In the Journals

Baraclude therapy for HBV leads to lower than expected HCC incidence

Patients with hepatitis B virus infection treated with Baraclude had an unexpected lower incidence of hepatocellular carcinoma over time, although the risk for hepatocellular carcinoma in this patient population still persisted, according to the results of a retrospective study.

“In this ‘real-world’ study of a large number of U.S. patients, treatment with [entecavir] was associated with a 64% lower observed than expected HCC incidence in [patients with chronic hepatitis B] without cirrhosis,” Joseph Ahn, MD, MS, AGAF, FACG, of the division of gastroenterology and hepatology, Oregon Health and Science University, and colleagues wrote.

Joseph Ahn, MD, MS, AGAF, FACG

Joseph Ahn

The researchers used the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model — a model that provides a virtual control group of patients whose HCC incidence may be estimated based on readily obtained clinical variables — to evaluate the impact of antiviral therapy with Baraclude (entecavir, Bristol-Myers Squibb) on HCC development. They evaluated 841 patients from 26 clinical sites enrolled in the ENUMERATE clinical study. The final analysis included 646 patients: 65% were male, 84% were Asian, 36% were hepatitis B e antigen-positive and 9.4% had cirrhosis at baseline.

Over the 4 years, 2.6% of all patients were diagnosed with HCC (n = 17) — 13.1% of patients with cirrhosis (n = 8) and 1.5% without (n = 9). The patients diagnosed with HCC were older than patients without HCC (53 vs. 47 years; P = .014) and were also more likely to have cirrhosis (47.1% vs. 8.4%; P < .001).

During the first year, three patients without cirrhosis developed HCC, whereas the REACH-B model predicted 4.7 cases, which led to a standardized incidence ratio (SIR) of 0.64. Over a median follow-up of 4 years, the SIR decreased to 0.37.

When comparing observed and predicted number of HCC cases between patients with and without cirrhosis, the researchers found that in patients without cirrhosis, HCC incidence was lower than predicted (95% CI, 0.166–0.82).

Over a maximum follow-up time of 8.2 years, according to sensitivity analysis of all patients, the REACH-B model predicted 30.2 cases of HCC, but researchers observed only 17 cases with an SIR of 0.56. This indicated a lower than predicted HCC incidence (95% CI, 0.35–0.905).

The researchers concluded: “[Entecavir] antiviral therapy was associated with a lower than expected incidence of HCC. However, the risk of HCC persisted in patients with [chronic HBV] and careful surveillance for HCC remains warranted in these patients regardless of the response to [entecavir] antiviral treatment.” – by Melinda Stevens

Disclosure: Ahn reports research grant support from Bristol-Myers Squibb and serves on the advisory board for Gilead Sciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Patients with hepatitis B virus infection treated with Baraclude had an unexpected lower incidence of hepatocellular carcinoma over time, although the risk for hepatocellular carcinoma in this patient population still persisted, according to the results of a retrospective study.

“In this ‘real-world’ study of a large number of U.S. patients, treatment with [entecavir] was associated with a 64% lower observed than expected HCC incidence in [patients with chronic hepatitis B] without cirrhosis,” Joseph Ahn, MD, MS, AGAF, FACG, of the division of gastroenterology and hepatology, Oregon Health and Science University, and colleagues wrote.

Joseph Ahn, MD, MS, AGAF, FACG

Joseph Ahn

The researchers used the Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B (REACH-B) model — a model that provides a virtual control group of patients whose HCC incidence may be estimated based on readily obtained clinical variables — to evaluate the impact of antiviral therapy with Baraclude (entecavir, Bristol-Myers Squibb) on HCC development. They evaluated 841 patients from 26 clinical sites enrolled in the ENUMERATE clinical study. The final analysis included 646 patients: 65% were male, 84% were Asian, 36% were hepatitis B e antigen-positive and 9.4% had cirrhosis at baseline.

Over the 4 years, 2.6% of all patients were diagnosed with HCC (n = 17) — 13.1% of patients with cirrhosis (n = 8) and 1.5% without (n = 9). The patients diagnosed with HCC were older than patients without HCC (53 vs. 47 years; P = .014) and were also more likely to have cirrhosis (47.1% vs. 8.4%; P < .001).

During the first year, three patients without cirrhosis developed HCC, whereas the REACH-B model predicted 4.7 cases, which led to a standardized incidence ratio (SIR) of 0.64. Over a median follow-up of 4 years, the SIR decreased to 0.37.

When comparing observed and predicted number of HCC cases between patients with and without cirrhosis, the researchers found that in patients without cirrhosis, HCC incidence was lower than predicted (95% CI, 0.166–0.82).

Over a maximum follow-up time of 8.2 years, according to sensitivity analysis of all patients, the REACH-B model predicted 30.2 cases of HCC, but researchers observed only 17 cases with an SIR of 0.56. This indicated a lower than predicted HCC incidence (95% CI, 0.35–0.905).

The researchers concluded: “[Entecavir] antiviral therapy was associated with a lower than expected incidence of HCC. However, the risk of HCC persisted in patients with [chronic HBV] and careful surveillance for HCC remains warranted in these patients regardless of the response to [entecavir] antiviral treatment.” – by Melinda Stevens

Disclosure: Ahn reports research grant support from Bristol-Myers Squibb and serves on the advisory board for Gilead Sciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.