A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

INTRODUCTION: Endoscopic variceal ligation (EVL) plus nonselective ß-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB. METHODS: After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups. RESULTS: The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%). DISCUSSION: EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation.

Risks of Proton Pump Inhibitors in Patients with Cirrhosis: Please Peruse the Indications.

The use of proton pump inhibitor (PPI) in cirrhotic patients can be associated with increased risks of long-term mortality, decompensation, hepatic encephalopathy, spontaneous bacterial peritonitis, and infection, but not with short-term mortality. Ensure clear indications at lowest effective dose of is mandatory for the use of PPI among cirrhotic patients.

Routine image-enhanced endoscopic surveillance for metachronous esophageal squamous cell neoplasms in head and neck cancer patients.

BACKGROUND: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy. METHODS: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed. RESULTS: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs. CONCLUSIONS: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality.

Risk of Attempted Suicide Among Patients With IBD: A Nationwide Longitudinal Follow-up Study.

BACKGROUND: Evidence suggests that IBD is related to an increased risk of depressive disorder and suicide. OBJECTIVES: Whether IBD is an independent risk factor for suicide remains unclear. DESIGN: A matched cohort study design. SETTINGS: Taiwan National Health Insurance Research Database. PATIENTS: A total of 3625 adults with IBD aged ≥20 years and 36,250 matched controls were selected between 1997 and 2013 and followed-up to the end of 2013. MAIN OUTCOME MEASURES: Any suicide attempt was identified during the study period. Stratified Cox regression analysis was conducted on each matched pair to investigate the attempted suicide risk between the IBD and control groups. RESULTS: The hazard ratio for any suicide attempt among the patients with IBD was 4.61 (95% CI, 3.29-6.48) compared with controls matched exactly for depressive disorder. No significant difference in suicide attempts was noted between patients with ulcerative colitis (HR, 4.12; 95% CI, 2.69-6.32) and patients with Crohn's disease (HR, 5.78; 95% CI, 3.27-10.22). LIMITATIONS: The incidence of any suicide attempt may be underestimated. CONCLUSION: IBD was an independent risk factor for attempted suicide. However, further studies are required to elucidate the definite pathomechanisms between IBD and suicide. RIESGO DE INTENTO DE SUICIDIO ENTRE PACIENTES CON ENFERMEDAD INFLAMATORIA INTESTINAL UN ESTUDIO DE SEGUIMIENTO LONGITUDINAL A NIVEL NACIONAL: ANTECEDENTES: La evidencia sugiere que la enfermedad inflamatoria intestinal (EII) está relacionada con un mayor riesgo de trastornos depresivos y de suicidios.OBJETIVOS: Sin embargo, aún no está claro si la EII es un factor de riesgo independiente para llegar al suicidio.DISEÑO: Estudio de cohortes de tipo pareado.AJUSTES: Investigación en la base de datos del seguro nacional de salud de Taiwán.PACIENTES: Se seleccionaron un total de 3.625 adultos con EII de ≥20 años y 36.250 controes emparejados entre 1997 y 2013, se les dio un seguimiento hasta finales de 2013.PRINCIPALES MEDIDAS DE RESULTADO: Se identificó cualquier intento de suicidio durante el período del estudio. Se realizó un análisis de regresión de Cox estratificado en cada dupla apareada dentro la investigación del riesgo de intento de suicidio comparado entre los grupos de EII y el grupo control.RESULTADOS: El cociente de riesgo instantáneo (HR) para cualquier intento de suicidio entre los pacientes con EII fue de 4,61 (el intervalo de confianza [IC] del 95 %: 3,29-6,48) en comparación con los controles apareados exactamente en casos de trastorno depresivo. No se observaron diferencias significativas en los intentos de suicidio entre los pacientes con colitis ulcerosa (HR: 4,12, IC 95 %: 2,69-6,32) y enfermedad de Crohn (HR: 5,78, IC 95 %: 3,27-10,22).LIMITACIONES: La incidencia de cualquier intento de suicidio puede estar subestimada.CONCLUSIÓN: La EII fué un factor de riesgo independiente para el intento de suicidio. Sin embargo, se requieren más estudios para dilucidar los mecanismos patogénicos definitivos entre la EII y el suicidio. (Traducción-Dr. Xavier Delgadillo ).

