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World J Gastroenterol. Jul 7, 2014; 20(25): 8005-8010
Published online Jul 7, 2014. doi: 10.3748/wjg.v20.i25.8005
Peculiar characteristics of portal-hepatic hemodynamics of alcoholic cirrhosis
Massimo Bolognesi, Alberto Verardo, Marco Di Pascoli
Massimo Bolognesi, Alberto Verardo, Marco Di Pascoli, Department of Medicine, University of Padua, Azienda Ospedaliera Università di Padova, 35128 Padova, Italy
Author contributions: Bolognesi M, Verardo A and Di Pascoli M have given substantial contributions to conception and design of the review, for drafting the article and revising it; all authors have given final approval of the version to be published.
Correspondence to: Massimo Bolognesi, MD, PhD, Department of Medicine, University of Padua, Azienda Ospedaliera Università di Padova, Clinica Medica 5, Via Giustiniani 2, 35128 Padova, Italy. massimo.bolognesi@unipd.it
Telephone: +39-49-8212383 Fax: +39-49-8754179
Received: October 24, 2013
Revised: December 31, 2013
Accepted: February 26, 2014
Published online: July 7, 2014

Abstract

Alcohol-related cirrhosis is a consequence of heavy and prolonged drinking. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis develop portal hypertension and the hepatic, splanchnic and systemic hemodynamic alterations that follow. However, in alcoholic cirrhosis, some specific features can be observed. Compared to viral cirrhosis, in alcohol-related cirrhosis sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced. Moreover, alcohol consumption can acutely increase portal pressure and portal-collateral blood flow. Alcoholic cardiomyopathy, another pathological consequence of prolonged alcohol misuse, may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis. The aim of this review was to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis. The knowledge of the specific characteristics of this pathological condition can be helpful in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.

Key Words: Alcohol-related cirrhosis, Portal hypertension, Splanchnic flow, Hyperdynamic circulatory syndrome, Alcohol-related cardiomyopathy

Core tip: Patients with alcoholic cirrhosis develop portal hypertension and hemodynamics alterations similarly to patients with cirrhosis of other etiologies, but some specific features can be observed. Compared to viral cirrhosis, sinusoidal pressure is generally higher, hepatic venous pressure gradient reflects portal pressure better, the portal flow perfusing the liver is reduced despite an increase in liver weight, the prevalence of reversal portal blood flow is higher, a patent paraumbilical vein is a more common finding and signs of hyperdynamic circulations, such as an increased cardiac output and decreased systemic vascular resistance, are more pronounced.



INTRODUCTION

Alcoholic liver disease is a consequence of heavy and prolonged drinking that can progress from hepatic steatosis through to steatohepatitis, liver fibrosis and eventually cirrhosis. The molecular pathogenesis is a multifactorial process involving alcohol metabolism and secondary mechanisms such as oxidative stress, endotoxin, cytokines and immune regulators[1]. Similarly to patients with cirrhosis of other etiologies, patients with alcoholic cirrhosis are prone to develop portal hypertension. Several studies show that only one third of patients with alcoholic cirrhosis are hospitalized before decompensation, and in the first year after discharge they have a 6% risk of developing variceal bleeding, a 4% risk of developing hepatic encephalopathy and a 20% risk of developing ascites[2]. The main factor leading to decompensation of alcohol-related cirrhosis is the persistence of regular alcohol consumption.

The aim of this review is to assess the portal-hepatic changes that occur in alcohol-related cirrhosis, focusing on the differences observed in comparison with patients with viral cirrhosis.

