Introduction

The liver is the largest parenchymal organ in the body and has a complicated circulatory system, with dual afferent blood supply from the portal vein and hepatic artery. Although the liver mass accounts for only 2.5% of adult body weight, it receives nearly 25% of the resting cardiac output and at any given time contains 10–15% of total body blood volume. In addition to serving as an important blood volume reservoir, the liver is also a complex metabolic organ with important functions in biosynthesis, innate immunity, metabolism and toxin/metabolite clearance. By virtue of its size, multiple metabolic functions, and prominent position in the circulatory system, the liver is frequently involved, either as an accomplice or as an innocent bystander, in a range of systemic, circulatory and inflammatory disorders. This chapter reviews hepatic involvement in common, and some uncommon, systemic diseases affecting children and young adults.

Hepatic Dysfunction in the Intensive Care Unit

Hepatic dysfunction is a common occurrence in the intensive care unit, affecting up to one-third of non-cirrhotic adults [1]. Severe shock (that requiring significant pressor support), sepsis, use of mechanical ventilation (specifically positive end-expiratory pressure ventilation), and major surgery are independent risk factors for hepatic dysfunction in critically ill patients [1]. In low-flow and hypoxic states, the liver is at particular risk because selective splanchnic vasoconstriction results in decreased inflow via the portal vein. Normally the hepatic artery buffer response can partially compensate for decreased portal flow; however, this is an energy-dependent process and becomes markedly less efficient with severe or prolonged hypoperfusion [2]. In addition, high-dose systemic vasopressors (dopamine, epinephrine, and norepinephrine) reduce total liver blood flow by up to 50% and decrease the ratio of hepatic oxygen supply to consumption, delivering a second hit to the liver.

The association between hepatic dysfunction and mechanical ventilation can be ascribed to the impact of positive inspiratory pressure and positive end-expiratory pressure on portal vein and hepatic artery hemodynamics, increased right-sided heart pressure, and increased intrahepatic resistance [3]. In addition to direct effects on hepatic blood flow and metabolism, the above mechanisms of liver injury simultaneously activate the inflammatory cascade, which itself has multiple effects on hepatic function. Although the causes are multifactorial, acute hepatic dysfunction in the intensive care unit generally presents in one of two clinical patterns – sepsis-associated cholestasis or hypoxic hepatitis.

Sepsis-Associated Cholestasis

Systemic infection, even in the absence of shock, is frequently associated with hepatic dysfunction. This pattern of hepatic dysfunction in this setting is predominantly a cholestatic one, with serum bilirubin levels elevated out of proportion to changes in other biochemical markers. Multiple pathways contribute to sepsis-associated cholestasis, including increased bilirubin production (hemolysis, gastrointestinal bleeding, and resorption of hematomas), decreased intrahepatic bilirubin processing (shock, pharmacologic effects, use of total parenteral nutrition) and/or decreased bilirubin excretion (sepsis, biliary obstruction). Classic sepsis-associated cholestasis occurs in the context of gram-negative bacteremia. While lipopolysaccharide (i.e., endotoxin), the macromolecule derived from gram-negative bacterial cell walls, is a potent initiator of local and systemic inflammation, cholestasis in association with systemic infection can be triggered by any infectious or inflammatory state.

In the setting of systemic infection, the liver participates as both a perpetrator and a victim. The systemic inflammatory response syndrome, whether triggered by sepsis or another insult, prompts the liver to increase production and release of a group of circulating proteins known as acute phase proteins. The goal of these is to minimize tissue damage, promote tissue repair, isolate and neutralize invading pathogens, and prevent further pathogen entry. These proteins include fibrinogen, C-reactive protein, complement factors C3 and C9, haptoglobin, ceruloplasmin, α2-macroglobulin, CD14, α₁-antichymotrypsin, α₁-cysteine proteinase inhibitor, α₁-antitrypsin, and lipopolysaccharide-binding protein. This acute phase response is initiated when injury at an extrahepatic site prompts local monocytes, macrophages, and other immunologically active cells to release pro-inflammatory cytokines, including interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNFα) [4]. Within the liver itself, Kupffer cells, the resident macrophages, play a critical role in protecting the organism by scavenging endotoxin from the portal circulation. However, in the process these cells themselves become a major source of pro-inflammatory cytokines that can mediate hepatocellular injury. These cytokines activate STAT3/NF-κB signaling pathways within hepatocytes resulting in increased transcription of acute phase proteins. These circulating acute phase proteins are responsible for the clinical phenomena which accompany systemic infection/inflammation, including leukocytosis, fever, altered mental status, changes in lipid metabolism, decreased gluconeogenesis, cachexia, insulin resistance, and muscle weakness.

