Clinical Case Summary

A 49-year-old female was referred to the hepatology outpatient clinic for abnormal liver enzymes and hepatic steatosis on ultrasound.
She had an extensive intestinal resection following acute thrombotic mesenteric artery ischemia 4 years ago, resulting in intestinal failure. Only the left colon and 130 cm of jejunum were preserved.
Her lowest BMI was 17 kg/m2. She was on parenteral nutrition (PN) during hospital admissions, totalizing 45 days. Two years ago she had an episode of biliary pancreatitis
As an outpatient, she was on a culinary diet supported by oral nutritional supplements, and her current BMI was 22kg/m2.
The patient was prescribed several antibiotics, octreotide, and was currently on warfarin, pantoprazole, loperamide, cholestyramine, ursodeoxycholic acid, and vitamin/oligo element supplementation. No steatosis, signs of liver disease, or hepatic ischemia were present in the first computed tomography, 4 years ago.
In the following imaging evaluations, progressive liver steatosis was noted. Labs showed an ALP and AST 2 times the upper limit of normal, with an AST/ALT ratio of 2:1.
Liver function was preserved, and fibrosis was staged with transient elastography (12 kPa). After excluding other etiologies of liver disease, we diagnosed intestinal failure-associated liver disease (IFALD).
One year later, the patient presented with clinically significant ascites and worsening liver function. A liver biopsy was performed, showing cirrhosis and macrovesicular steatosis with features of steatohepatitis, confirming the diagnosis (image 1). The patient was referred to a liver transplant center. We present a rare case of progressive IFALD three years after the last exposure to PN, questioning the possible role of other risk factors. Prevention should be the focus, mainly with personalized nutritional support and preserving intestinal length.

References

Pironi L, Sasdelli AS. Intestinal Failure-Associated Liver Disease. Clin Liver Dis. 2019 May;23(2):279-291. doi: 10.1016/j.cld.2018.12.009. Epub 2019 Feb 21. PMID: 30947877.
Lee, W.S., Chew, K.S., Ng, R.T. et al. Intestinal failure-associated liver disease (IFALD): insights into pathogenesis and advances in management. Hepatol Int 14, 305–316 (2020). https://doi.org/10.1007/s12072-020-10048-8
Clinical approach to the management of Intestinal Failure Associated Liver Disease (IFALD) in adults: A position paper from the Home Artificial Nutrition and Chronic Intestinal Failure Special Interest Group of ESPENAuthor links open overlay panel, Simon Lal et al.



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Introduction

The global burden of overweight and obesity-related diseases has been a growing public health concern over the past few decades. These conditions contribute significantly to morbidity and mortality worldwide and are associated with a wide range of chronic diseases. Understanding the trends and sex differences in disease burden attributable to overweight and obesity is essential for developing effective prevention and intervention strategies. This study aims to assess the burden of overweight and obesity-related diseases in males and females.

Aims & Methods

We analyzed data from the Global Burden of Diseases (GBD) study, covering overweight and obesity-related disease burdens in 26 diseases across 204 countries and territories. Key disease burden indicators, including mortality and disability-adjusted life years (DALYs), were studied. Linear regression analysis was applied to the natural logarithm of age-standardized outcomes to determine the annual percent change.

Results

In 2019, the global burden of overweight and obesity-related diseases reached 160.2 million DALYs, and the number of deaths associated with these conditions was approximately 5.02 million in males and females. The age-standardized death rates in males showed an increase from 58.19 per 100,000 person-years in 1990 to 66.55 per 100,000 person-years in 2019 (APC =0.36%, 95% CI 0.30% to 0.42%, P <.001), while in females it decreased from 59.31 per 100,000 person-years in 1990 to 58.14 per 100,000 person-years in 2019 (APC =-0.22%, 95% CI -0.29% to -0.14%, P <.001). There was a higher increase in age-standardized DALY rates in males, from 1632.5 per 100,000 years in 1990 to 2070.34 per 100,000 years in 2019 (APC =0.74%, 95% CI 0.70% to 0.78%, P <.001), while females experienced a smaller increase from 1618.26 per 100,000 years in 1990 to 1789.67 per 100,000 years in 2019 (APC =0.24%, 95% CI 0.19% to 0.29%, P <.001). These trends resulted in a higher male-to-female rate ratio in deaths and DALYs in 2019, which did not exist in 1990. The higher male-to-female rate ratio in deaths and DALYs were found in more than half of countries and territories. A large proportion of the higher burden in males compared to females can be explained by an increase in development.

