Budd-Chiari syndrome is a rare disease that affects the liver. It is caused by a blockage in the hepatic veins that carry blood out of the liver. In children, this mainly happens due to blood clots forming in the hepatic veins. Unfortunately, it means that blood cannot flow out of the liver in the normal way. This blocks blood flow from the liver to the heart and causes blood to back up inside the liver. It can lead to scarring (fibrosis) of the liver that gets worse over time.

Budd-Chiari syndrome mostly begins in adults between the ages of 20 and 40. It affects 1.4 to 4 adults per million in western countries like the UK. We do not know the exact number of children and young people affected. But we do know it is even rarer in this age group. Budd-Chiari syndrome affects boys and girls in equal numbers.

In children, Budd-Chiari syndrome is usually a long-term (chronic) condition. This means that a blockage in the veins carrying blood out of the liver develops slowly over time. But Budd-Chiari syndrome can also happen suddenly.

The symptoms of Budd-Chiari syndrome will vary from child to child. Some children will have no signs or symptoms. Sadly, other children will have severe symptoms.

Budd-Chiari syndrome is a serious condition that needs prompt treatment. This is because scarring (fibrosis) of the liver can become worse over time. This can lead to severe scarring, known as cirrhosis. Early diagnosis and treatment in children offers the best chance of a good outcome.

Budd-Chiari syndrome is caused by a blockage in the hepatic veins that carry blood out of the liver. When blood has passed through the liver, it flows out through the hepatic veins. It then passes into the inferior vena cava. This is a large blood vessel that carries blood back to the heart.

Blockages in the hepatic veins are usually caused by either:

• a blood clot (thrombosis) or
• a web (a thin film) which has formed in the space inside the vein

Around 3 out of 4 children with Budd-Chiari syndrome have an underlying blood condition. You may hear this called thrombophilia. This is where blood in the body clots too easily. It increases the risk of blood clots in the blood vessels.

There are other possible causes of Budd-Chiari syndrome. But they are uncommon in children:

• cancer (often liver cancer)
• cysts or abscesses that put pressure on veins
• inflammation of a vein (phlebitis)
• hormonal factors (e.g. use of oral contraceptives)
• inflammatory diseases (e.g. Behçet’s disease, Sjögren’s syndrome or inflammatory bowel disease)
• liver trauma

Signs and symptoms can vary a lot from child to child. Some children will have no symptoms. Some will have mild symptoms. Sadly, other children will have severe liver disease. The severity of symptoms will depend on the number of veins affected by blood clots. It will also depend how quickly or slowly they are blocked.

Signs and symptoms in children may include:

• tummy (abdominal) pain
• enlarged liver (hepatomegaly)
• fluid in the tummy (ascites)
• enlarged spleen (splenomegaly)
• tiredness (fatigue)
• itching (pruritus)
• feeling sick (nausea)
• being sick (vomiting)
• yellowing of the skin and whites of the eyes (jaundice)
• black, “tarry” poo (stools)
• swelling of the legs and ankles (oedema)
• vomiting blood (haematemesis)
• visible veins on the tummy wall

Portal hypertension, varices and ascites

In Budd-Chiari syndrome, blood cannot flow out of the liver in the normal way. Blood backs up inside the liver and this causes high pressure in the portal vein. This is a vein that carries blood from organs in the tummy (abdomen) to the liver. This complication is called portal hypertension.

Portal hypertension can make the spleen get bigger. It can also cause swollen blood vessels in the food pipe (oesophagus), stomach and intestines. These swollen blood vessels have thin walls and may bleed. They are known as varices. This may cause your child to vomit blood or pass black tarry poo (stools). Both symptoms need urgent medical attention.

Portal hypertension can also cause fluid to build up in the tummy (abdomen). This is known as ascites.

Liver scarring (fibrosis)

Problems with blood flow out of the liver can lead to scarring (fibrosis) of the liver. A normal liver is soft and squishy. But as scarring builds up it becomes hard and bumpy. This can get worse over time. It can lead to severe scarring, known as cirrhosis. The speed and severity of scarring will vary from child to child. Liver scarring could happen during childhood. Or it may happen when your child becomes an adult.

Liver failure

Liver failure happens when large parts of the liver become damaged and scarred. The liver can no longer do its job. It is said to be failing. This is a late stage of liver disease. It is difficult for doctors to predict who will develop liver failure. And if this will happen during childhood or adulthood.

Hepatic encephalopathy

This is a rare side effect of severe portal hypertension. It happens when the liver can’t remove toxins properly from the blood. This causes a rise in ammonia in the blood, which affects the brain. It can result in symptoms like confusion, forgetfulness and mood changes. In some children, hepatic encephalopathy can be very serious.

Budd-Chiari syndrome can be hard to diagnose. The signs and symptoms can be similar to those seen in other liver conditions. Doctors will do different tests to rule these out before they make a diagnosis of Budd-Chiari syndrome.

