Drug-induced cholestatic liver diseases

Area of Science:

• Hepatology
• Toxicology
• Gastroenterology

Background:

• Cholestatic drug-induced liver injury (DILI) presents diagnostic challenges with elevated alkaline phosphatase.
• Differential diagnoses include malignancy, choledocholithiasis, viral hepatitis, sepsis, cholangitis, and cardiac failure.
• Recent advances update knowledge on drug-induced cholestasis phenotypes, etiologies, risk factors, and genetics since 2011.

Purpose of the Study:

• To review diagnostic approaches for cholestatic DILI.
• To describe emerging clinical phenotypes, including secondary sclerosing cholangitis (SSC) and vanishing bile duct syndrome.
• To provide an overview of risk factors, genetic determinants, and pathophysiology of cholestasis.

Main Methods:

• Literature review focusing on recent advances in drug-induced cholestasis.
• Analysis of diagnostic strategies and clinical presentations.
• Synthesis of information on risk factors, genetics, and transporter pathophysiology.

Main Results:

• Checkpoint inhibitors and herbal/dietary supplements are identified as causes of DILI-induced SSC.
• New genetic risk factors and a clearer understanding of cholestatic injury pathogenesis have emerged.
• Secondary sclerosing cholangitis and vanishing bile duct syndrome represent significant clinical phenotypes.

Conclusions:

• Cholestatic DILI requires careful differential diagnosis, considering new etiologies and phenotypes.
• Understanding genetic factors and transporter mechanisms is crucial for defining cholestasis pathogenesis.
• Further research is needed for management strategies and addressing areas of uncertainty.