A presentation from a tutorial about an interesting case that came to the Pediatric Department of Sebha Medical Center and was imaged by the Radiology Department. The tutorial was a joint effort between Dr Zeinab Salem Ali (from Pediatric Department) and me (from Radiology Department). In her slides, Dr Zeinab presented the case history, examination, investigations, differential diagnosis and discussed the clinical presentation, investigations and management for chronic liver diseases in pediatric patients.In my slides, I discussed the definition, etiology, natural history of this condition and explained the role of imaging in its diagnosis. These are my slides after some modifications. I added an aknowlegement page to illustrate Dr Zeinab effort and to thank Dr Khaled Aljasem from Pediatric Department for his effort in revising the original presentations and the constructive feedback he provided which improved the quality of the presented material. Then I added a summary for the parts Dr Zeinab has presented to make this powerpoint presentation complete. This presentation was presented by Dr Zeinab Salem (from Pediatric Department) and me in a joint tutorial between Pediatric Department and Radiology Department of Sebha Medical Center.

1. Dr Zeinab Salem Ali
Pediatric Department
Sebha Medical Center
Dr Abdalla Mutwakil Gamal
Radiology Department
Sebha Medical Center
(Dr Abdalla Slides – modified version)

2. Acknowledgment
This presentation is a joint effort between Dr Zeinab Salem Ali (from Pediatric
Department) and me (from Radiology Department). In her slides, Dr Zeinab
presented the case history, examination, investigations, differential diagnosis
and discussed the clinical presentation, investigations and management for
chronic liver diseases in pediatric patients. In my slides, I discussed the
definition, etiology, natural history of this condition and explained the role of
imaging in its diagnosis.
Thanks are due to Dr Khaled Aljasem from Pediatric Department for his efforts
in revising the original presentations and the constructive feedback he
provided which improved the quality of the presented material.
These are my slides after some modifications. I added a summary for the parts
Dr Zeinab has presented to make this powerpoint presentation complete.

3. The case

4. History
6 years old libyan female presented with hematemesis
associated with headache, abdominal pain and
fatigue. She had 3 previous episodes of epistaxis and a
history of leg pain since 1 years that become more
severe in the last month. No other abnormalaity
detected on systemic review. The patient had normal
developmental, perinatal, vaccination. The dietary
history revealed that the patient eats clay, and that her
mother had the same habit when she was pregnant.

5. The family history revealed first degree consanguinity
between the patient parents, and also between her
grandparents from maternal and paternal sides. The
patient has multiple siblings having variable
complains including congenital cataract,
developmental delay, poor performance at school. The
patient father has blindness in his right eye since his
childhood, but he doesn’t recall the cause.
There is no history of animal contact or abortions in
the family.

6. Examination
The patient was febrile, dehydrated and in serious
general condition.
She had severe pallor.
Normal Cardiovascular and respiratory systems.
Distended abdomen with positive shifting dullness.

7. Investigations & imaging
Investigations were normal apart from severe
microcytic hypochromic anaemia (HB=2.9 mg/dl,
blood film showed microcytosis and anisocytosis),
hight while cell count (WBC=17,000) and prolonged
Prothrombin time (PT=20 seconds) and increased INR
(INR=1.6).
Abdomen and pelvis ultrasound showed mild
hepatomegaly, mild splenomegaly, mild ascites and
varices at porta hepatis.
Echocardiography showed mild degree of mitral
regurgitation.

14. Chronic liver disease
in pediatric

15. Contents
Definition
Etiology
Natural History
Clinical presentation
Investigation
Imaging
Management

16. Definition
Chronic liver disease in the clinical context is a disease
process of the liver that involves a process of progressive
destruction and regeneration of the liver parenchyma
leading to fibrosis and cirrhosis.

17. Etiology
Major congenital disorders leading to chronic disease
include biliary atresia, tyrosinemia, untreated
galactosemia, and α1-antitrypsin deficiency.
In older children, HBV, HCV, autoimmune hepatitis,
Wilson disease, primary sclerosing cholangitis, cystic
fibrosis, and biliary obstruction secondary to
choledochal cyst are leading causes.

18. Biliary atresia
It is a congenital or acquired
disease of the liver and one of
the principal forms of chronic
rejection of a transplanted liver
allograft.
nfants and children with biliary
atresia have progressive
cholestasis with all the usual
concomitant features: jaundice,
pruritus, malabsorption with
growth retardation, fat-soluble
vitamin deficiencies,
hyperlipidemia, and eventually
cirrhosis with portal
hypertension.
Tyrosinemia
It is an error of metabolism,
usually inborn, in which the
body cannot effectively break
down the amino acid tyrosine.
Symptoms include liver and
kidney disturbances and mental
retardation. Untreated,
tyrosinemia can be fatal.
Most inborn forms of
tyrosinemia produce
hypertyrosinemia (high levels of
tyrosine).

