Search

Background & Aims: Refining hepatocellular carcinoma (HCC) surveillance programs requires improved individual risk prediction. Thus, we aimed to develop algorithms based on machine learning approaches to predict the risk of HCC more accurately in patients with HCV-related cirrhosis, according to their virological status., Methods: Patients with compensated biopsy-proven HCV-related cirrhosis from the French ANRS CO12 CirVir cohort were included in a semi-annual HCC surveillance program. Three prognostic models for HCC occurrence were built, using (i) Fine-Gray regression as a benchmark, (ii) single decision tree (DT), and (iii) random survival forest for competing risks survival (RSF). Model performance was evaluated from C-indexes validated externally in the ANRS CO22 Hepather cohort (n = 668 enrolled between 08/2012-01/2014)., Results: Out of 836 patients analyzed, 156 (19%) developed HCC and 434 (52%) achieved sustained virological response (SVR) (median follow-up 63 months). Fine-Gray regression models identified 6 independent predictors of HCC occurrence in patients before SVR (past excessive alcohol intake, genotype 1, elevated AFP and GGT, low platelet count and albuminemia) and 3 in patients after SVR (elevated AST, low platelet count and shorter prothrombin time). DT analysis confirmed these associations but revealed more complex interactions, yielding 8 patient groups with varying cancer risks and predictors depending on SVR achievement. On RSF analysis, the most important predictors of HCC varied by SVR status (non-SVR: platelet count, GGT, AFP and albuminemia; SVR: prothrombin time, ALT, age and platelet count). Externally validated C-indexes before/after SVR were 0.64/0.64 [Fine-Gray], 0.60/62 [DT] and 0.71/0.70 [RSF]., Conclusions: Risk factors for hepatocarcinogenesis differ according to SVR status. Machine learning algorithms can refine HCC risk assessment by revealing complex interactions between cancer predictors. Such approaches could be used to develop more cost-effective tailored surveillance programs., Lay Summary: Patients with HCV-related cirrhosis must be included in liver cancer surveillance programs, which rely on ultrasound examination every 6 months. Hepatocellular carcinoma (HCC) screening is hampered by sensitivity issues, leading to late cancer diagnoses in a substantial number of patients. Refining surveillance periodicity and modality using more sophisticated imaging techniques such as MRI may only be cost-effective in patients with the highest HCC incidence. Herein, we demonstrate how machine learning algorithms (i.e. data-driven mathematical models to make predictions or decisions), can refine individualized risk prediction., Competing Interests: Conflict of interest Dr. Nahon has received honoraria from and/or consults for Abbvie, AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Gilead, Ipsen, MSD, Roche. He received research grants from Abbvie and Bristol-Myers Squibb. Dr. Pol consults for and has received grants from Bristol-Myers Squibb, Gilead, Roche, and MSD. He consults for Gilead, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Abbvie, Roche and MSD. Dr. Guyader has received honoraria and/or grants from Abbvie, Gilead, Janssen and MSD. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background & Aims: Retrospective studies have found an unexpectedly high incidence of hepatocellular carcinoma (HCC) among patients with hepatitis C virus (HCV)-associated cirrhosis who received direct-acting antiviral (DAA) agents. We analyzed data from the ANRS CO12 CirVir cohort to compare the incidence of HCC in patients with cirrhosis who received DAA therapy vs patients treated with interferon (IFN)., Methods: Data were collected from 1270 patients with compensated biopsy-proven HCV-associated cirrhosis recruited from 2006 through 2012 at 35 centers in France. For descriptive purpose, patients were classified as follows: patients who received DAA treatment (DAA group, n = 336), patients who achieved a sustained virologic response (SVR) following an IFN-based regimen (SVR-IFN group, n = 495), or patients who never received DAA treatment and never had an SVR following IFN therapy (non-SVR group, n = 439). The patients were included in HCC surveillance programs based on ultrasound examination every 6 months, and clinical and biological data were recorded. To account for confounding by indication due to differences in patient characteristics at treatment initiation, we constructed a time-dependent Cox regression model weighted by the inverse probability of treatment and censoring (IPTCW) to assess the treatment effects of DAA on time until HCC., Results: Compared with patients in the SVR-IFN group, patients in the DAA group were older, higher proportions had diabetes or portal hypertension, and liver function was more severely impaired. The crude 3-year cumulative incidences of HCC were 5.9% in the DAA group, 3.1% in the SVR-IFN group, and 12.7% in the non-SVR group (overall P < .001; unadjusted hazard ratio [HR] for HCC 2.03; 95% confidence interval [CI] 1.07-3.84; P = .030 for the DAA group vs the SVR-IFN group). HCC characteristics were similar among groups. Among patients with HCC, the DAA group received less-frequent HCC screening than the other 2 groups (P = .002). After Cox analyses weighted by the IPTCW, we found no statistically significant increase in risk of HCC associated with DAA use (HR 0.89; 95% CI 0.46-1.73; P = .73)., Conclusions: Analysis of data from the ANRS CO12 CirVir cohort reveals that the apparent increase in HCC incidence observed in patients with cirrhosis treated with DAAs compared with patients who achieved SVR following an IFN therapy can be explained by patient characteristics (age, diabetes, reduced liver function) and lower screening intensity., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Data on extrahepatic cancers (EHCs) in compensated viral cirrhosis are limited. The objective of the prospective multicenter Agence Nationale de Recherche sur le SIDA et les Hépatites virales CO12 CirVir cohort was to assess the occurrence of all clinical events in patients with compensated viral cirrhosis, including all types of cancer. Patients with the following inclusion criteria were enrolled in 35 French centers: (1) biopsy-proven hepatitis B virus (HBV) or hepatitis C virus (HCV) cirrhosis, (2) Child-Pugh A, or (3) absence of previous liver complications including primary liver cancer (PLC). Patients were followed up prospectively every 6 months. The standardized mortality ratio (SMR) was calculated according to age and gender using 5-year periods. The impact of sustained viral response (SVR) in HCV patients and maintained viral suppression in HBV patients were assessed using time-dependent analysis. A total of 1,671 patients were enrolled between 2006 and 2012 (median age, 54.9 years; men, 67.3%; HCV, 1,323; HBV, 317; HCV-HBV, 31). Metabolic features and excessive alcohol and tobacco consumption were recorded in 15.2%, 36.4%, and 56.4% of cases, respectively. After a median follow-up of 59.7 months, 227 PLCs were diagnosed (5-year cumulative incidence [CumI] 13.4%) and 93 patients developed EHC (14 patients with lymphoid or related tissue cancer and 79 with solid tissue cancer; 5-year EHC CumI, 5.9%). Compared to the general French population, patients were younger at cancer diagnosis, with significantly higher risk of EHC in HCV patients (SMR, 1.31; 95 confidence interval [CI], 1.04-1.64; P = 0.017) and after SVR (SMR = 1.57; 95% CI, 1.08-2.22; P = 0.013). EHC was the fourth leading cause of death in the whole cohort and the first in patients with viral control/eradication., Conclusion: Compared to the general French population, HCV cirrhosis is associated with a higher risk of EHC and the first cause of death in patients with viral cirrhosis who achieve virological control/eradication. (Hepatology 2018)., (© 2018 by the American Association for the Study of Liver Diseases.)

