Annals of Gastroenterology

All you need to know about the overlap between primary sclerosing cholangitis and inflammatory bowel disease

Joseph Sleiman, Fadi F. Fracis, Nayantara Coelho-Prabhu, Jana G. Hashash — Fri, 04 Apr 2025 10:47:53 +0300

Primary sclerosing cholangitis (PSC) is a progressive auto-inflammatory condition of the biliary ducts clinically characterized by painless cholestasis and jaundice. Histologically, the typical findings in PSC are periductal fibrosis with inflammation, bile duct proliferation, and ductopenia. These hallmarks eventually develop into end-stage liver disease requiring liver transplantation (LT), although the latency between diagnosis and LT is variable among patients. PSC is the leading indication for LT among patients with autoimmune liver disease. The interplay of PSC and inflammatory bowel disease (IBD) is intricate and poorly understood, as exemplified by the ongoing debate as to whether these are 2 distinct diseases or a complex 2-sided manifestation of the same disease spectrum. A true pathophysiological pathway has not been pinpointed, which explains the current lack of disease-specific therapies approved for this entity. This review summarizes our current knowledge about the epidemiology, pathophysiology, clinical presentation and management of PSC. We will also elucidate the relationship between PSC and IBD, specifically regarding the LT and pouchitis subpopulations.

Keywords Primary sclerosing cholangitis, liver transplantation, inflammatory bowel disease, ulcerative colitis, practice management

Ann Gastroenterol 2025; 38 (2): 107-120

Primary biliary cholangitis: a summary of pathogenesis and therapies

Imen Jallouli, Michael Doulberis, Jannis Kountouras — Fri, 04 Apr 2025 11:00:45 +0300

Primary biliary cholangitis (PBC) is a progressive autoimmune liver disease characterized by chronic inflammation and destruction of interlobular bile ducts. Its pathogenesis involves a complex interplay of genetic predisposition, environmental triggers, and immune-mediated mechanisms, particularly T-helper cell activity, leading to bile duct damage. First-line therapy includes ursodeoxycholic acid (UDCA), which improves liver biochemistry and slows disease progression, with obeticholic acid (OCA) as an option for non-responders. Double and/or triple therapy, including UDCA, OCA, and fibrates, appears to be superior in achieving therapeutic benefits in UDCA-nonresponsive PBC patients. Emerging therapies, such as peroxisome proliferator-activated receptor-α agonists, biologics such as dacetuzumab and rituximab, and experimental approaches such as stem-cell therapy, offer promising advances in managing PBC. Liver transplantation remains a final treatment option for advanced cases.

Keywords Primary biliary cholangitis, pathogenesis, therapy, peroxisome proliferator-activated receptor agonists, ileal bile acid transporter inhibitors

Ann Gastroenterol 2025; 38 (2): 121-132

Hepatocellular carcinoma in Fontan-associated liver disease

Fri, 04 Apr 2025 11:09:55 +0300

Fontan-associated liver disease (FALD) is a significant complication in patients with FontanBpalliation. The improved longevity following Fontan palliation has led to wider recognition of FALD and its association with hepatocellular carcinoma (HCC). This review examines the intricate link between FALD and HCC development, emphasizing the unique hemodynamic changes in Fontan circulation that promote hepatic congestion, fibrosis and cirrhosis, thereby facilitating carcinogenesis. The review comprehensively analyzes the existing literature, highlighting key risk factors, pathophysiological mechanisms, and diagnostic challenges in FALD-related HCC. While HCC incidence in FALD remains relatively low (1.5-5.0%), its higher mortality rate of 29.4% necessitates a thorough understanding of contributing factors and screening requirements. The management of FALD involves multidisciplinary approaches, addressing cardiac and hepatic aspects, with regular surveillance for liver disease progression and HCC using advanced imaging and biomarkers. Therapeutic considerations include interventions to manage hepatic congestion and fibrosis, although balancing these with the unique cardiac needs of Fontan circulation remains challenging. Interestingly, FALD management often mirrors that of other liver diseases, underscoring the need for tailored approaches. In severe cases, combined heart–liver transplantation offers a comprehensive solution for FALD-HCC. This review consolidates current knowledge on the epidemiology, pathogenesis and comprehensive management of HCC in the specific context of FALD, ultimately improving outcomes for this unique patient population.

