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PUBLISHED DATE: - 10-09-2024
https://doi.org/10.37547/TAJMSPR/Volume06Issue09-03
PAGE NO.: - 11-15
STRUCTURAL AND FUNCTIONAL STATE OF
THE LIVER IN PATIENTS WITH CHRONIC
HEART FAILURE
Davron K.Muminov
Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
Alisher M.Rakhmatullaev
Tashkent Pediatric Medical Institute, Tashkent, Uzbekistan
INTRODUCTION
Heart and liver diseases are considered a major
burden on the healthcare system and a leading
problem. cause a deterioration in the quality of life
and a reduction in life expectancy. In this review,
we discuss the complex cardiohepatic interactions
in major heart and liver diseases. This review aims
to highlight how acute and chronic heart failure can
lead to cardiogenic disorders. In each section, we
briefly discuss the likely mechanisms underlying
this association, clinical manifestations, and
diagnostic approaches.
Congestive hepopathy.
The interaction between the heart and liver has
been known for a long time. However, in recent
years, these cardiohepatic interactions have gained
greater interest, prompting the study of these
interactions and a rethinking of
their
pathophysiology. The relationship between the
liver and the heart is divided into three groups
depending on the role of each organ, which is the
primary source of damage. [1,2]: - liver diseases
resulting from heart disease; - heart disease
resulting from liver disease (for example, cirrhotic
cardiomyopathy); -systemic diseases affecting
both the heart and liver (for example, systemic
amyloidosis). The first group has generally been
called “cardiac hepatopathy,” although there is still
no consensus on terminology [3,4]. The two main
forms of cardiac hepatopathy are acute cardiogenic
liver injury (also called hypoxic hepatosis) and
congestive hepatopathy (CH). Both conditions
often coexist and enhance each other's harmful
effects on the liver [3
–
5]. Any cause of right-sided
heart failure due to diseases such as constrictive
pericarditis, mitral stenosis, severe tricuspid
regurgitation, congenital heart disease or end-
stage cardiomyopathy can lead to congestive
hepatopathy [7,8]. In summary, the incidence of
liver cirrhosis caused by noncongenital heart
RESEARCH ARTICLE
Open Access
Abstract
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failure is decreasing, and ischemic cardiomyopathy
is now the leading cause of right heart failure,
surpassing rheumatic heart disease and post-
Fontan heart failure, which creates non-pulsatile
high-pressure flow in the inferior vena cava and
this condition leads to chronic hepatic venous
congestion. [1,2,4,9].
Pathophysiology. The liver is a highly vascular
organ that receives up to 25% of total cardiac
output. The hepatic artery delivers well-
oxygenated blood and contains approximately
25% of the total hepatic blood flow, while the
remaining 75% is blood coming from the portal
vein. The liver has robust vascular mechanisms
that protect the liver from ischemic injury [1]. The
hepatic artery buffer response is a local regulatory
mechanism leading to an increase in the
concentration of the vasodilator adenosine with a
decrease in portal blood flow. [12]. In contrast, the
portal vein does not have the ability to self-regulate
its own blood flow and depends on cardiac output
and the pressure gradient in the portal and hepatic
veins [5,8]. The high permeability of the liver
sinusoids allows oxygen extraction up to 90%, and
during hypoxia, oxygen consumption by the liver
decreases, despite normal hepatic blood flow
[5,13,14]. This unique resistance to ischemic injury
contrasts with the paucity of protective
mechanisms. The resulting liver congestion leads
to liver damage through several pathogenic
mechanisms: Stress promotes fibrogenesis and
sinusoidal ischemia by activating hepatic stellate
cells and reducing the production of nitric oxide by
endothelial cells [10,15]; Reduced portal and
arterial flow to the liver aggravates liver ischemia.
