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Home > About Your Liver > Liver Disease: The Basics > Pediatric Liver Disease

Pediatric Liver Disease

  • 100+ liver diseases can affect children and young people; the signs and symptoms can vary greatly.
  • Some liver disorders in children can be minor, others can be more serious, causing liver injury and cirrhosis, and can even lead to liver failure. Childhood liver disease can be life-threatening without treatment.
  • Causes of pediatric liver disease: autoimmune conditions, infections, metabolic disorders, genetic disorders, cardiovascular problems, medication reactions, anatomical issues, among others.
  • Early identification of pediatric liver disease is very important, with one goal being preservation of liver function.
  • Signs and symptoms of pediatric liver disease include: jaundice (yellowed skin/eyes); abdominal pain/bloating/swelling; change in sleep patterns; grey/white/pale stools; blood in the stools/urine; loss of appetite; nausea; poor weight gain; pruritus (general and persistent itching); fatigue/loss of stamina; vomiting, esp. of blood; persistent dark-colored urine; bruising/bleeding; higher than normal levels of liver enzymes. Any of these symptoms or a combination of them should be reported immediately to the child’s doctor.
  • Globally, the incidence of cirrhosis in children and adolescents increased from 204,767 in 1990 to 241,364 in 2019, a 17.9% increase.
  • Approximately 15,000 children are hospitalized each year in the U.S. with pediatric liver diseases or disorders (as of 2016). Due to the absence of symptoms, especially in early stages, these disorders continue to be under-recognized or diagnosed late.

Alagille Syndrome

  • Alagille Syndrome (ALGS), a genetic disorder, affects the liver, heart, skeleton/spine, eyes/face, blood vessels, skin (itchy skin, hard skin bumps), and kidneys. Most patients with ALGS have liver disease.
  • ALGS causes destruction of the bile ducts. Bile then builds up in the liver because there are too few ducts to drain bile, resulting in liver damage (cholestasis).
  • Children with ALGS can have unique facial characteristics: a pointy chin, broad brow, and widely spaced eyes.
  • Chronic itchy skin/hard skin bumps are often symptoms for people with ALGS.
  • ALGS is caused by abnormal development of many organs.
  • ALGS is usually diagnosed in infancy in about one of every 30,000 to 70,000 births but can also be diagnosed in early childhood. It affects both sexes and all races equally.
  • ALGS is the most common rare cholestatic (slowing or stalling of bile flow) liver disease.
  • ALGS has a mortality rate of 10-17%.
  • About 75% of people diagnosed with ALGS in childhood live to at least age 20.

Alpha-1 Antitrypsin Deficiency (AATD)

  • Alpha-1 Antitrypsin Deficiency may also be referred to as AAT deficiency, AATD, Alpha-1, inherited emphysema, or genetic emphysema.
  • AATD is characterized by low levels of a protein (alpha-1 antitrypsin (A1AT)) in the blood, causing several illnesses, most commonly lung disease (chronic obstructive pulmonary disease (COPD), including bronchiectasis; emphysema) and liver disease (cirrhosis; hepatoma), or rarely, a skin condition (panniculitis).
  • Patients with at-risk genes usually develop symptoms in adulthood, but childhood manifestations present a serious pediatric health problem.
  • AATD is one of the most common genetic disorders among people with European ancestry. It is rare in non-European people, but all ethnicities can be affected.
  • AATD has a global incidence of 1 in every 1500 to 3500 people with European ancestry.
  • There is no known way to prevent AATD. There is a drug that replaces the antitrypsin that the body can't make.
  • Patients with AATD may have reduced life expectancies.
  • AATD affects 1 in every 3000 to 5000 people in the US.
  • AATD is often underdiagnosed or misdiagnosed.
  • Severe cases of AATD are estimated at 70,000 to 100,000 people in the US. It is projected that less than 10% have obtained an accurate diagnosis.
  • People with AATD are at increased risk for hepatocellular carcinoma (HCC).

How AATD Affects Children

  • AATD is the most frequent cause of genetic liver disease in infants and children and is the most common inherited indication for liver transplantation in children.
  • The first symptoms of AATD usually occur between 20 and 50 years, but some infants or children may be affected. Children with AATD usually present with jaundice at birth, white stools/dark urine, reduced stamina, wheezing, coughing, respiratory infections, fatigue, rapid heartbeat, vomiting, poor appetite, itching. Eventually, patients may develop emphysema. Some AATD patients develop liver disease, experiencing swollen abdomen, swollen feet or legs.
  • AATD is diagnosed with a simple blood test.
  • AATD affects about 1 in 2000 babies.
  • Some infants born with AATD end up with severe liver damage or cirrhosis.
  • About 5-10% of patients with severe AATD eventually require a liver transplant.
  • Emphysema in children with AATD is extremely rare. AATD-associated liver disease (neonatal cholestasis) is present in only a small portion of affected children. 10-15% present with neonatal cholestasis. The incidence of liver disease (cirrhosis and fibrosis) increases with age.
  • AATD and its symptoms in infants and children may be overlooked.

