December 18, 2013

Antiviral drug resistance increases hepatocellular carcinoma: A prospective decompensated cirrhosis cohort study

World J Gastroenterol. 2013 December 7; 19(45): 8373-8381.
Published online 2013 December 7. doi: 10.3748/wjg.v19.i45.8373.

Copyright ©2013 Baishideng Publishing Group Co., Limited. All rights reserved.

Lei Li, Wei Liu, Yu-Han Chen, Chun-Lei Fan, Pei-Ling Dong, Fei-Li Wei, Bing Li, De-Xi Chen and Hui-Guo Ding.

Lei Li, Yu-Han Chen, Chun-Lei Fan, Pei-Ling Dong, Bing Li, Hui-Guo Ding, Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Beijing 100069, China
Wei Liu, Department of Internal Medicine, Beijing Ji Shui Tan Hospital Affiliated with Peking University, Beijing 100035, China
Fei-Li Wei, De-Xi Chen, Viral Laboratory of Liver Diseases Research Institute, Capital Medical University, Beijing 100069, China
Author contributions: Li L, Liu W and Chen YH equally contributed to the data collection and follow-up of patients in this study; Li L and Ding HG analysed the data and wrote the manuscript; Wei FL and Chen DX supervised the drug resistance mutation detection; Ding HG was responsible for this project and the final manuscript; the other authors contributed to the data acquisition and patient care.

Correspondence to: Hui-Guo Ding, MD, PhD, Director, Department of Gastroenterology and Hepatology, Beijing You’an Hospital Affiliated with Capital Medical University, Fengtai district, Beijing 100069, China.

Telephone: +86-10-83997155 Fax: +86-10-63295525

Received July 24, 2013; Revised September 22, 2013; Accepted September 29, 2013;


AIM: To study the clinical outcome of antiviral therapy in hepatitis B-related decompensated cirrhotic patients.

METHODS: Three hundred and twelve patients with decompensated hepatitis B cirrhosis were evaluated in a prospective cohort. With two years of follow-up, 198 patients in the group receiving antiviral therapy with nucleos(t)ide analogues and 39 patients in the control group without antiviral treatment were analysed.

RESULTS: Among the antiviral treatment patients, 162 had a complete virological response (CVR), and 36 were drug-resistant (DR). The two-year cumulative incidence of hepatocellular carcinoma (HCC) in the DR patients (30.6%) was significantly higher than that in both the CVR patients (4.3%) and the control group (10.3%) (P < 0.001). Among the DR patients in particular, the incidence of HCC was 55.6% (5/9) in those who failed rescue therapy, which was extremely high. The rtA181T mutation was closely associated with rescue therapy failure (P = 0.006). The Child-Pugh scores of the CVR group were significantly decreased compared with the baseline (8.9 ± 2.3 vs 6.0 ± 1.3, P = 0.043).

CONCLUSION: This study showed that antiviral drug resistance increased the risk of HCC in decompensated hepatitis B-related cirrhotic patients, especially in those who failed rescue therapy.

Keywords: Hepatitis B, Decompensated cirrhosis, Nucleos(t)ide analogues, Hepatocellular carcinoma, Drug resistance

Core tip: This study was performed to analyse the clinical data of 312 patients with decompensated hepatitis B cirrhosis in a prospective cohort. These data showed that complete virological response could improve the clinical outcome in decompensated hepatitis B cirrhotic patients. However, clinicians should be aware of the high risk of hepatocellular carcinoma and liver failure in antiviral drug-resistant patients.


Chronic hepatitis B virus (HBV) infection, the main aetiology of liver cirrhosis and hepatocellular carcinoma (HCC), remains a major public health problem worldwide, especially in China[1-3]. Among these patients, the annual incidence of HCC is 2%-5%[3-5]. The most effective method to prevent HCC is to control HBV infection through vaccination[5,6]. In patients already infected with HBV, antiviral therapy remains the best strategy to prevent liver cirrhosis and HCC[6-9]. Major progress in the treatment of chronic hepatitis B has recently been made during the last decade with the development of antiviral drugs, especially nucleos(t)ide analogues (NUCs)[10-12]. Some data supporting the benefit of antiviral therapy on the prevention of HCC in chronic hepatitis B patients have been reported in several randomised controlled trials[12-15]. Nonetheless, antiviral drug resistance is important in determining the success of long-term therapy for chronic hepatitis B patients[16,17]. Based on recent clinical data, the development of resistance to NUCs is associated with an exacerbation of liver disease, including the development of cirrhosis and HCC[16]. In addition, the risk of HCC remains high in HBV-related cirrhosis patients who are treatment-naïve for NUCs[17]. Decompensated cirrhosis is the end stage of the disease and is characterised by high mortality and an extremely high risk of HCC. In HBV-related decompensated cirrhotic patients (DCPs), antiviral therapy using NUCs is recommended according to the 2005 global guidelines[18-20]. However, clinical data regarding the incidence of HCC in HBV-related DCPs with NUC antiviral therapies are limited. Therefore, the aim of the current study was to evaluate the two year outcomes in HBV-related decompensated cirrhotic, treatment-naïve patients using NUCs in a real life practical prospective cohort.

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