Awareness of chronic hepatitis B and C in men who have sex with men in Belgium: epidemiological survey and on-site screening.

OBJECTIVES: To eliminate hepatitis B and C virus (HBV/HCV) as a public health threat by 2030, the WHO focuses on screening key populations, including men who have sex with men (MSM).This study aims to assess HBV and HCV knowledge and awareness and HCV prevalence in MSM in Belgium. METHODS: First, a questionnaire was designed to assess MSM's knowledge of HBV and HCV infection (disease process, vaccination, treatment and transmission routes). This questionnaire was conducted online, and by means of a tablet-based face-to-face questionnaire at the Antwerp and Belgian Pride. Second, HCV and HIV prevalence data were collected during outreach projects and office screening for sexually transmitted infections (STIs) organised by Sensoa and Exaequo, a Flemish and Walloon sexual health organisation. RESULTS: 300 MSM completed the questionnaire (median age 36 years; 7.7% HIV+). Mean overall survey scores were low (HBV: 41.1%; HCV: 39.8%). Few participants identified all transmission routes correctly (HBV: 15%; HCV 1%).The degree of education was significantly correlated with HBV knowledge and showed a trend towards correlation with HCV knowledge. HCV knowledge was significantly correlated with high-risk sexual behaviour.The prevalence of HCV and HIV was 0.3% and 1.0%, respectively, in MSM attending commercial gay venues and 0% and 1.9% in MSM attending office STI screening. CONCLUSIONS: Knowledge of HBV and HCV infection in MSM is poor. More awareness campaigns are needed, focusing on frequent HCV risk factors (group sex, chemsex, receptive fisting, and sharing of anal toys and anal douching devices), especially targeting low-educated MSM. HBV vaccination of MSM requires continued attention.The prevalence of HCV and HIV was remarkably low in commercial gay venues and may be higher in older MSM or in subcultures where risk factors coexist (eg, chemsex). The cost-effectiveness of internet-based approaches with subsequent at-home testing needs to be evaluated in the future.

Viral clade is associated with severity of symptomatic genotype 3 hepatitis E virus infections in Belgium, 2010-2018.

BACKGROUND & AIMS: HEV genotype (gt) 3 infections are prevalent in high-income countries and display a wide spectrum of clinical presentations. Host - but not viral - factors are reported to be associated with worse clinical outcomes. METHODS: Demographic, clinical, and biochemical data laboratory-confirmed HEV infections (by PCR and/or a combination of IgM and IgG serology) at the Belgian National Reference Centre between January 2010 and June 2018 were collected using standardised case report forms. Genotyping was based on HEV open reading frame 2 sequences. Serum CXCL10 levels were measured by a magnetic bead-based assay. H&E staining was performed on liver biopsies. RESULTS: A total of 274 HEV-infected individuals were included. Subtype assignment was possible for 179/218 viraemic cases, confirming gt3 as dominant with an almost equal representation of clades abchijklm and efg. An increased hospitalisation rate and higher peak serum levels of alanine aminotransferase, bilirubin, and alkaline phosphatase were found in clade efg-infected individuals in univariate analyses. In multivariable analyses, clade efg infections remained more strongly associated with severe disease presentation than any of the previously identified host risk factors, being associated with a 2.1-fold higher risk of hospitalisation (95% CI 1.1-4.4, p = 0.034) and a 68.2% higher peak of bilirubin levels (95% CI 13.3-149.9, p = 0.010), independently of other factors included in the model. In addition, acute clade efg infections were characterised by higher serum CXCL10 levels (p = 0.0005) and a more pronounced liver necro-inflammatory activity (p = 0.022). CONCLUSIONS: In symptomatic HEV gt3 infections, clade efg is associated with a more severe disease presentation, higher serum CXCL10 levels, and liver necro-inflammatory activity, irrespective of known host risk factors. CLINICAL TRIAL REGISTRATION: The protocol was submitted to clinicaltrials.gov (NCT04670419). IMPACT AND IMPLICATIONS: HEV genotype (gt) 3 infections display a wide spectrum of clinical presentations currently ascribed to host factors. Here we examined the role of viral factors on liver disease outcomes by combining viral phylogeny with clinical, biochemical, cytokine, and histological data from 274 Belgian adults infected with HEV presenting between 2010 and 2018. HEV gt 3 clade efg infections were associated with a more severe disease presentation, higher serum CXCL10 levels and liver necro-inflammatory activity, irrespective of known host risk factors. HEV gt3 clade-dependent clinical outcomes call for broad HEV gt3 subtyping in clinical practice and research to help identify those at higher risk for worse outcomes and to further unravel underlying virus-host interactions.

Prevention and management of minor complications in percutaneous endoscopic gastrostomy.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) was developed by Ponsky-Gauderer in the early 1980s. These tubes are placed through the abdominal wall mainly to administer fluids, drugs and/or enteral nutrition but can also be used for drainage or decompression. The tubes consist of an internal and external retention device. It is a generally safe technique but major or minor complications may arise during and after tube placement. METHOD: A narrative review of the literature investigating minor complications after PEG placement. RESULTS: This review was written from a clinical viewpoint focusing on prevention and management of minor complications and documented with real cases from more than 21 years of clinical practice. CONCLUSIONS: Depending on the literature the incidence of minor complications after gastrostomy placement can be high. To decrease associated morbidity, prevention, early recognition and popper management of these complications are important.

