Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management

It is well known that hepatitis B virus reactivation (HBVr) can occur among patients undergoing treatment for hematological malignancies (HM). The evaluation of HBVr risk in patients undergoing immunosuppressive treatments is a multidimensional process, which includes conducting an accurate clinical history and physical examination, consideration of the virological categories, of the medication chosen to treat these hematological malignancies and the degree of immunosuppression induced. Once the risk of reactivation has been defined, it is crucial to adopt adequate management strategies (should reactivation occur). The purpose of treatment is to prevent dire clinical consequences of HBVr such as acute/fulminant hepatitis, and liver failure. Treatment will be instituted according to the indications and evidence provided by current international recommendations and to prevent interruption of lifesaving anti-neoplastic treatments. In this paper, we will present the available data regarding the risk of HBVr in this special population of immunosuppressed patients and explore the relevance of effective prevention and management of this potentially life-threatening event. A computerized literature search was performed using appropriate terms to discover relevant articles. Current evidence supports the policy of universal HBV testing of patients scheduled to undergo treatment for hematological malignancies, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and classes of immunosuppressive drugs.

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Hematological Malignancies and HBV Reactivation: Suggestions for Clinical Management

10.20944/preprints201907.0282.v1 ◽

2019 ◽

Author(s):

Alessandra Zannella ◽

Massimo Marignani ◽

Paola Begini

Keyword(s):

Hepatitis B Virus ◽

Hepatitis B ◽

Hematological Malignancies ◽

Immunosuppressive Drugs ◽

Viral Reactivation ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Hepatitis B Virus Reactivation ◽

B Virus ◽

Clinical Consequences

It is well known that the event of hepatitis B virus reactivation can occur among patients undergoing treatment for hematological malignancies. In this paper we will present the available data regarding the risk of hepatitis B virus reactivation in this special population of immunosuppressed patients and explore the relevance of an accurate prevention and management of this condition. A computerized literature search was performed using appropriate terms arrangement, including English-written literature only or additional relevant articles. The evaluation of hepatitis B reactivation risk is a multidimensional process, which includes conducting an accurate clinical and physical history, considering the virological categories, the knowledge of the medication chosen to treat these hematological malignancies and the induced grade of immunosuppression. Adopting adequate preventive strategies and surveillance according to the current international recommendations is crucial to prevent HBVr and its dire clinical consequences (hepatitis, liver failure, interruption of lifesaving anti-neoplastic treatments). Universal HBV screening of patients scheduled to undergo treatment for hematological malignancies should be the chosen policy, and clinicians should be aware of the inherent risk of viral reactivation among the different virological categories and the classes of immunosuppressive drugs.

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HBV Reactivation During the Treatment of Non-Hodgkin Lymphoma and Management Strategies

Frontiers in Oncology ◽

10.3389/fonc.2021.685706 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xing Cao ◽

Yafei Wang ◽

Panyun Li ◽

Wei Huang ◽

Xiaojuan Lu ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Immunosuppressive Agents ◽

Management Strategies ◽

Antiviral Agent ◽

Current Evidence ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Hematopoietic Stem ◽

Non Hodgkin Lymphoma ◽

Anti Cd20

Hepatitis B virus reactivation (HBV-R), which can lead to HBV-related morbidity and mortality, is a common and well-known complication that occurs during the treatment of non-Hodgkin lymphoma (NHL) patients with current or past exposure to HBV infection. HBV-R is thought to be closely associated with chemotherapeutic or immunosuppressive therapies. However, immunosuppressive agents such as anti-CD20 antibodies (e.g., rituximab and ofatumumab), glucocorticoids, and hematopoietic stem cell transplantation (HSCT) administered to NHL patients during treatment can cause deep immunodepression and place them at high risk of HBV-R. In this review, we explore the current evidence, the guidelines of several national and international organizations, and the recommendations of expert panels relating to the definition, risk factors, screening and monitoring strategies, whether to use prophylaxis or pre-emptive therapy, and the optimal antiviral agent and duration of antiviral therapy for HBV-R.

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Risk and Prevention of Hepatitis B Virus Reactivation during Immunosuppression for Non-Oncological Diseases

Journal of Clinical Medicine ◽

10.3390/jcm10215201 ◽

2021 ◽

Vol 10 (21) ◽

pp. 5201

Author(s):

Lorenzo Onorato ◽

Mariantonietta Pisaturo ◽

Clarissa Camaioni ◽

Pierantonio Grimaldi ◽

Alessio Vinicio Codella ◽

...

