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©The Author(s) 2015.
World J Hepatol. May 18, 2015; 7(8): 1112-1124
Published online May 18, 2015. doi: 10.4254/wjh.v7.i8.1112
Published online May 18, 2015. doi: 10.4254/wjh.v7.i8.1112
Table 1 Characteristics and outcomes of the included studies in critically ill cirrhotics
| Ref. | Study design; study period; country | No. of patients; type of liver disease | Adrenal failure | Other observations | Definition of adrenal failure |
| Etogo-Asse et al[49] | Prospective, observational; 2007-2009; United Kingdom | 163 patients; 89 ALF and 74 AOCLF-56 ALF and 36 AOCLF underwent SST | AOCLF: 21/36 58% ALF: 27/56 48% | Among those with AI 17/32 (47%) with HDL < 0.1 mmol/L vs 2/17 (12%) with HDL > 0.6 mmol/L had increment < 250 nmol/L HDL was lower in non survivors both in AOFLD and ALF | SST to those required vasopressor administration or cardiovascular instability CIRCI: Basal cortisol < 275 nmol/L or delta cortisol < 250 nmol/L |
| Triantos et al[5] | Prospective, observational; NR; NR | 20 patients; cirrhosis and variceal bleeding vs 74 controls (14 healthy and 60 stable cirrhosis) | SST: 6/20 30% LDSST: 6/10 60% Healthy (SST and LDSST): 0/14 0% Stable (LDSST): 24/50 48% Stable (SST): 3/10 30% | AI wasn't associated with outcome Those with AI and variceal bleeding had higher baseline and peak level of cortisol with stable cirrhotic, but similar delta cortisol With SST for albumin > 2.5 mg/dL, AI: 4/16 (25%) with variceal bleeding vs 1/8 (12.5%) in cirrhosis control With LDSST, for albumin > 2.5 mg/dL, AI: 6/10 (80%) with variceal bleeding vs 16/39 (41%) in cirrhosis control | SST AI: Peak cortisol < 500 nmol/L in non-stressed patients and delta cortisol of < 250 nmol/L or a random total cortisol < 276 nmol/L in stressed patients LDSST ΑΙ: Peak cortisol < 500 nmol/L in non-stressed patients and peak cortisol level of < 690 nmol/L or a delta cortisol < 250 nmol/L in stressed patients |
| Thevenot et al[7] | Prospective; 2008-2009; France | 30 patients; septic cirrhotic | 3/30 10% | Significant correlation between salivary and serum free cortisol (P < 0.0001) Serum total cortisol were significantly lower in Child-Pugh score C than B or A, in contrary with free cortisol which had a non significant rise | SST-AI: Post-SST SC < 510.4 nmol/L Salivary cortisol was also calculated |
| Arabi et al[48] | Randomized double blind; 2004-2007; Saudi Arabi | 75 patients; septic shock and cirrhosis in ICU | 57/75 76% | SST RAI: Delta cortisol < 250 nmol/L | |
| du Cheyron et al[6] | Prospective; 2003-2005; France | 50 patients; decompensated cirrhosis in ICU (critical ill with acute on chronic liver disease) | 31/50 62% | SST AI: Baseline cortisol value < 414 nmol/L, or delta cortisol < 250 nmol/L with a baseline value between 414 and 938 nmol/L | |
| Thierry et al[52] | Prospective; March to December 2005; France | 34 patients; septic shock, 14 with and 20 without cirrhosis | Cirrhotic: 11/14 77% Non cirrhotic: 10/20 50% | SST baseline cortisol < 414 nmol/L and/or delta cortisol < 250 nmol/L | |
| Fernández et al[53] | Prospective and retrospective; group 1 2004-2006, group 2 2001-2004 | Group 1: 25 patients; cirrhosis and septic shock Group 2: 50 patients; no assessment of adrenal function | 17/25 68% | SST RAI: (1) Baseline cortisol concentration < 414 nmol/L or (2) delta cortisol < 250 nmol/L in patients with baseline cortisol concentration < 966 nmol/L | |
| Tsai et al[54] | 2004-2005; Taiwan | 101; cirrhosis and severe sepsis required ICU | 52/101 51.4% Hemodynamically unstable: 43/54 79.61% Stable: 9/47 19.14% | ICU mortality: 71.4% vs 26.5% Hospital mortality: 80.7% vs 36.7% (AI vs normal) Correlation with the severity of liver disease | SST AI: Baseline value < 414 nmol/L, or delta cortisol < 250 nmol/L with a baseline value between 414 and 938 nmol/L |
| Marik et al[23] | Retrospective; NR; United States | 221 patients; LTICU | At admission: 120/221 54% In 3 d: 16/101 16% | Low HDL could predict the development of AI | LDSST AI: (1) a random (stress) cortisol < 552 nmol/L in patients with hypoxemic respiratory failure, hypotension or requiring vasopressor agents and (2) a random level < 414 nmol/L or a 30-min post-low-dose cosyntropin stimulation test level of < 552 nmol/L in non-highly stressed patients |
| Marik et al[4] | Retrospective; 2002-2004; United States | 340 patients; ALD, CLD, post OLT recently and remote LT | Overall: 245/340 72% ALD: 8/24 33% CLD: 97/146 66% Remote LT: 31/51 61% Recent LT: 109/119 92% Among those treated with vasopressors: 125/166 75% | Low HDL could predict the development of AI | LDSST AI: (1) a random (stress) cortisol < 552 nmol/L in patients with hypoxemic respiratory failure, hypotension or requiring vasopressor agents and (2) a random level < 414 nmol/L or a 30-min post-low-dose cosyntropin stimulation test level of < 552 nmol/L in non highly stressed patients |
