The 7S Domain of Type IV Collagen as a Noninvasive Surrogate of Portal Hypertension

Portal hypertension (pH) is a major determinant of complications associated with chronic liver disease, and high-risk varices (HRV) require prophylactic intervention. Hepatic venous pressure gradient (HVPG) measurement is the gold standard for assessment. However, it is invasive. This study examined the most reliable noninvasive biomarker for evaluating HVPG and diagnosing HRV.

Seventy-eight patients with chronic liver disease (including 44 with cirrhosis) underwent HVPG measurement. Noninvasive markers including 7S domain of type IV collagen (4COL7S), Mac-2-binding protein glycosylation isomer (M2BPGi), liver stiffness, enhanced liver fibrosis (ELF) score, hyaluronic acid and type III procollagen peptide levels, aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, platelet count, von Willebrand factor (vWF), a disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) activity, vWF-to-ADAMTS13 ratio, and vWF antigen-to-platelet ratio score were evaluated.

In the receiver operating characteristic analyses, 4COL7S had the highest diagnostic accuracy for both clinically significant HRV, with a superior area under the receiver operating characteristic curve compared with the other markers. 4COL7S showed the strongest correlation with HVPG (r = 0.713 and 95% confident interval: 0.617-0.84), outperforming M2BPGi and the ELF score. Vascular markers, such as the vWF antigen-to-platelet ratio and vWF-to-ADAMTS13 ratio, had additional but weaker predictive ability. However, 4COL7S remained the most consistent predictor across both variceal outcomes and HVPG.

4COL7S is the most reliable noninvasive biomarker for predicting HRV. Its superior diagnostic accuracy supports its use as a practical surrogate for HVPG and as a valuable tool in clinical risk stratification for variceal bleeding.