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cellular debris, scattered shrunken liver cells, and red blood cells (Fig. 10.1). Apoptotic bodies are often present at the

interface between preserved and necrotic areas. In addition, at the border of liver cell necrosis, fatty degeneration is

commonly observed. In more severe cases, the injury may affect much of the lobule, sparing periportal regions. In

some cases, a midzonal distribution of liver cell necrosis has been reported

[10,11].Somedegreeofpassivecongestion

is usually observed, demonstrated by the presence of sinusoidal dilation associated with liver cell plates compression.

Within days, inflammatory cells (neutrophils, lymphocytes, and pigmented macrophages) infiltrate necrotic areas.

While chronic passive congestion is usually secondary to right-sided heart failure, this morphological pattern is

often observed with centrilobular necrosis and may potentiate the development of lobular necrosis

[12].

Histologically, chronic passive congestion is defined by atrophy of hepatocellular plates, sinusoidal dilation, and in

themoreadvancedstagesfibrosisoccursinthecentrilobular areas and may further extend to portal zones (

Fig. 10.2).

HH may occur in specific conditions, including patients with cirrhosis, mostly resulting from associated hem-

orrhagic and sepsis complications

[13]. Presence of portosystemic shunting and impaired blood flow in cirrhotic

parenchyma may exacerbate the hypoxic damage

[14]. While its frequency is debated, reported in up to 15% of

cases, histological analysis shows liver cell necrosis in the center of the cirrhotic nodules [3,1315]. HH may also

occur in patients with diffuse metastatic infiltration of the liver, mainly breast adenocarcinomas

[16,17].

Histological analysis demonstrates hepatocellular necrosis related to hypoxia secondary to massive sinusoidal

infiltration by tumoral cells. Additional circumstances may lead to HH, including heatstroke, sickle cell disease,

and acute cases of BuddChiari syndrome

[1820].

In typical clinical cases, histological analysis, that is liver biopsy is not required

[3]. It is also important to

stress that some heterogeneity through the sample may be observed. In cases of severe disease, transjugular

biopsy is preferred in these patients with mu ltiple comorbidities, especially those with coagulation troubles.

When performed, liver biopsy allows the evaluation of the extent of tissue damages and indicates the potential

existence of chronic features, especially the presence of underlying fibrosis.

The differential diagnosis of HH in acute cases encompasses other causes of confluent centrilobular necrosis,

mainly toxicity of paracetamol (acetaminophen) or cocaine (

Fig. 10.3) [21]. Noteworthy, on the histological level,

lesions can be undistinguishable and only the clinical context may determine the diagnosis. While in viral hepati-

tis, well-demarcated necrotic regions may be observed, like in herpesvirus infection, there is not such a centrilob-

ular pattern.

FIGURE 10.1 Acute heart failure/Hypoxic hepatitis. (A) and (B) Sirius red stain showing normal liver architecture with extensive centri-

lobular necrosis sparing periportal hepatocytes. In damaged areas, hepatocellular dropout with sinusoidal dilation. (C) Hematoxylin and

Eosin stain showing the extensive necrotic areas with residual hepatocytes in periportal regions. (D) At higher magnification, marked sinusoi-

dal dilation and congestion (PT, portal tract).

134 10. Histopathology of the liver in heart failure

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FIGURE 10.2 Chronic heart failure/congestive hepatopathy (intermediate stage). (A) and (B) Sirius red stain showing a normal liver

architecture with enlarged portal tract and septa originating from the centrilobular vein; presence of pericellular fibrosis associated with sinu-

soidal dilation. Sinusoidal dilation with compressed hepatocellular plates on reticulin. (C) and (D) Hematoxylin and Eosin stain (PT, portal

tract; CLV, centrilobular vein).

FIGURE 10.3 Toxic hepatitis (acetaminophen-related). (A) Macroscopic view of a explanted liver showing normal architecture with

extensive necrosis (nutmeg pattern). (B) Sirius red stain showing normal liver architecture. (C) Hematein and Eosin stain showing the exten-

sive necrotic areas with sinusoidal dilation and congestion. (D) At higher magnification, few residual hepatocytes are observed in periportal

regions (PT, portal tract; CLV, centrilobular vein).

135Pathological analysis

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Patients with chronic heart failure, especially right-side heart failure, develop a liver injury that may coexist

with ischemic/hypoxic injury. Chronic passive congestion (congestive hepatopathy) is morphologically character-

ized by sinusoidal dilation and congestion, centrilobular hepatocellular drop-out, and fibrosis development

(

Fig. 10.2). In that context, compared to most other chronic liver diseases, inflammation is minimal to absent.

