Table 2.
Summarizes the reported hepatic side-effects of ICI therapy.
| Ref | CPIH (N) | CPIH Severe (N) | CS Tx | CS Type | Duration CS Tx | Non-CS Tx | Time to Normal LFT | ALT (IU) | Serology | ICI | Liver Biopsy (N) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| [42] | 17 | 11 (8- G3/3-G4) | 12 | 1 no CS 12 PR, 1 mg/kg/day 1 IV Dx 3 MPR 1 g/day |
42 (7–78) day | 1 Azathio-prine, 1 Cyclospo-rine | 31 days | 447 (59–2355) | N/A | Ipilimumab/ nivolumab/ Pembrolizumab/ indoximod/ Vemurafenib/ dabrafenib |
N/A |
| [43] | 10 | 9 (7-G3, 2-G4) | 5 | N/A | N/A | 0 | 2–55 weeks | 416 (155–1735) | ANA > 1:80 (1), AMA 1:1600 (1) PBC | anti-CTLA-4 (n = 6), Anti-PD-1/PD-L1 (n = 3), combination (n = 1) | 2 granulomatous hepatitis associated with a moderate and polymorphous inflammatory infiltrate, no interface hepatitis |
| [44] | 16 | 16 | 10 | 6 spontaneous improvement 7 oral CS 0.5–1 mg/kg/day; 2 oral CS 0.2 mg/kg/day 1 IV steroid 2.5 mg/kg/day | N/A | 1 MMF | N/A | 437 (147–2289) | ANA > 1:80 (8), ASMA > 1:80 (3) | Anti-CTLA-4 (n = 7) Anti-PD-1/PD-L1 (n = 9) | the portal inflamatory infiltrate contained numerous eosinophilic polynuclear cells |
| [44] | 1 | 1 | MPR 1 mg/kg/day then Steroid | 152 days | UDCA | N/A | N/A | ANA 1:3 (20) | Nivolumab | moderate lymphocytic inflammatory infiltrate, bile duct injury; mild periportal necrosis; PD-L1 IHC, using anti-PD-L1/CD274 (clone SP142); a strong granular immuno-reactivity in the cytoplasm of Kupffer cells and hepatocytes. | |
| [45] | 29 | 19 (G3/4) | 28 | 1 no CS 28 PR 0.5–1 mg/kg/day |
35 (5–240) | 3 MMF | N/A | N/A | N/A | Combination | N/A |
| [46] | 21 | 14 (9-G3, 5-G4) | 19 | 2 no CS; 11 Pr 7 MPR1 IV DX |
N/A | 8 MMF 1 Tacrolimus 1 Infliximab | 112 days | 732 (73–2857) | N/A | Combination | NO |
| [47] | 1 | 1 | 1 | MPR 500mg/day then PR 150 mg daily | 9 days then 6 weeks | MMF anti-thymocyte globulin | 37 | 1.peak 2521 2.peak 6362 | negative | Ipilimumab | NO |
| [48] | 1 | 1 | 1 | MPR 2 mg/kg/day then PR | 4 days then 6 weeks | MMF anti-thymocyte globulin | 30 | 4700 | Negative | Ipilimumab | NO |
| [49] | 3 | 3 | 3 | IV-MP 1g/kg then PR | 3-day pulse then tapering | 0 | rapidly | 886 (553–1211) | negative | Ipilimumab | NO |
| [50] | 1 | 1 | 1 | PR 1 mg/kg/day x 4 and 2 mg/kg/day | 30 days | 0 | 8 days | 250 | negative | Ipilimumab | N/A |
| [50] | 1 | 1 | 1 | PR 2 mg/kg/day | 15 days | Artificial liver plasma ex-change | LFT did not improve | 1269 | 0 | Pembro lizumab | N/A |
| [51] | 1 | G 3 | 0 | spontaneously recovered | N/A | N/A | N/A | N/A | N/A | Nivolumab | N/A |
| [52] | 1 | 1 | 1 | MPR 2 mg/kg/day and pulse therapy | N/A | Azathioprine | 30 | 539 | 0 | Nivolumab | N/A |
| [53] | 1 | 1 | 1 | MPR 2 mg/kg/day 10 days, PR 1 g/kg/day with tapering | ~90 days (all Cs tx with tape- ring) | MMF anti-thymocyte globulin | 27 | 1900 | 0 | Ipilimumab & nivolumab | N/A |
| [54] | 1 | 1 | 1 | MPR pulse for 6 day; MPR 1 g/kg/day then oral PR 1.25 mg/kg/day | 6-day pulse then tape ring | MMF | 104 | 1623 | 0 | Ipilimumab | N/A |
| [55] | 1 | G 4 | 1 | Oral MPR 0.6 mg/kg/day; half-pulse 500 mg/day | N/A | UDCA | 4 months after end of nivolu mab | 693 | 0 | Nivolumab | Portal area with inflammatory cells, including lymphocytes and eosinophils. |
| [55] | 1 | G 4 | 1 | MPR 2 mg/kg/day for 4 days; then, DX, 3 days MPR 1 g/day, followed by PR 150 mg | 7 days then tape ring | MMF anti- thymocyte globulin |
Persis- ted with grade 1–2 CPIH |
~1250 | ASMS 1:1 (60) | anti-PD-1 | inflammatory infiltrate around the portal tracts and central veins, focal necrosis. PD-L1 was expressed on hepatocytes; in the infiltrating lymphocytes, PD-1 was expressed at low levels |
| [55] | 1 | 1 | 1 | MPR 2 mg/kg/day, then 4 & 6 mg/kg/day | 14 days | MMF | 55 days | ~350 | Nega- tive |
nivolumab | Inflammation; eosinophilic and neutrophilic granulocytes; perivenular (zone 3) cholestasis. |
ALT—alanine aminotransferase; ASMA-anti-smooth muscle antibody; DX-oral dexamethasone; G-grade; ICI—immune checkpoint inhibitor; CPIH—Check point inhibitor hepatotoxicity; CS—corticosteroid; CS Tx—Corticosteroid therapy; IV—Intravenous; LFT—liver function test; MMF—Mycophenolate; MPR-Methylprednisolone; UDCA—urso-deoxycholic acid; Tx—Therapeutic agent.