What investigations would you order to assess progress of chronic liver disease?
Liver
- LFT’s
- Synthetic function (albumin, coagulation studies)
Nutrition
- Fat soluble vitamins (retinol level, vitamin E level)
- Calcium, magnesium, phophate
Portal hypertension
- Abdominal USS with Doppler studies and portal pressures.
- Endoscopy for varices.
Ascites
- Ascitic tap
Encephalopathy
- Clinical assessment
- Ammonia, glucose and electrolytes.
What are complications of liver transplantation?
Rejection (60%)
- Main cause of graft dysfunction
- Most often in first 3 months
- Increased transaminases, fever, malaise or jaundice.
- Responds to pulse steroids, increased tacrolimus and addition of another immunosuppressant like mycophenylate.
- If unresponsive treat with anti-T-cell antibody preperations (ATG, alemtuzumab).
- Chronic rejection loss of >50% of bile ducts - optimise immunosuppression and dilate strictures.
Infection (50%)
- Early (<1 month) - bacterial/fungal.
- Intrabdominal and lines most common.
- Fungal particularly with long ICU stays, reoperation or bowel perforation - prophylaxis with itraconazole, fluconazole or caspofungen.
- Later (2-6 months) - viral (EBV, CMV, HZVZ)
- Reduced with prophylactic ganciclovir or aciclovir.
Biliary obstruction (20%)
- 6 weeks - 6 years post.
- Percutaneous balloon dilatation, revision or retransplantation.
Hepatic vascular compromise (10%)
Post-transplant lymphoproliferative disorder (5-25%)
- Risk factors: primary EBV infection following transplant, young age, EBV negative resipient of EBV positive donor, CMV infection, significant immunocompromise.
Recurrence of disease
Medication toxicity
- Calcineuran inhibitors: tacrolimus and cyclosporine - renal impairment, hypertension, neurotoxicity and hyperlipidaemia
- Steroids - Cushingoid features, high BSLs, cataracts, immunosuppression, osteopenia, adrenal crisis, hypertension.
- Captopril - cough
Causes of chronic liver disease in child <5 years?
Infection
- TORCH, echovirus, adenovirus, parvovirus B19, E. coli UTI
Structural
- Extra hepatic biliary atresia, choledochal cyst, Alagille
Metabolic
- Cystic fibrosis, AAT deficiency, hereditary fructose intolerance
- Galactosaemia, tyrosinaemia, Niemann-Pick
- Glycogen storage diseases - type IA & IV (Von Gierke & Anderson)
Endocrine
- Hypothyroidism, hypopituitarism
TPN
Idiopathic neonatal hepatitis (25%)
Causes of chronic liver disease in children >5 years?
Infectious
- EBV, CMV, toxoplasmosis, hepatitis A, B, C
Metabolic
- Wilson disease, hereditary fructose intolerance, cystic fibrosis, AAT deficiency
Autoimmune chronic active hepatitis
- Associated with thyroiditis, glomerulonephritis, erythema nodosum
Primary sclerosis cholangitis from IBD (>10 years)
- Associated with arthritis, erythema nodosum, uveitis
What are the causes of portal hypertension?
Pre-hepatic
- Portal vein thrombosis
Hepatic
- Pre-sinusoidal - neoplasia, hepatic cyst, schistosomiasis.
- Sinusoidal - A1AT deficiency, biliary atresia, cirrhosis, neonatal hepatitis.
- Post- sinusoidal - veno-occlusive disease.
Post-hepatic
- Budd-Chiari syndrome
- Constrictive pericarditis
- Right ventricular failure
What are the signs and causes of portal hypertension?
Cardinal sign is splenomegaly.
- No hepatomegaly –> portal vein obstruction most likely.
- Hepatomegaly but no signs of CLD –> congenital hepatic fibrosis.
Clinical features:
- Splenomegaly
- Cutaneous porto-systemic shunts (caput medusae, haemorrhoids).
- Ascites, hypoalbuminaemia.
- Thrombocytopenia.
- Small, normal or enlarged liver.
- FTT, reduced muscle bulk
What are treatment options for portal hypertension?
Medical:
- B blockers
- IV vasopressin
Endoscopy (varices):
- Sclerotherapy
- Banding
- Balloon tamponade
Shunts:
- Splenorenal or portocaval shunts - potentially limits future transplant, may precipitate encephalopathy.