The importance of this cascade in the control of systemic infection/inflammation is illustrated in several animal models in which production of acute phase proteins is blocked. For example, with hepatocyte specific deletion of gp130, the signaling receptor of the IL-6 pro-inflammatory family of cytokines, mortality is significantly increased in a mouse model of polymicrobial sepsis, despite normal bacterial clearance [5]. The same is true in STAT-3 knock-out mice, which experienced significantly higher mortality and demonstrated decreased levels of acute phase proteins than control littermates after cecal ligation and puncture-induced peritonitis [6]. Unfortunately, the same pro-inflammatory cytokines that activate the protective arm of the acute phase response simultaneously inhibit hepatocyte and cholangiocyte transport mechanisms, including the sodium-dependent bile-salt transporter and the multispecific organic anion transporter 2, both located at the hepatocyte basolateral membrane, and the bile-salt export pump and conjugate export pump, which transport monovalent and divalent bile acids, respectively, at the canalicular membrane [7]. The end result is stagnant bile flow leading to cholestasis.

Alterations in the hepatic microvasculature also contribute to sepsis-associated cholestasis. The release of potent vasoconstrictors and physical obstruction of the hepatic sinusoids by inflammatory cells and fibrinous microthrombi lead to endothelial cell damage and hepatocyte necrosis. Circulation to the biliary tract, dependent on the most distal branches of the hepatic arterial tree, is particularly sensitive to altered intrahepatic blood flow.

Another component of the innate immune system, the neutrophil, plays a central role in the inflammatory response to systemic infection. Once neutrophils are activated, they disseminate throughout the body and can become sequestered in the capillary networks of internal organs, such as the liver. Within the liver, neutrophils can contribute to significant hepatocellular damage; however, they may also play a protective role. Sequestration of neutrophils within liver sinusoids may enhance bacterial trapping and clearance during sepsis, thus limiting the spread of infection, albeit at a cost to the liver itself [8].

A particularly severe and ominous form of sepsis-associated cholestasis is cholangitis lenta, or subacute nonsuppurative cholangitis. This unique entity has been described in association with a variety of systemic infections, particularly intra-abdominal infections, often with an indolent clinical course. Both adults and children have been reported, many of who had recently received liver transplants [9, 10]. The diagnosis of cholangitis lenta is based on classic histologic findings, including proliferation of bile ductules at the edges of portal tracts, inspissated bile within dilated bile ductules, and absence of bile accumulation in interlobular bile ducts, all in the absence of mechanical obstruction [10, 11]. This finding is associated with a high mortality rate, and suggests the presence of severe local, or systemic infection, even in the absence of an identified organism.

Hypoxic Hepatitis

The liver is unique in possessing a dual afferent blood supply, with two-thirds of hepatic blood flow comprised of partially deoxygenated blood rich in nutrients and hormones arriving from the abdominal organs via the low-pressure, low-resistance portal venous system, and the remainder compromised of well oxygenated blood delivered via the high-pressure, high-resistance hepatic artery. Of these two systems, only the hepatic artery supplies the major bile ducts, making the biliary tree particularly susceptible to altered hepatic arterial flow. As blood enters the liver through the portal triad (zone 1) and flows through the sinusoids (zone 2) to the central vein (zone 3) the concentrations of oxygen and other nutrients decrease. This oxygen-tension gradient in the hepatic lobule accounts for the increased susceptibility of pericentral hepatocytes (zone 3) to necrosis associated with hypoxia or poor perfusion.

Regulation of hepatic blood flow occurs not only through classic arterial autoregulation (the constrictive response of an artery in the setting of increased arterial pressure), but also through the hepatic arterial buffer response. This unique mechanism represents the ability of the hepatic artery to produce compensatory flow changes in response to changes in portal venous flow. These flow changes depend on the concentration of adenosine in the space of Mall, the small fluid-filled space surrounding the terminal branches of the hepatic artery and portal vein. The secretion of adenosine into the space of Mall occurs at a constant rate, while the washout of adenosine through the portal venules is dependent on portal flow. When portal vein flow is reduced, the concentration of adenosine increases, leading to dilatation of the hepatic artery, which helps to maintain consistent hepatic perfusion. Adenosine also activates sensory nerves in the space of Mall and initiates renal fluid retention (hepatorenal reflex), in an attempt to increase circulating blood volume [12, 13].

