Hepatology Flashcards
Liver Cysts
What are They?
Polycystic Liver Disease (PLD)
Clinical Features
Investigations
Management
1.) What are They? - fluid-filled epithelial-lined sacs
- mostly affect right lobe, ↑incidence w/ age
- due to congenitally malformed bile duct cells
- can be malignant cystadenomas (rare)
- differential: liver haemangioma
2.) Polycystic Liver Disease - the presence of >20 cysts within the liver parenchyma each >1cm in size
- caused by either autosomal dominant PKD/PLD
- aberrant ductal plate configurations which are not connected to intrahepatic bile ducts so cannot drain
3.) Clinical Features - normally (90%) asymptomatic
- sx: abdo pain, nausea, early satiety (mass effect)
- PLD: hepatomegaly, concurrent renal disease, if severe: liver cirrhosis, portal hypertension
4.) Investigations
- LFTs typically normal but ALP and/or gamma GT may be raised
- tumour markers (CEA, CA19-9) can be elevated
- renal function can be affected if renal cysts present
- simple cyst USS: anechoic, well-defined, thin-walled spherical lesion with no septations
- CT w/ contrast: if suspected neoplasm
5.) Management - mostly no intervention unless PLD
- follow up USS at 3,6,12 months if cysts >4cm in size
- PLD: somatostatin analogues e.g. octreotide (↓cyst volume/growth)
- US-guided aspiration: ↓pain due to cyst size (avoided if a neoplasm is suspected due to peritoneal seeding)
- laparoscopic de-roofing: ↓pain due to compression
- lobe resection for cystadenoma/cystadenocarcinomas
Liver Abscess
Pathophysiology
Clinical Features
Investigations
Management
1.) Pathophysiology - due to polymicrobial bacterial infection spreading from biliary or GI tract
- contiguous spread or from portal/hepatic veins
- causes: cholecystitis, cholangitis, diverticulitis, appendicitis, septicaemia, often by E.coli
2.) Clinical Features - RUQ pain w/ fever and rigors
- other sx: jaundice, fatigue, weight loss, N+V, bloating
- RUQ tenderness +/- hepatomegaly
- signs of shock if an abscess has ruptured
3.) Investigations
- bloods: ↑WCC, ↑ALP +/- ↑ALT and bilirubin
- microscopy: peripheral blood and fluid cultures
- USS: poor-defined lesions, hypo/hyperechoic areas, potential gas bubbles, and septations
- CT w/ contrast
4.) Management
- IV fluids (resus), appropriate antibiotic therapy
- drainage via US/CT guided aspiration of the abscess
- treat the underlying cause, surgery if ruptured
Hepatocellular Carcinoma
Pathophysiology
Risk Factors
Clinical Features
Investigations
Management
1.) Pathophysiology - chronic inflammatory processes affecting the liver
- most common cause is liver cirrhosis secondary to:
- viral hepatitis: hepB most common worldwide, hepC in Europe
- other causes/RF: alcohol, haemochromatosis, primary biliary cholangitis, alpha-1 antitrypsin disease, anabolic steroids, OCP
- smoking, ↑age (>70), FH, , , aflatoxin exposure (fungal metabolite)
2.) Clinical Features
- liver cirrhosis: fatigue, lethargy, weight loss
- dull ache in RUQ +/- features of liver failure
- irregular, enlarged, craggy, tender liver
3.) Investigations
- LFTs: AST:ALT >2 suggests alcoholic liver disease, AST:ALT roughly 1 suggests viral hepatitis
- ↓plts or prolonged clotting due to liver failure
- tumour marker: AFP > 400
- USS (mass >2cm) –> staging CT
- MRI if rising AFP and US nodules
- biopsy or fine-needle aspiration as a last resort
4.) Management
- curative: surgical resection, transplantation
