GI Flashcards
What is Crohn’s disease?
Site
Type
Clinical features (8)
Risk factors (6)
Site:
- whole GI tract, mainly at terminal ileum and caecum
Type: fibrostenotic, inflammatory, fistulizing
Clinical features:
- Constitutional: fever, weight loss
- RLQ abdominal pain
- RLQ palpable mass
- Bowel obstruction
- Watery diarrhoea ± steastorrhea
- Oral ulcers
- stomatitis
- anal fissure/skin tag
Risk factors
- smoking
- prior appendicectomy
- FHx
- Diet - refined sugar, low-fibre diet spicy food
- Hx of infectious GE in past year
- Drugs - NSAIDS, OCP, antibiotics
What is Crohn’s disease?
Pathology
Imaging
Endoscopy
Lab
Pathology:
Transmural inflammation with fistula
Lymphocytic infiltration
Globet cells
Non-caseating granuloma
—> DDx: TB colitis, with case acting granuloma, AFB stain & C/ST if suspected
Endoscopy:
- ileo-colonoscopy with biopsy
- patchy inflammation with skip lesion
- Deep linear ulcer (cobblestone appearance)
- Stricture, abscess, fistula
-spared rectum
Imaging:
- AXR —> dilated bowel, thumbprinting sign, mass in RIF, calcified calculi, sacroiliitis
- CT/MR enteroclysis —> inflammatory vs fibrotic stricture, extraluminal complication, fistula, perianal disease
- Capsule endoscopy (after r/o SB strictures - capsule retention)
- Anorectal USG —> fistulising perinatal CD
- CT colonography
- Interstitial USG
Lab:
- CBC, LRFT, ESR, CRP
- Ca, B12/folate, G6PD, Fe profile
- Antibodies: ASCA
- Stool: culture, microscopy, C.diff toxin PCR
- Faecal calprotectin
What is Ulcerative colitis?
Site
Clinical features (3)
Risk factors (3)
Protective factors (2)
Site:
Rectum +/- colon
Clinical features:
- Constitutional: fever, weight loss
- Diarrhoea (mucus/pus, bloody)
- Urgency/tenemus
Risk factors:
- FHx
- Diet: refined sugar, spicy food, low-fibre diet
- Drug: NSAIDS
Protective factors:
- smoking
- prior appendicectomy
What is Ulcerative colitis?
Pathology
Imaging (3)
Endoscopy
Lab
Pathology:
Mucosal inflammation, without fistula
Neutrophilic infiltration
No Globet cells
No granuloma
Endoscopy:
Colonscopy with biopsy
- Continuous lesion
- Superficial broad-based ulcer
- Rectal involvement
- Caecal patch (in E2)
- Clear demarcation between inflamed
and normal mucosa
- Touch friability, petechiae, bleeding
Imaging:
- AXR —> dilated LB, thumbprinting sign
- CT/MR enteroclysis
- Interstitial USG
Lab:
- CBC, LRFT, ESR, CRP
- Ca, Fe profile, B12/folate
- Antibodies: p-ANCA
- Stool: culture, microscopy, C. Diff toxin PCR
- Faecal calprotectin
Extra-intestinal manifestation of IBD
• Skin: clubbing, oral aphthous ulcer, stomatitis, perianal skin tag, erythema nodosum, pyoderma gangrenosum (a/w sterile abscess), psoriasis, Sweet syndrome (acute febrile neutrophilic dermatosis),
hidradenitis suppurativa
• MSK: peripheral arthropathy (Types 1* & 2^), axial SpA, osteoporosis (fat malabsorption à ↓fat-soluble Ca)
• Blood: anemia (active IBD, Fe / B12 malabsorption, sepsis, azathioprine-induced myelosuppression)
• Ocular: uveitis, episcleritis* (painless), scleritis (painful & vision-threatening)
• Hepatobiliary: fatty liver, liver abscess, gallstone (↓reabsorption of bile salt), PSC (a/w UC)
• Urologic: kidney stone (oxalate stone)
Classification and Disease activity of Crohn’s disease
Montreal phenotypic classification:
Age of onset
Location
Behaviour
Disease activity:
Harvey-Bradshaw Index
Crohn’s disease activity index
CRP level
Classification and disease activity of ulcerative colitis
Montreal phenotypic classification:
Extent
Modified Truelove and Witt’s criteria:
Severe disease if (STEPH) : ≥6 bloody stools/ day, T > 37.8, ESR/CRP > 30, P > 90, Hb < 10.5
—> require urgent admission
Complication of IBD
• Malnutrition: poor oral intake, protein-losing enteropathy, etc.
• Toxic megacolon
• Malignancy (CRC, SB cancer, cholangiocarcinoma): higher risk in UC; surveillance colonoscopy Q3y
• Stricture ( IO), fistula, abscess, perianal diseases (CD)
Toxic mega colon
Definition
Pathogenesis
Clinical features
Ix
Mx
Definition:
total or segmental non-obstructive colonic dilatation associated with systemic toxicity
Pathogenesis:
severe inflammation that paralyses colonic smooth muscle, causing colonic dilation
Clinical features:
- Severe bloody diarrhoea >10x/day
(Reduced stool frequency not necessarily sign of improvement: ¯stool frequency + abdominal distension +
abdominal pain strongly suggestive of impending perforation)
- Systemic toxicity: Fever, hypotension, tachycardia, dehydration, confusion
Ix:
- AXR (transverse colon > 6cm / caecum > 9cm), inflammatory pseudopolyps (mucosal islands)
- Avoid colonoscopy: risk of perforation
Mx
- Resuscitation and close observation of vitals, stool chart, weight
- Complete bowel rest: NPO ± TPN
- NG tube decompression
- IV Broad-spectrum antibiotics
- IV methylprednisolone (after antibiotics initiated)
- Subtotal colectomy + ileostomy if failed medical treatment (50%)
Medical treatment of IBD
Lifestyle:
- smoking cessation
- Avoid NSAIDS
- Exclusive Enteral Nutrition / PEN with exclusion CD diet
- Dairy free diet for acute colitis
Antibiotics:
For perianal disease in Crohn’s disease, sepsis, post-op (metronidazole for 3
months shown to reduce recurrence)
PPI: for upper GI involvement
Aminosalicylates (e.g. mesalazine, sulphasalazine; monitor CBC, RFT):
- For ulcerative colitis
- For induction + maintaining remission
mesalazine / 5-ASA,
• E1: suppository (distal 10cm of rectum)
• E2: enema (up to splenic flexure)
• E3: PO + enema
Cancer protection effect: lower risk of CRC
*Sulphasalazine is only useful in colitis (require colonic bacteria to cleave the drug to release 5-ASA moiety)
S/E of sulphasalazine (agranulocytosis, rash, hepatitis, pancreatitis, reversible oligospermia) vs mesalazine (nephrotoxicity)
Corticosteroid (Budesonide):
- For induction of mild-to-moderate CD
- Route: PO, IV (severe UC), PR enema (topical Tx for UC: Budenofalk)
- Prefer: budesonide CIR* (controlled ideal release) 9mg/day x 4-8 weeks (high first-pass effect to limit systemic S/E)
- If long-term use: Ca + vit D supplement
Immunosupression (azathioprine) (monitor CBC & LFT):
For maintenance of remission
Require > 3mo to have benefits
Examples:
• Azathioprine (S/E: macrocytosis) 1.5-2.5mg/kg/d: check TPMT^ and NUDT15 activity (risk: leucopenia)
• 6-mercaptopurine
• Methotrexate IM/SC weekly (if refractory): PO folic acid 5mg 3 days after each dose
Others: IV cyclosporin / PO tacrolimus used for rescue therapy in severe UC
Biologics:
Synergistic
- Anti-TNF: (S/E: paradoxical psoriasis, reactivate TB, optic neuritis, risk of
lymphoma esp. NHL, C/I: Hx of these)
o IV Infliximab (chimeric): 0, 2, 6 weeks —> Q8week, risk of ATI (antibodies to infliximab: SFI testing)
o SC Adalimumab (humanized): Q2 weeks
- Anti-α4β7 integrin: gut-selective, lower risk of serious infection, slower onset
o IV Vedolizumab: 0, 2, 6 week —> Q8week
- Anti-IL12/23
o Ustekinumab (Stelara): IV BW-based loading —> SC at 8 week —> SC Q12week
- JAK inhibitors: PO tofacitinib (S/E: herpes zoster infection)
Surgical treatment of IBD
Last resort:
aim at bowel conservation
Indications:
- Stricture / obstruction / fistula refractory to medical treatment
- Severe perianal disease
- Malignancy / high-grade dysplasia (prophylactic colectomy)
Post surgery: 6-9 months colonoscopy
Management of acute flare-up in IBD
Causes
o Triggers (e.g. NSAID use, smoking)
o Drug non-compliance
o GI infection
Investigations:
first rule out infection (esp. TB, CMV)
o Bloods: CBC (anemia), CRP/ ESR
o AXR daily (toxic megacolon)
o Stool: faecal calprotectin, virus (norovirus, CMV), bacteria (C/ST, GDH antigen, C. diff toxin), parasite
Management of severe flare-up
o Hydration & nutrition
o IV methylprednisolone
o Rescue therapy after 3-5d (infliximab / cyclosporine)
o Surgery if no improvement for 4-7d
Monitoring of IBD
- Clinical: BO frequency, PR bleeding, change in body weight, S/E of medications (e.g. hepatotoxicity, alopecia,
leucopenia, opportunistic infection, Cushingoid features) - Biochemical: ESR, CRP & faecal calprotectin
- Endoscopic:
o CD: disease extent, UGI involvement
o UC: mucosal healing
For UC - CRC screening
- chromo-endoscopy
- repeat colonoscopy every 1-2y
GI bleeding
Step 1: differentiate UGIB and LGIB
UGIB
- above ligament of Trietx
- hematesis, coffee ground vomiting, melena (must be semi-liquid)
- Increased urea/creatinine ratio
LGIB
- below ligament of Trietz
- hematochezia, fresh PR bleed
- Normal urea/creatinine ratio
Step 2:
Check the severity of bleeding
Step 3:
Alarming symptoms
- abdominal pain / fever —> perforation
- repeated vomiting -> GOO
- jardiniere, ascites —> cirrhosis, variceal bleeding
- drinking history
- Drug history: HSAID, ani-thrombotic
Step 4:
Rule out perforation, ACS, Aspiration
- erect chest ray for perforation
- ECG for ACS
Step 5:
Ix: Erect CXR, ECG, Type and screen, CBC, INR, LRFT, (HBsAg, anti-HCV, AFP)
Step 6:
Transfusion?