Autoimmune Liver Disease

  • Autoimmune hepatitis (AIH) and AIH/sclerosing cholangitis overlap syndrome known as autoimmune sclerosing cholangitis (ASC) (For general information see also section on Autoimmune Liver Disease).
  • Autoimmune Disorders: Immune system abnormalities: Your immune system protects your body from germs and toxins. But that system can attack certain parts of your body (autoimmune), including your liver; this is called autoimmune disease.  General examples of autoimmune diseases are rheumatoid arthritis and inflammatory bowel disease. Examples of autoimmune liver diseases include autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and others.
  • There are two types of autoimmune liver disease/hepatitis, with different types of autoantibodies:
    • Type 1 – Anti-nuclear (ANA) and/or anti-smooth muscle (SMA) antibodies Type 1 makes up two out of three of all cases of AIH and the majority of ASC cases. Type I is by far the most common type of autoimmune hepatitis. In children, it most commonly presents in schoolchildren and teenagers.
    • Type 2 – Liver kidney microsomal (LKM) antibodies Type 2 is less common, but more likely to affect younger children and can result in acute liver failure. Type 2 is rare in ASC.
  • Type 2 is very rare in the United States. This type of autoimmune hepatitis tends to be more severe and difficult to treat. It may appear at a younger age than Type 1.
  • Both types are only very rarely seen in infants.
  • Autoimmune hepatitis (AIH) with inflammation in the bile ducts can be further categorized into AIH/sclerosing cholangitis overlap syndrome or ASC.
  • Childhood autoimmune liver disease can be difficult to diagnose because the symptoms are similar to many other liver conditions. Manifestations can vary. Some children/young people may appear well, while others can be very ill.

 

Autoimmune Hepatitis (AIH)

  • A Canada-based study of AIH estimated its prevalence in children at 2.2–9.9 per 100,000.
  • The same study estimated the annual incidence of pediatric AIH to be between 0.1 and 0.23 per 100,000 children.

 

Autoimmune Sclerosing Cholangitis (ASC)

  • Autoimmune sclerosing cholangitis (ASC), also known as “overlap syndrome (OS),” refers to an autoimmune condition with characteristics of both autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) or primary biliary cholangitis (PBC).
  • The prevalence of AIH-PSC overlap (ASC) in children with AIH ranges from 20% to 49%.
  • The prevalence of AIH-PSC overlap (ASC)in adult patients with AIH ranges from 1.7% to 10%.
  • Autoimmune sclerosing cholangitis (ASC) in children is frequently associated with inflammatory bowel disease (IBD).

 

Biliary Atresia (BA)

  • Biliary atresia (BA) is a rare congenital disease, causing damage, scarring, and blockage of the bile ducts. It occurs in young infants (less than 3-4 months of age). The damage is progressive, so early diagnosis is important. BA is associated with significant morbidity and mortality.
  • BA is the most common cause of liver-related death in children.
  • Timely, early diagnosis is essential for best outcomes.
  • BA, though uncommon, is the leading indication for liver transplantation in the pediatric population.
  • BA must be treated with surgery.
  • BA usually affects girls more than boys.
  • Biliary atresia (BA) is mostly seen in full-term infants, (not in premature babies).
  • However, according to one study, each year in the US, 400-500 newborns are diagnosed with BA, often in babies that are premature, female, and non-Caucasian.
  • BA can also cause other problems in the heart, spleen (polyclinic), intestine (malrotation) and kidneys (cysts).
  • About 10-20% of infants with biliary atresia have abnormalities in other organs, such as heart defects or issues with their spleen.
  • Jaundice and pale stools starting in the first 4-8 weeks are the main signs of BA.
  • Jaundice is common in newborns and usually goes away in the first 1-2 weeks. Beyond 2 weeks, the doctor should order a test called direct or conjugated bilirubin to test for BA. Blood tests, abdominal ultrasound, and a liver biopsy may also be needed.
  • BA is rare, affecting 1 in 8,000 to 1 in 18,000 newborns worldwide.
  • BA incidence in the US is estimated at 1 in 10,000 to 15,000 births. Approximately 400-600 new cases of BA are found in the US each year.
  • We don’t know the etiology of BA. There is emerging evidence that BA may start in utero and can be picked up at birth (but this is not proven yet).
  • We do not know what causes BA, but the diagnosis of BA is time-sensitive, i.e., must occur as soon as possible.
  • Treatment of BA is surgical (Kasai procedure), and outcomes are better if the diagnosis and surgery occur as early as possible, before 30-45 days of life.
  • New clinical trials for treatment of BA are ongoing.

