(046) Associations between Laboratory Results and Mortality in Patients with Metabolic Dysfunction-Associated Steatohepatitis (MASH) by Diabetes and Antihypertensive Drug Status.

Background: MASH causes cirrhosis, cancer, and mortality with unclear mechanisms. Diabetes (DM) and hypertension (HTN) are coexisting conditions requiring complex drug patterns and monitoring.

Objectives: Describe associations between laboratory-based predictors and mortality among MASH patients, by DM and antihypertensive (anti-HTN) drug status.

Methods: Cohort study using electronic health records from the University of California, San Francisco (UCSF), linked to the California statewide death registry. Patients aged ≥18, with type 2 DM and/or HTN, receiving care at UCSF from 1/1/2012 to 1/1/2023 were included at diagnosis of MASH (baseline). MASH diagnoses were identified using rule-based natural language processing of clinical notes.
Patient characteristics, including demographics, comorbidities, laboratory results (including albumin, bilirubin, creatinine, and hemoglobin A1c (HbA1c) levels extracted from blood tests), and medications, were extracted from structured data from the year preceding MASH diagnosis. DM and anti-HTN drug status was determined by the number of different pharmacological drug classes. Cox proportional hazard models with bidirectional stepwise variable selection were employed to predict hazard ratios of death associated with baseline laboratory results, adjusting for patient characteristics.

Results: We identified 1869 MASH patients (52.7% women, 47.3% men) with a mean age of 57.5 years (SD 12.3). Of these, 59.8% had type 2 DM and 89.2% had HTN.
Elevated levels of alkaline phosphatase (ALP) blood level (Hazard ratio (HR) 1.99, 95% confidence interval (95%CI) [1.60 – 2.45]), low platelet count (HR 1.62, (95%CI) [1.21 – 2.17]) and elevated bilirubin (HR 1.53 [1,17 – 2.02]) were associated with an increased mortality. Conversely, although non significant elevated levels of thyroid hormones were associated with lower mortality (0.69 [0.36 – 1.33]).
Associations varied by drug status. In patients without DM and or HTN drug, elevated bilirubin (HR 2.01 [1.12 – 3.60]), ALP (HR 1.85 [1.23 – 2.81]) and LDL cholesterol (HR 1.58 [1.08 – 2.31]) were associated with mortality. In patients with 1 DM and/or HTN drug elevated ALK (HR 2.85 [1.70 – 4.76]), LDL cholesterol (HR 1.72 [1.03 – 2.89]) were associated with increase mortality while elevated triglycerides were associated with lower mortality (HR 0.31 [0.17 - 0.57]). In patients with ≥ 2 DM and/or HTN, elevated ALK (HR 2.42 [1.65 - 3.53], bilirubin (HR 1.90 [1.26 - 2.89]), low platelets (HR 1.57 [1.02 - 2.42]).

Conclusions: High ALK, bilirubin, LDL cholesterol, low platelets, and albumin levels were linked to higher mortality. Conversely, high thyroid hormones and hemoglobin A1c showed a non-significant trend towards lower mortality. These associations differed by medication status. Understanding these associations can enhance comprenhension of MASH and lead to hypothesis for intervention.