Objective Inadequate bowel preparation impairs the accuracy of colonoscopy and increases the burden on patients and healthcare systems. Consequently, the quality of bowel preparation is an important quality indicator. We aim to develop and validate multivariable prognostic models for the identification of patients at risk of inadequate bowel preparation using machine learning (ML). Methods Demographic and clinical data from consecutive patients ≥18 years of age who underwent colonoscopy at six centres in Germany were prospectively collected. Adequate bowel preparation was defined as Boston Bowel Preparation Scale ≥6 with a value ≥2 in each colonic segment. We used statistical and ML methods to build prognostic models and to compare them to published models. Results Overall, we analysed 2652 patients, including 699 (26.4%) inpatient procedures. The mean patient age was 57.6 years (SD 16 years), and 48.9% were women. In 1401 (52.8%) patients, the indication was screening or surveillance, and 1035 (39%) patients had a first-time colonoscopy. The rate of inadequate bowel preparation was 16%. Sensitivities, specificities and areas under the curve of predictive models obtained by generalised boosting models, Ranger, support vector machine (radial), CatBoost and Net Regularised Generalised Linear Models were 0.51–0.86, 0.52–0.83 and 0.71–0.74, respectively. They were only marginally superior to a logistic regression model. All models had high negative predictive values >0.9 for inadequate bowel preparation. To detect one patient with inadequate bowel preparation, 8–10 patients need to be evaluated. Conclusions Predictive models to identify patients at risk for inadequate bowel preparation obtained by ML showed comparable results compared with a logistic regression model. Trial registration number DRKS00018878.

Background and Aims:Metabolic dysfunction-associated steatotic liver disease (MASLD) affects >30% of adults and is becoming one of the leading causes of hepatocellular carcinoma (HCC). Reliable biomarkers are needed for the early diagnosis of HCC and detection of chronic liver diseases, like MASLD. Here we assessed the biomarker potential of circulating microRNAs in a cohort of patients genotyped for the risk allele of patatin-like phospholipase domain-containing protein 3 (PNPLA3), associated with increased susceptibility to chronic liver diseases. Methods:The cohort comprised 70 MASLD patients (40 with simple steatosis, 9 with metabolic dysfunction-associated steatohepatitis (MASH), 21 with cirrhosis), 47 HCC patients (32 with cirrhosis), and 14 healthy controls. Serum levels of miR-122-5p, miR-146a-5p, miR-146b-5p, miR-21-5p, miR-335-5p, miR-433-3p, miR-4530, miR-4651, miR-526a2, and miR-873-5p were quantified using custom qPCR plates. Their suitability for prediction of MASLD (steatosis/MASH/cirrhosis) or HCC was assessed by receiver operating characteristic curve analyses. Results:MiR-4651 and miR-21-5p were significantly reduced in sera from patients with MASLD, particularly in those with simple steatosis. Both microRNAs effectively distinguished MASLD patients with simple steatosis from healthy controls (area under the curve: 0.95 and 0.89, respectively). Moreover, miR-4651 emerged as the best predictor for differentiating "complicated" MASLD (i.e., MASH or cirrhosis) from simple steatosis; the predictive values could be increased by including additional parameters into the models (Fibroscan, thrombocytes, cytokines, or other miRNAs). miR-335-5p showed strong ability to differentiate HCC from healthy individuals (area under the curve: 0.86). The PNPLA3 p.I148M genotype was not associated with altered levels of microRNAs. Conclusion:Serum microRNAs, in particular miR-4651, may serve as additional biomarkers in patients with steatotic liver disease.

