Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, such as therapeutic vaccines and immune checkpoint inhibitors, offer new avenues for enhanced treatment efficacy. Special attention is given to the clinical complexities of managing HBV in patients with co-morbid conditions like HCC and PLA, emphasizing the necessity of a multidisciplinary approach. The interplay between antibacterial and antiviral therapies in PLA-associated HBV cases is critically examined to prevent treatment antagonism, ensuring optimal patient outcomes. Advanced therapeutic strategies, including nucleos(t)ide analogs, interferon therapy, and novel genomic interventions, are explored in both isolated HBV infection and PLA co-infections. Personalized regimens remain pivotal in enhancing therapeutic efficacy and long-term disease control. Current review advocates for a shift toward precision medicine, highlighting the critical need for interdisciplinary collaboration to bridge molecular discoveries with clinical innovations. Ultimately, these advancements promise to revolutionize the management of chronic HBV, paving the way for potential cures and improved patient outcomes.
[1]Near East Univ, Operat Res Ctr Healthcare, Nicosia, Turkiye.
[2]Fdn Univ Islamabad FUI, Fdn Univ Sch Hlth Sci FUSH, Dept Clin, Islamabad, Pakistan.
[3]Fdn Univ Islamabad FUI, Fdn Univ Sch Hlth Sci FUSH, Biomed Res Ctr CBRC, Islamabad, Pakistan.
[4]Riphah Int Univ, Al Mizan Islamic Int Med Coll Trust IIMCT Complex, Dept Med Lab Technol, Rawalpindi, Pakistan.
[5]Int Ctr Med Sci Res ICMSR, Austin, TX USA.
[6]Int Ctr Med Sci Res ICMSR, Essex, England.
[7]Int Ctr Med Sci Res ICMSR, Islamabad, Pakistan.
[8]Kunming Med Univ, Sch Rehabil, Kunming, Yunnan, Peoples R China.
[9]Akhtar Saeed Med & Dent Coll, Lahore, Pakistan.
[10]Tamil Nadu Dr MGR Univ, Dept Med Sci, Chennai, India.
[11]Univ Sharjah, Coll Hlth Sci, Dept Med Diagnost Imaging, Sharjah, U Arab Emirates.
[12]Univ Sharjah, Res Inst Med & Hlth Sci, Sharjah, U Arab Emirates.
[13]Chapman Univ, Dept Pharm, Irvine, CA 92618 USA.
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