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CHAPTER
8
Prognostic value of liver assessment (including
liver stiffness measurement) in cardiovascular
diseases
Yuki Saito
1
and Tatsunori Taniguchi
2
1
Department of Cardiology, Nihon University School of Medicine, Itabashi, Tokyo, Japan
2
Department of
Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
Introduction
The relationship between heart failure (HF) and liver dysfunction has been well-recognized for over two cen-
turies. Passive congestion and reduced hepatic perfusion impair liver function, causing cardiac hepatopathy. The
underlying complexities of this association still remain a topic of intense interest.
Liver assessment has prognostic importance in HF patients, mainly because the degree of hepatopathy reflects
the severity of the HF.
HF, because of its high mortality, remains a major challenge. High hospital readmission rates are characteristic.
Congestion, caused by elevated right-sided filling pressures, is considered to be a major cause of organ injury,
and it is related to adverse outcomes in patients with HF. Congestion can be difficult to detect, especially when
symptoms are mild, despite recent advances in imaging tools and biological markers.
Congestive hepatopathy is due to passive hepatic congestion arising from right-sided HF or elevated hepatic
venous pressure. Quantification of liver injury reflects the severity of organ congestion and hypoperfusion and
has been reported to have prognostic relevance in HF.
Patients with severe liver dysfunction are at risk for cirrhotic cardiomyopathy, with systolic and diastolic dys-
function. Again, risk stratification is important.
In this chapter, we discuss the prognostic value of markers of liver injury in HF and other cardiovascular
diseases.
Heart failure and liver impairment
The liver is vulnerable to circulatory disturbances due to its complex vascular supply and high metabolic
activity. In HF patients, hepatic injury termed as cardiac hepatopathy can be the result of passive congestion and
diminished perfusion. Congestive hepatopathy and acute cardiogenic liver injury (ischemic hepatitis) are well-
recognized forms of hepatic injury caused by HF
[1].
Any of the etiologies of right-sided HF, including mitral stenosis, tricuspid regurgitation (TR), and constrictive
pericarditis, can lead to hepatic congestion and congestive hepatopathy. This is due to high right atrial pressures
(RAPs) directly transmitted back into the hepatic veins. In patients with advanced right-sided HF, liver dysfunc-
tion caused by passive hepatic congestion is common. Most cases are asymptomatic and only diagnosed by liver
function testing.
115
Cardio-Hepatology.
DOI:
https://doi.org/10.1016/B978-0-12-817394-7.00007-3 © 2023 Elsevier Inc. All rights reserved.
https://t.me/medicina_free
Boland and Willius first demonstrated that nearly 50% of patients with severe right-sided HF had pathologic
changes consistent with chronic passive liver congestion
[1]. These changes include atrophy, necrosis, or both,
being most apparent in the central third of the hepatic lobule immediately adjacent to the central vein (zone 3 of
the acinus). Centrilobular hepatic necrosis is present in most cases. As right-sided HF worsens, the necrosis
spreads out more peripherally in the lobule. Reversal of the problem before fibrosis develops is associated with
decreasing RAP. Variable degrees of cholestasis are also noted.
Ischemic hepatitis is a diffuse injury caused by acute hypoperfusion, accounting for 1%2.5% of patients
admitted to the intensive care unit
[2]. The clinical and laboratory features of ischemic hepatitis are similar to
those of congestive hepatopathy, mostly because decreased cardiac output causes both conditions and the histo-
logical end result is the same. Although approximately 50% of patients with ischemic hepatitis were in cardio-
genic shock, any cause of shock or hemodynamic instability can cause ischemic injury to the liver. Ischemic
hepatitis is also associated with severe respiratory failure, hypoxemia, and obstructive sleep apnea. Ischemic hep-
atitis is usually first detected by elevations in liver function tests (LFTs).
The histologic appearance of ischemic hepatitis is also necrosis surrounding the central vein in the hepatic lob-
ule
[3]. Depending on the ischemia’s duration, different degrees of loss of cellular architecture can occur.
Necrosis can extend farther out with prolonged ischemia; but necrosis is usually confined to the centrilobular
region
[3].
