Retrospective Cohort Study
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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Nov 6, 2018; 6(13): 611-623
Published online Nov 6, 2018. doi: 10.12998/wjcc.v6.i13.611
Table 1 Baseline characteristics of patients
Variable1 Acute responders, n = 52 Acute nonresponders, n = 24 P valueAge in yr 57.8 ± 10.2 57.1 ± 8.7 0.764 Sex (male) 40 (76.9) 19 (79.2) 1 Body mass index 28.6 ± 5.0 28.5 ± 4.8 0.918 Associated diseases2 34 (65.4) 16 (66.7) 1 Regular medication Statins 3 (5.8) 3 (12.5) 0.373 Metformin 10 (19.2) 5 (20.8) 1 Antiplatelet agent 7 (13.5) 1 (4.2) 0.423 Anticoagulation 2 (3.8) 0 (0) 1 Etiology of liver disease3 0.971 Alcohol 34 (65.4) 17 (70.8) 0.794 Hepatitis C 4 (7.7) 2 (8.3) 1 Alcohol + hepatitis C 4 (7.7) 2 (8.3) 1 Other 10 (19.2) 3 (12.6) 0.744 Active alcoholism At first hemodynamic study 11 (27.5) 4 (20.0) 0.753 During follow-up 3 (7.9) 2 (10.5) 1 Active hepatitis C At first hemodynamic study 8 (100) 4 (100) 1 During follow-up 4 (50) 2 (50.0) 1 Esophageal varices 49 (94.2) 21 (87.5) 0.310 Small 3 (6.1) 3 (14.3) 0.355 Large 46 (93.9) 18 (85.7) Gastric varices 3 (5.8) 3 (12.5) 0.373 Red signs 10 (20.0) 3 (13.6) 0.742 Hemoglobin in g/dL 12.7 ± 2.1 12.7 ± 2.2 0.994 Platelet count as × 103 /μL 102 ± 45 122 ± 53 0.100 Prothrombin time as INR 1.36 ± 0.24 1.39 ± 0.26 0.685 Bilirubin in mg/dL3 1.7 ± 1.1 2.8 ± 4.5 0.235 Albumin in g/dL3 3.6 ± 0.6 3.6 ± 0.6 0.878 Creatinine in mg/dL 0.72 ± 0.24 0.73 ± 0.24 0.900 Sodium in mEq/L 139 ± 3 138 ± 4 0.108 Hyponatremia (< 135) 3 (6.0) 5 (20.8) 0.103 Ascites 31 (59.6) 14 (58.3) 1 Refractory ascites 1 (1.9) 1 (4.2) 0.535 Hepatic encephalopathy 8 (15.4) 4 (16.7) 1 Spontaneous bacterial peritonitis 4 (7.7) 0 (0) 0.301 Hepatocellular carcinoma 3 (5.8) 1 (4.2) 1 No previous decompensation 21 (40.4) 9 (37.5) 1 MELD 11.5 ± 3.2 12.3 ± 4.4 0.353 Child-Pugh score 6.5 ± 1.4 6.7 ± 1.6 0.560 A/B/C, % 58/40/2 50/42/8 0.388 Propranolol dose in acute test in mg 12.1 ± 2.4 12.6 ± 2.8 0.44 Free hepatic venous pressure in mmHg 10.8 ± 4.3 11.7 ± 4.7 0.386 Change from baseline, % +18.5 ± 23.5 +3.4 ± 11.2 < 0.001 Wedged hepatic venous pressure in mmHg 30.0 ± 5.4 30.4 ± 5.5 0.581 Change from baseline, % -6.6 ± 5.3 -1.2 ± 6.3 < 0.001 Hepatic venous pressure gradient in mmHg3 18.8 ± 3.7 18.7 ± 3.7 0.854 Change from baseline, % -17.8 ± 7.7 -3.9 ± 5.6 < 0.001 Decrease by > 10%, % 96.2 0 < 0.001 Decrease to < 12 mmHg, % 23.1 0 0.014 Mean arterial pressure in mmHg 99 ± 9 95 ± 11 0.145 Change from baseline, % -5.6 ± 12.2 +2.7 ± 9.7 0.008 Heart rate as bpm 78 ± 13 81 ± 15 0.315 Change from baseline, % -18.8 ± 8.5 -19.4 ± 7.3 0.779 Right atrial pressure in mmHg 7.0 ± 2.9 7.3 ± 3.8 0.712 Change from baseline, % +51.4 ± 41.1 +45.1 ± 45.3 0.565 Pulmonary arterial pressure in mmHg 18.3 ± 4.9 17.8 ± 5.0 0.700 Change from baseline, % +18.6 ± 18.9 +16.1 ± 14.9 0.606 Pulmonary wedge pressure in mmHg 11.8 ± 4.1 11.4 ± 5.0 0.711 Change from baseline, % +28.3 ± 37.2 +38.4 ± 54.9 0.384