Pericellular fibrosis starts in the centrilobular area and then extends with the development of central-central or

central-portal bridging, which may in the most severe cases lead to cirrhosis. By contrast to the other risk factors

for chronic liver disease, such as chronic viral infections, excessive alcohol consumption, or autoimmune dis-

eases, the cirrhotic nodules are centered by portal tract, defining the so-called “cardiac cirrhosis” or “inverted cir-

rhosis.” Importantly, it has been highlighted the significant he terogeneity of fibrosis, limiting the value of liver

biopsy to accurately assess the extent of the fibrotic process (

Fig. 10.4) [22,23].

A recent study on liver biopsies obtained from heart tran splant candidates reports variable fibrosis in 50% of

the cases and with significant heterogeneous fibrosis (defined as difference of stage by 2) in 26% of the cases

[23].

Among 16 biopsies, 5 showed uniform advanc ed fibrosis while advanced fibrosis was focal in seven liver biop-

sies

[23]. Accordingly, extensive sampling might improve the accuracy of the fibrosis assessment on liver biopsy

even though correlation with the co mplete clinical information including imaging is mandatory. In addition to

fibrosis, nodular regenerative hyperplasia (NRH), defined as normal hepatic parenchyma into small nodules

(13 mm) composed of nodules of hyperplastic hepatocytes surrounded by compressed atrophic cell plates with-

out significant fibrosis, may be observed. In congestive hepatopathy, NRH has been reported in 18% of biopsies

from heart transplant candidates. Noteworthy, such NRH changes coexist with the presence of significant fibrosis

in other areas of the liver

[23].

Pathogenesis

Several pathogenetic mechanisms involved in HH have been debated. Among them, a toxic mechanism

related to bacterial infection, related to the release of a toxin by bacteria into the circulation was initially pro-

posed

[9,24]. Later on, the involvement of passive congestion of the liver was preferred as a significant

FIGURE 10.4 Chronic heart failure/Congestive hepatopathy (heterogeneous distribution of fibrosis). (A) Liver biopsy showing on the

Sirius red stain various degrees of fibrosis with extensive fibrosis in some areas (*) and other areas showing quite normal architecture (**).

(B) Sirius red stain in a fibrotic zone showing extensive pericellular fibrosis with septal bridges. Hematoxylin and Eosin stains showing

sinusoidal dilation (C) and thickening of centrilobular vein wall (D) (PT, portal tract; CLV, centrilobular vein).

136 10. Histopathology of the liver in heart failure

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number of patients with heart failure and liver cell necrosis did not have bacterial infection. Finally, in the

early 1950s, reports of the association between shock, centrilobular liver necrosis, and a massive increase in

transaminases in patients who died in shock state suggested that liver ischemia, related to decreased hepatic

blood flow, was involved in the development of liver cell necrosis

[10,25,26]. Recently, based on hemody-

namic data, the key role of hypoxia has been highlighted, justifying to rename this liver injury as “HH”

instead of “shock liver” “or “ischemic hepatitis”

[1,2]. Moreover, in addition to hypoxia, reoxygenation,

occurring at the time of reperfusion, is also able to contribute to liver cell necrosis [2729].Accordingly,HH

has been presented as a typical setting of hypoxia/reperfusion injury, that implies various mechanisms,

including oxidative stress, Kupffer cell activation, and neutrophil chemoattraction

[28]. The occasional

description of midzonal necrosis also supports the involvement of reperfusion injury

[11,27]. In these cases ,

it is suggested that liver reperfusion is incomplete, sparing anoxic centrilobular hepatocytes, a nd the peripor-

tal h epatocytes survive, which is due to the preserved oxygen input

[27].

Pathophysiology of HH is in most cases multifactorial, and depending on the clinical conditions leading to

HH, sever al hemodynamic mechanisms of liver hypoxia are involved. In patients with HH related to heart fail-

ure, while liver ischemia is essential, passive congestion of the liver may also play a role by predisposing the

liver to hypoxia

[1,2,30,31]. Such a relationship has been explored in a large series of 1000 autopsy subjects, and

showed a strong correlation between chronic passive congestion and centrilobular necrosis, suggesting that the

local damages induced by one lesion may exacerbate preexisting morphologic features of the other

[12].In

patients with respiratory failure, hypoxemia is the main hemodynamic factor of HH while cardiac output and

hepatic blood flow are normal or increased

[32]. Some degree of passive liver congestion may also be present

[30]. By contrast, in toxic-septic shock, HH results from the increased demands to oxygen and the inability of

liver cells to use oxygen while cardiac output and hepatic blood flow are increased but insufficient

[33,34].In

that context, endotoxins and inflammatory mediators are potentially involved through their action toward s mod-

ulation of respiratory function of hepatocytes and liver microcirculation

[35].

