Hypophosphatemia as a prognostic tool for post-hepatectomy liver failure: A systematic review

Table 1 Characteristics of included studies

Ref.	Study type	NOS	N	Study population	Cutoff phosphorus level	Main outcomes	Results	Conclusions
George et al[28], 1992	Retrospective	6	44	Liver resections	≤ 2.5 mg/dL	Postoperative complications	Profound HP group had higher frequency rate of postoperative complications (P < 0.005)	Hypophosphatemia increased risk of postoperative complications
Buell et al[21], 1998	Retrospective	6	35	Liver resections and cryosurgery	< 2.5 mg/dL	Postoperative complications	More complications in HP group (80% vs 28%; P < 0.05)	Hypophosphatemia increased risk of postoperative complications
Giovannini et al[22], 2002	Retrospective	7	59	Liver resections	≤ 2.5 mg/dL	Postoperative complications	HP (< 1.5 mg/dL) associated with increase in rate of complications (P < 0.001)	Hypophosphatemia increased risk of postoperative complications
Smyrniotis et al[23], 2003	Prospective	7	30	Liver resections	< 1.5 mg/dL	Postoperative complications	Patients with HP (< 1.5 mg/dL) had more complications	Hypophosphatemia increased risk of postoperative complications
Yuan et al[24], 2011	Retrospective	6	132	LDLT	< 1 mg/dL	Liver insufficiency	MV binary logistic regression: Postoperative nadir serum phosphorus (P = 0.01) was independently related to hepatic functional impairment (ß = -5.927, odds ratio 0.003; 95%CI: 0.000-0.239). Postoperative nadir of serum phosphorus < 1 mg/dL (P = 0.006, AUC = 0.731) led to more severe hepatic dysfunction	Hypophosphatemia increased risk of postoperative liver insufficiency
Squires et al[11], 2014	Retrospective	7	719	Liver resections	< 2.4 mg/dL	Liver insufficiency	UV: Patients with POD2 phosphorus > 2.4 demonstrated a significantly increased risk of PHLF (P = 0.020). MV: POD2 phosphorus > 2.4 mg/dL remained independently associated with a significantly increased risk of PHLF (HR = 1.78; 95%CI: 1.02-3.17; P = 0.048)	Absence of postoperative hypophosphatemia increased risk of postoperative complications and liver insufficiency
Hallet et al[29], 2016	Retrospective	7	402	Liver resections	≤ 2.01 mg/dL	Liver insufficiency	More patients with HP recovered from LI compared to those with NP (90.9% vs 65.0%, P = 0.03)	Postoperative hypophosphatemia associated with better recovery from PHLF
Margonis et al[30], 2016	Retrospective	7	95	Liver resections	≤ 2.4 mg/dL	Liver insufficiency	LI was lower in patients with HP (P = 0.01). MV analysis: Normal/high serum phosphorus on POD2 (HR = 3.24, 95%CI: 1.23-8.56; P = 0.02) remained independently associated with a worse OS	Postoperative hypophosphatemia associated with better OS, better liver regeneration and lower rate of liver insufficiency
Serrano et al[31], 2019	Retrospective	7	161	LDLT	≤ 2.5 mg/dL	Liver insufficiency	LI 1.77 mg/dL vs no LI 2.01 mg/dL for no LI cohort at a median of 1.6 d (38 h) postoperatively (P = 0.003). ROC postoperative phosphate levels through the first 38 h best predicted LI (sensitivity, 90%; specificity, 55.6%; positive predictive value, 11.8%; negative predictive value, 98.8%; AUC, 0.731)	Hypophosphatemia increased risk of postoperative liver insufficiency

AUC: Area under the receiver operating characteristic curve; CI: Confidence interval; HP: Hypophosphatemia; HR: Hazards ratio; LDLT: Living donor liver transplantation; LI: Liver insufficiency; MV: Multivariate; NP: Normophosphatemia; OS: Overall survival; PHLF: Post-hepatectomy liver failure; POD: Postoperative day; NOS: Newcastle-Ottawa Scale; ROC: Receiver operating characteristic; UV: Univariate.