Pediatric Infectious

Diseases
Edited by

Dr. Edwin Dias

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Pediatric Infectious Diseases

Chapter: Liver Diseases
Edited by: Edwin dias
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Liver Diseases
Oumaima Stambouli*
M.Sc Genetic and Molecular Biology/Institute of Virology Essen,
University hospital Essen, Germany
*Corresoponding author: Oumaima Stambouli, M.Sc Genetic and
Molecular Biology/Institute of Virology Essen, University hospital
Essen, Germany, E-mail: oumaimastambouli@hotmail.fr

Abstract
The most important infectious diseases of the liver in pediatrics are hepatitis, cholangitis, cholecystitis, Reye syndrome and
pyogenic liver abscesses. The causative agents are very different: Viruses are the main cause of hepatitis, while bacteria are the most
frequent pathogens in cholangitis, cholecystitis and pyogenic liver abscesses; the etiology of Reye syndrome remains unclear. In this
chapter we will review the above syndromes, focusing on infants and young children.

Keywords: Cholangitis; Cholecystitis; Hepatitis; Pyogenic liver abscess; Reye syndrome

Liver Disease
I - Hepatitis
The viral causes of hepatitis can be divided into hepatotropic and non-hepatotropic viruses [1] and are summarized in tables 1
and 2 [2].
Non-hepatotropic viruses
Measles, rubella, enteroviruses (Coxsackie and echo), Flaviviruses (yellow fever, dengue fever), Filoviruses (Marburg and Ebola), Arenaviruses
(lassa fever), Parvovirus B19, Adenovirus, Herpesviruses (herpes simplex types 1 and 2), Varicella zoster virus, Cytomegalovirus, Epstein Barr virus and
human herpes virus type 6.
Table 1: Non-hepatotropic viruses.
Virus name

Genetic material

Mode of transmission

Hepatitis A

RNA
Single stranded

Oral-fecal
Rarely Parenteral

Hepatitis B

DNA
double stranded

Hepatitis C

Carrier state

Main clinical sydromes

Available
treatments

prevention

No

Acute hepatitis
Prolonged cholestasis

No treatment

Vaccination

Parenteral sexual contact

mother to child

yes

Acute hepatitis
Chronic hepatitis

Lamivudine
Tenofovir

Vaccination

RNA
Single stranded

Parenteral

yes

Acute hepatitis
Chronic hepatitis

Interferon/ ribavirin
No vaccination
Telaprevir/ Boceprevir

Hepatitis D

Defective RNA
Single stranded
Need HBV

Parenteral sexual contact

mother to child

yes

Parenteral sexual contact

Alpha interferon
mother to child

Vaccination
against HBV

Hepatitis E

RNA
Single stranded

Oral-fecal
Rarely Parenteral

No

Fluminant hepatitis in
pregnant women

No vaccination

Hepatitis G

RNA
Single stranded

Parenteral sexual contact

mother to child

Parenteral sexual contact

mother to child

No treatment
-

No vaccination

Table 2: Hepatotropic viruses.;

Hepatotropic viruses
Hepatitis A Virus (HAV) is a small, single-stranded RNA virus. The main way of transmission is oral-fecal; the virus can rarely
be transmitted parenterally. The most common clinical syndromes in children are acute hepatitis and prolonged cholestasis. There
is no chronic carrier state. Acute HA is diagnosed by the presence of serum immunoglobulin (Ig) M anti-HAV, but sometimes, liver
biopsy is necessary. In children, HAV infection is usually asymptomatic or has mild, nonspecific symptoms, whereas adolescents
and adults are more likely to be clinically ill [2] and can progress to fulminant hepatitis. The treatment is not available for acute
hepatitis A virus infection; as in most cases the infection is self-limiting and is followed by complete recovery without chronic squeal,
and no specific interventions are required. Patients with hepatic failure are highly recommended to transfer to centre capable of
performing liver transplants [3] (Table 3).
E antigen

