Impact of non-selective beta blockers on further decompensation and death in decompensated cirrhosis: Benefit and risk stratification by MELD score.

BACKGROUND: Non-selective beta blockers (NSBBs) can reduce the risk of decompensation, but their impact on further decompensation has been rarely investigated. AIMS: The aim is to evaluate the impact of NSBBs on further decompensation and death in decompensated cirrhosis stratified by the severity of liver disease. METHODS: Overall, 332 decompensated cirrhotic patients were retrospectively included, of whom 149 used NSBBs. Kaplan-Meier and Nelson-Aalen cumulative risk curves as well as Cox regression and competing risk analyses were used to estimate the associations of NSBBs with further decompensation and death, if appropriate. Hazard ratio (HR) and sub-distribution HR (sHR) were calculated. Subgroup analyses were performed based on the model for end-stage liver disease (MELD) score at admission. RESULTS: In the overall analysis, the use of NSBBs was not significantly associated with further decompensation in multivariate competing risk analysis (sHR = 1.09, p = 0.580). In the subgroup analysis of patients with a MELD score of ≤9, the use of NSBBs was significantly associated with decreased risk of further decompensation in multivariate competing risk analysis (sHR = 0.57, p = 0.021). In the subgroup analysis of patients with a MELD score of >9, the use of NSBBs was associated with increased risk of further decompensation in multivariate competing risk analysis (sHR = 1.45, p = 0.044). Regardless of overall and subgroup analyses, the use of NSBBs was not significantly associated with death in multivariate Cox regression analyses. CONCLUSION: NSBBs may be beneficial for the prevention of further decompensation in cirrhotic patients with a MELD score of ≤9, but deleterious in those with a MELD score of >9.

The role of dietary modification in the prevention and management of metabolic dysfunction-associated fatty liver disease: An international multidisciplinary expert consensus.

Metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction-associated steatotic liver disease (MASLD), has become the leading cause of chronic liver disease worldwide. Optimal dietary intervention strategies for MAFLD are not standardized. This study aimed to achieve consensus on prevention of MAFLD through dietary modification. A multidisciplinary panel of 55 international experts, including specialists in hepatology, gastroenterology, dietetics, endocrinology and other medical specialties from six continents collaborated in a Delphi-based consensus development process. The consensus statements covered aspects ranging from epidemiology to mechanisms, management, and dietary recommendations for MAFLD. The recommended dietary strategies emphasize adherence to a balanced diet with controlled energy intake and personalized nutritional interventions, such as calorie restriction, high-protein, or low-carbohydrate diets. Specific dietary advice encouraged increasing the consumption of whole grains, plant-based proteins, fish, seafood, low-fat or fat-free dairy products, liquid plant oils, and deeply colored fruits and vegetables. Concurrently, it advised reducing the intake of red and processed meats, saturated and trans fats, ultra-processed foods, added sugars, and alcohol. Additionally, maintaining the Mediterranean or DASH diet, minimizing sedentary behavior, and engaging in regular physical activity are recommended. These consensus statements lay the foundation for customized dietary guidelines and proposing avenues for further research on nutrition and MAFLD.

Incidence and type of adverse events in patients with cirrhosis receiving terlipressin: A systematic review and meta-analysis.

BACKGROUND: Terlipressin has been widely used for various cirrhosis-related complications, but its safety profile remains controversial. Herein, this issue was systematically evaluated. METHODS: All studies reporting adverse events (AEs) of terlipressin in cirrhosis were screened. Incidences were pooled using a random-effects model. Subgroup analyses were performed according to the patient's characteristics and treatment regimens. Interaction among subgroups was evaluated. RESULTS: Seventy-eight studies with 7257 patients with cirrhosis were included. The pooled incidences of any AEs, treatment-related AEs, any serious AEs (SAEs), treatment-related SAEs, treatment withdrawal due to AEs, and treatment withdrawal due to treatment-related AEs were 31%, 22%, 5%, 5%, 4%, and 4% in patients with cirrhosis receiving terlipressin, respectively. Patients with hepatorenal syndrome had higher incidences of any SAEs (29% vs. 0% vs. 0%, pinteraction = 0.01) and treatment-related SAEs (8% vs. 1% vs. 7%, pinteraction = 0.02) than those with variceal bleeding or ascites. Patients who received terlipressin with human albumin had higher incidences of any SAEs (18% vs. 1%, pinteraction = 0.04) and treatment-related SAEs (7% vs. 0%, pinteraction = 0.09) than those without albumin. Patients with total bilirubin level >4.3 mg/dL had higher incidences of any AEs (69% vs. 24%, pinteraction = 0.02), any SAEs (64% vs. 0%, pinteraction < 0.01), and treatment-related SAEs (8% vs. 1%, pinteraction = 0.04) than those ≤4.3 mg/dL. CONCLUSIONS: AEs are common in patients with cirrhosis receiving terlipressin and influenced by clinical scenarios, combination with albumin, and bilirubin levels.

