Key messages
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We could not estimate the effects of entecavir (a medicine used to treat infections caused by viruses) on death due to any cause in people with chronic hepatitis B (a common liver disease) as there were no deaths. No studies looked at health-related quality of life (a measure of a person's satisfaction with their life and health).
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We do not know whether entecavir is better than no treatment or placebo (a pretend treatment) regarding the proportion of people with serious harmful effects.
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We found 10 ongoing studies that may provide further evidence for the benefits and harms of entecavir for people with chronic hepatitis B in updates of this review.
What is chronic hepatitis B?
Chronic hepatitis B is a common liver disease and is frequently spread through unprotected sex (without using barrier methods such as condoms), or transmission from the mother to the child during pregnancy, labour, and birth, or while breastfeeding. There were 296 million people infected with chronic hepatitis B in 2019. It is estimated that every year, about 1.5 million people will become infected with hepatitis B. Chronic hepatitis B caused more than 800,000 deaths in 2019 and is also associated with the incidence of cirrhosis (severe scarring of the liver) and hepatocellular carcinoma (liver cancer).
How is chronic hepatitis B treated?
Antiviral medicines (which are used to treat infections caused by viruses) are widely accepted therapies for chronic hepatitis B. These include interferon-alpha therapy (medications that mimic a protein naturally produced by the body to combat viral infections) and nucleos(t)ide analogue therapy (medications that mimic the building blocks of viral genetic material to prevent the virus from replicating). Entecavir is a nucleos(t)ide analogue antiviral medicine and has comparable benefits and harms to other antiviral medicines, but it has a lower cost and it is not easy to develop resistance (where viruses no longer respond to antiviral medicines). Therefore, entecavir has been used as the preferred medicine in treating people with chronic hepatitis B.
What did we want to find out?
We wanted to find out if entecavir is useful and safe for children and adults with chronic hepatitis B compared with no treatment or placebo (a pretend treatment).
What did we do?
We searched for studies in which people with confirmed chronic hepatitis B were randomly allocated to one of two treatment groups. People in the studies received either entecavir or no treatment or placebo. We allowed other treatments, such as standard medical therapies and other supportive measures, if these were equally administered to the people in all study groups (which means that treatments administered to all study groups can be ignored). We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 22 studies involving 2940 people with chronic hepatitis B. No studies looked at the impact of using entecavir on health-related quality of life (a measure of a person's satisfaction with their life and health) in people with chronic hepatitis B. The effect of entecavir on the risk of death due to any cause could not be estimated as there were no deaths in any of the available studies. There was insufficient evidence to determine whether entecavir was better or worse than no treatment or placebo regarding the proportion of people with serious harmful effects.
What are the limitations of the evidence?
The included studies did not provide data on health-related quality of life. We could not estimate the effect of entecavir on death in people with chronic hepatitis B. Some studies were very small, and some studies used methods likely to introduce errors in their results. For example, it is possible that people in the studies were aware of which treatment they were receiving and the knowledge of the treatment may have influenced how they reported the effects. Therefore, we have very low confidence in our findings and the results of further studies may change the results of this review.
How up to date is this evidence?
The evidence is up to date to 19 July 2024.
Given the issues of risk of bias and insufficient power of the included trials and the very low certainty of the available evidence, we could not determine the effect of entecavir versus no treatment or placebo on critical outcomes such as all-cause mortality and serious adverse events. There is a lack of data on health-related quality of life. Given the first-line recommendation and wide usage of entecavir in people with chronic hepatitis B, further evidence on clinically important outcomes, analysed in this review, is needed.
To evaluate the benefits and harms of entecavir versus no treatment or placebo in children and adults with chronic hepatitis B, who are either hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative.
We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE Ovid, Embase Ovid, three other databases, online trial registries, and reference lists, and contacted authors. The latest search was on 19 July 2024.
This Cochrane review had no dedicated funding.
Registration: Entecavir for children and adults with chronic hepatitis B, CD015536 via DOI 10.1002/14651858.CD015536.