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Long-term natural history of liver disease in patients with chronic hepatitis B virus infection: an analysis using the Markov chain model

  • Original Article—Liver, Pancreas, and Biliary Tract
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Abstract

Background

The relationship between the hepatitis B e antigen (HBeAg) seroconversion and the long-term natural history of liver disease has not been sufficiently investigated.

Methods

A total of 408 [4352 person-year (PY) units] patients with chronic hepatitis B virus (HBV) without antiviral therapy were enrolled. The study patients were divided into three groups, as follows: Group A (2666 PY units), seroconverted of HBeAg at age < 40; Group B (413 PY units), seroconverted of HBeAg at age ≥ 40; Group C (1273 PY units), persistently HBeAg positive. Yearly transition probabilities from each liver state [chronic HBV infection, chronic hepatitis B, cirrhosis, hepatocellular carcinoma (HCC), and hepatitis B surface antigen (HBsAg) negativity] were calculated using the Markov chain model.

Results

In the analysis of 1 year liver disease state transition probabilities, the liver states remained almost the same in Group A. In Groups B and C, each liver state tended to progress to a worse state. Assuming a chronic hepatitis B state at age 40 as the starting condition for simulation over the next 40 years, the chronic hepatitis B state accounted for approximately 60% of males aged ≥ 50 and approximately 40% of females aged ≥ 60 in Group A, and the HBsAg-negative state accounted for approximately 30–40% of males and females aged ≥ 60. In Groups B and C, the probabilities of patients with cirrhosis and HCC gradually increased with age.

Conclusions

Not only patients with persistent HBeAg positive, but also patients with delayed HBeAg seroconversion showed poor prognosis of liver-related natural history.

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Abbreviations

HCC:

hepatocellular carcinoma

HBsAg:

hepatitis B surface antigen

HBV:

hepatitis B virus

HBeAg:

hepatitis B e antigen

AST:

aspartate aminotransferase

ALT:

alanine aminotransferase

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Funding

This work was supported by Health and Labour Sciences Research Grants (Research on Hepatitis) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Ogaki Municipal Hospital, 4-86 Minaminokawa, Ogaki, Gifu, 503-8502, Japan

    Toshifumi Tada, Takashi Kumada & Hidenori Toyoda

  2. Department of Epidemiology, Infectious Disease Control and Prevention, Hiroshima University Institute of Biomedical and Health Sciences, Hiroshima, Japan

    Masayuki Ohisa, Tomoyuki Akita & Junko Tanaka

Authors
  1. Toshifumi Tada
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  2. Takashi Kumada
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  3. Hidenori Toyoda
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  4. Masayuki Ohisa
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  5. Tomoyuki Akita
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  6. Junko Tanaka
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Corresponding author

Correspondence to Toshifumi Tada.

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The authors declare no conflicts of interest.

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Tada, T., Kumada, T., Toyoda, H. et al. Long-term natural history of liver disease in patients with chronic hepatitis B virus infection: an analysis using the Markov chain model. J Gastroenterol 53, 1196–1205 (2018). https://doi.org/10.1007/s00535-018-1467-x

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  • DOI: https://doi.org/10.1007/s00535-018-1467-x

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