Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial.

OBJECTIVE: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC). DESIGN: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression. RESULTS: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL. CONCLUSION: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D. TRIAL REGISTRATION NUMBER: NCT01970748.

Combination of carvedilol with variceal band ligation in prevention of first variceal bleed in Child-Turcotte-Pugh B and C cirrhosis with high-risk oesophageal varices: the 'CAVARLY TRIAL'.

OBJECTIVES: Beta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk varices is not clear. A comparison of these therapies alone or in combination to prevent the first variceal bleed in advanced cirrhosis patients was carried out. DESIGN: 330 Child-Turcotte-Pugh (CTP) B and C cirrhosis patients, with 'high-risk' varices were prospectively enrolled (n=110 per group) to receive carvedilol (group A), VBL (group B) or combination (group C). Primary endpoint was reduction in the incidence of first variceal bleed at 12 months. The secondary endpoints included overall mortality, bleed-related mortality, new-onset decompensation, change in hepatic vein pressure gradient (HVPG) and treatment-related adverse events. RESULTS: The patients were predominantly males (85.2%), aged 51.4±10.5 years with CTP score of 8.87±1.24, MELD score 15.17±3.35 and HVPG-16.96±3.57 mm Hg. The overall incidence of variceal bleed was 23.8% (n=78) at 1 year. Intention-to-treat analysis showed that the combination arm (group C) significantly reduced the incidence of first variceal bleed by 62.9% as compared with group B (HR 0.37, 95% CI 0.192 to 0.716, p<0.003) and by 69.3% as compared with group A (HR 0.31, 95% CI 0.163 to 0.578, <0.001). The overall mortality was 13.6% (45/330). The 1-year mortality in group C was lowest among the three groups (A, B, C=20%, 14.5%, 6.3%, p=0.012). Reduction in HVPG (20.8% vs 25.1%, p=0.54) and the rate of non-response to carvedilol (53.4% vs 41.25%, p=0.154) were not different between group A and C patients. The incidence of new-onset ascites, spontaneous bacterial peritonitis, shock, and acute kidney injury and postbleed organ failure was also comparable between the groups. CONCLUSION: In CTP B and C cirrhosis patients with high-risk varices, combination of carvedilol and VBL is more effective than either therapy alone, for primary prevention of variceal bleeding. TRIAL REGISTRATION NUMBER: NCT03069339.

Validation of Baveno VII criteria and other non-invasive diagnostic algorithms for clinically significant portal hypertension in hepatitis delta.

BACKGROUND & AIMS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) require validation in patients with hepatitis D virus (HDV)-related compensated advanced chronic liver disease (cACLD). Therefore, we aimed to validate existing NIT algorithms for CSPH in this context. METHODS: Patients with HDV-cACLD (LSM ≥10 kPa or histological METAVIR F3/F4 fibrosis) who underwent paired HVPG and NIT assessment at Medical University of Vienna or Hannover Medical School between 2013 and 2023 were retrospectively included. Liver stiffness measurement (LSM), von Willebrand factor to platelet count ratio (VITRO), and spleen stiffness measurement (SSM) were assessed. Individual CSPH risk was calculated according to previously published models (ANTICIPATE, 3P/5P). The diagnostic performance of Baveno VII criteria and refined algorithms (Baveno VII-VITRO, Baveno VII-SSM) was evaluated. The prognostic utility of NITs was investigated in the main cohort and an independent, multicenter, validation cohort. RESULTS: Fifty-one patients (HVPG ≥10 mmHg/CSPH prevalence: 62.7%, varices: 42.2%) were included. Patients with CSPH had significantly higher LSM (25.8 [17.2-31.0] vs. 14.0 [10.5-19.8] kPa; p <0.001), VITRO (n = 31, 3.5 [2.7-4.5] vs. 1.3 [0.6-2.0] %/[G/L]; p <0.001), and SSM (n = 20, 53.8 [41.7-75.5] vs. 24.0 [17.0-33.9] kPa; p <0.001). Composite CSPH risk models yielded excellent AUROCs (ANTICIPATE: 0.885, 3P: 0.903, 5P: 0.912). Baveno VII criteria ruled out CSPH with 100% sensitivity and ruled in CSPH with 84.2% specificity. The Baveno VII 'grey zone' (41.1%) was significantly reduced by Baveno VII-VITRO or Baveno VII-SSM algorithms, which maintained diagnostic accuracy. Hepatic decompensation within 2 years only occurred in patients who had CSPH or met Baveno VII rule-in criteria. The prognostic value of NITs was confirmed in the validation cohort comprising 92 patients. CONCLUSIONS: Standalone and composite NIT/diagnostic algorithms are useful for CSPH diagnosis in patients with HDV-cACLD. Thus, NITs may be applied to identify and prioritize patients with CSPH for novel antiviral treatments against chronic hepatitis D. IMPACT AND IMPLICATIONS: Non-invasive tests (NITs) for clinically significant portal hypertension (CSPH) have been developed to identify patients with compensated advanced chronic liver disease (cACLD) at risk of decompensation, but conflicting data has been published regarding the accuracy of liver stiffness measurement (LSM) for the staging of fibrosis in patients infected with hepatitis D virus (HDV). In our study, including 51 patients with HDV-cACLD, LSM- and lab-based NITs yielded high AUROCs for CSPH. Moreover, only patients with CSPH or high non-invasively assessed CSPH risk were at risk of decompensation within 2 years, with the prognostic value of NITs confirmed in a validation cohort. Thus, NITs should be applied and updated in yearly intervals in clinical routine to identify patients with HDV-cACLD at short-term risk of clinical events; NITs may also guide prioritization for novel antiviral treatment options.

