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Spontaneous bacterial peritonitis has no effect on the long-term prognosis of cirrhosis patients with ascites
Thomas Deleurana,b,
Corresponding author
thomas.deleuran@clin.au.dk

Corresponding author at: Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus 8200, Denmark.
, Hugh Watsona,c, Hendrik Vilstrupa, Peter Jepsena
a Department of Hepatology and Gastroenterology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, Aarhus 8200, Denmark
b Department of Gastroenterology, Aalborg University Hospital, Aalborg, Denmark
c Evotec ID, Lyon, France
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel A &#38; B</span> show the mortality hazard ratio with respect to time since first paracentesis for patients with spontaneous bacterial peritonitis &#40;SBP&#41; at the index date compared to those without SBP&#46; The mortality hazard ratio is highest in the first weeks after patients&#8217; first paracentesis &#40;i&#46;e&#46;&#44; the &#8216;index date&#8217;&#41; and then declines over time&#46; The dotted lines are 95&#37; CI&#39;s&#44; and when they cross the HR&#160;&#61;&#160;1&#44; the difference in mortality hazard between SBP-patients and those without is no longer statistically significant&#46; Note the logarithmic scales on the y-axis and that the y-scale differ between the two patient cohorts&#46; Panel C &#38; D show the cumulative all-cause mortality for patients with and without SBP&#46; The number at risk are written underneath the top x-axis for SBP patients &#40;top&#41; and no SBP &#40;bottom&#41;&#46; Danish Healthcare Cohort&#58; A &#38; C panels&#46; Satavaptan Trial Cohort&#58; B &#38; D panels&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="cesectitle0008">Introduction</span><p id="para0005" class="elsevierStylePara elsevierViewall">Spontaneous bacterial peritonitis &#40;SBP&#41; is a complication to cirrhosis patients with ascites that affects approximately 10&#37; at hospital admissions <a class="elsevierStyleCrossRef" href="#bib0001">&#91;1&#93;</a>&#46; It can present with abdominal discomfort or signs of infection&#44; but may also be clinically silent <a class="elsevierStyleCrossRef" href="#bib0002">&#91;2&#93;</a>&#46; The SBP diagnosis is defined by an ascites fluid sample with &#62; 250 polymorphonuclear &#40;PMN&#41; cells per &#181;L <a class="elsevierStyleCrossRef" href="#bib0001">&#91;1&#93;</a>&#46; Identification of SBP prompts immediate empirical antibiotic treatment and in those with renal impairment or jaundice also administration of human albumin <a class="elsevierStyleCrossRef" href="#bib0003">&#91;3&#93;</a>&#46; Before the advent of these measures&#44; the 1- year mortality of SBP exceeded 70&#37; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&#44; but it has decreased since&#44; and is currently expected to be 30&#8211;50&#37; <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&#46; However&#44; estimates on cirrhosis patients&#8217; cumulative mortality following an SBP episode are based on small and selected patient cohorts <a class="elsevierStyleCrossRefs" href="#bib0006">&#91;6&#8211;10&#93;</a>&#46; Only one population-based study has compared the impact of SBP on the mortality with a relevant control group without SBP and assessed the impact of SBP over time <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&#44; but their SBP definition was based on diagnosis codes rather than the ascites leukocyte count&#46; Their findings indicate that SBP could be a temporary phenomenon with no lasting effect on the mortality rate&#46; Yet&#44; it is widely believed that SBP is a marker of a permanent aggravation of cirrhosis &#91;<a class="elsevierStyleCrossRef" href="#bib0001">1</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0005">5</a>&#93;&#46; Valid estimates on the cumulative mortality following an SBP episode&#44; and a clarification of whether SBP is a permanent or a temporary complication may clarify clinical decisions and benefit patient counselling&#46;</p><p id="para0006" class="elsevierStylePara elsevierViewall">We examined the short-and long-term effect of SBP on mortality in two large&#44; independent&#44; and differently constructed patient cohorts&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="cesectitle0009">Methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0010">Setting and data sources</span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0011">Danish healthcare data</span><p id="para0007" class="elsevierStylePara elsevierViewall">Denmark&#39;s 5&#46;6 million residents benefit from universal tax-funded access to work-up and treatment at general practitioners and hospitals&#46; The Danish National Patient Registry &#40;NPR&#41; is a nationwide registry that covers non-psychiatric hospital