Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC
Incidence of non-alcoholic steatohepatitis (NASH), an advanced form of non-alcoholic fatty liver disease (NAFLD), is rapidly increasing globally and may progress to hepatocellular carcinoma (HCC) with or without cirrhosis. The progression cascade from NAFLD via NASH to HCC may be promoted by alterations in the gut microbiome and the bile acid homeostasis, both essential parts of the gut-liver axis.
This is what a recent study led by a German research group from the University Hospital Magdeburg aimed to investigate for NASH-related HCC. Stool and serum samples from 87 subjects divided into five groups (NASH, NASH with cirrhosis, NASH-HCC, NASH-HCC with cirrhosis, and healthy controls) were included in the analysis.
Serum levels of total bile acids and individual conjugated primary bile acids increased with disease severity, which is even more pronounced in patients with cirrhosis. Unlike in NASH, serum levels of the fibroblast growth factor 19 (FGF19), a suppressor of hepatic bile acid synthesis induced by the nuclear receptor farnesoid X receptor (FXR), were elevated in NASH-HCC patients. This indicates that different mechanisms lead to the accumulation of bile acids, independent from cirrhosis. Along with the alteration in bile acid homeostasis, the diversity of certain intestinal bacteria was affected. An increased abundance of Lactobacilli, for instance, is thought to be a consequence of the increased availability of primary conjugated bile acids as a substrate for deconjugating enzymes of these bacteria.
Overall, the researchers propose that an increase in bile acid levels might contribute to fibrogenesis, liver injury, and tumorigenesis in NASH-HCC, while there seem to be two distinct mechanisms in hepatocarcinogenesis, a cirrhosis-dependent and an –independent one, reflected by even higher serum BA levels.
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Sydor S, Best J, Messerschmidt I, Manka P, Vilchez-Vargas R, Brodesser S, Lucas C, Wegehaupt A, Wenning C, Aßmuth S, Hohenester S, Link A, Faber KN, Moshage H, Cubero FJ, Friedman SL, Gerken G, Trauner M, Canbay A, Bechmann LP: Altered Microbiota Diversity and Bile Acid Signaling in Cirrhotic and Noncirrhotic NASH-HCC (2020) Clin Transl Gastroenterol | https://doi.org/10.14309/ctg.0000000000000131