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Background & Aims: Liver stiffness measured with 2-dimensional shear wave elastography by Supersonic Imagine (2DSWE-SSI) is well-established for fibrosis diagnostics, but non-conclusive for portal hypertension. Methods: We performed an individual patient data meta-analysis of 2DSWE-SSI to identify clinically significant portal hypertension (CSPH), severe portal hypertension and large varices in cirrhosis patients, using hepatic venous pressure gradient and upper endoscopy as reference. We used meta-analytical integration of diagnostic accuracies with optimized rule-out (sensitivity-90%) and rule-in (specificity-90%) cut-offs. Results: Five studies from seven centres shared data on 519 patients. After exclusion, we included 328 patients. Eighty-nine (27%) were compensated and 286 (87%) had CSPH. 2DSWE-SSI&nbsp

The incidence of non-alcoholic fatty liver disease (NAFLD) is rising across the globe, with the presence of steatohepatitis leading to a more aggressive clinical course. Currently, the diagnosis of non-alcoholic steatohepatitis (NASH) is based on histology, though with the high prevalence of NAFLD, a non-invasive method is needed. The 13C-aminopyrine breath test (ABT) evaluates the microsomal liver function and could be a potential candidate. We aimed to evaluate a potential change in liver function in NASH patients and to evaluate the diagnostic power of ABT to detect NASH. We performed a retrospective analysis on patients suspected of NAFLD who underwent a liver biopsy and ABT. 440 patients were included. ABT did not decrease in patients with isolated liver steatosis but decreased significantly in the presence of NASH without fibrosis and decreased even further with the presence of significant fibrosis. The predictive power of ABT as a single test for NASH was low but improved in combination with ALT and ultrasonographic steatosis. We conclude that microsomal liver function of patients with NASH is significantly decreased, even in the absence of fibrosis. The ABT is thus a valuable tool in assessing the presence of NASH, and could be used as a supplementary diagnostic tool in clinical practice.

For many amphibians, high temperatures and limited precipitation are crucial habitat characteristics that limit species ranges and modulate life-history characteristics. Although knowledge of the ability of amphibians to cope with such environmental harshness is particularly relevant in the light of ongoing environmental change, relatively little is known about natural variation in age, maturation and associated life-history traits across species’ ranges. We used the analysis of growth rings in bones to investigate the link between environmental harshness and life-history traits, including age and body size distribution, in specimens from 20 populations of the Australian bleating froglet, Crinia pseudinsignifera. Despite the short lifespan of the species, bone slides revealed geographic variation in average age, body size and reproductive investment linked to variation in temperature and rainfall. We found no difference in age at maturation in different climatic harshness regimes. Frogs from harsher environments invested less in their first reproductive event but grew older than their counterparts in more benign environments, thereby allowing for more reproductive events and buffering them against the increased chance of reproductive failure in the harsher environments. For individual frogs, climatic harshness experienced during an individual’s life promoted larger body size. Overall, these results illustrate how bone structure analyses from preserved specimens allow both the testing of ecogeographic hypotheses and the assessment of the adaptive potential of species in the light of environmental change.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease. The presence of portal hypertension has been demonstrated in NAFLD prior to development of inflammation or fibrosis, and is a result of extrahepatic and intrahepatic factors, principally driven by vascular dysfunction. An increased intrahepatic vascular resistance potentially contributes to progression of NAFLD via intralobular hypoxia. However, the exact mechanisms underlying vascular dysfunction in NAFLD remain unknown. This study investigates systemic hemodynamics and both aortic and intrahepatic vascular reactivity in a rat model of severe steatosis. Wistar rats were fed a methionine-choline-deficient diet, inducing steatosis, or control diet for 4 weeks. In vivo hemodynamic measurements, aortic contractility studies, and in situ liver perfusion experiments were performed. The mean arterial blood pressure was lower and portal blood pressure was higher in steatosis compared to controls. The maximal contraction force in aortic rings from steatotic rats was markedly reduced compared to controls. While blockade of nitric oxide (NO) production did not reveal any differences, cyclooxygenase (COX) blockade reduced aortic reactivity in both controls and steatosis, whereas effects were more pronounced in controls. Effects could be attributed to COX-2 iso-enzyme activity. In in situ liver perfusion experiments, exogenous NO donation or endogenous NO stimulation reduced the transhepatic pressure gradient (THPG), whereas NO synthase blockade increased the THPG only in steatosis, but not in controls. Alpha-1-adrenergic stimulation and endothelin-1 induced a significantly more pronounced increase in THPG in steatosis compared to controls. Our results demonstrate that severe steatosis, without inflammation or fibrosis, induces portal hypertension and signs of a hyperdynamic circulation, accompanied by extrahepatic arterial hyporeactivity and intrahepatic vascular hyperreactivity. The arterial hyporeactivity seems to be NO-independent, but appears to be mediated by specific COX-2-related mechanisms. Besides, the increased intrahepatic vascular resistance in steatosis appears not to be NO-related but rather to vasoconstrictor hyperreactivity.

