GI Flashcards

Question

Peptic ulcer disease

Answer 1

Definitions • Erosion: break in mucosal lining < 5mm in stomach/ duodenum • Ulcers: break in mucosal lining > 5mm in stomach/ duodenum Pathology • Imbalance of acid secretion (histamine, gastrin, ACh) vs mucosal protection (mucus, HCO3, prostaglandin, mucosal blood flow) • Possible location o Duodenum: MC (75%), mostly in D1 within 2cm of pylorus, never malignant o Stomach (20%) – usually in lesser curve, 5% malignant potential o Jejunum: in Zollinger-Ellison syndrome (gastrinoma) – 50% malignant potential o Meckel's diverticulum: if contain ectopic gastric mucosa • GU is classified by modified Johnson’s classification [SUR] Aetiology • H pylori (flagellated G- rod): 70% cases of GU, 90% cases of DU • NSAID (PGE2 blockade —> reduced PG synthesis; COX1 blockade —> less platelet aggregation): can cause ulcer in all parts of GI tract; 25% cases of GU, 5% cases of DU • Aspirin, steroids • Smoking, excessive alcohol, caffeine • Zollinger-Ellison syndrome (hypergastrinemia) • Stress: Increased ICP (Cushing's ulcer: vagal nuclei irritation), severe burns (Curling's ulcer: hypoperfusion of mucosa) • Hiatal hernia —> Cameron’s ulcer • Crohn’s disease Clinical features • Epigastric pain / Dyspepsia: relieved with food (DU) or worsened by food (GU) • Complications of PUD: UGIB, perforation, GOO [SUR] • Complications of H pylori infection: gastric cancer, gastric MALToma Investigations • CBC D/C, CXR±AXR (rule out PPU before endoscopy!) • Test-and-treat approach: all patients should undergo non-invasive test for HP and treat accordingly o Exceptions: - Obvious GERD symptoms: PPI - NSAID use: discontinue NSAID +/- PPI - Indication for endoscopy: red flags (age > 45, UGIB/ anaemia, dysphagia, LOW) • OGD + biopsy o Indications: red flags as above, failed PPI trial o Roles: - Diagnostic: biopsy (all GU require 4-quadrant Bx), antral biopsy for CLO test - Prognostic: Forrest's classification, - Therapeutic: injection (ethanol / adrenaline), coagulation (heater probe), clipping Management • Lifestyle changes: avoid smoking & alcohol • Ulcer-healing drugs: o H2 antagonists x 8 weeks (e.g. famotidine 20mg BD) o PPI x 4-6 weeks: taken 30-60 min before meals • If HP +ve: standard triple therapy (high-dose PPI BD + clarithromycin 500mg BD + amoxicillin 1g BD x 7-14d) • NSAID/ aspirin-induced: First review indication of aspirin / NSAID use - NSAID user —> Change to COX2 inhibitor + PPI cover - Aspirin user —> Non-bleeding ulcer: continue aspirin + PPI cover (step up to BD if already OD) —> Bleeding ulcer: resume aspirin once hemostasis is secured (usually 3-5d) + PPI cover - SB ulcer —> Misoprostol (C/I in pregnancy) (PPI has no use as SB is already alkaline) • Secondary prevention of future ulcers - H. pylori: Maintenance PPI not required after HP eradication - NSAID / aspirin: Review indications Avoid NSAID if high GI risk* / prev. complicated PUD Give PPI cover - Idiopathic Consider long-term maintenance PPI * Definition of high GI risk: ≥2 of • Elderly > 65 years old • Hx of PUD • Concomitant use of aspirin / steroids / anticoagulant • Follow-up endoscopy at 6-8 weeks to ensure complete healing o GU: all o DU: only if complicated (bleeding/obstruction), giant (>2cm), persistent Sx despite medical therapy • Endoscopic/Surgical Tx: if refractory to medical Tx or with complications

Answer 2

Prevalence in HK: 50% Pathogenesis of H pylori Virulence of H pylori (fig.) H pylori-related diseases • Antral gastritis – most common • Non-ulcer dyspepsia • Peptic ulcer disease o GU: direct damage to acid-producing gastric body —> atrophic gastritis o DU: inflammation of non-acid-producing antral region —> gastrin —> excessive acid —> damage duodenal mucosa —> HP colonization • Gastric cancer • Gastric MALToma Diagnostic tests for H. pylori Indications • Peptic ulcer disease • Early gastric cancer or MALToma • Post-HP eradication therapy Test options • Stop antibiotics for 4 weeks, PPI for 2 weeks before test Non-invasive: 1. Urea breath test (UBT) MOA: urease present in HP converts isotope- labelled urea into ammonia & CO2 • 14C: radioactive, measured by scintillation • 13C: non-radioactive, measured by mass spectrometry False -ve: antibiotics, PPI - preferred when Young dyspeptic patients with no alarming features; Post-HP eradication (except GU – endoscopy is needed) 2. HP stool antigen test: Alternative to UBT Not convenient and not sensitive - preferred when Uncooperative or children 3. Serology (IgG): Positive up to 2y even after HP eradication Not useful Invasive: 1. Rapid urease test (CLO test) Antral biopsy (highest conc. of HP) ± 2 biopsy at body if chronic PPI use (HP migration) Add biopsy sample to urea + phenol red (ammonia turns phenol red from yellow to pink) False -ve: antibiotics, PPI, blood (buffer) - preferred when Old dyspeptic (>45y); Post-HP eradication in HP- related GU 2. Histology: Gold standard Biopsy at antrum & body False -ve: antibiotics, PPI (HP migrates from pylorus to body) -preferred when Inconclusive RUT 3. C/ST: Not for diagnosis (sensitivity 40%) - preferred in failed HP eradication x 2 4. PCR: Good but expensive H. pylori eradication therapy • Standard triple therapy: high dose PPI BD + amoxicillin 1g BD + clarithromycin 500mg BD x 7-14 days o Continue ulcer-healing drug (PPI) for 4-6 weeks o Switch amoxicillin to metronidazole 400mg BD if penicillin-allergic o Confirm eradication after stopping all drugs for 4 weeks: - DU: Urea breath test - GU: OGD for CLO test & histology - Failed eradication x 2: OGD for C/ST • Salvage therapy: if failed eradication o Bismuth quadruple therapy: PPI + bismuth subsalicylate + tetracycline + metronidazole o Levofloxacin-based triple therapy: PPI + amoxicillin + levofloxacin o Non-bismuth quadruple therapy: PPI + amoxicillin + clarithromycin + metronidazole • Precautions: Compliance issue due to S/E (e.g. GI upset, rash, deranged LFT) • DDI: o Clarithromycin: CYP3A4 inhibitor (e.g. simvastatin —> increase risk of myopathy & rhabdomyolysis) o Esomeprazole: CYP2C19 inhibitor (e.g. clopidogrel)