Endoscopic procedures in hepatology: Current trends and new developments.

Gastrointestinal endoscopy has long been a reliable backbone in the diagnosis and management of hepatobilary disorders and their complications. However, with evolving non-invasive testing, personalised medicine has reframed the utility and necessity of endoscopic screening. Conversely, the growing interest and use of endoscopic ultrasound (EUS) and advanced endoscopy within gastrointestinal units has also opened novel diagnostic and therapeutic avenues for patients with various hepatobiliary diseases. The integration of "advanced endoscopy" within the practice of hepatology is nowadays referred to as "endo-hepatology". In essence, endo-hepatology consists of two pillars: one focusing primarily on disorders of the liver parenchyma, vascular disorders, and portal hypertension, which is mainly captured via EUS, while the other targets the hepatobiliary tract via endoscopic retrograde cholangiopancreatography and advanced imaging. Applications under the umbrella of endo-hepatology include, amongst others, EUS-guided liver biopsy, EUS-guided portal pressure gradient measurement, coil and glue embolisation of gastric varices as well as cholangioscopy. As such endo-hepatology could become an attractive concept wherein advanced endoscopy might reinforce the medical management of patients with hepatobiliary disorders and their complications after initial basic work-up. In this review, we discuss current trends and future developments within endo-hepatology and the remaining hurdles to overcome.

Prognostic performance of non-invasive tests for portal hypertension is comparable to that of hepatic venous pressure gradient.

BACKGROUND & AIMS: Non-invasive tests to assess the probability of clinically significant portal hypertension (CSPH) - including the ANTICIPATE±NASH models based on liver stiffness measurement and platelet count±BMI, and the von Willebrand factor antigen to platelet count ratio (VITRO) - have fundamentally changed the management of compensated advanced chronic liver disease (cACLD). However, their prognostic utility has not been compared head-to-head to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient (HVPG). METHODS: Patients with cACLD (liver stiffness measurement ≥10 kPa) who underwent advanced characterization via same-day HVPG/non-invasive test assessment from 2007-2022 were retrospectively included. Long-term follow-up data on hepatic decompensation was recorded. RESULTS: Four hundred and twenty patients with cACLD of varying etiologies, with a CSPH prevalence of 67.6%, were included. The cumulative incidence of hepatic decompensation at 1 and 2 years was 4.7% and 8.0%, respectively. HVPG, VITRO, and ANTICIPATE±NASH-CSPH-probability showed similar time-dependent prognostic value (AUROCs 0.683-0.811 at 1 year and 0.699-0.801 at 2 years). In competing risk analyses adjusted for MELD score and albumin, HVPG (adjusted subdistribution hazard ratio [aSHR] 1.099 [95% CI 1.054-1.150] per mmHg; p <0.001), or VITRO (aSHR 1.134 [95% CI 1.062-1.211] per unit; p <0.001), or ANTICIPATE±NASH-CSPH-probability (aSHR 1.232 [95% CI 1.094-1.387] per 10%; p <0.001) all predicted first decompensation during follow-up. Previously proposed cut-offs (HVPG ≥10 mmHg vs. <10 mmHg, VITRO ≥2.5 vs. <2.5, and ANTICIPATE-CSPH probability ≥60% vs. <60%) all accurately discriminated between patients at negligible risk and those at substantial risk of hepatic decompensation. CONCLUSIONS: The prognostic performance of ANTICIPATE±NASH-CSPH-probability and VITRO is comparable to that of HVPG, supporting their utility for identifying patients who may benefit from medical therapies to prevent first hepatic decompensation. IMPACT AND IMPLICATIONS: Non-invasive tests have revolutionized the diagnosis and management of clinically significant portal hypertension in patients with compensated advanced chronic liver disease (cACLD). However, limited data exists regarding the prognostic utility of non-invasive tests in direct comparison to the gold standard for prognostication in cACLD, i.e. the hepatic venous pressure gradient. In our study including 420 patients with cACLD, the ANTICIPATE±NASH model and VITRO yielded similar AUROCs to hepatic venous pressure gradient for hepatic decompensation within 1 to 2 years. Thus, non-invasive tests should be applied and updated in yearly intervals in clinical routine to identify patients at short-term risk, thereby identifying patients who may benefit from treatment aimed at preventing hepatic decompensation.