| Nair et al[51] | India | Critical ill cirrhotic in ICU, without sepsis | 73.5% | AI is not associated with severity of liver disease, CRP or etiology of cirrhosis | SST RAI: random basal TC ≤ 276 nmol/L or delta cortisol ≤ 250 nmol/L |
| Saffioti et al[55] | 2009-2013 | 80; cirrhotic pre-LT | 18/80 22.5% | Patients with AI had higher MELD (19 vs 15; P = 0.003), pre-LT INR, bilirubin and potassium, and lower sodium and haemoglobin levels | SST AI: At least 2 of the following: baseline cortisol < 148 nmol/L, peak cortisol < 550 nmol/L, delta cortisol < 250 nmol/L |
| Graupera et al[50] | Spain | 37; cirrhotic with severe variceal bleeding | 14/37 38% | 6 wk survival 64% without and 31% with RAI No differences in overall survival | SST RAI: Baseline serum cortisol < 414 nmol/L or delta cortisol < 250 nmol/L |
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 |
Table 3 Characteristics and outcomes of the included studies in post transplanted patients
| Ref. | Study design; studyperiod; country | No. of patients; type of liver disease | Adrenal failure | Definition of adrenal failure |
| Kharb et al[10] | Cross sectional; 2010-2011; India | 10; OLT | Post LT: 4/10 (40%) RAI: Post LT: 7/10 (70%) | SST AI: Basal cortisol levels < 83 nmol/L or a peak cortisol response < 500 nmol/L RAI: Delta cortisol < 250 nmol/L |
| Marik et al[4] | Retrospective; 2002-2004; United States | 119 post OLT recently and 51 remote OLT | Recent LT: 109/119 (92%) Remote LT: 31/51 (61%) | LDSST AI: (1) a random (stress) cortisol < 552 nmol/L in patients with hypoxemic respiratory failure, hypotension or requiring vasopressor agents and (2) a random level < 414 nmol/L or a 30-min post-low-dose cosyntropin stimulation test level of < 552 nmol/L in non-highly stressed patients |
| Patel et al[65] | Retrospective; NR; United Kingdom | 90 patients; ICU post OLT; 45 patients received bolus dose of 1000 ng methylprednisolone intraoperative vs 45 patients not receiving | First group: significant reduced requirements for fluid administration (P = 0.02), vasopressors (P = 0.01), renal replacement therapy (P = 0.001), invasive ventilation (P = 0.01), and ICU stay (P = 0.02), compared to the second group |
Table 4 Characteristics and outcomes of the included studies of patients treated with steroids
| Ref. | Study design; studyperiod; country | No. of patients;type of liver disease | Hydrocortisone | Outcome |
| Etogo-Asse et al[49] | Prospective, observational; 2007-2009; United Kingdom | 51 critical ill cirrhotic patients required vasopressors | 31 received hydrocortisone of a median dose of 200 mg/d | Mortality: 13/20 (65%) in those who did not and 20/31 (65%) in those who received corticosteroid |
| Arabi et al[48] | Randomized double blind; 2004-2007; Saudi Arabi | 75 patients; septic shock and cirrhosis in ICU | 39 patients received 200 mg hydrocortisone iv/d vs 36 patients receiving normal saline until shock resolution | Shock reversal: 24/39 (62%) with hydrocortisone vs 14/36 (39%) with placebo (P = 0.05) Shock relapse after tapering: 13/39 (34%) vs 5/36 (14%) (P = 0.03) 28 d mortality: 33/39 (85%) vs 26/36 (72%), (P = 0.19) Increase in gastrointestinal bleeding (P = 0.02) in hydrocortisone group |
| du Cheyron et al[6] | Prospective; 2003-2005; France | 31 AOCLD with AI | 14 treated with stress doses of cortisol vs 17 not treated | 30 d mortality: 7/14 (50%) of those treated vs 12/17 (70%) not treated (P = 0.29) |
| Fernández et al[53] | Prospective and retrospective; group 1 2004-2006, group 2 2001-2004 | Group 1: 17 patients; cirrhosis and septic shock and AI Group 2: 50 patients; no assessment of adrenal function | 17 patients of group 1 treated with 200 mg hydrocortisone/d vs 50 patients not treated | Mortality: group 1 32% vs 62% in group 2 in ICU (P = 0.03), 36% vs 68% (P = 0.003) in hospital Septic shock resolved in 96% vs 58% in group 2 (P = 0.001) |
| Marik et al[4] | Retrospective; 2002-2004; United States | 140 patients vasopressor depended with ALD or CLD and AI | 300 mg hydrocortisone/d | Reduction in dose of norepinephrin in the 24 h (P = 0.02) in those with AI treated with hydrocortisone and increase in those with AI not treated (P = 0.04) Mortality: 26% in those treated with steroids and 46% in not treated (P = 0.002) |
| Harry et al[69] | Retrospective; 1999-2001; United Kingdom | 40 patients with ALD or AOCLD required vasopressors | 20 patients treated with 300 mg hydrocortisone/d vs 20 patients not treated | In the group of 20 patients treated, there was reduction in doses of norepinephrin, higher risk of infections and no benefit in survival compared with the 20 patients not treated |
- Citation: Karagiannis AK, Nakouti T, Pipili C, Cholongitas E. Adrenal insufficiency in patients with decompensated cirrhosis. World J Hepatol 2015; 7(8): 1112-1124
- URL: https://www.wjgnet.com/1948-5182/full/v7/i8/1112.htm
- DOI: https://dx.doi.org/10.4254/wjh.v7.i8.1112