admissions since 1977 and emergency room and outpatient visits since 1995&#46; The data includes admission and discharge dates along with up to 20 diagnoses&#46; The diagnoses are coded in accordance with the International Classification of Disease edition 10 &#40;ICD-10&#41; from 1994&#44; and the ICD-8 before that <a class="elsevierStyleCrossRefs" href="#bib0012">&#91;12&#8211;14&#93;</a>&#46; The NPR also holds data on surgical procedures coded in accordance with the Nordic Classification of Surgical Procedures &#40;NCSP&#41;&#46;</p><p id="para0008" class="elsevierStylePara elsevierViewall">The LABKA database holds data on the results of biochemical tests from blood and fluid samples analyzed at hospitals in the Danish Central and Northern Region&#44; including samples obtained at general practitioners&#46; The database was set up in 1995 at Aarhus University Hospital &#40;then Aarhus County Hospital&#41; and data from an increasing number of hospitals was gradually added until 2011 when the database became complete&#46; The data includes the date of each sample and the result coded according to the Nomenclature for Properties and Units &#40;NPU&#41;&#44; and the unit of the result <a class="elsevierStyleCrossRef" href="#bib0015">&#91;15&#93;</a>&#46;</p><p id="para0009" class="elsevierStylePara elsevierViewall">The Danish Central Office of Civil registration keeps track of all Danish residents&#8217; vital status&#44; including the date of death or emigration&#46; It also issues the unique ten digit personal identifier that enables time-true individual level linkage across the NPR&#44; the LABKA database&#44; and the civil registration system <a class="elsevierStyleCrossRef" href="#bib0016">&#91;16&#93;</a>&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0012">Satavaptan trial data</span><p id="para0010" class="elsevierStylePara elsevierViewall">From July 2006 to December 2008&#44; three multicenter randomized trials evaluated the clinical efficacy of satavaptan in ascites treatment&#46; A total of 1&#44;198 patients were randomized to satavaptan or placebo according to the same core protocol&#46; The trials had different target populations&#58; patients with diuretic-manageable ascites &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;462&#41;&#44; patients managed with diuretics and occasional therapeutic paracentesis &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;496&#41;&#44; and patients with diuretic-resistant ascites managed primarily with therapeutic paracentesis &#40;<span class="elsevierStyleItalic">n</span>&#160;&#61;&#160;240&#41; <a class="elsevierStyleCrossRef" href="#bib0017">&#91;17&#93;</a>&#46; The three trials excluded patients with a functioning transjugular intrahepatic systemic shunt&#44; patients with variceal bleeding&#44; and patients with spontaneus bacterial peritonitis in the 10 days before randomization&#46; Additional exclusion criteria were&#58; serum creatinine &#62; 150 &#181;mol&#47;L&#44; serum potassium &#62; 5&#46;0 mmol&#47;L&#44; serum sodium &#62; 143 mmol&#47;L&#44; serum bilirubin &#62; 150 &#181;mol&#47;L&#44; international normalized ratio &#62; 3&#46;0&#44; platelets &#60; 30&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#44; neutrophils &#60; 1&#44;000&#47;mm<span class="elsevierStyleSup">3</span>&#44; systolic arterial pressure &#60; 80 mmHg or orthostatic hypertension&#44; hepatocellular carcinoma beyond the Milan criteria&#44; need for medication with QT-interval prolonging drugs or drugs with potent modification of the cytochrome P450 3A pathway&#46;</p><p id="para0011" class="elsevierStylePara elsevierViewall">All three trials were intended to run for 52 weeks&#44; but the second and third trial were terminated prematurely due to futility&#46; During the trials&#44; all patients were seen every 4 weeks at their hepatology department&#46; At these visits&#44; patients underwent clinical examination&#44; had standard blood tests analyzed&#44; all current medications and their indications were recorded&#44; and all patients underwent paracentesis when needed&#46; All clinical events during follow-up were recorded&#44; and all patients were followed up for death until one year after inclusion in the trial&#46;</p></span></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0013">Study cohorts</span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0014">Danish healthcare cohort</span><p id="para0012" class="elsevierStylePara elsevierViewall">We included all patients with a first-time diagnosis for unspecified cirrhosis &#40;ICD&#8211;8&#58; 57&#46;192&#44; 57&#46;199&#59; ICD&#8211;10&#58; K74&#46;6&#41; or alcoholic cirrhosis &#40;ICD&#8211;8&#58; 57&#46;109&#59; ICD&#8211;10&#58; K70&#46;3&#44; K70&#46;4&#41; in the NPR from 1977 to 2014 <span class="elsevierStyleItalic">and</span> a