Introduction

Bile acid diarrhoea (BAD) is a common yet often underdiagnosed cause of chronic diarrhoea. Despite its prevalence, BAD remains frequently overlooked in clinical practice. It is estimated that up to 30% of patients with diarrhoea-predominant irritable bowel syndrome (IBS) have underlying BAD, highlighting the importance of distinguishing between these two conditions for effective management. SeHCAT testing remains the gold standard modality for diagnosing BAD. Management typically involves bile acid sequestrants; however, notable variation exists in management approaches across clinical settings.

Aims & Methods

We retrospectively reviewed all SeHCAT tests performed across Imperial College Hospitals, London between 01/01/2023 – 31/12/2023. Electronic health records were interrogated to extract patient demographics, including age, gender, and ethnicity. The results were analysed to determine the proportion of positive findings, which were subsequently stratified by severity. Corresponding management strategies were recorded to evaluate treatment patterns across clinical specialties.

Results

A total of 313 records were identified, of which 13 were excluded due to incomplete data. The average age of patients was 50 years. The predominant ethnicity was White (50.7%) and the majority of the patients were females (64.7%). Among the 300 remaining records, 154 had positive SeHCAT results with a 7 -day retention between 0 and 15%. Of these, 15.7% were categorised as having moderate bile acid malabsorption, followed by severe (13.3%), mild (11.0%), and borderline (11.3%) cases. The majority of the requests originated from Gastroenterologists (86%), with a smaller proportion from Endobariatrics (5.3%), Hepatobiliary Surgeons (3.7%), Hepatologists (2%), Colorectal Surgeons (1.3%) and other specialities (1.7%). Colestyramine was the most commonly prescribed treatment, with 91% of patients initiated on a 4g once-daily dose. Approximately 26.9% of patients on colestyramine experienced side effects, necessitating a switch to colesevelam. The common side effects noticed were abdominal bloating, abdominal cramps, constipation and reflux. Conversely, 87% of patients on colesevelam continued treatment due to better tolerability, with only 13% exhibiting no clinical improvement. The most frequently prescribed dose was 1.25g daily in 45.3% cases. Among patients with normal SeHCAT results, the majority were diagnosed with diarrhoea-predominant irritable bowel syndrome (47.3%).

Table 1: SeHCAT results

Conclusion

Bile acid diarrhoea continues to be a prevalent factor contributing to chronic diarrhoea in healthcare. While existing treatment modalities have proven effective in managing this condition, they remain poorly tolerated. Our study confirms that colesevelam demonstrates improved tolerability compared to colestyramine.

References

Walters JRF, Arasaradnam RP, Andreyev HJN, UK Bile Acid Related Diarrhoea Network. Diagnosis and management of bile acid diarrhoea: a survey of UK expert opinion and practice. Frontline Gastroenterology 2019; 11:358-363 dx.doi.org/10.1136/flgastro-2019-101301

Clinical Case Summary

Vertical banded gastroplasty (VBG) is a bariatric procedure which use the combination of staples and a band to create a small gastric pouch. Although its primary success, this procedure was not longer performed because of not ineffective weight loss over time and common complications such as stricture or complete obstruction at the level of the band side, resulting in vomiting and dysphagia.
A 59-year-old male presented to the ER with vomiting, significant weight loss, syncopal episodes and electrolyte imbalance. In his past medical history, he had a VBG performed in 2001 for obesity. These symptoms led him to visit different hospitals over the years. No diagnosis could be made, due to the presence of alimental residual every time he performed an esophagogastroduodenoscopy (EGD). Eventually, after different years, he came to our center. Since the high risk of finding alimental residual in the stomach, the EGD was performed under general anesthesia. After reaching the stomach, we observed the complete obliteration at the site of the bendage, and the presence of a bezoar inside the small gastric pouch, resulting in outflow obstruction. Behind the bezoar, the presence of a natural gastro gastric fistula was observed at the sight of the previous staple line. The remnant part of the stomach was explored, showing sign of mucosal atrophy. On retroflexion, the region of the band site was obstructed, and covered by normal mucosa, suggesting a complete embedment of the gastric bandage. During the years, the complete obliteration at the bendage site resulted in an increase in pressure inside the gastric pouch. This led to the formation of a gastro-gastric fistula, to allow the patient to feed himself. Once the bezoar has formed, this “mechanism” failed, resulting in symptoms of outlet obstruction. The bezoar was removed using a grasping forcep. After the remotion of the bezoar, he managed to resumed oral feeding, in the absence of vomiting or nausea.

References

1. Endoscopic removal of the bezoar using a net retriever
2. Endoscopic appearance of the gastro-gastric fistula
3. Endoscopic appearance of gastric bendage completely buried into the mucosa

Introduction

The prognosis for patients with hepatocellular carcinoma (HCC) remains extremely poor, with a 5-year survival rate of 20% without curative treatment. A recent studyⁱ demonstrated that the use of a computed CT score including muscle density and muscle area could identify frailty in cirrhotic patients and predict 6-month mortality. The objective of the study was to evaluate predictors of 6-month mortality in patients with HCC and to establish the impact of sarcopenia in this context.