PORTAL-HEPATIC HEMODYNAMICS

In cirrhosis, portal pressure increases because of enhanced resistance to portal outflow[3-5] and an increase in splanchnic blood flow[6,7]. Several vasoactive systems and molecules activated in portal hypertension, first of all nitric oxide (NO)[8,9], determine a marked splanchnic vasodilatation, which is responsible for the increased splanchnic blood flow and the onset of hyperdynamic circulation. This is characterized by increased cardiac output and heart rate, splanchnic arterial vasodilatation and reduced arterial blood pressure[10-13]. Central blood volume is reduced, because of its displacement to splanchnic circulation, resulting into a central hypovolemia[14]. These events lead to a secondary and massive activation of counter-regulatory systems, mainly the renin-angiotensin-aldosterone system and the sympathetic nervous system[15,16]. However, in cirrhosis, the presence of autonomic dysfunction causes a reduced sensitivity to vasoconstrictors in the systemic and splanchnic vessels that contributes to the splanchnic vasodilatation and hyperdynamic circulation caused by NO and other vasodilating systems[17-20].

In alcoholic cirrhosis, portal vein pressure is influenced by the consumption of alcohol: Klein et al[21] showed that after one year of abstinence, portal vein pressure and the size of esophageal varices almost halved. Resuming oral alcohol intake significantly increased portal pressure and portal-collateral blood flow, worsening the portal hypertensive syndrome[21]. In patients with alcohol-induced cirrhosis, besides the chronic effects on the liver tissue and hemodynamics, ethanol can acutely increase portal pressure and portal-collateral blood flow. The increase in hepatic venous pressure gradient is maximum at 15 min and remains significant at 45 min after oral ethanol intake[22]. Hepatocyte swelling, a characteristic of alcoholic liver disease observed after the acute administration of alcohol[23-25], may determine an acute increase in intrahepatic resistance and, in turn, increased portal pressure.

Specific-features of alcohol-related cirrhosis are listed in Table 1.

Table 1 Portal-hepatic hemodynamics in alcohol-related and viral cirrhosis.
Alcohol-related cirrhosisViral cirrhosis
Increase in intrahepatic resistanceIncrease in sinusoidal and postsinusoidal resistanceIncrease also in presinusoidal resistance
Portal pressureHigher increase in sinusoidal pressureLower increase in sinusoidal pressure
Hepatic venous pressure gradientAccurately reflects portal pressureLess accurately reflects portal pressure
Portal perfusion of the liver per gram of tissue in end-stage liver diseaseHigher reductionLower reduction
Reversal portal blood flowMore commonRare
Patent paraumbilical veinMore commonLess common
Hyperdynamic circulationMore pronouncedLess pronounced

Some studies have reported a higher portal pressure in patients with alcoholic cirrhosis compared with patients with viral cirrhosis at the same stage[26-28]. However, this finding may also relate to the methods used to determine portal pressure (vide infra).

In a study conducted by our group[29] the portal flow perfusing the liver per gram of liver tissue was lower in patients with alcoholic cirrhosis compared with patients with viral cirrhosis. On the other hand, despite a similar degree of severity of the disease, liver weight was higher in alcoholic cirrhosis. These findings suggest a more marked sinusoidal distortion and consequent higher sinusoidal resistance in alcoholic cirrhosis. Indeed, patients with alcohol-related liver disease show a marked reduction in relative sinusoidal area compared to patients with non-alcoholic cirrhosis. Moreover, only in patients with alcohol-related cirrhosis and markedly reduced sinusoidal area, portal pressure correlated inversely with sinusoidal area; this was not the case in patients with non-alcoholic liver disease[30]. These data are supported by another study in which portal venous tissue blood flow was evaluated in cirrhosis of different etiologies by Computerized Tomography[31]. In alcohol-related cirrhosis, portal venous and total hepatic tissue blood flow were significantly lower compared to hepatitis C virus (HCV)-related cirrhosis[31].

Reversal blood flow is a negative prognostic index in patients with liver cirrhosis. It is generally associated with the transit of blood from the portal vein to extrahepatic shunts or with the onset of ascites[32,33]. Hepato-fugal flow is a characteristic feature of alcoholic cirrhosis, while it is not commonly observed in viral cirrhosis[33]. In patients with alcohol-related cirrhosis, reversal portal blood flow correlates with a more severe degree of hepatic failure[33-36]. The reason why reversal blood flow has a higher prevalence in alcoholic liver cirrhosis may relate, at least to some extent, to the association between alcohol-related etiology and portal-systemic shunts and pericentral fibrosis[33].

