Radiation-induced liver disease

Nearly all the experimental and clinical data to date has been using external beam radiation. Furthermore, animal models are not good surrogates for human hepatic radiation response. Whole liver radiation by external beam causes radiation induced liver disease (RILD) in 5%-10% of patients [8-10]. RILD is a clinical syndrome of anicteric hepatomegaly, ascites, and elevated liver enzymes (especially alkaline phosphatase) which occurs usually from 2 weeks up to 90 days post radiation delivery and can lead to permanent, progressive and/or fatal liver dysfunction [11,12]. 

Radiation-induced liver disease [10] typically occurs 4-8 weeks after the end of radiation plan [11]. Patients develop fatigue, weight gain and ascites and blood tests tend to show moderate elevations of transaminases, a substantial rise in alkaline phosphatase and minimal or no increase in bilirubin. After external beam irradiation of primary liver tumors, this complication occurs in 5%-33% of patients [5, 12, 13], and may result in mortality rates as high as 50%, particularly among those patients with chronic liver disease [14]. Risk factors include the dose of radiation [14] and liver function prior to treatment [13]. This picture of anicteric ascites and elevated alkaline phosphatase was not seen among our patients but we observed an unexpected and protracted decline in liver func-... 

Cheng JC, Wu JK, Lee PC et al (2004) Biologic susceptibility of hepatocellular carcinoma patients treated with radiotherapy to radiation-induced liver disease. Int J Radiat Oncol Biol Phys 60 1502-1509... 

Cheng JC, Wu JK, Huang CM et al (2002) Radiation-induced liver disease after three-dimensional conformal radiotherapy for patients with hepatocellular carcinoma dosimetric analysis and implication. Int J Radiat Oncol Biol Phys 54 156-162... 

The most common complications of radioembolization include non-target radiation (pancreatitis, GI ulcers, cholecystitis), radiation pneumonitis, radiation induced liver disease (radiation hepatitis) and biliary complications. 

Fig. 14.1. TIPS placement in a 54-year-old woman who developed radiation induced liver disease. She developed abnormal liver function tests with elevated alkaline phosphatase levels and portal hypertension 1 month following radioembolization of liver metastasis from breast carcinoma...

Another possible area of investigation includes the prophylactic radioemboiization of remnant liver tissue in patients undergoing hepatic resection for HCC or colorectal metastases. Although initially attractive, this approach may hinder and limit the ability for future Y to the prophylactically radio-embolized lobe. Furthermore, the blood supply to small metastases is derived from the portal vein, not the hepatic artery, bringing into question whether prophylactic treatment would yield any radiation effect to microscopic metastases [59]. Therefore, if such a study is undertaken, since imaging of micro-metastases is not possible, improved survival or decreased time to disease recurrence would represent possible endpoints. It is clear that further research is needed to address possible treatment options for advanced stage HCC. Any studies in this patient population require careful consideration of the risk of therapy induced liver failure vs. the benefit of lesion stabilization. 

Regarding liver function, patients who are in general eligible for SIRT, based on the stage of their disease, must be considered able to tolerate the microsphere embolization. This is because SIRT radiation may induce hepatitis, such that pre-existing liver function deterioration may become irreversible loss of liver function. 

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