Hepatocellular carcinoma in alcoholic liver disease: mechanistic considerations and clinical facts

摘要

Alcoholic hepatocellular carcinoma(AHCC)represents a lethal stage,emerging in the course of severe injurious stages of alcoholic liver disease including cirrhosis.AHCC only affects a few alcohol consumers,certainly not all individuals who consume large amounts of alcohol over a long period of time,suggesting a role of yet unknown genetic risk or protection factors.Most likely,hepatic DNA is ultimately involved,attacked by intermediate products derived from reactive oxygen species(ROS)generated from cytochrome P4502E1 of the NADPH and oxygen dependent microsomal ethanol-oxidizing system whereby ethanol is metabolized.Ethanol and acetaldehyde are activated to procarcinogens,to be promoted to ultimate carcinogens by ROS and causatives for AHCC instead of any other putative chemical contained in alcoholic beverages.Prevention of HCC associated with cirrhosis is best accomplished by early recognition of alcohol abuse at the stage of alcoholic fatty liver rather than alcoholic hepatitis(AH)or alcoholic steatohepatitis(ASH),leading to the advice of consequent abstinence from alcohol.Abstinence early started effectively prevents AHCC development,as opposed to late begin of abstinence that lacks risk reduction.Although drug therapy may partially be effective in AH or ASH,no established drug options are available for a realistic therapy of AHCC.Liver transplantation is controversially discussed and can be considered,but may be an option for only a few patients on a case by case base.In conclusion,AHCC results from a ROS dependent conversion of ethanol and acetaldehyde to procarcinogens as promoters of AHCC.