Table 2 Summary of case reports of other BTK inhibitors-induced liver injuries

Author title and date

Nandikolla, 2017 [14]

Kahn 2017 [15]

Kleijwegt 2019 [16]

Tafesh 2019 [17]

Underlying illness

Relapsing, refractory CLL

Refractory WM

Refractory WM

Refractory WM

BTK inhibitor

Ibrutinib

Ibrutinib

Ibrutinib

Ibrutinib

Patient’s age and gender

62-year-old male

59-year-old female

48-year-old female

77-year-old Female

Time of liver injury since starting BTK inhibitor

2 weeks

9 months

11 weeks

2 months

Pattern of DILI

Hepatocellular

Hepatocellular

Hepatocellular

Hepatocellular

Causality assessment/RUCAM

1 “Unlikely”^a

7 “probable”

8 “probable”^a

6 “possible”^a

Liver histology

Centrilobular intrahepatic and canalicular cholestasis, ceroid-laden macrophages and minor apoptosis

Acute hepatitis with mixed acute and chronic inflammation and hepatocellular cholestasis

Not performed

Mixed inflammatory cell infiltrate, lobular disarray, hepatocellular ballooning, focal canalicular cholestasis, and necrosis

Intervention

Ibrutinib stopped

Ibrutinib stopped

Ibrutinib stopped

Ibrutinib stopped + oral prednisolone 60 mg daily for 12 days, then tapered down.

Outcome

Liver enzymes improved but did not normalise, and the patient died from the original illness.

Liver enzymes normalised after 60 days

Liver enzymes normalised after 5 weeks of stopping Ibrutinib

Liver enzymes normalised after 7 weeks and remained normal after 3 months