Keyword(s):

Neurological Diseases ◽

Immunosuppressive Drugs ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Occult Hbv Infection ◽

Occult Hbv ◽

Oncological Patients ◽

Oncological Diseases ◽

Life Threatening ◽

Few Data

Reactivation of overt or occult HBV infection (HBVr) is a well-known, potentially life-threatening event which can occur during the course of immunosuppressive treatments. Although it has been described mainly in subjects receiving therapy for oncological or hematological diseases, the increasing use of immunosuppressant agents in non-oncological patients observed in recent years has raised concerns about the risk of reactivation in several other settings. However, few data can be found in the literature on the occurrence of HBVr in these populations, and few clear recommendations on its management have been defined. The present paper was written to provide an overview of the risk of HBV reactivation in non-neoplastic patients treated with immunosuppressive drugs, particularly for rheumatological, gastrointestinal, dermatological and neurological diseases, and for COVID-19 patients receiving immunomodulating agents; and to discuss the potential strategies for prevention and treatment of HBVr in these settings.

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Infectious Complications of Multiple Sclerosis Therapies: Implications for Screening, Prophylaxis, and Management

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy174 ◽

2018 ◽

Vol 5 (8) ◽

Cited By ~ 40

Author(s):

David J Epstein ◽

Jeffrey Dunn ◽

Stan Deresinski

Keyword(s):

Multiple Sclerosis ◽

Opportunistic Infections ◽

Latent Tuberculosis ◽

Immunosuppressive Drugs ◽

Infectious Complications ◽

Hbv Reactivation ◽

Virus Reactivation ◽

Oral Agents ◽

Increased Risk ◽

Substantial Risk

Abstract Multiple sclerosis therapies include interferons, glatiramer, and multiple immunosuppressive drugs. Discerning infectious risks of immunosuppressive drugs requires understanding their mechanisms of action and analyzing interventional studies and postmarketing observational data. Though identical immunosuppressive therapies are sometimes used in non-neurologic conditions, infectious risks may differ in this population. Screening for and treatment of latent tuberculosis (TB) infection should be prioritized for patients receiving alemtuzumab; ocrelizumab is likely not associated with an increased risk of TB. Hepatitis B virus (HBV) reactivation can be devastating for patients treated with ocrelizumab and alemtuzumab, whereas the small molecule oral agents do not likely pose substantial risk of HBV. Progressive multifocal leukoencephalopathy is a particular concern with natalizumab. Alemtuzumab, and possibly natalizumab and fingolimod, risks herpes virus reactivation and may warrant prophylaxis. Unusual opportunistic infections have been described. Vaccination is an important tool in preventing infections, though vaccine timing and contraindications can be complex.

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Viral Hepatitis: Manifestations and Management Strategy

Hematology ◽

10.1182/asheducation-2006.1.375 ◽

2006 ◽

Vol 2006 (1) ◽

pp. 375-380 ◽

Cited By ~ 32

Author(s):

Roberto J. Firpi ◽

David R. Nelson

Keyword(s):

Hepatitis B ◽

Viral Hepatitis ◽

Management Strategies ◽

Clinical Manifestations ◽

Disease Recurrence ◽

Hcv Infection ◽

Morbidity And Mortality ◽

Viral Reactivation ◽

Virus Reactivation ◽

Significant Morbidity

AbstractViral hepatitis is the third most common cause of liver disease in allogeneic transplant recipients and causes significant morbidity and mortality. When treating patients with hematological malignancies, an emphasis should be placed on identification of patients at risk for viral hepatitis with appropriate screening. Initial screening serology should include anti-HCV, HBsAg, anti-HBs, and anti-HBc testing. When hepatitis B exposure has been documented, prophylaxis of viral reactivation for all HBsAg-positive patients with a nucleoside analogue should be implemented. HCV infection appears to have little short-term impact on survival after bone marrow transplantation, but is a risk factor for veno-occlusive disease (VOD) and graft-versus-host disease (GVHD). In the long-term survivor, HCV infection can lead to significant morbidity and mortality due to the development of cirrhosis, decompensation, and liver cancer. Since effective antiviral therapies are available for both hepatitis B and C, routine screening and selected intervention is recommended once reactivation and disease recurrence is documented. In this chapter we will highlight the mechanisms of virus reactivation, clinical manifestations, and management strategies to minimize acute and chronic morbidity in this population.