BACKGROUND AND AIMS:Decompensation of cirrhosis significantly decreases survival, thus, prevention of complications is paramount. We used machine learning techniques to identify parameters predicting decompensation. METHODS:Several machine learning techniques were applied to the INCA trial database containing pro- and retrospective data from 983 patients. Laboratory, clinical, and genetic data were analysed. After performing hierarchical clustering, Permutation Feature Importance was used to evaluate the impact of parameters on the prediction of decompensation. RESULTS:Achieving an accuracy of 81.6% on training and 70.5% on test data, Random Forests were best for retrospective prediction. In prospective assessment, Support Vector Machines performed best with an accuracy of 78.6% and 73.8%, respectively. Permutation Feature Importance demonstrated that baseline albumin and bilirubin levels and maximum bilirubin were the highest ranked parameters associated with former decompensation. In the prospective analysis, the maximum bilirubin value and the baseline values of sodium and albumin were ranked highest. In addition to the parameters of established scores, NOD2 genotype and inflammatory markers were highly ranked. CONCLUSIONS:Laboratory parameters, genetic variants and infections can help to predict the risk of cirrhosis decompensation. This proof-of-concept study adds data for the future development of advanced models to identify patients at risk.

BACKGROUND Bacterial infections (BI) negatively affect the natural course of cirrhosis. The most frequent BI are urinary tract infections (UTI), pneumonia, and spontaneous-bacterial peritonitis (SBP). AIM To assess the relevance of bacterial infections beyond the commonly recognized types in patients with cirrhosis and to investigate their relationship with other clinical variables. METHODS We retrospectively analyzed patients with cirrhosis and BI treated between 2015 and 2018 at our tertiary care center. BIs were classified as typical and atypical, and clinical as well as laboratory parameters were compared between the two groups. RESULTS In a cohort of 488 patients with cirrhosis, we identified 225 typical BI (95 UTI, 73 SBP, 72 pulmonary infections) and 74 atypical BIs, predominantly cholangitis and soft tissue infections (21 each), followed by intra-abdominal BIs (n = 9), cholecystitis (n = 6), head/throat BIs (n = 6), osteoarticular BIs (n = 5), and endocarditis (n = 3). We did not observe differences concerning age, sex, or etiology of cirrhosis in patients with typical vs atypical BI. Atypical BIs were more common in patients with more advanced cirrhosis, as evidenced by Model of End Stage Liver Disease (15.1 ± 7.4 vs 12.9 ± 5.1; P = 0.005) and Child-Pugh scores (8.6 ± 2.5 vs 8.0 ± 2; P = 0.05). CONCLUSION Atypical BIs in cirrhosis patients exhibit a distinct spectrum and are associated with more advanced stages of the disease. Hence, the work-up of cirrhosis patients with suspected BI requires detailed work-up to elucidate whether typical BI can be identified.

