What are the standard liver function tests?
Bilirubin AST ALT GGT ALP Albumin
What tests indicate liver function? (not just liver inflammation etc.)
Albumin
Bilirubin
PT time
What is the problem with LFTs?
Around 20% of the population have abnormal LFTs
Might not be liver in origin
- ALP elevation could be bone
- AST might be muscle
- isolate bilirubin might be haemolysis
Advanced cirrhosis might have normal LFTs
What investigations into chronic liver disease can you perform?
US Chronic viral hepatitis - HBV, HCV Autoimmune liver disease - ANA/SMA/LKM (AIH); AMA (PBC; Igs (raised IgG) Metabolic liver disease - ferritin (haemochromatosis) - caeruloplasmin (Wilson's disease) - alpha-1 antitrypsin deficiency
What investigations into acute liver disease can you perform?
US Acute viral hepatitis - HAV, HBV, (HCV), HEV and CMV Autoimmune liver disease - ANA/SMA/LKM (AIH); immunoglobulins (raised IgM) Paracetamol levels
What are the most common causes of abnormal liver blood tests?
Fatty liver - alcoholic liver disease - NAFLD Chronic viral hepatitis - chronic Hep C Autoimmune liver disease - primary biliary cirrhosis - autoimmune hepatitis Haemochromatosis
Describe how steatosis can progress to cirrhosis?
Macrovesicular stastosis with lipid vacuole filling the hepatocyte cytoplasm
Staetohepatitis
- neutrophils and lymphocytes surround the hepatocytes with Mallory hyaline
Pericellular fibrosis as well as bands of fibrous tracts between the portal tracts (fatty liver disease cirrhosis)
What risk factors increase the risk of getting NAFLD?
Obesity
Hypertension
Type 2 Diabetes
Hypertension and T2DM
What is the main way to tell the difference between alcohol fatty liver disease and NAFLD?
ALD - AST>AST - ratio >1.5 NAFLD - ratio <0.8
Why are rates of ALD increasing?
Alcohol is becoming more available and affordable
Describe the biochemical patterns of ALD.
Raised AST:ALT ratio - preferential AST elevation as mitochondrial disease and pyridoxine deficiency AST doesnt normallt go above 500 ALT isn't normally less than 300 May appear cholestatic
What are the clinical features of alcoholic hepatitis?
Recent alcohol excess Bilirubin >80mol/l AST:ALT ratio >1.5 Hepatomeagly Fever Leucocytosis Hepatic bruit
Describe the Glasgow Alcoholic Hepatitis Score.
1 point for each - age: <50 - WCC: <15 109/l - urea: <5mmol/l - PT ratio/INR: <1.5 - bilirubin: <125mol/l 2 points for each - age: >50 - WCC: >15 109/l - urea: >5mmol/l - PT ratio/INR: 1.5-2.0 - bilirubin: 125-250mol/l 3 points for each - PT ratio INR: >2.0 - bilirubin: >250mol/l
What accelerates the progression of fibrosis in Hep C infections?
Male sex Age >40 at time of acquisition Alcohol >50g/week HIV Hep B
What is the natural history of a chronic Hep C infection?
Slow, intermediate or rapid fibrosis progression
Cirrhosis
- leads to decompensated liver disease or hepatocellular carcinoma
Death
What are the risk factors for getting a HCV infection?
IVDU; bloos transfusions Sexual transmission - increased prevalence with multiple partners Vertical transmission Needle-stick transmission No risk factors in some patients
What are the signs and symptoms of chronic liver disease?
Stigmata - spider nevi - foetor - encephalpathy Synthetic dysfunction - PTT - hypoalbuminaemia
What are the signs and symptoms of portal hypertension?
Caput medusa - recanulisation of the umbilical veins Hypersplenism Ascites Thrombocytopenia (pancytopenia)
What grades are associated with severity of liver injury?
Childs-Turcotte-Pugh Score
- Grade A (score 5-6) - mild
- Grade B (score 7-9)
- Grade C (score 10-15) - decompensated
What is portal hypertension?
Increased resistance to flow in the portal venous system and sustained increase in portal venous pressure
Describe the pathophysiology of portal hypertension.
Pre-hepatic, hepatic and post-hepatic obstructions occur to block the portal venous system
- raised portal pressure occurs, which causes hypersplenism and porto-systemic shunting
Porto-systemic shunting means blood that should be in the liver is being forced into the system (encephalopathy)
- oesophago-gastric varices also form
The opening of new vessels causes NO release, which again increases the BP of the portal system
- splanchnic vasodilation
- reduced effective circulating volume leads to release of compensatory vasopressors (RAAS)
This causes sodium retention and renal vasoconstriction
- ascites
- hepato-renal syndrome
Name a pre-hepatic, hepatic and post-hepatic cause of portal hypertension.
Pre-hepatic - portal vein thrombosis Hepatic - cirrhosis Post-hepatic - Budd Chiari
How is a diagnostic tap of ascites assessed?
Cell count
- >500 WBC/cm3 and >250 neutrophils/cm3 suggest spontaneous bacterial peritonitis
Albumin
- serum ascites albumin gradient = serum albumin minus ascitic albumin
- SAAG>11g/l = portal hypertension
How is ascites treated?
Low salt diet (if sodium retention is a problem) Diuretics - spironolactone - frusemide Paracentesis
What is hepatorenal syndrome?
Rapid deterioration in kidney function in people with terminal liver failure and ascites
What are the two types of hepatorenal syndrome?
Type 1 - rapid decline in function, often triggered by spontaneous bacterial peritonitits - almost 100% mortality in 10 weeks Type 2 - moderate, stable decline - 3-6 months survival
Describe the Conn Score for Grading Mental State in Hepatic Encephalopathy.
Grade 0 - no personality of behavioural abnormality detected Grade 1 - lack of awareness - euphoria or anxiety - shortened attention span - impaired performance of addition Grade 2 - lethargy or apathy - minimal disorientation for time or place - subtle personality changes - inappropriate behaviour - impaired performance of subtraction Grade 3 - somnolence to semi-stupor, response to verbal - confusion - gross deterioration Grade 4 - coma
What are the precipitating factors for Hepatic Encephalopathy?
GI bleeding Infections Constipation Electrolyte imbalance Excess dietary protein
How is hepatic encephalopathy treated?
Don't make it worse - avoid regular sedation - caution with opiates - avoid hyponatraemia Laxatives - lactulose/phosphate enemas Non-absorbable antibiotics
