Liver Disorders Flashcards
What is the main feature of liver disorders in infants?
Prolonged neonatal jaundice, it can be physiological but if caused by liver diseased it is characterised by a raised conjugated bilirubin.
What are the clinical features of liver disease in infants?
Prolonged neonatal jaundice Pale stools Dark urine Bleeding tendency Failure to thrive
Is liver disease an important differential to consider?
Yes, there is an urgency to diagnose liver disease as early as possible in the neonatal period, because early diagnosis and management improves prognosis
What is biliary atresia?
A progressive disease, in which there is a destruction or absence of the extra hepatic biliary tree and tntrahepatic biliary ducts.
What are the clinical features of liver disease in children?
Encephalopathy Jaundice Epistaxis Cholestasis Ascites Hypotonia Peripheral neuropathy Rickets secondary to vit D deficiency Varices with portal HTN Spider nave Muscle wasting from malnutrition Bruising and petechiae Splenomegaly with portal HTN Hypersplenism Hepatorenal failure Liver palms Clubbing
What are some causes of unconjugated prolonged neonatal jaundice?
Breast milk jaundice Infection (particularly UTI) Haemolytic anaemia (G6PD deficiency) Hypothyroidism High GI obstruction Crigler - Najjar syndrome
What are some causes of conjugated prolonged neonatal jaundice?
Bile duct obstruction - biliary atresia, choleductal cyst
Neonatal hepatitis syndrome - congenital infection, inborn errors of metabolism, alpha1 antitrypsin deficiency, galactosaemia, CF
How would you investigate biliary atresia?
A fasting abdominal US may show a contracted or absent gallbladder. A radioisotope scan with TIBIDA shows good uptake by the liver, but no excretion into the bowel. The diagnosis is confirmed at laparotomy by operative cholangiography which fails to outline a normal biliary tree.
How would you treat biliary atresia?
Surgical bypass of the fibrotic ducts, hepatoportoenterostomy, in which a loop of jejunum is anastomosed to the cut surface of the porta hepatic, facilitating bile drainage. Success decreases with age
What are choledochal cysts?
These are cystic dilatations of the extra hepatic biliary system
How does choledochal cysts present?
About 25% present in infancy with cholestasis. In oder children, abdominal pain, a palpable mass and jaundice or cholangitis.
How would you diagnose choledochal cysts?
US or radionuclide scanning
How would you treat choledochal cysts?
Surgical excision of the cyst
What is neonatal hepatitis syndrome?
Prolonged hepatic jaundice and hepatic inflammation
How does neonatal hepatitis syndrome present?
They may have IUGR and hepatosplenomegaly at birth
What is alpha-antitrypsin deficiency?
Deficiency of the protease alpha-antitrypsin, it is associated with liver disease in infancy and childhood and emphysema in adults.
How is alpha-antitrypsin deficiency inherited?
It is inherited as an autosomal recessive disorder.
What are the clinical features of alpha-antitrypsin deficiency?
Prolonged neonatal jaundice or, less commonly, bleeding due to vitamin K deficiency (haemorrhagic disease of the newborn). Hepatomegaly is present. Splenomegaly develops with cirrhosis and portal hypertension.
How is alpha-antitrypsin deficiency confirmed?
Estimating the level of alpha-1-antitrypsin in the plasma and identifying the phenotype
What is the prognosis of alpha-1-antitrypsin deficiency?
50% of children have a good prognosis, but the remainder will develop liver disease and may require transplantation
What is progressive familial intrahepatic cholestasis?
A heterogenous group of cholestatic disorders of bile transporter defects caused by recessive mutations in different genes.
How does progressive familial intrahepatic cholestasis present?
Jaundice, intense pruritus, diarrhoea with failure to thrive, rickets and a variable progression of liver disease.
What are the clinical features of viral hepatitis?
Nausea, vomiting, abdominal pain, lethargy and jaundice (30-50% do not develop jaundice). A large tender liver is common and 30% will have splenomegaly. The liver transaminases are usually markedly elevated. Coagulation is usually normal.
What is acute liver failure?
In children, it is the development of massive hepatic necrosis with subsequent loss of liver function, with or without hepatic encephalopathy.
What are the main causes of acute liver failure in children?
