Entecavir in decompensated HBV cirrhosis: The future is looking brighter

Robert J. Fontana
2010 Journal of Hepatology  
See Article, pages 176-182 Practice guidelines recommend treatment of selected patients with chronic hepatitis B virus (HBV) infection who are at risk of developing progressive liver disease based upon their serum ALT and HBV DNA levels and/or liver histology [1, 2] . The seven approved medications for chronic HBV consistently lead to histological improvements in patients that suppress HBV replication during short-term treatment [3] . In addition, the rate of developing clinical outcomes and
more » ... ompensation can be significantly reduced by using prolonged lamivudine therapy in patients with advanced but compensated fibrosis compared to no treatment [4] . However, the clinical and histological benefit with the oral nucleos(t)ide analogues is substantially reduced when drugresistant variants of HBV emerge [3, 4] . As a result, the oral agents that most effectively suppress HBV replication with the lowest rate of drug resistance during prolonged use (entecavir, tenofovir) have emerged as preferred first line agents over the other available drugs (lamivudine, adefovir, telbivudine) [1, 2] . Practice guidelines also recommend prescribing an oral nucleos(t)ide analogue (but not the interferons) for patients with decompensated HBV cirrhosis independent of the patients serum ALT, HBV DNA level, and eAg status [1,2]. These latter recommendations are largely based upon open-label studies of lamivudine and adefovir in decompensated HBV patients wherein antiviral therapy was associated with improved outcomes including a delay or prevention in the need for liver transplantation (Table 1) [5-8]. For example, a prospective study of 154 decompensated HBV patients treated with lamivudine demonstrated improved laboratory and clinical parameters with treatment compared to baseline values. A biphasic survival pattern was also noted with most deaths occurring within the first 6 months of treatment; patients with higher pretreatment bilirubin, creatinine, and HBV DNA levels were at greatest risk for early death while early suppression of HBV replication was not associated with more favorable outcomes [6] . Adefovir treatment in 226 patients with lamivudine refractory decompensated HBV also led to significant improvements in their CTP and MELD scores at 1-year compared to baseline [7, 8] . However, 14% still died within the first year and at least 33% required liver transplantation for long-term survival. Although antiviral drug resistance is substantially less common with adefovir monotherapy compared to lamivudine, concerns remain regarding the slow rate of suppressing HBV replication with adefovir as well as the potential for dose-dependent nephrotoxicity in decompensated HBV patients [9,10]. Entecavir suppresses HBV replication more rapidly and effectively than lamivudine in patients with compensated chronic HBV [11] . In addition, entecavir was a more potent and rapid suppressor of HBV replication compared to adefovir in compensated patients [12] . Furthermore, entecavir does not have any reported nephrotoxicity and the resistance profile at 5 years in treatment naïve HBV patients has been excellent (i.e., $1%) [13] . Tenofovir is also a significantly more potent suppressor of HBV replication than adefovir and no drug-resistant variants have been reported with 3 years of continuous treatment in compensated patients [14, 15] . Expanded use of these two newer drugs has been sought in difficult to treat patient populations, including hemodialysis patients and subjects with decompensated HBV cirrhosis. However, safety and efficacy data are very sparse to non-existent in these special patient populations and this is due to uncertainties in drug dosing and difficulties in conducting adequately powered prospective studies. In this issue of the Journal, the effectiveness of entecavir (at a dose of 0.5 mg per day) in a cohort of 70 consecutive Korean patients with decompensated HBV is reported [16] . The virological responses in the 55 decompensated HBV patients at 1 year are also compared to 144 compensated patients treated with entecavir from the same center. Of note, none of these patients had previously been treated with an oral nucleos(t)ide analogue nor harbored drug-resistant variants of HBV. As expected, the mean MELD (11.5 vs. 7) and CTP scores (8.1 vs. 5.3) were significantly higher in the decompensated patients but the mean pretreatment HBV DNA levels (7.2 vs. 7.5 log 10 ) and proportion of HBeAg + patients (49.1% vs. 62.5%) was similar. Overall, the 1-year transplant-free survival rate was 87.1% in the decompensated patients. As previously reported with lamivudine, the majority of adverse outcomes occurred within the first 6 months of treatment and these nine patients had more severe liver failure at entry compared to the others. However, the baseline HBV DNA
doi:10.1016/j.jhep.2009.10.025 pmid:20006400 fatcat:h5uuutv3wfhxxonud3ctokuinm