Once a diagnosis is made, further tests will be done to help find out where the blood flow is blocked in the hepatic veins. This will help the medical team decide what treatments are possible for your child.

Budd-Chiari syndrome may be found by accident when your child is being tested for something else. Or when they are having tests for a complication called portal hypertension.

Tests used to help with the diagnosis may include:

• physical examination
• liver blood tests (also known as liver function tests / LFTs)
• blood tests to check for problems with blood clotting (thrombophilia)
• abdominal ultrasound scan
• computed tomography (CT) scan
• magnetic resonance imaging (MRI)
• endoscopy (if portal hypertension is suspected)
• hepatic vein catheterisation – to measure the pressure within veins
• angiography / venography – special X-rays to check blood vessels for blockages
• liver biopsy

Some of the tests will only be used if the doctors are unsure about the diagnosis.

Sadly, there is no cure for Budd-Chiari syndrome. The aim of treatment is to keep your child’s liver function stable by helping blood flow out of the liver.

Treatment will vary from child to child. Your child will be offered treatments depending on the number of veins that are blocked and the location of the blockage. Early diagnosis and treatment offer the best chance for a good outcome.

The main aims of treatment are:

1. To make sure that blood can flow easily from the liver back to the heart
2. To stop blood clots forming in veins or increasing in size
3. To reduce the build-up of blood in the liver
4. To manage any complications from the condition

Anticoagulants

These are medicines that stop blood clots from forming or growing. They are sometimes called blood thinners. They are often the first treatment used in children. They are also used for long-term (chronic) Budd-Chiari syndrome. Some children will need lifelong treatment with these medicines.

Angioplasty / stent insertion

This treatment widens veins that are blocked by a blood clot. This stops blood building up in blood vessels and the liver. It allows blood to flow around the clot. A thin plastic tube called a catheter is inserted into the blood vessel. It places a small balloon at the point of the blockage. The balloon is inflated to help blood flow through. A metal spring (stent) may be put in the space to keep it open.

Percutaneous hepatic vein recanalisation (HIVR) or inferior vena cava (IVC) recanalisation

HIVR and IVC recanalisation are types of angioplasty that are used to treat blocked veins inside the liver. They are carried out by a special doctor called an interventional radiologist. They are used if the clot can’t be reached using standard angioplasty. Like angioplasty, they are used to widen veins that are blocked by a blood clot. The exact treatment used will depend on the location of the blockage.

Endotherapy

There are three different types of endotherapy:

• banding
• glue injection
• sclerotherapy

They are used to treat swollen blood vessels in the food pipe (oesophageal varices). The swollen blood vessels are caused by portal hypertension.

Transjugular intrahepatic portosystemic shunt (TIPS)

This procedure is carried out by a special doctor called an interventional radiologist. A metal or plastic tube (stent) is placed between two large blood vessels in the liver (the portal vein and the hepatic veins). This creates a shunt, or bypass. It takes blood past any blocked veins. It may be used in older children. TIPS is used:

• to help manage severe portal hypertension
• if angioplasty and stenting are not possible
• in young people waiting for a liver transplant
• when a liver transplant is not possible

Meso-caval shunt

This is an operation carried out by a surgeon. It involves using a vein from the body or a synthetic vein to connect two blood vessels (the mesenteric vein and the inferior vena cava). This allows blood to escape from the liver and return to the heart.

Liver transplant

A liver transplant is usually only recommended if other treatments are no longer helpful, or if damage to the liver cannot be reversed. But a liver transplant is rare in children with Budd- Chiari syndrome. A liver transplant is an operation to remove a liver that does not work. It is replaced with a healthy liver from another person (donor).

CLDF can provide you with support and advice. Contact us on 0121 212 6023 or via email at: families@childliverdisease.org

Neonatal haemochromatosis (NH) is a rare condition. It is caused by severe damage to a baby’s liver. This happens during pregnancy when a baby is still in the womb. Damage to the liver leads to serious problems. It causes too much iron to build up in the liver and other parts of the body.

Neonatal haemochromatosis affects boys and girls in equal numbers. We do not know the exact number of babies affected by the condition. It could affect 15 babies in every 1 million births. But not all babies are diagnosed. This means the number could be higher.

Sadly, some babies with the condition are stillborn. And babies born with the condition usually show signs of severe liver disease or liver failure. This happens within the first hours and days of life. But some babies are less severely affected than others.

Current treatments aim to limit or prevent further damage to a baby’s liver. Doctors also use treatments to help prevent liver damage in future pregnancies.

We don’t know the exact cause of neonatal haemochromatosis. No single gene has been found for the disease. So it is not thought to be genetic. But it does seem that neonatal haemochromatosis can run in families.

We do know that most cases are caused by a condition called gestational alloimmune liver disease (GALD). For this reason, when doctors talk about NH, they nearly always mean this type of neonatal haemochromatosis. They might call it GALD-NH or alloimmune NH.