Keywords Fontan-associated liver disease, cirrhosis, hepatocellular carcinoma

Ann Gastroenterol 2025; 38 (2): 133-142

The Efficacy and safety of full-thickness versus circular peroral endoscopic myotomy for treatment of achalasia: a systematic review and meta-analysis

Fri, 04 Apr 2025 11:16:42 +0300

Background Peroral endoscopic myotomy (POEM) is a treatment for esophageal achalasia with 2 variations in myotomy depth: full-thickness myotomy (FTM) and circular myotomy (CM). This systematic review and meta-analysis compares the efficacy and safety of these variations.

Methods Major health databases and registers, including Embase, MEDLINE and Cochrane were searched systematically. The primary outcome was clinical success, while secondary outcomes included change in achalasia severity scores, post-POEM gastroesophageal reflux disease (GERD) measures, procedural time, and adverse events. Meta-analysis was conducted using randomeffects models, with risk ratios (RR) and mean differences (MD) calculated for dichotomous and continuous variables, respectively.

Results Nine observational studies compared FTM and CM in 1,203 patients. FTM was performed in more severe achalasia and demonstrated similar clinical success to CM (RR 1.01, 95% confidence interval [CI] 0.98-1.04; P=0.55; n=6) and procedural time (MD 3.49 min, 95%CI -2.79-9.78; P=0.28, I2=66%; n=3). FTM was associated with increased post-POEM GERD outcomes, post-POEM pain (RR 1.94, 95%CI 1.27-2.95; P=0.002; n=2), and length of stay (LOS) (MD 0.85 days, 95%CI 0.11-1.59; P=0.02; I2=0%; n=2); however, association with esophagitis disappeared when proton pump inhibitors use was accounted for (RR 1.68, 95%CI 0.89-3.16; P=0.11; I2=23%; n=4). CM was associated with higher rates of subcutaneous emphysema (RR 0.59, 95%CI 0.43-0.81;
P=0.001; n=5).

Conclusions FTM and CM have comparable observed clinical efficacy and procedural time, with minimal differences in complications. FTM may be preferred in more severe achalasia and its association with post-POEM GERD may have been overestimated, but it may increase post-POEM pain and LOS.

Keywords Peroral endoscopic myotomy, myotomy depth, efficacy, safety

Ann Gastroenterol 2025; 38 (2): 143-155

Efficacy and safety of esophageal stenting for esophageal perforation: a systematic review and meta-analysis

Fri, 04 Apr 2025 11:48:55 +0300

Background Esophageal perforations are managed with endoscopic stenting. However, surgical repair is still employed in many centers, if they lack endoscopic services, or for complex perforations.

Methods We searched PubMed, Scopus, and Web of Science for relevant clinical trials and observational studies. Quality assessment was evaluated according to GRADE. The studies included were assessed based on the National Heart, Lung, and Blood Institute criteria. We included the following outcomes: leak after primary repair, operative repair after endoscopic therapy, stent migration, length of hospital stay (days), and mortality. We analyzed continuous data using mean differences and 95% confidence intervals (CI), while dichotomous data were analyzed using odds ratios and 95%CI. Statistical heterogeneity was assessed using the I2 statistic.

Results Eight studies were analyzed and found to include 95 patients with esophageal perforation. Mortality rates decreased over time from 16.3% (Abbas, 2009) to 6.7% (Heel, 2020). Re-operative procedures were highest at 51.4%(D’Cunha, 2011) and lower in later studies. Stent migration rates varied from 16.2-22.3%. Leakage rates ranged from 8.8-16.2%. Hospital stays ranged from 5.0 days (D’Cunha, 2011) to 15.3 days (Law, 2017), with significant variability across studies.

Conclusion Esophageal stenting is considered an efficient and well-tolerated method for managing esophageal perforation.