Answer 3

Pathogenesis • Ingestion of C. diff spores —> colonisation of colon when colonic flora is changed by antibiotics —> release of toxin A (enterotoxin) and toxin B (cytotoxin) —> mucosal necrosis, forming pseudomembrane Risk factors • Recent use of antibiotics – especially 3rd generation cephalosporin, fluoroquinolone, clindamycin • PPI/ H2RA • Elderly/ nursing home residents • IBD, malignancy • Chemotherapy • GI surgery Clinical features • Acute watery diarrhoea +/- blood +/- mucus, with fever & lower abdominal pain • Pseudomembranous colitis (PMC): symptoms above + pseudomembrane & bowel wall thickening in endoscopy • Fulminant colitis (3%): toxic megacolon +/- bowel perforation Investigations • Stool for GDH antigen —> confirmed by PCR for C diff. toxin A & B • Flexible sigmoidscopy for presence of pseudomembrane (80%) o Indicated if Dx uncertain or no improvement with standard treatment o Avoid if suspected toxic megacolon (air insufflation may perforate) Management (SAQ!) • Discontinue antibiotics (if possible), PPI, antimotility agents • Mild disease: o Vancomycin 125mg Q6h PO 10-14d (1st line) – molecule too large —> cannot cross gut wall o Metronidazole 400mg TDS PO 10-14d (2nd line: not preferred due to low availability) • Severe disease (ileus / hypotension / megacolon): metronidazole IV + vancomycin PO / intra-colonic (never IV) • Fulminant colitis: CT abdomen, urgent consult SUR for subtotal colectomy • Recurrent infections: o 1st recurrence: vancomycin pulse and tapered, fidaxomicin o Subsequent recurrence: faecal microbial transplant, fidaxomicin, rifaximin, bezlotoxumab o FMT: anterograde infusion via OGD + retrograde infusion • Retesting for C. diff NOT required: stool carriage persists 3-6 weeks post-cessation (false +ve)

Answer 4

Pathophysiology • Altered motility, visceral hypersensitivity • Altered gut microbiota • Changes in brain-gut axis Features • Functional bowel disorder • Associations: chronic fatigue, fibromyalgia, depression/anxiety • Subtypes: IBS-D (diarrhea) / IBS-C (constipation) / IBS-M (mixed) / IBS-U (un-subtyped) Management Multidisciplinary approach • Diarrhea: low FODMAP diet, loperamide • Constipation: high fibre diet, laxatives (PEG) • Abdominal pain: antispasmodics, TCA/SSRI • Psychotherapy if refractory *FODMAP: fermentable oligosaccharides, disaccharides, monosaccharides & polyols —> poorly absorbed by SB —> fermented by bacteria to produce gas & osmotically active carbohydrates Rome-IV criteria • Recurrent abdominal pain on average ≥1 day/week in the last 3 months • Associated with ≥2 of: o Relieved by bowel opening o Change in stool frequency o Change in stool form (appearance)

Answer 5

Definitions: rapid decline (< 26 weeks) in liver function characterised by INR ≥ 1.5 and encephalopathy, in a patient without pre-existing liver disease Classification: Jaundice to encephalopathy interval, cerebral oedema, INR, bilirubin, prognosis Investigations • Bloods: CBC, clotting, LFT, ammonia (prognostic: high levels predictive of complications & mortality) • Drug history: prescribed meds (e.g. high dose steroids, immunosuppressants), OTC, herbal medicine, mushroom (Amanita phylloides), Ecstasy • Underlying causes: o Viral hepatitis: anti-HAV, anti-HEV, HBsAg/ anti-HBc IgM, anti-HCV o DILI: paracetamol level o Alcoholic hepatitis: AST o Wilson's disease: serum ceruloplasmin, urine Cu (suspect if < 50y) o Autoimmune hepatitis: ANA, ASMA, anti-LKM1 o Liver biopsy (transjugular): if unexplained by above Management • Supportive care: o Close monitoring in ICU o INR, NH3 daily o Nutrition: 1g protein/kg/day (lower for patients with worsening hyperammonaemia or high risk for intracranial hypertension o N-acetylcysteine (NAC) for BOTH paracetamol and non-paracetamol related cause - Loading dose 150mg/kg/h over 1h -> 12.5mg/kg/h x 4h —> 6.25mg/kg/h until total duration (21h for paracetamol, 72h for non-paracetamol related) o Nucleoside analogues (e.g. tenofovir) for HBV-related o Prophylactic famotidine / PPI to reduce stress-related GI bleeding • Management of complications: o Coagulopathy: IV vitamin K1 10mg, platelets & FFP – needed if haemorrhage or before invasive procedures o HE: monitor GCS & ICP, lactulose ± intubation / sedation o Intracranial hypertension (∵cerebral oedema): mannitol, hyperventilation, hypertonic saline, hypothermia o Haemodynamics/ renal failure: fluid + vasopressor; target MAP >75mmHg; r/o adrenal insufficiency o Hypoglycaemia: 50ml D50 if BG < 2 • Liver transplant: King's College Hospital prognostic criteria ± MELD score o C/I for liver transplant: alcoholic with <6 month abstinence, extra-hepatic malignancy, severe uncontrolled extra-hepatic infection (e.g. HIV), multi-system organ failure, inability to comply with transplant meds Paracetamol: - pH < 7.3 or PT>100s(INR>6.5) + Cr>300+grade III/IV hepatic encephalopathy Non-paracetamol: - PT>100(INR>6.5) / 3 out of following five - Age <10/>40 + drug-induced/undetermined Etiology + bilirubin>300 + jaundice to coma interval>7 days + PT>50(INR3.5)

