Position statement on how can we can implement the Greendeal in our gastrointestinal and gastrointestinal endoscopy department in Belgium.

The importance to reach the target to be carbon net zero by 2050, as presented by the European Commission in the European Green Deal, cannot be overestimated. In a current endoscopy world, where single use has found its place and techniques are constantly evolving, it will be a challenge to reach these goals. How can we reconcile this evolution to a carbon neutral status by 2050 without compromising patients care, clinical standards and training needs? The European Society of Gastrointestinal Endoscopy (ESGE) together with the European Society of Gastroenterology and Endoscopy Nurses and Associates (ESGENA) recently published a position statement (1) whereas in the UK there is the work from the green endoscopy group (2) in line with the strategy of the British Society of Gastroenterology (BSG) on sustainability (3). In Flanders, a project called "greendeal in duurzame zorg" had its kick off in March 2023 (4) so it is about time that we in Belgium, as gastroenterologists, start with tangible actions to a more sustainable daily practice. We wrote this position statement in cooperation with the Vlaamse Vereniging voor Gastro-Enterologie (VVGE), the Société royale belge de Gastro-entérologie (SRBGE) and the Belgian Society of Gastrointestinal Endoscopy (BSGIE). We will also work together in the coming years to continue to motivate our members to work on these initiatives and to co-opt new projects within the framework of the greendeal.

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.

Recent advances in the approach to hepatopulmonary syndrome and portopulmonary hypertension.

Liver disease, cirrhosis and portal hypertension can be complicated by pulmonary vascular disease, which may affect prognosis and influence liver transplantation (LT) candidacy. Pulmonary vascular complications comprise hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH). Although these two conditions develop on a same background and share a common trigger, pulmonary responses are distinct and occur at different anatomical sites of the pulmonary circulation. HPS affects 10-30% of patients referred for LT, and is characterized by gas exchange abnormalities due to pulmonary vasodilation and right-to-left shunting. POPH occurs in 5%, and is defined by pulmonary arterial hypertension due to increased pulmonary vascular resistance, which leads to hemodynamic failure. Even though HPS and POPH may have a substantial negative impact on survival, both entities are clinically underrecognized and frequently misdiagnosed. Without intervention, the 5-year survival rate is 23% in HPS and 14% in POPH. Their presence should be actively sought by organized screening in patients presenting with dyspnea and in all patients on the waitlist for LT, also because clinical symptoms are commonly non-specific or even absent. LT may lead to resolution, however, advanced stages of either HPS or POPH may jeopardize safe and successful LT. This implicates the need of proper identification of HPS and POPH cases, as well as the need to be able to successfully 'bridge' patients to LT by medical intervention. A review article on this topic has been published in this journal in 2007 (1). This updated review focuses on recent advances in the diagnosis and management of these 2 liver-induced pulmonary vascular disorders and incorporates results from our recent work.

Hepatitis C virus (HCV) prevalence estimation in the adult general population in Belgium : a meta-analysis.

BACKGROUND AND STUDY AIMS: Although multiple HCV prevalence studies were recently performed in the general population from Belgium, they suffer from a lack of geographical representativeness, an insufficient number of participants or a lack of inclusion of high prevalence groups. The aim of this study is to provide robust information on the HCV burden. METHODS: Recently performed HCV prevalence studies in the general, adult population were included in this study, based on well-defined selection criteria. A meta-analysis was performed to estimate the seroprevalence, the prevalence of participants with viremia and the prevalence estimation for people with viremia which were unaware of their status. RESULTS: Eight studies fulfilled the criteria for inclusion of the quantitative prevalence estimation. Based on the meta-analysis on these 8 studies, we estimated an HCV seroprevalence of 1.01% [95% CI : 0.66-1.42%], representing a total of 90,722 adult, HCV seropositives of which 64,412 individuals (0.71%) were confirmed seropositive. Based on the RNA presence, an estimated viremic prevalence of 0.33% [95% CI : 0.21-0.47 %] was determined, corresponding with 29,642 individuals. This is 46,0% of the true HCV seropositive residents. Further, based on the availability of patient information in 5 out of the 8 studies, a prevalence of 0.18% [95% CI : 0.07-0.33] representing 16,168 individuals from the adult Belgian population are unaware of their HCV status. CONCLUSIONS: We believe that the quantitative measurement by the meta-analysis will be more reliable for their use in the design of a screening strategy or in the development of prevention campaigns as compared to the prevalence estimations performed at local level.