Question: In a 52-year-old female patient with a history of sebaceous gland neoplasms of the skin (carcinoma resected in 2017 and several subsequent adenomas) and positive family history for early-onset colorectal cancer (father at the age of 39 years), Muir-Torre syndrome was suspected. This is a rare variant of Lynch syndrome (LS; approximately 10% of individuals with LS) clinically defined by the typical LS tumor spectrum (colorectal cancer as well as extracolonic tumors, eg, endomtetrial/ovarian cancer, urinary tract cancer) and additional increased risk for characteristic skin neoplasms (especially sebaceous gland neoplasms and keratoacanthoma). DNA mismatch-repair (MMR) deficiency resulting in an accumulation of somatic mutations throughout the genome, also affecting genes involved in carcinogenesis, causes LS. Genetic testing identified a pathogenic germline mutation in MSH2 (mutS homolog 2) on chromosome 2p21 and confirmed the diagnosis in 2018. Compliant with current international guidelines, the patient was included in a specific tumor-screening program. In dermatologic follow-up examinations, basal cell carcinoma and squamous cell carcinoma of the skin were detected. By annual surveillance colonoscopies up to the present, 4 colorectal adenomas with sizes from 2 to 15 mm were resected. On an individual basis, and not covered by guidelines, we performed yearly surveillance esophagogastroduodenoscopy (EGD). Interestingly, at the age of 57 years, a small irregular and slightly elevated lesion (8 mm) with small central erosion (Figure A, arrow) was observed (Paris 0-IIa) in the mid-esophagus (25 cm from incisors). The central part of the lesion stained negative during chromoendoscopy with Lugol’s iodine (1%) (Figure B, arrow) and showed an irregular surface pattern with virtual chromoendoscopy (NBI mode; narrow band imaging) (Figure C). Therefore, malignancy was suspected, and the lesion was removed en bloc by means of rubber-band ligation assisted endoscopic mucosal resection (Figures D and E). Of note, the patient was never a smoker and only occasionally consumed alcohol. Endoscopies were performed with Olympus GIF-H190 endoscopes (Olympus, Hamburg, Germany). Which diagnosis do you suspect and is this lesion LS associated? Look on page 189 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Histopathologic and immunohistochemical examination of the resected tumor revealed poorly differentiated invasive squamous cell carcinoma (pT1a, Pn0, V0, R0, G3) (Figure F, hematoxylin and eosin [HE] stain, ×40) with focal invasion of the lamina muscularis mucosae (Figure G, HE, ×200, arrow). Molecular microsatellite instability testing discovered instability in 4/5 markers (BAT-26, NR-21, BAT-25, and NR-24; NR-27 was stable). When an LS-associated tumor was suspected, MMR protein immunohistochemistry showed a loss of MSH2 expression within the neoplastic cells (Figure H, ×200, red arrow) while surrounding tissue stained positive for MSH2 (Figure H, black arrow) and MLH1 expression was unaffected in neoplastic (Figure I, ×200, red arrow) and nonneoplastic (Figure I, black arrow) cells. Computed tomography and endoscopic ultrasound did not find any distant or lymph-node metastases, and there was no residual tumor in a follow-up endoscopy. Because of poor tumor differentiation and invasion of the lamina muscularis mucosae (m3), additive radiotherapy (50.4 Gy/59.92 Gy boost in 28 fractions) was recommended after discussion by the tumor board. This is the first description of an LS/Muir-Torre syndrome–associated squamous cell carcinoma of the esophagus in a patient without typical risk factors for this tumor entity. Moreover, we show in-depth molecular characterization to prove LS association. Only rarely have adenocarcinomas of the esophagus been reported1Sweetser S. Chandan V.S. Baron T.H. Dysphagia in Lynch syndrome.Gastroenterology. 2013; 145: 1167-1168Abstract Full Text Full Text PDF Scopus (6) Google Scholar in LS. Until recently, squamous cell carcinoma of the skin was not counted as typical skin manifestation of Muir-Torre syndrome, but an association has been demonstrated.2Ykema B.L.M. Adan F. Crijns M.B. et al.Cutaneous squamous cell carcinoma is associated with Lynch syndrome: widening the spectrum of Lynch syndrome-associated tumours.Br J Dermatol. 2021; 185: 462-463Crossref PubMed Scopus (7) Google Scholar Of note, our patient also suffered from squamous cell carcinoma of the skin. In conclusion, clinicians should carefully consider esophageal neoplasms as a rare manifestation of LS. Despite limited data supporting EGD surveillance in LS and in contrast to current guidelines, upper endoscopy could be easily performed along with routine colonoscopy in an effort to prevent morbidity and mortality from upper GI manifestations of LS (early-stage cancer observed in about 1.5% of asymptomatic patients3Farha N. Hrabe J. Sleiman J. Beard J. et al.Clinically actionable findings on surveillance EGD in asymptomatic patients with Lynch syndrome.Gastrointest Endosc. 2022; 95: 105-114Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar).

