Liver disease in a child (incl. liver failure) Flashcards
Where should liver disease in a child be managed?
It is quite uncommon and should be managed by or in conjunction with national centres. Early referral is vital.
How should you manage a child acute liver failure/fulminant hepatitis before transfer to a specialist centre?
- Stabilise the child prior to transfer including:
- Keep the blood glucose >4mmol/L with IV dextrose
- Prevent sepsis with broad-spectrum antibiotics and antifungals
- Preventing haemorrhage (esp GI) with IV vitamin K and H2 blocking durgs or PPIs
- Prevent cerebral oedema by fluid restriction and mannitor diuresis if oedema develops
Which features suggest a poor prognosis in acute liver failure? What is the prognosis if the child progresses to coma?
- Shrinking liver
- Rising bilirubin
- Falling transaminases
- Worsening coagulopathy
- Progression to coma - without liver transplantation, 70% of children who progress to coma will die
What are some causes of prolonged neonatal jaundice?
In prolonged jaundice always look to see if the stools are pale, which suggests bile duct obstruction.
Biliary atresia occurs in 1 in 15,000 and if untreated will cause chronic liver failure and death within 2 years. Presents with mild jaundice and pale stools.
What are 3 causes of acute liver failure in children <2 years old and children >2 years old?
Children <2years:
- Infection (most common is herpes simplex)
- Metabolic disease
- Seronegative disease
- Drug induced
- Neonatal haemochromatosis
Children >2years:
- Seronegative hepatitis
- Paracetamol overdose
- Mitochondrial disease
- Wilson disease
- Autoimmune hepatitis
What are the most common causes of chronic liver disease in children?
- Postviral hepatitis B and C
- AI hepatitis and sclerosing cholangitis
- Drug-induced liver disease (NSAIDs)
- Cystic fibrosis
- Wilson disease
- Fibropolycystic liver disease
- Non-alcoholic fatty liver disease
- alpha1-Antitrypsin deficiency
What are the clinical features of liver disease in children?
What is the most common indication for liver transplantation in the paediatric age group?
Biliary atresia
What is the name given to cystic dilatations of the extrahepatic biliary system? What is the treatment and risks?
Choledochal cysts - may present with neonatal jaundice early or abdominal pain and palpable mass later; visualised with US or MRCP
Treated with surgical excision of cyts + formation of Roux-en-Y anastomosis to biliary duct
Complications are cholangitis and 2% risk of malignancy
What is neonatal hepatitis syndrome? What must be excluded?
Prolonged neonatal jaundice and hepatic inflammation - may be idiopathic
Must differentiate this from biliary atresia
Liver biopsy shows large cell hepatitis
Briefly describe Alagille syndrome. Name another genetic cause of cholestasis.
Rare autosomal dominant comdition with variable penetrance
Presents with triangular facies, butterfly vertebrae, peripheral pulmonary stenosis, renal and eye defects.
Problems include severe prurits (difficult to treat) and cholestasis but most survive into adulthood with nutrition and fat soluble vitamin supplementation
Another cause: progressive familial intrahepatic cholestasis (autosomal recessive)
How does alpha1-antitrypsin present in children vs adults?
Children - prolonged neonatal jaundice or bleeding due to Vit K deficiency (haemorrhagic disease of the newborn) with hepatomegaly.
Adults - emphysema due to lack of circulating alpha-1 antitrypsin
What are the complications of alpha-1 antitrypsin deficiency in childhood?
Up to 50% will have a good prognosis but the rest will develop liver disease and may require transplanttaion
What is the pathophysiology of alpha1-antitrypsin deficiency causing liver disease in children?
Abnormal folding of the protease alpha1-antitrypsin is associated with accumulation of the protein within the hepatocytes and hence liver disease in infancy and childhood
How does galactosaemia cause liver disease in children? What is the managememt and prognosis?
~ 1in 30,000 births
Poor feeding, vomiting, jaundice and hepatomegaly develops when fed milk. Diagnosed by detecting galactose in the urine and measuring galactose-1-phosphate-uridyl transferase in RBC.
Treated with galactose free diet but ovarian failure and learning difficulties may still occur
List the features of acute viral hepatitis in children.
- Nausea
- Vomiting
- Abdominal pain - large tender liver is common and splenomegalu in 30%
- Lethargy
- Jaundice
- High liver transaminases
- Coagulation normal
List whether hepatitis A to E are RNA or DNA viruses.
