Decompensated liver cirrhosis: assessment of complications and mortality in hospitalised patients

Background. Liver cirrhosis is a severe, progressively fatal disease if untreated. Hospitalised patients face high mortality rates, and current methods for assessing prognosis vary widely. The research aims to investigate complications and predictors of mortality in patients admitted for decompensated cirrhosis to a tertiary care centre in Tirana, Albania. Materials and methods. The retrospective study included 212 patients aged (58.67 ± 10.09) years: 174 (82.1 %) men, 38 (17.9 %) women. The Child-Turcotte-Pugh, MELD, MELD-Na, MELD 3.0, iMELD, MESO, and UKELD scales were used to assess the severity of the condition and risk stratification of patients. The number of patients with a fatal outcome was 43 (20.3 %). Results. Among participants with different etiological factors of liver cirrhosis, the mortality rate did not differ significantly (p = 0.873). The presence of hepatic encepha­lopathy (0.43; p = 0.001), acute-on-chronic liver failure (r = 0.47; p = 0.001) and hepatorenal syndrome (r = 0.49; p = 0.001), and, to a lesser extent, ascites (r = 0.18; p = 0.006) and spontaneous bacterial peritonitis (r = 0.23; p = 0.041) was a marker of unfavourable prognosis of hospitalisation. Also, the risk of death increased in the presence of leukaemia (hazard ratio = 4.21 (1.65; 10.74); p = 0.003). Conclusions. The MELD 3.0 and MELD-Na scores, calculated based on laboratory values obtained within 48–72 hours of hospitalisation, were found to be the prognostically significant (p < 0.05

Prevención secundaria tras un síndrome coronario agudo. Resultados a medio plazo de un programa de rehabilitación cardiaca

Introducción Los Programas de Rehabilitación Cardiaca han adquirido gran relevancia como herramienta para mejorar el pronóstico y la calidad de vida de pacientes que han presentado un síndrome coronario agudo. Objetivo Evaluar los resultados de un programa de rehabilitación cardiaca a medio plazo. Materiales y métodos Estudio descriptivo retrospectivo de 121 pacientes que presentaron un síndrome coronario agudo y fueron incluidos en el programa de rehabilitación cardiaca. Se analizaron las características demográficas, antropométricas, analíticas y de capacidad funcional a la inclusión, tras finalizar el programa presencial y a los 12 meses. Resultados La edad media fue 54 ± 7 años. El factor de riesgo cardiovascular más prevalente fue el sobrepeso/obesidad (88, 4%). Tras la finalización del programa de rehabilitación cardiaca disminuyeron significativamente los valores de colesterol LDL (81, 1 ± 28, 7 vs. 76, 5 ± 31, 5 mg/dl; p 0, 03). Un porcentaje significativo de diabéticos alcanzaron objetivos de Hb A1c < 7% (50% vs. 68, 5%; p 0, 01). El perímetro abdominal mostró una disminución estadísticamente significativa (100, 8 ± 12, 8 vs. 99, 5 ± 12, 3 cm; p 0, 004). El 89, 3% de los pacientes mejoraron su capacidad funcional. En la revisión anual la mayoría de los parámetros estudiados mostraron una discreta tendencia negativa. Un 47, 36% de los fumadores a la inclusión mantenían el hábito tabáquico al año. Conclusiones Los programas de rehabilitación cardiaca mejoran el control de los factores de riesgo cardiovascular, cambios de estilo de vida y capacidad funcional en los pacientes que han sufrido un síndrome coronario agudo. Es preciso reforzar las estrategias de control para mantener estos beneficios a medio-largo plazo. Introduction: Cardiac rehabilitation programmes have become a very important tool for improving the prognosis and quality of life of patients that have suffered an acute coronary syndrome. Objective: To evaluate the medium-term results of a cardiac rehabilitation programme. Materials and methods: A descriptive study of 121 patients that presented with an acute coronary syndrome and were included in a cardiac rehabilitation programme. An analysis was performed on the demographic and anthropometric characteristics, as well as laboratory tests and functional capacity on inclusion, after finishing the programme, and at 12 months. Results: The mean age of the patients was 54 ± 7 years. The most prevalent cardiovascular risk factor was overweight / obesity (88.4%). After finishing the cardiac rehabilitation programmes, the LDL Cholesterol values significantly decreased (81.1 ± 28.7 vs. 76.5 ± 31.5 mg/dl; P =.03). A significant percentage of diabetics reached objectives of an Hb A1c < 7% (50% vs. 68.5%; P =.01). The abdominal circumference showed a statistically significant decrease (100.8 ± 12.8 vs. 99.5 ± 12.3 cm; P =.004). An improvement in functional capacity was observed in 89.3% of the patients. In the annual review, the majority of the parameters studied showed a slight negative trend. Just under half (47.36%) of smokers at inclusion maintained the tobacco habit at one year. Conclusions: Cardiac rehabilitation programmes improve the control of cardiovascular risk factors, changes in life style and functional capacity in patients that had suffered an acute coronary syndrome. Control strategies need to be enforced in order to maintain these benefits in the medium-long term

Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories

BACKGROUND & AIMS: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. METHODS: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. RESULTS: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. CONCLUSIONS: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened. IMPACT AND IMPLICATIONS: There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into

Adjusted estimate of the prevalence of hepatitis delta virus in 25 countries and territories

Background &amp; Aims: Hepatitis delta virus (HDV) is a satellite RNA virus that requires the hepatitis B virus (HBV) for assembly and propagation. Individuals infected with HDV progress to advanced liver disease faster than HBV-monoinfected individuals. Recent studies have estimated the global prevalence of anti-HDV antibodies among the HBV-infected population to be 5-15%. This study aimed to better understand HDV prevalence at the population level in 25 countries/territories. Methods: We conducted a literature review to determine the prevalence of anti-HDV and HDV RNA in hepatitis B surface antigen (HBsAg)-positive individuals in 25 countries/territories. Virtual meetings were held with experts from each setting to discuss the findings and collect unpublished data. Data were weighted for patient segments and regional heterogeneity to estimate the prevalence in the HBV-infected population. The findings were then combined with The Polaris Observatory HBV data to estimate the anti-HDV and HDV RNA prevalence in each country/territory at the population level. Results: After adjusting for geographical distribution, disease stage and special populations, the anti-HDV prevalence among the HBsAg+ population changed from the literature estimate in 19 countries. The highest anti-HDV prevalence was 60.1% in Mongolia. Once adjusted for the size of the HBsAg+ population and HDV RNA positivity rate, China had the highest absolute number of HDV RNA+ cases. Conclusions: We found substantially lower HDV prevalence than previously reported, as prior meta-analyses primarily focused on studies conducted in groups/regions that have a higher probability of HBV infection: tertiary care centers, specific risk groups or geographical regions. There is large uncertainty in HDV prevalence estimates. The implementation of reflex testing would improve estimates, while also allowing earlier linkage to care for HDV RNA+ individuals. The logistical and economic burden of reflex testing on the health system would be limited, as only HBsAg+ cases would be screened. Impact and implications: There is a great deal of uncertainty surrounding the prevalence of hepatitis delta virus among people living with hepatitis B virus at the population level. In this study, we aimed to better understand the burden in 25 countries and territories, to refine techniques that can be used in future analyses. We found a lower prevalence in the majority of places studied than had been previously reported. These data can help inform policy makers on the need to screen people living with hepatitis B virus to find those coinfected with hepatitis delta virus and at high risk of progression, while also highlighting the pitfalls that other researchers have often fallen into

Hepatitis B, C and Delta virus infections in Albanian patients with chronic liver disease: evaluation of possible changes during the last 10 years