Liver disease is associated with poor outcome of heart failure
Liver damage can influence the prognosis of cardiac diseases, including HF. One well-recognized entity is
NAFLD. NAFLD is defined as any disease resembling alcoholic liver disease in nonalcoholic individuals. It is
now the commonest liver disease in the world, with marked morbidity and mortality. NAFLD is the third com-
monest indication for liver transplantation in the USA. NAFLD affects multiple systems and causes a great deal
of cardiovascular, including ischemic, disease, as well as subclinical myocardial remodeling and dysfunction that
may carry an increased risk for developing HF.
Adults with NAFLD tend to have increased left ventricular (LV) mass and diastolic dysfunction, in the
absence of other risk factors. The risk is also increased in Type II diabetics with NAFLD. A report analyzing
echocardiography data in 2,713 participants showed that those with NAFLD had lower early diastolic relaxation
velocities, higher LV filling pressures (E/e’ ratio), and worse absolute global longitudinal strain than those with-
out NAFLD
[4].
Recent studies have suggested that NAFLD is associated with an increased risk of incident HF and 1-year hos-
pital readmissions. In a clinical study involving 107 patients hospitalized for acute HF
[5], 1-year rehospitaliza-
tion rates were 5.5-fold higher in patients with NAFLD (diagnosed by ultrasonography) than in those without
NAFLD, independent of multiple HF risk factors, including preexisting CHD, diabetes, atrial fibrillation, renal
dysfunction, reduced ejection fraction, and elevated NT-pro brain natriuretic peptide (BNP). The cumulative rate
of 1-year all-cause rehospitalizations was 46.7% in a recent study of 212 elderly patients with acute HF. Patients
with NAF LD (n 5 109; 51.4%) had a fivefold increased risk of 1-year all-cause rehospitalization after adjustment
for established risk factors compared with patients without NAFLD. Both event rates were particularly increased
in those with advanced NAFLD fibrosis
[6]. In this study, the diagnosis of NAFLD was made with ultrasonogra-
phy, while the severity of fibrosis was based on noninvasive fibrosis scores.
Liver disease is associated with poor outcomes of cardiovascular diseases
NAFLD is a complex disorder that exacerbates man y nonhepatic diseases, especially malignancy and coronar y
artery disease and other cardiovascular illnesses. The relationship between NAFLD and the incidence of cardio-
vascular events has been investigated in several retrospective and prospective studies. Patients with more severe
NAFLD, defined as hepatic steatosis being present on imaging in addition to elevated serum GGT levels, high
NAFLD fibrosis scores, or increasing fibrosis stage on liver histology, are at higher risk for fatal and nonfatal car-
diovascular events. A meta-analysis of 25,837 patients from six studies revealed that patients with NAFLD had a
significantly higher risk of clinical cardiovascular events, defined as myocardial infarction, angina, cerebrovascu-
lar accident, transient ischemic attack, cardiovascular death, and symptomatic peripheral vascular disease. These
were associated with coronary or peripheral vascular revascularization. Coronary angiography displayed much
116 8. Prognostic value of liver assessment (including liver stiffness measurement) in cardiovascular diseases
II. Hepatobiliary system in heart failure
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higher rates of stenoses . 50%, and of composite endpoints, compared with those without NAFLD [7]. A large
meta-analysis of nearly 165,000 patients from 34 studies also reported an increased prevalence and incidence of
cardiovascular disease in NAFLD
[8]. It remains uncertain as to whether NAFLD confers an additional risk over
the usual cardiovascular risk factors, or is acting as a sur rogate marker. Further studies are clearly needed.
Liver function tests and prognosis of HF
Liver function tests in HF
HF affects multiple LFTs, such as serum bilirubin, alkaline phosphatase (ALP), γ-glutamyl transferase (GGT),
and transaminase levels. Several studies have reported the prognostic relevance of LFTs in chronic HF and
acutely decompensated heart failure (ADHF).
Liver enzyme abnormalities are usually classified as those related predominantly to cholestasis caus ed by pas-
sive congestion (signified by elevated serum bilirubin, ALP, and GGT) or those related to liver cell necrosis
caused by decreased cardiac output with impaired organ perfusion (signified by transaminase elevation).
