Introduction

Systemic sclerosis (SSc) is a rare autoimmune disease of the connective tissue that can affect multiple organs. The esophagus is the most affected gastrointestinal tract, while interstitial lung disease (ILD) is a main feature associated with SSc.

Aims & Methods

The aim of the present study was to evaluate the association and prognostic implication between motor esophageal disorders and pulmonary involvement in SSc patients. We retrospectively assessed patients with SSc who underwent both the high resolution manometry with the new Chicago Classification 4.0 and pulmonary evaluation comprehensive of function tests and high-resolution computer tomography (HrCT) with the use of Warrick score. A total Warrick score≥7 was considered predictive of ILD, while a score≥10 in a HrCT acquired prospectively from baseline evaluation was considered to establish significant interstitial involvement.

Results

Forty-two patients were included. We found a score≥7 in 11 patients with aperistalsis, in 6 subjects with ineffective esophageal motility and in 6 patients with a normal manometry. Otherwise, a Warrick score<7 was observed in 3 patients with aperistalsis, and in 2 and 14 patients with ineffective esophageal motility disorder and with a normal contractility, respectively. Higher scores were observed in subjects with absent contractility or ineffective esophageal motility than subjects with normal motility, indeed DCI and HrCT score were inversely correlated in linear and logarithmic regression analysis. Prospectively, lower baseline pressure of lower esophageal sphincter and greater HrCT scores at follow-up evaluation were significantly associated.

Conclusion

This study shows an association between motor esophageal disorder and pulmonary involvement in SSc patients: more severe is the esophageal involvement, more critical is the pulmonary disease.

Introduction

Response rates to the Low FODMAP Diet (LFD) in IBS vary and predictors of benefit remain poorly defined. While several studies from Western populations have identified microbial signatures linked to response, data from Asian cohorts remain limited.

Aims & Methods

This study aims to identify microbial predictors and longitudinal microbiome shifts in Asian IBS-D patients consuming a LFD. We recruited 20 adult Asian patients with IBS-D diagnosed according to the ROME-IV criteria. All subjects received LFD dietary advice from a dietitian at initiation and were followed-up for a total of 28-days. Clinical response was assessed by a ≥50-point improvement in the IBS Symptom Severity Score (IBS-SSS) from Day 0 (baseline) as compared to follow-up at Day 28. Stool samples were collected at baseline, Day 14, and Day 28. Microbial DNA was extracted using bead-beating and Qiagen PowerFecal kits, and the V3–V4 region of the 16S rRNA gene was amplified and sequenced on the Illumina MiSeq platform. Bioinformatic processing included denoising with DADA2, taxonomic assignment using the SILVA 138 database, and rarefaction to even sequencing depth. Microbiome metrics included alpha diversity (Shannon and Simpson), beta diversity (Bray-Curtis PCoA with PERMANOVA), and differential abundance testing with DESeq2.

Results

By Day 28, 11 of 20 patients (55%) achieved clinical response, with a median IBS-SSS reduction of 172 points (IQR: 88–248), compared to 24 points in non-responders (IQR: −11 to 55; p=0.003). Alpha diversity was not significantly different between groups, but responders exhibited a trend toward higher Shannon and Simpson diversity at baseline. Beta diversity analysis using Bray-Curtis dissimilarity revealed partial clustering by responder status (PERMANOVA p=0.06), and PCoA plots showed individual-specific shifts in community structure across time, indicating that the LFD induces personalized microbiome trajectories.
At baseline, responders had significantly higher relative abundances of butyrate-producing and anti-inflammatory genera, including Ruminococcus, Blautia, Eubacterium siraeum, and Bifidobacterium bifidum (adjusted p<0.05). These findings are consistent with prior reports, including Bennet et al. (2018) and Vervier et al. (2022), where such taxa were part of a “health-like” IBS-P (pathogen-enriched) to IBS-H (health-like) axis. The enrichment of Blautia and Ruminococcus is particularly noteworthy as these are established butyrate producers involved in maintaining colonic barrier function and reducing visceral hypersensitivity. By Day 28, differential abundance analysis revealed that responders exhibited increases in Ruminococcus bicirculans, Parabacteroides gordonii, and Weissella cibaria. In contrast, non-responders showed persistence or increases in taxa such as Tyzzerella and Olsenella, which have been associated with inflammation or IBS severity in prior studies (Chuah et al., 2024).

Conclusion

This study provides novel microbiome insights from an underrepresented Asian IBS population consuming a LFD. Despite dietary and baseline microbiota differences from Western populations, we observed remarkably consistent microbiome predictors of response, including higher baseline levels of butyrate-producing taxa and favorable microbial restructuring during the intervention. These results reinforce the reproducibility and functional relevance of microbiome predictors in IBS dietary therapy, and support microbiome profiling as a potential tool for personalized dietary guidance across a diverse global population.

