Liver histology is associated with long-term clinical outcomes in patients with metabolic dysfunction–associated steatohepatitis

Background: Few studies have examined the risk of long-term clinical outcomes in patients with metabolic dysfunction–associated steatohepatitis in relation to liver histology. We aimed to study this using a real-world cohort. Methods: Adults (N = 702) recorded on Vanderbilt University Medical Center’s Synthetic Derivative database (1984–2021) with evidence of metabolic dysfunction–associated steatohepatitis on liver biopsy were followed from the first biopsy until the first clinical event or last database entry (median: 4.7 y). Risks of cirrhosis (N = 650), other noncirrhotic liver-related (N = 702) and cardiovascular-related outcomes (N = 660), and mortality due to liver, cardiovascular, or cancer events (N = 660) were determined as a function of baseline histology (fibrosis stage F, lobular inflammation grade LI, hepatocyte ballooning grade HB, and steatosis score) adjusting for sex, age, diabetes, and weight-loss surgery. Results: Cirrhosis risk was reduced for lower versus higher fibrosis stage (HR: F0–1 vs. F3: 0.22 95% CI: 0.12–0.42), LI1 versus LI2–3 (0.42 0.19–0.97), and HB1 versus HB2 (0.20 0.08–0.50). Lower fibrosis stage was associated with significantly lower risks of liver-related outcomes versus F4 cirrhosis (eg, F0–1: 0.12 0.05–0.25), whereas no differences were seen across baseline lobular inflammation, hepatocyte ballooning, and steatosis grades/scores. Lower versus higher lobular inflammation grade was associated with lower risks for liver-related outcomes in patients with weight-loss surgery. There was a trend for lower risks for cardiovascular-related and any long-term outcomes with lower versus higher fibrosis stage. Conclusions: Fibrosis stage and lobular inflammation and hepatocyte ballooning grades predict the risk of long-term outcomes, supporting the use of these histological features as potential surrogate markers of disease progression or clinical outcomes.