Management of chronic liver disease complications, such as ascites, coagulopathy, and encephalopathy
Complications and their drivers
- Complications of cirrhosis flow from two things: portal hypertension and loss of hepatocyte function
| Complication | Driven by |
|---|---|
| Varices / portal hypertensive bleeding | Portal HTN |
| Ascites, hydrothorax | Portal HTN + splanchnic vasodilatation + Na retention |
| SBP | Ascites + bacterial translocation |
| Hepatorenal syndrome | Extreme splanchnic vasodilatation -> renal vasoconstriction |
| Hepatic encephalopathy | Portosystemic shunting + loss of function |
| Coagulopathy | Loss of function (rebalanced, not one-way) |
| Hyponatraemia | Non-osmotic ADH release |
| HCC | Chronic injury + regeneration |
- First decompensation drops median survival from >12 years to ~2 years - the trigger for transplant referral
- Recompensation (Baveno) is now a recognised endpoint: remove the aetiology + resolution of ascites/HE off drugs + stable improvement in liver function
Epidemiology
- ~5-7% of compensated cirrhotics decompensate per year
- Ascites is the commonest first decompensating event (~50%)
- SBP in ~10-30% of cirrhotic inpatients with ascites
- HE affects up to 80% (covert + overt) over the disease course
The haemodynamic cascade - one mechanism explains most of it
- inc intrahepatic resistance -> portal hypertension
- -> splanchnic arterial vasodilatation (NO, prostacyclin)
- -> dec effective arterial blood volume
- -> RAAS + SNS + ADH activation
- -> Na and water retention -> ascites; free water retention -> hyponatraemia
- -> renal vasoconstriction -> hepatorenal syndrome
- Hyperdynamic circulation: low BP, wide pulse pressure, high cardiac output - looks like sepsis
Hepatic encephalopathy - mechanism
Hepatic encephalopathy
- Portosystemic shunting + dec hepatic clearance -> ammonia crosses BBB
- Astrocyte glutamine accumulation -> osmotic swelling -> Alzheimer type II astrocytes
- Inflammation and sarcopenia amplify (muscle is the main extrahepatic ammonia sink - hence sarcopenia worsens HE)
- Serum ammonia does not correlate with grade and should not be used to diagnose or track HE
Coagulopathy - rebalanced haemostasis
- dec procoagulants (II, V, VII, IX, X, fibrinogen) and dec anticoagulants (protein C, S, antithrombin)
- inc factor VIII and vWF (endothelial)
- Net: rebalanced, but fragile. Cirrhotic patients get PVT and VTE as well as bleeding
- INR predicts mortality, not bleeding risk. Do not transfuse to "correct" it
Ascites - paracentesis on every new or deteriorating ascites
- Serum-ascites albumin gradient (SAAG)
- >=11 g/L = portal hypertension (cirrhosis, cardiac, Budd-Chiari)
- <11 g/L = peritoneal disease, malignancy, TB, pancreatic, nephrotic
- Ascitic protein <15 g/L = high SBP risk -> prophylaxis
- Cell count, differential, culture into blood culture bottles at the bedside, glucose, LDH, cytology if indicated
SBP - diagnosis
SBP
- Ascitic PMN >250 cells/microL (or total leucocytes >500/microL) = SBP, treat immediately
- Do not wait for culture - culture-negative neutrocytic ascites is still SBP
- Usually monomicrobial, gram-negative (E. coli, Klebsiella) or streptococci
- Secondary bacterial peritonitis if: polymicrobial, ascitic protein >10 g/L + glucose <2.8 + LDH > serum ULN, or failure to respond -> imaging + surgical review
- May be asymptomatic - a low threshold for tapping is the whole diagnosis
Hepatic encephalopathy - clinical, by exclusion
| Grade (West Haven) | |
|---|---|