Hepatitis A - RNA
Hepatitis B - DNA
Hepatitis C - RNA
Hepatitis D - defective RNA
Hepatitis E - RNA
How is hepatitis A transmitted? Which other hepatitis viruses are transmitted in this way?
Faeco-oral transmission
Hepatitis E is also enterally transmitted e.g. eating infected pork, although can be transmitted by blood transfusion too
How is HBV usually transmitted? How is this prevented?
- Perinatal transmission/horizontal spread within families - revented in the UK by maternal screening and giving the infant a course of hepatitis B vaccine with hepatitis B immunoglobulin if indicated. Universal hepatitis B immunization is given in many countries.
- Blood via transfusion, needlestick injury, or renal dialysis
- Sexual transmission in adults
How is HCV transmitted?
- Vertical transmission is most common cause in children - transmission is twice as common if there is coninfection with HIV
- IV drug use
Was responsible for 90% of post-transfusion hepatitis until screening of donor blood in 1991
Which types of hepatitis can cause chronic disease?
Hepatitis B and C
How is hepatitis A diagosed? What is the manegement?
Diagnosed by detecting IgM to the virus. Can be asymptomatic or cause mild illness lasting 2-4 weeks but some may develop prolonged cholestatic hepatitis (self-limiting) or fulminant hepatitis.
No treatment and no evidence that bed rest or change of diet is effective. Vaccinate close contacts within 2 weeks of the onset of illness.
What should you give to at risk contacts of hepatitis A e.g. with chronic liver disease?
HNIG = human normal immunoglobulin
What are the clinical features of HBV infection in children?
- Asymptomatic or classical features of acute hepatitis
- 1-2% develop fulminant hepatic failure
- Of older children 5-10% become chronic carriers BUT of neonates 90% become chronic carriers
How is HBV diagnosed and what is the management?
Detecting HBV antigens and antibodies (E antigen means very infectious) - IgM to anti-HBc means acute infection and HBsAg means ongoing infectivity
No treatment for acute HBV
What are the complications of chronic HBV carriage?
10% progress to cirrhosis
long-term risk of hepatocellular carcinoma
List some drugs used in chronic HBV.
Interferon or pegylated interferon
Antivirals - lamivudine, adefovir, entecavir, tenofovir, telbivudine
When is hepatitis B immunoglobulin given to babies alongside vaccination?
If the mother is HbeAg positive
What is the risk or chronic carriage with HCV? What is the lifetime risk fo progression to cirrhosis/hepatocellular carcinoma?
Majority infected become chronic carriers
25-30% lifetime risk of progression to cirrhosis/hepatocellular carcinoma
What is the management of HCV in children?
Treatment not undertaken before age 3 years as HCV may resolve spontaneously following vertical transmission
Peglated interferon + ribavirin is successful but new therapies like sofosbuvir may be curative in the future.
What is the risk of cirrhosis in those with HBV who develop HDV superinfection?
50-70%
What are the clinical features of HEV infection? When is it most risky?
Mild self-limiting illness
In pregnant women it causes fulminant hepatic failure with high mortality rate
What are the clinical features of fulminant hepatitis?
Pathophysiology - usually massive hepatic necrosis with subsequent loss of liver function +/- hepatic encephalopathy
- Jaundice
- Encephalopathy - early includes alternate periods of irritability and confusion with drowsiness or aggressiveness in older children
- Coagulopathy
- Hypoglycaemia
- Electrolyte dusturbance
- Complications - cerebral oedema, haemorrhage from gastritis, coagulopathy, sepsis and pancreatitis.
How is fulminant hepatitis diagnosed in children?
Bloods
- LFTs - transaminases greatly elevated (x10-100), ALP raised
- Coagulation screen - abnormal
- Plasma ammonia - elevated
- BM
- ABG - acid-base needs to be monitored
Imaging
- EEG - may show hepatic encephalopathy
- CT -may show cerebral oedema
What treatments can be given in fulminant hepatitis before the child is transferred to a specialist unit?
- BM maintained >4mmol/L
- Broad spectrum abx and antifungals to prevent sepsis
- IV vit K and H2 blockers or PPI - prevent haemorrhage
- Fluid restriction and mannitol - prevent cerebral oedema
What are the clinical features of AI hepatitis and sclerosing cholangitis in children?