Background & Aims: Semi-annual surveillance for hepatocellular carcinoma (HCC) is recommended for patients with cirrhosis. We aimed to determine how compliance with HCC surveillance guidelines affects survival times of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis who developed HCC., Methods: We collected data from the prospective ANRS CO12 CirVir study, from March 2006 through June 2012, on 1671 patients with biopsy-proven viral cirrhosis and no previous liver complications who were undergoing surveillance for HCC at 35 centers in France. Only 216 patients who developed HCC during the follow-up period were included in the analysis. Patients were considered to be compliant with surveillance guidelines if the time between their last surveillance image evaluation and diagnosis of HCC were fewer than 7 months and noncompliant if this time was 7 months or longer., Results: HCC was detected in 216 patients, at a median follow-up time of 59.7 months. Of these patients, 140 (80.5%) were Barcelona Clinic Liver Cancer stage 0/A, 135 (69.9%) received first-line curative treatment (15 underwent transplantation, 29 underwent resection, 89 received percutaneous ablation, and 2 received resection and percutaneous ablation), and 129 (60.0%) were compliant with surveillance guidelines. Seventy-nine of the patients with HCC died; 49 deaths were associated with tumor progression. After lead-time adjustment, overall survival (OS) time was longer in patients compliant with surveillance guidelines (median OS time, 53.2 months) than noncompliant patients (median OS time, 25.4 months) (P = .0107); this difference remained significant even when we changed lead time assumptions. In multivariate analysis adjusted for a propensity score, compliance with HCC surveillance guidelines was associated with low tumor burden, allocation of curative treatment, and increased OS time compared with noncompliance (hazard ratio for OS, 2.19; 95% confidence interval, 1.16-4.14; P = .0150)., Conclusions: In an analysis of data from the ANRS CO12 CirVir cohort, we associated compliance with HCC surveillance guidelines (fewer than 7 months between image evaluations) with early diagnosis, allocation of curative treatment, and longer adjusted OS of patients with hepatitis C virus- or hepatitis B virus-associated compensated cirrhosis and a diagnosis of HCC., (Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Optimally effective treatment for hepatitis C virus genotype 3 (GT3) is urgently needed, particularly in advanced liver disease. Daclatasvir plus sofosbuvir was efficacious in phase 3 studies. Real-world data for daclatasvir+sofosbuvir in advanced GT3 infection are presented from the French Temporary Authorisation for Use programme, which allowed patients in need without other treatment options access to daclatasvir ahead of its market authorization., Methods: Patients with F3/F4 fibrosis and/or extrahepatic hepatitis C virus manifestations, post-liver transplant hepatitis C virus recurrence and/or indication for liver/kidney transplant, were treated with daclatasvir+sofosbuvir (60+400 mg daily) for a recommended duration of 24 weeks. Addition of ribavirin and/or shorter treatment was at physician's discretion. The primary efficacy analysis was sustained virological response at post-treatment week 12 (SVR12; modified intention-to-treat). Safety was assessed by spontaneous adverse event reporting., Results: The efficacy population comprised 333 patients, mostly cirrhotic (77%, of whom 18% were decompensated) and treatment experienced (72%). After 24 weeks of daclatasvir+sofosbuvir, SVR12 was 89% (174/196) overall (95% CI 83.6-92.5%), 98% (43/44) without cirrhosis (95% CI 88.2-99.6%) and 86% (129/150) with any degree of cirrhosis (95% CI 79.5-90.7%), without SVR12 increase in those who received additional ribavirin for 24 weeks (SVR12 82% [50/61; 95% CI 70.5-89.6%]). Among 516 GT3-infected patients with safety data, 5 discontinued for adverse events and 11 died., Conclusions: Daclatasvir+sofosbuvir achieved high SVR12 rates and was well tolerated in this large real-world cohort of GT3-infected patients with advanced liver disease, without benefit of ribavirin in those treated 24 weeks., (© 2017 The Authors Liver International Published by John Wiley & Sons Ltd.)

