Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV.

BACKGROUND AND AIMS: Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. METHODS: This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. RESULTS: Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. CONCLUSION: Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.

Use of Plasma Fragments of Propeptides of Type III, V, and VI Procollagen for the Detection of Liver Fibrosis in Type 2 Diabetes.

OBJECTIVE: This study assessed the utility of plasma fragments of propeptides of type III (PRO-C3), V (PRO-C5), and VI (PRO-C6) procollagen for the detection of liver fibrosis in patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: Patients with T2DM (n = 191) underwent an oral glucose tolerance test, a liver 1H-MRS, and a liver biopsy when indicated. PRO-C3, PRO-C5, and PRO-C6 were blindly assessed. RESULTS: PRO-C3 performed well for the diagnosis of moderate-to-advanced (area under the receiver operating characteristic curve [AUROC] 0.81 [95% CI 0.74-0.88]) and advanced (AUROC 0.88 [0.80-0.95]) fibrosis in T2DM patients. Its performance was similar to that of AST to platelet ratio index (APRI) (AUROC 0.83 and 0.87, respectively) and Fibrosis-4 (FIB-4) (AUROCs 0.83 and 0.86, respectively) scores. Use of PRO-C5 and PRO-C6 did not improve the accuracy to detect liver fibrosis. After 18 months, PRO-C3 changes were associated with changes in fibrosis stages. CONCLUSIONS: PRO-C3 performed well for the detection of fibrosis in T2DM patients and showed promising results for prediction of histological changes in fibrosis stage with treatment.

The COL5A1 gene: a novel marker of endurance running performance.

BACKGROUND: Running economy, a key component of endurance ability, has been shown to be associated with flexibility. Increased stiffness (inflexibility) may improve running economy and therefore endurance running ability. The COL5A1 gene, which encodes the α1-chain of type V collagen, was found to associate with measures of flexibility. Type V collagen is a quantitatively minor fibrillar collagen, which is believed to regulate fibrillogenesis within tendons and other connective tissue. PURPOSE: The aim of this study was therefore to determine whether the COL5A1 gene is associated with endurance performance. METHODS: Three hundred thirteen Caucasian male participants who completed either the 2006 or the 2007 226-km South African Ironman triathlon (3.8-km swim, 180-km bike, and 42.2-km run) participated in this study. All participants were genotyped for the COL5A1 BstUI restriction fragment length polymorphism (RFLP). RESULTS: The COL5A1 BstUI RFLP was significantly associated with time to complete the running component of the triathlon. Participants with a TT genotype completed the running component of the race significantly faster than individuals with a CC genotype (P = 0.019; mean ± SD: TT = 294.2 ± 52.1 min, CC = 307.4 ± 48.6 min). In addition, there was a significant linear trend (P = 0.020) in the CC genotype distribution when the run times were divided into the fastest (13%), middle (17%), and slowest (25%) tertiles. There were no significant genotype differences for time to complete the swim, the bike, or the overall race. COL5A1 BstUI RFLP, body mass index, age, and 15 wk of running training history predicted 30% of the variance in running performance. CONCLUSION: This is the first study to identify the COL5A1 BstUI RFLP as a marker for endurance running performance. Further studies are required to replicate these findings.