Table 1.
Differential diagnosis of SSC-CIP in the ICU setting
| Diagnosis | Incidence in ICU patients | Clinical features and laboratory tests | Diagnosis | Treatment | Prognosis | References |
|---|---|---|---|---|---|---|
| Sepsis-induced cholestasis | 20% (most common cause of cholestasis in the ICU) | sepsis (mostly gram-negative); biphasic pattern: initial elevation of ALT/AST, followed by elevation of bilirubin; ALP and GGT may be normal | biphasic laboratory pattern in the setting of positive blood cultures (usually gram-negative) | aggressive antimicrobial treatment; circulatory and ventilatory support | two-fold increase in mortality compared to sepsis alone; cholestasis is reversible | 25, 73, 74 |
| TPN-associated cholestasis | 3% | TPN >1 week, RUQ and hepatomegaly; mixed pattern with cholestasis and hepato-cellular necrosis | cholestasis in the setting of TPN after exclusion of other causes | avoidance of excessive calories and appropriate dosing and formulation of lipids; discontinuation or cycling of TPN if feasible | liver dysfunction is self-limited but may progress to steatohepatitis and cirrhosis if TPN >6 months | 25, 26 |
| Choledocholithiasis | − | RUQ pain accompanied by nausea and vomiting; rise in ALT/AST followed by ALP and bilirubin; INR may be elevated; transient | US and CT scan may reveal dilated bile ducts and duct stones in the initial evaluation; diagnosis is usually confirmed by MRCP or EUS | ERCP with sphincterotomy and stone extraction | benign, but may complicate with acute pancreatitis and bacterial cholangitis | 62, 75 |
| DILI | − | idiosyncratic drug reaction (commonly antibiotics and anesthetics); hepatocellular, cholestatic, or mixed pattern; cholestatic pattern more common in patients aged >60 years, associated with antibiotics | establishment of causal relationship according to clinical scores such as RUCAM and Maria & Vitorino | rapid removal of the offending drug; UDCA may be beneficial in cholestatic DILI | mostly benign, but may lead to acute-liver failure requiring transplantation; cholestasis may persist for months | 76–79 |
| HLI | 10% | occurs in the setting of cardiac, respiratory, or circulatory failure, typically in the first 48 h after admission; rapid rise in ALT/AST >20× ULN with return to baseline within 1 week; cholestasis is seen in one-third of patients | clinical | correction of the underlying cause of ischemic injury; circulatory and ventilatory support | depends on underlying comorbidities, but mortality is >50% | 59, 61, 80 |
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CT, computed tomography; DILI, drug-induced liver injury; ERCP, endoscopic retrograde cholangiopancreatography; EUS, endoscopic ultrasound; GGT, gamma-glutamyl transpeptidase; HLI, hypoxic liver injury; ICU, intensive care unit; INR, international normalized ratio; MRCP, magnetic resonance cholangiopancreatography; RUCAM, Roussel Uclaf Causality Assessment Method; RUQ, right upper quadrant; SSC-CIP, secondary sclerosing cholangitis in critically ill patients; TPN, total parenteral nutrition; UDCA, ursodeoxycholic acid; ULN, upper limit of normal; US, ultrasound.