| Covert (0/minimal, I) | Trivial lack of awareness, sleep reversal, impaired attention. Needs psychometric testing - affects driving |
| II | Disorientation to time, lethargy, asterixis, personality change |
| III | Somnolent but rousable, gross disorientation |
| IV | Coma |
- Always look for a precipitant - HE without one is unusual
- Exclude hypoglycaemia, sepsis, intracranial event (subdural in the alcoholic patient), Wernicke, drugs
Hepatorenal syndrome (HRS-AKI)
- Diagnosis of exclusion: cirrhosis + ascites + AKI, no response to 2 days of diuretic withdrawal + albumin 1 g/kg/day, no shock, no nephrotoxin, no structural renal disease (bland urine, no proteinuria, normal renal ultrasound)
- HRS-AKI (type 1) - rapid; HRS-NAKI (type 2) - slower, with refractory ascites
- Precipitants: SBP, large-volume paracentesis without albumin, GI bleeding, sepsis, NSAIDs, aminoglycosides, over-diuresis
Variceal screening
Variceal bleeding
- Screening per Baveno rule of five:
- LSM <10 kPa rules out cACLD; LSM <15 kPa + platelets >150 rules out CSPH
- LSM >25 kPa rules in CSPH
- Endoscopy can be deferred where CSPH is ruled out
1. Ascites
- Salt restriction ~5 g salt (2 g sodium)/day
- Watch the IV fluids: normal saline ~3.5 g sodium/L, Hartmann's ~3 g/L - a litre exceeds the daily allowance
- Spironolactone first (aldosterone drives it), add frusemide; ratio ~100:40 mg
- Target weight loss 0.5 kg/day without oedema, 1 kg/day with
- Large-volume paracentesis for tense ascites
- Albumin 6-8 g per litre removed if >5 L - prevents post-paracentesis circulatory dysfunction
- Refractory ascites -> serial LVP + albumin, TIPS, transplant assessment
- Stop NSAIDs, ACE inhibitors, ARBs - they precipitate renal failure
- Fluid restriction only if Na <125 mmol/L; tolvaptan is not routinely recommended
2. SBP
2. SBP
- IV ceftriaxone (or piperacillin-tazobactam if already on norfloxacin or trimethoprim-sulfamethoxazole prophylaxis, or hospital-acquired)
- PLUS IV concentrated albumin 1.5 g/kg day 1 and 1 g/kg day 3
- dec hepatorenal syndrome and dec mortality - not optional
- Repeat tap at 48 h if not improving (expect >25% fall in PMN)
- Secondary prophylaxis: norfloxacin (or trimethoprim-sulfamethoxazole) indefinitely after an episode
- Primary prophylaxis if ascitic protein <15 g/L with advanced disease, or during GI bleeding (ceftriaxone 7 days)
- Stop non-selective beta-blockers if SBP with hypotension or AKI
3. Hepatic encephalopathy
- Treat the precipitant - infection, GI bleed, constipation, dehydration/over-diuresis, electrolytes (dec K, dec Na), sedatives/opioids, TIPS, renal failure, dietary indiscretion, PVT, HCC
- Lactulose - titrate to 2-3 soft bowel motions/day; PR if obtunded
- Rifaximin 550 mg BD - add to lactulose for recurrent or refractory HE
- Minimally absorbed; reduces recurrence and hospitalisation but not mortality; better tolerated than neomycin/metronidazole
- Nutrition: high protein 1.2-1.5 g/kg/day, frequent small meals, late-evening snack
- Protein restriction is obsolete and harmful - it worsens sarcopenia without preventing HE
- Branched-chain amino acids, LOLA, zinc - adjuncts
- Counsel about driving with covert HE
4. Hepatorenal syndrome
- Terlipressin + IV albumin (1 g/kg day 1, then 20-40 g/day)
- Terlipressin adverse effects: headache, diarrhoea, hypertension, ischaemia - coronary, mesenteric, peripheral, digital
- Cautious use in severe arteriopathy, ischaemic heart disease and the elderly; also respiratory failure/volume overload - monitor for it
- Noradrenaline in ICU as an alternative