Fibrosis development in patients with chronic heart failure represents a sequela of persistent dilation and con-

gestion of the liver microvasculature that may activate hepatic stellate cells into myofibroblasts. In addition, the

role of hepatic venous thrombosis in the progression of fibrosis has been proposed, and might explain the patchy

distribution of fibrosis

[22,36].

Conclusion

HH, morphologically defined by centrilobular necrosis, is a critical clinical condition needing to be recognized

to allow the best management of patients. While its diagnosis does not require a histological diagnosis, patholo-

gists should be aware of the morphological aspects that can overlap with liver toxicity, especially acetaminophen.

In patients with chronic heart disease, congestive hepatopathy encompasses a wide spectrum of lesions including

fibrosis and NRH.

References

[1] Henrion J, Schapira M, Luwaert R, Colin L, Delannoy A, Heller FR. Hypoxic hepatitis: clinical and hemodynamic study in 142 consecu-

tive cases. Medicine 2003;82(6):392406.

[2] Birrer R, Takuda Y, Takara T. Hypoxic hepatopathy: pathophysiology and prognosis. Intern Med Tokyo Jpn 2007;46(14):106370.

[3] Fuhrmann V, Kneidinger N, Herkner H, Heinz G, Nikfardjam M, Bojic A, et al. Hypoxic hepatitis: underlying conditions and risk factors

for mortality in critically ill patients. Intensive Care Med 2009;35(8):1397405.

[4] Raurich JM, Llompart-Pou JA, Ferreruela M, Colomar A, Molina M, Royo C, et al. Hypoxic hepatitis in critically ill patients: incidence,

etiology and risk factors for mortality. J Anesth 2011;25(1):506.

[5] Wallach HF, Popper H. Central necrosis of the liver. Proc Inst Med Chic 1948;17(8):189.

[6] Kisloff B, Schaffer G. Fulminant hepatic failure secondary to congestive heart failure. Am J Dig Dis 1976;21(10):895900.

[7] Nouel O, Henrion J, Bernuau J, Degott C, Rueff B, Benhamou JP. Fulminant hepatic failure due to transient circulatory failure in patients

with chronic heart disease. Dig Dis Sci 1980;25(1):4952.

[8] Fuhrmann V, Ja

ger B, Zubkova A, Drolz A. Hypoxic hepatitis - epidemiology, pathophysiology and clinical management. Wien Klin

Wochenschr 2010;122(56):12939.

[9] Mallory FB. Necroses of the liver. J Med Res 1901;6(1):26480.

[10] Bynum TE, Boitnott JK, Maddrey WC. Ischemic hepatitis. Dig Dis Sci 1979;24(2):12935.

[11] de la Monte SM, Arcidi JM, Moore GW, Hutchins GM. Midzonal necrosis as a pattern of hepatocellular injury after shock.

Gastroenterology 1984;86(4):62731.

137References

II. Hepatobiliary system in heart failure

https://t.me/medicina_free

[12] Arcidi JM, Moore GW, Hutchins GM. Hepatic morphology in cardiac dysfunction: a clinicopathologic study of 1000 subjects at autopsy.

Am J Pathol 1981;104(2):15966.

[13] Henrion J, Colin L, Schmitz A, Schapira M, Heller FR. Ischemic hepatitis in cirrhosis. Rare Lethal J Clin Gastroenterol 1993;16(1):359.

[14] Molino G, Avagnina P, Ballare

M, Torchio M, Niro AG, Aurucci PE, et al. Combined evaluation of total and functional liver plasma flows

and intrahepatic shunting. Dig Dis Sci 1991;36(9):118996.

[15] Pauwels A, Le

vy VG. Ischemic hepatitis in cirrhosis: not so rare, not always lethal. J Clin Gastroenterol 1993;17(1):889.

[16] Harrison HB, Middleton HM, Crosby JH, Dasher MN. Fulminant hepatic failure: an unusual presentation of metastatic liver disease.

Gastroenterology 1981;80(4):8205.

[17] Henrion J, Schapira M, Heller FR. Ischemic hepatitis: the need for precise criteria. J Clin Gastroenterol 1996;23(4):305.

[18] Charlotte F, Bachir D, Ne

nert M, Mavier P, Galacte

ros F, Dhumeaux D, et al. Vascular lesions of the liver in sickle cell disease. A clinico-

pathological study in 26 living patients. Arch Pathol Lab Med 1995;119(1):4652.

[19] Dilawari JB, Bambery P, Chawla Y, Kaur U, Bhusnurmath SR, Malhotra HS, et al. Hepatic outflow obstruction (Budd-Chiari syndrome).

Experience with 177 patients and a review of the literature. Medicine 1994;73(1):2136.