The former is associated with a decrease in the
hepatic venous pressure gradient due to increased
central venous pressure on the sinusoidal network,
although the latter may also be impaired in patients
with left-sided HF [8,10]; Reduced diffusion of
oxygen and nutrients due to the accumulation of
exudate in the space of Disse also promotes
fibrogenesis [8]; Sinusoidal congestion in turn
promotes sinusoidal thrombosis, which leads to
liver fibrosis by causing parenchymal necrosis and
activating hepatic stellate cells through protease-
activated receptors [16,17]. Wanless et al
demonstrated sinusoidal thrombi confined to areas
of fibrosis, suggesting that intrahepatic thrombosis
is involved in the progression of liver fibrosis [18].
This is now defined as an area with focal loss of
adjacent hepatocytes and adjacent microvascular
structures. This microvascular injury causes
venous obstruction to spread to larger vessels,
resulting in persistence of venous obstruction and
worsening congestion [19]. Clinical picture and
diagnosis. Chronic hepatosis can be asymptomatic
for a long time, and in these patients this is the only
sign that allows one to suspect its presence if there
are changes in the tests[8]. Hepatic symptoms are
usually masked by disorders associated with right-
sided HF [6]. Stretching of the liver capsule due to
liver congestion is the cause of some symptoms,
such as heaviness or dull pain in the right upper
quadrant, nausea. Other symptoms include
anorexia, general weakness, absence of ascites or
edema of the lower extremities [1]. Classic
complications of liver cirrhosis, such as hepatic
encephalopathy or hepatocarcinoma, occur in late
stages of cardiac cirrhosis and may eventually
become as clinically important as cardiac disease
and further complicate the course [10]. When
addressing a patient with new-onset ascites, it is
difficult to differentiate the cardiac etiology of
ascites since in both cases the serum-ascitic
albumin gradient is ≥1.1 g/dL [25]. However, with
cardiac ascites, the protein level is higher than >2.5
g/dl, which is due to the preservation of the
synthetic function of the liver and the lack of
capillarization of the sinusoidal structure of the
liver [1,8,26]. In cirrhosis, decreased endothelial
cell permeability due to loss of fenestrae and
development of the basement membrane prevents
the passage of proteins into the space of Disse and
from there into the peritoneal fluid, thus explaining
lower protein concentrations [27]. Other less
reliable indicators of cardiac ascites are increased
LDH levels and red blood cell counts due to red
blood cell leakage [26]. Recently, in a study,
investigators recommended measurement of
serum B-type natriuretic peptide (BNP) or its
inactive precursor (N-terminal proBNP) in serum
at the initial diagnosis of ascites as an adjuvant
method in idiopathic cases. In summary, Shire et al
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reported that serum NT-proBNP levels in
unexplained ascitenes have high sensitivity and
specificity in predicting heart failure [28]. Also in
another study, Farias et al also found that serum
BNP levels and protein concentrations in ascitic
fluid are elevated in cardiac ascites. A serum BNP
cutoff value of >364 pg/mL has been shown to have
a sensitivity of 98%, a specificity of 99%, and a
diagnostic accuracy of 99% in the diagnosis of
cardiac ascites. Conversely, a threshold serum BNP
level of <182 pg/mL excludes the cause of HF-
related ascites [25]. Differentiating cardiac
cirrhotic ascites from cardiac ascites without
cirrhosis is of particular importance and may
require invasive diagnostic methods, such as liver
biopsy and hepatic venous pressure gradient
(HVPG) testing. The low prevalence of
gastroesophageal varices in this population may be
explained by the fact that the varices are collateral
vessels from the high pressure portal system to the
low venous pressure system, and in cardiac
hepatosis without cirrhosis there is no pressure
gradient because the pressure remains high
throughout venous return pathways to the right
atrium [9].
Biochemical blood test results may remain within
normal limits. Mild hyperbilirubinemia may occur,
with a predominantly increased unconjugated
fraction. Elevations of other indicators of
cholestasis, such as serum alkaline phosphatase
and gamma-glutamyltransferase, are often
detected [1]. The degree of cholestasis is associated
with the severity of increased venous pressure in
the right atrium and tricuspid regurgitation
[11,29]. These data suggest that increased right
atrial pressure may contribute more to elevated
liver enzymes than to decreased cardiac output [6].
