Table 2.
Studies on HBV reactivation in patients treated with immunosuppressive therapy
| Studies (Location and year) |
Indication | Definition of HBVr used | Median/mean follow-up duration | HBV reactivation in HBsAg + patients | HBV reactivation in HBsAg-/anti-HBc + patients |
|---|---|---|---|---|---|
| Dexamethasone Recommended dose in COVID-19: 6 mg IV or PO daily for up to 10 days† | |||||
|
Yip et al. [4] (Hong Kong, 2021) |
COVID-19 | HBsAg + : > 1 log10 increase in HBV DNA compared with baseline level | 13 days | 0/8 (0%) with prophylaxis | Not studied |
| Methylprednisolone Recommended dose in COVID-19: 32 mg IV or PO daily for up to 10 days† | |||||
|
Rodriguez-Tajes et al. [40] (Spain, 2021) |
COVID-19 |
HBsAg + : not defined HBsAg-/anti-HBc + : detectable HBV DNA or HBsAg seroreversion‡ |
1–2 months after last dose | 0/3 (0%) with prophylaxis |
1/22 (4.5%) without prophylaxis 0/29 (0%) with prophylaxis |
|
Braun-Moscovici et al.[42] (Israel, 2016) |
Rheumatic diseases (mostly RA) |
HBsAg + or HBsAg-/anti-HBc + : elevation of ALT three times or more the upper limit of normal and/or > 1 log10 increase of HBV DNA compared with baseline level | 4.8 years |
0/7 (0%) without prophylaxis and concomitant immunosuppressive therapy 4/9 (44.4%) without prophylaxis and received concomitant DMARDs and/or prednisone 0/2 (0%) with prophylaxis and received concomitant DMARDs and/or prednisone |
0/1 (0%) without prophylaxis 1/3 (33.3%) without prophylaxis and received concomitant DMARDs and/or prednisone |
| Prednisolone Recommended dose in COVID-19: 40 mg IV or PO daily for up to 10 days† | |||||
|
Wong et al. [43] (Hong Kong, 2019) ¶ |
Not specified | HBsAg + : > 1 log10 increase in HBV DNA compared with baseline level | 1 year | 303/678 (44.7%) without prophylaxis | Not studied |
|
Wong et al. [44] (Hong Kong, 2020) ¶ |
Not specified | HBsAg-/anti-HBc + : HBsAg seroreversion | 4 years | Not studied | 28/502 (5.6%) without prophylaxis |
| Hydrocortisone Recommended dose in COVID-19: 160 mg IV or PO daily for up to 10 days† | |||||
|
Yip et al. [4] (Hong Kong, 2021) |
COVID-19 | HBsAg + : > 1 log10 increase in HBV DNA compared with baseline level | 13 days | 0/2 (0%) with prophylaxis | Not studied |
| Tocilizumab Recommended dose in COVID-19: 8 mg/kg (up to 800 mg) single IV dose | |||||
|
Rodriguez-Tajes et al.[40] (Spain, 2021) |
COVID-19 |
HBsAg + : not defined HBsAg-/anti-HBc + : detectable HBV DNA or HBsAg seroreversion‡ |
1–2 months after last dose | 0/3 (0%) with prophylaxis |
1/17 (5.9%) without prophylaxis 0/27 (0%) with prophylaxis |
|
Kuo et al. [49] (Taiwan, 2021) |
RA |
HBsAg + : > 2 log10 increase in HBV DNA compared with baseline level OR HBV DNA > 3 log10 IU/mL if previously undetectable HBV DNA OR absolute HBV DNA > 4 log10 IU/mL if baseline value unavailable‡ HBsAg-/anti-HBc + : detectable HBV DNA OR HBsAg seroreversion‡ |
9 years |
3/3 (100%) without prophylaxis 0/4 (0%) with prophylaxis |
1/64 (1.6%) without prophylaxis |
|
Serling-Boyd et al. [60] (US, 2021) |
RA | HBsAg-/anti-HBc + : > 1 log10 increase or absolute increase of 5 log10 copies/mL in HBV DNA compared with baseline level OR HBsAg seroreversion | 4 years | Not studied |
0/12 (0%) without prophylaxis 0/4 (0%) with prophylaxis |
|
Nakamura et al. [71] (Japan, 2019) |
