A prospective, multicenter, three-cohort study evaluating contrast-induced acute kidney injury (CI-AKI) in patients with cirrhosis.

BACKGROUND & AIMS: Nephrotoxicity of intravenous iodinated contrast media (ICM) in cirrhosis is still a debated issue, due to scarce, low-quality and conflicting evidence. This study aims to evaluate the incidence and predisposing factors of acute kidney injury (AKI) in patients with cirrhosis undergoing contrast-enhanced computed tomography (CECT). METHODS: We performed a prospective, multicenter, cohort study including 444 inpatients, 148 with cirrhosis (cohort 1) and 163 without cirrhosis (cohort 3) undergoing CECT and 133 with cirrhosis (cohort 2) unexposed to ICM. Kidney function parameters were assessed at T0, 48-72 h (T1), 5 and 7 days after CECT/enrollment. Urinary neutrophil gelatinase-associated lipocalin (U-NGAL) was measured in 50 consecutive patients from cohort 1 and 50 from cohort 2 as an early biomarker of tubular damage. RESULTS: AKI incidence was not significantly increased in patients with cirrhosis undergoing CECT (4.8%, 1.5%, 2.5% in cohorts 1, 2, 3 respectively, p = n.s.). Most AKI cases were mild and transient. The presence of concomitant infections was the only independent predictive factor of contrast-induced AKI (odds ratio 22.18; 95% CI 2.87-171.22; p = 0.003). No significant modifications of U-NGAL between T0 and T1 were detected, neither in cohort 1 nor in cohort 2 (median ΔU-NGAL: +0.2 [-7.6 to +5.5] ng/ml, +0.0 [-6.8 to +9.5] ng/ml, respectively [p = 0.682]). CONCLUSIONS: AKI risk after CECT in cirrhosis is low and not significantly different from that of the general population or of the cirrhotic population unexposed to ICM. It mostly consists of mild and rapidly resolving episodes of renal dysfunction and it is not associated with tubular kidney injury. Patients with ongoing infections appear to be the only ones at higher risk of AKI. IMPACT AND IMPLICATIONS: Nephrotoxicity due to intravenous iodinated contrast media (ICM) in patients with cirrhosis is still a debated issue, as the available evidence is limited and based on very heterogeneous studies, often conducted on small and retrospective cohorts. In this prospective three-cohort study we found that intravenous administration of ICM was associated with a low risk of AKI, similar to that of the general population and to that of patients with cirrhosis unexposed to ICM. Patients with ongoing infections were the only ones to have a significantly increased risk of contrast-induced AKI. Therefore, the actual recommendations of performing contrast imaging studies cautiously in cirrhosis do not seem to be reasonable anymore, with the exception of infected patients, who have a significantly higher risk of contrast-induced AKI.

The Predictive Role of Extracellular NAPRT for the Detection of Advanced Fibrosis in Biopsy-Proven Non-Alcoholic Fatty Liver Disease.

Intrahepatic oxidative stress is a key driver of inflammation and fibrogenesis in non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the role of extracellular Nicotinamide phosphoribosyltransferase (eNAMPT) and extracellular nicotinic acid phosphoribosyltransferase (eNAPRT) for the detection of advanced fibrosis. eNAMPT and eNAPRT were tested in 180 consecutive biopsy-proven NAFLD patients and compared with liver stiffness (LS) and the FIB-4 score. eNAMPT was similarly distributed across fibrosis stages, whereas eNAPRT was increased in patients with advanced fibrosis (p = 0.036) and was associated with advanced fibrosis (OR 1.08, p = 0.016). A multiple stepwise logistic regression model containing significant variables for advanced fibrosis (eNAPRT, type 2 diabetes, age, male sex, ALT) had an area under the curve (AUC) of 0.82 (Se 89.6%, Sp 67.3%, PPV 46.7%, NPV 93.8%) when compared to that of LS (0.79; Se 63.5%, Sp 86.2%, PPV 66.0%, NPV 84.8%) and to that of the FIB-4 score (0.73; Se 80.0%, Sp 56.8%, PPV 44.9%, NPV 86.6%). The use of eNAPRT in clinical practice might allow for the better characterization of NAFLD patients at higher risk of disease progression.

Screening and surveillance of oesophageal varices in patients with HCV-positive liver cirrhosis successfully treated by direct-acting antiviral agents.