High carriage rate of extended-spectrum ß-lactamase Enterobacterales and diarrheagenic Escherichia coli in healthy donor screening for fecal microbiota transplantation.

The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs.

Effectiveness of betadine-coating gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy: a randomized controlled trial.

BACKGROUND: Peristomal wound infection is a common complication in patients receiving percutaneous endoscopic gastrostomy (PEG). The main reason for peristomal infection might be the oral microbes coating the gastrostomy tube during implantation. Povidone-iodine solution can be applied for skin and oral decontamination. We designed a randomized controlled trial to test the effectiveness of a Betadine® (povidone-iodine) coated gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy. METHODS: A total of 50 patients were randomized to Betadine and control groups (25 patients in each group) from April 2014 to August 2021 at a tertiary medical center. All patients received the pull method for PEG implantation using a 24-french gastrostomy tube. The primary endpoint was peristomal wound infection rate 2 weeks after the procedure. RESULTS: Changes in Neutrophil/Lymphocyte ratio (N/L ratio) and C-Reative protein (Delta CRP) at 24 h after PEG were higher in the control group than in the Betadine group (N/L ratio, 3.1 vs. 1.2, p = 0.047; CRP, 2.68 vs.1.16, p = 0.009). The two groups did not differ in post-PEG fever, peristomal infection, pneumonia, or all-cause infection. Delta CRP could predict peristomal infection and all-cause infection within 2 weeks (AUROC 0.712 vs. 0.748; p = 0.039 vs. 0.008). The best cut-off-point of Delta CRP for the diagnosis of peristomal wound infection was 3 mg/dl. CONCLUSION: The betadine coating gastrostomy tube method could not reduce peristomal infection after percutaneous endoscopic gastrostomy. CRP elevation of less than 3 mg/dl may be used to exclude the potential peristomal wound infection. TRIAL REGISTRATION: NCT04249570 ( https://clinicaltrials.gov/ct2/show/NCT04249570 ).

Bidirectional association between inflammatory bowel disease and depression among patients and their unaffected siblings.

BACKGROUND AND AIM: Approximately 30% of inflammatory bowel disease (IBD) patients develop depression. Conversely, several studies reported increased IBD risk among patients with depression. Such bidirectional relationship has not been reported within one representative cohort, nor investigated among patients' family members. These associations may further implicate the gut-brain axis in IBD. METHODS: We conducted parallel retrospective cohort analyses to investigate depression risk among IBD patients and their unaffected siblings, and IBD risk among patients with depression and their unaffected siblings using the Taiwanese National Health Insurance Research Database. Individuals were followed up to 11 years for new-onset depression or IBD. Controls were matched to unaffected siblings based on predefined characteristics. RESULTS: To investigate depression risk among IBD - 422 IBD patients, 537 unaffected siblings, and 2148 controls were enrolled. During follow-up, 78 (18.5%) IBD patients, 26 (4.8%) unaffected siblings, and 54 (2.5%) controls developed depression. Adjusted odds ratios (ORs) for depression among IBD patients and unaffected siblings were 9.43 (95% CI 6.43-13.81; P < 0.001) and 1.82 (95% CI 1.14-2.91; P = 0.013), respectively. To investigate IBD risk among depression - 25 552 patients with depression, 26 147 unaffected siblings, and 104 588 controls were enrolled. During follow-up, 18 (0.70/1000) depression patients, 25 (0.96/1000) unaffected siblings, and 58 (0.55/1000) controls developed IBD. ORs for IBD among depression patients and unaffected siblings were 1.87 (95% CI 1.07-3.26; P = 0.028) and 1.69 (95% CI 1.05-2.69; P = 0.029), respectively. CONCLUSIONS: This population-based study elucidates bidirectional association between IBD and depression. Elevated risks for either disease among patients and their unaffected siblings suggest shared etiologic contributors, offering novel insight into the gut-brain axis' influence in IBD pathophysiology.