Regulation also occurs at the level of the hepatic sinusoidal network. In the healthy liver, balanced production and release of vasoconstrictors (cyclooxygenase 1 and thromboxane A₂) and vasodilators (nitric oxide) by hepatic stellate cells and liver sinusoidal endothelial cells maintains vascular tone and ensures adequate blood flow [14, 15]. Disruption of this normal balance plays a role in a variety of acute and chronic liver diseases [16, 17].

When hepatic oxygen delivery is critically insufficient for hepatocyte survival (due either to inadequate circulating blood volume, inadequate oxygen concentration, or impaired cellular oxygen uptake and utilization) the result is hypoxic hepatitis. Clinically, hypoxic hepatitis is characterized by a marked and rapid elevation of serum aminotransferases within 48 hours of the initial insult. Although some definitions require serum aminotransferases of at least 20 times the upper limit of normal, hypoxic hepatitis has been histologically confirmed in patients with enzyme levels well below this limit [18]. Classically, serum aminotransferase concentrations may reach 5,000 to 10,000 IU/L, while alkaline phosphatase levels are usually normal. Initially, aspartate aminotransferase (AST) exceeds alanine aminotransferase (ALT), but as ALT declines more slowly, a reversal of this ratio is often seen as the levels decline. Serum levels of creatinine, lactate and lactate dehydrogenase are often increased. Hepatomegaly, jaundice, and coagulopathy may be present, [18]. When coagulopathy is present, the timing mirrors that of aminotransferase elevation, while bilirubin levels tend to rise after aminotransferases have peaked, and are associated with a more severe clinical course and increased risk of complications [19]. Serum concentrations of AST and ALT can be expected to decrease by at least 50% within 72 hours of the insult and return to normal within 11 days if perfusion and oxygenation are restored and urine output is normal [20].

Hypoxic hepatitis is a common cause of severe acute liver injury in hospitalized adult patients, with an incidence of 2.5–4% in adult ICUs [21, 22]. Any clinical situation or primary disease that leads to inadequate hepatic oxygen delivery can cause hypoxic hepatitis. The most common underlying disorders are acute and chronic heart failure, respiratory failure, hypovolemic shock and septic shock; less common scenarios include pericardial tamponade, prolonged seizures, heatstroke, and cardiopulmonary bypass.

Patients with chronic liver congestion are particularly susceptible to hypoxic hepatitis when perfusion is compromised. In fact, in adults, some component of hepatic congestion is considered almost a pre-requisite for hypoxic hepatitis, as arterial hypotension itself is rarely associated with a significant increase in aminotransferases [21]. Many reports document the classic clinical and histologic picture of hypoxic hepatitis in patients with chronic congestive heart disease who experience an acute event leading to decreased perfusion, often without an obvious or significant decrease in systolic blood pressure [18, 21, 22]. The increased risk of hypoxic hepatitis in this setting is likely the result of a combination of insults: decreased cardiac output, which may lead to chronic recurrent subclinical hypoxic events; splanchnic vasoconstriction from activation of the renin-angiotensin system, which may further decrease hepatic arterial blood flow; increased sinusoidal pressure; and endotoxemia as a consequence of ischemic and/or congested bowel [18].

In septic shock, decreased arterial blood flow and oxygen delivery are often compounded by microcirculatory changes mediated by endotoxin and pro-inflammatory cytokines, leading to inability of hepatocytes to effectively extract oxygen and multiplying the hypoxic damage to the liver [23].

The histology in hypoxic hepatitis is marked by centrilobular necrosis with preservation of the periportal zone; however, liver biopsy is seldom indicated in the appropriate clinical setting.

The presence of hepatic dysfunction, whether manifest as sepsis-associated cholestasis or hypoxic hepatitis, is a significant factor in prognosticating short-term outcome of critically ill patients, as reflected by the inclusion of hepatic parameters in many adult and pediatric critical illness severity scores, including the Simplified Acute Physiology Score (SAPS) II and the Sequential Organ Failure Assessment (SOFA) score. In adult patients, the presence of hypoxic hepatitis is associated with all cause early mortality of 45–49% [21, 22]. Serum bile acid concentration is an independent risk factor for 28-day mortality in critically ill adult patients, while new-onset cholestasis accompanying hypoxic hepatitis is a risk factor for one-year mortality [19, 24]. That being said, the cause of death in critically ill patients with hepatic dysfunction is unlikely to be liver failure, but instead is the underlying insult and pathophysiology that led to critical illness.