Answer 6

Definition • Cirrhosis (pathological): diffuse, regenerative nodules separated by bridging fibrous septa • Decompensated cirrhosis (clinical): cirrhosis with complications Causes: - Infection: HBV, HCV - Metabolic: ALD, NAFLD - Immune: autoimmune hepatitis, PBC, PSC - drug-induced: methotrexate, amiodarone, isoniazid, phenytoin - Inherited: Wilson’s disease, Haemochromatosis - vascular: Budd-Chairi syndrome, cardiac cirrhosis Complications: - Haptocellular carcinoma - portal hypertension: ascites, esophageal varices, hypersplenism, hepatomegaly syndrome - Impaired metabolism: encephalopathy - synthetic dysfunction: coagulopathy, jaundice, hypoalbuminaemia * Cryptogenic cirrhosis (unknown cause): usually due to recovered HBV infection or non-alcoholic steatohepatitis Investigations • Bloods: o Liver function: LFT (↑bilirubin, reverse A:G ratio ∵IgA production), clotting profile (INR) o CBC D/C: pancytopenia – macrocytic anemia (B12/folate), neutropenia / thrombocytopenia (portal HT, hypersplenism) o Glucose (hypoglycaemia), lipid profile (hyperlipidemia), RFT (hepatorenal syndrome) • To determine underlying cause: o Hepatitis serology: HBsAg, anti-HCV o Autoimmune markers: ANA / ASMA (AIH), AMA (PBC), ANCA (PSC) o Cu studies (ceruloplasmin, urine Cu) o Fe profile (iron, TIBC) • To assess complications: USG (small shrunken liver, splenomegaly, ascites), AFP (HCC), OGD (varices) • To assess fibrosis and steatosis: FibroScan (LSM, CAP – refer above) • Definitive diagnosis: liver biopsy Severity: Child-Pugh score*** Management: • Treat underlying cause, e.g. quit alcohol, antiviral therapy for HBV • Surveillance: o HCC: USG + AFP Q6m o Varices: OGD surveillance, NSBB prophylaxis if varices seen • Treat complications (see separate section) • Consider liver transplantation

Answer 7

• Definition: elevated portal pressure resulting from resistance to portal flow • Diagnosis: hepatic venous pressure gradient (HVPG) ≥ 6mmHg o Varices usually >10mmHg; bleeding varices usually >12mmHg Aetiology • Pre-hepatic: portal vein thrombosis, compression by mass lesion • Hepatic: cirrhosis, non-cirrhotic (schistosomiasis), post-chemotherapy veno-occlusive syndrome • Post-hepatic: hepatic vein thrombosis (Budd-Chiari syndrome*), IVC thrombosis, right heart failure *Suspect when sudden-onset ascites + tender hepatomegaly (Ix: hepatic vein Doppler USG) Pathogenesis of portal hypertension in cirrhosis • increase vascular resistance: mechanical obstruction (fibrosis) and functional (increase endothelin, decrease NO in hepatic sinusoids) • portal blood flow due to splanchnic vasodilation (increase NO in gut)

Answer 8

Pathophysiology: • Portal hypertension —> Splanchnic vasodilation • decrease Albumin —> decrease ECV —> increase hepatic sinusoidal pressure —> increase RAAS —> Na and water retention Clinical features: Abdominal distension (at least Child B cirrhosis) Investigations: • Bloods: CBC, clotting (for tapping), AFP • USG abdomen • Diagnostic paracentesis: tap at LLQ (sigmoid is mobile!) o Appearance: turbid (SBP), milky (chylous ascites), bloody (malignancy, TB, traumatic tap, hemoperitoneum) o Biochemistry: total protein, albumin (SAAG: >1.1g/dL = portal HT likely) ± glucose, LDH, amylase, ADA o Cell count with differential (SBP) o Microbiology: see SBP o Cytology: malignant cells DDx of ascites in cirrhotic patients: • Cirrhotic ascites • SBP • Malignant ascites (HCC) Management: aim BW loss 0.5kg/day (to decrease AKI risk) • Vitals: monitor I/O, BW, urine Na, RFT • decrease Fluid intake: o Low salt diet (Na < 2g/day) o Fluid restriction 1L/day (only if dilutional hypoNa < 125) • Diuretics: spironolactone (50mg/day) +/- frusemide (20mg/day) – titrate up weekly and maintain 100:40 ratio o Discontinue if hypoNa <120, progressive AKI/HE, muscle cramps o Discontinue frusemide if hypoK < 3; discontinue spironolactone if hyperK > 6 o Substitute spironolactone with amiloride if tender gynaecomastia (c.f. painless: CLD) • Therapeutic paracentesis for refractory ascites o Exclude SBP first o Limit of tapping: - Usual: None, but give IV albumin 6-8g per liter tapped if large-volume paracentesis (drain > 5L) - Unstable haemodynamics, AKI, HE, sepsis (SBP), recent variceal bleed: controlled paracentesis (2-4 L/day) + mandatory IV albumin cover • TIPSS (PTFE stent): for refractory ascites • Consider liver transplant: 2-year mortality 50% in cirrhotic patients presenting with ascites Serum ascites albumin gradient: Serum albumin - ascites albumin > 1.1g/dL = portal HT likely

Answer 9

Pathophysiology: • Impaired hepatic RES • Ascites —> altered gut wall permeability —> bacterial translocation from gut • Pathogens: 70% G- (e.g. E coli, Klebsiella), 30% G+ (e.g. Strep pneumoniae, Enterococcus) Diagnostic criteria of SBP: ascitic fluid WCC > 500 or neutrophil (PMN) > 250 Clinical features • 1/3 asymptomatic: require high index of suspicion —> Ix essential in ascites • S/S: Fever, abdominal pain, confusion, AKI Investigations • Blood culture • Diagnostic paracentesis: same as [ascites], but add o Biochemistry: glucose, LDH, amylase, ADA (TB) o Microbiology: Gram stain, bacterial culture (only +ve in 50%). AFB smear, TB culture Management • Ascitic tap for Dx & Tx (drain 1-2L in total), may consider repeat 48h later • IV ceftriaxone 2g Q24h / IV cefotaxime 2g Q8h for 5-10 days • IV albumin 1.5g/kg on Day 0 and 1g/kg on Day 3 (reduce risk of HRS – see below) • Monitor for hepatic encephalopathy: lactulose prophylaxis • Long-term oral ciprofloxacin prophylaxis after 1st episode (recurrence: 70% in 1 year if no prophylaxis)

Answer 10

- perforated viscus - Runyon’s criteria require at least 2 of —> increase total protein >10 —> decrease glucose < 2.8 —> increase LDH > ULN serum LDH

