Hepatobiliary — Disease Index & Clinical Criteria

Written by Betra Youhanna, a medical student and not a doctor — check every detail against your own teaching.

Disease Index · 56 entries across 10 categories · deck-derived, finals-triage

Criteria & Scores · 34 scoring systems, classifications

C/P — Clinical Presentation

Inves — Investigations

Mng — Management

Special — Pathognomonic / disease-unique

Approach

3 entries

Jaundice — approach

C/P

Yellow skin/sclera; detectable when bilirubin >40 µmol/L (~2.5 mg/dL)
Pre-hepatic: isolated unconjugated rise, no LFT derangement (haemolysis, Gilbert)
Hepatocellular: both fractions rise; ALT/AST high; urine bilirubin +ve; urine urobilinogen ↑
Obstructive: conjugated rise; dark urine; pale stool; ↓urine urobilinogen; ALP/GGT high
Intrahepatic (hepatocellular) cholestasis causes: viral hepatitis, drugs, cirrhosis, pregnancy, autoimmune cholangitis

Inves

LFTs + FBC + abdominal US + urine bilirubin/urobilinogen dipstick = first-line
US first-line — duct dilatation, stones, GB pathology
MRCP — non-invasive biliary anatomy
ERCP — diagnostic AND therapeutic (stone extraction, stenting)

Mng

Treat underlying cause
Painless jaundice + weight loss + ↑↑ALP → pancreatic head adenocarcinoma
Acute hep A pattern: massive ALT, travel hx → supportive
Gilbert pattern: bilirubin rise unmasked by URTI/fasting → reassure

Special

Newborns: limited conjugation → kernicterus risk
Adult liver clears load up to 6× normal → adult haemolytic jaundice usually mild
Unconjugated bilirubin is albumin-bound → NO urinary bilirubin in Gilbert/haemolysis
Ligandin (Y protein) + Z protein = intrahepatic transport carriers taking unconjugated bilirubin from sinusoidal membrane to SER for conjugation
Faecal:urinary urobilinogen split ≈ 90:10 → ~90% excreted as stercobilin in stool, ~10% reabsorbed enterohepatic → renal urobilinogen
Conjugation enzyme = UDP-glucuronosyl transferase (microsomal); makes bilirubin water-soluble via mono/di-glucuronide
Hepatocellular urine urobilinogen ↑ mechanism: failure of hepatocyte reuptake of enterohepatically reabsorbed urobilinogen → spill into urine
Post-hepatic causes: gallstone; tumour (primary/secondary); biliary atresia (paediatric)
Intra- vs extrahepatic cholestasis = NOT biochemically distinguishable — need imaging (US → MRCP → ERCP)

Liver — patterns of injury (background)

Cellular patterns

Cloudy swelling → hydropic ballooning (non-specific water)
Steatosis: macrovesicular (alcohol, DM, obesity, drugs, starvation, HCV/NASH) vs microvesicular (acute fatty liver of pregnancy, Reye's, Amanita)
Cholestasis: bile arrest → feathery degeneration
Apoptosis: Councilman/acidophil bodies — shrunken eosinophilic pyknotic; no rupture
Necrosis: cell swells & ruptures; spotty/focal = lobular inflammation

Confluent necrosis zones

Centrilobular (perivenular) — acute viral hep, CVC, drugs
Midzonal — yellow fever
Peripheral / interface — chronic hepatitis ("interface hepatitis")
Bridging: P-P, P-C, C-C
Panlobular (submassive) → fulminant hep + coma; survivors → cirrhosis

Cells & zones

Hepatocytes (polygonal, eosinophilic vacuolated); Kupffer (macrophages); Ito/stellate (→fibrosis); pit cells (NK)
Zone 1 (periportal, highest O₂, GSH/sulfotransferase/gluconeogenesis/bile-acid secretion)
Zone 3 (centrilobular, lowest O₂, CYP2E1 → toxic injury)

Hepatobiliary surgical anatomy (Couinaud, Calot, ligaments)

Gross

Largest organ (~1/50 body weight); right hypochondrium + epigastrium + left epigastrium; wedge-shaped
4 anatomical lobes (right, left, quadrate, caudate) vs surgical 2-hemiliver division (Cantlie line = plane of middle hepatic vein / GB fossa to IVC)
~100 billion hepatocytes = 80% of hepatic cells
Storage: up to 65 g glycogen/kg tissue; gluconeogenesis peak at 24–48 h fasting

Couinaud segments (I–VIII)

Numbered counterclockwise on functional map; supplied by 3rd-order portal branches
Division order: hemilivers (1st-order) → sectors (2nd-order) → segments (3rd-order) → subsegments (4th-order)
Segment I = caudate (autonomous — drains directly to IVC, own portal supply — spared in Budd-Chiari)
II, III = left lateral sector (left of falciform); IVa/IVb = left medial (quadrate)
V, VI, VII, VIII = right hemiliver
Basis of anatomical resections (segmentectomy, hemihepatectomy, extended hepatectomy)

Ligaments & peritoneal reflections

Falciform ligament — anterior abdominal wall to liver; landmark between left medial/lateral sections
Coronary ligament (anterior + posterior layers) — bounds the bare area
Right + left triangular ligaments — lateral fusion of coronary layers
Hepatoduodenal ligament — hepatic artery + portal vein + CBD from duodenum to hilum → Pringle manoeuvre compresses it to control haemorrhage
Hepatogastric (lesser) omentum — may contain aberrant left hepatic artery
Round ligament (ligamentum teres) — obliterated left umbilical vein in free edge of falciform → segment 3 surgical approach
Ligamentum venosum — obliterated ductus venosus; landmark for L hepatic vein in left hepatectomy

Porta hepatis / hilar / umbilical plate

Portal pedicle contents: hepatic artery + portal vein + bile ducts + nerves + lymphatics — enveloped in vasculobiliary sheath
Hilar plate — connective tissue over R + L pedicles at hilum
Umbilical plate — continuous with hilar plate, covers left paramedian pedicle → gateway to segmental pedicles of left liver

Sulcus of Rouvière

Irregular fissure in continuity with right hilum → extrahepatic landmark for the right fissure + plane of CBD
Identification during laparoscopic cholecystectomy helps identify CBD + avoid injury

Calot's triangle

Boundaries: cystic duct (inferior) + common hepatic duct (medial) + inferior surface of liver (superior)
Contents (must be identified before clipping): cystic artery, cystic lymph node (of Lund), right hepatic artery (variable), lymphatics
Critical view of safety before dividing cystic structures in lap chole

Hepatic artery variants (~20–25%)

Accessory / replaced left hepatic artery from left gastric artery — runs in lesser omentum (may be injured in gastrectomy)
Accessory / replaced right hepatic artery from SMA — courses posterior to CBD/portal vein
Moynihan's hump / caterpillar turn = tortuous common or right hepatic artery mimicking cystic artery → inadvertent injury/bleeding risk during cholecystectomy

Extrahepatic biliary tree

R + L hepatic ducts → common hepatic duct → joined by cystic duct → CBD (4–5 cm, ≤0.6 cm on US)
CBD passes behind duodenum → through pancreatic head → ampulla of Vater in medial 2nd part of duodenum
Sphincter of Oddi prevents duodenal reflux into CBD + pancreatic duct
Cystic duct variants: low junction, adherent to CHD, high junction, drains into R hepatic duct, long/parallel behind duodenum, absent cystic duct, posterior/anterior spiral crossings

Gallbladder

Fundus + body + neck (Hartmann's pouch) + cystic duct
Muscular sac, single tall-columnar mucosa, highly folded; mucous glands only at neck
Spiral valve of Heister in proximal cystic duct

Special — sinusoidal cells (4 types)

Hepatic sinusoidal endothelial cells (fenestrated, no BM, sparse reticular fibres)
Kupffer cells (resident macrophages) — phagocytose microbes, effete RBCs, LDL, immune complexes; store Cu/Co/Fe; release IL-6, TNF-α priming regeneration
Lymphocytes / pit cells (NK, attached to endoluminal endothelium)
Stellate (Ito) cells — QUIESCENT = store vitamin A; ACTIVATED by injury/cytokines → myofibroblast-like → lay down collagen → cirrhosis

Special — Space of Disse & canalicular anatomy

Space of Disse: perisinusoidal space between hepatocyte microvilli + endothelium; no BM → free fluid movement; site of Ito cells
Bile canaliculi (1–2 µm) between hepatocyte apical domains → canals of Hering → bile ductules (cholangiocytes) → interlobular → septal → hepatic ducts

Special — enterohepatic + bilirubin split

Conjugated bilirubin → intestinal flora → urobilinogen: 70–85% stercobilinogen (→ faeces); 10% urinary; 15–20% reabsorbed enterohepatic
Bile acids from cholesterol; ~95% reabsorbed in terminal ileum → portal vein → re-excreted in bile

Special — foetal remnants

Round ligament = obliterated left umbilical vein
Ligamentum venosum = obliterated ductus venosus

Hepatitis & non-viral

10 entries

Hepatitis A

C/P

Faecal-oral; self-limited acute hepatitis
Mediterranean travel + massive ALT → classic case
Rarely fulminant; 95%+ complete recovery

Inves

Hepatocellular LFT pattern with bilirubin rise
Anti-HAV IgM acute

Mng

Supportive — no specific antiviral
HAV vaccination in unprotected HCV/HBV patients

Special

NO chronic hepatitis, NO carrier state

Hepatitis B

C/P

Transmission: perinatal, sexual, parenteral (IDU, needlestick), haemodialysis, transfusion
Incubation 2–3 months (up to 6)
Adults: 90–95% spontaneous clearance; 5–10% chronic
Infants: up to 90% chronic
Acute: flu-like fatigue, nausea, diarrhoea, rash, jaundice, pale stool, dark urine
Chronic: mostly asymptomatic; muscle/joint aches; eventually cirrhosis or HCC
Fulminant in 1–4%
Cirrhosis develops in ~15–20% of patients with chronic hepatitis B

Inves

HBsAg: active infection (>6 months = chronic)
HBeAg: high replication & infectivity; HBeAg+ mothers transmit much more
Anti-HBs: immunity (vaccine alone vs cleared = +anti-HBc)
Anti-HBc IgM = acute; IgG = chronic/past
HBV DNA: viral load, treatment decisions

Mng

Treat if: HBV DNA >2000 IU/mL + ALT >ULN ± moderate inflammation; ANY detectable DNA in cirrhosis
First-line NUC: entecavir or tenofovir — oral, long-term, until HBsAg loss; minimal resistance
PegIFN alternative: SC, 48 weeks, flu-like + mood AE; no resistance
Post-exposure: accelerated vaccine + HBIG (needlestick, newborns of HBV+ mothers)
Liver transplant for fulminant or ESLD

Special

Hepatocyte injury = host T-cell mediated (HBV not directly cytopathic)
Ground-glass hepatocytes (HBsAg-laden SER); orcein stain
Universal childhood vaccination = primary prevention
~250 million chronic HBsAg carriers; ~686 000 deaths/yr

physiology · background · low-yield

Microbiology

HBeAg is derived from the HBcore protein; HBcAg itself is not detectable in serum — expressed only within hepatocytes (hence anti-HBc, not HBcAg, is the serological exposure marker)

Other

On-treatment virological response terms: complete (HBV DNA undetectable), partial (>1 log₁₀ drop but still detectable at 12 mo), primary non-response (<1 log₁₀ drop at 3 mo), breakthrough (>1 log₁₀ rise above nadir on therapy → suggests resistance)
Reactivation risk with immunosuppressive therapy — a recognised HBV special group; preventing HBV reactivation is a stated treatment goal

Hepatitis C

C/P

Same transmission as HBV (parenteral predominant)
Most chronic asymptomatic = "silent epidemic"
Fatigue, brain fog, low-grade fever, abdo/digestive disturbance, migratory arthralgia, depression, anxiety
15–40% spontaneous clearance; 60–85% chronic (clinical lecture); pathology lecture cites 80–85% chronic
Chronic: 85–90% stable; 10–15% progress to cirrhosis (clinical); pathology lecture cites 20–30% cirrhosis in chronic HCV
HCV cirrhosis: 75% slowly progressive; 25% develop HCC/liver failure (annual 2–4%)
Fulminant hepatitis (rare, pathology lecture): 2–5%
HCV = most common chronic hep cause in Egypt

Inves

Anti-HCV Ab (97–100% sens) screen
HCV RNA confirms active infection
HCV genotype (6 main + subtypes)
Fibrosis: FibroScan, ARFI, FibroTest, FIB-4, APRI → biopsy if uncertain
Baseline: LFTs, FBC, INR, renal, HBV/HIV, US

Mng

Treat ALL infected — DAAs, pangenotypic regimens
Goal = SVR12 (undetectable RNA 12 wks post-treatment) = cure
Benefits: ↓fibrosis (regression F3/F4), ↓HCC, ↓decompensation, ↓transplant
HAV + HBV vaccination if unprotected
HCC surveillance if F3/F4
Screening 2-step (Ab → RNA); target PWID, MSM, dialysis, birth cohort, ≥2–5% prevalence

Special

Co-factors accelerating: alcohol, HBV/HIV, steatosis, iron overload, NASH

Hepatitis D (delta)

C/P

Defective RNA virus — needs HBsAg envelope
Co-infection (simultaneous HBV+HDV) — rarely chronic
Super-infection (HDV in HBsAg carrier) — usually chronic, high severe-disease risk

Inves

IgG + IgM anti-HDV; confirm HDV RNA
Quantitative HBsAg surrogate when HDV RNA unavailable

Mng

PegIFN-α ≥48 weeks
Liver transplant for fulminant or ESLD
Emerging: bulevirtide (HBV entry inhibitor); prenylation inhibitors

Special

Diagnostic assays not widely available; HDV RNA standardisation lacking

Hepatitis E

C/P

Usually self-limiting acute hepatitis
20–50% fatal fulminant hepatitis in pregnant women