Endoscopic Glue Injection vs Glue Plus BRTO or TIPSS for Preventing Gastric Variceal Bleeding: A Randomized Controlled Trial.

BACKGROUND AND AIMS: The study sought to compare the efficacy of endoscopic injection sclerotherapy with cyanoacrylate glue (EIS-CYA) vs EIS-CYA plus a radiologic intervention (RI) (either transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration) for secondary prophylaxis in patients with liver cirrhosis who presented with acute variceal bleeding from cardiofundal varices. Primary outcome measure was gastric varix (GV) rebleed rates at 1 year. METHODS: Consecutive cirrhosis patients with acute variceal bleeding from cardiofundal varices were randomized into 2 arms (45 in each) after primary hemostasis by EIS-CYA. In the endoscopic intervention (EI) arm, EIS-CYA was repeated at regular intervals (1, 3, 6, and 12 months), while in the RI arm, patients underwent transjugular intrahepatic portosystemic shunt or balloon-occluded retrograde transvenous obliteration followed by endoscopic surveillance. RESULTS: GV rebleed rates at 1 year were higher in the EI arm compared with the RI arm: 11 (24.4%; 95% confidence interval [CI], 12.9%-39.5%) vs 1 (2.2%; 95% CI, 0.1%-11.8%) (P = .004; absolute risk difference: 22.2%; 95% CI, 8.4%-36.6%). GV rebleed-related mortality in the EI arm (8 [17.8%; 95% CI, 8.0%-32.1%]) was significantly higher than in the RI arm (1 [2.2%; 0.1%-11.8%]) (P = .030; absolute risk difference: 15.6; 95% CI, 2.9%-29.2%); however, there was no difference in all-cause mortality between the 2 groups (12 [26.7%; 95% CI, 14.6%-41.9%] vs 7 [15.6%; 95% CI, 6.5%-29.5%]). The number needed to treat to prevent 1 GV-related rebleed at 1 year was 4.5. CONCLUSIONS: RI for secondary prophylaxis reduces rebleeding from GV and GV rebleeding-related mortality in patients with GV hemorrhage. (CTRI/2021/02/031396).

Unique risk factors for unplanned preterm delivery in the uterus transplant recipient.

STUDY QUESTION: Do characteristics of the lower uterine segment and cervix modify the risk of preterm delivery in uterus transplant (UTx) recipients? SUMMARY ANSWER: The cervical length showed little association with preterm delivery, however, cervical inflammation deserves further exploration as a cause of preterm delivery. WHAT IS KNOWN ALREADY: UTx recipients do not have the risk factors normally used to stratify pregnancies that would benefit from cervical length assessment. In addition, unique factors related to absent tissues, a different blood supply, inflammatory processes of rejection, cervical biopsies, and a different microbiome challenge the normal progressive remodeling of the cervix and thus cervical competence. STUDY DESIGN, SIZE, DURATION: This is a subanalysis of a clinical trial of 20 women undergoing uterus transplantation at Baylor University Medical Center from 2016 to 2020, in addition to two women who received transplantation outside of a research protocol at our institution through September 2022. In this report, the first 16 UTx recipients that achieved live birth are included. PARTICIPANTS/MATERIALS, SETTING, METHODS: The focus of this study was 20 pregnancies that reached the second trimester in 16 women following UTx. We analyzed recipient, transplant, and donor factors to determine if characteristics were associated with delivery outcome. We compared obstetrical outcomes, including planned versus unplanned delivery, by factors such as number of superior venous anastomoses, warm ischemia and cold ischemia times, donor factors including cesarean sections, cervical biopsy results, and cervical ultrasound results. MAIN RESULTS AND THE ROLE OF CHANCE: Planned term deliveries occurred in 44% (8/18) of live births. Of the preterm births, 30% (3/10) were planned and 70% (7/10) were unplanned. Unplanned deliveries occurred in women with spontaneous preterm labor, severe rejection, subchorionic hematoma, and placenta previa. Cervical length in UTx recipients averaged 33.5 mm at 24 weeks and 31.5 mm at 28 weeks, comparable to values from the general population. No relationship was seen between delivery outcome and number of veins used, ischemic time, or number of previous cesarean sections. LIMITATIONS, REASONS FOR CAUTION: The study's small size allows limited conclusions. The obstetric history of all donors was limited to mode of delivery. WIDER IMPLICATIONS OF THE FINDINGS: Cervical length measurements in the UTx population are not expected to deviate from those with a native uterus. While cervical length surveillance remains important, attention must be paid to the results of cervical biopsies which are obtained to monitor rejection. Inflammatory processes seem most predictive of preterm delivery. STUDY FUNDING/COMPETING INTEREST(S): No funding was provided for this study. The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: NCT02656550.