In patients with portal hypertension, portal-systemic collaterals develop as a consequence of the increased resistance to flow[37,38]. A patent paraumbilical vein is a common portal-systemic collateral in cirrhosis and its prevalence is significantly higher in patients with alcohol-related cirrhosis compared to those with viral cirrhosis[29,39]. Moreover, Le Moine et al[26] found that the prevalence of variceal bleeding was higher in patients with alcoholic cirrhosis compared to those with viral cirrhosis.

Also the severity of hyperdynamic syndrome seems to vary between patients with cirrhosis of different etiologies. A study including patients with both alcoholic and HCV-related cirrhosis showed that splanchnic arterial vasodilatation is more marked in the alcoholic group. As expected, in both groups cardiac output was higher and systemic vascular resistance lower compared to healthy volunteers, but the pathological modifications were more pronounced in the alcoholic group. Moreover, the hepatic congestion index measured by ultrasound was increased only in alcoholic patients with cirrhosis and ascites[40].

PORTAL PRESSURE MEASUREMENT

Portal pressure is currently estimated by the measurement of the hepatic venous pressure gradient, which is the difference between wedged and free hepatic vein pressure, measured by hepatic vein catheterization[41-43]. The method measures indirectly the sinusoidal pressure, thus estimating portal pressure[44,45]. Therefore, it is not able to detect an increase in presinusoidal resistance. Indeed, it has been shown that the measurement of wedged hepatic vein pressure closely reflects portal pressure in patients with alcoholic cirrhosis, but it underestimates portal pressure in patients with nonalcoholic cirrhosis[46], probably because of a pre-sinusoidal component to the portal hypertension of viral cirrhosis[47]. The measurement of wedged hepatic venous pressures in alcohol-related cirrhosis provides a reliable estimate of the severity of portal hypertension, while hemodynamic evaluation of nonalcoholic cirrhosis should include direct portal vein pressure measurement in order to avoid underestimation of the portal-hepatic gradient[46,48].

The different anatomical changes of intrahepatic portal circulation in alcoholic and viral cirrhosis was confirmed by a meta-analysis of the agreement between wedge hepatic vein pressure and portal vein pressure in cirrhotic patients[49]. Wedged hepatic pressure measurement correlated well with direct portal pressure measurement and the agreement was sufficiently good to use this as a surrogate measurement[49-51]. However, the agreement between the two measurements was lower in HCV-related cirrhosis compared to alcohol-related cirrhosis[49]. The lack of a presinusoidal component to portal hypertension in alcoholic cirrhosis may explain why an inverse relationship between portal blood velocity and flow, and hepatic venous pressure gradient was reported only in a study of patients with alcoholic cirrhosis[52].

