Cambios en las características epidemiológicas y en el pronóstico de la hepatitis crónica B en personas que viven con VIH / Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV

Introducción: La vacunación, los avances en el tratamiento frente al virus de la hepatitis B (VHB) y los cambios epidemiológicos producidos en España en las últimas décadas han podido modificar las características y el pronóstico de la hepatitis crónica B (HCB) en personas que viven con VIH (PVIH). Métodos: Estudio observacional retrospectivo donde se incluyeron PVIH-HCB en seguimiento en una unidad de referencia madrileña hasta el año 2019. Se comparó la incidencia y las características epidemiológicas y clínicas según el momento del diagnóstico (antes del año 2000 y posteriormente en periodos de cinco años). Además, se realizó un estudio longitudinal retrospectivo evaluando la tasa de mortalidad, descompensación hepática y factores asociados. Resultados: De 5.452 PVIH, 160 presentaban HCB en el momento basal (prevalencia 2,92%, IC 95%: 2,5-3,4), 85,6% hombres, edad mediana al diagnóstico 32,1 (27-37,2) años. La incidencia (2,4/100 pacientes-año) no varió en los diferentes periodos. Los pacientes diagnosticados antes del 2000 (n = 87) comparados con los diagnosticados entre 2015-2019 (n = 11) con mayor frecuencia eran nativos españoles (90,8 vs. 18,2%), habían consumido drogas intravenosas (55,2 vs. 0), tenían antecedentes de hepatitis C (40 vs. 9,1%) y delta (30,4 vs. 0) y mayor afectación hepática (24,1% cirróticos vs. 0). Tras un seguimiento de 20,4 años, 23 pacientes murieron (7,1/1.000 pacientes-año) y 19 presentaron descompensación hepática (4,9/1.000 pacientes-año), todos diagnosticados antes del año 2010. La mortalidad se asoció con mayor fibrosis hepática basal estimada por Fibroscan® (HR 1,06; IC 95%: 1,03-1,09). Conclusión: Las PVIH-HCB con diagnóstico previo al año 2000 son más frecuentemente de nacionalidad española, infectadas por vía parenteral y con mayor prevalencia de otras coinfecciones. Los pacientes diagnosticados antes del 2010 tienen peor pronóstico condicionado por presentar mayor grado de fibrosis hepática.(AU)

Introduction: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. Methods: Retrospective review of CHB–HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000–2004, 2005–2009, 2010–2014, 2015–2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. Results: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95% CI: 2.5–3.4), 85.6% were men, median age 32.1 (27–37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI: 1.03–1.09). Conclusion: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.(AU)

Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients.

BACKGROUND: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. METHODS: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. RESULTS: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29-68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of -0.8kPa in non-RPV-exposed patients (p=0.254) and -1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, -2.8kPa [p<0.001]; non-RPV-exposed, -1.1kPa [p=0.22]). CONCLUSION: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.

Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV.

INTRODUCTION: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. METHODS: Retrospective review of CHB-HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000-2004, 2005-2009, 2010-2014, 2015-2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. RESULTS: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95%CI 2.5-3.4), 85.6% were men, median age 32.1 (27-37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI 1.03-1.09). CONCLUSION: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.

Benefits of rilpivirine for liver stiffness in HIV/HCV-coinfected patients / Beneficios de la rilpivirina para la rigidez hepática en pacientes con coinfección por VIH/VHC

Background: Rilpivirine (RPV) is an antiretroviral drug characterized by good tolerability and a favorable liver safety profile. Recent research has shown that RPV ameliorates liver fibrosis in animal models of various chronic liver diseases. Our study aimed to analyze the effect of RPV on liver fibrosis by assessing changes in liver stiffness using transient elastography. Methods: Retrospective cohort study of HIV-infected patients who were exposed and not exposed to RPV. The change in liver stiffness during the period between two transient elastography measurements was analyzed and compared for patients exposed and not exposed to RPV. Results: We selected 118 RPV-exposed and 118 non-RPV-exposed HIV-infected patients. Median time between transient elastography (TE) measurements was 50 (29–68) months. A repeated-measures general linear model based on the main clinical characteristics revealed a significant decrease in the TE value of −0.8kPa in non-RPV-exposed patients (p=0.254) and −1.6kPa in the RPV-exposed group (p<0.001). The subgroup analysis showed a significant reduction in the TE value only patients cured of hepatitis C (RPV-exposed, −2.8kPa [p<0.001]; non-RPV-exposed, −1.1kPa [p=0.22]). Conclusion: RPV-based antiretroviral regimens significantly reduced liver stiffness, as measured by TE, in patients cured of chronic hepatitis C.(AU)

