Liver disease Flashcards
Define acute liver failure
Massive hepatic necrosis with loss of liver function ± hepatic encephalopathy
- Uncommon; high mortality
- Majority from paracetamol overdose, infection and metabolic disease
Symptoms of acute liver failure
Children may present within hours or weeks with:
- Jaundice
- Encephalopathy- features include irritability, confusion and drowsiness NOTE: older children may be aggressive
- Coagulopathy
- Hypoglycaemia
- Electrolyte disturbance
Investigations of acute liver failure
LFTs
- Liver inflammation: MASSIVELY elevated transaminases (10-100 times normal) - AST, ALT
- High ALP
- Liver function: Abnormal coagulation (INR)
- High plasma ammonia
IMPORTANT: Acid-base balance, blood glucose and coagulation should be monitored at all times
- EEG- may show acute hepatic encephalopathy
- CT- may show cerebral oedema
Management of acute liver failure
Referral to a national paediatric liver centre
Steps to stabilise the child:
- Maintaining blood glucose (> 4 mmol/L) with IV dextrose
- Preventing sepsis with broad-spectrum antibiotics and antifungals
- Preventing haemorrhage with IV vitamin K and H2 antagonists/PPIs
- Prevent cerebral oedema by fluid restriction and mannitol diuresis
- Management is dependent on the suspected cause of acute liver failure
Features of POOR prognosis:
- Shrinking liver
- Rising bilirubin
- Coma
- Falling transaminases
- Worsening coagulopathy
Complications of acute liver disease
COMPLICATIONS
- Cerebral oedema
- Haemorrhage from gastritis or coagulopathy
- Sepsis
- Pancreatitis
- Hepatic encephalopathy -> supportive, reduce N2 load (lactulose, ABx)
- Cirrhosis, portal HTN -> fluid restrict, diuretics
Outline the featuers of viral hep
- Nausea
- Vomiting
- Abdominal pain
- Lethargy
- Jaundice- NOTE: 30-50% do NOT develop jaundice
- Large, tender liver
- Splenomegaly
- Elevated transaminases
- NORMAL coagulation
Hep A
- Single stranded RNA virus
- Faecal-oral transmission
- Vaccination required if travelling to endemic areas
- May be asymptomatic
Presentation
* In children < 5 years- 80-95% of infections are ASYMPTOMATIC
Prodrome (3-10 days):
* Flu-like symptoms- fatigue, malaise, joint and muscle pain, low-grade fever up to 39oC
* GI symptoms- anorexia, N+V, RUQ discomfort
* Headache, cough, sore throat, constipation, diarrhoea, itch, urticaria
Icteric phase (1-3 weeks, up to 12 weeks)
* Jaundice
* Pruritis
* Fatigue, anorexia, N+V, hepatomegaly, splenomegaly, lymphadenopathy, hepatic tenderness
Convalescent phase (can be up to 6 months)
* Malaise, anorexia, muscle weakness, hepatic tenderness
Investigations
* Anti-HAV IgM antibodies (during acute illness, disappears after 3-5 months)
* Anti-HAV IgG antibodies (recovery phase and lifelong persistence)
MANAGEMENT (NICE Guidelines)
* Supportive treatment for pain, nausea or itch is required
* Pain: Paracetamol, Ibuprofen, weak opioid (e.g. codeine) if liver impairment is mild
* Nausea: Metoclopramide or cyclizine
* Itch: Maintain a cool, well-ventilated environment, wearing loose clothing and avoiding hot baths and showers, chlorphenamine may be used at night. Other options: ursodeoxycholic acid, colestyramine, corticosteroids
AVOID SCHOOL whilst infectious: typically 7 days after onset of jaundice or symptoms (if no history of jaundice)
Contacts
* May be given a Hepatitis A vaccine if not received previously
* May arrange administration of human normal immunoglobulin depending on timing and circumstances
Prevention
* Vaccination if at high risk of acquiring or developing complications or not immune and at high risk
* Usually single dose of HAV
* Booster 6-12 months later if long-term risk of contracting HAV
This is a NOTIFIABLE DISEASE
Complications
* In some people, fever, pruritis, diarrhoea, jaundice, weight loss and malabsorption can have a relapsing course, persisting for several months
RARE: fulminant liver failure
Prognosis
* 85% make a complete recovery within 3 months
* Most affected children have mild illness and recover clinically and biochemically within 2-6 weeks
* Does NOT cause chronic liver disease, has no chronic carrier state, results in lifelong immunity
Hep B
- DNA virus
- Can cause acute and chronic liver disease
- High prevalence in Sub-Saharan Africa and Far East
Transmitted by:
1. Perinatal transmission from carrier mothers or horizontal spread within families
2. Inoculation with infected blood via blood transfusion, needle stick injuries or renal dialysis
3. Among adults, it can also be transmitted sexually
- Infants who contract HBV are asymptomatic but at least 90% become chronic carriers
- Older children who contract HBV may be asymptomatic OR have features of acute viral hepatitis
- Most will resolve spontaneously
- 1-2% develop fulminant hepatic failure
- 5-10% become chronic carriers
Various viral proteins are produced such as:
Core antigen (HBcAg)
* Antibodies made to this (anti-HBc) implies past infection
Surface antigen (HBsAg)- present 1-6 months after exposure
* Antibodies to HBsAg imply vaccination has been given.
e antigen (HBeAg)- present for 1.5-3 months after acute illness.
