Effects of systemic chemotherapy on the liver

Abstract

The liver is the largest parenchymatous organ of the body and central for intermediate metabolism. Its close contact to the portal blood streaming back from the gut and the systemic circulation is a prerequisite for the various processes ongoing on cellular level. The spatial relationship of the hepatocytes with the different cellular structures of the liver, such as fenestrated sinusoidal endothelial cells, Kupffer cells, and bile canaliculi is important for the organization and performance of the intermediate metabolism of nutrients (proteins, glucose and fatty acids), for the clearance of toxic or infectious agents, for metabolic detoxification and for the excretion of waste products. The administration of chemotherapy is a challenge for the tight regulation and balance of these processes. As most drugs tend to be lipophilic, they are readily taken up by the liver. Under chemotherapy, up to 85% of patients develop liver steatosis. Steatohepatitis is the more serious event, especially if accompanied by an increase in bilirubin levels. Modern understanding of the efficacy, safety and tolerability of combination chemotherapy has to increasingly include the individual context of a patient, such as age, gender, nutritional status, underlying diseases, genetic predisposition, as well as the cross-reactivity of the different drugs. This review tries to capture the various effects of chemotherapy on the liver, with a focus on chemotherapeutical compounds used for the treatment of gastrointestinal cancers.