[20] Bouchama A, Knochel JP. Heat stroke. N Engl J Med 2002;346(25):197888.

[21] Wanless IR, Dore S, Gopinath N, Tan J, Cameron R, Heathcote EJ, et al. Histopathology of cocaine hepatotoxicity. report of four patients.

Gastroenterology 1990;98(2):497501.

[22] Louie CY, Pham MX, Daugherty TJ, Kambham N, Higgins JPT. The liver in heart failure: a biopsy and explant series of the histopatho-

logic and laboratory findings with a particular focus on pre-cardiac transplant evaluation. Mod Pathol 2015;28(7):93243.

[23] Dhall D, Kim SA, Mc Phaul C, Kransdorf EP, Kobashigawa JA, Sundaram V, et al. Heterogeneity of fibrosis in liver biopsies of patients

with heart failure undergoing heart transplant evaluation. Am J Surg Pathol 2018;42(12):161724.

[24] Mallory FB. Chronic passive congestion of the liver. J Med Res 1911;24(2):45562.

[25] Jervis G, Ladue JS, Wroblewski F. The diagnostic, prognostic and epidemiologic significance of serum glutamic oxaloacetic transaminase

(SGO-T) alterations in acute hepatitis. Ann Intern Med 1956;45(5):782800.

[26] Chinsky M, Sherry S. Serum transaminase as a diagnostic aid. AMA Arch Intern Med 1957;99(4):55668.

[27] Henrion J. Ischemia/reperfusion injury of the liver: pathophysiologic hypotheses and potential relevance to human hypoxic hepatitis.

Acta Gastro-Enterol Belg 2000;63(4):33647.

[28] Biasi F, Bosco M, Chiappino I, Chiarpotto E, Lanfranco G, Ottobrelli A, et al. Oxidative damage in human liver transplantation. Free

Radic Biol Med 1995;19(3):31117.

[29] Massip-Salcedo M, Rosello

-Catafau J, Prieto J, Avı

la MA, Peralta C. The response of the hepatocyte to ischemia. Liver Int J Int Assoc

Study Liver 2007;27(1):616.

[30] Seeto RK, Fenn B, Rockey DC. Ischemic hepatitis: clinical presentation and pathogenesis. Am J Med 2000;109(2):10913.

[31] 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(5):696703.

[32] Henrion J, Minette P, Colin L, Schapira M, Delannoy A, Heller FR. Hypoxic hepatitis caused by acute exacerbation of chronic respiratory

failure: a case-controlled, hemodynamic study of 17 consecutive cases. Hepatol Baltim MD 1999;29(2):42733.

[33] Ruokonen E, Takala J, Kari A, Alhava E. Septic shock and multiple organ failure. Crit Care Med 1991;19(9):114651.

[34] Edwards JD. Oxygen transport in cardiogenic and septic shock. Crit Care Med 1991;19(5):65863.

[35] Zhang H, Vincent JL. Oxygen extraction is altered by endotoxin during tamponade-induced stagnant hypoxia in the dog. Circ Shock

1993;40(3):16876.

[36] Wanless IR, Liu JJ, Butany J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology

1995;21(5):12327.

138 10. Histopathology of the liver in heart failure

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https://t.me/medicina_free

CHAPTER

The Fontan procedure and liver disease

Masanari Kuwabara

1,2

and Koichiro Niwa

Department of Cardiology, Toranomon Hospital, Minato, Tokyo, Japan

Department of Cardiology, Cardiovascular Center,

St. Luke’s International Hospital, Chuo, Tokyo, Japan

Introduction

There are many review articles that showed the association between congenital heart disease (CHD) and liver

disease

[16]. It is well recognized that acute heart failure causes liver injury but chronic heart failure also causes

congestive hepatopathy

[7]. One of the well-known chronic heart failure conditions is CHD, especially in patients

who have undergone the Fontan procedure. The Fontan procedure is accepted as the definitive palliation for

patients with single-ventricle physiology

[8]. However, the lack of subpulmonary ventricle alters the static resis-

tance and dynamic impedance, resulting in a profound impact on the hepatic circulation

[9]. Long-term hepatic

dysfunction is a late complication in patients, who have undergone the Fontan procedure

[10], which is called

the Fontan-associated liver disease (FALD). Hepatic fibrosis or cirrhosis, which are severe hepatic complication,

results from increased hepatic venous pressure caused by passive venous congestion, tissue hypoxia, and

decreased cardiac output

[11,12]. The first report of hepatocellular carcinoma (HCC) following Fontan procedure

was published in 2005

[12]. After this report, many case reports were published on HCC in patients who have

undergone the Fontan procedure

[1323]. Long duration after the Fontan procedure ( . 20 years) is one of

the risk factors for cirrhosis, and hyaluronic acid and gamma-GTP were reported as useful markers to evaluate

the progression of liver fibrosis in patients who have undergone the Fontan procedure

[24].However,theappropriate

interval for screening of liver function is unknown

[1]. This article reviewed recent articles and summarized

these recommendations to unveil the causes, manifestations, and diagnosis of FALD.