Simple Scoring System for Esophagogastric Varices Prediction in Hepatocellular Carcinoma Patients without Liver Stiffness Evaluation.

INTRODUCTION: For predicting esophagogastric varices (EGVs), the Virtual Baveno VII Consensus Workshop has proposed a combination of liver stiffness determination and platelet count measurement using a FibroScan®. However, FibroScan® is not available at all institutions. The present study aimed to develop a simple method to predict development of EGV using only general blood examination results. MATERIALS AND METHODS: A total of 1,090 hepatocellular carcinoma patients were enrolled, after excluding 956 with major portal vein tumor thrombus (Vp3/Vp4) or without upper gastrointestinal endoscopy examination results available. Those with EGV (≥ grade F2) or a history of treatment for the condition were defined as positive for significant EGV, and then clinical factors were retrospectively evaluated to determine indicators of occurrence. RESULTS: Logistic multivariate analysis showed platelet count (≤12 × 104/µL) (odds ratio [OR] 3.79, p < 0.001), mALBI grade 2a (OR 1.52, p = 0.036), and mALBI 2b or 3 (OR 3.46, p < 0.001) as significant predictive factors. Based on the OR values, platelet count (≤12 × 104/µL) and mALBI grade 2b/3 were each assigned 2 points and mALBI 2a was given 1 point, with the result termed recommendation for EGV screening (REGS) score. Significant EGV occurrence was noted in 2.9% (9/311) of the patients with a REGS score 0, 11.0% (13/118) with a score 1, 19.3% (53/274) with a score 2, 29.5% (39/132) with a score 3, and 38.0% (97/255) with a score 4 (p < 0.001). CONCLUSION: The findings indicate that REGS score can provide useful predictive information for development of significant EGV without the need for special equipment such as a FibroScan®.

Factors Affecting an Increase in Spleen Volume and Association of Spleen Volume Variation with the Clinical Outcomes of Atezolizumab and Bevacizumab Treatment for Hepatocellular Carcinoma: A Retrospective Analysis.

INTRODUCTION: Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev. METHODS: A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics. RESULTS: The median pretreatment SpV was 184 (130-257) cm3 and the median SpV variation was 27 (9-60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p = 0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively). CONCLUSION: Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy.

Non-invasive assessment of esophageal and fundic varices in patients with primary biliary cholangitis.

OBJECTIVES: The Baveno VII consensus recommends endoscopic screening for varicose veins in cases of liver stiffness measurement (LSM) ≥ 20 kPa or platelet count ≤ 150 × 109/L. Whether this approach was appropriate for patients with primary biliary cholangitis (PBC) remains uncertain. This study expanded the observed risk factors by adding analysis of ultrasound images as a non-invasive tool to predict the risk of esophageal or fundic varices. METHODS: We enrolled 111 patients with PBC whose complete ultrasound images, measurement data, and LSM data were available. The value of the periportal hypoechoic band (PHB), splenic area, and LSM in determining the risk of varicose veins and variceal rupture was analyzed. A prospective cohort of 67 patients provided external validation. RESULTS: The area under the receiver operating characteristic curve (AUC) for predicting varicose veins using LSM > 12.1 kPa or splenic areas > 41.2 cm2 was 0.806 (95% confidence interval (CI): 0.720-0.875) and 0.852 (95% CI: 0.772-0.912), respectively. This finding could assist in avoiding endoscopic screening by 76.6% and 83.8%, respectively, with diagnostic accuracy surpassing that suggested by Baveno VII guidelines. The AUCs for predicting variceal rupture using splenic areas > 56.8 cm2 was 0.717 (95% CI: 0.623-0.798). The diagnostic accuracy of PHB for variceal rupture was higher than LSM and splenic areas (75.7% vs. 50.5% vs. 68.5%). CONCLUSION: We recommend LSM > 12.1 kPa as a cutoff value to predict the risk of varicosity presence in patients with PBC. Additionally, the splenic area demonstrated high accuracy and relevance for predicting varicose veins and variceal rupture, respectively. The method is simple and reproducible, allowing endoscopy to be safely avoided. CLINICAL RELEVANCE STATEMENT: The measurement of the splenic area and identification of the periportal hypoechoic band (PHB) on ultrasound demonstrated high accuracy and relevance for predicting the risk of esophageal or fundic varices presence and variceal rupture, respectively. KEY POINTS: Predicting varices in patients with primary biliary cholangitis (PBC) can reduce the morbidity and mortality of gastrointestinal hemorrhage. Transient elastography (TE) and ultrasound play an important role in predicting patients with PBC with varices. TE and ultrasound can predict varicose veins and variceal rupture. Liver stiffness measurement and splenic area measurements can allow endoscopy to be safely avoided.