Budd-Chiari Syndrome (BCS)

  • Budd-Chiari syndrome (BCS) occurs when the veins that carry blood away from your liver develop blockages (like clots) or become too narrow. Prompt treatment for Budd-Chiari syndrome is essential. BCS is a lethal disease.
  • Budd-Chiari syndrome is rare, especially in children.
  • One study, taking place over a 19-year period, recorded the incidence of Budd Chiari increasing from 4.96 per 1,000,000 US population in 1998 to 10.44 per 1,000,000 in 2017.
  • Types of Budd-Chiari syndrome: acute syndrome with acute liver failure: acute without liver failure; subacute, the most common type; and chronic. Additionally, Budd-Chiari syndrome may be primary or secondary.
  • Budd-Chiari syndrome is treated with medications, nonsurgical procedures, and transplantation.
  • Oral contraceptives and pregnancy are responsible for about 20% of cases of Budd-Chiari syndrome.

 

Crigler-Najjar Syndrome

  • Crigler-Najjar syndrome may also be referred to as Glucuronyl transferase deficiency (type I Crigler-Najjar) and/or Arias syndrome (type II Crigler-Najjar).
  • Crigler-Najjar syndrome is a rare genetic condition occurring when the liver can’t break down bilirubin (a substance produced by the breakdown of red blood cells). Children with this condition have extended jaundice. Some symptoms are life-threatening. Too much bilirubin in the bloodstream causes irreversible nerve and brain damage if untreated.
  • Crigler-Najjar syndrome is very rare, with an incidence rate of 0.6 to 1 in 1 million newborns worldwide.
  • There are two types of Crigler-Najjar syndrome in pediatric patients. Both are treated with aggressive phototherapy (systematic exposure to intense blue LED light), which is needed throughout the patient’s life.
    • Type I is more serious and life-threatening and may require a liver transplant before adolescence to prevent brain damage.
    • Type II, the milder version, is treated with the drug phenobarbital, blood transfusions. Children with type 2 have a normal life expectancy.
  • Children with Crigler-Najjar syndrome experience symptoms of kernicterus, a complication of jaundice: clumsiness, spasms, sensory perception problems, problems with motor skills, twisting movements (choreoathetosis), underdeveloped teeth. Severe symptoms: hearing difficulties, fatigue, difficulties with feeding, fever, nausea/vomiting, weak (hypotonia) or tight muscles (hypertonia), cognitive issues. Pediatric patients may experience symptoms of kernicterus (high blood levels of bilirubin damaging the brain) if left untreated.
  • Early treatment is imperative in Crigler-Najjar syndrome type I to prevent the development of kernicterus during early life.

Cystic Fibrosis Liver Disease

  • Cystic fibrosis (CF) is a hereditary condition that causes damage to the lungs, digestive system and other organs. In the U.S., because of newborn screening, cystic fibrosis can be diagnosed within the first month of life. People born before the screenings became available may not be diagnosed until the symptoms appear later in life. CF affects the cells that make mucus, sweat and digestive juices, causing the secretions to become sticky and thick. The secretions then plug up pathways, in lungs, pancreas and liver.
  • With CF liver disease, bile ducts from the liver and gallbladder become blocked and inflamed, causing jaundice, fatty liver disease, cirrhosis (scarring; fibrosis), and gallstones.
  • CF gets worse over time and needs daily care, but people often have a better quality of life than in past decades. Improved treatments mean that people with CF now may live into their mid- to late 50s or longer.

Galactosemia, Classic galactosemia (CG)

  • Galactosemia is an inborn pediatric metabolic liver disease, caused by a problem with the enzymes that break down the sugar galactose. Lactose, the main type of sugar in milk, is made up of glucose and galactose. Babies with galactosemia have high levels of galactose in their blood. Babies with galactosemia can't have milk and dairy products. There are three types of galactosemia; the most common and severe is called “classic galactosemia.”
  • There are three types of galactosemia:
    • Type I: classic galactosemia
    • Type II: galactokinase deficiency galactosemia
    • Type III: epimerase-deficiency galactosemia
  • Galactosemia incidence:
    • Type I: Classic galactosemia incidence: 1 in 30,000 to 60,000 newborns. One estimate of classic galactosemia in the US is 1 in 53,000 newborns. Galactosemia type II and type III are less common.
    • Type II estimated at fewer than 1 in 100,000 newborns.
    • Type III appears to be very rare.
    • Worldwide epidemiology of classic galactosemia: Incidence of type I varies geographically: 1 in 30,000 to 40,000 in Europe; 1 in 1,000,000 in Japan.
  • Initial symptoms occur in first few weeks of life: refusal to feed, vomiting, lethargy, jaundice, diarrhea, cataracts, and sepsis (infection).
  • Prompt treatment is essential. The only treatment for galactosemia is avoiding foods that contain lactose and galactose. In order to prevent serious multiorgan involvement including death, a physician and a dietitian specializing in metabolic disorders need to create a special lactose-free diet for the child in the first 10 days.
  • After the first 10 days, the majority of untreated infants face life-threatening complications such as infection and liver failure. If they do survive the first month of life untreated, they develop cirrhosis.