Increased central venous pressure results in passiv e hepatic congestion, and ele vating ALP, GGT, and direct and
indirect serum bilirubin, indicati ve of cholestasis. The mechanism by which this causes cholestasis remains uncer-
tain. In HF patients, liver sinusoids receive the increased centr al venous and centrilobular pressure. It is believed
that congestion in liver sinusoids would compress and narrow bile canaliculi and ductules, impeding bile flow,
and directing bile production into the bloodstream. Hence, cholestasis indicates liver congestion and elevated
RAPs in HF patients.
Decreased cardiac output and organ perfusion impairment are associated with acute centrilobular hepatocellu-
lar damage and necrosis. Hepatic ischemic injury results in the elevation of serum transaminase levels.
In contrast to acute perfusion abnormalities, prolonged hemodynamic disturbances may result in bridging
fibrosis, “cardiac cirrhosis,” and hepatic function impairment with decreased synthesis of coagulation factors and
albumin. Hepatic congestion is asymptomatic in most cases.
Prevalence and prognostic value of abnormal liver function in chronic heart failure
Patients with chronic HF and those with ADHF show different patterns of LFT abnormalities. In chronic HF,
elevation of serum bilirubin and of liver enzymes indicating cholestasis is common. An analysis of data from
2,679 patients with symptomatic chronic HF from the Candesartan in Heart Failure: Assessment of Reduction in
Mortality and Morbidity program trial revealed elevated total bilirubin and alanine transaminase (ALT) in 13.0%
and 3.1% of patients, respectively
[9]. Total bilirubin (T-Bil) was higher in patients with physical signs of volume
overload (venous congestion, S3, pulmo nary crackles,) compared to those without. Elevated T-Bil was a strong
predictor of cardiovascular death or HF hospitalization and all-cause mortality. After adjustment for multiple
demographic, clinical, and biochemical risk factors, elevated total bilirubin was reported to be one of the stron-
gest independent predictors of poor prognosis.
Data from a recently published study also revealed a mostly cholestatic pattern in chronic HF, with elevated
cholestatic enzymes and transaminases in 19.2% and 8.3% of patients, respectively
[10]. In this study, elevation of
the cholestatic enzymes GGT and ALP, significantly correlated with HF severity. Transaminase levels showed no
association. T-Bil, GGT, and ALP were associated with the rates of death from HF and the need for heart trans-
plantation. Again, after adjustment for multiple demographic, clinical, and biochemical risk factors, GGT and
ALP were independently associated with the endpoint.
Prevalence and prognostic relevance of abnormal liver chemistry in acute decompensated heart failure
In ADHF patients, as opposed to chronic HF patients, the prevalence of elevated transaminase levels is sub-
stantially higher, indicating decreased cardiac output and impaired organ perfusion as the culprits in causing
hepatocellular damage. A post hoc analysis of the placebo group of the EVEREST (Efficacy of Vasopressin
Antagonism in Heart Failure Outcome Study with Tolvaptan) trial that enrolled patients hospitalized for ADHF
with an ejection fraction # 40% and no history of liver disease or acute hepatic failure fou nd baseline abnormali-
ties in the LFTs, with low albumin in 17%, and elevated levels of aspartate transaminase (AST) in 21%, ALT in
21%, ALP in 23%, and T-Bil in 26%
[11].
117Liver function tests and prognosis of HF
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In a substudy of the SURVIVE (Survival of Patients with Acute Heart Failure in Need of Intravenous Inotr opic
Support) trial, which included 1134 ADHF patients, abnormal LFTs were seen in 46%: isolated abnormal ALP
was present in 11%, isolated abnormal transaminases in 26%, and a combination of abnormal ALP and transami-
nases in 9%
[12]. Abnormal ALP was associated with signs of severe systemic congestion and high right-sided
filling pressures, including elevated central venous pressure, peripheral edema, ascites, TR, and elevations in cre-
atinine and BNP. ALP levels showed no relationship with 31-day mortality but were associated with significantly
worse 180-day mortality. Abnormal transaminases were associated with clinical signs of hypoperfu sion, includ-
ing hypotension, tachycardia, and cold extremities, and with greater 31-day and 180-day mortality rates com-
pared with normal transaminase profiles.