Non-contrast-enhanced MR angiography of left gastric vein in patients with gastroesophageal varices: morphology and blood supply analysis.

OBJECTIVES: To investigate the feasibility of non-contrast-enhanced MR angiography (NCE-MRA) in evaluating the morphology and blood supply of left gastric vein (LGV) in patients with gastroesophageal varices. METHODS: Between March 2021 and October 2022, patients with gastroesophageal varices and who underwent NCE-MRA were retrospectively reviewed. In order to evaluate the blood supply of LGV, superior mesenteric vein (SMV) and splenic vein (SV) were visualized separately by using inflow-sensitive inversion recovery sequence. Two radiologists independently assessed the image quality, determined the origination and the blood supply of LGV, and measured the diameter of LGV. The origination and diameter of LGV were compared between NCE-MRA and contrast-enhanced CT. Differences in blood supply were compared between LGVs with different originations. RESULTS: A total of 53 patients were enrolled in this study and the image quality was categorized as good or excellent in 52 patients. No significant differences were observed in visualizing the origination and the diameter of LGV between NCE-MRA and contrast-enhanced CT (p > .05). The blood supply of LGV was related to its origination (p < .001). Most LGVs with SV origination were supplied by SV. If LGV was originated from the portal vein (PV), about 70% of them were supplied by both SV and SMV. Compared with LGVs with SV origination, LGVs with PV origination showed more chance to receive blood from SMV (p < .001). CONCLUSION: Non-contrast-enhanced MR angiography appears to be a reliable technique in evaluating the morphology and blood supply of LGV in patients with gastroesophageal varices. CLINICAL RELEVANCE STATEMENT: Non-contrast-enhanced MR angiography provides valuable information for the management of gastroesophageal varices. Especially, it benefits patients with renal insufficiency. KEY POINTS: • Non-contrast-enhanced MR angiography using inflow-sensitive inversion recovery technique can be used for evaluating not only morphology as CT but also blood supply of left gastric vein. • The blood supply of left gastric vein is related to its origination and left gastric vein with portal vein origination shows more chance to receive blood from superior mesenteric vein.

Comparison of gastrointestinal bleeding in patients with and without liver cirrhosis.

OBJECTIVES: Upper gastrointestinal bleeding (GIB) in patients has been well-characterized in liver cirrhosis but studies on lower GIB are limited. The clinical characteristics, management and outcomes in patients with and without liver cirrhosis was compared to determine the overall features of GIB in patients with liver cirrhosis compared with non-cirrhotics. METHODS: A retrospective study on cirrhotics hospitalized for GIB 2010-2021, matched with control group of non-cirrhotics (1:4) for upper vs. lower GIB. Patients with overt bleeding leading to hospitalization were included. RESULTS: Overall, 396 patients had cirrhosis, 267 (67%) men, median age 62, alcoholic etiology 177/396 (45%), median MELD 12 (range 6-32). Overall 102 cirrhotics had GIB, matched with 391 non-cirrhotics. Overall 87 (85%) cirrhotic patients had upper and 15% lower GIB. Compared to non-cirrhotics, the cause of GIB was more commonly acute variceal bleeding (AVB) (42% vs. 1%), hemorrhoids 40% vs. 6% (p = 0.002), less commonly gastric ulcer 13% vs. 31% (p < 0.001), duodenal ulcer 9% vs. 29% (p < 0.001), 5% of cirrhotics used NSAIDs vs. 26% of controls (p < 0.001). Rebleeding occurred in 14% of cirrhotics vs. 3% in controls (p < 0.001). Only one cirrhotic patient (1%) died from GIB vs. 0.8% of controls within 45 days. Overall mortality 45 days after hospitalization was 10% in cirrhotics vs. 5% in controls (p < 0.001). CONCLUSIONS: Bleeding from gastric and duodenal ulcers were less common in cirrhotics than in controls. Bleeding from hemorrhoids was more common in cirrhotics. Mortality due to GIB was low in both groups but overall mortality was significantly higher in cirrhotics.