- image-guided ablation
- transarterial chemoembolisation (TACE): chemo drugs and embolising agent injected into the hepatic artery
- sorafenib: a multikinase inhibitor
Causes of Liver Cirrhosis
Main Causes x4
Autoimmune Biliary
Hereditary Haemochromatosis
Wilsons Disease
Others
1.) Main Causes
- alcoholic liver disease, non-alcoholic liver disease
- viral hepatitis, autoimmune hepatitis
2.) Autoimmune Biliary - primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC)
- PBC more common in women whilst PSC is in men and associated w/ IBD (mainly UC)
3.) Hereditary Haemochromatosis - iron accumulation
- presentation: >40, later in women (menstruation)
- sx: fatigue, arthralgia, alopecia, amenorrhea, ED
- diagnosis: ↑transferrin saturation + ↑serum ferritin + low TIBC and then confirmed w/ genetic testing (mutated HFE)
- treatment: repeated venesection to remove iron
4.) Wilsons Disease - copper accumulation
- occurs only in young adults
- low caeruloplasmin (copper transporting protein), low serum copper, ↑urinary copper excretion
- Kayser–Fleischer rings (copper deposition in cornea)
- treated w/ copper chelating agents e.g. penicillamine
5.) Others
- alpha-1 antitrypsin deficiency
- glycogen storage
- Budd-Chiari
Primary Sclerosing Cholangitis
Pathophysiology
Clinical Features
Investigations
Complications
1.) Pathophysiology - a biliary disease of unknown aetiology characterised by inflammation and fibrosis of the intra/extra-hepatic bile ducts
- associated conditions: UC (80% will also have UC), Crohn’s (less common than UC), HIV
2.) Clinical Features
- obstructive cholestasis: jaundice, raised bilirubin + raised ALP
- RUQ pain, fatigue, pruritis
3.) Investigations
- ERCP/MRCP: multiple biliary strictures giving a ‘beaded’ appearance
- p-ANCA may be positive (especially w/ negative anti-AMA (mitochondrial)
- liver biopsy (limited role): may show fibrous, obliterative cholangitis often described as ‘onion skin’
4.) Complications
- cholangiocarcinoma (in 10%)
- increased risk of colorectal cancer
Primary Biliary Cholangitis
Pathophysiology
Clinical Features
Investigations/Diagnosis
Management
Complications
1.) Pathophysiology - a chronic liver disorder where interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis
- unknown aetiology but thought to be an autoimmune condition
- typically seen in middle-aged females (female:male ratio of 9:1)
- associated conditions: Sjogren’s syndrome (seen in up to 80%), rheumatoid arthritis, systemic sclerosis, thyroid disease
2.) Clinical Features
- early: may be asymptomatic, fatigue, pruritis
- obstructive cholestasis: jaundice, raised bilirubin + raised ALP
- hyperpigmentation (esp over pressure points), RUQ pain (10%)
- finger clubbing, hepatosplenomegaly
- xanthelasma, xanthoma
- late: liver failure
3.) Investigations/Diagnosis
- immunology: positive anti-AMA (98% sensitivity), smooth-muscle antibodies (30%), raised serum IgM
- imaging: RUQ US or MRCP to exclude an extrahepatic biliary obstruction
4.) Management
- first-line: ursodeoxycholic acid (slows progression and improves sx)
- pruritus: cholestyramine
- fat-soluble vitamin supplementation
- liver transplantation: e.g. if bilirubin > 100 (PBC is a major indication)
recurrence in graft can occur but is not usually a problem
5.) Complications
- liver cirrhosis
- significantly increased risk of hepatocellular carcinoma (↑20x)
Liver Cirrhosis/Chronic Liver Disease
What is it?