IgG4-related disease of the hepatobiliary tract : 2 case reports and review of the literature.

IgG4-related disease is a rare inflammatory disorder that may mimic many infectious, malignant, and autoimmune conditions. The biliary tract is frequently involved, but hepatic lesions are rarely seen. Diagnosis is often delayed due to the absence of specific clinical and radiological signs, and the lack of an accurate diagnostic marker. Differential diagnosis includes cholangiocarcinoma, primary sclerosing cholangitis and intrinsic or metastatic liver disease. Corticosteroids are the cornerstone of therapy but treatment has not been standardized and relapse is common. Based on two cases of IgG4-related hepatobiliary disease, we review the current literature on this pathological entity.

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 induction of autoimmune hepatitis in the human leucocyte antigen-DR4 non-obese diabetic mice autoimmune hepatitis mouse model.

Autoimmune hepatitis (AIH) is a chronic liver disease characterized by progressive inflammation, female preponderance and seropositivity for autoantibodies such as anti-smooth muscle actin and/or anti-nuclear, anti-liver kidney microsomal type 1 (anti-LKM1) and anti-liver cytosol type 1 (anti-LC1) in more than 80% of cases. AIH is linked strongly to several major histocompatibility complex (MHC) alleles, including human leucocyte antigen (HLA)-DR3, -DR7 and -DR13. HLA-DR4 has the second strongest association with adult AIH, after HLA-DR3. We investigated the role of HLA-DR4 in the development of AIH by immunization of HLA-DR4 (DR4) transgenic non-obese diabetic (NOD) mice with DNA coding for human CYP2D6/FTCD fusion autoantigen. Immunization of DR4 mice leads to sustained mild liver injury, as assessed biochemically by elevated alanine aminotransferase, histologically by interface hepatitis, plasma cell infiltration and mild fibrosis and immunologically by the development of anti-LKM1/anti-LC1 antibodies. In addition, livers from DR4 mice had fewer regulatory T cells (Tregs ), which had decreased programmed death (PD)-1 expression. Splenic Tregs from these mice also showed impaired inhibitory capacity. Furthermore, DR4 expression enhanced the activation status of CD8+ T cells, macrophages and dendritic cells in naive DR4 mice compared to naive wild-type (WT) NOD mice. Our results demonstrate that HLA-DR4 is a susceptibility factor for the development of AIH. Impaired suppressive function of Tregs and reduced PD-1 expression may result in spontaneous activation of key immune cell subsets, such as antigen-presenting cells and CD8+ T effectors, facilitating the induction of AIH and persistent liver damage.

Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) or Rendu-Osler Weber syndrome.

BACKGROUND AND STUDY AIMS: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is usually asymptomatic and does not require treatment. However, when present, clinical manifestations can cause considerable morbidity and mortality. Current expertise in the variable clinical manifestations and recommendations for diagnostic approach and management of hepatic involvement in HHT are outlined. METHODS AND MATERIALS: A review of current literature was performed using the MEDLINE search string: "Hereditary hemorrhagic telangiectasia [ALL] OR Rendu-Osler-Weber [ALL] AND (liver OR hepatic [ALL])". RESULTS: Due to the lack of therapeutic consequence, systematic screening for hepatic involvement in asymptomatic patients with HHT is currently not recommended. In symptomatic patients, diagnostic tools include non-invasive techniques such as abdominal color Doppler ultrasound, CT and/or MRI. In any case, liver biopsy should be avoided in patients with suspected HHT because of the high bleeding risk. Liver transplantation is currently the only curative option for symptomatic hepatic involvement in HHT. Except for biliary or hepatocellular necrosis, which require urgent liver transplantation, consensus on the most appropriate timing of transplantation is lacking. Recent studies have shown a promising role for angiogenesis inhibitors as a causative treatment for hepatic involvement in HHT and its complications. CONCLUSIONS: Identification of specific risk factors for progression to the symptomatic phase is one of the main future challenges. This would subsequently allow for individualized and cost-effective screening of high-risk patients when they are still in the asymptomatic stage. However, until then screening in asymptomatic patients is not recommended. Additionally the effect of preventive measures in this high-risk population on the development of symptomatic liver involvement and on poor outcome should be established.