Background and Goal: International guidelines suggest combining a blood test and liver stiffness measurement (LSM) to stage liver fibrosis in chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Therefore, we compared the accuracies of these tests between the main etiologies of chronic liver diseases., Study: Overall, 1968 patients were included in 5 etiologies: CHC: 698, chronic hepatitis B: 152, human immunodeficiency virus/CHC: 628, NAFLD: 225, and alcoholic liver disease (ALD): 265. Sixteen tests [13 blood tests, LSM (Fibroscan), 2 combined: FibroMeters] were evaluated. References were Metavir staging and CHC etiology. Accuracy was evaluated mainly with the Obuchowski index (OI) and accessorily with area under the receiver operating characteristics (F≥2, F≥3, cirrhosis)., Results: OIs in CHC were: FibroMeters: 0.812, FibroMeters: 0.785 to 0.797, Fibrotest: 0.762, CirrhoMeters: 0.756 to 0.771, LSM: 0.754, Hepascore: 0.752, FibroMeter: 0.750, aspartate aminotransferase platelet ratio index: 0.742, Fib-4: 0.741. In other etiologies, most tests had nonsignificant changes in OIs. In NAFLD, CHC-specific tests were more accurate than NAFLD-specific tests. The combined FibroMeters had significantly higher accuracy than their 2 constitutive tests (FibroMeters and LSM) in at least 1 diagnostic target in all etiologies, except in ALD where LSM had the highest OI, and in 3 diagnostic targets (OIs and 2 area under the receiver operating characteristics) in CHC and NAFLD., Conclusions: Some tests developed in CHC outperformed other tests in their specific etiologies. Tests combining blood markers and LSM outperformed single tests, validating recent guidelines and extending them to main etiologies. Noninvasive fibrosis evaluation can thus be simplified in the main etiologies by using a unique test: either LSM alone, especially in ALD, or preferably combined to blood markers.

