Clinical Case Summary

The authors present a case of a 22-year-old male with no previous medical history, apart from COVID-19 in January 2022, which had a mild course. He was referred to a medical appointment in our department after routine blood tests, from March 2022, that revealed abnormal liver biochemistry elevation (ALT 476U/L, AST 139U/L, GGT 135U/L, normal ALP and total bilirubin), which was normal in the previous year. He reported no symptoms and physical examination was unremarkable. There was no chronic medication, recent introduction of drugs, herbal products or epidemiology for zoonoses.
Abdominal ultrasound and CT scan with IV contrast showed discrete hepatomegaly with homogeneous steatosis, without focal lesions, and splenomegaly.
An extensive work-up excluded hepatotropic agents, metabolic causes, autoimmune aetiologies and haematological or lymphoproliferative disorders. The serum protein electrophoresis and immunofixation, immunoglobulins count, tumour markers and celiac disease serology were also normal. During this period, the patient maintained the same liver elevation pattern with stable values, without any alteration in total bilirubin, albumin, coagulation and hemogram, except for the appearance of discrete thrombocytopenia. We remained asymptomatic, with no signs of hepatic decompensation or haemorrhagic diathesis.
The percutaneous liver biopsy documented septal fibrosis and regenerative nodules, interface hepatitis, focal hepatocellular necrosis and, notably, the presence of numerous multinucleated giant hepatocytes, allowing the diagnosis of post-infantile giant cell hepatitis (PIGCH), in cirrhotic phase.
We present a case of PIGCH, with rapid progression to cirrhosis, whose aetiology remains unknow. Viral aetiologies account for 20% of the cases. Given the temporal association between SARS-CoV-2 infection and liver enzymes’ elevation, we cannot exclude this agent as a possible culprit. To our knowledge, this is the first case reporting this possible trigger.

References

Xiao, Y., Gao, Z. H., & Deschenes, M. (2021). Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature. Canadian liver journal, 4(2), 104–109. https://doi.org/10.3138/canlivj-2020-0024;
Jiao, J., & Zhang, X. (2022). Post-infantile Giant Cell Hepatitis: A Literature Review and Meta-analysis. Journal of clinical and translational pathology, 2(3), 100–107. https://doi.org/10.14218/jctp.2022.00016.

Introduction

The randomized controlled OPTIC trial reported that optimised mercaptopurine treatment was superior to placebo in achieving clinical, endoscopic and histological outcomes at one year in ulcerative colitis (UC) patients failing 5-aminosalicylates after receiving induction treatment with corticosteroids.

Aims & Methods

We aimed to assess cost-effectiveness and cost-utility of therapeutic drug monitoring (TDM)-guided mercaptopurine treatment in UC. Data were collected during the OPTIC trial to perform a health economic evaluation for mercaptopurine treatment versus placebo in UC patients. The economic evaluation was performed from a health care and societal perspective using a cost-effectiveness and cost-utility analysis with a time horizon of one year. Volumes and costs of in-hospital care, out-of-hospital care, out-of-pocket expenses and productivity loss were assessed. Main outcomes were the costs per patient who achieved combined corticosteroid-free clinical remission and endoscopic improvement at one year and the costs per quality-adjusted life-year (QALY).

Results

In total, 59 patients were randomized to the intervention (n = 29) and control (n = 30) group. Patients on mercaptopurine treatment showed a non-significant gain in QALYs of 0.047 (-0.024 to 0.117) (P=0.184) corrected for baseline health utility. Non-significant differences in costs were €63 (-€1267 to €1434; P=0.927) in favour of placebo from a health care perspective and -€742 (-€3683 to €2016; P=0.644) in favour of mercaptopurine from a societal perspective, including patients’ out-of-pocket expenses and employers’ productivity loss. The probability of optimised mercaptopurine treatment being cost-effective was 0.80 at a willingness to pay per additional QALY of €20,000.

Conclusion

Optimised mercaptopurine treatment in UC patients failing 5-aminosalicylates is a cost-effective strategy from a societal perspective.

References

1. de Boer NKH, Peyrin-Biroulet L, Jharap B, et al. Thiopurines in inflammatory bowel disease: new findings and perspectives. J Crohns Colitis 2018;12:610–20.
2. Löwenberg, M., Volkers, A., van Gennep, S., Mookhoek, A., Montazeri, N., Clasquin, E., Duijvestein, M., van Bodegraven, A., Rietdijk, S., Jansen, J., van Asseldonk, D., van der Zanden, E., Dijkgraaf, M., West, R., de Boer, N., & D'Haens, G. (2023). Mercaptopurine for the Treatment of Ulcerative Colitis: A Randomized Placebo-Controlled Trial. Journal of Crohn's & Colitis, 17(7), 1055–1065.

Disclosure

NA

Introduction

Intestinal ultrasound (IUS), in particular bowel wall thickness (BWT), is accurate in determining endoscopic disease activity in ulcerative colitis (UC). Reduction of BWT six weeks into advanced anti-inflammatory treatment predicted endoscopic response and clinical remission. Filgotinib is a preferential JAK1-inhibitor effective in UC. Currently, there is no data on IUS-kinetics or early prediction of treatment response with filgotinib.

