| Invited Lecture(JSH) |
| Thu. November 21st 9:00 - 9:30 Room 5: Portopia Hotel South Wing Ohwada A |
| Recent advances in clinical research of HBV and HCC | |||
| Sang Hoon Ahn | |||
| Yonsei University College of Medicine | |||
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| Worldwide, the leading cause of chronic liver disease is hepatitis B virus (HBV) infection. Antiviral agents, such as interferon and nucleos(t)ide analogues (NAs), have been used to treat patients with chronic hepatitis B (CHB). NA-based treatment strongly suppresses HBV replication and slows progression to cirrhosis and hepatocellular carcinoma (HCC). However, NAs alone do not directly target covalently closed circular DNA (cccDNA). Theoretically, the combination of NAs and pegylated interferon (Peg-IFN) should increase the chance of hepatitis B surface antigen (HBsAg) seroconversion, given their different mechanisms of antiviral treatment. However, simultaneous or sequential administrations of Peg-IFN and NAs have yet to provide satisfactory outcomes, prompting the development of new drugs that interfere with the HBV life cycle in hepatocytes. A variety of therapeutic agents against HBV are currently in clinical development, including immunomodulatory agents, RNA interference agents, inhibitors of HBsAg release, polymerase inhibitors, inhibitors of nucleocapsid assembly, and agents that target cccDNA. A combination of current and new anti-HBV agents may promote HBsAg seroclearance; thus, validation of optimized regimens is warranted. As described in clinical practice guidelines, the biomarkers HBsAg, HBeAg, and HBV DNA are used to stage and monitor treatment of chronic HBV patients. With many new therapies for HBV infection in development, new diagnostic tools are needed to measure treatment response and progress. Tests to measure cccDNA, HBV RNA, anti-HBc, and hepatitis B core-related antigen (HBcrAg) are in development, but methods to quantify virus activity and anti-HBV immune response, and to identify genetic variants, are needed. More precise and targeted approaches may advance the application of adjuvant immunotherapy to patients with HCC. Recent reports present real-world data showing favorable therapeutic responses and safety profiles with first-, second- and third-line levanitanib, nivolumab, or pembrolizumab in broad patient populations. Several targeted therapies are in clinical trials, such as anti-angiogenic drugs, small-molecule tyrosine kinase inhibitors of the c-MET receptor, and immunotherapeutics. A major current challenge for HCC treatment is optimizing the various treatment modalities alone and in combination in a fashion that maximizes the best outcome for the patient. |
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