Antecedentes: La rilpivirina (RPV) es un fármaco antirretroviral caracterizado por una buena tolerabilidad y un perfil de seguridad hepática favorable. Las últimas investigaciones han mostrado que la RPV mejora la fibrosis hepática en modelos animales de varias enfermedades hepáticas crónicas. Nuestro estudio tenía como objetivo analizar el efecto de la RPV en la fibrosis hepática mediante la evaluación de cambios en la rigidez hepática utilizando una elastografía transitoria. Métodos: Estudio de cohortes retrospectivo de pacientes infectados por VIH expuestos y no expuestos a RPV. Se analizó el cambio en la rigidez hepática durante el período entre dos mediciones mediante elastografía transitoria y se comparó entre pacientes expuestos y no expuestos a RPV. Resultados: Seleccionamos a 118 pacientes infectados por VIH expuestos a RPV y 118 pacientes infectados por VIH no expuestos a RPV. La mediana del tiempo entre las mediciones mediante elastografía transitoria (ET) fue de 50 (29-68) meses. Un modelo lineal general de medidas repetidas basado en las principales características clínicas reveló una reducción significativa en el valor de ET, −0,8kPa en el grupo de pacientes no expuestos a RPV (p=0,254) y de −1,6kPa en el grupo de pacientes expuestos a RPV (p<0,001). El análisis de subgrupos mostró una reducción significativa en el valor de ET solo en pacientes curados de hepatitis C (expuestos a RPV, −2,8kPa [p<0,001]; no expuestos a RPV, −1,1kPa [p=0,22]). Conclusión: Las pautas antirretrovirales basadas en RPV redujeron significativamente la rigidez hepática, evaluada por las mediciones de ET, en los pacientes que se habían curado de hepatitis C crónica.(AU)

Screening Protocol and Prevalence of Venous Thromboembolic Disease in Hospitalized Patients With COVID-19.

BACKGROUND: SARS-CoV-2 disease (COVID-19) induces endothelial damage and sustained hypoxia and facilitates immobilization as factors of hypercoagulability. OBJECTIVES: The objective of our study was to assess the prevalence of venous thromboembolic disease (VTD) in COVID-19 patients and the usefulness of VTD screening based on age-adjusted D-dimer and point-of-care ultrasound (POCUS). PATIENTS/METHODS: We conducted a single cohort, prospective observational study in 102 consecutive hospitalized patients. RESULTS: A total of 102 POCUS and 39 pulmonary computed tomography angiography (PCTA) were performed diagnosing 27 VTD (26.5%): 17 deep vein thrombosis (DVT) (16.6% positive POCUS) and 18 pulmonary embolism (PE) (46.2% positive PCTA). COVID-19 patients with VTD were older (P < .030), had higher D-dimer (P < .001), higher International Society on Thrombosis and Hemostasis score (P < .001), and higher mortality (P = .025). However, there were no differences in inflammatory laboratory parameters neither in the cytokine storm syndrome (CSS) development. The ROC curve for D-dimer showed an AUC of 0.91. We have evidenced that patients with D-dimer between 2000 and 6000 ng/mL could benefit from a screening strategy with POCUS given the high sensitivity and specificity of the test. Furthermore, patients with D-dimer ≥6000 ng/mL should undergo POCUS and PCTA to rule out DVT and PE, respectively. CONCLUSIONS: In our cohort, 26.5% of the patients presented VTD. Screening strategy based on age-adjusted D-dimer and POCUS proved high sensitivity and specificity. Future trials focused on screening strategies are necessary to early detect the presence of DVT and PE and determine thromboprophylaxis strategies in patients with COVID-19.

Psoriasis and Liver Damage in HIV-Infected Patients.

Background/objectives: Psoriasis is the most frequent skin disease in HIV-infected patients. Nonalcohol fatty liver disease (NAFLD) is more prevalent in patients with psoriasis. We report the prevalence of psoriasis and NAFLD and investigate risk factors of liver damage in HIV-infected patients with psoriasis. Methods: We performed a retrospective observational study. Steatosis was defined as indicative abdominal ultrasound findings, CAP (controlled attenuated parameter by transient elastography) > 238 dB/m, and/or triglyceride and glucose index (TyG) > 8.38. Significant (fibrosis ≥ 2) and advanced liver fibrosis (fibrosis ≤ F3) were studied by transient elastography (TE) and/or FIB-4 using standard cutoff points. FIB-4 (Fibrosis 4 score) results were adjusted for hepatitis C (HCV)-coinfected patients. Results: We identified 80 patients with psoriasis (prevalence, 1.5%; 95% CI, 1.1-1.8). Psoriasis was severe (PASI > 10 and/or psoriatic arthritis) in 27.5% of cases. The prevalence of steatosis was 72.5% (95% CI, 65-85). Severe psoriasis was an independent risk factor for steatosis (OR, 12; 95% CI, 1.2-120; p = 0.03). Significant liver fibrosis (p < 0.05) was associated with HCV coinfection (OR 3.4; 95% CI, 1.1-10.6), total CD4 (OR 0.99; 95% CI, 0.99-1), and time of efavirenz exposure (OR 1.2; 95% CI, 1.0-1.3). Conclusions: The prevalence of psoriasis in HIV-infected patients was similar to that of the general population. Steatosis is highly prevalent, and severe psoriasis is an independent risk factor for steatosis in HIV-infected patients.