E antibody

Acute HBV, early phase

Surface antigen Surface antibody

Yes

No

Yes

No

Igm core antibody Igg core antibody

Yes

Yes or no

HBV DNA

Acute HBV, window phase

No

No

No

Yes

Yes

Yes or no

Low

E antigen-positive
chronichepatitis

Yes

No

Yes

No

No

Yes

High

E antigen-negative
chronichepatitis

Yes

No

No

Yes

No

Yes

Moderate

Inactive carrier state

Yes

No

No

Yes

No

Yes

Absent or low

Resolved hepatitis B

No

Yes or no

No

Yes

No

Yes

Absent

High

Table 3: Serologic patterns of hepatitis B virus (HBV) infection [4]

The Hepatitis B Virus (HBV) genetic material is a circular, partially double-stranded DNA molecule. It is transmitted by unprotected sexual contact, parenterally and from mother to child. HBV causes both acute and chronic hepatitis [2]. Infection in infancy

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Interpretation

003

and early childhood is usually asymptomatic or with mild nonspecific symptoms, although acute hepatitis and rarely fulminant hepatic
failure have been reported [5]. In neonates and infants, opposite to adults, the rate of progression to a carrier state is remarkably high.
The nucleoside analogues lamivudine, entecavir, and telbivudine, and the nucleotide analogues adefovir and tenofovir, are indicated for
the treatment of HBV infection [6]. HBV vaccine is available and it is developed using recombinated DNA technology [7].
The hepatitis C Virus (HCV) contains a single-stranded RNA molecule. Transmission occurs mostly through the parenteral route,
but the virus is significantly less contagious, compared to HBV. Clinically, the initial infection with HCV can be asymptomatic, or present
as acute hepatitis, with most infections progressing to carrier state and chronic hepatitis [2]. In childhood, there is a direct correlation
between age and the presence of lymphoid follicles, bile duct lesions, and increased activity [8]. Although there is still no vaccination for
HCV, panoply of treatments is available. The combination of pegylated interferon and ribavirin was the first treatment of hepatitis C and
recently boceprevir and telaprevir, two antiviral drugs, was approved by the FDA [9].
The hepatitis D Virus is a defective RNA virus who requires the presence of HBV for infection and it is transmitted in the same way.
The virus leads to more severe acute hepatitis in the setting of acute coinfection with HBV or a chronic rapidly progressive hepatitis if
superinfection in an HBV carrier occurs [2]. Vaccination against HBV will protect against HDV. Treatment of chronic HDV infections
is currently limited to extensive alpha-interferon therapy or in extreme situations, to liver transplantation [10].
Hepatitis E Virus contains a single-stranded small RNA. The common transmission is oral-fecal and rarely parenteral. The infection
is acute and self-limited, or it can leads to cholestatic hepatitis with no chronic carrier stage, particularly in solid organ transplant recipients [11]. An important exception is pregnancy, as pregnant women can develop fulminant hepatitis E with significant mortality rates. All
the studies have shown that pregnant women have a differential immune response that triggers fulminant liver failure. Hence, the logical
treatment should be to deliver the fetus as soon as possible [12].
Hepatitis F Virus also called GBV-C virus contains single-chain RNA with positive polarity. There are reports on the occurrence of
acute, fulminant and chronic (mild and moderate) hepatitis and hepatic fibrosis. The virus is transmitted parenterally, from mother to
child and by unprotected sexual contact [13].
Cases of typhoid hepatitis in traveling persons, which is a co-transmission of Salmonella typhi and hepatitis A or hepatitis C, were
reported in the Indian subcontinent. In fact, the Feco-oral route is the most common mode of transmission of the fever, hepatitis A and
E and thus infection by these agents have an association with poor sanitation [14,15].

