Dr Zeinab Salem Ali

Pediatric Department

Sebha Medical Center

Dr Abdalla Mutwakil Gamal

Radiology Department

Sebha Medical Center

(Dr Abdalla Slides – modified version)

AcknowledgmentThis presentation is a joint effort between Dr Zeinab Salem Ali (from PediatricDepartment) and me (from Radiology Department). In her slides, Dr Zeinabpresented the case history, examination, investigations, differential diagnosisand discussed the clinical presentation, investigations and management forchronic liver diseases in pediatric patients. In my slides, I discussed thedefinition, etiology, natural history of this condition and explained the role ofimaging in its diagnosis.

Thanks are due to Dr Khaled Aljasem from Pediatric Department for his effortsin revising the original presentations and the constructive feedback heprovided which improved the quality of the presented material.

These are my slides after some modifications. I added a summary for the partsDr Zeinab has presented to make this powerpoint presentation complete.

The case

History6 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 abnormalaitydetected 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.

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.

ExaminationThe patient was febrile, dehydrated and in serious general condition.

She had severe pallor.

Normal Cardiovascular and respiratory systems.

Distended abdomen with positive shifting dullness.

Investigations & imagingInvestigations 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.

Chronic liver disease in pediatric

ContentsDefinition

Etiology

Natural History

Clinical presentation

Investigation

Imaging

Management

DefinitionChronic 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.

EtiologyMajor 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.

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).

Galactosemia

It is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Galactosemiafollows 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.

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.

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.

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.

Natural History

Natural History of chronic Liver Disease

Clinical presentationSymptoms:

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:

InvestigationsThese 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.

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.

UltrasoundUS, 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

UltrasoundChecklist 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

Signs of portal hypertension:

& Doppler flow changes

Liver cirrhosis

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

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

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

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

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

CDS and WaveformThe 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

CTCT is insensitive in early cirrhosis. More established findings include:

surface and parenchymal nodularityregenerative nodules (most) are isodense to rest of liversiderotic nodules (minority) hyperdense due to accumulation of iron

segmental hypertrophy/atrophy (see above)parenchymal heterogeneity both on the pre and post IV contrast scansisodense/hyperdense regenerative nodulespredominantly portal venous supply to dysplastic nodules.In advanced cirrhosis, nodular margin and lobar hypertrophy/atrophy can be demonstrated.signs of portal hypertension

portal vein enlargementportal venous thrombosis +/- cavernous transformation

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

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)

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

MRIMRI 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

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.

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.

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).

Liver biopsyHistology 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.

MangamentThe 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.

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).

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 varicesor 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

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.