Single center validation of mortality scores in patients with acute decompensation of cirrhosis with and without acute-on-chronic liver failure

Objectives: Acute decompensation (AD) of cirrhosis is characterized by high mortality. We aimed to validate the performance in predicting mortality of both the chronic-liver-failure-consortium (CLIF-C) acute-on-chronic liver failure (ACLF) and CLIF-C AD scores in a cohort of patients admitted for AD.

Methods: In this prospective cohort study, patients were followed-up during their hospital stay and for 365 days thereafter.

Results: About 182 patients with AD were enrolled including 78 (42.8%) who met the criteria for ACLF (ACLF-group) while the remaining had AD without ACLF (AD-group). 56.4% and 56.7% of the ACLF- and AD-groups, respectively, had alcoholic cirrhosis and 85.9% of the ACLF-group hepatic encephalopathy. Only few patients were hospitalized in the intensive care unit (ICU) or transplanted. The probabilities of death estimated for both scores were similar to the overall mortality rates observed at all time points. The model had a good fit in the AD-group at 90 days (p?=?.974) but a worse, yet adequate, in the ACLF-group at 28 days (p?=?.08). The CLIF-C ACLF or AD scores had an adequate, predictive discrimination ability for mortality at all time points, with Harrel’s concordance index-C ranging between 0.64 and 0.65 or 0.64 and 0.68, respectively. Both scores showed a similar predictive accuracy for mortality compared to those of MELD, MELD-Na and Child-Pugh.

Conclusions: In this population without access to appropriate ICU treatment, the CLIF-C ACLF and AD performed worse than in studies with patients having ICU access. In addition, the CLIF scores were not superior to classical ones in this setting.     

Clinical characteristics of patients with liver cirrhosis and spontaneous portosystemic shunts detected by ultrasound in a tertiary care and transplantation centre

Abstract

Objectives: The clinical relevance of spontaneous portosystemic shunts detected by ultrasound is insufficiently investigated. The aim of this retrospective study was to assess the frequency and clinical relevance of spontaneous portosystemic shunts in patients with liver cirrhosis.

Methods: We evaluated portosystemic shunts, liver cirrhosis and spleen size by ultrasound in 982 patients with liver cirrhosis and correlated these with laboratory results, clinical data and the incidence of clinical endpoint deaths, liver transplantation and the development of HCC during the follow-up period (mean 1.26?±?1.53 years [range 0–7.2 years]).

Results: Portosystemic shunts were detected in 34% of the patients. These patients had a higher rate of alcohol-related cirrhosis (37% vs. 30%, p?=?.003), a higher MELD score (p?p?p?p?p?=?.041) and suffered more frequently from Child B/C stages (p?=?.03), hepatorenal syndrome (p?=?.03), massive ascites (p?=?.001) and spontaneous bacterial peritonitis (p?=?.011).

Conclusions: Patients with portosystemic shunts that are detected by ultrasound should be monitored carefully as these patients are associated with advanced liver disease and multiple clinical risk factors.     

Psychiatric symptoms among patients with acute abdominal pain

Abstract

Background: Abdominal pain is a common cause of visits to emergency facilities. It is related to psychiatric disorders in primary care, but it is unclear if this also holds in emergency departments.

Objective: Is to explore potential differences between diagnostic groups in patients with acute abdominal pain in an emergency ward regarding concurrent somatic-and psychiatric symptoms, ‘Length of stay’ (LOS) and perceived health.

Method: The patients (N?=?137) were divided into three groups; organic dyspepsia, specific abdominal diagnoses, and non-specific abdominal pain. The Prime-MD results for extra gastrointestinal symptoms (outside the gastrointestinal tract), psychiatric symptoms, frequency of symptoms, self-reported health, and LOS within the month before admittance were compared between the diagnostic groups.