Peripheral Stigmata of Liver Disease
Clinical Features
Investigations
1.) What is it? - irreversible end-result of chronic liver injury/disease, hepatocyte necrosis –> scar tissue
- impaired liver function due to ↓hepatocytes
2.) Peripheral Stigmata of Liver Disease - only present in chronic liver injury
- nail clubbing, leuconychia, palmar erythema
- asterixis (liver flap), spider naevi, alopecia
- caput medusae (distended paraumbilical veins)
- gynaecomastia and testicular atrophy due to endocrine dysfunction (↓clearance of androgens)
3.) Clinical Features
- jaundice, ascites, bilateral pitting oedema, pruritus
- hepatomegaly, splenomegaly, abdo pain, N+V
- systemic sx: fever (if viral), weight loss, anorexia, lethargy, muscle and joint aches
- haematemesis (varices), bleeding/easy bruising
- constipation can trigger liver decompensation due to the accumulation of toxic products in the body
4.) Scoring Systems
- Child-Pugh: assesses the severity of cirrhosis (5-15)
- MELD: gives % 3-month mortality, helps guide referral for transplant, used every 6 months in patients with compensated cirrhosis
Interpretation of LFTs
ALT, AST ALP, GGT
Hyperbilirubinemia
Albumin and Prothrombin Time
Acute vs Chronic Hepatocellular Injury
1.) ALT, AST ALP, GGT - ALT (3-40), AST (3-30), ALP (30-100), GGT (8-60)
- ALT and AST are direct markers of hepatocellular injury
- AST is more specific than ALT as it isn’t found in other organs
- ALP is an indirect marker of cholestasis (or bone turnover)
- gamma-GT can be suggestive of bile duct obstruction and biliary epithelial damage (can also be raised w/ alcohol or drugs e.g. phenytoin)
- hepatocellular injury = >10x ↑ALT + <3x ↑ALP
- cholestatic injury = >3x ↑ALP + <10x ↑ALT, AND raised GGT
- cholestasis w/o duct dilation (seen on USS) suggests hepatic cause OR drug-induced (flucloxacillin, co-amoxiclav, erythromycin, COCP, SU, anabolic steroids, testosterone)
- isolated rise in ALP: consider non-HBP causes such as bony metastases, paget’s disease of the bone bone tumours (e.g. sarcoma), vitD deficiency, recent bone fractures
2.) Hyperbilirubinemia - bilirubin (3-17)
- jaundice is only usually visible when the bilirubin is >60
- dark urine: suggests hepatic cause because there is an increase in conjugated bilirubin which is water-soluble and can be seen in urine
- pale stools: suggests post-hepatic (obstructive) cause as bile and pancreatic lipases are unable to reach the bowel because of a blockage
- normal urine + normal stools: ↑unconjugated bilirubin (pre-hepatic) causes inc: haemolysis, Gilbert’s syndrome, impaired hepatic uptake
- isolated rise in bilirubin is also suggestive of a pre-hepatic cause
3.) Albumin (35-50) and PT (10-14s) - assesses the synthetic function
- low albumin suggests liver disease affecting synthesis (e.g. cirrhosis)
- prolonged PT in the absence of anticoagulant use or vitK deficiency can suggest hepatic pathology as there are ↓production of clotting factors
- PT is a more sensitive indicator of liver function than albumin because low albumin may also be due to increased loss (HF, nephrotic syndrome) or an acute phase response which temporarily decreases production
4.) Acute vs Chronic Hepatocellular Injury
- acute injury will often have markedly raised ALT and bilirubin
- chronic injury may have normal LFTs or mild raise in some enzymes
- common causes of acute injury: poisoning (paracetamol overdose),
infection (Hepatitis A and B), liver ischaemia (ischaemic hepatitis)
- common causes of chronic injury: fatty liver disease (alcoholic and non-alcoholic), chronic infection (Hepatitis B or C), primary biliary cirrhosis