Table. Comparison of age-standardized mortality and disability-adjusted life years (DALYs) rates between males and females, 1990-2019
Metric	1990	2000	2010	2019	Annual percentage change (95% CI)	P-value
Mortality Rate (per 100,000 person-year)
Male	58.2	62.5	64.0	66.6	0.36% (0.30% to 0.42%)	<0.001
Female	59.3	61.0	58.3	58.1	-0.22% (-0.29% to -0.14%)	<0.001
Male to Female Ratio	0.98	1.02	1.10	1.14	0.58% (0.55% to 0.61%)	<0.001
DALYs Rate (per 100,000 year)
Male	1633	1798	1927	2070	0.74% (0.70% to 0.78%)	<0.001
Female	1618	1704	1719	1790	0.24% (0.19% to 0.29%)	<0.001
Male to Female Ratio	1.01	1.06	1.12	1.16	0.50% (0.48% to 0.52%)	<0.001

Conclusion

The study uncovers a significant increase in the burden of overweight and obesity-related diseases, with a marked disparity between males and females. These findings underscore the need for further research to investigate the underlying causes of this gender difference in overweight and obesity-related deaths and DALYs. Identifying the contributing factors will facilitate the development of targeted interventions and public health policies to address and resolve these disparities. It is crucial to ensure that both genders benefit equitably from efforts to combat the global burden of overweight and obesity-related diseases.

Introduction

The obesity paradox, in patients with cancer, is a hypothesis showing patients with obesity have a prolonged overall survival compared to the ones with a normal weight. This paradox is present in different types of cancer, lung cancer, renal cell cancer, and melanoma. For gastrointestinal cancers, there are conflicting results regarding the obesity paradox. Neuroendocrine neoplasms (NENs) are rare cancers arising anywhere in the body but mainly within the gastroenteropancreatic (GEP) tract. NENs differ from other gastrointestinal cancers as they have a relatively good prognosis even in metastatic disease. NENs are classified into three different grades (G1, G2, G3) based on mitotic count and Ki-67 staining. The grades are correlated with overall survival patients with G1 GEP-NENs have significantly better overall survival compared to patients with G2 or G3 GEP-NENs. The presence of the obesity paradox in patients with GEP-NENs is only described in one population-based study from the USA. However real-world data exploring the obesity paradox are lacking.

Aims & Methods

Aim: To explore the presence of the obesity paradox in patients with GEP-NENs in a single centre in the United Kingdom.
A cross-sectional study was performed regarding all patients with GEP-NENs and treatment with monthly somatostatin analogues (SSA’s) between August 2018 and February 2019. During this period all patients weight, height and BMI were collected. Additional demographic and histopathologic data were extracted from the local hospital database. Stable disease was classed as having no change in oncological treatment within 3 months of weight/height screening. Overall survival (OS) was calculated from the moment of weight/height screening until death or the last follow-up appointment (data cut-off June 2022). Kaplan Meier, log-rank tests and Cox regression analysis were performed.

Results

In total 118 patients, n=55 (47%) males with a median age of 67 years (IQR 56.8 – 75) were included. The primary tumour was in the small intestine in n=91 (77%) and pancreas in n=25 (21%) of patients, and grade 1 in n=74 (71%) or grade 2 in n=30 (29%) of patients. In 91 patients (77%) there was stage IV disease. The median period since diagnosis was 40 months (IQR 14 – 84 months) and median period on SSA 23 months (IQR 5.5 – 59 months). The median BMI is 24.8 (IQR 21.7 – 28.7), 7 patients (6%) are underweight (BMI <18.5), 52 patients (44%) had a normal weight (BMI 18.5 – 24.9), 33 patients (28%) were overweight (BMI 25 – 29.9), 26 patients (22%) were obese (BMI >30). There are significant OS differences between BMI categories p-value 0.002. When correcting for age HR 1 (0.97 – 1.05), sex HR 1.3 (0.49 – 3.66), grading 2.06 (0.74 – 5.72), stable disease versus progressive disease HR 5.4 (1.9 – 14.9), the BMI is still significantly associated with OS with HR 0.31 (0.16 – 0.62), p-value 0.002.