BACKGROUND & AIMS: limited evidence is available to guide hepatologists regarding endoscopic surveillance of oesophageal varices (EV) in Hepatitis C Virus (HCV)-positive cirrhotic patients achieving a sustained virologic response. To address these issues, we conducted a long-term prospective study on 427 HCV-positive cirrhotic patients successfully treated by Direct Antiviral Agents (DAAs). METHODS: Patients were divided into two groups according to their baseline Baveno VI status: Group 1 (92, 21.5%, favourable Baveno VI status) and Group 2 (335, 78.5%, unfavourable Baveno VI status). Each patient underwent baseline endoscopy and was endoscopically monitored for a median follow-up of 65.2 months according to Baveno VI recommendations. RESULTS: About 4.3% of Group 1 patients showed baseline EV compared with 30.1% of Group 2 patients (p < .0001). No patients belonging to Group 1 without baseline EV developed EV at follow-up endoscopy compared with 6.5% in Group 2 patients (p = .02); 69/107 (64.5%) patients with baseline EV showed small varices. During the endoscopic follow-up, EV disappeared/improved in 36 (33.6%), were stable in 39 (36.4%) and worsened in 32 (29.9%) patients, all belonging to Group 2 (p = .001). Improvement in Baveno VI status was observed in 118/335 (35.2%, p < .0001) of Group 2 patients and among those without pre-therapy EV, none developed EV throughout the follow-up. CONCLUSIONS: HCV-positive cirrhotic patients cured by DAAs showing baseline favourable Baveno VI status and no worsening during follow-up can safely avoid endoscopic screening and surveillance. Patients having unfavourable Baveno VI status without baseline EV who improve their status may suspend further endoscopic surveillance.

Interplay between Oxidative Stress and Metabolic Derangements in Non-Alcoholic Fatty Liver Disease: The Role of Selenoprotein P.

Background: Pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) are complex and multifactorial. We investigated oxidative stress through the measurement of selenoprotein P (SeP) in serum and we explored its relation to metabolic derangements and liver damage in a group of non-diabetic NAFLD subjects. Methods: 57 NAFLD patients underwent a double-tracer oral glucose tolerance test (OGTT). Insulin resistance (IR) components were calculated at baseline as follows: hepatic-IR = (endogenous glucose production*insulin); peripheral-IR = (glucose rate of disappearance(Rd)); adipose-tissue(AT)-IR as Lipo-IR = (glycerol rate of appearance (Ra)*insulin) or AT-IR = (free fatty acids (FFAs)*insulin). The lipid and amino acid (AA) profiles were assessed by gas chromatography-mass spectrometry. SeP levels were measured by enzyme immunosorbent assay. Results: Circulating SeP correlated with insulin (rS = 0.28), FFAs (rS = 0.42), glucose Rd (rS = -0.33) and glycerol Ra (rS = -0.34); consistently, SeP levels correlated with Lipo-IR and AT-IR (rS > 0.4). Among the AA and lipid profiles, SeP inversely correlated with serine (rS = -0.31), glycine (rS = -0.44) and branched chain AA (rS = -0.32), and directly correlated with saturated (rS = 0.41) and monounsaturated FFAs (rS = 0.40). Hepatic steatosis and fibrosis increased in subjects with higher levels of SeP. In multivariable regression analysis, SeP was associated with the degree of hepatic fibrosis (t = 2.4, p = 0.022). Conclusions: SeP levels were associated with an altered metabolic profile and to the degree of hepatic fibrosis, suggesting a role in the pathogenesis of NAFLD.

Vedolizumab for treatment of chronic refractory pouchitis: a systematic review with pool analysis.

BACKGROUND AND OBJECTIVES: about 1%-2% of patients with chronic refractory pouchitis, in the context of ulcerative colitis, end up with a permanent ileostomy. The aim of this systematic review was to collect all published studies involving patients treated with vedolizumab for chronic refractory or antibiotic-dependent pouchitis and then pool the data regarding the effectiveness of this therapeutic strategy. METHODS: a MEDLINE and Web of Science search of all studies published in English until March 17, 2019 was conducted using the terms "vedolizumab and pouchitis". RESULTS: seven studies with a total of 44 patients with chronic pouchitis were included. Twenty-three out of 44 patients (52.3%) had undergone previous treatment with anti-tumor necrosis factor (TNF) drugs. At week 12, 33 out of 44 patients (75%) reported clinical improvement. Endoscopic improvement, evaluated within 6 months of the start of vedolizumab therapy, was obtained in 28 out of the 38 patients in whom such data were available (73.7%). CONCLUSIONS: this first systematic review published in the literature on this issue suggests that vedolizumab has significant efficacy in chronic refractory or antibiotic-dependent pouchitis, also in patients who failed to respond to other treatments including those with anti-TNF agents.

Effectiveness and safety of adalimumab biosimilar ABP 501 in Crohn's disease: an observational study.