It is believed that the mechanism of cholestasis in
this case is due to compression of the bile ducts by
overloaded sinusoids [30]. Other laboratory
findings such as elevated serum aminotransferases
two to three times the upper limit of normal and
mild hypoalbuminemia may also be detected in
cardiac hepatosis. These changes can also be
secondary, and occur with malnutrition or protein-
losing enteropathy [8]. As liver disease progresses,
liver function tests will increase. Heart failure can
also lead to acute cardiogenic liver injury (ACLI) in
a variety of conditions. In this case, there is a
significant and rapid increase of 10
–
20 times in the
level
of
aminotransferases
and
lactate
dehydrogenase (LDH), usually from 1 to 3 days
after hemodynamic deterioration. It is important to
note that hemodynamic deterioration is not a
constant sign, since shock is observed only in half
of the cases. This is likely due to the fact that short
periods of hypotension (i.e., 15
–
20 min) are often
unrecognized enough to trigger acute liver injury
[22]. Thus, the diagnosis of acute liver injury
cannot be rejected due to the absence of shock, and
in case of uncertainty, cardiac evaluation is
warranted [4,5]. It is equally important to note that
after normalization of hemodynamics, these
laboratory parameters usually normalize within 7
–
10 days [1,31]. Progressive increase in bilirubin.
usually observed but rarely severe [1,5,20].
However, the mean bilirubin value in these studies
was below 103 µmol/L [21,32]. Higher values may
indicate progression of acute liver disease [4].
Thus, the liver is an important and complex organ,
and its high metabolic activity is associated with
many molecular and hemodynamic changes in
patients. Liver dysfunction is frequently observed
in patients with HF and is closely correlated with
hemodynamic parameters. The liver has a double
blood circulation, which is regulated by the activity
of smooth muscle microcirculation. Features of
liver damage depend on hepatic congestion and
decreased perfusion. The main targets of
congestive hepatopathy are hepatocytes and bile
duct epithelium. Most patients experience
congestion, pericentral necrosis and fibrosis, and
dilated sinusoids. Cardiac cirrhosis represents a
continuum of liver disease resulting from right-
sided HF. Ischemic hepatitis is massive
hepatocellular
necrosis,
which
may
be
accompanied
by
cardiogenic
shock
or
hemodynamic collapse. Although early detection
of clinical signs and symptoms of cardiac and liver
damage has led to important benefits in terms of
reduced morbidity and mortality.
REFERENCES
1.
Khadem, E.; Toosi, M.N.; Ilkhani, R. Liver- Heart
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(ISSN
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Inter- Relationship in Fatty Liver Disease Based
on the Avicenna’s Point of View. Iran. J. Public
Health 2013, 42, 648
–
649.
2.
Asrani, N.S.; Freese, D.K.; Phillips, S.D.;
Heimbach, J.; Asrani, S.K.; Warnes, C.A.; Kamath,
P.S. Congenital heart disease and the liver.
Hepatology 2012, 56, 1160
–
1169.
3.
Giallourakis, C.C.; Rosenberg, P.M.; Friedman,
L.S. The liver in heart failure. Clin. Liver Dis.
2002, 6, 947
–
967. 4. De Gonza
4.
lez, A.K.K.; Lefkowitch, J.H. Heart Disease and
the Liver. Gastroenterol. Clin. N. Am. 2017, 46,
421
–
435. Cells 2020, 9, 567 13 of 18
5.
Myers, R.P.; Cerini, R.; Sayegh, R.; Moreau, R.;
Degott, C.; Lebrec, D.; Lee, S.S. Cardiac
hepatopathy: Clinical, hemodynamic, and
histologic characteristics and correlations.
Hepatology 2003, 37, 393
–
400.
6.
Téllez, L.; Rodriguez-Santiago, E.; Albillos, A.
Fontan-Associated Liver Disease: A Review.
Ann. Hepatol. 2018, 17, 192
–
204.