Non-Alcoholic Steatohepatitis Decreases Microsomal Liver Function in the Absence of Fibrosis.

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.

2D shear wave liver elastography by Aixplorer to detect portal hypertension in cirrhosis: An individual patient data meta-analysis.

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 < 14 kPa ruled out CSPH with a summary AUROC (sROC), sensitivity and specificity of 0.88, 91% and 37%, and correctly classified 85% of patients, with minimal between-study heterogeneity. The false negative rate was 60%, of which decompensated patients accounted for 78%. 2DSWE-SSI ≥ 32 kPa ruled in CSPH with sROC, sensitivity, specificity and correct classifications of 0.83, 47%, 89% and 55%. In a subgroup analysis, the 14 kPa cut-off showed consistent sensitivity and higher specificity for patients with compensated cirrhosis, without ascites, viral aetiology or BMI < 25 kg/m2 . 2DSWE-SSI ruled out severe portal hypertension and large varices with fewer correctly classified and lower sROC, and with minimal benefit for ruling in. CONCLUSION: Liver stiffness using 2-dimensional shear wave elastography below 14 kPa may be used to rule out clinically significant portal hypertension in cirrhosis patients, but this would need validation in populations of compensated liver disease. 2DSWE-SSI cannot predict varices needing treatment.

Severe steatosis induces portal hypertension by systemic arterial hyporeactivity and hepatic vasoconstrictor hyperreactivity in rats.

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.

Belgian experience with direct acting antivirals in people who inject drugs.

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.

Shear-wave elastography of the liver and spleen identifies clinically significant portal hypertension: A prospective multicentre study.

BACKGROUND & AIMS: Clinically significant portal hypertension (CSPH) is associated with severe complications and decompensation of cirrhosis. Liver stiffness measured either by transient elastography (TE) or Shear-wave elastography (SWE) and spleen stiffness by TE might be helpful in the diagnosis of CSPH. We recently showed the algorithm to rule-out CSPH using sequential liver- (L-SWE) and spleen-Shear-wave elastography (S-SWE). This study investigated the diagnostic value of S-SWE for diagnosis of CSPH. METHODS: One hundred and fifty-eight cirrhotic patients with pressure gradient measurements were included into this prospective multicentre study. L-SWE was measured in 155 patients, S-SWE in 112 patients, and both in 109 patients. RESULTS: Liver-shear-wave elastography and S-SWE correlated with clinical events and decompensation. SWE of liver and spleen revealed strong correlations with the pressure gradient and to differentiate between patients with and without CSPH. The best cut-off values were 24.6 kPa:L-SWE and 26.3 kPa:S-SWE. L-SWE ≤16.0 kPa and S-SWE ≤21.7 kPa were able to rule-out CSPH. Cut-off values of L-SWE >29.5 kPa and S-SWE >35.6 kPa were able to rule-in CSPH (specificity >92%). Patients with a L-SWE >38.0 kPa had likely CSPH. In patients with L-SWE ≤38.0 kPa, a S-SWE >27.9 kPa ruled in CSPH. This algorithm has a sensitivity of 89.2% and a specificity of 91.4% to rule-in CSPH. Patients not fulfilling these criteria may undergo HVPG measurement. CONCLUSIONS: Liver and spleen SWE correlate with portal pressure and can both be used as a non-invasive method to investigate CSPH. Even though external validation is still missing, these algorithms to rule-out and rule-in CSPH using sequential SWE of liver and spleen might change the clinical practice.

Liver Fibrosis Evaluation Using Real-time Shear Wave Elastography in Hepatitis C-Monoinfected and Human Immunodeficiency Virus/Hepatitis C-Coinfected Patients.

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 (ρ = 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.

Validation of APRI and FIB-4 score in an Antwerp cohort of chronic hepatitis C patients.

BACKGROUND AND AIMS: Evaluation of liver fibrosis in chronic hepatitis C patients guides clinical decision-making. The aim of this study is to validate APRI and FIB-4, two easily calculated noninvasive tests to predict fibrosis, in chronic HCV patients using biopsy as a gold standard and to compare accuracy between HCV monoinfected and HIV/HCV coinfected patients. PATIENTS AND METHODS: We retrospectively studied HCV patients of two centres who underwent liver biopsy. Liver fibrosis was staged according to METAVIR. RESULTS: 136 patients were included. The AUROC of FIB-4 (0.896) to discriminate F0-F2 vs. F3-F4 was significantly higher (p=0.0186) than the AUROC of APRI (0.842). The difference in AUROC between HIV-negative and positive patients was not significant for APRI (p=0.471), nor for FIB-4 (p=0.495). Performance status was lower in HIV-positive patients with 46.7% and 69.0% of patients correctly classified using APRI and FIB-4, compared to 56.6% and 73.6% in HIV-negative patients, respectively. Conversion of transaminase values from one hospital to the other did not significantly change the AUROC of FIB-4 (p=0.928). CONCLUSIONS: APRI and FIB-4 have a better performance status in HCV monoinfected patients compared to HIV/HCV coinfected patients. FIB-4 has a better AUROC compared to APRI and is the preferred noninvasive fibrosis score to discriminate between F0-F2 and F3-F4. Different hospitals should use their local absolute serum transaminase values without conversion.

Environmental harshness shapes life-history variation in an Australian temporary pool breeding frog: a skeletochronological approach.

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.