Nonhepatotropic viruses
The nonhepatotropic viruses are often the cause of multisystem disease and may result in severe liver disease in neonates and immunocompromised patients [16].
Cytomegalovirus (CMV) is a cause of hepatitis in immunocompetent and immunocompromised individuals. A mononucleosis-like
syndrome can be seen in older children. In infancy, the biopsy may have features of giant cell hepatitis, with prominent extramedullary
hematopoiesis. Paucity of bile ducts may be present [17]. Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, is
often associated with elevated serum levels of transaminase as part of systemic disease and rarely with fulminant hepatic. Epstein-Barr
viral hepatitis is characterized by a prominent portal and sinusoidal lymphoid infiltrate that can have atypical cells. There may be hepatocyte ballooning, individual cell necrosis, and, in more severe cases, focal necrosis and cholestasis [18,19].
Herpes simplex virus is a cause of disseminated disease with fulminant hepatic failure in immunocompetent infants [20,21]. Transmission is usually vertical, but infection can be acquired postnatally. Hepatic pathology is characterized by randomly distributed, irregular areas of necrosis with hemorrhage but without inflammation.
Human herpesvirus-6associated neonatal giant cell hepatitis, fulminant hepatic failure, and chronic hepatitis have been reported
in young children [22,23]. We have seen a pediatric case of acute human herpesvirus-6-associated hepatitis with a prolonged cholestatic
phase [22,23].
Adenovirus, Echovirus, Parvovirus B19 (PVB19) are other viruses that can cause acute hepatitis [2]. Liver pathology in children with
HIV infection may reflect the patients state of immunodeficiency (opportunistic infections and tumors), a more direct effect of HIV,
antiretroviral drug-induced hepatitis, or other viral infections [24-26].

Cholangitis and Cholecystis

Cholangitis
The term Cholangitis refers to inflammation of the biliary system. Clinically, it is seen most often in the presence of biliary tract disease and obstruction and can often lead to (biliary) sepsis [27].

Etiology and pathogenesis

The pathogenesis of cholangitis at onset involves two factors: (1) increased bacteria in the bile duct, and (2) elevated intraductal
pressure in the bile duct, allowing translocation of bacteria into the vascular and lymphatic system (cholangio-venous/lymphatic reux).
Because of its anatomy, the biliary system is likely to be affected by the elevated intraductal pressure. In cholangitis, bile ductules tend to
become more permeable to the translocation of bacteria and toxins with the elevated intraductal biliary pressure. This process results in
serious and fatal infections, such as hepatic abscess and sepsis [29].
Bacteria that commonly cause cholangitis are Escherichia coli, Klebsiella, Enterococcus, Enterobacter, Pseudomonas, and anaerobes.
Although most infections are polymicrobial, this situation may not always prevail [28].
In pediatrics, the most common setting for acute cholagitis is in a child with biliary artesia who has undergone hepatic portojejunos-

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Bacterial cholangitis is a clinically defined syndrome caused by the regurgitation of infected bile into the circulation. The pathogenic
mechanism is unclear, and systemic sepsis may not occur. The central mechanisms leading to biliary tract infection are biliary colonization and stasis. Healthy bile is typically sterile, implying that bactibilia develops either hematogenously via the portal venous system or
directly via ascending infection from the gut lumen [28].

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tomy (HPJ) or the Kasai operation. The Kasai procedure provides a permissive setup for chlangitis to occur, generally secondary to base
line poor bile flow and damaged intrahepatic bile conducts in conjunction with obligate bacterial colonization of intestinal conduit with
enteric flora [29-33].
Cholangitis caused by viral infection is rare. However, the common association is seen with hepatocellular diseases, especially hepatitis C and B. those two hepatitis infection have been associated with pathologic findings of bile duct injury with apparent clinical significance [34]. Also, viral cholangiopathies are mostly associated with cytomoegalovirus (CMV) infection [35].