Answer 11

Definition: altered mental state / cognitive function in the presence of liver failure Normal physiology of ammonia: • Production: colonic bacterial catabolism of nitrogenous sources (e.g. proteins), urease-producing bacteria • Clearance: liver converts ammonia to urea / glutamine Pathophysiology: • Impaired liver function: reduced detoxification of NH3 • Portosystemic shunt: NH3 bypass liver and flow directly into systemic circulation • NH3 crosses BBB to enter brain à metabolized to glutamine à osmotic (cerebral edema) & neurotoxic effects Precipitating factors (SAQ!) • Nitrogen loads: GIB (e.g. variceal bleed), high-protein diet • Recent alcohol binge • Constipation • Infection (sepsis, SBP) • Large-volume paracentesis • Drugs: diuretics, sedatives, hepatotoxic drugs, nephrotoxic drugs • Portosystemic shunts (e.g. TIPS) Grading: Grade 0-1 = covert HE; Grade 2-4 = overt HE; note asterixis may be present in any stage • Grade 0: no clinical evidence, only psychometric alteration of tests • Grade 1: day-night sleep reversal • Grade 2: lethargy, disorientation • Grade 3: confusion, hypersomnolence • Grade 4: coma Investigations: Rule out other causes of neuropsychiatric disorders, e.g. renal failure, severe hypoNa • Plasma ammonia: NOT required for diagnosis, correlate poorly with severity of HE Management: • Resuscitation (ABC) + monitor vitals & neuro obs Q1h o Grade III-IV HE: early intubation (sedate with propofol ∵long half-life), elevate head 30°, limit neck rotation/flexion, control seizures with phenytoin, ICP monitoring • Identify and correct precipitating factors (as above) • Correct electrolyte disturbances: azotemia, hypoNa, hypoK, metabolic acidosis/alkalosis • Limit protein intake: temporary (sarcopenia further reduces ammonia & urea uptake) o Mild: start at 0.5g protein/kg/day (veg/ dairy sources preferred, consult dietician prn) o Severe: NPO for 24-48h + IV dextrose until improve —> step down to oral / tube feeding o Consider oral formulation of branched chain amino acids (BCAA) • Reduce generation of nitrogenous compounds o PO Lactulose 30-40mL Q8h - Mechanism —> Degraded into lactic acid by lactobacilli —> Acidify diffusible NH3 to non-diffusible NH4+ —> decrease colonic pH modifies colonic bacteria (displace urease-producing bacteria with Lactobacillus) —> Cathartic effect of hyperosmolar load (decrease colonic transit time) - Dose: titrated to 2-3 soft stools/ day - Route: oral, NG tube or enema - S/E: diarrhea, flatulence, NO effect on plasma glucose (not absorbed) o PO Rifaximin: add-on to lactulose for prevention of recurrence - Mechanism: antibiotic for selective decontamination (decrease urease-producing bacteria) • Antibiotics for suspected sepsis • Consider referral for liver transplant if intractable overt HE

Answer 12

• Order of pancytopenia: platelets à WBC à Hb • Reduced clotting factor: elevated INR

Answer 13

• Definition: renal failure in a patient with acute liver failure / ESLD with no identifiable cause of renal failure • Pathophysiology: portal HT —> splanchnic vasodilation (NO) —> decrease ECV —> compensatory renal vasoconstriction • Precipitating factors: dehydration (e.g. large-volume paracentesis), infection (esp. SBP), UGIB, severe alcoholic hepatitis o Add albumin + antibiotics in case of large-volume paracentesis & SBP • Diagnostic criteria: o Liver cirrhosis with ascites o AKI (refer to [renal] for KDIGO criteria) o Dx of exclusion: Exclude other causes of acute / subacute kidney injury - Volume depletion: improvement of serum Cr after 2 days of diuretics withdrawal & volume expansion with 1g/kg albumin - Haemodynamic shock - Nephrotoxic drugs e.g. NSAIDs, aminoglycosides, iodinated contrast - Structural kidney diseases: proteinuria (>500mg/day), microscopic hematuria (>50 RBC/hpf), abnormal USG Classification: Type 1 (HRS-AKI) - rapidly progressive oliguria renal failure (Cr doubling over 2 weeks) - severely ill, child’C patient - survival less than 2 weeks - Mx: Terlipressin +/- hemodialysis Type 2 (HRS non-AKI) - Chronic form, steady deterioration (Cr doubling over years) - Child B with relatively preserved LFT - survival less than 6 months - Mx: TIPSS • Management: generally unsuccessful in prolonging survival o Treat underlying liver failure and correct precipitating factors o Avoid excessive fluid (risk of fluid overload and hypoNa) o IV Terlipressin 1mg Q6h + albumin 1g/kg/day - Terlipressin: vasopressin analog (decrease splanchnic vasodilation —> divert blood to kidneys) —> C/I: IHD, PVD, stroke - Albumin: 1g/kg/day x 2 days —> 20-40g/day; expand ECV o TIPSS o Renal replacement therapy: bridge to liver transplant o Liver transplant

Answer 14

• Pathophysiology: bacterial translocation to lung —> intrapulmonary vascular dilatation (IPVD) (preferentially in lung bases) —> intrapulmonary shunting —> increase A-a gradient • Classical triad: o Liver disease o Increased A-a gradient by ABG o Intrapulmonary vascular dilatation (IPVD) on echo • Clinical features: o Dyspnea (MC) o Platypnoea: increased dyspnoea that is exacerbated by upright position (worsening V/Q mismatch) & relived by lying supine o Orthodeoxia: desaturation that is exacerbated by upright position & relieved by lying supine • Investigation: transthoracic contrast echocardiogram (TTCE) for IPVD o Normal: contrast only show up in right heart (∵filtered by pulmonary capillary bed) o IPVD: contrast in left heart a few cycles afterwards • Management: long-term O2, embolization of large IPVD, liver transplantation

Answer 15

• Definition: pleural effusion in cirrhotic patient with no evidence of other cardiopulmonary diseases • Pathophysiology: movement of ascitic fluid into pleural space through fistula in diaphragm • Clinical features: o Transudative effusion (usually unilateral on right side) • Management (similar to ascites): low Na diet, fluid restriction, therapeutic thoracentesis

Answer 16

• Definition: pulmonary hypertension in patient with existing portal hypertension • Pathophysiology: endothelin-1 (normally metabolised by liver) reaches pulmonary circulation by portosystemic collaterals —> pulmonary vasoconstriction • Management (similar to pul HT): prostacyclin agonists, endothelin antagonist, PDE5 inhibitor

Answer 17

Signs and symptoms: fever, n/v, RUQ pain, cholestasis, jaundice – cannot tell acute vs acute-on-chronic hepatitis Investigations: • CBC (WCC usually normal), LFT (ALT usually 200-2000, but can be low if fulminant hepatitis), amylase • Clotting profile: INR is best for reflecting liver function (∵short half-life of Factor VII) • Viral serology: o Anti-HAV IgM, anti-HEV IgM o HBsAg + anti-HBc IgM (only marker +ve if in “window period”) o Anti-HCV (may take 12 weeks to appear) ± HCV RNA (if certain exposure history) Initial management: • DAT, Obs Q4h, H’stix BD (liver failure can cause hypoglycemia) • Bloods x CBC, LRFT, INR, NH3 daily

