Delphine Weil

C-Reactive protein predicts short-term mortality in patients with cirrhosis

BACKGROUND & AIMS We aimed at improving prediction of short-term mortality in cirrhotic inpatients by evaluating C-reactive protein (CRP) as a surrogate marker of systemic inflammatory response syndrome (SIRS). METHODS One-hundred and forty-eight consecutive cirrhotic patients with Child-Pugh score ≥ B8 and without hepatocellular carcinoma were prospectively included and followed for 182 days. The primary end point was 6-month survival. RESULTS Main baseline characteristics were as follows: alcoholic liver disease in 88.5%; bacterial infection in 37%; hepatorenal syndrome in 7% of cases. CRP range was 1-240 mg/L (median 26 mg/L); 42 patients (28.4%) had SIRS as defined by ACCP/SCCM-criteria. CRP levels were higher in patients with SIRS (50 vs. 21 mg/L; p<0.0001), infection (46 vs. 27 mg/L; p<0.0001), and alcoholic hepatitis (44 vs. 32 mg/L, p=0.049). Forty-two patients died within the first 6 months of follow-up. Short-term mortality was associated with extrahepatic co-morbidities (p=0.002), high MELD score (p<0.001; AUROC=0.67), renal failure (p=0.008), elevated blood lactates (p<0.001), and high baseline CRP levels (p=0.003; AUROC=0.63; best cut-off value at 29 mg/L). Among patients with baseline CRP ≥ 29 mg/L, 32 still had CRP ≥ 29 mg/L at day 15 (group A). Group A was associated with 6-month mortality in the overall population (p<0.001) and also through sensitivity analyses restricted to patients without infection or alcoholic hepatitis. Multivariate analysis (Cox) adjusted for age identified three predictors of mortality: high MELD score (HR=1.08; 95% CI: 1.03-1.12; p<0.001), extrahepatic co-morbidities (HR=2.51; 95% CI: 1.31-4.84; p=0.006), and CRP level (group A) (HR=2.73; 95% CI: 1.41-5.26; p=0.003). The performance of the three variables taken together for predicting death was 0.80 (AUROC). CONCLUSIONS In Child-Pugh score ≥ B8 cirrhotic patients, persistent CRP levels ≥ 29 mg/L predicted short-term mortality independently of age, MELD, and co-morbidities, and better than infection or clinically-assessed SIRS.

Prognostic value of C-reactive protein levels in patients with cirrhosis

Identifying cirrhosis with a poor short‐term prognosis remains crucial for improving the allocation of liver grafts. The purpose of this study was to assess the prognostic value of a model combining the variation of C‐reactive protein (CRP) levels within 15 days, the Model for End‐Stage Liver Disease (MELD) score, and the presence of comorbidities in patients with decompensated cirrhosis with a Child‐Pugh score > B7 and to test the relevance of this model in patients with compensated cirrhosis. We collected data for cirrhotic patients without hepatocellular carcinoma, extrahepatic malignancy, human immunodeficiency virus infection, organ transplantation, seen between January 2010 and December 2011. Multivariate analyses of predictors of 3‐month mortality used Cox models adjusted with the age‐adjusted Charlson comorbidity index. The prognostic performance [area under receiver operating characteristic curves (AUROCs)] of the 3‐variable model was compared to that of the MELD score. The 241 patients who met the inclusion criteria included 109 patients with a Child‐Pugh score > B7 who were hospitalized for decompensation. In these patients with severe cases, the 3‐month mortality was independently predicted by the MELD score [hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.05‐1.14; P < 0.001] and a CRP level > 32 mg/L at the baseline and on day 15 (HR, 2.21; 95% CI, 1.03‐4.76; P = 0.042). This model was better than MELD alone (AUROC, 0.789 versus 0.734; P = 0.043). In the whole population with cirrhosis, the 3‐month mortality was also predicted by high MELD scores (HR, 1.11; 95% CI, 1.07‐1.16; P < 0.001) and a CRP level > 10 mg/L at the baseline and on day 15 (HR, 2.89; 95% CI, 1.29‐6.48; P < 0.001), but the AUROCs of the 3‐variable model and the MELD score alone were no longer significantly different (0.89 versus 0.88, not significant). In conclusion, prognostic models incorporating variations in CRP predict 3‐month mortality in patients with cirrhosis. Such models are particularly relevant for patients with decompensated cirrhosis but provide a limited increase in prediction in comparison with the MELD score in the whole population with cirrhosis. Liver Transpl 21:753–760, 2015.

High serum levels of free cortisol indicate severity of cirrhosis in hemodynamically stable patients

Background and Aim:  We investigated: (i) the association between severity of cirrhosis and serum levels of free cortisol (SFC) and total cortisol (STC), measured before and 30 min after (T30) the low‐dose 1‐µg short synacthen test (LD‐SST); and (ii) the prognostic value of SFC and STC.