Conclusion

This study shows some evidence for the presence of the obesity paradox in a real-world population of patients with GEP-NENs using an SSA. Patients with a low or normal BMI might benefit from extra attention to their nutritional status and nutritional support. Future research should focus on the pathophysiologic mechanism explaining the obesity paradox.

References

DECREASED INPATIENT MORTALITY IN OBESE PATIENTS WITH ABDOMINAL NETS, Evan S. Glazer, Kelley Stanko, Evan S. Ong, Marlon A. Guerrero, ENDOCRINE PRACTICE 2014

Disclosure

Nothing to disclose

Clinical Case Summary

Lysosomal acid lipase deficiency (LALD) is a rare autosomal-transmitted metabolic disease in which infants and adults show uncontrolled accumulation of cholesterol esters and triglycerides, resulting in multi-organ damage and premature death. Few cases of hepatocellular carcinoma (HCC) onset in LALD-related cirrhosis have been described, while the occurrence in the earlier disease stages remains unreported.
A 49-year-old (yo) male was admitted for chronic diarrhea and recurrent abdominal pain. History collection revealed his brother's death due to cryptogenic cirrhosis complications. Comorbidities were: statin-unresponsive dyslipidemia determining an episode of juvenile (27yo) Acute Myocardial Infarction (AMI). Physical examination evidenced splenic-hepatomegaly and emaciated facies with an aquiline nose. Laboratories abnormalities highlighted mainly: alanine-aminotransferase elevation and malabsorption. Ultrasonography revealed in the bright-liver not-coarse pattern a nodule (30 mm) appearing contrast-enhanced-suspected for HCC, subsequently histologically confirmed by a percutaneous biopsy. The colonoscopy was negative for malignancies; esophagogastroduodenoscopy showed an edematous duodenal mucosa with a marked foam cell infiltrate. In light of these findings, considering also the anamnestic (familiarity), clinic (facies, unexplainable diarrhea), and biochemical data, rare lysosomal accumulation diseases were suspected.
A Dried Blood Spot test evidenced low LAL activities and the genetics confirmed the LALD diagnosis. Due to the reported hepatic disorder recurrence, liver transplantation was not indicated, and thus microwave thermoablation was performed. Twelve months later, the patient would have benefited from Sebelipasi Alpha-based enzyme replacement therapy. Unfortunately, he died after a new AMI.
LALD should be suspected and early identified. HCC occurrence in a non-cirrhotic LALD context appears possible

References

Cunha-Silva M, de França EVC, Veiga CT, Greca RD, de Moraes PBS, de Campos Mazo DF, de Ataíde EC, Perales SR, Monici LT, Sevá-Pereira T. 15-Year progression to liver cancer in the lack of treatment for lysosomal acid lipase deficiency: A case report. Medicine (Baltimore). 2022 Sep 2;101(35):e30315. doi: 10.1097/MD.0000000000030315. PMID: 36107601; PMCID: PMC9439781.

Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure for class 1 and 2 obese subjects¹. The effects of smoking habits on weight are well known regarding bariatric surgery^2-6. However, given that this patient population is inherently weight-concerned, understanding the effects of tobacco use on post-operative weight loss in bariatric endoscopy is essential to guiding clinicians in counselling patients in this field.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in an Italian tertiary referral centre was assessed retrospectively. Data on smoking habits (smoker, non-smoker, and previous smoker) were collected. Efficacy and safety between the three smoking categories was evaluated using an ANOVA test.

