Review Finds Poor Outcomes, Limited Predictive Tools in MASH Cirrhosis

A new systematic review published in Liver International is underscoring the growing clinical burden of metabolic dysfunction-associated steatohepatitis (MASH) with cirrhosis, revealing poor survival outcomes, high complication rates, and limited evidence to guide risk prediction and management.¹

Despite its rising prevalence, increasing by 106% globally between 1990 and 2017,² treatment options for patients with cirrhosis due to MASH remain limited. To better understand the clinical landscape, researchers conducted a systematic literature review of studies published between 2014 and 2024, analyzing outcomes in patients with MASH-related cirrhosis. The review ultimately included 317 observational and interventional studies, with 74 providing data on clinical outcomes and non-invasive testing (NITs). The researchers noted that their search did not include the terms MASLD or non-alcohol fatty liver disease.

The findings paint a concerning picture of disease progression and survival. Across multiple studies, transplant-free survival rates were generally low and highly dependent on patient characteristics. For example, in one cohort of patients hospitalized with ascites, transplant-free survival at 5 years was 27.2%, highlighting the severe prognosis once complications develop.

Despite these significant risks, the review found limited and inconsistent data on tools to predict clinical outcomes. Non-invasive tests, such as the fibrosis-4 index (FIB-4), enhanced liver fibrosis test, and vibration-controlled transient elastography (VCTE), showed only modest accuracy in predicting liver-related events.

For example, most NITs demonstrated only poor-to-moderate predictive ability, with area under the curve (AUC) values generally below 0.70 in some analyses. While certain measures, such as liver stiffness thresholds using VCTE, showed stronger associations with outcomes, variability across studies limited their clinical applicability.

More advanced models, such as the ABIDE score that incorporates laboratory values and clinical features, demonstrated improved predictive performance, with AUC values approaching 0.80. However, these models remain under-validated and are not yet widely adopted in clinical practice.

The study also highlighted significant evidence gaps. Few studies reported long-term survival outcomes, and definitions of key events such as decompensation varied widely, making comparisons difficult. Data on the relative performance of different predictive tools were particularly sparse.

Across the studies, type 2 diabetes (T2D) emerged as a particularly important driver of outcomes. In a multinational study of patients with compensated cirrhosis, 10-year transplant-free survival was dramatically lower in those with T2D compared with those without (38% vs. 81%). T2D was also consistently associated with increased risk of mortality, disease progression, and complications, underscoring its role as a key comorbidity in this population.

“Survival in patients with MASH improved after liver transplant and was reported as ≥70% at 5years across different countries,” wrote the researchers. “However, it is difficult to ascertain the impact of MASH per se on post-transplant survival because the intervention is influenced by the complexity of pre- and post- operative factors that are often independent of the baseline liver disease.”

The risk of liver decompensation, defined by events such as ascites, variceal bleeding, and hepatic encephalopathy, was also substantial. In one study, 27% of patients with compensated cirrhosis experienced a decompensation event over a median follow-up of approximately 5 years. Ascites was the most common initial complication, followed by variceal bleeding and encephalopathy.

T2D again played a central role. Patients with diabetes had significantly higher rates of decompensation, with a 10-year cumulative incidence of 51% compared with 26% in those without diabetes. Additional predictors included the presence of esophageal varices, elevated bilirubin levels, and markers of liver dysfunction such as an increased international normalized ratio.

The development of hepatocellular carcinoma represented another major concern, with annual incidence rates at around 1.9 cases per 100 person-years across studies, with higher risks observed in men, older patients, and those with more advanced liver disease. In patients with T2D, the risk of developing HCC was more than 4 times higher than in those without diabetes, further highlighting the compounding impact of metabolic disease.

References

1. Hagström H, Hellmund C, Lazarus JV, et al. Clinical outcomes and non-invasive testing in metabolic dysfunction-associated steatohepatitis with cirrhosis: a systematic review. Liv Int. Published online March 28.,2026. doi:10.1111/liv.70608D

2. Zhai M, Liu Z, Long J, et al. The incidence trends of liver cirrhosis caused by nonalcoholic steatohepatitis via the GBD study 2017. Sci Rep. 2021;11:5195. doi:10.1038/s41598-021-84577-z