Clinical presentation
Clinical ndings associated with acute cholangitis include abdominal pain, jaundice, fever (Charcots triad), and rigors. The triad was
already reported as an indicator of hepatic fever by Charcot in 1877 [36] and has been, historically, cited as the typical clinical penetration
of acute cholangitis. About 50%70% of patients with acute cholangitis develop all three symptoms [37,38]. Reynolds pentad (Charcots
triad plus shock and a decreased level of consciousness) was first described in 1959, when Reynolds and Dargan [39] dened acute obstructive cholangitis. The pentad is often used to indicate severe (grade III) cholangitis, but shock and a decreased level of consciousness
are observed in only 30% or fewer patients with acute cholangitis [37,38]. A history of biliary disease, such as gallstones, previous biliary
procedures, or the placement of a biliary stent is factors suggestive of acute cholangitis. Clinical symptoms of acute cholecystitis include
abdominal (right upper quadrant) pain, nausea-vomiting, and fever [40,41].
In children, fever is the most common presenting symptom [42] In addition, either stool discoloration (acholic stool) or an increase
in serum bilirubin concentration occurs in 68 %. Older children and teenagers with cholangiitis typically report abdominal pain. Patients
may report new-onset pruritus as a consequence of biliary salt retention [27].

Figure 1: Flowchart for the management of acute cholangitis [45].

Diagnostic evaluation
Physical examination may reveal a varied range of toxic appearances, with vital signs suggesting serious systemic infection in more
advanced cases (fever, tachycardia, hypotension). Physical examination typically reveals icteric sclera and a distended abdomen, with
tenderness localized to the mid or right upper quadrant. Palpation of the liver edge may reveal tenderness. Laboratory studies may reveal
an elevated erythrocyte sedimentation rate (81%), leukocytosis or leucopenia (56%), and increased serum levels of conjugated bilirubin
[42]. Laboratory evaluations in children should include a standard complete blood count with differential and liver panel (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase, and fractionated bilirubin [unconjugated
and conjugated]). The differential diagnosis of fever, abdominal pain, and jaundice also should include sepsis and hepatitis [27].
Abdominal ultrasound (US) and abdominal computerized tomography (CT) with intravenous contrast are very helpful studies in
evaluating patients with acute Suspicion of acute biliary tract disease. Abdominal US should be performed in all patients suspected of
having acute biliary inammation/infection [43,44].

Differential diagnosis

Diseases which should be differentiated from acute cholangitis are acute cholecystitis, gastric and duodenal ulcer, acute pancreatitis,
acute hepatitis, and non-biliray sepsis. Diseases which should be differentiated from acute cholecystitis are gastric and duodenal ulcer,
hepatitis, pancreatitis, gallbladder cancer, hepatic abscess, Fitz-Hugh-Curtis syndrome, right lower lobar pneumonia, angina pectoris,
myocardial infarction, and urinary infection [45].

Treatment
The selection of an antibiotic agent should be based on potentially infecting bacteria, the severity of the disease, and the presence of
comorbidities, such as hepatic or renal failure, patient allergies, local susceptibility patterns, and the patients history of antibiotic usage.
Biliary penetration of antibiotic agents should be considered as well, though this is less important than the antibiotic agents efficacy
against the suspected bacteria [46].

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The differential diagnosis for an acutely ill child with fever and clinical evidence of hyperbilirubinemia (jaundice) is broad; both infectious and noninfectious causes should be considered. A thorough investigation for hepatic and biliary tract pathology with blood and
radiologic studies must be initiated to evaluate for stones or other obstructive processes that may cause characteristic symptoms, such as
the Charcot triad [27].

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In addition, the clinical context should be considered when selecting an antibiotic, as it has been shown that anaerobic bacteria are
found more frequently in severe cholangitis than in mild cases. Similarly, hospital-acquired cholangitis is often caused by multiple and/or
resistant organisms, such as Pseudomonas, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant enterococci, whereas
infection in community-acquired cases is mostly caused by a single species of an intestinal micro organism, such as Escherichia coli,
Klebsiella, or Enterococcus [46].
The type and duration of antibiotic therapy should also be based on disease severity. For mild cases of acute cholangitis, 2-3 days
of a penicillin/-lactamase inhibitor combination (ie, piperacillin/tazobactam or ampicillin/ sulbactam) is usually sufficient. Moderate
and severe disease should be treated for a minimum of 5-7 days with broad-spectrum agents, such as third- or fourth-generation cephalosporins or penicillin/-lactamase inhibitors. If the drug of first choice is ineffective, fluorquinolones and carbapenems are alternative
agents [46].
The duration of treatment in all cases will ultimately depend on the response to treatment. If results of biliary or blood cultures become available, empirically initiated, broader-spectrum antibiotic regimens should be changed to narrower-spectrum agents [46].