Results: There was a significant positive correlation between the number of physical extra gastrointestinal and psychiatric symptoms (p?<?.001), especially regarding anxiety (p?<?.001) and depression (p?=?.002). Patients with organic dyspepsia reported significantly more total (p?=?.016), extragastrointestinal (p?=?.026) (chest pain; p?=?.017, dizziness; p?=?.004, palpitations; p?=?.005, insomnia; p?=?.005 and worries; p?=?.001), and summarized anxiety and depression symptoms (p?=?.001–0.002) besides poorer general health (p?<?.001) compared to other abdominal conditions. Also, organic dyspepsia patients needed longer hospital stay than the non-specific abdominal group (p?=?.002) but similar to the specific abdominal disorders group.

Conclusion: Organic dyspepsia is accompanied by more co-occurring physical, anxiety and depression symptoms as well as poorer perceived health than other abdominal pain conditions and comparably increased LOS. This suggests that psychiatric consultations might be beneficial for diagnosing and treating psychiatric comorbidity in emergency care.     

Elevated neopterin levels are associated with acute-on-chronic liver failure and mortality in patients with liver cirrhosis

BackgroundMacrophage activation plays a central role in hepatic and systemic inflammation and is involved in the pathogenesis of acute-on-chronic liver failure (ACLF).AimsThis study aimed to investigate neopterin levels in patients admitted for acute decompensation (AD) of cirrhosis, evaluating its relationship with ACLF and prognosis.MethodsThis prospective cohort study included 205 adult subjects hospitalized for AD of cirrhosis. Twenty-one healthy subjects and 89 patients with stable cirrhosis were evaluated as controls.ResultsCirculating neopterin was higher in AD as compared to stable cirrhosis and healthy controls (p<0.001). ACLF was independently associated with higher neopterin levels (OR 1.015, 95% CI 1.002–1.028, p = 0.025). In the multivariate Cox regression analysis, neopterin levels (HR = 1.002, IC 95% 1.000–1.004, p = 0.041), Child–Pugh class C, and ACLF were predictors of 30-day survival. Among patients with ACLF, the Kaplan–Meier survival probability was 71.4% in those with neopterin levels < 25 nmol/L and 31.0% if neopterin ≥ 25 nmol/L (p<0.001).ConclusionsHigher circulating neopterin was associated with ACLF in patients hospitalized for AD of cirrhosis. Neopterin levels were also independently predictors of high short-term mortality, especially among patients with ACLF, and could represent a useful biomarker of macrophage activation in clinical practice.     

Hyperkalemia influences the outcome of patients with cirrhosis with acute decompensation (AD) and acute-on-chronic liver failure (ACLF)

IntroductionThe presence of hyperkalemia in different clinical scenarios has been described as a risk factor for mortality. Information about this electrolyte disorder in patients with cirrhosis is limited and there are no data in patients with acute-on-chronic liver failure (ACLF).AimThe aim of this study was to investigate whether hyperkalemia is a risk factor for mortality in patients with cirrhosis and acute decompensation (AD) with and without ACLF.MethodsWe performed an analysis of the Chronic Liver Failure Consortium CANONIC database in 1,314 consecutive patients admitted to 29 European centers with AD both with and without associated ACLF (294 and 1020 respectively). Hyperkalemia was defined as serum potassium ≥ 5.0 mEq/L. All patients had at least one valid measure of serum potassium from admission and/or through the whole hospitalization.Results1314 patients were admitted with AD and 294 of them had ACLF at admission. Prevalence of hyperkalemia was significantly higher in ACLF versus AD (22.4% and 8.6% respectively, p<0.001). Hyperkalemia was associated with an increased 90, 180 and 360-day mortality risk in ACLF compared to AD (HR 10 vs 2.3 at 90-day p<0.001, 8.9 vs 3.1 at 180-day, p<0.001 and 5.8 vs 3.8 at 360-day, p<0.001). In a multivariate analysis, the presence of hyperkalemia during admission was independently associated with 90-day mortality [HR 2.4 (1.7 – 3.4)]. Variability of potassium between two valid measures ≥ 0.9 mg/dl was always also associated with a higher mortality rate. Addition of hyperkalemia to MELD score (MELD-K model) improved the accuracy to predict 90-day mortality risk.ConclusionsHyperkalemia is an independent risk factor of mortality in patients with AD and ACLF. Addition of hyperkalemia to the MELD score improves diagnostic accuracy to predict 90-day mortality in patients with AD and ACLF.     

