A Clinical Algorithm for Screening Compensated Advanced Chronic Liver Disease Utilizing Ultrasonography, Platelet...

Background and aims Compensated advanced chronic liver disease (cACLD) refers to asymptomatic patients with advanced fibrosis who do not yet exhibit clinical or radiological signs of portal hypertension. Early detection of cACLD is essential for effective risk stratification and timely management, potentially preventing progression to more severe and irreversible stages of liver disease. Transient elastography (TE) is the primary diagnostic method for cACLD, with several diagnostic thresholds commonly used. Ultrasonography (USG) is widely used as an initial diagnostic tool for liver disease, but its effectiveness in diagnosing cACLD is not well established. To the best of our knowledge, this study is the first to systematically evaluate the diagnostic accuracy of USG in detecting cACLD, using TE as a reference standard based on validated diagnostic thresholds. We also examined whether combining USG findings with platelet count and serum albumin could enhance diagnostic utility. Additionally, we discuss the strengths and limitations of established non-invasive scoring systems, including the Enhanced Liver Fibrosis (ELF) test, Fibrosis-4 (Fib-4) index, and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS), to determine if our approach offers a more accessible and practical solution in clinical settings Methods This retrospective cross-sectional study was conducted at the Royal Wolverhampton NHS Trust, Wolverhampton, England, including patients with suspected liver disease who underwent USG, TE, and blood tests. Valid TE readings followed manufacturer guidelines, and patients with USG-detected portal hypertension or confounding conditions (e.g., acute hepatitis, heart failure) were excluded. We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of USG against TE, with TE values >15 kPa confirming and <10 kPa excluding cACLD. Results Among 1,528 patients (mean age 51 years, range 16-89), 982 were male (64.3%) and 546 were female (35.7%). The cohort predominantly comprised Caucasian (n=1,087, 71.1%) and South-East Asian (n=256, 16.8%) patients. USG showed a sensitivity of 64.6% (95%CI: 58.3-70.6%) and specificity of 78.2% (95%CI: 75.6-80.6%) for cACLD, with a PPV of 40.2% (95%CI: 36.7-43.7%) and an NPV of 90.7% (95%CI: 89.2-92.1%). High NPV was consistent across all etiologies. In patients with a normal liver on USG, NPV improved to 92.7% (95%CI: 90.9-94.6%) when serum albumin >35 g/L and platelet count >150 x 10⁹/L were present. In patients with sonographic signs of liver disease, PPV increased to 84.1% (95%CI: 73.3-94.9%) when platelet count and albumin were low but dropped to 20.8% (95%CI: 15.4-26.3%) when both were normal. Conclusions USG alone has limited reliability in diagnosing cACLD but is valuable for ruling out advanced fibrosis in asymptomatic patients due to its high NPV. Adding platelet and albumin levels improves diagnostic accuracy, though TE remains essential for definitive diagnosis. This approach may streamline screening and optimize resource use, particularly in settings with limited TE access. USG combined with platelet count and serum albumin offers a cost-effective, accessible, and practical solution for the initial assessment of cACLD. Further studies are needed to validate these findings in broader populations.