Predictive factors of portal hypertensive enteropathy exacerbations based on long-term outcomes.

BACKGROUND: Portal hypertensive enteropathy (PHE) is a small-bowel lesion observed in patients with portal hypertension. The clinical significance of endoscopic findings in PHE remains unclear. We aimed to clarify the clinical significance and predictive factors of capsule endoscopic findings in patients with PHE based on long-term outcomes. METHODS: This retrospective study enrolled 55 patients with PHE (33 males and 22 females; median age, 64 years; range, 23-87) followed for > 3 years using capsule endoscopy (CE) between February 2009 and May 2023. We evaluated the clinical factors affecting PHE exacerbations and the effects of PHE exacerbations on gastrointestinal bleeding by comparing exacerbated and unchanged PHE groups. RESULTS: Overall, 3 (5%) patients showed improvement, 33 (60%) remained unchanged, and 19 (35%) showed exacerbation on follow-up CE. In the exacerbated group, the rates of worsened fibrosis-4 index, exacerbated esophageal varices, and exacerbated portal hypertensive gastropathy were significantly higher than those in the unchanged group (21%, 32%, and 42% vs. 3%, 6%, and 12%, respectively; P < 0.05), and the rate of splenectomy was significantly lower in the exacerbated group than in the unchanged group (5% vs. 39%, respectively; P < 0.01). In multivariate analysis, exacerbation of esophageal varices and absence of splenectomy were significantly associated with PHE exacerbation. The rate of gastrointestinal bleeding after follow-up CE was significantly high in the exacerbated group (log-rank, P = 0.037). CONCLUSIONS: Exacerbation of esophageal varices and splenectomy were significantly associated with exacerbation of PHE. Exacerbated PHE requires specific attention to prevent gastrointestinal bleeding.

A new criterion including the aspartate aminotransferase-to-platelet ratio index and liver and spleen stiffness to rule out varices needing treatment in children with biliary atresia: Modification of the Baveno VII criteria.

AIMS: Biliary atresia (BA) is a congestive biliary disease that develops in the neonatal period or early infancy. It may present with portal hypertension and varices needing treatment (VNT) even after successful Kasai portoenterostomy. This study aimed to stratify the risk of VNT in children and adolescents with BA. METHODS: In this prospective cross-sectional study, we measured liver stiffness (LS) and spleen stiffness (SS) by two-dimensional shear wave elastography and checked for VNT endoscopically in 53 patients with BA who attended for follow-up between July 2018 and September 2022. Varices needing treatment were defined as large esophageal varices, esophageal varices of any size with red color signs, and/or gastric varices along the cardia. RESULTS: Twenty-five patients (aged 0-18 years) had VNT. Eighteen patients met the Baveno VI criteria (LS <20 kPa; platelet count >150 000/L) and were deemed to be at low risk of VNT (spared endoscopies) while three had missed VNT (16.7%). Applying the Baveno VII criteria, which combines the SS cut-off value of 40 kPa with the Baveno VI criteria, resulted in five missed VNTs among 22 spared endoscopies (22.7%). A modification of the Baveno VII criteria using the aspartate aminotransferase-to-platelet ratio index (APRI) instead of the platelet count with cut-off values of 25 kPa, 30 kPa, and 1.04 for LS, SS, and APRI, respectively, missed only one VNT (5.0%) among 20 spared endoscopies. CONCLUSIONS: A novel diagnostic criterion that combines LS, SS, and APRI reduced the risk of missing VNT to 5% in children and adolescents with BA.

Ratio of von Willebrand factor to ADAMTS13 is a useful predictor of esophagogastric varices progression after sustained virologic response in patients with hepatitis C virus-related liver cirrhosis.

