Alcoholic hepatitis (AH) is a life-threatening condition characterized by profound hepatocellular dysfunction for which targeted treatments are urgently needed. Identification of molecular drivers is ...hampered by the lack of suitable animal models. By performing RNA sequencing in livers from patients with different phenotypes of alcohol-related liver disease (ALD), we show that development of AH is characterized by defective activity of liver-enriched transcription factors (LETFs). TGFβ1 is a key upstream transcriptome regulator in AH and induces the use of HNF4α P2 promoter in hepatocytes, which results in defective metabolic and synthetic functions. Gene polymorphisms in LETFs including HNF4α are not associated with the development of AH. In contrast, epigenetic studies show that AH livers have profound changes in DNA methylation state and chromatin remodeling, affecting HNF4α-dependent gene expression. We conclude that targeting TGFβ1 and epigenetic drivers that modulate HNF4α-dependent gene expression could be beneficial to improve hepatocellular function in patients with AH.
The aim of this study was to identify a readily available, reproducible, and internationally applicable cost assessment tool for surgical procedures.
Strong economic pressure exists worldwide to slow ...down the rising of health care costs. Postoperative morbidity significantly impacts on cost in surgical patients. The comprehensive complication index (CCI), reflecting overall postoperative morbidity, may therefore serve as a new marker for cost.
Postoperative complications and total costs from a single tertiary center were prospectively collected (2014 to 2016) up to 3 months after surgery for a variety of abdominal procedures (n = 1388). CCI was used to quantify overall postoperative morbidity. Pearson correlation coefficient (rpears) was calculated for cost and CCI. For cost prediction, a linear regression model based on CCI, age, and type of surgery was developed and validated in an international cohort of patients.
We found a high correlation between CCI and overall cost (rpears = 0.75) with the strongest correlation for more complex procedures. The prediction model performed very well (R = 0.82); each 10-point increase in CCI corresponded to a 14% increase to the baseline cost. Additional 12% of baseline cost must be added for patients older than 50 years, or 24% for those over 70 years. The validation cohorts showed a good match of predicted and observed cost.
Overall postoperative morbidity correlates highly with cost. The CCI together with the type of surgery and patient age is a novel and reliable predictor of expenses in surgical patients. This finding may enable objective cost comparisons among centers, procedures, or over time obviating the need to look at complex country-specific cost calculations (www.assessurgery.com).
The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in ...different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.
A decade ago we proposed to enlist for transplantation those patients with resected hepatocellular carcinoma in whom pathology registered pejorative histological markers (microvascular invasion ...and/or satellites; ab initio indication) and not wait for the appearance of recurrence. This study evaluates the outcome of this approach. From 1995 to 2012, 164 patients with hepatocellular carcinoma underwent resection. Eighty‐five patients were potential candidates for liver transplantation and were considered for it upon detection of pejorative histological markers. Patients without these markers were followed, and salvage liver transplantation was considered upon development of tumor recurrence/liver function impairment. Thirty‐seven patients were at high risk and 48 at low risk of recurrence at pathology. Twenty‐three out of 37 high‐risk patients recurred during follow‐up, but in nine of them the tumor burden extent contraindicated liver transplantation. Seventeen were finally transplanted: 10 of them presented recurrence at imaging/explant. After a median posttransplant follow‐up of 50.9 months, hepatocellular carcinoma had recurred in two patients and five patients had died, the 5‐year survival being 82.4%. Twenty‐six of the 48 low‐risk patients developed recurrence, and 11 of them were transplanted. After a median posttransplant follow‐up of 59 months, two patients developed recurrence and five died, their 5‐year survival being 81.8%. Conclusion: Enlistment of patients at high risk of HCC recurrence after resection but before recurrence development seems a valid strategy and is associated with excellent long‐term outcome; as early (<6 months) recurrence reflects an aggressive tumor behavior leading to tumor extent exceeding transplant criteria, we propose to wait at least 6 months before enlistment; however, once included on the waiting list, priority strategies should be implemented in order to reach effective transplantation prior to the appearance of recurrence. (Hepatology 2016;63:839–849)
Summary
There are scarce data on the impact of COVID‐19 pandemic on liver transplantation (LT) in Europe. The aim of this study was to obtain a preliminary data on incidence, management, and outcome ...of COVID‐19 in liver transplant recipients and candidates in Europe. An Internet‐based survey was sent to the centers affiliated with European Liver Transplant Registry (ELTR). One hundred nine out of 149 (73%) of ELTR centers located in 28 European countries (93%) responded. Ninety‐four (86%) of the centers tested all donors, and 75 (69%) centers tested all LT recipients for SARS‐CoV‐2. Seventy‐three (67%) centers selected recipients for LT in the COVID‐19 pandemic, whereas 33% did not. Eighty‐eight centers reported COVID‐19 infection in 57 LT candidates and in 272 LT recipients. Overall crude incidence of COVID‐19 among LT candidates and recipients was estimated 1.05% (range 0.5–20%) and 0.34% (range 0.1–4.8%), respectively, and it was significantly higher among candidates (P < 0.001). Crude rate of death was 18% (10/57) among candidates and 15% (36/244) among recipients. This first large‐scale European snapshot study clearly shows that both LT candidates and recipients are at a high risk for COVID‐19. These results plead for an early and pro‐active screening of COVID‐19 symptoms in these populations.