Aims & Methods

We performed a retrospective analysis of 86 patients with HCC treated at the Hôtel Dieu de France in Beirut between 2016 and 2024. The collection included clinical and biological data, prognostic indices (Child Pugh scores, MELD) as well as CT parameters for measuring sarcopenia and myosteatosis, including skeletal muscle index, muscle densities, and muscle surfaces at L3 level. The coreslicer® software was used to calculate muscle and fat surfaces on CT. The measurements evaluated included the surfaces at L3 of the psoas and paravertebral and parietal muscles, as well as the density of the psoas. Among these, the “L3 skeletal muscle area adjusted to height and density ratio (L3- SMHDR)” which is calculated by the total muscle area at the L3 level * Average size / density of the psoas muscles at the L3 level. This measurement helps include myosteatosis in the assessment of sarcopenia.

Results

• Our population included 86 patients with HCC, 74 men, 12 women, with a mean age of 66.1 ± 10.7 years. MELD-Na score was 16.1 ± 8.2, and Child-Pugh score was A, B, and C in 39%, 27%, and 34%, respectively. Twelve patients (14%) were eligible for curative treatment, in accordance with BCLC guidelines.
• Decreased survival is significantly associated with increasing L3-SMHDR. An AUROC analysis for L3-SMHDR as a predictor of mortality at 1 month found the same cutoff values as a previously published study with cutoffs of 5.4 and 4.7 in men and women, respectively. Populations with low L3-SMHDR vs. high L3-SMHDR had a survival time of 31.2 months vs. 11.09 months (P=0.035).
• In order to determine the different factors linked to a decrease in survival at 6 months, we conducted a univariate analysis which identified the following parameters: muscle density at scan (p=0.016), L3-SMHDR (p=0.004), L3-DRMI (p=0.034) and the MELD-Na score (P=0.077). A value of L3-SMHDR > threshold had a risk of mortality OR= 7.8 [1.8-34, P=0.003] and 5.64 [1.3-23.8, P=0.013] at 6 and 12 months respectively.
• In multivariate analysis, the two independent prognostic factors were the MELD-Na score and L3-SMHDR, which allowed us to arrive at the following equation:
• Probability = 0.112* MELDNa + 2.518* L3-SMHDR – 3.11.
• This analysis allowed us to classify patients according to the above function categories, and to estimate the risk of mortality at 6 and 12 months at respectively OR = 10 [2-50, P=0.003] and 11.4 [2.2-58.6, P=0.002].

Conclusion

The 6-month prognosis of patients with HCC depends primarily on liver function and the severity of sarcopenia and myosteatosis, not tumor stage. This should provide additional prioritization for patients eligible for liver transplantation. Confirmation of these results should be considered in a larger-scale study.

References

i. El Khoueiry C, Slim R, Rida M, Khoury B, Honein K, Smayra T, Yaghi C. New Scanographic Index for the Detection of Frailty in Patients with Cirrhosis with a Prognostic Impact. Middle East J Dig Dis. 2024 Apr;16(2):102-108. doi: 10.34172/mejdd.2024.376. Epub 2024 Apr 30. PMID: 39131107; PMCID: PMC11316193.

Introduction

Sarcopenia, the progressive loss of skeletal muscle mass, is related to metabolic-dysfunction associated steatotic liver disease (MASLD) and cardiovascular damage (CVD). Genetic variants like PNPLA3, TM6SF2, and HSD17B13 influence MASLD risk. The prevalence of CVD is higher in MASLD patients, however the impact of sarcopenia on CVD in MASLD patients is undefined. Moreover, the role of genetic variants in sarcopenia and CV damage is unexplored.

Aims & Methods

To assess the impact of sarcopenia, metabolic comorbidities, and genetic variants on liver and CVD in a cohort of non-cirrhotic MASLD patients.
We enrolled 841 MASLD patients. Fibrosis was assessed by liver stiffness measurement (LSM) (LSM≥8 kPa for advanced fibrosis) and steatosis by controlled attenuation parameter (CAP) at Fibroscan (CAP>280 dB/m for severe steatosis). Sarcopenia was defined by the lowest tertile of skeletal muscle index (SMI = skeletal muscle mass/height^2) at bioimpedance analysis. CV damage markers included carotid intima-media thickness (cIMT)≥0.9 mm, carotid plaques, epicardial fat thickness (EFT) ≥5.2 mm. Increased waist circumference (WC) >102/88 cm in men/women. Genetic polymorphisms in PNPLA3, TM6SF2, and HSD17B13 were assessed in 424 patients.