If hemodynamically unstable: Yes
Otherwise, may not
—> any active CVS event, such as MI, if have MI then sim higher Hb, if not, restricted transfusion, aim at 7-8
exceptions of restrictive transfusion —> massive bleeding with haemodynamic instability, IHD
Step 7:
Pre-medications
- Peptic ulcer
—> PPI 80 mg stats then 8mg/hour
—> +/- prokinetics
- variceal bleeding
—> Octreotide 50mcg stat, then 50 mcg/hr or Terlipresin (AKI patient) 1-2 mg Q4H ppcS/E: ischemic event, e.g. limb/MI
Step 8:
Stop bleeding in endoscope
- Hemospray
- over size clip
- adrenaline
- heat probe
Alternative to surgery: transcatheter arterial embolisation, risk: contrast nephropathy, bowel ischemia
—> antibiotic (cephalosporin)
Worry for rebleeding
- ongoing hb decrease despite transfusion
- melena after normal stool already passed
Acute cholangitis case
- hepatitis no fever *
Charcot’s triad = acute cholangitis
- fever, RUQ pain, deranged LFT
before ERCP
clinical assessment
- fever
- hemodynamic status
- respiratory status
- GOO / duodenal obstruction
- altered anatomy
Pre-med
- Antibiotics
- rectal NSAID (indomethicin / diclofenac)—> reduce risk of post-ERCP pancreatitis
*after ERCP
- epigastric pain —> pancreatitis, retroperitoneal perforation, MI
- GI bleed —> post-sphincterotomy bleeding
- recurrent fever, stent migration or blockage, concurrent liver abscess
Acute colitis
Definition of diarrhea- x3 BO to > 200 gram per day
- acute (<4 weeks) or chronic (>4 weeks)
Causes of diarrhea
- Infective (bacterial, viral, CDAC)
- Inflammatory (IBD)
- Dysmotility (autonomic neuropathy, thyroitoxicosis)
- Osmotic (malabsorption)
- Secretory (SIBO)
- Functional (IBS)
Complications:
1. Pseudomembranous colitis
- very suggestive of C.difficile infection
2. Toxic megacolon (dilate bowel + severe infection)
- Dilation of colon (>6 cm transverse colon)
- Systemic toxicity
Treatment:
First episode:
1. Fulminant (shock / ileus / megacolon) —> PO vancomycin + IV metronidazole
2. Non-fulminant —> PO vancomycin / PO metronidazole
Recurrent episode:
1. First recurrence —> PO vancomycin (pulsed-taper regimen)
2. Subsequent recurrence —> PO vancomycin / Fidaxomicin / Bezlotoxumab / Faecal Microbiota Transplantation (FMT)
Acute diarrhea
• Definition: diarrhoea (≥3 stools/day) < 4 weeks
Classification:
1. Inflammatory
- bloody
- LLQ cramp
- small volume
2. Non-inflammatory
- non-bloody
- +/- pain
- large volume
Differential diagnosis:
• Inflammatory:
o Bacteria: Campylobacter, Yersinia (undercooked poultry), Salmonella, Shigella, EHEC, Vibrio parahaemolyticus (undercooked seafood), Salmonella typhi (typhoid fever)
o Parasites: Entamoeba histolytica
o Virus: CMV (immunosuppressed)
• Non-inflammatory:
o Preformed toxin (<12h): S aureus (meat), B cereus (fried rice), C perfringens (rewarmed meat)
o Bacteria: ETEC, Vibrio cholerae
o Virus: rotavirus, norovirus
o Parasites: Giardia, Cryptosporidium
o Drug-induced: antibiotics (CDAD), Mg-containing antacid, metformin, colchicine
Investigations
• Bloods: RFT, electrolytes
• If diarrhoea is inflammatory or severe,
o Stool: faecal WBC/ calprotectin (PMN products), culture, C. diff toxins A&B, stool O&P
o Flexible sigmoidoscopy: biopsy x 2 at rectum & sigmoid: distinguish IBD from other causes of colitis
Management
• Fluid replacement
• Anti-diarrheals: loperamide (caution toxic megacolon), Kaolin (absorbant)
• Antibiotics: rarely indicated
o Risks: prolonged excretion of enteric pathogen (Salmonella), HUS (EHEC), development of resistant strains
o Indications: sepsis, certain infections (Shigella, V cholerae, S typhi, CDAD, Traveller’s diarrhea - ETEC/ Giardia)
Ix of GI bleed of obscured origin
• Video capsule endoscopy
o Contraindications: dysphagia,
suspected GI obstruction, cardiac
pacemakers, pregnancy
o Complications: capsule retention
(~2%), aspiration, bowel
perforation, capsule disintegration
o Patency capsule can be given
beforehand if high risk of capsule
retention (e.g. Crohn’s disease,
previous RT, chronic use of high-
dose NSAID)
• CT/MR enterography / enteroclysis
o Not sensitive for luminal pathology
• Deep enteroscopy
o Techniques: double balloon enteroscopy, single balloon enteroscopy, manual spiral enteroscopy
o Indications: small bowel polyp/tumor, uncomplicated GI tract stenosis for biopsy/dilation, removal of SB
foreign body (e.g. retained capsule), ERCP in altered anatomy
o Newer technique: motorized spiral enteroscopy (MSE) – higher total enteroscopy rate with shorter time
• Intra-op enteroscopy
LFT pattern
Hepatocellular: ALT, AST
Cholestatic: GGT, ALP, bilirubin
Jaundice
Differential diagnosis
• Pre-hepatic: haemolysis, Gilbert’s syndrome – unconjungated
• Hepatic: cirrhosis, PBC – conjugated
• Post-hepatic: intraluminal (acute cholangitis, Mirizzi’s syndrome), mural (cholangiocarcinoma, PSC), extramural
(CA pancreas, lymphoma) – conjugated
Important questions
• Dark urine, pale smelly stool, pruritis (obstructive jaundice)
o Dark urine only (severe haemolysis)
• Fever, RUQ pain (infection)
• Weight loss, LOA (malignancy)
• Complications of cirrhosis
o Abdominal distension, leg swelling (hypoalbuminaemia/ ascites)
o Abdominal pain, fever (SBP)
o Haematemesis, tarry stool (variceal bleeding)
o Reversal of sleep-wake cycle, confusion (HE)
Investigations:
Unconjugated: CBC, blood film, DCT
Conjugated: LFT to differentiate hepatocellulor or cholestatic pattern
Hepatocellular pattern: HAV, HBV, toxicology screen, serum ceruloplasmin, urine Cu, ASMA, ANA
Cholestatic pattern: MRCP, ERCP, liver biopsy
Gastro-esophageal reflux disease (GERD)
Definition:
• Excessive retrograde flow of gastro-duodenal content into esophagus causing symptoms / complications
• Disease entities
o Non-erosive reflux disease (NERD): typical reflux symptoms, but normal esophageal mucosa
o Erosive esophagitis: OGD sees mucosal lesion +/- local complications (e.g. stricture, Barrett’s, adenoCA)
o Extra-esophageal disease: asthma, chronic cough, globus sensation, etc.
• Reflux esophagitis: GERD + endoscopic / histopathological evidence of inflammation
Anti-reflux mechanism
• Oesophagus: peristalsis
• OGJ: LES(lower esophageal sphincter), intra-abdominal part of oesophagus, angle of His (ball valve effect), crural muscle of diaphragm, mucosal fold
• Stomach: gastric emptying
Risk factors
• Defective LES (MC): alcohol, caffeine, smoking, hiatus hernia, drugs (e.g. CCB, nitrates, bisphosphonates), scleroderma
• Increased intra-abdominal pressure: obesity, constipation, chronic cough, pregnancy
• Increased acid production, e.g. Zollinger-Ellison syndrome (rare)
Clinical features
• Oesophageal: dyspepsia (aggravated by meals & posture), heartburn, acid regurgitation with water brash
• Extraoesophageal: asthma, sore throat, dental erosion, chronic cough, hoarseness of voice
• Complications: erosive oesophagitis (dysphagia), Barrett’s oesophagus, stricture
Los Angeles classification of reflux esophagitis
- Grade A, B, C, D
Investigations
Usually diagnosed clinically
• Empirical PPI trial (BD x 4 weeks) if typical GERD symptoms (exclude IHD if chest pain) and no alarming S/S
• OGD with biopsy: indications include
- Presence of alarming S/S (e.g. dysphagia, odynophagia, unintentional weight loss, UGIB, recurrent vomiting, FHx of CA, chronic NSAID use): rule out CA
- Persistent symptoms after empirical PPI trial (stop PPI for 1 week before OGD)
- Diagnosis of GERD complications (e.g. esophagitis, Barrett’s esophagus)
- Evaluation before anti-reflux surgery
• If anti-reflux surgery is indicated:
o Manometry: insert pressure-sensitive tube through nose down to esophagus and swallow
- Locate LES before 24h esophageal pH monitoring
- Rule out esophageal motility disorders before anti-reflux surgery
- Evaluate LES patency —> decide Nissen vs partial fundoplication
o Ambulatory 24h oesophageal pH monitoring: stop PPI for 1 week à place pH probe at 5cm above LES
- Gold standard for diagnosis: acid exposure time (AET) (pH < 4) > 6%
- Demeester score: >14.72 = abnormal, >100 = severe GERD
Management (SAQ!)
