Serum Fibrosis Markers Identify Patients With Mild and Progressive Hepatitis C Recurrence After Liver Transplantation

Background & Aims

Significant fibrosis (fibrosis stage [F] ≥ 2) and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) in patients 1 year after liver transplantation indicate progressive hepatitis C recurrence. This study evaluated whether serum fibrosis markers can predict hepatitis C recurrence during the first year after liver transplantation.

Methods

Hyaluronic acid, amino-terminal propeptide of type-III-procollagen, tissue inhibitor of matrix metalloproteinase type-1 concentrations were measured in serum samples from 133 patients infected with hepatitis C virus (HCV) at 3, 6, and 12 months after liver transplantation; routine laboratory tests were also performed. Liver biopsy samples (n = 133) and HVPGs (n = 94) were analyzed 1 year after transplantation. Sixteen patients who were not infected with HCV served as controls.

Results

An algorithm, including the 3 markers (3-M-ALG) and 3 published scores (aspartate aminotransferase [AST]-to-alanine aminotransferase ratio, AST-to-platelet ratio index, and Benlloch) were analyzed. One year after liver transplantation, 50 patients (38%) had significant fibrosis (F ≥ 2) and 31 (32%) had an HVPG ≥ 6 mm Hg. The area under the receiver operator characteristic curve of the 3-M-ALG used to identify F ≥ 2 at 3, 6, and 12 months after transplantation (0.67, 0.77, and 0.78) and of those with HVPG ≥ 6 at the same time points (0.75, 0.87, and 0.90) were significantly higher than values obtained with the 3 published scores. At 12 months, a 3-M-ALG ≥ 2 identified most patients at risk of decompensation/death.

Conclusions

Serum markers can accurately discriminate between patients with mild and progressive hepatitis C recurrence after liver transplantation.

Abbreviations used in this paper: APRI, AST-to-platelet ratio index, AST, aspartate aminotransferase, ALT, alanine aminotransferase, AUROC, area under the receiver operator characteristic curve, BMI, body mass index, F, fibrosis stage, HA, hyaluronic acid, HCV, hepatitis C virus, HVPG, hepatic venous pressure gradient, LSM, liver stiffness measurements, LT, liver transplantation, NPV, negative predictive value, PIIINP, amino-terminal propeptide of type III procollagen, PPV, positive predictive value, S, sensitivity, Sp, specificity, TE, transient elastography, TIMP-1, tissue inhibitor of matrix metalloproteinase type-1, 3-M-ALG, algorithm combing 3 biomarkers