A NATIONWIDE PROSPECTIVE COHORT STUDY ON CHRONIC HEPATITIS B IN KOREA: AN INTERIM ANALYSIS

Abstract

Background: We aimed to report the interim analysis of patients with Korean chronic hepatitis B (CHB) in a prospective longitudinal cohort. Methods: This cohort funded by the Korea Centers for Disease Control and Prevention was established in 2015, and patients with CHB in this cohort were registered from five tertiary hospital in four provinces of the Republic of Korea during the corresponding 10-year follow-up period. Results: From 2015 to 2020, a total of 2052 patients (1287 male), with a mean age of 52.5, years participated in this study. Male patients smoked and ingested hazardous alcohol intakes more than female patients (P<0.001), and 560 (27.3%), 692 (33.7%), and 185 patients were found to have a mother, sibling, and child with an HBV infection, respectively. Female patients (n=765, 37.3%) were older, had a lower body mass index, education level, prevalence and amount of smoking and alcohol intake, and higher HBV infection prevalence in their children (21.7% vs. 1.5%) (all P<0.001). Plasma (28,171 vials) and plasma and peripheral blood mononuclear cells (16,539 vials) were serially collected; 97 (11.0%), 607 (68.9%), 804 (39.2%), and 544 (26.5%) patients were in the immune-tolerant phase, hepatitis B e antigen (HBeAg)-positive CHB, HBeAg-negative CHB, and liver cirrhosis, respectively. The most common antiviral regimen was tenofovir disoproxyl fumarate (TDF, n=802, 39.1%), followed by entecavir (ETV, n=515, 25.1%), tenofovir alafenamide (TAF, n=121, 5.9%), and besifovir (BSV, n=58, 2.8%). ETV (45.9%), and TDF (57.4%) were the first choices for first-line AVT between 2007 and 2011 and 2012 and 2016, respectively. TAF and BSV were initially administered in 72 (18.5%) and 39 (10.0%) patients as first-line AVTs since 2017. Including rescue therapy, the first choice for CHB treatment changed from lamivudine to ETV and TDF. Combination regimens mostly included adefovir plus lamivudine between 1999 and 2006 (n=106, 12.9%) and ETV plus TDF between 2012 and 2016 (n=59, 5.8%). Since 2017, combination therapy has rarely been selected, and TDF alone was preferred over combination therapy among study participants. Among 245 patients who initiated antiviral agents after study enrollment, serum HBV-DNA effectively decreased within 6 months (from 5.80 to 1.40 log10 IU/mL, P<0.0001). No definite estimated mean changes in non-invasive fibrosis surrogates and eGFR levels was revealed during the follow-up (all P>0.05). Hepatocellular carcinomas occurred in 23 (1.1%) patients, which all met the Milan criteria. Conclusion: This longitudinal cohort study covering Korean CHB patients sufficiently reflected current antiviral strategies for Korean patients with CHB and showed the sufficient efficacy for treating these patients. Future researches using this cohort and corresponding blood samples may reveal new requirements for CHB treatment.