Published cases of HBV and HCVr in patients with cancer treated with immunotherapy
| A/a | First author, year | Age (gender) | Cancer type | Type of ICPI | Baseline HBV DNA (IU/mL) | Baseline hepatitis panel | Baseline AST/ALT | Antiviral prophylaxis | Duration on ICPI at reactivation | Reactivation HBV DNA (IU/mL) and hepatitis panel | Reactivation AST/ALT (U/L) | Management of ICPI | Antiviral treatment | Time for undetectable HBV DNA (weeks) | Time for ALT (ULN:56 U/L) and AST (ULN:40 U/L) recovery (weeks) |
| 1 | Lake, 20175 | 72 (M) | NSCLC stage IIIa TTF-1 (+) | Nivolumab (April 2016) | <20 | Anti-HBc: (+) HBsAg: (−) HIV infection (ART: dolutegravir 50 mg once daily, abacavir 600 mg once daily since February 2016) | Normal | Two doses of HBV vaccine (July 2014 and November 2015) | 4 weeks | HBV DNA>170,000,000 | AST: 301 U/L ALT: 332 U/L | Delayed for 3 months | Switched from abacavir to TDF but patient declined adding of third drug to ART | Not achieved on follow-up (16 weeks) but significantly decreasing | ALT/AST: normalized after 12 and 16 weeks, respectively |
| 2 | Pandey, 20186 | 51 (M) | NSCLC stage IV TTF-1 (+) | Pembrolizumab | No baseline hepatitis panel | No baseline hepatitis panel | Normal | None | 4 weeks | HBV DNA: RT-PCR>8.23 log HBsAg: (+) Anti-HBsAb: (−) Anti-HBcAb total: (+) Anti-HBcAbIgM: (−) HbeAg: (−) Anti-HbeAb: (+) | AST: 670 U/L, ALT: 994 U/L | Delayed | TNF before hepatitis workup, administration high-dose steroids for potential autoimmune hepatitis | 10 weeks | 10 weeks |
| 3 | Koksal, 20177 | 56 (M) | Melanoma stage IV | Ipilimumab (September 2016) after four cycles switched to Nivolumab due to AST/ALT increase | Unknown | HBsAg: (+) Anti-HBs: (−) Anti- HbcIgM: unknown HbeAg: unknown Anti-HBe: unknown | Normal | None | 8 weeks (after four cycles on ipilimumab) | HBV DNA: 244.259 IU/mL HbeAg: (−) Anti-HBe: (+) Anti- HbcIgM: (+) Anti- HBs: (−) (after first cycle of nivolumab) | AST: 164 U/L, ALT: 246 U/L, after fourth cycle of ipilimumab AST: 845 U/L, ALT: 888 U/L after first cycle of nivolumab | Switched ipilimumab to nivolumab Continued nivolumab | TDF 245 mg once daily (started after the first cycle of nivolumab) | HBV DNA: 183 IU/mL, after 8 weeks of TNF | ALT/AST significantly decreased (56 U/L and 50 U/L, respectively) after 8 weeks of TNF |
| 4 | Akar, 20198 | 62 (M) | Clear-cell RCC stage IV | Nivolumab (prior treatments: sunitinib, axitinib and RT) | Undetectable | HBsAg: (+) HDV DNA: (+) after sunitinib | Normal | Entecavir | 40 weeks (18 cycles) | No HBV reactivation after 18 cycles of nivolumab and antiviral prophylaxis with entecavir (HBV DNA (−)) | AST: 28 U/L, ALT: 19 U/L | Continued | Entecavir, since HBV/HDV reactivation under sunitinib | Negative HBV DNA after 40 weeks ofnivolumab (underentecavir) | AST 28 U/L, ALT 19 U/L, after 40 weeks of nivolumab (under entecavir) |
| 5 | Zhang, 20199 | 48 (M) | NPC | Camrelizumab | Undetectable | HBsAg (+) | Not defined | None | 3 weeks | HBV DNA: 7.81 × 103 | ALT: 191.4 U/L | Delayed | Entecavir | 1 week | 2 weeks |
| 6 | Zhang, 20199 | 47 (M) | NPC | Camrelizumab | Undetectable | HBsAg (+) | Not defined | None | 16 weeks | HBV DNA: 6.98 × 104 | ALT: 203.0 U/L | Delayed | Entecavir | 4 weeks | 4 weeks |
