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)
- Iloeje UH, "Predicting cirrhosis risk based on the level of circulating hepatitis B viral load", Gastroenterology, 130, pp.678~686 (2006)
- 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)
- Liaw YF, "Asian-Pacific consensus statement on the management of chronic hepatitis B : a 2012 update", Hepatol Int, 6, pp.531~561 (2012)
- Liaw YF, "Lamivudine for patients with chronic hepatitis B and advanced liver disease", N Engl J Med, 351, pp.1521~1531 (2004)
- Papatheodoridis GV, "Risk of hepatocellular carcinoma in chronic hepatitis B : assessment and modification with current antiviral therapy", J Hepatol, 62, pp.956~967 (2015)
- 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)
- Wong GL, "Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients with liver cirrhosis", Hepatology, 58, pp.1537~1547 (2013)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- Yasunaka T, "Entecavir reduces hepatocarcinogenesis in chronic hepatitis B patients", Acta Med Okayama, 70, pp.1~12 (2016)
- 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)
- 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)
- 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)
- 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)
- 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)
- Bruix J, "Management of hepatocellular carcinoma: an update", Hepatology, 53, pp.1020~1022 (2011)
- 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)
- 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)
- 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)
- 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)
- 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)
- 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)
- Lok AS, "Chronic hepatitis B : update 2009", Hepatology, 50, pp.661~662 (2009)
- Lee KS, "Management of chronic hepatitis B", Korean J Hepatol, 13, pp.447~488 (2007)
- 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)
- 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)
- Kim GA, "High risk of hepatocellular carcinoma and death in patients with immune-tolerant-phase chronic hepatitis B", Gut, 67, pp.945~952 (2018)
- 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)
- Orito E, "Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside", nucleotide analog therapy, 2015, pp.45, 872~879
- 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)
- 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)
- Wong GL, "Personalized management of cirrhosis by non-invasive tests of liver fibrosis", Clin Mol Hepatol, 21, pp.200~211 (2015)
- Martin J, "Accuracy of ultrasound and noninvasive markers of fibrosis to identify patients with cirrhosis", Dig Dis Sci, 60, pp.1841~1847 (2015)
- Martínez SM, "Noninvasive assessment of liver fibrosis", Hepatology, 53, pp.325~335 (2011)
- Kim MN, "Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with transient elastography-defined subclinical cirrhosis", Hepatology, 61, pp.1851~1859 (2015)
- 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)
- 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)
- 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)
- 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)
