The journey from hepatitis to hepatocellular carcinoma. Bridging role of Helicobacter species.

Hepatocellular carcinoma (HCC) is a long-term consequence of chronic liver disease, whose aetiology could result from viral, environmental and hereditary causes. Viral infection, by itself, could only partially explain the pathogenesis of cirrhosis and HCC. A new aetiologic agent capable of inducing chronic active hepatitis and hepatocellular tumours was discovered: it is a bacterium belonging to the genus Helicobacter, and named H. hepaticus. Presence of sequences belonging to the 16S rRNA of Helicobacter species (spp.) has been demonstrated in liver of most patients with cirrhosis and HCC. H. pylori and related bacteria, such as H. hepaticus, produce toxins that kill hepatocyte by a granulating effect on liver cell lines. In vivo, such toxins might reach the liver through the portal tract, thereby causing hepatocellular damage. The recognition of Helicobacter spp. as a possible risk factor for cirrhosis and HCC might have a practical impact on the general population: the treatment of this infection is easy and far less expensive than liver transplantation or any long term treatment for the other risk factors of HCC. Any confirmation of the involvement of Helicobacter in liver disease would eventually come from the success of culturing the bacterium from liver tissues. Future research is needed to clarify the importance of Helicobacter spp. in respect to the other pathogens already known as causative agents of chronic inflammation of the liver and its long term sequelae, namely cirrhosis and HCC.