Photo Credit: Leonid Eremeychuk

Liver histologic features play a crucial role in forecasting long-term clinical outcomes in patients with MASLD and its inflammatory subtype, MASH.

A real-world study published in Hepatology Communications suggested that liver histologic features play a crucial role in forecasting long-term clinical outcomes in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its inflammatory subtype, metabolic dysfunction-associated steatohepatitis (MASH).

Zobair M. Younossi, MD, MPH, and colleagues conducted an observational cohort study to investigate the correlation between baseline liver histology and long-term hepatic- and cardiovascular-related outcomes. They also examined whether less severe histologic features were associated with a lower risk for adverse outcomes among patients with MASH-like liver histology.

“It is difficult to observe these histology outcomes in the real world through liver biopsies because of the potential risk of complications and cost associated with liver biopsies, leading to their limited usage. The result of this is little direct evidence regarding the association between liver histology and the long-term clinical outcomes in patients with MASH, especially from real-world practice,” Dr. Younossi and colleagues wrote.

The researchers used de-identified EMR data from the Vanderbilt University Medical Center’s Synthetic Derivative database. They gathered information on patients aged 18-89 who were diagnosed with MASLD or MASH between June 1984 and June 2021. There were 43,475 patients with MASLD, of which 5,311 had an available liver biopsy pathology report. Based on random selection, 2,181 biopsy reports were available at the initiation of the study.

“A total of 702 patients with MASH-like histology were therefore included in the analyses of liver-related outcomes; 660 of these individuals—with no history of cardiovascular events—were included in the analysis of cardiovascular-related outcomes and any long-term outcome, and 650 patients (with no evidence of cirrhosis at baseline) were included in the analysis of cirrhosis outcomes,” the researchers reported.

The study team followed patients from their first biopsy until their first clinical event or the last entry in the database if there were no clinical events. The average follow-up was 4.7 years. The researchers assessed the following histological features: fibrosis stage, grade of lobular inflammation, grade of hepatocyte ballooning, and steatosis score.

Findings showed a comparatively lower risk for cirrhosis among patients with lower-grade fibrosis stage (HR, 0.22; 95% CI, 0.12-0.42), lower hepatocyte ballooning (HR, 0.20; 95% CI, 0.08-0.50), and lower lobular inflammation (HR, 0.42; 95% CI, 0.19-0.97). Patients with a lower fibrosis stage also had lower risks for cardiovascular-related and any long-term adverse outcomes.

In addition, lower fibrosis stage was associated with notably lower risks for liver-related outcomes (HR, 0.12; 95% CI, 0.05-0.25), including HCC, liver transplant, and hepatic decompensation. However, the study authors found no differences in risk related to baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores.

Lower lobular inflammation grade correlated with lower risks for adverse liver outcomes in patients who underwent weight loss surgery.

“Because the sample size of patients without weight-loss surgery was limited and the number of events was low, the presence of a potential bias cannot be excluded; therefore, weight loss may still have an effect on long-term outcomes,” Dr. Younossi and colleagues explained. “Nevertheless, it is worth noting that in a previous study, patients with severe MASLD had a greater than 3-fold risk of death following weight-loss surgery, suggesting that the risk of [adverse] outcomes may be associated with MASLD even after weight-loss surgery.”

The authors concluded that their study provides real-world clinical evidence that fibrosis stage can predict adverse outcomes. They also linked lower liver inflammation and hepatocyte ballooning with a lower risk of incident cirrhosis, underscoring the significance of these histologic features in forecasting long-term outcomes in patients with MASH.

“Our findings from real-world practice support existing published tertiary care data on the importance of liver histology in signaling long-term risk of adverse outcomes in people with MASH. We confirm that stage of fibrosis is predictive of adverse outcomes and show that lower liver inflammation and hepatocyte ballooning are associated with a lower risk of incident cirrhosis, highlighting the relevance of these histologic features in predicting long-term outcomes,” Dr. Younossi and colleagues concluded.