A large real‐world cohort study examining the effects of long‐term entecavir on hepatocellular carcinoma and HBsAg seroclearance

Abstract

Real‐world studies examining reduction in risk of hepatocellular carcinoma (HCC) in patients receiving antivirals are limited by the small size of the studies, or by data insufficiency and heterogeneity with short follow‐up duration. We aimed to examine the real‐world long‐term outcome of patients receiving entecavir treatment on HCC incidence and HBsAg seroclearance. The incidence of HCC in 1225 entecavir‐treated patients between 2002 and 2015 was compared with the HCC incidence estimated using the REACH‐B, GAG‐HCC and CU‐HCC scores. Standardized incidence ratios (SIR) were calculated. The impact of entecavir treatment on HBsAg seroclearance was also explored. The median follow‐up of the cohort was 6.6 years, with 66 cases of HCC development. Using the REACH‐B model, the reduction of HCC risk was significant from year 6 onwards with SIR of 0.68 (95% CI 0.535‐0.866) at year 10. In subgroup patients without cirrhosis, consistent risk reduction was observed from the fifth year and the SIR reached 0.51 (95% CI 0.271‐0.704) by year 10. Benefit in cirrhotic patients was demonstrated when using the GAG‐HCC and CU‐HCC score, with the SIR at year 10 being 0.38 (95% CI 0.259‐0.544) and 0.46 (95% CI 0.314‐0.659), respectively. The cumulative rate of HBsAg seroclearance was 5.2%. HBsAg level at third year of treatment and baseline‐to‐3‐year percentage reduction was predictive of subsequent HBsAg seroclearance. In conclusion, long‐term entecavir therapy was associated with significant reduction in the risk of HCC in the real world. However, HBsAg seroclearance rate remained low. Additional therapy may be considered in patients with adverse predictive factors for subsequent HBsAg seroclearance.

Treatment for Viral Hepatitis as Secondary Prevention for Hepatocellular Carcinoma

“…The reduction in HCC risk achieved with ETV was significant starting from year six of treatment with a standardized incidence ratio of 0.68 (95% CI: 0.535-0.866). Notably, the HCC-preventing effect of ETV was seen in both cirrhotic and non-cirrhotic patients [76].…”

“…Their long-term use induces sustained virological suppression in the vast majority of patients (>95%), along with histological improvements and regression of fibrosis and cirrhosis [73,74]. Furthermore, cohort and population studies carried out all across the world demonstrate that long-term use (>5 years) of either ETV or TDF prevents the development of HCC in the majority of patients [11,[75][76][77]. A cohort study from Hong Kong including 1225 chronic HBV patients who were treated with ETV between 2002 and 2015 compared the HCC incidence among ETV-treated patients to the expected HCC incidence calculated with well-established HCC risk scores for a patient with chronic HBV [76].…”

“…Furthermore, cohort and population studies carried out all across the world demonstrate that long-term use (>5 years) of either ETV or TDF prevents the development of HCC in the majority of patients [11,[75][76][77]. A cohort study from Hong Kong including 1225 chronic HBV patients who were treated with ETV between 2002 and 2015 compared the HCC incidence among ETV-treated patients to the expected HCC incidence calculated with well-established HCC risk scores for a patient with chronic HBV [76]. The reduction in HCC risk achieved with ETV was significant starting from year six of treatment with a standardized incidence ratio of 0.68 (95% CI: 0.535-0.866).…”

Secondary prevention for hepatocellular carcinoma in patients with chronic hepatitis B: are all the nucleos(t)ide analogues the same?

“…Under long-term entecavir or tenofovir therapy, patients continue to have histological improvement and regression of liver fibrosis and even cirrhosis [48,49]. Long-term therapy also prevents disease progression and HCC development [29,[50][51][52]. In terms of safety profile, long-term use of entecavir is generally safe [53].…”

Efficacy of entecavir versus tenofovir in preventing hepatocellular carcinoma in patients with chronic hepatitis B with maintained virologic response

“…2,3 Currently, nucleos(t)ide analogs (NAs) that can effectively suppress viral replications are available, 4 and their use can decrease the risk of cirrhosis and HCC. [5][6][7][8][9][10][11] During NA therapy, virologic response to treatment is linked to the outcomes of patients with CHB. 12 Hence, international HBV guidelines recommend maintained virologic response (MVR), defined as a persistently undetectable HBV DNA level in the serum, as a goal of NAs therapy.…”