A novel machine learning-based algorithm to identify and classify lesions and anatomical landmarks in colonoscopy images.

OBJECTIVES: Computer-aided diagnosis (CAD)-based artificial intelligence (AI) has been shown to be highly accurate for detecting and characterizing colon polyps. However, the application of AI to identify normal colon landmarks and differentiate multiple colon diseases has not yet been established. We aimed to develop a convolutional neural network (CNN)-based algorithm (GUTAID) to recognize different colon lesions and anatomical landmarks. METHODS: Colonoscopic images were obtained to train and validate the AI classifiers. An independent dataset was collected for verification. The architecture of GUTAID contains two major sub-models: the Normal, Polyp, Diverticulum, Cecum and CAncer (NPDCCA) and Narrow-Band Imaging for Adenomatous/Hyperplastic polyps (NBI-AH) models. The development of GUTAID was based on the 16-layer Visual Geometry Group (VGG16) architecture and implemented on Google Cloud Platform. RESULTS: In total, 7838 colonoscopy images were used for developing and validating the AI model. An additional 1273 images were independently applied to verify the GUTAID. The accuracy for GUTAID in detecting various colon lesions/landmarks is 93.3% for polyps, 93.9% for diverticula, 91.7% for cecum, 97.5% for cancer, and 83.5% for adenomatous/hyperplastic polyps. CONCLUSIONS: A CNN-based algorithm (GUTAID) to identify colonic abnormalities and landmarks was successfully established with high accuracy. This GUTAID system can further characterize polyps for optical diagnosis. We demonstrated that AI classification methodology is feasible to identify multiple and different colon diseases.

Alteration of gut microbial composition associated with the therapeutic efficacy of fecal microbiota transplantation in Clostridium difficile infection.

BACKGROUND/PURPOSE: Clostridium difficile infection (CDI) leads to a significant cause of hospital-acquired morbidity and mortality. Fecal microbiota transplantation (FMT) is effective to treat recurrent or refractory CDI (rCDI). However, the change of microbial composition contributed by FMT and its association with treatment outcomes is not well determined in Taiwan. We aimed to investigate the efficacy of FMT and the association with microbial alteration endemically. METHODS: Twelve patients who received FMT for rCDI in Taipei Veterans General Hospital were prospectively enrolled from April 2019 to July 2020. The clinical assessments and fecal microbial analyses in comparison with fecal materials of unrelated donors were conducted before and after FMT. RESULTS: The overall success rate of FMT for rCDI was 91.7%. A prominence of Proteobacteria, Gammaproteobacteria and Enterobacteriales were observed in the feces of patients with rCDI. Increased fecal phylogenetic diversities and a significant microbial dissimilarity were provided by successful FMT compared to patients before treatment. However, the distinctness was not obvious between patients' feces at baseline and after unsuccessful FMT. Moreover, dynamic change of fecal microbial composition after FMT was observed during follow-up but did not interrupt the treatment effects of FMT. CONCLUSION: Gut dysbiosis commonly co-exists in patients with rCDI. Restoration of gut microbial communities by FMT provides a promising strategy to treat antibiotic-failed CDI, and the extent of microbial change would be related to the treatment outcomes of FMT. Besides, the effectiveness of FMT for CDI could be maintained even the gut microbiota has diverged over time.

Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study.

