22.2 Complications of Cirrhosis: Alcohol-Associated Hepatitis, Hepatorenal Syndrome & Pulmonary Vascular Syndromes

Alcohol-Associated Hepatitis

• Presentation: jaundice developing over weeks in a patient with heavy recent alcohol use, with tender hepatomegaly, fever, leukocytosis, AST above ALT (usually with AST below 400 U/L), and a rising bilirubin and INR.
• Severity scores:
  • Maddrey discriminant function $= 4.6 \times (\text{patient PT} - \text{control PT}) + \text{total bilirubin (mg/dL)}$. A value of 32 or more indicates severe disease with high short-term mortality.
  • MELD and the Glasgow alcoholic hepatitis score are alternatives.
• Treatment:
  • Prednisolone 40 mg daily for 28 days (prednisolone rather than prednisone, which requires hepatic conversion) for severe disease without contraindications. In the STOPAH trial, prednisolone showed a borderline 28-day mortality benefit without longer-term benefit, and pentoxifylline did not help.
  • Assess response at day 7 with the Lille score: a value above 0.45 indicates non-response, and steroids are stopped to limit infection risk.
  • Contraindications or cautions: uncontrolled infection, active gastrointestinal bleeding, acute kidney injury, and multiorgan failure.
  • Infection surveillance is essential: these patients have impaired immunity, and steroids add risk.
  • Nutrition: aggressive enteral nutrition, thiamine and other vitamins, and treatment of alcohol withdrawal.
  • N-acetylcysteine combined with steroids has shown benefit in some trials.
  • Early liver transplantation in carefully selected patients with a first episode and good psychosocial support produces survival far better than medical therapy; fixed abstinence intervals are no longer universally required.
• Mimics to exclude: acetaminophen injury, ischemic hepatitis, biliary obstruction, drug-induced liver injury, and Budd-Chiari syndrome.

Hepatorenal Syndrome-AKI

• Concept: splanchnic vasodilation reduces effective arterial volume, which activates the renin-angiotensin and sympathetic systems and constricts the renal circulation. The kidneys are structurally normal.
• Diagnosis (current terminology): acute kidney injury in cirrhosis with ascites, no improvement after withdrawal of diuretics and volume expansion with albumin (1 g/kg daily for 2 days), absence of shock, no recent nephrotoxins, and no evidence of structural kidney disease (no significant proteinuria, hematuria, or abnormal renal ultrasound).
• Differential: hypovolemia from diuresis, lactulose-induced losses or bleeding (responds to volume), acute tubular necrosis (often with granular casts and a higher urine sodium), abdominal compartment syndrome, and glomerular disease (IgA nephropathy in cirrhosis, hepatitis-associated nephropathy).
• Treatment:
  • Vasoconstrictor plus albumin:
    • Terlipressin plus albumin is the most effective option. In CONFIRM, terlipressin improved reversal of hepatorenal syndrome compared with placebo, but respiratory failure was more common, so avoid it in patients with hypoxemia or volume overload and monitor closely.
    • Norepinephrine plus albumin in the ICU is an effective alternative requiring central access.
    • Midodrine with octreotide and albumin is a weaker outpatient option.
  • Treat precipitants: spontaneous bacterial peritonitis (with albumin), bleeding, and overdiuresis.
  • Avoid NSAIDs, aminoglycosides, and contrast when possible, and reconsider beta-blockers in severe circulatory dysfunction.
  • Kidney replacement therapy as a bridge in transplant candidates; TIPS in selected patients.
  • Liver transplantation is the definitive therapy; combined liver-kidney transplantation is considered with prolonged dialysis dependence.

Other Complications of Portal Hypertension

Severe Pancreatitis Variants Worth Separating

• Hypertriglyceridemia-induced pancreatitis: suspect it when triglycerides exceed 1,000 mg/dL. Treat with nil by mouth, an insulin infusion (which activates lipoprotein lipase) with dextrose to prevent hypoglycemia, fibrates once enteral intake resumes, and plasmapheresis in severe or refractory cases. Note that marked hypertriglyceridemia can cause spuriously low sodium and amylase measurements.
• Gallstone pancreatitis: urgent ERCP within 24 hours only for concurrent cholangitis or persistent biliary obstruction; otherwise early cholecystectomy during the same admission for mild disease.
• Drug-induced pancreatitis: azathioprine, valproate, didanosine, GLP-1 receptor agonists, and others.
• Fluid strategy: the WATERFALL trial found that aggressive fluid resuscitation caused more fluid overload without benefit compared with moderate resuscitation, so moderate goal-directed fluids are now preferred.