Hepatocellular carcinoma surveillance with liver imaging is not associated with improved survival

Abstract

Objective: International guidelines recommend hepatocellular carcinoma (HCC) surveillance with ultrasound in high-risk patients with chronic liver diseases. However, there is low-strength evidence about the effects on mortality. The aim of our study was to assess the impact of surveillance on the clinical course and survival of HCC patients seen at a tertiary referral center in Germany.

Material and methods: We retrospectively evaluated the data of 401 HCC patients, who presented to our clinic between 1997 and 2015. Two groups were compared regarding patient and disease outcomes: one group included patients who received at least two ultrasound examinations for surveillance purposes prior to first diagnosis (n?=?111). The other group consisted of patients with HCC at first presentation without foregoing HCC surveillance (n?=?290).

Results: Median follow-up in the surveillance group was 76?months (range 4–310?months). Patients in the surveillance group had smaller median tumor sizes (3.5?cm vs. 4.5?cm; p?<?.001), fulfilled more often Milan criteria (64% vs. 42%; p?<?.001) and received more often liver transplantation (27% vs. 9%, p?<?.001) when compared with the non-surveillance group. However, HCC surveillance was not associated with an improved survival (14?months in the surveillance group vs. 12?months in the non-surveillance group, p?=?.375), hazard ratio regarding overall mortality for the surveillance group: 0.80 (95% CI: 0.62–1.04, p?=?.09).

Conclusions: HCC surveillance with ultrasound led to the detection of earlier disease stages but was not significantly associated with improved survival. Further prospective and long-term studies are needed to clarify benefits and harms of HCC surveillance programs on mortality.     

Muscle performance and fatigue in compensated chronic liver disease

Abstract

Background: A common and debilitating symptom in patients with chronic liver disease is fatigue (CLD). Muscle dysfunction has been suggested to be a key mechanism of fatigue in CLD.

Objective: We aimed to evaluate fatigue and the potential association with muscle performance and physical activity in outpatients with CLD.

Methods: Two-hundred seventy outpatients with CLD were included, (52?±?15 years, mean?±?SD; 151 females) with autoimmune hepatitis (n?=?49), primary biliary cholangitis (n?=?45), primary sclerosing cholangitis (n?=?46), chronic hepatitis B (n?=?57) or C (n?=?73). Patients with a Child-Pugh >6 were excluded. The questionnaire Fatigue Impact Scale (FIS) was used to evaluate fatigue, and physical activity was evaluated through a self-reported level of physical activity. Muscle function was assessed with four muscle tests, walking speed, handgrip strength, standing heel-rise test (SHT) and ‘Timed Up and Go’ test (TUG).

Results: The median total FIS score was 30 (40% had FIS > 40, considered high-fatigue). Diminished muscle performance was observed in the SHT (% of predicted value: 53?±?26%) and with maximum grip strength (85?±?20%). The FIS score was significantly different between groups of CLDs (p?=?.004). In multivariate analysis the TUG (p?=?.001), SHT (p?=?.005), antidepressants (p?p?=?.001) were associated with fatigue (R²?=?29%). Subjects with higher levels of physical activity had lower FIS (p?Conclusions: In patients with CLD, fatigue was associated with low muscle performance and reduced level of physical activity, which could be a potential therapeutic target.     

Clinical and virological implications of A1846T and C1913A/G mutations of hepatitis B virus genome in severe liver diseases

Objective: Mutations occurring within different genes of hepatitis B virus (HBV) genome may have different clinical implications. This study aimed to observe the clinical and virological implications of the A1846T and C1913A/G mutations of HBV genome in the development and treatment outcome of severe liver diseases, which has not been previously determined.

Materials and methods: A total of 438 cases of patients with liver diseases were retrospectively reviewed, including 146 with mild chronic hepatitis B infection (CHB-M), 146 with severe chronic hepatitis B infection (CHB-S), and 146 with acute-on-chronic liver failure (ACLF). Partial or full-length HBV genome was directly sequenced. Replicons containing A1846T, C1913A or other mutant sequences, or the wild-type counterparts were constructed respectively, and then transfected into HepG2 cells for phenotype analysis.