Keywords Esophageal rupture, perforation, esophageal stenting

Ann Gastroenterol 2025; 38 (2): 156-162

Effective endoscopic management of gastric neoplastic complications in patients with autoimmune gastritis: results of a monocentric study of 88 patients

Fri, 04 Apr 2025 15:32:40 +0300

Background We evaluated the efficacy of endoscopic treatment (ET) for gastric neoplastic complications of autoimmune gastritis (AIG). We also assessed the safety of ET and the risk factors for the occurrence of neuroendocrine tumors (NETs) and gastric adenocarcinoma (GA).

Methods This was a retrospective, single-center, observational study. All patients diagnosed with AIG between 1987 and 2019 and had at least 1 upper endoscopy available were included.

Results The study population comprised 88 patients (68.2% female). The median follow up was 5 years (range 1-28). A total of 132 NETs were diagnosed in 39/88 patients (44.3%) (median age 50.0 years, range 27.0-85.0 years). The mean lesion size was 7.1 mm (range 1-30); there were 80 G1 NETs and 52 G2 NETs. Among the 132 lesions, 86.3% (114/132) were endoscopically resected, mostly by endoscopic mucosal resection (105/114, 92.1%), without complications. Only 1 patient underwent surgery. Twelve patients (13.6%) (7 females; median age, 76.0 years; range, 53.0-90.0 years) presented with GA. Of these, 66.7% (8/12) needed surgery, while 4 patients underwent exclusive endoscopic resection. Only 2 patients presented with NETs and GA (2.8%). Patients who presented with NETs were significantly younger at AIG diagnosis than patients with GA: 52.0 (18.0-85.0) vs. 67.0 (44.0-81.0) years (P=0.008). Patients who presented with GA were significantly older than those who presented with NETs: 76.0 (53.0-90.0) vs. 50.0 (27.0-85.0) years (P<0.001).

Conclusion ET of NETs for AIG is effective and safe. GA is rarer, occurs in significantly older patients, and usually requires surgery.

Keywords Autoimmune gastritis, gastric adenocarcinoma, neuroendocrine tumors, endoscopic treatment

Ann Gastroenterol 2025; 38 (2): 163-173

Patients’ and gastroenterologists’ preferences regarding outcomes and medication attributes in ulcerative colitis

Fri, 04 Apr 2025 15:41:45 +0300

Background Patients’ and gastroenterologists’ views on the relative importance of treatment outcomes and medication attributes for ulcerative colitis (UC) may differ. We aimed to explore which treatment outcomes and medication attributes are considered important by both for therapeutic decisions.

Methods Eight gastroenterologists and 23 patients with UC in Greece participated in semistructured interviews and focus groups, respectively. The focus groups and interviews were audiorecorded, transcribed and coded, utilizing thematic analysis until data saturation was achieved.

Results Themes that were discussed included the impact of UC on daily life, UC-related outcomes, drug-related attributes and the patient–doctor relationship. Within these themes, disparities between the perspectives of gastroenterologists and patients were evident on 2 main issues. Gastroenterologists prioritized clinical remission and emphasized long-term objectives, such as mucosal healing, while patients focused on shorter-term outcomes, such as the early and sustained relief of symptoms. Regarding medication attributes, important factors for patients were primarily those that impacted their daily life, such as route of administration, dosage and the need for hospital visits. In contrast, gastroenterologists were more concerned about potential adverse events and non-responsiveness to treatment. There was a consensus regarding the importance of shared decision-making for UC management, emphasized by both patients and clinicians.

Conclusions Gastroenterologists mostly prioritize objective measures of remission, while patients mainly focus on factors related to their quality of life and overall well-being. Enhancing communication regarding different goals and expectations may strengthen the physician–patient relationship, ultimately resulting in better shared therapeutic decision-making.