OBJECTIVE: Increasing evidence supports reciprocal communication between the enteric and the central nervous system in disease, termed the 'gut-brain axis'. Recent findings suggest a connection between IBD and development of Parkinson's disease. The role of IBD in dementia, another insidious neurodegenerative disorder, has not been explored. DESIGN: Using the Taiwanese National Health Insurance Research Database, we performed comparative analysis of 1742 patients with IBD ≥45 years old against 17 420 controls to assess dementia risk following IBD diagnosis. Controls were matched on bases of sex, access to healthcare, income and dementia-related comorbidities. All individuals were followed for dementia diagnosis for up to 16 years. Subanalyses included the relationship between sex, ulcerative colitis (UC) and Crohn's disease (CD), and dementia risk. RESULTS: Overall incidence of dementia among patients with IBD was significantly elevated (5.5% vs 1.4% among controls). Patients with IBD were diagnosed with dementia at 76.24 years old on average, compared with 83.45 among controls. The HR of developing dementia among patients with IBD was 2.54 (95% CI 1.91 to 3.37). Among dementia types, the risk of developing Alzheimer's dementia demonstrated the greatest increase. Dementia risk did not differ between sex differences nor UC versus CD. CONCLUSION: This population-based cohort study demonstrates significant association between IBD and subsequent development of dementia. Dementia was diagnosed at an earlier age among patients with IBD, and disease risk appeared to increase with IBD chronicity. These findings highlight the need for future research to elucidate the relationship between IBD and dementia.

Increased risk of short-term depressive disorder after Helicobacter pylori eradication: A population-based nested cohort study.

BACKGROUND: Depressive disorder is a major psychiatric illness, and a disturbed brain-gut-microbiome axis may contribute to its pathophysiology. Chronic Helicobacter pylori (H. pylori) infections are common in the general population and using multiple antibiotics is required for its eradication, which is associated with gut dysbiosis and may lead to depression. We aimed to evaluate the risk of psychiatrist-diagnosed depression in patients with peptic ulcer diseases (PUD) receiving anti-H. pylori therapy. MATERIALS AND METHODS: We collected data from the National Health Insurance Research Database (NHIRD) in Taiwan on PUD patients undergoing antibiotic treatment for H. pylori infection; patients and controls were matched for age, sex, income, level of urbanization, and comorbidities. RESULTS: Of the 1 million beneficiaries in the NHIRD, we identified 7087 patients for inclusion in the eradication cohort and 7087 matched non-eradication controls with PUD. Antibiotic therapy is associated with a short-term (<30 days) increase in the incidence of psychiatrist-diagnosed depressive disorder (p = 0.009, after multiple comparisons with Bonferroni correction) in the eradication cohort compared with the controls. Female (OR: 4.55, 95% CI: 1.53-13.48) PUD patients were more likely to display an increased risk of depression within 30 days after eradication therapy. Clarithromycin use was related to an elevated likelihood (OR: 3.14, 95% CI: 1.45-6.80) of subsequent depressive disorder within 30 days after eradication therapy. CONCLUSIONS: Antibiotic eradication treatment for H. pylori infection is associated with a significant short-term (less than 30 days) increase in the incidence of psychiatrist-diagnosed depressive disorder, which can be overlooked by gastroenterologists and general practitioners.

Fish Segmentation in Sonar Images by Mask R-CNN on Feature Maps of Conditional Random Fields.

Imaging sonar systems are widely used for monitoring fish behavior in turbid or low ambient light waters. For analyzing fish behavior in sonar images, fish segmentation is often required. In this paper, Mask R-CNN is adopted for segmenting fish in sonar images. Sonar images acquired from different shallow waters can be quite different in the contrast between fish and the background. That difference can make Mask R-CNN trained on examples collected from one fish farm ineffective to fish segmentation for the other fish farms. In this paper, a preprocessing convolutional neural network (PreCNN) is proposed to provide "standardized" feature maps for Mask R-CNN and to ease applying Mask R-CNN trained for one fish farm to the others. PreCNN aims at decoupling learning of fish instances from learning of fish-cultured environments. PreCNN is a semantic segmentation network and integrated with conditional random fields. PreCNN can utilize successive sonar images and can be trained by semi-supervised learning to make use of unlabeled information. Experimental results have shown that Mask R-CNN on the output of PreCNN is more accurate than Mask R-CNN directly on sonar images. Applying Mask R-CNN plus PreCNN trained for one fish farm to new fish farms is also more effective.

