Introduction

Aims & Methods

Results

Conclusion

References

Introduction

Chronic liver disease is a major global health concerns, contributing to over 1.4 million annual deaths worldwide¹. Its primary fatal outcomes, hepatic complications^2,3, arise from liver cirrhosis, hepatocellular carcinoma and hepatic decompensation. The early, reversible stages of chronic liver disease are frequently asymptomatic and overlooked, leading to delayed diagnoses and irreversible complications that treatment options are limited.^4,5. Therefore, reliable tools to identify whether a person will develop hepatic complications in the future have become a public health priority, enabling early diagnosis and timely intervention in high-risk populations.

Aims & Methods

This study aimed to employ machine learning to develop proteomics-based models for the early identification of hepatic complications. In this study, 37,178 adults without hepatic complications at baseline were analyzed from a prospective cohort from United Kingdom, with plasma levels of 2,736 proteins measured using Olink technology. Cox regression was used to identify significant proteins associated with incident hepatic complications. Models based on importance-top-ranking proteins were constructed using LightGBM learners of Automated Machine Learning (AutoML) and internal validated through 5-fold cross validation in the derivation set (n = 37,178). Independent validation was then conducted in a geographically distinct UKB cohort (n = 15,767).

Results

Over a median follow-up of 13.8 years, 338 participants developed hepatic complications. Cox regression identified 593 proteins significantly associated with incident hepatic complications. Among them, GDF15, PROC, GGT1, ANXA10, IL18, MFAP4, COL4A1, CDCP1 and IL6 were ranked highest in protein importance ordering. The protein model showed a considerable predictive accuracy for hepatic complications under different time scenarios in the UKB validation set: all-year (area under the curve [AUC] = 0.89), within 5 years (AUC = 0.88), within 10 years (AUC = 0.91), over 10 years (AUC = 0.81), and achieved superior predictive performance compared to models with demographic predictors, laboratory indicators, polygenic risk score (PRS) and traditional risk score models (Protein 0.89 vs. Demographics 0.83, Laboratory 0.85, PRS 0.49; Fibrosis-4 index [FIB-4] 0.76, Aspartate aminotransferase to platelet ratio index [APRI] 0.78; all P < 0.05). Combined with clinical data and PRS, the predictor performance is further enhanced: all-year (AUC = 0.91), within 5 years (AUC = 0.91), within 10 years (AUC = 0.90), over 10 years (AUC = 0.83). Individuals in the high-risk group stratified by the protein model were 16.27 times more likely to develop hepatic complications.

Conclusion

Our study constructed a novel protein model for hepatic complications risk stratification and could be used to predict individuals who will develop hepatic complications up to 16 years in advance in the general population.

References

1. Tham EKJ, Tan DJH, Danpanichkul P, et al. The Global Burden of Cirrhosis and Other Chronic Liver Diseases in 2021. Liver Int 2025;45:e70001.
2. Åberg F, Asteljoki J, Männistö V, et al. Combined use of the CLivD score and FIB-4 for prediction of liver-related outcomes in the population. Hepatol Baltim Md 2024;80:163–172.
3. Innes H, Morling JR, Buch S, et al. Performance of routine risk scores for predicting cirrhosis-related morbidity in the community. J Hepatol 2022;77:365–376.
4. Karlsen TH, Sheron N, Zelber-Sagi S, et al. The EASL–Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. The Lancet 2022;399:61–116.
5. Serra-Burriel M, Juanola A, Serra-Burriel F, et al. Development, validation, and prognostic evaluation of a risk score for long-term liver-related outcomes in the general population: a multicohort study. Lancet Lond Engl 2023;402:988–996.

Introduction

Endoscopic submucosal dissection (ESD) offers effective, en bloc resection of large colorectal lesions (1), but can be technically challenging, especially for lesions with poor access. This video showcases successful use of the saline-immersion/irrigation technique (SITE), double-balloon endoscopy (DBE) and a novel type of advanced imaging for resection of such a lesion, in a patient with a long sigmoid colon which compromised stability.