subsequent first-time paracentesis with a leukocyte count in the LABKA database &#40;see appendix for NPU codes&#41;&#46; We defined the date of the first-time paracentesis as the index date&#46; To ensure we studied first time and not recurrent SBP&#44; we excluded those with a procedure code for a paracentesis &#40;NCSP&#58; KTJA10x or KJAA00x&#41; more than one day before the index date according to the NPR&#46; We also excluded those with a diagnosis for ascites &#40;ICD-10&#58; R18&#46;x&#41; made at a hospital discharge&#44; an outpatient visit&#44; or an emergency room visit before the index date according to the NPR&#46; To ensure we studied <span class="elsevierStyleItalic">spontaneous</span> bacterial peritonitis and not peritonitis secondary to surgery&#44; we excluded patients that underwent intra-abdominal surgery &#40;NCSP&#58; KJxxxxx&#41; except paracentesis within 30 days before the index date&#46; However&#44; we allowed that patients underwent endoscopic or catheter-based procedures &#40;see <a class="elsevierStyleCrossRef" href="#sec0030">Supplementary material</a> for procedure codes&#41; during the 30-day time-period before the index date&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">We divided patients with a first-time paracentesis according to ascites PMN cell count &#40;see Appendix 1 for NPU codes&#41;&#46; We defined those with an ascites PMN cell count &#8805;250 cells per &#181;L as spontaneous bacterial peritonitis &#40;SBP&#41; patients&#44; and those with a PMN cell count &#60; 250 per &#181;L as not having SBP&#46; We followed these patients from the index date to death or end of follow-up on 1 January 2015 whichever occurred first&#46; We defined comorbidity with the CirCom score based on diagnoses recorded in the NPR up to two years before the index date <a class="elsevierStyleCrossRef" href="#bib0018">&#91;18&#93;</a>&#46; We also used ICD-10 codes recorded before the index date to classify the patients&#8217; cirrhosis etiology and to identify those diagnosed with hepatocellular carcinoma &#40;HCC&#41; &#40;see <a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a> for ICD&#8211;10 codes&#41;&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0015">Satavaptan trial cohort</span><p id="para0014" class="elsevierStylePara elsevierViewall">We excluded patients who had SBP before inclusion and identified patients with an SBP episode during the three randomized trials &#40;defined by an ascites PNM cell count &#62; 250 per &#181;L&#41;&#46; We defined the date of the first SBP episode as the index date&#46; We matched up to five patients controls to each patient with SBP on model-of-end-stage-liver-disease &#40;MELD&#41; score&#44; serum sodium&#44; serum albumin&#44; inpatient status at the time of paracentesis &#40;yes&#47;no&#41;&#44; refractory ascites &#40;yes&#47;no&#41; &#40;incidence density sampling&#41; <a class="elsevierStyleCrossRef" href="#bib0019">&#91;19&#93;</a>&#46; We followed SBP patients and patient controls from the index date to death or end of follow-up&#44; whichever occurred first&#46;</p></span></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="cesectitle0016">Statistical analysis</span><p id="para0015" class="elsevierStylePara elsevierViewall">We estimated cumulative all-cause mortality with the Kaplan-Meier method in both patient cohorts&#46; First&#44; we estimated the 30-&#44; 90-day&#44; 120-day &#40;4-month&#41; and 1-year cumulative all-cause mortality after the index date for patients with and without SBP&#46; Next&#44; we estimated the cumulative all-cause mortality for the patients in each cohort that were alive 4 months &#40;120 days&#41;&#41; after the index date&#46; In the Danish Healthcare Cohort&#44; we followed these patients until death or end of follow-up&#46; We followed patients in the Satavaptan Trial Cohort until 12 months &#40;365 days&#41; after the index date&#46;</p><p id="para0016" class="elsevierStylePara elsevierViewall">We also used another method&#8212;Cox regression&#8212;to clarify when the mortality hazard after an SBP episode was similar to and when it was different from patients without SBP&#46; We used this analysis to produce a Schoenfeld residuals plot that visualizes the mortality hazard ratio&#39;s interaction with time&#46; It enabled us to examine how the mortality hazard for patients with vs&#46; without SBP changes through follow-up&#46; Finally&#44; we divided follow-up into two time-periods based on inspection on these plots&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall">In the Danish Healthcare Cohort&#44; we estimated the mortality hazard ratio for patients with SBP compared to those without&#46; In the primary analysis&#44; we adjusted for age&#44; sex&#44; comorbidity&#44; HCC&#44; MELD score&#44; serum