Cholangitis and specific populations

Cholangitis and biliary artesia: In infants, the Kassai procedure is the most frequently surgical therapy that can predispose to ascending cholangitis. This procedure is nowadays the first line surgical treatment of infant biliary artesia [47,48].
Cholangitis after liver transplantation: In the pediatric population, the incidence of cholangitis after liver transplantation for biliary
artesia is approximately 5-11% [49].
Cholangitis in immunocompromised patients: Acquired Immunodeficiency syndrom (AIDS)-related cholangitis tends to appear
later in the course of the disease and is commonly seen in adults [27]. Cholangitis may occur in the setting of non-AIDS immunodeficiency with children with primary immunodeficiency, IgA/IgG deficiency and X-linked hyper-IgM syndrome [50,51]. Mycobacterium
avium-intracellulare and cytomegalovirus are among the causes of AIDS-related biliary disease.
Cholangitis in association with congenital anatomic abnormalities (choledochal cyst and Caroli Disease): Choledochal cysts occur in 1/15000 births in western nations and in 1/1000 in Japan [52]. Diagnosed late or untreated choledochal cysts may results in severe
complications secondary to biliary tract obstruction, including cholangitis [27]. Caroli Disease is a congenital dilatation of intra-hepatic
and extra-hepatic biliary ducts characterized by pure ductal ectasia [53,54]. Dilatation of the intrahepatic bile ducts results in biliary obstruction and places the patient at increased risk for development of cholangitis and increase morbidity [27].
Cholangitis following Endoscopic procedures: The use of endoscopic procedures in the pediatric population is rare, but growing;
cholangitis is a known complication of these procedures in adults [55].

Cholecystitis
Cholecystitis is an acute inammation of the gallbladder, most of the time caused by gallstones, but many other factors, such as ischemia, motility disorders, direct chemical injury, infections by bacteria, and parasites, collage vascularn disease, and allergic reactions
have also been implicated [29].

Etiology and pathogenesis

Gallstones generally are classified as either pigment stones or cholesterol stones. Pigment stones can be divided further into either
black or brown pigment stones. Black pigment stones occur in the face of a superabundance of unconjugated bilirubin in the bile and
are seen most commonly in hemolytic disease, leading to increased biliary concentration of bilirubin and to calcium-bilirubinate stones.
Brown pigment stones are less common and are associated with biliary infection or parasitic infestation, or with the presence of a foreign
body (e.g., retained suture material) or biliary obstruction. Cholesterol stones are the end result of biliary cholesterol supersaturation
secondary to an imbalance in the cholesterol: phospholipid: bile salt equilibrium or other precipitating factors [56].
Pigment stones occur more frequently in infants than cholesterol stones which is in direct contrast to adult population [27]. Pigmented gallstones in children appears with hemolystic diseases, primiraly sickle-cell, anemia, thalassemia, hereditary spherocytosis and
other red cell membrane defects, pyruvate kinase deficiency, glucose-6-phosphate deshydrogenase and autoimmune hemolytic anemia
[52,57,58]. Total parenteral nutrition (TPN) predisposes children to develop biliary tract diseases including gallstones formation [27].
Just like adults, the incidence in females is higher than boys in infants [59,60]. Also obesity seems to be an important risk factor [59].
Acalculous cholecystitis is a rare but important cause of cholecystitis in children. In general, acalculous gallbladder disease in children
occurs in various clinical settings. Congenital gallbladder abnormalities, idiopathic gallbladder distention without inflammation and
acute acalculous chplecystitis have been seen. [27]

Acute cholecystitis typically manifests with abdominal pain and vomiting. Pain may be localized to the right upper quadrant; however, in pediatric patients, this making distinction can be difficult, and it may be difficult to differentiate from other causes of acute
abdominal pain in children. In gallbladder inflammation, the pain becomes parietal-more localized to the right upper quadrant and associated with some peritoneal signs, such as pain with movement. With regard to the duration of pain, cholecystitis should produce pain
that is long-standing. Although obstruction of the cystic duct is associated with the acute onset of pain followed by resolution within 3 to
6 hours, true gallbladder inflammation may produce a more persistent pain, lasting 6 to 12 hours or longer [27].
Local signs of inflammation, fever, elevated WBC count and imaging findings (cholecystrography) are the criteria of confirming the
presence of cholecystitis [60,61].

