Introduction to hepatology Flashcards
Abnormal liver tests - acute
6 weeks
- Drugs
- Viral hep A, B, C, E
- Autoimmune hep
- Wilsons disease
Abnormal liver tests - subacute
6-26 weeks
- Drugs
- Viral hep A, B, C
- Autoimmune hepatitis
- Wilsons disease
Abnormal liver tests - chronic
> 26 weeks
- Viral hep B, C
- Alcohol
- NAFLD
- Autoimmune hepatitis
- Wilsons disease
- Hemochromatosis
- A1 antitrypsin deficiency
Liver tests
- Bilirubin
- Liver enzymes
- Albumin
- Prothrombin time
- INR
Liver enzymes
- Aspartate aminotransferase (AST)
- Alanine aminotransferase
- Alkaline phosphatase
- Gamma GT
- Albumin
What is INR a measure of
- Measures extrinsic coagulation pathway. II, V, VII, X and fibrinogen
Abnormal LFT’s - liver screen
Hepatitis serology - Hep A IgM, hep B surface antigen, hep C antibody, hep E IgG and IgM
- ANA, SMA LKM (for autoimmune hepatitis)
- AMA (for primary biliary cholangitis)
- Alpha 1 antitrypsin
- Copper, caeruloplasmin (Wilson’s disease)
- Ferritin (genetic haemachromatosis)
- Ultrasound
What is raised in hepatitic damage
AST and ALT
What is raised in cholestatic damage
Bilirubin and ALP
Abnormal liver tests - hepatitic
- Viral hepatitis A, B, C, E
- Drug induced liver injury
- Autoimmune hepatitis
Abnormal liver tests - cholestatic
- Biliary obstruction
- Viral hepatitis A, B, E
- DILI
- Autoimmune hepatitis
- Primary biliary cirrhosis cholangitis
- Primary sclerosing cholangitis
What is the main feature of cirrhosis
- Increased pressure in the portal circulation, also known as portal hypertension
Which readings have prognostic value
Bilirubin and PT/INR have prognostic value
Features of acute liver failure
- No pre existing liver disease
- Coagulopathy
- Confusion (hepatic encephalopathy)
- Jaundice
- Abnormal liver tests
- Cerebral oedema
- Increased risk of infections
- Renal failure (hepatorenal syndrome)
Causes of most cases of acute liver failure
- Indeterminate
What causes a significant proportion of liver failure cases in the UK
- Paracetamol overdose
Recommended dose of paracetamol per day
- 4gms/day
- toxic dose > 15 gms
- Lower toxic dose if pre existing liver disease, alcohol excess
Metabolism of paracetamol
1) Glucuronidation
2) Sulfation
3) N-hydroxylation and dehydration, then glutathione conjugation, (less than 15%). The hepatic cytochrome P450 enzyme system metabolises paracetamol (mainly CYP2E1), forming a minor yet significant alkylating metabolite known as NAPQI (N-acetyl-p-benzoquinone imine) (also known as N-acetylimidoquinone) NAPQI is then irreversibly conjugated with the sulfhydryl groups of glutathione
NAPQI
- Toxic reactions with proteins and nucleic acids
How does NAC help with paracetamol overdose
- N acetyl cysteine (NAC) replenishes glutathione which conjugates with NAPQI and detoxifies it
How does paracetamol overdose present
- Presents with nausea, vomiting, RUQ pain, confusion
- Jaundice and liver failure usually develops after 3-4 days
- Very high liver enzymes and prothrombin time
Paracetamol overdose - prognosis
- If receive N acetyl cysteine within 16 hours liver failure rare
- Some benefit of NAC even up to 36 hrs
- In severe cases liver transplant only option
Features of cirrhosis
Portal hypertension
- Varices
- Ascites
- Hepatic encephalopathy
- Jaundice
- Spiders
- Enlarged spleen/pancytopenis
- Renal failure (HRS)
- Hepatocellular cancer
Ascites management in cirrhosis
- Salt restriction
- Fluid restriction if low sodium