Results: There was significant difference in the detection rates of A1846T (30.82%, 40.41% and 55.48%, respectively) and C1913A/G (15.52%, 28.77%, and 35.62%, respectively) among patients with CHB-M, those with CHB-S, and those with ACLF (p?p?=?.041). In vitro experiment revealed that A1846T mutant resulted in 3.20-fold and 1.85-fold increase of replication capacity and promoter activity, respectively compared with wild type counterpart (p?p?Conclusion: Occurrence of A1846T and C1913A is positively associated with clinical presentations of severe liver disease. A1846T mutation is significantly associated with poor prognosis of ACLF.     

31Phosphorus magnetic resonance spectroscopy of the liver for evaluating inflammation and fibrosis in autoimmune hepatitis

Background: Liver biopsy is the gold standard in evaluating inflammation and fibrosis in autoimmune hepatitis.

Aims: In search of non-invasive follow-up tools in autoimmune hepatitis, we evaluated ³¹phosphorus magnetic resonance spectroscopy (³¹P MRS).

Methods: Twelve consecutive AIH patients (mean age 42.8 years, 10 women) underwent liver biopsy, routine laboratory liver function tests, which were compared to findings in ³¹P MRS and transient elastography (TE).

Results: Phosphoenolpuryvate (PEP) correlated with the grade of inflammation (r?=?0.746, p?=?.005) and thromboplastin time (r?=?0.592, p?=?.043). It also differentiated patients with active inflammation from patients without (t?=?3.781, p?=?.009). There was no correlation between PEP and aminotransferase or immunoglobulin G levels.

The phosphoethanolamine (PE)/phosphocholine (PC) ratio, PE/glyserophosphoethanolamine (GPE) ratio and PC/[total phosphomonoester (PME)?+?phosphodiester (PDE)] ratios correlated with immunoglobulin G (r?=?0.764, p?=?.006; r?=?0.618, p?=?.043; and r=??0.636, p?=?.035, respectively).

PME/PDE and PE/GPE correlated with fibrosis (r?=?0.668, p?=?.018 and r?=?0.604, p?=?.037). PE/GPE also differentiated F3 from F0-2 patients (t?=?3.810, p?=?.003).

Phosphorus metabolites did not correlate with TE results and TE did not correlate with liver histology or laboratory parameters.

Conclusions: ³¹P MRS seems to detect active inflammation and advanced fibrosis in AIH patients. TE was ineffective in fibrosis quantification.     

Prognostic value of lectin pathway molecules and complement proteins in ascitic fluid and blood in patients with liver cirrhosis

Background and aim: Patients with liver cirrhosis and ascites have a poor prognosis with increased risk of infection related death, as advanced stages of cirrhosis are associated with immunodeficiency. We aimed to investigate immunologically active molecules in ascitic fluid and blood and their potential association to survival.

Materials and methods: In an exploratory pilot study; blood and ascitic fluid from 34 patients with liver cirrhosis of different etiology were analyzed for pattern recognition molecules (ficolin-1, ficolin-2, ficolin-3 and MBL) and complement proteins (C4 and C3). An observational follow-up study (minimum 17 months) was conducted to assess the association to all-cause mortality or liver transplantation.

Results: Ficolin-1, ficolin-2, MBL, C4 and C3 in ascitic fluid and ficolin-1, C4 and C3 in blood were significantly (p?=?.001–.027) lower in patients with Child-Pugh stage C (n?=?16, 47%) compared to Child-Pugh stage B cirrhosis (n?=?18, 53%). In multivariate COX-regression analysis low levels of ficolin-1(p?=?.036) and C3 (p?=?.025) in ascitic fluid and C4(p?=?.005) and C3 (p?=?.032) in serum were associated with all-cause mortality or liver transplantation independent of Child-Pugh score.

Conclusion: Levels of lectin-complement pathway molecules in ascitic fluid and blood are lower in patients with more advanced stage of cirrhosis. Low C4 and C3 in serum and C3 and ficolin-1 in ascitic fluid are risk factors for all-cause mortality or liver transplantation independently of liver function in patients with cirrhosis and ascites.     