Keywords Ulcerative colitis, qualitative research, patient-centered approach

Ann Gastroenterol 2025; 38 (2): 174-181

Age of onset of inflammatory bowel disease is the strongest risk factor for the development of malignancy

Fri, 04 Apr 2025 16:14:52 +0300

Background Inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, is a multifactorial inflammatory disorder of the gastrointestinal system that impairs the patient’s quality of life. Its presentation includes a spectrum of symptoms that may also be secondary to IBD complications, such as malignancy. On the other hand, immunosuppressive treatment to maintain remission also carries a risk of malignancy, which can cause patients distress due to the risk/benefit balance of IBD control and malignancy.

Methods In this nationwide retrospective study, we aimed to elucidate which patient and treatment factors have the greatest impact on the development of malignancy in IBD patients. Statistical analysis was performed on patient factors, including treatment types, and nominal regression analysis was carried out to assess the effects of multiple risk factors on the incidence of malignancy in patients with IBD.

Results Age at diagnosis of IBD correlated significantly with malignancy development, as did the diagnosis of ulcerative colitis. IBD patients diagnosed with malignancy had an older age of onset of IBD than those who did not develop malignancy. Sex, treatment type, treatment duration, and extent or location of disease did not correlate significantly with malignancy development.

Conclusion We conclude that age of onset of IBD plays the greatest role in malignancy development, whilst immunosuppressive treatment is not a significant risk factor.

Keywords Malignancy, inflammatory bowel disease, risk factors

Ann Gastroenterol 2025; 38 (2): 182-186

Use of nailfold capillaroscopy for the early diagnosis of systemic sclerosis in patients with primary biliary cholangitis

Fri, 04 Apr 2025 16:19:14 +0300

Background Primary biliary cholangitis (PBC) is a cholestatic autoimmune disease and is often associated with systemic sclerosis (SSc). The prevalence of SSc in PBC patients ranges from 1-22% and the diagnosis is often delayed. The aim of this study was to evaluate the role of nailfold capillaroscopy (NFC) for early SSc diagnosis in PBC patients.

Methods In this monocentric, cross-sectional study, NFC was performed in 56 PBC patients. Raynaud’s phenomenon (RP) was assessed in each patient. Patients with major NFC abnormalities and those with a scleroderma pattern were screened for SSc-specific antibodies. The SSc diagnosis was established using the 2013 American College of Rheumatology and European League Against Rheumatism (ACR/AULAR) and Very Early Diagnosis Of Systemic Sclerosis (VEDOSS) criteria.

Results NFC abnormalities were found in 31 patients (55%): 11 (20%) presented minor abnormalities, 17 (30%) had major abnormalities and 3 (5%) presented a scleroderma pattern. RP was found in 12 patients. Two patients with a scleroderma pattern were newly diagnosed with SSc. All patients newly diagnosed with SSc presented RP. No patient without RP was diagnosed with SSc.

Conclusions Performing NFC in PBC patients can help anticipate the SSc diagnosis. RP should always be checked in PBC patients and should be an indication to perform NFC for early SSc diagnosis. A diagnostic algorithm is proposed.

Keywords Primary biliary cholangitis, systemic sclerosis, nailfold capillaroscopy

Ann Gastroenterol 2025; 38 (2): 187-194

Treatment patterns and outcomes in hepatocellular carcinoma: Real-world experience in Greece from the retrospective OPAL study

Fri, 04 Apr 2025 16:32:17 +0300

Background Newer advances involving immunotherapies are changing the hepatocellular carcinoma (HCC) landscape. In the multinational OPAL study, we described the characteristics of patients with HCC during 2014-2021 in Greece.

Methods This was a retrospective chart review study of adults (alive/dead) with newly diagnosed HCC between 2014-2021.