Aims & Methods

A 64-year-old woman was referred for evaluation of a sessile (Paris 0-Is) 80mm adenomatous lesion of the transverse colon. Focal surface irregularity (JNET 2B) was also identified. Multidisciplinary team discussion favored en bloc excision using ESD, under conscious sedation. Stable access to the lesion was challenging due to irreducible looping of the sigmoid colon, hindering any attempt at ESD using a standard colonoscope. A DBE was utilized to enhance access and stability, equipped with a conical short, transparent hood to allow for ESD using the pocket-creation method (PCM) (2-4) . ESD was performed using SITE (4-5), which offers several advantages: enhanced optical clarity and magnification, buoyancy of the lesion, improved conductivity (facilitating of vessel pre-coagulation and bleed-management). SITE also enhances patient comfort due to reduced distension, particularly when combined with external drainage of excess saline (6). Here, the DBE overtube was used for drainage. Severe fibrosis and muscle retraction was also observed at the center of the lesion, impeding access to the submucosal plane, this was overcome through clip-band traction. Additionally, a novel type of imaging: Amber-red color Imaging (ACI) (Fujifilm Healthcare, Tokyo, Japan), designed to enhance visualization of the muscularis propria and any vessels was also used, which further improved visualization of the dissection planes.

Results

The lesion was successfully resected en bloc in 180 minutes (dissection speed of 16.68 mm2/min), without significant adverse events. Hemostasias was achieved with knife-tip coagulation and intra-procedural application of protein-matrix gel coupled with scope-tamponade. The patient was prescribed a 5-day course of antibiotics and discharged on the same day. Histopathology confirmed a tubulo-villous adenoma with low-grade dysplasia, completely excised (R0).

Conclusion

DBE allows optimal access to challenging colonic lesions, where stability is critical for successful ESD. This example highlights the importance of adopting a tailored approach for each case, through a combination of established techniques, such as SITE, the PCM, and clip-band traction, to enhance ESD safety, efficacy and efficiency. Utilization of the latest-generation equipment, with optimized maneuverability, ergonomic comfort, and enhanced imaging, further supports these outcomes. Collectively, these strategies serve to overcome technically difficult scenarios.

References

1. Libânio D, Pimentel-Nunes P, Bastiaansen B, Bisschops R, Bourke MJ, Deprez PH, u. a. Endoscopic submucosal dissection techniques and technology: European Society of Gastrointestinal Endoscopy (ESGE) Technical Review. Endoscopy. 29. März 2023;55(4):361–89
2. Hayashi Y, Sunada K, Takahashi H, et al. Pocket-creation method of endoscopic submucosal dissection to achieve en bloc resection of giant colorectal subpedunculated neoplastic lesions. Endoscopy 2014;46:E421-2
3. Hayashi Y, Miura Y, Yamamoto H. Pocket-creation method for the safe, reliable, and efficient endoscopic submucosal dissection of colorectal lateral spreading tumors. Dig Endosc 2015;27:534-5
4. Yamamoto H, Hayashi Y, Despott EJ. The pocket-creation method for endoscopic submucosal dissection combined with saline-immersion: another potential option to overcome challenges in colorectal endoscopic submucosal dissection. Gastrointest Endosc [Internet]. 1. August 2019 [zitiert 6. August 2023];90(2):288–9
5. Despott EJ, Murino A. Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection. Digestive and Liver Disease [Internet]. 1. Dezember 2017 [zitiert 25. August 2023];49(12):1376. ​
6. Takaaki Morikawa, Alberto Murino, Hiroaki Ishii, Yoshikazu Hayashi, Yuka Kagaya, Hisashi Fukuda, Edward John Despott, Hironori Yamamoto. The ‘Asclepius tube’: a slim drainage tube wrapped around the distal part of the endoscope, for cecal endoscopic submucosal dissection, VideoGIE, 2024, ISSN 2468-4481

Disclosure

The authors declare the following conflict of interest:
EMB: No disclosures
GK: No disclosures
AR: No disclosures
AM: Personal payments/honoraria/fees: Olympus Medical, Laborie, Boston Scientific, Fujifilm Healthcare Europe
EJD: Educational grants in support of conference organization, and honoraria, from Fujifilm Healthcare Europe, Pentax, and Olympus Medical, and honoraria from Ambu and Fujifilm Healthcare Europe