Table I.
Summary recommendations and dosing adjustments for biologic and immunosuppressant agents in patients with cirrhosis/advanced liver disease and chronic and resolved hepatitis B
| Medication | Recommendations for use in patients with cirrhosis/advanced liver disease | Recommendations for use in patients with positive HBsAg* | Recommendations for use in HBsAg-negative but HBcAb-positive (resolved HBV infection)* |
|---|---|---|---|
| Medications used in RA | |||
| MTX | Avoid | Low risk of viral reactivation, may be used at lower doses in RA patients with HBV carrier state or chronic hepatitis unless ALT > 2 × ULN, or ongoing or active infection [12, 14] | Rare [12], relatively safe |
| LEF | Avoid | Low risk [13, 14, 17] | Relatively safe |
| Antimalarials | Used with caution/or lower doses | Can be used [13] | Can be used [13] |
| SSZ | Avoid | Low risk [13] | Low risk [13], relatively safe, one case report of de novo hepatitis activation in a patient with prior HBV infection |
| TNFi | No dose adjustment, high prevalence of serious infections, should be avoided in decompensated cirrhosis | High risk [43], moderate [12], antiviral therapy should be initiated 1 week prior to starting treatment with RTX and should continue for at least 12 months after stopping | Low risk of HBV reactivation (0–8.3%) [12], moderate risk for anti-TNF agents with higher potency: adalimumab, infliximab, golimumab, certolizumab, low risk for anti-TNF agents with lower potency: etanercept [2] |
| RTX | No dose adjustment needed | Very high risk of HBV reactivation (10–20%) [2] | |
| TCZ | Avoid | Moderate to very high risk of HBV reactivation in different literature (1–60% chance) [37] | Low (1.6%) risk [13, 14] |
| JAKi | Avoid | High risk of viral reactivation [14] | High risk [12, 43] |
| Ixekizumab | No dose adjustment | Moderate to high risk of increased HBV reactivation [16] | Low risk [63] |
| ABT | No need for dose adjustment | Medium risk [14], medium to high risk [13] | Low risk [14] |
| Prednisone | No need for dose adjustment | High risk (> 10 mg, > 4 week), medium risk (< 10 mg, > 4 week), low risk (< 10 mg, < 1 week) [14] High risk of viral reactivation for high dose ≥ 20 mg/day for ≥ 4 weeks Moderate risk of viral reactivation for median dose: 10–20 mg/day for ≥ 4 weeks Low risk of viral reactivation for low dose < 10 mg/day [2] Intra-articular < 1% [13] |
Low risk of viral reactivation for high dose (≥ 20 mg/day), intra-articular < 1% [13] |
| Medications used in SLE | |||
| AZA | Use with caution, no dose adjustment | Low risk of viral reactivation [2, 12, 13] | Low risk, rare [12] |
| CP | Avoid | Moderate risk [2], high risk [13] | Low risk, rare [12] |
| CsA and TAC | Avoid | High [12], moderate [13] | Low [13], moderate [12, 16] |
| Mycophenolate mofetil | No dose adjustment (no more than 2 g/day) | Low risk [13] | Low [13] |
| Belimumab | No dose adjustment | No study | No study |
| Medications used in spondyloarthropathies | |||
| Secukinumab | No dose adjustment | Moderate risk [3] | Very low [63] |
| Apremilast | Safe, no dose adjustment | Low risk [63] | Safe [63] |
| Ustekinumab | No dose adjustment | Moderate risk [2, 3], high risk [13] | Moderate risk [13] |
It is recommended that in the case of high- and moderate-risk medications in HBsAg-positive patients and high-risk medications in HBsAg-negative but anti-HBc-positive patients, potent nucleos(t)ide analogues should be initiated at least 1 week (ideally 2 weeks) before starting them [14]. For those with moderate risk, all HBsAg positive and those HBsAg-negative but anti-HBc-positive patients with advanced liver fibrosis or cirrhosis should be administered potent nucleos(t)ide analogues. For HBsAg-negative and anti-HBc-positive patients without advanced fibrosis or cirrhosis, serum ALT should be monitored every 3 months. If elevated ALT > 2 × baseline is detected at monitoring, HBsAg and HBV DNA should be performed and potent nucleos(t)ide analogues initiated if either test positive. For those with low risk, potent nucleos(t)ide analogues should be initiated in both HBsAg positive and HBsAg-negative but anti-HBc-positive patients with advanced fibrosis or cirrhosis. Serum ALT should be monitored every 3 months in both HBsAg-positive and HBsAg-negative but antiHBc-positive patients with low-risk. Antiviral treatment should be continued for at least 6 months after discontinuation of biologics and immunosuppressants and at least 12 months for B cell-depleting agents [2]. The most frequently used potent nucleos(t)ide analogues are lamivudine, entecavir, adefovir, tenofovir disoproxil fumarate, and tenofovir alafenamide. Entecavir has the greatest efficacy in prophylactic treatment [60].
ABT – abatacept, AZA – azathioprine, CP – cyclophosphamide, CsA – cyclosporine A, JAKi – Janus kinase inhibitors, LEF – leflunomide, MTX – methotrexate, RTX – rituximab, SLE – systemic lupus erythematosus, SSZ – sulfasalazine, TAC – tacrolimus, TCZ – tocilizumab, TNFi – tumor necrosis factor α inhibitors.