Decreased Long-Term Severe Acute Respiratory Syndrome Coronavirus 2-Specific Humoral Immunity in Liver Transplantation Recipients 12 Months After Coronavirus Disease 2019.

Long-term humoral immunity and its protective role in liver transplantation (LT) patients have not been elucidated. We performed a prospective multicenter study to assess the persistence of immunoglobulin G (IgG) antibodies in LT recipients 12 months after coronavirus disease 2019 (COVID-19). A total of 65 LT recipients were matched with 65 nontransplanted patients by a propensity score including variables with recognized impact on COVID-19. LT recipients showed a lower prevalence of anti-nucleocapsid (27.7% versus 49.2%; P = 0.02) and anti-spike IgG antibodies (88.2% versus 100.0%; P = 0.02) at 12 months. Lower index values of anti-nucleocapsid IgG antibodies were also observed in transplantation patients 1 year after COVID-19 (median, 0.49 [interquartile range, 0.15-1.40] versus 1.36 [interquartile range, 0.53-2.91]; P < 0.001). Vaccinated LT recipients showed higher antibody levels compared with unvaccinated patients (P < 0.001); antibody levels reached after vaccination were comparable to those observed in nontransplanted individuals (P = 0.70). In LT patients, a longer interval since transplantation (odds ratio, 1.10; 95% confidence interval, 1.01-1.20) was independently associated with persistence of anti-nucleocapsid IgG antibodies 1 year after infection. In conclusion, compared with nontransplanted patients, LT recipients show a lower long-term persistence of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, SARS-CoV-2 vaccination after COVID-19 in LT patients achieves a significant increase in antibody levels, comparable to that of nontransplanted patients.

Changes in humoral immune response after SARS-CoV-2 infection in liver transplant recipients compared to immunocompetent patients.

The protective capacity and duration of humoral immunity after SARS-CoV-2 infection are not yet understood in solid organ transplant recipients. A prospective multicenter study was performed to evaluate the persistence of anti-nucleocapsid IgG antibodies in liver transplant recipients 6 months after coronavirus disease 2019 (COVID-19) resolution. A total of 71 liver transplant recipients were matched with 71 immunocompetent controls by a propensity score including variables with a well-known prognostic impact in COVID-19. Paired case-control serological data were also available in 62 liver transplant patients and 62 controls at month 3 after COVID-19. Liver transplant recipients showed a lower incidence of anti-nucleocapsid IgG antibodies at 3 months (77.4% vs. 100%, p < .001) and at 6 months (63.4% vs. 90.1%, p < .001). Lower levels of antibodies were also observed in liver transplant patients at 3 (p = .001) and 6 months (p < .001) after COVID-19. In transplant patients, female gender (OR = 13.49, 95% CI: 2.17-83.8), a longer interval since transplantation (OR = 1.19, 95% CI: 1.03-1.36), and therapy with renin-angiotensin-aldosterone system inhibitors (OR = 7.11, 95% CI: 1.47-34.50) were independently associated with persistence of antibodies beyond 6 months after COVID-19. Therefore, as compared with immunocompetent patients, liver transplant recipients show a lower prevalence of anti-SARS-CoV-2 antibodies and more pronounced antibody levels decline.

Impact of Everolimus-based Immunosuppression on Renal Function in Liver Transplant Recipients.

BACKGROUND: Calcineurin inhibitors have been implicated in acute and chronic kidney disease after liver transplant (LT). Everolimus (EVR) is a mammalian target of rapamycin inhibitor efficacious in preventing acute cellular rejection while preserving renal function among LT recipients. We evaluated the benefits on renal function of EVR immunosuppression in LT recipients. METHODS: We performed a retrospective and observational study in 477 LT recipients in Virgen de las Nieves Hospital from 2002 to 2019 on the use of EVR with tacrolimus minimization or withdrawal in LT recipients with renal dysfunction. The study included 100 patients starting EVR (20.96%); in 66 (66%) the indication was renal dysfunction. The change in renal function was assessed by estimated glomerular filtration rate. Statistical analyses were performed using SPSS 17.0 software (IBM, Munich, Germany). RESULTS: Fifty 8 patients received mycophenolate mofetil (87.8%), and tacrolimus therapy was stopped in 27 patients (40.9%). Induction therapy with basiliximab was administered in 41 patients (62.12%). There was significant difference between estimated glomerular filtration rate at the time of starting EVR and the first month at last follow-up (49.42 mL/min/1.73 m2 vs 75.27 mL/min/1.73 m2; P < .001) and at end of follow-up (24 months) (49.42 mL/min/1.73 m2 vs 64.32 mL/min/1.73 m2; P = .001). The rate of incidence of adverse events was 48.48% (32/66). Seven patients died during follow-up (10.6%), but there were no EVR-related deaths. Eleven patients (16.6%) developed biopsy-proven acute rejection. CONCLUSION: This study showed that EVR is associated with a beneficial effect on glomerular filtration rate in both the short and long term in LT recipients.

