Radiation-Induced Liver Toxicity.

Area of Science:

• Hepatology
• Radiation Oncology
• Biomarkers

Background:

• Highly conformal radiation therapy (RT) is increasingly used for liver cancer, but radiation-induced liver disease (RILD) remains a significant concern.
• Classic RILD is rare with RT doses ≤30Gy in patients with Child-Pugh A liver function, but nonclassic RILD presents as a spectrum of liver dysfunction.
• Accurate scoring and quantification of RILD are challenging, with Child-Pugh score being a common parameter, and albumin-bilirubin score showing potential for hepatocellular carcinoma.

Purpose of the Study:

• To review the current understanding of radiation-induced liver disease (RILD) in liver cancer treatment.
• To discuss the challenges in scoring and quantifying RILD.
• To explore emerging biomarkers and potential therapeutic strategies for managing RILD.

Main Methods:

• Literature review of radiation therapy techniques, RILD classification, and current assessment methods.
• Analysis of existing scoring systems like Child-Pugh and albumin-bilirubin scores.
• Overview of ongoing research into novel biomarkers and pharmacological/cellular therapies for RILD.

Main Results:

• RT doses ≤30Gy in 2Gy fractions are unlikely to cause classic RILD in Child-Pugh A patients.
• Nonclassic RILD involves a broader range of liver toxicities and is less predictable, especially in patients with pre-existing liver conditions.
• No current pharmacological therapies consistently mitigate RILD once clinically manifested.

Conclusions:

• While classic RILD is manageable with dose constraints, nonclassic RILD requires further investigation for better prediction and management.
• Serum and imaging biomarkers are under development to improve liver function assessment for RT planning and adaptation.
• Future RILD treatment may involve targeted therapies such as TGFβ inhibition, Hedgehog inhibition, CXCR4 inhibition, and cell-based therapies.