The clinical course of alcoholic cirrhosis: effects of hepatic metabolic capacity, alcohol consumption, and hyponatremia – a historical cohort study

BMC Research Notes

Hendrik Vilstrup²  Per Kragh Andersen¹  Peter Ott²  Peter Jepsen³ 

[1]Department of Biostatistics, Institute of Public Health, University of Copenhagen, Copenhagen, Denmark

[2]Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, Aarhus, Denmark

[3]Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark

关键词: Prognosis;    Variceal bleeding;    Ascites;    Hepatic encephalopathy;    Alcoholic liver disease;   

Others  :  1165659
DOI  :  10.1186/1756-0500-5-509

 received in 2012-06-20, accepted in 2012-09-14,  发布年份 2012

【 摘 要 】

Background

The cirrhosis complications hepatic encephalopathy, ascites, and variceal bleeding increase mortality but develop in random sequence. Therefore prognoses based on the presence or absence of these clinical complications are inherently inaccurate, and other determinants of the clinical course should be identified. Here we present our study of patho-etiological factors that may be causally involved in the development of specific complications to alcoholic cirrhosis; it was based on a model of cirrhosis pathophysiology encompassing hepatic metabolic capacity, continued alcohol consumption, and circulatory dysfunction.

Methods

We followed a Danish community-based cohort of 466 patients with alcoholic cirrhosis. Stratified Cox regression was used to examine the effects of GEC (a measure of hepatic metabolic capacity), alcohol consumption, and plasma sodium concentration (a measure of circulatory dysfunction) on the hazard rates of first-time hepatic encephalopathy, first-time ascites, first-time variceal bleeding, and mortality. We adjusted for confounding by comorbidity, gender, and age. Data on risk factors and confounders were updated during follow-up.

Results

A low GEC increased the risk of first-time hepatic encephalopathy (hazard ratio [HR] 1.21 per 0.1 mmol/min GEC loss, 95% CI 1.11-1.31), but was unassociated with other adverse events. Alcohol consumption increased the risk of first-time ascites (HR 3.18, 95% CI 1.19-8.47), first-time variceal bleeding (HR 2.78, 95% CI 1.59-4.87), and mortality (HR 2.45, 95% CI 1.63-3.66), but not the risk of first-time hepatic encephalopathy. Hyponatremia increased the risk of all adverse events.

Conclusions

Reduced hepatic metabolic capacity, alcohol consumption, and hyponatremia were causally involved in the development of specific complications to alcoholic cirrhosis.

【 授权许可】

   
2012 Jepsen et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Jepsen P, Ott P, Andersen PK, Sørensen HT, Vilstrup H: The clinical course of alcoholic liver cirrhosis: A Danish population-based cohort study. Hepatology 2010, 51:1675-1682.
• [2]Gerlach JC, Brayfield C, Puhl G, Borneman R, Müller C, Schmelzer E, Zeilinger K: Lidocaine/monoethylglycinexylidide test, galactose elimination test, and sorbitol elimination test for metabolic assessment of liver cell bioreactors. Artif Organs 2010, 34:462-472.
• [3]Jepsen P, Vilstrup H, Ott P, Keiding S, Andersen PK, Tygstrup N: The galactose elimination capacity and mortality in 781 Danish patients with newly-diagnosed liver cirrhosis: A cohort study. BMC Gastroenterol 2009, 9:50. BioMed Central Full Text
• [4]Saunders JB, Walters JRF, Davies P, Paton A: A 20-year prospective study of cirrhosis. BMJ 1981, 282:263-266.
• [5]Kim WR, Biggins SW, Kremers WK, Wiesner RH, Kamath PS, Benson JT, Edwards E, Therneau TM: Hyponatremia and mortality among patients on the liver-transplant waiting list. N Engl J Med 2008, 359:1018-1026.
• [6]Jepsen P, Vilstrup H, Andersen PK, Lash TL, Sørensen HT: Comorbidity and survival of Danish cirrhosis patients: A nationwide population-based cohort study. Hepatology 2008, 48:214-220.
• [7]D'Amico G, Garcia-Tsao G, Pagliaro L: Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. J Hepatol 2006, 44:217-231.
• [8]Frank L: When an entire country is a cohort. Science 2000, 287:2398-2399.
• [9]Christensen E, Altman DG, Neuberger J, de Stavola BL, Tygstrup N, Williams R: Updating prognosis in primary biliary cirrhosis using a time-dependent Cox regression model. Gastroenterology 1993, 105:1865-1876.
• [10]Yun BC, Kim WR: Hyponatremia in hepatic encephalopathy: An accomplice or innocent bystander? Am J Gastroenterol 2009, 104:1390-1391.
• [11]Green RM, Flamm S: AGA technical review on the evaluation of liver chemistry tests. Gastroenterology 2002, 123:1367-1384.
• [12]Prakash R, Mullen KD: Mechanisms, diagnosis and management of hepatic encephalopathy. Nat Rev Gastroenterol Hepatol 2010, 7:515-520.
• [13]Luca A, Garcia-Pagan JC, Bosch J, Feu F, Caballeria J, Groszmann RJ, Rodes J: Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology 1997, 112:1284-1289.
• [14]Vorobioff J, Groszmann RJ, Picabea E, Gamen M, Villavicencio R, Bordato J, Morel I, Audano M, Tanno H, Lerner E, Passamonti M: Prognostic value of hepatic venous pressure gradient measurements in alcoholic cirrhosis: A 10-year prospective study. Gastroenterology 1996, 111:701-709.
• [15]Kleber G, Sauerbruch T, Ansari H, Paumgartner G: Prediction of variceal hemorrhage in cirrhosis: A prospective follow-up study. Gastroenterology 1991, 100:1332-1337.
• [16]Linderoth G, Jepsen P, Schønheyder HC, Johnsen SP, Sørensen HT: Short-term prognosis of community-acquired bacteremia in patients with liver cirrhosis or alcoholism: A population-based cohort study. Alcohol Clin Exp Res 2006, 30:636-641.
• [17]Boffetta P, Hashibe M: Alcohol and cancer. Lancet Oncol 2006, 7:149-156.
• [18]Lucey MR, Connor JT, Boyer TD, Henderson JM, Rikkers LF: Alcohol consumption by cirrhotic subjects: Patterns of use and effects on liver function. Am J Gastroenterol 2008, 103:1698-1706.
• [19]Guevara M, Baccaro ME, Torre A, Gómez-Ansón B, Ríos J, Torres F, Rami L, Monte-Rubio GC, Martín-Llahí M, Arroyo V, Ginès P: Hyponatremia is a risk factor of hepatic encephalopathy in patients with cirrhosis: A prospective study with time-dependent analysis. Am J Gastroenterol 2009, 104:1382-1389.
• [20]Sanyal AJ, Bosch J, Blei A, Arroyo V: Portal hypertension and its complications. Gastroenterology 2008, 134:1715-1728.