ALCOHOLIC CARDIOMYOPATHY

In patients with cirrhosis, progressive stages of cardiac disease have been documented. Cirrhotic cardiomyopathy is characterized by impaired cardiac contractility during preload and afterload, decreased β-adrenergic receptor function, post-receptor dysfunction, defective excitation-contraction coupling, conductance abnormalities[53] and decreased heart rate variability[54], regardless of the etiology of cirrhosis. Alcohol-related cardiomyopathy, one of the consequences of prolonged alcohol consumption, can occur in subjects both with and without cirrhosis[55,56]. While chronic (10-12 years) consumption of amounts of ethanol as low as 25 g/d in males and 12 g/d in females is associated with an increased risk of cirrhosis, > 90 g/d for at least 5 years seem to be needed for inducing changes in cardiac structure and function[2,57-60]. The pathogenesis of such dysfunction is probably related to cell death and modifications in myocyte homeostasis[61], including oxidative damage, deposition of triglycerides, impaired myofilament calcium sensitivity, altered protein synthesis and direct effect of acetaldehyde, a major product of alcohol metabolism[62]. The dysfunction of the autonomic nervous system which is typical of alcohol misusers also contributes to the cardiac alterations observed in this condition[63]. Alcoholic cardiomyopathy is characterized by left ventricular hypokinesis, left ventricular dilatation, tachyarrhythmias (transient atrial fibrillation), QT interval prolongation and sudden cardiac death[64-66]. Despite the different pathogenesis, the distinction with cirrhotic cardiomyopathy can be difficult, since some features, such as QT interval prolongation and autonomic dysfunction, are common. On the other hand, 4-chamber dilatation with normal or decreased left ventricular wall thickness is more commonly observed in alcohol-related cirrhosis[67,68], while cirrhotic cardiomyopathy is more often characterized by hypertrophy, at least in the early stages[69]. It is plausible that the cardiac dysfunction which characterizes alcohol-related cardiomyopathy may contribute to the hemodynamic changes occurring in alcohol-related cirrhosis.

CONCLUSION

Alcohol-related cirrhosis is characterized by some peculiar features of portal-hepatic hemodynamics, compared to cirrhosis of other etiologies. The knowledge of the specific characteristics of this condition may help in the management of portal hypertension and its complications in patients with alcohol-related cirrhosis.

Footnotes

P- Reviewers: de Franchis R, Kluess HA S- Editor: Ma YJ L- Editor: A E- Editor: Zhang DN