Results Of 406 patients, 37.7%, 33.0%, 25.9% and 3.4% had Barcelona Clinic Liver Cancer (BCLC) stage 0/A, B, C and D, respectively. Common etiologies were hepatitis B virus (32.9%), alcohol use (31.6%), hepatitis C virus (27.6%), and metabolic dysfunction-associated steatotic liver disease (26.3%); viral+non-viral: 15.5%. The first treatment was resection, embolization, ablation, systemic therapy and transplant, in 35.5%, 30.7%, 22.9%, 3.3% and 0.7% of BCLC-0/A; 14.9%, 48.5%, 9.0%, 15.7% and 0% of BCLC-B; and 4.8%, 18.1%, 3.8%, 49.5% and 0% of BCLC-C patients; 7.2%, 11.9% and 23.8% of patients in the respective BCLC groups remained untreated. Tyrosine-kinase inhibitor monotherapy was the commonest systemic therapy (76.7%). Among BCLC-0/A, BCLC-B, and BCLC-C patients, median progression-free survival was 15.8, 8.0 and 3.2 months, and overall survival (OS) was 45.7, 21.8 and 7.9 months from treatment initiation, respectively. Among BCLC-D patients, median OS was 3.4 months from HCC diagnosis. By multivariate Cox regression analysis, hepatitis B virus etiology (P=0.016) and Eastern Cooperative Oncology Group performance status ≥1 (P=0.015) were independent factors associated with poorer OS among BCLC-C patients.

Conclusion Real-life clinical practice in Greece is aligned with European guidelines, while poor clinical outcomes underscore the need for implementation of new therapies.

Keywords Hepatocellular carcinoma, risk factors, survival, treatment patterns

Ann Gastroenterol 2025; 38 (2): 195-207

The role of intraductal ultrasound in endoscopic biliary brushing for sampling in patients with malignant biliary strictures: a bicentric retrospective study

Fri, 04 Apr 2025 16:41:10 +0300

Background Endoscopic biliary brushing is the first line modality for sampling in patients with indeterminate biliary stricture (BS); however, its sensitivity is limited. Endoscopic intraductal ultrasound (IDUS) is also a useful approach for the diagnosis of biliary malignancies. However, whether IDUS can guide the sampling by biliary brushing has not been reported.

Methods We retrospectively analyzed patients who underwent endoscopic retrograde cholangiopancreatography for BS in 2 tertiary care hospitals and assessed the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of IDUS and brush cytology.

Results The study involved 530 patients with BS, including 333 in the IDUS group and 197 in the non-IDUS group. Both groups exhibited similar baseline characteristics. The diagnostic ability of IDUS imaging was as follows: sensitivity 70.7%, specificity 82.4%, PPV 81.5%, NPV 72.0%, and accuracy 76.3%. Brush cytology alone demonstrated an overall sensitivity of 45.2%, with specificity 98.2%, PPV 97.2%, NPV 56.0%, and accuracy 67.2%. The sensitivity was similar in patients with or without IDUS, whereas it was significantly higher in patients with biliary mucosal invasion indicated by IDUS (55.1% vs. 30.3%, P=0.003).

Conclusion Although IDUS cannot improve the detection rate of biliary brushing for malignancy, it helps identify patients with malignant BS to be sampled more easily by brushing.

Keywords Endoscopic retrograde cholangiopancreatography, biliary stricture, intraductal ultrasound, brush cytology

Ann Gastroenterol 2025; 38 (2): 208-213

Forty-five-year trends in intra- and extrahepatic cholangiocarcinoma: sex- and race-based insights

Fri, 04 Apr 2025 17:21:34 +0300

Background A comprehensive review of 45-year trends in intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) in the United States has not been published. Given their rising incidence, our study aimed to analyze trends in incidence and survival, comparing ICC and ECC.

Methods We extracted a 45-year dataset (1975-2020) from the Surveillance, Epidemiology, and End Results database. Age-adjusted incidence rates were calculated using SEERStat®. Annual Percent Change (APC) was estimated via weighted least squares. Relative survival (1- and 5-year) was calculated using the Ederer II method and compared across sexes and races.

Results A significant rise in ICC and ECC incidence was observed in both sexes (APC 3.71 for ICC vs. 6.16 for ECC; P<0.001). In females, ECC incidence increased more than ICC (APC 5.96 vs. 4.09, P<0.05), whereas males showed a fluctuating ECC trend and a steady ICC rise. Survival rates significantly improved across all races and sexes (P<0.05). ICC survival rose from 17.45% to 41.41% (1-year) and 2.83% to 10.99% (5-year), while ECC increased from 30.33% to 41.12% (1-year) and 5.96% to 10.44% (5-year). Among white and other-race females, ECC showed less improvement than ICC. Black individuals lacked statistically significant data.