Hepatitis B (HBV) in Children and Mothers

(For general information, see also section on Hepatitis)

  • The World Health Organization (WHO) estimates the global prevalence of all hepatitis B at 254 million people (2022).
  • 12% of total hep B and C cases are in children under 18.
  • Hepatitis B (HBV; Hep B) is the most common liver infection in the world. Hepatitis B is a type of liver infection caused by the hepatitis B virus (HBV); it can be short-term (acute) but can progress to a long-term or life-long illness (chronic), including liver disease/liver cancer. Hepatitis B is spread with blood, semen, or other body fluids, or can be passed through birth. It is preventable with vaccines. Testing is the only way to know if you are infected. Treatment can control hepatitis B in infected people.
  • Hepatitis B disproportionately affects children. Younger children are more prone to chronic hepatitis B. The hep B virus can be passed on through the mother. However, hepatitis B can be prevented with a vaccine given soon after birth with boosters a few weeks later, offering nearly 100% protection against the virus.
  • Untreated, hepatitis B and C can cause liver damage, cirrhosis, cancer, and death.
  • At risk for HBV: Anyone can get HBV, but among the highest-risk people are infants of infected mothers.
  • HBV in children is passed mostly during delivery and at birth, as well as through contact with blood and body fluids.
  • Symptoms of acute HBV: jaundice; fatigue; poor appetite; nausea, vomiting, abdominal pain; low fever; rash and itching; dark urine; joint pain.
  • Most children younger than 5 years of age with HBV have few or no symptoms. Older children may develop symptoms 3 to 4 months after exposure if left untreated.
  • A child can’t get HBV from hugging, kissing, coughing, or sneezing, if left untreated.
  • Breastfeeding by a mother with HBV is safe if the child is treated at the time of birth.
  • HBV comes in two forms, acute and chronic. Acute hepatitis B does not cause any lasting problems. Chronic HBV is long-term and life-threatening and causes damage to the liver.
  • If the body is able to fight acute HBV, children’s symptoms end in weeks to 6 months.
  • If not vaccinated, 9 out of 10 infants infected with the hepatitis B virus at birth will develop chronic, life -threatening, HBV infections.
  • Approximately one-third of children (under age 6) who get HBV develop the chronic form. A blood test after 6 months is used to diagnose chronic hepatitis B in children.
  • Children can and should be tested for HBV if deemed at risk. These tests can help diagnose: a new infection (acute HBV); chronic or long-term infection (chronic HBV); a past infection.
  • Treatment: Acute hepatitis B does not need treatment; the child's immune system fights the disease. While the virus is present, the child can pass the virus onto others; special steps are needed to help prevent the disease from spreading. Chronic hepatitis B needs treatment. Treatment is to relieve any symptoms, preventing disease transmission, and preventing liver disease.
  • Around the world, two billion people (one in three) are estimated to have been infected with the hepatitis B virus.
  • 1 out of 2 people with hepatitis B are unaware.
  • A person can spread the hepatitis B virus and not know it.
  • Only 5% of adults who are infected by hep B develop a chronic infection, but 30% (1 in 3) of children under age 6 do.
  • The younger a person’s age when they are infected with hep B, the greater the chance of the infection becoming chronic and lifelong, the risk going down as a child gets older. The majority of children 6 and older infected with the hepatitis B virus recover completely. Approximately 9 in 10 infants infected with hepatitis B will develop life-long, chronic infection.
  • All pregnant women should be screened for HBV.
  • Doctors recommend a series (2-3) doses of the hepatitis B shot for children as the best way to protect against hepatitis B. There is typically a 3-shot series for hep B for children from birth to 18 y/o. The first dose is given at birth. The hepatitis B shot is very safe and is effective. Side effects are usually mild and go away on their own.
  • Children only receive immunoglobulins if they are born to a hep B positive mom. Newborns should get the first hepatitis B vaccine does and a dose of immunoglobulin (IG) in the first 12 hours.
  • People who have not gotten vaccinated for HBV can and should get “catch-up” doses.
  • 464,000 children’s lives have been saved by hepatitis B vaccines since 1974. Every 10 seconds, one child’s life is saved from a fatal disease by a vaccine.

Hepatitis C (HCV) in Children (neonatal hepatitis C)

(For general information, see also: Hepatitis)