• Lifestyle:
o Avoid fatty foods and precipitants (alcohol, smoking, caffeine, chocolate)
o Weight reduction and avoid tight-fitting garments
o Night time symptoms: avoid large meals < 3h before bed, elevate head of bed (6-8 inches)
• Medical: step-down approach (PPI double dose —> full dose —> half dose —> H2RA(histamine type 2 receptor antagonist) / antacids)
Non-erosive (NERD) / Mild esophagitis (LA Grade A-B)
- acute treatment: standard dose H2RA / PPI x 8 weeks
- maintanecnce therapy: H2RA prn
Severe esophagitis (LA Grade C-D) / Barrett’s esophagus
- acute: Standard dose PPI x 8 weeks
(double / BD if not well controlled)
Repeat OGD to assess healing and r/o Barrett’s
- maintenance: low-dose PPI
- anti-reflux surgery
H2RA: cimetidine
PPI: omeprazole
Esophagitis
Etiology
• GERD: Reflux esophagitis (MC)
• Chronic vomiting
• Surgery
• Use of medications e.g. aspirin, NSAIDs
Classification
• Los Angeles (LA) classification
• Savary-Miller classification
Esophageal motility disorders
Clinical features
• Functional dysphagia: solid + fluid
• Chest pain
Investigations
• Barium swallow
• Oesophageal manometry
• OGD: complications + to rule out other DDx
- Achalasia
- Definition: Aperistalsis + high resting LES pressure + poor LES relaxation in response to
swallowing
- Etiology: Primary; Secondary: Chagas’ disease
- Ix:
Barium swallow: bird’s beak
Manometry: diagnostic
OGD: complications (e.g. oesophagitis)
- Mx:
Medical: CCB, nitrates
Endoscopic: Botox, graded pneumatic
dilation of LES, POEM (per-oral
endoscopic myotomy)
Surgical: Heller’s myotomy +/- Dor
fundoplication (partial anterior) - Scleroderma
- Definition: systemic disease characterised by vasculopathy and tissue fibrosis
- Etiology: autoimmune
- Ix: Barium swallow: dilated distal
oesophagus, loss of peristalsis
Manometry: diagnostic
- Mx: High-dose PPI
Anti-reflux surgery
Esophageal varices
Definition:
engorgement of oesophageal venous plexuses secondary to increased collateral blood flow from portal
system due to portal hypertension
• Hepatic venous pressure gradient (HVPG): diff in pressure between portal vein & IVC (normal 1-5mmHg)
• Rules of 2/3:
o 2/3 of patients with cirrhosis will develop portal HT (HVPG ≥6 mmHg)
o 2/3 of patients with portal HT will develop oesophageal varices (predictor: HVPG ≥ 10mmHg)
o 2/3 of patients with oesophageal varices will bleed from the varices (predictor: HVPG ≥ 12mmHg)
Clinical features:
UGIB (haematemesis, tarry stool, coffee ground vomiting), HBV carrier, chronic alcoholism
OGD:
endoscopic grading (F1: flattened by air insufflation; F2: <1/3 lumen; F3: >1/3 lumen); red wale marks (=high portal pressure)
Management:
1. Prevent SBP:
- IV ceftriaxone 1g daily for 7 days (poor LFT) / ciprofloxacin 400mg BD (normal LFT)
- Prevent HE:
- NPOEM, correct fluid & electrolyte imbalance, routine NG tube not recommended
- IV thiamine (for alcoholics)
- PO/NGT Lactulose 10-20mL Q4-8h (titrate to BO 2-3/day, can be given as enema over 1h) - Stop bleeding and reduce rebleeding
- Resuscitation: cautious volume expansion increase portal pressure —> early rebleeding)
• Fluid: permissive hypotension (aim SBP 90-100)
• Blood transfusion: aim Hb 7-9 (restrictive strategy to decrease transfusion-related adverse
events)
• Correct coagulopathy/thrombocytopenia (FFP/PCC)
- Vasoactive agents for mesenteric vasoconstriction: before OGD until 2-5 days post-OGD
• IV terlipressin 2mg bolus Q4h (V1 agonist) ± nitroglycerin – first line!
o S/E: bowel ischemia, myocardial ischemia, PVD, HT
• IV octreotide 50mcg bolus then 50mcg/h infusion (somatostatin analogue)
• IV somatostatin 250mcg bolus then 250mcg/h infusion
- Urgent OGD asap (within 12h) once hemodynamics are stabilized (SBP > 70)– 1st line
• Endoscopic band ligation (EBL) (1st line for oesophageal varices – less strictures /
rebleeding, but need to repeat every 3 weeks until variceal obliteration)
• Sclerosant therapy with histoacryl glue (1st line for gastric varices - EBL cannot catch
whole varices due to thick gastric wall, Lmore strictures/dysphagia)
• Post-OGD secondary prophylaxis:
o NSBB (propranolol / nadalol / carvedilol): start low, titrate till 25% drop in
resting HR (but HR ≥ 55)
o ± PPI for 2 weeks: prevent post-banding ulcers (long-term PPI is NOT advised
for cirrhotic patients)
Uncontrolled variceal bleeding:
• Repeat OGD
• Sengstaken-Blakemore tube – temporary (max 24h)
o Intubate before inserting (risk of aspiration)
o Fill gastric balloon with 450-500mL water & methylene blue —> then insufflate
esophageal balloon to 20-40 mmHg —> confirm position with X-ray
o Release pressure for 5min Q12h to avoid pressure necrosis
o Complications: oesophageal ulceration, aspiration pneumonia
• TIPSS: transjugular intrahepatic portosystemic shunt – 2nd line
o Approach: right IJV -> hepatic vein -> PTFE stent to portal vein (fig.)
o C/I: portal vein occlusion
o Complications:
- Early: intraperitoneal bleeding (perforated Glisson capsule)
- Late: post-shunt encephalopathy (40%), stent stenosis (50% in 1 year)
• Surgical porto-systemic shunts – 3rd line
o Selective: proximal splenorenal, distal splenorenal (Warren-Zeppa)
o Non-selective: portocaval, mesocaval (SMV to IVC)
Primary prophylaxis for cirrhotic patients
• OGD screening Q1y (decompensated) / Q2y (compensated)
• If high-risk small varices / large varices:
o NSBB – first line, decrease CO —> decrease portal flow
o EBL: require surveillance OGD Q1y afterwards (NSBB not required after
EBL)
Peptic ulcer disease
Definitions
• Erosion: break in mucosal lining < 5mm in stomach/ duodenum
• Ulcers: break in mucosal lining > 5mm in stomach/ duodenum
Pathology
• Imbalance of acid secretion (histamine, gastrin, ACh) vs mucosal protection (mucus, HCO3, prostaglandin, mucosal blood flow)
• Possible location
o Duodenum: MC (75%), mostly in D1 within 2cm of pylorus, never malignant
o Stomach (20%) – usually in lesser curve, 5% malignant potential
o Jejunum: in Zollinger-Ellison syndrome (gastrinoma) – 50% malignant potential
o Meckel’s diverticulum: if contain ectopic gastric mucosa
• GU is classified by modified Johnson’s classification [SUR]
Aetiology
• H pylori (flagellated G- rod): 70% cases of GU, 90% cases of DU
• NSAID (PGE2 blockade —> reduced PG synthesis; COX1 blockade —> less platelet aggregation): can cause ulcer in all parts of GI tract; 25% cases of GU, 5% cases of DU
• Aspirin, steroids
• Smoking, excessive alcohol, caffeine
• Zollinger-Ellison syndrome (hypergastrinemia)
• Stress: Increased ICP (Cushing’s ulcer: vagal nuclei irritation), severe burns (Curling’s ulcer: hypoperfusion of mucosa)
• Hiatal hernia —> Cameron’s ulcer
• Crohn’s disease
Clinical features
• Epigastric pain / Dyspepsia: relieved with food (DU) or worsened by food (GU)
• Complications of PUD: UGIB, perforation, GOO [SUR]
• Complications of H pylori infection: gastric cancer, gastric MALToma
Investigations
• CBC D/C, CXR±AXR (rule out PPU before endoscopy!)
• Test-and-treat approach: all patients should undergo non-invasive test for HP and treat accordingly
o Exceptions:
- Obvious GERD symptoms: PPI
- NSAID use: discontinue NSAID +/- PPI
- Indication for endoscopy: red flags (age > 45, UGIB/ anaemia, dysphagia, LOW)
• OGD + biopsy
o Indications: red flags as above, failed PPI trial
o Roles:
- Diagnostic: biopsy (all GU require 4-quadrant Bx), antral biopsy for CLO test
- Prognostic: Forrest’s classification,
- Therapeutic: injection (ethanol / adrenaline), coagulation (heater probe), clipping
Management
• Lifestyle changes: avoid smoking & alcohol
• Ulcer-healing drugs:
o H2 antagonists x 8 weeks (e.g. famotidine 20mg BD)
o PPI x 4-6 weeks: taken 30-60 min before meals
• If HP +ve: standard triple therapy (high-dose PPI BD + clarithromycin 500mg BD + amoxicillin 1g BD x 7-14d)
• NSAID/ aspirin-induced: First review indication of aspirin / NSAID use
- NSAID user —> Change to COX2 inhibitor + PPI cover
- Aspirin user —> Non-bleeding ulcer: continue aspirin + PPI cover (step up to BD if already OD)
—> Bleeding ulcer: resume aspirin once hemostasis is secured (usually 3-5d) + PPI cover
- SB ulcer —> Misoprostol (C/I in pregnancy) (PPI has no use as SB is already alkaline)
• Secondary prevention of future ulcers
- H. pylori: Maintenance PPI not required after HP eradication
- NSAID / aspirin:
Review indications
Avoid NSAID if high GI risk* / prev. complicated PUD
Give PPI cover
- Idiopathic Consider long-term maintenance PPI
- Definition of high GI risk: ≥2 of
• Elderly > 65 years old
• Hx of PUD
• Concomitant use of aspirin /
steroids / anticoagulant
• Follow-up endoscopy at 6-8 weeks to ensure complete healing
o GU: all
o DU: only if complicated (bleeding/obstruction), giant (>2cm), persistent Sx despite medical therapy
• Endoscopic/Surgical Tx: if refractory to medical Tx or with complications
Helicobacter pylori infection
Prevalence in HK: 50%
Pathogenesis of H pylori
Virulence of H pylori (fig.)