Cutaneous infection by Alternaria infectoria in a liver transplant recipient: a case report.

We report the case of a 65-year-old man who developed multiple crusty ulcerative skin lesions on both lower extremities six months after liver transplantation. The causative pathogen was identified as Alternaria Infectoria, an opportunistic fungal agent. The patient was successfully treated with fluconazole for 27 weeks, with complete regression of the lesions. Due to the lack of well-designed clinical studies it is difficult to determine the best treatment course regarding solid organ transplant recipients presenting with invasive fungal infections. And for now, the clinician must lean upon case-reports or retrospective analyses to compose the most suited therapy for his patient. Based upon literature, it seems that the combination of a broad spectrum azole and reducing the dose of immunosuppressive drugs is the cornerstone of treating invasive fungal infections in solid organ transplant patients.

Calciphylaxis: a rare complication in alcoholic liver disease.

Calciphylaxis, or calcific uremic arteriolopathy (CUA) is a rare but well described entity in patients with endstage renal disease (ESRD) and/or hyperparathyroidism. CUA is characterized by systemic acute calcification of the small and intermediate dermal vasculature that can lead to epidermal ischemia, ulceration, and necrosis. Cutaneous lesions of calciphylaxis characteristically begin as tender, violaceous, livedoid discolorations. The mechanisms of disease remain poorly understood although abnormal bone and mineral metabolism and hyperparathyroidism can contribute to CUA. Therapeutic strategies are of unproven benefit and mortality remains high. Calciphylaxis has also been extremely rarely reported in patients without ESRD and/or hyperparathyroidism. We report an unusual case of calciphylaxis in a patient with alcoholic liver cirrhosis and normal renal function, without any alteration in the phosphocalcic and parathyroid hormone (PTH) metabolisms.

Coinfection of hepatitis B and hepatitis delta virus in Belgium: a multicenter BASL study. Prospective epidemiology and comparison with HBV mono-infection.

Epidemiological data on hepatitis delta virus (HDV) infection in Belgium are lacking. A multicenter questionnaire-based registry on HDV infection was collated between March 1, 2008 and February 28, 2009. It consisted of patients coinfected with hepatitis B virus (HBV) and HDV. The data samples were compared to those of a concurrent registry on HBV infection. Prospective data of patients with HBV-HDV coinfection were collected. Active HBV replication is defined as HBeAg positivity or HBV DNA > 2,000 IU/ml. Forty-four patients from 15 centers were registered. A comparison of 29 patients infected with HDV (registered in the concurrent HBV registry) was made against 785 HBV mono-infected patients. The seroprevalence of patients coinfected with HBV and HDV in Belgium is reported to be 3.7% (29/785), consisting solely of the HBV-HDV coinfected patients in the HBV registry. This rises to 5.5% (44/800) if all patients infected with HDV from the two registries combined are included. The patients coinfected with HBV and HDV had higher (P < 0.05) ALT values and more advanced liver disease (Metavir score ≥F2), but had less active HBV replication and lower HBV DNA titers when compared with the patients infected only with HBV. Additionally, the majority of HBV-HDV coinfected patient was male, and 13.6% (6/44) of the patients that were coinfected HBV and HDV were also infected with HCV. In conclusion, this study provided much needed epidemiological data on the current state of HDV infection in Belgium.

Pathophysiology and management of post resection liver failure.

Post resection liver failure (PRLF) is defined by the occurrence of jaundice, coagulopathy and encephalopathy after liver resection. When PRLF is present, it has a high morbidity and mortality. The incidence of PRLF ranges between 0-30%. For having a healthy regeneration of the liver remnant an adequate number of hepatocytes and nonparenchymal cells, a normal functional and regenerative capacity and also a good accommodation of haemodynamic changes without congestion are needed. To avoid the presence of PRLF ongoing parenchymal damage after the liver resection should be avoided. So, ischemia reperfusion injury should be minimalized, infection and sepsis should be treated immediately and small for size syndrome should be avoided.

