Biomarkers of innate immunity and immunological susceptibility to viral Infection in patients with alcoholic cirrhosis

© 2024 by the authors. This manuscript version is made available under the CC-BY 4.0 license http://creativecommons.org/licenses/by/4.0/ This document is the Published version of a Published Work that appeared in final form in Biomedicines. To access the final edited and published work see https://doi.org/10.3390/biomedicines12020336Background: The harmful effect of alcohol on the immune system may be due to both a direct action of the alcohol or its metabolites on immune cells as an indirect action modifying the different mechanisms of intercellular interaction. The interplay between stimulatory (aKIR) and inhibitory (iKIR) natural killer (NK) cell receptors and their corresponding human leukocyte antigen (HLA) ligands influences the outcome of virus infection. The aim was to analyze the influence of the KIR/HLA pair genetic profile in male alcoholic cirrhosis (AC) patients with and without viral infections to find susceptibility biomarkers that can help establish the risks and prevent viral infections. Methods: A total of 281 male AC patients were analyzed. The sociodemographic characteristics, viral hepatitis C (HCV), hepatitis B (HBV), and cytomegalovirus (CMV) infections were analyzed. Genomic DNA was extracted, and genetic the KIR/HLA profiles were investigated. A total of 6 KIR genes and their corresponding ligands (HLA-C) were analyzed. Patients were grouped into two groups: with and without associated viral infection. Results: A statistically significant increase in the combination of KIR2DL2+/C1C1 was observed in male AC patients with viral infection compared to those without viral infection (45.9% vs. 24.5%, p = 0.021). The analysis of KIR2DL3+/C1+ showed a high frequency comparing healthy controls and male AC patients without virus infection (85% vs. 76.4%; p = 0.026). The analysis of KIR2DL3+/C2C2 frequency showed a statistically significant increase comparing male AC patients without viral infection and healthy controls (23.6% vs. 15%; p = 0.026). Conclusions: The genetic KIR2DL2+/C2C2 profiles may play a significant role in determining the vulnerability of male AC patients to viral infections, providing valuable insights for future research and potential therapeutic interventions

Patient sex in the setting of liver transplant in alcoholic liver disease

© Baskent University 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published version of a Published Work that appeared in final form in Experimental and Clinical Transplantation. To access the final edited and published work see https://doi.org/10.6002/ect.2017.0302Objectives: The aim of this study was to analyze alcoholic cirrhosis in women who were to undergo liver transplant, including their biochemical and clinical characteristics, main complications, survival rates, and main causes of death compared with men with alcoholic cirrhosis. Materials and Methods: Our study included 400 patients with alcoholic cirrhosis, which we divided according to sex and viral infections. Biochemical parameters and the presence and degree of ascites and encephalopathy, liver function status, and liver rejection and survivalrates were analyzed from 1 to 10 years and the main cause of death at 10 years. Results: Patients with nonviral alcoholic cirrhosis and liver transplant had significantly better survival rates (84.1%) at 1 year versus those with viral alcoholic cirrhosis (74.5%; P = .036). Men with nonviral alcoholic cirrhosis (14%) and women with hepatitis C virus (29%) had the lowest short-term survival rates. In long-term survival analysis, the lowest rate was observed in women with nonviral alcoholic cirrhosis (26.1%), and the highest rate was observed in women with hepatitis C virus (42.9%). Liver graft failure was one of the main causes of death in male patients (19.5%). Conclusions: Women with alcoholic cirrhosis showed a higher rate of ascites and encephalopathy but lower liver graft rejection than men with alcoholic cirrhosis. Survival rates were similar between men and women, although slightly lowerin women who had hepatitis C virus

Pretransplant ascites and encephalopathy and their influence on survival and liver graft rejection in alcoholic cirrhosis disease