Fontan procedure

The Fontan procedure was first performed in 1968 [25], and the operation and the modified Fontan operation

have been widely applied to thousands of patients with single-ventricular physiology worldwide

[26]. The

Fontan procedure creates an anastomosis generally between the vena cava or right atrium and the pulmonary

arteries (

Fig. 11.1), which allow systemic venous blood to bypass a pumping subpulmonary chamber [4].Asa

result, the Fontan physiology characterized elevated central venous pressure and low cardiac output

[27].

A prospective multicenter study showed that the 5-year survival rate was 93.5% by following 600 adult Fontan

survivors from 40 Japanese institutions

[28]. The study indicated that left isomerism heart (one of the heterotaxy

syndromes), prior hospitalization, protein-losing enteropathy, pulmonary arter iovenous fistulae, higher New

York Heart Association (NYHA) functional classes, impaired hemodynamics, hyponatremia, hepatorenal dys-

function, and use of diuretics were associated with a high mortality rate in Fontan survivors. Ohuchi et al.

insisted that Fontan pathophysiology is a multiorgan disease that requires a multidisciplinary management strat-

egy to improve the long-term outcome

[28].

139

Cardio-Hepatology.

DOI:

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Physiology and prevalence of Fontan-associated liver disease

Long-term hepatic dysfunction is a late complication in patients who have undergone the Fontan procedure

[10] and it is known as the FALD. Increased hepatic venous pressure caused by passive venous congestion, tissue

hypoxia, and decreased cardiac output after Fontan procedure induces liver damage, which in turn causes

hepatic complications, including cirrhosis and HCC

[6,11,12].

The mechanisms of FALD are different from those of cirrhosis and HCC caused by a hepatitis virus infection

or fatty liver

[9]. Low cardiac output in CHD decreases the hepatic blood supply, which induces a hepatic

hypoxic state and results in damage in zone 3 of the liver. Damaged hepatocytes induce fibrosis that leads to

cirrhosis. Moreover, follow-up of patients who have undergone the Fontan procedure revealed that the systemic

venous pressure was three- to fourfold higher than normal and extremely high during exercise, which chronically

elevated the right atrial or vena caval pressure, that in turn increased hepatic vein pressure

[11,12]. A study con-

firmed that time after the Fontan procedure was the sole factor significantly associated with collagen deposition,

which suggested that liver fibrosis was an inherent feature of Fontan physiology

[29]. However, no inflammation

or hepatocellular damage was evident in patients who have undergone the Fontan procedure, which suggested

that fibrosis may be mediated by a noninflammatory mechanism

[30].

Previous studies showed that cirrhosis may develop into HCC in 1.5%5.0% of cases per year

[4] and the preva-

lence of HCC in this study population could increase in further follow-up period. A Japanese cross-sectional

study showed that the prevalence of HCC was estimated at only 0.18% and the mortality of HCC was as high as

40% in more than 20 years of follow-up among patients who have undergone the Fontan procedure

[9]. The

mean periods of first diagnosis of cirrhosis and/or HCC from the first Fontan procedure were 14.5 (524) years

and 21.6 (731) years

[9]. Moreover, in a murine model, Simonetto et al. observed that sinusoidal thrombosis and

mechanical strain secondary to blood stasis were the main fibrogenic promoters

[31]. These authors also con-

firmed minimal inflammatory activity, supporting that inflammation is not a common feature of FALD

[32].

Wanless et al. have also argued that intrahepatic thrombosis is one of the main causes of cirrhosis

[33]. A cross-

sectional study showed the prevalence of hepatic complications using data of 139 Fontan patients who under-

went cardiac computed tomography (CT) scans out of a total of 204 patients; the mean age was 19.0 6 6.3 years

old and the mean elapsed time since the initial Fontan operation was 11.5 6 4.7 years. The results showed that

57 Fontan patients (41%) had hepatic complications, including radiological features of cirrhosis (25.9%), thrombo-

cytopenia (7.2%), hepatic masses (2.9% ), and hyperbilirubinemia (20.9%). Moreover, elapsed time since the initial

(A) (B) (C)

SVC

IVC

Conduit

FIGURE 11.1 Anatomic variants of Fontan anatomy. (A) A bidirectional cavopulmonary shunt that entails ligation of the superior vena

cava (SVC) to the right pulmonary artery (PA) is depicted. The inferior vena cava (IVC) is anastomosed to the PA to supply blood to the

lungs. (B) Fontan with an intra-atrial conduit that channels blood from the IVC to the PA through the RA. Blood from the SVC is channeled to

the PA. (C) An extracardiac Fontan uses a conduit from the IVC to the right PA with anastomosis of the SVC to the PA. Source: This figure and

figure legends are cited and copied from reference

[4]: Hilscher MB, Kamath PS. Congenital heart disease and the liver. Clin Liver Dis. 2019;14:138141.