GALD is a condition where antibodies from the mother attack the baby’s liver cells (hepatocytes). This damages the liver inside the womb. The damage causes iron to build up in the liver and other parts of the body. It leads to scarring of the liver (cirrhosis). It may also cause acute liver failure. This is where the liver stops working. This happens before a baby is born.

We do not know why these antibodies develop in the mother during pregnancy. We also don’t know why they attack liver cells when a baby is in the womb.

There are other possible causes of neonatal haemochromatosis. But they are very rare. They include:

• Down’s syndrome (Trisomy 21)
• Severe foetal growth restriction
• Rare metabolic diseases

The rest of this guide is about neonatal haemochromatosis caused by gestational alloimmune liver disease. We call this GALD-NH. Speak to your medical team for more information if your child’s NH has another cause.

Signs and symptoms of GALD-NH can be picked up by ultrasound scans during pregnancy.

The following signs might mean that your baby has GALD-NH:

• slow growth in the womb (fetal growth restriction)
• a build-up of fluid in the placenta and umbilical cord (placental oedema)
• not enough amniotic fluid (oligohydramnios)
• too much amniotic fluid (polyhydramnios)
• too much fluid in your baby’s body (hydrops fetalis)
• a build-up of fluid in your baby’s tummy (ascites)

These problems can also be caused by many other things. So having any of them doesn’t mean your baby definitely has GALD-NH. But they do suggest there could be a problem. This should alert the medical team, who will monitor your baby closely for the rest of the pregnancy. They will also monitor your baby straight after birth.

Signs and symptoms of GALD-NH after birth are usually seen in the first few hours and days of life. They may include:

• premature birth
• low blood sugar (hypoglycaemia)
• problems with blood clotting (coagulopathy)
• yellowing of the skin and whites of the eyes (jaundice)
• weeing less than normal (oliguria)
• low levels of albumin (albumin is a protein made by the liver)
• swelling caused by fluid trapped in the body’s tissues (oedema/hydrops)

In many cases, the symptoms are life-threatening. Babies with GALD-NH can develop severe liver scarring (cirrhosis) with end stage liver disease or acute liver failure. Sometimes this happens within hours of birth.

GALD-NH isn’t always diagnosed. So women who have miscarried, had a stillbirth or whose baby died in the first 90 days might have a higher chance of having a baby with GALD-NH in the future.

Diagnosis before birth

A diagnosis during pregnancy means that treatment can be offered quickly. This gives your baby a much better chance of recovering.

Getting diagnosed is different depending on whether:

• you have already had a baby with GALD-NH
• you have had a miscarriage or a stillbirth in the past
• it is your first pregnancy.

GALD-NH is known to keep affecting some women. So women who have had a baby with GALD-NH can have checks in any future pregnancies.

1. Mothers who have already had a baby with neonatal haemochromatosis  →  Doctors should be looking for evidence of GALD-NH. An ultrasound scan can usually help confirm a diagnosis.
2. A first pregnancy or in mothers who have had a miscarriage or stillbirth  →   Mothers will have routine antenatal scans. If GALD-NH is suspected, an MRI scan may be used. This cannot confirm a diagnosis but can help guide the medical team.

Diagnosis after birth

If doctors think your baby has GALD-NH they will do tests including:

• a detailed family history
• blood tests
• ultrasound scan
• magnetic resonance imaging (MRI) – this is used to look for a build-up of iron in organs outside the liver
• lip biopsy (a small sample of tissue is taken from the lip and examined under a microscope) – this is used to look for a build-up of iron in the salivary glands

Treatments for GALD-NH aim to limit or prevent further damage to your baby’s liver. These treatments cannot reverse damage to the liver that has already happened. But the liver of a newborn baby has a great ability to repair itself. With time, the liver can fully recover. This can take several years. Your doctor will talk to you about what to expect for your child.

The choice of treatment will depend on the timing of diagnosis. This will be different if it is during pregnancy or after birth. The earlier that treatment is started, the more successful it is likely to be.

Treatment if diagnosed before birth

If GALD-NH is suspected during pregnancy, doctors use a treatment called intravenous immunoglobulin (IVIG). It is given to the mother straight into the bloodstream using a needle in a vein. A fluid containing IVIG goes into the vein using a drip. This is called an infusion.

This treatment uses a type of protein called immunoglobulins. They are taken from donated human blood. They are used to try and block antibodies that are attacking liver cells. IVIG treatment should be started straight away. The success of this treatment will depend on the stage of pregnancy that treatment was started. Some babies will develop severe liver disease. Others will develop no liver disease at all.

Treatment if diagnosed after birth

If GALD-NH is suspected in a newborn baby, treatment will start straight away. This will involve giving your baby intravenous immunoglobulin (IVIG). It is given straight into the bloodstream using a needle in a vein.