H pylori-related diseases
• Antral gastritis – most common
• Non-ulcer dyspepsia
• Peptic ulcer disease
o GU: direct damage to acid-producing gastric
body —> atrophic gastritis
o DU: inflammation of non-acid-producing antral region —> gastrin —> excessive acid —> damage duodenal mucosa —> HP colonization
• Gastric cancer
• Gastric MALToma
Diagnostic tests for H. pylori
Indications
• Peptic ulcer disease
• Early gastric cancer or MALToma
• Post-HP eradication therapy
Test options
• Stop antibiotics for 4 weeks, PPI for 2 weeks before test
Non-invasive:
1. Urea breath test (UBT)
MOA: urease present in HP converts isotope-
labelled urea into ammonia & CO2
• 14C: radioactive, measured by scintillation
• 13C: non-radioactive, measured by mass
spectrometry
False -ve: antibiotics, PPI
- preferred when Young dyspeptic patients
with no alarming features; Post-HP eradication (except GU – endoscopy is needed)
- HP stool antigen test:
Alternative to UBT
Not convenient and not sensitive
- preferred when Uncooperative or children - Serology (IgG):
Positive up to 2y even after HP eradication
Not useful
Invasive:
1. Rapid urease test (CLO test)
Antral biopsy (highest conc. of HP)
± 2 biopsy at body if chronic PPI use (HP migration)
Add biopsy sample to urea + phenol red (ammonia turns phenol red from yellow to pink)
False -ve: antibiotics, PPI, blood (buffer)
- preferred when Old dyspeptic (>45y); Post-HP eradication in HP- related GU
- Histology:
Gold standard
Biopsy at antrum & body
False -ve: antibiotics, PPI (HP migrates from
pylorus to body)
-preferred when Inconclusive RUT - C/ST:
Not for diagnosis (sensitivity 40%)
- preferred in failed HP eradication x 2 - PCR:
Good but expensive
H. pylori eradication therapy
• Standard triple therapy: high dose PPI BD + amoxicillin 1g BD + clarithromycin 500mg BD x 7-14 days
o Continue ulcer-healing drug (PPI) for 4-6 weeks
o Switch amoxicillin to metronidazole 400mg BD if penicillin-allergic
o Confirm eradication after stopping all drugs for 4 weeks:
- DU: Urea breath test
- GU: OGD for CLO test & histology
- Failed eradication x 2: OGD for C/ST
• Salvage therapy: if failed eradication
o Bismuth quadruple therapy: PPI + bismuth subsalicylate + tetracycline + metronidazole
o Levofloxacin-based triple therapy: PPI + amoxicillin + levofloxacin
o Non-bismuth quadruple therapy: PPI + amoxicillin + clarithromycin + metronidazole
• Precautions: Compliance issue due to S/E (e.g. GI upset, rash, deranged LFT)
• DDI:
o Clarithromycin: CYP3A4 inhibitor (e.g. simvastatin —> increase risk of myopathy & rhabdomyolysis)
o Esomeprazole: CYP2C19 inhibitor (e.g. clopidogrel)
Clostridium difficile-associated diarrhea (CDAD)
Pathogenesis
• Ingestion of C. diff spores —> colonisation of colon when colonic flora is changed by antibiotics —> release of toxin A (enterotoxin) and toxin B (cytotoxin) —> mucosal necrosis, forming pseudomembrane
Risk factors
• Recent use of antibiotics – especially 3rd generation cephalosporin, fluoroquinolone, clindamycin
• PPI/ H2RA
• Elderly/ nursing home residents
• IBD, malignancy
• Chemotherapy
• GI surgery
Clinical features
• Acute watery diarrhoea +/- blood +/- mucus, with fever & lower abdominal pain
• Pseudomembranous colitis (PMC): symptoms above + pseudomembrane & bowel wall thickening in endoscopy
• Fulminant colitis (3%): toxic megacolon +/- bowel perforation
Investigations
• Stool for GDH antigen —> confirmed by PCR for C diff. toxin A & B
• Flexible sigmoidscopy for presence of pseudomembrane (80%)
o Indicated if Dx uncertain or no improvement with standard treatment
o Avoid if suspected toxic megacolon (air insufflation may perforate)
Management (SAQ!)
• Discontinue antibiotics (if possible), PPI, antimotility agents
• Mild disease:
o Vancomycin 125mg Q6h PO 10-14d (1st line) – molecule too large —> cannot cross gut wall
o Metronidazole 400mg TDS PO 10-14d (2nd line: not preferred due to low availability)
• Severe disease (ileus / hypotension / megacolon): metronidazole IV + vancomycin PO / intra-colonic (never IV)
• Fulminant colitis: CT abdomen, urgent consult SUR for subtotal colectomy
• Recurrent infections:
o 1st recurrence: vancomycin pulse and tapered, fidaxomicin
o Subsequent recurrence: faecal microbial transplant, fidaxomicin, rifaximin, bezlotoxumab
o FMT: anterograde infusion via OGD + retrograde infusion
• Retesting for C. diff NOT required: stool carriage persists 3-6 weeks post-cessation (false +ve)
Irritable bowel syndrome
Pathophysiology
• Altered motility, visceral hypersensitivity
• Altered gut microbiota
• Changes in brain-gut axis
Features
• Functional bowel disorder
• Associations: chronic fatigue, fibromyalgia, depression/anxiety
• Subtypes: IBS-D (diarrhea) / IBS-C (constipation) / IBS-M (mixed) / IBS-U (un-subtyped)
Management
Multidisciplinary approach
• Diarrhea: low FODMAP diet, loperamide
• Constipation: high fibre diet, laxatives (PEG)
• Abdominal pain: antispasmodics, TCA/SSRI
• Psychotherapy if refractory
*FODMAP: fermentable oligosaccharides, disaccharides, monosaccharides & polyols —> poorly absorbed by SB —> fermented
by bacteria to produce gas & osmotically active carbohydrates
Rome-IV criteria
• Recurrent abdominal pain on average ≥1
day/week in the last 3 months
• Associated with ≥2 of:
o Relieved by bowel opening
o Change in stool frequency
o Change in stool form (appearance)
Acute liver failure
Definitions:
rapid decline (< 26 weeks) in liver function characterised by INR ≥ 1.5 and encephalopathy, in a patient without pre-existing liver disease
Classification:
Jaundice to encephalopathy interval, cerebral oedema, INR, bilirubin, prognosis
Investigations
• Bloods: CBC, clotting, LFT, ammonia (prognostic: high levels predictive of complications & mortality)
• Drug history: prescribed meds (e.g. high dose steroids, immunosuppressants), OTC, herbal medicine, mushroom (Amanita phylloides), Ecstasy
• Underlying causes:
o Viral hepatitis: anti-HAV, anti-HEV, HBsAg/ anti-HBc IgM, anti-HCV
o DILI: paracetamol level
o Alcoholic hepatitis: AST
o Wilson’s disease: serum ceruloplasmin, urine Cu (suspect if < 50y)
o Autoimmune hepatitis: ANA, ASMA, anti-LKM1
o Liver biopsy (transjugular): if unexplained by above
Management
• Supportive care:
o Close monitoring in ICU
o INR, NH3 daily
o Nutrition: 1g protein/kg/day (lower for patients with worsening hyperammonaemia or high risk for intracranial hypertension
o N-acetylcysteine (NAC) for BOTH paracetamol and non-paracetamol related cause
- Loading dose 150mg/kg/h over 1h -> 12.5mg/kg/h x 4h —> 6.25mg/kg/h until total duration (21h for paracetamol, 72h for non-paracetamol related)
o Nucleoside analogues (e.g. tenofovir) for HBV-related
o Prophylactic famotidine / PPI to reduce stress-related GI bleeding
• Management of complications:
o Coagulopathy: IV vitamin K1 10mg, platelets & FFP – needed if haemorrhage or before invasive procedures
o HE: monitor GCS & ICP, lactulose ± intubation / sedation
o Intracranial hypertension (∵cerebral oedema): mannitol, hyperventilation, hypertonic saline, hypothermia
o Haemodynamics/ renal failure: fluid + vasopressor; target MAP >75mmHg; r/o adrenal insufficiency
o Hypoglycaemia: 50ml D50 if BG < 2
• Liver transplant: King’s College Hospital prognostic criteria ± MELD score
o C/I for liver transplant: alcoholic with <6 month abstinence, extra-hepatic malignancy, severe uncontrolled
extra-hepatic infection (e.g. HIV), multi-system organ failure, inability to comply with transplant meds
Paracetamol:
- pH < 7.3 or PT>100s(INR>6.5) + Cr>300+grade III/IV hepatic encephalopathy
Non-paracetamol:
- PT>100(INR>6.5) / 3 out of following five
- Age <10/>40 + drug-induced/undetermined Etiology + bilirubin>300 + jaundice to coma interval>7 days + PT>50(INR3.5)
Cirrhosis
Definition
• Cirrhosis (pathological): diffuse, regenerative nodules separated by bridging fibrous septa
• Decompensated cirrhosis (clinical): cirrhosis with complications
Causes:
- Infection: HBV, HCV
- Metabolic: ALD, NAFLD
- Immune: autoimmune hepatitis, PBC, PSC
- drug-induced: methotrexate, amiodarone, isoniazid, phenytoin
- Inherited: Wilson’s disease, Haemochromatosis
- vascular: Budd-Chairi syndrome, cardiac cirrhosis
Complications:
- Haptocellular carcinoma
- portal hypertension: ascites, esophageal varices, hypersplenism, hepatomegaly syndrome
- Impaired metabolism: encephalopathy
- synthetic dysfunction: coagulopathy, jaundice, hypoalbuminaemia
- Cryptogenic cirrhosis (unknown cause): usually due to recovered HBV infection or non-alcoholic steatohepatitis
Investigations
• Bloods:
o Liver function: LFT (↑bilirubin, reverse A:G ratio ∵IgA production), clotting profile (INR)
o CBC D/C: pancytopenia – macrocytic anemia (B12/folate), neutropenia / thrombocytopenia (portal HT, hypersplenism)
o Glucose (hypoglycaemia), lipid profile (hyperlipidemia), RFT (hepatorenal syndrome)
• To determine underlying cause:
o Hepatitis serology: HBsAg, anti-HCV
o Autoimmune markers: ANA / ASMA (AIH), AMA (PBC), ANCA (PSC)
o Cu studies (ceruloplasmin, urine Cu)
o Fe profile (iron, TIBC)
• To assess complications: USG (small shrunken liver, splenomegaly, ascites), AFP (HCC), OGD (varices)
• To assess fibrosis and steatosis: FibroScan (LSM, CAP – refer above)
• Definitive diagnosis: liver biopsy
Severity: Child-Pugh score***
Management:
• Treat underlying cause, e.g. quit alcohol, antiviral therapy for HBV
• Surveillance:
o HCC: USG + AFP Q6m
o Varices: OGD surveillance, NSBB prophylaxis if varices seen
• Treat complications (see separate section)
• Consider liver transplantation
Portal hypertension
• Definition: elevated portal pressure resulting from resistance to portal flow
• Diagnosis: hepatic venous pressure gradient (HVPG) ≥ 6mmHg
o Varices usually >10mmHg; bleeding varices usually >12mmHg
Aetiology
• Pre-hepatic: portal vein thrombosis, compression by mass lesion
• Hepatic: cirrhosis, non-cirrhotic (schistosomiasis), post-chemotherapy veno-occlusive syndrome
• Post-hepatic: hepatic vein thrombosis (Budd-Chiari syndrome*), IVC thrombosis, right heart failure
*Suspect when sudden-onset ascites + tender hepatomegaly (Ix: hepatic vein Doppler USG)
Pathogenesis of portal hypertension in cirrhosis
• increase vascular resistance: mechanical obstruction (fibrosis) and functional (increase endothelin, decrease NO in hepatic sinusoids)
• portal blood flow due to splanchnic vasodilation (increase NO in gut)
Ascites
Pathophysiology:
• Portal hypertension —> Splanchnic vasodilation
• decrease Albumin —> decrease ECV —> increase hepatic sinusoidal pressure —> increase RAAS —> Na and water retention
Clinical features: Abdominal distension (at least Child B cirrhosis)
Investigations:
• Bloods: CBC, clotting (for tapping), AFP
• USG abdomen
• Diagnostic paracentesis: tap at LLQ (sigmoid is mobile!)
