Serum hyaluronic acid predicts protein-energy malnutrition in chronic hepatitis C

Abstract

Serum hyaluronic acid (HA) is a well-established marker of fibrosis in patients with chronic liver disease (CLD). However, the relationship between serum HA level and protein-energy malnutrition (PEM) in patients with CLD is an unknown. We aimed to examine the relationship between serum HA level and PEM in patients with chronic hepatitis C (CHC) compared with the relationships of other serum markers of fibrosis. A total of 298 CHC subjects were analyzed. We defined patients with serum albumin level of ≤3.5 g/dL and nonprotein respiratory quotient <0.85 using indirect calorimetry as having PEM. We investigated the effect of serum HA level on the presence of PEM. Receiver operating characteristic curve (ROC) analysis was performed for calculating the area under the ROC (AUROC) for serum HA level, platelet count, aspartate aminotransferase (AST) to platelet ratio index, FIB-4 index, AST to alanine aminotransferase ratio, and Forns index for the presence of PEM. The median serum HA level in this study was 148.0 ng/mL (range: 9.0-6340.0 ng/mL). In terms of the degree of liver function (chronic hepatitis, Child-Pugh A, B, and C), the analyzed patients were well stratified according to serum HA level (overall significance, P < 0.0001). The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6-6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0-783.0 ng/mL) (P < 0.0001). Among 6 fibrosis markers, serum HA level yielded the highest AUROC with a level of 0.849 at an optimal cut-off value of 151.0 ng/mL (sensitivity 93.4%; specificity 62.0%; P < 0.0001). In the multivariate analysis, serum HA level was found to be a significant prognostic factor related to the presence of PEM (P = 0.0001).In conclusion, serum HA level can be a useful predictor of PEM in patients with CHC.

Figure 1

Prevalence of PEM in different fibrosis stages (F0–1, F2, F3, and F4) and different Child-Pugh stages (A, B, and C). (A) The proportions of PEM in different fibrosis stages were 1.6% (1/62) in F0–1, 6.7% (2/30) in F2, 4.8% (2/42) in F3, and 34.1% (56/164) in F4 (overall significance, P < 0.0001). (B) The proportions of PEM in different Child-Pugh stages were 16.5% (16/97) in Child-Pugh A, 52.6% (30/57) in Child-Pugh B, and 100% (10/10) in Child-Pugh C (overall significance, P < 0.0001). PEM = protein-energy malnutrition.

Figure 2

(A) Serum HA levels among patients with different degree of liver damage. The median values (range) of serum HA levels among patients with different degree of liver damage are 62.5 ng/mL (9.0–568.0 ng/mL) in patients with chronic hepatitis (CH [F0–F3], n = 134), 203.0 ng/mL (22.0–1290.0 ng/mL) in patients with Child-Pugh A (CP-A, n = 97), 358.0 ng/mL (55.8–3730.0 ng/mL) in patients with Child-Pugh B (CP-B, n = 57), and 775.0 ng/mL (165.0–6340.0 ng/mL) in patients with Child-Pugh C (CP-C, n = 10) (overall significance, P < 0.0001). (B) Comparison of serum HA level between patients with serum albumin value of >3.5 g/dL and those with serum albumin value of ≤3.5 g/dL. The median value (range) of serum HA level in patients with serum albumin value of ≤3.5 g/dL (n = 104) was 346.0 ng/mL (43.6–6340.0 ng/mL) and that in patients with serum albumin value of >3.5 g/dL (n = 194) was 87.8 ng/mL (9.0–783.0 ng/mL) (P < 0.0001). (C) Comparison of serum HA level between patients with npRQ value of ≥0.85 g/dL and those with npRQ of <0.85. The median value (range) of serum HA level in patients with npRQ value of <0.85 (n = 141) was 199.0 ng/mL (9.0–6340.0 ng/mL) and that in patients with serum albumin value of ≥0.85 (n = 157) was 102.0 ng/mL (9.0–783.0 ng/mL) (P = 0.0006). (D) Comparison of serum HA level between patients with and without PEM. The median value (range) of serum HA level in patients with PEM (n = 61) was 389.0 ng/mL (43.6–6340.0 ng/mL) and that in patients without PEM (n = 237) was 103.0 ng/mL (9.0–783.0 ng/mL) (P < 0.0001). HA = hyaluronic acid, npRQ = nonprotein respiratory quotient, PEM = protein-energy malnutrition.

Figure 3

Receiver operating curve analyses of 6 fibrosis markers for the presence of PEM. (A) Serum hyaluronic acid level, (B) AST to platelet ratio index, (C) FIB-4 index, (D) AST to ALT ratio, (E) platelet count, and (F) Forns index. ALT = alanine aminotransferase, AST = aspartate aminotransferase, PEM = protein-energy malnutrition.