Partial Virological Response after 2 Years of Entecavir Therapy Increases the Risk of Hepatocellular Carcinoma in Patients with Hepatitis B Virus-Associated Cirrhosis
2
조회
0
다운로드
3
인용
0
참고문헌
키워드
초록
Background/Aims: The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. Methods: A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. Results: After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. Conclusions: PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
Abstract
Background/Aims: The clinical significance of partial virological response (PVR) in patients undergoing antiviral therapy is not well known. This study investigated whether PVR after 2 years of entecavir (ETV) therapy is associated with hepatocellular carcinoma (HCC) development in cirrhotic patients. Methods: A total of 472 naïve patients with hepatitis B virus (HBV)-associated cirrhosis who were treated with ETV for at least 2 years were retrospectively enrolled. Clinical characteristics, laboratory data, PVR, and noninvasive fibrosis markers (aspartate aminotransferase to platelet ratio and FIB-4 index) at 2 years after ETV commencement were analyzed for HCC risk. Results: After excluding those who developed HCC within 2 years of ETV therapy, 359 patients (mean age, 51±10 years; male 64.3%) were examined. During a median follow-up of 82 months, 80 patients developed HCC. In the univariate analysis, older age (hazard ratio [HR], 1.056; p<0.001), PVR (HR, 2.536; p=0.002), higher aspartate aminotransferase (HR, 1.018; p=0.005), lower albumin level (HR, 0.463; p<0.001), lower platelet count (HR, 0.993; p=0.01), and higher FIB-4 index (HR, 1.141; p<0.001) at 2 years after ETV commencement were risk factors for HCC. In the multivariate analysis, older age (HR, 1.046; 95% confidence interval [CI], 1.022 to 1.072; p<0.001), PVR (HR, 2.358; 95% CI, 1.310 to 4.245; p=0.004), and higher FIB-4 index (HR, 1.103; 95% CI, 1.035 to 1.177; p=0.003) were independent risk factors. Conclusions: PVR and higher FIB-4 index after 2 years of ETV therapy were independent risk factors for HCC. Therefore, efforts to accomplish a complete virological response and reduce the FIB-4 index should be made.
참고문헌 (25)
- Chen CJ, "Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level", JAMA, 295, pp.65~73 (2006)
- Kim JH, "Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment", Hepatology, 66, pp.335~343 (2017)
- Kim SS, "Effect of virological response to entecavir on the development of hepatocellular carcinoma in hepatitis B viral cirrhotic patients : comparison between compensated and decompensated cirrhosis", Am J Gastroenterol, 109, pp.1223~1233 (2014)
- Terrault N, "Is low level viremia acceptable during antiviral therapy of patients with HBV infection and decompensated cirrhosis?", Clin Gastroenterol Hepatol, 16, pp.1876~1878 (2018)
- European Association for the Study of the Liver, "EASL 2017clinical practice guidelines on the management of hepatitis B virus infection", J Hepatol, 67, pp.370~398 (2017)
- Wong GL, "Normal on-treatment ALT during antiviral treatment is associated with a lower risk of hepatic events in patients with chronic hepatitis B", J Hepatol, 69, pp.793~802 (2018)
- Kim EJ, "Rapid alanine aminotransferase normalization with entecavir and hepatocellular carcinoma in hepatitis B virus-associated cirrhosis", Dig Dis Sci, 62, pp.808~816 (2017)
- Terrault NA, "Update on prevention, diagnosis, and treatment of chronic hepatitis B : AASLD 2018 hepatitis B guidance", Hepatology, 67, pp.1560~1599 (2018)
- Shin SK, "Improvement of liver function and non-invasive fibrosis markers in hepatitis B virusassociated cirrhosis : 2 years of entecavir treatment", J Gastroenterol Hepatol, 30, pp.1775~1781 (2015)
- Chen CF, "Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma", Gastroenterology, 141, pp.1240~1248 (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)
- Sarin SK, "Asian-Pacific clinical practice guidelines on the management of hepatitis B : a 2015update", Hepatol Int, 10, pp.1~98 (2016)
- Chang TT, "Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B", Hepatology, 51, pp.422~430 (2010)
- Hosaka T, "Long-term entecavir treatment reduces hepatocellular carcinoma incidence in patients with hepatitis B virus infection", Hepatology, 58, pp.98~107 (2013)
- Suh B, "High liver fibrosis index FIB4 is highly predictive of hepatocellular carcinoma in chronic hepatitis B carriers", Hepatology, 61, pp.1261~1268 (2015)
- Paik N, "Non-invasive tests for liver disease severity and the hepatocellular carcinoma risk in chronic hepatitis B patients with low-level viremia", Liver Int, 38, pp.68~75 (2018)
- Tseng TC, "Fibrosis-4 index helps identify HBV carriers with the lowest risk of hepatocellular carci-noma", Am J Gastroenterol, 112, pp.1564~1574 (2017)
- Nishikawa H, "Comparison of FIB-4 index and aspartate aminotransferase to platelet ratio index on carcinogenesis in chronic hepatitis B treated with entecavir", J Cancer, 8, pp.152~161 (2017)
- Tada T, "Impact of FIB-4 index on hepatocellular carcinoma incidence during nucleos(t)ide analogue therapy in patients with chronic hepatitis B : an analysis using time-dependent receiver operating characteristic", J Gastroenterol Hepatol, 32, pp.451~458 (2017)
- Kim BK, "Validation of FIB-4 and comparison with other simple noninvasive indices for predicting liver fibrosis and cirrhosis in hepatitis B virusinfected patients", Liver Int, 30, pp.546~553 (2010)
- Jin W, "Diagnostic accuracy of the aspartate aminotransferase-to-platelet ratio index for the prediction of hepatitis B-related fibrosis : a leading meta-analysis", BMC Gastroenterol, 12, pp.14~ (2012)
- Lu L, "Tenofovir-based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir", J Viral Hepat, 22, pp.675~681 (2015)
- Yip B, "Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders", Dig Dis Sci, 57, pp.3011~3016 (2012)
- Choi J, "Risk of hepatocellular carcinoma in patients treated with entecavir vs tenofovir for chronic hepatitis B : a Korean nationwide cohort study", JAMA Oncol, 5, pp.30~36 (2019)
- Pang Q, "FIB-4 as a prognostic model for patients with hepatitis B-associated hepatocellular carcinoma", Hepatology, 62, pp.1325~1326 (2015)