Comparison of clinical characteristics and outcomes of spontaneous bacterial peritonitis and culture negative neutrocytic ascites

Objective: Ascitic fluid infections (AFI) in cirrhotic patients can be classified into two groups: spontaneous bacterial peritonitis (SBP) and culture-negative neutrocytic ascites (CNNA). The aim of this study was to compare the clinical characteristics and outcomes of the two groups of patients with AFI.

Methods: We retrospectively reviewed the medical records of cirrhotic patients with AFI. We evaluated demographic data, clinical presentations of AFI, laboratory findings, liver function, and mortality rates.

Results: Between January 2005 and December 2014, 533 patients with AFI were evaluated; 259 (48.6%) had SBP and 274 (51.4%) CNNA. Ascites neutrophil count (4410/mm³ versus 1046/mm³, p?<?.001) and the blood culture positive rate (38.1% versus 20.1%, p?<?.001) were higher in the SBP group, which also had a higher MELD score (24.29 versus 22.05, p?=?.004). Seven-day mortality was higher in the SBP group (9.4% versus 4.5%, p?=?.027) but there was no significant difference in 30-day (22.1% versus 17.5%) or 90-day mortality rate (36.1% versus 36.4%).

Conclusions: Patients in the SBP group had a higher MELD score, ascites neutrophil count, and positive blood culture rate. Although seven-day mortality rate was higher in the SBP group, the 30-day and 90-day mortality rates were similar in the two groups.     

Does transient elastography correlate with liver fibrosis in patients with PSC? Laennec score-based analysis of explanted livers

Background and aims: Previous studies demonstrated a close correlation between transient elastography (TE) and liver histology in chronic liver diseases. Data on the accuracy of TE in primary sclerosing cholangitis (PSC) remains scarce. Here, we investigated the association between TE, serum marker of liver injury and histology of explanted livers in PSC patients.

Methods: Thirty patients were prospectively recruited. TE (Fibroscan^®) and blood sampling were performed during evaluation for liver transplantation (LT); the second blood sampling was performed on the day of LT. Fibrosis of explanted livers according to the seven-point Laennec staging system and liver collagen contents were measured.

Results: TE correlated with Laennec stages of fibrosis (p?=?.001), collagen contents (p?p?=?.034) in explanted livers. It also correlated with serum indices of liver injury, namely AST, bilirubin as well as FIB-4 and APRI scores (all p?p?=?.035) or collagen contents (p?=?.005), was significantly associated with TE. Finally, patients with cirrhosis had increased liver stiffness (p?=?.002) and the TE cut-off of 13.7?kPa showed the best predictive value (AUC?=?.90, 95% CI: 0.80–1.00, p?Conclusions: TE correlates with liver fibrosis and markers of liver injury in patients with PSC. However, liver fibrosis seems to be the strongest predictor of liver stiffness assessed with TE. Hence, we postulate that TE is a reliable tool for non-invasive monitoring of PSC.     

Localization of Helicobacter pylori gastritis and the relation of existing histopathological features with reflux esophagitis

Abstract

Background/aims: Interactions between Helicobacter pylori (Hp) and gastroesophageal reflux disease (GERD), which are common diseases worldwide, are confusing. In this study, the aim was to compare and evaluate the relationship between reflux esophagitis (RE) and Hp infection in adult patients with both the gastric localization of Hp and its histopathologic features.

Materials and methods: 248 patients with RE were compared with 249 age and sex matched control groups. Biopsy specimens obtained from the gastric antrum and corpus were histologically evaluated.

Findings: The incidence of Hp infection was significantly lower in patients with RE than in the control group (Ratio 1.53, 95% CI 1.07–2.20; p?=?.02, p?<?.05). Corpus Hp colonization and corpus gastritis scores were notably lower in the study group (p?=?.01, p?<?.05), whereas there was no significant difference in Hp colonization and antrum gastritis scores in the antrum. Corpus Hp colonization and gastritis scores were found to be negatively correlated with esophagitis development (r?=??0.11; p?=?.01; (r?=??0.14; p?=?.00 respectively, p?<?.05). There was no difference between the groups in terms of atrophy development (p?>?.05).

