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Clin Transl Gastroenterol. 2019 May 17. doi: 10.14309/ctg.0000000000000036. [Epub ahead of print]

Prognosis of Untreated Minimally Active Chronic Hepatitis B Patients in Comparison With Virological Responders by Antivirals.

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Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Yonsei Liver Center, Severance Hospital, Seoul, Republic of Korea.
Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Infectious Diseases, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia.



Serum hepatitis B virus (HBV)-DNA > 2,000 IU/mL is associated with higher risk of disease progression. However, without hepatocellular carcinoma (HCC) or cirrhosis, nucleos(t)ide analogs (NUCs) are recommended only for patients with elevated serum HBV-DNA and alanine aminotransferase ≥2 × upper normal limit.


We evaluated prognosis of untreated minimally active (MA) hepatitis patients (defined as HBV-DNA > 2,000 IU/mL, but never fulfilling current criteria for NUCs during follow-up) (untreated MA group), compared to virological responders by NUCs (NUC-VR group). Eligible patients undergoing transient elastography were consecutively enrolled. Patients with an immune-tolerant or inactive phase and with cirrhosis or HCC at enrollment were excluded. Cumulative risks of disease progression were assessed using the Kaplan-Meier method.


The untreated MA group (n = 152) had higher HBV-DNA, alanine aminotransferase, and total bilirubin levels, and lower proportions of male and positive hepatitis B e antigen, compared to the NUC-VR group (n = 641). The untreated MA group had higher risks of HCC (adjusted hazard ratio [HR] 3.485, 95% confidence interval [CI] 1.234-9.846; P = 0.018), but similar risks of cirrhotic complications (adjusted HR 0.649, 95% CI 0.227-1.854; P = 0.420), compared to the NUC-VR group. Inverse probability of treatment weighting analysis using propensity score showed that the untreated MA group had higher risks of HCC (HR 4.464, 95% CI 2.008-9.901; P < 0.001), but similar risks of cirrhotic complications (HR 1.171, 95% CI 0.594-2.309; P = 0.649), compared to the NUC-VR group.


Through appropriate adjustment of potential prognostic factors, the untreated MA group consistently showed higher risks of HCC, but similar risks of cirrhotic complications, compared to the NUC-VR group. HCC risk might be reduced through earlier NUCs for the untreated MA group.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

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