Table 2 Characteristics of chronic hemodynamic responders and chronic nonresponders in each group
Traditional NSBB Carvedilol Variable1 CR, n = 15 CNR, n = 12 P valueCR, n = 9 CNR, n = 4 P valueAge in yr 58.9 ± 8.3 57.8 ± 10.3 0.766 59.2 ± 9.2 57.3 ± 6.8 0.685 Sex (male) 12 (80.0) 9 (75.0) 1 8 (88.9) 3 (75.0) 1 Body mass index 28.8 ± 2.1 29.1 ± 4.3 0.795 30.5 ± 5.9 28.0 ± 3.6 0.370 Associated diseases2 12 (80.0) 10 (83.3) 1 7 (77.8) 2 (50) 0.530 Regular medication Statins 2 (13.3) 1 (8.3) 1 2 (22.2) 0 (0) 1 Metformin 3 (20) 2 (16.7) 1 1 (11.1) 2 (50.0) 0.203 Antiplatelet agent 1 (6.7) 3 (25) 0.294 0 (0) 0 (0) 1 Anticoagulation 1 (6.7) 1 (8.3) 1 0 (0) 0 (0) 1 Etiology of liver disease 0.063 1 Alcohol 14 (93.3) 6 (50.0) 0.024 8 (88.9) 4 (100) 1 Hepatitis C 0 (0) 2 (16.7) 0.188 0 (0) 0 (0) 1 Alcohol + hepatitis C 0 (0) 2 (16.7) 0.188 0 (0) 0 (0) 1 Other 1 (6.7) 2 (16.6) 0.569 1 (11.1) 0 (0) 1 Active alcoholism 0 (0) 1 (9.1) 0.440 1 (12.5) 1 (25.0) 1 Active hepatitis C 0 (0) 0 (0) 1 0 (0) 0 (0) 1 Esophageal varices 14 (93.3) 11 (91.7) 6 (66.7) 4 (100) Small, % 0 0 1 33.3 0 0.467 Large, % 100 100 66.7 100 Gastric varices 1 (6.7) 1 (8.3) 1 3 (33.3) 0 (0.0) 0.497 Red signs 3 (20.0) 1 (8.3) 0.605 1 (12.5) 1 (25.0) 1 Baseline MELD 11.5 ± 2.9 11.0 ± 3.4 0.660 12.3 ± 6.3 12.8 ± 1.0 0.852 Change from baseline, % -4.1 ± 14.2 0.8 ± 16.8 0.426 -0.8 ± 28.0 -7.9 ± 14.5 0.565 Baseline Child-Pugh score 6.7 ± 1.4 6.1 ± 1.1 0.225 6.8 ± 2.0 7.0 ± 0.0 0.753 Change from baseline, % -3.0 ± 12.1 0.3 ± 9.9 0.465 -7.2 ± 13.7 0.0 ± 11.6 0.363 Baseline Child-Pugh class A/B/C, % 53/47/0 42/58/0 1 67/11/22 0/100/0 0.010 Change from baseline A/B/C, % 67/33/0 67/33/0 1 67/33/0 75/25/0 0.266 Hemoglobin in g/dL 12.8 ± 2.1 14.0 ± 2.2 0.150 12.8 ± 2.0 14.5 ± 2.7 0.319 Platelet count as × 103 /μL 107 ± 35 86 ± 27 0.102 91 ± 32 114 ± 41 0.367 Prothrombin time as INR 1.37 ± 0.18 1.32 ± 0.15 0.498 1.28 ± 0.21 1.35 ± 0.04 0.358 Bilirubin in mg/dL 1.3 ± 0.7 1.6 ± 0.8 0.349 1.57 ± 0.96 1.93 ± 1.19 0.619 Albumin in g/dL 3.5 ± 0.5 3.7 ± 0.4 0.397 3.9 ± 0.4 3.5 ± 0.4 0.080 Creatinine in mg/dL 0.72 ± 0.18 0.78 ± 0.16 0.415 0.71 ± 0.25 0.66 ± 0.05 0.590 Sodium in mEq/L 140 ± 2 140 ± 3 0.342 139 ± 2 139 ± 2 0.638 Ascites 9 (60.0) 6 (50.0) 0.707 5 (55.6) 4 (100) 0.228 Hepatic encephalopathy 4 (26.7) 0 (0) 0.106 0 (0) 1 (25.0) 0.308 SBP 3 (20.0) 0 (0) 0.231 0 (0) 0 (0) 1 Hepatocellular carcinoma 0 (0) 0 (0) 1 0 (0) 0 (0) 1 Hemodynamic variables Weeks between studies 24.2 ± 12.3 29.1 ± 13.4 0.327 26.2 ± 14.0 31.9 ± 29.4 0.732 Propranolol dose in mg 136 ± 111 165 ± 123 0.677 Nadolol dose in mg 87 ± 47 95 ± 21 0.659 Carvedilol dose in mg 18.8 ± 12.5 