19. Galactosemia
It is a rare genetic metabolic
disorder that affects an individual's
ability to metabolize the sugar
galactose properly. Galactosemia
follows an autosomal recessive
mode of inheritance that confers a
deficiency in an enzyme responsible
for adequate galactose degradation.
The disease usually appears in the
first few days of life following the
ingestion of breast milk or formula.
Vomiting, liver enlargement, and
jaundice are often the earliest signs
of the disease, but bacterial
infections (often severe), irritability,
failure to gain weight, and diarrhea
may also occur. If unrecognized in
the newborn period, the disease
may produce liver, brain, eye and
kidney damage.
Alpha 1-antitrypsin deficiency
It is a genetic disorder that causes
defective production of alpha 1-
antitrypsin (A1AT), leading to
decreased A1AT activity in the blood
and lungs, and deposition of
excessive abnormal A1AT protein in
liver cells.
There are several forms and degrees
of deficiency, principally depending
on whether the sufferer has one or
two copies of the affected gene
because it is a co-dominant trait.
Severe A1AT deficiency causes
panacinar emphysema or COPD in
adult life in many people with the
condition (especially if they are
exposed to cigarette smoke), as well
as various liver diseases in a
minority of children and adults, and
occasionally more unusual
problems.

20. Pediatric Hepatitis B
The hepatitis B virus (HBV), discovered
in 1966, infects more than 350 million
people worldwide. HBV can cause acute
and chronic liver disease. The clinical
presentation ranges from subclinical
hepatitis to symptomatic hepatitis and,
in rare instances, fulminant hepatitis.
Long-term complications of hepatitis B
include cirrhosis and hepatocellular
carcinoma.
Perinatal or childhood infection is
associated with few or no symptoms but
has a high risk of becoming chronic. A
limited number of medications can be
used to effectively treat chronic hepatitis
B; a safe and effective vaccine is available
to prevent hepatitis B infection caused
by HBV.
Pediatric Hepatitis C
Hepatitis C infection (HCV) is a chronic
viral infection of the liver that affects
upwards of 1-2 percent of adults.
Fortunately, in children and adolescents,
hepatitis C is less common, but it
remains a significant health issue.
Most children are infected with HCV at
birth. This is called vertical transmission
of infection (from mother to child). If a
mother has HCV, her child has a 1 in 20
chance of becoming infected at birth.
The higher the viral load in the mother
the higher the risk of infection. To date,
interventions at birth such as C-section
delivery have not been shown to alter the
risk of infection at birth.

21. Wilson's disease
It is an autosomal recessive genetic
disorder in which copper
accumulates in tissues; this
manifests as neurological or
psychiatric symptoms and liver
disease. It is treated with
medication that reduces copper
absorption or removes the excess
copper from the body, but
occasionally a liver transplant is
required.
The condition is due to mutations in
the Wilson disease protein (ATP7B)
gene. A single abnormal copy of the
gene is present in 1 in 100 people,
who do not develop any symptoms
(they are carriers).
Primary sclerosing cholangitis
Primary sclerosing cholangitis
(PSC) is a disease of the bile ducts
that causes inflammation and
subsequent obstruction of bile ducts
both inside and outside of the liver.
The inflammation impedes the flow
of bile to the gut, which can
ultimately lead to cirrhosis of the
liver, liver failure, and liver cancer.
The underlying cause of the
inflammation is believed to be
autoimmunity;[1] and more than
80% of those with PSC have
ulcerative colitis.[2] The definitive
treatment is a liver transplant.

22. Cystic fibrosis
It is an autosomal recessive genetic
disorder that affects mostly the
lungs but also the pancreas, liver,
and intestine. Difficulty breathing is
the most serious symptom and
results from frequent lung
infections. Other symptoms—
including sinus infections, poor
growth, and infertility—affect other
parts of the body.
The average life expectancy is 37 to
40 years in the United States. CF is
most common among people of
Central and Northern European
ancestry, but occurs in many
different groups around the world.
It is rarest among Asians and the
Middle Easterns.
Choledochal cysts
They are congenital conditions
involving cystic dilatation of bile
ducts. They are uncommon in
western countries but not as rare in
East Asian nations like Japan and
China.
Most of them present in 1st year of
life; adult presentation is rare and
usually at this stage is associated
with complication . Classic triad of
intermittent abdominal pain,
jaundice, and a right upper
quadrant abdominal mass is found
only in minority of patients.
Choledochal cysts are treated by
surgical excision of the cyst with the
formation of a roux-en-Y
anastomosis to the biliary duct.