Aims & Methods

In this study, we aimed to identify early IUS predictors of treatment response to filgotinib in patients with moderate to severe UC. This prospective observational study included UC patients with active endoscopic disease (i.e. endoscopic MAYO score (EMS) ≥2) starting with filgotinib. Clinical scores (UCEIS, Lichtiger), biochemical parameters and IUS parameters of the sigmoid were assessed at baseline, after 4 weeks (W4) and at the time of the second endoscopy (between W8 and W23). Endoscopic remission (i.e. EMS=0), endoscopic response (i.e. decrease in EMS ≥1 compared to baseline) and clinical remission (SCCAI ≤2 or Lichtiger score ≤3) were assessed. IUS response (i.e. defined as a reduction in BWT of >25% or >2.0 mm, or >1.0 mm and one colour Doppler signal) was assessed at week 4. All normally distributed data were reported in mean ± standard deviation [SD] and non-normally distributed in median and interquartile range [IQR]. Mann–Whitney U tests were used to compare continuous non-parametric variables, chi square tests for dichotomous variables.

Results

A total of 20 patients were included. 13 patients underwent second endoscopy, 2 refused a follow-up endoscopy and 5 patients were still in follow-up. At baseline, 9 patients (9/20, 45%) had received ≥2 biologicals, 16 patients (16/20, 80%) had previous anti-TNF exposure, and no patients were exposed to other JAK-inhibitors. 8 patients (8/20, 40%) had severe endoscopic disease at baseline (i.e. EMS=3). 5 patients (5/13, 38%) were endoscopic responders at W8-23, and no patient reached endoscopic remission. BWT was significantly lower in the sigmoid colon from W4 onwards for patients reaching endoscopic response (Table 1). Decrease in BWT compared to baseline was statistically greater in endoscopic responders from W4 onwards (Table 1). IUS response was seen at W4 in 6 patients, of which 5 were endoscopic responders (83%, p=0.002). Decrease in BWT from W4 onwards was statistically greater in patients reaching clinical remission at W8-23 (-45% (-55% to -36.6%) vs -9% (-25% to +8%), p=0.014).

Conclusion

On IUS, UC patients treated with filgotinib have significantly lower BWT from week 4 onwards compared to baseline, which could predict endoscopic response.

Disclosure

MP received speakers fees from Janssen and Tillotts
CT received speakers fees from Tillotts
FV received speaker or honoraria fees from AbbVie, Janssen and Tillotts
ML received consultancy/lecturefees from Abbvie, Bristol Myers Squibb , Eli Lilly, Galapagos, Janssen-Cilag, Johnson & Johnson, Medtronic, Pfizer, Takeda and Tillotts.
RG Received speakers fee from Janssen and Tillotts
GD has served as a consultant and/or received speaker’s fees from AbbVie, Alimentiv, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion Healthcare, Cytoki Pharma, Eli Lilly, Ferring, Galapagos, Glaxo SmithKline, Gossamer Bio, Immunic, InDex Pharmaceuticals, Janssen, Johnson & Johnson, Kaleido, Pfizer, Progenity, Prometheus Biosciences, Prometheus Laboratories, Protagonist Therapeutics, Takeda, Tillotts, Ventyx Biosciences.
KG has received grants from Pfizer Inc, Celltrion and Galapagos; consultancy fees from AbbVie, Arena Pharmaceuticals, Galapagos, Gilead, Immunic Therapeutics, Janssen Pharmaceuticals, Novartis, Pfizer Inc., Samsung Bioepis and Takeda and speaker’s honoraria from Abbvie, Celltrion, Ferring, Janssen Pharmaceuticals, Novartis, Pfizer Inc, Samsung Bioepis, Takeda and Tillotts.

Clinical Case Summary

We present a case of a 37-year-old woman with ulcerative pancolitis (diagnosis in 2004), under therapy with salicylates until 2016. At that time, the patient had a flare up with need of corticosteroid therapy and started infliximab and azhatioprine. In 2018, she was in deep remission, so azathioprine was stopped. In may 2022, the patient developed intermittent fever and palpable purpura on lower limbs. It was evaluated by Dermatology who, after extensive negative ethiological study and partial response to corticosteroids, decided to perform a skin biopsy - leukocytoclastic vasculitis. Subsequently, she started intermittent episodes of hematuria, fatigue and arthralgias. Laboratory tests showed an increase in creatinine twice above the patient's baseline value, large amounts of red blood cells in the urinary sediment and moderate (subnephrotic) proteinuria. From the additional study, only an immunoglobulin A (IgA) elevation of 538 (LSN < 400) is reported. At this time, due to suspicion of IgA nephropathy, a renal biopsy was performed, which confirmed the presence of IgA deposits in the glomerular mesangium. After ruling out infectious, autoimmune and neoplastic causes, Henoch-Schönlein purpura (non-thrombocytopenic purpura and IgA nephropathy) secondary to anti-TNFα was assumed. In an IBD meeting, it was decided to stop anti-TNF and start azathioprine. Due to gastrointestinal intolerance and herpetic infection, vedolizumab was proposed, with a favorable response so far.
The approach of the adverse effects of IBD therapy can be challenging and not very consensual, requiring a multidisciplinary discussion. Henoch-Schönlein purpura is a rare adverse effect of anti-TNFα, particularly in adulthood, which in the present case appeared several years after the start of therapy. We intend to emphasize the need for a high degree of suspicion in this condition, as an early diagnosis has an impact on discontinuation of therapy and can radically change the prognosis.