Negligible risks of hepatocellular carcinoma during biomarker-defined immune-tolerant phase for patients with chronic hepatitis B - PubMed (original) (raw)

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

Mi Young Jeon et al. Clin Mol Hepatol. 2021 Apr.

Abstract

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).

Conclusion: 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.

Keywords: Antiviral agent; Carcinoma, Hepatocellular; Hepatic fibrosis; Hepatitis B; Immune tolerance.

PubMed Disclaimer

Conflict of interest statement

Conflicts of Interest: The authors have no conflicts to disclose.

Figures

Figure 1.

Figure 1.

Cumulative probability of HCC for the IT-group and AVT-group. (A) ITT analysis and (B) PP analysis. HCC, hepatocellular carcinoma; AVT, antiviral therapy; IT, immune-tolerant; ITT, intention-to-treat; PP, per-protocol.

Figure 2.

Figure 2.

Cumulative probability of HCC according to FIB-4 scores for untreated patients belonging to IT-phase. HCC, hepatocellular carcinoma; FIB-4, fibrosis-4; IT, immune-tolerant.

Figure 3.

Figure 3.

Cumulative probability of HCC according to FIB-4 scores for patients undergoing AVT. HCC, hepatocellular carcinoma; FIB-4, fibrosis-4; AVT, antiviral therapy.

Figure 4.

Figure 4.

Distribution of FIB-4 score depending on HCC development among patients belonging to the IT-phase (A) and those undergoing AVT (B). FIB-4, fibrosis-4; HCC, hepatocellular carcinoma; IT, immune-tolerant; AVT, antiviral therapy.

None

Comment in

References

    1. Chen CJ, Yang HI, Su J, Jen CL, You SL, Lu SN, et al. Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level. JAMA. 2006;295:65–73. - PubMed
    1. Kumar M, Sarin SK, Hissar S, Pande C, Sakhuja P, Sharma BC, et al. Virologic and histologic features of chronic hepatitis B virus-infected asymptomatic patients with persistently normal ALT. Gastroenterology. 2008;134:1376–1384. - PubMed
    1. Yang HI, Yuen MF, Chan HL, Han KH, Chen PJ, Kim DY, et al. Risk estimation for hepatocellular carcinoma in chronic hepatitis B (REACH-B): development and validation of a predictive score. Lancet Oncol. 2011;12:568–574. - PubMed
    1. Chen CF, Lee WC, Yang HI, Chang HC, Jen CL, Iloeje UH, et al. Changes in serum levels of HBV DNA and alanine aminotransferase determine risk for hepatocellular carcinoma. Gastroenterology. 2011;141:1240–1248. 1248.e1-e2. - PubMed
    1. European Association for the Study of the Liver EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J Hepatol. 2017;67:370–398. - PubMed

MeSH terms

Substances

LinkOut - more resources