The suppressive effect of nucleos(t)ide analogue treatment on the incidence of hepatocellular carcinoma in chronic hepatitis B patients

Abstract

The development of nucleos(t)ide analogues (NA) has influenced hepatitis B virus management. However, the annual incidence rate during NA treatment has been reported to be 0.3-1.2% in non-cirrhosis cases and 1.8-6.0% in cirrhosis cases, indicating that the suppressive effect of NA treatment on hepatocellular carcinoma (HCC) would be insufficient. Past studies, including one randomized control trial that compared lamivudine treatment with placebo, have revealed that NA treatment could suppress the incidence of HCC in patients with advanced fibrosis. However, it remains unknown whether NA treatment can suppress the incidence of HCC in chronic hepatitis patients without advanced fibrosis. The HCC incidence in patients treated with entecavir was similar to that of those treated with lamivudine, although entecavir exhibits a stronger viral suppression than lamivudine. The following risk factors related to the incidence of HCC during NA treatment have been identified: older age, male gender, pre-existing cirrhosis, a family clustering of hepatitis B virus, lower platelet counts, and higher hepatitis B core-related antigens as baseline factors and higher alpha fetoprotein levels as an on-treatment factor. Conversely, the loss of the hepatitis B surface antigen (HBsAg) by interferon or NA was correlated with a lower HCC incidence rate. Because interferon treatment has much more effects on reducing HBsAg levels compared with NA treatment, a combination treatment with NA and pegylated interferon can bring additional reduction of HBsAg levels compared with NA monotherapy. Further study is needed to clarify this.

Predictive value of the preoperative neutrophil-to-lymphocyte ratio for the development of hepatocellular carcinoma in HBV-associated cirrhotic patients after splenectomy

“…Nucleoside analogues effectively suppress HBV DNA levels. Several studies have shown that long-term nucleoside analogue therapy reduced the risk for developing HBV-related HCC[ 31 – 33 ]. Nucleoside analogue therapy has now become standard treatment modalities for chronic HBV infection.…”

Clinical features of hepatocellular carcinoma with hepatitis B virus among patients on Nucleos(t) ide analog therapy

“…NUC has been shown to decrease the risk of developing HCC [15,16]; however, patients with chronic HBV are still at the risk for developing HCC [17,18], even when they have maintained virologic remission under long-term therapy with NA(s), particularly in patients with cirrhosis [19,20]. The annual incidence rate during NUC therapy has been reported to be 0.3 to 1.2% in non-cirrhosis cases and 1.8 to 6.0% in cirrhosis cases, indicating that the suppressive effect of NUC therapy on HCC would be insufficient [21]. There are few reports about clinical features of HCC with HBV among patients with NUC therapy.…”

Association between HLA‐DQA1/DRB1 polymorphism and development of hepatocellular carcinoma during entecavir treatment

“…NA treatment for chronic HBV infection has been reported to not only prevent the progression of hepatitis but also reduce the risk of HCC development . A previous randomized control trial indicated that lamivudine treatment could suppress the incidence of HCC among patients with advanced fibrosis compared with placebo control .…”

“…NA treatment for chronic HBV infection has been reported to not only prevent the progression of hepatitis but also reduce the risk of HCC development. 4 A previous randomized control trial indicated that lamivudine treatment could suppress the incidence of HCC among patients with advanced fibrosis compared with placebo control. 5 Furthermore, previous studies, including some using a matched case-control design, have indicated a suppressive effect of NA treatment on HCC incidence by comparison between NA treatment and historical controls.…”