Improved survival of cirrhotic patients with variceal bleeding over the decade 2000–2010

BACKGROUND AND OBJECTIVE Advances in the management of variceal bleeding (VB) have been highlighted recently. We aimed at assessing whether changing the management of VB has improved the outcome (mortality and rebleeding rates). METHODS The files of two cohorts (n=57, 2000-2001 and n=64, 2008-2009) of patients referred to our university center were reviewed after a cross-searching using two coding systems. Data were recorded during the six months after VB. RESULTS As compared to 2000-2001, more use of general anesthesia (25.4% vs. 11.1%; P=0.049), band ligations (96.1% vs. 71.4%; P=0.001), octreotide (95.3% vs. 80.7%; P=0.012) and antibiotic prophylaxis (93.8% vs. 82.5%; P=0.09) were performed in 2008-2009, whereas the number of red-cell units transfused during the hospital stay (4.3 ± 3.2 vs. 7.1 ± 5.7; P=0.005) decreased. Surprisingly, more than 60% of patients reached the emergency department from home without medical assistance in both periods. In 2008-2009, patients had more comorbidities and no patients underwent early-TIPS but the 6-week mortality rate (24.6% vs.10.9%; P=0.048) was lower. The 6-week mortality was associated with high MELD score (HR=1.13; 95%CI: 1.08-1.18) and hypovolemic shock (HR=5.36; 95%CI: 1.96-14.67) at admission. In multivariate analysis adjusted on MELD and comorbidities, the 2008-2009 period (HR: 0.42; 95%CI: 0.20-0.87; P=0.02) was associated with a lower 6-month mortality rate. CONCLUSIONS Although cirrhotic patients with VB had more comorbidities in 2008-2009 and received no early-TIPS, their prognosis has improved during this last decade concomitantly to a more intensive care and a lower transfusion strategy.

The Periscreen Strip Is Highly Efficient for the Exclusion of Spontaneous Bacterial Peritonitis in Cirrhotic Outpatients

Objectives:We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP).Methods:Ascitic fluid (AF) of cirrhotic patients hospitalized between March 2014 and August 2015 was independently tested by two readers using the new strip, which has four colorimetric graduations (negative, trace, small, and large). SBP was diagnosed on neutrophils in ascites>250/mm3. Ascites not related to portal hypertension were excluded.Results:Overall, 649 patients from 21 French centers were included and 1,402 AF (803 AF samples from 315 outpatients and 599 samples from 334 inpatients) were assessed. Eighty-four AF samples (17 AF in 9 outpatients and 67 AF in 31 inpatients) were diagnosed as SBP. The prevalence of SBP was 6% (2.1% in outpatients vs. 11.2% in inpatients; P<0.001) and 7.2% in patients with symptoms suggestive of SBP (3% in outpatients vs. 11.3% in inpatients; P<0.001). The κ value for inter-reader agreement was 0.81 (95% confidence interval: 0.77–0.84) when using the “trace” threshold. Considering discordant results (n=131) as positive to interpret the diagnostic performance of the strip at the “trace” threshold, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 91.7, 57.1, 12.0, and 99.1%, respectively. At this “trace” threshold, sensitivity and NPV were both 100% in outpatients, and 89.5 and 97.9% in inpatients, respectively. At the “small” threshold, sensitivity, specificity, PPV and NPV were 81.0, 85.9, 25.9 and 98.7%, respectively.Conclusions:The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.

Copeptin is an independent prognostic factor for transplant-free survival in cirrhosis.

Copeptin is a stable cleavage product of the arginine vasopressin (AVP) precursor and is equimolarly secreted with AVP. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. We aimed to investigate the association between severity of cirrhosis and copeptin concentrations and to confirm whether copeptin is of prognostic significance in cirrhosis.

Accuracy of calprotectin using the Quantum Blue Reader for the diagnosis of spontaneous bacterial peritonitis in liver cirrhosis: Calprotectin and spontaneous bacterial peritonitis

We aimed to evaluate the accuracy of the dosage of calprotectin in ascitic fluid (AF) using the Quantum Blue assay, for the prompt diagnosis of spontaneous bacterial peritonitis (SBP).