Endoscopic management of strictures in patients with Crohn's disease - A multi-center experience in Taiwan.

BACKGROUND/PURPOSE: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) disorder that causes relapsing inflammation and severe mucosal damage in the intestine. Crohn's disease (CD)-related stricturing complications are a major cause of surgery, disability, and reduced quality of life. Endoscopic balloon dilation (EBD) has been shown to reliably delay or prevent surgery in patients with stricturing CD. However, cases of EBD performed for stricture in CD in Taiwan are rare. In this study, we want to evaluate the experiences regarding EBD for stricturing CD in Taiwan. METHODS: We conducted a retrospective analysis of 9 medical centers in Taiwan. Patients with CD-related strictures who were treated with EBD were included and analyzed. RESULTS: In nine medical centers, a total of 26 CD patients (19 male, 7 female, mean disease duration 75.4 ± 65.2 months) underwent 42 EBD procedures during the study period. Among the subjects, an 83.3% (35/42) EBD success rate was seen, but 26.9% (7/26) patients underwent surgery after ineffective EBD. In the surgery group, the the small bowel strictures was high compared with the non-surgery group (p = 0.01). There were no significant differences in disease phenotype, disease duration or history of fistulizing disease. In the surgery group, immunosuppressant use was high, and 5-aminosalicylic acid (5-ASA) use was low compared with the non-surgery group. After EBD, the physicians tended to change the drugs, especially increasing the use of biologic agents. CONCLUSION: EBD is a safe and effective procedure for CD-related stricture, with a 83.3% success rate in Taiwan.

Addition of Carvedilol to Gastric Variceal Obturation Does Not Decrease Recurrence of Gastric Variceal Bleeding in Patients With Cirrhosis.

BACKGROUND & AIMS: Gastric variceal bleeding (GVB) frequently recurs after hemostasis by gastric variceal obturation (GVO). We performed a multicenter, randomized controlled trial to determine the efficacy of carvedilol plus GVO in secondary prophylaxis of GVB. METHODS: We performed a prospective study of 121 patients with cirrhosis (ages 20-80 years) with GVB proven by endoscopy within 24 hours of bleeding and stable hemodynamics for at least 3 days after initial GVO. Patients were randomly assigned into a group that underwent repeated GVO (n = 61) or a group received repeated GVO plus carvedilol (n = 60). Recurrent GVB, upper gastrointestinal bleeding (UGIB), adverse events, and survival were compared between the groups. RESULTS: GVB recurred in 21 patients (34%) in the group that received repeated GVO and 14 patients (23%) in the group that received repeated GVO plus carvedilol (P = .18). Ascites (relative risk [RR], 2.69; 95% CI, 1.33-5.48; P = .006) and hepatoma (RR, 2.10; 95% CI, 1.03-4.28; P = .04) were associated with recurrent GVB. Twenty-nine patients (48%) in the group that received repeated GVO and 17 patients (28%) in the group that received repeated GVO plus carvedilol had recurrent UGIB (P = .03). Carvedilol (RR, 0.44; 95% CI, 0.24-0.80; P = .007) was associated with reduced risk of UGIB recurrence. Ascites (RR, 3.02; 95% CI, 1.59-5.73; P = .001) and hepatoma (RR, 2.07; 95% CI, 1.10-3.88; P = .02) were associated with recurrent UGIB. A higher proportion of patients in the group that received repeated GVO plus carvedilol (53%) had adverse events than the group that received repeated GVO (15%) (P < .001). Mean survival times were 21 ± 18 months in the group that received repeated GVO vs 25 ± 20 months in the group that received repeated GVO plus carvedilol (P = .30). CONCLUSION: In a randomized controlled trial, we found that addition of carvedilol to GVO did not decrease recurrence of GVB in patients with cirrhosis but was associated with decreased recurrence of UGIB. However, carvedilol plus GVO produced significantly more adverse events. Mean survival times did not differ significantly between groups. ClinicalTrials.gov no: NCT02504723.

Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in A Population Study.

BACKGROUND & AIMS: Hepatic encephalopathy (HE) is a serious complication of cirrhosis and is associated with gut dysbiosis. Proton pump inhibitors (PPIs), frequently prescribed to patients with cirrhosis, can contribute to small-bowel bacterial overgrowth. We investigated whether PPI predisposes patients with cirrhosis to HE using a large database of patients. METHODS: We performed a case-control study nested within a sample of Taiwan National Health Insurance beneficiaries (n = 1,000,000), followed up longitudinally from 1998 through 2011. Patients with cirrhosis and an occurrence of HE (n = 1166) were selected as the case cohort and matched to patients without HE (1:1, controls) for sex, enrollment time, end point time, follow-up period, and advanced cirrhosis. Information on prescribed drugs, drug dosage, supply days, and numbers of dispensed pills was extracted from the Taiwan National Health Insurance database. PPI use was defined as more than 30 cumulative defined daily doses (cDDDs); PPI nonuse was defined as 30 cDDDs or fewer. We performed logistic regression analyses to estimate the association between PPI use and the occurrence of HE. RESULTS: Among patients with cirrhosis and an occurrence of HE, 38% (n = 445) had a history of PPI use before HE occurrence. We observed a relationship between dose of PPI taken and HE risk. The confounder-adjusted odd ratios were 1.41 (95% confidence interval [CI], 1.09-1.84), 1.51 (95% CI, 1.11-2.06), and 3.01 (95% CI, 1.78-5.10) for patients with 30-120 cDDDs, 120-365 cDDDs, and more than 365 cDDDs, respectively, compared with PPI nonusers. All categories of PPIs, except rabeprazole, were associated with an increased risk of HE. CONCLUSIONS: Based on an analysis of data from Taiwan National Health Insurance beneficiaries, we found that use of PPIs in patients with cirrhosis increases the risk for HE; risk increases with dose. It therefore is important for health care providers to carefully consider prolonged PPI use by patients with cirrhosis.

Statins decrease the risk of decompensation in hepatitis B virus- and hepatitis C virus-related cirrhosis: A population-based study.

Statin use decreases the risk of decompensation and mortality in patients with cirrhosis due to hepatitis C virus (HCV). Whether this beneficial effect can be extended to cirrhosis in the general population or cirrhosis due to other causes, such as hepatitis B virus (HBV) infection or alcohol, remains unknown. Statin use also decreases the risk of hepatocellular carcinoma (HCC) in patients with chronic HBV and HCV infection. It is unclear whether the effect can be observed in patients with pre-existing cirrhosis. The goal of this study was to determine the effect of statin use on rates of decompensation, mortality, and HCC in HBV-, HCV-, and alcohol-related cirrhosis. Patients with cirrhosis were identified from a representative cohort of Taiwan National Health Insurance beneficiaries from 2000 to 2013. Statin users, defined as having a cumulative defined daily dose (cDDD) ≥28, were selected and served as the case cohort. Statin nonusers (<28 cDDD) were matched through propensity scores. The association between statin use and risk of decompensation, mortality, and HCC were estimated. A total of 1350 patients with cirrhosis were enrolled. Among patients with cirrhosis, statin use decreased the risk of decompensation, mortality, and HCC in a dose-dependent manner (P for trend <0.0001, <0.0001, and 0.009, respectively). Regression analysis revealed a lower risk of decompensation among statin users with cirrhosis due to chronic HBV (adjusted hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.25-0.62) or HCV infection (HR, 0.51; 95% CI, 0.29-0.93). The lowered risk of decompensation was of borderline significance among statin users with alcohol-related cirrhosis (HR, 0.69; 95% CI, 0.45-1.07). CONCLUSION: Statin use decreases the decompensation rate in both HBV- and HCV-related cirrhosis. Of borderline significance is a decreased decompensation rate in alcohol-related cirrhosis. (Hepatology 2017;66:896-907).