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/mm 3 . 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.

Background: Few studies have assessed access to postoperative chemotherapy and survival in cirrhotic patients with colorectal cancer. Aim of this study was to analyse short and long-term outcomes in these patients compared to non-cirrhotics., Methods: A retrospective, single-centre, comparative, case-matched study comparing 40 cirrhotic patients who had undergone colorectal resection between January 2006 and January 2014, and a matched cohort of 80 non-cirrhotic patients. Data collection included rate of postoperative outcomes, chemotherapy regimen, overall and disease-free 3-year survival., Results: Cirrhotics had more major postoperative complications than non-cirrhotics (57.5% vs. 26.5%, respectively; p=0.002) but no difference in anastomotic leakage (p=0.1); a higher mortality rate (p=0.0006) was observed in Child-Pugh class B patients. Cirrhotics had no difference in adjuvant chemotherapy rate compared to non-cirrhotics (55% vs. 65%, respectively p=0.8); 3-year overall survival was 71% in the Child A group vs. 92% in non-cirrhotics (p=0.03)., Conclusion: Despite a higher postoperative complication rate and a lower overall survival of cirrhotic patients compared to non-cirrhotics, cirrhosis had no impact on oncological outcomes and access/tolerance to postoperative chemotherapy. Thus cirrhosis should not be considered as a contraindication to curative treatment of colon cancer., (Copyright © 2015. Published by Elsevier Ltd.)

Introduction: The incidence of cirrhosis is increasing in parallel with that of hepatitis C and non-alcoholic steatohepatitis. Patients with colon cancer and liver cirrhosis constitute an important at-risk group. Many colorectal surgeons and oncologists are not familiar with the management of colon cancer in patients with cirrhosis. Here, we review the literature on the management and prognosis of patients with both colon cancer and cirrhosis., Methods: The MEDLINE, PubMed and the Cochrane Library electronic databases were systematically searched with appropriate keywords. Only publications in French or English were selected., Results/conclusion: For most studies, the level of evidence is weak. Child A patients should probably be managed in the same way as general population, although they have an elevated risk of morbidity and a five-year survival rate of just 70%. Child B and C patients should be managed more cautiously, although no specific recommendations can be made at present. For colon surgery, laparotomy should be preferred in patients with cirrhosis. The role of adjuvant chemotherapy is unclear, since survival is strongly associated with the improvements in liver function. Oxaliplatin appears to be associated with an elevated post-chemotherapy morbidity rate in patients with portal hypertension., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background & Aims: Albumin infusion improves renal function and survival in cirrhotic patients with spontaneous bacterial peritonitis (SBP) but its efficacy in other types of infections remains unknown. We investigated this issue through a multicenter randomized controlled trial., Methods: A total of 193 cirrhotic patients with a Child-Pugh score greater than 8 and sepsis unrelated to SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kg on day 1 and 1g/kg on day 3; albumin group [ALB]: n=96) or antibiotics alone (control group [CG]: n=97). The primary endpoint was the 3-month renal failure rate (increase in creatinine ⩾50% to reach a final value ⩾133 μmol/L). The secondary endpoint was 3-month survival rate., Results: Forty-seven (24.6%) patients died (ALB: n=27 vs. CG: n=20; 3-month survival: 70.2% vs. 78.3%; p=0.16). Albumin infusion delayed the occurrence of renal failure (mean time to onset, ALB: 29.0 ± 21.8 vs. 11.7 ± 9.1 days, p=0.018) but the 3-month renal failure rate was similar (ALB: 14.3% vs. CG: 13.5%; p=0.88). By multivariate analysis, MELD score (p<0.0001), pneumonia (p=0.0041), hyponatremia (p=0.031) and occurrence of renal failure (p<0.0001) were predictors of death. Of note, pulmonary edema developed in 8/96 (8.3%) patients in the albumin group of whom two died, one on the day and the other on day 33 following albumin infusion., Conclusions: In cirrhotic patients with infections other than SBP, albumin infusion delayed onset of renal failure but did not improve renal function or survival at 3 months. Infusion of large amounts of albumin should be cautiously administered in the sickest cirrhotic patients., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Treatment of ascitic cirrhosis requires monitoring of blood biochemistry. A direct measure of ascites could simplify the medical procedure. We aimed to assess the correlation of sodium (Na), potassium (K), chloride (Cl), urea (U), and creatinine (Creat) in ascitic fluid and venous blood., Methods: Ascitic fluid and venous blood samples were collected simultaneously from 70 cirrhotic patients. Na, K, Cl, U, and Creat were measured in all samples using a biochemical auto-analyzer., Results: Results are expressed as the mean and SD of 200 concomitant samples of ascitic fluid and venous blood (mmol/L for Na, K, and Cl; g/L for U; mg/L for Creat). In ascites and blood the results were, respectively: 133.1+/-6.6 and 131.8+/-6.3 for Na (p<0.0001, r=0.95), 4.1+/-0.8 and 4.3+/-0.9 for K (p<0.0001, r=0.90), 107.2+/-7.6 and 101+/-7 for Cl (p<0.0001, r=0.93), 0.54+/-0.52 and 0.53+/-0.5 for U (p<0.0001, r=0.99), and 9.8+/-7.5 and 11+/-7 for Creat (p<0.0001, r=0.99). Analysis of ascites predicted blood results for different cut-offs (Na< or =125, K< or =3.2, K> or =5.5 and Creat> or =14) with a sensitivity of 1.00, 0.89, 0.71, and 0.92, and a specificity of 1.00, 0.95, 0.98, and 0.92, respectively., Conclusions: Correlations for Na, K, Cl, U, and Creat are strong between ascites and venous blood in cirrhotic patients. These parameters could, therefore, be assayed directly in ascitic fluid to monitor diuretic therapy in patients without venous access or when biochemical measurements, such as liver tests or coagulation tests, are not required, and in patients with poor venous access.