Results

Between May 2017 and October 2021, 290 subjects underwent ESG. Out of the total, smoking habits were available for 275 subjects: 144 non-smokers (NS; 52,4%), 51 smokers (S; 18,5%) and previous smokers (EX-S; 29,1%). No statistically significant differences in BMI was observed between the three groups.
In each group, no major complication were reported in the perioperative period. Adherence to follow-up was 93,1%, 92,4% and 73,5% for non-smokers, 90,2%, 84,3% and 82,4% for smokers, 91,3%, 90,0% and 71,9% for EX-smokers, at 6,12 and 24 months.
Average TBWL, EWL and WL were similar between the three groups at 6,12 and 24 months (see Table below). In the non-smoker group, five subjects underwent revision procedures (4 Re-ESG, 1 Surgery) after 24 months, whereas one previous smoker underwent Re-ESG after six months. No revision was reported in the smoker group.

	Smoker	Non-Smoker	Ex-Smoker
6-months TBWL (%)	18,1 (5,6)	16,9 (6,4)	18,1 (6,4)
6-months EWL (%)	53,8 (20,4)	53,3 (23,6)	54,7 (21,8)
6-months WL (kg)	20,4 (7,2)	17,9 (8,0)	19,7 (7,7)
12-months TBWL (%)	17,0 (9,1)	15,7 (9,1)	16,0 (10,1)
12-months EWL (%)	51,0 (29,8)	49,4 (30,9)	48,3 (30,4)
12-months WL (kg)	19,0 (10,6)	15,5 (10,3)	17,3 (12,1)
24-months TBWL (%)	12,2 (12,5)	13,3 (10,0)	14,9 (8,7)
24-months EWL (%)	32,5 (37,0)	39,6 (29,8)	43,6 (24,4)
24-months WL (kg)	14,4 (14,0)	14,7 (11,9)	16,2 (10,6)

Conclusion

Our analysis, with the strengths of a large cohort and a long-term follow-up, showed that smoking habits do not influence the efficacy and safety of ESG for up to 24 months.
Finally, proper counseling of patients should advise the cessation of the smoking habit.

References

¹ Abu Dayyeh BK, et al. Lancet. 2022
² Dittrich L. Surg Obes Relat Dis. 2020
³ łuszyńska P. J Clin Med. 2022
⁴ Chow A. Surg Endosc. 2021
⁵ Mohan S. Surg Endosc. 2021
⁶ Srikanth N. J Addict Dis. 2021

Introduction

Eosinophilic esophagitis (EoE) is a chronic, condition linked to a type 2 inflammatory response and frequently associated to other atopic conditions. EoE may presents either sporadically, or with aggregation of cases within a same family. Limited information has been provided on the differences in clinical characteristics and disease features between sporadic and familiar EoE, largely due to the lack of large patient cohorts.

Aims & Methods

To find differences in sporadic and familiar cases of EoE which may support distinct clinical management, a cross-sectional analysis of the multicenter EoE CONNECT registry was performed. Demographic and clinical from patients recruited at 42 hospitals in 4 European countries were extracted on March 28th, 2025. Information extracted included 1) age at diagnosis and diagnostic delay; 2) symptoms leading to diagnosis; 3) disease endoscopic and histologic features at diagnosis; and 4) atopic concomitances.

Results

	S-EoE	F-EoE
Age at diagnosis (n= 3,179) <18 years old	18.5%	30.6%
Inflammatory Score (n= 2,723)	1.62 ± 1.3	1.93 ± 1.32
Fibrosis Score (n=2,723)	1.04 ± 1.04	0.97 ± 1.08
Fibrosis (n=1,701)	58.6 %	62.8 %
EoE-Phenotype (n=3,017)
Inflammatory	75.9 %	79.6 %
Mixed	12.6 %	8.6 %
Stricturing	11.5 %	11.8 %