Objective and methods The prevalence of viral hepatitis markers and of alcohol intake was evaluated in 106 and 99 Albanian patients with the diagnosis of viral and/or alcoholic chronic liver disease who were consecutively admitted to the University Hospital Center of Tirana, during 1995 and 2005, respectively. Results A slight decrease in HBsAg (78 vs. 70%) and HBeAg (18 vs. 12%) prevalences were observed in patients admitted to the hospital during 2005 compared with those admitted during 1995, respectively. In both periods of time, hepatitis B virus (HBV) DNA (genotype D) tested positive in all HBsAg-positive patients and in 36% of HBsAg-negative patients. Anti-hepatitis C virus (HCV) prevalence (mainly observed after 30 years of age) was 14 versus 11 %; anti-hepatitis Delta virus (HDV) prevalence (more frequently present in young age group patients) was 9 versus 7% during 1995 and 2005, respectively. Among patients who reported alcohol intake, alcoholic liver disease (HBsAg and anti-HCV negative) was diagnosed in 35 and in 57% of patients admitted during 1995 and 2005, respectively (P=0.05). Conclusion In Albanian patients with chronic liver disease, we have found that: (i) HBV remained the most important aetiologic factor of chronic liver disease; HDV and HCV prevalences were still low, (ii) in HBsAg-positive patients, HBeAg-negative chronic hepatitis prevailed, (iii) in HBsAg-negative patients, HBV DNA prevalence was high, (iv) during the last decade, an increased prevalence of alcohol intake in the aetiology of chronic liver disease was observed. Eur J Gastroenterol Hepatol 22:167-171 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins

Abstract 1017: Lipid metabolic reprogramming drives resistance to PD1 blockage

Abstract The mechanisms underlying immunosuppression and resistance to PD1 inhibitors in cancer are not well understood. We attempted to fill this gap with an integrated analysis of mRNA, microRNA, and protein expression in an anti-PD1-resistant lung adenocarcinoma mouse model. The model was created by in vivo passage of 344SQ murine lung cancer cells (p53R172HΔg/+K-rasLA1/+) in a syngeneic host repeatedly dosed with anti-mouse PD1 antibodies. Anti-PD1-resistant 344SQ (344SQ_R) and 344SQ parental (344SQ_P) cells were then inoculated into syngeneic 129Sv/ev mice, which were then dosed twice with anti-PD1 or control IgG antibodies. Tumor tissues were collected and analyzed as follows: transcriptome with Affymetrix; protein levels by reverse phase protein array analysis; signature enrichment by gene set enrichment analysis; metabolome by mass spectrometry; and lipid content with fluorescent probes Oil O rad and BODIPY. We also isolated tumor-infiltrating immune cells for flow cytometry and gene expression analyses. We identified lipid-related metabolic pathways as being the most highly enriched in anti-PD1-resistant tumors (344SQ_R) vs. their 344SQ_P counterparts; the resistant cells also had more lipid droplets than the 344SQ_P cells. The anti-PD1-resistant tumors overexpressed several genes involved in lipogenesis and fatty acid pathways (e.g., fatty acid binding proteins [FABPs], fatty acid synthase, acetyl-coA-acyltransferase 2, fatty acid elongases). Specifically, FABP overexpression promoted fatty acid uptake and lipid-droplet accumulation in resistant tumors. Lipid-sensitive targets linked to inflammation and insulin signaling (e.g,. stress-activated kinases such as JNK and NFκB) were altered in 344SQ_R vs. 344SQ_P tumors. Mechanistically, JNK downregulation by NFκB-regulated microRNAs protected PD1-resistant tumors from lipotoxicity caused by FABPs upregulation and fatty acid uptake. FABP levels were higher in plasma from 344SQ_R than from 344SQ_P tumors. Tumor-infiltrating macrophages from 344SQ_R tumors had 4 times the amount of FABP mRNA than parental tumors and a correspondingly higher percentage of M2-like macrophages. 344SQ_R tumors promoted immune suppressive cells by upregulating FABPs expression in M2-like macrophages, marked by increased fatty acid intake and fatty acid oxidation. Conversely, percentages of CD4+ and CD8+ tumor-infiltrating lymphocytes were reduced in the resistant tumors. These results suggest that lipid metabolic rewiring drives resistance PD1 inhibitors supporting the accumulation of immunosuppressive cells, including M2-like macrophages, preventing type I immune responses elicited by T cells. Collectively, these findings reveal new potential lipid-related targets for drug development or new treatments combining inhibitors of these targets with anti-PD1 therapy. Citation Format: Maria A. Cortez, Sharareh Niknam, Efrosini Cuko, Jonathan E. Schoenhals, Hampartsoum Barsoumian, Ahmed I. Younes, Ailin Li, Jody V. Vykoukal, Cristina Ivan, George A. Calin, Patrick Hwu, James W. Welsh. Lipid metabolic reprogramming drives resistance to PD1 blockage [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1017. doi:10.1158/1538-7445.AM2017-1017</jats:p