BACKGROUND AND AIMS:Endoscopic mucosal resection (EMR) of non-pedunculated colorectal polyps ≥20mm is technically demanding and should preferentially be performed by specialist endoscopists in referral centres. Little is known about the outcome in institutions establishing this competency. Here, we report the learning curve on 100 consecutive large non-pedunculated polyps resected by a single endoscopist with self-taught acquisition of skills.METHODS:We analysed data on 100 non-supervised EMR procedures performed at our academic endoscopy centre (2016-2021), representing a single endoscopist's learning curve beginning with the first polyp ≥20 mm.RESULTS:The median polyp size was 30 mm (20-70mm), and 61% of all polyps were ≥30 mm. Predominant polyp morphology was 0-Is (34%) or 0-IIa (47%), and most polyps developed in the ascending colon (36%). In total, 20% of polyps showed high-grade intraepithelial neoplasia, and 8% included pT1 carcinoma. Adenoma recurrence rate after piecemeal resection was 21%. All but one recurrent adenoma were treated endoscopically. Deep mural injury, intra-procedural bleeding and post-procedural bleeding were detected and managed endoscopically in 3%, 21%, and 4% of procedures, respectively. Overall, surgery could be avoided in 91% of all and 98% of non- malignant polyps. Results for the first 50 polyps did not differ from results for the following polyps.CONCLUSIONS:Structured training is advisable to acquire advanced EMR skills. Our data show that autonomous acquisition of skills after finishing a training course represents an acceptable alternative with good results in the setting of an open error culture. Continuous review of outcome parameters and complication rate is mandatory during the learning process.

BACKGROUND:Individuals carrying the risk variant p.I148M of patatin-like phospholipase domain-containing protein 3 (PNPLA3) have a higher susceptibility to fatty liver diseases and associated complications, including HCC, a cancer closely linked to chronic inflammation. Here, we assessed circulating cytokine profiles for patients with chronic liver diseases genotyped for PNPLA3. METHODS:Serum concentrations of 22 cytokines were measured by multiplex sandwich-ELISA. The cohort comprised 123 individuals: 67 patients with NAFLD without cirrhosis (57 steatosis, 10 NASH), 24 patients with NAFLD with cirrhosis, 21 patients with HCC (15 cirrhosis), and 11 healthy controls. Receiver operator characteristic analyses were performed to assess the suitability of the cytokine profiles for the prediction of steatosis, cirrhosis, and HCC. RESULTS:HGF, IL-6, and IL-8 levels were increased in patients, with ∼2-fold higher levels in patients with cirrhosis versus healthy, while platelet derived growth factor-BB (PDGF-BB) and regulated on activation, normal T cell expressed and secreted (RANTES) showed lower concentrations compared to controls. Migration inhibitory factor and monocyte chemoattractant protein-1 (MCP-1) were found at higher levels in NAFLD samples (maximum: NAFLD-cirrhosis) versus healthy controls and HCC samples. In receiver operator characteristic analyses, migration inhibitory factor, IL-8, IL-6, and monocyte chemoattractant protein-1 yielded high sensitivity scores for predicting noncirrhotic NAFLD (vs. healthy). The top combination to predict cirrhosis was HGF plus PDGF-BB. Migration inhibitory factor performed best to discriminate HCC from NAFLD; the addition of monokine induced gamma (MIG), RANTES, IL-4, macrophage colony-stimulating factor (M-CSF), or IL-17A as second parameters further increased the AUC values (> 0.9). No significant impact of the PNPLA3I148M allele on cytokine levels was observed in this cohort. CONCLUSIONS:Cytokines have biomarker potential in patients with fatty liver, possibly suited for early HCC detection in patients with fatty liver. Patients carrying the PNPLA3 risk allele did not present significantly different levels of circulating cytokines.

BACKGROUND:Whereas Artificial Intelligence (AI) based tools have recently been introduced in the field of gastroenterology, application in inflammatory bowel disease (IBD) is in its infancies. We established AI-based algorithms to distinguish IBD from infectious and ischemic colitis using endoscopic images and clinical data.METHODS:First, we trained and tested a Convolutional Neural Network (CNN) using 1796 real-world images from 494 patients, presenting with three diseases (IBD [n = 212], ischemic colitis [n = 157], and infectious colitis [n = 125]). Moreover, we evaluated a Gradient Boosted Decision Trees (GBDT) algorithm using five clinical parameters as well as a hybrid approach (CNN + GBDT). Patients and images were randomly split into two completely independent datasets. The proposed approaches were benchmarked against each other and three expert endoscopists on the test set.RESULTS:For the image-based CNN, the GBDT algorithm and the hybrid approach global accuracies were .709, .792, and .766, respectively. Positive predictive values were .602, .702, and .657. Global areas under the receiver operating characteristics (ROC) and precision recall (PR) curves were .727/.585, .888/.823, and .838/.733, respectively. Global accuracy did not differ between CNN and endoscopists (.721), but the clinical parameter-based GBDT algorithm outperformed CNN and expert image classification.CONCLUSIONS:Decision support systems exclusively based on endoscopic image analysis for the differential diagnosis of colitis, representing a complex clinical challenge, seem not yet to be ready for primetime and more diverse image datasets may be necessary to improve performance in future development. The clinical value of the proposed clinical parameters algorithm should be evaluated in prospective cohorts.