Inves

Anti-HEV serology

Mng

Supportive

Special

NO chronic hepatitis or carrier state
Pregnancy = unique catastrophic outcome

Autoimmune hepatitis (AIH)

C/P

F:M ~5:1; may present acutely, chronic at heart
Asymptomatic (↑LFTs) or symptomatic (acute hep, ALF, chronic hep, cirrhosis)
African American = highest cirrhosis at presentation
Type 1 (worldwide, any age) — assoc. autoimmune thyroid, Graves, UC, coeliac
Type 2 (rare in US; children/young adults) — assoc. T1DM, APECED
HLA-DR3, HLA-DR4

Inves

Autoantibodies: ASMA, ANA, ±AMA; anti-LKM1 >1:80 (Type 2); AAA, LC1
γ-globulin >1.5×ULN
Negative viral serology distinguishes from chronic viral hep
Histology: interface hepatitis + prominent plasma cells; lobular inflammation, bridging fibrosis; bile ducts intact
Ductopenia / ductular inflammation → suspect AIH-PBC overlap
TPMT activity before azathioprine
Screen coeliac + thyroid

Mng

Prednisone monotherapy: 60 → 40 → 30 → ≤20 mg/day taper
Combination: prednisone 20–40 mg + azathioprine 50 mg (or 1–2 mg/kg)
Budesonide alt: 3 mg TID + azathioprine — NOT in acute severe hep or cirrhosis
Severe acute: IV methylprednisolone 60 mg/day
Monitor q2–4 wks induction; taper steroids over 6 months; maintenance q3–4 months
Transplant: highly successful; 12–50% recurrence at 8–10 yrs (median 2 yr)
AIH improves in pregnancy; up to 50% flare postpartum
DEXA + calcium + vit D
Inactive cirrhosis → no benefit from immunosuppression
Do NOT use budesonide/azathioprine in decompensated cirrhosis

Special — drug-induced AIH

Mostly women, acute onset, fever/rash/eosinophilia
ALT-stratified ladder (see Criteria tab)

NAFLD / NASH

C/P

Most common cause of incidental ↑transaminases
Asymptomatic; some fatigue, malaise, RUQ discomfort
Metabolic syndrome assoc. (≥2 of: obesity, IR, dyslipidaemia, HTN)
BMI >30 (whites) / >25 (Asians); ↑TG, ↓HDL, ↑LDL
T2DM + obesity = best predictors of severe fibrosis
Contributes to many "cryptogenic" cirrhoses

Inves

Steatosis on imaging/histology + exclude secondary (alcohol, steatogenic drugs, monogenic)
Significant alcohol cutoff: >21 drinks/wk men; >14 drinks/wk women
US = "bright liver" (↑echogenicity)
Biopsy if competing aetiologies or coexisting CLD unclear non-invasively
Modern name: MAFLD

Mng

Lifestyle: –500–1000 kcal/day + moderate exercise
Weight loss ≥3–5% improves steatosis; 7–10% improves NASH histology incl. fibrosis
Pioglitazone (biopsy-proven NASH ± T2DM)
Vitamin E 800 IU/day in non-diabetic biopsy-proven NASH
Resmetirom (Rezdiffra) — oral THR-β agonist; FDA-approved 2024 for moderate-to-advanced non-cirrhotic MASH
Bariatric surgery in eligible (not established as specific NASH Rx)
Liver transplant for NAFLD cirrhosis; enrol in HCC screening
Do NOT use as specific NASH Rx: metformin, GLP-1, omega-3 (omega-3 OK for hyperTG)

Special

NASH = steatosis + ↑transaminases + histological hepatitis
Mechanism: IR → impaired β-oxidation + ↑hepatic FA synth/uptake + ↓VLDL secretion

Alcoholic liver disease (ASH / Laennec's)

C/P — epidemiology

Lifetime prevalence: 10% males, 4% females; peak 40s–50s; ♂ > ♀
~50% of heavy drinkers have abnormal liver; 10–20% develop cirrhosis
3 sequential stages: steatosis → alcoholic hepatitis → cirrhosis (Laennec's)
Steatosis in >90% of heavy drinkers — reversible with abstinence
Alcoholic hepatitis in 10–35% of patients with steatosis
Cirrhosis in 8–20% of alcohol abusers; HCC in 10–20% of alcoholic cirrhotics
Parallel to NAFLD → NASH → nutritional cirrhosis (also Laennec's)
Decompensation features: ascites, jaundice, variceal bleed, HE
UK CMO guideline: max 14 units/week (6 pints 4% beer OR 7 × 175 mL 11.5% wine OR 14 × 40% spirit shots); no safe upper limit (alcohol)

C/P — alcoholic hepatitis presentation

Rapid onset jaundice + D&V + RUQ pain + confusion; tender hepatomegaly
Fever (~37.7°C), tachycardia, tachypnoea; may have SBP-like picture
1-yr mortality post-admission for alcoholic hepatitis = 40% (Oxford Handbook)
80% of alcoholic hepatitis → cirrhosis if drinking continues

Inves — screening

CAGE (4 items; ≥2 = concerning) — Cut down, Annoyed, Guilty, Eye-opener
AUDIT (WHO 10-item; ≥8 hazardous)

Inves — bloods in alcoholic hepatitis

FBC: ↑WCC, ↑MCV (macrocytosis), ↓platelets
U&E: hyponatraemia; ↑creatinine
LFTs: AST:ALT ratio >2; ↑ALP; ↑bilirubin (often 300–500 µmol/L); ↓albumin; ↑PT/INR
↑GGT (highly inducible by alcohol; monitors abstinence)
Dx mostly clinical + biochemistry; biopsy not always required
Microscopy + culture blood/urine/ascites; US liver + biliary tree

Mng — steatosis (reversible)

Stop drinking + specialist CNS nurse referral
Diet control + HbA1c + lipid profile monitoring

Mng — severe alcoholic hepatitis

Screen for infections ± ascitic tap → treat SBP if positive
Withdrawal cover: chlordiazepoxide PO or lorazepam IM; CIWA-Ar to titrate benzodiazepine dose
Vitamins: vitamin K 10 mg/d IV × 3 days; thiamine (Pabrinex) 100 mg/d PO (Wernicke prophylaxis); folate + multivitamins
Nutrition: NG tube if needed; ≥1.2 g/kg/d protein
Prednisolone 40 mg/d × 5 days tapered over 3 weeks IF Maddrey's DF >32 (severe, poor prognosis)
Alternative / adjunct: pentoxifylline
Assess steroid response at day 7 using Lille score (<0.16 → 96% 28-day survival; ≥0.56 → 55% → stop steroids)
Glasgow AH score (age, WCC, urea, bilirubin, INR) — total >9 = poor prognosis

Mng — cirrhosis

Treat underlying: abstinence + nutrition
Manage complications: ascitic tap, treat HE, drugs for portal HTN
Absolute alcohol abstinence — may regress decompensated → compensated

Special — pathogenesis

Acetaldehyde: lipid peroxidation, protein binding → cytoskeletal + membrane dysfunction
Alcohol itself: ↓mitochondrial function, ↓membrane fluidity, cytoskeletal disruption → Mallory-Denk bodies
ROS → membrane + protein damage; neutrophil-driven hepatocyte necrosis
Cytokine-mediated (mainly TNF, stimulated by ROS + gut microbial products)

Special — histology

ASH: steatosis >5%, lobular neutrophilic inflammation, ballooning, Mallory-Denk bodies (damaged cytokeratins), satellitosis, neutrophil-predominant portal infiltrate
Chicken-wire pericellular/perisinusoidal fibrosis on trichrome
Micronodular cirrhosis pattern

Special — long-term multi-organ effects

CNS: loss of motor control, alcoholic neuropathy, blackouts, anxiety/depression
CVS: irregular heartbeat, HTN, stroke, dilated cardiomyopathy
Respiratory: aspiration pneumonia, aggravates COPD/bronchitis/emphysema
GI: throat cancer, ulcers, fatty liver + cirrhosis, pancreatitis
Renal: dehydration, renal failure
MSK: Ca deficiency, osteoporosis, falls

Drug-induced liver injury (DILI)

C/P

3–10% of all ADRs; ~1 in 10 000–100 000 exposed
<5% jaundice cases; 30–50% of ALF
Mimics every other liver disease — no pathognomonic picture
Immune-allergic: rash, fever, eosinophilia
Viral-prodrome features sometimes precede jaundice

Inves

No specific test; clinical suspicion + drug hx + timing + exclusion
ALT >1000 U/L DDx: DILI, acute viral hep, hepatic ischaemia
Peripheral eosinophilia → allergic DILI
US to exclude biliary obstruction in cholestatic DILI
Biopsy: eosinophil infiltrate + granulomas hint at drug reaction
Avoid diagnostic re-challenge (severe reaction risk)

Mng

STOP causative agent (failure = high mortality)
Multi-drug culprit: most recently started most likely; stop all non-essential
NAC for paracetamol (may help non-paracetamol ALF, early-grade HE)
Corticosteroids for severe allergic/immune-mediated reactions
UDCA for cholestatic reactions (no clear trial benefit)
Transplant referral: INR >1.5 or HE

Special — Intrinsic vs Idiosyncratic

Intrinsic: dose-dependent, predictable, obligate, reproducible, short-latency; usually necrosis/steatosis; paracetamol, CCl₄, Amanita phalloides
Idiosyncratic: optional, host-dependent, unpredictable; broad histology; variable latency; biochemical ± immunological
Idiosyncratic subtypes: immunoallergic (weeks; rash/fever/eosinophilia; prompt rechallenge) vs metabolic (months; liver-only; delayed) vs mixed

Special — patterns by drug

Necrosis: paracetamol, methotrexate, tetracycline, valproate, salicylates, HAART, aflatoxin, amiodarone
Cholestatic hep: chlorpromazine, erythromycin, amitriptyline, co-amoxiclav, flucloxacillin, phenytoin, co-trimoxazole, NSAIDs, statins
Pure canalicular cholestasis: anabolic steroids, OCPs (oestrogens)
Granulomatous: hydralazine, carbamazepine, allopurinol, diltiazem, quinidine, quinine
Non-cirrhotic portal HTN: vitamin A, methotrexate
Avoid sulfonamides + chloramphenicol in pre-existing liver disease (inhibit P450)
Tetracyclines = directly hepatotoxic

Special — mechanisms (A–F)

A — cell lysis (membrane binding → ↑Ca²⁺ → mitochondrial damage → lysis; paracetamol)
B — cholestasis (duct damage, tight-junction disruption, BSEP inhibition; anabolic steroids, chlorpromazine)
C — adduct formation with proteins/lipids/DNA/CYP450 → ER damage (paracetamol, CCl₄)
D — allergen formation (hapten + carrier → immune destruction; idiosyncratic; diclofenac)
E — direct apoptosis triggering
F — mitochondrial damage (β-oxidation block, respiratory chain; CCl₄)

Special — Rappaport zonation & drug susceptibility

Zone 1 (periportal, near portal triad): highest O₂; high glutathione + sulfotransferase; fatty-acid oxidation; gluconeogenesis; most bile-acid secretion
Zone 2 (midzonal): shared functions
Zone 3 (centrilobular, near central vein): lowest O₂; highest CYP450 (esp. CYP2E1) → most susceptible to reactive-metabolite injury → paracetamol zone-3 necrosis

Special — idiosyncratic subtype rechallenge behaviour

Hypersensitivity: exposure weeks; systemic (rash, fever, eosinophilia); rechallenge PROMPT
Aberrant metabolism: exposure months; liver-only; rechallenge DELAYED
Mixed: variable; both features; rechallenge prompt

Special — hepatotoxic drug classes (know the class)

Antibiotics: amoxicillin-clavulanate, trimethoprim-sulfamethoxazole, fluoroquinolones, macrolides, nitrofurantoin, minocycline
Antiepileptics: phenytoin, carbamazepine, lamotrigine, valproate
Anti-TB: rifampicin, isoniazid
NSAID/analgesic: paracetamol, nimesulide, diclofenac
Hypolipidaemics: statins, niacin, fibrates
Anaesthetics: halothane, chloroform, isoflurane/enflurane/desflurane, nitrous oxide
Antirheumatic: sulfasalazine, gold, azathioprine, methotrexate
Antiretrovirals: PIs (ritonavir, indinavir, nelfinavir); NRTIs (lamivudine, tenofovir, zidovudine, didanosine); NNRTIs (nevirapine, efavirenz)

Paracetamol hepatotoxicity

C/P

Most common cause of ALF in Europe/US
Phase I (1–4 h): nausea, vomiting, abdominal discomfort
Phase II (1–3 days): latent — deceptively well
Phase III (3–10 days): overt damage / ALF — ~15% with overt injury die

Inves

Paracetamol level + toxicology screen
LFTs, INR, ABG/lactate, creatinine

Mng

Activated charcoal if within 4 h of ingestion
IV N-acetylcysteine (NAC) immediately — replenishes glutathione → detoxifies NAPQI
Liver transplant per King's College Criteria

Special

Zone 3 (centrilobular) necrosis — high CYP2E1 → toxic NAPQI
NAPQI = N-acetyl-p-benzoquinone imine, electrophilic
Glutathione conjugates NAPQI normally; depleted in overdose
NAC may help non-paracetamol ALF (except possibly ischaemic hep), esp. early-grade HE

Acute & end-stage

7 entries

Acute liver failure (ALF)

C/P

Definition: severe acute liver injury + INR ≥1.5 + ANY HE + <26 wks duration, no pre-existing liver disease
Fulminant hepatic failure (traditional): severe liver injury, potentially reversible, HE within 8 wk of first symptoms, no pre-existing liver disease
Hx: prior liver disease; symptom timeline; medications/toxins/herbal; FH (Wilson, thrombotic); recent surgery/anaesthetic
O/E: hypotension, altered mental status, fever, RUQ tenderness, nausea, jaundice, fluid overload