BACKGROUND AND OBJECTIVE: there are no studies in the literature about the effectiveness of adalimumab biosimilar ABP 501 in Crohn's disease. The aim of this study was to evaluate its effectiveness and safety. METHODS: an observational study was performed in Crohn's disease patients treated with ABP 501, with the classic induction and maintenance regimen and in Crohn's disease patients who were switched from the adalimumab originator to ABP 501. RESULTS: eighty-seven patients were included in the study, of which 25 were naïve to the adalimumab originator and 62 were switched to ABP 501. In adalimumab-naïve patients, clinical response at three months was 60% (15/25) and clinical remission at three months was 56% (14/25). At six months, 95.2% (59/62) of the patients switched to ABP 501 were still in therapy, without a significant increase of clinical activity (Harvey-Bradshaw index from 3.4, 95% CI = 2.4-4.4, to 3.8, 95% CI = 2.7-4.9, p = 0.23) and inflammatory biomarkers (C-reactive protein from 4.2 mg/l, 95% CI = 2.5-5.9 mg/l, to 3.6 mg/l, 95% CI = 2.2-5 mg/l, p = 0.32). There were no unexpected adverse events during the study period. CONCLUSIONS: our results support ABP 501 as an effective and well-tolerated drug, with a good interchangeability with its originator for the treatment of Crohn's disease.

Incidence of Prostate Cancer in Inflammatory Bowel Disease: A Meta-Analysis.

Background and objectives: Inflammatory bowel disease (IBD) is associated with an increased risk of developing colorectal cancer as well as some extra-intestinal tumors, but there are still limited data about the risk of prostate cancer (PC). To analyze if there is an increased risk of PC in patients affected by IBD, we performed a systematic review with meta-analysis. Materials and Methods: A Pubmed search of all studies comparing standardized incidence ratio (SIR) or odds ratio (OR) or relative risks (RR) of PC between IBD and non IBD groups, published until March 2020 was conducted. The study protocol was registered on PROSPERO. Twelve studies, mostly population studies, were included. The quality score of these studies, evaluated by the Newcastle-Ottawa Scale, was 7. The heterogeneity was high among the studies in which ulcerative colitis (UC) was considered separate from Crohn's disease (CD) and in the studies that considered UC and CD together ("IBD-studies"), while it was low in the studies which considered CD separate from UC. Results: The relative risk of developing PC was 1.71 (95% confidence interval [CI] 1.16-2.51, p = 0.007) in IBD, 1.10 (95%CI 0.98-1.25, p = 0.116) in CD, and 1.22 (95%CI 0.98-1.51, p = 0.07) in UC. Conclusions: Patients with IBD appear to have a slightly increased risk of PC compared to the general population.

Dual biological therapy with anti-TNF, vedolizumab or ustekinumab in inflammatory bowel disease: a systematic review with pool analysis.

Background: Inflammatory bowel diseases patients eligible for biological therapy represent a group with considerable disease burden and biologics only achieve 40% clinical remission rates in responders after 1 year of therapy. Aims: To collect all the published data about patients treated with dual biological therapy with an Anti-TNF, vedolizumab or ustekinumab, for a period of at least 3 months and to pool the data about the effectiveness and safety. Methods: A MEDLINE, and Web of Science search of all studies published in English until 1 January 2019 was conducted. Results: We included 7 studies with a total of 18 patients. Fifteen patients were treated with a combination of an anti-TNF and vedolizumab, 3 patients were treated with vedolizumab and ustekinumab. Fifty-six percent of patients were affected by Crohn's disease and 50% of patients were treated with an immunosuppressant drug or steroid too. A clinical improvement was obtained in 100% of patients, and an endoscopic improvement in 93% of patients. No serious adverse events were reported. Conclusions: The use of dual biological therapy is an attractive therapeutic option and may be an opportunity to better tailor and personalize the therapies for patients. Further studies, as randomized control trials, to provide comparative efficacy and safety endpoints of combination therapies, and to clarify potential advantages of combined biological therapies, are needed.

Adalimumab versus azathioprine to halt the progression of bowel damage in Crohn's disease: application of Lémann Index.

Background: The Lémann Index (LI) was recently developed to evaluate the cumulative bowel damage in patients with Crohn's disease (CD).Aims: To search for a difference between adalimumab and azathioprine to halt the progression of bowel damage in active CD, using the LI.Methods: A single-centre, retrospective study was conducted. Patients with CD were included if they had colonoscopy and magnetic resonance enterography performed within 4 months from the start of adalimumab or azathioprine and repeated after 12 months of therapy. Primary outcome was reached if the increase of LI after 12 months of treatment was <0.3, the drug was not stopped, and the use of systemic steroids was continued for no more than 3 months.Results: Ninety-one patients were enrolled, 31 (34.1%) of them treated with adalimumab and 60 (65.9%) with azathioprine. Sixty-seven percent of patients treated with adalimumab reached the primary outcome compared to 28.3% of patients treated with azathioprine (p = .0006). The LI in the group on adalimumab therapy decreased after 12 months (from 9.9 to 8.8), while in the group on azathioprine therapy it increased (from 7.7 to 8.8).Conclusion: Treatment with adalimumab halts the progression of bowel damage in CD while that with azathioprine does not.