The myth of the stigma of fatty liver: What does the evidence show?

Recent efforts to reclassify non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated fatty liver disease (MAFLD) and metabolic dysfunction-associated steatotic liver disease (MASLD) are intended to divert attention to the metabolic basis of the disease rather than to alcohol consumption. This reclassification recognizes the role of obesity, sedentary lifestyles and poor dietary habits in the development of the disease, leading to a better understanding of its etiology. Nevertheless, the transition has posed its own challenges, particularly with regard to communication between patient and healthcare professional. Many healthcare professionals report difficulty in explaining the nuanced concepts, especially the term "steatosis". In addition, the change in terminology has not yet removed the stigma, with ongoing debates about the appropriateness of the terms "fatty" and "steatotic". Surveys suggest that while "obesity" may be perceived as more stigmatizing, the medical term "steatotic liver disease" is not considered as stigmatizing, indicating a disconnect in perceptions between healthcare professionals and patients.

Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.

Successful corticosteroid therapy for severe liver injury secondary to herbal traditional Chinese medicine, Mega Defends X, assessed for causality by the updated RUCAM: A case report.

RATIONALE: In China, herbal traditional Chinese medicine products are readily obtained without any requirement of prescription and widely used in real life, thereby increasing the incidence of their related herb-induced liver injury (HILI). However, the diagnosis of HILI is still challenging because its clinical manifestations are variable due to lack of any specific biomarkers. Misdiagnosis and inappropriate treatment may result in the progression of HILI. PATIENT CONCERNS: A 55-year-old female patient was admitted to the hospital due to progressive jaundice. DIAGNOSES: The diagnoses of HILI secondary to Mega Defends X, an herbal traditional Chinese medicine product, for which the score was 9 based on the updated Roussel Uclaf Causality Assessment Method of 2016. INTERVENTIONS: The patient received corticosteroid with a stepwise dosage reduction. OUTCOMES: The liver injury significantly improved by corticosteroid treatment. LESSONS: Corticosteroids should be potentially effective and safe in patients with severe HILI.

Association of Helicobacter pylori infection with colorectal polyps/adenomas: A single-center cross-sectional study.

BACKGROUND: Helicobacter pylori (H. pylori) infection may be associated with colorectal polyps/adenomas, but the current evidence remains controversial. METHODS: We retrospectively screened the medical records of 655 participants who underwent both colonoscopy and H. pylori test from June 15, 2020 to April 30, 2023. The number, size, location, and pathological type of colorectal polyps/adenomas were compared between H. pylori positive and negative groups. Adjusting for age, gender, smoking, drinking, hypertension, diabetes, fatty liver, body mass index, and inflammatory and metabolic indicators, multivariate logistic regression analyses were performed to evaluate the association of H. pylori infection with the number, size, location, and pathological type of colorectal polyps/adenomas, where no polyp/adenoma was used as reference. RESULTS: Overall, 508 participants were included, of whom 154 and 354 were divided into H. pylori positive and negative groups, respectively. H. pylori positive group had significantly higher colorectal polyps/adenomas (74.7 % vs. 65.8 %, P=0.048), low-grade adenomas (55.7 % vs. 47.6 %, P=0.026), advanced adenomas (22.6 % vs. 13.3 %, P=0.008), and colorectal polyps/adenomas with sizes of ≥6 mm (61.7 % vs. 48.5 %, P=0.002) and ≥10 mm (25.2 % vs. 14.6 %, P=0.004) than H. pylori negative group. In multivariate logistic regression analyses, H. pylori infection was independently associated with low-grade adenomas (OR=2.677, 95 %CI=1.283-5.587, P=0.009), advanced adenomas (OR=3.017, 95 %CI=1.007-9.036, P=0.049), right-side colon polyps/adenomas (OR=5.553, 95 %CI=1.679-18.360, P=0.005), and colorectal polyps/adenomas with sizes of ≥10 mm (OR=4.436, 95 %CI=1.478-13.310, P=0.008), but not number of colorectal polyps/adenomas. CONCLUSION: H. pylori infection is associated with increased risk of colorectal polyps/adenomas, especially low-grade adenomas, advanced adenomas, right-side colon polyps/adenomas, and large colorectal polyps/adenomas.

