Diseases of the Liver Flashcards
2 presentations of liver disease
Acute liver failure
Chronic Liver disease/cirrhosis
What presentation of liver disease is more common?
Chronic/cirrhosis
What are the causes of acute liver failure?
Drugs - paracetamol Infections Ischaemia Toxins Metabolic Vascular
What is the commonest cause of acute liver failure in the UK?
Paracetamol
What are the causes of chronic liver disease?
Alcohol Viral Hepatitis B and C Non alcoholic fatty liver disease Auto immune hepatitis Primary biliary cirrhosis Primary sclerosing cholangitis Haemochromatosis & Wilson's Disease
What are the 3 commonest causes of cirrhosis?
Alcohol
Viral Hepatitis B and C
Non alcoholic fatty liver disease
What are the 2 phases of liver disease?
Asymptomatic - 20-40 years
Symptomatic - 1 to 5 years
What are the complications of cirrhosis?
Ascites Haemorrhage Encephalopathy Jaundice HCC
Extra-hepatic impacts of alcohol
HTN Coronary Heart Disease Ischaemic Stroke Haemorrhagic stroke Oral pharyngeal cancer Pancreatitis Liver Disease
Pathway of alcohol induced liver injury
Normal liver can becomes a fatty liver -> steatohepatitis -> fibrosis/cirrhosis -> HCC
Or normal liver can go straight to steatohepatitis or fibrosis/cirrhosis and continue from there
What does a fatty liver look like?
Fat laden globules on microscopy
What does steatohepatitis look like?
Fat and inflammation (purple infiltrates -> inflammatory mediators)
What can you see on fibrosis?
Reticulin staining shows collagen = area of scarring
How does HCC occur from fibrosis?
Constant regeneration and scarring can mean some cells undergo changes and form dysplastic nodules
How is HCC monitored in those with cirrhosis?
Regular 6 months ultrasound of liver and AFP tumour marker blood test to spot dysplastic nodules before HCC becomes untreatable
What is the commonest biopsy finding/stage in alcohol related liver diseases? (most to least common)
Steatosis
Steatohepatitis
Fibrosis/cirrhosis
HCC
3 mechanisms of alcohol injury to the liver
Metabolic
Inflammatory
genetic
Metabolic mechanism of alcohol injury to liver
High alcohol intake often comes with obesity and insulin resistance which both also damage the liver
Inflammatory mechanism of alcohol injury to the liver
Lipid signals - attract chemokines, cytokines, Kupffer cells, Stellate cells, endothelial cells
Genetic mechanism of alcohol injury to the liver
Some genes are associated with steatosis - explains why some individuals who drink the same volume are more predisposed than others to liver injury
Protocols of managing alcohol related liver disease
Identify Risk
Address dependence
Manage disease
How to identify risk of alcohol related liver disease
Calculate units per week
Low risk = 14U
Increasing = 15-50 for men, 15-35 for women
Higher = More than 8U/day or 50 per week for men, more than 6U/day or 35 per week for women
What is the alcohol limit?
No more than 14U per week and spread over 3 days
AUDIT scores
Scores risk of alcohol dependence
Can determine level of intervention required
Types of alcohol withdrawal syndromes
Minor = 6-36 hrs after last drink
Seizures = 6-48 hours
Alcoholic hallucinosis = 12-48 hours
Delirium tremens = 48-96 hours
Medications for alcohol withdrawal
Chlordizepoxide
Lorazepan if underlying cirrhosis as effects more easily reversible
Fixed dose or symptom triggered dose
Symptom triggered dose vs. fixed
Shorted
Lower dose
Need training with CiWAr
2 phases of alcoholic related liver disease
Alcoholic Hepatitis
Alcohol related liver cirrhosis
Features of alcoholic hepatitis
Recent onset jaundice With or without ascites Alcohol abuse ongoing for less than 2 months Fever Not really fibrosis Potentially reversible
What is the gold standard test for alcoholic hepatitis?
Liver biopsy
Ix findings in alcoholic hepatitis
May have raised WCC, platelets
AST:ALT>1
Negative liver screen
Liver biopsy = steatosis, hepatocyte ballooning, inflammatory infiltrate
Tx for alcoholic hepatitis
Sepsis Tx as high risk Nutrition - NG feed Maddrey's Criteria = prognostic criteria Alcohol abstinence determines LT prognosis Liver transplant? Steroids?
What is NAFLD?
- NASH = steatohepatitis
OR - NAFLD
Features of NASH?
Features of alcohol hepatitis on biopsy but absence on alcohol excess on history
Pathways/spectrum of NAFLD?
Normal -> fatty liver -> NASH -> fibrosis/cirrhosis
Or normal straight to NASH
Pathogenesis of NAFLD?
Accumulation of hepatic triglyceride
Free fatty acids released from lipid stores
Oxidative stress
Inflammatory mediators -> fibrosis -> cirrhosis -> HCC/failure
NASH or NAFLD - which has worse prognosis?
NASH - higher risk of cirrhosis and liver death
Presentation of NAFLD
- abnormal LFTs
- ALT:AST>1
- if develop fibrosis ^ratio may not be present
- fatigue
- RUQ
- hepatomegaly
- no other symptoms unless cirrhosis
Associated conditions with NAFLD
Obesity - central/visceral T2DM Hypertriglyceridemia HTN Liver manifestation of insulin resistance metabolic syndrome CV risk profile
Commonest cause of death in patient of NAFLD
CV death
Associations with NAFLD
Drugs = steroids, Amiodarone, MTX Genetic predisposition Weight reducing surgery - jejuno-ileal bypass Protein calories malnutrition Total parenteral nutrition Iron overload
How is NAFLD diagnosed?