Conclusions Our study highlights disparities in ICC and ECC incidence, with higher rates in males, but better survival for ECC in males and ICC in females. The underrepresentation of Black individuals warrants further study to explore contributing factors such as risk, access to care, and treatment.

Keywords Cholangiocarcinoma, intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, biliary ductal carcinoma, bile duct malignancy

Ann Gastroenterol 2025; 38 (2): 214-220

Early versus late drainage of pancreatic necrotic fluid collections: a systematic review and meta-analysis

Fri, 04 Apr 2025 17:26:29 +0300

Background Necrotizing pancreatitis can be complicated by necrotic fluid collections (NFCs). International guidelines recommend waiting 4 weeks for the collection to mature before interventional management. With the advances in endoscopic drainage, the need to delay drainage by 4 weeks is unclear. We aimed to compare early drainage (ED: <4 weeks) vs. late drainage (LD: ≥4 weeks) of NFCs.

Methods Literature searches through multiple databases were performed to identify studies that investigated outcomes of ED vs. LD of NFCs. Our primary outcome was the complication rate among these groups. The secondary outcomes included the number of patients requiring subsequent necrosectomies, and mortality.

Results We identified 9 studies with 855 patients (320 ED and 535 LD). The complication rates (rate ratio 1.060, 95% confidence interval [CI] 0.79-1.42; P=0.69; I2=51.61) and the number of patients requiring subsequent necrosectomies (odds ratio [OR] 2.15, 95% CI 0.86-5.35; P=0.099; I2=79.81) were similar in both groups. Mortality was slightly higher in the ED group (OR 1.94, 95%CI 1.05-3.59; P=0.033; I2=0).

Conclusions Our study suggests that ED can be performed if needed in carefully selected patients without an increase in complications or subsequent necrosectomies. However, mortality was slightly higher compared to LD. A multidisciplinary team approach is necessary for considering ED.

Keywords Necrotizing pancreatitis, necrotic fluid collections, acute necrotic collections, walledof necrosis, early drainage

Ann Gastroenterol 2025; 38 (2): 221-229

Endoscopic removal of proximally migrated pancreatic duct stents: a case series and literature review

Fri, 04 Apr 2025 17:33:28 +0300

Background Proximal migration of pancreatic stents is an uncommon but significant problem that poses risks of pain and pancreatitis. It is often a challenging situation for endoscopists, necessitating surgical retrieval in 10% of cases.

Method A 10-year retrospective review was performed of stent removal procedures performed at a tertiary care center in northern India between January 2010 and December 2019.

Results Sixteen patients (mean age 39.52 years, 13 [81.25%] males) with proximally migrated pancreatic stents (PMPSs) were studied. Thirteen (81.25%) patients had a dilated pancreatic duct (PD) and 3 (18.75%) had a non-dilated PD. In the majority of patients, the PMPSs were located at the genu (50%), while 62% were 10 cm in length. Three (18.75%) patients had fragmented stents, whereas the remaining 13 (81.25%) had intact stents in situ. Complete retrieval of the PPMS and stent fragments was possible in 12 (75%) patients, with grasping forceps being used in the majority (50%). In patients with fragmented stents and difficult locations (n=3), pancreatoscopy-assisted techniques resulted in the retrieval of the stent or fragments. PMPSs could not be retrieved in 3 patients: all these failures were during the study period when a SpyGlass pancreatoscope was not available in our unit. Two patients (12.5%) reported post-procedural pain that responded to intravenous analgesics.

Conclusions Endoscopic retrieval of proximally migrated stents, using a combination of techniques and accessories, is safe and effective. Pancreatoscopy increases the success rates. Surgery is rarely required for stent removal.

Keywords Endoscopy, pancreas, stents, endoscopic retrograde cholangiopancreatography, pancreatitis

Ann Gastroenterol 2025; 38 (2): 230-236