Mac-2-Binding Protein Glycosylation Isomer to Albumin Ratio Predicts Bacterial Infections in Cirrhotic Patients.

INTRODUCTION: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications. METHODS: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes. RESULTS: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p < 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival. DISCUSSION/CONCLUSION: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections.

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.

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.

Triage policy to postpone endoscopy for patients with low-risk varices is safe during the lockdown period of COVID-19 pandemic.

BACKGROUND & AIMS: During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended. We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic. METHODS: Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. One experienced gastroenterologist reviewed the prior-scheduled list of patients for the EVL prophylaxisprogram. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020. RESULTS: Of the 124 patients receiving EVL, a higher percentage of esophageal variceal bleeding (EVB) was noted (9/32, 28.1% vs. 8/92, 8.7%, p = 0.006) during the lockdown period, with a higher percentage of EVB in the referrals (7/9, 77.8% vs. 2/14, 14.2%, p = 0.007). Among patients who received prophylactic EVL, 6 of 78 (7.7%) experienced EVB during the normal period, which is no different to 2 of 23 (8.7%) during the lockdown period. Twenty-three patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB during the lockdown period. Child-Turcotte-Pugh (CTP) class C was predictive of EVB (relative risk 8.400, P = 0.033), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.016, P = 0.002). CONCLUSION: Entrance into the prophylaxis program does not only decreases risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period.

Antiperistaltic effect and safety of L-menthol for esophagogastroduodenoscopy in the elderly with contraindication to hyoscine-N-butylbromide.

Hyoscine-N-butylbromide (HBB) is the most used antiperistaltic agent during esophagogastroduodenoscopy (EGD). However, almost half of the elderly have a contraindication to HBB. We aimed to evaluate L-menthol's antiperistaltic effect and safety for EGD in the elderly with contraindication to HBB. This prospective, randomized, double-blind, placebo-controlled study screened 86 elderly patients (≥ 65 years old) scheduled to undergo EGD, and 52 of them with contraindication to HBB were enrolled. The participants were randomized to receive L-menthol (n = 26) or a placebo (n = 26), which was locally sprayed on the gastric antrum endoscopically. The proportion of patients with no or mild peristalsis after medication and at the end of EGD was significantly higher in the L-menthol group (76.9%) than in the placebo group (11.5%, p < 0.001). L-Menthol administration significantly reduced peristaltic grade, improved contraction parameters, and eased intragastric examination relative to the placebo (p < 0.001, respectively). Hemodynamic changes, adverse events, and discomfort levels of patients were similar between the two groups. L-Menthol is an effective and safe alternative antiperistaltic medication for EGD in elderly patients with contraindication to HBB. Further large, randomized trials are required to clarify whether L-menthol can lead to better detection yield in the elderly.Clinical trial registration: The study was registered at ClinicalTrials.gov (NCT04593836).

Comparison of prognoses between cirrhotic and noncirrhotic patients with hepatocellular carcinoma and esophageal varices undergoing surgical resection.

BACKGROUND: Esophageal varices (EV) is common and is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). However, the outcomes between cirrhotic and noncirrhotic HCC patients with EV is not well studied. The present study aimed to investigate the clinical manifestations and prognoses of HCC patients after surgical resection stratified by the cirrhosis status. METHODS: A total of 111 patients with HCC and EV, who underwent surgical resection, were retrospectively enrolled between July 2003 and July 2019. The diagnosis of liver cirrhosis was established using the Ishak fibrosis score F5 or F6 in the nontumor part of liver specimens. Prognostic factors were analyzed using the Cox proportional hazards model. RESULTS: There were 85 (76.6%) and 26 (23.4%) patients with and without cirrhosis, respectively. Compared with those without cirrhosis, there were more females, less seropositive rate of hepatitis B surface antigen (HBsAg), more seropositive rate of antibody against to hepatitis C virus (HCV), less albumin-bilirubin (ALBI) grade 1, lower platelet count, and more had tumor burden within the Milan criteria in cirrhotic patients. Cirrhotic patients had a higher risk of posthepatectomy decompensation compared to noncirrhotic patients (hazard ratio 9.577, p = 0.017). No difference was observed in overall survival and recurrence-free survival between patients with or without cirrhosis. CONCLUSION: Compared with patients without cirrhosis, cirrhotic patients with HCC and EV are vulnerable to posthepatectomy decompensation. However, cirrhosis is not a poor prognostic factor of overall survival and recurrence for HCC patients after surgical resection.

The clinical significance of esophagogastric varices in patients with advanced pancreatic cancer.

BACKGROUND: The prevalence of esophagogastric varices (EGV) in patients with advanced pancreatic cancer is not rare. However, its clinical significance has never been investigated. This study was aimed to explore the clinical implication and outcomes of these patients. METHODS: A retrospective analysis comprising 224 patients with advanced pancreatic cancer managed from October 2012 to December 2019 at a tertiary medical center identified 35 patients who had presented with EGV. Clinical characteristics and outcomes were analyzed with special emphasis on comparison between patients with early-onset and late-onset EGV. RESULTS: Patients with EGV had lower platelet count and a higher proportion of splenomegaly but no difference in overall survival in comparison to those without EGV. Patients with early-onset EGV had a poorer bleeding survival (hazard ratio, 8.347; CI, 2.509-27.772; p = 0.001) in comparison to those with late-onset EGV. On multivariate analysis, initial serum bilirubin, γ-Glutamyltransferase, lactate dehydrogenase, cancer stage, and the response to cancer treatment determine the patient's survival. Patients with tumor invasion to superior mesenteric and portal vein are more likely to have esophageal varices (EV) (EV: 13/15 vs gastric varices [GV]: 4/20; p < 0.001); those with splenic vein invasion are more likely to have GV (EV: 4/15 vs GV: 20/20; p < 0.001). CONCLUSION: Patients with advanced pancreatic cancer and early-onset EGV had poorer bleeding-free survival than those with late-onset EGV. Further studies are needed to clarify the benefits of the prophylactic intervention.

