Absolute quantification of microparticles by flow cytometry in ascites of patients with decompensated cirrhosis: a cohort study

Background: Microparticles (MPs) are small (488.4 MP/mu L 94.7%, log rank p = 0.001) and such patients had a higher relative amount of ascites microparticles derived from neutrophils and lymphocytes. Low levels of ascites MPs, high MELD score and antibiotic treatment were independent risk factors for death within 30 days. Conclusions: Ascites MP levels predict short-term survival along with the liver function in patients with decompensated cirrhosis. Further studies which evaluate ascites MPs as disease specific biomarker with a validation cohort and which investigate its underlying mechanisms are needed. Neutrophils and lymphocytes contributed more frequently to the release of microparticles in patients with low ascites levels, possibly indicating an immune activation in this cohort

Two‐year outcomes in initial survivors with acute liver failure: results from a prospective, multicentre study

Background & AimsThe long‐term clinical outcomes in initial survivors with acute liver failure (ALF) are not well known. The aim of this study was to provide an overview of the 2‐year clinical outcomes among initial survivors and liver transplant (LT) recipients that were alive 3 weeks after enrolment in the Acute Liver Failure Study Group (ALFSG).MethodsOutcomes in adult ALFSG patients that were enrolled between 1998 and 2010 were reviewed.ResultsTwo‐year patient survival was significantly higher in the 262 LT recipients (92.4%) compared to the 306 acetaminophen (APAP) spontaneous survivors (SS) (89.5%) and 200 non‐APAP SS (75.5%) (P < 0.0001). The causes of death were similar in the three groups but the time to death was significantly longer in the LT recipients (P < 0.0001). Independent predictors of 2‐year mortality in the APAP group were a high serum phosphate level and patient age (c‐statistic = 0.65 (0.54, 0.76)), patient age and days from jaundice to ALF onset in the non‐APAP group (c‐statistic = 0.69 (0.60, 0.78)), and patient age, days from jaundice, and higher coma grade in the LT recipients (c‐statistic = 0.74 (0.61, 0.87)). The LT recipients were significantly more likely to be employed and have a higher educational level (P < 0.05).ConclusionsTwo‐year outcomes in initial survivors of ALF are generally good but non‐APAP patients have a significantly lower survival which may relate to pre‐existing medical comorbidities. Spontaneous survivors with APAP overdose experience substantial morbidity during follow‐up from ongoing psychiatric and substance abuse issues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/110589/1/liv12632.pd

Acute extrahepatic infectious or inflammatory diseases are a cause of transient mosaic pattern on CT and MR imaging related to sinusoidal dilatation of the liver

Purpose: To report the association of a mosaic enhancement pattern on contrast-enhanced CT or MR imaging and hepatic sinusoidal dilatation (SD) with acute inflammatory conditions affecting extrahepatic organs. Methods: From 2007 to 2012, patients with acute inflammatory diseases who underwent contrast-enhanced CT and/or MRI of the liver with a mosaic enhancement pattern were selected. Clinico-biological and other imaging features were collected at diagnosis and during follow-up. Results: Sixteen patients were included (15 women, median age 27\ua0years; range 18\u201368). Five women (33\ua0%) were receiving oral contraceptives. Acute inflammatory diseases included pyelonephritis (n = 10), pancreatitis (n = 2), pneumonia (n = 1), septicemia (n = 1), active Crohn's disease (n = 1), and infectious colitis (n = 1). Median white blood cell count was 13,250 cells/\u3bcL (range 11,500-18,000 cells/\u3bcL) and CRP level 94\ua0mg/L (range 60\u2013121\ua0mg/L). Mosaic enhancement pattern was present in the whole liver and was prominent in the subcapsular areas. Four patients underwent liver biopsy confirming SD. Eleven patients underwent follow-up imaging showing normalized aspect in 9/11 patients after a median of 2\ua0months. Conclusion: Acute diseases of extrahepatic organs, associated with a marked systemic inflammatory syndrome should be added to the list of conditions causing a reversible hepatic sinusoidal dilatation as manifested by a mosaic enhancement pattern on contrast-enhanced CT or MR imaging. Key Points: \u2022 Acute extrahepatic infectious/inflammatory diseases are a cause of transient MP. \u2022 In most patients, MP was seen during both arterial and portal venous phase. \u2022 In all patients, the mosaic enhancement pattern was diffuse, but more conspicuous in subcapsular areas. \u2022 MP was no longer seen after resolution of the acute disease. \u2022 No liver biopsy should be performed

Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B virus infection, and 21 with no or mild liver abnormalities at histological examination) were included. Autophagy was assessed by means of electron microscopy and microtubule-associated protein light chain 3 immunoblotting. Using light chain 3 immunoblotting, the form present on autophagic vesicle (light chain 3-II) was significantly higher in CHC patients than in controls (P < 0.05). Using quantitative electron microscopy analysis, the median number of autophagic vesicles observed in hepatocytes from CHC patients was sixfold higher than in overall controls (P < 0.001). In contrast, there was no difference between CHC patients and controls in the number of mature lysosomes with electron-dense contents arguing in favor of a lack of fusion between autophagosome and lysosome. Neither genotype nor viral load influenced the autophagy level. In conclusion, autophagy is altered in hepatocytes from CHC patients, likely due to a blockade of the last step of the autophagic process

EASL-ERN position paper on liver involvement in patients with Fontan-type circulation

Fontan-type surgery is the final step in the sequential palliative surgical treatment of infants born with a univentricular heart. The resulting long-term haemodynamic changes promote liver damage, leading to Fontan-associated liver disease (FALD), in virtually all patients with Fontan circulation. Owing to the lack of a uniform definition of FALD and the competitive risk of other complications developed by Fontan patients, the impact of FALD on the prognosis of these patients is currently debatable. However, based on the increasing number of adult Fontan patients and recent research interest, the European Association for The Study of the Liver and the European Reference Network on Rare Liver Diseases thought a position paper timely. The aims of the current paper are: (1) to provide a clear definition and description of FALD, including clinical, analytical, radiological, haemodynamic, and histological features; (2) to facilitate guidance for staging the liver disease; and (3) to provide evidence- and experience-based recommendations for the management of different clinical scenarios.</p

Hepatocyte tissue factor contributes to the hypercoagulable state in a mouse model of chronic liver injury

BACKGROUND & AIMS: Patients with chronic liver disease and cirrhosis have a dysregulated coagulation system and are prone to thrombosis. The basis for this hypercoagulable state is not completely understood. Tissue factor (TF) is the primary initiator of coagulation in vivo. Patients with cirrhosis have increased TF activity in white blood cells and circulating microparticles. The aim of our study was to determine the contribution of TF to the hypercoagulable state in a mouse model of chronic liver injury. METHODS: We measured levels of TF activity in the liver, white blood cells and circulating microparticles, and a marker of activation of coagulation [thrombinantithrombin complexes (TATc)] in the plasma of mice subjected to bile duct ligation for 12 days. We used wild-type mice, mice with a global TF deficiency (low TF mice), and mice deficient for TF in either myeloid cells (TF(flox/flox), LysM(Cre) mice) or in hepatocytes (TF(flox/flox), Alb(Cre)). RESULTS: Wild-type mice with liver injury had increased levels of white blood cell, microparticle TF activity and TATc compared to sham mice. Low TF mice and mice lacking TF in hepatocytes had reduced levels of TF in the liver and in microparticles and exhibited reduced activation of coagulation without a change in liver fibrosis. In contrast, mice lacking TF in myeloid cells had reduced white blood cell TF but no change in microparticle TF activity or TATc. CONCLUSIONS: Hepatocyte TF activates coagulation in a mouse model of chronic liver injury. TF may contribute to the hypercoagulable state associated with chronic liver diseases in patients

Behcet's disease in Budd-Chiari syndrome.

International audienceBackground/aimsBehcet's disease (BD) is a well-known cause of Budd-Chiari syndrome (BCS). Data are lacking on the presentation and outcome of BCS related to BD.MethodsWe investigated the relationship between BD and BCS in 14 patients with both diseases and compared the results to 92 BCS patients without BD.ResultsMale gender (p=0.003), North African origin (P=0.007) and inferior vena cava obstruction (P <0.0001) were more frequent in patients with BD and BCS than in those with BCS alone and the plasma C-reactive protein level was higher (p=0.003). Two of the patients with the combined diseases underwent recanalization of the vena cava and the hepatic veins, none received transjugular intrahepatic portosystemic shunts (TIPS), one received a surgical shunt and one underwent liver transplantation. TIPS were less frequent in patients with BD and BCS than in those with BCS alone (P=0.019). Eighty six per cent of patients with BCS and BD received corticosteroids and immunosuppressive therapy. The 5-year transplantation-free survival rate was 63% in patients with BCS alone and 91% in those without BD (P=0.11). In our series and in the literature, a high number of patients [12 (61.5%) and 11 (64.7%) respectively] treated with anticoagulation and corticosteroids and/or immunosuppressants did not require invasive treatment.ConclusionThis study shows a higher frequency of IVC obstruction in patients with BCS and BD. Medical treatment with anticoagulation and immunosuppressive agents may improve the symptoms of BCS. Therefore early management with immunosuppressive and anticoagulation therapy appears to be the treatment of choice in patients with BCS and BD