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Subclinical Hypothyroidism: A Review on Clinical Consequences and Management Strategies

Journal of Medicine ◽

10.3329/jom.v18i1.31174 ◽

2017 ◽

Vol 18 (1) ◽

pp. 30-36 ◽

Cited By ~ 1

Author(s):

Nazma Akter ◽

Nazmul Kabir Qureshi ◽

Hossain Shahid Ferdous

Keyword(s):

Subclinical Hypothyroidism ◽

Management Strategies ◽

Elevated Serum ◽

Thyroid Stimulating Hormone ◽

Current Evidence ◽

Clinical Aspects ◽

Overt Hypothyroidism ◽

Cardiac Events ◽

Clinical Consequences ◽

Serum Tsh

Subclinical hypothyroidism (SCH) is defined as an elevated serum thyroid-stimulating hormone (TSH) level with normal free thyroid hormone values. The prevalence of subclinical hypothyroidism is 3 to 8 percent in the general population, and up to 15 to 18 percent in women who are older than 60 years. It is more common in women than men, and its prevalence increases with age. Of patients with SCH, 80% have a serum TSH of less than 10 mIU/L. Management strategies including screening and treatment of subclinical hypothyroidism are still controversial. The strongest arguments for levothyroxine therapy are the high risk of progression to overt hypothyroidism. Initiating levothyroxine replacement therapy is recommended for all patients with a TSH greater than 10 mIU/L, even if the free thyroxine concentration is within normal laboratory range. However, treatment of patients with a serum TSH level between 5 and 10 mIU/L remains controversial. There was insufficient evidence for a clinically significant relationship between subclinical hypothyroidism and adverse cardiac events or cardiac dysfunction. Conflicting results have been found on the association between subclinical hypothyroidism and cognitive impairment, depression and the risk of fractures. This narrative review aims to assess current evidence on the clinical aspects, as well as screening and treatment recommendations in adults with subclinical hypothyroidism.J MEDICINE January 2017; 18 (1) : 30-36

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Trauma-Induced Coagulopathy: Overview of an Emerging Medical Problem from Pathophysiology to Outcomes

Medicines ◽

10.3390/medicines8040016 ◽

2021 ◽

Vol 8 (4) ◽

pp. 16

Author(s):

Gabriele Savioli ◽

Iride Francesca Ceresa ◽

Luca Caneva ◽

Sebastiano Gerosa ◽

Giovanni Ricevuti

Keyword(s):

Major Trauma ◽

Management Strategies ◽

Medical Problem ◽

Current Evidence ◽

Potential Drug ◽

The Past ◽

Trauma Induced Coagulopathy ◽

Threatening Condition ◽

Life Threatening ◽

Trauma Mortality

Coagulopathy induced by major trauma is common, affecting approximately one-third of patients after trauma. It develops independently of iatrogenic, hypothermic, and dilutive causes (such as iatrogenic cause in case of fluid administration), which instead have a pejorative aspect on coagulopathy. Notwithstanding the continuous research conducted over the past decade on Trauma-Induced Coagulopathy (TIC), it remains a life-threatening condition with a significant impact on trauma mortality. We reviewed the current evidence regarding TIC diagnosis and pathophysiological mechanisms and summarized the different iterations of optimal TIC management strategies among which product resuscitation, potential drug administrations, and hemostatis-focused approaches. We have identified areas of ongoing investigation and controversy in TIC management.

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Review on the Regional Effects of Gastrointestinal Luminal Stimulation on Appetite and Energy Intake: (Pre)clinical Observations

Nutrients ◽

10.3390/nu13051601 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1601

Author(s):

Jennifer Wilbrink ◽

Gwen Masclee ◽

Tim Klaassen ◽

Mark van Avesaat ◽

Daniel Keszthelyi ◽

...

Keyword(s):