sodium&#44; and serum albumin&#46; We used multiple imputation to account for missing data on biochemistry &#40;see Appendix 2 for details&#41;&#46; We repeated this analysis without serum creatinine to see whether the missing data on serum creatinine in 20&#37; of the patients affected our results&#46; Finally&#44; we repeated our analyses and restricted them to patients with a diagnosis for alcoholic cirrhosis &#40;ICD&#8211;10&#58; K70&#46;3 and K70&#46;4&#41;&#46;</p><p id="para0018" class="elsevierStylePara elsevierViewall">The SBP patients in the Satavaptan Trial Cohort were matched to patients without SBP on MELD score&#44; serum sodium&#44; serum albumin&#44; inpatient status at the time of paracentesis &#40;yes&#47;no&#41;&#44; and refractory ascites &#40;yes&#47;no&#41;&#46; We used stratified Cox regression to estimate the mortality hazard ratio for patients vs&#46; those without SBP&#46; Each stratum consisted of one SBP patient and his or her matched cohort members&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="cesectitle0021">Ethical approval statement</span><p id="para0031" class="elsevierStylePara elsevierViewall">According to Danish law&#44; studies based on Danish healthcare registers do not require approval from an ethical committee&#46; The three satavaptan trials were approved by ethical committee in each of the countries were trial participants were recruited&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;5</span><span class="elsevierStyleSectionTitle" id="cesectitle0022">Patient consent statement</span><p id="para0032" class="elsevierStylePara elsevierViewall">Informed consent is not mandatory for data based on the national patient registry according to Danish law&#46; All trial participants in the three trials concerning the clinical efficacy of satavaptan treatment of ascites in cirrhosis patients gave informed consent&#46;</p></span></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="cesectitle0017">Results</span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;1</span><span class="elsevierStyleSectionTitle" id="cesectitle0018">Danish Healthcare cohort</span><p id="para0019" class="elsevierStylePara elsevierViewall">We included 1282 patients that underwent paracentesis from 2000 to 2014 of whom 133 &#40;10&#46;4&#37;&#41; had SBP&#46; Those with SBP had almost the same age&#44; sex&#44; biochemistry and comorbidity composition as those without &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>a&#41;&#46; Moreover&#44; they were more likely to have cirrhosis from viral hepatitis and less likely to have alcohol-related cirrhosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>a&#41;&#46; SBP patients&#8217; 4-month cumulative all-cause mortality was significantly higher at 51&#46;2&#37; &#40;95&#37; CI&#58; 43&#46;0&#8211;59&#46;9&#37;&#41; compared with 34&#46;7&#37; &#40;95&#37; CI&#58; 32&#46;0&#8211;37&#46;6&#41; in patients without SBP &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table&#160;2</a> and <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0020" class="elsevierStylePara elsevierViewall">The difference in mortality was smaller for the patients that were alive four months after the index date&#58; For those with SBP&#44; the cumulative all-cause mortality was 21&#46;5&#37; &#40;95&#37; CI&#58; 13&#46;1&#8211;34&#46;1&#41; one year &#40;12 months&#41; after the index date&#44; compared with 16&#46;0&#37; &#40;95&#37; CI&#58; 13&#46;5&#8211;18&#46;9&#41; for those without SBP &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46;&#160;2</a>&#41;&#46; Moreover&#44; the cumulative all-cause mortality was similar two years after the index date at 32&#46;3&#37; &#40;95&#37; CI&#58; 21&#46;9&#8211;45&#46;9&#41; for those with SBP compared with 31&#46;7&#37; &#40;28&#46;4&#8211;35&#46;3&#41; in those without &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46;&#160;2</a>&#41;&#46;</p><elsevierMultimedia ident="fig0002"></elsevierMultimedia><p id="para0021" class="elsevierStylePara elsevierViewall">The Cox regression analysis revealed a similar pattern&#46; In the time-period beginning at the index date and lasting until four months &#40;120 days&#41; after&#44; we found a mortality hazard that was 1&#46;54-fold higher &#40;95&#37; CI&#58; 1&#46;18&#8211;2&#46;00&#41; for SBP patients than for those without SBP &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>&#41;&#46; In the time-period beginning 4 months after the index date the mortality hazards were similar for patients with and without SBP &#40;mortality hazard ratio 1&#46;02&#44; 95&#37; 0&#46;72&#8211;1&#46;46&#41;&#46; Our results were similar when we repeated our analysis controlling for only HCC&#44; comorbidity&#44; sodium&#44; and albumin indicating a minimal impact of the 20&#37; of patients