14.1 ± 7.9 0.434 FHVP in mmHg 10.0 ± 2.7 11.2 ± 2.4 0.250 11.9 ± 3.9 11.0 ± 2.1 0.583 Change from baseline, % 36.4 ± 62.6 -3.5 ± 30.4 0.054 10.4 ± 31.1 1.8 ± 8.4 0.458 WHVP in mmHg 29.6 ± 2.5 29.0 ± 2.9 0.622 28.5 ± 5.7 31.1 ± 5.1 0.437 Change from baseline, % -8.5 ± 15.9 0.7 ± 10.6 0.100 -9.5 ± 9.5 5.8 ± 9.2 0.034 HVPG in mmHg 19.5 ± 2.9 17.9 (2.5) 0.126 16.4 ± 2.5 20.1 ± 3.2 0.100 Change from baseline, % - 26.0 ± 12.5 5.7 ± 17.7 < 0.0001 -21.2 ± 12.8 -7.6 ± 13.3 0.012 Decrease by > 10% 15 (100) 0 (0) < 0.0001 8 (88.9) 0 (0) 0.007 Decrease < 12 mmHg 3 (20) 0 (0) 0.231 4 (44.0) 0 (0) 0.228 MAP in mmHg 99 ± 9 98 ± 8 0.642 96 ± 12 97 ± 11 0.897 Change from baseline, % -5.6 ± 7.3 0.3 ± 12.1 0.192 6.6 ± 17.8 -2.0 ± 7.7 0.273 Heart rate as bpm 77 ± 11 77 ± 16 0.902 82 ± 11 76 ± 9 0.311 Change from baseline, % -26.2 ± 12.5 -19.8 ± 14.9 0.265 -26.8 ± 10.6 -17.1 ± 7.7 0.102 Right atrial pressure in mmHg 6.4 ± 2.1 7.4 ± 2.3 0.264 8.4 ± 5.0 7.0 ± 1.4 0.458 Change from baseline, % 74.2 ± 82.3 24.1 ± 66.5 0.100 35.5 ± 97.2 23.2 ± 27.0 0.733 PAP in mmHg 18.3 ± 4.2 17.9 ± 4.3 0.813 20.1 ± 4.8 17.5 ± 3.1 0.281 Change from baseline, % 35.3 ± 42.8 17.4 ± 27.6 0.222 -4.5 ± 18.7 27.5 ± 43.9 0.242 PWP in mmHg 11.5 ± 3.3 11.8 ± 3.5 0.819 12.8 ± 5.3 12.0 ± 3.2 0.751 Change from baseline, % 50.9 ± 57.5 32.0 ± 61.2 0.417 5.5 ± 37.1 14.8 ± 10.8 0.506
Table 3 Clinical outcomes during follow-up in patients with acute response treated with traditional nonselective beta-blockers and in patients without acute response treated with carvedilol
Variable1 Traditional NSBB, n = 52 Carvedilol, n = 24 P valueDecompensation (global)2 12 (23.1) 8 (33.3) 0.405 First decompensation 3 (14.3) 2 (22.2) 0.622 Further decompensation 9 (29.0) 6 (40.0) 0.514 Portal hypertension-related bleeding 2 (3.8) 3 (12.5) 0.318 Ascites Overall 7 (13.5) 4 (16.7) 0.734 De novo ascites3 (5.8) 1 (4.2) 1 Spontaneous bacterial peritonitis 1 (1.9) 2 (8.3) 0.233 Hepatorenal syndrome 1 (1.9) 1 (4.2) 0.535 Hepatic encephalopathy Overall 7 (13.5) 5 (20.8) 0.502 De novo hepatic encephalopathy3 (5.8) 4 (16.7) 0.191 Hepatocellular carcinoma (de novo ) 3 (6.1) 0 (0) 0.546 Portal thrombosis 5 (9.6) 3 (12.5) 0.702 Nonselective beta-blocker Propranolol dose, n /mg per day 35 / 107.6 Nadolol dose, n /mg per day 17 / 83.5 Carvedilol dose, n /mg per day 24 / 9.2 Chronic hemodynamic response Change from baseline HVPG, % -11.9 ± 21.8 -12.2 ± 18.5 0.965 ≥ 10% reduction in HVPG 15 (55.6) 9 (69.2) 0.503 ≥ 20% reduction in HVPG 8 (29.6) 4 (30.8) 1 Decrease to < 12 mmHg 3 (11.1) 4 (30.8) 0.187 Lost to follow-up, n /% 14 (26.9) 3 (12.5) 0.238 Betablocker intolerance 6 (11.5) 1 (4.2) 0.421 Change to carvedilol after second hemodynamic study 5 (7.7) Ceased follow-up 3 (5.8) 2 (8.3) 0.648
Table 4 Results of univariate and multivariate analyses for variables associated with risk of decompensation