Classification by jaundice → HE interval

O'Grady: hyperacute (<1 wk) / acute (1–4 wk) / subacute (5–12 wk)
Bernuau: fulminant (<2 wk) / subfulminant (2–12 wk)
Japanese: acute (<10 d) / subacute (10 d–8 wk) / late-onset (8–24 wk)

Inves

Triage: hospital/ICU admit, transplant assessment, identify cause
Bloods: PT/INR, biochem panel, ABG+ammonia+lactate, FBC, paracetamol+tox, viral serology, ceruloplasmin, pregnancy test, autoimmune markers
US + Doppler — parenchyma + Budd-Chiari
Trans-jugular biopsy preferred (safer in coagulopathy)

Mng

4 main concerns: hypoglycaemia, raised ICP (cerebral oedema), renal impairment + metabolic acidosis, sepsis
Cautious fluids; nutrition; vasopressin for refractory hypotension; vit K; glucose monitoring; PPI prophylaxis
FFP/platelets only for active bleeding or pre-procedure (INR = prognostic)
Airway protection as HE worsens
Raised ICP: head up 30°, avoid stimulation, intubation, mannitol, hypertonic saline, controlled hyperventilation; ICP monitor in selected
Infection: continuous surveillance + prompt Rx (no routine prophylaxis)
Aetiology: activated charcoal for paracetamol if presented <4 h post-ingestion + NAC (also non-paracetamol ALF, esp. early HE — except ischaemic hep); HBV → entecavir/tenofovir; AIH → IV methylprednisolone 60 mg/day; Wilson/Budd-Chiari → transplant ± TIPS + anticoagulation
Extracorporeal support: MARS (non-biologic); HepatAssist (bio-artificial)
Renal: vasopressors (norepinephrine/dopamine); RRT as bridge
Herpesvirus (HSV/VZV) ALF → aciclovir
Pregnancy-related ALF (AFLP/HELLP) → delivery of the fetus

Special

Aetiology: viral (HAV/HEV pregnancy; HBV new/reactivation; HDV); drugs (paracetamol, idiosyncratic); toxins (Amanita, aflatoxin); ischaemic hep; ecstasy/cocaine; Budd-Chiari; AIH; Wilson; infiltrative malignancy; HELLP / acute fatty liver of pregnancy
King's College Criteria predict transplant need
Most common cause of death = cerebral oedema → raised ICP
Most common cause of overall death = sepsis
Untreated mortality >75% without transplant
Post-transplant mortality highest in first year (esp. first 3 months) from neuro complications or sepsis

physiology · background · low-yield

Mechanism

Hepatic failure without overt necrosis — hepatocytes viable but unable to perform function; e.g. tetracycline toxicity, acute fatty liver of pregnancy

Liver cirrhosis

C/P

Hand: clubbing, palmar erythema, Dupuytren's, leukonychia, asterixis
Face/oral: jaundice, pale mucous membranes, telangiectasia
Chest/endocrine: gynaecomastia, loss of secondary sexual hair, spider naevi
Compensated (asymptomatic): median >12 yr
Decompensated (ascites + jaundice + variceal bleed + HE): median 2 yr
Decompensation may regress with alcohol abstinence
Oesophageal varices on endoscopy = key prognostic factor in compensated cirrhosis

5-stage natural history (HVPG-anchored, 1-yr mortality)

Stage 1 — no varices, no ascites (HVPG 5–12 mmHg) → 1% 1-yr mortality
Stage 2 — varices, no ascites → 3%
Stage 3 — variceal bleeding (HVPG ≥12) → 20%
Stage 4 — first non-bleeding decompensation (HE) → 57%
Stage 5 — second decompensation (e.g. haematemesis after HE) → highest
Presence of varices distinguishes compensated Stage 1 vs Stage 2 (main prognostic split in compensated cirrhosis)

Inves

↑AST/ALT ratio in cirrhosis (also ischaemic, congestive, Budd-Chiari, TPN); test for coeliac in unexplained transaminitis
ALT/AST >1000 IU/L DDx: drug-induced hepatitis, acute viral hep, ischaemic hepatitis (LDH also ↑), mushroom poisoning
US + CT (ascites = black on US)
Child-Pugh: bilirubin, albumin, INR, ascites, HE (NOT ALT/AST)
MELD: bilirubin, INR, creatinine; recalc q3–6 months

Cirrhosis scoring — three uses

Diagnostic: International AIH group score (AIH dx)
Prognostic: MELD, UKELD, Child-Pugh, Maddrey DF, Lille model, Glasgow AH score
Descriptive: Knodell, NAFLD fibrosis score

Mng — compensated

Aetiology-specific: antiviral HBV/HCV; alcohol abstinence
Screen for oesophageal varices (endoscopy)
Primary prevention 1st bleed: NSBB or band ligation
HCC screen: 6-monthly US + AFP indefinitely
Lifestyle: abstinence, weight, careful drugs, avoid NSAIDs, vaccinate HAV/HBV

Mng — decompensated

Ascites: diuretics → LVP → TIPS
HE: lactulose → rifaximin if recurrent
MELD recalc q3–6 months
Liver transplant referral

Special — nutrition (ESPEN 2006)

Do NOT fast (rapid muscle catabolism — reduced glycogen storage → early gluconeogenesis on fasting; basal energy ↑, protein needs ↑)
Avoid fasting >3 h; several small meals; include bedtime snack (≥50 g complex CHO — but beware glucose intolerance)
Requirements ~2800 kcal + 105 g protein for a 70 kg man
Limit salt (esp. ascites)
Do NOT routinely limit protein (only briefly in active HE)
Compensated: gently ↓ total intake if obese; decompensated: ↓ fat/CHO but maintain/increase protein (esp. vegetable protein)
Weight-based nutritional assessment misleading — patients often centrally obese but muscle-depleted; inspection is vital

Special — gross

Yellow → nutritional/alcoholic; green → biliary; dark brown → haemochromatosis
Usually reduced size (except biliary — may enlarge)
Macronodular = poorer prognosis
Masson trichrome highlights fibrosis (blue) + regeneration nodules

Special — morphology

Micronodular <3 mm (uniform, e.g. alcoholic)
Macronodular >3 mm (up to 1–6 cm) — poorer prognosis
Mixed micro-macronodular

Special — aetiology (formal 7-category classification)

Post-hepatitic — HBV, HCV
Nutritional / alcoholic — Laennec's
Post-necrotic — after massive necrosis (drug, toxin, fulminant hep)
Primary biliary — intrahepatic (PBC, PSC)
Secondary biliary — extrahepatic obstruction (biliary atresia, gallstones, external LN compression)
Metabolic — haemochromatosis ("pigment cirrhosis" = "bronzed diabetes"), Wilson, α-1 antitrypsin, glycogen storage
Circulatory / vascular — cardiac cirrhosis (chronic venous congestion), veno-occlusive disease (VOD), Budd-Chiari

Special — collaterals

Gastro-oesophageal junction; rectum (rectal varices); diaphragm; retroperitoneum; umbilicus (caput medusae)

Ascites / SBP

C/P

Black on US; cardinal decompensation feature

Inves — SAAG

Every diagnostic paracentesis: cell count + diff, total protein, albumin
SAAG = serum albumin − ascitic albumin (see Criteria tab)
SBP: PMN ≥250 cells/mm³ without surgical source

Mng

Ladder: Na restriction ≤88 mEq (2 g)/day → spironolactone ± furosemide → LVP → TIPS for refractory
Avoid NSAIDs, ACEi, ARBs (worsen renal)
SBP: sample BEFORE antibiotics
SBP Rx: IV ceftriaxone (or PO norfloxacin BD) × 7 days
SBP adjunct: albumin 1.5 g/kg day 1 + 1 g/kg day 3 (↓HRS + mortality)
Repeat paracentesis: confirm >25% drop in PMN

Special

TIPS = transjugular intrahepatic porto-systemic shunt

Hepatic encephalopathy (HE)

C/P — West Haven

Stage 1: trivial unawareness, ↓attention, sleep abnormality, euphoria/depression, asterixis, tremor, incoordination
Stage 2: lethargy/apathy, disorientation, inappropriate behaviour, slurred speech, asterixis, ataxia
Stage 3: gross disorientation + confusion; arousable; asterixis usually absent
Stage 4: stupor and coma
Minimal HE: language/verbal skills preserved

Inves

Clinical staging; ammonia (prognostic only)

Mng

Treat precipitants: hypovolaemia, renal failure, GI bleed, infection (SBP, UTI, pneumonia), metabolic (hypokalaemic alkalosis, hypoglycaemia), sedatives/narcotics
First-line: lactulose (acidifies colon → ammonia trapping)
Recurrent: add rifaximin (semisynthetic rifampin; oral bioavailability <0.4%)

Special

Brain dysfunction from hepatic insufficiency or porto-systemic shunting

Hepatorenal syndrome (HRS)

C/P

Functional renal failure in advanced acute/chronic liver disease with portal HTN
Most common precipitant = bacterial infection, esp. SBP

Inves — AKI staging

Stage 1: creatinine ↑ ≥0.3 mg/dL or up to 2× baseline
Stage 2: 2–3× baseline
Stage 3: >3× baseline OR >4 mg/dL OR initiation of RRT

Mng

Initial: ↓/stop diuretics; volume replacement; stop nephrotoxics (antibiotics, NSAIDs, ACEi/ARBs); treat infection
Vasoconstrictors: terlipressin; midodrine + octreotide; norepinephrine
Albumin infusion for volume
Liver transplant = definitive

Special

Mechanism: splanchnic vasodilation → perceived hypovolaemia → RAAS → intra-renal vasoconstriction

Portal hypertension

C/P

Sequelae: collaterals + splenomegaly; ascites; HE; hyperdynamic circulation; multi-organ dysfunction

Inves

HVPG gold standard (invasive); ≥5 mmHg PHT; ≥10 mmHg clinically significant; varices at 10–12
Doppler US most widely used; B-mode, CT, MR, EUS, angiography
Haematological clues: ↑NLR; hypersplenism cytopenias
Normal portal pressure 5–10 mmHg

Mng — staged variceal therapy

Pre-primary prophylaxis (no varices) → prevent formation
Primary prophylaxis (varices but never bled): NSBB (propranolol) OR EVL
Acute haemorrhage → stop bleed + prevent early rebleed
Secondary prophylaxis: NSBB + EVL; TIPS or surgical shunt if fails
Recurrent bleed → transplant evaluation

Special — anatomy

Pre-hepatic: splenic vein thrombosis; portal vein thrombosis
Intrahepatic: pre-sinusoidal (schistosomiasis); sinusoidal (cirrhosis = most common); post-sinusoidal (VOD/SOS)
Post-hepatic: IVC thrombosis; hepatic vein thrombosis (Budd-Chiari); constrictive pericarditis
NCPHT <10%

Special — mediators

↑portal flow (hyperkinetic splanchnic) + ↑intrahepatic resistance (cirrhotic distortion)
Vasodilators: NO, glucagon, prostaglandins, bile acids, TNF-α, CO

Variceal haemorrhage

C/P

Annual rate ~15%/yr; mortality of 1st bleed 7–15%
Highest risk: large varices; red wales; severe liver disease (Child-Pugh)

Inves

Emergency endoscopy within 12 h

Mng

ABC + ICU + haemodynamic stabilisation
Restrictive transfusion: Hb 7–8 g/dL (over-transfusion → ↑portal pressure → rebleed)
Prophylactic antibiotics: fluoroquinolone (norfloxacin/ciprofloxacin) OR ceftriaxone
Vasoactive BEFORE endoscopy: terlipressin, vasopressin, somatostatin, octreotide
EVL (banding) endoscopy of choice; sclerotherapy if EVL difficult; 4–5 sessions typical
Salvage: TIPS

Special — secondary prophylaxis

NSBB + EVL combination first-line
Child-Pugh = main predictor of rebleeding and death
Failure → TIPS or surgical porto-caval shunt; evaluate for transplant

Vascular

3 entries

Budd-Chiari syndrome

C/P

Triad: hepatomegaly + ascites + RUQ pain (Glisson's capsule stretching)
Forms: acute fulminant (with ALF), acute, subacute, chronic
Acute/subacute very painful; chronic less so
Pregnant women at risk of fulminant
Chronic: may be asymptomatic; hepatomegaly ± jaundice, abdominal pain, ascites, splenomegaly + PHT
IVC obstruction: lower-limb oedema; dilated abdominal-wall veins filling from below upwards
Untreated acute mortality high; chronic 5-yr survival >2/3

Inves

US/CT/MRI — hepatic-vein occlusion + diffuse abnormal parenchymal enhancement
Pulsed/colour Doppler — abnormal hepatic-vein flow
Hepatic venography pre-intervention
Mandatory thrombophilia screen (multiple coag defects)
~2% concurrent portal vein thrombosis
Ascites = high-protein
Histology: centrizonal congestion, centrilobular haemorrhage, fibrosis, eventual cirrhosis
Negative hepatojugular reflux (vs +ve in right-sided HF)

Mng

Medical: anticoagulation ± thrombolytics; diuretics; treat underlying (e.g. polycythaemia)
Interventional: TIPS; angioplasty ± stenting; surgical porto-caval shunt
Caval stent first if caval obstruction before surgical shunting
Liver transplant — first choice for chronic + fulminant
Lifelong anticoagulation post-TIPS or transplant

Special

Hypercoagulable: APS, antithrombin/factor V Leiden/protein C-S deficiency, MPDs (esp. polycythaemia vera), pregnancy/postpartum, OCPs, PNH, intra-abdominal cancers (esp. HCC)
Misc: Behçet disease
Distinguishes from cirrhosis by acute/subacute onset
Additional aetiologies beyond hypercoagulability: infection (hydatid cyst, liver abscess) and malignant compression (tumour compressing/invading hepatic veins ± hypercoagulable state)

20a

Portal vein thrombosis (PVT)