Another recent study showed the prognostic value of direct bilirubin (D-Bil) in ADHF. The study, including 556
ADHF patients, showed that the prognostic value of D-Bil may be superior to that of T-Bil in ADHF
[13].Patients
with elevated D- and T-Bil levels shared some features, such as hepatomegaly, jugular venous distention, dilated infe-
rior vena cava (IVC), and elevated GGT and decreased cardiac output (cold extremities, low pulse pressure, and
hypotension), as well as increased plasma renin activity, sodium, and total cholesterol; but only patients with elevated
D-Bil showed a significant difference in the number of prior episodes of ADHF and at the time of the study and had
more elevated ALP values, suggesting that D-Bil more accurately reflected HF severity and end-organ damage. A
multivariate Cox hazards model showed that D-Bil was an independent predictor of adverse events, whereas T-Bil
was not, suggesting that elevated D-Bil may more accurately reflect hemodynamic deterioration.
Abnormal LFTs may signify the presence of cardi o-hepatic syndromes, are indicative of an adverse long-term
outcome, and, most importantly, can suggest the mechanism of liver injury by their pattern. Treatment goals are
the same as for the underlying illness, that is, reducing congestion and improving perfusion.
Abnormal liver synthetic function and heart failure
Synthetic function impairment secondary to chronic liver congestion leads to reduced serum albumin concen-
tration and prolonged prothrombin time. Hypoalbuminemia in HF is a common condition. It has an approxi-
mately 25% prevalence, higher in older, frailer patients, Recent evidence suggests that not only nutritional status,
but also systemic inflammation, may affect hepatic protein metabolism
[14]. Hypoalbuminemia is an independent
predictor of mortality in acute and chronic HF
[1]. Low albumin levels are associated with significantly increased
1- and 5-year all-cause mortalities, HF death, and risk of urgent cardiac transplantation in a cohort of patients
with NYHA class III/IV symptoms
[15] and have prognostic value in ADHF after adjusting for other prognostic
variables such as N-terminal proB-type natriuretic peptide
[16]. Preoperative albumin is an independent predic-
tor of short- and intermediate-term outcomes after implantation of LV assist devices (LVADs) in patients with
advanced HF
[17].
Prognostic relevance of markers of hepatic and renal dysfunction in heart failure
The model for end-stage liver disease (MELD) score was originally developed to assess the short-term survival
of cirrhosis patients undergoing the transjugular intrahepatic portosystemic shunt (TIPS) procedure
[18]. Using
three objective biochemical values, serum total bilirubin, creatinine, and international normalized ratio (INR) for
prothrombin time, it reflects the state of hepatic and renal function after the TIPS procedure
[18]. Since congestion
due to impaired cardiac function causes multiple end-organ dysfunction, the MELD score has been reported to
be an excellent predictor for major cardiac adverse events in HF patients
[19]. Subsequently, the model for end-
stage liver disease excluding INR (MELD-XI) score was developed to assess cirrhotic patients receiving anticoa-
gulation therapy with vitamin K antagonists
[20], as HF patients often receive the identical therapy. MELD-XI
appears to be an improvement over the MELD score
[21]. A high MELD-XI score is associated with a poor prog-
nosis in HF patients who have had a heart transplant and/o r have a ventricular assist device.
Markers of hepatic fibrosis and prognosis of HF
Serologic markers of hepatic fibrosis in HF
Any chronic liver injury will cause hepatic fibrosis. Its stages are collapse of hepatic lobules, fibrous septa for-
mation, and regeneration of hepatocytes with nodule formation. As a result of imbalances in their production,
118 8. Prognostic value of liver assessment (including liver stiffness measurement) in cardiovascular diseases
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deposition, and degradation, extracellular matrix components, including procollagen types I and III, hyaluronic
acid, and proteoglycans, accumulate in the liver. This may ultimately progress to cirrhosis, with the accompa-
nying consequences of portal hypertension and further impairment of hepatic function.
