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. 2024 Sep 18.
doi: 10.1111/hepr.14111. Online ahead of print.

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs

Emi Sometani  1 , Hayato Hikita  1 , Kazuhiro Murai  1 , Hidenori Toyoda  2 , Satoshi Tanaka  3 , Tsugiko Oze  4 , Jihyun Sung  1 , Akiyoshi Shimoda  1 , Makoto Fukuoka  1 , Satoshi Shigeno  1 , Keisuke Fukutomi  1 , Kumiko Shirai  1 , Yuki Tahata  1 , Yoshinobu Saito  1 , Akira Nishio  1 , Kunimaro Furuta  1 , Takahiro Kodama  1 , Ryotaro Sakamori  3 , Tomohide Tatsumi  1 , Eiji Mita  3 , Akihiro Umezawa  5 , Yasuhito Tanaka  6 , Tetsuo Takehara  1
Affiliations

High serum growth differentiation factor 15 is a risk factor for the occurrence of hepatocellular carcinoma in chronic hepatitis B patients treated with nucleos(t)ide analogs

Emi Sometani et al. Hepatol Res. .

Abstract

Aim: Patients with chronic hepatitis B (CHB) remain at risk for hepatocellular carcinoma (HCC) even with nucleos(t)ide analog therapy. We evaluated risk factors for HCC development, including serum hepatitis B virus (HBV) RNA, hepatitis B core-related antigen level, and growth differentiation factor 15 (GDF15) level, a predictor of HCC development in patients with chronic hepatitis C.

Methods: We collected clinical data and stored serum from CHB patients without a history of HCC who were receiving nucleos(t)ide analog treatment for more than 1 year and whose HBV DNA level was less than 3.0 log IU/mL. We measured the serum levels of HBV RNA and GDF15.

Results: Among 242 CHB patients, 57 had detectable HBV RNA, and GDF15 was quantified in all patients. The median GDF15 level was 0.86 ng/mL. Cox proportional hazards analysis revealed that male sex and higher GDF15, FIB-4 index, alpha-fetoprotein and gamma-glutamyl transpeptidase were independent risk factors for HCC. The presence of HBV RNA above the lower limit of quantification was not a risk factor. When we set cutoff values based on the Youden index, the cumulative incidence of HCC was significantly higher in the male, AFP ≥3.0 ng/mL, gamma-glutamyl transpeptidase ≥22 U/L, FIB-4 index ≥1.93, and GDF-15 ≥1.17 ng/mL groups. In patients with no or more than three of these five risk factors, the 10-year HCC cumulative incidence rates were 0% and 41.0%, respectively.

Conclusions: High serum GDF15 is an independent risk factor for the occurrence of HCC in CHB patients treated with nucleos(t)ide analogs.

Keywords: CHB; NUC; cccDNA.

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