A real-world retrospective single-centre study of the cost-effectiveness and long-term outcomes of pegylated interferon for chronic hepatitis B.

Background: Pegylated interferon (Peg-IFN) is recommended as first-line therapy for chronic hepatitis B (CHB) but has significant side effects and is rarely used compared to oral nucleos(t)ide analogues (NA). There are limited recent clinical efficacy or economic analysis data comparing approved CHB therapy in North America. Methods: This retrospective study examined clinical outcomes, off-treatment durability, and cost-effectiveness of Peg-IFN versus NA for CHB. Demographic (age, sex, ethnicity), clinical data (i.e., liver tests, hepatitis B virus DNA, serology, transient elastography) and documented side effects were collected by retrospective chart review of patients followed in the University of Calgary Liver Unit who received Peg-IFN therapy from January 2007 to December 2020. The cost-effectiveness of Peg-IFN versus NA therapy was modelled over a 10-year time horizon. Results: Sixty-eight CHB patients were treated with Peg-IFN (median age 45.65, 74% male, 84% Asian); 50/68 (74%) completed 48 weeks of treatment with a median follow-up of 6.54 years (interquartile range 5.07). At the last known follow-up, 23/68 (34%) have not required NA treatment and one had HBsAg loss; 27 have been started on NA. Predictors of obtaining a sustained virological response included being hepatitis B e antigen-negative at treatment end and a quantitative hepatitis B surface antigen <1000 IU/mL. Economic modelling showed that finite Peg-IFN was not cost-effective versus NA at a 10-year time horizon. Conclusions: PEG-IFN remains a potential treatment for CHB although there is a significant intolerance/failure rate. Using PEG-IFN based on patient preference is reasonable and optimal patient selection may improve treatment cost-effectiveness.

Real-world tertiary referral centre experience stopping nucleos(t)ide analogue therapy in patients with chronic hepatitis B.

BACKGROUND: Identifying strategies for stopping nucleos(t)ide analogues (NUC) in patients with chronic hepatitis B (CHB) is a major goal in CHB management. Our study describes our tertiary-centre experience stopping nucleos(t)ide analogues (NUC) in CHB. METHODS: We conducted a retrospective cohort study of all individuals with CHB seen at the Calgary Liver Unit between January 2009 and May 2020 who stopped NUC. We collected baseline demographics and HBV lab parameters before and after stopping NUC with results stratified by off-treatment durability. Clinical flare was defined as alanine aminotransferase (ALT) over twice the upper limit of normal and virological flare as HBV DNA >2000 IU/mL. RESULTS: Forty-seven (3.5%) of the 1337 individuals with CHB stopped NUC therapy. During follow-up, six patients (12.8%) restarted NUCs because of a flare. All flares occurred within six months of discontinuation. Median time to restart treatment was 90 days (Q1 65, Q3 133). Upon restarting, all showed suppression of HBV DNA and ALT normalization. Factors associated with restarting NUC therapy included hepatitis B e antigen (HBeAg) positive status at first appointment and longer NUC consolidation therapy. Age, sex, ethnicity, liver stiffness measurement, choice of NUC, and quantitative hepatitis B surface antigen (qHBsAg) level at stopping were not associated with sustained response off-treatment. Six patients had functional cure with HBsAg loss. CONCLUSIONS: Stopping long-term NUC is feasible in HBeAg negative CHB. Hepatic flares can occur despite low levels of qHBsAg. Finite NUC therapy can be considered in eligible patients who are adherent to close monitoring and follow-up, particularly in the first six months after stopping NUC therapy.

Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America.

BACKGROUND: There are limited long-term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)-treated women during pregnancy. AIMS: To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post-partum in a low HBV endemic region. METHODS: Retrospective real-world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post-partum. RESULTS: In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7-39.5) post-partum, 19% (65/341) received TDF (11 initiated pre-pregnancy, 53 for mother-to-child transmission (MTCT) prevention). During follow-up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re-treated. In all TDF-treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow-up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post-partum, requiring re-treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post-partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post-partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23-40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12-26) post-partum. CONCLUSIONS: Post-partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long-term follow-up.