Background: Systematic screening for liver fibrosis in heavy-drinking patients is a challenge. Aims To assess Fibroscan for non-invasive diagnosis of asymptomatic liver fibrosis in alcohol abuse patients, to determine diagnostic liver stiffness cut-off values and to compare performance of Fibroscan with seven non-invasive laboratory tests., Methods: One hundred and three alcoholic patients were studied. Liver fibrosis was staged by METAVIR system. Fibroscan, Fibrotest, Fibrometer, Hepascore, APRI, PGA, PGAA and hyaluronic acid tests were performed. Liver stiffness cut-offs were determined using receiver-operating characteristic (ROC) curves., Results: Liver stiffness was correlated with fibrosis (r = 0.72, P < 0.014), with median at 5.7, 6.3, 8.4, 15 and 47.3 kPa for F0 (n = 8), F1 (n = 18), F2 (n = 24), F3 (n = 20) and F4 (n = 33) stage fibrosis respectively. For Fibroscan, areas under ROC curves (AUROCs) were 0.84 (95% CI: 0.73-0.95) (F > or = 1), 0.91 (0.85-0.98) (F > or = 2), 0.90 (0.82-0.97) (F > or = 3) and 0.92 (0.87-0.98) (F = 4), yielding diagnostic stiffness cut-offs of 5.9 (F > or = 1), 7.8 (F > or = 2), 11 (F > or = 3) and 19.5 (F4) kPa. Sensitivity, specificity, PPV and NPV were 80%, 90.5%, 93% and 70% for F > or = 2, and 85.7%, 84.2%, 68.6% and 87.9% for F = 4. Performance of Fibroscan was higher than seven laboratory tests, for which AUROCs ranged from 0.66 to 0.77 (F > or = 1), from 0.54 to 0.82 (F > or = 2), from 0.43 to 0.88 (F > or = 3) and from 0.56 to 0.89 (F = 4), with significant difference only vs. APRI (P < 0.001) and Hepascore (P = 0.04). Combining Fibroscan with each tests did not improve performance., Conclusions: Fibroscan is effective to assess liver fibrosis in alcoholic patients. Instant screening of liver fibrosis in heavy drinkers is feasible without liver biopsy.

