Liver Disease Flashcards
What are the general functions of the liver?
Synthesis of compounds
Detoxification
Immune function
Storage
What does the liver synthesise?
Clotting factors
Bile acids
CHOs (gluconeogenesis, glycogenolysis, glycogenesis)
Proteins e.g. albumin
Lipids (cholesterol, lipoprotein, TG synthesis)
Hormones (angiotensinogen, insulin-like GF)
What does the liver detoxify?
Urea production from ammonia
Bilirubin metabolism
Breakdown of insulin and hormones
Drug metabolism
What does the liver store?
Glycogen
Vitamins A, D, B12, K
Also copper and iron
What are the different types of liver function tests?
Bilirubin Alanine Transaminase Aspartate aminotransferase Alkaline Phosphatase Gamma GT Albumin Prothrombin time Creatinine Platelet count
What are symptoms and signs of deteriorating liver function? (Seen during examination, not lab results)
Serious: Jaundice Ascites Variceal bleeding Hepatic encephalopathy
Spider naevi Palmar erythema JVP elevation Gynaecomastia Loss of axiliary and pubic hair Muscle wasting?
What investigations might be done in suspected liver failure/disease?
EUS/USS
ERCP/MRCP
Percutaneous transhepatic cholangiogram
Liver screen
- Hep B/C serology
- Autoantibody profile, serum Ig
- caeruloplasmin and copper
- ferritin and transferrin saturation
- alpha-1 anti-trypsin
- fasting glucose and lipid profile
What are ERCP/MRCP and how do they compare?
Endoscopic retrograde cholangiopancreatography
Magnetic resonance cholangiopancreatography
Usual comparisons between invasive imaging vs MRI
- radiation vs no radiation
- complications
- failure rate
- range
ERCP therapeutic however
What is percutaneous transhepatic cholangiography?
More invasive than ERCP
Used when ERCP not possible due to duodenal obstruction or previous surgery
Hilar stenting
What is the definition of ‘Chronic’ liver disease?
Any liver disease persisting for over 6 months
- chronic hepatitis
- chronic cholestasis
- fibrosis and cirrhosis
- others e.g. steatosis
- liver tumours
What is the clinical presentation of cirrhosis?
Compensated chronic liver disease
- routinely detected on screening tests
- abnormality of LFTs
Decompensated chronic liver disease
- ascites
- variceal bleeding
- hepatic encephalopathy
Loss of normal liver structure
Replaced by nodules of hepatocytes and fibrous tissue
Complications
- altered liver function
- abnormal blood flow
- increased risk of hepatocellular carcinoma
Causes of cirrhosis?
Alcohol Hep B/C Immune-mediated liver disease (autoimmune, primary biliary cholangitis) Metabolic disorders (excess iron, excess copper) Obesity/Diabetes mellitus Cryptogenic (most common) NAFLD Drugs (MTX, amiodarone) CF, alpha-1 antitrypsin deficiency Vascular problems Sarcoidosis, amyloid, schistosomiasis
What is ascites and how is it confirmed?
Fluid in peritoneal cavity Shifting dullness (~1500mL) Ultrasound can confirm Corroborating evidence - spider naevi, palmar erythema, abdominal veins, fetor hepaticus - umbilical nodule - JVP elevation - flank haematoma
What tests are done on ascitic fluid?
Diagnostic paracentesis
- protein/albumin concentration
- cell count and differential
- SAAG
> 1.1g/dL = portal HTN related (97% accuracy)
< 1.1g/dL = non portal HTN related (97% accuracy)
Optional
- Culture, gram staining
- Glucose, amylase
- LDH
Unusual
- TB culture, cytology
- triglyceride, bilirubin
Treatment for ascites?
Diuretics Large volume paracentesis TIPS Aquaretics Liver transplantation
How is variceal haemorrhage related to liver disease and how is it treated?
Portal hypertension can cause varices (oesophageal, gastric, skin, rectal, abdomen, stomal) Medical emergency - resus - IV access - transfusion if required - emergency endoscopy - endoscopic band ligation - Terlipressin - Sengstaken-Blakemore tube for uncontrolled bleeding - TIPS for rebleeding after banding
What is hepatic encephalopathy? What can cause it and what are associated symptoms? How is it treated?
Confusion due to liver disease
Graded 1-4
Precipitants
- GI bleed
- infection
- constipation
- dehydration
- medication especially sedation
Flapping tremor and foetor hepaticus are associated
Treat cause
Laxatives - phosphate enema and lactulose
Neomycin, rifaximin
Repeated admissions with HE is indicator for liver transplant
What is viral hepatitis? What are the possible outcomes?
Inflammation of liver resulting in death of liver cells
Outcomes
- resolution (A, E) - enteric viruses - usually self-limiting
- liver failure (A, B, E)
- chronic hepatitis and cirrhosis (B, C)
What is the treatment for hepatitis B?
Pegylated interferon Oral antivirals - Lamivudine - adelovir - entecavir - telbivudine - tenofovir
Positive lab findings in liver disease (specifically alcoholic liver disease)?