(This is reprinted from Asrani SK, Asrani NS, Freese DK, Phillips SD, Warnes CA, Heimbach J, Kamath PS, et al. Congenital heart disease and the liver.

Hepatology 2012;56(3):11601169 [1], used with permission from Mayo Foundation for Medical Education and Research).

140 11. The Fontan procedure and liver disease

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Fontan operation correlated with hepatic complications. It suggests that late hepatic dysfunction and cirrhotic

change were often seen in Fontan

[34].

Examination to detect Fontan-associated liver disease

The appropriate interval for screening of liver function is not yet fixed [1]. A study showed that low platelet

counts, increased hemoglobin, aspartate aminotransferase, γ-guanosine triphosphate, total bilirubin, and elevated

international normalized ratio of prothrombin time could be the risk markers for FALD

[9]. To detect FALD,

contrast-enhanced CT or magnetic resonance imaging (MRI) is recommen ded to be performed to further evaluate

hepatic nodules detected on ultrasound imaging

[4,9].

Hilscher et al. mentioned that hepatic nodules should be diagnosed and treated as HCC, if they have charac-

teristic features on either CT or MRI (i.e., arterial hyperenhancement and portal venous washout, heterogeneous

appearance, necrosis) or if concomitant AFP levels exceed 200 ng/mL

[4].

A recent study evaluated ultrasonography (US) and abdominal CT/MRI scan to detect liver nodules using the

data of 152 Fontan patients; the mean age was 27.3 years old and the meantime elapsed from surgery to inclusion

was 18.3 years. The results showed that the prevalence of liver nodules was 29.6% on US and 47.7% on MRI/CT.

The sensitivity and specificity of US were 50% and 85.3%, respectively. It suggested that MRI/CT is superior to

US in detecting liver nodules

[35]. Another study showed that liver US revealed abnormal results in 92.3% of

patients but liver function tests did not correlate with imaging studies. However, white blood cell count, platelet

count, and N-terminal pro-brain natriuretic peptide were correlated with severity in transient elastography. CT

seems to be more useful for differentiation of severe hepatic changes evaluated by post-Fontan high pulmonary

vascular resistance and high mean pulmonary artery pressure

[36].

Recommendation

The mortality of patients who developed liver diseases after undergoing the Fontan procedure is not so high.

However, the mortality was nearly 30%40% after patients are diagnosed with HCC. In contrast, the mortality in

the Fontan patients diagnosed with cirrhosis is still unclear. Some Fontan patients with LC can have extended

survival (more than 10 years). We must account for the different etiology of HCC and cirrhosis between Fontan

patients and other chronic liver diseases. Further long-term observational studies are needed.

References

[1] Asrani SK, Asrani NS, Freese DK, Phillips SD, Warnes CA, Heimbach J, et al. Congenital heart disease and the liver. Hepatology.

2012;56:11609. Available from:

https://doi.org/10.1002/hep.25692.

[2] Tellez L, Rodriguez-Santiago E, Albillos A. Fontan-associated liver disease: a review. Ann Hepatol. 2018;17:192204. Available from:

https://doi.org/10.5604/01.3001.0010.8634.

[3] Gordon-Walker TT, Bove K, Veldtman G. Fontan-associated liver disease: a review. J Cardiol. 2019;74:22332. Available from:

https://

doi.org/10.1016/j.jjcc.2019.02.016

[4] Hilscher MB, Kamath PS. Congenital heart disease and the liver. Clin Liver Dis. 2019;14:13841. Available from:

https://doi.org/

10.1002/cld.828.

[5] Komatsu H, Inui A, Kishiki K, Kawai H, Yoshio S, Osawa Y, et al. Liver disease secondary to congenital heart disease in children. Expert

Rev Gastroenterol Hepatol. 2019;13:65166. Available from: https://doi.org/10.1080/17474124.2019.1621746.

[6] Tellez L, Rodriguez de Santiago E, Albillos A. Fontan-associated liver disease. Rev Esp Cardiol. 2018;71:192202. Available from:

https://doi.org/10.1016/j.rec.2017.10.052.