Answer 18

- Faecal-oral route - 2-4 weeks incubation - rare fulminant hepatitis - Ix: Anti-HAV IgM - Prevention: avoid uncooked seafood, vaccination - never chronicity or re-infection Management: usually self-limiting • Alcohol abstinence x 6 months is recommended for acute hepatitis • Hepatitis A vaccine (IMI inactivated whole virus vaccine) o Indications: travel to endemic areas, MSM, patients with CLD, IVDA o Regimen: monovalent (2 doses 6-12 months apart) / bivalent (combined with HBV) o Effective around 4 weeks after 1st dose – urgent travellers may require passive immunization by IVIG

Answer 19

- Faecal oral route, Zoonotic: pigs, shellfish (genotypes 3 & 4), rodents - 3-8 weeks incubation - reare fulminant hepatitis except in pregnant women (25%) - Ix: Anti-HEV IgM +/- stool HEV RNA RT-PCR - avoid internal organs especially pig liver for prevention - chornicity: rare except in transplant patients - re-infection: possible • Chronic hepatitis E (detection of HEV RNA in serum / stool > 6 months) in transplant recipients o Mx: Reduce immunosuppressants, ribavirin monotherapy x 12 weeks

Answer 20

Acute hepatitis B infection • Clinical features: jaundice, n/v, anorexia, RUQ pain • Outcomes: o Full recovery (MC) o Chronic hepatitis B (10%) o Acute liver failure (1%) • Management o Supportive care o Antiviral not required except acute liver failure —> entecavir o Monitor HBsAg + anti-HBc IgM 6 mo later Chronic hepatitis B infection Definition: HBsAg +ve for ≥6 months —> further classified by HBeAg status Prevalence: ~8% in HK (lower in young population due to vaccination), ~4% globally Hepatitis B serology • Acute infection: HBsAg, anti-HBc IgM* • Chronic infection: HBeAg, HBV DNA • Inflammation of liver: LFT (ALT >> AST in acute phase) Window period: 3-6 months after HBV exposure HBsAg -ve but anti-HBs not yet developed —> Only marker for Dx is anti-HBc IgM Stage: 1. Immune tolerance - immature immune system fails to recognise virus —> no clearance, +v2 HBeAg, -ve Anti-HBe, +++ HBV DNA, Normal ALT, not increased risk of cirrhosis 2. Immune clearance - active immune response: cytotoxic T cells kill HBV-infected hepatocytes —> Increase ALT, + -> - HBeAg, - -> + Anti-HBe, ++ HBV DNA, +++ ALT, increased risk of cirrhosis (antiviral indicated) 3. Immune control: Normalization of HBV DNA and ALT over 12 months, -ve HBeAg, +ve Anti-HBe, ow HBV DNA, normal ALT, not increased risk of cirrhosis 4. Immune escape: elevated HBV DNA with progressive liver damage, -ve HBeAg, +ve Anti-HBe, +++ HBV DNA, +++ ALT, increased risk of cirrhosis (antiviral indicated) Management of chronic Hep B: Education: • Avoid alcohol • Avoid hepatotoxic drugs • Immunization for hepatitis A • Prevent transmission: o Sexual: vaccination of spouse, steady sexual partners, safe sex with barrier contraception o MTCT: C-section, perinatal TDF (refer below), HBV vaccine + HBIG for newborn o Environmental: avoid sharing razors/toothbrushes/needle, avoid donating blood/organs Disease monitoring Is HBV active? • HBV DNA Q6-12mo (if active: Q3mo until undetectable x 2 visits) • HBeAg & anti-HBe Q6-12mo until seroconversion Is the liver inflamed? • LFT Q6-12mo (if active: Q3mo until normalized or undetectable HBV DNA) Is there cirrhosis? • Fibroscan, OGD ± liver biopsy (gold standard) Is there HCC? • USG + AFP (Q6mo ideally)* o ≥1cm: triphasic CT scan / MRI o <1cm: repeat USG at 4 months *Rationale: tumor doubling time of HCC ~140 days, if missed at initial scan (<1cm), will be ≤2cm 6 months later and still operable HCC surveillance • Methods o USG: limitations in obese patients / cirrhosis with multiple regenerative nodules o AFP: false +ve (active hepatitis, pregnancy); false -ve (tumors not producing AFP, sensitivity ~60-70%) – benefit marginal if USG can be arranged Q6mo • Target patients: Asian hep B carriers (male >40y; female >50y) o Not all patients benefit: e.g. Child C cirrhosis unless transplant candidate, limited life expectancy • Scoring o CUHK-HCC score: age, albumin, bilirubin, cirrhosis, HBV DNA o LI-RADS system based on USG findings

Answer 21

Aim: Sustained viral suppression —> lower necroinflammation of liver —> lower risk of cirrhotic complications & HCC • REVEAL study: increase HBV DNA level —> increase risk of progression to cirrhosis and HCC Indications (important!) • Non-cirrhotic patients o Elevated HBV DNA (HBV DNA > 20,000 IU/mL if HBeAg +, >2000 IU/mL if HBeAg -) o PLUS persistent ALT elevation (> 2x ULN) OR significant fibrosis (≥F2) • Cirrhotic patients o Detectable HBV DNA (esp. >2000 IU/mL; if <2000, treat if ALT) o Decompensated liver cirrhosis • Pre-emptive Tx if on potent immunosuppressants (see separate section) • Pregnant women (28-32wk of gestation – 4-12wk postpartum) if HBV DNA > 200,000 IU/mL: give TDF • HBV reactivation during chemotherapy • Hx of HCC with detectable HBV DNA • Transplant patient with HBV infection • Acute liver failure (e.g. fulminant acute Hep B) When to stop antivirals: only allowed in non-cirrhotic patients • Primary endpoint reached (HBsAg seroclearance i.e. HBsAg becomes -ve) • HBe seroconversion: HBeAg -ve & undetectable HBV DNA for 1 year (~30-40% risk of relapse) 1. Nucleotide/nucleotide analogue - MOA: decrease reverse transcription —> decrease viral replication - example: entecavir 0.5mg PO daily, 2h before meal - lifelong duration - high viral suppression - HBeAg seroconversion:15-20% in 1 year - HBsAg seroclearance Rare: <1% per year (~untreated) - Other benefits Low resistance: entecavir ~1% —> add tenofovir (no resistance reported) Potential reversal of liver cirrhosis Reduced risk of HCC - Side effects Virtually no S/E - Entecavir: C/I in pregnancy - Tenofovir: 1% chance of nephrotoxicity (type 2 RTA —> osteomalacia) - Preferred when Decompensated cirrhosis (lifelong Tx) Pregnancy: use tenofovir (TDF)/ telbivudine 2. interferon (not used in cirrhosis) - MOA: increase immune response against virus - Pegylated-interferon alpha2a 180mcg SC weekly - 48 weeks duration - moderate viral suppression - HBeAg seroconversion 30-40% in 1 year - HBsAg seroclearance up to 10% upon follow up - other benefits: Finite duration of treatment Good durability: maintain response after stopping the drug - side effects: Numerous -> Flu-like syndrome: fever, myalgia -> Neuropsychiatric: depression, etc -> Myelosuppression -> Autoimmune thyroiditis - preferred when Long-term therapy not desired (e.g. young female to achieve drug-free period for few years to get pregnant)