COVID-19 and Pembrolizumab-Induced Secondary Hemophagocytic Lymphohistiocytosis: a Case Report.

Our case highlights SARS-CoV-2 and pembrolizumab as trigger of secondary hemophagocytic lymphohistiocytosis. Although it is a rare complication, it must be suspected in order to start specific treatment. In this context, intravenous immunoglobulins could be a therapeutic option.

Cancer-Associated Retinopathy and Treatment with Intravenous Immunoglobulin Therapy. A Seldom Used Approach?

Purpose: To report a case of cancer-associated retinophaty (CAR) treated with intravenous immunoglobulin (IGIV) and review the use of IGIV in the treatment of CARMethods: Case report: A 68-year-old woman, former smoker, presented with bilateral subacute decreased visual acuity with 1 month of evolution, without other symptoms. Clinical examination revealed retinal atrophy and a mild vitritis component. Treatment with corticosteroid and IGIV was initiated empirically with the stabilization of visual loss. Anti-recoverin antibodies tested positive and a small cell lung carcinoma was diagnosed. In a review of the literature, we found that only 12 cases of patients treated with intravenous immunoglobulins have been reported.Conclusions: the early use of IVIG could contribute to an improvement and/or stabilization of visual symptoms in this patient group due to its rapid effect and lower profile of adverse effects when administered with chemotherapy.

Pacientes con hepatitis C perdidos en el sistema: aspectos éticos-legales y resultados de su búsqueda / No disponible

INTRODUCCIÓN: se conoce la existencia de pacientes con hepatitis C perdidos en el sistema, pero se desconocen su prevalencia y características. Además, su identificación colisiona con la barrera de la protección de datos. MÉTODOS: se presentó un protocolo de identificación y contacto al Comité de Ética Asistencial. Se obtendrían las serologías anti-VHC+ de Microbiología entre 2010-18. Se analizaría su situación en la base de datos hospitalaria y regional. Se clasificarían: a) hepatitis C crónica, si última determinación de ARN-VHC+; b) hepatitis C curada, si última determinación de ARN-VHC- tras 12 semanas de tratamiento; c) hepatitis C posible, si anti-VHC+ sin determinación de ARN-VHC. Se considerarían perdidos aquellos con hepatitis C crónica o posible sin seguimiento en Digestivo o Medicina Interna. Se contactaría con ellos mediante correo postal y, posteriormente, por teléfono para ofrecerles tratamiento. RESULTADOS: el Comité de Ética consideró que el protocolo cumplía los principios bioéticos de autonomía, beneficencia, no maleficencia y justicia, y que el contacto era éticamente deseable. Sobre 4.816 serologías anti-VHC+ identificamos 677 pacientes perdidos (14,06 %; IC 95 %: 13,2-15,2): edad 54 años, 61 % hombres, 12 % extranjeros y 95 % monoinfectados. Se consumieron 1,3 minutos en el estudio de cada serología. Un 25 % de las perdidas habían sido solicitadas por Digestivo o Medicina Interna. De los 677 perdidos, 228 (33,7 %) tenían también ARN-VHC+ y 449 (66,3 %) solo tenían solicitada la serología. CONCLUSIÓN: un número importante de pacientes con hepatitis C se encuentran perdidos en el sistema. Su búsqueda y contacto es posible desde el punto de vista ético-legal

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Patients with hepatitis C lost to follow-up: ethical-legal aspects and search results.

INTRODUCTION: data on the prevalence and characteristics of hepatitis C patients lost to follow-up are lacking. In addition, the identification of this population clashes with data protection regulations. METHODS: the identification and contact protocol was submitted to the Health Care Ethics Committee. The protocol was based on anti-HCV serology test results for 2010-2018, which were obtained from the Microbiology Department. In addition, the situation of the patients in the hospital and regional database was analyzed, based on the following classification: a) chronic hepatitis C, if the last HCV RNA determination was positive; b) cured hepatitis C, if the last HCV RNA determination was negative after 12 weeks of treatment; and c) possible hepatitis C, if anti-HCV antibodies were positive with no result for HCV RNA. Lost patients were defined as those with chronic or possible hepatitis C and no follow-up in the Digestive Diseases or Internal Medicine Departments. The patients were contacted by postal mail and then by telephone, so that they could be offered treatment. RESULTS: the Ethics Committee considered that the protocol fulfilled the bioethical principles of autonomy, beneficence, non-maleficence and justice and that contact was ethically desirable. From 4,816 positive anti-HCV serology results, 677 patients were identified who were lost to follow-up (14.06 %; 95 % CI, 13.2-15.2). The mean age was 54 years, 61 % were male, 12 % were foreign born and 95 % were mono-infected. The study of each serology result took 1.3 minutes. One-quarter (25 %) of the losses corresponded to the Digestive Diseases and Internal Medicine Departments. Of the 677 losses, serology testing had only been ordered for 449 patients (66.3 %) and the remaining 228 (33.7 %) also had a positive HCV RNA result. CONCLUSION: a large number of patients with hepatitis C are lost to follow-up. Searching for and contacting these patients is legally and ethically viable.