This treatment will do no harm if your baby does not have GALD-NH. But if it is GALD-NH, giving IVIG early may greatly improve your baby’s condition.

Some hospitals use a second treatment called exchange transfusion. This involves removing blood from the body. It is replaced with blood or blood products from a donor. This treatment helps remove antibodies that are causing liver damage from the blood.

If you have been treated with IVIG during pregnancy, the medical team will carry out tests on your baby in the first few days of life. This is to check for signs of liver failure. If there are signs of early liver failure, the medical team will start your baby on IVIG treatment.

Liver transplant

If these treatments don’t work well enough, your baby may need a liver transplant. But a liver transplant can be very difficult in small, very ill babies. Sadly, only about 1 in 3 babies who have a liver transplant for this condition will live.

Future pregnancies

If you have a child with GALD-NH, the chances are very high that any future babies will have it too. The chances are around 9 in 10 for each future pregnancy. This is the same if your next pregnancy is with a different partner. But knowing you are at risk means action can be taken early to protect your baby.

Make sure that you are referred to a specialist straight away in any future pregnancies. This will help protect your baby. You should be offered regular IVIG treatment. This has a high success rate. It stops GALD-NH happening again in most cases.

CLDF can provide you with support and advice whenever you need it. Contact us on 0121 212 6023 or via email at: families@childliverdisease.org

Other useful organisations:

Sands – www.sands.org.uk
Miscarriage Association – www.miscarriageassociation.org.uk
Tommy’s – www.tommys.org
Bliss – www.bliss.org.uk

Fibropolycystic liver disease is a collective term for a group of rare conditions. These conditions affect the liver and the biliary tract. They may also involve the kidneys.

This leaflet covers the following conditions:

• Congenital hepatic fibrosis
• Caroli disease
• Caroli syndrome
• Biliary hamartomas
• Polycystic liver disease

These conditions are grouped together because they all begin in the body in the same way. This also means there is often overlap between them. Your child may have one of these conditions or a combination of more than one.

The conditions are all caused by changes (mutations) in a person’s genes. Some genetic changes are ‘autosomal recessive’. This happens when both parents are carriers of the change and pass it on to their child. Other genetic changes are ‘autosomal dominant’. This means that only one parent carries the change and they pass this on to their child.

Fibropolycystic liver diseases begin before birth. They happen when ductal plates do not form properly during the early stages of development. Ductal plates are layers of cells that form the basis for the development of bile ducts. You may hear this called ‘ductal plate malformation’.

The signs, symptoms and complications for each condition can vary widely. They almost always involve the development of cysts or unusually shaped bile ducts.

Due to the different organs involved, your child may see a range of professionals. This may include:

• liver doctors (hepatologists)
• kidney doctors (nephrologists)
• specialist nurses
• radiologists
• surgeons

Cysts are pockets of tissue filled with fluid that develop inside an organ. They can grow larger over time. This may reduce the ability of an organ to carry out its normal job. It can also cause a
range of symptoms.

What is congenital hepatic fibrosis?

Congenital hepatic fibrosis (CHF) is a rare genetic condition. It happens in around 1 in every 20,000 births.

If CHF happens on its own, it is called isolated congenital hepatic fibrosis. This is very rare. In most cases, CHF happens alongside other diseases that affect the liver and kidneys. This
is why liver doctors, when making a diagnosis of CHF in a child, will always screen for kidney disease.

CHF is generally not associated with cysts. The main problem in this condition is stiffening of the liver. This is caused by liver scarring (fibrosis). This scarring generally gets worse as children and young people get older. But the speed and severity of scarring will vary from child to child. Most cases first show in children and teenagers. But some people are diagnosed as adults.

In CHF, scarring mainly affects the structure of the liver and not the liver cells. This means that the liver will usually keep doing its job. This is why some children show no symptoms.

In children with congenital hepatic fibrosis, scarring (fibrosis) of the liver can become worse over time. This can lead to severe scarring, known as cirrhosis. This may happen in adulthood.

In some children, when CHF is diagnosed, scans also reveal cysts or unusually shaped bile ducts. This is called Caroli syndrome.

How is congenital hepatic fibrosis diagnosed?

CHF may only be diagnosed when your child is being tested for something else. A diagnosis may also happen if they have portal hypertension. This is a complication of liver scarring.

Tests used to help with the diagnosis may include:

• physical examination
• blood tests
• genetic tests
• abdominal ultrasound scan
• liver biopsy
• endoscopy (if portal hypertension is suspected)
• magnetic resonance imaging (MRI) / magnetic resonance cholangiopancreatography (MRCP)
• endoscopic retrograde cholangiopancreatography (ERCP)

What are the symptoms of congenital hepatic fibrosis?

Children can start getting symptoms at any age. Some children never have symptoms.

Symptoms are often caused by a complication called portal hypertension. Symptoms may also be caused by infections in the bile ducts. Even if your child has symptoms, their liver will
usually still be working well.