Invasive aspergillosis in patients with cirrhosis, a case report and review of the last 10 years.

BACKGROUND: Untreated invasive aspergillosis (IA) is lethal, yet diagnosis is often delayed. Recognising the risk factors can lead to earlier diagnosis. We present a case of an invasive pulmonary aspergillosis in a patient with cirrhosis, who had been treated with corticosteroids for 2.5 weeks for alcoholic hepatitis. He was successfully treated with liposomal amphotericin B and caspofungin (first in combination, then caspofungin monotherapy). PURPOSE: To evaluate the role of aspergillosis in cirrhosis. METHODS: A literature search on aspergillosis in cirrhosis and liver failure patients was conducted in PubMed/Medline (2002-dec 2012), according to pre-set selection criteria. RESULTS: 20 out of 330 articles were retrieved, representing 43 patients with cirrhosis and/or liver failure who had an aspergillosis infection. Most Aspergillus (A.) infections were due to A. fumigatus and the lungs were the most frequent organ involved (42/43). 58% of the patients used steroids and mortality was 53.5%. The most frequent used antifungal was caspofungin. DISCUSSION: Diagnosis of IA is difficult and there might be a delay in diagnosis since cirrhosis is not recognised as one of the classical risk factors. Mortality was 53.5%, but this is lower than in previous decades. Since voriconazole is hepatotoxic, treatment with caspofungin and/or amphotericin is preferable. CONCLUSION: Early recognition of aspergillosis in a cirrhosis/liver failure patient is crucial and should prompt direct treatment.

Hepatitis E seroprevalence in east and west Flanders, Belgium.

BACKGROUND AND STUDY AIM: Hepatitis E virus (HEV) infection is increasingly recognized as a cause of hepatitis in developed countries. The goal of this study is to provide an estimate of the seroprevalence of HEV in Belgium, more precisely in East and West Flanders, since data for this country are currently lacking. PATIENTS AND METHODS: One hundred patients presenting at the gynecological (mainly fertility center) or orthopedic clinics of our hospital were randomly selected to be tested for anti-HEV IgG antibodies using a sensitive indirect ELISA and, in the case of a borderline result, a strip immunoassay. RESULTS: The anti-HEV IgG seroprevalence was found to be 14%. CONCLUSIONS: The observed seroprevalence rate suggests that HEV infection is not an uncommon occurrence in Belgium. Comparisons with published seroprevalence data of other Western European countries should be made with caution due to differences in the analytical performance of anti-HEV IgG assays.

Ascites: not always the usual suspects.

A case report of a 44-year-old woman with an infrequent cause of ascites, i.e. intraperitoneal urine leakage, is presented. Urinary ascites due to spontaneous bladder rupture or fistula after radiation therapy for cervical cancer is not a rare complication and can develop several years after initial treatment. Diagnosis of urinary ascites should be suspected in patients with ascites and a history of radiation therapy for a bladder or a gynaecological disease. Measurement of urea and creatinine levels in urine, ascites and plasma is a simple and non-invasive diagnostic test. In physiological conditions, the ascites/plasma creatinine ratio approximates a ratio of one to one. This ratio is elevated to a value of 5/1 in case of urinary ascites. Although cystoscopy and imaging techniques such as cystography and computed tomography (with or without cystography) are extremely helpful, definitive diagnosis is frequently based on intraoperative findings, because of the lack of pathognomonic symptoms or signs. Surgery is the treatment of choice.

The influence of laboratory-induced MELD score differences on liver allocation: more reality than myth.