- Withdraw diuretics, beta-blockers and nephrotoxins
- Renal replacement therapy as a bridge; liver transplantation is the definitive treatment
5. Varices and portal hypertensive bleeding
- Primary prophylaxis: carvedilol (3.125 mg daily -> 12.5 mg, max 25 mg) if CSPH, to prevent decompensation - not just bleeding
- Band ligation if beta-blocker not tolerated
- Acute variceal bleed:
- Resuscitate; restrictive transfusion, target Hb 70-80 g/L (over-transfusion raises portal pressure and rebleeding)
- Terlipressin (or octreotide) + IV ceftriaxone prophylaxis - both reduce mortality
- Endoscopy within 12 h -> band ligation (oesophageal) or cyanoacrylate glue (gastric)
- Failure -> Sengstaken-Blakemore/Minnesota tube or oesophageal stent as a bridge -> rescue TIPS
- Pre-emptive (early) TIPS within 72 h in high-risk patients (Child C <14, or Child B with active bleeding)
- Secondary prophylaxis: carvedilol/NSBB + band ligation programme
6. TIPS
| Indications | Contraindications |
|---|---|
| Variceal bleeding not controlled endoscopically | Severe or progressive liver failure |
| Refractory ascites or hepatic hydrothorax | Hepatic encephalopathy |
| Budd-Chiari syndrome | Portal vein thrombosis |
| Right heart failure / pulmonary hypertension | |
| Hepatocellular carcinoma |
- TIPS itself precipitates encephalopathy (~25-50%) and can worsen liver function
7. Coagulopathy
- Do not correct INR prophylactically - it does not reflect bleeding risk
- Vitamin K if deficiency suspected; fibrinogen if <1.0-1.5 g/L and bleeding
- Platelets if <50 x10^9/L and bleeding or before a high-risk procedure; thrombopoietin agonists (avatrombopag, lusutrombopag) as a platelet-transfusion alternative
- Anticoagulate PVT or VTE - cirrhosis is not protective
Other complications
- Portal vein thrombosis - screen at HCC surveillance; anticoagulate if recent/occlusive or transplant candidate
- Cirrhotic cardiomyopathy - blunted contractile response to stress, prolonged QT, diastolic dysfunction
- Hepatopulmonary syndrome - intrapulmonary vascular dilatation; platypnoea-orthodeoxia; contrast echo with delayed shunting
- Portopulmonary hypertension - a contraindication to transplant above a mPAP threshold
- Hepatic hydrothorax - usually right-sided; never insert an intercostal catheter - high mortality
- Sarcopenia and frailty - independent mortality predictors; drive HE
- Relative adrenal insufficiency in critical illness
- Umbilical hernia with ascites - risk of rupture and incarceration
- Cirrhosis-associated immune dysfunction -> sepsis
Prognosis
- After first decompensation median survival ~2 years
- Acute-on-chronic liver failure (ACLF) - decompensation + organ failure + very high short-term mortality; graded by number of organ failures
- SBP - ~20% inpatient mortality; 1-year recurrence ~70% without prophylaxis
- HRS-AKI untreated - median survival weeks
- Variceal bleed: ~15-20% 6-week mortality; rebleeding ~60% within 1 year without secondary prophylaxis
- HCC ~2-4%/yr in cirrhosis
What changes the trajectory
- Removing the aetiology - abstinence, antiviral cure, weight loss - can produce recompensation and even fibrosis regression
- Transplant referral at first decompensation, not at the second
Monitor
- 6-monthly ultrasound +/- AFP; variceal surveillance by stage
- MELD/MELD-Na and Child-Pugh at each review
- Nutrition and sarcopenia assessment
- Medication review at every visit - NSAIDs, aminoglycosides, sedatives, ACE inhibitors/ARBs
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