Introduction

Anti-TNF alfa and Azathioprine (AZA) are treatments of choice in the setting of steroid-dependent Inflammatory Bowel Disease (IBD). Thanks to its low cost (with the advent of biosimilars),manageability and lack of immunogenicity Adalimumab (ADA) is the most used anti-TNF. Comparative data between ADA and AZA are scanty.

Aims & Methods

The aim of this study was to compare ADA and AZA in terms of efficacy, safety and persistence in treatment in patients with steroid dependent IBD naive to biologics and/or immunosuppresive therapy. A retrospective-prospective observational study was conducted on consecutive IBD-patients in follow up in our tertiary referral center, who started ADA or AZA between 01/2016 and 01/2022. A minimum follow up of 12 weeks was required. Drug choice was upon clinical judgement. Primary outcome was clinical remission at week 12, 36, 60 and 84, assessed by HBI for CD and p-Mayo score for UC. Secondary outcomes were probability of persistence in treatment and safety.

Results

100 patients were enrolled (54 CD, 46 UC), The two treatment groups showed similar baseline characteristics regarding age, sex, familial predisposition, smoking, previous surgery, and concomitant therapies. The use of systemic steroids at week 0 was documented in 25/48 (52,1%) of patients who started ADA and in 18/52 (28,9%) patients on AZA (p=0,079). The results on primary outcome are described in the table below. In CD both treatments showed similar effectiveness, while patients affected by UC had a significant higher rate of clinical remission when treated with AZA. Six adverse events were registered in the ADA group, 13 AE occurred in the AZA group (p=0,113). Overall retention rate was 38/48 (79,2%) for ADA and 29/52 (55,7%) for AZA (p=0,013). The cumulative probabilities of persistence in treatment was similar in the two groups (p=0,554), but after 84 week a higher trend to treatment discontinuation was observed with AZA. According to IBD type, treatment persistence with ADA was higher in patients with CD (p=0,007) with a retention rate of 92,9% for ADA versus 42,3% for AZA (P<0,001); while in UC the cumulative probability of persistence in treatment was higher for patients treated with AZA (p=0,016) with a retention rate of 69,2% versus 60% for ADA (p=0,519).

Conclusion

Our results show good effectiveness, in terms of clinical remission, in patients with CD in both treatment groups, although ADA has a significant higher probability of persistence in treatment. In UC, AZA group have significant better effectiveness and higher retention rate compared to ADA, while the cumulative probability of persistence in treatment is not statistically significant. These findings suggest the need of a different therapeutic approach in steroid-dependent CD and UC; in particular AZA should be preferred to ADA in patients with UC. In CD both treatments represent a valuable therapeutic option, but ADA may guarantee a better persistence in treatment. These data need to be confirmed in larger series.

Clinical Case Summary

A 34 year old female attended electively for liver biopsy for investigation of deranged liver function tests (LFTs).
Ultrasound guided percutaneous liver biospy was complicated by immediate abdominal pain with computed tomography (CT) abdomen revealing right subphrenic intracapsular fluid contained within the liver capsule in keeping with post biopsy haemorrhage. This was managed conservatively with overnight admission for observation.
The patient represented within 48h hours with worsening jaundice and severe abdominal pain. LFTs had significantly worsened with a hyperbilirubinaemia of 153 umol/L with a cholestatic pattern. Repeat CT abdomen showed new intrahepatic and extrahepatic bile duct dilation with common bile duct (CBD) measuring up to 16 mm in diameter. In the lower CBD, there was an obstructing opacity measuring approximately 7 mm in diameters by 24 mm longitudinal and given the clinical history, a blood clot was to be the most felt likely be the underlying aetiology.
Urgent endoscopic retrograde cholangiopancreatography (ERCP) was performed. An initial cholangiogram revealed a dilated biliary system with ill-defined opacity distally. Following sphincterotomy a large clot was extracted with a 12 millimetre balloon. Final cholangiogram showed clearance of bile ducts with no post procedural complications. The next day updated imaging with CT abdomen showed complete resolution of the biliary duct dilatation and LFTs had improved to pre-liver biopsy baseline. The patient was discharged with no further complications.
Discussion: Haemobilia is recognised as a rare complication from percutaneous liver biopsy with incidence rate of less than 1% (1). The management of haemobilia may be conservative in minor cases with transcatheter arterial embolization usually recommended as first line intervention and ERCP used for biliary drainage (2). In this case we demonstrated a successful outcome in biliary decompression following clot extraction with ERCP.