7.
Fauci, A.S.; Braunwald, E.; Hauser, S.L.; Longo,
D.L.; Jameson, J.; Loscalzo, J. Harrison’s
Principles of Internal Medicine; McGraw-Hill
Medical: New York, NY, USA, 2008; Volume 2.
8.
Kiesewetter, C.H.; Sheron, N.; Vettukattill, J.J.;
Hacking, N.; Stedman, B.; Millward-Sadler, H.;
Haw, M.; Cope, R.; Salmon, A.P.; Sivaprakasam,
M.C.; et al. Hepatic changes in the failing Fontan
circulation. Heart 2006, 93, 579
–
584.
9.
Weisberg, I.S.; Jacobson, I.M. Cardiovascular
Diseases and the Liver. Clin. Liver Dis. 2011, 15,
1
–
20.
10.
Vasconcelos, L.A.B.A.; De Almeida, E.A.; Bachur,
L.F. Clinical evaluation and hepatic laboratory
assessment in individuals with congestive
heart failure. Arq. Bras. Cardiol. 2007, 88, 590
–
595.
11.
Poelzl, G.; Eberl, C.; Achrainer, H.; Doerler, J.;
Pachinger, O.; Frick, M.; Ulmer, H. Prevalence
and Prognostic Significance of Elevated γ
-
Glutamyltransferase in Chronic Heart Failure.
Circ. Heart Fail. 2009, 2, 294
–
302.
12.
Fuhrmann, V.; Jäger, B.; Zubkova, A.; Drolz, A.
Hypoxic
hepatitis
–
epidemiology,
pathophysiology and clinical management.
Wien. Klin. Wochenschr. 2010, 122, 129
–
139.
13.
Dunn, G.D.; Hayes, P.; Breen, K.J.; Schenker, S.
The liver in congestive heart failure: A review.
Am. J. Med. Sci. 1973, 265, 174
–
189.
14.
Shah, H.; Kuehl, K.; Sherker, A.H. Liver Disease
After the Fontan Procedure. J. Clin.
Gastroenterol. 2010, 44, 1.
15.
Wells, M.L.; Fenstad, E.R.; Poterucha, J.T.;
Hough, D.M.; Young, P.M.; Araoz, P.A.; Ehman,
R.L.; Venkatesh, S.K. Imaging Findings of
Congestive Hepatopathy. Radiographics 2016,
36, 1024
–
1037.
16.
Dai, D.-F.; Swanson, P.; Krieger, E.; Liou, I.W.;
Carithers, R.L.; Yeh, M.M. Congestive hepatic
fibrosis score: A novel histologic assessment of
clinical severity. Mod. Pathol. 2014, 27, 1552
–
1558.
17.
Sherlock, S. The Liver in Heart Failure Relation
of Anatomical, Functional, and Circulatory
Changes. Heart 1951, 13, 273
–
293.
18.
Maleki, M.; Vakilian, F.; Amin, A. Liver diseases
in heart failure. Heart Asia 2011, 3, 143
–
149.
19.
Russell, S.D.; Rogers, J.; Milano, C.A.; Dyke, D.B.;
Pagani, F.D.; Aranda, J.M.; Klodell, C.T.; Boyle,
A.J.; John, R.; Chen, L.; et al. Renal and Hepatic
Function Improve in Advanced Heart Failure
Patients During Continuous-Flow Support With
the HeartMate II Left Ventricular Assist Device.
Circulation 2009, 120, 2352
–
2357.
20.
Dichtl, W.; Vogel, W.; Dunst, K.M.; Grander, W.;
Alber, H.F.; Frick, M.; Antretter, H.; Laufer, G.;
Pachinger, O.; Pölzl, G. Cardiac hepatopathy
before and after heart. transplantation.
Transpl. Int. 2005, 18, 697
–
702.
21.
Seeto, R.K.; Fenn, B.; Rockey, D.C. Ischemic
hepatitis:
Clinical
presentation
and
pathogenesis. Am. J. Med. 2000, 109, 109
–
113.