[7] Koehne de Gonzalez AK, Lefkowitch JH. Heart disease and the liver: pathologic evaluation. Gastroenterol Clin North Am.

2017;46:42135. Available from: https://doi.org/10.1016/j.gtc.2017.01.012.

[8] Driscoll DJ. Long-term results of the Fontan operation. Pediatr Cardiol. 2007;28:43842. Available from:

https://doi.org/10.1007/s00246-

007-9003-4

[9] Kuwabara M, Niwa K, Toyoda T, Shirai T, Tateno S, Ohuchi H, et al. Liver cirrhosis and/or hepatocellular carcinoma occurring late after

the Fontan procedure- a nationwide survey in Japan. Circ J. 2018;82:115560. Available from:

https://doi.org/10.1253/circj.CJ-17-1053.

[10] Warnes CA, Williams RG, Bashore TM, Child JS, Connolly HM, Dearani JA, et al. ACC/AHA 2008 guidelines for the management of

adults with congenital heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice

Guidelines (Writing Committee to Develop Guidelines on the Management of Adults with Congenital Heart Disease). Developed in col-

laboration with the American Society of Echocardiography, Heart Rhythm Society, International Society for Adult Congenital Heart

Disease, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2008;52:

e143263. Available from:

https://doi.org/10.1016/j.jacc.2008.10.001.

141References

II. Hepatobiliary system in heart failure

https://t.me/medicina_free

[11] Kiesewetter CH, Sheron N, Vettukattill JJ, Hacking N, Stedman B, Millward-Sadler H, et al. Hepatic changes in the failing Fontan circula-

tion. Heart. 2007;93:57984. Available from:

https://doi.org/10.1136/hrt.2006.094516.

[12] Ghaferi AA, Hutchins GM. Progression of liver pathology in patients undergoing the Fontan procedure: chronic passive congestion, car-

diac cirrhosis, hepatic adenoma, and hepatocellular carcinoma. J Thorac Cardiovasc Surg. 2005;129:134852. Available from:

https://doi.

org/10.1016/j.jtcvs.2004.10.005

[13] Asrani SK, Warnes CA, Kamath PS. Hepatocellular carcinoma after the Fontan procedure. N Engl J Med. 2013;368:17567. Available

from:

https://doi.org/10.1056/NEJMc1214222.

[14] Martinez-Quintana E, Monescillo A, Rodriguez-Gonzalez F. Hepatocellular carcinoma in a non-failing Fontan circulation. Rev Esp

Enferm Dig. 2017;109:375. Available from:

https://www.ncbi.nlm.nih.gov/pubmed/28480728.

[15] Takuma Y, Fukada Y, Iwadou S, Miyatake H, Uematsu S, Okamoto R, et al. Surgical resection for hepatocellular carcinoma with cardiac

cirrhosis after the Fontan procedure. Intern Med. 2016;55:326572. Available from:

https://doi.org/10.2169/internalmedicine.55.6869.

[16] Oh C, Youn JK, Han JW, Kim GB, Kim HY, Jung SE. Hepatocellular carcinoma after the Fontan procedure in a 16-year-old girl: a case

report. Medicine. 2016;95:e4823. Available from:

https://doi.org/10.1097/MD.0000000000004823.

[17] Josephus Jitta D, Wagenaar LJ, Mulder BJ, Guichelaar M, Bouman D, van Melle JP. Three cases of hepatocellular carcinoma in Fontan

patients: review of the literature and suggestions for hepatic screening. Int J Cardiol. 2016;206:216. Available from:

https://doi.org/

10.1016/j.ijcard.2015.12.033

[18] Maeda A, Shibata SC, Okitsu K, Imada T, Takahashi A, Uchiyama A, et al. Pain management with bilateral continuous thoracic paraver-

tebral block in a patient with Fontan-associated hepatocellular carcinoma undergoing hepatectomy. Reg Anesth Pain Med.

2015;40:71819. Available from:

https://doi.org/10.1097/AAP.0000000000000316.

[19] Yamada K, Shinmoto H, Kawamura Y, Wakamatsu H, Kawauchi T, Soga S, et al. Transarterial embolization for pediatric hepatocellular

carcinoma with cardiac cirrhosis. Pediatr Int. 2015;57:76670. Available from:

https://doi.org/10.1111/ped.12619.

[20] Rajoriya N, Clift P, Thorne S, Hirschfield GM, Ferguson JW. A liver mass post-Fontan operation. QJM. 2014;107:5712. Available from:

https://doi.org/10.1093/qjmed/hcu020.

[21] McCabe N, Farris AB, Hon H, Ford R, Book WM. Hepatocellular carcinoma in an adult with repaired tetralogy of fallot. Congenit Heart

Dis. 2013;8:E13944. Available from:

https://doi.org/10.1111/j.1747-0803.2012.00700.x.