  • Worldwide, hepatitis C virus (HCV) is a major public health problem and cause of chronic liver disease that leads to approximately 399 000 deaths annually (2019).
  • Only 21% of 58 million with chronic HCV had been diagnosed, and 13%, treated (2019).
  • 1 out of 3 people with HCV in the US are unaware.
  • Hepatitis B and hepatitis C have similar symptoms; they are both viral infections that attack the liver. The main difference between hepatitis B and C is that people may get hep B from contact with bodily fluids, hep C is typically transmitted through blood-to-blood contact.
  • Like hep B, hepatitis C comes in acute and chronic forms.
  • 75–85% of people with acute hepatitis C will also develop chronic hepatitis C, which can be a lifelong if left untreated.
  • Since 2013, doctors have been able to treat and even cure hepatitis C. Treatments can cure more than 95% of hepatitis C cases.
  • A pregnant woman can pass HCV to her baby (neonatal hepatitis C). If the mother has HCV, her baby should be tested for the virus.
  • Approximately 6% of infants born to infected mothers will get hep C. There is no treatment to prevent hep C at birth.
  • In addition to being born to an infected mother, children can also contract hepatitis C virus through receiving virus-infected blood transfusions (before 1992) or blood-clotting products (before 1987); receiving a virus-infected organ transplant; kidney dialysis treatment; sharing personal hygiene items (such as toothbrushes, nail-clippers).
  • Adolescents and teens can also get hepatitis C. There are many causes of hepatitis C in teens, including: being stuck with an infected needle; contact with infected blood; using street drugs; unprotected sex; tattoos/acupuncture with infected needles.
  • Hepatitis C is not spread by breastfeeding, hugging, kissing, coughing, or sneezing.
  • Hepatitis C is the most common cause of chronic viral hepatitis in children in industrialized nations.
  • A factor that increases maternal transmission of HCV: IV drug use during pregnancy.
  • Hepatitis C goes away without treatment 25-40% of the time before a child's second birthday. The virus has disappeared in some children as old as 7.
  • After age two, the chance of spontaneous clearance prior to age 19 decreases to 6-12%.
  • All children suspected to be “at risk” should be tested for HCV.
  • In 2020, because of continued increases in HCV infections in the US, CDC released screening recommendations, including screening for pregnant people.
  • Children make up a small percentage of hepatitis C virus (HCV) infections, compared to adults.
  • However, a significant number of children do have chronic HCV infection and are at risk of complications: cirrhosis, portal hypertension, hepatic decompensation with hepatic encephalopathy, and hepatocellular carcinoma (cancer) in adulthood.
  • Children with untreated chronic HCV infection should have regular physical exams, especially children with comorbidities such as coinfection with HIV or HBV infection.
  • The CDC has designated the elimination of hepatitis C as a national priority.

Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD)

(See also general section on MASLD)

  • There have been recent changes to the medical terminology covering “fatty” type liver disease to reduce stigma.  The term “fatty liver disease” (FLD) has been replaced by “steatotic liver disease” (SLD). SLD is an umbrella term covering “nonalcoholic fatty liver disease” (NAFLD)/”metabolic dysfunction-associated steatotic liver disease” (new term; MASLD); nonalcoholic steatohepatitis (NASH)/metabolic-associated steatohepatitis (new term; MASH); as well as alcohol-related liver disease (ARLD)/ alcohol-associated liver disease(new term; ALD), and the new category, MetALD (metabolic with alcohol-associated liver disease), a continuum which can have elements of MASLD and/or ALD.
  • Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of liver disease.
  • MASLD happens when excess fat builds up in the liver. It is a “silent” disease with few or no symptoms. Causes are still being studied, but research points to genetics, digestive disorders, and diet.
    • Causes include diet and nutritional causes, genetics, being overweight/obesity, type 2 diabetes/ insulin resistance, high blood fat/triglyceride levels. One or more traits of metabolic syndrome (traits and medical conditions linked to overweight/obesity), and others.
    • Risk factors include family history, older age, growth hormone deficiency, high cholesterol/triglycerides, type 2 diabetes/insulin resistance, metabolic syndrome, obesity, polycystic ovary syndrome, sleep apnea, hypothyroidism, hypopituitarism.
    • Some get MASLD even without risk factors.
    • The two basic kinds steatotic liver disease (SLD) are metabolic dysfunction-associated steatotic liver disease (MASLD) and the more severe metabolic-dysfunction associated steatohepatitis (MASH). And there is also a new category, MetALD (metabolic with alcohol-associated liver disease), a continuum which can have elements of MASLD and/or ALD.
  • MASLD is the most common cause of liver disease. Approximately 30%% of U.S. adults are estimated to have it. An estimated 80-100 million people in the U.S. have MASLD.
  • Globally, MASLD is the most common liver disease, affecting about 25% to about a third of the world’s population.    
  • Worldwide prevalence of MASLD is increasing at an alarming rate.

