Radiation Induced Liver Injury - A Case Report

Introduction

Radiation oncology has evolved over time. Today it is more precise and conformal. Classical liver injury is uncommon manifesting as severe acute liver failure. It results from hepatocellular injury due to radiation. The non-classical focal liver injury is confused with tumor progression or metastasis. Radiological appearance as a focal hypoattenuating circumscribed region, the straight edge sign can prevent this confusion and unwarranted invasive biopsies.

Case Presentation

A 42-year female, a case of invasive ductal carcinoma of the right breast, grade 2 ER/PR and Her2neu positive with axillary and pectoral lymph nodal involvement was treated with adjuvant chemotherapy.

Post chemotherapy, there was significant metabolic regression of the primary mass and the involved lymph nodes which were prior PET active with high SUV. Subsequently the patient underwent modified radical mastectomy and lymph nodal dissection. Patient received radiation to the tumor bed, 40 GY in 15 fractions for three weeks with IG-3D CRT. Patient was put on tablet Tamoxifen 20 mg once a day and was followed by an oncologist. During the surveillance ultrasound examination of the abdomen, the sonologist reported an altered area of echogenicity in the liver. In view of concern for metastasis, this was followed by PET CT.

A subcapsular hypoattenuating lesion was reported and referred to the radiology team for further work up and biopsy consideration. MRI of the liver was done which showed an altered signal area with increased diffusion in the right lobe. This was also T1 hypointense T2 hyperintense with no significant enhancement (Figure 1 and 2).

Rest of the liver appeared normal. Patient’s CBC and liver enzymes were in normal range. There was no abdominal discomfort reported and the abdomen was soft on palpation. The classical straight edge sign demarcation was noted on the MRI as well as on the PET CT. Diagnosis of focal liver injury post radiation was made. Patient is being followed up closely and continues to be asymptomatic.

Discussion

Radiation induced liver injury is a form of hepatocellular injury due to radiation.¹ Focal liver injury is also described as a non-classical form of liver injury as it involves only a focal area of liver damage. Unlike classical radiation induced liver injury that occurs when the liver threshold of 30 gy is exceeded presenting with severe hepatic failure, the non-classical form could have mild to severe presentation depending on liver reserve.² Radiation induced liver injury as noted above could be Classical and segmental or Non-classical type. The classical type usually happens 1-3 months after radiation treatment, presents with fatigue, increasing abdominal girth due to ascites. It is usually anicteric type with classical elevation of alkaline phosphatase (ALP) to more than two-fold.

Histopathology reveals a pattern of veno occlusive changes. Erythrocytes trapped in reticulin are noted obliterating the central venous lumina leading to central hepatocyte congestion and cellular injury.³ Secondary fibrotic changes are seen with functional parenchymal loss. The focal involvement which is now more common results due to hepatocyte damage in few segments of the liver. This may go unnoticed; however can manifest as abdominal discomfort and elevation of liver enzymes. In poor hepatic reserve, such as in those with cirrhosis and hepatitis B infection can present with liver decompensation.

On CT imaging, the irradiated areas appear as focal hypoattenuating regions conforming to the radiation ports. In the acute phase of PET CT, these areas can show increased activity and can be confused with metastasis or disease progression. On MRI, the involved areas show T2 hyperintensity due to hepatocellular swelling and edema. These changes can be easily confused for pseudoprogression or metastasis.

In a study conducted involving 205 patients undergoing chemo radiotherapy for esophageal cancer, eight patients developed localized radiation induced liver injury in the caudate and adjacent lobes mimicking metastasis during restaging and therapeutic response assessment.⁴ The observed incidence was three percent. Concurrent chemotherapy can be additive in liver injury. Radiotherapy is known to have immunosuppressive effects.⁵

This mechanism has been potentially suspected for reactivation of hepatitis B virus in patients treated with liver-directed radiotherapy for Hepatocellular carcinoma (HCC). Hepatitis B DNA titers should be monitored preand post therapy.

Prevention of liver injury can be achieved by identifying any risk factors for liver decompensation. Using advanced techniques for precise dose delivery, preventing dose spill over and reducing the total liver dose can help in reducing radiation induced liver damage. Various monitoring criteria exist. These include the Child-Pugh score, model for end-stage liver disease (MELD), CLIP, GRETECH albumin-bilirubin (ALBI), protein induced by vitamin K absence (PIVKA) and albumin scores.

Conclusion

In the present era, the classical liver injury which manifests as severe liver failure is rare. Non-classical focal liver injury is more common which can be identified by its radiological appearance and more benign outcome. It should not be confused with metastasis. Applying dose constraints and reducing the dose to the non-target tissues can be preventative, reducing the incidence and severity.

Financial Support

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Conflict of Interest

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