Combination of albumin-bilirubin grade and platelets to predict a compensated patient with hepatocellular carcinoma who does not require endoscopic screening for esophageal varices.

BACKGROUNDS AND AIMS: There is no consensus on screening for high-risk esophageal varices (HRV) in patients with hepatocellular carcinoma (HCC). Here, we aimed to investigate the prevalence and risk factors of HRV in patients with HCC and to assess the combination of albumin-bilirubin grade and platelet count (ALBI-PLT score) for predicting compensated patients who do not need unnecessary endoscopic screening for HRV. METHODS: The ALBI-PLT score was calculated by adding the ALBI grade and points for platelet count (1 point if platelet count >150,000/mm3 and 2 points if ≤150,000/mm3). The predictive value of the ALBI-PLT score for HRV was analyzed in 887 compensated patients enrolled from October 2007 to April 2014 (study cohort). This was validated in 215 compensated patients from May 2014 to December 2015 (validation cohort). RESULTS: In the study cohort, the rates of HRV were 2.9% and 21.1% in compensated HCC patients with an ALBI-PLT score of 2 and >2, respectively. The negative predictive values of the ALBI-PLT score for predicting HRV were 97.1% and 98.1% in the study and validation cohorts, respectively. For compensated patients who did not receive endoscopic screening at the time of HCC diagnosis, the 5-year cumulative variceal hemorrhage rate was lower in patients with an ALBI-PLT score of 2 than in those with an ALBI-PLT score >2 (1.7% vs 9.1%, P = .007). CONCLUSION: In patients with HCC with compensated liver function, an ALBI-PLT score of 2 predicted a very low risk of HRV and variceal hemorrhage; therefore, endoscopic screening for esophageal varices is not recommended for these patients.

Second primary malignancy risk among patients with gastric cancer: a nationwide population-based study in Taiwan.

BACKGROUND: Several studies have reported an increase in second primary malignancies (SPMs) among gastric cancer patients. METHODS: Patients who were newly diagnosed with gastric cancer between 1997 and 2011 were recruited from the Taiwan National Health Insurance database. Those who had antecedent malignancies or gastrointestinal stromal tumor were excluded. Standardized incidence ratios (SIRs) of SPMs were calculated. Risk factors for cancer development were analyzed by Cox proportional hazards models. Effects of treatments for gastric cancer were treated as time-dependent variables. RESULTS: During the 15-year study period, 47,729 gastric cancer patients were recruited. Overall, 2,110 SPMs developed during a total follow-up of 137,798 person-years. The SIR for all cancers was 1.46. The SIRs for specific follow-up periods were 1.43, 1.41, and 1.21 at >10 years, 5-10 years, and 1-5 years, respectively. After excluding SPMs that developed within 1 year, significantly higher SIRs were seen for cancers of the head and neck (1.34), esophagus (2.16), colon and rectum (1.37), bones and soft tissues (1.95), ovaries (2.89), bladder (1.47), or kidneys (1.44), as well as non-Hodgkin's lymphoma (5.56). Multivariate analysis showed that age ≥70 years [hazard ratio (HR) 1.19], being male (HR 1.37), diabetes mellitus (HR 1.30), chronic obstructive pulmonary disease (HR 1.17), and liver cirrhosis (HR 1.94) were independent risk factors. Radiotherapy (HR 1.24) and chemotherapy (HR 1.87) were independent risk factors, but surgery (HR 0.67) was not. CONCLUSIONS: Patients with gastric cancer are at increased risk of developing SPM. Close surveillance of patients with risk factors over a longer period should be considered.