- ALT > AST is associated with chronic liver disease
- AST > ALT is associated with cirrhosis and acute alcoholic hepatitis
Other Blood Tests for Investigating Liver Disease
FBC
Synthetic Function
U+Es
Others
1.) Full Blood Count
- thrombocytopenia: a sensitive marker for liver fibrosis (most diagnostic for liver cirrhosis), can present w/ easy bleeding and bruising
- ↑neutrophils: suggests acute inflammation
- ↑MCV: occurs in alcoholic liver disease
2.) Synthetic Function
- albumin: hypoalbuminaemia (<35), measured in LFTs
- bilirubin: ↑conjugated bilirubin (presents as jaundice)
- clotting factors: ↑PT/INR (bleeding/bruising)
3.) U+Es
- hyponatraemia due to fluid retention
- urea+creatinine deranged in hepatorenal syndrome
4.) Others/Liver Screen
- viral serology: hep A/B/C, EBV, CMV
- autoantibodies: anti-AMA, anti-smooth muscle antibody, p-ANCA, ANA
anti-Liver/Kidney Microsomal (anti-LKM)
- immunoglobulins: IgM and IgG
- serum ferritin and transferrin: hereditary haemochromatosis
- serum copper and ceruloplasmin: Wilson’s Disease
- alpha-1 antitrypsin
Imaging for Liver Cirrhosis
Ultrasound
Fibroscan
CT/MRI
Liver Biopsy
Endoscopy
1.) Ultrasound
- fatty changes: ↑echogenicity
- cirrhosis: ascites, splenomegaly, nodularity, arteries have a ‘corkscrew’ appearance, coarse texture
- USS-abdo if cholestatic LFTs: confirm dilated ducts
2.) Fibroscan - transient elastography
- checks elasticity to assess degree of cirrhosis
- measures fatty change and fibrosis,
- retest every 2 years in patients at risk of cirrhosis: hepB/C, alcoholic/non-alcoholic liver disease
3.) CT/MRI - to look for:
- HCC, hepatosplenomegaly, ascites, abnormal blood vessel changes
4.) Liver Biopsy - to confirm diagnosis of alcoholic hepatitis or cirrhosis
5.) Endoscopy
- to assess and treat oesophageal varices
- every 3 years in patients w/o known varices
Management of Complications of Liver Cirrhosis
Malnutrition
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepatic Encephalopathy
Hepato-Renal Syndrome
1.) Malnutrition - ↑use of muscle as fuel so ↓protein
- regular meals, (every 2-3hrs), avoid alcohol
- low salt, high protein and high-calorie diet
2.) Ascites - due to portal hypertension
- reduce dietary sodium, fluid restriction if Na <125
- spironolactone +/- loop diuretics
- tense ascites: therapeutic drainage (paracentesis), large volume (>5L) drainage needs albumin cover to reduce mortality and paracentesis-induced circulatory dysfunction (ascites recurrence, development of hepatorenal syndrome, dilutional hyponatraemia)
- spontaneous bacterial peritonitis: ascites, fever, abdominal pain, ascitic tap (neutrophil count >250, often E.coli), treat w/ IV cefotaxime, prophylactic IV ciprofloxacin on discharge (if low protein <15g/L),
3.) Hepatic Encephalopathy - build-up of ammonia in the systemic system due ↓metabolism of NH3 into urea
- sx: ↓consciousness, confusion, altered memory, mood
- treat w/ laxatives e.g. lactulose (↑excretion of NH3)
- Abx (rifaximin) to ↓bacteria producing NH3
- embolisation of portosystemic shunt
- may need NG-tube due to ↓ consciousness
4.) Hepato-Renal Syndrome - portal hypertension causing renal vasoconstriction –> pre-renal AKI
- fatal within a week, requires a liver transplant
Screening for Complications of Liver Cirrhosis
Oesophageal Varices
Hepatocellular Carcinoma
Osteoporosis
1.) Oesophageal Varices - due to portal hypertension
- stable: prophylactic propranolol, elastic band ligation, or TIPS to reduce risk of potential bleeding
- bleeding: see upper GI bleeding
- endoscopy every 3 years in patients w/o known varices