Associations of gallbladder and gallstone parameters with clinical outcomes in patients with cirrhosis.

Background: Morphologic changes in the gallbladder and gallstones are common in cirrhotic patients, but their associations with outcomes of cirrhotic patients are unclear. Methods: We retrospectively enrolled 206 cirrhotic patients and measured their gallbladder length and width, gallbladder wall thickness, presence of gallstones, and gallstones' length and width in axial contrast-enhanced computed tomography (CT) images. X-tile software was utilized to calculate the optimal cutoff values of these parameters for evaluating survival and hepatic decompensation events in the cirrhosis group. Their associations with survival were explored by Cox regression analyses and Kaplan-Meier curve analyses. Their associations with hepatic decompensation events were evaluated by competing risk analyses and Nelson-Aalen cumulative risk curve analyses where death was a competing event. Results: Cirrhotic patients with gallbladder length < 72 mm had a significantly higher cumulative survival rate than those with a length of ≥ 72 mm (P = 0.049 by log-rank test), but gallbladder width, gallbladder wall thickness, presence of gallstones, and gallstones' length and width were not significantly associated with survival (P = 0.10, P = 0.14, P = 0.97, P = 0.73, and P = 0.73 by log-rank tests, respectively). Cirrhotic patients with gallbladder wall thickness < 3.4 mm had a significantly lower cumulative rate of hepatic decompensation events than those with a wall thickness of ≥ 3.4 mm (P = 0.02 by Gray's test), but gallbladder length and width, presence of gallstones, and gallstones' length and width were not significantly associated with hepatic decompensation events (P = 0.15, P = 0.15, P = 0.54, P = 0.76, and P = 0.54 by Gray's tests, respectively). Conclusion: Changes in gallbladder length and gallbladder wall thickness, rather than gallstone parameters, may be in parallel with the long-term outcomes of cirrhotic patients.

Shortening Oral Simethicone-to-Colonoscopy Interval Increases Bowel Preparation Quality.

BACKGROUND Simethicone can improve bowel preparation quality, but the optimal timing of oral simethicone before colonoscopy has not been determined. This study aimed to explore the effect of the time interval between oral simethicone and the start of colonoscopy (S-C) on bowel preparation quality. MATERIAL AND METHODS A total of 364 patients undergoing colonoscopy at our department from August 1, 2021 to November 30, 2021 were included in the training cohort, and 420 consecutive patients from December 15, 2021 to January 31, 2022 comprised the validation cohort. They were classified into short and long S-C groups according to the median S-C. Bowel preparation quality evaluated by the Boston Bowel Preparation Scale was compared between the 2 groups. Logistic regression analyses were performed to explore the correlation between S-C and bowel preparation quality, and we explored the effect of run-way time and time of starting colonoscopy on bowel preparation quality. RESULTS In the training cohort, 182 and 182 patients were classified into the short and long S-C groups, respectively; in the validation cohort, 210 and 210 patients were classified into the 2 groups, respectively. In the 2 cohorts, the short S-C group had a significantly higher rate of adequate/excellent bowel preparation than the long S-C group. Logistic regression analyses showed that shorter S-C, shorter run-way time, and colonoscopy in the morning were all correlated with adequate/excellent bowel preparation. CONCLUSIONS Bowel preparation quality may be affected by S-C, run-way time, and time of starting colonoscopy. S-C shortening should be given equal importance as run-way time shortening.