Overall, 4,053 patients (75.4 % males, mean age 33.3 ±15.2 years) were analyzed, including 3028 (74.7 %) sporadic (S-EoE), 714 (17.6%) without familiar data and 311 (7.7 %) familiar (F-EoE) cases including 89 families. Among the family forms, n= 76 families showed 2 affected members, n= 11 presented 3 members, and n= 2 with 4 members. In 85/89 families we identified the index case consisting in sons (13), parents (23), siblings (38), or other distant kinships.
The F-EoE forms were diagnosed at younger mean ± SD ages than S-EoE (29.8±15.6 vs. 33.7±15.1; p<0.001) and included a higher proportion of pediatric patients (considered as those below 18 at diagnosis; 30.6% vs. 18.5%; p<0.001)
Symptoms leading to EoE diagnosis were similar across study groups, with slightly higher presences of abdominal pain (as they included more pediatric cases; 7.7% vs. 4.5%; p=0.01) and chocking episodes (7.7% vs. 4.5%; p=0.01) among F-EoE.
Endoscopy presented more severe features according to EREFS among F-EoE (mean ± SD being 2.86 ± 1.66 vs. 2.64 ± 1.68; p=0.054) at the expense of both fibrotic and inflammatory features, despite only the later reach statistical significance (1.93 ± 1.32 vs. 1.62 ± 1.3; p<0.001). Esophageal biopsies exhibited higher mean ± SD peak eosinophil counts in F-EoE cases (57.11 ± 40.7 vs. 52.87 ± 37.97; p=0.04).
F-EoE were more allergic patients, as they presented a higher mean ± SD number of concomitant atopies (1.44 ± 1.25 vs. 1.25 ± 1.22; p=0.009) and all were more common among them, with conjunctivitis and hives reaching statistical significance (p=0.01 and p=0.002 respectively). Overall, a higher proportion of F-EoE had at least one atopy compared to S-EoE (69.4 % vs. 63.8%).

Conclusion

F-EoE seems to present more severely, with earlier onset, more inflammatory load in endoscopy and biopsies and higher concomitant allergic manifestations.

Introduction

Endoscopic sleeve gastroplasty (ESG) is a safe and effective procedure in class 1 and 2 obese subjects.The effects of menopause on weight are well known. However, given that this patient population is inherently weight-concerned, understanding the effects of ESG on women in menopause is essential to guiding clinicians in counselling this patient population.

Aims & Methods

A prospective dataset collecting data on all ESG procedures performed in a tertiary referral centre was assessed retrospectively. Data on fertility status (menopause and non-menopause women) were collected. A comparison was performed using the Mann-Whitney U test.

Results

Between May 2017 and October 2021, 209 women underwent ESG. Out of the total, fertility status was available for 204 women: 79 menopause (M; 38,7%) and 125 non-menopause women (NM; 61,3%).At baseline, non-menopause women were younger, whereas there were no differences in BMI and weight.
Adherence to follow-up was 92,4%, 87,3% and 80,0% for menopause, 88,8%, 90,4% and 72,9% for non-menopause, at 6,12 and 24 months, respectively.
Six months after the procedure, non-menopause women showed significantly higher TBWL, WL and BAROS score compared to the menopausal group. In contrast, EWL showed no significant difference between the groups.Average TBWL, WL and EWL were not significantly different between the groups at 12 and 24 months (as shown in Table below).
Seven menopausal women needed revision procedures (5 Re-ESG, 1 Surgery), whereas ten non-menopausal women underwent revision (8 Re-ESG, two surgery).

Table. Weight loss trajectories of subjects who underwent Endoscopic Sleeve Gastroplasty, based on menopausal status. Data are reported as median (Interquartile range).

		WL (kg)	EWL (%)	TBWL (%)	BAROS
6-months follow-up	Menopause (n=73)	15,0 (10)	50,8 (24,7)	15,2 (8,6)	3,5 (1,5)
	Non-menopausa (n=111)	17,0 (9,0)	54,9 (34,6)	17,2 (8,6)	4,0 (2,0)
	p	0,017	0,068	0,0190	0,039
12-months follow-up	Menopause (n=69)	13,0 (11,0)	47,8 (31,4)	14,1 (13,0)	3,5 (2,3)
	Non-menopausa (n=113)	16,0 (13,5)	52,5 (41,5)	16,3 (13,5)	3,5 (2,8)
	p	0,162	0,318	0,223	0,506
24-months follow-up	Menopause (n=40)	13,0 (15,6)	40,5 (39,3)	13,6 (14,8)	2,6 (2,9)
	Non-menopausa(n=62)	10,0 (11,8)	35,4 (45,0)	10,4 (13,4)	2,5 (3,4)
	p	0,4	0,716	0,519	0,776

Conclusion

Non-menopausal women who undergo ESG show better outcomes in the short term. However, this advantage does not persist in the medium and long term.