o Appearance: turbid (SBP), milky (chylous ascites), bloody (malignancy, TB, traumatic tap, hemoperitoneum)
o Biochemistry: total protein, albumin (SAAG: >1.1g/dL = portal HT likely) ± glucose, LDH, amylase, ADA
o Cell count with differential (SBP)
o Microbiology: see SBP
o Cytology: malignant cells
DDx of ascites in cirrhotic patients:
• Cirrhotic ascites
• SBP
• Malignant ascites (HCC)
Management: aim BW loss 0.5kg/day (to decrease AKI risk)
• Vitals: monitor I/O, BW, urine Na, RFT
• decrease Fluid intake:
o Low salt diet (Na < 2g/day)
o Fluid restriction 1L/day (only if dilutional hypoNa < 125)
• Diuretics: spironolactone (50mg/day) +/- frusemide (20mg/day) – titrate up weekly and maintain 100:40 ratio
o Discontinue if hypoNa <120, progressive AKI/HE, muscle cramps
o Discontinue frusemide if hypoK < 3; discontinue spironolactone if hyperK > 6
o Substitute spironolactone with amiloride if tender gynaecomastia (c.f. painless: CLD)
• Therapeutic paracentesis for refractory ascites
o Exclude SBP first
o Limit of tapping:
- Usual: None, but give IV albumin 6-8g per liter tapped if large-volume paracentesis (drain > 5L)
- Unstable haemodynamics, AKI, HE, sepsis (SBP), recent variceal bleed: controlled paracentesis (2-4 L/day) + mandatory IV albumin cover
• TIPSS (PTFE stent): for refractory ascites
• Consider liver transplant: 2-year mortality 50% in cirrhotic patients presenting with ascites
Serum ascites albumin gradient:
Serum albumin - ascites albumin
> 1.1g/dL = portal HT likely
Spontaneous bacterial peritonitis
Pathophysiology:
• Impaired hepatic RES
• Ascites —> altered gut wall permeability —> bacterial translocation from gut
• Pathogens: 70% G- (e.g. E coli, Klebsiella), 30% G+ (e.g. Strep pneumoniae, Enterococcus)
Diagnostic criteria of SBP:
ascitic fluid WCC > 500 or neutrophil (PMN) > 250
Clinical features
• 1/3 asymptomatic: require high index of suspicion —> Ix essential in ascites
• S/S: Fever, abdominal pain, confusion, AKI
Investigations
• Blood culture
• Diagnostic paracentesis: same as [ascites], but add
o Biochemistry: glucose, LDH, amylase, ADA (TB)
o Microbiology: Gram stain, bacterial culture (only +ve in 50%). AFB smear, TB culture
Management
• Ascitic tap for Dx & Tx (drain 1-2L in total), may consider repeat 48h later
• IV ceftriaxone 2g Q24h / IV cefotaxime 2g Q8h for 5-10 days
• IV albumin 1.5g/kg on Day 0 and 1g/kg on Day 3 (reduce risk of HRS – see below)
• Monitor for hepatic encephalopathy: lactulose prophylaxis
• Long-term oral ciprofloxacin prophylaxis after 1st episode (recurrence: 70% in 1 year if no prophylaxis)
Secondary bacterial peritonitis
- perforated viscus
- Runyon’s criteria require at least 2 of
—> increase total protein >10
—> decrease glucose < 2.8
—> increase LDH > ULN serum LDH
Hepatic encephalopathy
Definition: altered mental state / cognitive function in the presence of liver failure
Normal physiology of ammonia:
• Production: colonic bacterial catabolism of nitrogenous sources (e.g. proteins), urease-producing bacteria
• Clearance: liver converts ammonia to urea / glutamine
Pathophysiology:
• Impaired liver function: reduced detoxification of NH3
• Portosystemic shunt: NH3 bypass liver and flow directly into systemic circulation
• NH3 crosses BBB to enter brain à metabolized to glutamine à osmotic (cerebral edema) & neurotoxic effects
Precipitating factors (SAQ!)
• Nitrogen loads: GIB (e.g. variceal bleed), high-protein diet
• Recent alcohol binge
• Constipation
• Infection (sepsis, SBP)
• Large-volume paracentesis
• Drugs: diuretics, sedatives, hepatotoxic drugs, nephrotoxic drugs
• Portosystemic shunts (e.g. TIPS)
Grading: Grade 0-1 = covert HE; Grade 2-4 = overt HE; note asterixis may be present in any stage
• Grade 0: no clinical evidence, only psychometric alteration of tests
• Grade 1: day-night sleep reversal
• Grade 2: lethargy, disorientation
• Grade 3: confusion, hypersomnolence
• Grade 4: coma
Investigations: Rule out other causes of neuropsychiatric disorders, e.g. renal failure, severe hypoNa
• Plasma ammonia: NOT required for diagnosis, correlate poorly with severity of HE
Management:
• Resuscitation (ABC) + monitor vitals & neuro obs Q1h
o Grade III-IV HE: early intubation (sedate with propofol ∵long half-life), elevate head 30°, limit neck rotation/flexion, control seizures with phenytoin, ICP monitoring
• Identify and correct precipitating factors (as above)
• Correct electrolyte disturbances: azotemia, hypoNa, hypoK, metabolic acidosis/alkalosis
• Limit protein intake: temporary (sarcopenia further reduces ammonia & urea uptake)
o Mild: start at 0.5g protein/kg/day (veg/ dairy sources preferred, consult dietician prn)
o Severe: NPO for 24-48h + IV dextrose until improve —> step down to oral / tube feeding
o Consider oral formulation of branched chain amino acids (BCAA)
• Reduce generation of nitrogenous compounds
o PO Lactulose 30-40mL Q8h
- Mechanism
—> Degraded into lactic acid by lactobacilli —> Acidify diffusible NH3 to non-diffusible NH4+
—> decrease colonic pH modifies colonic bacteria (displace urease-producing bacteria with Lactobacillus)
—> Cathartic effect of hyperosmolar load (decrease colonic transit time)
- Dose: titrated to 2-3 soft stools/ day
- Route: oral, NG tube or enema
- S/E: diarrhea, flatulence, NO effect on plasma glucose (not absorbed)
o PO Rifaximin: add-on to lactulose for prevention of recurrence
- Mechanism: antibiotic for selective decontamination (decrease urease-producing bacteria)
• Antibiotics for suspected sepsis
• Consider referral for liver transplant if intractable overt HE
Hypersplenism
• Order of pancytopenia: platelets à WBC à Hb
• Reduced clotting factor: elevated INR
Hepatorenal syndrome
• Definition: renal failure in a patient with acute liver failure / ESLD with no identifiable cause of renal failure
• Pathophysiology: portal HT —> splanchnic vasodilation (NO) —> decrease ECV —> compensatory renal vasoconstriction
• Precipitating factors: dehydration (e.g. large-volume paracentesis), infection (esp. SBP), UGIB, severe alcoholic hepatitis
o Add albumin + antibiotics in case of large-volume paracentesis & SBP
• Diagnostic criteria:
o Liver cirrhosis with ascites
o AKI (refer to [renal] for KDIGO criteria)
o Dx of exclusion: Exclude other causes of acute / subacute kidney injury
- Volume depletion: improvement of serum Cr after 2 days of diuretics withdrawal & volume expansion with 1g/kg albumin
- Haemodynamic shock
- Nephrotoxic drugs e.g. NSAIDs, aminoglycosides, iodinated contrast
- Structural kidney diseases: proteinuria (>500mg/day), microscopic hematuria (>50 RBC/hpf), abnormal USG
Classification:
Type 1 (HRS-AKI)
- rapidly progressive oliguria renal failure (Cr doubling over 2 weeks)
- severely ill, child’C patient
- survival less than 2 weeks
- Mx: Terlipressin +/- hemodialysis
Type 2 (HRS non-AKI)
- Chronic form, steady deterioration (Cr doubling over years)
- Child B with relatively preserved LFT
- survival less than 6 months
- Mx: TIPSS
• Management: generally unsuccessful in prolonging survival
o Treat underlying liver failure and correct precipitating factors
o Avoid excessive fluid (risk of fluid overload and hypoNa)
o IV Terlipressin 1mg Q6h + albumin 1g/kg/day
- Terlipressin: vasopressin analog (decrease splanchnic vasodilation —> divert blood to kidneys)
—> C/I: IHD, PVD, stroke
- Albumin: 1g/kg/day x 2 days —> 20-40g/day; expand ECV
o TIPSS
o Renal replacement therapy: bridge to liver transplant
o Liver transplant
Hepatopulmonary syndrome
• Pathophysiology: bacterial translocation to lung —> intrapulmonary vascular dilatation (IPVD) (preferentially in lung bases) —> intrapulmonary shunting —> increase A-a gradient
• Classical triad:
o Liver disease
o Increased A-a gradient by ABG
o Intrapulmonary vascular dilatation (IPVD) on echo
• Clinical features:
o Dyspnea (MC)
o Platypnoea: increased dyspnoea that is exacerbated by upright position (worsening V/Q mismatch) & relived by lying supine
o Orthodeoxia: desaturation that is exacerbated by upright position & relieved by lying supine
• Investigation: transthoracic contrast echocardiogram (TTCE) for IPVD
o Normal: contrast only show up in right heart (∵filtered by pulmonary capillary bed)
o IPVD: contrast in left heart a few cycles afterwards