With advances in critical care and the ability to support patients through life-threatening systemic illnesses, a number of new, ICU-associated diseases are emerging, including a particularly severe form of rapidly progressive biliary tract disease termed secondary sclerosing cholangitis in critically ill patients (SSC-CIP). This disorder evolves in patients with no history of liver or biliary tract disease who require prolonged ICU admission accompanied by mechanical ventilation and vasopressor support [25]. It is believed to be a form of ischemic cholangiopathy with sloughing of the biliary epithelium leading to the formation of protein-rich bile casts. These bile casts are pathognomonic for this disorder, and can be identified early by ribbon-like intraductal filling defects visible by either ERCP or MRCP [26]. Later changes are classic of sclerosing cholangitis, with strictures and dilatations of the intrahepatic bile ducts but relative sparing of the common bile duct. Unlike sepsis-associated cholestasis, SSC-CIP has an insidious onset as patients recover from critical illness. In contrast to hypoxic hepatitis, serum aminotransferases are only mildly elevated, while gamma-glutamyl transferase, alkaline phosphatase, and eventually bilirubin are 5 to 50 times the upper limit of normal.

Sclerosing cholangitis in critically ill patients can be complicated by acalculous cholecystitis, bacterial cholangitis, liver abscesses, and nutritional failure [26]. The clinical course is unusually rapid, with progression to cirrhosis at a mean of six months after diagnosis, and a high mortality rate without liver transplantation [25].

Congenital/Acquired Heart Disease

In addition to facilitating the development of classic hypoxic hepatitis with markedly elevated serum aminotransferases and centrilobular necrosis, chronic hepatic congestion is itself associated with a distinct liver lesion marked by a spectrum of fibrotic changes ranging from mild sinusoidal fibrosis to the appearance of broad fibrous septa to frank cirrhosis (cardiac cirrhosis) [27]. Although most frequently described in association with right-sided heart failure, this lesion can also complicate ischemic heart disease, restrictive lung disease, constrictive pericarditis, pericardial effusion, and any other entity resulting in elevated central venous pressure. Clinically, liver injury due to chronic passive congestion is often silent. Biochemical abnormalities may have an insidious onset, with a profile that is predominantly cholestatic, with elevations in serum gamma-glutamyltransferase (GGT) and alkaline phosphatase levels out of proportion to elevations in serum aminotransferases.

In children, the most common causes of heart failure are congenital heart diseases. Among these, anomalies such as pulmonary atresia, ventricular septal defect and transposition of the great arteries may lead to pulmonary hypertension and chronic passive liver congestion. In addition, as new approaches for surgical and medical management of congenital heart lesions have increased the long-term survival of infants with critical complex heart disease, the long-term impact of these therapies is becoming obvious. A prime example is the development of liver disease in patients following Fontan palliation. This procedure, used in patients with single ventricle physiology, re-establishes normal systemic oxygen saturation by directly routing systemic venous return (via the superior vena cava or right atrium) to the pulmonary arteries, bypassing the sub-pulmonary ventricle. In doing so, it creates, and in fact depends upon, chronically elevated central venous pressure.

Fontan-associated liver disease (FALD) can manifest with either acute or chronic liver dysfunction. Acute dysfunction, usually around the surgery itself, represents classic hypoxic liver injury related to hypoperfusion, while long-term liver dysfunction may reflect a combination of chronic passive congestion and decreased cardiac output intrinsic to the Fontan circulation [28, 29]. While most Fontan patients are asymptomatic from a liver disease perspective and have only mild biochemical abnormalities (an elevated GGT in 40–60%), they are at significant risk of ongoing liver fibrosis and cirrhosis, with attendant complications [30]. A long-term follow-up study of liver biopsies in adolescents and young adults >10 years post-Fontan found some degree of hepatic fibrosis in >95% of clinically stable patients [31]. The most devastating complication of FALD is hepatocellular carcinoma, which is being reported with increased frequency in long-term Fontan survivors [32–34].

While time since Fontan consistently emerges as a risk factor for FALD, additional risk factors have not been clearly elucidated [31]. The best modality for disease surveillance and prognostication is also unknown. Magnetic resonance elastography (MRE) has emerged as a popular choice, as MRE-derived liver stiffness has been associated with worse hemodynamics and clinical outcomes in Fontan patients, and simultaneously allows for hepatocellular carcinoma surveillance [35]. In the absence of specific therapy for FALD, comprehensive supportive care and close surveillance for early identification of complications is paramount. In the setting of advanced liver disease or hepatocellular carcinoma, combined heart–liver transplant may be the best treatment option.