BACKGROUND:Patients with cirrhosis who carry NOD2 mutations are susceptible to bacterial infections. The aim was to evaluate the association of NOD2 mutations with hepatic and systemic hemodynamics in cirrhosis. PATIENTS AND METHODS:This is a secondary analysis of a prospectively collected database in the context of the screening for the INCA trial (EudraCT 2013-001626-26). This cross-sectional study compared hemodynamic findings according to NOD2 status in 215 patients. Patients were genotyped for NOD2 variants (p.N289S, p.R702W, p.G908R, c.3020insC, rs72796367). Hepatic hemodynamic study and right heart catheterization were performed. RESULTS:Patients had a median age of 59 (IQR 53-66) years, and 144 (67%) were men. Most patients (64%) were Child-Pugh stage B. Sixty-six patients (31%) carried a NOD2 mutation, which was slightly more common among Child-Pugh stage C (p = 0.05), without differences in MELD [wild-type: 13 (10-16); NOD2 variants 13 (10-18)]. No differences in hepatic and systemic hemodynamics were observed according to NOD2 status. If excluding patients on prophylactic or therapeutic antibiotics, again no association between hepatic or systemic hemodynamics and NOD2 status could be observed. CONCLUSION:NOD2 mutations are not associated with hepatic or systemic hemodynamic abnormalities in patients with decompensated cirrhosis, suggesting that other mechanisms leading to bacterial translocation predominate.

Key words gastrointestinal endoscopy - chromoendoscopy - squamous cell carcinoma

Background Digital single-operator pancreatoscopy (DSOP)-guided lithotripsy is a novel treatment modality for pancreatic endotherapy, with demonstrated technical success in retrospective series of between 88 % and 100 %. The aim of this prospective multicenter trial was to systematically evaluate DSOP in patients with chronic pancreatitis and symptomatic pancreatic duct stones. Methods Patients with symptomatic chronic pancreatitis and three or more stones of > 5 mm in the main pancreatic duct (MPD) of the pancreatic head or body were included. The primary end point was complete stone clearance (CSC) in three or fewer treatment sessions with DSOP. Current guidelines recommend extracorporeal shock wave lithotripsy (ESWL) for MPD stones > 5 mm. A performance goal was developed to show that the CSC rate of MPD stones using DSOP was above what has been previously reported for ESWL. Secondary end points were pain relief measured with the Izbicki pain score (IPS), number of interventions, and serious adverse events (SAEs). Results 40 chronic pancreatitis patients were included. CSC was achieved in 90 % of patients (36/40) on intention-to-treat analysis, after a mean (SD) of 1.36 (0.64) interventions (53 procedures in total). The mean (SD) baseline IPS decreased from 55.3 (46.2) to 10.9 (18.3). Overall pain relief was achieved in 82.4 % (28/34) after 6 months of follow-up, with complete pain relief in 61.8 % (21/34) and partial pain relief in 20.6 % (7/34). SAEs occurred in 12.5 % of patients (5/40), with all treated conservatively. Conclusion DSOP-guided endotherapy is effective and safe for the treatment of symptomatic MPD stones in highly selected patients with chronic pancreatitis. It significantly reduces pain and could be considered as an alternative to standard ERCP techniques for MPD stone treatment in these patients.

Aims SOVP-guided treatment of pancreatolithiasis offers an alternative to extracorporeal shock wave lithotripsy(ESWL) in patients with symptomatic chronic obstructive pancreatitis(SCOP). We present early results of a prospective evaluation of the efficacy, safety and clinical outcome of SOVP-guided lithotripsy.

