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Hepatitis Flares Are Associated With Better Outcomes Than No Flare in Patients With Decompensated Cirrhosis and Chronic Hepatitis B Virus Infection

  • Author Footnotes
    b Authors share co-senior authorship.
    Ming-Ling Chang
    Correspondence
    Reprint requests Address requests for reprints to: Ming-Ling Chang, MD, PhD, Liver Research Center, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, No. 5 Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan; fax: (88) 6-3-3272236.
    Footnotes
    b Authors share co-senior authorship.
    Affiliations
    Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan

    Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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  • Jur-Shan Cheng
    Affiliations
    Clinical Informatics and Medical Statistics Research Center, College of Medicine, Chang Gung University, Taoyuan, Taiwan

    Department of Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
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  • Rong-Nan Chien
    Affiliations
    Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan

    Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
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  • Author Footnotes
    b Authors share co-senior authorship.
    Yun-Fan Liaw
    Footnotes
    b Authors share co-senior authorship.
    Affiliations
    Liver Research Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Taoyuan, Taiwan

    Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan
    Search for articles by this author
  • Author Footnotes
    b Authors share co-senior authorship.
Published:January 23, 2020DOI:https://doi.org/10.1016/j.cgh.2020.01.018

      Background & Aims

      Little is known about the effects of baseline hepatitis flares (level of alanine aminotransferase ≥5-fold above the upper limit of normal) on the outcomes of patients with chronic hepatitis B virus (HBV) infection with decompensated cirrhosis treated with nucleos(t)ide analogues. We aimed to investigate these effects.

      Methods

      We performed a cohort study of 511 consecutive patients (78.1% men; 58.7% with flares at baseline) with chronic HBV infection and decompensated cirrhosis who were treated with nucleos(t)ide analogues as soon as decompensation was noted. Patients were enrolled from January 2002 to March 2018 at a tertiary care center in Taiwan and followed up for 16 years.

      Results

      Patients with hepatitis flares had higher mean baseline levels of HBV DNA (6.44 ± 1.52 vs 6.08 ± 1.46 log10 IU/mL; P = .003), hepatitis B surface antigen, and total bilirubin; prolonged prothrombin time; higher platelet counts (108.0 ± 42.9 vs 83.6 ± 44.7 103/μL; P < .001); and a higher proportion were infected with HBV genotype B, compared with patients without flares. Patients with flares had lower ratios of neutrophils to lymphocytes than patients with flares (6.14 ± 9.18 vs 9.12 ± 1.36; P = .019); were less likely than patients without flares to be positive for hepatitis B e antigen, ascites, esophageal varices, or splenomegaly; and a lower proportion died or underwent liver transplantation (46.5% vs 73.2% of patients without flares; P < .001), even though the patients without flares had similar short-term (<3 mo) outcomes. Factors associated independently with baseline flares were esophageal varices (odds ratio [OR], 0.165; 95% CI, 0.067–0.406), ascites (OR, 0.415; 95% CI, 0.178–0.969), levels of total bilirubin (OR, 1.158; 95% CI, 1.041–1.269), prolonged prothrombin time (OR, 1.095; 95% CI, 1.033–1.168), and higher platelet counts (OR, 1.009; 95% CI, 1.00–1.018). After we used propensity score matching to match patients with and without baseline flares, factors associated with the cumulative incidence of death or liver transplantation were flares (hazard ratio [HR], 0.491; 95% CI, 0.317–0.76), ratio of neutrophils to lymphocytes (HR, 1.278; 95% CI, 1.027–1.591), and prolonged prothrombin time (HR, 1.223; 95% CI, 1.052–1.423).

      Conclusions

      In a 16-year study of patients with chronic HBV infection and decompensated cirrhosis treated with nucleos(t)ide analogues, a baseline flare of hepatitis was associated independently with better long-term (≥3 mo) outcomes than no flare.

      Keywords

      Abbreviations used in this paper:

      AFP (α-fetoprotein), ALT (alanine aminotransferase), bili-t (total bilirubin), CHB (chronic hepatitis B), CHB-LC (chronic hepatitis B–related liver cirrhosis), ETV (entecavir), EV (esophageal varices), HBeAg (hepatitis B e antigen), HBsAg (hepatitis B surface antigen), HBV (hepatitis B virus), HCC (hepatocellular carcinoma), HCV (hepatitis C virus), LAM (lamivudine), MELD (model for end-stage liver disease), NLR (neutrophil-to-lymphocyte ratio), Nuc (nucleos(t)ide analogue), δPT (prolonged prothrombin time), qHBsAg (quantitative hepatitis B surface antigen), TDF (tenofovir)
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