How MASLD Affects Children

  • One study of 408 children with obesity (mean age of 13.2 years; 2018), MASLD was present in nearly one-third of boys and one-fourth of girls.
  • MASLD is the most common form of pediatric liver disease in the U.S., more than doubling the past 20 years, in part because of increasing childhood obesity.
  • Some studies estimate 5% to 10% of children have MASLD.
  • MASLD is on the rise among children of all ethnicities, but especially Hispanic/Latino and Asian American children.
  • In the next decade, untreated childhood MASLD will be a significant contributor to liver transplantation in adults (including some teenagers).
  • MASH is the second most common reason for adult liver transplants, after alcohol-related liver disease. It recently superseded HCV as a cause.
  • Pediatric MASLD is often associated with metabolic syndrome.
  • A story in the Washington Post (10/3/2023) covering the growing crisis of childhood liver disease highlighted the following facts:
    • Before the turn of the century, pediatric steatotic liver disease (formerly called fatty liver disease) was relatively rare. Now millions are affected; the journal Clinical Liver Disease estimates 5% to 10 % of all children in the US have MASLD — about as common as childhood asthma.
    • There were large jumps in MASLD incidence across all ages in the US; the steepest increase by far was in children (data 2017-2021).
    • The rate of MASLD diagnosis more than doubled in children up to age 17 (insurance claim data analyzed for The Post by Trilliant Health). Some of that increase is because of more vigilant reporting and testing recently. The trend, however, holds true.
    • The crisis is acute in the Southeast, where pediatric obesity rates are highest.
    • When more than 5% of liver cells contain fat, steatotic liver disease (SLD) is indicated (5-10%). Pediatric specialists are finding children with livers of 30-40% fat, or even as high as 60% fat.
    • There is a rise in transplants for steatotic liver disease in people in their 20s and 30s.
    • The story also highlighted the link between ultra-processed foods and pediatric/childhood obesity/MASLD.
  • Studies estimate that 20% to 50% of children with MASLD have MASH.
  • When compared to people who develop MASLD during adulthood, people who develop MASLD during childhood are more likely to have MASH and its complications or liver disease as adults.
  • Children with MASH can develop cirrhosis, but the complications of cirrhosis, such as liver failure and liver cancer, usually happen in adulthood.
  • MASLD is more common in boys than in girls.
  • MASLD occurs in children of all races and ethnicities but is most common in Hispanic/Latino children and Asian American children, followed by White children.
  • MASLD is less common in younger children and African American/Black children.
  • One study:Prevalence of MASLD in children broken down by race/ethnicity (2006 data):
    • Children of Hispanic/Latino ethnicity (11.8%)
    • Asian children (10.2%)
    • White children (8.6%)
    • Black/African American children (estimate of 1.5%)

Glycogen Storage Disease Type 1

  • Glycogen storage disease type I (GSD I; Von Gierke disease) is an inherited disorder caused by deficiencies of enzymes, and the buildup of a sugar called glycogen in the body's cells. This accumulation of glycogen in organs and tissues, especially the liver, kidneys, and small intestines, impairs their function.
  • GSD is hereditary, from parents to children). It is seen mostly in babies and young children. Some forms of GSD may appear in adults.
  • There are many types of glycogen storage disease (GSD) – at least 19 have been identified. The types of GSD are categorized by the enzyme missing in each one. Each GSD has its own symptoms and treatments.
  • The most common types of GSD are types I, III, and IV.
  • GSD 1 is a serious, debilitating illness. Signs/symptoms of GSD 1 usually appear around age 3 or 4 months. Affected infants may have low blood sugar (hypoglycemia), which can result in seizures. They can also have a buildup of lactic acid (lactic acidosis); high levels of uric acid (hyperuricemia); and high fat levels in the blood (hyperlipidemia).
  • Older children with GSD 1 can have thin arms/legs; short stature; enlarged liver with a protruding abdomen; enlarged kidneys; diarrhea and cholesterol deposits in the skin (xanthomas).
  • Puberty in people with GSD 1 may be delayed.
  • People with GSD 1 in young to mid-adulthood, can have osteoporosis; gout; kidney disease; and pulmonary hypertension.
  • Females with GSD 1 can have abnormal development of the ovaries (polycystic ovaries).
  • In teens and adults with GSD 1, tumors called adenomas may form in the liver. Adenomas are usually benign but can occasionally become cancerous (malignant).
  • GSD 1 affects children’s appearance. Afflicted people have doll-like faces and full cheeks, thin extremities, short height, and a protuberant belly.
  • Incidence of type I glycogen storage disease is 1 in 100,000 births. The prevalence of GSD 1 in Ashkenazi Jews is estimated at 1 in 20,000.
  • GSD 1 affects males and females equally.
  • Type 1 accounts for 25% of all GSD cases in the U.S.

Primary Sclerosing Cholangitis (PSC)

(For general information see also section Autoimmune Disorders, PSC)

  • Primary sclerosing cholangitis (PSC) is an autoimmune disorder, where the body’s immune system attacks healthy cells. In an afflicted child, the bile ducts become narrow, slowing the bile flow out of the liver. The abnormal flow and buildup of bile in the liver can cause chronic liver problems and damage. Over time, PSC can lead to cirrhosis and liver failure.
  • PSC is usually accompanied by inflammatory bowel disease (IBD), often ulcerative colitis and sometimes Crohn’s disease. This combination of PSC and IBD is found in about 80% of pediatric PSC patients.
  • Children with PSC usually present without complications but often progress to end-stage liver disease (liver failure). Within 10 years of diagnosis, 50% of children will develop complications, with 30% requiring liver transplantation.
  • PSC is rare, with a prevalence of 1.5 cases per 100,000 children.
  • Liver transplantation is the treatment for end‐stage liver disease resulting from pediatric PSC.
  • PSC accounts for ∼2% of all pediatric liver transplants in the U.S.