C/P

Pre-hepatic cause of portal hypertension
Acute: abdominal pain, fever, may have mesenteric ischaemia if extension to SMV
Chronic (cavernous transformation): features of portal HTN — variceal bleed, splenomegaly, ascites (less prominent than cirrhotic)
Often asymptomatic if partial + chronic; may be incidental

Aetiology

Cirrhosis (most common; up to 25% of cirrhotics on imaging)
Malignancy: HCC, pancreatic, gastric (tumour thrombus or bland)
Prothrombotic: MPDs (JAK2 V617F), APS, factor V Leiden, protein C/S/AT deficiency, PNH, OCP/pregnancy
Intra-abdominal sepsis / inflammation: pancreatitis, cholangitis, appendicitis, IBD, diverticulitis (pylephlebitis)
Post-splenectomy; abdominal surgery; trauma

Inves

Doppler US = first-line (absent/reversed flow; echogenic thrombus)
Contrast CT / MR venography — extent, cavernoma, mesenteric involvement
Thrombophilia screen (esp. JAK2 V617F for occult MPD)
Endoscopy for varices (all chronic PVT)

Mng

Acute non-cirrhotic PVT: anticoagulation (LMWH → warfarin/DOAC) ≥6 months; lifelong if underlying prothrombotic state
Consider thrombolysis / TIPS in selected acute cases with mesenteric ischaemia
Chronic PVT with varices: standard variceal management (NSBB + EVL); anticoagulation individualised
Treat underlying cause (MPD → hydroxycarbamide; sepsis → antibiotics)
Liver transplant candidacy: non-malignant non-extensive PVT is NOT a contraindication

Special

Cavernous transformation = network of hepatopetal collaterals around occluded PV; sign of chronic PVT
Concurrent PVT in ~2% of Budd-Chiari
Splenic + PVT → left-sided portal HTN with large gastric varices (may bleed)

Sinusoidal obstruction syndrome (SOS / VOD)

C/P

Formerly veno-occlusive disease
Originally Jamaican "bush tea" drinkers (pyrrolizidine alkaloids)
Resembles Budd-Chiari clinically; severe non-resolving by 3 months may be fatal
Post-BMT: first 20–30 days; ~20% of recipients

Inves

Clinical + imaging

Mng

Supportive

Special

Cyclophosphamide + total-body irradiation in BMT setting
Pathology: toxic injury to sinusoidal endothelium → thrombi → RBC into space of Disse → stellate-cell proliferation → fibrosis of terminal hepatic veins

Tumours

5 entries

Hepatocellular carcinoma (HCC)

C/P

5th most common cancer; 2nd cancer death; ~7% of all cancers
~90% of primary liver cancers
~90% have known aetiology; biggest single cause = cirrhosis
Western: up to 90% on background cirrhosis
Aetiologies: HCV, HBV, alcohol, aflatoxin; rising with NAFLD

Inves

Surveillance: 6-monthly US + AFP in high-risk
Non-invasive Dx: multiphasic CT, dynamic CE-MRI, CEUS
Characteristic: arterial-phase hyperenhancement + portal-venous/delayed "washout"
Mechanism: tumour 100% hepatic artery supplied (normal liver 75% portal, 25% artery)

Mng

BCLC staging (tumour burden + liver function + performance status)
MDT decisions
Options: surgical resection; transplantation; TACE; systemic (atezolizumab/bevacizumab, TKIs); best supportive care
Prevention: universal HBV vaccination; antiviral HBV/HCV; NAFLD lifestyle

Special — gross/micro

Gross: multinodular; single mass; diffuse/massive
Micro: trabecular (thickened plates, little stroma); acinar; solid (anaplasia)
Fibrolamellar variant: columns of large eosinophilic hepatocytes + parallel lamellar collagen; younger non-cirrhotic; much better prognosis

Special — full primary liver tumour classification (pathology lecture)

Benign: cavernous haemangioma (most common), focal nodular hyperplasia (FNH), hepatocellular adenoma (HCA), bile duct adenoma
Malignant primary: HCC (~90%), cholangiocarcinoma (intrahepatic ICCA), fibrolamellar HCC, hepatic angiosarcoma (vinyl chloride, arsenic, thorotrast), hepatoblastoma (paediatric)
Malignant secondary: metastases (colorectal, breast, lung, pancreas, stomach, melanoma) — commonest liver malignancy overall
Other malignant infiltrative: primary hepatic lymphoma (rare); hepatic sarcoma; leukaemic infiltration

Cholangiocarcinoma (CCA)

C/P

Intrahepatic (ICCA) vs extrahepatic
1-yr survival ~27.6%; 5-yr <10% (advanced at diagnosis)
Non-specific: abdominal pain, ↓appetite, weight loss, malaise, night sweats

Inves

CT + MRI
ICCA: progressive enhancement through arterial + venous phases (delayed, opposite to HCC washout)
Capsular retraction; vascular encasement → lobar atrophy; peripheral bile-duct dilatation
Biopsy required (imaging not specific)
CA 19-9: sens 62%, spec 63%; also raised in pancreatic adenocarcinoma

Mng

Resection median survival ~36 months
<30% resectable even at expert centres
Inoperable: gemcitabine + cisplatin

Special

Single most important RF = PSC (~1.5%/yr after PSC diagnosis)
Other RFs: smoking, alcohol, age >65, liver fluke, Caroli's disease, choledochal cyst, bile-duct adenoma, chronic intrahepatic stones, vinyl chloride, cirrhosis

Hepatic haemangioma

C/P

Most common primary liver tumour; ~5% prevalence
F > M; 30–50 yr
Usually solitary <4 cm (rarely 20 cm)
Most asymptomatic; >10 cm may compress and become symptomatic
Complications rare

Inves

US: homogeneous hyperechoic + sharp margin + posterior acoustic enhancement
US alone sufficient if <3 cm and no underlying liver disease
CEUS/CT/MRI: peripheral nodular arterial enhancement → centripetal fill-in → homogenisation

Mng

Conservative — benign course, no imaging follow-up
OCPs/pregnancy NOT contraindicated
MDT referral if growing or symptomatic

Focal nodular hyperplasia (FNH)

C/P

~0.03% prevalence; up to 90% female; 35–50 yr
Most solitary <5 cm, stable
Asymptomatic; complications extremely rare

Inves

CEUS/CT/MRI ~100% specific when typical
MRI best — central scar pathognomonic; otherwise homogeneous

Mng

Conservative observation
OCPs NOT contraindicated
Pregnancy follow-up unnecessary

Special

Central scar = pathognomonic imaging feature

Hepatocellular adenoma (HCA)

C/P

~0.001–0.004% prevalence; F:M ~10:1; peak 35–40 yr
30–40× ↑ incidence with long-term OCP use; androgenic steroids in males
Rising with obesity + metabolic syndrome
Serious complications: haemorrhage/rupture; malignant transformation to HCC — both especially with ≥5 cm

Inves

MRI = imaging of choice; subtypes HCA in ~80% (fat + vascular space)
Biopsy needed for ~20% MRI cannot subtype
β-catenin mutation → higher malignant transformation

Mng

Universal: STOP OCPs (only benign liver tumour where OCPs must stop); weight loss
Resection regardless of size: males; any β-catenin mutation
Resection in women: ≥5 cm or any growing lesion
<5 cm not meeting criteria: reassess at 1 year then annual imaging
Bleeding HCA + instability → trans-arterial embolisation

Special

History of OCP use → suspect HCA
Drugs to ask about: OCPs, methotrexate, tamoxifen, androgens/anabolic steroids

Metabolic & cholestatic

5 entries

Hereditary haemochromatosis

C/P

AR; HFE C282Y homozygous (or compound het C282Y/H63D); low penetrance
Liver (most common end-organ): cirrhosis → HCC; ↑transaminases + RUQ pain
Cardiac: restrictive or dilated cardiomyopathy; late arrhythmias
"Bronze diabetes" — pancreatic iron → DM
Arthropathy: 2nd & 3rd MCP joints; does NOT improve with iron depletion
Skin hyperpigmentation ("bronze")
↑infection susceptibility
Hypogonadism (amenorrhoea / impotence)

Inves

Serum transferrin saturation (TS) >45% → further eval; more sens + spec than ferritin
Ferritin non-specific (inflammation, NAFLD, alcohol)
HFE genotype if TS >45% or ferritin ↑
Screen 1st-degree relatives
Parenchymal iron on liver biopsy demonstrated with Perls' Prussian blue stain

Mng

Therapeutic phlebotomy 500 mL weekly/bi-weekly
Check ferritin q10–12 phlebotomies
Target ferritin 50–100 µg/L; maintenance intermittent
AVOID vitamin C supplements (enhances iron absorption)
Chelators if phlebotomy contraindicated: deferoxamine (Desferal), deferasirox (Exjade)

Special

Other organs: pituitary, thyroid
Mechanism: direct oxidative + stimulation of fibrogenesis
Rare non-HFE: HFE2 (hemojuvelin), HAMP (hepcidin), TfR2, SLC40A1 (ferroportin)
Iron overload → ↑ susceptibility to iron-loving organisms, classically Vibrio vulnificus and Yersinia enterocolitica

physiology · background · low-yield

Mechanism

Core mechanism = low hepcidin → ferroportin remains active on enterocytes → unregulated intestinal iron absorption (up to ~3.5 mg/day) → transferrin-bound iron deposits in tissues

Physiology

Dietary iron ~7 mg/1000 kcal: haem iron <10% of intake but ~30% absorbed vs non-haem >90% of intake but <5% absorbed (absorption ↑ by vitamin C/amino acids, ↓ by phytates/tannins/phosphates); total body iron distribution = Hb 65%, ferritin 29%, myoglobin 4%, enzymes 2%

Wilson's disease

C/P

AR; defective ATP7B → ↓biliary Cu excretion + ↓ceruloplasmin incorporation
Hepatic: presents earlier (mean 10–12 yr); cirrhosis ± ALF
Neurological: 3rd–4th decade; dysarthria, clumsiness, tremor, drooling, gait disturbance, mask-like facies, ↓handwriting → rigidity/Parkinsonism, flexion contractures, spasticity, athetosis
Psychiatric: early subtle behavioural/academic ↓; late personality change, lability, antisocial, depression, ↑sexual preoccupation, psychosis
Ophthalmologic: Kayser-Fleischer rings (~100% with neuro; 40–50% hepatic-only); sunflower cataracts (Descemet membrane)
Renal: prox & distal RTA; proteinuria/haematuria
Skeletal: osteopenia/osteoporosis, arthropathy

Inves

Low ceruloplasmin (normal 20–40 mg/dL) in ~95%
Non-ceruloplasmin (free) Cu to monitor chelation
24-h urinary Cu >100 µg/24h
Liver biopsy hepatic Cu >250 µg/g dry liver
ATP7B genetic testing; slit-lamp for K-F rings; MRI brain (basal ganglia)

Mng

Low-Cu diet (avoid shellfish, organ meat, mushrooms, chocolate, nuts)
D-penicillamine ~20 mg/kg/day divided (first-line chelator)
Alternatives: trientine; zinc
Baseline: 24-h urinary Cu, serum Cu, ceruloplasmin, FBC+platelets, INR+LFTs, urinalysis
Liver transplant for fulminant/ALF

Special

Free Cu drives extrahepatic deposition — basal ganglia + Descemet membrane

physiology · background · low-yield

Mechanism

Pathogenesis: defective ATP7B → hepatocellular Cu accumulation → free-radical oxidative injury (lipids/proteins/nucleic acids) + antioxidant depletion + copper-metallothionein polymerisation → hepatocyte necrosis & apoptosis

Mechanism

Zinc blocks intestinal copper absorption; preferred sequence = chelator (D-penicillamine or trientine) to "de-copper" first → maintenance with zinc; trientine reserved for D-penicillamine-intolerant patients

α-1 antitrypsin deficiency

C/P

Most common metabolic liver disease in childhood
AR co-dominant; up to 1 in 1800 live births
Liver — gain of function (retained misfolded protein in hepatocyte ER); ~10% adults, 10–15% children develop CLD
Infancy: persistent cholestatic jaundice; small for gestational age
10–30% children develop moderate-severe liver disease (coagulopathy, poor growth, ascites)
Lung — loss of anti-elastase → emphysema (60–70% adults >25 yr; peak 4th–5th decades)

Inves

Serum α-1 AT level (caveat: acute-phase reactant — falsely ↑)
Pi genotype
Liver histology
Pi genotype — PiZZ is the most severe phenotype
Liver histology: characteristic PAS-positive, diastase-resistant globules in hepatocytes (retained misfolded α-1 AT)

Mng

Paediatric supportive: fat-soluble vitamins (A, D, E, K); MCT-oil infant formula
Absolute avoidance of cigarette smoking + environmental pollutants
Purified/recombinant α-1 AT replacement → ↓FEV₁ decline (lung disease)
Liver transplant curative for hepatic disease + corrects α-1 AT deficiency

Special

No specific therapy for hepatic disease — supportive only

physiology · background · low-yield

Background

Consider the diagnosis in all adults/children with chronic hepatitis or cirrhosis of unknown origin

Primary biliary cholangitis (PBC)

C/P

F:M = 9:1; onset >30 yr; insidious; more common in smokers
Earliest symptom = fatigue (often years before Dx)
Most common presenting complaint = pruritus (may precede jaundice by months/years)
Bone pain/fragility (cholestasis → vit D malabsorption → osteoporosis)
Xanthelasma (hyperlipidaemia)
NO fever/rigors in uncomplicated PBC (vs ascending cholangitis)
Mild hepatomegaly common; splenomegaly with portal HTN

Inves

Cholestatic LFTs: ↑ALP + bilirubin out of proportion to transaminases
ALP non-specific (liver, intestine, bone, placenta)
AMA in >95% (vs pyruvate dehydrogenase complex)
ANA + ASMA in ~15%
HLA-DR8 associated
US first-line (exclude obstruction); MRCP imaging of choice
Biopsy only if diagnostic uncertainty
Histology: chronic granulomatous portal inflammation → loss of small/medium intrahepatic bile ducts → fibrosis → biliary cirrhosis

