Appeal type: Medical necessity
Decision: Overturned

Diagnosis: Breast cancer
Treatment: Inpatient Hospital Admission
The insurer denied: Inpatient Hospital Admission
The denial is overturned.

The patient is an adult female with breast cancer on Keytruda with development of elevation in liver function tests (LFTs) and jaundice. She presented to the emergency room with a bilirubin of 9.5 and weakness. Ultrasound showed concern for possible cholelithiasis. The patient was admitted. Surgery evaluated the patient and felt that this was not a surgical issue. The patient underwent hepatobiliary iminodiacetic acid (HIDA) scans and was placed on N-acetylcysteine. A magnetic resonance cholangiopancreatography (MRCP) was also performed. The patient underwent a liver biopsy. She was eventually started on steroids and was then discharged.

The proposed treatment was medically necessary.


In patients with grade 3 or 4 immune checkpoint inhibitor (ICI) hepatotoxicity who present with a predominantly hepatocellular pattern of liver injury and no other identifiable cause, immune checkpoint inhibitor therapy is held, other hepatotoxic medications are discontinued, and glucocorticoids should be initiated. Patients should also be referred to a hepatologist or gastroenterologist with expertise in immune checkpoint inhibitor (ICI) hepatitis. Select patients with an atypical presentation (e.g., cholestatic pattern of injury without a clear etiology) may be evaluated for possible liver biopsy.
The American Society of Clinical Oncology (ASCO) guidelines recommend methylprednisolone at a daily dose ranging between 1 to 2 milligrams per kilogram (mg/kg). Limited data suggest that a higher dose of 2 milligrams per kilogram does not reduce the likelihood of developing steroid refractory hepatotoxicity, does not shorten the time to resolution of hepatotoxicity, and is associated with a higher risk of steroid-related complications, when compared with the lower 1 milligram per kilogram dose.
Liver tests and a basic metabolic panel with serum glucose should be monitored every one to two days in patients with grade 3 hepatotoxicity, and daily in patients with grade 4 hepatotoxicity. 
Close inpatient monitoring has been recommended by the American Society of Clinical Oncology for patients with an aspartate aminotransferase (AST) / alanine aminotransferase (ALT) greater than 8 times the upper limit of normal (ULN) and/or a total bilirubin greater than 3 times the upper normal limit.
In patients who exhibit a biochemical response to glucocorticoids with a reduction in liver tests to grade 1 or lower, the dose of methylprednisolone can be converted to an equivalent dose of oral glucocorticoid such as prednisone, which can then be tapered (generally by 10 to 20 milligrams weekly over six to ten weeks, although the optimal tapering duration is unclear). 
Glucocorticoids can be re-escalated if liver function tests worsen during the tapering period. This patient had grade 4 hepatotoxicity with a bilirubin of 9.5, elevated aspartate aminotransferase (AST) / alanine aminotransferase (ALT), jaundice and weakness. As per the American Society of Clinical Oncology, this patient would require admission for monitoring and management of grade 3/4 hepatoxicity from immuno-oncology (I/O) therapy. Per the American Society of Clinical Oncology, for grade 3/4, "consider inpatient monitoring for patients with AST/ALT > 8 x ULN and/or elevated bilirubin 3 x > ULN". As this patient's bilirubin was greater than 3 times the upper limit of normal (ULN), and she was symptomatic, inpatient level of care was medically necessary. In addition, the American Society of Clinical Oncology recommends "Labs daily or every other day". The level of monitoring / testing / treatment this patient required met medical necessity for inpatient level of care.