Conclusion: This study showed that the presence of Hp infection in the corpus and corpus gastritis score was significantly lower in patients with erosive reflux esophagitis than in the control group. It also showed that Hp colonization and corpus gastritis scores were negatively correlated with esophagitis development. This inverse relationship was independent of atrophy.     

Non-selective beta-blocker treatment does not impact on kidney function in cirrhotic patients with varices

Goals and background: Non-selective beta-blockers (NSBBs) are used for bleeding prophylaxis in cirrhotic patients with gastroesophageal varices (GEVs). Recent data suggested that NSBB treatment might increase the risk of renal dysfunction in patients with refractory ascites due to an impaired response to acute haemodynamic stress.

Study: Retrospective longitudinal assessment of kidney function in a cohort of cirrhotic patients with GEVs with vs. without NSBB therapy. Serum creatinine (SCre), estimated glomerular filtration rate (eGFR), incidence of acute kidney injury (AKI), new onset of large volume ascites and TIPS-/transplant-free survival were compared.

Results: Among 176 patients, 93 patients received NSBBs, while 83 did not. Most patients were male (77.8%), had alcoholic aetiology (52.3%) and compensated cirrhosis (51.1% Child-A, MELD: 12.1?±?3.8). Over a 3-year follow-up, renal function was comparable between patients with and without NSBB treatment. Incidence of AKI was similar in NSBB vs. no-NSBB patients (p?=?.323). Even in potential risk groups (ascites, MAP <90?mmHg, baseline creatinine?>?ULN, hyponatraemia, MELD score ≥15 points, Child–Pugh B/C), there was no difference in SCre or eGFR with vs. without NSBBs (p?=?n.s. at 74/78 and 76/78 of analysed time points). However, multivariate analysis revealed that the presence of ascites (HR: 3.901, 95%CI: 1.352–11.251; p?=?.012) and pre-existing renal impairment (HR: 4.315, 95%CI: 1.054–17.672; p?=?.042) were independent risk factors for AKI. Importantly, NSBB use (HR: 0.319, 95%CI: 0.120–0.848; p?=?.022) was independently associated with improved TIPS-/transplant-free survival.

Conclusions: In our cohort of unselected, mostly compensated cirrhotic patients with GEVs, NSBB treatment was neither associated with worsening of kidney function nor with increased incidence of AKI. On the contrary, NSBB treatment improved TIPS-/transplant-free survival.     

Acute biliary pancreatitis: focus on recurrence rate and costs when current guidelines are not complied

Background: International guidelines recommend cholecystectomy within 2–4 weeks after mild to moderate acute biliary pancreatitis (ABP) to prevent recurrence. We aimed to investigate the compliance to guidelines concerning early cholecystectomy and the associated costs.

Methods: Admissions for ABP 2011–2013 were retrospectively reviewed. Classification was made according to the revised Atlanta classification. Treatment, time to surgery and recurrence, as well as cost analysis for both in-hospital costs and loss of production (LOP) were performed.

Results: In total, 254 patients were included. Some 202 of the ABP patients (80%) underwent definitive treatment during their first attack of ABP (68% cholecystectomy, 17% endoscopic retrograde cholangiopancreatography (ERCP), 15% both interventions) and 186 (73%) were treated within 1 month of discharge. Patients with ERCP alone were significantly older than cholecystectomy cases (p?<?.001), but no significant difference was observed between those who underwent ERCP or no treatment (p?=?.071). Mild ABP had intervention earlier (p?<?.001). In all, 52 patients (20%) had no intervention, out of which 15 were readmitted due to pancreatitis, compared to 3 patients of those treated at the initial admission (p?<?.001). The mean cost for hospital care and LOP in mild ABP was €6882?±?3010 and €9580?±?7047 for moderate ABP (p?=?.001). The cost for a recurrent episode was €16,412?±?22,367.

