Higher Spleen-to-Liver Stiffness Ratio in MASH May Signal Portal Hypertension

Individuals with metabolic dysfunction–associated steatohepatitis (MASH) have a distinctly higher spleen-to-liver stiffness ratio than peers with alcohol-related liver disease (ALD), according to a prospective study published in Liver International.¹

According to the authors, this study of nearly 400 adults with compensated chronic liver disease reinforces the idea that portal hypertension (PH) in MASH often includes a presinusoidal component that traditional hemodynamic testing may miss.

To come to these findings, researchers at the Medical University of Vienna enrolled 399 consecutive patients who underwent same-day hepatic venous pressure gradient (HVPG) measurement and 2D shear-wave elastography (SWE) of the liver and spleen, looking at the ratio of liver stiffness measurement (LSM) to spleen stiffness measurement (SSM). The study included 200 patients with ALD, 49 with MASH, 59 with viral liver disease, and 18 with portal sinusoidal vascular disease.

Although patients with ALD in this cohort had higher LSM and HVPG values than those with MASH, their spleen stiffness was not significantly different. SSM values were similar between the MASH and ALD groups, but LSM was lower in patients with MASH. This yielded a higher median SSM/LSM ratio in MASH (1.66) than ALD (1.28), which remained significant even after adjusting for differences in disease severity.

At equivalent HVPG levels—particularly above 12 mm Hg, when variceal bleeding risk becomes clinically relevant—researchers found that patients with MASH consistently showed higher SSM than those with ALD. According to the authors, this finding supports the notion that MASH involves hemodynamic stress in the presinusoidal vascular bed, which HVPG alone does not adequately reflect.

Effects of Size and Stiffness

In terms of spleen size, both groups had comparable diameters—13.1 cm in the ALD group and 13.6 cm in the MASH group. Once adjusted for HVPG, though, patients with MASH exhibited larger spleen diameters per mm Hg of HVPG (1.15) than those with ALD (0.85). The authors suggested this pattern provides further evidence of a presinusoidal contribution to PH in MASH.

“This study demonstrates that SSM/LSM ratios vary across different liver disease aetiologies,” the authors said. “Since MASH patients—after adjusting for liver disease severity—show higher SSM/LSM ratios and larger spleen diameters than ALD, our results support the concept of a presinusoidal component of PH in MASH patients.”

When correlation patterns were assessed, 2D-SWE-LSM showed a moderate correlation with HVPG in MASH, while 2D-SWE-SSM demonstrated a fair-to-moderate correlation. The SSM/LSM ratio, however, was inversely correlated with HVPG in both groups, highlighting its distinct diagnostic role. Even after accounting for body mass index, diabetes, statin use, and arterial hypertension, MASH remained independently associated with a higher SSM/LSM ratio compared with ALD.

“This finding suggests that the elevated ratio in MASH is not merely a reflection of its associated comorbidities but rather stems from intrinsic pathophysiological alterations unique to the disease,” the authors said.

Liver-Related Complications

The study also observed an early prognostic signal: among patients with MASH, those with higher SSM/LSM ratios experienced more liver-related complications. Within 1 year, 18% of patients with ratios above the median experienced decompensation or liver-related death compared with 5% of those below the median. This trend did not reach statistical significance due to the small sample size (P = .67).

“While this relevant observation was only a nonsignificant trend, it represents the first evidence for the prognostic utility of the SSM/LSM ratio as a novel, noninvasive biomarker in MASH patients,” the authors said. “Larger, prospective studies are warranted to definitively establish the SSM/LSM ratio as a tool for clinical risk stratification in patients with MASH.”

The authors acknowledged several limitations, including the relatively small number of patients with MASH and the absence of direct portal pressure measurements, which are rarely performed in routine clinical care. Still, they emphasized that the consistency of the findings across spleen stiffness, spleen diameter, and the SSM/LSM ratio strengthens the evidence for a presinusoidal mechanism in MASH.

These findings come at a time when nearly 40% of the world population lives with fatty liver disease.² In the US alone, experts project more than 122 million adults will be living with metabolic dysfunction–associated steatotic liver disease by 2050. This rise in cases will be joined by increased liver cancer cases and deaths, among other complications, reinforcing the need for early identification and effective intervention.

References

1. Sebesta C, Jachs M, Hartl L, et al. Diagnostic and clinical implications of high spleen-to-liver stiffness ratio in MASH—a prospective, comparative study. Liver Int. 2025;45(10):e70261. doi:10.1111/liv.70261
2. Klein HE. Alarming rise in liver disease amid global fatty liver day 2025. AJMC^®. June 12, 2025. Accessed September 23, 2025. https://www.ajmc.com/view/alarming-rise-in-liver-disease-amid-global-fatty-liver-day-2025