Descriptive Analysis of Everolimus Conversion in Liver Transplant Recipients With Malignant Neoplastic Disease.

BACKGROUND: Calcineurin inhibitors are associated with the development of de novo tumors and increased recurrence of hepatocellular carcinoma after liver transplant. It has been suggested that mammalian target of rapamycin inhibitors (everolimus [EVR]) may improve prognosis. We analyzed our experience on the use of EVR in malignant neoplasms in liver transplantation. METHODS: We performed a retrospective descriptive analysis of 477 transplants performed between 2002 and 2019 at Virgen de las Nieves Hospital. A total of 100 patients received EVR; 23 transplants were because of tumor disease (23%), with de novo tumor in 12 patients and hepatocarcinoma in 11. The statistical study was carried out using the statistical program SPSS 17.0 software. RESULTS: The study included 18 male patients (78.3%) and 5 female patients (21.7%) with an average age of 59.67 years. The most common indications of liver transplant have been alcoholic cirrhosis in 39% and hepatitis C virus cirrhosis in 21.7%. De novo tumors were lung neoplasm in 4 patients (33.3%), lymphoma in 2 patients(16.7%), oropharynx in 2 patients (16.7%), skin tumors in 2 patients (16.7%), and a kidney tumor (8.3%) in 1 patient. As for hepatocellular carcinoma, 8 patients met Milan criteria on the explant (61.5%). Tacrolimus was discontinued in all cases. The average onset time of post-transplant EVR was 2231.42 days in the de novo neoplasms and 307.45 days in those receiving transplants because of hepatocellular carcinoma (P = .05). We observed 5 deaths (21.7%). CONCLUSION: Although the beneficial long-term role of EVR in liver transplant recipients with tumor disease is not demonstrated, it is used by most transplant units, both in de novo neoplasms and those receiving transplants because of hepatocellular carcinoma.

Serum zinc and copper concentrations and ratios in cirrhotic patients: correlation with severity index.

INTRODUCTION: zinc (Zn) and copper (Cu) are essential elements that play an important role in the whole-body metabolism and seems to have a role in the pathogenesis of the liver cirrhosis (LC). OBJECTIVE: the aim of this study is to evaluate the influence on serum Zn and Cu concentrations and Cu/Zn ratios of different factors like cirrhosis, severity index, age, sex, death, and disease complications. METHODS: ninety-three patients with LC were included. The severity index was measured by the Child-Pugh index (CPI). RESULTS: mean serum Cu concentration and Cu/Zn ratio were significantly higher in patients than in healthy controls (p ≤ 0.001). Serum Zn concentrations were reduced with higher cirrhosis severity (specifically low vsmedium severity CPI, p < 0.05). Mean serum Cu concentration was significantly higher in the oldest (> 50 years) versusyoungest (< 30 years) age group. Serum Zn concentrations were lower and Cu/Zn ratios were higher (p < 0.05) in patients that died. Among complications, significantly higher serum Zn concentrations were found in cirrhotic patients with ascites than in those with bacteremia-sepsis. CONCLUSIONS: levels of Zn, Cu and Cu/Zn ratio are affected by the presence of hepatic cirrhosis. Serum Zn concentrations are lower with higher severity of cirrhosis, while those for Cu are increased in cirrhotic patients. We can observe that the presence of elevated Cu/Zn ratios in these patients might be useful in the evaluation of suspected liver cirrhosis.

Serum zinc and copper concentrations and ratios in cirrhotic patients: correlation with severity index / Concentraciones séricas de zinc, cobre y sus cocientes correspondientes en pacientes cirróticos: correlación con el índice de severidad

Introduction: zinc (Zn) and copper (Cu) are essential elements that play an important role in the whole-body metabolism and seems to have a role in the pathogenesis of the liver cirrhosis (LC).Objective: the aim of this study is to evaluate the influence on serum Zn and Cu concentrations and Cu/Zn ratios of different factors like cirrhosis, severity index, age, sex, death, and disease complications. Methods: ninety-three patients with LC were included. The severity index was measured by the Child-Pugh index (CPI).Results: mean serum Cu concentration and Cu/Zn ratio were significantly higher in patients than in healthy controls (p ≤ 0.001). Serum Zn concentrations were reduced with higher cirrhosis severity (specifically low vsmedium severity CPI, p < 0.05). Mean serum Cu concentration was significantly higher in the oldest (> 50 years) versusyoungest (< 30 years) age group. Serum Zn concentrations were lower and Cu/Zn ratios were higher (p < 0.05) in patients that died. Among complications, significantly higher serum Zn concentrations were found in cirrhotic patients with ascites than in those with bacteremia-sepsis. Conclusions: levels of Zn, Cu and Cu/Zn ratio are affected by the presence of hepatic cirrhosis. Serum Zn concentrations are lower with higher severity of cirrhosis, while those for Cu are increased in cirrhotic patients. We can observe that the presence of elevated Cu/Zn ratios in these patients might be useful in the evaluation of suspected liver cirrhosis

