Radiation-Induced Liver Toxicity

The advent of highly conformal radiation therapy (RT) has defined a new role for RT in the treatment of both primary and metastatic liver cancer. Despite major advances in how RT is delivered, radiation-induced liver disease (RILD) remains a concern. Classic RILD, characterized by anicteric ascites and hepatomegaly, is unlikely to occur if treating to doses of ≤30 Gy in 2 Gy per fraction in patients with baseline Child-Pugh A liver function. On the other hand, nonclassic RILD is a spectrum of liver toxicity, including a general decline in liver function and elevation of liver enzymes. It is less well defined and less predictable, especially in patients with underlying liver disease. Scoring and quantifying RILD remains a challenge. The Child-Pugh score has been the most consistently used parameter. Other scoring systems such as the albumin-bilirubin score provide further discrimination in patients with hepatocellular carcinoma, although their value in patients treated with RT remains to be established. Many serum and imaging biomarkers of liver function are currently being investigated, and they will provide further useful information in the future for local and global liver function assessment, for planning optimization, and for treatment adaptation. To date, no pharmacological therapies have provided consistent results in mitigating RILD once it has manifested clinically. Numerous promising treatment strategies including TGFβ inhibition, Hedgehog inhibition, CXCR4 inhibition, hepatocyte transplantation, and bone marrow-derived stromal cell therapy, have potential to be helpful in the treatment of RILD in the future.