In a retrospective analysis of almost 2000 patients, we found 60% to have SPSS; prevalence increases with deterioration of liver function. SPSS increase risk for HE and with a chronic course. In patients with preserved liver function, SPSS increase risk for complications and death. ClinicalTrials.gov ID NCT02692430.

5mm 5 mm Highlights Total cross-sectional SPSS area (TSA) predicts survival in patients with advanced chronic liver disease. The cutoff for TSA that is associated with worse survival corresponds to a single shunt of >10 mm diameter. This study may impact on the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.

The extent of inflammatory infiltrates in arteries from patients with giant-cell arteritis (GCA) have been described using different terms and definitions. Studies investigating the relationship between GCA histological features and clinical manifestations have produced controversial results. The aims of this study were to characterize and validate histological patterns in temporal artery biopsies (TABs) from GCA patients, to explore additional histological features, including the coexistence of different patterns, and also to investigate the relationship of the inflammatory patterns with clinical and laboratory features.We performed histological examination of TAB from patients with GCA consecutively diagnosed between 1992 and 2012. Patterns of inflammation were defined according to the extent and distribution of inflammatory infiltrates within the artery. Clinical and laboratory variables were recorded. Two external investigators underwent a focused, one-day training session and then independently scored 77 cases. Quadratic-weighted kappa was calculated.TAB from 285 patients (200 female/85 male) were evaluated. Four histological inflammatory patterns were distinguished: 1 – adventitial (n = 16); 2 – adventitial invasive: adventitial involvement with some extension to the muscular layer (n = 21); 3 – concentric bilayer: adventitial and intimal involvement with media layer preservation (n = 52); and 4 – panarteritic (n = 196). Skip lesions were observed in 10% and coexistence of various patterns in 43%. Raw agreement of each external scorer with the gold-standard was 82% and 77% (55% and 46% agreement expected from chance); kappa = 0.82 (95% confidence interval [CI] 0.70–0.95) and 0.79 (95% CI 0.68–0.91). Although abnormalities on temporal artery palpation and the presence of jaw claudication and scalp tenderness tended to occur more frequently in patients with arteries depicting more extensive inflammation, no statistically significant correlations were found between histological patterns and clinical features or laboratory findings.In conclusion, we have described and validated 4 histological patterns. The presence of different coexisting patterns likely reflects sequential steps in the progression of inflammation and injury. No clear relationship was found between these patterns and clinical or laboratory findings. However, several cranial manifestations tended to occur more often in patients with temporal arteries exhibiting panarteritic inflammation. This validated score system may be useful to standardize stratification of histological severity for immunopathology biomarker studies or correlation with imaging.

Computed tomography angiography (CTA) detects signs of large-vessel vasculitis (LVV) in about 67.5% of patients with giant-cell arteritis (GCA) at the time of diagnosis and early aortic dilatation in 15%. The outcome of CTA-findings of LVV upon glucocorticoid treatment has not been prospectively evaluated.The aim of our study was to prospectively assess glucocorticoid-induced changes in CTA findings of LVV in patients with GCA.Forty biopsy-proven GCA patients evaluated by CTA at diagnosis were prospectively followed and scheduled a new CTA approximately after 1 year of treatment. Vessel wall thickening, diameter, and contrast enhancement of the aorta and its tributaries were evaluated. Results were compared to those obtained at the time of diagnosis.CTA was repeated to 35 patients after a median follow-up of 13.5 months (IQ25–75% 12.4–15.8). Arterial wall thickening was still present in 17 patients (68% of the patients who initially had LVV). The number of affected segments and wall thickness at various aortic segments significantly decreased and no patients developed new lesions, new aortic dilation or increase in previous dilation. Contrast enhancement disappeared in 15 (93.75%) of 16 patients in whom this finding could be assessed.Signs of LVV improve with treatment. While contrast enhancement resolves in the majority of patients, vessel wall thickening persists in two thirds. However, the number of affected aortic segments as well as aortic wall thickness significantly decreases. Longer follow-up is necessary to determine the clinical significance of persisting wall thickening and its relationship with relapses or subsequent development of aortic dilatation or large-vessel stenoses.

BackgroundOsteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, tissue inflammation and remodelling. We explored the role of serum OPN (sOPN) as a biomarker in patients with giant cell arteritis (GCA).MethodssOPN was measured by immunoassay in 76 treatment-naïve patients with GCA and 25 age-matched and sex-matched controls. In 36 patients, a second measurement was performed after 1 year of glucocorticoid treatment. Baseline clinical and laboratory findings, as well as relapses and glucocorticoid requirements during follow-up, were prospectively recorded. sOPN and C reactive protein (CRP) were measured in 32 additional patients in remission treated with glucocorticoids or tocilizumab (interleukin 6 (IL-6) receptor antagonist). In cultured temporal arteries exposed and unexposed to tocilizumab, OPN mRNA expression and protein production were measured by reverse transcription polymerase chain reaction (RT-PCR) and immunoassay, respectively.ResultssOPN concentration (ng/mL; mean±SD) was significantly elevated in patients with active disease (116.75±65.61) compared with controls (41.10±22.65; p<0.001). A significant decline in sOPN was observed in paired samples as patients entered disease remission (active disease 102.45±57.72, remission 46.47±23.49; p<0.001). sOPN correlated with serum IL-6 (r=0.55; p<0.001). Baseline sOPN concentrations were significantly higher in relapsing versus non-relapsing patients (relapsers 129.08±74.24, non-relapsers 90.63±41.02; p=0.03). OPN mRNA expression and protein production in cultured arteries were not significantly modified by tocilizumab. In tocilizumab-treated patients, CRP became undetectable, whereas sOPN was similar in patients in tocilizumab-maintained (51.91±36.25) or glucocorticoid-maintained remission (50.65±23.59; p=0.49).ConclusionssOPN is a marker of disease activity and a predictor of relapse in GCA. Since OPN is not exclusively IL-6-dependent, sOPN might be a suitable disease activity biomarker in tocilizumab-treated patients.

Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is a rare and often unrecognized disease with prominent inflammatory cutaneous and articular manifestations. Since the identification of the syndrome many immunosuppressive drugs have been used for the management of SAPHO, with variable results. The use of anti- TNF-α agents as a therapeutic option for SAPHO cases unresponsive or refractory to conventional drugs, demonstrated their efficacy for bone, skin and joints manifestations. TNF-α is a pro-inflammatory cytokine and pivotal regulator of other cytokines, including IL-1 β , IL-6 and IL-8, involved in inflammation, acute-phase response induction and chemotaxis. IL-1 inhibition strategies with Anakinra have proven their efficacy as first and second line treatment. We herein review the literature concerning the use of biological drugs in patients with SAPHO syndrome. In addition, we describe for the first time the use of Ustekinumab, an antibody against the p40 subunit of IL-12 and IL-23, after failure of multiple drugs including anti-TNF-α and Anakinra. This anti-IL12/IL23 agent could be a promising therapeutic option, also considering the opportunity to interfere with the IL23/TH17 pathway, which we recently found disturbed. Furthermore, a rationale emerges for the use of the new anti-IL-1 antagonists or the IL-17 blockade, in particular for the most difficult-to-treat SAPHO cases.

Obesity and steatosis have been associated with liver disease progression in patients with compensated advanced chronic liver disease (cACLD) (liver stiffness measurement [LSM] ≥ 10 kPa). The controlled attenuation parameter (CAP) estimates steatosis during LSM by transient elastography. We aimed to evaluate whether CAP is associated with the development of clinically relevant events in cACLD. Consecutive patients with cACLD and CAP measurements observed between September 2013 and September 2015 were retrospectively studied. Classical decompensation and severe bacterial infections on follow‐up were recorded. A predefined CAP cut‐off for steatosis was used (220 dB/m; 90% sensitivity). The association among LSM, CAP, and events was assessed by univariate and multivariate Cox regression. Among the 193 patients (viral etiology = 58%; median Child score = 5; LSM = 15.1 kPa; CAP = 255 ± 62 dB/m) who were followed up in median for 18 months, 18 developed clinically relevant events (11 liver decompensation, 7 severe bacterial infections). Patients developing events had higher LSM (median: 30.8 versus 14.3 kPa, P < 0.001) and showed trends for higher CAP (275 ± 46 versus 252 ± 63 dB/m, P = 0.07), lower platelet count (134 ± 74 versus 167 ± 74 G/L, P = 0.07), and worse liver function versus patients remaining compensated. Body mass index was similar in the two groups. All events were more frequent in patients with CAP being greater than or equal to 220 dB/m (12.9% versus 1.6% in CAP < 220; P = 0.013), and 10 of 11 episodes of liver decompensation occurred in patients with CAP being greater than or equal to 220 dB/m. Following multivariate analysis, LSM and CAP greater than or equal to 220 dB/m remained independently associated with clinical events in the whole population and in patients with clinically significant portal hypertension. Conclusion: The CAP being greater than or equal to 220 dB/m is associated with increased risk of clinical decompensation and bacterial infections independent of LSM in patients with cACLD and allows refining the noninvasive risk stratification in this population. (Hepatology Communications 2018; 00:000‐000)

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