Adrenal insufficiency in patients with decompensated cirrhosis

Table 2 Characteristics and outcomes of the included studies in not critically ill cirrhotic patients

Ref.	Study design; study period; country	No. of patients; type of liver disease	Adrenal failure	Other observations	Definition of adrenal failure
Fede et al[56]	Prospective, observational; NR; United Kingdom	79 patients; cirrhotics for pretransplatation or decompensation of cirrhosis	TC: 27/79 (34%) FC: 22/79 (28%) [for FC < 25: 15/79 (19%)] FCI: 24/79 (30%)	AI was not correlated with the outcome	LDSST AI: Peak TC < 494 nmol/L at 20 or 30 min FC < 33 nmol/L FCI < 12
Acevedo et al[57]	Prospective, observational; 2008-2010 Spain	143 patients; acute decompensation of cirrhosis - follow up for 3 mo	37/143 (26%)	RAI was similar between different Child-Pugh scores and various causes of decompensations with the exception of HRS type-1 (trend for higher proportions) RAI was correlated with worse outcome both during hospitalization and in 3 mo period	SST RAI: Delta cortisol < 250 nmol/L in patients with basal serum TC < 938 nmol/L
Kharb et al[10]	Cross sectional; 2010-2011; India	25 ALD, 50 CLD, 10 post liver transplanted	ALD: 9/25 (34.6%) CLD: 20/50 (40%) (18/30 with child 2, 3 and 2/20 with child 1) Post LT: 4/10 (40%) RAI: ALD: 17/25 (65.4%), CLD: 23/50 (46%), post LT: 7/10 (70%)	AI was correlated with severity of liver disease	SST AI: Basal cortisol levels < 83 nmol/L or a peak cortisol response < 500 nmol/L RAI: Delta cortisol < 250 nmol/L
Thevenot et al[7]	Prospective; 2008-2009; France	95 patients; hemodynamiccally stable cirrhotic mainly alcoholic	7/95 (7.4%) 18/95 (19%) 26/95 (27.4%) 47/95 (49.4%) (According each threshold)	Patients with Child C cirrhosis and those with ascites had higher non significant rise in basal and stimulated serum FC Serum FC levels were directly associated with the risk of non transplant-related mortality	LDSST AI: (1) basal serum TC < 138 nmol/L and a T30 serum TC < 440 nmol/L; (2) T30 serum TC < 500 nmol/L; (3) delta cortisol < 250 nmol/L
Fede et al[8]	Prospective, observational; NR; United Kingdom	101 patients; stable cirrhosis	(1) 38/101 (38%) (2) 29/101 (29%) (3) 61/101 (60%) (4) 0/41 (0%)	AI was more frequent in hypoalbuminemic patients, according TC and delta cortisol and related with the severity of liver disease TC and cFC were significantly related FCI was lower in patients with AI	LDSST, FCI, cFC AI: Peak (1) TC < 500 nmol/L (2) TC < 442 nmol/L (3) Delta cortisol < 250 nmol/L (4) FCI < 12
Tan et al[9]	Prospective, observational; 2008-2009; Australia	43 patients; stable cirrhosis	(1) 18/43 (39%) (2) 20/43 (47%) (3) 5/43 (12%) (4) 25/43 (58%) (5) 10/43 (23%)	With serum FC criteria, patients with AI had significantly higher MELD score (P = 0.03) and mortality (P = 0.0007) Serum TC was correlated well with serum FC in pts with albumin both > and < 30 g/L Serum FC correlated significantly with FCI at baseline but less strongly with peak FC Overall survival at 6 and 12 mo was similar between AI and non AI group according TC	SST (1) Standard criteria: peak TC < 500 nmol/L (2) CIRCI criteria: delta cortisol < 250 nmol/L (3) Peak serum FC < 33 nmol/L (4) Any set of criteria (5) FCI < 12
Galbois et al[36]	Prospective, observational; 2006-2009; France	88 patients; complication of cirrhosis - alcoholic mainly	TC: 29/88 (33%) SC: 8/88 (9.1%)	There was correlation between cFC and SC Between SC and TC there was correlation for alb > 2.5 mg/dL whereas for alb < 2.5 mg/dL there was correlation for T0 but no for T60 or delta cortisol Acites and HDL were independent risk factors for AI	SST TC: basal TC < 250 nmol/L or in T60 < 500 nmol/L or delta cortisol < 250 nmol/L SC: T0 < 1.8 ng/mL or T60 < 12.7 ng/mL or delta cortisol < 3 ng/mL
Vincent et al[58]	Retrospective; NR; NR	26 patients; 15 CLD and 11 ALD	TC: 12/26 (46%) FCI: 3/26 (13%)		SST TC < 550 nmol/L FCI < 12
Shin et al[62]	Prospective; 2011-2012; South Korea	50 patients; stable cirrhosis	22/50 (44%)	AI was not related with the etiology of cirrhosis or alcohol consumption but only with the severity of liver disease	SST TC < 550 nmol/L
Privitera et al[63]	NR; NR; Italy	82 patients; cirrhotic stable	26/82 (32%)	In cirrhotic with AI, there was significant reduction in total cholesterol, TRG and ApoA1, but not in total HDL, HDL2 and HDL3	LDSST TC < 500 nmol/L
Cholongitas et al[60]	Prospective; 2010-2012; Greece	89 patients; stable decompensated cirrhosis	TC: 49/89 (55%) SC: 33/89 (37%)	For albumin > 2.5, TC and SC correlated for T0 and T60 Urinary potassium was the only factor significant associated with SC-AI	SST TC, SC
Acevedo et al[59]	Prospective; 2007-2009; Spain	198 patients; 10 with compensated and 188 with decompensated cirrhosis	(1) 120/188 (64%), 8/10 (80%) (2) 51/188 (27%), 2/10 (22%)	No significant difference in mortality between patient with or without RAI	SST RAI: Basal TC < 414 nmol/L and/or delta cortisol < 250 nmol/L (criteria 1) or delta cortisol < 250 nmol/L (criteria 2)
Acevedo et al[64]	Prospective; 2007-2010; Spain	166 patients; advanced cirrhosis	43/166 (26%)	Those with RAI had higher degree of circulatory dysfunction, SIRS (P = 0.01), septic shock (P = 0.01) and hospital mortality (P = 0.04)	SST RAI: Delta cortisol < 250 nmol/L
Risso et al[61]	NR; NR; NR	85; stable cirrhotic with ascites	33/85 (39%)	AI was associated with reduced survival (P = 0.03)	SST RAI: Delta cortisol < 250 nmol/L and/or peak cortisol < 500 nmol/L

NR: Not reported; TC: Total cortisol; FC: Free cortisol; FCI: Free cortisol index; LDSST: Low dose short synacthen test; SST: Short synacthen test; AI: Adrenal insufficiency; RAI: Relative adrenal insufficiency; ALD: Acute liver disease; CLD: Chronic liver disease; LT: Liver transplantation; cFC: Calculated free cortisol; HDL: High density lipoprotein; TRG: Triglycerides; CIRCI: Critical illness related adrenal insufficiency; SC: Salivary cortisol; HRS: Hepatorenal syndrome; MELD: Model for end-stage liver disease.