Hepatology Flashcards
Acute liver failure
A syndrome of acute liver dysfunction without underlying chronic liver disease
Characterised by coagulopathy (derangement in clotting) of hepatic origin & altered levels of consciousness due to hepatic encephalopathy
Drug-induced liver injury is the most common reason in Europe
Acute liver failure vs acute liver injury
Acute liver failure – severe acute liver injury with development of coagulopathy and hepatic encephalopathy within 28 weeks of disease onset
Acute liver injury – severe acute liver injury from a primary liver aetiology, characterised by liver damage and impaired liver function, hepatic encephalopathy is absent
Acute liver failure aetiology
Primary cause of ALF – viruses (A,B, E), paracetamol, budd-chiari syndrome, pregnancy-related, autoimmune hepatitis (emergency liver transplantation may be an option for these aetiologies)
Secondary cause of ALF – ischaemic hepatitis, liver resection, severe infection (emergency liver transplantation is not an options for these aetiologies)
Acute liver failure clinical features
Jaundice
RUQ pain, hepatomegaly, ascites
Coagulopathy – bruising
Hepatic encephalopathy – confusion, altered mental status, asterixis and/or coma
GI bleeding – haematemesis, melaena
Hypotension & tachycardia
Raised ICP – papilloedema, bradycardia, hypertension, low GCS
Acute liver failure investigations
Urgent blood tests – FBC, U&Es, LFTs, bone profile, blood glucose, arterial ammonia, ABG, coagulation, LDH, lipase/amylase, blood cultures
Non-invasive liver screen – toxicology screen, paracetamol serum level, autoimmune markers, viral screen for hepatitis
Imaging – doppler USS, CT abdomen
Acute liver failure management
Managed in intensive care in a transplant centre
Cardiovascular – fluid resus +/- use of inotropic agents
Respiratory – intubation & ventilation may be needed for HE/respiratory failure
GI – nutrition, gastric ulcer prophylaxis, and assess for pancreatitis, manage GI bleeding as require
Metabolic – manage electrolyte disturbances
Acute liver failure complications
Sepsis
Progressive multi-organ failure
Cerebral dysfunction
High output cardiac failure – low vascular resistance from the widespread inflammatory response
Paracetamol overdose pathophysiology
Primarily metabolised in the liver, occurs via conjugation with the addition of glucuronide to form a water soluble metabolite that can be excreted in the urine
Excess paracetamol, such as with overdose, conjugation become saturated and paracetamol is converted into the metabolite NAPQI
When glutathione stores are depleted, excess NAPQI binds to hepatocellular proteins and results in oxidative damage, mitochondrial dysfunction & ultimately hepatocellular injury
Paracetamol overdose natural history of symptoms
May be completely asymptomatic in the early stages following overdose
Around 12-36 hours following overdose patients may experience abdominal pain
At 48-72 hours, patients may develop clinical features due to hepatic necrosis, with include RUQ pain, N&V, jaundice, AKI and hepatic encephalopathy
Paracetamol overdose clinical features
Asymptomatic in the early stages of paracetamol overdose
Symptoms – N&V, anorexia, malaise, abdominal pain, altered mental status, confusion, scars
Signs – asterixis, bruising, jaundice, RUQ pain, oliguria/anuria, tachycardia/hypotension, coma
Paracetamol overdose diagnosis & investigations
Based on the history
Bloods – FBC, U&Es, LFTs, bone profile, venous/arterial blood gas, blood glucose, paracetamol levels, salicylates levels
Nomogram – determine if treatment with N-acetylcysteine is needed
Paracetamol overdose treatment
Principle treatment of paracetamol overdose – IV administration of N-acetylcysteine (precursor to glutathione)
- Consider chlorphenamine & nebulised salbutamol if anaphylactic reaction
Chronic liver disease
Caused by repeated insults to the liver, which can result in inflammation, fibrosis and ultimately cirrhosis
Chronic liver disease aetiology
Alcohol
Viral – hepatitis A, B, C, D & E
Inherited – alpha-1-antitrypsin deficiency, Wilson’s disease, hereditary haemochromatosis
Metabolic – NAFLD, NASH
Autoimmune – autoimmune hepatitis
Biliary – primary biliary cholangitis, primary sclerosing cholangitis
Vascular – ischaemic hepatitis, budd-chiari syndrome, congestive hepatopathy
Chronic liver disease pathophysiology
May result from repeated insults that cause inflammation or cholestasis
Over time, chronic damage can lead to scarring known as fibrosis
If fibrogenesis continues then the end result is cirrhosis, which describes irreversible liver remodelling that is associated with significant morbidity & mortality
Compensated cirrhosis vs decompensated cirrhosis
Compensated – patients are typically asymptomatic as a small amount of residual function allows the liver to continue carrying out normal function despite extensive damage
Decompensated – liver no longer has the capacity to carry out its normal functions which results in multiple complications
