Clinical and virological features of non-breakthrough and severe exacerbation due to lamivudine-resistant hepatitis B virus mutants

Suzuki, Fumitaka; Akuta, Norio; Suzuki, Yoshiyuki; Sezaki, Hitomi; Arase, Yasuji; Hosaka, Tetsuya; Someya, Takashi; Kobayashi, Masahiro; Saitoh, Satoshi; Ikeda, Kenji; Kobayashi, Mariko; Matsuda, Masamichi; Satoh, Junko; Watahiki, Sachiyo; Kumada, Hiromitsu

doi:10.1002/jmv.20546

Cited by 18 publications

(19 citation statements)

References 33 publications

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“…During treatment, nucleotide sequences of the polymerase gene were determined by polymerase chain reaction (PCR) direct sequencing, as previously described 14. The viral polymerase reverse transcriptase (rt) gene at the baseline of LAM treatment (September 2006) showed the wild type sequence (with no LAM, ADV, ETV, or TDF resistance substitutions).…”

Section: Case Reportmentioning

confidence: 99%

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

Suzuki¹,

Sezaki²,

Akuta³

et al. 2014

DDDT

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Tenofovir disoproxil fumarate (TDF) is widely used to treat hepatitis B virus (HBV) patients in the USA and Europe. No confirmed report of resistance selection during treatment with TDF in treatment-naïve and nucleoside/nucleotide analog-treated chronic hepatitis B patients has yet been reported. Here, we report for the first time a patient with chronic hepatitis B and cirrhosis who emerged with virologic breakthrough during combination therapy with TDF and entecavir (ETV), against ETV-resistant virus. A 51-year-old Japanese woman with hepatitis B e-antigen (HBeAg), whose genotype was C, received ETV monotherapy continuously followed by TDF and ETV combination therapy, because her HBV DNA levels had been >3.5 log copies/mL. At the start of combination therapy, amino acid substitutions of the reverse transcriptase (rt) gene, rtL180M, rtT184I/M, and rtM204V, were detected. After this, serum HBV DNA decreased to less than 2.1 log copies/mL and remained at this level until 31 months of combination therapy, when it again began to increase. Amino acid substitutions of rtL180M, rtS202G, and rtM204V emerged and were associated with an increase in serum HBV DNA at virologic breakthrough. Long-term therapy with TDF against the ETV-resistant virus has the potential to induce virologic breakthrough and resistance, and careful follow-up should be carried out.

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Section: Case Reportmentioning

confidence: 99%

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

Suzuki¹,

Sezaki²,

Akuta³

et al. 2014

DDDT

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“…However, the viral factors that may influence the severity of this hepatitis remain to be clarified. A recent study indicated that patients with a normal ALT level even after the emergence of a YMDD motif mutant are characterized by HBeAg negativity during pretreatment, HBeAg loss during therapy, a longer duration from the commencement of therapy until the emergence of YMDD mutant, and lack of mixed-type YMDD mutants [26] . In contrast, patients with severely exacerbated hepatitis after the emergence of a YMDD mutant tend to have more substitutions in the reverse transcriptase (rt) region within the polymerase gene at the time of hepatitis exacerbation than those without hepatitis exacerbation [26] .…”

Section: Discussionmentioning

confidence: 99%

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

Suzuki

Yotsuyanagi²,

Okuse³

et al. 2007

WJG

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We present a case of fetal liver failure caused by the activation of lamivudine-resistant hepatitis B virus (HBV) nine months after lamivudine treatment. A 57-year old man visited our hospital for the treatment of decompensated chronic hepatitis B. Lamivudine was started in December 2001. Subsequently, serum HBV was negative for HBV DNA with seroconversion from HBeAg to anti-HBe and improvement of liver function. However, HBV DNA and HBeAg were again detected in September 2002. He was complicated by breakthrough hepatitis and admitted to our hospital in November for severely impaired liver function. Vidarabine treatment was started and serum HBV DNA and alanine aminotransferase (ALT) decreased transiently. However, after the start of α-interferon treatment, HBV DNA level increased and liver function deteriorated. He died 1 mo after admission. An analysis of amino acid sequences in the polymerase region revealed that rtM204I/V with rtL80I/V occurred at the time of viral breakthrough. After the start of antiviral treatment, rtL180M was detected in addition to rtM204I/V and rtL80I/V, and became predominant in the terminal stage of the disease. HBV clone with a high replication capacity may be produced by antiviral treatment leading to the worsening of liver function. Antiviral therapy for patients with breakthrough hepatitis in advanced liver disease should be carefully performed.

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“…Although the incidence of amino acid mutation of polymerase is high in patients with hepatitis, no specifi c mutation has been observed. 12 The case of a patient who was LAM-resistant despite the absence of mutation in the YMDD motif was reported recently. The 181st alanine (A) in the Pol domain was replaced by threonine (T) (rtA181T) in this patient.…”

Section: Emergence Of Antiviral Resistance In Hbv Infectionmentioning

confidence: 95%

Drug resistance in antiviral treatment for infections with hepatitis B and C viruses

Yotsuyanagi

Koike

2007

J Gastroenterol

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Treatments for infections with hepatitis B and C viruses have recently developed markedly, and range from nonspecific interferon-based treatments to specific antiviral treatments, such as those that inhibit hepatitis virus-coded protein production or activity. These developments have contributed to the achievement of excellent enhancement of the antiviral effect. On the other hand, the development of specific antiviral therapies has created unprecedented problems. Antiviral drug-resistant strains of viruses have emerged, leading to a poor prognosis for infected patients. Clarification of the mechanisms underlying the emergence of such resistance to drugs will be useful for the treatment of such patients. In this review, we outline pathological conditions associated with hepatitis B and C viruses and their treatments, and discuss the current situation and mechanisms underlying the emergence of antiviral drug-resistant strains.

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Clinical and virological features of non-breakthrough and severe exacerbation due to lamivudine-resistant hepatitis B virus mutants

Cited by 18 publications

References 33 publications

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

Virologic breakthrough in a patient with chronic hepatitis B by combination treatment with tenofovir disoproxil fumarate and entecavir

Fatal liver failure caused by reactivation of lamivudine-resistant hepatitis B virus: A case report

Drug resistance in antiviral treatment for infections with hepatitis B and C viruses

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