AIM: Esophagogastric varices (EGV) are a serious complication of hepatitis C virus (HCV)-related liver cirrhosis (HCV-LC). In most cases, portal hypertension improves after a sustained virologic response (SVR) is achieved with direct-acting antiviral (DAA) treatment; however, in some cases, EGV exacerbation occurs after HCV elimination. We investigated whether von Willebrand factor (VWF) and a disintegrin-like metalloproteinase with thrombospondin type-1 motif 13 (ADAMTS13) can predict EGV progression with HCV-LC after SVR achievement. METHODS: This retrospective study enrolled 47 patients with HCV-LC who achieved an SVR after DAA treatment. Eighteen patients experienced EGV progression after the SVR was achieved (EGV progression group). Twenty-nine patients did not experience EGV progression after the SVR was achieved (non-EGV progression group). Plasma VWF antigen levels and ADAMTS13 activity were measured the day before DAA treatment. RESULTS: The EGV progression group had significantly higher plasma VWF antigen levels (p = 0.00331) and VWF-to-ADAMTS13 ratios (p = 0.000249) than the non-EGV progression group. Multivariate logistic regression models found that a VWF-to-ADAMTS13 ratio >2.3 was the only risk factor for EGV progression after the SVR was achieved (hazard ratio [HR], 18.4; 95% confidence interval [CI], 3.08-109; p = 0.00138). During the observation period, patients with a VWF-to-ADAMTS13 ratio >2.3 had a significantly higher cumulative incidence of EGV progression after SVR achievement than patients with a VWF-to-ADAMTS13 ratio ≤2.3 (HR, 6.4; 95% CI, 1.78-22.96; p = 0.0044). CONCLUSIONS: The VWF-to-ADAMTS13 ratio before DAA treatment for HCV could predict EGV progression after SVR achievement.

Performance of Baveno VII criteria for the screening of varices needing treatment in patients with biliary atresia.

OBJECTIVE: Biliary atresia (BA) is the leading cause of liver cirrhosis and chronic liver insufficiency in children in the world. Gastroesophageal varices bleeding is an ominous complication of cirrhosis in BA patients and is associated with high morbidity and mortality. In this study, we aimed to investigate the utility of noninvasive Baveno VI and Baveno VII criteria for the screening of varices need treatment (VNT) and the need for liver transplantation in BA patients. METHODS: This study enrolled 48 BA patients (23 females and 25 males) who underwent an esophagogastroduodenoscopy (EGD) and transient elastography at a mean age of 11.18 ± 1.48 years; the clinical data were surveyed in a retrospective design. RESULTS: The sensitivity and negative predictive value of Baveno VI and Baveno VII criteria for the prediction of VNT in BA patients are both 100% and 100%, respectively. The VNT missing rate of Baveno VI and Baveno VII criteria are both 0% in our cohort. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are also predictive of the need for liver transplantation in our cohort (OR = 10.33, 4.24, and 21.33; p = 0.009, 0.03, and 0.007, respectively). CONCLUSION: The Baveno VI and Baveno VII criteria are useful for the screening of VNT and minimize non-necessary invasive EGD in BA patients with low VNT missing rates. The Baveno VI, expanded Baveno VI, and Baveno VII criteria are associated with the need for liver transplantation.

Systematic review of machine learning models in predicting the risk of bleed/grade of esophageal varices in patients with liver cirrhosis: A comprehensive methodological analysis.

Esophageal varices (EV) in liver cirrhosis carry high mortality risks. Traditional endoscopy, which is costly and subjective, prompts a shift towards machine learning (ML). This review critically evaluates ML applications in predicting bleeding risks and grading EV in patients with liver cirrhosis. Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we conducted a systematic review of studies using ML to predict the risk of variceal bleeding and/or grade EV in liver disease patients. Data extraction and bias assessment followed the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies) checklist and PROBAST (Prediction model Risk Of Bias Assessment Tool) tool, respectively. Due to the heterogeneity of the study, a meta-analysis was not feasible; instead, descriptive statistics summarized the findings. Twelve studies were included, highlighting the use of various ML models such as extreme gradient boosting, artificial neural networks, and convolutional neural networks. These studies demonstrated high predictive accuracy, with some models achieving area under the curve values above 99%. However, significant heterogeneity was noted in input variables, methodologies, and outcome measures. Moreover, a substantial portion of the studies exhibited unclear or high risk of bias, mainly due to insufficient participant numbers, unclear handling of missing data, and a lack of detailed reporting on endoscopic procedures. ML models show significant promise in predicting the risk of variceal bleeding and grading EV in patients with cirrhosis, potentially reducing the need for invasive procedures. Nonetheless, the current literature reveals considerable heterogeneity and methodological limitations, including high or unclear risks of bias. Future research should focus on larger, prospective trials and the standardization of ML assessment criteria to confirm these models' practical utility in clinical settings.

Clinical characteristics and management of patient with portal hypertension at tertial level hospital in Tanzania.