Symptoms may include:

• enlarged liver (hepatomegaly)
• enlarged spleen (splenomegaly)
• tummy (abdominal) pain
• vomiting blood (haematemesis)
• black, “tarry” poo (stools)
• high temperature (fever)
• yellowing of the whites of the eyes and skin (jaundice)
• being sick (vomiting)
• gallstones (cholelithiasis)

What are the possible complications of congenital hepatic fibrosis?

Possible complications include:

Liver scarring (fibrosis)
In children with CHF, scarring (fibrosis) of the liver can become worse over time. This can lead to severe scarring, known as cirrhosis. The speed and severity of scarring varies from child
to child. Your child may never develop cirrhosis or they may develop it as an adult.

When scarring happens inside the liver, it stiffens. This makes it more difficult for blood to flow through it. This can cause high pressure in the portal vein.

Portal hypertension
High pressure in the portal vein is also known as portal hypertension. Portal hypertension causes swollen blood vessels in the food pipe, stomach and intestine. These blood vessels
have thin walls and may bleed. This can cause your child to vomit blood or pass black tarry poo (stools). Portal hypertension can also cause fluid to build up in the tummy (abdomen). This is known as ascites.

Cholangitis
This is inflammation (swelling) and infection of the bile ducts. This mainly occurs when CHF is linked with cysts or problems with the bile ducts. This is known as Caroli syndrome.

How is congenital hepatic fibrosis treated?

There is no cure or specific treatment for congenital hepatic fibrosis. Medical care focuses on reducing symptoms and managing complications. Treatment varies from child to child
depending on the severity of symptoms.

Treatments for portal hypertension and its complications may include:

• endotherapy to treat swollen blood vessels in the food pipe
• medication to help reduce blood pressure in the portal vein
• transjugular intrahepatic portosystemic shunt (TIPS)
• liver transplant

Treatments for bile duct infection (cholangitis) and its complications may include:

• antibiotics injected into a vein (intravenous antibiotics)
• draining fluid from cysts (cyst aspiration) to reduce their size
• endoscopic retrograde cholangiopancreatography (ERCP) to treat narrow or blocked bile ducts
• percutaneous transhepatic cholangiogram (PTC) to treat narrow or blocked bile ducts
• liver transplant when there is repeated bile duct infection (cholangitis) and/or severe sepsis

What are Caroli disease and Caroli syndrome?

Caroli disease and Caroli syndrome are both rare, genetic conditions. They affect the larger bile ducts that can be found inside and outside the liver. The two conditions are often grouped together because they share some features. But there are also some differences.

Caroli disease

Caroli disease happens in around 1 in every 1 million births. It usually happens at random, but it has been known to run in families.

The main features of Caroli disease are:

• cysts inside the larger bile ducts within the liver
• widening (dilation) of the larger bile ducts inside the liver

If the bile ducts become too wide, bile can collect and cause swelling and infection. This is known as cholangitis. The swelling stops bile from getting out of the liver. If the bile builds up, it can form stones. Often, these stones won’t cause problems. In a small number of people, they can block the bile duct and cause symptoms.

Caroli syndrome

Caroli syndrome is more common than Caroli disease. It happens in around 1 in every 100,000 births.

Caroli syndrome and Caroli disease share a key feature. In both conditions, children are born with cysts and widening of the bile ducts inside the liver.

But Caroli syndrome has some differences. This condition also features congenital hepatic fibrosis. This means that children with Caroli syndrome have scarring and stiffening of the liver. They also have the symptoms and complications associated with CHF. This includes portal hypertension.

Children and young people with Caroli syndrome may also develop cysts on their kidneys. This is why Caroli syndrome is often linked with autosomal recessive polycystic kidney disease
(ARPKD). In this genetic condition, multiple cysts develop in the kidneys.

How are Caroli disease and Caroli syndrome diagnosed?

Tests used to help with the diagnosis may include:

• physical examination
• blood tests
• genetic tests
• abdominal ultrasound scan
• magnetic resonance imaging (MRI) / magnetic resonance cholangiopancreatography (MRCP)
• endoscopy (if portal hypertension is suspected)

What are the symptoms of Caroli disease and Caroli syndrome?

The symptoms of Caroli disease and Caroli syndrome can appear at any age. But symptoms are most likely to appear in teenagers and young adults.

Symptoms are usually linked to bile duct infection (cholangitis) and the development of gallstones (cholelithiasis).

Symptoms may include:

• high temperature (fever)
• tummy (abdominal) pain
• yellowing of the whites of the eyes and skin (jaundice)
• being sick (vomiting)

If your child has Caroli syndrome, there may also be signs of portal hypertension. Extra symptoms may include:

• enlarged spleen (splenomegaly)
• tummy (abdominal) pain
• vomiting blood (haematemesis)
• black, “tarry” poo (stools)

What are the possible complications of Caroli disease and Caroli syndrome?