References

(1) Thomaides-Brears, H.B., Alkhouri, N., Allende, D. et al. Incidence of Complications from Percutaneous Biopsy in Chronic Liver Disease: A Systematic Review and Meta-Analysis. Dig Dis Sci 67, 3366–3394 (2022).
(2) Yilmaz N: Hemobilia Causing Acute Cholecystitis and Pancreatitis after Percutaneous Liver Biopsy: A Case Report and Review of the Literature. Visc Med 2020;36:246-250.

Introduction

Adalimumabe (ADA) 160/80 mg is efficacious for induction of clinical remission in patients with intestinal Crohn’s disease (CD), but data on its long-term efficacy for perianal CD are more limited.

Aims & Methods

To determine whether treatment with Adalimumab is effectiveness in patients with perianal CD. A prospective randomized study , from January 2019 until January 2023 was enrolled with 100 patients (38f/62m, mean age 41, 15 smokers). The patients presented ( trans or suprasphinteric, horse-shoes, multiple with or without rectal involvement), perianal fistulising disease or resistant to immunosuppressive. All patients received 160/80 mg of Adalimumab as induction dose. Immunosupressive therapy was suspended at the start of treatment and steroid dose was reduced of 5 mg/week after the induction phase. The study was performed in a reference public/medical school hospital in Porto Velho, north region of Brazil
Definition of remission: complete closure of the fistula assessed with colonoscopy and magnetic resonance imaging ( MRI ).

Results

Medical charts of 100 patients with perianal CD receiving Adalimumab were investigated. Among them, 42 had infliximab failure, 67/100 colonic disease, 82/100 rectal involvement, 42/100 were also using steroid. At week 6, 18/100 patients (18%), were in remission; at week 30, 29/100 patients (29%) were in remission; at week 52, 66/100 (66%), were in remission and at 3 years, 77/96 patients (80%) were in remission. 4 patients loss response and moved to a temporary loop-ileostomy. No serious adverse events were registered.

Conclusion

Adalimumabe treatment was effective in the remission of perianal CD in 80% of the patients after a 4 years follow-up, showing the effectiveness of adalimumabe.

References

- Hanauer S.B. Sandborn W.J. Rutgeerts P. Fedorak R.N. Lukas M. MacIntosh D. et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial Gastroenterology 130 2006 323 - 333
- Sandborn W.J. Hanauer S.B. Rutgeerts P. Fedorak R.N. Lukas M. MacIntosh D.G. et al. Adalimumab for maintenance treatment of Crohn's disease: results of the CLASSIC II trial Gut 56 2007 1232 123
- Colombel J.F. Sandborn W.J. Rutgeerts P. Enns R. Hanauer S.B. Panaccione R. et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial Gastroenterology 132 2007 52 - 65

Introduction

A strict lifelong gluten-free diet (GFD) is the mainstay of treatment for coeliac disease (CD). However, persistence of gastrointestinal symptoms in coeliac patients despite a GFD is a relevant clinical scenario. The impact of highly processed foods (HPF) intake and the adherence to a correct Mediterranean diet (MD) on these symptoms, the quality of life (QOL), and the metabolic profile of coeliac patients on a GFD is not well understood. This study aimed to investigate the influence of HPF and MD on gastrointestinal symptoms, QOL, and metabolic profile in coeliac patients on a GFD. We hereby present partial data of this ongoing study.