Conventional laboratory tests are not helpful in the assessment of fibrosis. Histopathologic examination of a
liver biopsy specimen is currently the gold standard for hepatic fibrosis assessment. However, liver biopsy may
be associated with complications such as bleeding and infection. In addition, it is susceptible to sampling varia-
tion and inter- and intraobserver variability. This has led to the development of newer noninvasive techniques.
Serologic markers of hepatic fibrosis can be categorized as indirect or direct. Indirect markers reflect hepatic
function alterations but do not reflect extracellular matrix metabolism. Examples include platelet count, coagula-
tion studies, and hepati c aminotransferase levels. The FIB-4 index combines biochemical values (platelet count,
ALT, and AST) and age. It displayed high predictive accuracy for advanced fibrosis in at least two studies
involving chronic HCV patients. In another report, its performance was more accurate than that of any other
serologic markers for detecting advanced fibrosis in NAFLD. A recent clinical study including 1058 HF patien ts
reported an association of the FIB4 index with biochemical markers including type IV collagen 7S, procollagen
type III peptide hyaluronic acid, and BNP. It was also predictive of increased right and left heart volume over-
load and higher mortality in HF patients
[22].
Both qualitative and quantitative changes in extracellular matrix markers occur in liver fibrosis. Direct markers
of fibrosis reflect the turnover of the extracellular matrix. One marker of liver fibrosis, the 7S domain of collagen
type IV (P4NP 7S), may be correlated with pulmonary capillary wedge pressure and right ventricular and atrial
pressures in HF. P4NP 7S also helps to refine risk classification when added to conventional risk factors in
patients with acute HF
[23].
Of course, all serum tests have limitations. None of the markers is specific to liver. Other locations affected by
inflammation may contribute to marker serum levels. Clearance rates affect serum levels. Impaired biliary excre-
tion or dysfunction of sinusoidal endothelial cells will alter clearance.
Liver specific micro-RNAs in heart failure
Micro-RNAs (miRNAs), single-stranded endogenous RNAs that regulate posttranscription gene expression,
play important parts in a wide range of physiological and pathologic processes. Of note, miRNAs are emerging
as participants in liver health and disease, and involvement of miRNAs in hepatocyte apoptosis, obstructive jaun-
dice, and liver fibrosis has been uncovered. Circulating miRNAs are a new route towards molecular diagnosis of
cancer and acute myocardial infarction.
MicroRNA-122 (miR-122) is a liver-specific microRNA that accounts for 70% of liver miRNAs-expression
[24].
It is a regulator of cholesterol and fatty acid metabolism. The liver constantly secretes miR-122 into the circula-
tion, with its production increasing in the event of liver injury. miR-122 has associations with the risk of develop-
ing metabolic syndrome and type 2 diabetes. Treatment with statins reduces circulating miR-122
[25]. miR-122 is
also elevated in acute heart failure
[26].
In a study evaluating the prognostic value of circulating miRNAs in chronic systolic HF, baseline miR-122
blood levels were higher in the 40 patients that died during the follow-up, compared with the 36 patients who
survived. miR-122 was an independent predictor of all-cause mortality in a validation cohort that included 234
patients with chronic systolic HF, miR-122 has also been found to be associated with right ventricular dysfunc-
tion, and remained an independent predictor of all-cause mortality in heart failure with reduced LV ejection frac-
tion after adjusting for right ventricular dysfunction and for cholinesterase and GGT levels
[27].
Imaging markers of hepatic fibrosis in HF
Transient elastography is the commonest imaging test for fibrosis. Other imaging methods for assessing hepatic fibro-
sis include magnetic resonance elastography, acoustic radiation force impulse imaging, and cross-sectional imaging.
Elastography estimates liver stiffness (LS) by applying mechanical waves and measuring their propagation
speed through tissue. Modality options include ultrasound and magnetic resonance imaging. Ultrasound-based
elastography is primarily used as a noninvasive alternative method to liver biopsy for the assessment of hepatic
fibrosis. Two primary ultrasound-based elastography techniques are used for evaluating LS: shear wave elasto-
graphy (SWE) and strain elastography. There are several methods of performing SWE: transient elastography,
119Imaging markers of hepatic fibrosis in HF
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point-SWE, and two-dimensional (2D) SWE. Methods differ in how the shear wave is generated and in what
measurements are taken. In transient elastography, acoustic radiation impulses are generated by a mechanical
piston with a single-element ultrasound transducer. The transducer lightly pushes the skin over a right upper
quadrant intercostal space, and the impulses produce a shear wave that is propagated through the liver.
