W10.4_Liver Therapeutics

Question 1

Define ascites and discuss how it should be treated. What should be monitored during the treatment? Are there any other treatments for large volume ascites?

Answer 1

• Ascites: accumulation of fluid in peritoneal cavity (due to reduced albumin level) -> swollen abdomen and abdominal pain
• Diuretics: induce negative fluid balance and reduce amount of ascites, relying on high circulating levels of aldosterone in liver
• Spironolactone as first-line treatment with possible addition of furosemide (combination of aldosterone antagonist and loop diuretic causes more rapid diuretic effect)
• Amiloride can be an alternative to spironolactone if not tolerated (due to gynaecomastia)
• Monitoring: body weight, renal function (U&E), side-effects and tolerability
• Other treatment: fluid and sodium restriction, paracentesis for large volume ascites

Question 2

Define spontaneous bacterial peritonitis (SBP), explain its symptoms and diagnositic method, and discuss how it should be treated.

Answer 2

• Spontaneous bacterial peritonitis (SBP): infection of ascitic fluid without source of sepsis
• Symptoms: severe pain, raised temperature, raised white-cell count
• Diagnosis: sample of ascitic fluid (neutrophil count >250 cells/mm3)
• High mortality rate of 40%
• Initially treat with broad spectrum IV antibiotic -> review after 5 days -> ciprofloxacin/ co-trimoxazole may be required for long-term prophylaxis

Question 3

Define hepatic encephalopathy, its possible causes, symptoms, and treatment plans (3).

Answer 3

• Neuropsychiatric changes in mood and behaviour, confusion
• May be due to accumulation of toxins (ammonia)/increased protein load/electrolyte disturbance/ drugs/infection
• Symptoms: similar to hypoglycemia, alcohol intoxication/withdrawal
• High dose laxatives (lactulose liquid 20-30mL BD/TDS or phosphate enema OD/BD)
• Aim: 2-3 soft stools per day -> change pH of gut lumen and reduce colonic bacterial load -> inhibits intestinal ammonia production -> reduce/prevent hepatic encephalopathy
• Antibiotics (rifaximin 550mg BD): low systemic absorption (only act in guts) -> kills gut bacteria
• L-ornithine L-aspartate sachets (unlicensed): increases ammonia removal
• Dietary protein restriction not recommended

Question 4

Define portal hypertension and varices. What is the resuscitation plan for severe blood loss? Explain the diagnostic method, treatment plans (3) and secondary prophylaxis treatment plan.

Answer 4

• Portal hypertension caused by increased resistance to flow from disruption in hepatic architecture and compression of hepatic venules after regenerating nodules
• Varices (collateral vessels) enable blood to bypass liver: very weak, can burst and cause GI bleeding (usually severe)
• Severe blood loss: resuscitation by fluids and blood transfusion
• Endoscopy: to find root cause (banding + sclerotherapy)
• Potent vasoconstriction to reduce blood loss: terlipressin IV 1-2mg bolus then every 4-6 hours
• Antibiotics: IV broad spectrum for ≥5 days to reduce infection risk
• PPI: reduce GI bleeding
• Secondary prophylaxis: propranolol tabs 20-40mg BD to cause splanchnic vasoconstriction (ß-2 blockade) and reduce heart/cardiac index (ß-1 blockade) -> reduce portal flow and portal pressure -> prevent re-bleeding to increase survival chance (nadolol/carvedilol can be used as alternatives)

Question 5

Define pruritus and discuss how it should be treated (4).

Answer 5

• Pruritus: itching of skin caused by bile salts accumulation
• Colestyramine (anion-exchange resin): bind bile salts (polypharmacy: can bind to other drugs)
• Ursodeoxycholic acid: help with metabolism (possible underlying cause)
• Unlicensed: rifampicin, sertraline, naltrexone
• Topical treatments: calamine lotion, menthol 2% in aqueous cream
• Antihistamines: ineffective

Question 6

Explain the screening tool, symptoms, and general treatment plan for alcohol withdrawal.

Answer 6

• Screening tool: CIWA-Ar assessment tool to determine severity and optimise treatment plan
• Symptoms: delirium, agitation, fever, rapid pulse, dehydration, seizures
• Treatment: 24-hour assessment and monitoring in hospital -> fixed dose regimen and reduce dose to zero over 7-10 days

Question 7

Discuss different pharmacological interventions, vitamin supplementation, absitnence treatment, and pharmacological treatments of alcohol withdrawal.

Answer 7

• Chlordiazepoxide (quick-acting and long-acting benzodiazepine): prevents agitation and seizures due to its sedative and anticonvulsant properties (low potency)
• Oral lorazepam (short-acting): for delirium tremens
• Poor diet + alcohol prevents thiamine absorption -> vitamin deficiency
• Vitamin supplementation: IV Pabrinex (vitamin B+C) 1-3 pairs BD/TDS or thiamine oral tabs to treat potential thiamine (vitamin B1) deficiency and prevent Wernicke’s encephalopathy
• Abstinence treatment: psychological (cognitive behavioural treatment) + pharmacological
• Medications that work with addiction pathways in brain: acamprosate, oral naltrexone, nalmefene, disulfiram (only when requested by patient, as it is a punishment treatment)

Question 8

Discuss the different lines of prevention or treatment plans for NAFLD.

Answer 8

• Management of NAFLD: initially focus on lifestyle modifications
• Second-lines: treating components of metabolic syndrome, liver-directed pharmacotherapy
• Last-line: managing complications of cirrhosis

Question 9

Explain the principles of prescribing to patients with hepatic impairment in terms of ADME.

Answer 9

• Absorption: may be reduced in presence of ascites, lipid soluble drugs less well absorbed
• Hypoalbuminemia: reduced protein binding and increased toxicity for highly protein-bound drugs
• Impaired drug metabolism: reduced intrahepatic blood flow and production of drug-metabolising enzymes slows metabolism down and increases toxicity
• Excretion: CrCl may overestimate eGFR in patients with cirrhosis

Question 10

Explain the principles of prescribing to patients with hepatic impairment in terms of medication types (5).

Answer 10

• Sedating medications, opioid analgesics, constipating medicines, diuretics that cause hypokalemia: may precipitate/worsen encephalopathy
• Anticoagulants and antiplatelets: increased risk of bleeding due to higher sensitivity
• Drugs that cause fluid retention (ex. NSAIDs, corticosteroids): exacerbate oedema and ascites
• Medicines with high sodium content: precipitate/worsen ascites
• Nephrotoxic/hepatotoxic medicines: more frequent DILI/happen at lower dose

Question 11

Explain the principles of prescribing to patients with hepatic impairment in terms of drug formulations (4).

Answer 11

• MR preparations: should be avoided as they could accumulate
• IM injections: should be avoided as they could cause haematoma at injection site
• Topical preparations/patches: may cause more skin irritation
• Rectal preparations: should be assessed for possible rectal varices and increased bleeding risk