Mng

UDCA 13–15 mg/kg/day lifelong — first-line for all
Pruritus: cholestyramine
Fat-soluble vit replacement (A, D, E, K)
Screen for coeliac (prevalence ↑)
DEXA baseline + follow-up
Calcium + vit D; bisphosphonates for osteoporosis (caution with varices)
Transplant referral: complications of cirrhosis; severe disease; severe medically resistant pruritus

Special

AMA targets pyruvate dehydrogenase complex
Associations: Hashimoto's thyroiditis; Sjögren (dry eye, dry mouth); coeliac; systemic sclerosis
PSC (not PBC) associates with IBD

physiology · background · low-yield

Mechanism

Cholestyramine acts by binding intestinal pruritogens → ↑faecal excretion

Background

Cholestasis termed chronic if lasting >6 months; hepatic origin of ↑ALP supported by concurrent ↑GGT and/or ↑conjugated bilirubin

Primary sclerosing cholangitis (PSC)

C/P

Male predominance ~2:1; age 25–40
Fatigue, intermittent jaundice, RUQ pain, pruritus
Strongest association: IBD, particularly ulcerative colitis

Inves

Cholestatic LFTs — ALP and bilirubin fluctuate widely
p-ANCA in ~80%
MRCP = first-line imaging
ERCP only for tissue/therapy
Cholangiographic hallmark: patchy "beading" — strictures + normal/dilated segments
Histology: periductal "onion-skin" fibrosis + periductal inflammation/portal oedema + bile-ductular proliferation; late = obliterative cholangitis → "vanishing bile-duct syndrome" → biliary cirrhosis
Diagnostic criteria: generalised beading/stenosis + no choledocholithiasis/prior duct surgery + exclude bile-duct cancer

Mng

No medical cure
UDCA controversial; NOT routine; high-dose 28–30 mg/kg/day reported harm
Pruritus: cholestyramine
Dominant stricture → biliary dilatation preferred over stenting
Transplant for end-stage

Special

Most common cause of death (untransplanted) = cholangiocarcinoma
Associations: IBD (UC esp.), coeliac, thyroid, Sjögren, T1DM, systemic sclerosis, retroperitoneal fibrosis, autoimmune haemolytic anaemia, sarcoidosis, RA
Complicated cholangitis (fever + rigors) — typical of PSC superinfection
Vanishing bile-duct syndrome = late ductopenia

Infections

3 entries

Amoebic liver abscess

C/P

Entamoeba histolytica protozoan
Incubation 2–4 weeks
~50 M invasive cases/yr; 40 000–100 000 deaths/yr; 10–20% symptomatic
2nd leading parasitic cause of death
Most common extraintestinal amoebiasis; ~10× more frequent in men
~80% present within 2–4 wks; 95% travel cases within 5 months
Fever 85–90%; tender hepatomegaly 30–50%; right lower intercostal tenderness 84–90%
Weight loss 33–50%; basal rales / ↓breath sounds right lung base
Jaundice unusual (6–10%)
Amoebic colitis: gradual onset 1–2 weeks; bloody/watery diarrhoea; cramping pain; weight loss; fever in only 10–30%
Atypical in children: rectal bleeding without diarrhoea; mimics appendicitis

Inves

Leucocytosis early; anaemia in chronic; LFTs not useful
Serology: indirect haemagglutination + complement fixation; negative serology excludes Dx
Stool microscopy not useful for liver abscess
US: solitary homogeneous hypoechoic round lesion postero-superior right lobe (70–80%)
CT contrast: rounded low-attenuation + enhancing rim ± septated ± fluid levels
MRI: high T2 signal, peri-lesional oedema, ~86% rim enhancement after gadolinium
Resolution may take up to 2 yrs on imaging
Aspirate: "anchovy paste" — odourless thick yellow-brown; NO leucocytes (lysed by trophozoites)

Mng

Metronidazole 750 mg PO TDS × 5–10 days (intestinal + hepatic)
Alternatives: emetine, dehydroemetine, chloroquine
Luminal post-metronidazole: diloxanide furoate, di-iodohydroxyquinoline
Aspiration indications: abscess >12 cm; imminent rupture; medical failure; left-lobe
Aspiration: 9th-10th IC space between anterior + posterior axillary lines under US/CT
Start drug therapy several days before aspiration; NEVER inject drug into cavity
Surgical drainage rarely — great morbidity/mortality
Endoscopy for intestinal amoebiasis if stool negative
Contraindication: fulminant amoebic colitis (perforation risk)

Special

Aspirate has NO leucocytes
Extra-hepatic: pleuropulmonary (right-sided effusion/empyema/pneumonia/lung abscess); peritoneal (tender rigid distended abdomen); pericardial (CHF + friction rub); cerebral (altered conscious + focal); cutaneous/genital (punched-out ulcers + profuse discharge)
Colitis complications: fulminant/necrotising colitis, toxic megacolon, ameboma (granulomatous mass mimicking carcinoma), recto-vaginal fistula
Liver abscess complications: rupture (peritoneal/thoracic/pericardial) ± 2° bacterial; direct extension; haematogenous → brain abscess
Mortality uncomplicated <1%; rupture 2–7%
E. dispar ~10× more common; morphologically identical; non-pathogenic

32a

Pyogenic liver abscess

C/P

Bacterial liver abscess — key DDx to amoebic (clinically + radiologically similar)
Fever + rigors + RUQ pain + tender hepatomegaly + jaundice more common than in amoebic
Sepsis features may dominate (esp. cryptogenic + biliary origin)
Right lobe most common; solitary or multiple (multiple → biliary or haematogenous source)
Mortality still ~10% even with modern treatment

Aetiology / route

Biliary tract (most common): ascending cholangitis, cholangiocarcinoma, biliary stones/strictures, post-ERCP
Portal (pylephlebitis): appendicitis, diverticulitis, IBD, perforated viscus
Haematogenous (hepatic artery): systemic bacteraemia, endocarditis
Contiguous spread: cholecystitis, subphrenic abscess
Traumatic / iatrogenic: post-biopsy, post-embolisation, penetrating trauma
Cryptogenic (up to ~50%)

Organisms

E. coli, Klebsiella pneumoniae (increasingly — SE Asia, DM patients, metastatic infection risk incl. endophthalmitis)
Streptococcus milleri group, Enterococcus, Bacteroides fragilis + other anaerobes
Often polymicrobial (esp. biliary/portal source)
Fungal (Candida) in immunocompromised

Inves

Leucocytosis, ↑CRP, ↑ALP/GGT (>>bilirubin often)
Blood cultures (positive in ~50%)
US → CT with contrast: rim-enhancing multiloculated collection ± gas
Percutaneous aspiration → Gram, culture, sensitivities (aspirate = frank pus, foul-smelling, WITH leucocytes — unlike amoebic "anchovy paste")
Serology to exclude amoebic if endemic exposure

Mng

Empiric broad-spectrum IV antibiotics ASAP (piperacillin-tazobactam OR ceftriaxone + metronidazole); tailor to culture; 4–6 weeks total (2 wk IV → oral)
Percutaneous drainage under US/CT (needle aspiration for small <5 cm; catheter drainage for larger/multiloculated) — cornerstone of source control
Surgical drainage: failed percutaneous, ruptured, multiple large, associated surgical pathology
Treat underlying source (ERCP for biliary obstruction, appendicectomy, etc.)

Special

Klebsiella "invasive syndrome" (esp. K1 serotype): liver abscess + metastatic endophthalmitis + meningitis, associated with DM + SE Asian ethnicity
Distinguishing amoebic vs pyogenic clinically difficult → serology + aspirate cytology differentiate; CT >98% accurate at excluding hydatid

Hydatid disease

C/P

Larval cestodes; dogs = definitive host; humans = accidental intermediate
Many asymptomatic for years
History: residence/travel endemic; food/water contaminated by dog faeces
Symptoms if cyst >5 cm (smaller in brain/eye)
Liver 63%; lungs 25%
Allergic: urticaria, erythema (leaked antigens)
Jaundice → biliary obstruction; hypotension → anaphylaxis (cyst leak)
Tender hepatomegaly ± palpable mass; ascites rare
Tender hepatomegaly + fever + chills → 2° infection
Splenomegaly: primary splenic cyst or PHT
Pulmonary: ↓breath sounds, airway obstruction

Inves

Bilirubin/ALP ↑ if biliary involvement
Leucocytosis → 2° infection; eosinophilia ~25%
Hypogammaglobulinaemia ~30%
Serology: IHA + ELISA; ~80% sens (~90% hepatic; ~40% pulmonary)
Confirmation: immunodiffusion + immunoelectrophoresis (antigen 5)
Plain film: "eggshell calcification" rim
US 90–95% hepatic; daughter cysts + hydatid sand (snowstorm)
CT ~98% accurate — best for distinguishing from amoebic/pyogenic
MRI no advantage over CT
Casoni intradermal NO longer used

Mng

Prevention: hygiene, food cleansing, livestock regulation, stray-dog control, praziquantel 5 mg/kg deworming pet dogs in endemic areas; stop feeding viscera
Medical (benzimidazoles): inoperable; ≥2 organs; peritoneal
Albendazole 10–15 mg/kg/day in 1-month courses with 14-day intervals × 3–6 months
Mebendazole 40–50 mg/kg/day × 3–6 months
BMZ contraindications: pregnancy, BM suppression, chronic hepatic disease, large rupture-risk cysts, inactive/calcified
BMZ outcomes: ~30% cure; 30–50% improvement; 20–40% no change
PAIR (Puncture, Aspiration, Injection scolicidal ≥15 min, Re-aspiration): >5 cm + Gharbi I/II; peri-op BMZ 4 days pre + 1–3 months post
PAIR indications: inoperable, refuse surgery, segments I/II/III multiple, relapse
PAIR contraindications: pregnancy, lung cysts, inaccessible, superficial, Gharbi II honeycomb/IV, biliary communication
PAIR risks: spillage/anaphylaxis (use transhepatic puncture for superficial), chemical sclerosing cholangitis, biliary fistulas
Surgery: large liver cysts + daughter cysts; biliary communication; infected; lung/brain/kidney/eye/bone
Radical: total pericystectomy or partial liver resection
Conservative: open cystectomy; simple tube drainage
Peri-op BMZ 4 days pre + 1 month post → ↓2° echinococcosis

Special

Cyst structure: pericyst (fibrous) → laminated membrane (acellular permeable) → germinal layer (produces scolices)
Complications: recurrence; metastasis (esp. alveolar); 2° infection; spillage/seeding → anaphylactic shock
BMZ AEs: hepatotoxicity, anaemia, thrombocytopenia, alopecia, embryotoxicity, teratogenicity
Operative spillage 2–25%; mortality 0.5–4%
Alveolar echinococcosis untreated 10-yr mortality 94% → 10% with long-term chemotherapy

Transplant

1 entries

Liver transplantation

Indications

Top: ESLD (LCF + complications); HCC within criteria
Less frequent: AIH; fulminant hep failure (per KCC); PSC; metabolic liver diseases; Budd-Chiari

Listing criteria

Recipient eval: pulmonary, cardiac, renal, psychological
Who/When/How decision framework
MELD components: creatinine, bilirubin, INR
MELD ≤14 → not routinely listed
MELD >15 valid; Child-Pugh >9 (Child C) + MELD >15 accepted
MELD >30 → individual review (prohibitive)
MELD <15 + Child B → monitor for progression

Contraindications

Absolute: uncontrolled active sepsis; advanced cardiopulmonary disease; HCC beyond criteria; active alcoholism; extrahepatic malignancy
Relative: age >70; HIV; extensive splanchnic venous occlusion; BMI >30; previous upper-abdominal surgery
Non-malignant non-extensive PVT NOT contraindication

Donor & outcomes

Living donor: age <45; BMI <28; relative recommended; no chronic disease/drug abuse; no pregnancy/hormonal for >1 yr post-op; no prior upper-abdo surgery (cholecystectomy excepted); ABO compatible; serologically negative; psychologically stable
Donor workup: hx + exam, labs, drug screen, virology (HAV, HBV, HCV, HIV, HSV, VZ, EBV, CMV), tumour markers (AFP, PSA, CEA, CA19-9), HBV vaccination, chest/cardiac/psych, US, CXR, duplex, mammography, MRCP + biopsy
Right-lobe graft 60–80% liver mass
Graft-to-recipient body-weight ≥0.8%
Survival: 1 yr 88–90%; 2 yr 80–85%; 5 yr 70–75%
Early complications: primary non-function ~2%; technical (arterial/biliary) 10–12%; acute rejection; infection
Long-term: recurrence of primary disease; HTN/renal/dyslipidaemia/DM/malignancy (PTLD, skin) — 5/6 immunosuppression-related
Donor: 30–40% complications; PE, PVT, bile-duct injury, liver insufficiency

Immunosuppression

Liver transplant requirement DECREASES over time (vs kidney/heart)
Combination: CNI (tacrolimus or cyclosporine) + steroids (methylprednisolone) + antiproliferative (mycophenolate mofetil) + sirolimus (mTOR)
Phases: induction → maintenance → rescue (during rejection)
Mechanisms: steroids ↓cytokine transcription; azathioprine/mycophenolate ↓lymphocyte proliferation (anti-purine); CNI block IL-2 transcription → T-cell activation; mTOR block IL-2 receptor signal; ALG depletes lymphocytes; anti-CD25 (activated T), anti-CD52 (broad), anti-CD20 (B cells)
Cyclosporine classic renal toxicity

Infection windows

First 6 months: viral (CMV, HBV, HSV)
First month: bacterial (wound, respiratory, urinary)
First 3 months: fungal (Pneumocystis jirovecii, Candida, Aspergillus); chemoprophylaxis up to 6 months
TB reactivation in previously infected / endemic-area patients

