肠外营养相关肝病鱼油疗法的失败

　　既往研究表明，肠外补充鱼油可缓解胆汁淤积，是肠外营养相关肝病（PNALD）安全有效的治疗手段，但仍有15%的患者使用鱼油治疗失败，发展为终末期肝病，需要接受肝移植或死亡。

　　哈佛医学院教学医院：波士顿儿童医院、贝斯以色列女执事医疗中心（贝斯以色列医院、新英格兰女执事医院合并而成）对188例使用鱼油治疗PNALD儿童进行回顾分析，发现13.6%儿童治疗失败。

　　出生时体重较低、起始治疗年龄较大、肝脏损伤较重，血小板数目较低、外院转入等因素都与治疗失败密切相关。

　　因此，强调鱼油对PNALD患者的早期治疗。

JPEN J Parenter Enteral Nutr. 2016;40(4):129.

Failures of Fish Oil Therapy for Treatment of Parenteral Nutrition-Associated Liver Disease.

Meredith A. Baker; Prathima Nandivada; Paul Mitchell; Alison O'Loughlin; Alexis K. Potemkin; Kathleen M. Gura; Gillian L. Fell; Lorenzo Anez-Bustillos; Duy T. Dao; Bennet S. Cho; Mark Puder.

Boston Children's Hospital, Boston, MA, USA; Beth Israel Deaconess Medical Center, Boston, MA, USA.

Purpose: Parenteral fish oil (FO) therapy is a safe and effective treatment for parenteral nutrition-associated liver disease (PNALD), with successful resolution of cholestasis and avoidance of liver transplantation in 85% of infants. However, patients with PNALD who do not achieve resolution of cholestasis with parenteral FO therapy progress to end-stage liver disease requiring liver transplantation or resulting in death. The purpose of this study is to identify early patient factors associated with subsequent failure of parenteral FO therapy to guide prognostication and patient referral guidelines.

Methods: A retrospective review of prospectively collected data for children with PNALD treated with parenteral FO at Boston Children's Hospital (BCH) between January 2004 and December 2014 was performed. PNALD was defined as a direct bilirubin (DB) >2 mg/dL. Resolution of cholestasis was defined as a sustained DB ≤2 mg/dL. Treatment failure was defined as undergoing liver or multivisceral transplantation or death while DB was >2 mg/dL as of July 31, 2015. Patient demographics, hospital transfer status, and laboratory values at initiation of therapy were compared between patients who achieved resolution of cholestasis with parenteral FO therapy and those who failed therapy. Comparisons are expressed as median (interquartile range [IQR]) and compared by Wilcoxon rank-sum test unless otherwise indicated.

Results: One hundred and eighty-eight patients with PNALD treated with parenteral FO at BCH were identified. Twelve patients were excluded because they transferred care or weaned off PN prior to resolution of cholestasis but did not fail FO therapy (ie, undergo transplant or die). Twenty-four patients (13.6%) failed therapy, with 8 of the children undergoing transplantation and 16 PNALD-associated deaths. Patients who failed therapy had lower birth weight (1220 [731, 1800] vs 1760 [830, 2445] g, P = .03) and older age at FO therapy initiation (20.4 [10.4, 37.9] vs 11.7 [7.4, 24.0] weeks, P = .02) than patients whose cholestasis resolved. There was no significant difference in gestational age or age at starting PN between patients who responded to parenteral FO therapy and those who failed therapy. Patients who failed therapy had more advanced liver disease at the time of therapy initiation as evidenced by lower gamma-glutamyl transferase (54 [41, 98] vs 112 [76, 168] U/L, P < .0001), suggestive of a "burned out" liver. Moreover, patients who failed therapy had higher DB (10.4 [7.3, 15.4] vs 4.4 [3.1, 6.6] mg/dL, P < .0001), higher international normalized ratio (1.27 [1.16, 1.71] vs 1.12 [1.05, 1.21], P < .0001), lower platelet counts (67 [39, 104] vs 194 [131, 306] × 103/μL, P < .0001), and higher pediatric end-stage liver disease score (22.2 [17.0, 27.2] vs 14.1 [11.9, 17.5], P < .0001) at the time of FO therapy initiation than patients who did not fail therapy. A higher proportion of patients who transferred from outside hospitals failed parenteral FO therapy compared with patients who developed PNALD at BCH (20 of 114 [17.5%] vs 4 of 62 [6.5%], P = .04 by Pearson chi-square test).

Conclusions: Birth weight, age at FO therapy initiation, severity of biochemically measured liver disease at FO therapy initiation, and institutional transfer are factors that appear to impact resolution of cholestasis. These data suggest that liver disease progression at time of FO initiation may be a determinant of ultimate outcome, and they highlight the importance of early initiation of FO therapy once biochemical cholestasis is detected. Earlier referral of infants and children with PNALD at institutions without access to parenteral FO to centers where parenteral FO therapy is available may further improve response rates.

Financial support: None.