Elasticity (kilopascals [kPa]) and velocity (m/s) measurements are then taken of the area of interest.
LS depends on many factors, of which fibrosis is an important contributor. However, other factors also influ-
ence LS, including inflammation, fatty infiltration, cholestasis, and elevated central venous pressure in HF. The
liver itself is not easily distensible; liver congestion due to elevated RAP may lead to increased LS. One study in
Landrace pigs showed that LS measured by transient elastog raphy is directly influenced by central venous pres-
sure
[28]. The influence of increased RAP on LS in HF patients has been investigated. One clinical study analyzed
the relationship between LS measured with TE with the HF patient’s clinical course [29]. This study of 27 hospi-
talized HF patients with no signs of liver disease showed increased LS in most cases; it decreased in response to
treatment.
Another study investigated the relationship between the LS value and RAP measured during right-heart car-
diac catheterization in 80 HF patients without chronic liver disease
[30]. LS was measured using TE in 31 of the
patients (the test group). The correlation found between LS and RAP in the patients undergoing TE was used to
derive a best-fit model to predict RAP. The applicability of the model was then tested in the 49 additional
patients (the validation group). They found a significant correlation between LS and RAP in the test group
(RAP 525.8 1 6.7 3 ln [LS]). Natural log transformation (ln) of LS provided the regression equation to pre-
dict RAP. The predicted RAP correlated significantly with actual RAP when the equation model derived from
the test group was applied to the validation group. In the validation group, LS with a cutoff value of 10.6 kPa for
identifying RAP . 10 mm Hg had a higher sensitivity and accuracy than echocardiography, suggesting its use
as a marker of increased RAP and liver congestion in HF patients.
The prognostic value of TE-measured LS at discharge was measured in another study in 171 HF inpatients
[31]. The patients were divided into three groups corresponding to the LS value at discharge. Those in the high-
est LS tercile ( . 6.9 kPa) were in an advanced NYHA functional class, a high rate of jugular venous distention,
moderate/severe TR, increased IVC diameter, and higher serum D-Bil levels compared to the lower terciles.
Eight (5%) deaths and 33 (19%) hospitalizations for HF occurred during follow-up periods (median: 203 days).
The patients in the highest LS tercile had significantly higher mortality and HF rehospitalization rates compared
with the other terciles. LS correlated with IVC diameter, serum D-Bil and BNP levels, but only LS values were
predictive of worse outcomes, even after adjustment. This suggests that an LS .6.9 kPa at discharge can be an
indicator of residual subclinical residual liver congestion, which reflects the severity of HF and the risk of
adverse cardiac events, even in patients with optimized HF treatment and without visible edema or elevated
LFTs.
A recent study showed that TE-diagnosed LS may be a predictor of RV failure (RVF) after LVAD implantation.
Although RVF is a major concern after LVAD implantation, its prediction is difficult. One clinical study investi-
gated the prognostic value of LS to RVF detection after LVAD implantation in 55 patients
[32]. A total of 17
patients presented with RVF, defined as a requirement for inotropic support for $ 30 days, nitric oxygen inhala-
tion for $ 5 days, and/or mechanical RV support following LVAD implantation. Preoperative LS, LV diastolic
dimension, RV stroke work inde x, and being in the dilated phase of hypertrophic cardiomyopathy were identi-
fied as significant risk factors using multivariate logistic regression analysis. Therefore, in addition to dilated
hypertrophic cardiomyopathy, reduced RV stroke work index and small LV dimension, noninvasively measured
LS was a predictor of post-LVAD RVF.