without a measurement of serum creatinine &#40;see <a class="elsevierStyleCrossRef" href="#sec0030">Supplementary material</a> for details&#41;&#46; All these results were essentially unaltered when we restricted our analyses to patients with alcoholic cirrhosis&#46;</p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3&#46;2</span><span class="elsevierStyleSectionTitle" id="cesectitle0019">Satavaptan trial cohort</span><p id="para0022" class="elsevierStylePara elsevierViewall">We included 93 patients with SBP and 371 matched patients without SBP&#46; The age&#44; sex&#44; and biochemical profiles were similar &#40;<a class="elsevierStyleCrossRef" href="#tbl0001">Table&#160;1</a>b&#41;&#44; but alcoholic etiology was more prevalent among those with SBP&#46; Patients with SBP had a four-month cumulative all-cause mortality of 38&#46;6&#37; &#40;95&#37; CI&#58; 29&#46;3&#8211;49&#46;7&#41;&#44; whereas it was 11&#46;4&#37; &#40;95&#37; CI&#58; 8&#46;5&#8211;15&#46;2&#41; in patients without SBP&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall">In comparison&#44; when we followed the patients alive four months &#40;120 days&#41; after the index date until 12 months after index date&#44; the difference in mortality was much smaller&#58; The cumulative all-cause mortality for those with SBP was 20&#46;3&#37; &#40;9&#46;0&#8211;41&#46;7&#41; compared with 15&#46;8&#37; &#40;95&#37; CI&#58; 11&#46;2&#8211;21&#46;8&#41; in those without SBP &#40;<a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46;&#160;2</a>&#41;&#46; The higher cumulative all-cause mortality during the first four months after an SBP episode was reflected in a 3&#46;86-fold higher &#40;95&#37; CI&#58; 2&#46;44&#8211;6&#46;12&#41; mortality hazard &#40;<a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46;&#160;1</a>b&#41;&#46; By contrast&#44; the mortality hazard ratio for patients with SBP vs&#46; those without was 1&#46;23 &#40;95&#37; CI&#58; 0&#46;54&#8211;2&#46;83&#41; in the period beginning four months after the index date&#46;</p></span></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="cesectitle0020">Discussion</span><p id="para0024" class="elsevierStylePara elsevierViewall">This study examined the prognosis of SBP in two differently constructed cohorts of cirrhosis patients&#46; One population-based and one based on trial data&#46; The results were broadly similar&#58; We found a markedly higher cumulative mortality and mortality hazard in the first four months following an SBP-episode compared to patients without SBP&#44; but not in the time-period beginning four months after the SBP episode&#46;</p><p id="para0025" class="elsevierStylePara elsevierViewall">The strength of our study is its foundation in two detailed&#44; independent&#44; and large datasets&#46; In the Danish Healthcare Cohort&#44; we believe that the high positive predictive value of a diagnosis for cirrhosis or alcoholic cirrhosis of about 85&#37; <a class="elsevierStyleCrossRef" href="#bib0020">&#91;20&#93;</a>&#44; was further increased by the fact that we only included patients with a diagnosis for cirrhosis that underwent paracentesis&#46; In addition&#44; the average ascites-protein content was &#60;16 g&#47;&#44; which indicates they were transudates <a class="elsevierStyleCrossRef" href="#bib0021">&#91;21&#93;</a>&#46; Finally&#44; all patients in the Satavaptan Trial Cohort had cirrhosis and ascites by inclusion criteria&#46; The association between SBP and death during the first four months after the index date was present even after adjustment for MELD score&#44; serum albumin&#44; and sodium&#46; In the Danish Healthcare Cohort&#44; we also adjusted for comorbidity and HCC&#46; However&#44; data on the hepatic venous pressure gradient&#44; nutritional status and medication use &#40;diuretics and non-selective betablockers&#41; would have strengthened our conclusion&#46; Moreover&#44; the mortality hazard ratio obtained from the Satavaptan Trial Cohort of 1&#46;20 in the period starting four months after the SBP episode&#44; does suggests a remote chance&#44; that we could have reached a different conclusion in a larger dataset with more precisely estimated hazard ratios&#46; On the other hand&#44; there is no such evidence in the Danish Healthcare data&#44; because the mortality hazard ratio essentially is 1&#46;00&#46; Finally&#44; we addressed missing data with appropriate methods <a class="elsevierStyleCrossRef" href="#bib0022">&#91;22&#93;</a>&#46;</p><p id="para0026" class="elsevierStylePara elsevierViewall">Our 30-day mortality estimate from the Danish Healthcare Cohort of 35&#37; in SBP patients resembles the 30-day mortality of 32&#37; found by Bac in 2003 <a class="elsevierStyleCrossRef" href="#bib0007">&#91;7&#93;</a>&#44; but slightly higher than the 21&#37; found