On-Treatment Low Serum HBV RNA Level Predicts Initial Virological Response in Chronic Hepatitis B Patients Receiving Nucleoside Analogue Therapy

Huang, Yi‐Wen; Takahashi, Shoichi; Tsuge, Masataka; Chen, Chi Ling; Wang, Ting‐Chung; Abe, Hiromi; Hu, Jersan; Chen, Ding‐Shinn; Yang, Shwu Huey; Chayama, Kazuaki; Kao, Jia‐Horng

doi:10.3851/imp2777

Cited by 65 publications

(77 citation statements)

References 20 publications

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“…However, 2 other reports by Huang et al, showed that serum HBV RNA was undetectable in all the 19 studied patients and only found in 40% (21/52) of the untreated ones (11,17). The difference between the results of the current study and those of others may be attributed to the differences between the studied populations.…”

Section: Discussioncontrasting

confidence: 89%

“…It also showed that serum HBV RNA level is a valuable early predictor for the occurrence of antiviral resistant mutations (10) and reactivation of chronic hepatitis B (CHB) after antiviral therapy cessation (8). Serum HBV RNA is a novel biomarker of HBV infection and is useful to optimize antiviral strategies (9,11). However, to understand the factors affecting its serum level and detection, and its biological and clinical significance, large cohorts of untreated patients are required.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

et al. 2018

Hepat Mon

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Background: The serum hepatitis B virus (HBV) RNA is suggested as a potential new biomarker of HBV infection. However, it is not fully understood. Objectives: The current study aimed at characterizing serum HBV RNA in patients with untreated chronic hepatitis B (CHB) and genotype B and C HBV infection. Methods: A large cohort of 483 patients with hepatitis B e antigen (HBeAg)-positive and -negative was performed. The routine serum biomarkers of HBV infection were tested. HBV genotyping was carried out by direct sequencing. Serum HBV RNA levels were quantified using a method described in the authors' previous study (lower limit of detection: 66.7 IU/mL). Results: Serum HBV RNA was detected in 92.5% (394/426) of the patients with HBeAg-positive and 31.6% (18/57) of HBeAg-negative ones; a positive association was observed between HBeAg and HBV RNA statuses in the subjects. Alanine aminotransferase (ALT), HBV DNA, and genotype were the independent predictors in patients with HBeAg-positive CHB (P = 0.024, 0.001 and 0.014, respectively), while it was HBV DNA in the negative ones (P = 0.000) for serum HBV RNA detectability. Serum HBV RNA was positively correlated with ALT, aspartate transaminase (AST) and HBV DNA, regardless of HBeAg status, and with hepatitis B surface antigen (HBsAg) in HBeAg-positive ones (P < 0.05). Conclusions: Serum HBV RNA may be affected by HBeAg status, serum HBV DNA, HBsAg levels, HBV genotype, ALT, and AST levels. There might be some similarities between the characteristics of serum HBV RNA, and serum HBV DNA and HBsAg, regardless of its distinctive features. The roles of serum HBV RNA in viral replication, infection, survival, disease progression, and antiviral responses need to be investigated in further studied.

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Section: Discussioncontrasting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

et al. 2018

Hepat Mon

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“…In this context, serum HBV RNA has been reported as an important potential predictor of the YMDD resistance mutation [11], efficacy [9,[12][13][14] and prognosis [10] of CHB treatment. Whether dynamic changes in serum HBV RNA can be used as a potential marker for the safe discontinuation of NAs therapy remains an open question.…”

Section: Introductionmentioning

confidence: 99%

“…Importantly, in addition to HBV DNA, HBV RNA has also been detected in the serum of chronic hepatitis B (CHB) patient [7][8][9][10][11][12][13][14]. However, the life cycle of HBV cannot fully explain the generation of serum HBV RNA.…”

Section: Introductionmentioning

confidence: 99%

Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound

Wang

Shen

Huang

et al. 2016

Journal of Hepatology

377

502

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“…Thus, before and during treatment with nucleos(t)ide analogue (NA) or pegylated interferon alfa (PEG‐IFN), a correlation between serum HBV RNA and the transcriptional activity of cccDNA was demonstrated 6. In addition, serum HBV RNA levels were found to be associated with the probability of response to treatment with either NAs or PEG‐IFN 2, 4, 7, 8, 9. However, before the further development of serum HBV RNA as a response‐predicting marker, it is mandatory to evaluate which factors which may influence HBV RNA levels in individuals who are eligible for treatment.…”

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confidence: 99%

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

et al. 2018

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Hepatitis B virus (HBV) RNA in serum is a novel biomarker for intrahepatic HBV replication and treatment response. For its proper use, it is essential to identify factors influencing serum HBV RNA level. Using a rapid amplification of complimentary DNA (cDNA) ends (RACE) PCR technique (lower limit of detection [LLD], 800 copies/mL [c/mL]), serum HBV RNA levels were measured in samples of 488 untreated individuals with chronic HBV infection who were eligible to treatment according to currently used recommendations. We explored the association of serum levels of HBV RNA with patient‐ and virus‐associated factors. HBV genotype distribution was 21/10/20/46/3% for A/B/C/D/other. Mean HBV RNA serum level was 5.9 (1.6) log10 c/mL (hepatitis B e antigen [HBeAg]‐positive chronic hepatitis B [CHB], 6.5 [1.2] log c/mL; HBeAg‐negative CHB, 4.1 [1.2] log c/mL; P < 0.001). By multivariable linear regression, factors associated with lower HBV RNA level were HBeAg negativity (β = –0.69; P < 0.001), HBV genotypes A (β = –0.13; P = 0.002), B (β = –0.07; P = 0.049), and C (β = –0.61; P < 0.001) in comparison to D, and presence of HBV basal core promoter mutation either alone (β = –0.14; P = 0.001) or in combination with precore mutation (β = –0.22; P < 0.001). Higher serum alanine aminotransferase (ALT) was associated with higher HBV RNA (β = 0.23; P < 0.001). HBV RNA correlated strongly with HBV DNA (HBeAg‐pos, r = 0.72; P < 0.001; HBeAg‐neg, r = 0.78; P < 0.001) and moderately with quantitative hepatitis B surface antigen (qHBsAg; HBeAg‐pos, r = 0.54; P < 0.001; HBeAg‐neg, r = 0.19; P = 0.04) and quantitative hepatitis B surface antigen (qHBeAg; r = 0.41; P < 0.001). Conclusion: In this multiethnic cohort of 488 untreated individuals with CHB, factors associated with serum HBV RNA level were HBeAg status, serum ALT, HBV genotype, and presence of basal core promotor mutations. For the future use of serum HBV RNA as a clinical marker, it seems mandatory to take these factors into consideration. (Hepatology 2018).

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On-Treatment Low Serum HBV RNA Level Predicts Initial Virological Response in Chronic Hepatitis B Patients Receiving Nucleoside Analogue Therapy

Abstract: Low serum HBV RNA level at week 12 of nucleoside analogue therapy independently predicts initial virological response in treated chronic hepatitis B patients. Serum HBV RNA levels may thus be useful for optimizing treatment of chronic hepatitis B.

Cited by 65 publications

References 20 publications

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

Characterization of Serum HBV RNA in Patients with Untreated HBeAg-Positive and -Negative Chronic Hepatitis B Infection

Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound

Host and viral factors associated with serum hepatitis B virus RNA levels among patients in need for treatment

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