The nucleoside analogue entecavir (Baraclude, Bristol-Myers Squibb) achieves a high response rate and progressive decline in liver stiffness in patients with chronic hepatitis B, according to results from the first study in ‘real-life’ clinical practice reported at the Annual Meeting of the American Association for the Study of Liver Diseases (31 October – 3 November, 2009).
Clinical trials have shown that entecavir is an effective and safe treatment for patients with chronic hepatitis B who have not previously been treated with a nucleoside analogue, but the long-term efficacy has not previously been reported. Italian researchers followed 376 consecutive patients, recruited from 16 centres across Italy during 2007-08, who were treated with entecavir (0.5mg once daily). The patients were generally older than those included in previous clinical trials, with a median age of 58 years, and had more severe liver disease (47% had cirrhosis). More than half (54%) had concomitant disease.
Results showed that nearly two-thirds (64%) of the patients achieved undetectable virus levels (HBV DNA < 12 U/ml) by 24 weeks. This increased to 91% of patients by 48 weeks and to 96% at 72 weeks. Patients with a low level of viraemia at baseline (DNA < 5 log U) were more likely to achieve undetectable virus levels (100% by 12 months), than those with higher viral loads. However, 96% of patients with medium levels of viraemia (DNA 5-8 log U) achieved a virological response by 18 months. And more than three-quarters (77%) of patients with high baseline viral load (DNA > 8 log U) reached this by 18 months.
The lead researcher, Dr Pietro Lampertico, from the University of Milan, Italy, said: “We found we can stop replication of the virus in most patients, which we found surprising as many of these patients would be considered difficult to treat because of the severity of their liver disease,” he reported. “An important message for clinicians is not to stop treating patients after one year even if they have residual virus, because the drug will continue to reduce viral levels.”
Further results showed that patients’ liver enzyme levels (alanine aminotransferase, ALT) improved with entecavir, with the proportion of patients with ALT levels below the upper limit of normal increasing from 14% at baseline to 85% after 72 weeks of treatment. “This is very important. If we can stop the disease, and stop the inflammation of the liver, we may be able to stop disease progression and reduce the risk of liver cancer.”
Liver stiffness, assessed by Fibroscan in 73 patients, decreased from 9.3 to 7.0KPa, independently of cirrhosis. More than two-thirds (68%) of patients who had a baseline liver stiffness greater than 12.5KPa achieved a level below this cut-off at their last visit.
A further study showed that entecavir (1.0mg once daily) was superior to adefovir (10mg once daily) in achieving undetectable HBV DNA levels (< 300 copies/ml) in patients with chronic hepatitis B and hepatic decompensation (severe disease, where the liver is no longer functioning adequately). After 48 weeks, 57% of patients treated with entecavir achieved undetectable viral levels, compared to 20% of those on adefovir (p Susan Mayor, PhD
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