Answer 22

High risk” - Anticipated incidence of reactivation > 10% - HBsAg+ or *anti-HBc+ patients with • B cell-depleting agents (rituximab, ofatumumab) or HSCT HBsAg+ patients with • Anthracycline chemo (e.g. doxorubicin) • Prednisolone 10mg/day or higher for > 4 weeks - Antiviral prophylaxis Monitor HBV DNA Q6m Continue antiviral for 6 mo after cessation of immunosuppressive (12 mo if on B-cell depleting agents or HSCT) Moderate risk: - Anticipated incidence of reactivation 1-10% - HBsAg+ patients with • Other biologics • Low-dose steroid > 4 weeks - Consider antiviral prophylaxis Low risk: - Anticipated incidence of reactivation < 1% - All other patients, including HBsAg+ patients with • Traditional immunosuppressive agents (e.g. MTX, azathioprine, intra-articular steroid) • Steroid use daily < 1 week - Antiviral prophylaxis NOT required

Answer 23

• Definition: HBsAg -ve but HBV DNA +ve (HBV as a DNA virus forms cccDNA (closed circuit covalent DNA) that remains dormant in hepatocytes • Seropositive OBI (anti-HBc/ anti-HBs +ve) or seronegative OBI (both -ve) • Implications: o HBV transmission during blood transfusion/ liver transplant o HBV reactivation during potent immunosuppressant

Answer 24

Definition: - presence of HCV RNA ≥6 months after exposure - Global prevalence: 0.7% - Route of transmission: blood (IVDA, transfusion), mother-to-child transmission, sexual (less common) - 6 genotypes: 1b & 6a are most common in HK Clinical course • Acute infection: usually asymptomatic / subclinical hepatitis in 80% • Most progress to chronic carrier irrespective of age, c.f. HBV • Extrahepatic manifestations: o Type 2 / 3 cryoglobulinemia (decrease C3/C4, RF+, cryoglobulin+) o Membranoproliferative GN o Autoimmune: thyroiditis, hepatitis, Sjogren’s syndrome o Dermatological: porphyria cutanea tarda, lichen planus o Haematological: lymphoma, myeloma Acute-on-chronic HCV infection: increase HCV RNA, anti-HCV +ve Acute HCV infection: increase HCV RNA, anti-HCV -ve initially but +ve within 12 weeks HCV seroclearance: decrease HCV RNA, anti-HCV +ve Investigations • Anti-HCV: +ve within 12 weeks after infection, remain positive after viral clearance • HCV RNA: indicate active disease (indication for antiviral!) • HCV genotype testing: different disease course and DAA o Genotype 1b & 3: more rapid progression and higher risk of HCC • ± Screening of complications: urinalysis, TFT, anti-thyroid antibodies, ANA Antiviral treatment • Indication: all patients with detectable HCV RNA • Direct-acting antivirals (DAA) x 12 weeks o MOA: inhibit replication, post-translational processing and assembly of HCV o Treatment endpoint: sustained virologic response (SVR) as defined by absent HCV RNA by PCR 12 weeks after stopping treatment (a/w 99% chance of long-term HCV RNA negative) - SVR achieved: check ALT & HCV RNA at 48 weeks —> consider cured if normal - SVR not achieved: continue treatment for 12 weeks o Drug classes NS3/4A protease inhibitors (-previr): - decrease replication - glecaprevir, voxilaprevir, paritaprevir NS5A RNA-polymerase inhibitors (-asvir): - decrease replication - velpatasvir, pibrentasvir, ledipasvir NS5B RNA-polymerase inhibitors (-buvir) - decrease assembly, secretion - sofosbuvir o Regimen: combination of drugs ( decrease resistance) - depends on cirrhotic status (IFN is C/I), viral genotype, viral load, concomitant drugs, etc. - Maviret (glecaprevir/pibrentasvir) – taken with food - Esclusa (velpatasvir/sofosbuvir) o Minimal side effects: rash, fatigue, etc o Drug interactions: DM meds (hypoglycemia), warfarin (monitor INR), amiodarone, rifampicin, dabigatran, anticonvulsants, rosuvastatin • Conventional treatment: PO ribavirin + SC peg-interferon (SVR 60-80%) x 48 weeks, C/I in pregnancy & cirrhosis

