Management of HBV Infection During Immunosuppressive Treatment

The literature on hepatitis B virus (HBV) in immunocompromised patients is heterogeneous and refers mainly to the pre-antivirals era. Currently, a rational approach to the problem of hepatitis B in these patients provides for: a) the evaluation of HBV markers and of liver condition in all subjects starting immunosuppressive therapies (baseline), b) the treatment with antivirals (therapy) of active carriers, c) the pre-emptive use of antivirals (prophylaxis) in inactive carriers, especially if they are undergoing immunosuppressive therapies judged to be at high risk, d) the biochemical and HBsAg monitoring (or universal prophylaxis in case of high risk immunosuppression, as in onco-haematologic patients and bone marrow transplantation) in subjects with markers of previous contact with HBV (HBsAg-negative and antiHBc-positive), in order to prevent reverse seroconversion. Moreover in solid organ transplants it is suggested a strict adherence to the criteria of allocation based on the virological characteristics of both recipients and donors and the universal prophylaxis or therapy with nucleos(t)ides analog

Glucocorticoids and Antivirals for HBV Reactivation in Onco-Hematologic Patients.

Patients with inactive or occult hepatitis B virus infection and onco-hematological malignancies are at risk of hepatitis flare, hepatic failure and death due to chemotherapy-mediated reactivation. Nucleot(s)ide analogues can reduce reactivation risks and/or hepatitis. However, immuno-mediated phenomena combine to determine liver damage and clinical outcome. We describe in this report two patients with onco-hematological malignancies and hepatitis B reactivation after chemotherapy in whom glucocorticoids were added to nucleot(s)ide. Antiviral therapy was effective on replication, while glucocorticoids managed hyperergic response. One patient without underlying liver disease survived, while the second died and the autopsy demonstrated cirrhosis undetected before death. This clinical trial suggests that in patients with onco-hematological malignancies and altered liver function tests in spite of effective antiviral response, glucocorticoids could control the effects of immune response. However prognosis and survival are related to the underlying liver status

Hepatitis B Virus Reactivation and Efficacy of Prophylaxis with Lamivudine in Patients Undergoing Allogeneic Stem Cell Transplantation

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Social intervention for an articulated execution of research projects in high Andean communities: Case of installation of the real-time monitoring system of the Arhuay- cocha glacier lake, Cordillera Blanca

In Peru, the communities located along the Andes Mountains at more than 3000 meters above sea level, have a behavior highly susceptible to any type of research activity on the mountain areas, mainly due to the past wrong management of mountain resources by mining companies for many decades, without an eco-efficient or optimal mineral extraction process from an environmental point of view. The biggest problem in conducting research activities in these areas is demonstrating to communities that research activities are of great common benefit and not of private interest. Here are strategies for awareness-raising work in mountain communities, prior to the execution of a research project. The study case was taken on the project to install a monitoring system over high danger Arhuaycocha glacier lake at Río Blanco-Santa Cruz Sub-basin, Ancash, Peru, where the Santa Cruz district is located on the alluvial path. Awarenessraising activities were carried out, identification of actors, analysis of the social situation and perspectives of the inhabitants for the project. It was concluded that all research activities must be carried out with a high degree of sense of belonging on the part of the communities, showing direct benefits, and reach agreements with local authorities. A key point was the inclusion of the residents in the project activities, making it transparent and making it clear that science activities are carried out within their community.En el Perú las comunidades localizadas a lo largo de la cordillera de los Andes a más de 3000 metros sobre el nivel del mar tienen un comportamiento altamente susceptible a cualquier tipo de actividad de investigación sobre las áreas de montañas, debido principalmente al mal manejo de las empresas mineras durante muchas décadas, sin un proceso de extracción mineral ecoeficiente u óptimo desde un punto de vista ambiental. El mayor problema que surge al buscar realizar actividades de investigación en dichas áreas consiste en demostrar a las comunidades que las actividades de investigación son de un gran beneficio común y no de intereses particulares. En este artículo se muestran estrategias de trabajos de sensibilización en comunidades de montaña, previos a la ejecución de un proyecto de investigación. Se tomó el caso de estudio el proyecto de instalación de un sistema de monitoreo de la laguna peligrosa de origen glaciar Arhuaycocha, en la subcuenca Río Blanco-Santa Cruz, Áncash, donde el distrito Santa Cruz se ubica en el camino aluviónico. Se realizaron actividades de sensibilización, identificación de actores, análisis situación social y de perspectivas de los pobladores para con el proyecto.Se concluyó que en toda actividad de índole de investigación se debe de realizar con un grado alto de sentimiento de pertenencia por parte de las comunidades, mostrar beneficios directos y lograr acuerdos con las autoridades locales. Un punto clave fue la inclusión de los pobladores en las actividades del proyecto, transparentando y dejando en claro la realización de actividades de ciencia dentro de su comunidad