[22] Elder RW, Parekh S, Book WM. More on hepatocellular carcinoma after the Fontan procedure. N Engl J Med. 2013;369:490. Available

from: https://doi.org/10.1056/NEJMc1306854.

[23] Saliba T, Dorkhom S, O’Reilly EM, Ludwig E, Gansukh B, Abou-Alfa GK. Hepatocellular carcinoma in two patients with cardiac cirrho-

sis. Eur J Gastroenterol Hepatol. 2010;22:88991. Available from:

https://doi.org/10.1097/MEG.0b013e32832e2bec.

[24] Shimizu M, Miyamoto K, Nishihara Y, Izumi G, Sakai S, Inai K, et al. Risk factors and serological markers of liver cirrhosis after Fontan

procedure. Heart Vesseles. 2016;31:151421. Available from: https://doi.org/10.1007/s00380-015-0743-4.

[25] Fontan F, Baudet E. Surgical repair of tricuspid atresia. Thorax. 1971;26:2408. Available from:

https://doi.org/10.1136/thx.26.3.240.

[26] Gewillig M, Brown SC. The Fontan circulation after 45 years: update in physiology. Heart. 2016;102:10816. Available from:

https://doi.

org/10.1136/heartjnl-2015-307467

[27] Gewillig M, Goldberg DJ. Failure of the fontan circulation. Heart Fail Clin. 2014;10:10516. Available from:

https://doi.org/10.1016/j.

hfc.2013.09.010

[28] Ohuchi H, Inai K, Nakamura M, Park IS, Watanabe M, Hiroshi O, et al. Mode of death and predictors of mortality in adult Fontan survi-

vors: a Japanese multicenter observational study. Int J Cardiol. 2019;276:7480. Available from: https://doi.org/10.1016/j.ijcard.2018.09.002.

[29] Goldberg DJ, Surrey LF, Glatz AC, Dodds K, O’Byrne ML, Lin HC, et al. Hepatic fibrosis is universal following Fontan operation, and

severity is associated with time from surgery: a liver biopsy and hemodynamic study. J Am Heart Assoc. 2017;26:e004809. Available

from:

https://doi.org/10.1161/JAHA.116.004809.

[30] Kendall TJ, Stedman B, Hacking N, Haw M, Vettukattill JJ, Salmon AP, et al. Hepatic fibrosis and cirrhosis in the Fontan circulation: a

detailed morphological study. J Clin Pathol. 2008;61:5048. Available from:

https://doi.org/10.1136/jcp.2007.052365.

[31] Simonetto DA, Yang HY, Yin M, de Assuncao TM, Kwon JH, Hilscher M, et al. Chronic passive venous congestion drives hepatic fibrogen-

esis via sinusoidal thrombosis and mechanical forces. Hepatology. 2015;61:64859. Available from: https://doi.org/10.1002/hep.27387.

[32] Tomkiewicz-Pajak L, Hoffman P, Trojnarska O, Lipczynska M, Podolec P, Undas A. Abnormalities in blood coagulation, fibrinolysis, and

platelet activation in adult patients after the Fontan procedure. J Thorac Cardiovasc Surg. 2014;147:128490. Available from:

https://doi.

org/10.1016/j.jtcvs.2013.06.011

[33] Wanless IR, Liu JJ, Butany J. Role of thrombosis in the pathogenesis of congestive hepatic fibrosis (cardiac cirrhosis). Hepatology

1995;21:12327. Available from:

https://doi.org/10.1002/hep.1840210504.

[34] Baek JS, Bae EJ, Ko JS, Kim GB, Kwon BS, Lee SY, et al. Late hepatic complications after Fontan operation; noninvasive markers of

hepatic fibrosis and risk factors. Heart. 2010;96:17505. Available from: https://doi.org/10.1136/hrt.2010.201772.

[35] Tellez L, Rodriguez de Santiago E, Minguez B, Payance A, Clemente A, Baiges A, et al. Prevalence, features and predictive factors of

liver nodules in Fontan surgery patients: The VALDIG Fonliver prospective cohort. J Hepatol. 2020;72:70210. Available from:

https://

doi.org/10.1016/j.jhep.2019.10.027

[36] Song J, Kim K, Huh J, Kang IS, Kim SH, Yang JH, et al. Imaging assessment of hepatic changes after Fontan surgery. Int Heart J.

2018;59:100814. Available from: https://doi.org/10.1536/ihj.17-349.

142 11. The Fontan procedure and liver disease

II. Hepatobiliary system in heart failure

https://t.me/medicina_free

PART III

Cardiovascular system in liver failure

https://t.me/medicina_free

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