Serum fibrosis markers can predict rapid fibrosis progression after liver transplantation for hepatitis C

Abstract

Although recurrent hepatitis C virus (HCV) after liver transplantation (LT) is universal, a minority of patients will develop cirrhosis within 5 years of surgery, which places them at risk for allograft failure. This retrospective study investigated whether 2 serum fibrosis markers, serum hyaluronic acid (HA) and YKL-40, could be used to predict rapid fibrosis progression (RFP) post-LT. These markers were compared with conventional laboratory tests, histological assessment, and hepatic stellate cell activity (HSCA), a key step in fibrogenesis, as assessed by immunohistochemical staining for alpha-smooth muscle actin. Serum and protocol liver biopsy samples were obtained from 46 LT recipients at means of 5 Ϯ 2 (biopsy 1) and 39 Ϯ 6 (biopsy 2) months post-LT, respectively. RFP was defined as an increase in the fibrosis score Ն 2 from biopsy 1 to biopsy 2 (a mean interval of 33 Ϯ 6 months). The ability of parameters at biopsy 1 to predict RFP was compared with the areas under receiver operating characteristic curves (AUROCs). Of the 46 subjects, 15 developed RFP. Serum HA and YKL-40 performed significantly better than conventional parameters and HSCA in predicting RFP post-LT for HCV at biopsy 1, with AUROCs of 0.89 and 0.92, respectively. The accuracy of serum HA Ն 90 g/L and YKL-40 Ն 200 g/L in predicting RFP at biopsy 1 was 80% and 96%, respectively. In conclusion, we found that elevated levels of serum HA and YKL-40 within the first 6 months after LT accurately predicted RFP. See Editorial on Page 1237End-stage liver disease from chronic hepatitis C virus (HCV) infection is the leading indication for liver transplantation (LT) in the United States. Although virologic recurrence of HCV is universal, the histologic and clinical course of HCV after LT is highly variable.1 Progression to cirrhosis occurs in 6% to 23% of patients at a median of 3 to 4 years post-LT. 1 Several donor, recipient, viral, and transplant-related factors have been associated with more severe recurrent HCV disease after transplantation.2,3 Efforts to identify individuals at risk for rapid fibrosis progression (RFP) have included histological assessment of allograft biopsies, measurement of liver stiffness by transient elastography (TEG),

Plasma YKL-40 is elevated in patients with recurrent atrial fibrillation after catheter ablation

“…Plasma YKL-40 is also suggested to be a biomarker of inflammation and tissue remodelling in several inflammatory conditions such asthma [27], infection [28], rheumatoid arthritis [28], giant cell arteritis [17], inflammatory bowel disease [29,30], diabetes [31,32], and cancer [33]. YKL-40 may also reflect the rate at which fibrosis is progressing in an affected organ such as the liver with hepatitis [29,34,35] and in pulmonary sarcoidosis [36].…”

The Chitinase-like Protein YKL-40 Is Secreted by Airway Epithelial Cells at Base Line and in Response to Compressive Mechanical Stress

“…Since it was identified as a secreted product of articular chondrocytes and synovial cells in 1993 (11), a growing body of evidence has accumulated showing that high serum levels of YKL-40 are associated with various pathological conditions including chronic inflammation (7,8,12,13), hepatic fibrosis (14,15), poor prognosis cancers (16), and allergic diseases (17)(18)(19).…”

Liver Transplantation for Hepatitis C: Disease Management

“…A composite score of the three markers together was successful in discriminating mild to more progressive HCV recurrence after transplantation. Another group measured HA and YKL-40, also known as human cartilage glycoprotein 39 [26]. YKL-40 had been shown previously to be predictive of liver fibrosis in other nontransplant patient studies.…”