Background and aim Hepatitis C viral infection (HCV) has become a curable disease due to the development of direct acting antivirals (DAA). The WHO has set a target to eliminate HCV completely. Therefore, people who inject drugs (PWID) also need to be treated. In this study, we compared the real-life uptake and outcome of DAA treatment for HCV in PWID and non-PWID. Methods We performed a nation-wide, retrospective cohort study in 15 hospitals. All patients who were treated with simeprevir-sofosbuvir, daclatasvir-sofosbuvir, or ombitasvir/paritaprevir ritonavir–dasabuvir between December 2013 and November 2015 were included. Results The study population consisted of 579 patients: 115 PWID (19.9%) and 464 non-PWID (80.1%). Of the PWID 18 were active PWID (15.6%), 35 still received opiate substitution therapy (OST) (30.4%) and 62 were former PWID without OST (53.9%). PWID were more infected with genotype 1a and 3 (p = 0.001). There were equal rates of side-effects (44.7% vs. 46.6%; p = 0.847), similar rates of treatment completion (95.7% vs 98.1%; p = 0.244) and SVR (93.0% vs 94.8%; p = 0.430) between PWID and non-PWID, respectively. Conclusion PWID, especially active users, are underserved for DAA treatment in real life in Belgium. Reimbursement criteria based on fibrosis stage make it difficult to treat PWID. Treatment adherence is similar in PWID and the general population, even in patients with active abuse. DAA were safe and effective in PWID despite the higher prevalence of difficult-to-treat genotypes. Based on these data more efforts to treat PWID are needed and policy changes are necessary to reach the WHO targets.

Introduction Direct antiviral agents (DAA) have made HCV treatment very effective and safe these last years. Recently, concerns were raised of high rates of HCC recurrence in patients treated with DAA. We investigated the HCC occurrence and recurrence rates within six months after treatment with DAA with or without Pegylated Interferon (PEG-IFN). Methods and materials This is a national, retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Data were available from two earlier trials investigating the outcome of treatment with DAA with and without PEG-IFN. A new data collection based on the patient files was executed by medical doctors. Populations were matched based on fibrosis score starting from F3. Patients with a Child-Pugh score ≥ B were excluded. In total, 472 patients were included in this trial, of whom 72 were treated with DAA with PEG-IFN from 2008 to 2013 and 400 with DAA without PEG-IFN from 2013 until November 2015. In this cohort also an analysis of the rates of follow up by radiographic analysis was performed. Results Patients treated with DAA with PEG-IFN (53y±8) were younger than patients treated with DAA without PEG-IFN (59y±12) (p=0.001). 48% (38/72) of patients treated with DAA with PEG-IFN were in the F4 stage versus nearly 65% (259/399) of patients treated with DAA without PEG-IFN (p=0.004). The rates of radiographic follow up were 77.8% (n=56/72) in patients treated with DAA with PEG-IFN, and 78.0% (n=312/400) in patients treated with DAA without PEG-IFN. The early occurrence rate of HCC in patients treated with DAA with PEG-IFN was 3.6 % (n=2/55) and 1.1% (n=3/277) in patients treated with DAA without PEG-IFN. The early recurrence rate was 0% (n=0/1) in patients treated with DAA with PEG-IFN, and 20.0% (n=7/35) in patients treated with DAA without PEG-IFN. This is visualized in figure 1. Conclusion There is no difference in early occurrence of new HCC between patients treated with DAA with and without PEG-IFN. We did observe a high early recurrence rate of HCC in patients treated with DAA without PEG-IFN. However, we cannot state that this difference is significant to patients treated with DAA with PEG-IFN, especially since there were significant differences in patient characteristics such as age and fibrosis stage. In 20%, screening for HCC was inadequate. More efforts are necessary as we need to remain vigilant when treating high risk patients.

