Bile Acids and Viral Hepatitis and Hepatocellular Carcinoma

  • Yasuaki TakeyamaEmail author
  • Shotaro Sakisaka


Serum total bile acid levels are increased in viral hepatitis and correlate with the degree of liver fibrosis and are also high in hepatocellular carcinoma (HCC). In this chapter, we describe how accumulation of bile acids affects hepatitis viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) and carcinogenesis of HCC. Viral hepatitis: Na+/taurocholate cotransporting polypeptide (NTCP) is an uptake transporter of bile acids and an HBV entry receptor. Several NTCP inhibitors reduce HBV infection. Bile acids promote HBV replication via nuclear receptor transduction. HBV infection increases bile acid synthesis. In patients with high bile acids, interferon therapy shows higher failure rates in chronic hepatitis C. Bile acids increase HCV replication. HCC: Bile acids can induce cell death and inflammation, leading to promotion of carcinogenesis. Bile acid uptake transporters (NTCP and organic anion transporter peptide [OATP]1B3) and bile salt export pump expression are reduced in most cases of HCC. Because OATP1B3 also uptakes gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (Gd–EOB–DTPA), HCC lesions show low signal intensity in the hepatobiliary phase of Gd–EOB–DTPA-enhanced magnetic resonance imaging. Ursodeoxycholic acid (UDCA): UDCA is a hydrophilic bile acid and a safe and effective medical therapy in chronic hepatitis B and C. UDCA improves abnormal liver transaminase levels; however, it cannot eradicate viruses in the liver. UDCA-induced inhibition of DLC1 (deleted in liver cancer 1) protein degradation leads to suppression of HCC cell growth. DLC1 is a tumor suppressor gene for HCC.


Bile acids Hepatitis B virus Hepatitis C virus Hepatocellular carcinoma Hepatobiliary transporter 


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© Springer Japan KK 2017

Authors and Affiliations

  1. 1.Department of Gastroenterology and MedicineFukuoka University Faculty of MedicineFukuokaJapan

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