Incidence and prevalence of primary biliary cholangitis in the Netherlands - A nationwide cohort study.

Background & Aims: Although primary biliary cholangitis (PBC) is considered a rare disorder, accurate determination of its incidence and prevalence remains challenging due to limited comprehensive population-based registries. We aimed to assess the incidence and prevalence of PBC in the Netherlands over time through the nationwide Dutch PBC Cohort Study (DPCS). Methods: DPCS retrospectively included every identifiable patient with PBC in the Netherlands from 1990 onwards in all 71 Dutch hospitals. Incidence and prevalence were assessed between 2008-2018 by Poisson regression between sex and age groups over time. Results: On the 1st of January 2008, there were 1,458 patients with PBC in the Netherlands. Between 2008-2018, 2,187 individuals were newly diagnosed, 46 were transplanted and 468 died. The yearly incidence of PBC in 2008 was 1.38, increasing to 1.74 per 100,000 persons in 2018. When compared to those aged <45 years, females aged 45-64 years (adjusted incidence rate ratio 4.21, 95% CI 3.76-4.71, p <0.001) and males ≥65 years (adjusted incidence rate ratio 14.41, 95% CI 9.62-21.60, p <0.001) were at the highest risk of being diagnosed with PBC. The male-to-female ratio of patients newly diagnosed with PBC during the study period was 1:14 in those <45 years, 1:10 in patients aged 45-64 years, and 1:4 in those ≥65 years. Point prevalence increased from 11.9 in 2008 to 21.5 per 100,000 persons in 2018. Average annual percent change in this time period was 5.94% (95% CI 5.77-6.15, p <0.05), and was the highest among the population aged ≥65 years (5.69%, 95% CI 5.32-6.36, p <0.001). Conclusions: In this nationwide cohort study, we observed an increase in both the incidence and prevalence of PBC in the Netherlands over the past decade, with marked age and sex differences. Impact and implications: This nationwide Dutch primary biliary cholangitis (PBC) Cohort Study, including all hospitals in the Netherlands, showed that the incidence and prevalence of PBC have increased over the last decade. The age-dependent PBC incidence rate differed for males (highest risk ≥65 years) and females (highest risk between 45 and 65 years), which may be related to a difference in the timing of exposure to environmental triggers of PBC. The largest increase in PBC prevalence over time was observed in the population aged ≥65 years, which may have implications for the use of second-line therapies. These results therefore indicate that further studies are needed to elaborate on the advantages and disadvantages of add-on therapies in the elderly population.

Outcomes after hybrid minimally invasive treatment of Boerhaave syndrome: a single-institution experience.

BACKGROUND: Spontaneous esophageal perforation or Boerhaave syndrome is a life-threatening emergency, associated with significant morbidity and mortality. In this retrospective series we describe our single-center experience with a hybrid minimally invasive treatment approach for the treatment of Boerhaave syndrome. METHODS: Clinical data of all patients who presented with spontaneous esophageal rupture between January 2009 and December 2019 were analyzed. All patients underwent esophageal endoscopic stenting to seal the perforation and debridement of the contaminated mediastinal and pleural cavity through video-assisted thoracoscopic surgery (VATS). Primary outcome measure was defined as in-hospital death and 30-day mortality. RESULTS: Twelve patients were included with a median age of 63 years (interquartile range [IQR] 51-74 years) of whom 58% (n = 7) were male. The median Pittsburg perforation severity score was 6.5 (IQR 6-9). Endoscopic reintervention was required in 8 patients (67%), primarily due to stent dislocation. In addition, 5 patients (42%) required re-VATS due to empyema formation. Thirty-day mortality and in-hospital mortality were respectively 17% (n = 2) and 25% (n = 3). CONCLUSION: Endoscopic stenting in combination with thoracoscopic debridement is an effective and safe minimally invasive hybrid approach for the treatment of Boerhaave syndrome. This is depicted by the relatively low mortality rates, even among patients with high perforation severity scores. The relatively low mortality rates may be attributed to the combined approach of rapidly sealing the defect and decontamination of the thorax. Future studies should aim to corroborate this evidence which is limited by its sample size and retrospective nature.

