Beyond fibrosis: The imperative for dual steatosis and fibrosis assessment in chronic hepatitis B and metabolic dysfunction-associated steatotic liver disease co-pathology

Abstract

We read with great interest the article by Dai et al recently published in World Journal of Hepatology. The authors developed a novel nomogram incorporating L59, platelet count (PLT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) that demonstrates impressive discriminative performance (area under the curve 0.921-0.959) for predicting evident histological liver injury in patients with chronic hepatitis B (CHB). This model represents a meaningful advance in non-invasive risk stratification and holds promise for optimizing clinical decision-making and resource allocation. Particularly noteworthy is the inclusion of L59, a degradation product of the latency-associated peptide (LAP) of transforming growth factor-β (TGF-β). As highlighted in foundational studies, L59 reflects in vivo TGF-β activation-a central driver of hepatic stellate cell activation and collagen deposition. Its elevation in blood correlates with early fibrogenic activity, providing insight into ongoing fibrosis that may not be captured by static markers. Concurrently, ALT and AST serve as well-established surrogates for hepatocellular inflammation and necroinjury, while thrombocytopenia (low PLT) mirrors portal hypertension and advancing architectural distortion. Together, these markers account for the two fundamental disease-driving processes of CHB progression: Inflammation-driven injury and fibrosis-mediated scarring. This commentary discusses the conceptual advance represented by the L59-based model while highlighting practical limitations related to assay availability, cost, and standardization that currently restrict its routine clinical implementation. Using the Dai et al model as a framework, we further argue that non-invasive evaluation in CHB should increasingly adopt a dual approach that assesses both fibrosis and steatosis, particularly in patients with concurrent metabolic dysfunction-associated steatotic liver disease. In this growing population, reliance on fibrosis assessment alone may underestimate disease severity and delay appropriate risk stratification. Overall, this commentary highlights the need for an integrated non-invasive evaluation of both steatosis and fibrosis, particularly in patients with mixed viral and metabolic liver disease etiologies.

Keywords: Chronic hepatitis B; Metabolic dysfunction-associated steatotic liver disease; Liver fibrosis; Non-invasive tests; Transforming growth factor-β; L59 (LAP degradation product); Platelet count; Fibrogenesis

Core Tip: Non-invasive assessment of liver injury in chronic hepatitis B is evolving beyond static fibrosis markers toward biologically driven models. The L59-based nomogram proposed by Dai et al captures active fibrogenesis through transforming growth factor-βactivation, integrating molecular, inflammatory, and hematologic parameters. This approach is particularly relevant in patients with concurrent metabolic dysfunction-associated steatotic liver disease, where steatosis may be deceptively mild despite advanced fibrosis. A dual, non-invasive evaluation of fibrosis and steatosis is therefore essential to avoid underestimation of disease severity and to optimize risk stratification in dual-etiology liver disease.