22.
Harjola, V.-P.; Mullens, W.; Banaszewski, M.;
Bauersachs, J.; Rocca, H.-P.B.-L.; Chioncel, O.;
Collins, S.P.; Doehner, W.; Filippatos, G.S.;
THE USA JOURNALS
THE AMERICAN JOURNAL OF MEDICAL SCIENCES AND PHARMACEUTICAL RESEARCH
(ISSN
–
2689-1026)
VOLUME 06 ISSUE09
15
https://www.theamericanjournals.com/index.php/tajmspr
Flammer, A.; et al. Organ dysfunction, injury
and failure in acute heart failure: From
pathophysiology
to
diagnosis
and
management. A review on behalf of the Acute
Heart Failure Committee of the Heart Failure
Association (HFA) of the European Society of
Cardiology (ESC). Eur. J. Heart Fail. 2017, 19,
821
–
836.
23.
Eipel, C.; Abshagen, K.; Vollmar, B. Regulation of
hepatic blood flow: The hepatic arterial buffer
response revisited. World J. Gastroenterol.
2010, 16, 6046
–
6057.
24.
Henrion, J.; Descamps, O.; Luwaert, R.; Schapira,
M.; Parfonry, A.; Heller, F. Hypoxic hepatitis in
patients with cardiac failure: Incidence in a
coronary care unit and measurement of hepatic
blood flow. J. Hepatol. 1994, 21, 696
–
703.
25.
Naschitz, J.E.; Yeshurun, D.; Shahar, J.
Cardiogenic Hepatorenal Syndrome. Angiology
1990, 41, 893
–
900.
26.
Birrer, R.; Takuda, Y.; Takara, T. Hypoxic
hepatopathy: Pathophysiology and prognosis.
Intern. Med. 2007, 46, 1063
–
1070. Cells 2020,
9, 567 14 of 18
27.
Henrion, J.; Schapira, M.; Luwaert, R.; Colin, L.;
Delannoy, A.; Heller, F.R. Hypoxic hepatitis:
Clinical and hemodynamic study in 142
consecutive cases. Medicine 2003, 82, 392
–
406.
28.
Denis, C.; De Kerguennec, C.; Bernuau, J.;
Beauvais, F.; Cohen-Solal, A. Acute hypoxic
hepatitis (‘liver shock’): Still a frequently
overlooked cardiological diagnosis. Eur. J.
Heart Fail. 2004, 6, 561
–
565.
29.
Giannini, E.G.; Testa, R.; Savarino, V. Liver
enzyme alteration: A guide for clinicians. Can.
Med. Assoc. J. 2005, 172, 367
–
379.
30.
Cassidy, W.M.; Reynolds, T.B. Serum Lactic
Dehydrogenase in the Differential Diagnosis of
Acute
Hepatocellular
Injury.
J.
Clin.
Gastroenterol. 1994, 19, 118
–
121.
31.
Alvarez,
A.M.;
Mukherjee,
D.
Liver
Abnormalities in Cardiac Diseases and Heart
Failure. Int. J. Angiol. 2011, 20, 135
–
142.
32.
De La Monte, S.M.; Arcidi, J.M.; Moore, G.W.;
Hutchins, G.M. Midzonal Necrosis as a Pattern
of Hepatocellular Injury After Shock.
Gastroenterology 1984, 86, 627
–
631.
33.
Waseem, N.; Chen, P.-H. Hypoxic Hepatitis: A
Review and Clinical Update. J. Clin. Transl.
Hepatol. 2016, 4, 263
–
268.
34.
Limas, C.J.; Guiha, N.H.; Lekagul, O.; Cohn, J.N.
Impaired Left Ventricular Function in Alcoholic
Cirrhosis with Ascites. Circulation 1974, 49,
755
–
760.
35.
Møller,
S.;
Henriksen,
J.H.
Cirrhotic
cardiomyopathy. J. Hepatol. 2010, 53, 179
–
190.
