The risk of early occurrence and recurrence of hepatocellular carcinoma in hepatitis C-infected patients treated with direct-acting antivirals with and without pegylated interferon: A Belgian experience.

Recently, concerns were raised of high rates of HCC recurrence in patients treated with direct-acting antivirals (DAA) for hepatitis C infection. We investigated the HCC occurrence and recurrence rates within 6 months after treatment with DAA with or without pegylated interferon (PEG-IFN) in real life. This is a retrospective, multicenter cohort trial, executed in 15 hospitals distributed across Belgium. Populations were matched based on fibrosis score (Metavir F3-F4). Patients with a Child-Pugh score ≥ B were excluded. In total, 567 patients were included, of whom 77 were treated with PEG-IFN+DAA between 2008 and 2013 and 490 with DAA without PEG-IFN between 2013 and 2015. Patients treated with PEG-IFN+DAA (53±9y) were younger than patients treated with DAA without PEG-IFN (59±12y) (P=.001). 47% of patients treated with PEG-IFN+DAA were in the F4 stage vs 67% of patients treated with DAA without PEG-IFN (P=.001). Screening was inadequate in 20% of both patient groups (P=.664). The early occurrence rate of HCC was 1.7% and 1.1% in patients treated with DAA with and without PEG-IFN, respectively (P=.540). The early recurrence rate was 0% in patients treated with PEG-IFN+DAA and 15.0% in patients treated with DAA without PEG-IFN (P=.857). 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, these patients were at baseline more at risk for HCC. Finally, in 20%, screening for HCC was inadequate.

Unexpected outcome of a sigmoid lesion believed to be malignant.

A 69-year-old male with a past medical history of an Olfactory nerve meningioma and left-sided Bell's palsy presented with 6 weeks of lower abdominal pain and weight loss of 4 kg in 6 months. His current medications included acetylsalicylic acid 80 mg once daily, Amlodipine 5 mg once daily and Allopurinol 300 mg once daily. Physical examination was benign without signs of acute abdomen. The abdomen was nondistended and soft but tender to palpation over the left lower quadrant. Laboratory studies showed no acute outliers. The patient was followed up by his pulmonologist because of thoracic lesions which required a PET-CT for further evaluation. This PET-CT revealed a focal zone of oedematous rectosigmoid colon with a strong suspicion of a semi-circular sigmoid neoplasia with continuation to the bladder (Figure 1a). A presumptive diagnosis of a primary colonic malignancy was made. Colonoscopy was performed and visualised a foreign linear object lodged in both walls of the diverticular sigmoid with surrounding inflammation, but otherwise normal mucosa (Figure 1b). No arguments could be made endoscopically to support the diagnosis of an underlying primary colonic malignancy.

The contribution of inflammatory astrocytes to BBB impairments in a brain-chip model of Parkinson's disease.

Astrocyte dysfunction has previously been linked to multiple neurodegenerative disorders including Parkinson's disease (PD). Among their many roles, astrocytes are mediators of the brain immune response, and astrocyte reactivity is a pathological feature of PD. They are also involved in the formation and maintenance of the blood-brain barrier (BBB), but barrier integrity is compromised in people with PD. This study focuses on an unexplored area of PD pathogenesis by characterizing the interplay between astrocytes, inflammation and BBB integrity, and by combining patient-derived induced pluripotent stem cells with microfluidic technologies to generate a 3D human BBB chip. Here we report that astrocytes derived from female donors harboring the PD-related LRRK2 G2019S mutation are pro-inflammatory and fail to support the formation of a functional capillary in vitro. We show that inhibition of MEK1/2 signaling attenuates the inflammatory profile of mutant astrocytes and rescues BBB formation, providing insights into mechanisms regulating barrier integrity in PD. Lastly, we confirm that vascular changes are also observed in the human postmortem substantia nigra of both males and females with PD.

Comorbidities and concomitant medications in patients with chronic hepatitis C virus infection receiving second-generation direct-acting antiviral regimens in Belgium: an observational study.

Objective: To describe comorbidities and concomitant medications in patients initiating treatment for hepatitis C virus (HCV) infection with direct-acting antiviral (DAA) regimens in Belgium. Methods: This was a noninterventional, observational, multicenter study of data from patient charts. Adult patients with HCV infection receiving second-generation DAA therapy were included. Comorbidities were assessed at the time of HCV treatment initiation. Concomitant medications were recorded at the time of diagnosis and at treatment initiation. Potential clinically relevant drug-drug interactions (DDIs) were assessed based on information available at www.hep-druginteractions.org. The primary objective was to describe concomitant medication use ; secondary objectives were to describe modifications in concomitant therapies and comorbidities. Results: 405 patients were included. A total of 956 comorbidities were reported by 362 patients (median, 2 ; range, 0-15). The most common comorbidities were hypertension (27.2%) ; HIV coinfection (22.5%), and type 2 diabetes mellitus (14.3%). Overall, 1455 concomitant medications were being taken by 365 patients (90.1% ; median, 3 ; range 0-16). The most common concomitant medications were psycholeptics (28.6%), antiviral agents (24.2%), and medications for acid-related disorders (21.0%) Overall, 74/365 (20.3%) patients receiving a concomitant medication required an adaptation to their concomitant medication. The medications that most frequently required change were drugs for acid-related disorders (n = 14) and antiviral drugs (n = 5) ; those that were most frequently stopped were lipid-modifying drugs (n = 25) and drugs for acid-related disorders (n = 13). Conclusion: Physicians are aware of the potential for DDIs with DAAs, but improved alignment between clinical practice and theoretical recommendations is required.