Introducción: el zinc (Zn) y el cobre (Cu) son elementos esenciales ya que juegan un papel fundamental en el metabolismo en general y parecen tener implicación en la patogénesis de la cirrosis hepática (CH). Objetivos: el objetivo del presente estudio es evaluar la influencia sobre los niveles séricos de Zn y Cu, y sobre los cocientes entre los niveles de Cu y Zn de diferentes factores como la cirrosis, el índice de severidad, la edad, el sexo, la mortalidad y las complicaciones de la enfermedad. Metodología: noventa y tres pacientes con CH fueron incluidos en el estudio y el grado de severidad se midió utilizando el índice Child-Pugh (ICP). Resultados: las concentraciones séricas de Cu y los cocientes entre los niveles de Cu y Zn se encontraron significativamente aumentados en los pacientes con respecto a los controles sanos (p ≤ 0.001). A mayor grado de severidad cirrótica, se obtuvieron valores medios de Zn significativamente disminuidos (concretamente en los enfermos con ICP bajo frente a los que tenían un ICP medio, p < 0.05). La media de las concentraciones séricas de Cu fue significativamente superior en el grupo de sujetos de mayor edad (> 50 años) con respecto al grupo más joven (< 30 años). En aquellos pacientes que habían sufrido un deceso, las concentraciones séricas de Zn estaban significativamente disminuidas, mientras que los cocientes entre los niveles de Cu y Zn se encontraron elevadas (p < 0.05). En cuanto a las complicaciones de la enfermedad, obtuvimos valores séricos significativamente elevados de Zn en aquellos pacientes cirróticos que padecían ascitis respecto a los que presentaban bacteriemia-sepsis. Conclusiones: los valores de Zn, Cu y los cocientes entre los niveles de Cu y Zn se encuentran afectados en la enfermedad cirrótica. Las concentraciones séricas de Zn son bajas cuando existe un mayor grado de severidad de la cirrosis hepática, mientras que los valores de Cu apararen incrementados en los pacientes con esta enfermedad. Podemos observar que la presencia de valores elevados de los cocientes entre los niveles de Cu y Zn podría ser de utilidad en la evaluación de la posible presencia de la enfermedad

Ulcerative Colitis and Crohn's Disease Are Associated with Decreased Serum Selenium Concentrations and Increased Cardiovascular Risk.

The incidence of inflammatory bowel disease (IBD) and associated oxidative stress is increasing. The antioxidant mineral selenium (Se) was measured in serum samples from 106 IBD patients (53 with ulcerative colitis (UC) and 53 with Crohn's disease (CD)) and from 30 healthy controls. Serum Se concentrations were significantly lower in UC and CD patients than in healthy controls (p < 0.001) and significantly lower in CD patients than in UC patients (p = 0.006). Se concentrations in patients were significantly influenced by sex, body mass index (BMI), the inflammatory biomarker α-1-antitrypsin, surgery, medical treatment, the severity, extent, and form of the disease and the length of time since onset (p < 0.05). Se concentrations in IBD patients were positively and linearly correlated with nutritional (protein, albumin, prealbumin, cholinesterase and total cholesterol) and iron status-related (hemoglobin, Fe and hematocrit) parameters (p < 0.05). A greater impairment of serum Se and cardiovascular status was observed in CD than in UC patients. An adequate nutritional Se status is important in IBD patients to minimize the cardiovascular risk associated with increased inflammation biomarkers, especially in undernourished CD patients, and is also related to an improved nutritional and body iron status.

Serum selenium levels in cirrhotic patients are not influenced by the disease severity index.

Selenium (Se) is an antioxidant element that protects against cellular damage by reactive oxygen species. Therefore, total serum Se concentration may reflect protection during the development of cirrhosis, an oxidative stress-related disease. We hypothesized that serum Se levels are diminished in cirrhotic patients due to their enhanced oxidative stress, and serum Se levels are reduced the most in patients with the highest severity of cirrhosis. A case-control study was performed to determine whether cirrhosis is associated with changes in serum Se levels. Blood samples from 30 healthy controls and 93 cirrhotic patients were analyzed for total serum Se by hydride generation atomic absorption spectrometry. The Child-Pugh index score was used to evaluate the severity of liver disease. The mean serum Se concentration was significantly lower in patients vs controls (0.721 ± 0.239 vs 0.926 ± 0.241 µmol/L; P = .001). Mean serum Se levels were not significantly lower in patients with higher severity of cirrhosis (0.691 ± 0.229 vs 0.755 ± 0.255 µmol/L; P = .144). A positive and significant correlation was found between age and serum Se levels in patients (r = 0.277, P = .007). Patients showed significant sex differences in serum Se level (higher in male) and severity index (higher in female). The significantly decreased serum Se level in patients indicates that the Se component of the antioxidant system is severely impaired in cirrhosis. However, serum Se levels were not influenced by the severity of the disease.