Predictors of In-Hospital Mortality in patients with hepatocellular carcinoma and Acute Variceal bleeding
Keywords:
acute upper gastrointestinal bleeding, MELD score, complications of liver cirrhosis, hepatocellular carcinoma, prognosisAbstract
Introduction: Detection of hepatocellular carcinoma (HCC) in cirrhotic patients remains a serious, unsolved problem, and the risk factors for acute variceal bleeding (AVB) in HCC patients remain unclear. This study aimed to determine the in-hospital mortality (IHM) and factors influencing the clinical outcomes of AVB in patients with liver cirrhosis and HCC.
Methods: This was a retrospective, non-randomized, clinical study that was conducted in 2014. The study was conducted on 70 patients with liver cirrhosis and HCC presenting by acute upper gastrointestinal bleeding (AUGIH). All patients were examined endoscopically within 24 hours from presentation and bleeding varices accounted for AUGIH. Full medical history, clinical examination, and laboratory and radiologic data were collected from admission charts, and hospital medical records were statistically analyzed with SSPS version 22.
Results: Thirty-two patients (45.7%) survived and 38 died (54.3%). Survivors are more likely to be Child-Pugh class A or B, and the non-survivors were class C. The Model for End-Stage Liver Disease (MELD) was highly predictive of IHM at an optimized cut-off value of ≥ 12.9. Higher esophageal varices grades and presence of active bleeding on index endoscopy were significant (p < 0.01) in the non-survivors compared to survivors. Complications of liver cirrhosis and associated major comorbidity were significantly higher (p < 0.01) in the non-survivors than the survivors. Univariate logistic regression analysis identified higher Grade Esophageal Varices and number of transfused packed red blood cells units as two independent predictors of IHM.
Conclusions: IHM was particularly high (54.3%) among HCC patients with AVB who had MELD score > 12.9, higher grade Esophageal Varices, active bleeding on index endoscopy, more increased needs for blood transfusion, longer hospital stay, decompensated liver disease with major comorbidity.
References
El-Serag HB, Mason AC. Rising incidence of hepatocellular carcinoma in the United States. N Engl J Med
; 340: 745-50. doi: 10.1056/NEJM199903113401001, PMid: 10072408
Centers for Disease Control and Prevention (CDC). Hepatocellular carcinoma - United States, 2001-2006.
MMWR Morb Mortal Wkly Rep. 2010;59: 517-20. PMid: 20448528
Sayana H., Yousef O. and Clarkston WK. Massive upper gastrointestinal hemorrhage due to invasive
hepatocellular carcinoma and hepato-gastric fistula. World J Gastroenterol. 2013; 19 (42): 7472-5. doi:
3748/wjg.v19.i42.7472, PMid: 24259980, PMCid: PMC3831231
Yeo W, Sung JY, Ward SC, Chung SC, Lee WY, Li AK, et al. A prospective study of upper gastrointestinal
hemorrhage in patients with hepatocellular carcinoma. Dig Dis Sci. 1995; 40: 2516-21. doi:
1007/BF02220435, PMid: 8536505
Smith JL, Graham DY. Variceal hemorrhage: a critical evaluation of survival analysis. Gastroenterology 1982;
: 968. PMid: 7037525
De Dombal FT, Clarke JR, Clamp SE, et al. Prognostic factors in upper GI bleeding. Endoscopy 1986; 18:6s.
doi: 10.1055/s-2007-1018418, PMid: 3519197
Graham DY, Smith JL. The course of patients after variceal hemorrhage. Gastroenterology 1981; 80: 800.
PMid: 6970703
Grace ND. Prevention of initial variceal hemorrhage. Gastroenterol Clin North Am.1992; 21:149. PMid:
Bettinger D., Knuppel E, Euringer W, Spangenberg HC, Rossle M, Thimme R and Schultheiss M. Efficacy and
safety of transjugular intrahepatic portosystemic shunt (TIPS) in 40 patients with hepatocellular carcinoma.
