Editor’s Note: The 32nd annual meeting of the Asia-Pacific Association for the Study of the Liver (APASL) was held at the Taipei International Convention Center in Taiwan, China, from February 15 to 19, 2023. During the conference, the APASL Executive Committee awarded four prestigious honors, including the third APASL Highest Honor Award, the Okuda-Omata Outstanding Achievement Award, to Professor George Lau. Professor Lau, Chairman of the Universal Benevolence Medical Group in Hong Kong, China, and Co-Director of the Liver Disease and Transplant Center at the Fifth Medical Center of the PLA General Hospital in Beijing, in collaboration with the Universal Benevolence Medical Group, was recognized for his distinguished achievements. In his acceptance speech, Professor Lau delivered an inspiring message, encouraging his peers in hepatology to continue their relentless pursuit of curing liver diseases. We extend our heartfelt congratulations to Professor Lau and are pleased to share a translated version of his speech for our readers’ encouragement and inspiration.
Respected Conference Chair and Esteemed Colleagues,
Good afternoon!
As a hepatologist practicing in China, we continue to face significant challenges in managing Acute-on-Chronic Liver Failure (ACLF), End-Stage Liver Cirrhosis (ESLC), and Hepatocellular Carcinoma (HCC). These severe liver diseases are primarily caused by underlying chronic viral infections like Chronic Hepatitis B (CHB) and Chronic Hepatitis C (CHC), as well as the increasingly prevalent Metabolic Associated Fatty Liver Disease (MAFLD). Seeking a “cure” for these patients has always been the dream of all clinicians and researchers dedicated to hepatology.
By 2016, eight drugs had been registered as effective treatments for CHB: conventional interferon, pegylated interferon-alpha, lamivudine, adefovir dipivoxil, telbivudine, entecavir, tenofovir disoproxil, and tenofovir alafenamide. Their indications have been clearly defined by authoritative liver societies like AASLD, APASL, and EASL. These treatments effectively suppress viral replication, significantly reducing the risk of ACLF, ESLC, and HCC in CHB patients.
However, as our research team has confirmed, the clearance of HBsAg (the goal of functional cure for CHB, indicating discontinuation of treatment) can only occur when the host’s immune response to the virus is restored. Therefore, the current registered treatments offer very limited “success.” In HBeAg-positive and -negative CHB patients, the functional cure rates for a 48-week treatment with Peg-IFNα2a are 3% and 8% respectively, while long-term use of nucleos(t)ide analogs (NUCs) with a high barrier to resistance has a functional cure rate of less than 1% per year. Consequently, most CHB patients require lifelong NUC treatment.
To improve the functional cure rate of CHB with NUCs, strategies like initial combination therapy, sequential therapy, and the addition of Peg-IFNα2a have been attempted. Notably, one-quarter of chronic hepatitis B patients maintained a functional cure after 96 weeks of Peg-IFNα2a treatment, and low levels of HBcAg and high levels of anti-HBs antibodies at the end of treatment were associated with sustained functional cure.
On the other hand, new drug development is ongoing. Success is limited due to the integration of covalently closed circular DNA (cccDNA) in the infected liver cells. As reported in the CLEAR-B Phase II clinical study, there are still other “unknown confounding factors” that hinder the functional cure of CHB. In this study, a highly selected group of CHB patients under NUC treatment were randomly assigned to three groups, receiving the same treatment (bepirovirsen) for the initial 12 weeks. The study design is shown in Figure 1. The results showed that the proportion of patients in the three groups with a reduction in HBsAg levels of ≥3 log10 IU/mL was 34%, 37%, and 16%, respectively, with a statistically significant difference (P=0.005), as shown in Figure 2.
In combating Chronic Hepatitis C (CHC), our systematic understanding of the HCV virus sequence, biology, and replicon has enabled the development of effective Direct-Acting Antivirals (DAAs). Initially estimated through mathematical models, the duration of treatment has since been validated through large-scale clinical trials and practical research. Currently, in CHC treatment, we can eliminate HCV infection through a limited course of treatment, with minimal adverse reactions.
Overall, we now have effective methods to suppress HBV and eradicate HCV. However, currently only 2.4% of CHB patients and 16.9% of CHC patients worldwide are receiving treatment. This low treatment rate largely explains why global statistics show a persistently high and rising incidence of liver cancer in 2020. It is estimated that the East Asian region has 450,000 cases of liver cancer and 410,000 deaths due to liver cancer, with China alone accounting for 45.3% of global liver cancer cases and 47.1% of liver cancer-related deaths. Therefore, it is crucial to increase public awareness of CHB and CHC, expand community-level HBV and HCV screening, and improve diagnosis and treatment rates.
In the future, the use of a better naming convention for MAFLD should help us better define patient phenotypes and develop targeted therapies with sufficient precision. Meanwhile, with our improved understanding of the molecular biology and immunology of liver cancer, there is hope for significant breakthroughs in liver cancer treatment. Building on the recent advancements, exploring the combination of molecular targeted drugs and immune checkpoint inhibitors with traditional treatments, such as surgery, TACE, radiofrequency ablation, etc., holds promise for curing inoperable liver cancer.
TAG: APASL 2023, Master Class, Okuda-Omata Outstanding Achievement Award