* This is a marker for high infectivity
Presentation
* Acute infection
* Prodromal illness- fever, arthralgia, rash (appears 2 weeks before onset of jaundice then resolves in acute Hepatitis B)
* RUQ pain
* Jaundice (dark urine and/or pale stools if cholestasis)
* Extrahepatic manifestations- glomerulonephritis, vasculitis, polyarteritis
* Chronic Infection- can get signs of chronic liver disease
Investigations
* LFTs: Raised ALT and AST, ALP
* Raised bilirubin
* In chronic: usually just mildly elevated ALT/AST
* HBV antigens and antibodies
- IgM HBcAb (IgM antibodies against hepatitis B core antigen) – positive in ACUTE infection
- HBsAg (hepatitis B surface antigen) – suggestive of ONGOING infection
Viral serology:
Acute HBV: HBsAg +ve, IgM anti-HBcAg
Chronic HBV: HBsAg +ve, IgG anti-HBcAg + HBeAg +ve/-ve
HBV Cleared: Anti-HBsAg antibody +ve, IgG anti-HBcAg
Vaccinated against HBV: Anti-HBsAg antibody +ve
MANAGEMENT (NICE Guidelines)
Acute (if HBsAg positive)
* REFER to hepatologist, gastroenterologist or ID specialist
* Supportive treatment for pain, nausea or itch is required (as per Hepatitis A)
* Contacts are offered Hepatitis B vaccination if in contact with confirmed HBV
* Anti-viral therapy with/ without liver transplant
(ARTs: Lamivudine, entecavir, tenofovir disoproxil)
Acute Hepatitis B is a NOTIFIABLE DISEASE
Chronic
* Supportive- usually symptomatic
* IFNa or antiviral monotherapy is recommended in some patients e.g. entecavir, pegylated interferon alfa, tenofovir disoproxil, lamivudine
Prevention
* ALL pregnant women should have antenatal screening for HBsAg
* Babies of all HBsAg +ve mothers should receive hepatitis B vaccination
* 1st dose- given within 24 hours of birth
* 2nd dose- given around 4 weeks
* Next 3 doses: 8, 12, 16 weeks – as part of routine immunisation schedule
Final dose- at 1 year (and check levels)
* Other members of the family should also be vaccinated
Complications
- Acute: Symptoms and jaundice last for 1-3 months
- Fulminant hepatitis (RARE)
- There is a long-term risk of hepatocellular carcinoma
Prognosis
- 30-50% of asymptomatic carrier children will develop chronic HBV disease, which may progress to cirrhosis
Hep C
- RNA virus
- Prevalence is high amongst IVDUs
- Vertical transmission is the MOST COMMON cause of HCV transmission in children
- Transmission is much more common if there is co-infection with HIV
MANAGEMENT (NICE Guidelines)
* Referral for specialist assessment and treatment
* Treatment decisions are based on the genotype of HCV
* SC Pegylated IFNa weekly
* PO Ribavirin OD
* New drugs are particularly effective- e.g. sofobuvir
NOTE: treatment is NOT undertaken until > 3 years of age because vertically acquired infections may resolve spontaneously
- Liver transplant may be needed
- This is a NOTIFIABLE DISEASE
Complications and Prognosis
* Rarely causes an acute infection
* Most become chronic carriers (50-80%)
* Progression to cirrhosis or hepatocellular carcinoma
* HCV is cured in > 99% of people who achieve a sustained viral response
Hep D and E
Hepatitis D
* Defective RNA virus, coated with HBsAg
* Depends on Hepatitis B virus for replication (co-infection or superinfection)
* Cirrhosis develops in 50-70% of those that develop chronic HDV infection
Hepatitis E
* RNA virus
* Faeco-oral transmission usually from contaminated water
* Causes mild self-limiting illness in most people
* Can also be transmitted by blood transfusion or eating contaminated pork
* It is particularly DANGEROUS in pregnant women- it causes fulminant hepatic failure with a high mortality rate
Management of autoimmune hepatitis
Management of Autoimmune Hepatitis:
N.B. PBC = anti-mitochondrial AB
N.B. PSC = pANCA, anti-smooth muscle AB
- Prednisolone and azathioprine
- Sclerosing cholangitis -> ursodeoxycholic acid (aids bile flow
- Liver transplants may be considered in severe cases
Management of Wilson’s Disease:
Management of Wilson’s Disease:
- Zinc (blocks intestinal copper resorption)
- Trientine / Penicillamine (increases urinary copper excretion)
- Pyridoxine (vitamin B6; given to prevent peripheral neuropathy – improvement may take up to 12m)
- Symptomatic treatment for tremor, dystonia and speech impediment
- Liver transplantation - considered in children with end-stage liver disease
Management of Non-Alcoholic Fatty Liver Disease
Management of Non-Alcoholic Fatty Liver Disease:
- Weight loss (and bariatric surgery
- Treatment of insulin resistance and diabetes
- Statins Vitamin E and C
- Ursodeoxycholic acid (improved bile flow)
Management of paracetamol overdose
<1 hour à activated charcoal -> Ix: paracetamol level ≥4 hours after ingestion -> NAC if indicated
o >1 hour -> Ix: paracetamol level ≥4 hours after ingestion -> NAC if indicated
NAC = N-acetylcysteine