Transjugular intrahepatic portosystemic shunt placement for symptomatic non- bleeding anorectal varices in nodular regenerative hyperplasia.

In this paper we present the case of a male 55-year old patient with known ulcerative colitis and nodular regenerative hyperplasia, a rare form of noncirrhotic portal hypertension. He presented four visits to the emergency department with rapidly progressive anal discomfort. After two weeks a transjugular intrahepatic portosystemic shunt was placed using the gun-sight technique with immediate relief of the unbearable anal pain and pressure. To our knowledge, this is the first case where transjugular intrahepatic portosystemic shunt placement is applied for non- bleeding, congestive anorectal varices.

Current practice in approaching controversial diagnostic and therapeutic topics in gastroenteropancreatic neuroendocrine neoplasm management. Belgian multidisciplinary expert discussion based on a modified Delphi method.

BACKGROUND AND STUDY AIMS: Neuroendocrine neoplasms (NENs) are relatively rare, with marked clinical and biological heterogeneity. Consequently, many controversial areas remain in diagnosis and optimal treatment stratification for NEN patients. We wanted to describe current clinical practice regarding controversial NEN topics and stimulate critical thinking and mutual learning among a Belgian multidisciplinary expert panel. PATIENTS AND METHODS: A 3-round, Delphi method based project, coordinated by a steering committee (SC), was applied to a predefined multidisciplinary NEN expert panel studying the following controversial topics : factors guiding therapeutic decision making, the use of somatostatin analogues (SSA) in adjuvant setting, the interference between non-radioactive and radioactive SSAs, challenging small intestine neuroendocrine tumor (NET) cases, the approach of the carcinoid syndrome, the role of chemotherapy in well differentiated NET, the relevance of NET G3 and neuroendocrine carcinoma subclassification and the role of imaging techniques in NEN management. RESULTS: A high level of consensus exists regarding the necessary diagnostic work-up, use of imaging techniques and interference between non-radioactive and radioactive SSAs. However, the prognostic impact of tumor functionality might be overrated and adequate diarrhea differential diagnostic work-up in these patients is underused. Significant differences are seen between individual experts and centers regarding treatment preferences both on the treatment modality level, as well as the choice of specific drugs (e.g. chemotherapy regimen). CONCLUSIONS: A Delphi-like multi-round expert discussion proves useful to boost critical thinking and discussion among experts of different background, as well as to describe current clinical practice and stimulate mutual learning in the absence of high-level scientific guidance.

Stopping nucleos(t)ide analogue treatment in Caucasian hepatitis B patients after HBeAg seroconversion is associated with high relapse rates and fatal outcomes.

BACKGROUND: Stopping nucleos(t)ide analogues (NA) after hepatitis B e antigen (HBeAg) seroconversion is associated with high relapse rates in Asian patients, but data in Caucasian cohorts are scarce. Clinical course, outcomes and immunological aspects of chronic hepatitis B infections differ substantially between distinct ethnicities. AIM: The aim of this study was to determine relapse rates, factors predicting relapse and clinical outcomes after nucleos(t)ide analogue cessation in a large, predominantly Caucasian cohort of chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion. METHODS: This is a nationwide observational cohort study including HBeAg positive, mono-infected chronic hepatitis B patients with nucleos(t)ide analogue-induced HBeAg seroconversion from 18 centres in Belgium. RESULTS: A total of 98 patients with nucleo(s)tide analogue-induced HBeAg seroconversion were included in the study. Of the 62 patients who stopped treatment after a median consolidation treatment of 8 months, 30 relapsed. Higher gamma-glutamyl transferase levels at both treatment initiation (HR 1.004; P = 0.001 per unit increment) and HBeAg seroconversion (HR 1.006; P = 0.013 per unit increment) were associated with an increased risk of clinically significant relapse in a multivariate Cox regression model. Treatment cessation led to liver-related death in 2 patients, of whom one showed a severe flare. Of the patients who continued treatment after HBeAg seroconversion, none relapsed or developed severe hepatic outcomes. CONCLUSION: Treatment withdrawal in Caucasian chronic hepatitis B patients after nucleos(t)ide analogue-induced HBeAg seroconversion results in viral relapses in more than half of patients with potential fatal outcomes. These real-world data further lend support to preferentially continue NA treatment after HBeAg seroconversion until HBsAg loss.

Azathioprine induced serious portal hypertension: a case series of three IBD patients and review of the literature.

We report 3 male IBD patients (2 Crohn's Disease, 1 Ulcerative Colitis) developing thrombocytopenia and splenomegaly on azathioprine treatment. All patients were diagnosed with significant portal hypertension due to histological proven nodular regenerative hyperplasia (NRH) of the liver. In two of three patients, liver function tests remained completely normal. In addition we provide a short literature review of azathioprine induced NRH covering etiology, imaging, pathology, prognosis and treatment.