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

Table 1 Tiered non-invasive assessment strategies for liver fibrosis and steatosis: A synthesis of international guidelines (2017-2025)

Guideline body & Ref.	Tier 1: Initial risk stratification (screening)	Tier 2: Confirmatory/definitive assessment	Key considerations for dual HBV/MASLD etiology
APASL (Shiha et al[34], 2017); resource-aware, global perspective	Fibrosis: APRI or proprietary panels (e.g., FibroTest). Steatosis: Ultrasound	Fibrosis: VCTE or MRE	In resource-limited settings, a low threshold for specialist referral is needed if metabolic risk factors (T2DM, hypertension) are present, as they are strong independent drivers of fibrosis in co-infected patients[22]
AACE/AASLD endocrine (Cusi et al[35], 2022); high-risk metabolic patients	Fibrosis: FIB-4 index (universal screening in T2D). Steatosis: Risk factor-based	Fibrosis: (LSM by VCTE) or ELF test. Steatosis: CAP or MRI-PDFF for quantification	Endocrinologists must recognize that in patients with HBV, the presence of T2DM and hypertension should trigger aggressive fibrosis assessment, as these metabolic factors are strongly linked to significant fibrosis in this population[22]
EASL-EASD-EASO (European Association for the Study of the Liver et al[36], 2024); rule-out strategy in MASLD	Fibrosis: FIB-4 index (stepwise with LSM). Steatosis: Often integrated via CAP during LSM	Fibrosis: LSM by VCTE (primary), or MRE. Steatosis: CAP, MRI-PDFF	A key paradox: Low steatosis scores (e.g., CAP) should not be used to de-prioritize fibrosis evaluation. The viral component may be the dominant fibrogenic driver, necessitating elastography even with normal CAP[14,20,23]
AASLD practice guideline on blood-based NITs (Sterling et al[37], 2025); primary care & hepatology screening	Fibrosis: FIB-4 Index (preferred). Steatosis: Not routinely specified in Tier 1; often via risk factor assessment	Fibrosis: Imaging-based NITs (VCTE, MRE) or enhanced blood tests (ELF). Steatosis: CAP (with VCTE) or MRI-PDFF	The 2025 guideline emphasizes using NITs for risk stratification but does not specify dual-etiology cut-offs. Heightened suspicion for advanced fibrosis is warranted despite potentially mild steatosis scores[23]

This table chronologically presents the tiered diagnostic approach (Tier 1: Initial screening; Tier 2: Confirmatory testing) recommended by major international societies, highlighting considerations for the dual hepatitis B virus (HBV)/metabolic dysfunction-associated steatotic liver disease (MASLD) etiology. Traditional frameworks from the Study of Liver Diseases, Study of the Liver, and AACE rely heavily on the fibrosis-4 Index index to rule out advanced fibrosis, typically utilizing a low cutoff of < 1.3 (or < 2.0 in patients over 65) to minimize false negatives in primary care settings. For individuals with indeterminate scores, imaging-based tests such as vibration-controlled transient elastography or magnetic resonance elastography (MRE) provide significantly higher precision for “ruling in” advanced disease, with MRE demonstrating diagnostic accuracy often exceeding 0.90. Dual etiology note: All cut-offs (e.g., FIB-4, LSM) are validated primarily in single-etiology cohorts. Performance may differ in HBV/MASLD, underscoring the need for clinical correlation and lower thresholds for specialist referral. APRI: Aspartate aminotransferase to platelet ratio index; CAP: Controlled attenuation parameter; ELF: Enhanced liver fibrosis; FIB-4: Fibrosis-4 index; LSM: Liver stiffness measurement; MRI-PDFF: Magnetic resonance imaging - proton density fat fraction; NIT: Non-invasive test; T2DM: Type 2 diabetes mellitus; VCTE: Vibration-controlled transient elastography; MRE: Magnetic resonance elastography; MASLD: Metabolic dysfunction-associated steatotic liver disease; AASLD: Study of Liver Diseases; EASL-EASD-EASO: European Association for the Study of the Liver - European Association for the Study of Diabetes - European Association for the Study of Obesity; AACE: American Association of Clinical Endocrinology.