Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients

Park, Eun Sook; Lee, Ah Ram; Kim, Doo Hyun; Lee, Jeong Hoon; Yoo, Jeong‐Ju; Ahn, Seung Ho; Sim, Heewoo; Park, Soree; Kang, Hong Seok; Won, Juhee; Ha, Yea Na; Shin, Gu Choul; Kwon, So Young; Park, Yong Kwang; Choi, Boseung; Lee, Yun Bin; Jeong, Nakcheol; An, Yohan; Ju, Young Seok; Yu, Su Jong; Chae, Hee Bok; Yu, Kyung‐Sang; Kim, Yoon Jun; Yoon, Jung Hwan; Zoulim, Fabien; Kim, Kyun-Hwan

doi:10.1016/j.jhep.2019.02.006

Cited by 116 publications

(134 citation statements)

References 34 publications

Supporting

Mentioning

119

Contrasting

Unclassified

Order By: Relevance

“…A recent study described a quadruple mutation in two patients with previous exposure to NA who developed a virological breakthrough during TDF treatment. 24 One patient died due to HCC and the other did not achieve virological suppression following a TDF/ETV combination and a new capsid inhibitor was started. Cross-resistance mechanisms between low-and high-barrier NAs have been described in patients previously exposed to these drugs.…”

Section: Patients With Treatment Failurementioning

confidence: 99%

“…The resistance rate to ETV in naïve patients can reach 1.2% and rescue therapy with TDF is clinically effective. A recent study described a quadruple mutation in two patients with previous exposure to NA who developed a virological breakthrough during TDF treatment . One patient died due to HCC and the other did not achieve virological suppression following a TDF/ETV combination and a new capsid inhibitor was started.…”

Section: Choice Of Treatment With Nucleos(t)ide Analoguesmentioning

confidence: 99%

See 1 more Smart Citation

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

Buti

Roade

Riveiro‐Barciela

et al. 2020

Liver International

View full text Add to dashboard Cite

Management of chronic hepatitis B (CHB) is still considered a challenge in clinical practice. Patients must be carefully evaluated before starting therapy. This includes virology and laboratory assessments, an estimation of fibrosis by invasive and/or noninvasive methods, and an estimation of the risk of hepatocellular carcinoma (HCC). Nucleos(t)ide analogues (NAs) with a high barrier to resistance (tenofovir disoproxil fumarate [TDF], entecavir [ETV] and tenofovir alafenamide [TAF]) are the most frequently used treatments because of their good long‐term efficacy and tolerability. None of these options has been shown to be more effective than the other, but certain factors should be considered when selecting the best therapy for specific populations. Most patients achieve a virological and biochemical response to these agents, with a low rate of emerging resistance during long‐term treatment. However, the rate of hepatitis B surface antigen (HBsAg) loss is low and in most cases NAs therapy is lifelong. Safety concerns for long‐term NA use have become a priority in the management of CHB, in particular, the risk of impaired kidney function and bone marrow density loss described with TDF regimens. The risk of HCC is not completely eliminated by NAs. Thus, patients at higher risk should be identified and provided with appropriate surveillance.

show abstract

Section: Patients With Treatment Failurementioning

confidence: 99%

Section: Choice Of Treatment With Nucleos(t)ide Analoguesmentioning

confidence: 99%

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

Buti

Roade

Riveiro‐Barciela

et al. 2020

Liver International

View full text Add to dashboard Cite

show abstract

“…Five studies reported the duration in which individuals were on TFV prior to treatment failure, with virological breakthrough occurring between 48 weeks and 48 months of therapy (48 weeks (32), 18 months (34), 20 months (41), 26 months (16), and 48 months (15,33)).…”

Section: Duration Of Therapy and Treatment Compliance Prior To Detectmentioning

confidence: 99%

Hepatitis B virus resistance to tenofovir: fact or fiction? A synthesis of the evidence to date

Mokaya

McNaughton

Bester

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Tenofovir (TFV) is a widely used antiviral treatment for chronic hepatitis B virus (HBV) infection. There is a high genetic barrier to the selection of TFV resistance-associated mutations (RAMs), but the distribution and clinical significance of TFV RAMs are not well understood, and the topic remains contentious. We here present assimilated evidence for putative TFV RAMs with the aims of cataloguing and characterising mutations that have been reported, and starting to develop insights into the mechanisms of resistance and potential clinical significance. Methods: We carried out a systematic literature search in PubMed to identify clinical, in vitro and in silico evidence of TFV resistance. The structure of HBV reverse transcriptase (RT) has not been solved; we therefore compared HBV RT to the crystal structure for HIV RT to map the likely sites of RAMs. Results: We identified a long-list of 37 putative TFV RAMs in HBV RT, occurring within and outside sites of enzyme activity, some of which can be mapped onto a homologous HIV RT structure. Based on quality and quantity of supporting data, we generated a short-list of nine sites that are supported by the most robust evidence. Most resistance arises as a result of suites of multiple RAMs. Other factors including adherence, viral load, HBeAg status, HIV coinfection and NA dosage may also influence viraemic suppression. Conclusion: There is emerging evidence for polymorphisms that may reduce susceptibility to TVF. A better understanding of HBV drug resistance is imperative to optimise approaches to public health elimination targets.

show abstract

“…To the Editor: Park et al recently reported a quadruple mutation that conferred resistance to tenofovir in South Korean patients with chronic hepatitis B virus (HBV) infection. 1 In 2 patients who experienced viral breakthrough during treatment, the CYEI mutation within the HBV reverse transcriptase (RT) gene resulted in resistance to tenofovir with IC 50 and IC 90 values of 15.3-and 26.3-fold higher than those of wild-type virus, respectively. A triple mutation (CYE) also reduced tenofovir susceptibility by 3.7-fold.…”

mentioning

confidence: 99%

In response to identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients

Blackard

Kwara

Sherman

2019

Journal of Hepatology

View full text Add to dashboard Cite

Identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients

Cited by 116 publications

References 34 publications

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

Optimal management of chronic hepatitis B patients receiving nucleos(t)ide analogues

Hepatitis B virus resistance to tenofovir: fact or fiction? A synthesis of the evidence to date

In response to identification of a quadruple mutation that confers tenofovir resistance in chronic hepatitis B patients

Contact Info

Product

Resources

About