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Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

Background

Little is known about stopping rules of nucelos(t)ide analog (NA) treatment for chronic hepatitis B (CHB).

Methods

A total of 113 consecutive patients with CHB (45 HBeAg-positive and 68 HBeAg-negative CHB patients), who met the cessation criteria of NA treatment as per the Asian-Pacific Association for the Study of the Liver (APASL) guideline, were enrolled in this prospective cohort study. The primary endpoint was to evaluate virological relapse (VR) rate within 1 year, which was defined as reappearance of hepatitis B virus (HBV)–DNA > 2000 IU/mL after cessation of NA treatment. In this cohort, entecavir was used in 81 (71.7 %) and lamivudine in 32 (28.3 %) patients.

Results

Within 1 year after NA treatment, VR occurred in 26 (57.8 %) HBeAg-positive patients and in 37 (54.4 %) HBeAg-negative patients. In univariate and subsequent multivariate analysis, age > 40 years [odds ratio (OR) 10.959; 95 % confidence interval (CI) 2.211–54.320; P = 0.003) and a pre-treatment HBV DNA level >2000,000 IU/mL (OR 9.285; 95 % CI 1.545–55.795; P = 0.036) were identified as independent risk factors for VR in HBeAg-positive patients, and age > 40 years (OR 6.690; 95 % CI 1.314–34.057; P = 0.022) and an end-of-treatment HBcrAg level >3.7 log IU/mL (OR 3.751; 95 % CI 1.187–11.856; P = 0.024) were identified in HBeAg-negative patients. During follow up, neither hepatic decompensation nor hepatocellular carcinoma (HCC) occurred, and HBV DNA suppression was achieved in all patients who received antiviral re-treatment.

Conclusion

Our data suggested that the APASL stopping rule could be applied if a candidate was properly selected using individual risk factors. However, regular monitoring should be performed after cessation of NA treatment and long-term outcomes need to be evaluated further.

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Abbreviations

HBV:

Hepatitis B virus

CHB:

Chronic hepatitis B

PEG-IFN:

Pegylated interferon

NA:

Nucelos(t)ide analog

HBsAg:

Hepatitis B surface antigen

AASLD:

American Association for the Study of Liver Disease

EASL:

European Association for the Study of the Liver

APASL:

Asian-Pacific Association for the Study of the Liver

LAM:

Lamivudine

ETV:

Entecavir

PCR:

Polymerase chain reaction

VR:

Virological relapse

ALT:

Alanine aminotransferase

ULN:

Upper limit of normal

HBcrAg:

HBV core-related antigen

IP-10:

Interferon gamma-induced protein 10

LS:

Liver stiffness

AST:

Aspartate aminotransferase

kPa:

Kilopascals

IQR:

Interquartile range

IQR/M:

IQR to median value ratio

SD:

Standard deviation

OR:

Odd ratio

CI:

Confidence interval

TDF:

Tenofovir

cccDNA:

Covalently closed circular DNA

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Acknowledgments

The authors are grateful to Dong-Su Jang (Medical Illustrator, Medical Research Support Section, Yonsei University College of Medicine, Seoul, Korea) for his help with the figures.

Grant support

This study was supported by following Grants; (a) a fund of the HBV cohort study from the Korea Centers for Disease Control and Prevention (4800-4845-300-260, 2015-ER5101-00), (b) a faculty research Grant of Yonsei University College of Medicine (No. 6-2012-0008).

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    Authors and Affiliations

    1. Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 120–752, Korea

      Kyu Sik Jung, Jun Yong Park, Young Eun Chon, Wonseok Kang, Beom Kyung Kim, Seung Up Kim, Do Young Kim, Kwang-Hyub Han & Sang Hoon Ahn

    2. Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea

      Jun Yong Park, Beom Kyung Kim, Seung Up Kim, Do Young Kim, Kwang-Hyub Han & Sang Hoon Ahn

    3. Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea

      Hyon-Suk Kim

    4. Liver Cirrhosis Clinical Research Center, Seoul, Korea

      Jun Yong Park, Beom Kyung Kim, Seung Up Kim, Do Young Kim, Kwang-Hyub Han & Sang Hoon Ahn

    5. Brain Korea 21 Project of Medical Science, Seoul, Korea

      Kwang-Hyub Han & Sang Hoon Ahn

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    Kyu Sik Jung and Jun Yong Park have equally contributed to this work.

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    Supplementary Figure 1

    Cumulative relapse rate after cessation of antiviral therapy in HBeAg-positive patients (A) and HBeAg-negative patients (B). The 1-year cumulative relapse rate is not significantly different between the two groups (P > 0.05, log-rank test;

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    Jung, K.S., Park, J.Y., Chon, Y.E. et al. Clinical outcomes and predictors for relapse after cessation of oral antiviral treatment in chronic hepatitis B patients. J Gastroenterol 51, 830–839 (2016). https://doi.org/10.1007/s00535-015-1153-1

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