Variables Univariable Multivariable HR (95%CI) P valueHR (95%CI) P valueAge as per year increase 0.96 (0.91-1.01) 0.093 0.97 (0.92-1.02) 0.246 Active alcoholism 2.55 (0.71-9.16) 0.152 Size of varices 1.71 (0.23-12.90) 0.602 Red signs 1.89 (0.62-5.73) 0.262 MELD as per 1 point increase1 1.12 (0.99-1.26) 0.072 Child class 0.039 0.071 B vs A 2.66 (1.03-6.87) 0.044 2.39 (0.90-6.36) 0.081 C vs A 5.87 (1.20-28.63) 0.029 6.00 (1.09-32.97) 0.039 Platelets as per 1 × 106 1.00 (0.99-1.01) 0.641 Creatinine as per 1 mg/dL increase 0.17 (0.01-2.74) 0.209 Bilirubin as per 1 mg/dL increase2 1.21 (1.09-1.35) < 0.001 Albumin as per 1 g/L increase2 0.43 (0.20-0.94) 0.035 INR as per 1 point increase 1.16 (0.20-6.56) 0.871 HVGP as per 1 mmHg increase 1.07 (0.96-1.20) 0.209 MAP as per 1 mmHg increase 0.98 (0.94-1.03) 0.497 Previous ascites2 2.42 (0.88-6.65) 0.088 Previous hepatocellular carcinoma 2.44 (0.55-10.77) 0.240 Previous hepatic encephalopathy 7.29 (2.78-19.13) < 0.001 8.03 (2.76-23.37) < 0.001 No previous decompensation1 0.42 (0.15-1.16) 0.093 Acute hemodynamic response 0.70 (0.29-1.71) 0.434 0.74 (0.28-1.95) 0.545 Chronic hemodynamic response-10% 0.49 (0.13-1.83) 0.287 Chronic hemodynamic response-20% 0.24 (0.03-1.89) 0.174
Table 5 Results of univariate analysis for variables associated with risk of death
Variables Univariable HR (95%CI) P valueAge as per year increase 1.01 (0.93-1.09) 0.896 Active alcoholism 0.04 (0.00-2577625.31) 0.731 Size of varices 0.28 (0.03-2.55) 0.259 MELD as per 1 point increase 0.91 (0.72-1.16) 0.448 Child score as per 1 point increase 0.98 (0.59-1.67) 0.941 Platelets as per 1 × 106 0.98 (0.95-1.00) 0.088 Creatinine as per 1 mg/dL increase 0.01 (0.00-4.55) 0.134 Bilirubin as per 1 mg/dL increase 0.90 (0.59-1.39) 0.642 Albumin as per 1 g/L increase 0.65 (0.17-2.43) 0.521 INR as per 1 point increase 0.06 (0.00-4.39) 0.196 HVGP as per 1 mmHg increase 1.12 (0.94-1.33) 0.195 MAP as per 1 mmHg increase 1.01 (0.93-1.10) 0.791 Previous ascites 1.73 (0.34-8.96) 0.511 Previous hepatocellular carcinoma 3.41 (0.40-29.45) 0.264 Previous hepatic encephalopathy 2.72 (0.53-14.08) 0.233 No previous decompensation 0.58 (0.11-3.01) 0.518 Acute hemodynamic response 2.99 (0.36-24.91) 0.312 Chronic hemodynamic response-10% 0.23 (0.02-2.57) 0.234 Chronic hemodynamic response-20% 0.02 (0.00-427.79) 0.455
Citation: Fortea JI, Puente Á, Ruiz P, Ezcurra I, Vaquero J, Cuadrado A, Arias-Loste MT, Cabezas J, Llerena S, Iruzubieta P, Rodríguez-Lope C, Huelin P, Casafont F, Fábrega E, Crespo J. Impact of an acute hemodynamic response-guided protocol for primary prophylaxis of variceal bleeding. World J Clin Cases 2018; 6(13): 611-623
URL: https://www.wjgnet.com/2307-8960/full/v6/i13/611.htm
DOI: https://dx.doi.org/10.12998/wjcc.v6.i13.611