Hempel Felix, Roderfeld Martin, Müntnich Lucas John, Albrecht Jens, Oruc Ziya, Arneth Borros, Karrasch Thomas, Pons-Kühnemann Jörn, Padberg Winfried, Renz Harald, Schäffler Andreas, Roeb Elke
Department of Gastroenterology, Justus Liebig University, D-35392 Giessen, Germany.
Department of General, Visceral, Thoracic, Transplantation, and Pediatric Surgery, Justus Liebig University, D-35392 Giessen, Germany.
J Clin Med. 2021 Mar 16;10(6):1233. doi: 10.3390/jcm10061233.
Bariatric surgery has emerged as an effective treatment option in morbidly obese patients with non-alcoholic fatty liver disease (NAFLD). However, worsening or new onset of non-alcoholic steatohepatitis (NASH) and fibrosis have been observed. Caspase-cleaved keratin 18 (ccK18) has been established as a marker of hepatocyte apoptosis, a key event in NASH development. Thus, ccK18 measurements might be feasible to monitor bariatric surgery patients. Clinical data and laboratory parameters were collected from 39 patients undergoing laparoscopic Roux-en-Y gastric bypass at six timepoints, prior to surgery until one year after the procedure. ccK18 levels were measured and a high-throughput analysis of serum adipokines and cytokines was carried out. Half of the cohort's patients (20/39) presented with ccK18 levels indicative of progressed liver disease. 21% had a NAFLD-fibrosis score greater than 0.676, suggesting significant fibrosis. One year after surgery, a mean weight loss of 36.87% was achieved. Six and twelve months after surgery, ccK18 fragments were significantly reduced compared to preoperative levels ( < 0.001). Yet nine patients did not show a decline in ccK18 levels ≥ 10% within one year postoperatively, which was considered a response to treatment. While no significant differences in laboratory parameters or ccK18 could be observed, they presented with a greater expression of leptin and fibrinogen before surgery. Consecutive ccK18 measurements monitored the resolution of NAFLD and identified non-responders to bariatric surgery with ongoing liver injury. Further studies are needed to elicit the pathological mechanisms in non-responders and study the potential of adipokines as prognostic markers.
减重手术已成为治疗重度肥胖且患有非酒精性脂肪性肝病（NAFLD）患者的一种有效选择。然而，已观察到非酒精性脂肪性肝炎（NASH）和纤维化病情恶化或新发。半胱天冬酶切割角蛋白18（ccK18）已被确立为肝细胞凋亡的标志物，而肝细胞凋亡是NASH发展过程中的关键事件。因此，测量ccK18可能有助于监测减重手术患者。收集了39例行腹腔镜Roux-en-Y胃旁路手术患者在六个时间点（术前直至术后一年）的临床数据和实验室参数。测量了ccK18水平，并对血清脂肪因子和细胞因子进行了高通量分析。该队列中有一半患者（20/39）的ccK18水平表明肝病进展。21%的患者非酒精性脂肪性肝病纤维化评分大于0.676，提示存在显著纤维化。术后一年，平均体重减轻了36.87%。术后6个月和12个月，ccK18片段与术前水平相比显著降低（<0.001）。然而，有9名患者在术后一年内ccK18水平下降未≥10%，而这被视为治疗反应。虽然在实验室参数或ccK18方面未观察到显著差异，但他们术前瘦素和纤维蛋白原的表达更高。连续测量ccK18可监测NAFLD的消退情况，并识别出对减重手术无反应且存在持续肝损伤的患者。需要进一步研究以阐明无反应者的病理机制，并研究脂肪因子作为预后标志物的潜力。
