Recent studies have shown that the diagnosis of spontaneous bacterial peritonitis (SBP) can be rapidly obtained using leukocyte esterase reagent strips. However, published studies were restricted to ...one or two centers, and the number of patients with SBP was thus limited. The aims of the current prospective multicenter study were: (1) to assess the diagnostic accuracy of the Multistix 8SG urine test for the diagnosis of SBP; and (2) to assess the prevalence of SBP. From January to May 2004, 2 reactive strips were tested independently in inpatients with cirrhosis and in outpatients undergoing paracentesis. Cultures of ascitic fluid were performed at the bedside using aerobic and anaerobic blood culture bottles. Two thousand one hundred twenty‐three paracenteses were performed in 1,041 patients from 70 centers. One hundred seventeen samples, obtained from 91 patients, had ascites polymorphonuclear cell (PMN) counts ≥250/μl (range, 250–34,000), among which 56 were associated with positive ascitic fluid cultures. The prevalence of SBP was 5.5% in the whole population, 9% in inpatients, and 1.3% in outpatients (P < 0.0001). The prevalence of SBP was 0.57% in asymptomatic outpatients versus 2.4% in symptomatic outpatients (P = 0.04). Using a threshold of 2+ for positivity of the reagent strip, sensitivity was 45.3% for the diagnosis of SBP, specificity was 99.2%, positive predictive value was 77.9%, and negative predictive value was 96.9%. Conclusion: This study confirms the low prevalence of SBP in asymptomatic outpatients according to a priori defined criteria, and indicates an absence of diagnostic efficacy for this specific strip test. (HEPATOLOGY 2007;45:1275–1281.)
The pathophysiological background of decompensated cirrhosis is characterised by a systemic proinflammatory and pro-oxidant milieu that plays a major role in the development of multiorgan ...dysfunction. Such abnormality is mainly due to the systemic spread of bacteria and/or bacterial products from the gut and danger-associated molecular patterns from the diseased liver triggering the release of proinflammatory mediators by activating immune cells. The exacerbation of these processes underlies the development of acute-on-chronic liver failure. A further mechanism promoting multiorgan dysfunction and failure likely consists with a mitochondrial oxidative phosphorylation dysfunction responsible for systemic cellular energy crisis. The systemic proinflammatory and pro-oxidant state of patients with decompensated cirrhosis is also responsible for structural and functional changes in the albumin molecule, which spoil its pleiotropic non-oncotic properties such as antioxidant, scavenging, immune-modulating and endothelium protective functions. The knowledge of these abnormalities provides novel targets for mechanistic treatments. In this respect, the oncotic and non-oncotic properties of albumin make it a potential multitarget agent. This would expand the well-established indications to the use of albumin in decompensated cirrhosis, which mainly aim at improving effective volaemia or preventing its deterioration. Evidence has been recently provided that long-term albumin administration to patients with cirrhosis and ascites improves survival, prevents complications, eases the management of ascites and reduces hospitalisations. However, variant results indicate that further investigations are needed, aiming at confirming the beneficial effects of albumin, clarifying its optimal dosage and administration schedule and identify patients who would benefit most from long-term albumin administration.
Methotrexate is a key component of the treatment of inflammatory rheumatic diseases and the mainstay of therapy in rheumatoid arthritis. Hepatotoxicity has long been a concern for prescribers ...envisaging long-term treatment with methotrexate for their patients. However, the putative liver toxicity of methotrexate should be evaluated in the context of advances in our knowledge of the pathogenesis and natural history of liver disease, especially non-alcoholic fatty liver disease (NAFLD). Notably, patients with NAFLD are at increased risk for methotrexate hepatotoxicity, and methotrexate can worsen the course of NAFLD. Understanding the mechanisms of acute hepatotoxicity can facilitate the interpretation of elevated concentrations of liver enzymes in this context. Liver fibrosis and the mechanisms of fibrogenesis also need to be considered in relation to chronic exposure to methotrexate. A number of non-invasive tests for liver fibrosis are available for use in patients with rheumatic disease, in addition to liver biopsy, which can be appropriate for particular individuals. On the basis of the available evidence, practical suggestions for pretreatment screening and long-term monitoring of methotrexate therapy can be made for patients who have (or are at risk for) chronic liver disease.
We aimed to assess the performance of a new strip (Periscreen) for the rapid diagnosis of spontaneous bacterial peritonitis (SBP).