Are we still searching for the fifth element of MELD

level of CRP had the worst prognosis [7,8]. Prospective studies providing serial copeptin measurements to evaluate the potential effects on survival of variations in serum copeptin concentrations over time are still lacking. Like CRP, a persistently high level of plasma copeptin may be harmful, especially for the heart. Indeed, chronic overexpression of the V1A receptor (or persistent stimulation of these receptors) may lead to cardiac dysfunction by remodeling the myocardium via V1A receptors on cardiac myocytes [9]. Cardiac dysfunction, reflected by an altered cardiac index, predicts the development of hepatorenal syndrome, a condition associated with significantly increased mortality in cirrhotic patients [10]. Consequently, it would not be surprising that a long-standing increase in copeptin may accurately predict death. For future research, it would be interesting to investigate the effect of V1A-selective vasopressin antagonists in cirrhotic patients with high levels of copeptin (i.e., vasopressin). We wonder whether prognostic models using CRP would be as well fitted as those built with leukocyte count in the study by Solà [1]. Patients included in this latter cohort study had a complication of liver cirrhosis but did not suffer from acute on chronic liver failure (ACLF), as previously defined [3]. it would be interesting to investigate whether there is an association between copeptin levels and the risk of development of ACLF in patients admitted for acute decompensation of cirrhosis, since ACLF is the most common cause of death in patients with decompensated cirrhosis. We also suggest assessing copeptin in the ‘‘selected population” of cirrhotic patients waiting for liver transplantation, because we need to know whether copeptin may improve the efficacy of MELD for prioritizing candidates for transplantation according to the ‘‘sickest first” policy.

L’hypertension porto-pulmonaire en 2016

L’hypertension porto-pulmonaire (HTPP) est definie par une hypertension arterielle pulmonaire (HTAP) precapillaire associee a une hypertension portale (avec ou sans cirrhose). Le diagnostic de l’HTAP repose sur le catheterisme cardiaque droit mettant en evidence une pression arterielle pulmonaire (PAP) moyenne ≥ 25 mmHg au repos, une PAP occluse ≤ 15 mmHg et des resistances vasculaires pulmonaires > 240 dyn.s.cm-5. La prevalence de l’HTPP est estimee entre 2 % et 6 %. Sa physiopathologie associe des phenomenes de vasoconstriction et surtout de remodelage vasculaire conduisant progressivement a l’obstruction des arteres pulmonaires de petit calibre. La dyspnee est souvent de revelation tardive. Le depistage precoce de cette maladie par l’echocardiographie Doppler est recommande pour tous les patients cirrhotiques en attente de greffe de foie. La prise en charge de l’HTPP devrait associer l’expertise des hepatologues, des anesthesistes et des centres de competence de l’hypertension pulmonaire car nous ne disposons pas d’attitude therapeutique bien validee par des essais controles. Les anticoagulants sont le plus souvent contre-indiques du fait des troubles de la coagulation inherents a la cirrhose. Les beta-bloquants sont a eviter car ils peuvent diminuer les capacites fonctionnelles et aggraver l’hemodynamique. Nous disposons actuellement de trois classes de traitements specifiques de l’HTPP : les analogues de la prostacycline, les antagonistes des recepteurs de l’endotheline-1 et les inhibiteurs de la phosphodiesterase de type 5. La presence d’une HTPP peut dans certains cas faire contre-indiquer une transplantation hepatique (TH). Neanmoins, lorsqu’une TH est indiquee en raison de la severite de l’atteinte hepatique, les traitements medicaux de l’HTAP permettent parfois d’ameliorer suffisamment l’hemodynamique pour autoriser une TH sans majoration du risque cardio-vasculaire.

Le syndrome de réponse inflammatoire systémique (SRIS) : un facteur pronostique majeur au cours de la cirrhose

La reaction inflammatoire, lorsqu’elle est limitee a l’organe lese, est benefique car elle concourt au processus de cicatrisation. Lorsqu’elle se generalise a l’ensemble de l’organisme et donne lieu au syndrome de reponse inflammatoire systemique (SRIS), le relargage massif de cytokines pro-inflammatoires et l’activation deregulee des cellules de l’immunite peuvent conduire a une perte de l’homeostasie et a une defaillance multiviscerale. Les modifications physiopathologiques (notamment la translocation bacterienne) induites par la cirrhose sur la reponse inflammatoire, sur l’etat hemodynamique et sur l’hemostase semblent propices a la survenue ou a l’exacerbation d’un SRIS. La valeur pejorative du SRIS a ete largement demontree chez les patients hospitalises en reanimation. Au cours de la cirrhose, le SRIS pourrait aussi constituer un facteur pronostique majeur. Ainsi la presence d’un SRIS est frequente chez les patients hospitalises pour une complication de cirrhose et celui-ci est associe aux risques d’apparition ou d’aggravation d’une encephalopathie, de developpement d’un syndrome hepato-renal, et de deces intra-hospitalier. Sa detection precoce ou la validation de marqueurs de SRIS (tels que la C-reactive proteine) pourraient ouvrir de nouvelles perspectives dans la prise en charge des patients cirrhotiques a haut risque de complications.