Paracetamol overdose, non-A to G viral hepatitis and metabolic conditions (Wilson’s disease, tyrosinaemia).
How does acute liver failure present in children?
May present within hours or weeks with jaundice, encephalopathy, coagulopathy, hypoglycaemia and electrolyte disturbance.
What are the signs of encephalopathy secondary to acute liver failure?
early signs include alternate periods of irritability and confusion with drowsiness. Older children may be aggressive and unusually difficult.
What are the complications of acute liver failure?
Cerebral oedema, haemorrhage from gastritis or coagulopathy, sepsis and pancreatitis.
How would you diagnose acute liver failure?
Bilirubin may be normal. Transaminases are greatly elevated (10-100 times normal), alkaline phosphatase is increased, coagulation is very abnormal and plasma ammonia is elevated.
What would you monitor during acute liver failure?
The acid-base balance, blood glucose and coagulation times. An EEG will show acute hepatic encephalopathy and a CT scan may demonstrate cerebral oedema.
How would you manage acute liver failure?
Maintaining the blood glucose with IV dextrose.
Preventing sepsis with broad-spectrum antibiotics and antifungals.
Preventing haemorrhage, particularly from GI tract with IV vit K, FFP and cryoprecipitate and H2-blocking drugs or PPIs
treating cerebral oedema by fluid restriction and mannitol diuresis
Urgent transfer to a specialist liver unit.
What are the features of poor prognosis of acute liver failure?
A shrinking liver, rising bilirubin with falling transaminases, a worsening coagulopathy or progression to coma.
What is Reye’s syndrome?
An acute non-inflammatory encephalopathy with microvesicular fatty infiltration of the liver.
What drug is Reye’s syndrome linked with?
Aspirin therapy
What are the causes of chronic liver disease in children?
Chronic hepatitis - post-viral hepatitis B, C; autoimmune hepatitis; drugs (nitrofurantoin, NSAIDs); IBD; primary sclerosing cholangitis Wilson's disease (>3 years) Alpha-1-antitrypsin deficiency CF Neonatal liver disease Bile duct lesions
What is the clinical presentation of chronic liver disease in children?
It can vary from an apparent acute hepatitis to the insidious development of hepatosplenomegaly, cirrhosis and portal HTN with lethargy and malnutrition.
What is the mean age of presentation of autoimmune hepatitis and what sex is it most common?
7-10 years, most common in girls
How does autoimmune hepatitis present?
It may present as an acute hepatitis, as fulminant hepatic failure or chronic liver disease with autoimmune features such skin rash, SLE, arthritis, haemolytic anaemia or nephritis.
How is autoimmune hepatitis diagnosed?
It is based on elevated total protein, hypergammaglobulinaemia (IgG > 20g/L); positive autoantibodies, a low serum complement (C4) and typical histology.
How would you treat autoimmune hepatitis?
90% of children will respond to prednisolone and azathioprine
What is the most common liver abnormality associated with cystic fibrosis?
Hepatic steatosis (fatty liver). It may be associated with protein energy malnutrition or micronutrient deficiencies.
After hepatic steatosis, what is the potential, more significant liver disease that could occur with CF
Progressive biliary fibrosis due to thick tenacious bile with abnormal bile acid concentration. Cirrhosis and portal HTN develop in 20% of children by mid-adolescence.
How would you treat chronic liver disease secondary to CF?
It does not generally progress and treatment involves ensuring optimal nutritional support. It could be treated with ursodeoxycholic acid if further treatment is indicated. In end-stage liver failure, liver transplantation may be considered
What is Wilsons disease?
The basic genetic defect is a combination of reduced synthesis of caeruloplasmin (the copper-binding protein) and defective excretion of copper in the bile, which leads to an accumulation of copper in the liver, brain, kidney and cornea
How is Wilson’s disease inherited?
It is an autosomal recessive disorder
When does Wilson’s disease often present?
It does not often present below 3 years
How does Wilson’s disease often present at younger ages?
In those presenting in childhood, a hepatic presentation is more likely. The may present with almost any form of liver disease, including acute hepatitis, fulminant hepatitis, cirrhosis and portal HTN
How does Wilson’s disease often present in the second decade?