Treatment
Treatments strategies in children vary from each case [27], but generally treatment of cholecystitis and cholelithiasis should be surgical and cholecystectomy should be the normal procedure [59].

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Clinical presentation

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Complications
Even when acute cholecystitis is promptly diagnosed, it may still lead to serious complications. An inflammed obstructed gallbladder
may wall off and form an intraluminal abcess or empyema. Performation of the gallbladder and secondary peritonitis is the most serious
complication [27].

Pyogenic Liver Abscesses

Pyogenic liver abscesses are rare in children. In pediatric patients, impaired host defense mechanisms seem to play an important role.
However, pyogenic liver abscess also occurs in healthy children. The rarity of liver abscesses may be explained in part by the rich blood
supply, unique architecture and extensive reticuloendothelial system of the liver, all of which present an effective barrier against bacterial
invasion [62]. Liver abscess (LA) is a frequently encountered disease in children from developing countries, especially those living in the
tropical and subtropical zones. It has become relatively uncommon in the western world.
Liver abscesses are in general classified as amoebic vs. non-amoebic (bacterial). Staph aureus and gram negative aerobic (Klebsiella
and E. Coli) or anaerobic (Bacteroides sp.) enteric organisms are the most common bacterial causes [63].

Etiology and pathogenesis

Historically, liver abscesses in children have been reported secondary to perforated appendicitis [63]. LA is often seen in children
with major debilitating diseases, granulocyte dysfunction, sickle cell disease, and congenital or acquired immunodeficiencies.
The biliary tract is an important source of pyogenic LA. Congenital anomalies, biliary strictures and other anatomic abnormalities
lead to obstruction of bile flow, resulting in bacterial proliferation. When the biliary tract is the source of LA, there are usually multiple
abscesses.
Pyogenic abscesses, particularly when multiple, may be caused by hematogenous dissemination (of either gastrointestinal infection
via the portal vein or disseminated sepsis via the hepatic artery), ascending cholangitis, or superinfection of necrotic tissue. A solitary
hepatic abscess is often cryptogenic and has no clear-cut predisposing cause [64]. Although biliary tract disease occurs relatively uncommonly in children, ascending cholangitis is a particularly frequent complication of the hepatic portoenterostomy procedure for
congenital biliary atresia and may lead to infections of the liver in such patients. Children have a unique set of predisposing factors for
liver abscesses. In poor income settings, parasitic infestations are thought to predispose to pyogenic liver abscesses in children. Almost all
parasites (Ascaris, Schistosomae, Fasciolia, Trichuris, Necator, Angylostoma and Toxocara) have been associated with LA. Significantly
higher proportions of parasitic infestation have been demonstrated in children with pyogenic liver abscesses, when compared to controls
from a similar background [27]. Experimental studies have shown that bacteremia especially from Staphylococcus species in presence of
parasitic infestation predisposes to liver abscess formation. Salmonella infection has also been associated with parasitoses. The pathogenic mechanism is thought to be stimulation of TH2 immunity in patients with worm infestations. This is hypothesized to suppress the
TH1 effector limb, thereby compromising phagocyte killing of bacteria and fungi. Furthermore, liver granulomas around parasites, their
larvae and eggs are believed to trap bacteria in the grannulomatous reaction around them serving as a nidus of infection. Tissues from
liver biopsies or surgical and autopsy specimens in patients with liver abscesses have documented eggs, larvae, and antigens of parasites.
An important laboratory clue to an underlying parasitosis is often peripheral eosinophilia (as high as 40% in some patients), elevated IgE
levels, antibodies to various parasites and detection of eggs and larvae in stool. Sometimes tropical myositis may point towards a Toxocara infestation. Appropriate tests are therefore recommended to confirm such infestation and appropriate treatment should be initiated.
Biliary ascariasis associated with cholangitis and liver abscesses continues to be common in endemic areas [65].