BACKGROUND: Liver allocation in Eurotransplant (ET) is based on the MELD score. Interlaboratory MELD score differences in INR and creatinine determination have been reported. The clinical implication of this observation has not been demonstrated. METHODS: MELD scores were calculated in 66 patients with liver cirrhosis using bilirubin, creatinine, and INR analyzed in six liver transplant centers. Based on allocation results of ET, patients transplanted from December 2006 to June 2007 were divided according to MELD score in four groups. For each group, the influence of the match MELD on the probability of receiving a transplant was studied (Cox proportional hazards model). RESULTS: Laboratory-dependent significant differences in MELD score were demonstrated. Cox proportional hazards model showed a significant association between MELD score and the probability of organ allocation. The unadjusted hazard ratio for receiving a liver transplant was significantly different between group 2 and group 4 (group 2: MELD 19-24; group 4: MELD > 30). CONCLUSION: Laboratory-dependent significant differences in MELD score were observed between the six transplant centers. We demonstrated a significant association between the MELD score and the probability of organ allocation. The observed interlaboratory variation might yield a significant difference in organ allocation in patients with high MELD scores.

Progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis: a review.

Progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BRIC) are two rare autosomal recessive disorders, characterized by cholestasis. They are related to mutations in hepatocellular transport system genes involved in bile formation. The differentiation between PFIC and BRIC is based on phenotypic presentation: PFIC is a progressive disease, with evolution to end-stage liver disease. BRIC is characterized by intermittent recurrent cholestatic episodes, with irresistible pruritus, mostly without evident liver damage. Between symptomatic periods, patients are completely asymptomatic. In this article, a short overview of the aetiology, the clinical and diagnostic characteristics and the therapy of both PFIC and BRIC are given.

Upper gastrointestinal tract bleeding management: Belgian guidelines for adults and children.

UNLABELLED: Upper gastrointestinal bleeding (UGIB) remains a common disease affecting 100 to 170 per 100 000 adults per year and causing thereby a significant burden to healthcare resources. Despite the improvements in the management of this disorder, the associated mortality ranges from 5 to 14%. Since the general management of UGIB is not uniform, the main objective of this work is to provide guidelines for the care of adults and children presenting with bleeding caused by gastro-duodenal ulcer or variceal rupture. METHODS: In the absence of evidence-based recommendations, these guidelines were proposed after expert opinions reconciliation and graded accordingly. They are based on the published literature up to September 2010 and graded according to the class of evidence. RESULTS: The current guidelines for the management of UGIB include recommendations for the diagnostic process, general supportive care, pharmacological therapy aiming at bleeding control, specific and endoscopic treatment of acute bleeding and follow-up for both gastro-duodenal ulcers and portal hypertension-induced bleeding.

Early arterial revascularization after hepatic artery thrombosis may avoid graft loss and improve outcomes in adult liver transplantation.

BACKGROUND: Hepatic artery thrombosis (HAT) represents a devastating complication after liver transplantation (LT), occurring in 1.6%-9.2% of adult recipients. Treatments of HAT include thrombectomy and thrombolysis (with or without redo of the arterial anastomosis), percutaneous thrombolysis through an angiogram, liver retransplantation, and clinical observation. METHODS: We retrospectively analyzed data from 739 adult LTs between January 1992 and September 2009. HAT was classified as early (E-HAT), when occurring within the first 30 days after LT, or late HAT (L-HAT), when diagnosed from the 2nd month onward. HAT suspected clinically was confirmed by Doppler ultrasound and angiography in all cases. Attempted revascularization was defined as early (ER) if performed within the first 2 weeks after LT and late (LR) if performed between 15 and 30 days. RESULTS: After a median follow-up (FU) of 62 months (range, 1-227 months), HAT occurred in 31/739 grafts (4.3%). E-HAT was recorded in 25/31 cases (3.4%) and L-HAT in 11/31 cases (0.8%). ER was performed in 20/31 patients (65%) leading to 62% graft salvage; it was 81% when the revascularization was performed within the first week after LT (P = ns). LR was unsuccessful in all cases (P = .08). The overall incidence of BC among rescued grafts was 54% without graft loss during FU. Graft survival was 79% versus 71%; and 50% versus 50% at 1 and 3 years for E-HAT and L-HAT, respectively (P = ns). CONCLUSIONS: Urgent revascularization in cases of early HAT may decrease graft loss, especially when performed within the first week after LT, with improved overall outcomes.