2.) Hepatocellular Carcinoma
- AFP and USS every 6 months
3.) Osteoporosis - in longer-term patients
- DEXA Scan
Alcoholic Liver Disease
Stages
Investigations
Management
Managing Alcohol Withdrawal
1.) Stages - fatty liver (wks) -> hepatitis (yrs) -> cirrhosis
- fatty liver: alcohol -> fat build-up, reversible process (2wks), also associated w/ hepatomegaly
- alcoholic hepatitis: after yrs, inflammation, jaundice, tender RUQ, initially reversible w/ stopping drinking
- cirrhosis: irreversible end-stage, the liver is small
2.) Investigations
- FBC, LFTs (AST:ALT 2:1) U+Es, clotting screen,
- imaging: USS/fibroscan, CT/MRI
- liver biopsy
- CAGE questionnaire for alcohol addiction screening
3.) Management
- stop drinking, consider detoxicating regime
- ascites: spironolactone, or paracentesis (if tense)
- treat underlying infections or GI bleeds
- PO prednisolone 40mg OD for 28 days in severe alcoholic hepatitis (provided no ongoing infections)
4.) Managing Alcohol Withdrawal
- benzos: chlordiazepoxide (Librium), diazepam used for sx relief of withdrawal
- IV Pabrinex –> oral thiamine to prevent Wernicke’s encephalopathy (confusion, ataxia, ophthalmoplegia)
Non-Alcoholic Fatty Liver Disease (NAFLD)
What is it?
Excluding DIfferentials
Confirming Diagnosis
Management
1.) What is it? - similar pathophysiology to alcoholic
- - w/ inflammation is called NASH (steatohepatitis)
- stages: fatty liver –> NASH –> fibrosis -> cirrhosis
- risk factors: obesity, DM, familial hyperlipidaemia, metabolic syndrome, smoking, HTN
2.) Excluding Differentials - full non-invasive liver screen required to exclude all other potential causes
- FBC, LFTs, U+Es, clotting screen, lipid profile
- viral serology, autoantibodies, immunoglobulins
- iron studies, caeruloplasmin, a-1 antitrypsin levels
3.) Confirming Diagnosis
- USS Liver can confirm the diagnosis of fatty liver
- enhanced liver fibrosis (ELF) blood test (can measure severity) or NAFLD fibrosis score (can exclude fibrosis)
- fibroscan: gives an indication of fibrosis, only performed if ELF blood test or NAFLD fibrosis score indicates fibrosis
4.) Management - general
- weight loss, exercise, stop smoking, avoiding alcohol
- control diabetes, blood pressure and cholesterol
- if liver fibrosis, refer to a liver specialist for treatment with vitamin E or pioglitazone
Viral Hepatitis
Hepatitis B
Screening for Hep B
Hepatitis C
Other Viral Hepatitis
Management
1.) Hepatitis B - DNA virus
- direct contact w/ blood or bodily fluids, (e.g. sex, IVDUs, tattoos), vertical transmission
- 10% become chronic hep B carriers
- vaccines are available (inject surface antigen, HBsAg, to produce surface antibodies, HBsAb)
2.) Screening for Hep B
- active infection: +ve surface antigen, check E antigen for viral load (infectivity)
- previous infection: +ve surface antibody and +ve core antibody
- vaccinated: +ve surface antibody (HbsAb) only
- HBVDNA used to measure disease activity
3.) Hepatitis C - RNA virus
- 75% become chronic hep C carriers
- more associated w/ liver cirrhosis and HCC
- Hep C antibody is screening test
- no vaccines but curable w/ antiviral medication
4.) Other Viral Hepatitis - A, D, E
- hep A is faecal-oral and causes cholestasis: prodromal sx w/ RUQ pain, fever, jaundice, hepatomegaly, deranged LFTs, self-limiting
- hep D can only survive w/ hep B infection
- hep E is rare, only chronic in immunocompromised
5.) Management
- antivirals to slow progression and reduce infectivity
- screen for other blood-borne viruses and STDs
- complications: fibroscan for cirrhosis, USS for HCC
- notify public health
