Assessment of Bone Mineral Density in Tenofovir-Treated Patients With Chronic Hepatitis B: Can the Fracture Risk Assessment Tool Identify Those at Greatest Risk?

Gill, Upkar S.; Zissimopoulos, Alexandra; Al-Shamma, S; Burke, Katherine; McPhail, Mark; Barr, David; Kallis, Yiannis; Marley, Richard; Kooner, Paul; Foster, Graham R.; Kennedy, Patrick

doi:10.1093/infdis/jiu471

Cited by 81 publications

(81 citation statements)

References 38 publications

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“…In addition, studies using sensitive markers of glomerular and tubular kidney function and of bone mineral density have also reported chronic tubular damage and decline of eGFR and bone mineral density in TDF treated patients. 70,[79][80][81][82][83][84][85][86][87] Therefore, it seems appropriate for now to monitor all CHB patients treated with TDF therapy for adverse renal effects with serum creatinine (eGFR) and serum phosphate levels. Moreover, CHB patients at high renal risk undergoing any NA therapy should be monitored with serum creatinine (eGFR) levels.…”

Section: Monitoring Of Patients Treated With Etv Tdf or Taf Recommenmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,198

3,081

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Section: Monitoring Of Patients Treated With Etv Tdf or Taf Recommenmentioning

confidence: 99%

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Lampertico¹,

Agarwal²,

Berg³

et al. 2017

Journal of Hepatology

4,198

3,081

View full text Add to dashboard Cite

“…However, there are still issues concerning their use that are unrelated to their effect on HBV replication. For instance, there are concerns that lifetime treatment with antivirals may have adverse, unforeseen, side effects [54]. In addition, discontinuation of therapy may lead to significant liver disease if or when virus titers rebound so that the decision to treat also implies careful monitoring post treatment cessation.…”

Section: When To Initiate Antiviral Therapymentioning

confidence: 99%

Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks

Kennedy

Litwin

Dolman

et al. 2017

Viruses

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Chronic infection with hepatitis B virus (HBV) progresses through multiple phases, including immune tolerant, immune active, immune control, and, in a subset of patients who achieve immune control, reactivation. The first, the immune tolerant phase, is considered to be prolonged in duration but essentially benign in nature, lacking long-term consequences, and thus not recommended for antiviral therapy. This review challenges the notion that the immune tolerant phase is truly benign and considers the possibility that events during this phase may contribute significantly to cirrhosis, hepatocellular carcinoma (HCC), and the premature death of 25% of HBV carriers worldwide. Thus, earlier treatment than recommended by current guidelines should be considered. Low therapeutic coverage exacerbated by restrictive treatment guidelines may facilitate disease progression in many patients but also increase the risk of neonatal and horizontal transmission from untreated mothers to their children. While a prophylactic vaccine exists, there are many areas worldwide where the treatment of adults and the delivery of an effective vaccination course to newborns present difficult challenges.

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“…Life-long NUC therapy, which is therefore required in the majority, represents a financial burden for patients and national health systems. Concerns of potential drug toxicity (4) and the selection of mutants that could possibly escape prophylactic vaccination are also important considerations (5). Thus, a major unmet need in the management of chronic HBV patients is the definition of bio-IU/ml (7) in HBV e-antigen-negative (HBeAg-negative) patients is recommended by some as a safe stopping point; however, such values are observed in a minority of NUC-treated patients.…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation

Rivino

Bert

Gill

et al. 2018

Journal of Clinical Investigation

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182

183

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BACKGROUND.The clinical management of chronic hepatitis B virus (HBV) patients is based exclusively on virological parameters that cannot independently determine in which patients nucleos(t)ide-analogue (NUC) therapy can be safely discontinued. NUCs efficiently suppress viral replication, but do not eliminate HBV. Thus, therapy discontinuation can be associated with virological and biochemical relapse and, consequently, therapy in the majority is life-long. METHODS.Since antiviral immunity is pivotal for HBV control, we investigated potential biomarkers for the safe discontinuation of NUCs within immune profiles of chronic HBV patients by utilizing traditional immunological assays (ELISPOT, flow cytometry) in conjunction with analyses of global non-antigen-specific immune populations (NanoString and CyTOF). Two distinct cohorts of 19 and 27 chronic HBV patients, respectively, were analyzed longitudinally prior to and after discontinuation of 2 different NUC therapy strategies. RESULTS.Absence of hepatic flares following discontinuation of NUC treatment correlated with the presence, during NUC viral suppression, of HBV core and polymerase-specific T cells that were contained within the ex vivo PD-1 + population.CONCLUSIONS. This study identifies the presence of functional HBV-specific T cells as a candidate immunological biomarker for safe therapy discontinuation in chronic HBV patients. Furthermore, the persistent and functional antiviral activity of PD-1 + HBV-specific T cells highlights the potential beneficial role of the expression of T cell exhaustion markers during human chronic viral infection.

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Assessment of Bone Mineral Density in Tenofovir-Treated Patients With Chronic Hepatitis B: Can the Fracture Risk Assessment Tool Identify Those at Greatest Risk?

Cited by 81 publications

References 38 publications

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection

Immune Tolerant Chronic Hepatitis B: The Unrecognized Risks

Hepatitis B virus–specific T cells associate with viral control upon nucleos(t)ide-analogue therapy discontinuation

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