by Melcarne et&#160;al&#46; &#91;<a class="elsevierStyleCrossRef" href="#bib0009">9</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0011">11</a>&#93;&#46; They are lower than those found in the original paper describing SBP by Kerr et&#160;al&#46; <a class="elsevierStyleCrossRef" href="#bib0004">&#91;4&#93;</a>&#46; Since the Danish Healthcare Cohort is the hitherto largest population-based patient material with detailed clinical information <a class="elsevierStyleCrossRef" href="#bib0023">&#91;23&#93;</a>&#44; our estimates provide a sound basis for the prognostic impact of SBP&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">The different cumulative mortality following an SBP episode in the Danish Healthcare Cohort and the Satavaptan Trial Cohort might appear incoherent&#46; However&#44; the difference is likely rooted in the fact that we examined mortality in a population-based patient material of cirrhosis patients and in a cohort of trial-recruited cirrhosis patients&#44; respectively&#46; The latter had fewer comorbidities and the necessary compliance to participate in a randomized controlled trial&#46; Moreover&#44; we acknowledge that neither of the two patient cohorts were collected with the intention to answer the research question of this study&#46; Importantly&#44; both datasets were collected prospectively&#46; Finally&#44; since the results of two such different patient cohorts agree on the time dependent mortality hazard after an SBP episode&#44; it provides a strong argument for its validity&#46;</p><p id="para0028" class="elsevierStylePara elsevierViewall">We assume that securing the PMN cell count in both cohorts went hand-in-hand with a subsequent administration of intravenous antibiotics to those with SBP&#46; However&#44; the lack of data on in-hospital care prevents us from confirming our assumption&#44; and that is a limitation&#46; Recommendations for the long-term clinical management of SBP patients also include the possibility for antibiotic prophylaxis <a class="elsevierStyleCrossRef" href="#bib0005">&#91;5&#93;</a>&#46; Therefore&#44; it is also a limitation that we were unable to present data on quinolone antibiotics prescription after discharge&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">Our results shed a new light on the consequences of decompensated cirrhosis&#44; but do not motivate changes in the classification of the clinical course of cirrhosis&#46; Concerning liver transplantation&#44; the added 15&#8211;25&#37; in mortality in those with SBP compared with those without SBP occurred within four months&#44; which indicate that this time-window is when patients with SBP will profit the most from liver transplantation compared to patients without SBP&#46; Moreover&#44; this time-window suggests that patient with SBP may benefit from close clinical attention and care beyond the usual 5-day course of intravenous antibiotics&#46; Our results parallel those of Hung et&#160;al&#46;&#44; although they defined SBP by diagnosis codes rather than ascites PMN cell count <a class="elsevierStyleCrossRef" href="#bib0011">&#91;11&#93;</a>&#46; Altogether&#44; we suggest investigating a practice&#44; where considerations about liver transplantation and antibiotic prophylaxis in patients alive four months after an SBP episode rely on current clinical status&#44; rather than on the previous SBP episode <span class="elsevierStyleItalic">per se</span>&#46; Nevertheless&#44; a previous SBP episode should not hinder liver transplantation in an otherwise well-suited candidate&#46;</p></span><span id="sec0013a" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">5</span><span class="elsevierStyleSectionTitle" id="cesectitle0020a">Conclusions</span><p id="para0030" class="elsevierStylePara elsevierViewall">In conclusion&#44; we found that from one-third to half of cirrhosis patients with ascites and SBP die within 4 months&#44; which is markedly more than in those with the same clinical characteristics but without SBP&#46; However&#44; for those surviving these four months&#44; their SBP episode had no further negative impact on their mortality compared with those without SBP in the past&#46; Thus&#44; an SBP episode was not a marker of generally advancing cirrhosis&#44; but rather reflected a temporary but severe complication&#46;</p></span></span>"
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            1 => "Ascites"
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            3 => "Cirrhosis"
            4 => "End-stage liver disease"
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            0 => "SBP"
            1 => "PMN"
            2 => "NPR"