Raised bilirubin AAT/ALT ratio >2 Raised gamma glutamyl transferase and AlkP Macrocytosis Thrombocytopenia (low platelets) USS fatty liver Alcohol
What staging/scoring systems are used in alcohol abuse?
CAGE FAST - 20+ possible dependency - 16-19 higher risk - 8-15 increasing risk
Treatment for alcoholic liver disease?
Encephalopathy treatment Treat infection Treat alcohol withdrawal Protect against GI bleed Airway protection/ICU care Steroids (only if severe (alcoholic hepatitis score >9)) Nutritional treatment - thiamine
What is the prognosis for alcoholic hepatitis?
40% mortality
90% in severe
Dependent on abstinence
Steatohepatitis»_space;> Cirrhosis
Any sign of decompensating liver disease - 30% 5YS
Encephalopathy 36% 1YS
How can spontaneous bacterial peritonitis be caused? What are the symptoms?
Occurs almost exclusively in those with portal hypertension, usually as a result of liver cirrhosis
Symptoms include
- abdominal pain
- fever/rigors
- renal impairment
- signs of sepsis, tachycardia, high temperature
What investigations might be done in bacterial peritonitis?
Ascitic tap
- fluid protein and glucose levels
- cultures
- white cell count
Neutrophil count >0.25x10^9/L
Protein <25g/L
Exclude surgical causes of peritonitis
What is the treatment for bacterial peritonitis?
IV Antibiotics
Ascitic fluid drainage
IV albumin infusion (20% ALBA)
What is Non-alcoholic fatty liver disease?
Umbrella term encompassing
- Simple Steatosis
- Non-alcoholic steatohepatitis
- Fibrosis and Cirrhosis
What are the risk factors/causes of NAFLD?
Associated with components of metabolic syndrome
- diabetes mellitus
- obesity
- hypertriglyceridaemia
- hypertension
Other risk factors
- age
- ethnicity e.g. Hispanics
- genetic factors e.g. PNPLA3 gene
What investigations might be done in suspected NAFLD?
Biochemical tests e.g. AST/ALT ratio Enhanced liver fibrosis panel (hyaluronic acid, TIMP-1, PIINP) Cytokeratin-18 USS Fibroscan MRI/CT MR spectroscopy - quantify fat Liver biopsy
NAFLD scoring
- 3+ = high risk
(age, diabetes, BMI, AST:ALT, platelets, albumin)
What is the treatment for NAFLD?
Diet and weight reduction
Exercise
Insulin sensitisers e.g. Metformin, Pioglitazone
Glucagon-like peptide-1 (GLP-1) analogues e.g. Liraglutide
Farnesoid X Nuclear Receptor ligand e.g. Obeticholic acid
Vit E
Weight reduction surgery
What different type of autoimmune liver disease are there?
Autoimmune hepatitis Primary biliary cholangitis Primary sclerosing cholangitis Overlap syndromes Autoimmune cholangiopathy IgG 4 disease
What are the stages of bilirubin metabolism?
Pre-hepatic
- breakdown of Hb in spleen to form haem and globin
- haem converted to bilirubin
- release of bilirubin into circulation
Hepatic
- uptake of bilirubin by hepatocytes
- conjugation of bilirubin in hepatocytes
- excretion of conjugated bilirubin into biliary system
Post-hepatic
- transport of conjugated bilirubin in biliary system
- breakdown of bilirubin conjugate in intestine
- re-absorption of bilirubin
What are the different problems that may occur in each stage of bilirubin metabolism, resulting in jaundice?
Pre-hepatic
- increased release of Hb from RBCs (haemolysis)
- increased quantity of bilirubin (haemolysis)
- impaired transport
Hepatic
- Defective uptake of bilirubin
- Defective conjugation
- Defective excretion
- Cholestasis
- Intra-hepatic bile duct obstruction (PBC, PSC, tumour)
Post-hepatic
- Cholelithiasis
- Diseases of gallbladder
- Extra-hepatic duct obstruction (stones, tumour of duct, stricture, tumour outside duct
Who is targeted for liver transplantation?
CLD with poor predicted survival CLD with poor QOL Hepatocellular carcinoma Acute Liver Failure Genetic diseases e.g. primary oxaluria, tyrosemia
When is liver transplantation contraindicated?
Active extrahepatic malignancy
Hepatic malignancy with macrovascular or diffuse tumour invasion
Active and uncontrolled infection outside of the hepatobiliary system
Active substance/alcohol abuse
Severe cardiopulmonary or other comorbid conditions
Psychosocial factors that may affect recovery
Technical/anatomical barriers
Brain death
What tests are done to prioritise those in acute liver failure for transplantation?
Arterial pH/lactate Hepatic encephalopathy INR Creatinine Bilirubin
Child’s Pugh scoring, MELD, UKELD in cirrhosis
What actually are ERCP/MRCP?
Endoscopic retrograde cholangio-pancreatography
Magnetic resonance cholangio-pancreatography
Visualise ampulla, biliary system and pancreatic ducts
Allows biopsy/cytology, stone removal, stenting, dilatation