Possible complications include:

• repeated infection of the bile ducts (cholangitis)
• narrowing of the bile ducts (strictures)
• liver abscesses
• infection of the bloodstream (septicaemia)
• stones in the bile ducts (cholelithiasis)
• liver failure
• slightly increased risk of developing bile duct cancer (cholangiocarcinoma)

Extra complications in Caroli syndrome may include:

• portal hypertension
• ascites

How are Caroli disease and Caroli syndrome treated?

There are no cures or specific treatments for Caroli disease and Caroli syndrome. Medical care focuses on reducing symptoms and managing complications. Treatment varies from child to child depending on the severity of symptoms.

Treatments for portal hypertension and its complications may include:

• endotherapy to treat swollen blood vessels in the food pipe
• medication to help reduce blood pressure in the portal vein
• transjugular intrahepatic portosystemic shunt (TIPS)
• liver transplant

Treatments for bile duct infection (cholangitis) and its complications may include:

• antibiotics injected into a vein (intravenous antibiotics)
• draining fluid from cysts (cyst aspiration)
• endoscopic retrograde cholangiopancreatography (ERCP) to treat narrow or blocked bile ducts
• percutaneous transhepatic cholangiogram (PTC) to treat narrow or blocked bile ducts
• liver transplant when there is repeated bile duct infection (cholangitis) or severe sepsis

What are biliary hamartomas?

Biliary hamartomas are very small, dense cysts. They are usually scattered all over the liver. They are rare and affect less than 1 in 100 children. They are not a type of cancer and do not cause any problems.

Biliary hamartomas are also known as ‘bile duct hamartomas’ or ‘Von Meyenburg complexes’. They are often found in normal livers. Most children have no symptoms. The liver will continue to work, and no treatment or monitoring is needed.

Biliary hamartomas can happen alongside other diseases that affect the liver and kidneys. They are more common in children and young people with:

• autosomal dominant polycystic kidney disease (ADPKD)
• congenital hepatic fibrosis (CHF)
• Caroli syndrome

How are biliary hamartomas diagnosed?

Biliary hamartomas are often found by accident. This can happen when doctors are doing scans to look for something else. The cysts may be mistaken for cancer when they are first
found. Your child will have more tests to confirm the diagnosis.

Tests used may include:

• abdominal ultrasound scan
• magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP)

What are the symptoms of biliary hamartomas?

Most children show no signs or symptoms. If symptoms do happen, they may be similar to the symptoms for bile duct infection (cholangitis). They can include:

• high temperature (fever)
• tummy (abdominal) pain
• yellowing of the whites of the eyes and skin (jaundice)
• being sick (vomiting)

How are biliary hamartomas treated?

Biliary hamartomas do not usually cause problems. In most children, the liver continues to work normally, and no treatment is needed. Treatments will only be used if your child develops
symptoms that cause concern.

What are the possible complications of biliary hamartomas?

Biliary hamartomas are not a type of cancer. But there is a very small risk they could transform and progress to bile duct cancer (cholangiocarcinoma).

What is polycystic liver disease?

Polycystic liver disease (PLD) is a condition in which 10 or more cysts grow inside the liver. The cysts are not a type of cancer. In children and young people, the cysts are usually very small.

In a small number of people the cysts grow and increase in number with age. This is why symptoms may only appear in adulthood.

Polycystic liver disease can run in the family (be inherited). But people can still have different experiences of it. Some people may become very unwell, but others will have no problems, even though they are related.

There are two forms of polycystic liver disease:

Isolated polycystic liver disease
Polycystic liver disease can happen on its own without kidney disease. This is sometimes called autosomal dominant polycystic liver disease (ADPLD). In this type of PLD, cysts only happen in the liver. This type is very rare.

Polycystic liver disease with polycystic kidney disease (PKD)
Polycystic liver disease usually happens as part of a condition called autosomal dominant polycystic kidney disease (ADPKD). In this type, cysts grow in the liver and in the kidneys. Around 80 or 90 out of every 100 people with ADPKD will also have polycystic liver disease.

How is polycystic liver disease diagnosed?

Polycystic liver disease is often found by accident when doctors are doing scans to look for something else.

Tests used to help with the diagnosis may include:

• abdominal ultrasound scan
• magnetic resonance imaging (MRI) scan
• blood tests
• genetic tests

What are the symptoms of polycystic liver disease?

Most children and young people show no signs or symptoms. Even if your child has a lot of cysts in their liver, it will carry on working as normal. The liver cells around the cysts are not damaged.

Even in adulthood, most people have no symptoms from liver cysts. Symptoms only happen if the liver cysts grow larger over time.

What are the possible complications of polycystic liver disease?