The pool of livers for transplantation consists of an increasingly greater proportion of marginal grafts, in particular those arising through donation after circulatory determination of death (DCD). ...However, a primary factor limiting the use of marginal livers, and, thereby, the applicability of liver transplantation in general, is concern over the subsequent development of ischemic‐type biliary lesion (ITBL). ITBL is a devastating complication of liver transplantation; in its most severe forms, recipients suffer frequent infectious complications that require repeated invasive biliary procedures and ultimately result in either retransplantation or death. In the present review article, we discuss our current understanding of ITBL pathogenesis as it pertains to DCD, in particular. We discuss the most relevant theories regarding its development and provide a comprehensive overview of the most promising strategies we have available today to prevent the appearance of ITBL, strategies that may, furthermore, allow us to transplant a greater proportion of marginal livers in the future. Liver Transplantation 22 1025–1033 2016 AASLD
Xanthogranulomatous cholecystitis(XGC) is an uncommon variant of chronic cholecystitis. The perioperative findings in aggressive cases may be indistinguishable from those of gallbladder or biliary ...tract carcinomas. Three patients presented mass lesions that infiltrated the hepatic hilum,provoked biliary dilatation and jaundice,and were indicative of malignancy. Surgical excision was performed following oncological principles and included extirpation of the gallbladder,extrahepatic bile duct,and hilar lymph nodes,as well as partial hepatectomy. Postoperative morbidity was minimal. Surgical pathology demonstrated XGC and absence of malignancy in all three cases. All three patients are alive and well after years of follow-up. XGC may have such an aggressive presentation that carcinoma may only be ruled out on surgical pathology. In such cases,the best option may be radical resection following oncological principles performed by expert surgeons,in order that postoperative complications may be minimized if not avoided altogether.
Over the course of the COVID19 pandemic, global healthcare delivery has declined. Surgery is one of the most resource-intensive area of medicine; loss of surgical care has had untold health and ...economic consequences. Herein, we evaluate resource utilization, outcomes, and healthcare costs associated with unplanned surgery admissions during the height of the pandemic in 2020 versus the same period in 2019. Retrospective analysis on patients greater than or equal to18 years admitted from the emergency department to General & Digestive and Gastrointestinal Surgery Services between February and May 2019 and 2020 at our center; clinical outcomes and unadjusted and adjusted per-person healthcare costs were analyzed. Consults and admissions to surgery declined between February and May 2020 by 37% and 19%, respectively, relative to the same period in 2019, with even greater relative decline during late March and early April. Time between onset of symptoms to diagnosis increased from 2±3 days 2019 to 5±22 days 2020 (P = 0.01). Overall hospital stay was two days less in 2020 (P = 0.19). Complications (Comprehensive Complication Index 10.3±23.7 2019 vs. 13.9±25.5 2020, P = 0.10) and mortality rates (3% vs. 4%, respectively, P = 0.58) did not vary. Mean unadjusted per-person costs for patients in the 2019 and 2020 cohorts were 5,886.72euro±12,576.33euro and 5,287.62±7,220.16euro, respectively (P = 0.43). Following multivariate analysis, costs remained similar (4,656.89euro±390.53euro 2019 vs. 4,938.54±406.55euro 2020, P = 0.28). Healthcare delivery and spending for unplanned general surgery admissions declined considerably due to COVID19. These results provide a small yet relevant illustration of clinical and economic ramifications of this healthcare crisis.
Somatostatin and the "Small-For-Size" Liver Hessheimer, Amelia J; Martínez de la Maza, Lilia; Adel Al Shwely, Farah ...
International journal of molecular sciences,
05/2019, Letnik:
20, Številka:
10
Journal Article
Recenzirano
Odprti dostop
"Small-for-size" livers arising in the context of liver resection and transplantation are vulnerable to the effects of increased portal flow in the immediate postoperative period. Increased portal ...flow is an essential stimulus for liver regeneration. If the rise in flow and stimulus for regeneration are excessive; however, liver failure and patient death may result. Somatostatin is an endogenous peptide hormone that may be administered exogenously to not only reduce portal blood flow but also offer direct protection to different cells in the liver. In this review article, we describe key changes that transpire in the liver following a relative size reduction occurring in the context of resection and transplantation and the largely beneficial effects that peri-operative somatostatin therapy may help achieve in this setting.
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