Estimation of lifetime costs for patients receiving a transplant: the case of liver transplantation related to hepatitis B in Italy

IntroductionIn Italy, post-liver transplant (LT) hepatitis B virus (HBV) reinfection prophylaxis is frequently based on a combined regimen of anti-HBV immunoglobulin (HBIG) and oral antivirals. However, little information is available at the national level on the cost of LT and the contribution of HBV prophylaxis. This study aimed to quantify the direct healthcare cost for adult patients undergoing LT for HBV-related disease over a lifetime horizon and from the perspective of a National Healthcare Service.MethodsA pharmaco-economic model was implemented with a 4-tiered approach consisting of 1) preliminary literature research to define the research question; 2) pragmatic literature review to retrieve existing information and inform the model; 3) micro-simulated patient cycles; and 4) validation from a panel of national experts.ResultsThe average lifetime healthcare cost of LT for HBV-related disease was €395,986. The greatest cost drivers were post-transplant end-stage renal failure (31.9% of the total), immunosuppression (20.6%), and acute transplant phase (15.8%). HBV reinfection prophylaxis with HBIG and antivirals accounted for 12.4% and 6.4% of the total cost, respectively; however, lifetime HBIG prophylaxis was only associated with a 6.6% increase (~€422 k). Various sensitivity analyses have shown that discount rates have the greatest impact on total costs.ConclusionThis analysis showed that the burden of LT due to HBV is not only clinical but also economic

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and H-1-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA(1c) levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D

HBV DNA suppression and HBsAg clearance in HBeAg negative chronic hepatitis B patients on lamivudine therapy for over 5 years

BACKGROUND & AIMS: In long-term responder patients, it is unclear whether lamivudine (LAM) monotherapy should be continued or switched to a high-genetic-barrier analogue. This study aims at assessing LAM efficacy over a 5-year period and the residual risk of drug resistance. The rate of HBsAg clearance and LAM long-term safety profile were also evaluated. METHODS: One hundred and ninety-one patients with chronic HBeAg-negative hepatitis B successfully treated with LAM monotherapy for at least 5years were included. Biochemical and virological tests were assessed every 3months in all patients and HBsAg quantification was performed in 45/191. Reverse-transcriptase (RT) region was directly sequenced in virological breakthrough patients. RESULTS: One hundred and ninety-one patients (148 males, median age 53years, 72 with compensated cirrhosis) responding to 60-month LAM monotherapy continued to receive LAM monotherapy beyond the initial 5years and were followed for an additional 36-month median period (range 1-108). Virological response was maintained in 128/191 patients (67%) and HBsAg clearance was observed in 15/128 (11.7%) after a 32-month median period (range 1-65). The 63 remaining patients (33%) showed virological breakthrough after a 15-month median treatment (range 1-78). RT region analysis was performed in 38/63 breakthrough patients and LAM resistant mutations were found in 37/38. No significant side effects were observed. CONCLUSIONS: In long-term responder patients, continuation of LAM monotherapy resulted in persistent viral suppression in most cases with undetectable HBV DNA by real-time PCR; moreover, 11.7% of these patients cleared HBsAg. Selection of LAM resistance, however, can still occur even after successful long-term therapy, thus emphasising the importance of a careful virological monitorin

Update of the statements on biology and clinical impact of occult hepatitis B virus infection

Summary In October 2018 a large number of international experts with complementary expertise came together in Taormina to participate in a workshop on occult hepatitis B virus infection (OBI). The objectives of the workshop were to review the existing knowledge on OBI, to identify issues that require further investigation, to highlight both existing controversies and newly emerging perspectives, and ultimately to update the statements previously agreed in 2008. This paper represents the output from the workshop