Answer 25

Three main forms: alcoholic fatty liver disease (AFLD) —> alcoholic hepatitis —> alcoholic cirrhosis Pathology • Histological hallmark: ballooning degeneration, Mallory-Denk bodies • Pathophysiology: excessive alcohol saturates alcohol dehydrogenase —> shunted to microsomal ethanol-oxidising system (MEOS) —> release free radicals and pro-inflammatory cytokines to damage hepatocytes Assessment of alcoholism CAGE questionnaire: Cut down, Annoyed, Guilty, Eye-opener (≥2: positive) Safety drinking limit (1 unit = 8g): 2-3 units/day (male), 1-2 units/day (female) Investigations for alcoholism • Blood alcohol level (BAL) • LFT: AST: ALT ≥2:1 (both elevated but never sky-high >500) + GGT (enzyme induction) • CBC: MCV • Plasma glucose (hypoglycemia), lipid profile (hyperlipidemia) Score: Maddrey’s discriminant function (DF) – if >32 give steroids • DF = 4.6 x (prothrombin time – control time) + bilirubin (mg/dL) Treatment of alcoholic liver disease • Total abstinence • Prevention of withdrawal: long-acting benzodiazepines (e.g. chlordiazepoxide) • Nutritional support: thiamine replacement, HE prophylaxis • Prednisolone 32mg/day x 4 weeks: indicated if DF ≥ 32 • Pentoxifylline (weak TNF inhibitor) Other systemic effects of alcoholism Signs: - Parotid enlargement, Dupuytren’s contracture, cachexia (malnutrition) GI: - Oesophagus: Mallory-Weiss syndrome, oesophageal varices (portal HT) - Stomach: peptic ulcer - Pancreas: chronic pancreatitis CVS: - Hypertension - Beriberi (thiamine deficiency —> high-output HF) Hemat: - Macrocytic anemia ± thrombocytopenia (hypersplenism) - Zieve’s syndrome: hemolytic anemia (with spur cells & acanthocytes) + jaundice + abdominal pain + hyperlipidemia – altered red cell metabolism (pyruvate kinase instability) Neuro: - Peripheral neuropathy (sensory-predominant) - Proximal myopathy - Cerebellar degeneration - Alcoholic dementia Psychiatric: - Acute withdrawal: delirium tremens • Onset: 24-48h after last drink, last 1-5 days • S/S: delirium, gross tremor, VH, truncal ataxia, autonomic dysfunction (e.g. hyperthermia) • Mortality 5% (hyperthermia, associated seizure) • Management: o Environment: well lit, quiet room o Supportive: - Rehydration - IV high-dose thiamine + folate + multivitamins + MgSO4 in NS ("banana bag") - Correct hypoK, hypoMg, hypoglycemia; watch out for rhabdomyolysis o Benzodiazepines: esp. if CIWA-Ar ≥8 § Chlordiazepoxide PO / Diazepam PO or lorazepam IM Wernicke's encephalopathy: vitamin B1 deficiency • Pathology: haemorrhage in periventricular grey matter • Clinical diagnosis – classical triad (confusion, ataxia, ophthalmoplegia) only occur in 15-30% of patients, difficult to differentiate from acute alcoholic intoxication • Ix (supportive): RBC transketolase, serum Mg (co-factor) • Mx: high dose IV thiamine (500mg Q8h x 2 days), correct hypoMg, closely monitor BP/P, neuro obs, • Prognosis: 20% mortality, 80% develop Korsakoff's syndrome Korsakoff's syndrome: • Irreversible amnesic syndrome (anterograde amnesia) • Mx: long-term thiamine Caine’s criteria for alcoholics: 2 out of 4 - Dietary deficiency - Oculomotor abnormalities - Cerebellar dysfunction - Consciouness decrease / Memory decrease

Answer 26

• Most common chronic liver disease (prevalence: 27%, M>F for most age groups except after 70y ∵menopause) • Spectrum: hepatic steatosis (fat within hepatocytes) —> Non-alcoholic steatohepatitis (NASH) —> Cirrhosis • Histology: steatosis >5% + lobular inflammation + ballooning degeneration Clinical features • Usually asymptomatic: incidental finding of deranged LFT • Associated with metabolic syndrome (BMI, central obesity, T2DM, dyslipidemia, HT) • Hepatomegaly in 50% Diagnosis • Demonstration of hepatic steatosis on imaging, blood • Exclude significant alcohol consumption • Exclude other causes of hepatic steatosis Other causes of fatty liver • Rapid weight loss (body fat consumption biomarkers/scores, or histology generates FFA) • Chronic hepatitis C (esp. genotype 3) • Wilson’s disease • Drug-induced: methotrexate, steroid, tamoxifen • Reye’s syndrome • Acute fatty liver of pregnancy Investigations • LFT: can be normal, AST < ALT (c.f. alcoholic liver disease) • Metabolic workup: FBG, lipid profile, BP, RFT • USG: bright liver (hyperechoic parenchyma), deep attenuation, vascular blunting Management • Control metabolic risk factors (1st line): weight loss, treat HT/HL/DM, refrain from alcohol • Possible pharmacological treatment to decrease liver fat & inflammation o Vitamin E: anti-oxidant, neutral effect on insulin resistance, uncertain effects on CVS and malignancy o Pioglitazone: insulin sensitizer, but note S/E (weight gain, heart failure, risk of bladder cancer) o GLP-1 agonists (e.g. semaglutide) • Bariatric surgery if morbidly obese **** Resmetirom: liver specific thyroid hormone receptor beta agonist, Oral, MASH (metabolic-dysfunction steatotic hepatitis) resolution+improve fibrosis, decrease total and CO2 cholesterol

Answer 27

Pathophysiology • AR defect in copper metabolism (ATP7B gene on Chr 13 —> codes for copper-transporting ATPase) • Cu cannot incorporate into apoceruloplasmin (unstable form) —> decrease ceruloplasmin (excessive breakdown) • Defective Cu excretion into bile —> accumulate inside liver causing damage (hepatic Cu) • Damaged hepatocytes release stored Cu in free form —> increase serum free Cu, increase 24h urine Cu Clinical features Usually hepatic manifestations in children / young adults but neurological manifestations in older adults • Liver: acute liver failure, cirrhosis • CNS: basal ganglia (Parkinsonism), cerebellum (wing-beating tremor, ataxia, incoordination, dysarthria, dysphagia), cerebrum (psychosis, mood disorder) • Eyes: Kayser-Fleischer rings (copper deposits in Descemet's membrane), sunflower cataract (copper deposits in lens) • Kidney: haematuria, Fanconi's syndrome (proximal tubule transport defect) • Hemat: Coombs negative haemolytic anemia (Cu deposit in RBC) Investigations Suspect if abnormal LFT with clinical presentations (e.g. dystonia, psychiatric symptoms) at young age (<30) • ↓serum ceruloplasmin (<20 mg/dL): normal in up to 10% of patients • ↑24h urine Cu >100µg • Slit lamp exam (KF rings): present in 99% if neuropsychiatric symptoms and 30-50% if hepatic symptoms • CBC (hemolytic anemia), LFT (AST/ALT > 2) • ± Liver biopsy: hepatic Cu • ± MRI brain: ‘face of giant panda’ in midbrain • Confirmative: ATP7B gene mutation Leipzig score Management • Genetic counselling • Pharmacotherapy: o Copper chelator: penicillamine preferred due to lower cost, but similar efficacy as trientine - Penicillamine: given with vit B6, S/E: initial decrease neuro Sx, nephrotoxicity, MG, drug-induced lupus - Trientine: S/E: chelate iron / zinc to form ineffective complexes —> separate 1hr when taking o Copper absorption inhibitor: - PO Zinc: maintenance treatment in asymptomatic patients, S/E: GI upset • Management of acute liver failure: o Hemodialysis: rapid Cu removal o Liver transplant

Answer 28

ATP7A mutation (XR) —> Defective Cu uptake from intestine • Severe neurological deterioration during early childhood • “Kinky” hair, hypopigmentation MEDNIK syndrome: mixed features of Menkes disease and Wilson’s disease