23. Natural History
Natural History of chronic Liver Disease

24. Clinical presentation
Symptoms:
Fatigue.
Yellowing of the skin (jaundice).
Itching.
Swelling from fluid buildup in the legs (edema).
Bruising easily and having heavy nosebleeds.
Redness of the palms.
Small red spots and tiny lines on the skin called spider angiomas.
Weight loss and muscle wasting.
Belly pain or discomfort.
Frequent infections.
Confusion.
Signs:

27. Investigations
These will depend to a considerable extent upon clinical suspicion of the
aetiology.
LFTs: should include aspartate transaminase (AST), alanine transaminase
(ALT), alkaline phosphatase (ALP), bilirubin, gamma-glutamyltransferase
(gamma-GT); AST and ALT are raised due to hepatocyte damage; gamma-GT is
high in active alcoholics.
Albumin: there is hypoalbuminaemia in advanced cirrhosis.
FBC: occult bleeding may produce anaemia; hypersplenism may cause
thrombocytopenia; macrocytosis can suggest alcohol abuse.
Renal function tests and electrolytes: hyponatraemia may be present (due to
increased activity of antidiuretic hormone). Poor renal function may represent
hepatorenal syndrome.
Red cell folate: alcohol abuse is often associated with a diet inadequate in
folate.
Coagulation screen: abnormalities of coagulation are a sensitive test of liver
function; prothrombin time is reduced in advanced cirrhosis.

28. Ferritin: low ferritin may indicate iron deficiency from diet or blood loss;
ferritin is raised in haemochromatosis.
Viral antibody screen: to look for evidence of hepatitis B or C infection.
Fasting glucose/insulin/triglycerides and uric acid levels: these should be
measured if non-alcoholic steatohepatitis (NASH) is suspected.
Autoantibody screen: anti-mitochondrial antibodies are a very strong indicator
of primary biliary cirrhosis.[10]
Alpha-1-antitrypsin level: to assess for alpha-1-antitrypsin deficiency.
Ceruloplasmin and urinary copper: to look for Wilson's disease.
Fasting transferrin saturation and HFE (haemochromatosis C282Y) mutation:
along with a raised ferritin, these tests can screen for haemochromatosis.

29. Ultrasound
US, with high-frequency transducers and Doppler, is the
first modality of choice, directs the rest of the
investigations and guides interventional radiology.
1 – liver cirrhosis
2 – portal hypertension

30. Ultrasound
Checklist for liver cirrhosis:
surface nodularity: (88% sensitive, 82-95% specific)
overall coarse and heterogeneous echotexture
caudate width: right lobe width >0.65 (43-84%
sensitive, 100% specific)
signs of portal hypertension

31. Signs of portal hypertension:
& Doppler flow changes

32. Liver cirrhosis

33. Female patient with cirrhosis showing "coarsened" echo texture and
enlarged left lobe of liver

34. Advanced cirrhosis. A nodular liver, echogenic in comparison to renal parenchyma
(R), is seen. Ascites also is present

35. Diameter of the portal vein at the porta hepatis more than 15mm

36. Duplex power Doppler sonogram shows an enlarged spleen; varices are
apparent at the splenic hilum

37. curved-array transducer vs high-frequency linear-array transducer

38. CDS and Waveform
The aim of the Doppler examination is to assess the
presence and direction of flow in:
The Splanchnic veins
The main portal vein and its segmental intrahepatic
branches
The hepatic veins
The IVC

39. CT
CT is insensitive in early cirrhosis. More established findings include:
surface and parenchymal nodularity
regenerative nodules (most) are isodense to rest of liver
siderotic nodules (minority) hyperdense due to accumulation of iron
segmental hypertrophy/atrophy (see above)
parenchymal heterogeneity both on the pre and post IV contrast scans
isodense/hyperdense regenerative nodules
predominantly portal venous supply to dysplastic nodules.
In advanced cirrhosis, nodular margin and lobar hypertrophy/atrophy can be
demonstrated.
signs of portal hypertension
portal vein enlargement
portal venous thrombosis +/- cavernous transformation

