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.

Association of 1-deoxy-sphingolipids with steatosis but not steatohepatitis nor fibrosis in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most important cause of chronic liver disease in the western world. Steatosis can be accompanied by inflammation and cell damage (non-alcoholic steatohepatitis, NASH), and even liver fibrosis. Sphingolipids are a heterogeneous class of lipids and essential components of the plasma membrane and plasma lipoproteins. The atypical class of deoxy-sphingolipids has been implicated in the metabolic syndrome and type 2 diabetes. AIM: To determine if circulating (deoxy)sphingolipids are associated with NAFLD and its different entities, steatosis, inflammatory changes (inflammation and ballooning) and fibrosis. METHODS: Sphingolipids were analysed by LC-MS after hydrolysing the N-acyl and O-linked headgroups in plasma of obese adults who underwent a liver biopsy in suspicion of NAFLD. RESULTS: Two-hundred and eighty-eight patients were included. There was no association between typical sphingolipids and NAFLD and its different entities. There was a significant association between the presence of steatosis and the concentrations of deoxy-sphinganine [exp(B) 11.163 with CI (3.432, 36.306) and p < 0.001] and deoxy-sphingosine [exp(B) 8.486 with CI (3.437, 20.949) and p < 0.001]. There was no association between these deoxy-sphingolipids and activity of the steatohepatitis, nor was there any association with fibrosis. Differences in deoxy-sphingolipids also correlated independently with the presence of the metabolic syndrome, but not diabetes. CONCLUSION: Deoxy-sphingolipids are elevated in patients with steatosis compared to those without fatty liver, but not different between the different NAFLD subtypes, suggesting that deoxy-sphingolipid bases might be involved in steatogenesis, but not in the further progression of NAFLD to NASH nor in fibrogenesis.

Liver transplantation during the COVID-19 epidemic : recommendations from the Belgian Liver Intestine Transplant Committee (BeLIAC).

Since January 2020, the Novel Coronavirus Disease 2019 (COVID-19) pandemic has dramatically impacted the world. In March 2020, the COVID-19 epidemic reached Belgium creating uncertainty towards all aspects of life. There has been an impressive capacity and solidarity of all healthcare professionals to acutely reconvert facilities to treat these patients. In the context of liver transplantation (LTx), concerns are raised about organ donation shortage and safety, the ethics of using limited healthcare resources for LTx, selection criteria for LTx during the epidemic and the risk of de novo COVID-19 infection on the waiting list and after LTx. BeLIAC makes several recommendations to try to mitigate the deleterious effect that this epidemic has/will have on donation and LTx, taking into account the available resources, and trying to maximize patients and healthcare professionals' safety.

Cytomegalovirus pleuropericarditis after orthotopic liver transplantation.

Cytomegalovirus (CMV) reactivation is a common complication after liver transplantation. In patients with CMV infection, indicated by a positive CMV DNA titer, the presence of any clinical symptom is termed CMV disease. The most common organ affected in CMV disease is the gastrointestinal tract, causing esophagitis, gastritis, enteritis or colitis. CMV infection of the pleura and pericard has been reported in immunocompromised patients, but is rarely seen following liver transplantation.We report a case of a 59-year-old male who developed CMV pleuropericarditis after liver transplantation. Initial ganciclovir treatment did not improve the patient's symptoms and therapy was switched to Foscarnet which ultimately resulted in resolution of infection. However, a few weeks after Foscarnet cessation, the patient again developed bilateral pleural effusion. Ultimate biochemical and clinical response was achieved with IV ganciclovir treatment. The patient was discharged from the hospital with oral Valganciclovir for 3 weeks and has since remained relapse free for >1 year.

Screening for therapeutic trials and treatment indication in clinical practice: MACK-3, a new blood test for the diagnosis of fibrotic NASH.

BACKGROUND: The composite histological endpoint comprising nonalcoholic steatohepatitis (NASH) and NAFLD activity score ≥4 and advanced fibrosis (F ≥ 2) ("fibrotic NASH") is becoming an important diagnostic target in NAFLD: it is currently used to select patients for inclusion in phase III therapeutic trials and will ultimately be used to indicate treatment in clinical practice once the new drugs are approved. AIM: To develop a new blood test specifically dedicated for this new diagnostic target of interest. METHODS: Eight Hundred and forty-six biopsy-proven NAFLD patients from three centres (Angers, Nice, Antwerp) were randomised into derivation and validation sets. RESULTS: The blood fibrosis tests BARD, NFS and FIB4 had poor accuracy for fibrotic NASH with respective AUROC: 0.566 ± 0.023, 0.654 ± 0.023, 0.732 ± 0.021. In the derivation set, fibrotic NASH was independently predicted by AST, HOMA and CK18; all three were combined in the new blood test MACK-3 (hoMa, Ast, CK18) for which 90% sensitivity and 95% specificity cut-offs were calculated. In the validation set, MACK-3 had a significantly higher AUROC (0.847 ± 0.030, P ≤ 0.002) than blood fibrosis tests. Using liver biopsy in the grey zone between the two cut-offs (36.0% of the patients), MACK-3 provided excellent accuracy for the diagnosis of fibrotic NASH with 93.3% well-classified patients, sensitivity: 90.0%, specificity: 94.2%, positive predictive value: 81.8% and negative predictive value: 97.0%. CONCLUSION: The new blood test MACK-3 accurately diagnoses fibrotic NASH. This new test will facilitate patient screening and inclusion in NAFLD therapeutic trials and will enable the identification of patients who will benefit from the treatments once approved.

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.

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.