© 2019 Termedia & Banach. This manuscript version is made available under the CC-BY-NC-SA 4.0 license http://creativecommons.org/licenses/by-nc-sa/4.0/ This document is the Published version of a Published Work that appeared in final form in Archives of Medical Science. To access the final edited and published work see https://doi.org/10.5114/aoms.2018.80651Introduction The Child-Pugh and model for end-stage liver disease (MELD) scores are widely used to predict the outcomes of liver transplant (LT). Both have similar prognostic values in most cases, although their benefits might differ in some specific conditions. The aim of our study was to analyze the influence of pre-transplant ascites and encephalopathy in post-transplant liver rejection development and survival in alcohol cirrhosis (AC) patients undergoing LT to determine the usefulness of the Child-Pugh score for the assessment of prognosis in such patients. Material and methods Two hundred and eighty-one AC patients, classified according to viral infections and pre-transplant complications, were analyzed. Acute (AR) and chronic (CR) liver rejections and Child-Pugh, MELD and albumin-bilirubin (ALBI) scores were studied in all cases. Results Similar AC rejection percentages were observed in ascites or encephalopathy groups (18.5% and 16.5%, p = 0.735), although a higher but not statistically significant AC rate was observed in patients with grade III ascites (p = 0.777) and with grade II encephalopathy (p = 0.089). Chronic rejection was only developed by 9.1% of AC patients, regardless of the presence of ascites (6.2%) or encephalopathy (5.5%). The presence of ascites and encephalopathy complications did not seem to influence post-transplant survival. Neither the Child-Pugh nor the ALBI score can be considered the best for predicting patient survival in the short or long term. Conclusions Ascites and encephalopathy do not seem to influence AC or CR in patient survival, regardless of the presence of viral infections, so in our study neither the Child-Pugh nor ALBI score seems to be the best score to predict the outcomes of these patients

Biomarkers of Innate Immunity and Immunological Susceptibility to Viral Infection in Patients with Alcoholic Cirrhosis

Background: The harmful effect of alcohol on the immune system may be due to both a direct action of the alcohol or its metabolites on immune cells as an indirect action modifying the different mechanisms of intercellular interaction. The interplay between stimulatory (aKIR) and inhibitory (iKIR) natural killer (NK) cell receptors and their corresponding human leukocyte antigen (HLA) ligands influences the outcome of virus infection. The aim was to analyze the influence of the KIR/HLA pair genetic profile in male alcoholic cirrhosis (AC) patients with and without viral infections to find susceptibility biomarkers that can help establish the risks and prevent viral infections. Methods: A total of 281 male AC patients were analyzed. The sociodemographic characteristics, viral hepatitis C (HCV), hepatitis B (HBV), and cytomegalovirus (CMV) infections were analyzed. Genomic DNA was extracted, and genetic the KIR/HLA profiles were investigated. A total of 6 KIR genes and their corresponding ligands (HLA-C) were analyzed. Patients were grouped into two groups: with and without associated viral infection. Results: A statistically significant increase in the combination of KIR2DL2+/C1C1 was observed in male AC patients with viral infection compared to those without viral infection (45.9% vs. 24.5%, p = 0.021). The analysis of KIR2DL3+/C1+ showed a high frequency comparing healthy controls and male AC patients without virus infection (85% vs. 76.4%; p = 0.026). The analysis of KIR2DL3+/C2C2 frequency showed a statistically significant increase comparing male AC patients without viral infection and healthy controls (23.6% vs. 15%; p = 0.026). Conclusions: The genetic KIR2DL2+/C2C2 profiles may play a significant role in determining the vulnerability of male AC patients to viral infections, providing valuable insights for future research and potential therapeutic interventions

Forensic avaluation and population genetic study of KIR2DS4 insertion/deletion polymorphisms in a Spanish population

© 2020 Romanian Society of Legal Medicine. This document is the Published version of a Published Work that appeared in final form in Romanian Journal of Legal Medicine. To access the final edited and published work see https://doi.org/10.4323/rjlm.2020.419Polymorphisms (Indels) of insertion/deletion are a class of diallelic genetic markers resulting from a single mutation event and reflect the insertion or deletion of genomic DNA bases. The aim of this study was to analyze the distribution of the allelic variants of KIR2DS4 in the Spanish Caucasian population and compared it with other populations described in the literature. Genotyping of allelic variants of KIR2DS4 was performed by PCR-SSO in 127 healthy Spanish Caucasian individuals and were subsequently compared with 26 different world populations. A frequency of KIR2DS4-full (36.2%) allelic variants was found in the Spanish population, similar to those found European populations, but different and higher frequency in South and Central America and the Caribbean, Saudi Arabia, Sub-Saharan African as well as Hong Kong and Korean populations. A frequency of 77.2% of KIR2DS4-delected variant was found in Spanish population, while lower percentages were found in Sub-Saharan Africa, China, Hong Kong and Korea. No differences in the distribution of KIR2DS4 variants were observed between AA/BX KIR haplotypes and genotypes. In conclusion, our results enrich the Caucasian genetic information of the KIR2DS4 allelic variants between the Spanish Caucasian and other populations that could be useful in clinical, forensic and anthropological studies