Hepatic Venous Outflow Obstruction

Effective obstruction of hepatic venous outflow can occur at several levels. When the obstruction is at the level of the hepatic sinusoids it is termed veno-occlusive disease (VOD; discussed below). Obstruction at the level of the heart is chronic passive congestion (discussed above), while obstruction to outflow at any level from the small hepatic veins to the junction of the inferior vena cava (IVC) with the right atrium constitutes Budd–Chiari syndrome. Budd–Chiari syndrome can be classified as primary when there is intraluminal obstruction by a thrombus or web, or secondary when there is extrinsic compression by an abscess, cyst or tumor.

While membranous obstruction of the hepatic veins or IVC is a common cause of Budd–Chiari syndrome in Africa and Asia, and has been described in children as well as adults, the most common cause of Budd–Chiari syndrome in western countries is hepatic vein thrombosis [36]. Thrombosis of the hepatic veins, or, less commonly, the IVC, can occur as a consequence of pro-thrombotic disorders, anti-fibrinolytic disorders, local endothelial cell damage, or some combination of these factors. Pro-thrombotic disorders in turn can be classified as either genetic or acquired.

The most common inherited thrombotic disorders associated with Budd–Chiari syndrome are the gain of function mutations in Factor V Leiden (leading to activated protein C resistance) and prothrombin/Factor II deficiency (leading to excessive prothrombin generation), and loss of anticoagulant function due to Protein C, Protein S, or antithrombin deficiencies [37, 38]. The reported prevalence of one or more of these inherited defects in patients with Budd–Chiari syndrome is variable, and often both inherited and acquired risk factors co-exist. Investigation for thrombotic risk factors in patients with established thrombosis can be challenging, as acquired deficiencies, related to the thrombosis or secondary effects, are common, and levels of Proteins C, S, and antithrombin are interpretable only when all other coagulation factors are normal.

Hyperhomocysteinemia, frequently resulting from a polymorphism in MHTR (677TT), encoding methylene tetrahydrofolate reductase, is also a risk factor for Budd–Chiari syndrome. This is particularly true in China, where a higher frequency of MHTR polymorphisms likely interacts with lifestyle factors such as smoking and alcohol use to increase the incidence of hyperhomocysteinemia [39].

Theoretically, anti-fibrinolytic disorders might also potentiate the development of Budd–Chiari syndrome. While increased plasma levels of plasminogen activator inhibitor 1 and decreased levels of thrombin-activatable fibrinolysis inhibitor, plasmin inhibitor and apolipoprotein A1 have been described in patients with Budd–Chiari syndrome, the genetic basis for these differences is not yet understood [40].

The most common acquired cause of thrombophilia is myeloproliferative disorder. Although rare, thrombocythemia, polycythemia, and thrombocytosis may all occur in children, and may be associated with a risk for venous thrombosis. Mutations in JAK2, encoding the JAK2 tyrosine kinase, have been associated with both myeloproliferative disorder and Budd–Chiari syndrome in children and adults. JAK2 gene mutations result in the production of a constitutively activated JAK2 protein, which leads to increased red blood cell survival and thrombotic risk [41–43]. The association between myeloproliferative disorders and JAK2 mutations is so strong that the mutation itself may serve as a marker for occult or evolving myelodysplasia in the setting of Budd–Chiari syndrome [44].

Other acquired risk factors for Budd–Chiari syndrome include the presence of antiphospholipid and anticardiolipin antibodies, often associated with rheumatologic conditions; other chronic inflammatory states such as Behçet disease, inflammatory bowel disease, sarcoidosis, pregnancy and the peripartum period; paroxysmal nocturnal hemoglobinuria; use of oral contraceptives; and intra-abdominal infection. Each of these factors, genetic and/or acquired, is unlikely to lead to Budd–Chiari syndrome individually. In many cases, multiple thrombophilic risk factors have been identified, and in those for whom only one risk factor was evident, an as yet unidentified predisposition may be at play.

Budd–Chiari syndrome most often presents as chronic obstruction with hepatomegaly, ascites, abdominal distension and abdominal pain. In children, lethargy and anorexia may also be present. Often, abdominal and chest wall collaterals are prominent and distended. Serum aminotransferase and bilirubin levels are generally only mildly to moderately elevated, although hypoalbuminemia and coagulopathy are present in almost half of patients [45, 46]. The histology of chronic Budd–Chiari syndrome is microscopically indistinguishable from chronic passive congestion and VOD, with zone 3 congestion, necrosis and fibrosis [45]. A liver biopsy is rarely necessary for diagnosis, as the clinical picture and imaging findings are the key.