• Management: long-term O2, embolization of large IPVD, liver transplantation
Hepatic hydrothorax
• Definition: pleural effusion in cirrhotic patient with no evidence of other cardiopulmonary diseases
• Pathophysiology: movement of ascitic fluid into pleural space through fistula in diaphragm
• Clinical features:
o Transudative effusion (usually unilateral on right side)
• Management (similar to ascites): low Na diet, fluid restriction, therapeutic thoracentesis
Pulmonary hypertension
• Definition: pulmonary hypertension in patient with existing portal hypertension
• Pathophysiology: endothelin-1 (normally metabolised by liver) reaches pulmonary circulation by portosystemic collaterals —> pulmonary vasoconstriction
• Management (similar to pul HT): prostacyclin agonists, endothelin antagonist, PDE5 inhibitor
Viral hepatitis
Signs and symptoms: fever, n/v, RUQ pain, cholestasis, jaundice – cannot tell acute vs acute-on-chronic hepatitis
Investigations:
• CBC (WCC usually normal), LFT (ALT usually 200-2000, but can be low if fulminant hepatitis), amylase
• Clotting profile: INR is best for reflecting liver function (∵short half-life of Factor VII)
• Viral serology:
o Anti-HAV IgM, anti-HEV IgM
o HBsAg + anti-HBc IgM (only marker +ve if in “window period”)
o Anti-HCV (may take 12 weeks to appear) ± HCV RNA (if certain exposure history)
Initial management:
• DAT, Obs Q4h, H’stix BD (liver failure can cause hypoglycemia)
• Bloods x CBC, LRFT, INR, NH3 daily
Hepatitis A
- Faecal-oral route
- 2-4 weeks incubation
- rare fulminant hepatitis
- Ix: Anti-HAV IgM
- Prevention: avoid uncooked seafood, vaccination
- never chronicity or re-infection
Management: usually self-limiting
• Alcohol abstinence x 6 months is recommended for acute hepatitis
• Hepatitis A vaccine (IMI inactivated whole virus vaccine)
o Indications: travel to endemic areas, MSM, patients with CLD, IVDA
o Regimen: monovalent (2 doses 6-12 months apart) / bivalent (combined with HBV)
o Effective around 4 weeks after 1st dose – urgent travellers may require passive immunization by IVIG
Hepatitis E
- Faecal oral route, Zoonotic: pigs, shellfish (genotypes 3 & 4), rodents
- 3-8 weeks incubation
- reare fulminant hepatitis except in pregnant women (25%)
- Ix: Anti-HEV IgM +/- stool HEV RNA RT-PCR
- avoid internal organs especially pig liver for prevention
- chornicity: rare except in transplant patients
- re-infection: possible
• Chronic hepatitis E (detection of HEV RNA in serum / stool > 6 months) in transplant recipients
o Mx: Reduce immunosuppressants, ribavirin monotherapy x 12 weeks
Hepatitis B
Acute hepatitis B infection
• Clinical features: jaundice, n/v, anorexia, RUQ pain
• Outcomes:
o Full recovery (MC)
o Chronic hepatitis B (10%)
o Acute liver failure (1%)
• Management
o Supportive care
o Antiviral not required except acute liver failure —> entecavir
o Monitor HBsAg + anti-HBc IgM 6 mo later
Chronic hepatitis B infection
Definition: HBsAg +ve for ≥6 months —> further classified by HBeAg status
Prevalence: ~8% in HK (lower in young population due to vaccination), ~4% globally
Hepatitis B serology
• Acute infection: HBsAg, anti-HBc IgM*
• Chronic infection: HBeAg, HBV DNA
• Inflammation of liver: LFT (ALT»_space; AST in acute phase)
Window period: 3-6 months after HBV exposure
HBsAg -ve but anti-HBs not yet developed —> Only marker for Dx is anti-HBc IgM
Stage:
1. Immune tolerance - immature immune system fails to recognise virus —> no clearance, +v2 HBeAg, -ve Anti-HBe, +++ HBV DNA, Normal ALT, not increased risk of cirrhosis
2. Immune clearance - active immune response: cytotoxic T cells kill HBV-infected hepatocytes —> Increase ALT, + -> - HBeAg, - -> + Anti-HBe, ++ HBV DNA, +++ ALT, increased risk of cirrhosis (antiviral indicated)
3. Immune control: Normalization of HBV DNA and ALT over 12 months, -ve HBeAg, +ve Anti-HBe, ow HBV DNA, normal ALT, not increased risk of cirrhosis
4. Immune escape: elevated HBV DNA with progressive liver damage, -ve HBeAg, +ve Anti-HBe, +++ HBV DNA, +++ ALT, increased risk of cirrhosis (antiviral indicated)
Management of chronic Hep B:
Education:
• Avoid alcohol
• Avoid hepatotoxic drugs
• Immunization for hepatitis A
• Prevent transmission:
o Sexual: vaccination of spouse, steady sexual partners, safe sex with barrier contraception
o MTCT: C-section, perinatal TDF (refer below), HBV vaccine + HBIG for newborn
o Environmental: avoid sharing razors/toothbrushes/needle, avoid donating blood/organs
Disease monitoring
Is HBV active? • HBV DNA Q6-12mo (if active: Q3mo until undetectable x 2 visits)
• HBeAg & anti-HBe Q6-12mo until seroconversion
Is the liver inflamed? • LFT Q6-12mo (if active: Q3mo until normalized or undetectable HBV DNA)
Is there cirrhosis? • Fibroscan, OGD ± liver biopsy (gold standard)
Is there HCC? • USG + AFP (Q6mo ideally)*
o ≥1cm: triphasic CT scan / MRI
o <1cm: repeat USG at 4 months
*Rationale: tumor doubling time of HCC ~140 days, if missed at initial scan (<1cm), will be ≤2cm 6 months later and still operable
HCC surveillance
• Methods
o USG: limitations in obese patients / cirrhosis with multiple regenerative nodules
o AFP: false +ve (active hepatitis, pregnancy); false -ve (tumors not producing AFP, sensitivity ~60-70%) – benefit marginal if USG can be arranged Q6mo
• Target patients: Asian hep B carriers (male >40y; female >50y)
o Not all patients benefit: e.g. Child C cirrhosis unless transplant candidate, limited life expectancy
• Scoring
o CUHK-HCC score: age, albumin, bilirubin, cirrhosis, HBV DNA
o LI-RADS system based on USG findings
Antivirals in hepatitis B patients
Aim: Sustained viral suppression —> lower necroinflammation of liver —> lower risk of cirrhotic complications & HCC
• REVEAL study: increase HBV DNA level —> increase risk of progression to cirrhosis and HCC
Indications (important!)
• Non-cirrhotic patients
o Elevated HBV DNA (HBV DNA > 20,000 IU/mL if HBeAg +, >2000 IU/mL if HBeAg -)
o PLUS persistent ALT elevation (> 2x ULN) OR significant fibrosis (≥F2)
• Cirrhotic patients
o Detectable HBV DNA (esp. >2000 IU/mL; if <2000, treat if ALT)
o Decompensated liver cirrhosis
• Pre-emptive Tx if on potent immunosuppressants (see separate section)
• Pregnant women (28-32wk of gestation – 4-12wk postpartum) if HBV DNA > 200,000 IU/mL: give TDF
• HBV reactivation during chemotherapy
• Hx of HCC with detectable HBV DNA
• Transplant patient with HBV infection
• Acute liver failure (e.g. fulminant acute Hep B)
When to stop antivirals: only allowed in non-cirrhotic patients
• Primary endpoint reached (HBsAg seroclearance i.e. HBsAg becomes -ve)
• HBe seroconversion: HBeAg -ve & undetectable HBV DNA for 1 year (~30-40% risk of relapse)
- Nucleotide/nucleotide analogue
- MOA: decrease reverse transcription —> decrease viral replication
- example: entecavir 0.5mg PO daily, 2h before meal
- lifelong duration
- high viral suppression
- HBeAg seroconversion:15-20% in 1 year
- HBsAg seroclearance Rare: <1% per year (~untreated)
- Other benefits Low resistance: entecavir ~1% —> add
tenofovir (no resistance reported)
Potential reversal of liver cirrhosis
Reduced risk of HCC
- Side effects Virtually no S/E
- Entecavir: C/I in pregnancy
- Tenofovir: 1% chance of nephrotoxicity
(type 2 RTA —> osteomalacia)
- Preferred when Decompensated cirrhosis (lifelong Tx)
Pregnancy: use tenofovir (TDF)/ telbivudine - interferon (not used in cirrhosis)
- MOA: increase immune response against virus
- Pegylated-interferon alpha2a 180mcg SC weekly
- 48 weeks duration
- moderate viral suppression
- HBeAg seroconversion 30-40% in 1 year
- HBsAg seroclearance up to 10% upon follow up
- other benefits: Finite duration of treatment
Good durability: maintain response after
stopping the drug
- side effects: Numerous
-> Flu-like syndrome: fever, myalgia
-> Neuropsychiatric: depression, etc
-> Myelosuppression
-> Autoimmune thyroiditis
- preferred when Long-term therapy not desired (e.g. young female to achieve drug-free
period for few years to get pregnant)
Pre-emotive antiviral HBV carriers
High risk”
- Anticipated incidence of reactivation > 10%
- HBsAg+ or *anti-HBc+ patients with
• B cell-depleting agents (rituximab,
ofatumumab) or HSCT
HBsAg+ patients with
• Anthracycline chemo (e.g.