Rejection

Lifelong immunosuppression mandatory
Acute cellular rejection = most common; within first 3 months (any time); cytotoxic T-cell attack
Acute Rx: high-dose IV methylprednisolone 500–1000 mg pulse × 1–3 days + taper; escalate baseline IS
Treated acute rejection — no adverse long-term impact
Chronic rejection: doesn't resolve; permanent tissue change → graft loss; incidence 3–17% (↓ with tacrolimus)
Chronic Rx: escalate IS + add mTOR (sirolimus/everolimus) — reverses ~50%; re-transplant if no response

Gallbladder & biliary

11 entries

Cholelithiasis (gallstones)

C/P

Adult prevalence: 10–15% (clinical lecture); pathology lecture cites "up to 20% of Western adults"
75% asymptomatic; ~1–2%/yr become symptomatic
20% intermittent biliary pain; 10% acute cholecystitis; <0.1% Mirizzi; 5% gallstone pancreatitis; long-standing → GB carcinoma <0.1%

Inves

US first-line; AXR — only 10% radio-opaque
CT: emphysematous cholecystitis (intramural/luminal gas) or porcelain GB (mural opacification)

Mng

Asymptomatic → observe
Symptomatic → elective laparoscopic cholecystectomy
Prophylactic cholecystectomy: pre-organ transplant; porcelain GB; large stone >2–3 cm or paediatric/congenital haemolytic anaemia about to undergo major op
General rule: fix the complication first, then deal with GB
MRCP diagnostic; ERCP diagnostic + therapeutic

Special — normal bile composition

70% bile salts/bile acids | 10% cholesterol | 5% phospholipids (mainly lecithin) | 5% proteins | 1% conjugated bilirubin | water/electrolytes/bicarbonate
Cholesterol water-insoluble; kept in solution by amphiphilic bile salts + lecithins → mixed micelles

Special — stone composition & mechanisms

Cholesterol stones (80%): supersaturation of bile with cholesterol → precipitation → nucleation (GB hypomotility, mucus hypersecretion as scaffold) → stone
— Pure cholesterol: rare, single, oval, large, smooth/granular, yellow-white; radiating crystals on cut section; radiolucent (no Ca)
— Mixed cholesterol: 50–99% cholesterol monohydrate + small CaCO₃ ± bilirubin; multiple, multifaceted, <2 cm; laminated; 15% radiopaque
Pigment stones (20%):
— Black (mostly in GB): NONbacterial/NONenzymatic hydrolysis of conjugated bilirubin → unconjugated → COO⁻ anion at bile pH → binds Ca²⁺ → calcium bilirubinate + mucin + cholesterol; 50–75% radiopaque; haemolysis, severe ileal dysfunction, cirrhosis, sclerosing cholangitis
— Brown (mostly in bile ducts): bacterial enzymatic hydrolysis (E. coli β-glucuronidase + phospholipase) → Ca bilirubinate + Ca palmitate + mucin/cholesterol; radiolucent; laminated soft soapy/greasy; requires bile-duct infection (cholangitis, choledocholithiasis)

Special — risk (6 F's)

Fair, Female, Forty, Fat, Fertile, Family hx
Female via OCPs + pregnancy
>50% prevalence in >80 yr
Additional: rapid weight loss; GB stasis; bile-acid metabolism inborn errors; clofibrate

Biliary colic

C/P

Spasmodic RUQ pain ~30 min after fatty meal
Mechanism: rhythmic GB contraction against stone in cystic duct
Pain subsides when stone falls back into GB or passes into CBD
Duration <6 h (vs cholecystitis >6 h); no inflammation
Referred to right shoulder tip; hyperaesthesia in back
May fluctuate but continuous; vomiting + retching common

Mng

Elective laparoscopic cholecystectomy + perioperative antibiotics

Acute cholecystitis

C/P

90–95% calculous (cystic duct or GB neck obstruction by stone, typically Hartmann's pouch)
5–10% acalculous — ICU, postop, burns, sepsis, major trauma, postpartum
Pain duration >6 h (vs colic <6 h)
Severe steady RUQ pain radiating to right shoulder (C3–C5 phrenic referral)
Below tip of 9th costal margin; to right shoulder + interscapular back
Fever, nausea/vomiting, anorexia, leukocytosis, prostration
Murphy's sign: inspiratory arrest on RUQ palpation
Boas' sign: cutaneous hyperaesthesia 9th–11th ribs posteriorly
Jaundice rare; if present → suspect CBD obstruction
Mild: spontaneous resolution 1–10 days; ~25% worsen requiring surgery
Acalculous: insidious symptoms obscured by primary critical illness; failure to diagnose can be fatal

Inves

Leucocytosis (neutrophilia); mild ↑bilirubin/ALP/ALT/AST; ALP+GGT cholestatic; mild lipase/amylase
US first-line, sens ~85% spec ~95%: gallstone + acoustic shadow; pericholecystic fluid; GB wall thickening; sonographic Murphy
HIDA for suspected acalculous/equivocal US: non-visualisation of GB = cystic duct obstruction
Tender mass DDx: empyema, omental phlegmon, abscess from localised perforation

Mng — conservative

NPO; NG if vomiting; IV fluids; broad-spectrum antibiotics; IV analgesia; close observation

Mng — definitive

Gold standard: laparoscopic cholecystectomy
Early lap chole same admission if presented within 2–3 days
Cool down + interval cholecystectomy after 6 weeks if presented >3 days
Pregnancy: 2nd trimester for cholecystectomy
Percutaneous cholecystostomy if too sick/unfit for surgery

Special

Pathogenesis chain: stone obstructs Hartmann's pouch/cystic duct → bile stasis → wall oedema → bacterial infection
Trapped concentrated bile → chemical inflammation (bile-salt detergent) first; bacterial infection 2° in ~50%
Complications: empyema; perforation; gangrene; ascending cholangitis + sepsis; cholecysto-ileal/colonic fistula
Gangrenous: GB wall green/black (mural ischaemia from vascular obstruction)
Gross: GB enlarged + tense; serosa opaque/haemorrhagic; wall thickened, oedematous, hyperaemic; mucosa often ulcerated; lumen turbid bile ± pus/blood
Micro: non-specific acute inflammation — mucosal shedding, dilated capillaries, oedema, neutrophil/pus-cell infiltrate ± abscess/necrosis

Chronic cholecystitis

C/P

90% calculous
Develops after recurrent acute attacks OR chronically from prolonged irritation
Recurrent upper-abdominal pain, often at night after meal; milder than acute
Pre-existing renal/hepatic/cardiac/pulmonary disease can decompensate

Inves

Gross: shrunken contracted small non-functioning fibrotic thick-walled GB; pericholecystic adhesions; dulled serosa
Mucosa preserved (vs shed/ulcerated in acute)
Microscopy: variable subepithelial chronic inflammation (lymphocytes + plasma cells) + fibrosis
Rokitansky-Aschoff sinuses = diagnostic histology (diverticula through muscle) → chronically raised intraluminal pressure

Mng

Elective laparoscopic cholecystectomy + antibiotics

Special

Cystic duct obstructed → hydrops (clear bile) or mucocele (mucus); patent → contracted shrunken adherent GB

GB mucocele / hydrops / empyema

C/P

Mucocele: cystic-duct obstruction WITHOUT infection; distended GB full of mucus; visible/palpable soft non-tender mass + dyspepsia
Hydrops: distended GB full of clear transudate
Empyema: progression of acute cholecystitis + persistent obstruction → pus; high-grade fever, severe pain/tenderness, marked leukocytosis

Mng

Mucocele: laparoscopic cholecystectomy
Empyema: IV antibiotics (cefotaxime/ceftriaxone + anaerobic cover) → percutaneous cholecystostomy → interval lap chole

Ascending cholangitis

C/P

Bacterial biliary infection 2° to obstruction
Most serious and lethal gallstone complication; main biliary cause of sepsis
85% due to CBD stone
Charcot's triad: jaundice + RUQ pain + fever (with rigors)
Reynolds pentad adds: hypotension + confusion

Inves

US: CBD + intrahepatic biliary dilatation
MRCP: non-invasive biliary tree
ERCP: diagnostic + therapeutic (stone removal/stenting)

Mng

IV fluids + blood cultures + broad-spectrum IV antibiotics (anaerobic cover if severe/shocked)
ERCP = first-line decompression
PTBD if ERCP fails
Interval cholecystectomy once controlled

Special

Cascade: biliary obstruction → ↑intra-biliary pressure → bacteraemia → fever/sepsis/shock → urgent decompression mandatory

Mirizzi syndrome

C/P

Stone impacted in cystic duct/GB neck (Hartmann's pouch) causes external compression of CHD
<0.1% prevalence among gallstone patients

Inves

See Csendes classification in Criteria tab

Mng

Per Csendes type; surgical reconstruction commonly required

Gallstone ileus / Bouveret syndrome

C/P

Mechanical obstruction (NOT true ileus — misnomer)
Large stone (>2.5 cm) erodes through GB wall into duodenum via cholecystoenteric fistula
Common in elderly
Impaction at ileocaecal valve (narrowest fixed lumen)
Cardinal: distension, vomiting, absolute constipation, colicky pain
Bouveret syndrome: stone in duodenum → gastric outlet obstruction

Mng

Laparotomy + enterolithotomy

Gallstone pancreatitis

C/P

Stone impacts at ampulla of Vater → blocks common bilio-pancreatic outflow channel → obstructed pancreatic outflow → enzyme activation → autodigestion
5% of gallstone patients

Mng

See Acute pancreatitis
Urgent ERCP if concomitant cholangitis
Definitive: cholecystectomy after recovery

Gallbladder carcinoma

C/P

Uncommon overall but most frequent malignant tumour of biliary tract
F > M; typically women >70 yr
Gallstones present in 60–90% (major RF)

Inves

Gross: exophytic (fungating polypoid) vs infiltrating (diffuse wall thickening, scirrhous; more common)
Adenocarcinoma 90%
Variants: papillary, mucinous, SCC, adenosquamous, neuroendocrine
Perineural invasion common

Mng

Resection if feasible

Special

Prognosis dismal; most invaded liver/bile ducts/portal hepatic LNs at Dx
Papillary subtype best prognosis — delayed wall invasion + exophytic + earlier obstructive presentation

Porcelain gallbladder

C/P

Mural opacification on CT/AXR

Mng

Prophylactic cholecystectomy regardless of symptoms — markedly ↑GB carcinoma risk

Pancreas

8 entries

Acute pancreatitis

C/P

Inflammation on previously normal pancreas; can return to normal
Mild self-limiting (~80%) vs severe (~20% — extensive necrosis + haemorrhage; ~10% most-severe 40–80% mortality)
Epigastric pain radiating to back + nausea + vomiting
Severe: tachycardia, hypotension, oliguria
Mild abdo: widespread tenderness + guarding; severe: ↓bowel sounds (ileus)
Cullen's sign: periumbilical bruising
Grey Turner's sign: flank bruising
5% die of shock within first week
Annual incidence 10–20/100 000

Inves

2 of 3: pain consistent + amylase/lipase >3×ULN + characteristic imaging
Amylase peaks 24 h; lipase peaks 48 h
Magnitude does NOT correlate with severity
Other ↑amylase causes: perforated ulcer, ruptured ectopic, DKA, renal failure, mumps (salivary), macroamylasaemia
US first-line (gallstones); CT delayed 2–4 days (renal contrast; underestimates early necrosis)
CT indications (rarely first week): clinical deterioration + ↑CRP; suspected local complications; bowel ischaemia; acute bleed; abdominal compartment syndrome
CT necrosis: <30% enhancement diagnostic
Emphysematous pancreatitis: intra-collection gas
Aetiology workup: US + alcohol hx + TG + Ca + IgG4
Balthazar CT grading: A = normal; B = pancreatic enlargement; C = pancreatic/peripancreatic fat inflammation; D = single peripancreatic fluid collection; E = two or more collections and/or retroperitoneal air
Serum lipase more sensitive + specific than amylase → preferred diagnostic enzyme

Mng — first 4 h

Analgesia (NOT morphine — ↑sphincter of Oddi pressure)
Aggressive fluid resuscitation
Predict severity: Ranson, HAPS; SIRS; SOFA / modified Marshall
Pillars: haemodynamic, fluid, pain, nutrition, infection prevention, identify cause, specialist referral

Mng — feeding

Do NOT withhold food unless contraindicated
EARLY enteral nutrition preferred — ↓complications
NJ post-pyloric if NG not tolerated; parenteral by day 4 if still inadequate

Mng — reassessment

Response: MAP, HR, urine output, haematocrit
ICU: deterioration / persistent organ failure / specialist MDT
NO prophylactic antibiotics or probiotics — treat only proven infection
Only firm urgent ERCP indication = concomitant cholangitis

Mng — infected local complications (step-up)

Drainage guided by current CT first — percutaneous or endoscopic
Delay invasive 3–4 weeks with ICU support → demarcation + walling-off
If drainage fails: VARD (video-assisted retroperitoneal debridement) or percutaneous nephroscopic; endoscopic transluminal debridement; large-bore drainage + continuous irrigation
Confirm infection: CT-guided FNA Gram + culture; air in retroperitoneum on CT = pathognomonic

Mng — surgery indications

Infected collections or necrosis
Impacted ampullary gallstone when endoscopic/radiologic unavailable/unsuccessful
Delay >3-4 weeks (early SIRS-phase surgery worsens; infection rare in first week; sterile necrosis rarely needs debridement)
Approach: midline or bilateral subcostal; transmesocolic via lesser sac (left of middle colic artery); closed drainage + post-op saline lavage OR open packing

Special — aetiology (GET SMASHED)

G: gallstones; E: ethanol/ERCP; T: toxins/tumours/trauma; S: steroids; M: mumps + infections; A: autoimmune (IgG4); S: sphincter of Oddi dysfunction; H: hyperTG + hyperCa; E: genetic (CF, hereditary); D: drugs
Drugs: azathioprine/mercaptopurine, didanosine, oestrogens, tetracycline, valproic acid, furosemide/sulphonamides
Most common 2: gallstones + alcohol (~70%); ~20% idiopathic
HyperTG pancreatitis: TG >1000 mg/dL
Tumour eval if >40 yr; genetic testing if <30 yr
Post-ERCP prevention in high-risk: pancreatic-duct stents + rectal NSAID