Decompensated cirrhosis clinical features
Coagulopathy (reducing clotting factor synthesis) – evidence of bruising and deranged coagulation tests
Jaundice (impaired breakdown of bilirubin) – yellow appearance of the skin and sclera
Encephalopathy (poor detoxification of harmful substances) – confusion
Ascites (poor albumin synthesis and increased portal pressure due to scarring) – accumulation of fluid in the abdominal cavity
GI bleeding (increase portal pressure causing varices)
Chronic liver disease clinical features
Early clinical features are usually non-specific – anorexia, lethargy, weight loss, hepatomegaly, nausea or disturbed sleep pattern
Stigmata of CLD – caput medusa, splenomegaly, palmar erythema, dupuytren’s contracture, leukonychia, gynaecomastia, spider naevi
Features of hepatic decompensation – encephalopathy, ascites, jaundice, GI bleeding, coagulopathy
Chronic liver disease diagnosis
Liver biopsy – gold-standard diagnostic method
LFTs
Transient elastography (fibroscan) – assesses liver stiffness, measures sound wave to indicate the degree of fibrosis
Imaging – USS, CT, MRI
Liver biopsy – can be performed percutaneously using US or CT-guidance or transjugular
Chronic liver disease management
Treating the underlying pathology, preventing progression and managing complications
Hepatic encephalopathy – laxatives, long-term use of abx to reduce the proportion of ammonia-producing colonic bacteria
Ascites (fluid accumulation within the peritoneal cavity: due to combination of portal hypertension & loss of oncotic pressure) – aldosterone antagonists, paracentesis
GI bleeding – non-selective beta-blockers to reduce portal pressure in patients with cirrhosis * significant varices
Spontaneous bacterial peritonitis – abx, human albumin solution, prophylaxis
HCC – six-monthly surveillance with USS +/- AFP blood test
Transplantation
Chronic liver disease complications
Hepatic encephalopathy
Ascites
Hyponatraemia
GI bleeding
Bacterial infections
AKI
HCC
Hepatorenal syndrome
Hepatopulmonary syndrome
Acute-on-chronic liver failure
Alcoholic hepatitis
Clinical syndrome due to progressive alcohol-mediated liver inflammation and injury
Generally refers to the acute onset of symptomatic hepatitis due to heavy alcohol consumption
Alcoholic liver disease
Refers to a spectrum of conditions that result from alcohol-mediated liver damage
Refers to three conditions:
1) Alcoholic fatty liver – metabolism of alcohol leads to deposition of excess fat in the liver, occur with/without inflammation
2) Alcoholic hepatitis – severe inflammation of the liver, acute symptomatic hepatitis
3) Cirrhosis – irreversible scarring of the liver associated with numerous complications
Alcoholic liver disease pathophysiology
Ethanol is taken to the liver where it is metabolised via different pathways:
1) Oxidative metabolism
2) Microsomal enzyme oxidative system
Liver damage – immunological dysfunction, disruption of the liver-gut axis, increased gut permeability & direct toxic effects of ethanol metabolism
Alcoholic hepatitis clinical features
Symptoms – jaundice, fever, anorexia, abdominal pain, abdominal distension, muscle wasting, confusion
Signs – jaundice, tender hepatomegaly, ascites, asterixis, tremor, bruising, stigmata of CLD
Alcoholic hepatitis diagnosis
Routine tests – FBC, U&Es, LFTs, bone profile, CRP, magnesium, coagulation +/- septic screen
Non-invasive liver screen – USS doppler
Liver biopsy only used in severe cases
Alcoholic hepatitis management
Managing alcohol withdrawal
Alcohol cessation
Hydration
Nutrition
Aggressive treatment of infections
Pharmacological therapy – corticosteroids
Liver transplant
Alcoholic hepatitis complications
Hepatic encephalopathy
Systemic infection
GI bleeding
Coagulopathy and thrombocytopaenia
Ascites
Multi-organ failure
NAFLD
Refers to the presence of excess fat in the liver in the absence of excess alcohol consumption
NAFLD encompasses a spectrum of pathological conditions including:
1) NAFL
2) NASH – presence of liver inflammation and injury
3) Liver fibrosis
4) Cirrhosis
NAFLD clinical features
Symptoms – asymptomatic, fatigue, RUQ pain
Signs – hepatomegaly, obesity, high BP, features of CLD, features of decompensated cirrhosis
NAFLD investigations
Liver ultrasound
Routine blood tests – deranged LFTs are suggestive of liver inflammation consistent with NASH
Full non-invasive liver screen
Fibrosis risk assessment
NAFLD management
Centres on dietary advice, exercise and managing co-morbidities
Principal treatment – weight loss based on dietary advice and exercise
No licensed pharmacological therapies are currently available
Bariatric surgery
Liver transplantation
NAFLD complications
Liver-related complications – decompensated cirrhosis, HCC, sepsis
Non-liver complications – CVD, HTN, T2DM, CKD, heart disease
Hereditary haemochromatosis
Autosomal recessive disorder that results in iron overload
One of the most common genetic disorders seen in Northern European populations