Exclude other liver diseases = liver screen
Screen for metabolic syndrome
Liver biopsy
Fibroscan - measures liver stiffness (non invasive, fibrosis detect)
What is metabolic syndrome?
Impaired glucose tolerance
Central Obesity
Elevated S. trigylcerides, Low HDL
HTN
NAFLD Treatment
Weight loss address - bariatric surgery?
Treat metabolic factors = HTN, diabetes, lipid lowering drugs
Which hepatitis infection type is associated with acute hepatitis?
Hep A and E Both RNA viruses Both faecal-oral route of transmission Incubation between 2-6 weeks Dx = IgM association
Which hepatitis infection type is associated with chronic hepatitis?
Hep B and C
Hep B is DNA and C is RNA virus
Body fluids exposure is route of transmission
1 month - 6 month incubation
Hep C rarely acute but Hep B can be but self limiting in healthy
Worldwide burden of both
How is hepatitis B transmitted?
Maternal (vertical) - neonates more common to remain chronically infected and increased risk of HCC in 30-40s
Blood contact
Sexual - acute infection with jaundice, healthy can often clear it
Hepatitis D
Rare
IVDU
Requires Hep S surface antigen so need to have Hep B
Prognosis of Hep B
Most patients asymptomatic -> recover
Others have acute hepatitis -> recover
Minority -> chronic infection as weak immune response -> asymptomatic chronic carriers but very small number get cirrhosis -> HCC?
Diagnosis of Hepatitis B
- Hepatitis B surface antigen (HbsAg) = positive means active infection
- HbsAb (antibody to surface antigen) = marker of immunity if no other markers present
- HbcAb = another AB
- HbeAg/Ab = natural history of disease
- HBV DNA = confirms virus presence and used to monitor treatment
- HDV IgG and HDV RNA = check for hepatitis delta
What is a marker of chronic hepatitis B?
> 6 months HbsAg
HbcAb
- another antiody, IgG, shows previous exposure to virus if surface antigen is not present
- another one is IgM = shows acute infection
Stages of Hepatitis B
Tolerance = high HBV DNA, HbeAg presence, liver enzyme elevated/normal suggesting tolerance to virus
Clearance = can fight virus, HBV DNA disappears, HBsAg, ALT levels improved
Latency = unable to clear, HbeAb appears, persistence of surface antigen
Reactivation - fluctuation of liver tests, HbeAb, resurface of HBV DNA
When is ALT normal in Hep B?
HBeAg positive infection
vs. HBeAg positive hepatitis when enzymes raised
Treatment of Hepatitis B
- reduce viral replication = nucleoside/nucleotide analogues = entecavir, tenofovir
- improve immunological response = PEG-IFN
- reduce progression to cirrhosis
- reduce risk of HCC
What is the main difference between Hep B and Hep c?
Hep C has large risk of becoming chronic Therefore increased risk of cirrhosis and HCC
RF of Hep C
High Risk = IVDU, clotting factors received before 1987
Moderate = haemodialysis, blood/organ transplant before 1992, undiagnosed liver problems, infants born to infected mothers
Low = occupational exposure, sexual practices
How is Hep C diagnosed?
- IgG test screened
- if IgG positive then check Hep C RNA (viral load and genotype)
- LFTs
- Liver US
- AFP for HCC risk (tumour marker associated with HCC)
- Fibroscan for fibrosis
Co-morbidities of Hep C
Alcohol
High BMI
Mood disorder
Lifestyle
- higher risk of reinfection
Tx of Hep C
8-12 weeks therapy
Very successful
Antiviral agents
Combination depends on genotype (6 possible genotypes) and fibrosis stage
What is the WHO target with Hep C?
Eradicate by 2025
Haemochromatosis features
Excess iron absorption and deposition Multi organ involvement Autosomal recessive More males than females High HCC risk
Ix results of haemochromatosis
Increased ferritin Increased transferrin saturation HFE gene mutations Liver biopsy MRI (ferriscan)
What organs are involved in haemochromatosis?
Pancreas
Pituitary
Cardiac
Skin & Joints
Treatment for haemochromatosis
Venesection
Iron chelation therapy
Wilson’s Disease Features
Autosomal Recessive ATP7B gene Dysregulated copper metabolism Rare Acute liver failure rarely Cirrhosis often
Diagnosis Ix of Wilson’s
Liver biopsy
MRI brain
Reduced Ceruloplasmin -> then asses urinary copper which is elevated
Associations of Wilsons disease
Kayser-Fleischer rings
haemolytic anaemia
Neurological - movement disorders, psychiatric
treatment of Wilson’s disease
Copper chelation therapy
Liver Transplant
HCC
Major risk factor is cirrhosis as can progress to HCC
- particularly if cirrhosis where cause is HepB/c, haemochromatosis
What happens if on screening there is possible HCC?
Further Dx needed
CT triple phase
MRI
Biopsy
Treatment of HCC
Curative Early Stages
- surgical resection
- transplant
- radiofrequency ablation
Palliative Later
- Transcatheter Arterial Chemoembolisation
- radioembolization
- Sorafenib
- Radiofrequency ablation
