Peter Michielsen

This study compares venepuncture versus point-of-care (POC) HBsAg tests on screening cost and linkage to care in prospective outreach screenings in an Asian population in three major cities in Belgium between 10/2014 and 5/2018. Two community outreach screening programs were organised between 10/2014 and 5/2018. The first screening program used venepuncture and serologic testing for HBsAg. In the second program, HBsAg was tested in finger stick blood POC tests. Positive results were confirmed during outpatient visits with serologic testing. Linkage to care was defined as having received specialist care follow-up with at least one abdominal ultrasound within three months of screening. For 575 participating individuals, 571 valid results were obtained, 456 with venepuncture, and 115 using POC testing. Overall HBsAg seroprevalence was 6.8%. Linkage to care was higher when using POC testing compared to venepuncture (86% or n = 6/7 versus 34% or n = 11/32; p = 0.020). The POC screening program was economically more attractive with a total cost of € 1,461.8 or € 12.7 per person screened compared to € 24,819 or € 54.0 per person screened when using venepuncture testing. Results and an appointment for specialist care follow-up were given onsite with POC testing, while with venepuncture testing; results were sent within 20–45 days. In an Asian migrant population in Belgium with an HBsAg seroprevalence of 6.8%, HBV screening based on POC tests resulted in lower costs per person screened (76.5% lower), and higher linkage to care (2.5 times).

Recent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort‐specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log‐log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero‐)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1‐5.1) and 5.8% (121/2087, CI 4.8‐6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.

Nonalcoholic fatty liver disease prevalence is soaring with the obesity pandemic, but the pathogenic mechanisms leading to the progression toward active nonalcoholic steatohepatitis (NASH) and fibrosis, major causes of liver-related death, are poorly defined. To identify key components during the progression toward NASH and fibrosis, we investigated the liver transcriptome in a human cohort of NASH patients. The transition from histologically proven fatty liver to NASH and fibrosis was characterized by gene expression patterns that successively reflected altered functions in metabolism, inflammation, and epithelial-mesenchymal transition. A meta-analysis combining our and public human transcriptomic datasets with murine models of NASH and fibrosis defined a molecular signature characterizing NASH and fibrosis and evidencing abnormal inflammation and extracellular matrix (ECM) homeostasis. Dermatopontin expression was found increased in fibrosis, and reversal of fibrosis after gastric bypass correlated with decreased dermatopontin expression. Functional studies in mice identified an active role for dermatopontin in collagen deposition and fibrosis. PPARα activation lowered dermatopontin expression through a transrepressive mechanism affecting the Klf6/TGFβ1 pathway. Liver fibrotic histological damages are thus characterized by the deregulated expression of a restricted set of inflammation- and ECM-related genes. Among them, dermatopontin may be a valuable target to reverse the hepatic fibrotic process.

Autophagy and the unfolded protein response (UPR) are key cellular homeostatic mechanisms and are both involved in liver diseases, including nonalcoholic fatty liver disease (NAFLD). Although increasing but conflicting results link these mechanisms to lipid metabolism, their role and potential cross talk herein have been poorly investigated. Therefore, we assessed the effects of hepatocyte-specific autophagy deficiency on liver parenchyma, the UPR, and lipid metabolism. Adult hepatocellular-specific autophagy-deficient mice ( Atg7^F/FAlb-Cre⁺) were compared with their autophagy-competent littermates ( Atg7^+/+Alb-Cre⁺). Livers were analyzed by electron microscopy, histology, real-time qPCR, and Western blotting. Atg7^F/FAlb-Cre⁺mice developed hepatomegaly with significant parenchymal injury, as shown by inflammatory infiltrates, hepatocellular apoptosis, pericellular fibrosis, and a pronounced ductular reaction. Surprisingly, the UPR exhibited a pathway-selective pattern upon autophagy deficiency. The activity of the adaptive activating transcription factor 6 (ATF6) pathway was abolished, whereas the proapoptotic protein kinase RNA-like ER kinase pathway was increased compared with Atg7^+/+Alb-Cre⁺mice. The inositol-requiring enzyme-1α signal was unaltered. Fasting-induced steatosis was absent in Atg7^F/FAlb-Cre⁺mice. Remarkably, some isolated islands of fat-containing and autophagy-competent cells were observed in these livers. Hepatocellular autophagy is essential for parenchymal integrity in mice. Moreover, in the case of autophagy deficiency, the three different UPR branches are pathway selectively modulated. Attenuation of the ATF6 pathway might explain the observed impairment of fasting-induced steatosis. Finally, autophagy and lipid droplets are directly linked to each other.

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.