Case report: Isolated immunoglobulin G4-related sclerosing cholangitis misdiagnosed as hilar cholangiocarcinoma.

Background: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) is frequently accompanied with type 1 autoimmune pancreatitis (AIP). Isolated IgG4-SC which is not accompanied with AIP is uncommon in clinical practice, and its manifestations are similar to those of hilar cholangiocarcinoma. Case presentation: A 55-year-old male presented with persistent aggravation of icteric sclera and skin. He was initially diagnosed with hilar cholangiocarcinoma and underwent surgery. However, positive IgG4 plasma cells were found in the surgical specimens. Thus, a pathological diagnosis of IgG4-SC was established. After that, steroid therapy was given and initially effective. But he was steroid dependent, and then received rituximab therapy twice. Unfortunately, the response to rituximab therapy was poor. Conclusion: It is crucial to differentiate isolated IgG4-SC from hilar cholangiocarcinoma to avoid unnecessary surgery. Future studies should further explore effective treatment strategy in patients who do not respond to steroids therapy. It is also required to develop novel and accurate diagnostic approaches to avoid unnecessary surgical procedures.

Association of Gastrointestinal Symptoms with Depression and Anxiety in Recruits: A Validation Cross-Sectional Study.

INTRODUCTION: Gastrointestinal symptoms as well as depression and anxiety can negatively affect the effectiveness of military training and combat in general. This cross-sectional study aimed to determine the prevalence of gastrointestinal symptoms in recruits and further validate their associations with depression and anxiety. METHODS: A self-report questionnaire was sent to the recruits in an army in April 2022, which primarily included the Symptom Rating Scale (GSRS) for the assessment of gastrointestinal symptoms, the Bristol Stool Scale (BSS) for stool consistency and shape, the Patient Health Questionnaire-9 (PHQ-9) for depression, and the 7-item Generalized Anxiety Disorder scale (GAD-7) for anxiety. Correlation of gastrointestinal symptoms with depression and anxiety was evaluated. RESULTS: Overall, 467 recruits were included. Their median age was 21.0 years old (range: 18.0-24.0), and 98.1% of them were male. The proportion of gastrointestinal symptoms, abnormal stools, depression, and anxiety was 69.2% (n = 323), 11.3% (n = 53), 17.6% (n = 82), and 12.2% (n = 57), respectively. The recruits with gastrointestinal symptoms evaluated by GSRS had significantly higher prevalence of depression (P < 0.001) and anxiety (P < 0.001) than those without. GSRS score positively correlated with PHQ-9 (rs = 0.440, P < 0.001) and GAD-7 score (rs = 0.386, P < 0.001). CONCLUSION: Gastrointestinal symptoms are very common in recruits, and positively correlate with depression and anxiety.

Case report: Rapid development of acute symptomatic portal vein system thrombosis after endoscopic variceal therapy in a patient with liver cirrhosis.

Acute portal vein thrombosis (PVST), a serious complication of liver cirrhosis, is characterized as abdominal pain secondary to intestinal ischemia, and even intestinal necrosis. Anticoagulation is recommended for the treatment of acute PVST, but is often postponed in cirrhotic patients with acute variceal bleeding or those at a high risk of variceal bleeding. Herein, we reported a 63-year-old male with a 14-year history of alcoholic liver cirrhosis who developed progressive abdominal pain related to acute portal vein and superior mesenteric vein thrombosis immediately after endoscopic variceal ligation combined with endoscopic cyanoacrylate glue injection for acute variceal bleeding. Fortunately, acute PVST was successfully recanalized by the use of low molecular weight heparin. Collectively, this case suggests that acute symptomatic PVST can be secondary to endoscopic variceal therapy in liver cirrhosis, and can be safely and successfully treated by anticoagulation.

Neutrophil extracellular traps formation may be involved in the association of propranolol with the development of portal vein thrombosis.