Conclusion: By improved compliance to current guidelines concerning the management of ABP, recurrence rate and associated costs can potentially be reduced.     

The relationship between dectin-1 and mast cells in patients with diarrhea-predominant irritable bowel syndrome

Abstract

Background/Aims: Currently, the role of the microbiome GBA is being widely studied in the pathogenesis of visceral hypersensitivity in IBS. To investigate the role of fungus, the current study aimed to i) investigate the expression of Syk/CARD9-coupled Dectin-1 receptors in the ileocecal mucosa in D-IBS patients and (ii) explore the relationships between Dectin-1 and plasma MCT levels as well as anorectal sensory function in patients with D-IBS.

Methods: Thirty-eight D-IBS patients who met the Rome III criteria and 2 groups of age- and sex-matched asymptomatic healthy controls were recruited from March 2015 to January 2017. Anorectal sensory function was quantified by HR-ARM. Plasma MCT titers were identified by ELISA, while the expression of Syk/CARD9 Dectin-1 receptors in ileocecal mucosa was identified by RT-qPCR.

Results: (i) The expression of Syk/CARD9-coupled Dectin-1 receptors was significantly higher in D-IBS patients than in controls (p?<?.001). ii) The threshold values of first sensation and desire to defecate were significantly lower in D-IBS patientsthan in controls (the P value was0.007 and 0.001 respectively). (iii) There were negative correlations between plasma MCT levels and first sensation thresholds in D-IBS patients (r = ?0.513, p?=?.012) and the desire to defecate thresholds (r = ?0.423, p?=?.044). (iiii) There was a positive correlation between plasma MCT titers and the expression of Dectin-1 receptors in D-IBS patients (r?=?0.565, p?=?.005).

Conclusions: These results suggested that fungi may partially participate in the genesis of visceral hypersensitivity by activating mast cells, which is mediated by activation of the Dectin-1 receptor-mediated Syk/CARD9 signaling pathway.     

KL-6 is a long-term disease-activity biomarker for interstitial lung disease associated with polymyositis/dermatomyositis,but is not a short-term disease-activity biomarker

Abstract

Objectives: We aimed to evaluate the usefulness of serum KL-6 for interstitial lung disease (ILD) with polymyositis/dermatomyositis (PM/DM).

Methods: All consecutive and previously untreated adult patients with PM/DM who were admitted to our hospital from 2010 to 2015 were included. The associations between serum KL-6 levels and clinical information were retrospectively analyzed.

Results: Baseline serum KL-6 levels were significantly higher in patients with ILD than in those without (n?=?41 and 15, respectively; p?<?.001). In the 14 patients whose ILD improved within 4 weeks post-treatment, their serum KL-6 levels did not significantly decrease at 2 weeks, 4 weeks, or 3 months post-treatment (p?=?1.00, 1.00, and .83, respectively). Conversely, their serum KL-6 levels significantly decreased at 6, 9, and 12 months post-treatment (p?=?.01 in all comparisons). In the 12 patients whose ILD remained unchanged or deteriorated in 4 weeks post-treatment, only the difference between their serum KL-6 levels at 3 and 12 months was significant (p?=?.003).

Conclusions: The present study validated the serum KL-6 as a diagnostic marker for ILD in PM/DM. However, serum KL-6 is not a short-term disease-activity biomarker for ILD with PM/DM, but it is a long-term disease-activity biomarker.     

Predictive factors for 28-day mortality in acute-on-chronic liver failure patients admitted to the intensive care unit