Background: Spontaneous bacterial peritonitis (SBP) can be diagnosed via leucocyte esterase reagent strips, although diagnostic performances vary., Aim: To perform critical review of literature on the use of reagent strips in SBP., Methods: Nineteen studies were analysed (Medline search), comparing reagent strips in cirrhotic ascites vs. cytobacteriological methods. Diagnostic grades (G) were: GO = 0 leucocytes/mm3; G1 = 15; G2 = 70; G3 = 125; G4 = 500 for Multistix, GO = 0; G1 = 25; G2 = 75; G3 = 500 for Nephur, Combur, UriScan, and GO = 0; G1 = 25; G2 = 75; G3 = 250; G4 = 500 for Aution., Results: Medians per study were: 75 patients (range: 31-1041), 136 ascites (47-2123), 17 SBP (5-117). For Multistix (12 studies), the sensitivities fell within the ranges 64.7-100% (G > or = 1), 45.7-83% (G > or = 2) and 45.3-89% (G > or = 3). For Nephur (n = 2), Combur (n = 6), UriScan (n = 1), sensitivities ranged 80.4-100% (G > or = 1), 63-100% (G > or = 2) and 67.7-97% (G > or = 3). For Aution (n = 3), sensitivities ranged 93-96% (G > or = 2) and 89% (G > or = 3). Nephur, Combur, UriScan displayed higher sensitivities than Multistix. However, in larger studies, sensitivities dramatically fell at 45.3% for Multistix (G > or = 3) if ascites polymorphonuclear count <1000/mm3 and 22.2% for bacterascites or 16.7-25% for asymptomatic patients., Conclusion: Use of reagent strips for the diagnosis of SBP cannot be recommended, in view of low sensitivity and a high risk of false negatives, especially in patients with SBP and low polymorphonuclear count.

Unlabelled: Although it is often functional at presentation, acute renal failure has a poor prognosis in patients with cirrhosis. The role of inflammation, a key event in the outcome of cirrhosis, has never been studied in this setting. We aimed to investigate the predictive factors of mortality in patients with cirrhosis and acute functional renal failure, specifically in relation to inflammatory events. One hundred consecutive patients with cirrhosis from 5 French hospitals were prospectively included at the day of onset of acute renal failure. Medical history, treatments, and procedures during the month before inclusion were recorded. Physical examination, blood and urinary chemistries, and renal ultrasound examination were performed. The presence of systemic inflammatory response syndrome (SIRS), infection, and sepsis was assessed. The primary outcome was in-hospital mortality. The mechanism of renal failure was functional in 83 patients. Causes of renal failure were hypovolemia (34%), hepatorenal syndrome without ongoing infection (17%), hepatorenal syndrome with ongoing infection (16%), nephrotoxicity (2%), and multifactorial (31%). SIRS was observed in 41% of patients, 56% of them with infection. In-hospital mortality was 68% in patients with SIRS and 33% in patients without (P = 0.001). In multivariate analysis, only model for end-stage liver disease score and presence of SIRS, but not infection, remained associated with a poor outcome., Conclusion: The presence of SIRS, with or without infection, is a major independent prognostic factor in patients with cirrhosis and acute functional renal failure. This suggests that preventing and treating SIRS could decrease mortality in patients with cirrhosis and acute renal failure.

Background and Aims: Diagnosis of liver fibrosis by transient elastography (Fibroscan) is a new and non-invasive method. We report its results, and compare them with the non-invasive biological tests., Results: Fibroscan is validated for chronic hepatitis C, allowing to diagnose the fibrosis (Métavir) F2, F3 and F4 with areas under the ROC curve of 0.79-0.83, 0.90-0.91 and 0.91-0.97 respectively. The non-invasive diagnosis of the cirrhosis can be made with positive and negative predictive values from 70 to 95% and 77 in 95%. Preliminary data concern the HCV-HIV co-infections, primary biliary cirrhosis, NASH, portal hypertension, and the follow-up of the hepatic fibrosis. These results are altogether comparable to the various non-invasive biological tests, for cirrhosis diagnosis., Conclusions: It's remain to determine the respective places of Fibroscan and non-invasive biological tests, in the liver fibrosis diagnosis.