RA | HBsAg-/anti-HBc + : HBV DNA > 2 log10 copies/mL | 1.5 years | Not studied | 2/18 (11.1%) without prophylaxis |
|
Lin et al. [72] (Taiwan 2019) |
RA | No definition provided | 3 years | Not studied | 0/11 (0%) without prophylaxis |
|
Watanabe et al. [73] (Japan 2019) |
RA | HBsAg-/anti-HBc + : detectable HBV DNA | 1.25 years | Not studied | 1/25 (4.0%) without prophylaxis |
|
Ahn et al. [74] (Korea, 2018) |
RA | HBsAg-/anti-HBc + : detectable HBV DNA | 10.8 months | Not studied | 0/15 (0%) without prophylaxis |
|
Chen et al. [48] (China, 2017) |
RA | All: > 2 log10 increase in HBV DNA compared with baseline level OR detectable HBV DNA OR HBsAg or HBeAg seroreversion | 3 months |
3/5 (60.0%) without prophylaxis 0/2 (0%) with prophylaxis |
0/41 (0%) without prophylaxis |
|
Chen et al. [50] (Taiwan, 2017) |
RA | HBsAg + : > 1 log10 increase in HBV DNA compared with baseline level OR HBV DNA > 3 × increase in ALT level with HBV DNA > 20,000 IU/mL if baseline value unavailable | 28.1 months | 0/2 without prophylaxis | Not studied |
|
Mok et al.[75] (Hong Kong, 2014) |
RA | No definition provided | 1.3 years | Not distinguished from past HBV |
0/159 (0%) No details given regarding prophylaxis |
| Tofacitinib Recommended dose in COVID-19: 10 mg PO twice daily for up to 14 days† | |||||
|
Wang et al.[61] (Taiwan, 2021) |
RA |
HBsAg + : > 2 log10 increase in HBV DNA compared with baseline level OR HBV DNA > 3 log10 IU/mL if previously undetectable HBV DNA OR absolute HBV DNA > 4 log10 IU/mL if baseline value unavailable‡ HBsAg-/anti-HBc + : detectable HBV DNA OR HBsAg seroreversion‡ |
Unclear |
2/6 (33.3%) without prophylaxis 0/2 (0%) with prophylaxis |
2/64 (3.1%) without prophylaxis |
|
Serling-Boyd et al. [60] (US, 2021) |
RA | HBsAg-/anti-HBc + : > 1 log10 increase or absolute increase of 5 log10 copies/mL in HBV DNA compared with baseline level OR HBsAg seroreversion | 3.1 years | Not studied |
0/4 (0%) without prophylaxis 0/2 (0%) with prophylaxis |
|
Chen et al. [59] (Taiwan, 2018) |
RA | All: > 2 log10 increase in HBV DNA cases with baseline level | 3–6 months after last dose |
2/4 (50.0%) without prophylaxis 0/2 (0%) with prophylaxis |
0/75 (0%) without prophylaxis |
| Baricitinib Recommended dose in COVID-19: 1–4 mg PO daily depending on eGFR for up to 14 days† | |||||
|
Rodriguez-Tajes et al. [40] (Spain, 2021) |
COVID-19 |
HBsAg + : not defined HBsAg-/anti-HBc + : detectable HBV DNA or HBsAg seroreversion |
1–2 months after last dose | Not studied | 0/2 (0%) without prophylaxis |
|
Harigai et al. [62] (Japan, 2021) |
RA | HBsAg-/anti-HBc + : ≥ 2 log increase from baseline levels or new appearance of HBV DNA to a level of ≥ 100 IU/mL§ | 2.4 years | Not studied |
4/215 (1.9%) without prophylaxis But 32/215 (14.9%) if using detectable HBV DNA as definition of HBVr |
ALT = alanine aminotransferase, anti-Hbc = antibody to hepatitis B core antigen, HBeAg = hepatitis B e antigen, HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, HBVr = hepatitis B virus reactivation, RA = rheumatoid arthritis
†Or until hospital discharge
‡American Association for the Study of Liver Diseases guidelines definition [64]
§Asian Pacific clinical practice guidelines definition [12, 65]
¶All steroid uses were standardized to prednisolone equivalent dose