NATURAL HISTORY MODELING OF ALL-CAUSE DECOMPENSATED CIRRHOSIS: LONG-TERM CLINICAL AND ECONOMIC BURDEN AND CONSIDERATIONS FOR FUTURE ECONOMIC EVALUATIONS
Author(s)
Lindsey Fox, PhD1, Megan Kathryn Schroeder, MSc2, William L. Herring, PhD1, Carl Haakon Samuelsen, MPhil3, Nikolas Goyert-Stephens, MA3.
1RTI Health Solutions, Durham, NC, USA, 2Boehringer Ingelheim, Dresden, Germany, 3Boehringer Ingelheim International GmbH, Ingelheim, Germany.
1RTI Health Solutions, Durham, NC, USA, 2Boehringer Ingelheim, Dresden, Germany, 3Boehringer Ingelheim International GmbH, Ingelheim, Germany.
OBJECTIVES: Decompensated cirrhosis (dF4) is a progressive condition characterized by recurrent liver-related events, high mortality, and potential need for liver transplant (LT). Evaluating emerging therapies requires a framework reflecting dF4 natural history, including event types, prior events, and downstream complications. We developed a model to characterize the long-term clinical and economic burden of all-cause dF4 and inform future economic evaluations.
METHODS: A Markov-based model included health states for non-acute dF4 (stratified by prior dF4 event count), hepatocellular carcinoma (HCC), LT, and death. An embedded decision tree captured acute dF4 events (ascites, variceal hemorrhage, hepatic encephalopathy, bacterial infection), acute-on-chronic liver failure (ACLF), and event-related mortality. Transition probabilities were derived from an Optum Market Clarity claims analysis; other inputs came from the literature. The base-case population comprised adults with 1 prior dF4 event. Outcomes included survival, number of events, quality-adjusted life-years (QALYs), and disease-related costs per patient over a lifetime time horizon.
RESULTS: Predicted overall survival (undiscounted) was 4.38 years, with 1.31 years spent in states with ≥2 prior dF4 events and 0.93 years in advanced disease (HCC, LT). Patients experienced a mean of 1.67 dF4 (0.74 ascites, 0.47 variceal hemorrhage, 0.34 hepatic encephalopathy, 0.13 bacterial infection), 1.35 ACLF, and 0.06 LT events over their remaining lifetime. Total lifetime discounted (3.0% annually) QALYs and disease-related costs were 2.10 and $353,814, respectively. Scenario analyses confirmed sensitivity of outcomes to population characteristics, event rates, and LT probabilities.
CONCLUSIONS: To our knowledge, this is the first model comprehensively capturing all-cause dF4 natural history by event types, prior event history, and advanced disease. Our results reflect the lifetime burden of dF4 and highlight uncertainty in the contribution of LT outcomes (i.e., facilitating access versus helping avoid) to the value of potential treatments for dF4. Other key uncertainties, including the role of etiology and data gaps, warrant further research.
METHODS: A Markov-based model included health states for non-acute dF4 (stratified by prior dF4 event count), hepatocellular carcinoma (HCC), LT, and death. An embedded decision tree captured acute dF4 events (ascites, variceal hemorrhage, hepatic encephalopathy, bacterial infection), acute-on-chronic liver failure (ACLF), and event-related mortality. Transition probabilities were derived from an Optum Market Clarity claims analysis; other inputs came from the literature. The base-case population comprised adults with 1 prior dF4 event. Outcomes included survival, number of events, quality-adjusted life-years (QALYs), and disease-related costs per patient over a lifetime time horizon.
RESULTS: Predicted overall survival (undiscounted) was 4.38 years, with 1.31 years spent in states with ≥2 prior dF4 events and 0.93 years in advanced disease (HCC, LT). Patients experienced a mean of 1.67 dF4 (0.74 ascites, 0.47 variceal hemorrhage, 0.34 hepatic encephalopathy, 0.13 bacterial infection), 1.35 ACLF, and 0.06 LT events over their remaining lifetime. Total lifetime discounted (3.0% annually) QALYs and disease-related costs were 2.10 and $353,814, respectively. Scenario analyses confirmed sensitivity of outcomes to population characteristics, event rates, and LT probabilities.
CONCLUSIONS: To our knowledge, this is the first model comprehensively capturing all-cause dF4 natural history by event types, prior event history, and advanced disease. Our results reflect the lifetime burden of dF4 and highlight uncertainty in the contribution of LT outcomes (i.e., facilitating access versus helping avoid) to the value of potential treatments for dF4. Other key uncertainties, including the role of etiology and data gaps, warrant further research.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
EE629
Topic
Economic Evaluation
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)