References
1.  Seth D, Haber PS, Syn WK, Diehl AM, Day CP. Pathogenesis of alcohol-induced liver disease: classical concepts and recent advances. J Gastroenterol Hepatol. 2011;26:1089-1105.  [PubMed]  [DOI]
2.  European Association for the Study of Liver. EASL clinical practical guidelines: management of alcoholic liver disease. J Hepatol. 2012;57:399-420.  [PubMed]  [DOI]
3.  Cichoz-Lach H, Celiński K, Słomka M, Kasztelan-Szczerbińska B. Pathophysiology of portal hypertension. J Physiol Pharmacol. 2008;59 Suppl 2:231-238.  [PubMed]  [DOI]
4.  Bosch J, Pizcueta P, Feu F, Fernández M, García-Pagán JC. Pathophysiology of portal hypertension. Gastroenterol Clin North Am. 1992;21:1-14.  [PubMed]  [DOI]
5.  Okumura H, Aramaki T, Katsuta Y. Pathophysiology and epidemiology of portal hypertension. Drugs. 1989;37 Suppl 2:2-12; discussion 47.  [PubMed]  [DOI]
6.  Maruyama H, Yokosuka O. Pathophysiology of portal hypertension and esophageal varices. Int J Hepatol. 2012;2012:895787.  [PubMed]  [DOI]
7.  Benoit JN, Granger DN. Splanchnic hemodynamics in chronic portal hypertension. Semin Liver Dis. 1986;6:287-298.  [PubMed]  [DOI]
8.  Bolognesi M, Sacerdoti D, Di Pascoli M, Angeli P, Quarta S, Sticca A, Pontisso P, Merkel C, Gatta A. Haeme oxygenase mediates hyporeactivity to phenylephrine in the mesenteric vessels of cirrhotic rats with ascites. Gut. 2005;54:1630-1636.  [PubMed]  [DOI]
9.  Bomzon A, Blendis LM. The nitric oxide hypothesis and the hyperdynamic circulation in cirrhosis. Hepatology. 1994;20:1343-1350.  [PubMed]  [DOI]
10.  Groszmann RJ. Hyperdynamic circulation of liver disease 40 years later: pathophysiology and clinical consequences. Hepatology. 1994;20:1359-1363.  [PubMed]  [DOI]
11.  Kowalski HJ, Abelmann WH. The cardiac output at rest in Laennec’s cirrhosis. J Clin Invest. 1953;32:1025-1033.  [PubMed]  [DOI]
12.  Bech JN, Aagaard NK, Pedersen RS, Sorensen TB, Vilstrup H, Pedersen EB. Renal effects of NO-inhibition in patients with cirrhosis vs. healthy controls: a randomized placebo-controlled crossover study. Liver Int. 2014;34:211-219.  [PubMed]  [DOI]
13.  Hu LS, George J, Wang JH. Current concepts on the role of nitric oxide in portal hypertension. World J Gastroenterol. 2013;19:1707-1717.  [PubMed]  [DOI]
14.  Blendis L, Wong F. The hyperdynamic circulation in cirrhosis: an overview. Pharmacol Ther. 2001;89:221-231.  [PubMed]  [DOI]
15.  Henriksen JH, Møller S, Ring-Larsen H, Christensen NJ. The sympathetic nervous system in liver disease. J Hepatol. 1998;29:328-341.  [PubMed]  [DOI]
16.  Møller S, Henriksen JH. Neurohumoral fluid regulation in chronic liver disease. Scand J Clin Lab Invest. 1998;58:361-372.  [PubMed]  [DOI]
17.  Møller S, Iversen JS, Henriksen JH, Bendtsen F. Reduced baroreflex sensitivity in alcoholic cirrhosis: relations to hemodynamics and humoral systems. Am J Physiol Heart Circ Physiol. 2007;292:H2966-H2972.  [PubMed]  [DOI]
18.  Hendrickse MT, Triger DR. Peripheral and cardiovascular autonomic impairment in chronic liver disease: prevalence and relation to hepatic function. J Hepatol. 1992;16:177-183.  [PubMed]  [DOI]
19.  Genovesi S, Prata Pizzala DM, Pozzi M, Ratti L, Milanese M, Vincenti A, Stella A, Mancia G. Baroreceptor sensitivity and baroreceptor effectiveness index in cirrhosis: the relevance of hepatic venous pressure gradient. Liver Int. 2010;30:232-239.  [PubMed]  [DOI]