| 7 | Zhang, 20199 | 39 (M) | Melanoma | Camrelizumab | Undetectable | HBsAg (+) | Not defined | None | 28 weeks | HBV DNA: 2.10 × 103 | ALT: 27.6 U/L | Continued | None | 5 weeks | N/A |
| 8 | Zhang, 20199 | 36 (M) | HCC | Nivolumab | Undetectable | HBsAg (+) | Not defined | Entecavir | 12 weeks | HBV DNA: 1.80 × 103 | ALT: 298 U/L | Discontinued | Entecavir + TNF | 1 week | 3 weeks |
| 9 | Zhang, 20199 | 45 (M) | HNSCC | Toripalimab | Undetectable | HBsAg (+) Baseline HBV | Not defined | None | 35 weeks | HBV DNA: 4.04 × 106 | ALT: 281.2 U/L | Delayed | Entecavir | 3 weeks | 6 weeks |
| 10 | Zhang, 20199 | 41 (F) | Soft tissue sarcoma | Nivolumab | Undetectable | HBsAg (+) | Not defined | None | 20 weeks | HBV DNA: 6.00 × 107 | ALT: 465.1 U/L | N/A | Entecavir | 8 weeks | 4 weeks |
| A/a | First author, year | Age (gender) | Cancer type | Type of ICPI |
Baseline
HCV RNA | Baseline hepatitis profile |
Baseline
AST/ALT | Antiviral prophylaxis | Duration on ICPI at reactivation |
Reactivation
HCV RNA (IU/mL) |
Reactivation
AST/ALT (U/L) | Management of ICPI | Antiviral treatment | Time for achieving undetectable HCV RNA (weeks) | Time for ALT (ULN:56 U/L) and AST (ULN:40 U/L) recovery (weeks) |
| 1 | Kothapalli, 2018 58 | 54 (M) | Melanoma stage IV | Pembrolizumab | HCV RNA: (+) | Hepatitis panel work-up performed after ALT elevation | Normal | None | 8 weeks | Chronic HCV infection (HCV RNA (+)) | Grade II ALT rise | Continued | Ledipasvir 90 mg/sofosbuvir 400 mg | Not defined | 12 weeks |
| 2 | Davar, 2015 59 | 59 (F) | Melanoma stage IV | Pembrolizumab | HCV RNA: 2.290.867 IU/mL (genotype 1A) | Not defined | Mildly elevated AST/ALT | None | No HCVr: antiviral treatment after 9 cycles of pembrolizumab | HCV RNA stable after 3 cycles of pembrolizumab | Stable | Continued | Ledipasvir 90 mg/sofosbuvir 400 mg (after 9 cycles of pembrolizumab) Duration of antiviral treatment: 12 weeks | 21 weeks (time of antiviral treatment) | 41 weeks from pembrolizumab and 18 weeks from antiviral treatment |
| 3 | Davar, 201559 | 47 (M) | Melanoma stage IV | IFN followed by ipilimumab followed by IL-2 and dabrafenib/trametinib followed by pembrolizumab | HCV RNA: 863 475 IU/mL (genotype 1c) | Not defined HIV viral load: undetectable (under ART treatment) | Normal | None |
No HCVr:
two cycles of pembrolizumab before PD | HCV RNA stable after 2 cycles of pembrolizumab | Stable | Discontinued due to PD | ART treatment (2 NRTIs+1 NNRTI) | – | – |
ALT, alanine aminotransferase; ART, antiretroviral therapy; AST, aspartate aminotransferase; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HCV, hepatitis C virus; HCVr, HCV reactivation; HNSCC, head and neck squamous cell carcinoma; ICPI, Immune checkpoint inhibitor; IFN, interferon; NNRTI, non-nucleoside reverse transcriptase inhibitor; NPC, nasopharyngeal carcinoma; NRTIs, nucleoside reverse transcriptase inhibitors; NSCLC, non-small-cell lung cancer; PD, progression of disease; RCC, renal cell carcinoma; RT, radiotherapy; RT-PCR, reverse transcription polymerase chain reaction; TDF, tenofovir disoproxil fumarate; TNF, tumor necrosis factor; TTF-1, thyroid transcription factor 1.