Neuropsychiatric features are more common including deterioration in school performance, mood and behaviour change, and extrapyramidal signs such as incoordination, tremor and dysarthria. Renal tubular dysfunction, with vitamin D-resistant rickets, and haemolytic anaemia also occur.
What are Kayser-Fleischer rings and when are they seen?
They are copper accumulation in the cornea and they are not seen before 7 years of age.
What are the investigation results in Wilson’s disease?
A low serum ceruloplasmin and copper is characteristic, but not universal. Urinary copper excretion is increased and this further increases after administrating the chelating agent penicillamine.
How is Wilson’s disease confirmed?
Elevated hepatic copper on liver biopsy or identification of the gene mutation.
How do you treat Wilson’s?
Treatment is with penicillamine or trientine. Both promote urinary copper excretion, reducing hepatic and CNS copper. Zinc can reduce copper absorption. Liver transplant is considered for severe end-stage liver disease
What can be used to prevent peripheral neuropathy in Wilson’s?
Pyridoxine. Neurological improvement may take up to 12 months of therapy
What is fibropolycystic liver disease?
A range of inherited conditions affecting the development of the intrahepatic biliary tree.
How does fibropolycystic liver disease present?
Liver and renal disease. The liver disease may include cystic disease of the liver or the biliary tree or congenital hepatic fibrosis.
How and when does congenital hepatic fibrosis present?
In children over 2 years old with hepatosplenomegaly, abdominal distention and portal HTN.
How does congenital hepatic fibrosis differ from cirrhosis?
Liver function tests are normal in the early stage of congenital hepatic fibrosis
What does histology show in congenital hepatic fibrosis?
Large bands of hepatic fibrosis containing abnormal bile ductules.
What are the main pathophysiological effects of cirrhosis?
Diminished hepatic function and portal HTN with splenomegaly, varices and ascites. Hepatocellular carcinoma may develop
What are the physical signs of cirrhosis?
Palmar and plantar erythema and spider naevi, malnutrition and hypotonia. Dilated abdominal veins and splenomegaly suggest portal HTN, although the liver may impalpable
What are the investigations for cirrhosis?
Screening for known causes of chronic liver disease.
Upper GI endoscopy to detect the presence of oesophageal varices and/or erosive gastritis.
Abdo US - may show shrunken liver and splenomegaly gastric and oesophageal varices.
What would the bloods show as cirrhosis worsens?
Elevation aminotransferases and alkaline phosphatase.
The plasma albumin falls.
Prothrombin time is prolonged
When do oesophageal varices develop? Is this a quick process?
They are inevitable consequences of portal hypertension and may develop rapidly in children
How do you investigate oesophageal varices?
Upper GI endoscopy because barium swallow may miss small varices
How do you acutely treat oesophageal varices?
Acute bleeding is treated conservatively with blood transfusions and H2 blockers (ranitidine) or omeprazole.
How do you treat oesophageal varices if the bleeding continues?
Octreotide infusion, vasopressin analogues, sclerotherapy or band ligation
What are the contributing factors to ascites?
Hypoalbuminaemia, sodium retention, renal impairment and fluid redistribution.
How do you treat ascites?
Sodium and fluid restriction and diuretics
When should spontaneous bacterial peritonitis be considered?
If there is an undiagnosed fever, abdominal pain, tenderness or an unexplained deterioration in hepatic or renal function.
What may precipitate encephalopathy secondary to end-stage liver disease?
GI haemorrhage, sepsis, sedatives, renal failure or electrolyte imbalance
How is nutrition altered in liver disease?
High protein, high carbohydrate diet with 50% more calories than the recommended daily allowance.
How would you treat pruritus?
Loose cotton clothing, avoid overheating
Emollients or evening primrose oil
Phenobarbital to stimulate bile flow; cholestyramine which is a bile salt resin; ursodeoxycholic acid, an oral bile acid
What are the indications for liver transplant in chronic liver disease?
Severe malnutrition unresponsive to intensive nutritional therapy.
Recurrent complications (bleeding varices, resistant ascites)
Failure of growth and development
Poor quality of life
What are some absolute contraindications to liver transplantation?
Sepsis
Untreatable cardiopulmonary disease
Cerebrovascular disease
What are some complications of liver transplantation?
Primary non-function of the liver Hepatic artery thrombosis Biliary leaks and strictures Rejection Sepsis, the main cause of death