20.  Veglio F, Melchio R, Calva S, Rabbia F, Gallo V, Molino P, Mengozzi G, Mulatero P, Martini G, Riva P. Noninvasive assessment of spontaneous baroreflex sensitivity in patients with liver cirrhosis. Liver. 1998;18:420-426.  [PubMed]  [DOI]
21.  Klein CP, Kalk JF, Müting D, Klein CG. [The effect of alcohol on portal vein hemodynamics in nutritional-toxic liver cirrhosis]. Dtsch Med Wochenschr. 1993;118:89-93.  [PubMed]  [DOI]
22.  Luca A, García-Pagán JC, Bosch J, Feu F, Caballería J, Groszmann RJ, Rodés J. Effects of ethanol consumption on hepatic hemodynamics in patients with alcoholic cirrhosis. Gastroenterology. 1997;112:1284-1289.  [PubMed]  [DOI]
23.  Nakano M, Maruyama K, Okuyama K, Takahashi H, Yokoyama K, Takagi S, Shiraki H, Ishii H. The characteristics of alcoholics with HCV infection: histopathologic comparison with alcoholics without HCV infection and chronic type C hepatitis. Alcohol Alcohol Suppl. 1993;1B:35-40.  [PubMed]  [DOI]
24.  Elmér O, Bengmark S, Göransson G, Sundqvist K, Söderström N. Acute portal hypertension after gastric administration of ethanol in the pig. Eur Surg Res. 1982;14:298-308.  [PubMed]  [DOI]
25.  Wondergem R, Davis J. Ethanol increases hepatocyte water volume. Alcohol Clin Exp Res. 1994;18:1230-1236.  [PubMed]  [DOI]
26.  Le Moine O, Hadengue A, Moreau R, Sogni P, Soupison T, Yang S, Hartleb M, Lebrec D. Relationship between portal pressure, esophageal varices, and variceal bleeding on the basis of the stage and cause of cirrhosis. Scand J Gastroenterol. 1997;32:731-735.  [PubMed]  [DOI]
27.  Perelló A, Escorsell A, Bru C, Gilabert R, Moitinho E, García-Pagán JC, Bosch J. Wedged hepatic venous pressure adequately reflects portal pressure in hepatitis C virus-related cirrhosis. Hepatology. 1999;30:1393-1397.  [PubMed]  [DOI]
28.  Nagula S, Jain D, Groszmann RJ, Garcia-Tsao G. Histological-hemodynamic correlation in cirrhosis-a histological classification of the severity of cirrhosis. J Hepatol. 2006;44:111-117.  [PubMed]  [DOI]
29.  Bolognesi M, Sacerdoti D, Mescoli C, Bombonato G, Cillo U, Merenda R, Giacomelli L, Merkel C, Rugge M, Gatta A. Different hemodynamic patterns of alcoholic and viral endstage cirrhosis: analysis of explanted liver weight, degree of fibrosis and splanchnic Doppler parameters. Scand J Gastroenterol. 2007;42:256-262.  [PubMed]  [DOI]
30.  Vidins EI, Britton RS, Medline A, Blendis LM, Israel Y, Orrego H. Sinusoidal caliber in alcoholic and nonalcoholic liver disease: diagnostic and pathogenic implications. Hepatology. 1985;5:408-414.  [PubMed]  [DOI]
31.  Takahashi H, Suzuki M, Ikeda H, Kobayashi M, Sase S, Yotsuyanagi H, Maeyama S, Iino S, Itoh F. Evaluation of quantitative portal venous, hepatic arterial, and total hepatic tissue blood flow using xenon CT in alcoholic liver cirrhosis-comparison with liver cirrhosis related to hepatitis C virus and nonalcoholic steatohepatitis. Alcohol Clin Exp Res. 2010;34 Suppl 1:S7-S13.  [PubMed]  [DOI]
32.  Gaiani S, Bolondi L, Li Bassi S, Zironi G, Siringo S, Barbara L. Prevalence of spontaneous hepatofugal portal flow in liver cirrhosis. Clinical and endoscopic correlation in 228 patients. Gastroenterology. 1991;100:160-167.  [PubMed]  [DOI]
33.  Hirata M, Kurose K, Minami H, Kumagi T, Akbar SM, Michitaka K, Horiike N, Onji M. Clinical characteristics of portal hemodynamics in alcoholic liver cirrhosis. Alcohol Clin Exp Res. 2004;28:148S-152S.  [PubMed]  [DOI]
34.  Dömland M, Gebel M, Caselitz M, Bleck J, Manns MP. Comparison of portal venous flow in cirrhotic patients with and without paraumbilical vein patency using duplex-sonography. Ultraschall Med. 2000;21:165-169.  [PubMed]  [DOI]