Progressive Familial Intrahepatic Cholestasis (PFIC)

  • Progressive familial intrahepatic cholestasis (PFIC) is a genetic disorder causing progressive liver disease, leading to liver failure. In PFIC, liver cells cannot secrete bile normally and the buildup of bile causes liver disease, or the secreted bile is abnormal and damages the bile ducts to injure the liver.
  • There are many types of PFIC - each type is classified by the specific genetic cause. The genetic mutations lead to “shortages” of particular proteins.
  • Prevalence of PFIC is unknown but estimates range from 1 in 50,000 to 1 in 100,000 births.
  • Of all the cases of cholestasis in the pediatric population, scientists believe that nearly 10-15% are due to PFIC.
  • Approximately 10% of liver transplants in children result from this condition.

Gilbert's Syndrome

  • Gilbert (zheel-BAYR) syndrome is a common, harmless genetic liver condition in which the liver doesn't properly process bilirubin, produced by the breakdown of red blood cells.
  • Gilbert syndrome requires no treatment.
  • Doctors may consider Gilbert syndrome if patients have unexplained jaundice (yellowish skin and eyes) or if their level of bilirubin is elevated.
  • Gilbert syndrome can be discovered by accident because people may not know they have it. Approximately 1 in 3 people with Gilbert's syndrome don’t have symptoms.
  • People with Gilbert's can lead long, healthy lives and don’t experience long-term health problems from the disease.
  • Gilbert syndrome has a prevalence rate of 3%-16%.
  • Gilbert's Syndrome is more common in males than females, and affects all ages, races and ethnicities.
  • Symptoms of Gilbert syndrome can be similar to those of: Crigler-Najjar syndrome, Rotor syndrome, Dubin-Johnson syndrome. These diseases can also be similar in that all the diseases can cause jaundice, but the severity of jaundice and elevation of bilirubin are different.
  • According to one study, in children, Gilbert's syndrome manifests 2.22 times more often in boys than girls.
  • Gilbert syndrome may become more noticeable during puberty.
  • Gilbert syndrome can manifest during triggers such as fasting, hemolytic reactions, febrile illnesses, menstruation, and physical exertion.

Pediatric Acute Liver Failure (PALF)

  • Acute liver failure (ALF) happens when many cells in the liver die in a short period of time, or it becomes damaged, and the liver is no longer able to perform critical functions. Pediatric acute liver failure (PALF) is a complex, rapidly progressive syndrome that is the result of many conditions, some known and others to be identified.
  • Pediatric liver failure (PALF) is not as common as adult liver failure. Liver failure in children is very rare.
  • The frequency of ALF is estimated at 500-600 cases per year in the US, but the frequency in children is unknown.
  • PALF accounts for approximately 10 percent of pediatric liver transplants (LTs) in the US each year.
  • PALF is characterized by evidence of liver dysfunction within 8 weeks of onset of symptoms; no evidence of past or present chronic liver disease.
  • Symptoms include fevers, abdominal pain, vomiting, lethargy, jaundice, confusion, enlarged liver/spleen, bleeding/bruising.
  • Acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT) may be a complication of PALF.
  • Causes (etiologies) include viral hepatitis (A-G), infections, drug reactions, toxins, immune and metabolic disorders (including Wilson’s disease), cardiovascular conditions.
  • The cause of PALF is undetermined in 30-50% of cases.
  • There is a separate entity of PALF called “indeterminate PALF” in which, after a thorough work up, the etiology is still not discovered. This is an area of exciting and active research within the field but thought to be driven by immune dysregulation.
  • Sepsis (body overreacts to an infection, damaging healthy tissue/organs, leading to shock, organ failure) is a major cause of mortality in PALF in infants in which the underlying cause of PALF is infection.
  • Other causes, such as severe hepatic dysfunction that leads to multiorgan failure (hepatic encephalopathy, cardiovascular and pulmonary failure) may be leading causes of mortality.
  • Mortality may reach 80-90% without liver transplantation.
  • PALF is a rapidly evolving disease state needing prompt recognition and management at an intensive care unit or pediatric liver transplant center.
  • PALF continues to be rare but potentially lethal in otherwise healthy children.

Reye's Syndrome (RS; Reye Syndrome)