Acute Budd–Chiari syndrome can present with similar clinical findings but is more likely to include jaundice and coagulopathy. Acute congestion leading to massive centrilobular necrosis and fulminant hepatic failure is occasionally the presenting scenario of hepatic venous outflow obstruction, particularly if it occurs in the setting of pre-existing chronic liver disease.

The first step in evaluation of a patient with suspected hepatic venous outflow obstruction is pulsed Doppler ultrasonography of the hepatic vessels and IVC. When experienced practitioners use this modality, the presence of specific findings in the hepatic or caval veins, such as stenosis, thrombosis, fibrotic cord, or insufficient recanalization of the vessel, along with caudate lobe hypertrophy, can identify Budd–Chiari syndrome with a high specificity [47, 48]. Contrast-enhanced cross-sectional imaging is the second line of investigation, and is useful for identifying indirect signs of Budd–Chiari syndrome. These include alterations in hepatic morphology and perfusion, from the classic fan-shaped enhancement of the caudate lobe and central liver to parenchymal changes consistent with cirrhosis, as well as the presence of intra- and extrahepatic collateral vessels [48, 49]. MRI and CT also allow better visualization and anatomic orientation of the mesenteric and portal vasculature for therapeutic planning. With improvements in cross-sectional imaging, hepatic venography is rarely required for the diagnosis of Budd–Chiari syndrome and tends to be used only in those cases for which endovascular therapy is indicated.

Therapy for Budd–Chiari syndrome ranges from supportive medical management of complications to liver transplantation, and depends on the site and chronicity of the obstruction, the degree of liver dysfunction, and, in children, the size of the patient. Initial therapy is conservative, emphasizing diuresis, treatment of predisposing factors and prophylactic anticoagulation to decrease the risk of additional thromboses. In patients with long-standing obstruction and evidence of either decompensated portal hypertension or synthetic dysfunction, early evaluation for liver transplantation may be the most appropriate and expedient course. In all other cases, acute or chronic, the focus is on removing or bypassing the obstruction and re-establishing normal portal and hepatic vein pressures.

While directed thrombolytic therapy of hepatic vein/IVC thrombosis has been reported, the role in managing children, either primarily or as adjunctive therapy, is not defined. In adults, percutaneous transluminal angioplasty is a mainstay of therapy; with recent data suggesting that routine stenting with angioplasty is superior to angioplasty alone at preventing restenosis [50, 51]. While there is growing experience with angioplasty in small children, the use of stents is controversial, as placement is technically more challenging, and stents carry a risk of migration as well as obstruction, mandating long-term anticoagulation.

Transjugular intrahepatic portosystemic shunting (TIPS) is the most common endovascular procedure employed for Budd–Chiari syndrome in adults, and there is growing experience using this technology in small children [46, 52]. However, open surgical procedures, including thrombosis or web resection with pericardial patch grafting, and mesocaval, splenocaval, splenoatrial and splenojugular shunts, are still commonly employed in both children and adults. Liver transplantation remains the salvage therapy for patients with inadequate response to shunting procedures or recurrent shunt thrombosis. Importantly, in patients with underlying thrombophilia, long-term anticoagulation is necessary to prevent recurrence post-transplant.

Hematologic Disorders

Allogeneic Stem Cell Transplantation

Hepatic complications are common in children undergoing stem cell transplant and can be classified based on etiology (primary disease, drug-induced liver injury, infectious, vascular, parenteral nutrition-associated, immunologic), or by timing related to stem cell transplant (pre-transplant, early post-transplant, late post-transplant). A structured approach is necessary when evaluating the patient with hepatic abnormalities following stem cell transplant, with the primary goal of identifying conditions amenable to therapy. Because of the complex clinical and treatment scenarios of these patients, more than one pathologic process is frequently operant.

Related posts:

Chapter 5 – Cirrhosis and Chronic Liver Failure in Children Chapter 13 – Familial Hepatocellular Cholestasis Chapter 14 – Alagille Syndrome Chapter 25 – α1-Antitrypsin Deficiency Chapter 38 – Urea Cycle Disorders in Children Chapter 43 – Liver Transplantation in Children: Indications and Surgical Aspects

Stay updated, free articles. Join our Telegram channel

Join