Department of Internal Medicine I, University of Bonn, Bonn, Germany.
German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Bonn, Germany.
PLoS One. 2019 Jul 11;14(7):e0219526. doi: 10.1371/journal.pone.0219526. eCollection 2019.
Although combined antiretroviral treatment (cART) has improved overall survival of HIV infected patients, liver fibrosis and liver related-mortality still constitute major challenges in HIV positive patients. Collagen accumulates in the liver during fibrogenesis. Recent studies showed that circulating levels of extracellular matrix (ECM) fragments might reflect degree of portal hypertension and fibrosis stage in liver disease. In this study, we analyzed the correlation between liver fibrosis assessed by Fibroscan and levels of the formation and degradation markers of type III and IV collagen in HIV positive patients receiving cART.
116 HIV positive patients (82.7% male, median age 47 years) were enrolled into the study. Liver stiffness and liver fat content were determined using a Fibroscan with integrated CAP function. We quantified ECM formation and degradation fragments of collagen III and IV: PRO-C3, PRO-C4, C3M and C4M. These fragments were measured in peripheral serum by using specific ELISAs.
Fifteen (12.9%) out of the 116 HIV positive patients had relevant fibrosis with a liver stiffness ≥ 7.1 kPa, and 79 patients had relevant steatosis with a CAP value > 248 dB/m. Circulating PRO-C3 levels significantly correlated with increasing degree of liver fibrosis assessed by Fibroscan (p = 0.0005), as well as with APRI score (p = 0.015). Interestingly, circulating PRO-C3 levels were significantly correlated with bilirubin (p = 0.022), reduced platelet count (p = 0.0008) and low albumin levels (p = 0.001), suggesting the association of type III collagen deposition with impaired liver function. None of the other measured ECM components significantly correlated with fibrosis or steatosis.
The formation marker of type III collagen, PRO-C3 not only reflects liver fibrosis, but might also mirror liver dysfunction in HIV positive patients receiving cART. Therefore, the circulating levels of PRO-C3 might be suitable to monitor progression of liver fibrosis and deterioration of liver function in HIV positive patients receiving cART.
尽管联合抗逆转录病毒治疗（cART）提高了 HIV 感染者的总体生存率，但肝纤维化和与肝脏相关的死亡率仍然是 HIV 阳性患者的主要挑战。在肝纤维化过程中，胶原会在肝脏中积聚。最近的研究表明，细胞外基质（ECM）片段的循环水平可能反映肝脏疾病的门脉高压程度和纤维化阶段。在这项研究中，我们分析了接受 cART 的 HIV 阳性患者中，通过 Fibroscan 评估的肝纤维化与 III 型和 IV 型胶原的形成和降解标志物水平之间的相关性。
纳入 116 例 HIV 阳性患者（82.7%为男性，中位年龄 47 岁）进行研究。使用具有集成 CAP 功能的 Fibroscan 测定肝硬度和肝脂肪含量。我们通过使用特定的 ELISA 定量测定 III 型和 IV 型胶原的形成和降解片段：PRO-C3、PRO-C4、C3M 和 C4M。这些片段在外周血清中进行测量。
116 例 HIV 阳性患者中，有 15 例（12.9%）存在相关纤维化，肝硬度≥7.1kPa，79 例存在相关脂肪变性，CAP 值>248dB/m。循环 PRO-C3 水平与 Fibroscan 评估的肝纤维化程度呈显著正相关（p=0.0005），与 APRI 评分也呈显著正相关（p=0.015）。有趣的是，循环 PRO-C3 水平与胆红素（p=0.022）、血小板计数降低（p=0.0008）和低白蛋白水平（p=0.001）显著相关，提示 III 型胶原沉积与肝功能受损有关。其他测量的 ECM 成分均与纤维化或脂肪变性无显著相关性。
III 型胶原的形成标志物 PRO-C3 不仅反映肝纤维化，而且可能反映接受 cART 的 HIV 阳性患者的肝功能障碍。因此，循环 PRO-C3 水平可能适合监测接受 cART 的 HIV 阳性患者肝纤维化进展和肝功能恶化。