It is very unusual for complications to happen in children and young people. But in a small number, the liver cysts get larger as they age. This happens in around 1 in 20 people with PLD. If the number, or size of cysts gets very big, it can cause symptoms. This is due to the space the cysts take up in the tummy (abdomen). Symptoms may include:

• tummy (abdominal) pain
• tummy (abdominal) swelling
• back pain
• feeling short of breath (dyspnoea)
• feeling full early in a meal
• indigestion (dyspepsia)
• heartburn (gastro-oesophageal reflux)

In rare cases, the cysts get so big that the liver grows and pushes on other organs and blood vessels. This can lead to further complications including:

• enlarged liver (hepatomegaly)
• portal hypertension and ascites
• cyst infection
• cyst bleeding
• cyst rupture (bursting)
• yellowing of the whites of the eyes and skin (jaundice)

How is polycystic liver disease treated?

Polycystic liver disease does not usually cause problems in children and young people. It is very rare for them to need treatment. This will only be needed if your child develops serious
symptoms that cause concern.

Treatments in rare cases may include:

• antibiotics for cyst infection
• draining fluid from cysts (cyst aspiration)
• medication to slow down cyst growth
• surgery – procedures such as removing the wall from cysts (cyst fenestration), liver resection and liver transplant.

If your child is diagnosed with polycystic liver disease, they will be monitored over time. This is done to check for any changes in the size or number of cysts.

As they age, hormones may play a role in the number and size of cysts. In adulthood, women are more likely to have symptoms and need treatment. The medical team may recommend
avoiding contraceptives that contain oestrogen. This is because oestrogen can increase the growth of liver cysts.

Polycystic Kidney Disease Charity
www.pkdcharity.org.uk
A UK charity dedicated to improving the lives of individuals and families affected by polycystic kidney disease (PKD). They provide information, advice and personalised support.

Primary sclerosing cholangitis (PSC) is a rare, progressive liver disease in which bile ducts inside (intrahepatic) and outside (extrahepatic) the liver may narrow or become blocked due to inflammation and scarring.

In a healthy, functioning liver, bile is made by liver cells and then transported through the bile ducts to the gallbladder. When a meal is eaten, the gallbladder contracts and bile flows into the intestine. This allows toxins to be eliminated from the body in the stool. Bile in the intestine also helps with the absorption of some fats and essential vitamins (vitamins A, D, E and K). In PSC, the bile ducts become progressively scarred and narrow so that bile is unable to flow normally. This allows toxins to accumulate and damage the biliary tree and the liver.

The cause of PSC is unknown but researchers suggest there are both genetic and environmental factors involved.
Current research suggests that PSC may be associated with an immune reaction against the liver generated by changes in the gut (an autoimmune condition). This leads to inflammation causing scarring and subsequently damage to the bile ducts.
Other research suggests that there may be an imbalance in the microorganisms or bacteria (gut flora) in the bowel.

A child may have PSC for years before they develop symptoms. In some children, it may be identified due to routine blood tests, medical investigations for IBD or vague symptoms such as tiredness. As with most diseases, there is a range of severity of symptoms. Most children and young people have no symptoms if the disease is mild, whereas in advanced disease there may be:

• Jaundice (yellowing of the skin and eyes)
• Itching
• Dark coloured urine and pale stools (usually occurs if the bile ducts are blocked)
• Infection of the bile duct (cholangitis)
• Tiredness and reduced energy
• Loss of appetite
• Weight loss
• Abdominal pain
• A high temperature (in rare cases)

If a child or young person is displaying symptoms of PSC, there are number of tests which may be used to confirm a diagnosis:

Family history
There may be other people in the family with other autoimmune diseases (such as diabetes, thyroid disease, coeliac disease or IBD).

Blood tests
Liver blood tests may be carried out over multiple days or weeks to show a pattern that would be in keeping with the bile ducts being damaged (ALP, GGT or bilirubin being raised). These blood results are suggestive but not diagnostic.
Blood tests for autoantibodies may show a positive p-ANCA result. Autoantibodies can also be found in some other autoimmune diseases. Again, this is not diagnostic.
Liver blood tests may also indicate if the liver is not working normally due to the damage caused. This may include clotting tests such as INR and measuring albumin levels.

Ultrasound scan
An ultrasound is often a key diagnostic tool in liver disease. It may show an enlarged gallbladder, areas of dilated bile ducts or areas of narrowing.
An ultrasound can also show changes associated with advanced liver disease such as fluid in the abdomen (ascites) and an enlarged spleen (portal hypertension).

Magnetic resonant cholangio-pancreatogram (MRCP scan)
This is a specialist magnetic resonance imaging (MRI) scan of the bile ducts. It can show the changes in the bile ducts inside the liver by using a special contrast dye to identify these areas on the scan. This is better at diagnosing PSC than an ultrasound.

Liver biopsy
A liver biopsy may be useful if the diagnosis is not clear from the above tests. A biopsy can show scarring around the bile ducts and bile duct damage. The biopsy may also show how much scarring there is in the liver (fibrosis). Advanced fibrosis is known as cirrhosis.