Background In response to the COVID-19 pandemic, endoscopic societies initially recommended reduction of endoscopic procedures. In particular non-urgent endoscopies should be postponed. However, this might lead to unnecessary delay in diagnosing gastrointestinal conditions. Methods Retrospectively we analysed the gastrointestinal endoscopies performed at the Central Endoscopy Unit of Saarland University Medical Center during seven weeks from 23 March to 10 May 2020 and present our real-world single-centre experience with an individualized rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy. We also present our experience with this strategy in 2021. Results Altogether 359 gastrointestinal endoscopies were performed in the initial period. The testing strategy enabled us to conservatively handle endoscopy programme reduction (44% reduction as compared 2019) during the first wave of the COVID-19 pandemic. The results of COVID-19 rtPCR from nasopharyngeal swabs were available in 89% of patients prior to endoscopies. Apart from six patients with known COVID-19, all other tested patients were negative. The frequencies of endoscopic therapies and clinically significant findings did not differ between patients with or without SARS-CoV-2 tests. In 2021 we were able to unrestrictedly perform all requested endoscopic procedures (> 5000 procedures) by applying the rtPCR-based pre-endoscopy SARS-CoV-2 testing strategy, regardless of next waves of COVID-19. Only two out-patients (1893 out-patient procedures) were tested positive in the year 2021. Conclusion A structured pre-endoscopy SARS-CoV-2 testing strategy is feasible in the clinical routine of an endoscopy unit. rtPCR-based pre-endoscopy SARS-CoV-2 testing safely allowed unrestricted continuation of endoscopic procedures even in the presence of high incidence rates of COVID-19. Given the low frequency of positive tests, the absolute effect of pre-endoscopy testing on viral transmission may be low when FFP-2 masks are regularly used.

Background & Aims The host genetic background for hepatocellular carcinoma (HCC) is incompletely understood. We aimed to determine if four germline genetic polymorphisms, rs429358 in APOE, rs2642438 in MARC1; rs2792751 in GPAM and rs187429064 in TM6SF2, previously associated with progressive alcohol-related and non-alcoholic fatty liver disease are also associated with HCC.

As a consequence of the continued Covid-19 lockdown in Germany, in-hospital teaching for medical students was impossible. While lectures and other theoretical training were relatively easily converted into online sessions using platforms such as Moodle, Zoom and Microsoft Teams, this was not the case for practical skills and clinical interventions, such as bronchoscopy or colonoscopy. This study describes a workaround that was implemented at the Saarland University Hospital utilizing virtual reality equipment to convey the impressions of shadowing clinical procedures to the students without physical presence. To achieve this, 3D 180° videos of key clinical interventions of various internal medicine specialities were recorded, cut, and censored. The videos were uploaded to the e-learning YouTube channel of our institution and shared with the students via the private share function. The students could choose whether to use a VR-viewer to watch the videos immersively or to watch them without a viewer on a screen non-immersively. At the end of the course after 1 week, the students completed a questionnaire anonymously focusing on learning-success regarding the presented topics, a self-assessment, and an evaluation of the course. A total of 27 students watched the videos with a VR-Viewer and 74 watched non-immersively. Although the VR-viewer group self-assessed their expertise higher, there was no significant difference between the two groups in the learning-success test score. However, students in the VR-viewer group rated the learning atmosphere, comprehensibility, and overall recommendation of the course significantly higher. They also agreed significantly more to the statement, that they gained a better conception of the presented procedures, and that virtual reality might be an appropriate tool for online teaching. Video-assisted teaching facilitates learning and might be a valuable add-on to conventional teaching.Abbreviations: Covid-19: severe acute respiratory syndrome coronavirus 2; 3D: three-dimensional; 2D: Two-dimensional; VR: virtual reality.

Casper, Markus MD1; Thurner, Lorenz MD2; Holz, Robert MD1; Krawczyk, Marcin MD1,3; Link, Andreas MD4 Author Information

Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case–control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41×10 −9 , OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94×10 −5 , OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12×10 −44 ). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.