Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B

Chang, Ting Tsung; Liaw, Yun Fan; Wu, Shouzhen; Schiff, Eugene R.; Han, Kwang Hyub; Lai, Ching–Lung; Safadi, Rifaat; Lee, Samuel S.; Halota, Waldemar; Goodman, Zachary; Chan, Yat‐Sun; Zhang, Hui; Hindes, R.; Iloeje, Uchenna H.; Beebe, S. P.; Kreter, Bruce

doi:10.1002/hep.23785

Cited by 889 publications

(717 citation statements)

References 39 publications

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“…Long-term viral suppression was found to be associated with histologic improvement in the reduction of fibrosis and ultimately regression of cirrhosis [13]. Furthermore, a study has demonstrated that adult patients with CHB need over 2 years of NUC treatment to reduce risk of cirrhosis, HCC or CHB-related death [14].…”

Section: Introductionmentioning

confidence: 99%

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B

Liu

Farazi

et al. 2018

Global Health Action

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Background: Globally, of the 248 million people chronically infected with the hepatitis B virus (HBV), 74 million reside in China. Five oral nucleot(s)ide analogs (NUCs) have been approved for the treatment of chronic hepatitis B (CHB) in China. Objectives: The aims of this study were to determine rates of adherence to NUC therapy in patients with CHB, to identify the self-perceived barriers to adherence, and to examine the factors associated with adherence. Methods: Questionnaire-based interviews were administered among Chinese patients with CHB at hepatology clinics of a tertiary hospital in the city of Wuhan, China. Adults aged 18 years or older prescribed with NUCs were recruited and interviewed to complete a 27-item questionnaire in a private setting, and adherence was measured using the Morisky Medication Adherence Scale (MMAS-8). Results: Among 369 participants, only 16.5% had high adherence (score of 8), 32.2% had medium adherence (score of 6 to <8), and 51.2% were measured with low adherence (score of <6). A logistic regression model was used to determine the factors associated with medication adherence. Significant predictors of high adherence consisted of urban residency, non-cirrhotic status, not using prescribed pills other than HBV medications, and reminders from family members. The five most common reasons for skipping NUCs were that medication(s) are expensive (48.7%), forgetfulness (45.1%), have experienced or worry about potential side effects (19.8%), do not want others to know about my medication(s) usage (18.5%), and ran out of pills and do not have time to refill (15.9%). Conclusions: This study revealed that adherence rates to oral antiviral therapy were far from optimal. This finding should generate public attention, and it would be beneficial for interventional programs to target Chinese patients from rural regions, as well as patients with low socioeconomic status, cirrhosis, and taking multiple medications.

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Section: Introductionmentioning

confidence: 99%

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B

Liu

Farazi

et al. 2018

Global Health Action

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“…14,15 Histological improvement was observed in 66 of the 69 patients (96%) who had received entecavir for 3 to 7 years. 16 In a randomized trial of 191 patients with decompensated cirrhosis, entecavir-treated patients tended to have lower incidence of HCC than those treated with adefovir at 48 weeks. 17 However, due to the short duration of follow-up, the difference between the two groups was uncertain, and some patients might have already harbored undiagnosed HCC before antiviral therapy.…”

mentioning

confidence: 99%

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

et al. 2013

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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 ...

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“…All these factors may elicit significant bias between groups. Use of entecavir is proven to be beneficial for hepatitis B virus patients to reverse fibrosis and cirrhosis 6 ; however, the evidence of reduction in hepatic events and incidence of HCC, as revealed by the current study and previous work, 7 was still flawed with significant bias. Long-term follow-up of controlled studies would be more convincing.…”

Section: Finite Entecavir Therapy Is a Feasible Alternative To Indefimentioning

confidence: 52%

“…In our recent analysis, the specificity of AFP was as high as 99% at a cut-off value of 20 mg/L in patients receiving entecavir. 6 …”

Section: Replymentioning

confidence: 99%

Finite entecavir therapy is a feasible alternative to indefinite therapy

Jeng

2014

Hepatology

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however, that on multivariate analysis of lack of secondary prophylaxis, BCLC classification and liver failure as measured by ChildPugh score were independent predictors of death.We agree with the concerns that Drs. Chen and Hou express regarding the grouping of BCLC C/D patients. This was done due to the similarities in the survival curves of these patients (see Supporting fig. 1 of the article). Taking into account the subjective nature of some aspects of this classification, such as the performance status, it is possible that the difference between BCLC C and D patients is not so clear-cut.We would like to underline that not all patients received the standard secondary prophylaxis in our study. In Spain, standard secondary prophylaxis is done with a combination of beta-blockers and endoscopic band ligation. 2 Many patients received only betablockers as secondary prophylaxis, and only a minority of patients received endoscopic treatment as the sole prophylactic measure. The reason for this is not clear, but it could be due to the fact that endoscopic band ligation is perceived as a more aggressive option than beta-blocker therapy. Unfortunately, our study cannot answer the question of whether the administration of beta-blockers without endoscopic band ligation offers a better risk-benefit balance than standard secondary prophylaxis. However, we disagree with the comment made by Drs. Chen and Hou regarding the possible association between beta-blocker use and poor survival in patients with more advanced liver failure. The study they refer to 3 is also a retrospective study with major baseline differences between groups, including the presence or absence of varices, which has a wellknown impact on survival.In conclusion, we agree that the decision for secondary prophylaxis in patients with BCLC C/D should be made carefully, but our data suggest that secondary prophylaxis does offer a survival benefit in these patients. Physicians taking care of patients with advanced hepatocellular carcinoma should individualize therapies according to common sense and patient need.

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Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B

Cited by 889 publications

References 39 publications

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B

Adherence and perceived barriers to oral antiviral therapy for chronic hepatitis B

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

Finite entecavir therapy is a feasible alternative to indefinite therapy

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