J Korean Med Sci.  2021 Apr;36(16):e105. 10.3346/jkms.2021.36.e105.

Revised Korean Antiviral Guideline Reduces the Hepatitis B-related Hepatocellular Carcinoma Risk in Cirrhotic Patients

• Kim DS
• Park SY
• Kim BK
• Park JY
• Kim DY
• Han KH
• Lee YR
• Tak WY
• Kweon YO
• Jung I
• Han M
• Kim EH
• Ahn SH
• Kim SU

• KMID: 2515086
• DOI: http://doi.org/10.3346/jkms.2021.36.e105

Abstract

Background
Since September 2015, the initiation of antiviral therapy (AVT) for patients with chronic hepatitis B (CHB)-related cirrhosis has been reimbursed according to the revised Korean Association for the Study of Liver (KASL) guideline, if the patient had hepatitis B virus DNA level ≥ 2,000 IU/L, regardless of aminotransferase or alanine aminotransferase levels. This study investigated whether the KASL guideline implementation reduced the risk of CHB-related hepatocellular carcinoma (HCC) in patients with cirrhosis in South Korea.
Methods
A total of 429 patients with CHB-related cirrhosis who initiated AVT between 2014 and 2016 were recruited. The risk of HCC development was compared between patients who initiated AVT before and after September 2015 (pre-guideline [n = 196, 45.7%] vs. postguideline implementation [n = 233, 54.3%]).
Results
Univariate analysis showed that AVT initiation before guideline implementation, older age, male gender, and diabetes significantly predicted increased risk of HCC development (all P < 0.05). Subsequent multivariate analysis showed that AVT initiation before guideline implementation (HR = 1.941), older age (HR = 5.762), male gender (HR = 2.555), and diabetes (HR = 1.568) independently predicted increased risk of HCC development (all P < 0.05). Additionally, multivariate analysis showed that AVT initiation before guideline implementation (HR = 2.309), male gender (HR = 3.058), and lower platelet count (HR = 0.989) independently predicted mortality (P < 0.05). The cumulative incidences of HCC and mortality were significantly higher in patients who initiated AVT before guideline implementation than in those who initiated AVT after guideline implementation (all P < 0.05, log-rank test).
Conclusion
The prognosis of patients with CHB-related cirrhosis who initiated AVT improved after guideline implementation according to the revised KASL guideline.

Keyword

Hepatitis B; Antiviral Therapy; Hepatocellular Carcinoma; Management; Guideline

Figure

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  Fig. 1 Diagram of cohort enrollment and follow-up period. Patients were enrolled based on AVT start date. The pre- and post-guideline implementation cohort was separated in September 1st, 2015, which is the start date for National Health Insurance Service medical insurance reimbursement for cirrhotic chronic hepatitis B patients with HBV DNA > 2,000 IU/mL, regardless of AST/ALT levels. The enrollment period for the pre-guideline implementation cohort was from July 1st, 2014 to August 31st, 2015 and the post guideline implementation cohort was from September 1st, 2015 to October 31st, 2016 (both 14 months). Follow up periods were matched for both cohorts to a maximum of 45 months, until April 30th, 2018 and June 30th, 2019 for the previous and current AVT guideline cohort, respectively.AVT = antiviral therapy, AST = aspartate aminotransferase, ALT = alanine aminotransferase, HBV = Hepatitis B virus.

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  Fig. 2 Flow of study population selection process. A total of 218 patients from YUHS and 323 patients from KNUH with CHB treated with entecavir or tenofovir between July 2014 and October 2016 were considered eligible for participation. After exclusion of 50 and 37 patients from YUHS and KNUH, respectively, according to our exclusion criteria, 168 patients from YUHS and 261 patients from KNUH were ultimately included for statistical analysis.YUHS = Yonsei University Health System, KNUH = Kyungpook National University Hospital, CHB = chronic hepatitis B, HIV = human immunodeficiency virus.

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  Fig. 3 The cumulative incidence rates of HCC (A) and mortality or transplantation (B) according to antiviral therapy guideline implementation. The cumulative incidence risk of HCC and mortality or transplantation of patients in the pre-guideline implementation cohort was significantly higher than that of patients in the post-guideline implementation cohort (P = 0.041 and P = 0.022 respectively, log-rank test).HCC = hepatocellular carcinoma.

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