1847 (2015)
  33. Martínez SM, "Noninvasive assessment of liver fibrosis", Hepatology, 53, pp.325~335 (2011)
  34. Kim MN, "Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis", Hepatology, 61, pp.1851~1859 (2015)
  35. Seo YS, "Risk assessment of hepatocellular carcinoma using transient elastography vs. liver biopsy in chronic hepatitis B patients receiving antiviral therapy", Medicine (Baltimore), 95, pp.e2985~ (2016)
  36. Kim BK, "Risk assessment of clinical outcomes in Asian patients with chronic hepatitis B using enhanced liver fibrosis test", Hepatology, 60, pp.1911~1919 (2014)
  37. Suh B, "High liver fibrosis index FIB-4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers", Hepatology, 61, pp.1261~1268 (2015)
  38. Kim HS, "Association between level of fibrosis, rather than antiviral regimen, and outcomes of patients with chronic hepatitis B", Clin Gastroenterol Hepatol, 14, pp.1647~1656 (2016)

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