XIV) HBV/HCC Symposiums

Symposium (XIV)

HBV/HCC SYMPOSIUMS

RISK OF OCCURRENCE AND RECURRENCE OF HCC UNDER NUCS TREATMENT

I-Cheng Lee Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

HBV infection is the leading cause of hepatocellular carcinoma (HCC) worldwide, and patients with HBV infection are exposed to the risk of HCC occurrence throughout their life. Patients with high HBV viral load or cirrhosis are at highest risk of HCC development, and antiviral therapy has been shown to decrease the risk of HCC occurrence and recurrence. However, HCC may still occur in patients without cirrhosis, in patients with low viral loads, in patients under antiviral therapy, and even in patients achieving HBsAg seroclearance. In this topic we will summarize the current knowledge of the mechanisms of HCC occurrence and recurrence under NUCs treatment, the predictors and risk scores of HCC occurrence and recurrence, and strategies to minimize the risk of HCC.

Symposium (XIV)

HBV/HCC SYMPOSIUMS

APPLICATION OF BIOMARKERS TO PREDICT AND MONITOR HBVRELATED HCC PATIENTS

Tai-Chung Tseng Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Patients with chronic hepatitis B virus (HBV) infection are at risk of developing hepatocellular carcinoma (HCC), and serum markers reflecting active viral replication or fibrosis are potential predictors for HCC development. Levels of serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) are known as HCC predictors. The current data show that not only the baseline levels but also the kinetic are associated with HCC development in treatment-naïve patients. Taking HBcrAg level as an example, our published data has shown that HBcrAg level of 4 log U/mL was effective to stratify HCC risk in HBeAg-negative patients with intermediate viral loads. Their HCC risk could be further stratified by combining the HBcrAg levels at baseline and 3 years after follow-up. Surrogate markers of liver fibrosis, such as M2BPGi or fibrosis-4 index (FIB-4), are also important HCC predictors. In both untreated and treated patients, the kinetic of FIB-4 are shown to be associated with HCC development. Finally, not only HBV activity itself but also superinfection of other heaptotropic viruses could increase the HCC risk. Our recently published data have shown that superinfection of hepatitis E virus could increase liver mortality in HBV-related cirrhotic patients and HCC risk in patients with low viral load. In summary, we believe the monitoring the levels of these HCC biomarkers provides an accurate prediction of HBV-related HCC.

Symposium (XIV)

HBV/HCC SYMPOSIUMS

IMMUNE MICROENVIRONMENT IN HBV-RELATED HCC

Valerie Chew Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre, Singapore, Singapore

Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical trials (approximately 20% for monotherapy). Therefore, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial in the design of more effective immunotherapeutics. We performed in-depth and multidimensional interrogation of the immune landscapes comparing immune microenvironments of HBV-related versus nonviral related HCC and revealed multiple distinct immune features in both HCC subtypes with important implications for future immunotherapy.

Symposium (XIV)

HBV/HCC SYMPOSIUMS

RISK AND MANAGEMENT OF ALT FLARE AND HBV REACTIVATION IN ICI-TREATED HCC

Grace Lai-Hung Wong Institute of Digestive Disease, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China

Immunotherapy with immune checkpoint inhibitors (ICI) has dramatically improved the survival of patients with advanced hepatocellular carcinoma (HCC). Recent studies suggest that immunotherapy may increase the risk of hepatitis; whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy. We reported a territory-wide observational cohort study of 396 HCC patients who had received ICI in Hong Kong. Hepatitis flare (ALT > 2xULN) occurred in 39.3% HBsAgpositive and 30.4% HBsAg-negative patients. High baseline ALT and combination of immunotherapy increased the risk of hepatitis. HBV reactivation (≥ 2 log increase in HBV DNA from baseline) occurred in two HBsAg-positive patients; HBsAg seroclearance and seroreversion was observed in one HBsAg-positive and one HBsAg-negative patient respectively (<1%). In conclusions, hepatitis flare occurs in approximately 40% of HBsAgpositive patients and 30% of HBsAg-negative patients during immunotherapy. HBV reactivation, HBsAg seroclearance and seroreversion are rare. Current or past HBV infection has no impact on the emergence of hepatic flare associated with immunotherapy.