40. Patient with cirrhosis showing tortuous hepatic arteries in addition to
enlarged left lobe and caudate (C)

41. More advanced cirrhosis. Computed tomography (CT) scan with a portal
venous–phase image shows a markedly enlarged left lobe (L) and caudate (C),
with an area of focal fibrosis and atrophy of the posterior right lobe, deforming
contour (open arrow). Incidental note of prominent collaterals in lesser
curvature region (white arrow)

42. Very advanced cirrhosis with small nodular liver with hypertrophy of the caudate
lobe and extensive ascities.

43. MRI
MRI is also insensitive in early cirrhosis, but has a significant role in assessing
from small HCCs. Findings include:
morphologic changes (same as on CT and ultrasound)
regenerative nodules (or cirrhotic nodules)
T1
variable, usually isointense
occasionally mildly hyperintense
no early enhancement and washout as most supply is from the portal
vein
T2
usually isointense
hypointense if siderotic
dysplastic nodules
may be of low or high grade, and thus have variable appearance
low-grade nodules will resemble regenerative nodules
high-grade nodules will resemble HCCs

44. small hepatocellular carcinoma (HCC)
T1: hyperintense, with early arterial enhancement and washout
T2: typically hyperintense
MR angiography may also be used to asses portal vein patency and
portosystemic collaterals.

45. This magnetic resonance imaging (MRI) scan of the abdomen in transverse view
demonstrates a small, nodular liver with cirrhosis. The spleen is enlarged from portal
hypertension.

46. Unenhanced T1-weighted image (a) shows hypointense reticulations (arrows) and
numerous regenerative nodules (arrowheads), which are iso to hyperintense.
Unenhanced T2-weighted fat-saturated image (b) allows a clearer visualization of the
reticulations throughout the liver parenchyma visible as hyperintense septa (arrows).

47. Liver biopsy
Histology is usually needed for the definitive
diagnosis of cirrhosis and liver biopsy is the gold
standard.
It may also give a clue to the underlying cause.
Any coagulation defect must be corrected first and
blood must be available for transfusion.
If there are clear signs of cirrhosis, such as ascites,
coagulopathy, and a shrunken nodular-appearing liver,
then confirmation of diagnosis by biopsy may not be
necessary.

48. Mangament
The treatment of chronic liver disease depends on the
cause. While some conditions may be treated with
medications, others may require surgery or a transplant.
Transplant is required when the liver fails and there is no
other alternative.

49. Preventing further liver damage
Regardless of underlying cause of cirrhosis, paracetamol, as well as
other potentially damaging substances, are discouraged. Vaccination of
susceptible patients should be considered for Hepatitis A and Hepatitis
B.
Transplantation
If complications cannot be controlled or when the liver ceases
functioning, liver transplantation is necessary. Survival from liver
transplantation has been improving over the 1990s, and the five-year
survival rate is now around 80%. The survival rate depends largely on the
severity of disease and other medical problems in the recipient.[35] In
the United States, the MELD score is used to prioritize patients for
transplantation.[36] Transplantation necessitates the use of immune
suppressants (cyclosporine or tacrolimus).

50. Decompensated cirrhosis
In patients with previously stable cirrhosis, decompensation may occur
due to various causes, such as constipation, infection (of any source),
increased alcohol intake, medication, bleeding from esophageal varices
or dehydration. It may take the form of any of the complications of
cirrhosis listed below.
Patients with decompensated cirrhosis generally require admission to
hospital, with close monitoring of the fluid balance, mental status, and
emphasis on adequate nutrition and medical treatment - often with
diuretics, antibiotics, laxatives and/or enemas, thiamine and
occasionally steroids, acetylcysteine and pentoxifylline. Administration
of saline is avoided as it would add to the already high total body sodium
content that typically occurs in cirrhosis.
Palliative care

51. Palliative care is specialized medical care that focuses on providing
patients with relief from the symptoms, pain, and stress of a serious
illness, such as cirrhosis. The goal of palliative care is to improve quality
of life for both the patient and the patient's family and it is appropriate
at any stage and for any type of cirrhosis.
Especially in the later stages, people with cirrhosis experience
significant symptoms such as abdominal swelling, itching, leg edema,
and chronic abdominal pain which would be amenable for treatment
through palliative care. Because the disease is not curable without a
transplant, palliative care can also help with discussions regarding the
person's wishes concerning health care power of attorney, Do Not
Resuscitate decisions and life support, and potentially hospice. People
with cirrhosis are rarely referred to palliative care.