B cell receptor-associated protein 31 levels in serum-derived extracellular vesicles are associated with therapeutic response and prognosis in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab: a multicenter study.

For suspected ICI colitis, exclude infectious causes of diarrhea (including C. difficile) before treating. In grade 2 or higher colitis/diarrhea, early stool inflammatory markers (lactoferrin, calprotectin) may help stratify patients for endoscopy, and endoscopic confirmation of the diagnosis and severity should be considered before starting high-dose systemic glucocorticoids; abdominal imaging is reserved for dominant pain, fever, or bleeding and should not be done routinely for diarrhea alone. The AGA cautions that no validated severity index for ICI colitis exists and that symptoms correlate poorly with endoscopic, radiologic, and treatment-response severity, and that rapid progression over days can occur, particularly with ipilimumab. ICI colitis typically responds to high-dose systemic glucocorticoids at 0.5-2 mg/kg prednisone-equivalent daily tapered over 4-6 weeks (the AGA explicitly notes these doses and schedules have not been rigorously examined). If there is no improvement after 2-3 days, add infliximab or vedolizumab while continuing glucocorticoids; both are reasonable options for glucocorticoid-refractory colitis. Budesonide is ineffective as prophylaxis and is not a standard treatment for ICI colitis, it is reserved for ICI-associated microscopic colitis. Retreatment with immunotherapy is possible under select conditions. For hepatitis, obtain baseline liver chemistries (total bilirubin, alkaline phosphatase, AST, ALT) and HBV serologies before ICI; grade by CTCAE and manage as follows: grade 1 (AST/ALT 1-3x ULN or bilirubin 1-1.5x ULN), monitor liver chemistries 1-2 times weekly; grade 2 (AST/ALT >3-5x ULN or bilirubin >1.5-3x ULN), hold ICI until resolution to grade 1, and if symptomatic give prednisone 0.5-1.0 mg/kg/d or equivalent; grade 3 (AST/ALT >5-20x ULN or bilirubin >3-10x ULN), discontinue ICI and start methylprednisolone 1-2 mg/kg/d or equivalent; grade 4 (AST/ALT >20x ULN or bilirubin >10x ULN or hepatic decompensation), permanently discontinue ICI and start methylprednisolone 2 mg/kg/d. For ICI hepatitis that does not adequately improve after 3-5 days of high-dose glucocorticoids, escalate to a second-line immunosuppressant, mycophenolate mofetil (with azathioprine as an accepted alternative), while continuing glucocorticoids; infliximab is not recommended for ICI hepatitis because of its potential for hepatotoxicity. Evaluate all ICI-related liver-chemistry elevations for alternate etiologies (consider liver biopsy), and obtain biliary imaging when alkaline phosphatase and/or bilirubin are elevated.