35.  Mostbeck GH, Wittich GR, Herold C, Vergesslich KA, Walter RM, Frotz S, Sommer G. Hemodynamic significance of the paraumbilical vein in portal hypertension: assessment with duplex US. Radiology. 1989;170:339-342.  [PubMed]  [DOI]
36.  von Herbay A, Frieling T, Häussinger D. Color Doppler sonographic evaluation of spontaneous portosystemic shunts and inversion of portal venous flow in patients with cirrhosis. J Clin Ultrasound. 2000;28:332-339.  [PubMed]  [DOI]
37.  Zardi EM, Uwechie V, Caccavo D, Pellegrino NM, Cacciapaglia F, Di Matteo F, Dobrina A, Laghi V, Afeltra A. Portosystemic shunts in a large cohort of patients with liver cirrhosis: detection rate and clinical relevance. J Gastroenterol. 2009;44:76-83.  [PubMed]  [DOI]
38.  Garcia-Tsao G. Portal hypertension. Curr Opin Gastroenterol. 2002;18:351-359.  [PubMed]  [DOI]
39.  Chen CH, Wang JH, Lu SN, Tung WC, Hung CH, Lee CM, Changchien CS. Comparison of prevalence for paraumbilical vein patency in patients with viral and alcoholic liver cirrhosis. Am J Gastroenterol. 2002;97:2415-2418.  [PubMed]  [DOI]
40.  Momiyama K, Nagai H, Sumino Y. Comparison of the hemodynamics between patients with alcoholic or HCV-related cirrhosis. Hepatogastroenterology. 2011;58:2036-2040.  [PubMed]  [DOI]
41.  Merkel C, Bolognesi M, Bellon S, Zuin R, Noventa F, Finucci G, Sacerdoti D, Angeli P, Gatta A. Prognostic usefulness of hepatic vein catheterization in patients with cirrhosis and esophageal varices. Gastroenterology. 1992;102:973-979.  [PubMed]  [DOI]
42.  Kumar A, Sharma P, Sarin SK. Hepatic venous pressure gradient measurement: time to learn! Indian J Gastroenterol. 2008;27:74-80.  [PubMed]  [DOI]
43.  Albilllos A, Garcia-Tsao G. Classification of cirrhosis: the clinical use of HVPG measurements. Dis Markers. 2011;31:121-128.  [PubMed]  [DOI]
44.  Merkel C, Montagnese S. Hepatic venous pressure gradient measurement in clinical hepatology. Dig Liver Dis. 2011;43:762-767.  [PubMed]  [DOI]
45.  Viallet A, Joly JG, Marleau D, Lavoie P. Comparison of free portal venous pressure and wedged hepatic venous pressure in patients with cirrhosis of the liver. Gastroenterology. 1970;59:372-375.  [PubMed]  [DOI]
46.  Pomier-Layrargues G, Kusielewicz D, Willems B, Villeneuve JP, Marleau D, Côté J, Huet PM. Presinusoidal portal hypertension in non-alcoholic cirrhosis. Hepatology. 1985;5:415-418.  [PubMed]  [DOI]
47.  Boyer TD, Triger DR, Horisawa M, Redeker AG, Reynolds TB. Direct transhepatic measurement of portal vein pressure using a thin needle. Comparison with wedged hepatic vein pressure. Gastroenterology. 1977;72:584-589.  [PubMed]  [DOI]
48.  Vanbiervliet G, Pomier-Layrargues G, Huet PM. [Invasive diagnosis of portal hypertension in cirrhosis: a critical evaluation of the hepatic venous pressure gradient measurement]. Gastroenterol Clin Biol. 2005;29:988-996.  [PubMed]  [DOI]
49.  Thalheimer U, Leandro G, Samonakis DN, Triantos CK, Patch D, Burroughs AK. Assessment of the agreement between wedge hepatic vein pressure and portal vein pressure in cirrhotic patients. Dig Liver Dis. 2005;37:601-608.  [PubMed]  [DOI]
50.  Saito M, Ohnishi K, Terabayashi H, Tanaka H, Iida S, Nomura F. Measurement of intrahepatic pressure as an index of hepatic sinusoidal pressure. Am J Gastroenterol. 1987;82:1057-1061.  [PubMed]  [DOI]
51.  Lin HC, Tsai YT, Lee FY, Chang TT, Wang SS, Lay CS, Lee SD, Lo KJ. Comparison between portal vein pressure and wedged hepatic vein pressure in hepatitis B-related cirrhosis. J Hepatol. 1989;9:326-330.  [PubMed]  [DOI]