Answer 29

Definition: hepatitis characterised by a strong association with other autoimmune diseases, hypergammaglobulinaemia and autoantibodies Clinical features • Bimodal age distribution: young & middle-aged females • Acute liver failure (25%) • Chronic liver disease • S/S of other autoimmune diseases, e.g. Graves', Hashimoto's thyroiditis, T1DM, UC, RA/SLE Diagnosis • LFT: increase ALT, increase AST • Serology o increase total IgG (usually normal IgM, IgA) o Type 1 AIH: ANA, ASMA (anti-smooth muscle Ab), atypical p-ANCA o Type 2: anti-LKM1 (anti-liver kidney microsomal Ab type 1), anti-liver cytosol 1 • Diagnosis by exclusion: viral hepatitis, Drug-induced liver injury, alcoholic liver disease • ± Liver biopsy: to confirm diagnosis Management • Induction: high-dose prednisolone 40-60mg/day (check TB, HBV/HCV) • Maintenance: prednisolone + azathioprine (check TPMT)

Answer 30

• Clinical features: can present all forms of liver injury (hepatitic, cholestatic, mixed pattern, cirrhosis) Paracetamol-induced liver injury • Acute toxic dose: >150mg/kg (4-6g in alcoholic/ anticonvulsant user) • Clinical features: o 0-24h: n/v o 24-48h: asymptomatic (ongoing hepatic necrosis) o >48h: resolution, or acute liver failure • Management o Within 1st hour: activated charcoal o Not within 1st hour: check paracetamol level at 4h, LRFT o N-acetylcysteine (NAC) if toxic level about treatment line: - Dose 150mg/kg in 1h, then infusion over 20h - Most effective if within 8h post-ingestion, but give regardless of time o Markers of liver injury: clotting, LFT, ABG, lactate, AFP, PO4

Answer 31

Definition • Gilbert's syndrome: mild decrease in glucuronyl transferase activity due to AD mutation in UGT1A1 gene • Crigler-Najjar syndrome: complete deficiency in GT; rapid death in neonates (kernicterus) Clinical features: jaundice during stress/ fasting Investigations • Isolated unconjugated bilirubin • Rule out haemolysis: CBC, retic, blood smear Management: reassuranc

Answer 32

Definition: Granulomatous inflammation of intrahepatic bile ducts M:F: 1:9 (middle aged women) Etiology: Autoimmune: Sjogren's syndrome (70%), limited SSc, RA, Hashimoto’s thyroiditis Diagnostic criteria: 2 out of 3 features • ALP ≥1.5x ULN • AMA >1:40 (esp. M2 fraction) • Histology: non-suppurative destruction of intrahepatic bile ducts (seldom done) S/S: Asymptomatic, fatigue, pruritus, jaundice Steatorrhea, hepatomegaly & cirrhosis PBC only: xanthoma / xanthelasma (xanthoma on eyelids) Ix: LFT: cholestatic pattern (ALP, bilirubin) Autoimmune markers: AMA +ve (anti- mitochondrial Ab), ANA (70%, a/w poor prognosis) Lipid profile: increase LDL (but not CV risk) USG: undilated bile duct DEXA: osteoporosis ± MRCP: not diagnostic, to r/o extrahepatic biliary obstruction esp. CA ± Liver biopsy (not routine) Mx: Dietary modifications • Low fat diet with medium chain TG supplements (not require bile acid for absorption) • Fat-soluble vitamin supplement • Ca ± bisphosphonates Pharmacological therapy • Ursodeoxycholic acid (UDCA) 15mg/kg/day: 1st line, only disease-modifying Tx (2° bile salt: ¯endogenous production of bile salts) • Fibrates: 2nd line Symptomatic treatment • Pruritis: cholestyramine (bile salt chelator: excretion), naloxone, rifampicin • Cholangitis: RADO, endoscopic stenting of dominant strictures Malignancy screening (PSC) • USG + MRCP + CA19-9 yearly (cholangioCA, gallbladder CA) • Colonoscopy yearly (if IBD), routine (if no IBD) • USG + AFP Q6mo (if cirrhotic) Liver transplant: Cx: Cirrhosis, HCC Osteoporosis (hepatic osteodystrophy)

Answer 33

Definition: Obliterative fibrosis of biliary tree, mainly medium/large intrahepatic and/or extrahepatic ducts M:F: 2:1 (young men) Etiology: Primary: IBD 70% (UC* > CD) Secondary: long-term choledocholithiasis, cholangioCA, parasitic infection (Clonorchis), post-ERCP S/S: Asymptomatic, fatigue, pruritus, jaundice Steatorrhea, hepatomegaly & cirrhosis PSC only: features of IBD (e.g. bloody diarrhoea, oral ulcers, arthralgia) Ix: LFT: cholestatic pattern (ALP, bilirubin) USG: dilated bile duct Autoimmune markers: p-ANCA (30-80%), AMA -ve, increase IgM, may have increase IgG4 MRCP: "beads on string" appearance Colonoscopy: look for IBD ± Liver biopsy (not routine): “onion skin” periductal fibrosis & inflammation, obliterated bile ducts Mx: Dietary modifications • Low fat diet with medium chain TG supplements (not require bile acid for absorption) • Fat-soluble vitamin supplement • Ca ± bisphosphonates Pharmacological therapy • Ursodeoxycholic acid (UDCA) 15mg/kg/day: 1st line, only disease-modifying Tx (2° bile salt: decrease endogenous production of bile salts) • Fibrates: 2nd line Symptomatic treatment • Pruritis: cholestyramine (bile salt chelator: excretion), naloxone, rifampicin • Cholangitis: RADO, endoscopic stenting of dominant strictures Malignancy screening (PSC) • USG + MRCP + CA19-9 yearly (cholangioCA, gallbladder CA) • Colonoscopy yearly (if IBD), routine (if no IBD) • USG + AFP Q6mo (if cirrhotic) Liver transplant: Cx: Cirrhosis, HCC, osteoporosis CholangioCA (10-15% lifetime risk), gallbladder CA, CRC (esp. if IBD + PSC) Recurrent cholangitis

Answer 34

• Mechanisms: o increase lipoprotein-X (abnormal lipoprotein particle rich in free cholesterol) due to regurgitation of biliary lipids into plasma o decrease LDL receptors due to hepatic injury • No increased CV risk: lipoprotein-X inhibits LDL oxidation • Reduced by ursodeoxycholic acid

Answer 35

Albumin >3.5 g/dL (>35 g/L) +1 2.8-3.5 g/dL (28-35 g/L) +2 <2.8 g/dL (<28 g/L) +3 Bilirubin (Total) <2 mg/dL (<34.2 µmol/L) +1 2-3 mg/dL (34.2-51.3 µmol/L) +2 >3 mg/dL (>51.3 µmol/L) +3 INR <1.7 +1 1.7-2.3 +2 >2.3 +3 Ascites Absent +1 Slight +2 Moderate +3 Encephalopathy No Encephalopathy +1 Grade 1-2 +2 Grade 3-4 +3

GI Flashcards

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