Energy Intake ◽

Oral Delivery ◽

Regional Differences ◽

Management Strategies ◽

Inhibitory Effect ◽

Current Evidence ◽

Ileal Brake ◽

Regional Effects ◽

Clinical Observations ◽

Intestinal Delivery

Macronutrients in the gastrointestinal (GI) lumen are able to activate “intestinal brakes”, feedback mechanisms on proximal GI motility and secretion including appetite and energy intake. In this review, we provide a detailed overview of the current evidence with respect to four questions: (1) are regional differences (duodenum, jejunum, ileum) present in the intestinal luminal nutrient modulation of appetite and energy intake? (2) is this “intestinal brake” effect macronutrient specific? (3) is this “intestinal brake” effect maintained during repetitive activation? (4) can the “intestinal brake” effect be activated via non-caloric tastants? Recent evidence indicates that: (1) regional differences exist in the intestinal modulation of appetite and energy intake with a proximal to distal gradient for inhibition of energy intake: ileum and jejunum > duodenum at low but not at high caloric infusion rates. (2) the “intestinal brake” effect on appetite and energy appears not to be macronutrient specific. At equi-caloric amounts, the inhibition on energy intake and appetite is in the same range for fat, protein and carbohydrate. (3) data on repetitive ileal brake activation are scarce because of the need for prolonged intestinal intubation. During repetitive activation of the ileal brake for up to 4 days, no adaptation was observed but overall the inhibitory effect on energy intake was small. (4) the concept of influencing energy intake by intra-intestinal delivery of non-caloric tastants is intriguing. Among tastants, the bitter compounds appear to be more effective in influencing energy intake. Energy intake decreases modestly after post-oral delivery of bitter tastants or a combination of tastants (bitter, sweet and umami). Intestinal brake activation provides an interesting concept for preventive and therapeutic approaches in weight management strategies.

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Toward the diagnosis of rare childhood genetic diseases: what do parents value most?

European Journal of Human Genetics ◽

10.1038/s41431-021-00882-1 ◽

2021 ◽

Author(s):

Samantha Pollard ◽

Deirdre Weymann ◽

Jessica Dunne ◽

Fatemeh Mayanloo ◽

John Buckell ◽

...

Keyword(s):

Focus Groups ◽

Genetic Disease ◽

Diagnostic Yield ◽

Management Strategies ◽

Health Benefit ◽

Sampling Technique ◽

Evidence Base ◽

Current Evidence ◽

Genomic Testing ◽

Current Evidence Base

AbstractGenomic testing is becoming routine for diagnosing rare childhood genetic disease. Evidence underlying sustainable implementation is limited, focusing on short-term endpoints such as diagnostic yield, unable to fully characterize patient and family valued outcomes. Although genomic testing is becoming widely available, evidentiary and outcomes uncertainty persist as key challenges for implementation. We examine whether the current evidence base reflects public tolerance for uncertainty for genomics to diagnose rare childhood genetic disease. We conducted focus groups with general population parents in Vancouver, Canada, and Oxford, United Kingdom, to discuss expectations and concerns related to genomic testing to diagnose rare childhood genetic disease. Applying a purposive sampling technique, recruitment continued until thematic saturation was reached. Transcripts were analysed using thematic analysis. Thirty-three parents participated across four focus groups. Participants valued causal diagnoses alongside management strategies to improve patient health and wellbeing. Further, participants valued expanding the evidence base to reduce evidentiary uncertainty while ensuring security of information. Willingness to pay out of pocket for testing reflected perceived familial health benefit. Diagnostic yield fails to fully capture valued outcomes, and efforts to resolve uncertainty better reflect public priorities. Evaluations of genomic testing that fully integrate valued endpoints are necessary to ensure consistency with best practices and public willingness to accept the uncertain familial benefit.

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Social networks and type 2 diabetes: a narrative review

Diabetologia ◽

10.1007/s00125-021-05496-2 ◽

2021 ◽

Author(s):

Miranda T. Schram ◽

Willem J. J. Assendelft ◽

Theo G. van Tilburg ◽

Nicole H. T. M. Dukers-Muijrers

Keyword(s):

Social Support ◽

Type 2 Diabetes ◽

Social Networks ◽

Social Network ◽

Narrative Review ◽

Current Evidence ◽

Favourable Effect ◽

Effective Prevention ◽

Network Variable

AbstractIt has been known for decades that social networks are causally related to disease and mortality risk. However, this field of research and its potential for implementation into diabetes care is still in its infancy. In this narrative review, we aim to address the state-of-the-art of social network research in type 2 diabetes prevention and care. Despite the diverse nature and heterogeneity of social network assessments, we can draw valuable lessons from the available studies. First, the structural network variable ‘living alone’ and the functional network variable ‘lack of social support’ have been associated with increased type 2 diabetes risk. The latter association may be modified by lifestyle risk factors, such as obesity, low level of physical activity and unhealthy diet. Second, smaller network size and less social support is associated with increased risk of diabetes complications, particularly chronic kidney disease and CHD. Third, current evidence shows a beneficial impact of social support on diabetes self-management. In addition, social support interventions were found to have a small, favourable effect on HbA1c values in the short-term. However, harmonisation and more detailed assessment of social network measurements are needed to utilise social network characteristics for more effective prevention and disease management in type 2 diabetes. Graphical abstract

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