doxorubicin)
• Prednisolone 10mg/day or higher
for > 4 weeks
- Antiviral prophylaxis
Monitor HBV DNA Q6m
Continue antiviral for 6 mo after cessation of immunosuppressive (12 mo if on B-cell depleting agents or HSCT)
Moderate risk:
- Anticipated incidence of reactivation 1-10%
- HBsAg+ patients with
• Other biologics
• Low-dose steroid > 4 weeks
- Consider antiviral prophylaxis
Low risk:
- Anticipated incidence of reactivation < 1%
- All other patients, including HBsAg+
patients with
• Traditional immunosuppressive
agents (e.g. MTX, azathioprine,
intra-articular steroid)
• Steroid use daily < 1 week
- Antiviral prophylaxis NOT required
Occult HBV infection (OBI)
• Definition: HBsAg -ve but HBV DNA +ve (HBV as a DNA virus forms cccDNA
(closed circuit covalent DNA) that remains dormant in hepatocytes
• Seropositive OBI (anti-HBc/ anti-HBs +ve) or seronegative OBI (both -ve)
• Implications:
o HBV transmission during blood transfusion/ liver transplant
o HBV reactivation during potent immunosuppressant
Chronic hepatitis C infection
Definition:
- presence of HCV RNA ≥6 months after exposure
- Global prevalence: 0.7%
- Route of transmission: blood (IVDA, transfusion), mother-to-child transmission, sexual (less common)
- 6 genotypes: 1b & 6a are most common in HK
Clinical course
• Acute infection: usually asymptomatic / subclinical hepatitis in 80%
• Most progress to chronic carrier irrespective of age, c.f. HBV
• Extrahepatic manifestations:
o Type 2 / 3 cryoglobulinemia (decrease C3/C4, RF+, cryoglobulin+)
o Membranoproliferative GN
o Autoimmune: thyroiditis, hepatitis, Sjogren’s syndrome
o Dermatological: porphyria cutanea tarda, lichen planus
o Haematological: lymphoma, myeloma
Acute-on-chronic HCV infection: increase HCV RNA, anti-HCV +ve
Acute HCV infection: increase HCV RNA, anti-HCV -ve initially but +ve within 12 weeks
HCV seroclearance: decrease HCV RNA, anti-HCV +ve
Investigations
• Anti-HCV: +ve within 12 weeks after infection, remain positive after viral clearance
• HCV RNA: indicate active disease (indication for antiviral!)
• HCV genotype testing: different disease course and DAA
o Genotype 1b & 3: more rapid progression and higher risk of HCC
• ± Screening of complications: urinalysis, TFT, anti-thyroid antibodies, ANA
Antiviral treatment
• Indication: all patients with detectable HCV RNA
• Direct-acting antivirals (DAA) x 12 weeks
o MOA: inhibit replication, post-translational processing and assembly of HCV
o Treatment endpoint: sustained virologic response (SVR) as defined by absent HCV RNA by PCR 12 weeks after stopping treatment (a/w 99% chance of long-term HCV RNA negative)
- SVR achieved: check ALT & HCV RNA at 48 weeks —> consider cured if normal
- SVR not achieved: continue treatment for 12 weeks
o Drug classes
NS3/4A protease inhibitors (-previr):
- decrease replication
- glecaprevir, voxilaprevir, paritaprevir
NS5A RNA-polymerase inhibitors (-asvir):
- decrease replication
- velpatasvir, pibrentasvir, ledipasvir
NS5B RNA-polymerase inhibitors (-buvir)
- decrease assembly, secretion
- sofosbuvir
o Regimen: combination of drugs ( decrease resistance) - depends on cirrhotic status (IFN is C/I), viral genotype, viral load, concomitant drugs, etc.
- Maviret (glecaprevir/pibrentasvir) – taken with food
- Esclusa (velpatasvir/sofosbuvir)
o Minimal side effects: rash, fatigue, etc
o Drug interactions: DM meds (hypoglycemia), warfarin (monitor INR), amiodarone, rifampicin, dabigatran, anticonvulsants, rosuvastatin
• Conventional treatment: PO ribavirin + SC peg-interferon (SVR 60-80%) x 48 weeks, C/I in pregnancy & cirrhosis
Alcoholic liver disease
Three main forms: alcoholic fatty liver disease (AFLD) —> alcoholic hepatitis —> alcoholic cirrhosis
Pathology
• Histological hallmark: ballooning degeneration, Mallory-Denk bodies
• Pathophysiology: excessive alcohol saturates alcohol dehydrogenase —> shunted to microsomal ethanol-oxidising
system (MEOS) —> release free radicals and pro-inflammatory cytokines to damage hepatocytes
Assessment of alcoholism
CAGE questionnaire: Cut down, Annoyed, Guilty, Eye-opener (≥2: positive)
Safety drinking limit (1 unit = 8g): 2-3 units/day (male), 1-2 units/day (female)
Investigations for alcoholism
• Blood alcohol level (BAL)
• LFT: AST: ALT ≥2:1 (both elevated but never sky-high >500) + GGT (enzyme induction)
• CBC: MCV
• Plasma glucose (hypoglycemia), lipid profile (hyperlipidemia)
Score: Maddrey’s discriminant function (DF) – if >32 give steroids
• DF = 4.6 x (prothrombin time – control time) + bilirubin (mg/dL)
Treatment of alcoholic liver disease
• Total abstinence
• Prevention of withdrawal: long-acting benzodiazepines (e.g. chlordiazepoxide)
• Nutritional support: thiamine replacement, HE prophylaxis
• Prednisolone 32mg/day x 4 weeks: indicated if DF ≥ 32
• Pentoxifylline (weak TNF inhibitor)
Other systemic effects of alcoholism
Signs:
- Parotid enlargement, Dupuytren’s contracture, cachexia (malnutrition)
GI:
- Oesophagus: Mallory-Weiss syndrome, oesophageal varices (portal HT)
- Stomach: peptic ulcer
- Pancreas: chronic pancreatitis
CVS:
- Hypertension
- Beriberi (thiamine deficiency —> high-output HF)
Hemat:
- Macrocytic anemia ± thrombocytopenia (hypersplenism)
- Zieve’s syndrome: hemolytic anemia (with spur cells & acanthocytes) + jaundice + abdominal pain + hyperlipidemia – altered red cell metabolism (pyruvate kinase instability)
Neuro:
- Peripheral neuropathy (sensory-predominant)
- Proximal myopathy
- Cerebellar degeneration
- Alcoholic dementia
Psychiatric:
- Acute withdrawal: delirium tremens
• Onset: 24-48h after last drink, last 1-5 days
• S/S: delirium, gross tremor, VH, truncal ataxia, autonomic dysfunction (e.g. hyperthermia)
• Mortality 5% (hyperthermia, associated seizure)
• Management:
o Environment: well lit, quiet room
o Supportive:
- Rehydration
- IV high-dose thiamine + folate + multivitamins + MgSO4 in NS (“banana bag”)
- Correct hypoK, hypoMg, hypoglycemia; watch out for rhabdomyolysis
o Benzodiazepines: esp. if CIWA-Ar ≥8
§ Chlordiazepoxide PO / Diazepam PO or lorazepam IM
Wernicke’s encephalopathy: vitamin B1 deficiency
• Pathology: haemorrhage in periventricular grey matter
• Clinical diagnosis – classical triad (confusion, ataxia, ophthalmoplegia) only occur in 15-30% of patients, difficult to differentiate from acute alcoholic intoxication
• Ix (supportive): RBC transketolase, serum Mg (co-factor)
• Mx: high dose IV thiamine (500mg Q8h x 2 days), correct hypoMg, closely monitor BP/P, neuro obs,
• Prognosis: 20% mortality, 80% develop Korsakoff’s syndrome
Korsakoff’s syndrome:
• Irreversible amnesic syndrome (anterograde amnesia)
• Mx: long-term thiamine
Caine’s criteria for alcoholics:
2 out of 4
- Dietary deficiency
- Oculomotor abnormalities
- Cerebellar dysfunction
- Consciouness decrease / Memory decrease
Non-alcoholic fatty liver disease (Metabolic dysfunction-associated steatotic liver disease)
• Most common chronic liver disease (prevalence: 27%, M>F for most age groups except after 70y ∵menopause)
• Spectrum: hepatic steatosis (fat within hepatocytes) —> Non-alcoholic steatohepatitis (NASH) —> Cirrhosis
• Histology: steatosis >5% + lobular inflammation + ballooning degeneration
Clinical features
• Usually asymptomatic: incidental finding of deranged LFT
• Associated with metabolic syndrome (BMI, central obesity, T2DM, dyslipidemia, HT)
• Hepatomegaly in 50%
Diagnosis
• Demonstration of hepatic steatosis on imaging, blood
• Exclude significant alcohol consumption
• Exclude other causes of hepatic steatosis
Other causes of fatty liver
• Rapid weight loss (body fat consumption
biomarkers/scores, or histology generates FFA)
• Chronic hepatitis C (esp. genotype 3)
• Wilson’s disease
• Drug-induced: methotrexate, steroid, tamoxifen
• Reye’s syndrome
• Acute fatty liver of pregnancy
Investigations
• LFT: can be normal, AST < ALT (c.f. alcoholic liver disease)
• Metabolic workup: FBG, lipid profile, BP, RFT
• USG: bright liver (hyperechoic parenchyma), deep attenuation, vascular blunting
Management
• Control metabolic risk factors (1st line): weight loss, treat HT/HL/DM, refrain from alcohol
• Possible pharmacological treatment to decrease liver fat & inflammation
o Vitamin E: anti-oxidant, neutral effect on insulin resistance, uncertain effects on CVS and malignancy
o Pioglitazone: insulin sensitizer, but note S/E (weight gain, heart failure, risk of bladder cancer)