Aliment. Pharmacol.Ther. 2015; 41(1): 126-36. doi: 10.1111/apt.12994, PMid: 25329493
Ruzzenente A, Valdegamberi A, Campagnaro T, et al. Hepatocellular carcinoma in cirrhotic patients withportal
hypertension: is liver resection always contraindicated? World J. Gastroenterol. 2011; 17: 5083–8. doi:
3748/wjg.v17.i46.5083, PMid: 22171142, PMCid: PMC3235591
Santambrogio R, Kluger MD, Costa M, et al. Hepatic resection for hepatocellular carcinoma in patients with
Child-Pugh’s A cirrhosis: is clinical evidence of portal hypertension a contraindication? HPB 2013; 15: 78-84.
doi: 10.1111/j.1477-2574.2012.00594.x,PMid: 23216782, PMCid: PMC3533715
Kanwal F, Befeler A, Chari RS, et al. Potentially curative treatment inpatients withhepatocellular cancer–results
from the liver cancer research network. Aliment Pharmacol Ther.2012; 36: 257–65. doi: 10.1111/j.1365- 2036.2012.05174.x, PMid: 22670798
Villanueva C, Piqueras M, Aracil C, et al. A randomized controlled trial comparing ligation and sclerotherapy
as emergency endoscopic treatment added to somatostatin in acute Variceal bleeding. J. Hepatol. 2006; 45: 560- 7. doi: 10.1016/j.jhep.2006.05.016, PMid: 16904224
Singal AK, Jampana SC, Singal V, KuoYF. Hepatocellular carcinoma predicts in-hospital mortality from acute
variceal hemorrhage among patients with cirrhosis. J Clin Gastroenterol. 2012; 46: 613–9. doi:
1097/MCG.0b013e318256b670, PMid: 22772741
European Association For The Study Of The Liver; European Organization For Research And Treatment Of
Cancer. EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma. J. Hepatol. 2012;
: 908-43. doi: 10.1016/j.jhep.2011.12.001, PMid: 22424438
Bruix J, Sherman M. Management of hepatocellular carcinoma: an update. Hepatology 2011; 53: 1020–2. doi:
1002/hep.24199, PMid: 21374666, PMCid: PMC3084991
Bettinger D, Knuppel E, Euringer W, Spangenberg HC, Rossle M, Thimme R, et al. Efficacy and safety of
transjugular intrahepatic portosystemic shunt (TIPS) in 40 patients with hepatocellular carcinoma." Aliment
Pharmacol Ther. 2015; 41(1): 126-36. doi: 10.1111/apt.12994, PMid: 25329493
Pagliaro L, D’Amico G, Pasta L, Tine` F, Aragona E, Politi F, et al. Efficacy and efficiency of treatments in
portal hypertension. In: de Franchis R, ed. Portal Hypertension II. Proceedings of the second Baveno
International Consensus Workshop on Definitions, Methodology and Therapeutic Strategies. Oxford: Blackwell
Science 1996; 159-179.
D’Amico G, De Franchis R, and a Cooperative Study Group. Upper Digestive Bleeding in Cirrhosis. Posttherapeutic Outcome and Prognostic Indicators. Hepatology 2003;38: 599-612. doi: 10.1053/jhep.2003.50385,
PMid: 12939586
El-Serag HB, Everhart JE. Improved survival after variceal hemorrhage over an 11-year period in the
Department of Veterans Affairs. Am J Gastroenterol. 2000; 95: 3566-73. doi: 10.1111/j.1572- 0241.2000.03376.x, PMid: 11151893
Chalasani N, Kahi C, Francois F, Pinto A, Marathe A, Bini EJ, et al. Improved patient survival after acute
variceal bleeding: a multicenter, cohort study. Am J Gastroenterol. 2003; 98: 653-9. doi: 10.1111/j.1572- 0241.2003.07294.x, PMid: 12650802
Garcia-Tsao G, D´Amico G, Abraldes JG. Predictive models in Portal Hypertension. In Portal Hypertension
Proceedings of the fourth Baveno International Consensus Workshop on methodology of diagnosis and
treatment. Ed de Franchis R. 2006; 47-100.
Chen CH, Sheu JC, Huang GT, et al. Characteristics of hepatocellular carcinoma presenting with variceal
bleeding. J Gastroenterol Hepatol. 1998; 13:170-4. doi: 10.1111/j.1440-1746.1998.tb00633.x, PMid: 10221819
Magliocchetti N, Torchio P, Corraco G, Arico S, Favilli S. Prognostic factors for long-term survival in cirrhotic
patients after the first episode of liver decompensation. Ital. J. Gastroenterol Hepatol. 1997; 29:38-46. PMid:
D’Amico G, Garcia-Tsao G. and Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: A
systematic review of 118 studies. Journal of Hepatology 2006; 44, 217-31. doi: 10.1016/j.jhep.2005.10.013,
PMid: 16298014
Bambha K, Kim WR, Pedersen R, et al. Predictors of early rebleeding and mortality after acute variceal
hemorrhage in patients with cirrhosis. Gut 2008; 57, 814-20. doi: 10.1136/gut.2007.137489, PMid: 18250126
Maruyama A, Murabayashi K, Hayashi M, Nakano H, Isaji S, Uehara S, et al. Hepatocellular carcinoma
complicated by gastrointestinal hemorrhage caused by direct tumor invasion of stomach. J. Hepatobiliary
Pancreat. Surg. 2004; 6: 90-3. doi: 10.1007/s005340050089
Nicoll AJ, Ireton HJ, Crotty B. Gastrointestinal bleedingfrom hepatocellular carcinoma invading the stomach. J.