BACKGROUND: Portal hypertension is a common diagnosis in Sub-Saharan African countries, with the majority of patients presenting late. This study aimed to understand Clinical characteristics, aetiology, the treatment offered in our setting, and factors associated with portal hypertension at a tertiary-level hospital, in Tanzania. METHODOLOGY: A prospective cross-sectional observational single hospital-based study was conducted at MNH, from May 2021 to April 2022. A minimum of 152 subjects were required with an error of less than 5% and a study power of 80% at a 95% confidence interval. A structured questionnaire was used to collect data. Ethical clearance was obtained from the MUHAS/MNH IRB. RESULTS: A total of 154 eligible participants consented and participated in this study. The mean age of participants was 42 ± 15.8 years (range 2-87). Most of the study participants were males 64.9% with a male-to-female (M: F) ratio of 1.8:1. Vomiting blood was the common symptom among the study participants 51.3%. Schistosomiasis 53.9% and viral infection 26.6% were the common etiologies followed by alcohol abuse 7.8%. Most were medically treated at 89.61% followed by radiological treatment at 8.44% while only 1.95% of patients received surgical treatment. There was a significant association between the grade of oesophagal varices and bleeding consequences (p-value < 0.01). CONCLUSION: The majority of patients were medically treated while patients who require surgical care are unable to assess it. We recommend the establishment of a transplant services program to counteract the unmet need and more retrospective research toward policy establishment.

Application of Indian ink markers for locating gastric varices under endoscopic ultrasonography.

OBJECTIVE: The present study aimed to investigate the accuracy of endoscopic ultrasonography (EUS) combined with Indian ink in locating target vessels of gastric varices (GVs) compared with conventional endoscopic techniques. Additionally, the characteristics of GVs under conventional endoscopy were also explored. METHODS: All 50 cirrhotic patients with GVs between August 2021 and December 2022 were included in the study. Firstly, conventional endoscopy was employed to identify GVs and to record the expected injection sites. Subsequently, EUS was used to locate the perforated vessel and the injection site was them marked with India ink followed by injection with cyanoacrylate (CYA). Finally, conventional endoscopy was used to examine GVs, to identify the marker points of Indian ink and to compare whether the injection points under conventional endoscopy were consistent with those marked with Indian ink. Furthermore, patients with consistent and inconsistent distribution of endoscopic markers and injection sites were divided into two groups. RESULTS: EUS could detect the perforating vessels in real time and intuitively. The distribution of markers using EUS was significantly different compared with the injection points obtained by conventional endoscopy (P < 0.001). Therefore, 20 cases were allocated to the consistent group and 30 cases to the non-consistent group. 16 patients who showed red wale signs were obtained in the consistent group and 11 patients in the non-consistent group (P = 0.048). The diameter of the largest GVs was 13.5 (10-15) mm in the consistent group compared with 10 (7.5-10) mm in the non-consistent group (P = 0.006). CONCLUSION: EUS could provide the exact location of GVs, thus more accurately describing the endoscopic characteristics of the GVs. Furthermore, the red wale signs and diameter of the largest GVs obtained using conventional endoscopy were helpful in determining the location of target GVs.

Risk Factors for Rebleeding After Endoscopic Injection of Cyanoacrylate Glue for Gastric Varices: A Systematic Review and Meta-Analysis.

BACKGROUND: Rebleeding is a significant complication of endoscopic injection of cyanoacrylate in gastric varices in cirrhotic patients. AIM: This systematic review and meta-analysis aimed to evaluate the efficiency of endoscopic cyanoacrylate injection and summarized the risk factors for rebleeding. METHODS: Databases were searched for articles published between January 2012 and December 2022. Studies evaluating the efficiency of endoscopic injection of cyanoacrylate glue for gastric varices and the risk factors for rebleeding were included. RESULTS: The final analysis included data from 24 studies. The hemostatic rates ranged from 65 to 100%. The pooled rate of gastric varices recurrence was 34% [95% CI 21-46, I2 = 61.4%], early rebleeding rate was 16% [95% CI 11-20, I2 = 37.4%], late rebleeding rate was 39% [95% CI 36-42, I2 = 90.9%], mild and moderate adverse events rate were 28% [95% CI 24-31, I2 = 91.6%], 3% [95% CI - 2 to 8, I2 = 15.3%], rebleeding-related mortality rate was 6% [95% CI 2-10, I2 = 0%], all-cause mortality rate was 17% [95% CI 12-22, I2 = 63.6%]. Independent risk factors for gastric variceal rebleeding included portal venous thrombosis, ascites, cyanoacrylate volume, fever/systemic inflammatory response syndrome, red Wale sign, previous history of variceal bleeding, active bleeding and paragastric veins. The use of proton pump inhibitors could be a protective factor. CONCLUSIONS: Endoscopic cyanoacrylate glue injection is an effective and safe treatment for gastric varices. Cirrhotic patients with the above risk factors may benefit from treatment aimed at reducing portal hypertension, antibiotic prophylaxis, and anticoagulation if they meet the indications.