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. 2025 Feb;42(2):1165-1195.
doi: 10.1007/s12325-024-03085-4. Epub 2024 Dec 30.

Understanding MASH: An Examination of Progression and Clinical Outcomes by Disease Severity in the TARGET-NASH Database

Rakesh Luthra  1 , Aarth Sheth  2
Affiliations

Understanding MASH: An Examination of Progression and Clinical Outcomes by Disease Severity in the TARGET-NASH Database

Rakesh Luthra et al. Adv Ther. 2025 Feb.

Abstract

Introduction: Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated steatotic liver disease (MASLD), is linked to cardiometabolic risk factors such as obesity and type 2 diabetes (T2D). The rising prevalence of MASH and risk of hepatic and extra-hepatic complications emphasize the need for a better understanding of disease progression and associated outcomes. This study aimed to evaluate the incidence of, and demographic and clinical characteristics associated with, progression to MASH-related complications by disease severity in patients with non-cirrhotic MASH or MASH cirrhosis. Alignment between noninvasive tests (NITs) and biopsy-determined fibrosis stage was also assessed.

Methods: This analysis used data from the TARGET-NASH cohort that includes adults with MASH across academic and community sites in the United States. Patients with non-cirrhotic MASH or MASH cirrhosis were stratified by disease severity based on fibrosis stage or cirrhosis. Progression to MASH-related outcomes, including all-cause mortality, cirrhosis, and liver transplantation, was assessed.

Results: Among the 2378 patients included in this analysis, 48% had MASH cirrhosis. Incidence of all-cause mortality increased with disease severity from 0.14/100 person-months (100PM) at fibrosis stage 0-1 (F0-F1) to 2.02/100PM with compensated cirrhosis and 4.62/100PM with decompensated cirrhosis. Compared with patients with F0-F1, risk of progression to cirrhosis was higher in patients with F3 [hazard ratio (HR), 95% confidence interval (CI); 18.66, 10.97-31.73] and F2 (HR, 95% CI; 3.74, 2.00-6.98). Among those who progressed to MASH-related outcomes, 67.9% had T2D and 73.9% had hypertension. Vibration-controlled transient elastography showed better alignment with biopsy-determined fibrosis stage than Fibrosis-4 Index (FIB-4).

Conclusions: Progression to all-cause mortality in patients with MASH was significantly associated with the presence of higher fibrosis stage and cirrhosis. Cardiometabolic comorbidities such as T2D and hypertension were prevalent in patients with MASH progression. Early identification and management of MASH may mitigate disease progression and liver-related complications.

Keywords: Cirrhosis; Disease progression; Fibrosis; Metabolic dysfunction-associated steatohepatitis (MASH); Noninvasive test (NIT).

Plain language summary

Metabolic dysfunction-associated steatotic liver disease is a common liver condition linked to metabolic health problems such as obesity and type 2 diabetes. Metabolic dysfunction-associated steatohepatitis (MASH) is a severe form of this condition characterized by liver inflammation and damage that can progress to cirrhosis, or scarring of the liver. Data from the TARGET-NASH cohort were analyzed to understand how MASH progresses and affects people’s health over time as well as the demographic and clinical characteristics of those who experience MASH progression. Patients were divided into groups based on severity of liver damage determined by fibrosis stage or cirrhosis. The study found that people with more severe liver damage (higher stage of fibrosis or cirrhosis) had a higher risk of serious health outcomes such as worsening liver damage, the need for a liver transplant, or death.

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Conflict of interest statement

Declarations. Conflict of Interest: Aarth Sheth, PharmD and Rakesh Luthra, MS are employees of Novo Nordisk Inc. Ethical Approval: This article is based on analyses of previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors. Additional Information: The manuscript uses data collected in TARGET-NASH (NCT02815891).

Figures

Fig. 1
Fig. 1
Incidence rates and cumulative incidence for progression to all-cause mortality among patients with non-cirrhotic MASH and MASH with cirrhosis stratified by disease severity. Incidence rates are reported per 100PM. Forest plots display hazard ratios and the dashed line depicts x = 1. Hazard ratios shown in bold are statistically significant. Cumulative incidence curves are depicted as a function of time in months. Cumulative incidence curves are displayed as follows: F0–F1 dotted pink line, F2 dashed light blue line, F3 solid green line, compensated cirrhosis solid blue line, decompensated cirrhosis solid dark blue line. 100PM 100 person-months, CI confidence interval, F0–F1 fibrosis stage 0 or 1, F2 fibrosis stage 2, F3 fibrosis stage 3, MASH metabolic dysfunction-associated steatohepatitis
Fig. 2
Fig. 2
Incidence rates and cumulative incidence for progression to liver transplantation among patients with non-cirrhotic MASH and MASH with cirrhosis stratified by disease severity. Incidence rates are reported per 100PM. Forest plots display hazard ratios and the dashed line depicts x = 1. Hazard ratios shown in bold are statistically significant. Cumulative incidence curves are displayed as a function of time in months. Cumulative incidence curves are displayed as follows: F0–F1 solid green line, F2 N/A, F3 N/A, compensated cirrhosis solid dark blue line, decompensated cirrhosis solid blue line. 100PM 100 person-months, CI confidence interval, F0–F1 fibrosis stage 0 or 1, F2 fibrosis stage 2, F3 fibrosis stage 3, MASH metabolic dysfunction-associated steatohepatitis
Fig. 3
Fig. 3
Incidence rates and cumulative incidence for progression to cirrhosis among patients with non-cirrhotic MASH stratified by disease severity. Incidence rates are reported per 100PM. Forest plots display hazard ratios and the dashed line depicts x = 1. Hazard ratios shown in bold are statistically significant. Cumulative incidence curves are displayed as a function of time in months. Cumulative incidence curves are displayed as follows: F0–F1 solid green line, F2 solid dark blue line, F3 solid blue line. 100PM 100 person-months, CI confidence interva,l F0–F1 fibrosis stage 0 or 1, F2 fibrosis stage 2, F3 fibrosis stage 3, MASH metabolic dysfunction-associated steatohepatitis
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