Table 2.
Clinical and serological characteristics of patients experiencing OBI reactivation in the pre-emptive cohort and in the 12-month LAM prophylaxis cohort.
| Patients no. | Age (y) | Sex | Stage | Cohort § | Baseline | Time of diagnosis of OBI reactivation | At OBI reactivation | Type of antiviral therapy | Antiviral therapy duration | Time to HBV recovery (weeks) | Follow up HBsAg status | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| HBsAg (+/-) | HBV-DNA (IU/ml) | ALT (U/L) | weeks after ICHT start | HBV-DNA (x106 UI/ml) | Peak ALT (X N.V) | LAM/TDF | weeks | weeks after antiviral therapy | +/- | |||||
| 1 | 64 | F | III | Pre-emptive | – | Neg | 23 | 40 | 3,5 | 2.2x | LAM | 28 | 8 | – |
| 2 * | 73 | M | II | Pre-emptive | – | Neg | 18 | 24 | 4.5 | 10x | LAM | 36 | 4 | – |
| 3 * | 64 | F | IV | Pre-emptive | – | Neg | 25 | 12 | 6.5 | 12x | LAM | 22 | 3 | – |
| 4 | 71 | M | IV | Pre-emptive | – | Neg | 31 | 24 | 1,6 | 11x | LAM | 48 | 3 | – |
| 5 | 62 | M | IV | Pre-emptive | – | Neg | 34 | 52 | 1,3 | 2.1x | LAM | 34 | 8 | + |
| 6 * | 66 | M | II | Pre-emptive | – | Neg | 29 | 20 | 1.7 | 2.7x | LAM | 41 | 5 | + |
| 7 | 59 | M | III | Pre-emptive | – | Neg | 34 | 72 | 1,6 | 2.4x | LAM | 38 | 3 | + |
| 8 | 54 | F | IV | Pre-emptive | – | Neg | 32 | 32 | 3.1 | 2.8x | LAM | 34 | 3.8 | + |
| 9 * | 71 | F | III | Pre-emptive | – | Neg | 22 | 14 | 5.5 | 14x | LAM | Until death | 3.5 | – |
| 10 | 58 | F | IV | Pre-emptive | – | Neg | 24 | 60 | 3,4 | 2x | LAM | 25 | 5 | + |
| 11 * | 53 | M | IIII | Pre-emptive | – | Neg | 26 | 18 | 2.2 | 3.2x | LAM | 48 | 4.2 | – |
| 12 * | 53 | F | III | Pre-emptive | – | Neg | 19 | 48 | 9.1 | 20x | LAM | 44 | 6 | – |
| 13 | 63 | F | III | 12-month LAM | – | Neg | 32 | 52 | 2,1 | 7x | TDF | 24 | 4.5 | – |
| 14 | 80 | F | III | 12-month LAM | – | Neg | 25 | 60 | 8,4 | 5x | TDF | 20 | 6 | – |
| 15 | 72 | M | IV | 12-month LAM | – | Neg | 30 | 58 | 4,8 | 3x | TDF | 24 | 7 | + |
| 16 | 67 | F | IV | 12-month LAM | – | Neg | 16 | 72 | 5,2 | 2.7x | TDF | 22 | 6.5 | + |
| 17 | 56 | M | III | 12-month LAM | – | Neg | 21 | 48 | 3,9 | 2.8x | TDF | 42 | 3,8 | + |
| 18 | 48 | F | II | 12-month LAM | – | Neg | 29 | 40 | 1,9 | 4.3x | TDF | 38 | 5 | – |
| 19 | 40 | F | II | 12-month LAM | – | Neg | 21 | 60 | 4,5 | 2x | TDF | 30 | 5.5 | – |
LAM, Lamivudine; TDF, Tenofovir disoproxil fumarate; HBsAg, Hepatitis B surface antigen; HBV-DNA, Hepatitis B Virus-DNA; ALT, alanine transaminase.
§ No reactivation events were registered in the 24-month LAM series.
* Patients with OBI reactivation experiencing R-CHOP-21 (24) disruption. For patient n° 2 and 9, ICHT was prematurely terminated; for patient n° 3, both Hydroxydaunorubicin (H) and Vincristine (O) dose was reduced by 25% (with 14 days of delay), whereas for patient n° 11, H and O dose was reduced by 25% and 20%, respectively (with 16 days of delay); for patients n° 6 and 12, ICHT was delayed by 7 and 21 days, respectively, and resumed without dose modification.
OBI reactivation: occult hepatitis B virus infection reactivation defined as HBsAg seroconversion and HBV-DNA detectable in the serum (>2000 IU/mL); Acute hepatitis: ≥3-fold increase in serum AST that exceeded the reference range; ICHT disruption: premature termination of immune-chemotherapy (ICHT) of R-CHOP21+2R or delay ≥7 days between immune-chemotherapy cycles or any modification of dose density/intensity (28).
In the 12-month LAM cohort and 24-month LAM series, HBV monitoring consisted in monthly ALT and HBsAg analysis and 3-monthly HBV-DNA analysis for 12 months after prophylaxis end. In the pre-emptive cohort, HBV monitoring consisted in monthly ALT and HBsAg analysis.