Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis

Abstract

Entecavir is a potent antiviral agent with high genetic barrier to resistance, hence it is currently recommended as first-line antiviral therapy for chronic hepatitis B (CHB). The aim of this study was to investigate the efficacy of entecavir on clinical outcomes and deaths. It was a retrospective-prospective cohort study based on two cohorts of patients. The entecavir cohort included consecutive CHB patients who had received entecavir 0.5 mg/day for at least 12 months. The historical control cohort included untreated patients recruited since 1997 who underwent routine clinical care. The primary outcome was the 5-year cumulative probability of hepatic events, defined as any cirrhotic complications, hepatocellular carcinoma (HCC), and/or liver-related mortality. A total of 1,446 entecavir-treated patients (72% men; age, 51 6 12 years; follow-up, 36 6 13 months) and 424 treatment-naïve patients (65% men; age, 41 6 13 years; follow-up, 114 6 31 months) were studied. Overall, there was no difference in hepatic events between the entecavir and control cohorts. Among patients with liver cirrhosis (482 entecavir-treated, 69 treatment-naïve), entecavir-treated patients had reduced risks of all clinical outcomes when compared with treatment-naïve patients with cirrhosis after adjusted for model for end-stage liver disease score: hepatic events (hazard ratio [HR], 0.51; 95% confidence interval [CI], 0.34-0.78; P 5 0.002), HCC (HR, 0.55; 95% CI, 0.31-0.99; P 5 0.049), liver-related mortality (HR, 0.26; 95% CI, 0.13-0.55; P < 0.001), and all-cause mortality (HR, 0.34; 95% CI, 0.18-0.62; P < 0.001). Entecavir-treated patients with cirrhosis who failed to achieve undetectable hepatitis B virus DNA (105/482 [22%]) had comparable risk of hepatic events as the untreated patients. Conclusion: Entecavir therapy reduces the risks of hepatic events, HCC, liver-related and all-cause mortality of CHB patients with liver cirrhosis in 5 years, particularly among those who had maintained viral suppression. (HEPATOLOGY 2013;58:1537-1547 C hronic hepatitis B (CHB) is the leading cause of liver cirrhosis and hepatic events, including various cirrhotic complications and hepatocellular carcinoma (HCC) in Asia. 1 A high level of hepatitis B virus (HBV) DNA has been consistently shown to be an independent risk factor for the development of cirrhosis and HCC. 2,3 Antiviral therapy is effective in suppressing HBV DNA and reducing the risk of hepatic events and HCC. 4,5 Lamivudine, the first generation oral nucleoside analogue was shown to reduce the incidence of hepatic events in patients with advanced fibrosis or compensated cirrhosis by 50%. 6 However, the clinical benefit may be negated by lamivudine resistance and virologic relapse after cessation of treatment. 6,7 Therefore, lamivudine is no longer the firstline antiviral therapy for CHB. Instead, nucleos(t)ide analogues with high genetic barrier to resistancenamely, entecavir and tenofovir disoproxil fumarateare recommended by international guidelines. [8][9][10] Entecavir is a more potent ...

Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

“…Therefore investigators reasoned that the same nucleos(t)ide analogues (NAs) that have been proven so effective against chronic HBV infection may also benefit patients with HBV-related HCC. Indeed, randomized controlled trials (RCTs) [6] and large retrospective studies [7][8][9] have shown that NAs can dramatically reduce the risk of HCC in patients with chronic HBV infection or cirrhosis. While this suggests that NAs are effective against primary HCC, the question of whether they can also prevent HCC recurrence after radical resection remains controversial [10] .…”

Transient elastography is useful for evaluating hepatocellular carcinoma development during entecavir treatment of chronic hepatitis B virus infection

“…However, although an undetectable HBV DNA level and ALT level normalization are achieved with ETV treatment, complete elimination of intracellular HBV remains difficult [20,21]. It was reported that although ETV can considerably reduce the risk of HCC development [9], HCC development persists, and the details remain unclear. In a recent report, the cumulative incidence of HCC was not affected by HBV DNA negativity or by ALT level normalization at 24 weeks [22].…”

“…Hence, entecavir (ETV) and tenofovir, more effective oral NAs, are now the first-line antiviral agents for patients with chronic HBV infection [4][5][6] because of their low risk for the development of drug resistance [7,8]. ETV can substantially improve liver function and reduce both cirrhotic complications and HCC development [9,10]. However, a randomized controlled ETV treatment study of patients with chronic HBV infection has not been performed, and the suppressive effect of ETV on HCC development remains unclear.…”

Oral antiviral therapy reduces the risk of hepatocellular carcinoma in persons with chronic hepatitis B infection: combining evidence and common sense

“…A widely cited double-blind, randomized, placebo-controlled trial reported by Liaw et al demonstrated that, in patients with advanced fibrosis or early cirrhosis, treatment with lamivudine could reduce the HCC if cases found within the first year were excluded from both groups, but the emergence of drug resistance compromised the benefit [10]. Clinical cohort studies from other centers in Hong Kong and Taiwan also showed a consistent trend of reduced incidence of HCC in patients treated with NAs [11,12]. Furthermore, a population-based study carried out in Taiwan suggested that, compared with the pre-antiviral era, the incidence and mortality of HCC in the general population were decreasing with the increasing coverage rate of antiviral therapy for HBV and HCV, as shown in databases of medical insurance [13].…”

“…Therefore, later investigations on this topic usually adopted a cohort study design, with untreated or different treatment arm(s) as historical or external control group(s). The imbalance of known confounding factors across different arms can be minimized by special statistical techniques such as propensity score matching (PSM) analysis [11,17]. However, this would need much bigger sample sizes in order to have a large enough number of patients left after PSM.…”