Improvement of the WBC calibration of the Internal Dosimetry Laboratory of the CDTN/CNEN using the physical phantom BOMAB and MCNPX code.

The Laboratory of Internal Dosimetry of the Center for Development of Nuclear Technology (LDI/CDTN) is responsible for routine internal monitoring of occupationally exposed individuals. The determination of photon emitting radionuclides in the human body requires calibration of the detector in specific counting geometries. The calibration process uses physical phantoms containing certified activities of the radionuclides of interest. The objective of this work was to obtain calibration efficiency curves of the Whole Body Counter in operation at the LDI/CDTN using a BOMAB physical phantom and Monte Carlo simulations.

Disabling acne fulminans.

Acne fulminans is a rare manifestation that may occur during the evolution of acne vulgaris primarily in male adolescents. Use of isotretinoin, testosterone, and exacerbated immune responses in the body are related triggers. Signs, symptoms and laboratory findings such as fever, hepatomegaly, polyarthralgia, leukocytosis, plaquetose, increased inflammatory markers and transaminases, are characteristic. A bone scan can detect osteolytic lesions in multiple skeletal sites. The treatment is performed with prednisolone, isotretinoin and antibiotics if secondary infection is present. This case describes a male patient with a diagnosis of grade III acne, who developed acne fulminans and bilateral sacroiliitis with inability to ambulate, after initiation of therapy with isotretinoin.

Acne fulminans incapacitante / Disabling Acne Fulminans

Acne fulminans é uma manifestação rara, que pode ocorrer durante a evolução da acne vulgar, principalmente, em adolescentes masculinos. Uso de isotretinoína, testosterona, e reações imunológicas exacerbadas no organismo são desencadeantes relacionados. Sinais, sintomas e alterações laboratoriais como: febre, hepatomegalia, poliartralgia, leucocitose, plaquetose, aumento de provas inflamatórias e transaminases, são característicos. A cintilografia óssea pode detectar lesões líticas em vários sítios do esqueleto. O tratamento é realizado com prednisolona, isotretinoína e antibióticos se infecções secundárias. Este caso relata um paciente masculino com diagnóstico de acne grau III, que desenvolveu acne fulminans e sacroileíte bilateral, com incapacidade de deambulação após início de terapia com isotretinoína.

Acne fulminans is a rare manifestation that may occur during the evolution of acne vulgaris primarily in male adolescents. Use of isotretinoin, testosterone, and exacerbated immune responses in the body are related triggers. Signs, symptoms and laboratory findings such as fever, hepatomegaly, polyarthralgia, leukocytosis, plaquetose, increased inflammatory markers and transaminases, are characteristic. A bone scan can detect osteolytic lesions in multiple skeletal sites. The treatment is performed with prednisolone, isotretinoin and antibiotics if secondary infection is present. This case describes a male patient with a diagnosis of grade III acne, who developed acne fulminans and bilateral sacroiliitis with inability to ambulate, after initiation of therapy with isotretinoin.

The effect of orthodontic forces on calcitonin gene-related peptide expression in human dental pulp.

INTRODUCTION: The purpose of this study was to quantify the effect of moderate and severe orthodontic forces on calcitonin gene-related peptide (CGRP) expression in healthy human dental pulp. METHODS: Thirty human dental pulp samples were obtained from healthy premolars in which extraction was indicated for orthodontic reasons. Before extraction, teeth were divided into 3 groups of 10 premolars each: (1) the control group: healthy premolars without application of orthodontic forces; (2) the moderate force group: a 56-g force was applied to the premolars for 24 hours; and (3) the severe force group: a 224-g force was applied to the premolars for 24 hours. All dental pulp samples were processed, and CGRP was measured by radioimmunoassay. RESULTS: Greater CGRP expression was found in the severe force group followed by the moderate force group. The lower CGRP values were for the control group. The Kruskal-Wallis test showed statistically significant differences between groups (P < .0001). Least significant difference (LSD) post hoc tests showed statistically significant differences in CGRP expression between the control group and the severe force group (P < .0001) but not with the moderate force group (P = .06). Differences between the moderate and severe force groups were statistically significant (P < .0001). CONCLUSIONS: CGRP expression in human dental pulp increases when teeth are submitted to severe orthodontic forces.