Special — pathophysiology

Initiating: acinar-cell injury → zymogen activation outside ducts
Co-localisation of lysosomal + zymogen → cathepsin B activates trypsinogen (needs ↑Ca²⁺)
Cathepsin B → cytochrome c release → apoptosis
NF-κB activated downstream PKC → cytokines
Trypsin self-activates; activates phospholipases + elastases (autodigestion); activates factor XII (Hageman) → clotting + kinins
Elastase → pseudoaneurysm/arterial rupture
4 mechanisms: defective intracellular zymogen transport; duct obstruction; hyperstimulation (alcohol, hyperTG); reflux (sphincter of Oddi dysfunction)
Lipase secreted active (not zymogen) → early fat necrosis

Special — morphology

Acute interstitial (mild): swollen oedematous + superficial chalky-white fat necrosis
Acute necrotising (severe): black-brown haemorrhage/necrosis + chalky yellow-white fat necrosis + peritoneal brown serous fluid + fat globules
Histology: neutrophilic infiltrate + interstitial oedema + fat necrosis ± haemorrhage

Special — complications

Systemic: SIRS, ARDS, hyperglycaemia (insulin disrupted), hypocalcaemia (Ca sequestered by saponification of necrotic fat), ↓albumin, obstructive jaundice, DIC, multi-organ failure, electrolyte abnormalities, coagulopathy
Local pancreatic: pseudocyst, abscess, necrosis
GI: upper-GI bleed, variceal haemorrhage (splenic-vein thrombosis), pseudocyst erosion into colon, duodenal obstruction
Extrapancreatic: gastric outlet obstruction (duodenal oedema/mass) — NG decompression + fluid + surgical drainage; CBD obstruction — Roux-en-Y hepaticojejunostomy or choledochoduodenostomy if refractory; splenic/portal vein thrombosis → left-sided portal HTN + gastric varices → splenectomy
Atlanta: APFC (<3 wk, no necrosis); ANC (with necrosis); pseudocyst >4 wk; walled-off necrosis >4 wk
Mortality severe ~30%; early = multi-organ failure; late = infection of necrotic debris
Determinants of severity: infected local complications + persistent organ dysfunction
1/3 of patients develop complications; 1/4 of those die

Pancreatic pseudocyst

C/P

75% of pancreatic cystic lesions
Post-AP or chronic pancreatitis OR abdominal trauma
Persistent abdominal pain + raised pancreatic enzymes
Usually solitary up to 10 cm within or adjacent to pancreas; often calcified

Inves

US/CT
EUS-FNA + cyst-fluid CEA/amylase to distinguish from true cystic neoplasm

Mng

Many spontaneously resolve
Endoscopic drainage: EUS-guided cystogastrostomy or ERCP transpapillary (for head)
Detail: transgastric cystogastrostomy over guidewire + balloon dilatation; lumen-apposing metal stents; ERCP transpapillary
Surgery if endoscopic fails: open cystogastrostomy + closure; open cystojejunostomy (Roux-en-Y); laparoscopic necrosectomy

Special

Not a true cyst — NO epithelial lining (wall is granulation acute / fibrous chronic)
Outcomes: resolution; 2° infection → abscess + peritonitis; erosion into vessels (esp. splenic artery) + haemorrhage; compression; perforation

Chronic pancreatitis

C/P

Long-standing inflammation → irreversible structural + functional damage
~10/100 000; 5th decade
Episodic abdominal pain (recurrent acute exacerbations) radiating to back
Anorexia + severe weight loss
Exocrine insufficiency: malabsorption, steatorrhoea
DM late (~30%); occasional jaundice

Inves

↑amylase/lipase may persist
IgG4 >2×ULN → autoimmune
Faecal elastase reduced in moderate-severe exocrine insufficiency
Genetic: PRSS1 (cationic trypsinogen), SPINK1 (trypsin inhibitor), CFTR
US first-line; CT (calcification + dilated duct); MRI/MRCP (subtle ductal; has replaced diagnostic ERCP); EUS (confirm, complications, exclude malignancy)

Mng

Goals: prevent further destruction + treat symptoms
Avoid alcohol; treat cause; stent obstructed duct
Pancreatic enzyme supplements + fat-soluble vitamins
Pain control escalating to celiac-plexus blockade
Surgery (decompression, resection) for refractory

Special — morphology

Early: enlarged + septal fibrosis + intra-pancreatic fat necrosis
Late: shrunken firm + extensive fibrosis + calcification + ductal dilatation; pseudocysts
Microscopy: fibrosis + loss of exocrine glands (atrophic lobules) + chronic inflammation (lymphocytes, plasma cells, monocytes)
RELATIVE sparing of endocrine islets (exocrine destroyed first)
Cystic fibrosis = most common cause of chronic pancreatitis in CHILDREN (vs alcohol in adults)

Special — aetiology & complications

Most common = alcohol
Others: CKD; hereditary pancreatitis; CF; SPINK1; obstructive; trauma; recurrent acute; hyperCa; autoimmune IgG4; ~40% idiopathic
Central mechanism: ↑prolonged intra-pancreatic trypsin → protein plugs → ductal HTN
~70% develop local complications: pseudocyst, biliary/intestinal obstruction, haemorrhage, ascites, gastric varices (splenic-vein thrombosis)
Functional: DM (islet damage), fat malabsorption
↑pancreatic carcinoma risk (alcohol + smoking)

physiology · background · low-yield

Exam technique

Exocrine-function tests — direct: Secretin-CCK stimulation test (most sensitive/specific but needs duodenal intubation + IV hormones); indirect: Lundh test meal, 72-h faecal fat, NBT-PABA / fluorescein-dilaurate (detect only severe dysfunction)

Mechanism

Pathophysiology: repeated inflammation (modified by regulatory T cells) → activation of pancreatic stellate cells → self-perpetuating inflammation–fibrosis cycle

Pancreatic adenocarcinoma

C/P

Advanced disease at presentation
Male predominance; ≥60 yr; 5th cancer death Western world
RFs: smoking + chronic pancreatitis (major modifiable)
Genetic: PRSS1 (hereditary pancreatitis), HNPCC (Lynch), FAMMM
Insidious; abdominal pain, weight loss, anorexia, vomiting
Central pain radiating to back (coeliac plexus invasion); partly relieved by leaning forward — pain = poor prognosis
Almost universal weight loss/cachexia
Obstructive jaundice + severe pruritus (head tumours invading CBD)
Duodenal obstruction with vomiting
New-onset DM
Trousseau syndrome — migratory thrombophlebitis (~10%); recurrent venous thrombosis
Acute pancreatitis
Courvoisier's law: palpable non-tender GB in jaundiced patient → distal biliary obstruction (typically pancreatic head)
~10/100 000 incidence

Inves

US + contrast-enhanced CT first-line
EUS ± FNA cytology; CT-guided cytology/biopsy; MRCP/ERCP if doubt
~50% present with jaundice

Mng

Most palliative — only ~15% resectable
ERCP CBD stent for obstructive jaundice in inoperable
Chemotherapy → median survival ~11 months
Pain: analgesics escalating to coeliac-plexus neurolysis
Jaundice relief: choledochojejunostomy (fit) or percutaneous/endoscopic biliary stenting (elderly/advanced)

Special — morphology

Site: head 60%; body 15%; tail 5%; diffuse 20%
Gross: gritty hard pale + poorly defined infiltrating edges + invades adjacent
Moderately-to-poorly differentiated adenocarcinoma + infiltrating cell-cluster + marked desmoplastic stroma; hyperchromatic pleomorphic nuclei
Perineural invasion → severe pain
>90% of pancreatic tumours are ductal adenocarcinoma; 95% exocrine overall
Grading: mitoses, pleomorphism, differentiation, necrosis, vascular invasion
Staging: T1–T4; N; M0/M1
5-yr survival 3–4% overall; up to ~25% with early-stage radical resection
Local spread: peritoneum, spine, liver; distant: lungs, bone

Special — full pancreatic tumour classification (pathology lecture)

Exocrine benign: serous cystadenoma; mucinous cystadenoma (Bo); solid-pseudopapillary tumour (Bo); intraductal papillary mucinous neoplasm (IPMN) — branch-duct vs main-duct
Exocrine malignant ductal: ductal adenocarcinoma (~90% of all pancreatic tumours); ampullary adenocarcinoma
Exocrine malignant non-ductal: acinar cell carcinoma; pancreatoblastoma (mainly paediatric); mucinous cystadenocarcinoma; serous cystadenocarcinoma; solid-pseudopapillary carcinoma
Endocrine (5% of pancreatic tumours): pancreatic NETs — insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma, non-functioning (MEN1 association)
Non-epithelial (rare): lymphoma, sarcoma
Metastatic to pancreas (rare): RCC, melanoma, lung, breast, colon

Special — normal pancreatic islet cell types

α cells (15–20%): glucagon
β cells (60–70%): insulin
δ cells (~10%): somatostatin
F / PP cells (3–5%): pancreatic polypeptide
ε (epsilon) cells (<1%): ghrelin
G cells (absent in normal islet — normally in gastric antrum; ectopic in gastrinoma)

Ampullary adenocarcinoma

C/P

Arises from ampulla of Vater or adjacent duodenum
Polypoid, may ulcerate, frequently infiltrate duodenum
Less aggressive than pancreatic adenocarcinoma

Autoimmune (IgG4) pancreatitis

C/P

Chronic inflammation with IgG4 lymphoplasmacytic infiltration
Most common presentation: painless obstructive jaundice
Extra-pancreatic IgG4: biliary tree, salivary glands, retroperitoneum, lymph nodes

Inves

Serum IgG4 >2×ULN

Mng

Corticosteroids = cornerstone

Cystic fibrosis (pancreatic involvement)

C/P

AR; CF gene on long arm chromosome 7
CFTR = chloride channel in apical epithelial membrane
Most prominent: respiratory disease (small-airway dehydration, mucus stasis, recurrent infection, obstruction, bronchiectasis)
Non-respiratory: pancreatic exocrine insufficiency, malabsorption/failure to thrive, CF-related diabetes, CF liver disease up to cirrhosis, meconium ileus in infancy

Inves

Neonatal heel-prick immunoreactive trypsinogen (newborn screen)
Sweat-chloride test
Confirmatory genetic testing

Mng — pancreatic

Pancreatic enzyme supplements
Maintain fat intake (avoid nutritional deficit)
Add PPI to enhance supplemental enzyme efficacy

Special

Most common hereditary exocrine pancreatic disease

physiology · background · low-yield

Other

Sweat-chloride test = gold-standard diagnostic test

Pancreas divisum / annular pancreas / cystic neoplasms

Pancreas divisum

Failure of dorsal + ventral pancreatic ducts to fuse
Most drainage through smaller accessory ampulla
Usually asymptomatic; some develop pancreatitis or atypical abdominal pain

Annular pancreas

Pancreas encircles 2nd or 3rd part of duodenum
Gastric outlet obstruction
Associated: intestinal malrotation; cardiac anomalies

Cystic neoplasms

True cystic neoplasms → resection (high malignant transformation risk; incl. main-duct IPMN)
Limited resection: small <3 cm in head without confirmed malignancy; significant comorbidity
Branch-duct IPMN <3 cm → surveillance
Distinguish pseudocyst vs true cystic: EUS-FNA + cyst-fluid CEA/amylase

Child-Pugh score

Components — numeric scoring (1 / 2 / 3 points)

Component	1 pt	2 pt	3 pt
Bilirubin (mg/dL)	<2	2–3	>3
Albumin (g/dL)	>3.5	2.8–3.5	<2.8
PT prolongation (sec over control)	<4	4–6	>6
— or INR	<1.7	1.7–2.3	>2.3
Ascites	Absent	Slight (diuretic-controlled)	Moderate (refractory)
Hepatic encephalopathy	None	Grade 1–2	Grade 3–4

Class thresholds & survival

Class	Points	1-yr survival	2-yr survival
A	5–6	100%	85%
B	7–9	80%	60%
C	10–15	45%	35%

Notes

ALT/AST NOT a component — elevated in many liver conditions, doesn't reflect severity
Child C = Child-Pugh score >9 (i.e. 10–15)
Child-Pugh >9 (Child C) + MELD >15 = accepted transplant candidates
Main predictor of rebleeding/death after first variceal haemorrhage

MELD score

Components (3)

Serum creatinine
Serum bilirubin
INR

Original formula (derived from 231 TIPS patients)

R = 0.957 × ln(creatinine mg/dL) + 0.378 × ln(bilirubin mg/dL) + 1.120 × ln(INR) + 0.643 × (cause: 0 alcoholic/cholestatic, 1 other)
All values <1.0 rounded up to 1.0
Result multiplied ×10, rounded to nearest integer

Thresholds & use

Originally for TIPS short-term prognosis
Best predicts liver-related death (short-term mortality from ESLD)
MELD ≤14 → transplant mortality exceeds non-transplant; not routinely listed
MELD >15 = valid transplant indication
MELD >30 → individual case review (prohibitive morbidity/mortality)
Lower scores may list under MELD exceptions
Recalculate q3–6 months in decompensated cirrhosis

King's College Criteria (KCC)

Paracetamol-induced ALF — EITHER

pH <7.3 OR arterial lactate >3.0 mmol/L after adequate fluid resuscitation
OR all three: grade 3/4 HE + INR >6.5 + creatinine >3.4 mg/dL

Non-paracetamol ALF — EITHER

INR >6.5 + HE of any grade
OR any 3 of 5 with HE of any grade:
— Age <10 or >40 years
— Jaundice >7 days before HE onset
— INR >3.5
— Bilirubin >17 mg/dL
— Unfavourable aetiology (Wilson, idiosyncratic drug reaction, seronegative hepatitis)