- Diuretics (spironolactone and furosemide)
- Large volume paracentesis(LVP) with albumin cover
If refractory ascites - recurrent LVP
- Transjugular intrahepatic portosystemic shunt
- Consider liver transplant
- Long-term drains(if palliative) - still undergoing research
Variceal bleed
- Haemodynamically stable, correct coagulopathy and thrombocytopenia
- IV terlipressin and IV antibiotics
- Endoscopy in theatre with an anaesthetist present - variceal banding
- If blood bath - balloon tamponade
- Non selective B blockers for secondary prophylaxis(propanolol and carvedilol)
Hepatorenal syndrome (AKI)
- ‘Functional’ and fairly rapid renal impairment due to reduced renal perfusion
- Increase in serum creatinine by 50% from baseline within 3 months
- Type 1 and 2
- Treat underlying cause, terlipressin
- Liver transplant
Hepatic encephalopathy
- Elevated ammonia
- Diagnosis of exclusion
- Treat precipitating cause - constipation, diuretics, infection, sedatives, GI bleed
- Lactulose
- Non absorbable antibiotics (rifaximin)
Types of liver failure
A - compensated cirrhosis
B - Compensated cirrhosis —> hepatic and extrahepatic organ failure
C - Compensated cirrhosis –jaundice, ascites, variceal bleeding, hepatic encephalopathy–> decompensated cirrhosis
Severe alcoholic hepatitis
- Most serious form of alcohol related injury
- Characterised by jaundice and coagulopathy
- In patient untreated mortality - 40%
- Various prognostic scores(discrimant function)
- Steroids and pentoxyfilline
Hep C virus risk factors
- Recipients of clotting factors made before 1987
- Injection drug use
- Long-term hemodialysis
- Individuals with multiple sex partners
Precipitants to chronic liver failure
- Viruses
- Drugs
- Alcohol
- Ischaemia
- Surgery
- Sepsis
- Idiopathies
Factors associated with disease progression
- Alcohol consumption
- Disease acquisition at>40 years
- Male gender
- HIV coinfection
- Hep B virus coinfection
- Immunosuppression
Hep C natural history
- Normal liver –> acute infection –> chronic infection develops in 80% –> chronic hepatitis –> cirrhosis develops in 20% –> risk –> risk of carcinoma, 1-4% per year
<20 years
Non-alcoholic fatty liver disease
- Resemble alcoholic liver disease but occur in absence of alcohol abuse
- Usually associated with metabolic syndrome - type 2 dm, obesity, HTN, and elevated TG
- Underlying mechanism is insulin resistance (IR)
Indications for liver transplant in acute liver failure - with paracetamol usage
- pH<7.3 after fluid resucitations or
- Arterial lactate>3.5mmol at 4 hrs or
- Arterial lactate > 3.0 mmol/L at 12 hrs or
- PT>100 secs(INR>6.5), serum creatinine>300 mmol/l (3.4 mg/dl) grade 3 or 4 encephalopathy
Indications for liver transplant in acute liver failure - non paracetamol
- Prothrombin time greater than 100 secs (INR?6.5) (irrespective of grade of encephalopathy) or any three of the following
- Age less than 11 years or greater than 40 years
- Etiology of non-A/non-B hepatitis, halothane hepatitis, or idiosyncratic drug reactions
- Duration of jaundice of more than 7 days before onset of encephalopathy
- Prothrombin time greater than 50 secs (INR>3.5)
- Serum bilirubin level greater than 17 mg/dL (300 micromol/l)
Indications for liver transplant in cirrhosis
- Ascites/SBP
- Variceal bleeding
- Hepatic encephalopathy
- Hepatocellular cancer
Prognostic scores to prioritise liver transplant in cirrhosis
MELD and UKELD score: Bilirubin INR Creatinine Na