Assessing the efficacy and safety of mycophenolate mofetil versus azathioprine in patients with autoimmune hepatitis (CAMARO trial): study protocol for a randomised controlled trial.

BACKGROUND: Currently, the standard therapy for autoimmune hepatitis (AIH) consists of a combination of prednisolone and azathioprine. However, 15% of patients are intolerant to azathioprine which necessitates cessation of azathioprine or changes in therapy. In addition, not all patients achieve complete biochemical response (CR). Uncontrolled data indicate that mycophenolate mofetil (MMF) can induce CR in a majority of patients. Better understanding of first-line treatment and robust evidence from randomised clinical trials are needed. The aim of this study was to explore the potential benefits of MMF as compared to azathioprine, both combined with prednisolone, as induction therapy in a randomised controlled trial in patients with treatment-naive AIH. METHODS: CAMARO is a randomised (1:1), open-label, parallel-group, multicentre superiority trial. All patients with AIH are screened for eligibility. Seventy adult patients with AIH from fourteen centres in the Netherlands and Belgium will be randomised to receive MMF or azathioprine. Both treatment arms will start with prednisolone as induction therapy. The primary outcome is biochemical remission, defined as serum levels of alanine aminotransferase and immunoglobulin G below the upper limit of normal. Secondary outcomes include safety and tolerability of MMF and azathioprine, time to remission, changes in Model For End-Stage Liver Disease (MELD)-score, adverse events, and aspects of quality of life. The study period will last for 24 weeks. DISCUSSION: The CAMARO trial investigates whether treatment with MMF and prednisolone increases the proportion of patients in remission compared with azathioprine and prednisolone as the current standard treatment strategy. In addition, we reflect on the challenges of conducting a randomized trial in rare diseases. TRIAL REGISTRATION: EudraCT 2016-001038-91 . Prospectively registered on 18 April 2016.

Retrieval and re-evaluation of previously diagnosed chronic hepatitis C infections lost to medical follow-up in the Netherlands.

OBJECTIVES: Many individuals previously diagnosed with chronic hepatitis C virus (HCV) infection are likely to be lost to medical follow-up and, therefore, remain untreated despite new highly effective drug treatment, direct acting antivirals. We aim to identify and retrieve these chronic HCV-infected individuals to re-evaluate them and offer treatment. METHODS: Possible chronic HCV infections were identified from test results of the medical microbiological laboratory, notifications to the public health service, and the hospital registries over the past 15 years were checked in South Limburg, the Netherlands. Individuals were contacted based on the physician-patient relationship of the gastroenterologist or microbiologist (retrieval). Individuals were informed about the new treatment options, offered an HCV-RNA test, and if still positive, referred to the gastroenterologist for treatment (re-evaluation). RESULTS: In total, 689 individuals with a positive anti-HCV test in the past were identified, 308 (45%) were eligible for retrieval, 90 (29%) of them were retrieved, 34 (38%) of those retrieved were re-evaluated, 19 (56%) of those tested were HCV-RNA positive, and 12 (63%) of these individuals were offered treatment. CONCLUSION: During every step of the retrieval chain, many patients were lost. Nevertheless, with substantial effort, we were able to identify, retrieve, and positively re-evaluate a limited number of individuals with a possible chronic HCV infection who were lost to medical follow-up (19 patients). With this case-finding approach, we were able to prevent potential severe complications in these patients and contribute to a small step in the eradication of HCV in the Netherlands.

Acute gastrointestinal bleeding from a submucosal gastric mass.

We report a case of a 44-year-old male patient who presented with melena and hemodynamic instability. The endoscopic investigation of the upper and lower gastrointestinal tract was initially negative, but a repeat gastroduodenoscopy revealed a submucosal mass in the lesser curvature of the stomach with central erosion, primarily perceived as ectopic pancreas, but it was later discovered that it pertained to a gastrointestinal stromal tumor.