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
. Ascites not related to portal hypertension were excluded.
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.
The Periscreen strip is a rapid and highly efficient tool for excluding SBP in the outpatient setting.
Data on infectious endocarditis (IE) in patients with liver cirrhosis (LC) are sparse. We aimed to describe the characteristics and predictors of mortality from IE in patients with LC.
Overall, 101 ...patients with LC and 101 controls with IE matched for sex, age, date of IE, and diabetes were retrospectively selected in 23 liver units between 2000 and 2013.
Mean age was 60.8±10.5 and 60.6±11.5 years in LC and controls, respectively. Causes of cirrhosis (Child-Pugh A/B/C: 10.4%/41.7%/47.9%, MELD score: 17±7.8) were excess alcohol intake (79.6%), viral hepatitis (17.3%), and metabolic syndrome (14.3%). Previous history of cardiopathy was found in 24.8% of LC (prosthetic valve 8.9%) and 37.6% of controls (P=0.07). The most frequent bacteria involved were gram-positive cocci. LC had significantly fewer aminoglycosides (P=0.0007), rifamycin (P=0.03), and valve surgery (P=0.02) than controls. The proportion of patients who died following cardiac surgery was similar between the two groups (9.7% for LC vs. 8.7% for controls, P=1). In-hospital mortality for Child-Pugh C patients was significantly higher than controls (61.4 vs. 23%, P<0.001), but not for Child-Pugh A (33.3%) or B patients (25.0%). A Child-Pugh score of above C10 was the best predictor of in-hospital mortality. In LC, Child-Pugh score (odds ratio=1.5; 95% confidence interval: 1.2-2.0; P=0.002) and history of decompensation (odds ratio=3.1; 95% confidence interval: 1.1-9.0; P=0.003) were independent predictive factors for in-hospital mortality.
Severe liver failure but not cirrhosis is the strongest predictive factor of mortality related to IE in LC. Use of aminosides and rifamycin should be reassessed in LC, and cardiac surgery should be considered for selected patients.
The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity, such as estimated glomerular filtration rate (eGFR) and phosphatemia, are late markers of proximal tubulopathy. ...Multiple early markers are available, but no consensus exists on their use.
To determine the 24 mo prevalence of subclinical proximal tubulopathy (SPT), as defined with early biomarkers, in treated
untreated hepatitis B virus (HBV)-monoinfected patients.
A prospective, non-randomized, multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted. The patients were separated into three groups: Naïve, starting entecavir (ETV) treatment, or starting tenofovir disoproxil (TDF) treatment. Data on the early markers of SPT, the eGFR and phosphatemia, were collected quarterly. SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%. The prevalence and cumulative incidence of SPT at month 24 (M24) were calculated. Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests, whereas chi-squared or Fisher's exact tests were used to analyze qualitative data. Multivariate analyses were used to adjust for any potential confounding factors.
Of the 196 patients analyzed, 138 (84 naïve, 28 starting ETV, and 26 starting TDF) had no SPT at inclusion. At M24, the prevalence of SPT was not statistically different between naïve and either treated group (21.1%
30.7%,
0.42 and 50.0%
30.7%,
= 0.32 for ETV and TDF, respectively); no patient had an eGFR lower than 50 mL/min/1.73 m² or phosphatemia less than 0.48 mmoL/L. In the multivariate analysis, no explanatory variables were identified after adjustment. The cumulative incidence of SPT over 24 mo (25.5%, 13.3%, and 52.9% in the naïve, ETV, and TDF groups, respectively) tended to be higher in the TDF group
the naïve group (hazard ratio: 2.283,
= 0.05). SPT-free survival at M24 was 57.6%, 68.8%, and 23.5% for the naïve, ETV, and TDF groups, respectively. The median survival time without SPT, evaluated only in the TDF group, was 5.9 mo.
The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients. SPT in the naïve population suggests that HBV can induce renal tubular toxicity.