References

Bennet SMP et al. Multivariate modelling of faecal bacterial profiles of patients with IBS predicts responsiveness to a diet low in FODMAPs. Gut. 2018 May;67(5):872-881.
Vervier K et al. Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet. Gut. 2022 Sep;71(9):1821-1830.
Chuah KH, Mahadeva S. Can we predict who will respond to a low-FODMAP diet in irritable bowel syndrome? J Gastroenterol Hepatol. 2024 Feb;39(2):217-218. ​

Introduction

The LiverRisk score has been developed as blood-based tool to estimate liver stiffness measurement (LSM) in the general population (i.e., in subjects without known chronic liver disease (CLD), and thus, detect compensated advanced chronic liver disease (cACLD; LSM ≥10kPa) and stratify their risk of liver-related events. Notably, its utility in other settings is unclear as a one-size-fits-all blood-based test. We aimed to evaluate its diagnostic/prognostic performance in patients referred to specialized hepatology outpatient clinics (i.e., tertiary care).

Aims & Methods

Subjects with known/suspected CLD at first LSM (cohort-I, n=5897) or first referral & LSM (cohort-II, n=1558) were retrospectively included. Calibration/agreement of the LiverRisk score with LSM was assessed as well as its diagnostic accuracy for LSM-defined cACLD compared to FIB-4/APRI. Finally, its predictive performance for hepatic decompensation was evaluated.

Results

In cohort-I/II, mean age was 48.3/51.8years, 44.2%/44.7% were female, predominant etiologies were viral hepatitis (51.8%)/MASLD (63.7%), median LSM was 6.9 [5.1-10.9]/ 5.8 [4.5-8.8]kPa, and 1690 (28.7%)/ 322 (20.7%) had cACLD.
Despite a moderate correlation (Pearson’s r: 0.325/0.422), the LiverRisk score systematically underestimated LSM (mean difference according to the Bland-Altman-method: -2.9/-1.8 points≙kPa). Variation of observed differences was considerable (95%CI of agreement: 39.4 and 35.2 points≙kPa), and showed a clear pattern towards larger disagreement at higher values with lower LiverRisk score than LSM.
The diagnostic accuracy of the LiverRisk for cACLD (AUROC: 0.757 [95%CI: 0.744-0.770]/ 0.790 [95%CI: 0.762-0.819]) was comparable to FIB-4 (0.769/0.813) and APRI (0.747/0.765). The cut-off of 10points≙kPa yielded an overall accuracy of 74.2%/81.2%, high specificity (91.9/93.4%), but low negative predictive value (76.6/84.5%) with false-negative results in 20.0%/13.5% in cohort-I/II, respectively.
In cohort-I, 208 (3.5%) patients developed hepatic decompensation (median follow-up: 4.7years). The LiverRisk score showed a reasonable accuracy for predicting hepatic decompensation within 2 years (AUROC: 0.817); however, it was inferior to LSM (0.891, p<0.001) and FIB-4 (0.912, p<0.001). The strata of LiverRisk score (and of LSM/FIB-4) discriminated patient groups of distinct risks for hepatic decompensation.

Conclusion

While being a major step forward for screening subjects without known liver disease in primary care, the LiverRisk score was not superior (vs. FIB-4) for diagnosis of cACLD or (vs. FIB-4/LSM) for prediction of hepatic decompensation in a tertiary care setting, i.e., in cohorts with a higher pre-test probability of cACLD. Notably, FIB-4 even outperformed the LiverRisk score in terms of prognostic utility.

Clinical Case Summary

Introduction: Kaposi sarcoma is the most common digestive malignancy in Human Immunodeficiency Virus (HIV)-positive patients, but it can also occur in HIV-negative individuals. It is a low-grade vascular tumor associated with Human Herpes Virus-8 (HHV-8) and can appear in immunosuppressed patients. Lesions can develop on the skin, but they could also be found in internal organs and lymph nodes.
Case-report: A 61-year-old Caucasian female with alcoholic liver cirrhosis and diabetes mellitus presented in the Dermatology Department with multiple painless red-to-purple papular nodules across the thorax, cervical area, limbs, and face. Skin biopsies from the posterior cervical area and internal part of the right foot revealed a well-defined nodular dermal tumor with submucosal vascular spindle cells forming slits containing red blood cells and low mitotic activity. Immunohistochemistry confirmed CD34, CD31, HHV-8, and Ki67>30% expression, indicative of cutaneous Kaposi sarcoma. HIV serological tests were negative. Further assessments performed in the Gastroenterology Department established decompensated liver cirrhosis. Moreover, upper digestive endoscopy revealed esophageal varices, portal hypertension gastropathy, along with multiple umbilicated nodules with central ulcerations in the gastric fundus and body. Biopsy samples from these lesions described histopathological findings suggestive of Kaposi sarcoma, while immunostaining for HHV-8 and CD31 was positive. Proposed systemic chemotherapy was declined by the patient. Tumors of the gut with spindle-shaped cells such as leiomyomas, rhabdomyosarcomas, or gastrointestinal stromal tumors must be considered in the differential diagnosis of Kaposi sarcoma.
Conclusion: Kaposi sarcoma can develop in HIV-negative immunosuppressed patients, with conditions such as liver cirrhosis and HHV-8 infections, potentially affecting the digestive tract.

References

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Disclosure

No conflict of interest.