Methods for diagnosing hepatic fibrosis have progressed significantly over the last few years--notably with the appearance of minimally invasive biological tests (which avoid the need for liver needle biopsy but nevertheless require a blood sample). Hepatic ultrasonic transient elastography (Fibroscan) is a new diagnostic method for hepatic fibrosis: it is totally noninvasive and gives an immediate result. Here, we review the currently available data on the use of the Fibroscan. Today's main field of application is chronic, viral hepatitis C, with areas under the receiver operation characteristic curve of 0.79-0.83, 0.90-0.91 and 0.91-0.97 for the diagnosis of F2, F3 and F4 fibrosis (defined according to the Metavir classification system), respectively. Furthermore, the Fibroscan enables the noninvasive diagnosis of cirrhosis (regardless of the latter's aetiology), with positive and negative predictive values of 70-95% and 77-95%, respectively. Chronic viral hepatitis B, HIV-hepatitis C virus and HIV-hepatitis B virus coinfections, alcohol-related liver diseases and intrahepatic cholestatic diseases are the device's other main fields of application in hepatology. Today, the Fibroscan is a reliable alternative for the noninvasive diagnosis of hepatic fibrosis. Various diagnostic strategies and performing cost/benefit analyses are now necessary, to assess fully the value of hepatic elastography relative to biological tests for hepatic fibrosis.

Objective: Spontaneous bacterial peritonitis (SBP) is one of the potentially life-threatening complications in ascitic cirrhotic patients with a mortality rate ranging between 30 and 50%. The improved survival might be explained by a more rapid diagnosis and treatment. The aim of our study was to assess the utility of two reagent strips, the Multistix test and the Combur(2) test LN, for the rapid diagnosis of SBP., Methods: Thirty-one unselected consecutive cirrhotic patients with ascites were included and a total of 100 paracenteses were performed. All ascitic fluid was analysed with the two reagent strips, leucocyte and polymorphonuclear (PMN) leucocyte cell count and blood-bottle culture if the strips were positive. The strips were considered positive if the colour turned to purple: i.e. grade 3 or 4 for the Multistix test and 2 or 3 for the Combur(2) test LN on a colorimetric scale., Results: We diagnosed nine infections of which four were SBP defined by PMN > or = 250 cells/mm(3) and a positive culture in ascitic fluid and five were culture negative neutrocytic ascites (PMN > or = 250 cells/mm(3) and a negative culture). The results of the two strips were concordant and were negative in only one SBP. The sensitivity, specificity, positive and negative predictive values of these two strips were 89%, 100%, 100% and 99%, respectively., Conclusions: These reagent strips are very sensitive and specific for the diagnosis of SBP, allowing immediate commencement of empirical antibiotic therapy. These strips should be used for the diagnosis of SBP, especially on an emergency basis.

In cirrhotic patients with gastrointestinal bleeding, antibiotic prophylaxis decreases the incidence of infections but most randomized trials have not shown an increase in survival. The aim of this meta-analysis was to assess the efficacy of antibiotic prophylaxis in the prevention of infections and its effect on survival rate in cirrhotic patients with gastrointestinal bleeding. Four end points were assessed: infection, bacteremia and/or spontaneous bacterial peritonitis (SBP), incidence of SBP, and death. For each end point, heterogeneity and treatment efficacy were assessed by Der Simonian and Peto methods. Five trials including 534 patients, 264 treated with antibiotic prophylaxis for 4 to 10 days and 270 without, were identified. Mean follow-up was 12 days. Antibiotic prophylaxis significantly increased the mean percentage of patients free of infection (32% mean improvement rate, 95% confidence interval [CI]: 22-42, P <.001), bacteremia and/or SBP (19% mean improvement rate, 95% CI: 11-26, P <.001), and SBP (7% mean improvement rate, 95% CI: 2.1-12.6, P =.006). Antibiotic prophylaxis also significantly increased the mean survival rate (9. 1% mean improvement rate, 95 % CI: 2.9-15.3, P =.004), without significant heterogeneity. In cirrhotic patients with gastrointestinal bleeding, short-term antibiotic prophylaxis significantly increases the mean percentage of patients free of infection and significantly increases short-term survival rate.