52.  Taourel P, Blanc P, Dauzat M, Chabre M, Pradel J, Gallix B, Larrey D, Bruel JM. Doppler study of mesenteric, hepatic, and portal circulation in alcoholic cirrhosis: relationship between quantitative Doppler measurements and the severity of portal hypertension and hepatic failure. Hepatology. 1998;28:932-936.  [PubMed]  [DOI]
53.  Møller S, Henriksen JH. Cirrhotic cardiomyopathy: a pathophysiological review of circulatory dysfunction in liver disease. Heart. 2002;87:9-15.  [PubMed]  [DOI]
54.  Mani AR, Montagnese S, Jackson CD, Jenkins CW, Head IM, Stephens RC, Moore KP, Morgan MY. Decreased heart rate variability in patients with cirrhosis relates to the presence and degree of hepatic encephalopathy. Am J Physiol Gastrointest Liver Physiol. 2009;296:G330-G338.  [PubMed]  [DOI]
55.  Kelbaek H, Nielsen BM, Eriksen J, Rabøl A, Christensen NJ, Lund JO, Bonnevie O, Munck O, Godtfredsen J. Left ventricular performance in alcoholic patients without chronic liver disease. Br Heart J. 1987;58:352-357.  [PubMed]  [DOI]
56.  Fernandez-Sola J, Estruch R, Grau JM, Pare JC, Rubin E, Urbano-Marquez A. The relation of alcoholic myopathy to cardiomyopathy. Ann Intern Med. 1994;120:529-536.  [PubMed]  [DOI]
57.  Cerqueira MD, Harp GD, Ritchie JL, Stratton JR, Walker RD. Rarity of preclinical alcoholic cardiomyopathy in chronic alcoholics less than 40 years of age. Am J Cardiol. 1991;67:183-187.  [PubMed]  [DOI]
58.  Pavan D, Nicolosi GL, Lestuzzi C, Burelli C, Zardo F, Zanuttini D. Normalization of variables of left ventricular function in patients with alcoholic cardiomyopathy after cessation of excessive alcohol intake: an echocardiographic study. Eur Heart J. 1987;8:535-540.  [PubMed]  [DOI]
59.  Abramson JL, Williams SA, Krumholz HM, Vaccarino V. Moderate alcohol consumption and risk of heart failure among older persons. JAMA. 2001;285:1971-1977.  [PubMed]  [DOI]
60.  Møller S, Hove JD, Dixen U, Bendtsen F. New insights into cirrhotic cardiomyopathy. Int J Cardiol. 2013;167:1101-1108.  [PubMed]  [DOI]
61.  Piano MR. Alcoholic cardiomyopathy: incidence, clinical characteristics, and pathophysiology. Chest. 2002;121:1638-1650.  [PubMed]  [DOI]
62.  Ren J, Wold LE. Mechanisms of alcoholic heart disease. Ther Adv Cardiovasc Dis. 2008;2:497-506.  [PubMed]  [DOI]
63.  Milovanovic B, Milinic N, Trifunovic D, Krotin M, Filipovic B, Bisenic V, Djuric D. Autonomic dysfunction in alcoholic cirrhosis and its relation to sudden cardiac death risk predictors. Gen Physiol Biophys. 2009;28 Spec No:251-261.  [PubMed]  [DOI]
64.  Dancy M, Bland JM, Leech G, Gaitonde MK, Maxwell JD. Preclinical left ventricular abnormalities in alcoholics are independent of nutritional status, cirrhosis, and cigarette smoking. Lancet. 1985;1:1122-1125.  [PubMed]  [DOI]
65.  De Keulenaer GW, Brutsaert DL. Dilated cardiomyopathy: changing pathophysiological concepts and mechanisms of dysfunction. J Card Surg. 1999;14:64-74.  [PubMed]  [DOI]
66.  Takehana H, Izumi T. [Alcoholic heart disease]. Nihon Rinsho. 2000;58:151-156.  [PubMed]  [DOI]
67.  Iacovoni A, De Maria R, Gavazzi A. Alcoholic cardiomyopathy. J Cardiovasc Med (Hagerstown). 2010;11:884-892.  [PubMed]  [DOI]
68.  George A, Figueredo VM. Alcoholic cardiomyopathy: a review. J Card Fail. 2011;17:844-849.  [PubMed]  [DOI]
69.  Møller S, Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013;34:2804-2811.  [PubMed]  [DOI]