Aims & Methods

Adult CD patients were prospectively enrolled between November-2023 and March-2024 at four Italian referral centers. For each enrolled patient, the following data were recorded: persistent symptoms over the previous 12 months and in the 7 days prior to enrolment by using the GSRS-CeD, adherence to a GFD, adherence to a MD evaluated by means of the Pyramid-based Mediterranean Diet Score (PyrMDS), the consumption of highly processed food evaluated by means of the sQ-HPF, the Celiac Disease-specific Quality of Life Scale (CD-QOL) and metabolic profile. These data were subsequently statistically analized.

Results

A total of 121 patients (83F, mean age 44±15 years) were enrolled. Overall, 61% of patients reported persistent gastrointestinal symptoms despite a GFD. Patients with persistent symptoms were more likely to be female (78% vs 53%, p<0.01), to have a lower HPF intake (26% vs 30%, p=0.02), a higher GSRS-CeD score (median 3 vs 18.5, p<0.001), and lower CD-QoL scores (mean CD-QoL 80 vs 88, p<0.001), but did not have higher PyrMDS scores (p=0.21). PyrMDS was inversely correlated with HPF intake (r=-0.20, p=0.03) and serum triglycerides (r=-0.22, p=0.05), and positively correlated with HDL cholesterol (r=0.20, p=0.08). At multivariate logistic regression adjusted for age and sex, persistence of gastrointestinal symptoms despite a GFD was associated with female sex (p<0.01), lower HPF intake (p=0.04), but not adherence to MD (p=0.31).

Conclusion

Persistence of gastrointestinal symptoms in coeliac patients despite a GFD is common, but unrelated to the adherence to a MD. Female sex and lower intake of HPF were associated with persistence on gastrointestinal symptoms despite a GFD despite a better metabolic profile. Optimising dietary treatment of coeliac patients with persistent gastrointestinal symptoms despite a GFD requires expert nutritional counselling.

Introduction

Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) is one of the best imaging modalities to visualize tumor blood flow, but conventional observation can sometimes be insufficient, particularly in lesions characterized by rapid changes in blood flow. Inflow-time mapping (ITM) is a colored parametric display of time-to-peak enhancement for each pixel in the display that allows a better differentiation of tissues by their speed of contrast agent uptake. ITM is a simple, easily reproducible computer-aided color parametric imaging (CPI) technique that can bring a more objective approach to CEH-EUS analysis and further improve the differential diagnosis of pancreatic masses.

Aims & Methods

To investigate the potential advantages and limitations of Inflow-time Mapping - a novel computer-aided color parametric imaging technique - in assessing focal pancreatic lesions using contrast-enhanced harmonic endoscopic ultrasound.
A total of 15 patients including 8 cases of pancreatic ductal adenocarcinomas (PDAC), 3 cases of chronic pancreatitis, 2 cases of pancreatic neuroendocrine tumors (NETs), one case of serous cystadenoma (SCA) and one case of intraductal papillary mucinous neoplasm (IPMN) were enrolled. CEH-EUS and ITM examinations were performed for the frames obtained during the arterial phase. All CEH-EUS and ITM images were retrospectively reviewed and two sets of criteria were assigned: (1) Routine CEH-EUS alone, focusing on the degree and pattern of enhancement, and (2) CEH-EUS and ITM, focusing on differentiating pancreatic lesions based on their speed of ultrasound contrast agent (UCA) uptake, compared to adjacent tissue. Final diagnosis was based on EUS-guided tissue fine needle aspiration biopsy (EUS-FNAB).

Results

Based on CEH-EUS, 11 pancreatic lesions were initially considered PDAC based on their hypoenhanced appearance. ITM analysis could not provide additional information in 8 patients due to insufficient vascularization. In 3 patients, by showing no difference in the speed of UCA uptake in the enhanced regions of the lesion compared to the surrounding parenchyma, ITM analysis was able to correctly identify chronic pancreatitis, as proven by histology. Among the 2 hyperenhanced pancreatic lesions described on CEH-EUS, ITM analysis was able not only to correctly diagnose but also to provide an extensive characterization of 2 pancreatic NETs by showing a greater speed of UCA uptake in the lesion and a typical pattern of the parametric map. ITM analysis also proved useful in objectively highlighting the speed and pattern of enhancement (septal/mural) of 2 included cystic lesions, IPMN and SCA.

