Steatosis in Cirrhosis: A Prognostic Marker for Liver‐Related Outcomes in Metabolic‐Dysfunction Associated Steatotic Liver Disease

BACKGROUND AND AIMS: The predictive ability of histological components in Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) has not been well studied. Here, we look at the ability of digital pathology through the components of qFIBs (qfibrosis, qInflammation, qBallooning, qSteatosis) in predicting the risk of Major Adverse Liver Outcomes (MALO). METHOD: 235 liver biopsy images were retrieved, and the composite end point of MALO, including overall death, hepatic encephalopathy (HE), ascites, variceal haemorrhage and hepatocellular carcinoma (HCC), was studied in parallel with the Non-alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) score and qFIBs. RESULTS: The predictive power of qFibrosis for MALOs (qF3/4 vs. qF0/1/2, HR 6.64, 95% CI 1.69-26.06, log rank p-value 0.001) was comparable to NASH-CRN (F3/4 vs. F0/1/2, HR 7.02, 95% CI 2.37-20.84, log rank p-value < 0.001). Interestingly, a lower steatosis grade, rather than being a protective factor, correlated with poorer outcomes for both the qFIBs (qS0/1 vs. qS2/3 HR 17.24, 95% CI 3.12-95.32, log rank p value < 0.001) and NASH-CRN (S0/1 vs. S2/3 HR 6.30, 95% CI 2.14-18.61, log rank p value < 0.001). Lower qSteatosis scores of qS1 and below among the cirrhotic group (n = 35) also showed a six-fold higher risk of MALOs (< 1.50 vs. ≥ 1.50, HR 6.40, 95% CI 1.08-37.92, log rank p value < 0.011), likely due to the reduction of steatosis in the cachectic state of a patient with end stage liver disease. Samples with lower percentages of macro-vesicular vacuoles had a fourfold increased risk of MALOs (HR 4.41, 95% CI 1.06-18.43, log rank p value 0.017). CONCLUSION: Lower steatosis grades in higher fibrosis stages correlate significantly with the occurrence of MALO. Our findings instigate exploration of the process of fat resorption in MASLD and its relation to outcomes.