BackgroundAcute-on-chronic liver failure (ACLF) is an entity comprising an acute deterioration of liver function in cirrhotic patients, associated with organ failure(s) and high short-term mortality. We aimed to identify predictive factors for short-term mortality in patients admitted with ACLF that may benefit most from liver transplantation.MethodsRetrospective analysis of patients admitted in ACLF to a tertiary intensive care unit between 2013 and 2017 was performed. The EASL-CLIF acute-on-chronic liver failure in cirrhosis (CANONIC) criteria were used to define ACLF grade. Multivariable analysis using 28-day mortality as an end-point was performed, including severity-of-disease scores and clinical parameters.ResultsSeventy-seven patients were admitted in ACLF over the study period. The commonest aetiology of liver disease was alcohol related 52/77(68%) and the commonest precipitant of ACLF was variceal haemorrhage 38/77(49%). Overall 28-day mortality was 42/77(55%) [ACLF-(grade)1:3/42(7%); ACLF-2:10/42(24%); and, ACLF-3:29/42(69%);p = 0.002]. On multivariable analysis MELD ≥ 26 [odds ratio(OR) = 11.559; 95% confidence interval(CI):2.820–47.382;p = 0.001], ACLF-3 (OR = 3.287; 95%CI:1.047–10.325;p = 0.042) at admission and requirement for renal replacement therapy (OR = 5.348; 95%CI:1.385–20.645;p = 0.015) were independently associated with 28-day mortality.ConclusionPatients admitted with ACLF to intensive care have a high mortality rate. Defined early thresholds at admission can identify patients at the highest risk that may benefit most from liver transplantation.     

Haematological response and overall survival in two consecutive Dutch patient cohorts with AL amyloidosis diagnosed between 2008 and 2016

Abstract

Background: Although survival has improved in recent decades, the short-term prognosis of patients with immunoglobulin light chain (AL) amyloidosis remains grim. We aimed to assess overall survival (OS) of AL amyloidosis patients by comparing cohorts in two consecutive time periods.

Methods: Data were collected and compared on 126 patients from two tertiary referral centres in The Netherlands during the time periods 2008–2012 and 2013–2016.

Results: There was a non-significant trend to improved 6-month OS in the last cohort (78% vs. 67%, p?=?.216, crude odds ratio 1.66, 95%CI 0.74–3.70, adjusted odds ratio 2.22, 95%CI 0.88–5.56). Patients in this cohort had higher Mayo risk scores (stage III 40% vs. 24%, p?<?.001 and revised stage IV 14% vs. 11%, p?<?.001), higher use of bortezomib (50% vs. 30%), and better haematological response (complete response/very good partial response in 39% vs. 27%, p?<?.001). Diagnostic delay was similar in both time periods.

Conclusions: In the 2013–2016 cohort there was a trend toward improved 6-month OS, and an improved haematological response. Patients in this cohort had more advanced cardiac disease and received bortezomib more frequently, but diagnostic delay was similar to the 2008–2012 cohort. For further prognostic improvement, practitioners should be more alert, especially for cardiac amyloidosis.     

Serum chitotriosidase: a circulating biomarker in polycythemia vera

ABSTRACT

Objectives: Serum chitotriosidase activity (CHIT1) is a biomarker of macrophage activation with an important role in inflammation-induced tissue remodeling and fibrosis. Macrophages have been described to play a crucial role in regulating pathological erythropoiesis in polycythemia vera (PV). The aim of this study was to evaluate CHIT1 in patients diagnosed with Philadelphia-negative myeloproliferative neoplasms (MPNs).

Methods: Using fluorometric assay, we measured CHIT1 in 28 PV, 27 essential thrombocythemia (ET), 17 primary myelofibrosis (PMF), 19 patients with secondary myelofibrosis and in 25 healthy controls.

Results: CHIT1 was significantly higher in PV (p?<?.001) and post-PV myelofibrosis (MF) transformation (post-PV MF) (p?=?.020), but not in ET (p?=?.080), post-ET MF transformation (p?=?.086), and PMF patients (p?=?.287), when compared to healthy controls. CHIT1 in PV was positively correlated with hemoglobin (p?=?.026), hematocrit (p?=?.012), absolute basophil count (p?=?.030) and the presence of reticulin fibrosis in the bone marrow (p?=?.023).

Discussion: A positive correlation between CHIT1 and these distinct laboratory PV features might imply macrophages closely related to clonal erythropoiesis as cells of CHIT1 origin. In addition, a positive association between CHIT1 and reticulin fibrosis might indicate its potential role in PV progression.

Conclusion: CHIT1 might be considered as a circulating biomarker in PV. Additional studies are needed to clarify the role of CHIT1 in promoting disease progression and bone marrow fibrosis in PV.