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. 2021 Jul 31;21(1):306.
doi: 10.1186/s12876-021-01884-5.

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Yuko Nagaoki  1   2 , Hideyuki Hyogo  1   2 , Yuwa Ando  1 , Yumi Kosaka  1 , Shinsuke Uchikawa  1 , Yuno Nishida  1 , Yuji Teraoka  1   2 , Kei Morio  1   2 , Hatsue Fujino  1   2 , Atsushi Ono  1   2 , Takashi Nakahara  1   2 , Eisuke Murakami  1   2 , Masami Yamauchi  1   2 , Wataru Okamoto  3 , Tomokazu Kawaoka  1   2 , Masataka Tsuge  2   4 , Akira Hiramatsu  1   2 , Daiki Miki  1   2 , Michio Imamura  1   2 , Shoichi Takahashi  1   2 , Kazuaki Chayama  2   5   6 , Hiroshi Aikata  7   8
Affiliations

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

Yuko Nagaoki et al. BMC Gastroenterol. .

Abstract

Background: We previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018.

Methods: The study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018.

Results: NBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5-60.3%: P = 0.008), hypertension (48.5-57.4%: P = 0.047), and hyperlipidemia (39.2-53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37-3.61: P = 0.026) and the median platelet count increased (15.1-17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC.

Conclusions: The prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Keywords: Cryptogenic; HCC; NASH; NBNC-HCC.

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Conflict of interest statement

Kazuaki Chayama has received honoraria from Bristol-Myers Squibb, MSD K.K., AbbVie Inc., Gilead Sciences and Dainippon Sumitomo Pharma; and research funding from Dainippon Sumitomo Pharma, MSD K. K and AbbVie Inc. Hiroshi Aikata has received honoraria from Bayer Yakuhin, Ltd and Eisai.

Figures

Fig. 1
Fig. 1
Trends in the causes of liver disease in patients with HCC over time. We show that distributions in the etiologies of liver disease in patients with HCC among 2171 patients from 1992 to 2018. The graph shows the actual number of NBNC-HCC. formula image : NBNC; formula image : HCV; formula image : HBV; formula image : B + C
Fig. 2
Fig. 2
The FIB-4 index of patients with NBNC-HCC stratified by age. Lines within the boxes represent median values; the upper and lower lines of the boxes represent the 75th and 25th percentiles, respectively; the upper and lower bars outside the boxes represent the 90th and 10th percentiles, respectively. NS not significant
Fig. 3
Fig. 3
The proportion of patients with NBNC-HCC who underwent hepatic resection according to stages of fibrosis as assessed in nonmalignant regions of resected liver. formula image : F0; formula image : F1; formula image : F2; formula image : F3; formula image : F4
See this image and copyright information in PMC

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