Taking Aim at the Shotgun Approach: Tiered vs Non-tiered Evaluation of Inpatients with Acute Liver Injury

From the 2022 HVPA National Conference

Thejas Kamath MD (Department of Medicine, University of California San Diego), Shravan Dave MD, Greg Seymann MD


Bundled, non-directed blood testing (sometimes referred to as the “shotgun approach”) is a common strategy for the evaluation of patients hospitalized with undifferentiated acute liver injury (ALI). Non-directed testing fails to account for clinical presentations, pre-test likelihoods, and healthcare costs. The few studies which have examined this concern recommend a tiered approach—testing for rare diseases only after more common etiologies have been investigated. There has been no significant quality improvement initiative at our institution to evaluate the cost, efficacy, and impact of extensive testing of undifferentiated ALI.


To evaluate testing patterns for inpatients with undifferentiated ALI, specifically to quantify how often a non-tiered approach was taken.


We used Epic Systems’ SlicerDicer self-service reporting tool to evaluate adult patients hospitalized between January 1 and December 31, 2020 with a diagnosis of “acute and subacute hepatic failure” as defined by ICD-10 codes K72.01 or K72.00. We excluded patients with clinically suspected acute liver failure, patients being worked up for liver transplant, and patients with any history of chronic liver disease or biliary pathology. We defined a tiered approach as viral hepatitis studies, ultrasound, and acetaminophen level (first-tier studies) ordered prior to additional studies (second-tier studies). We used descriptive statistics to characterize testing patterns.


74 patients met inclusion criteria, 37 patients in the tiered approach group and 37 patients in the non-tiered approach group (50% non-tiered approach). Among second tier studies, autoimmune hepatitis serologies, A1AT, ceruloplasmin, AMA, and ferritin were obtained in at least 40% of cases. The Hepatology consult service most frequently requested second-tier studies in non-tiered approaches (45.9%), followed by Hospital Medicine (29.7%). Among all patients, the most common etiologies included DILI (36.5%), ischemic/congestive hepatitis (16.2%), and biliary causes (14.9%). There were four total cases (5.4%) of autoimmune hepatitis, and there were no cases of Wilson disease, hemochromatosis, A1AT deficiency, or PBC. Among tiered approaches, 96.9% of cases were among first-tier diagnoses, with only one additional case of a second-tier diagnosis (autoimmune hepatitis). A non-tiered approach resulted in first-tier diagnoses in 90.1% of cases, with the only type of second-tier diagnosis yielded being autoimmune hepatitis.


We find a non-tiered or “shotgun” approach to ALI to be as common as a tiered approach at our institution, utilized most frequently on the Hepatology and Hospital Medicine services. The distribution of our most common etiologies is consistent with known epidemiological data. Given the rarity with which second-tier diagnoses were identified, there is a significant opportunity for laboratory cost savings at an institutional level. The delay to a second-tier diagnosis introduced by first-tier studies would be at maximum one day at our institution, which would be unlikely to impact a patient’s clinical course. We support a tiered approach and find limited value in a non-tiered work-up.

Clinical Implications

Our study identifies opportunities for quality improvement in laboratory stewardship in the work-up of undifferentiated ALI in the inpatient setting. An appropriate next step would be the creation of a clinical decision-support system.

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