Hereditary vs acquired haemochromatosis
Hereditary – underlying genetic variant that leads to iron accumulation
Acquired – state of chronic iron overload often due to frequent red blood cells transfusions or from excessive intake of dietary iron
Hereditary haemochromatosis aetiology
HFE gene is located on chromosome 6, majority of cases relate to C282Y mutations in this gene
Mutations are required in both copies of the gene since it is an autosomal recessive condition
Hereditary haemochromatosis clinical features
Presents after age 40 when the iron overload becomes symptomatic (presents later in females -> menstruation acting to eliminate iron from the body regularly)
Chronic tiredness, joint pain, pigmentation (bronze skin), testicular atrophy, ED, amenorrhoea, cognitive symptoms, hepatomegaly
Hereditary haemochromatosis investigations
Serum ferritin
Transferrin saturation – helps distinguish between high ferritin caused by iron overload & other causes
Liver biopsy with Perl’s stain – can be used to establish the iron concentration in the liver
MRI can quantify iron concentration
Haemochromatosis complications
Secondary diabetes
Liver cirrhosis
Endocrine and sexual problems
Cardiomyopathy
HCC
Hypothyroidism
Chrondrocalcinosis (calcium pyrophosphate deposits in joints) causes arthritis
Haemochromatosis management
Venesection – initially weekly
Monitoring serum ferritin
Monitoring and treating complications
Hepatitis
Inflammation in the liver
5 types of viral hepatitis
Notifiable disease
Other causes – alcoholic, NASH, autoimmune, drug induced
Viral hepatitis presentation
Asymptomatic/present with non-specific symptoms of:
Abdominal pain
Fatigue
Flu-like illness
Pruritis (itching)
Muscle and joint aches
N&V
Jaundice
Hepatitis LFTs
High transaminases – AST and ALT, with proportionally less of a rise in ALP
- Liver enzymes released into the blood due to the inflammation of the liver cells
Bilirubin can also rise as a result of inflammation of the liver cells -> causes jaundice
Hepatitis B
Double-stranded DNA virus
Transmitted by direct contact with blood or bodily fluids, eg. sexual intercourse or sharing needles
Can be passed from mother to child during pregnancy and delivery (vertical transmission)
Hepatitis B viral markers
HBsAb (surface antibody) – may indicate that have been vaccinated, past or current infection
HBcAb (core antibody) – IgM = active infection (high = acute, low = chronic), IgG = past infection
HBeAg (e antigen) – if present, it implies the patient is in acute phase of infection where virus is actively replicating (high = highly infectious), if negative but HBeAb is positive = less infectious
Hepatitis B vaccination
Involves injecting the hepatitis B surface antigen
Vaccinated patients are tested for HBsAb to confirm their response to the vaccine
Requires 3 doses at different intervals
Included as part of the UK routine vaccination schedule (6 in 1 vaccine)
Hepatitis B management
Low threshold for screening patients at risk, screen for other viral infections
Referral to specialists
Avoid alcohol
Education about reducing transmission
Contract tracing & informing potential at-risk contacts
Testing for complications (eg. fibroscan for cirrhosis and USS for HCC)
Antiviral medication – can be used to slow progression of the disease & reduce infectivity
Liver transplantation for liver failure
Hepatitis C
RNA virus
Spread by blood and body fluids
No vaccine but now curable with direct-acting antiviral medications (eg. sofosbuvir, daclatasvir)
Hepatitis C complications
Liver cirrhosis
HCC
Hepatitis C testing
Hepatitis C antibody – screening test
Hepatitis C RNA testing – used to confirm the diagnosis, calculate the viral load and identify the genotype
Hepatitis C management
Same general principles as hepatitis B
Direct-acting antivirals is tailored to specific viral genotype
Typical duration of treatment is 8-12 weeks
Autoimmune hepatitis
Rare cause of chronic hepatitis (inflammation in the liver)
Appears to occur due to a combination of genetic and environmental factors
Autoimmune hepatitis types
Type 1 – typically affects women in their late forties or fifties, presents around/after menopause with fatigue & features of liver disease on examination (takes a less acute course than type 2)
Type 2 – usually affects children or young people, more commonly girls, it presents with acute hepatitis with high transaminases and jaundice
Autoimmune hepatitis investigations
LFTs – will show high transaminases and minimal change in ALP levels
Raised IgG levels
Autoantibodies
- Type 1: ANA, anti-actin, anti-SLA/LP
- Type 2: anti-LKM1, anti-LC1
Liver biopsy – interface hepatitis and plasma cell infiltration
Autoimmune hepatitis management
High dose steroids
Other immunosuppressants are also used, particularly azathioprine
Immunosuppressant treatment – usually successful at inducing remission
Liver transplant may be required in end-stage liver disease (can reoccur in the new liver)