Killer Cell Immunoglobulin-like Receptors (KIR) and Human Leucocyte Antigen C (HLA-C) Increase the Risk of Long-Term Chronic Liver Graft Rejection

Chronic liver rejection (CR) represents a complex clinical situation because many patients do not respond to increased immunosuppression. Killer cell immunoglobulin-like receptors/Class I Human Leukocyte Antigens (KIR/HLA-I) interactions allow for predicting Natural Killer (NK) cell alloreactivity and influence the acute rejection of liver allograft. However, its meaning in CR liver graft remains controversial. KIR and HLA genotypes were studied in 513 liver transplants using sequence-specific oligonucleotides (PCR-SSO) methods. KIRs, human leucocyte antigen C (HLA-C) genotypes, KIR gene mismatches, and the KIR/HLA-ligand were analyzed and compared in overall transplants with CR (n = 35) and no-chronic rejection (NCR = 478). Activating KIR (aKIR) genes in recipients (rKIR2DS2+ and rKIR2DS3+) increased CR compared with NCR groups (p = 0.013 and p = 0.038). The inhibitory KIR (iKIR) genes in recipients rKIR2DL2+ significantly increased the CR rate compared with their absence (9.1% vs. 3.7%, p = 0.020). KIR2DL3 significantly increases CR (13.1% vs. 5.2%; p = 0.008). There was no influence on NCR. CR was observed in HLA-I mismatches (MM). The absence of donor (d) HLA-C2 ligand (dC2−) ligand increases CR concerning their presence (13.1% vs. 5.6%; p = 0.018). A significant increase of CR was observed in rKIR2DL3+/dC1− (p = 0.015), rKIR2DS4/dC1− (p = 0.014) and rKIR2DL3+/rKIR2DS4+/dC1− (p = 0.006). Long-term patient survival was significantly lower in rKIR2DS1+rKIR2DS4+/dC1− at 5–10 years post-transplant. This study shows the influence of rKIR/dHLA-C combinations and aKIR gene-gene mismatches in increasing CR and KIR2DS1+/C1-ligands and the influence of KIR2DS4+/C1-ligands in long-term graft survival

Seguimiento de las cenizas del Eyjafjalla sobre la Península Ibérica por la red de lidares hispano-portuguesa SPALINET

La reciente erupción del volcán Eyjafjallajökull es una muestra – extremada, pero de probabilidad no despreciable – de la influencia que los aerosoles atmosféricos pueden tener en la vida diaria de miles de personas y en la economía mundial. Este acontecimiento ha sido seguido desde tierra por – entre otros instrumentos – radares láser (lidares) que han permitido determinar la evolución en el espacio y el tiempo de las nubes de ceniza proyectadas por el volcán y han proporcionado información de valor a las agencias meteorológicas y a las administraciones responsables de la seguridad de la navegación aérea

Seguimiento de las cenizas del Eyjafjalla sobre la Península Ibérica por la red de lidares hispano-portuguesa SPALINET

La reciente erupción del volcán Eyjafjallajökull es una muestra – extremada, pero de probabilidad no despreciable – de la influencia que los aerosoles atmosféricos pueden tener en la vida diaria de miles de personas y en la economía mundial. Este acontecimiento ha sido seguido desde tierra por – entre otros instrumentos – radares láser (lidares) que han permitido determinar la evolución en el espacio y el tiempo de las nubes de ceniza proyectadas por el volcán y han proporcionado información de valor a las agencias meteorológicas y a las administraciones responsables de la seguridad de la navegación aérea.Postprint (published version

Seguimiento de las cenizas del Eyjafjalla sobre la Península Ibérica por la red de lidares hispano-portuguesa SPALINET

La reciente erupción del volcán Eyjafjallajökull es una muestra – extremada, pero de probabilidad no despreciable – de la influencia que los aerosoles atmosféricos pueden tener en la vida diaria de miles de personas y en la economía mundial. Este acontecimiento ha sido seguido desde tierra por – entre otros instrumentos – radares láser (lidares) que han permitido determinar la evolución en el espacio y el tiempo de las nubes de ceniza proyectadas por el volcán y han proporcionado información de valor a las agencias meteorológicas y a las administraciones responsables de la seguridad de la navegación aérea