The prognostic relevance of LS in chronic and acute decompensated HF has also been investigated. One study
investigated the correlation of LS measured by TE with clinical and echocardiographic variables and outcomes in
105 patients with chronic and acute decompensated HF
[33]. Patients were divided into two groups based on
median LS at admission (low LS , 8.8 kPa [n 5 52] vs. high LS $ 8.8 kPa [n 5 53]). T-Bil and GGT levels, IVC
diameters, and TR severity were greater in the high-LS group. Patients in the high-LS group had significantly
higher mortality and HF rehospitalization rates compared to the low-LS group. After adjusting for variables that
influence organ congestion, LS $ 8.8 kPa still significantly correlated with mortality and HF rehospitalization
rates, indicating that increased LS upon admission may be a useful prognostic marker in patients with chronic
and acute decompensated HF. Another clinical study showed the prognostic value of LS in ADHF measured by
point-shear wave (virtual touch quantification)
[34].
LS measurements may be especially helpful when hemodynamic status cannot be easily assessed at the bed-
side, as the ass essment of LS by transient elastography is rapid and simple.
120 8. Prognostic value of liver assessment (including liver stiffness measurement) in cardiovascular diseases
II. Hepatobiliary system in heart failure
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Summary
There are emerging da ta on the correlation between HF and liver impairment. Assessment of liver status is an
important aspect in the risk stratification of HF. Abnormalities in LFTs, synthetic function, and fibrosis markers
are associated with the severity of HF and are useful biomarkers to predict outcomes in HF. Ultrasound elasto-
graphy may detect liver congestion and impairment more sensitively than routine laboratory tests. Evaluation of
liver status by these modalities may be a useful adjunct to HF manageme nt.
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CHAPTER
9
Passive liver congestion and hypoxic hepatitis
Shaz Iqbal and Po-Hung Chen
Division of Gastroenterology & Hepatology, Department of Medicine, Johns Hopkins University School of Medicine,
Baltimore, MD, United States
Introduction
Vascular injury to the liver is a broad topic, with a variety of circulatory disturbances potentially impacting
hepatic blood flow and function. Some of these disturbances in clude Budd-Chiari syndrome, hepatic sinusoidal
obstruction syndrome, hepatic infarction, passive hepatic congestion, and hypoxic (sometimes referred to as
ischemic) hepatitis. In this chapter, the latter two will be discussed in detail as we highlig ht the complex inter-
play between the circulatory system and hepatic function.
Passive liver congestion
It is not uncommon for diseases affecting the heart and liver to coexist. This can occur in the setting of sys-
temic diseases affecting both organs, such as alcohol-related dilated cardiomyopathy and cirrhosis, as well as
numerous inflammatory, autoimmune, and infectious conditions
[1]. This can also occur as the result of primary
cardiac diseases, such as heart failure or constrictive pericarditis, resulting in hepatic dysfunction, or more rarely
in primary liver disease resulting in cardiac dysfunction in the absence of primary cardiovascular abnormalities
[2]. Congestive hepatopathy refers to a collection of hepatic manifestations resulting from passive hepatic conges-
tion in the setting of right-sided heart failure, whether that be due to constrictive pericarditis, mitral stenosis, tri-
cuspid regurgitation, or cardiomyopathy
[3]. In this section, we will discuss the hepatic circulatory system, how
passive congestion can disrupt it, and the clinical manifestations of this interplay.
Hepatic circulation
The liver derives its blood supply from the portal vein and the hepatic artery [4]. This dual blood supply offers
a buffer that allows for compensation when one system becomes compromised. For instance, in the event of the
portal vein demonstrating decreased blood flow, the hepatic arterial buffer system can respond and provide
25%60% of the diminished flow from the portal system
[5]. The liver receives 25% of cardiac output, a number
that far outstrips the 2.5% of total body weight it occupies
[4]. The total volume of blood flow through the liver
ranges between 800 and 1,200 mL/min
[2]. Whether via the portal venous or hepatic arterial system, once blood
enters the liver, it mixes and enters the hepatic sinusoids, where it interfaces with hepatocytes before draining
through the hepatic veins. The hepatic veins then take blood out of the liver into the inferior vena cava for even-
tual return to the right atrium
[6]. It is through this final connection that diseases of the heart can lead to passive
hepatic congestion.
123
Cardio-Hepatology.
DOI:
https://doi.org/10.1016/B978-0-12-817394-7.00016-4 © 2023 Elsevier Inc. All rights reserved.
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