Recently, the UK guidelines on variceal bleeding1 and other reports have introduced the role of elastography for the diagnosis of oesophageal varices (OVs).2 ,3 Development of OVs is likely when the hepatic venous pressure gradient is higher than 10 mm Hg, which defines clinically significant portal hypertension (CSPH). Baveno VI implemented transient elastography (TE) as a tool to rule in CSPH in viral aetiologies and to rule out varices (need of screening endoscopy for varices).4 Furthermore, CSPH has a strong prognostic value in patients with cirrhosis. Recent studies introduced Shear-wave elastography of the liver (L-SWE) as a promising tool to diagnose portal hypertension. These studies find good diagnostic accuracy of L-SWE with specificity and sensitivity ranging around 80% and superior to TE. However, in more than 30% of the patients CSPH could not be ruled in or ruled out, since their SWE values were between the cut-offs. This prospective multicentre study investigated the …

Objectives-A few studies have evaluated real-time shear wave elastography (SWE) for assessing liver fibrosis by measuring liver stiffness in patients with chronic hepatitis C virus (HCV) infection, but they excluded human immunodeficiency virus/HCV-coinfected patients. We investigated the diagnostic performance of liver stiffness measured by SWE as a noninvasive predictor of liver fibrosis in HCV using liver biopsy as a reference standard, including monoinfected and coinfected patients. Methods-We measured liver stiffness in patients with HCV undergoing liver biopsy (METAVIR fibrosis staging). Results-Eighty patients (53 monoinfected and 27 coinfected) were included. There was a significant correlation between liver stiffness and fibrosis stage (rho = 0.685; P < .001). Areas under the receiver operating characteristic curve were 0.841, 0.879, and 0.975 when comparing fibrosis stages F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. Suggested cutoff values were 8.5 kPa for F2, 10.4 kPa for F3, and 11.3 kPa for F4, with sensitivity and specificity of 81% and 84%, 81% and 95%, and 100% and 90%. There was no significant difference between the liver stiffness of monoinfected and coinfected patients (P = .453). When combining SWE with the fibrosis-4 score, accuracy increased from 82% to 88% and from 88% to 96%, with incongruent results of 26% and 29%, for F0-F1 versus F2-F4 and F0-F2 versus F3-F4. Conclusions-Shear wave elastography of the liver is an effective noninvasive predictor of liver fibrosis in patients with HCV. There was no significant difference between monoinfected and coinfected patients; hence, the same cutoff values can be used for both groups. Combination of SWE with the fibrosis-4 score leads to higher accuracy, although at the expense of inconclusive results in some patients.

Background : The treatment of fecal incontinence (FT) depends upon the dominant pathophysiology: impaired sphincter contractility or overflow due to pelvic floor dvssynergia and insufficient rectal emptying. In this study, we aimed to define the manometric and anorectal ultrasound characteristics in FI patients with and without constipation. Methods: We did a retrospective study of365 anal manometries, performed between October 2012 and July 2015, in patients with FI. Clinical information was obtained from questionnaires. In 220 of these patients an anorectal ultrasound was also available. Key results : A high prevalence of self-reported constipation was seen in the total population of FI patients (66%). This number was lower (31%) when Rome IV criteria were applied. A very high percentage of manometric pelvic floor dyssynergia was seen in the total population with FI (81%). However, patients with FI and constipation did not show pelvic floor dyssynergia more often than patients without constipation. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity were not different when comparing patients without and with constipation. The prevalence of a functional defecation disorder (FDD) in our study population of FI patients was 20%. Wexner score in this subgroup was lower compared with patients without FDD. Anal sphincter defects were more prevalent in women than men, and were associated with diminished sphincter contractility. Conclusion and inferences : A very high percentage of FI patients showed manometric pelvic floor dyssynergia. The coexistence of fecal incontinence and constipation did not increase this percentage. Key messages - Constipation is a frequent and underestimated cause of FI. A correct diagnosis has a major impact on treatment. - We aimed to characterize the manometric and transrectal ultrasound profile of FI patients with and without signs of coexisting constipation. - A very high percentage of incontinent patients showed pelvic floor dyssynergia, however no significant difference between the group with and the group without constipation was seen. Anal resting pressure, squeeze pressure and anorectal pressure sensitivity did not differ significantly either.