Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy

Etsuro Orito; Chitomi Hasebe; Masayuki Kurosaki; Yukio Osaki; Kouji Joko; Hiroshi Watanabe; Hiroyuki Kimura; Norihiro Nishijima; Atsunori Kusakabe; Namiki Izumi; Japanese Red Cross Liver Network

doi:10.1111/hepr.12427

Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside/nucleotide analog therapy

Hepatol Res. 2015 Aug;45(8):872-9. doi: 10.1111/hepr.12427. Epub 2014 Nov 20.

Affiliations

¹ Department of Gastroenterology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan.
² Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Asahikawa, Japan.
³ Department of Gastroenterology, Japanese Red Cross Musashino Hospital, Musashino, Japan.
⁴ Department of Gastroenterology, Japanese Red Cross Osaka Hospital, Osaka, Japan.
⁵ Department of Gastroenterology, Japanese Red Cross Matsuyama Hospital, Matsuyama, Japan.
⁶ Department of Gastroenterology, Japanese Red Cross Fukuoka Hospital, Fukuoka, Japan.
⁷ Department of Gastroenterology, Japanese Red Cross Kyoto Daiichi Hospital, Kyoto, Japan.

PMID: 25244601
DOI: 10.1111/hepr.12427

Abstract

Aim: Some patients develop hepatocellular carcinoma (HCC) during nucleoside/nucleotide analog (NA) therapy even if alanine aminotransferase (ALT) or hepatitis B virus (HBV) DNA levels are sufficiently reduced. The aim of this study is to identify the risk factors of development of HCC during NA therapy.

Methods: Six hundred and two patients were analyzed who were continuously receiving NA for chronic HBV infection. The patients who developed HCC previously or within 1 year of therapy were excluded. In the patients studied, the median duration of therapy was 90 months. A total of 492 patients had chronic hepatitis (CH) and 110 had liver cirrhosis (LC).

Results: In 602 patients, the rate of normalization of ALT, loss of serum HBV DNA and development of HCC were 90.4%, 55.4%, and 6.1%, respectively. The significant risk factors of development of HCC were LC status and duration of therapy. The annual incidence of HCC in LC patients was 2.53%/year, compared with 0.34%/year in CH patients. When the relation between the incidence of HCC and the response to therapy was evaluated, in patients with normalization of ALT level, loss of HBV DNA by real-time polymerase chain reaction or hepatitis B e-antigen seroconversion, the incidences of HCC was reduced to some extent. However, none of the patients who achieved hepatitis B surface antigen (HBsAg) seroclearance during NA therapy developed HCC.

Conclusion: LC status was the significant risk factor of development of HCC during NA therapy. However, none of the patients who showed HBsAg seroclearance developed HCC. The ultimate goal of therapy for reduced risk of HCC may be HBsAg seroclearance.

Keywords: hepatitis B surface antigen seroclearance; hepatitis B virus DNA; hepatocellular carcinoma; liver cirrhosis; nucleoside/nucleotide analog therapy; risk factors.