Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B

• Published in: Clinical and molecular hepatology Vol. 27; no. 2; pp. 295 - 304
• Main Authors: Jeon, Mi Young, Kim, Beom Kyung, Lee, Jae Seung, Lee, Hye Won, Park, Jun Yong, Kim, Do Young, Ahn, Sang Hoon, Han, Kwang-Hyub, Kim, Seung Up
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association for the Study of the Liver 01.04.2021; The Korean Association for the Study of the Liver; 대한간학회
• Subjects: Alcohol; Antigens; antiviral agent; Antiviral drugs; carcinoma, hepatocellular; Diabetes; Disease; hepatic fibrosis; Hepatitis B; immune tolerance; Infections; Liver cancer; Liver cirrhosis; Liver transplants; Mortality; Original; Patients; Population; Proteins; Ultrasonic imaging; 내과학; Hepatic fibrosis; Antiviral agent; Carcinoma, Hepatocellular; Immune tolerance; Hepatitis B
• ISSN: 2287-2728; 2287-285X; 2287-285X
• DOI: 10.3350/cmh.2020.0216

Background/Aims: The immune-tolerant (IT) phase of chronic hepatitis B (CHB) patients is not generally indicative of antiviral therapy (AVT). We assessed and compared the risk of hepatocellular carcinoma (HCC) during the IT-phase stringently defined by a low fibrosis-4 (FIB-4) index, compared to that in patients undergoing AVT.Methods: Among 125 untreated patients that were hepatitis B e-antigen positive, hepatitis B virus-DNA >20,000 IU/mL, with normal alanine aminotransferase level from 2012 to 2018, those with a FIB-4 index of <1.45 were classified into the IT-group. The cumulative probability of HCC was estimated using Kaplan-Meier analysis. All patients were assessed until HCC development (intention-to-treat [ITT] analysis), whereas those suspected of experiencing CHB phase switch were assessed using the per-protocol (PP) and censored at the time of phase switch.Results: The cumulative probability of HCC at 1-, 3-, and 5-years among the IT-group was zero, compared to AVT-treated patients with FIB-4 indices <1.45 during the same period: 0.2%, 0.6%, and 1.4%, respectively (P=0.264 for ITT and P=0.533 for PP). Among the initially screened 125 untreated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to the IT-group (P=0.005). Furthermore, among AVT-treated patients, those with a FIB-4 index of ≥1.45 had a higher risk of HCC compared to their counterpart (P<0.001).Conclusions: The risk of HCC was negligible in the IT-group stringently defined by a low FIB-4 index. However, given that a higher HCC risk exists among untreated patients with higher FIB-4, appropriate criteria for AVT should be established.