            3 => "ICD"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Introduction and objectives</span><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Spontaneous bacterial peritonitis &#40;SBP&#41; is a frequent complication to cirrhosis with an unclear long-term prognosis&#46; We aimed to examine its effect on mortality in two independent patient cohorts&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Patients and methods</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">We used Danish healthcare data on cirrhosis patients with a first-time paracentesis in 2000&#8211;2014 and data from three randomized controlled trials on satavaptan treatment of ascites conducted in 2006&#8211;2008&#46; We used the Kaplan-Meier method to estimate cumulative mortality&#44; and Cox regression to compare the confounder-adjusted mortality hazard for patients with vs&#46; without SBP&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">In the Danish Healthcare Cohort&#44; we included 1&#46;282 patients of whom 133 &#40;10&#46;4&#37;&#41; had SBP&#46; The SBP patients&#8217; cumulative 4-month mortality was 51&#46;2&#37; &#40;95&#37; CI&#58; 43&#46;0&#8211;59&#46;9&#37;&#41; vs&#46; 34&#46;7&#37; &#40;95&#37; CI&#58; 32&#46;0&#8211;37&#46;6&#41; in those without SBP&#46; The SBP patients&#8217; confounder-adjusted mortality hazard was 1&#46;54-fold higher &#40;95&#37; CI&#58; 1&#46;18&#8211;2&#46;00&#41; in the four months after paracentesis&#44; but was not increased thereafter &#40;confounder-adjusted mortality hazard 1&#46;02&#44; 95&#37; 0&#46;72&#8211;1&#46;46&#41;&#46; In the satavaptan trial data of 1&#44;198 cirrhosis patients with ascites&#44; the 93 patients with SBP had a cumulative 4-month mortality of 38&#46;6&#37; &#40;95&#37; CI&#58; 29&#46;3&#8211;49&#46;7&#41; compared with 11&#46;4&#37; &#40;95&#37; CI&#58; 8&#46;5&#8211;15&#46;2&#41; in those without&#46; The SBP patients&#8217; confounder-adjusted mortality hazard ratio was 3&#46;86 &#40;95&#37; CI&#58; 2&#46;44&#8211;6&#46;12&#41; during the first four months&#44; and was 1&#46;23 &#40;95&#37; CI&#58; 0&#46;54&#8211;2&#46;83&#41; thereafter&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusions</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">In both cohorts of patients with cirrhosis&#44; an SBP episode had a high short-term mortality compared to patients without SBP&#44; and had no lasting effect on the long-term mortality&#46;</p></span>"
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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">Panel A &#38; B</span> show the mortality hazard ratio with respect to time since first paracentesis for patients with spontaneous bacterial peritonitis &#40;SBP&#41; at the index date compared to those without SBP&#46; The mortality hazard ratio is highest in the first weeks after patients&#8217; first paracentesis &#40;i&#46;e&#46;&#44; the &#8216;index date&#8217;&#41; and then declines over time&#46; The dotted lines are 95&#37; CI&#39;s&#44; and when they cross the HR&#160;&#61;&#160;1&#44; the difference in mortality hazard between SBP-patients and those without is no longer statistically significant&#46; Note the logarithmic scales on the y-axis and that the y-scale differ between the two patient cohorts&#46; Panel C &#38; D show the cumulative all-cause mortality for patients with and without SBP&#46; The number at risk are written underneath the top x-axis for SBP patients &#40;top&#41; and no SBP &#40;bottom&#41;&#46; Danish Healthcare Cohort&#58; A &#38; C panels&#46; Satavaptan Trial Cohort&#58; B &#38; D panels&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "fig0002"
        "etiqueta" => "Fig&#46; 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr2.jpeg"
            "Alto" => 1297
            "Ancho" => 2500
            "Tamanyo" => 263617
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0002"
            "detalle" => "Fig "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Cumulative all-cause mortality for the patients that were alive four months &#40;120 days&#41; after the index date in the Danish Healthcare Cohort &#40;A&#41; and the Satavaptan Trial Cohort &#40;B&#41;&#46; Note that the scale on the x-axis differs between the two patient cohorts&#46; The number at risk are written underneath the top x-axis for SBP patients &#40;top&#41; and no SBP &#40;bottom&#41;&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0022"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0023"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Danish Healthcare Cohort &#40;1&#44;282&#41;</th><a name="en0024"></a><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_colgroup " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Satavaptan Trial cohort &#40;464&#41;</th></tr><tr title="table-row"><a name="en0025"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0026"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SBP &#40;<span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;133&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0027"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">No SBP &#40;<span class="elsevierStyleItalic">N</span>&#160;&#61;&#160;1149&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0028"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">SBP &#40;93&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0029"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">No SBP &#40;371&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0030"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Median age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58 &#40;51&#8211;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58 &#40;51&#8211;65&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">58 &#40;51&#8211;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">57 &#40;51&#8211;63&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0035"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sex &#40;&#37; males&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">73&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">71&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">74&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">72&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0040"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Comorbidity &#40;&#37; Circom score&#62;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">HCC &#91;ICD&#8211;10&#58; C22&#46;0&#93; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">4&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">MELD &#40;median&#41;<a class="elsevierStyleCrossRef" href="#tb1fn1"><span class="elsevierStyleSup">&#8270;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;8 &#40;7&#46;1&#8211;22&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;6 &#40;8&#46;5&#8211;18&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">13&#46;0 &#40;9&#8211;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#46;5 &#40;9&#8211;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0055"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Albumin &#40;g&#47;L&#44; median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">23 &#40;19&#8211;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24 &#40;20&#8211;28&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32 &#40;28&#8211;35&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33 &#40;29&#8211;33&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0060"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Sodium &#40;mmol&#47;L&#44; median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">132 &#40;129&#8211;136&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">133 &#40;129&#8211;137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">134 &#40;132&#8211;137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">135 &#40;132&#8211;139&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0065"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Ascites protein content &#40;g&#47;L&#44; median&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15 &#40;8&#8211;27&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">11 &#40;7&#8211;16&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0070"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Cirrhosis etiology<a class="elsevierStyleCrossRef" href="#tb1fn2"><span class="elsevierStyleSup">&#8270;&#8270;</span></a>&#58;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0075"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Alcohol-related &#91;K70&#46;x&#93; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">79&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">86&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">70&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">56&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0080"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic viral hepatitis &#91;B18&#46;x&#93; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">9&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">32&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0085"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Primary biliary cholangitis &#91;K74&#46;3&#93; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0090"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><span class="elsevierStyleHsp" style=""></span>Autoimmune hepatitis &#91;K73&#46;2&#44; K75&#46;4&#93;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">1&#46;0&nbsp;\t\t\t\t\t\t\n
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ISSN: 16652681
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es en pt

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?

Você é um profissional de saúde habilitado a prescrever ou dispensar medicamentos