  • Reye's syndrome, also known as Reye syndrome, is a very rare but serious condition that causes swelling in the liver and brain.
  • RS is generally a disease in children/young adults but can also occur at any age.
  • Reye's syndrome (RS) affects all organs of the body but is most harmful to the brain and the liver. It can cause an acute increase in pressure within the brain and massive fat accumulations in the liver and other organs.
  • RS generally occurs during recovery from a viral infection, such as the flu or chicken pox, but can develop 3 to 5 days after the onset of the viral illness.
  • RS is often misdiagnosed.
  • Symptoms of RS include vomiting; drowsiness/fatigue; confusion; behavior changes, irritability or aggression; breathing quickly/fast heart rate; difficulty breathing; seizures; loss of consciousness.
  • Most children and teenagers who have RS survive, but degrees of lasting brain damage are possible.
  • Cause(s) of RS is unknown. It has been linked to certain medications (salicylates), particularly aspirin, children under 16, and young people. Children with a rare genetic condition, (e.g., MCADD) can get Reye's syndrome.
  • Because of this association between aspirin (salicylate) and the onset of Reye's syndrome, healthcare professionals do not recommend the use of aspirin for children.
  • RS has no cure. Treatment focuses on preventing brain damage. Recovery is related to the severity of brain swelling. Some recover, while others may have degrees of brain damage.
  • Reye syndrome is very rare. Fewer than 2 cases annually have been reported since 1994.
  • The incidence of RS may not be accurately known because reporting cases to the CDC is no longer mandatory.
  • The peak age for RS is 5 to 14 years; but cases have been reported in children of less than one year.
    Gender is not a risk factor for RS.
  • There is seasonal variation with RS. Most RS cases are reported from December through April.
  • Surveillance of RS in the US began in 1973. CDC reported 555 cases 1979 - 1980. December 1980 -November 1997, the CDC reported 1207 cases. The incidence fell from an average of 100 cases per year 1985-1986 to 36 cases per year 1987-1993. Incidence has fallen since 1991 with 0.2 to 1.1 cases per million reported in the US 1991-1994.

Wilson Disease (WD)

  • Wilson disease is sometimes referred to as Wilson’s Disease, hepatolenticular degeneration, hepatolenticular degeneration syndrome, or copper storage disease.
  • Wilson disease is a rare, progressive, genetic disorder characterized by copper accumulating in body tissues, particularly the liver, brain, kidneys, and corneas. If untreated, it can cause liver disease, nervous system dysfunction, and death. In summary, Wilson disease is a genetic defect that causes excessive copper accumulation in the liver or brain. The excess copper poisons the liver or brain, causing liver, neurologic or psychiatric symptoms. Wilson is a multisystem disorder.
  • Wilson disease is fatal unless detected and treated before serious illness from copper poisoning develops. The mortality rate for Wilson disease complicated by acute liver failure (ALF) without liver transplantation is 95 percent, with death occurring in days to weeks. However, liver transplantation cures Wilson disease with ALF, and prognosis following liver transplantation is excellent.
  • Other organs can be involved, including kidneys, heart, and skin.
  • Wilson disease carries a risk of liver cancer.
  • Symptoms start to appear at all ages, as early as 2-11 to 65+ years. Symptoms usually appear in late adolescence to early adulthood, but can also occur in early childhood, middle or old age.
  • Wilson disease symptoms: weakness, abdominal pain, jaundice, personality change/Psychiatric symptoms, seizures, migraine headaches, insomnia, tremors, Parkinsonian movement disorder, etc.
  • In addition to liver injury, patients can have neurological and mental health issues.
  • Early diagnosis is crucial to prevent serious disability and life- threatening complications.
  • Treatment reduces the amount of copper in the body and focuses on maintaining normal levels.
  • If both parents carry a defective Wilson disease gene, there is a 25% chance each child will have the disorder.
  • Children with Wilson disease can have asymptomatic liver disease, cirrhosis, or ALF, with or without neurological and psychiatric symptoms.
  • Fewer than 50,000 people in the U.S. have Wilson disease.
  • Wilson disease affects males and females equally and is found in all races and ethnicities.
  • Wilson disease incidence is approximately 1 in 30,000 to 40,000 people worldwide, though estimates vary.
  • Wilson disease is more common in certain geographic areas, such as Sardinia, Sicilians, southern Italians, and some Eastern European countries.
  • About 1 in 90 people may be carriers of Wilson disease, though estimates vary. (One study puts the range at 1:90 to 1:150. Another study in the UK showed 1:7,000 have the Wilson disease gene mutation.)
  • In younger children the liver is most often affected by Wilson disease.
  • In teens and adults, the brain may be more affected.
  • Age of onset for WD is 5 to 35 years.
  • 40-50% of WD patients experience liver disease as initial symptoms around the age of 15 years.
  • Other people with Wilson disease may be misdiagnosed with other neurological, liver or psychiatric disorders. Many doctors aren’t familiar with Wilson symptoms that can be wide-ranging.
  • 50-60% of Wilson patients present with liver symptoms. About 5% of patients with Wilson disease have ALF with severe liver damage.
  • 5% of acute liver failure is due to WD in adults.
  • 3.2% of acute liver failure is due to WD in pediatric population.
  • Approximately 20%–30% of WD patients present with ALF; most other untreated patients have chronic progressive hepatitis or cirrhosis.
  • One summary of studies of organ-specific Wilson disease manifestations at presentation:
    • Liver disease: 18%-84% of patients
    • Neurologic symptoms: 18%-73%
    • Psychiatric symptoms: 10%-100%
    • Most symptomatic pediatric patients (<18 years) present with liver disease alone.
    • It is estimated that 35%-45% percent of patients have cirrhosis at diagnosis of Wilson disease.

Last updated on December 10th, 2025 at 04:52 pm

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