Usually 7-10 yr old girls affected. May also occur in conjuncion with IBD, coeliac or other AI diseases.
Hepatitis (acute/chronic) + autoimmune features (rahs, arthritis, haemolytic anaemia, nephritis)
What investigations can be used to diagnose autoimmune hepatitis/SC?
- Elevated total protein
- Hypergammaglobulinaemia (IgG >20g/L)
- Positive autoantibodies
- Low C4
- Histology
What are the 2 most common causes of death in cystic fibrosis?
- Respiratory - most common
- Liver
What liver complications occur in cystic fibrosis?
Hepatic steatosis (fatty liver) is the most common - does not usually progress but requires optimal nutritional support
Biliary fibrosis - may occur due to thick tenacious bile with abnormal bile duct concentation eventually causing fibrosis
Cirrhosis and portal hypertension - develop in 20% by mid-adolescence
What is the pathophysiology of Wilson’s disease and the clinical features?
Genetic defect (but many mutations identified) causes (1) reduced synthesis of caeruloplsmin/copper-binding protein and (2) defective excretion of copper in bile
This causes copper to accumulate in…
- Liver –> acute/fulimnant hepatitis, cirrhosis, portal hypertension
- Brain –> reduced school performance, mood and behaviour changes, extrapyramidal signs
- Kidney –> renal tubular dysfunction, vit D resistant rickets, haemolytic anaemia
- Cornea –> Kayser-Fleischer rings (>7yrs old)
What is shown?
Kayser Fleischer rings (on the ouside fo the iris) - Wilson’’s disease
What are the different stages of NAFLD?
- Fatty deposition (steatosis)
- Inflammation (steatohepatitis)
- Fibrosis
- Cirrhosis - few children develop this
- End-stage liver failure
What is NAFLD associated with in childhood?
Metabolic syndrome and obesity
Pathogenesis may be linked to insulin resistance but is not fully understood
What is the management of NAFLD in children?
Weight loss through diet and exercises
What are the nutrition complications in chronic liver disease in children?
Fat malabsorption - bile is needed to absorb long chain fatty acids, fat soluble vitamins are also carried on these long chain fatty acids so without bile will be deficient
Protein malnutrition - poor intake + high catabolic rate of the diseased liver; although protein may need to be restricted in encephalopathy
Anorexia - may require NG tube or parenteral nutrition
Name the fat soluble vitamins and some effects of their deficiencies.
What is the management of pruritus in chronic liver disease?
Difficult to manage and may lead to excoriation of the skin which can cause permanent scarring.
Conservative - loose cotton clothing, avoid overheating, keep nails short, mosisturise skin with emollients
Medication - phenobarbital (to stimulate bile flow), cholestyramine (to absorb bile salts), ursodeoxycholic acid (to solubilise bile), rifampicin (enzyme inducer)
What events can trigger encephalopathy in chronic liver disease?
- GI haemorrhage
- Sepsis
- Sedatives
- Renal failure
- Electrolyte imbalance
How is encephalopathy confirmed in chronic liver disease?
EEG is always abnormal
Raised ammonia
What are the signs of cirrhosis and portal hypertension?
- Splenomegaly - abdomen will look distended; liver may be shrunken and impalpable
- Varices
- Ascites - may cause scrotal swelling in boys
- Jaundice
- Palmar/plantar erythema
- Telangiectasia
- Spider naevi
- Malnutrition
- Hypotonia
What is a dangerous complication of ascites in chronic liver disease which should be suspected in undiagnosed fever, pain, or unexplained deterioration in hepatic/renal function?
Spontaneous bacterial peritonitis = diagnosed with paracentesis and fluid sent for WCC and differential culture. Treated with broad spectrum antibiotics
What are 4 indications for transplantation in chronic liver disease?
- Severe malnutrition unresponsive to intensive nutritional therapy
- Complications refractory to medical management (bleeding, varices, resistant ascites)
- Failure of growth and development
- Poor quality of life
What are the most common complications of liver transplantation?
- Primary non-fuction of the liver (5%)
- Hepatic artery thrombosis (10-20%)
- Biliary leaks and strictures (20%)
- Rejection (30-60%)
- Sepsis (main cause of death)
1yr survival is 90% and 20 year survival is 80%