There is currently no definitive treatment for PSC. Supportive treatment is focused on managing symptoms and improving bile flow and the consistency of bile in the bile ducts.

One of these symptoms may be pruritus. This is an intense itch beneath the skin that can cause severe discomfort and can be difficult to control. The cause is not completely understood but is thought to be due to increased levels of bile acids/salts in the
blood. Management of pruritus will be discussed by your multidisciplinary medical team and treatment given accordingly.

In children where PSC is associated with IBD, improvement of the bowel disease may also improve the liver.

Medicines

• Ursodeoxycholic acid (UDCA)
  This can improve bile flow out of the liver which may reduce jaundice and/or itching. Data from adult patients suggests that UDCA does not change the natural history of the disease.
• Antibiotics
  If an infection has occurred in the bile ducts (cholangitis), antibiotics are used to reduce the risk of the infection occurring again.

Medication and treatment options may vary and your child’s medical team will discuss the most appropriate options available.

As with other chronic liver diseases, medicines such as aspirin and ibuprofen should be avoided as they can make bleeding in the gut more likely. Paracetamol (Calpol) is a safer alternative.

Vitamins
Additional vitamin supplements may be necessary because poor bile flow can reduce the absorption of fat-soluble vitamins i.e., A, D, E and K. These are normally given orally, although an injection may be needed.

Diet
The development of fluid in the abdominal cavity (ascites) can occur, but usually only in patients with advanced disease (cirrhosis). When ascites occurs, a low salt diet is sometimes recommended but management will most likely involve the use of diuretics to increase excretion of the excess fluid through the urine. Advice and support will be provided by your dietetic team if changes to your child’s diet are required.

Endoscopic procedures

In a small number of cases endoscopic procedures may be needed. These include:

• Children and young people with IBD who will need regular colonoscopies.
• Children and young people with cirrhosis who may need a gastroscopy to look for dilated blood vessels in the gullet (oesophagus) or stomach. These dilated vessels (varices) are a result of a condition called portal hypertension.
• An endoscopic retrograde cholangio-pancreatography (ERCP) may be required to make the diagnosis in certain individuals if their MRI scan is inconclusive. This is usually performed under general anaesthetic at a specialist centre.

An ERCP is more often used to treat blockages (strictures) in the bile duct and can involve the insertion of a plastic or metal tube (stent). Brushings of strictures are usually taken to allow the cells to be assessed. After the insertion of a stent, the flow of bile will be improved. ERCPs are rarely required in children but takes place more often in adolescents. Your specialist centre will assess the need for this procedure.

If the disease progresses, the following complications may be experienced:

• Biliary strictures – narrowing of a bile duct from scar tissue within the duct itself. A stricture can block the release of bile and lead to infection (cholangitis). An ERCP may be required.
• Progressive itch
• Portal hypertension – high blood pressure in the portal vein which may occur due to scarring of the liver or a blockage in the portal vein. The spleen may become enlarged (splenomegaly) due to a back flow of blood from the liver and cause abdominal distension.
• Varices – swollen veins in the intestine, oesophagus and stomach which can bleed if not treated. An endoscopy is usually required.
• Ascites – collecting of fluid in the abdomen. Ascites can be managed by diuretic medicines to increase urine output and minimise fluid accumulation.

Further information about portal hypertension, varices and ascites is available in on our website.

• Weight loss
• Development of bile duct cancer (cholangiocarcinoma). This is extremely rare in children.

The role of liver transplantation

A liver transplant may be discussed as a treatment option if the liver begins to fail or if there is severe recurrent cholangitis. If a transplant is the best treatment option, the medical team will focus on preventing complications and treating symptoms while waiting for an organ.
Outcomes after transplantation for PSC are positive and many children go on to have a good quality of life. However, there is a chance that PSC can reoccur in the transplanted liver. The underlying reasons for this are not yet fully understood. Risk factors taken from studies of adult patients include a younger age at transplant and the co-existence of IBD. Further information about liver transplantation is available on our website.

Your child’s growth and development will be followed up by periodic visits to hospital. How often you will need to go to hospital varies for each child. These visits may occur more frequently if your child’s disease appears to be active (e.g. persistently abnormal blood results or other tests) and/or progressing.

Children’s Liver Disease Foundation (CLDF) is in touch with families who have a child with PSC. PSC does not have to hold your child back from reaching their full potential. You can contact CLDF for further support.
You may benefit from contacting PSC Support (pscsupport.org.uk). They are a UK based charity and although they work more widely with adults, they are a good source of safe information and have useful videos and events specifically for patients with PSC.

The slow progressive nature of PSC has made clinical trials more difficult but new treatments are constantly under investigation. There are multi-centre clinical trials for paediatric patients taking place internationally to find answers. Furthermore, there are several areas of active investigation in this field with promising clinical data from adults with PSC. Personalised medicine and treatments tailored to individual patients may be the future of PSC therapy.