Atlanta classification (revised) — AP morphology

Acute peripancreatic fluid collection (APFC)

Peripancreatic fluid with interstitial oedematous pancreatitis WITHOUT necrosis
First 3 weeks; no pseudocyst features

Acute necrotic collection (ANC)

Variable fluid + necrosis with necrotising pancreatitis
Necrosis can involve parenchyma and/or peripancreatic tissue

Pseudocyst

Usually >4 weeks from onset

Walled-off necrosis (WON)

Usually >4 weeks from onset

Severity definitions

Transient organ failure <48 h → moderately severe AP
Persistent organ failure >48 h → severe AP

Glasgow severity criteria — AP

Threshold

>3 factors = severe disease

Eight components

Age >55 yr
PO₂ <8 kPa (60 mmHg)
WBC >15 × 10⁹/L
Albumin <32 g/L
Serum Ca <2 mmol/L (8 mg/dL, corrected)
Glucose >10 mmol/L (180 mg/dL)
Urea >16 mmol/L (after rehydration)
ALT >200 U/L and LDH >600 U/L

Ranson criteria — AP

Structure

11 total: 5 on admission + 6 at 48 hours
Requires full 48 hours to be fully calculated — cannot guide immediate triage

Criteria

On admission: age >55, WBC >16 000, glucose >200 mg/dL, LDH >350, AST >250
At 48 h: Hct fall >10%, BUN rise >5 mg/dL, Ca <8 mg/dL, PaO₂ <60 mmHg, base deficit >4 mEq/L, fluid sequestration >6 L

APACHE II — AP

Applicable as early as 24 hours post-admission

Modified Marshall score — AP organ failure

Grades severity of organ failure (respiratory / renal / cardiovascular)
Used at assessment + prospectively over time

C10

West Haven staging — Hepatic encephalopathy

Stage	Features
Minimal	Language/verbal skills preserved
1	Trivial unawareness; ↓attention; sleep abnormalities; euphoria/depression; asterixis; tremor; incoordination
2	Lethargy/apathy; disorientation; inappropriate behaviour; slurred speech; asterixis; ataxia
3	Gross disorientation + confusion; arousable; asterixis usually absent
4	Stupor and coma

C11

SAAG — Serum-Ascites Albumin Gradient

Formula

SAAG = serum albumin − ascitic-fluid albumin

SAAG	Total protein	Cause
≥1.1 g/dL	<2.5 g/dL	Cirrhotic ascites
≥1.1 g/dL	≥2.5 g/dL	Cardiac (CHF, constrictive pericarditis) or Budd-Chiari
<1.1 g/dL	<2.5 g/dL	Nephrotic
<1.1 g/dL	≥2.5 g/dL	Peritoneal carcinomatosis or TB ascites

C12

SBP diagnostic threshold

Ascitic-fluid PMN ≥250 cells/mm³, in absence of intra-abdominal infection from treatable surgical cause
Sample BEFORE antibiotics
Confirm response with repeat paracentesis showing >25% drop in PMN

C13

ICA-AKI staging in HRS / cirrhosis

Stage	Creatinine criterion
1	↑ ≥0.3 mg/dL OR up to 2× baseline
2	2–3× baseline
3	>3× baseline OR >4 mg/dL OR initiation of RRT

C14

HVPG thresholds — portal hypertension

HVPG (WHVP − FHVP)	Interpretation
5–10 mmHg	Normal portal pressure
≥5 mmHg	Portal hypertension
≥10 mmHg	Clinically significant portal hypertension
10–12 mmHg	Varices develop
>5–12 mmHg	Diagnostic range

Notes

WHVP = wedged hepatic venous pressure; FHVP = free hepatic venous pressure
Combined diagnostic: portal pressure >12 mmHg + WHVP-to-inferior-jejunal-vein gradient >2–6 mmHg

C15

Ishak grading & staging — chronic hepatitis

Component	Range
Interface hepatitis	0–4
Confluent necrosis	0–6
Spotty necrosis / lobular inflammation	0–4
Portal inflammation	0–4
Maximum total	18
Stage = cirrhosis	6/6

C16

METAVIR grading & staging — chronic hepatitis

Grade (inflammation): A0–A4
Stage (fibrosis): F0–F4
F4 = cirrhosis

C17

Csendes classification — Mirizzi syndrome

Type	Definition
I	External compression of CHD only (no fistula)
II	Cysto-biliary fistula <1/3 CHD circumference
III	Cysto-biliary fistula up to 2/3 CHD circumference
IV	Complete destruction of CHD wall by fistula

C18

Charcot's triad & Reynolds' pentad — ascending cholangitis

Charcot's triad

Jaundice
RUQ pain
Fever (with rigors)

Reynolds' pentad (adds)

Hypotension
Confusion / altered mental state

C19

6 F's — cholesterol gallstone risk

Fair
Female
Forty
Fat
Fertile
Family history

C20

BCLC staging — HCC

Domains

Tumour burden
Liver function
Performance status

Treatment allocation

Surgical resection
Liver transplantation
TACE (trans-arterial chemoembolisation)
Systemic therapy (atezolizumab/bevacizumab; tyrosine-kinase inhibitors)
Best supportive care

C21

GET SMASHED — AP aetiology

Letter	Cause
G	Gallstones
E	Ethanol / ERCP
T	Toxins / Tumours / Trauma (3 T's)
S	Steroids
M	Mumps + other infections
A	Autoimmune (IgG4)
S	Sphincter of Oddi stenosis/dysfunction
H	Hypertriglyceridaemia / Hypercalcaemia
E	Genetic (CF, hereditary)
D	Drugs

C22

AIH treatment indications

Absolute (any one)

Acute liver failure
AST or ALT >10×ULN
AST/ALT >5×ULN AND γ-globulin >2×ULN
Bridging or multilobular necrosis on biopsy

Relative

Incapacitating fatigue, arthralgia, or jaundice
Modest AST/ALT or γ-globulin elevation (below absolute)
Interface hepatitis on biopsy without bridging necrosis

Doesn't benefit

Biopsy-proven cirrhosis WITHOUT active inflammation (inactive cirrhosis)

C23

DILI ALT-stratified management ladder

ALT	Action
<3×ULN	Monitor
3–5×ULN	Hold drug; resume if normalises; consider steroids
>5×ULN	Stop drug; give steroids
>10×ULN or no improvement	Permanently stop offending agent

C24

DILI transplant referral thresholds

INR >1.5
Hepatic encephalopathy

C25

Gharbi US classification — hydatid cysts

PAIR eligible: cysts >5 cm + Gharbi type I or II
PAIR contraindicated: Gharbi type II honeycomb + type IV

C26

Tokyo Guidelines (TG18) — acute cholangitis severity

Grade III (severe) — cholangitis + any organ dysfunction

Cardiovascular: hypotension requiring vasoactive drugs
Neurological: disturbance of consciousness
Respiratory: PaO₂/FiO₂ <300
Renal: oliguria, serum creatinine >2.0 mg/dL
Hepatic: PT-INR >1.5
Haematological: platelets <100 × 10⁹/L

Grade II (moderate) — cholangitis + any 2 of 5

WBC >12 or <4 × 10⁹/L
Fever ≥39°C
Age ≥75 yr
Total bilirubin ≥5 mg/dL
Albumin <0.7 × lower limit normal

Grade I (mild)

Cholangitis not meeting Grade II or III criteria

Implications

Grade III → urgent biliary drainage (ERCP) + organ support in ICU
Grade II → early biliary drainage
Grade I → antibiotics + elective drainage if response poor within 24 h

C27

Tokyo Guidelines (TG18) — acute cholecystitis severity

Grade I (mild): no organ dysfunction, mild disease in GB → laparoscopic cholecystectomy
Grade II (moderate): local complications (empyema, gangrene, pericholecystic abscess), WBC >18 or palpable mass or >72 h, marked local inflammation
Grade III (severe): organ dysfunction (cardiovascular, neurological, respiratory, renal, hepatic, haematological)

C28

Maddrey's Discriminant Function (mDF) — alcoholic hepatitis severity

Formula

mDF = 4.6 × (patient PT − control PT in seconds) + serum bilirubin (mg/dL)

Threshold

mDF ≥32 = severe alcoholic hepatitis, poor prognosis → treat with corticosteroids (prednisolone 40 mg/d × 5 days, taper over 3 weeks) unless contraindicated

C29

Lille model — alcoholic hepatitis steroid response

Uses

Age, albumin day 0, bilirubin change day 0 → day 7, renal insufficiency, PT/INR

Interpretation at day 7

Lille <0.16 → good responders → 96% 28-day survival → continue steroids
Lille ≥0.56 → non-responders → 55% 28-day survival → stop steroids (futility)
Intermediate → clinical judgement

C30

Glasgow alcoholic hepatitis score (GAHS)

Components (scored 1–3)

Score	1	2	3
Age	<50	≥50	—
WBC (×10⁹/L)	<15	≥15	—
Urea (mmol/L)	<5	≥5	—
Bilirubin (µmol/L)	<125	125–250	>250
INR	<1.5	1.5–2.0	>2.0

Threshold

Total >9 = poor prognosis

C31

CAGE questionnaire — alcohol misuse screen

4 items (≥2 positive = screen positive)

Cut down — ever felt you should cut down on your drinking?
Annoyed — annoyed by criticism of your drinking?
Guilty — ever felt guilty about drinking?
Eye-opener — ever needed a morning drink to steady nerves / cure hangover?

C32

AUDIT — Alcohol Use Disorders Identification Test

WHO 10-item screening; each 0–4 points (total 0–40)
Domains: consumption, dependence symptoms, alcohol-related problems
≥8 (men) / ≥7 (women) = hazardous / harmful drinking

C33

CIWA-Ar — Clinical Institute Withdrawal Assessment for Alcohol

Score-guided benzodiazepine dosing in alcohol withdrawal
Items: nausea/vomiting, tremor, sweats, anxiety, agitation, tactile/auditory/visual disturbances, headache, orientation
Guides symptom-triggered chlordiazepoxide or lorazepam regimen

C34

UK alcohol guideline (Chief Medical Officers)

Both sexes: ≤14 units/week spread over ≥3 days
Equivalents: 6 pints beer (4%) OR 7 × 175 mL wine (11.5%) OR 14 × single spirits (40%)

C35

Drug-Induced Hepatotoxicity (DILI)

Importance & risk factors

3–10% of all adverse drug reactions; 30–50% of acute liver failure cases; <5% of jaundice; can mimic all forms of liver disease
Risk factors: alcohol (enzyme-inducing), dose & duration of therapy, extremes of age, genetics (CYP450 polymorphisms, N-acetyltransferase), nutrition (starvation, obesity), pre-existing liver disease
Pre-existing liver disease — usually same risk, but avoid: methotrexate/antineoplastics; hepatically-metabolised antibiotics (sulfonamides, chloramphenicol inhibit P450; tetracyclines directly hepatotoxic); ↑ anti-TB & HAART risk in chronic viral hepatitis
Zone 3 (centrilobular) = lowest O₂, highest CYP450 (esp. CYP2E1) → site of most drug injury; Zone 1 (periportal) = high glutathione

Two types of toxic reaction

	Intrinsic (direct/obligate)	Idiosyncratic (optional)
Incidence	High	Low
Predictable / dose-dependent	Yes	No
Host-dependence	No	Yes (broad spectrum)
Mechanism	Usually necrosis or steatosis	Metabolic (aberrant metabolism) or immunologic (allergic)
Examples	Paracetamol, carbon tetrachloride, Amanita phalloides	Metabolic: isoniazid, ketoconazole, valproate. Immunologic: methyldopa, diclofenac, nitrofurantoin, phenytoin, sulfonamides, dapsone

Idiosyncratic subtypes: hypersensitivity (weeks; systemic rash/fever/eosinophilia; prompt rechallenge) vs aberrant metabolism (months; liver only; delayed rechallenge)

Paracetamol — the key intrinsic example

Most common cause of acute liver failure in Europe/USA (accidental overdose or self-harm)
Toxic metabolite NAPQI (via CYP2E1) → zone 3 necrosis once glutathione detox capacity is exceeded
Three phases: I acute GI symptoms (1–4 h) → II latent (1–3 days) → III liver damage/failure (3–10 days); ~15% with overt injury die
Treatment: N-acetylcysteine (replenishes glutathione)

Patterns by site of injury (know one example each)

Pattern	Examples
Hepatocellular necrosis	Paracetamol
Steatosis	Methotrexate, tetracycline, valproate, salicylates, HAART, amiodarone
Acute/chronic hepatitis	Isoniazid, sulfonamides, ketoconazole, minocycline, methyldopa, nitrofurantoin, halothane
Cholestasis	Chlorpromazine, erythromycin, amitriptyline, co-amoxiclav, flucloxacillin, co-trimoxazole, NSAIDs, statins; anabolic steroids & OCP (canalicular)
Granulomas	Hydralazine, carbamazepine, allopurinol, diltiazem, quinidine, quinine
Fibrosis	Methotrexate
Vascular (veno-occlusive)	Azathioprine, busulfan; non-cirrhotic portal HTN — vitamin A, methotrexate
Tumours	Oral contraceptives, aflatoxin

Clinical features, diagnosis & management

Clinical: no specific features; allergic idiosyncratic → fever/rash/lymphadenopathy/eosinophilia; cholestatic → pruritus/jaundice mimicking biliary obstruction
Diagnosis: no specific test (except paracetamol OD); careful drug history + timing + exclusion; ALT >1000 U/L strongly suggests drug/viral/ischaemic injury; eosinophilia → allergic; US excludes biliary obstruction; avoid diagnostic re-challenge
Management: STOP the causative agent (failure → high mortality); if on multiple drugs stop all (most-recently-started = likeliest culprit); N-acetylcysteine for paracetamol; corticosteroids for severe allergic reactions; UDCA for cholestatic; liver transplant if INR >1.5 or hepatic encephalopathy