Gastroenterol Hepatol. 2004; 9: 533-5. doi: 10.1111/j.1440-1746.1994.tb01290.x
Chen CH, Sheu JC, Huang GT, Lee HS, Yang PM, Wong JM. Characteristics of hepatocellular carcinoma
presenting with variceal bleeding. J. Gastroenterol. Hepatol. 2004;13: 170-4. doi: 10.1111/j.1440- 1746.1998.tb00633.x
Han ML, Chen CC., Wu MS, et al. Predictors of in-hospital mortality after acute varicealbleeding in patients
with hepatocellular carcinoma and concurrent main portal vein thrombosis. Journal of Gastroenterology and
Hepatology 2004; 29: 344-51. doi: 10.1111/jgh.12341, PMid: 23870023
Lang BH, Poon RT, Fan ST, Wong J. Outcomes of patients with hepatocellular carcinoma presenting with
variceal bleeding. Am. J. Gastroenterol. 2004; 99: 2158-65. doi: 10.1111/j.1572-0241.2004.40336.x, PMid:
Sarin SK, Kumar A, Angus PW, Baijal SS, Baik SK, Bayraktar Y. Diagnosis and management of acute variceal
bleeding: Asian Pacific Association for Study of the Liver recommendation. Hepatol. Int. 2004; 5: 607-24. doi:
1007/s12072-010-9236-9, PMid: 21484145, PMCid: PMC3090560
Chojkier M, Laine L, Conn HO, Lerner E. Predictors ofoutcome in massive upper gastrointestinal hemorrhage.
J Clin Gastroenterol. 2004; 8:16-22. doi: 10.1097/00004836-198602000-00005
Patch D, Nikolopoulou V, McCormick A, Dick R, Armonis A, Wannamethee G. Factors related to early
mortality after TIPS for failed endoscopic therapy in acute variceal bleed. J Hepatol. 1997; 28:454-60. doi:
1016/S0168-8278(98)80320-6
Conn HO. Quantifying the severity of hepatic encephalopathy. In: Conn HO, Bircher J. Eds. Hepatic
Encephalopathy: Syndromes and Therapies. Bloomington Illinois: Medi-Ed Press. 1997; 13-26.
Meza-Junco J, Montano-Loza AJ, Baracos VE, Prado CM, Bain VG, Beaumont C, et al. Sarcopenia as a
prognostic index of nutritional status in concurrent cirrhosis and hepatocellular carcinoma. J Clin Gastroenterol.
; 47: 861-70. doi: 10.1097/MCG.0b013e318293a825, PMid: 23751844
Hsu CY, Huang YH, Hsia CY, Su CW, Lin HC, Loong CC, et al. A new prognostic model for hepatocellular
carcinoma based on total tumor volume: the Taipei Integrated Scoring System. J Hepatol. 2010; 53: 108-17.
doi: 10.1016/j.jhep.2010.01.038, PMid: 20451283
Lo GH. The use of transjugular intrahepatic portosystemic stent shunt (TIPS) in the management of portal
hypertensive bleeding. Journal of the Chinese Medical Association 1997;77 395-402. doi:
1016/j.jcma.2014.05.010, PMid: 25028297
Park DK, Um SH, Lee JW, et al. Clinical significance of variceal hemorrhage in recent years inpatients with
liver cirrhosis and esophageal varices. Journal of Gastroenterology and Hepatology 2004; 19, 1042-51. doi:
1111/j.1440-1746.2004.03383.x, PMid: 15304123
Sarin SK, Laiioid, Saxena SP, Murif NS, Makwana UK. Prevalence, Classification and Natural History of
Gastric Varices: A Long-term Follow-up Study in 568 Portal Hypertension Patients. Hepatology 1992; 16
(6).1343-9.
Amitrano L., Guardascione M A, Bennato R, Manguso F, Balzano A. MELD score and hepatocellular
carcinoma identify patients at different risk of short-term mortality among cirrhotics bleeding from esophageal
varices. Journal of Hepatology. 2005;42, 820-5. doi: 10.1016/j.jhep.2005.01.021, PMid: 15885352
Published
Issue
Section
License
Copyright (c) 2020 knowledge kingdom publishing
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.