Emerging treatments
Investigational therapies
Several novel treatments are in development including small molecule drugs, next-generation nucleoside/nucleotide analogues with reduced toxicity and higher barriers to resistance, direct-acting antivirals (e.g., core inhibitors, entry inhibitors, nucleic acid polymers, capsid assembly modulators, translation inhibitors), and therapeutic vaccines.[159][160] Gene therapy has also shown promise, and different strategies have been used, including gene editing, hepatitis B virus-specific gene silencing, and nucleic acid-based vaccination.[161] Other drugs in development include REP 2139 (hepatitis B surface antigen [HBsAG] inhibitor); selgantolimod, CB06, and GSK 5251738 (toll-like receptor-8 agonists); cavrotolimod (toll-like receptor-9 agonist); xalnesiran, imdusiran, daplusiran/tomligisiran, elebsiran, BW-20507, JNJ-3989, HRS-5635, RBD1016, and HT-101 (RNAi gene silencers); cledvudine (HBV DNA polymerase inhibitor); ZM-H1505R, ALG-000184, ABI-4334, and EDP-514 (capsid inhibitors); bepirovirsen and AHB-137 (antisense molecules); ASC22, and AB-101 (checkpoint inhibitors); and tobevibart, burfiralimab, BJT-778, and GIGA-2339 (monoclonal antibodies).[162] However, so far, novel antiviral therapies have been shown to have limited efficacy in terms of functional cure and HBsAg loss and reduction compared with available nucleoside/nucleotide analogue, with a higher risk of adverse events.[163]
Statins
Statin use has been associated with a decreased incidence of cirrhosis and hepatocellular carcinoma (HCC) in patients with viral hepatitis. One systematic review found that use of statins was associated with a 42% reduction in the risk of cirrhosis, with the protective effect more pronounced in Asian countries.[164] A Swedish cohort study of over 16,000 patients found that patients who used lipophilic statins (e.g., atorvastatin, simvastatin, fluvastatin, lovastatin) had a lower 10-year cumulative incidence of HCC (3.3%) compared to patients who do not take statins (8.1%). However, the same effect was not seen with hydrophilic statins. Ten-year mortality rates were significantly lower with both types of statins.[165] A large meta-analysis including over 195,000 patients with chronic viral hepatitis found that the risk of HCC, fibrosis, and cirrhosis decreased by 53%, 45%, and 41% respectively, in statin users compared with those not using statins. Overall mortality rates did not differ between groups, although there was a 39% reduction in mortality in statin users who were followed up for more than 3 years. The review found no significant reduction in liver function related to statin therapy.[166] Other meta-analyses also support the finding that statins reduce the risk of HCC in patients with HBV infection.[167]
Plasma exchange
Plasma exchange is an emerging treatment for treating acute-on-chronic liver failure. Among patients with HBV-related acute-on-chronic liver failure, there was a significant reduction in 90-day mortality among patients treated with plasma exchange compared with standard medical therapy.[168] A combination of plasma exchange with the double plasma molecular adsorption system has also been investigated with promising results.[169] Further research is required.
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