Although coronary artery disease (CAD) and advanced liver fibrosis (AdLF) are commonly associated in patients with non-alcoholic fatty liver disease (NAFLD), the prevalence of AdLF and the diagnostic ...performance of non-invasive fibrosis tests (NITs) in CAD patients remains unknown. We aimed to prospectively screen for AdLF in patients with documented CAD using NITs and Fibroscan. High and intermediate zones of NITs were combined to define AdLF. AdLF was suspected whenever APRI ≥ 0.5, Forns index ≥ 4.2, NAFLD fibrosis score (NFS) ≥ -1.455/0.12 for age </≥ 65 yrs), Fib4 (≥ 1.30/2.0 for age </≥ 65 yrs) and eLIFT≥ 8. A presumed AdLF assessed by Fibroscan ≥ 8 kPa was the primary outcome measure. Results were given on the basis of intent-to-diagnose liver stiffness ≥ 8 kPa. Among 189 patients (age 60±7years), 10 (5.3%) had a Fibroscan ≥ 8 kPa, of whom 5 underwent liver biopsy (F3/F4: n = 3; no fibrosis: n = 2). AdLF was suspected in 31% of cases using eLIFT (specificity, Sp 70%), 85% with Forns (Sp 16%), 38% with NFS (Sp 63%), 25% with Fib4 (Sp 74%), and 10% with APRI (Sp 91%). In 149 patients "at-risk" of NAFLD (i.e., elevated ALT or diabetes or hypertriglyceridemia or BMI ≥25 kg/m2), AdLF ranged between 10% (APRI) to 84% (Forns). In this subgroup, the most efficient NITs to predict Fibroscan ≥ 8 kPa were eLIFT (Se 60%, Sp 70%) and NFS (Se 70%, Sp 60%). Finally, in CAD patients with risk factors for NAFLD, NFS or the more user-friendly eLIFT are the most attractive first-line biochemical NITs to discriminate good candidates for Fibroscan.
Portopulmonary hypertension: An unfolding story Thévenot, Thierry; Savale, Laurent; Sitbon, Olivier
Clinics and research in hepatology and gastroenterology,
January 2021, 2021-01-00, 20210101, 2021-01, Volume:
45, Issue:
1
Journal Article
The benefits of prophylactic antibiotics for hospitalized patients with severe alcohol-related hepatitis are unclear.
To determine the efficacy of amoxicillin-clavulanate, compared with placebo, on ...mortality in patients hospitalized with severe alcohol-related hepatitis and treated with prednisolone.
Multicenter, randomized, double-blind clinical trial among patients with biopsy-proven severe alcohol-related hepatitis (Maddrey function score ≥32 and Model for End-stage Liver Disease MELD score ≥21) from June 13, 2015, to May 24, 2019, in 25 centers in France and Belgium. All patients were followed up for 180 days. Final follow-up occurred on November 19, 2019.
Patients were randomly assigned (1:1 allocation) to receive prednisolone combined with amoxicillin-clavulanate (n = 145) or prednisolone combined with placebo (n = 147).
The primary outcome was all-cause mortality at 60 days. Secondary outcomes were all-cause mortality at 90 and 180 days; incidence of infection, incidence of hepatorenal syndrome, and proportion of participants with a MELD score less than 17 at 60 days; and proportion of patients with a Lille score less than 0.45 at 7 days.
Among 292 randomized patients (mean age, 52.8 SD, 9.2 years; 80 27.4% women) 284 (97%) were analyzed. There was no significant difference in 60-day mortality between participants randomized to amoxicillin-clavulanate and those randomized to placebo (17.3% in the amoxicillin-clavulanate group and 21.3% in the placebo group P = .33; between-group difference, -4.7% 95% CI, -14.0% to 4.7%; hazard ratio, 0.77 95% CI, 0.45-1.31). Infection rates at 60 days were significantly lower in the amoxicillin-clavulanate group (29.7% vs 41.5%; mean difference, -11.8% 95% CI, -23.0% to -0.7%; subhazard ratio, 0.62; 95% CI, 0.41-0.91; P = .02). There were no significant differences in any of the remaining 3 secondary outcomes. The most common serious adverse events were related to liver failure (25 in the amoxicillin-clavulanate group and 20 in the placebo group), infections (23 in the amoxicillin-clavulanate group and 46 in the placebo group), and gastrointestinal disorders (15 in the amoxicillin-clavulanate group and 21 in the placebo group).
In patients hospitalized with severe alcohol-related hepatitis, amoxicillin-clavulanate combined with prednisolone did not improve 2-month survival compared with prednisolone alone. These results do not support prophylactic antibiotics to improve survival in patients hospitalized with severe alcohol-related hepatitis.
ClinicalTrials.gov Identifier: NCT02281929.
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