Conclusion

ITM is a promising tool for an objective, simplistic approach, in the assessment of hypervascular pancreatic lesions, particularly pancreatic NETs. It can also become an important step in the evaluation of focal pancreatic masses in patients with chronic pancreatitis, where parenchymal inhomogeneity and altered local perfusion might influence the purely visual assessment of CEH-EUS.

References

Dietrich CF, Dong Y, Froehlich E, Hocke M. Dynamic contrast-enhanced endoscopic ultrasound: A quantification method. Endosc Ultrasound. 2017 Jan-Feb;6(1):12-20. doi: 10.4103/2303-9027.193595. PMID: 28218195; PMCID: PMC5331837

Introduction

The incidence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) are notably higher in individuals diagnosed with type 2 diabetes mellitus (T2DM). However, studies evaluating the progression of MASLD in patients with T2DM and normal serum aminotransferase (ALT) levels are limited.

Aims & Methods

This 5-year prospective cohort study aimed to evaluate the progression of MASLD in T2DM patients with normal ALT. People with type 2 diabetes who had MASLD (defined by controlled attenuation parameter (CAP) >250 dB/min) and ALT levels that stayed normal (defined by ALT ≤40 IU/L for at least two occasions spanning at least six months) at Rajavithi Hospital, Bangkok, from November 2016 to 2017 were included. We excluded patients with viral hepatitis and alcohol consumption exceeding moderate levels. Transient elastography (TE) and CAP measurements were performed at baseline and ≥5 years of follow-up. The cutoffs to define significant and advanced fibrosis were TE >8 kPa and TE >12 kPa, respectively. All patients were instructed to reduce their weight and abstain from herbal remedies; medications for comorbidities were prescribed without limitations, subject to the physician's assessment. (most patients were under endocrinologist care.)

Results

The study included 84 patients, 57% of whom were female and had a mean age of 58.5 years. Of these, 62% were obese, with a mean BMI of 28.6 kg/m2. At baseline, the median TE was 6.92±3.35 kPa; 57 (68%) had no significant fibrosis, 22 (26%) had significant fibrosis, and 5 (6%) had advanced fibrosis, and after a 5-year follow-up, the median TE was 6.54±3.57 kPa; 69 (82%) had no significant fibrosis, 15 (18%) had significant fibrosis, and 2 (2%) had advanced fibrosis. During the follow-up, fibrosis decreased in 45 (54%), remained stable in 6 (7%), and increased in 33 (39%) patients, while a small proportion of patients experienced changes in the stages of fibrosis: 1.2% progressed from significant to advanced fibrosis; 17.4% regressed from advanced to significant fibrosis or transitioned from significant to no fibrosis; 12.8% remained stable with significant and advanced fibrosis; and the majority (66.3%) remained without significant fibrosis. A significant factor associated with fibrosis progression was alcohol consumption (p=0.013), while the use of angiotensin receptor blockers (p=0.042) was associated with fibrosis regression. Significant factors associated with steatosis progression included high baseline BMI (p=0.013), an increase in BMI ≥ 5% (p=0.04), high fasting plasma glucose, and LDL cholesterol levels, while a decrease in BMI ≥ 5% (p=0.002) the use of calcium channel blockers (p=0.038) and coffee consumption >3 cups per day (p=0.031) were associated with steatosis regression. ALT elevation during the follow-up occurred in a small proportion of patients, and it was not significantly associated with fibrosis or steatosis progression.

Conclusion

The majority of MASLD patients with T2DM and normal ALT maintained a relatively stable liver disease during 5 years of follow-up. Obesity, weight gain, alcohol consumption, and inadequate metabolic control were all associated with the progression of MASLD, whereas weight loss, coffee consumption, angiotensin receptor blockers, and calcium channel blockers were all associated with the improvement of MASLD.

Disclosure

I have nothing to disclose