The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients

Chih-Wei Tseng; Wen-Chun Liu; Ping-Hung Ko; Yen-Chun Chen; Kuo-Chih Tseng; Ting-Tsung Chang

doi:10.3390/v14081812

The Predictive Role of Hepatitis B Biomarkers on HBV Reactivation following Direct-Acting Antiviral Therapy in HBV/HCV Coinfected Patients

Viruses. 2022 Aug 18;14(8):1812. doi: 10.3390/v14081812.

Authors

Chih-Wei Tseng^{1

2}, Wen-Chun Liu^{3

4

5}, Ping-Hung Ko¹, Yen-Chun Chen^{1

2}, Kuo-Chih Tseng^{1

2}, Ting-Tsung Chang^{3

4

5}

Affiliations

¹ Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi 62247, Taiwan.
² School of Medicine, Tzuchi University, Hualien 97004, Taiwan.
³ Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70101, Taiwan.
⁴ College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
⁵ Center of Infectious Disease and Signaling Research, National Cheng Kung University, Tainan 70101, Taiwan.

Abstract

Hepatitis B and C (HBV/HCV) coinfected patients have a potential risk of hepatitis B reactivation (HBVr) after direct-acting antivirals (DAAs) treatment. The study intends to investigate the predictive role of HBV biomarkers in HBVr. Forty-six HBV/HCV coinfected patients receiving DAAs were enrolled. All patients completed treatment and follow-up to the 12th-week post-DAA treatment (P12). Blood samples were measured for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), and HBV pregenomic RNA (HBV pgRNA). The predictive factors for HBVr after DAA treatment were analyzed. Among 31 patients without nucleot(s)ide analogue (NA) treatment, seven (22.5%, 7/31) developed HBVr without hepatitis flare-up. Patients with HBVr had higher HBsAg titers than those without HBVr from baseline to P12 (p = 0.008, 0.009, 0.004, and 0.006 at baseline, week 4, end of treatment, and P12, respectively). The baseline HBsAg level was the only predictive factor associated with HBVr (HR, 2.303; 95% CI, 1.086−4.882; p = 0.030). In predicting HBVr, a baseline HBsAg titer > 20 IU/mL had a sensitivity, specificity, positive predictive value, and negative predictive value of 85.7%, 75.0%, 50%, and 94.7%, respectively. No patient had HBVr if the baseline HBsAg titer was <8 IU/mL. Serum HBcrAg and HBV pgRNA levels had no role in predicting HBVr. In conclusion, HBV/HCV coinfected patients are at risk of HBVr after DAA treatment. The baseline HBsAg level was the predictive factor associated with HBVr. Patients with a baseline HBsAg titer < 8 IU/mL can be considered as not having HBVr.

Keywords: HBV pregenomic RNA; HBV reactivation; HBV/HCV coinfection; direct-acting antiviral; hepatitis B core-related antigen; hepatitis B surface antigen; hepatitis C.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiviral Agents / pharmacology
Biomarkers
Coinfection* / drug therapy
Hepatitis B Surface Antigens
Hepatitis B virus / physiology
Hepatitis B* / complications
Hepatitis B* / drug therapy
Hepatitis B, Chronic* / drug therapy
Hepatitis C, Chronic* / drug therapy
Humans
Symptom Flare Up
Virus Activation

Substances

Antiviral Agents
Biomarkers
Hepatitis B Surface Antigens

Grants and funding

This study was supported by research funds from the Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation [DTCRD110-E-14], and Buddhist Tzu Chi Medical Foundation [TCMF-MP 109-01-01; TCMF-A110-07; TCMF-A 107-02-09(111)]. The sponsor played no role in the study design, collection, analysis, and interpretation of data, in the writing of the report, or in the decision to submit the article for publication.