Results

Mean age was 51 ys, 63% male. 43% were obese, 65% had increased WC. 50% were dyslipidemic, 25% diabetic. 24% had advanced fibrosis, 71% severe steatosis. 22% had increased cIMT, 35% had carotid plaques, 83% had increased EFT. Sarcopenia (SMI<10.35/7.75 kg/m2 in men/women) was linked to older age (54 vs 48 ys, p<0.001), lower BMI (27 vs 33.4 kg/m2, p<0.001), WC (99 vs 110 cm, p<0.001), CAP (293 vs 317 dB/m, p<0.001), and LSM (4.9 vs 6.4 kPa, p<0.001) compared to non-sarcopenic. Sarcopenic also had higher dyslipidemia (56% vs 46%, p=0.03), increased cIMT (28% vs 18%, p=0.01), and EFT (85% vs 77%, p=0.05). At adjusted multivariate analysis, sarcopenia remained associated with low BMI (OR 0.61; 95% CI 0.5-0.7, p<0.001), WC (OR 0.92; 95% CI 0.8-0.97, p=0.001), female sex (OR 2.21; 95% CI 1.2-4.0, p=0.008), and increased cIMT (OR 2.1; 95% CI 1.1-3.97). In sarcopenic, PNPLA3 CG/GG variant was linked to increased LSM (OR 1.82, 95% CI 1.1-3.1, p=0.03) but lower cIMT (OR 0.39, 95% CI 0.15-0.96, p=0.04). TM6SF2 wild-type allele was associated with increased cIMT (OR 3.4, 95% CI 1.3-5.8, p=0.004), and WC (OR 2.3, 95% CI 1.4-3.6, p=0.001). No differences were seen in HSD17B13 variant.
Analyzing different metabolic subgroups, in diabetic and hypertensive patients, prevalence of carotid plaques was higher in sarcopenic vs non-sarcopenic (56% vs 30%, p=0.04, 58% vs 20%, p<0.001). In hypertensive patients sarcopenia remained an independent risk factor for carotid plaques (OR 1.9, CI 95% 1.05-3.5, p=0.03) and high/very high CV risk (OR 3.0, CI 95% 1.2-7.2, p=0.01) in multivariate analysis adjusted for age, sex, diabetes, dyslipidemia, smoke and BMI, whereas in non-diabetic subjects for high/very high CV risk (OR 1.44, CI 95% 1.1-2.1, p=0.04).

Conclusion

MASLD patients, particularly non-obese, have a high prevalence of sarcopenia and increased subclinical CVD. Despite lower visceral adiposity, in hypertensive patients sarcopenia seems to potentiate the CVD. In sarcopenic patients, the PNPLA3 variant correlated with lower subclinical atherosclerosis, while TM6SF2 polymorphism showed a protective role against CV damage.
MASLD patients would need a prompt evaluation and treatment of sarcopenia to prevent the onset of CVD, particularly if hypertensive. Combining genetic data is required to clarify the role of sarcopenia in MASLD.

Clinical Case Summary

A 54-year-old man with no significant medical history underwent his first screening colonoscopy, during which four polyps were removed from the recto-sigmoid colon. Histopathologic analysis revealed adenocarcinoma arising in one of the polyps, prompting subsequent surgical resection of the sigmoid. While surgical pathology was negative for residual adenocarcinoma, incidental findings in regional lymph nodes revealed features consistent with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Flow cytometry revealed a kappa light chain-restricted B-cell population with immunophenotypic features of CLL/SLL, but the cell count was below the threshold required for a diagnosis of CLL. The patient had no symptoms, cytopenias, or lymphadenopathy, and he was ultimately diagnosed with monoclonal B-cell lymphocytosis (MBL). The patient required no immediate treatment and was placed under annual surveillance.
MBL is defined by the presence of a monoclonal B-cell population with a CLL immunophenotype that does not meet the diagnostic criteria for CLL. It is categorized as either low- or high-count based on B-cell count. Low-count MBL rarely progresses to CLL, while high-count MBL progresses to CLL requiring treatment at a rate of 1-2% annually. Signs of progression to CLL include doubling of white blood cell count, anemia, thrombocytopenia, night sweats, weight loss, enlarged lymph nodes or spleen, and recurrent infections. If a patient does not show any clinical evidence of progression to CLL, they can continue annual surveillance. In this case, the rare detection of neoplastic B-cells in the colon led to the early identification of MBL, which has not been previously reported as an incidental finding alongside adenocarcinoma. In summary, this case underscores the importance of thorough histopathological review and interdisciplinary collaboration with clinical correlation of incidental findings to guide monitoring of a premalignant hematologic condition.

References

There is no evidence of residual or metastatic adenocarcinoma in the tissue submitted from the resected sigmoid colon. Incidentally, the submitted lymph nodes have ill-defined capsular borders with loss of normal nodal architecture, suggestive of a clonal lymphoproliferative process. Immunohistochemistry performed on the lymph nodes demonstrates the following immunophenotype: the neoplastic B-cell population is positive for CD20, CD5, and CD23 and negative for CD3, CD10, and Cyclin D1. Overall, the findings are consistent with a diagnosis of CLL/SLL.