- Transjugular intrahepatic portosystemic shunt (TIPS) - temporising measure, used only in kids awaiting transplant.
Splenectomy
- Avoid if possible, risk of infection.
- Increased risk of bleeding
Liver transplant
What are common causes of need for liver transplant?
Structural
- Extrahepatic biliary atresia (>50%)
- Other (<5%)
Metabolic (15%)
- A1AT, CF, galactosaemia, glycogen storage disorder (IA and IV), mitochondrial, Wilsons, organic acidaemia.
Acute hepatic necrosis (10%)
Infective (10%)
- Chronic active hepatitis
- Primary biliary cirrhosis
Primary malignancy (2%)
What are indications for liver transplant?
Poor quality of life
- Intractable pruritis, lethargy, anorexia or recurrent infections.
Complications
- Malnutrition (catabolic state)
- Life-threatening variceal haemorrhage
- Poor synthetic function (alb <20, INR >3.5)
- Refractory hepatic encephalopathy
- Refractory ascites
- Hepatorenal syndrome
Underlying disease
- Refractory primary sclerosing cholangitis
- Hyperammonaemia - inborn error of metabolism
What substances can be checked for on stool sample and what do they indicate?
Fat globules
- Fat malabsorption
- Coeliac disease, pancreatic insufficiency, cholestasis, bacterial overgrowth
Fatty acid crystals
- Fat malabsorption (partial hydrolysis)
- Coeliac disease, cholestasis, bacterial overgrowth
White cells
- Inflammation/infection
- IBD, infection
Red cells
- Inflammation/infection
- Bleeding
- IBD, infection
pH and reducing substances
- CHO malabsorption
- Lactose intolerance, sucrase isomaltase deficiency
A1 antitrypsin
- Protein malabsorption
- Intestinal lymphangiectasia, inflammatory bowel disease.
What are causes of hepatomegaly?
SHIRT
Structural
- Extrahepatic biliary atresia
- Choledocal cyst
- Intahepatic biliary hypoplasia (Alagille)
- Polycystic disease
- Congenital hepatic fibrosis
Storage/Metabolic
- Fat - CF, obesity, malnutrition
- Lipid - Gaucher, Niemann Pick
- Carbohdrate - DM, glycogen storage disorder (1 3 4 6), hereditary fructose intolerance, galactosaemia, Cushings, muccopolysccharidosis.
- Protein - tyrosinaemia 1, urea cycle disorders.
- Wilsons disease
- A1AT
- TPN cholestasis
Haematological
- Thalassaemia
- Sickle cell disease
- ALL, AML, CML
- Langerhan cell histiocytosis
Heart
- Congestive cardiac failure
- Constrictive pericarditis
- Obstructed IVC
Infection - congenital or acquired
- Viral - congenital rubella, CMV, EBV, coxsackie, echovirus, hepatitis A, B, C, D, E
- Bacteria - E. coli UTI, Tb
- Parasitic - hydatid, malaria, schistosomiasis, toxoplasmosis, visceral lava migrans
Infammatory
- Chronic active hepatitis
- Inflammatory bowel disease
Infiltrative
- Langerhans cell histiocytosis
- Sarcoiosis
Reticuloendothelial sytem
- Non-Hodgkins
- Hodgkins
Rheumatological
- Systemic JIA
- SLE
- Sarcoidosis
Tumour/hamartoma/cysts
- Primary - hepatoblastoma, hepatocellular carcinoma
- Secondary - neuroblastoma, Wilms, gonadal
- Haemangioma
- Liver transplant
Trauma
- Hepatic haematoma
What are causes of splenomegaly?
Cardiac - SBE
Connective tissue - sJIA, SLE
Haematological - chronic haemolytic anaemias
Infection
- Viral - EBV, CMV
- Bacterial - SBE, typhoid
- Protozoal - malaria, toxoplasma
Injury - haematoma
Malignancy - leukaemia, lymphoma
Portal hypertension
- Extrahepatic: post-neonatal umbilical vessel catheterisation/sepsis
- Hepatic: cirrhosis, congenital heptic fibrosis
- Suprahepatic: Budd-Chiari syndrome
Storage diseases - Gaucher, Neimann-Pick
Splenic cyst or hamartoma