Diagnostic evaluation
To diagnose this condition, a physician may order a combination of blood cultures and imaging tests. The following tests may be
used:
- Computed tomography (CT) scan-to localize the abscess
- CT with intravenous contrast-to pinpoint and measure the abscess (very useful when planning a surgery)
- Blood tests-elevated white blood count and high neutrophil level indicate infection
- Blood cultures for bacteria-to identify the bacteria so the provider knows which antibiotic to prescribe
- Abdominal ultrasound-to visualize an abscess in the right upper quadrant.
A pyogenic liver abscess may appear as a mass on the liver when viewed with CT scans.

Treatment

Some people can be successfully treated for PLA with antibiotics alone. Nevertheless, the majority will require drainage. This involves
inserting a needle or tube into the abscess and aspiration of pus. The physician may perform a liver biopsy at the same time to determine
the overall health of the liver. This procedure is performed with the aid of a CT scan or ultrasound.
Some specialists may try to treat PLA without surgery, if possible. However, in more severe cases, surgery may be required to fully
remove the abscess materials. After surgery, most patients will need prolonged antibiotic treatment, in order to prevent recurrence.

Complications
The main complication of PLA is sepsis, a body-wide bacterial infection that causes inflammation and a dangerous drop in blood
pressure. If not treated promptly with antibiotics, sepsis will be ultimately fatal.

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There are different modes of medical and surgical treatment and it is difficult to prove the superiority of one modality over the other.
Rather, a judicious application of conservative and surgical methods is what is mostly resorted to. This review attempts to study the trends
in various aspects of LA in children and present the conclusions of several studies from different parts of the world [63].

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Reye Syndrome
Reye syndrome is sudden (acute) brain damage and liver dysfunction of unknown cause. The syndrome has occurred in children who
have been given aspirin when they have chicken pox or the flu. Reye syndrome has become very uncommon since aspirin is no longer
recommended for routine use in children [66,67].

Diagnostic evaluation
Reyes syndrome may be suspected in a child who begins vomiting three to six days after a viral illness, followed by altered mental status. Diagnosis involves blood tests to determine the levels of certain liver enzymes, which are highly elevated in Reyes syndrome. Other
blood changes may occur as well, including an increase in the level of ammonia and amino acids, a drop in blood sugar, and prolonged
clotting time. A liver biopsy may also be done after clotting abnormalities are corrected with vitamin K or blood products, if necessary. A
lumbar puncture (spinal tap) may be needed to rule out central nervous system infections (meningitis or encephalitis) [68].

Treatment
Children with Reye syndrome are usually treated in the hospital; those who are seriously ill will be cared for in the intensive care
unit (ICU). Treatment is supportive, as there is no cure. The clinical care team focuses on making sure a child with Reye syndrome stays
hydrated and maintains her electrolyte balance, and monitors nutrition intake and cardiorespiratory status. Chances of recovery are
greatest when key organ systems stay as balanced as possible. Tests that might be done include blood tests to monitor electrolytes and
liver function and an imaging study of the brain (CAT scan or MRI). Mechanical ventilation (a breathing machine or respirator) can be
necessary if breathing becomes too slow or ineffective. Intracranial pressure (pressure of the fluid within the brain) and blood pressure
might be monitored. Small quantities of insulin may be given to increase glucose metabolism, corticosteroids to reduce brain swelling,
and diuretics to get rid of excess fluid. If seizures occur, they are treated with antiepileptic medications. The prognosis for children with
Reye syndrome has improved. Thanks to earlier diagnosis and better treatment, the survival rate has risen to about 80%. The earlier the
syndrome is detected, the better the chances for survival. Children who progress to the late stages of the syndrome may suffer brain damage and disability [69,70].

Complications
The main complications of Reye syndrome are coma, permanent brain damage and seizures [71].

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