o GLP-1 agonists (e.g. semaglutide)
• Bariatric surgery if morbidly obese
** Resmetirom: liver specific thyroid hormone receptor beta agonist, Oral, MASH (metabolic-dysfunction steatotic hepatitis) resolution+improve fibrosis, decrease total and CO2 cholesterol
Wilson’s disease
Pathophysiology
• AR defect in copper metabolism (ATP7B gene on Chr 13 —> codes for copper-transporting ATPase)
• Cu cannot incorporate into apoceruloplasmin (unstable form) —> decrease ceruloplasmin (excessive breakdown)
• Defective Cu excretion into bile —> accumulate inside liver causing damage (hepatic Cu)
• Damaged hepatocytes release stored Cu in free form —> increase serum free Cu, increase 24h urine Cu
Clinical features
Usually hepatic manifestations in children / young adults but neurological manifestations in older adults
• Liver: acute liver failure, cirrhosis
• CNS: basal ganglia (Parkinsonism), cerebellum (wing-beating tremor, ataxia, incoordination, dysarthria, dysphagia), cerebrum (psychosis, mood disorder)
• Eyes: Kayser-Fleischer rings (copper deposits in Descemet’s membrane), sunflower cataract (copper deposits in lens)
• Kidney: haematuria, Fanconi’s syndrome (proximal tubule transport defect)
• Hemat: Coombs negative haemolytic anemia (Cu deposit in RBC)
Investigations
Suspect if abnormal LFT with clinical presentations (e.g. dystonia, psychiatric
symptoms) at young age (<30)
• ↓serum ceruloplasmin (<20 mg/dL): normal in up to 10% of patients
• ↑24h urine Cu >100µg
• Slit lamp exam (KF rings): present in 99% if neuropsychiatric symptoms and 30-50% if hepatic symptoms
• CBC (hemolytic anemia), LFT (AST/ALT > 2)
• ± Liver biopsy: hepatic Cu
• ± MRI brain: ‘face of giant panda’ in midbrain
• Confirmative: ATP7B gene mutation
Leipzig score
Management
• Genetic counselling
• Pharmacotherapy:
o Copper chelator: penicillamine preferred due to lower cost, but similar efficacy as trientine
- Penicillamine: given with vit B6, S/E: initial decrease neuro Sx, nephrotoxicity, MG, drug-induced lupus
- Trientine: S/E: chelate iron / zinc to form ineffective complexes —> separate 1hr when taking
o Copper absorption inhibitor:
- PO Zinc: maintenance treatment in asymptomatic patients, S/E: GI upset
• Management of acute liver failure:
o Hemodialysis: rapid Cu removal
o Liver transplant
Menkes disease
ATP7A mutation (XR) —> Defective Cu uptake from intestine
• Severe neurological deterioration
during early childhood
• “Kinky” hair, hypopigmentation
MEDNIK syndrome: mixed features of
Menkes disease and Wilson’s disease
Autoimmune hepatitis
Definition: hepatitis characterised by a strong association with other autoimmune diseases,
hypergammaglobulinaemia and autoantibodies
Clinical features
• Bimodal age distribution: young & middle-aged females
• Acute liver failure (25%)
• Chronic liver disease
• S/S of other autoimmune diseases, e.g. Graves’, Hashimoto’s thyroiditis, T1DM, UC, RA/SLE
Diagnosis
• LFT: increase ALT, increase AST
• Serology
o increase total IgG (usually normal IgM, IgA)
o Type 1 AIH: ANA, ASMA (anti-smooth muscle Ab), atypical p-ANCA
o Type 2: anti-LKM1 (anti-liver kidney microsomal Ab type 1), anti-liver cytosol 1
• Diagnosis by exclusion: viral hepatitis, Drug-induced liver injury, alcoholic liver disease
• ± Liver biopsy: to confirm diagnosis
Management
• Induction: high-dose prednisolone 40-60mg/day (check TB, HBV/HCV)
• Maintenance: prednisolone + azathioprine (check TPMT)
Drug-induced liver injury
• Clinical features: can present all forms of liver injury (hepatitic, cholestatic, mixed pattern, cirrhosis)
Paracetamol-induced liver injury
• Acute toxic dose: >150mg/kg (4-6g in alcoholic/ anticonvulsant user)
• Clinical features:
o 0-24h: n/v
o 24-48h: asymptomatic (ongoing hepatic necrosis)
o >48h: resolution, or acute liver failure
• Management
o Within 1st hour: activated charcoal
o Not within 1st hour: check paracetamol level at 4h, LRFT
o N-acetylcysteine (NAC) if toxic level about treatment line:
- Dose 150mg/kg in 1h, then infusion over 20h
- Most effective if within 8h post-ingestion, but give regardless of time
o Markers of liver injury: clotting, LFT, ABG, lactate, AFP, PO4
Gilbert’s syndrome
Definition
• Gilbert’s syndrome: mild decrease in glucuronyl transferase activity due to AD mutation in UGT1A1 gene
• Crigler-Najjar syndrome: complete deficiency in GT; rapid death in neonates (kernicterus)
Clinical features: jaundice during stress/ fasting
Investigations
• Isolated unconjugated bilirubin
• Rule out haemolysis: CBC, retic, blood smear
Management: reassuranc
Primary biliary cholangitis
Definition:
Granulomatous inflammation of
intrahepatic bile ducts
M:F: 1:9 (middle aged women)
Etiology:
Autoimmune: Sjogren’s syndrome (70%),
limited SSc, RA, Hashimoto’s thyroiditis
Diagnostic criteria:
2 out of 3 features
• ALP ≥1.5x ULN
• AMA >1:40 (esp. M2 fraction)
• Histology: non-suppurative destruction of
intrahepatic bile ducts (seldom done)
S/S:
Asymptomatic, fatigue, pruritus, jaundice
Steatorrhea, hepatomegaly & cirrhosis
PBC only: xanthoma / xanthelasma (xanthoma on eyelids)
Ix:
LFT: cholestatic pattern (ALP, bilirubin)
Autoimmune markers: AMA +ve (anti-
mitochondrial Ab), ANA (70%, a/w poor
prognosis)
Lipid profile: increase LDL (but not CV risk)
USG: undilated bile duct
DEXA: osteoporosis
± MRCP: not diagnostic, to r/o
extrahepatic biliary obstruction esp. CA
± Liver biopsy (not routine)
Mx:
Dietary modifications
• Low fat diet with medium chain TG supplements (not require bile acid for absorption)
• Fat-soluble vitamin supplement
• Ca ± bisphosphonates
Pharmacological therapy
• Ursodeoxycholic acid (UDCA) 15mg/kg/day: 1st line, only disease-modifying Tx (2° bile salt:
¯endogenous production of bile salts)
• Fibrates: 2nd line
Symptomatic treatment
• Pruritis: cholestyramine (bile salt chelator: excretion), naloxone, rifampicin
• Cholangitis: RADO, endoscopic stenting of dominant strictures
Malignancy screening (PSC)
• USG + MRCP + CA19-9 yearly (cholangioCA, gallbladder CA)
• Colonoscopy yearly (if IBD), routine (if no IBD)
• USG + AFP Q6mo (if cirrhotic)
Liver transplant:
Cx:
Cirrhosis, HCC
Osteoporosis (hepatic osteodystrophy)
Primary sclerosing cholangitis
Definition:
Obliterative fibrosis of biliary tree, mainly
medium/large intrahepatic and/or extrahepatic ducts
M:F: 2:1 (young men)
Etiology:
Primary: IBD 70% (UC* > CD)
Secondary: long-term choledocholithiasis, cholangioCA, parasitic infection (Clonorchis), post-ERCP
S/S:
Asymptomatic, fatigue, pruritus, jaundice
Steatorrhea, hepatomegaly & cirrhosis
PSC only: features of IBD (e.g. bloody diarrhoea, oral ulcers, arthralgia)
Ix:
LFT: cholestatic pattern (ALP, bilirubin)
USG: dilated bile duct
Autoimmune markers: p-ANCA (30-80%), AMA -ve, increase IgM, may have increase IgG4
MRCP: “beads on string” appearance
Colonoscopy: look for IBD
± Liver biopsy (not routine): “onion skin” periductal fibrosis & inflammation, obliterated bile ducts
Mx:
Dietary modifications
• Low fat diet with medium chain TG supplements (not require bile acid for absorption)
• Fat-soluble vitamin supplement
• Ca ± bisphosphonates
Pharmacological therapy
• Ursodeoxycholic acid (UDCA) 15mg/kg/day: 1st line, only disease-modifying Tx (2° bile salt: decrease endogenous production of bile salts)
• Fibrates: 2nd line
Symptomatic treatment
• Pruritis: cholestyramine (bile salt chelator: excretion), naloxone, rifampicin
• Cholangitis: RADO, endoscopic stenting of dominant strictures
Malignancy screening (PSC)
• USG + MRCP + CA19-9 yearly (cholangioCA, gallbladder CA)
• Colonoscopy yearly (if IBD), routine (if no IBD)
• USG + AFP Q6mo (if cirrhotic)
Liver transplant:
Cx:
Cirrhosis, HCC, osteoporosis
CholangioCA (10-15% lifetime risk), gallbladder CA, CRC (esp. if IBD + PSC)
Recurrent cholangitis
Hypercholesterolaemia in cholestatic liver disease
• Mechanisms:
o increase lipoprotein-X (abnormal lipoprotein particle rich in free cholesterol) due to regurgitation of biliary lipids into plasma
o decrease LDL receptors due to hepatic injury
• No increased CV risk: lipoprotein-X inhibits LDL oxidation
• Reduced by ursodeoxycholic acid
Child-Pugh score
Albumin
>3.5 g/dL (>35 g/L)
+1
2.8-3.5 g/dL (28-35 g/L)
+2
<2.8 g/dL (<28 g/L)
+3
Bilirubin (Total)
<2 mg/dL (<34.2 µmol/L)
+1
2-3 mg/dL (34.2-51.3 µmol/L)
+2
>3 mg/dL (>51.3 µmol/L)
+3
INR
<1.7
+1
1.7-2.3
+2
>2.3
+3
Ascites
Absent
+1
Slight
+2
Moderate
+3
Encephalopathy
No Encephalopathy
+1
Grade 1-2
+2
Grade 3-4
+3
