Abstract B72: Characteristic features of serum bile acids profile in patients with non-alcoholic steatohepatitis with hepatocellular carcinoma
Authors: Ikegami Tadashi , Honda Akira , Miyazaki Teruo , Yara Shoichiro , Matsuzaki Yasushi 
Published: May 2016

Background: It has been reported that modulation of gut microbiota can be a possible cause of non-alcoholic steatohepatitis (NASH). Furthermore, recent report revealed that increase of secondary bile acids (BA) triggers senescence-associated secretory phenotype, and associate with hepatocarcinogenesis in a rodent model. As formation of various secondary BAs and deconjugation of BAs are regulated by specific intestinal bacterial taxa, it is possible that serum BA profile, reflecting re-absorbed BAs from intestine, can be a functional marker of individual intestinal microbiota.

Materials and Methods: Sera obtained from healthy volunteer (CTL) (n=40), biopsy-proven NASH with hepatocellular carcinoma (NASH-HCC) (n=11) and without HCC (NASH w/o HCC) (n=28), were subjected to analysis of serum BA composition by using LC-MS/MS.

Results: (1) Increase in total serum BA concentration: Serum total BA concentration in NASH (7.67 ± 5.5 µM) was significantly higher regardless of the presence of HCC compared to CTL (4.13 ± 0.42 µM, P&lt; 0.001). No significant difference was seen between NASH w/o HCC and NASH-HCC. Serum 7alpha-hydroxy-4-cholestene-3-one (C4), a biomarker of BA synthesis, was not significantly different between CTL and NASH, suggesting enhanced BA synthesis is not a direct cause of the increased serum BA concentration. (2) Decrease in unconjugated BAs: The proportion of unconjugated BA in total BA was significantly lower in NASH (44.5 ± 21 %) compared to CTL (60.5 ± 20.5 %)(P&lt;0.01). No difference was seen between NASH-HCC and w/o HCC . (3) Decrease in secondary BAs: Serum concentrations of various secondary BAs were not different between CTL and NASH. However, the ratio of secondary BAs to total BA was significantly lower in NASH (24.5 ± 2 %) compared to CTL (37.8 ± 2 %, P&lt; 0.01). Free cholic acid (FCA) and free chenodeoxycholic acid (FCDCA), unconjugated primary BAs, were significantly higher in NASH-HCC (FCA 1.18 ± 1.6 μM, FCDCA 2.10 ± 2.5 µM) compared to NASH w/o HCC (FCA 0.27 ± 0.2 µM, FCDCA 0.83 ± 0.8 µM, P&lt;0.05, respectively).

Conclusions: It is speculated that the presence of these specific serum BA pattern in NASH and NASH-HCC supports possible alteration of intestinal microbiota in these diseases as previously reported. However, increase of secondary BA reported in animal model study was not observed, suggesting inter-species difference of BA metabolism. Since only modest change between NASH and NASH -HCC was observed, altered BA profile may not be a screening marker for high-risk group of HCC development among NASH patients.

Citation Format: Tadashi Ikegami, Akira Honda, Teruo Miyazaki, Shoichiro Yara, Yasushi Matsuzaki. Characteristic features of serum bile acids profile in patients with non-alcoholic steatohepatitis with hepatocellular carcinoma. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B72.