BACKGROUND & AIMS: Nonselective ß blockers (NSBBs) facilitate the development of portal vein thrombosis (PVT) in liver cirrhosis. Considering the potential effect of NSBBs on neutrophils and neutrophil extracellular traps (NETs), we speculated that NSBBs might promote the development of PVT by stimulating neutrophils to release NETs. MATERIALS AND METHODS: Serum NETs biomarkers were measured, use of NSBBs was recorded, and PVT was evaluated in cirrhotic patients. Carbon tetrachloride and ferric chloride (FeCl3) were used to induce liver fibrosis and PVT in mice, respectively. After treatment with propranolol and DNase I, neutrophils in peripheral blood, colocalization and expression of NETs in PVT specimens, and NETs biomarkers in serum were measured. Ex vivo clots lysis analysis was performed and portal vein velocity and coagulation parameters were tested. RESULTS: Serum MPO-DNA level was significantly higher in cirrhotic patients treated with NSBBs, and serum H3Cit and MPO-DNA levels were significantly higher in those with PVT. In fibrotic mice, following treatment with propranolol, DNase I significantly shortened the time of FeCl3-induced PVT formation, lowered the peripheral blood neutrophils labelled by CD11b/Ly6G, inhibited the positive staining of H3Cit and the expression of H3Cit and MPO proteins in PVT tissues, and reduced serum nucleosome level. Furthermore, the addition of DNase I to tissue plasminogen activator (tPA) significantly accelerated clots lysis as compared with tPA alone. Propranolol reduced portal vein velocity in fibrotic mice, but did not influence coagulation parameters. CONCLUSION: Our study provides a clue to the potential impact of NETs formation on the association of NSBBs with the development of PVT.

Systemic Thrombolysis for Isolated Splenic Vein Thrombosis Secondary to Oral Contraceptives: A Case Report.

Isolated splenic vein thrombosis (ISVT) is a very rare venous thromboembolism in the absence of pancreatic diseases, which can cause acute abdominal pain and chronic left-side portal hypertension. Herein, we reported a 40-year-old female patient who developed ISVT after taking oral contraceptives. Anticoagulation with oral rivaroxaban was the first-line choice of therapy in this case. Since then, abdominal pain alleviated, but she did not achieve vessel recanalization. Thus, a 7-day systemic thrombolysis with urokinase was given. Abdominal pain disappeared, but ISVT was not significantly improved. During follow-up period, long-term anticoagulation with oral rivaroxaban was given. Collectively, this case indicates the possibility of oral contraceptives as a risk factor of ISVT as well as anticoagulation combined with systemic thrombolysis as a choice of treatment for ISVT. Certainly, long-term follow-up is necessary in this case.

Effect of Body Mass Index on Cecal Intubation Time During Unsedated Colonoscopy: Variation Across the Learning Stages of an Endoscopist.

BACKGROUND Body mass index (BMI) and endoscopists' experiences can be associated with cecal intubation time (CIT), but such associations are controversial. This study aimed to clarify the association between BMI and CIT during unsedated colonoscopy at 3 learning stages of a single endoscopist. MATERIAL AND METHODS A total of 1500 consecutive patients undergoing unsedated colonoscopy by 1 endoscopist at our department from December 11, 2020, to August 21, 2022, were reviewed. They were divided into 3 learning stages according to the number of colonoscopies performed by 1 endoscopist, including intermediate (501-1000 colonoscopies), experienced (1001-1500 colonoscopies), and senior stages (1501-2000 colonoscopies). Variables that significantly correlated with CIT were identified by Spearman rank correlation analyses and then included in multiple linear regression analysis. RESULTS Overall, 1233 patients were included. Among them, 392, 420, and 421 patients were divided into intermediate, experienced, and senior stages, respectively. Median CIT was 7.83, 6.38, and 5.58 min at intermediate, experienced, and senior stages, respectively (P.

Case Report: First attempt by off-label use of tenecteplase to treat acute extensive portal venous system thrombosis.

Acute extensive portal venous system thrombosis (PVST) can cause lethal complications. Herein, we have for the first time reported the use of anticoagulation combined with systemic thrombolysis by tenecteplase in a male patient with a diagnosis of acute extensive PVST but without liver cirrhosis. After thrombolytic therapy, abdominal pain obviously alleviated. However, urinary bleeding developed, which was reversible by stopping thrombolytic drugs. Finally, this case developed cavernous transformation of the portal vein without portal venous recanalization. In future, the efficacy and safety of tenecteplase should be explored in acute extensive PVST cases.