Prophylactic clipping after endoscopic mucosal resection of large nonpedunculated colorectal lesions: A meta-analysis.

BACKGROUND AND AIM: It is not clear whether prophylactic clipping after endoscopic mucosal resection (EMR) of large nonpedunculated colorectal lesions (LNPCLs) prevents delayed bleeding (DB). We aimed to conduct a meta-analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs. METHODS: We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, and ClinicalTrials.gov for studies that compared clipping versus (vs) nonclipping in prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled ORs of DB, perforation, and post-polypectomy syndrome in the clipping group compared with the nonclipping group comprised the outcomes. Subgroup analyses based on study design, polyp location, and completeness of wound closure were performed. RESULTS: Five studies with a total of 3112 LNPCLs were extracted. Prophylactic clipping reduced the risk of DB compared with nonclipping (3.3% vs 6.2%, OR: 0.494, P = 0.002) following EMR of LNPCLs. In subgroup analysis, prophylactic clipping reduced DB of LNPCLs at proximal location (3.8% vs 9.8%, P = 0.029), but not of them at distal location (P = 0.830). Complete wound closure showed superior efficacy to prevent DB compared with partial closure (2.0% vs 5.4%, P = 0.004). No benefit of clipping for preventing perforation or post-polypectomy syndrome was observed (P = 0.301 and 0.988, respectively). CONCLUSIONS: Prophylactic clipping can reduce DB following EMR of LNPCLs at proximal location. Besides, complete wound closure showed superior efficacy to prevent DB compared with partial closure. Further cost analyses should be conducted to implement the most cost-effective strategies.

Magnifying endoscopy with narrow-band image for diagnosing diffuse type of gastric antral vascular ectasia in cirrhotic patients.

OBJECTIVE: Gastric antral vascular ectasia (GAVE) and portal hypertensive gastropathy (PHG) can cause gastrointestinal bleeding in cirrhotic patients. Distinguishing diffuse-type GAVE and severe PHG is important but difficult by conventional endoscopy and endoscopic biopsy. The aim of this study is to evaluate the value of magnifying endoscopy with narrow-band image for diagnosing diffuse-type GAVE in cirrhotic patients. METHODS: From January 2010 to December 2013, cirrhotic patients with diffuse red spots of stomach in suspicion of diffuse-type GAVE on conventional endoscopy in a tertiary medical center were included. The detection of diffuse red spots on magnifying endoscopy with narrow-band image (NBI) was classified into ring-pattern which suggested GAVE and mosaic-pattern which suggested non-GAVE. The golden diagnosis of GAVE was based on histological criteria of GAVE score ≥3 by any one of two endoscopic sessions. RESULTS: Total 27 cirrhotic patients were included. Twenty-two patients reached the diagnosis of GAVE and five patients were diagnosed of non-GAVE by histology. The diagnostic rate of conventional endoscopy was 81.5% (22/27). The positive rate of initial endoscopic biopsy was 77.2%. On magnifying endoscopy with NBI, the sensitivity, specificity, positive, negative predicted rate and accuracy of ring-pattern for the diagnosis of GAVE were 100, 90, 96.4, 100 and 97.3%. Kappa coefficient of inter-observer agreement for differentiating the ring and mosaic-pattern was 0.92. CONCLUSIONS: The efficacy and accuracy of magnifying endoscopy with NBI for diagnosing diffuse-type GAVE in cirrhotic patients have been demonstrated. It can avoid repeated endoscopy to confirm diagnosis and obviate the invasive biopsy in cirrhotic patients.

The indocyanine green retention test as a noninvasive marker for esophageal varices in patients with hepatocellular carcinoma.

BACKGROUND: The indocyanine green 15-minute retention (ICG-r15) test was considered as a noninvasive marker of esophageal varices (EV) in cirrhotic patients. However, the performance of ICG-r15 in patients with hepatocellular carcinoma (HCC) has rarely been assessed. The aim of this study is to evaluate the value of ICG-r15 as a noninvasive marker of EV in patients with HCC. METHODS: From October 2007 to December 2018, the study retrospectively enrolled 137 HCC patients with compensated hepatic function who received ICG-r15 tests and endoscopy screening for EV. The predictive value of the ICG-r15 test and other noninvasive markers was also evaluated for the diagnosis of EV, including the aspartate aminotransferase (AST)/alanine aminotransferase ratio, platelet count/spleen diameter ratio, AST/platelet ratio index, Lok index, FIB-4, and Park index. RESULTS: In the study cohort, 30 (21.9%) patients had EV. The area under the receiver operating characteristic curve for determining EV by ICG-r15 was 0.784 (95% CI: 0.686-0.881, -2 ln (L): 77.889, Akaike information criterion: 79.889), and it had the best predictive value compared with other noninvasive markers. The cutoff value of ICG-r15 to identify EV was 31.0%, and it had 40.0% sensitivity and 98.1% specificity. The cutoff value to exclude EV was 9.5% with 86.7% sensitivity and 50.5% specificity. In the multivariate analysis, ICG-r15 (odds ratio [OR]: 1.062, 1.014-1.114; p = 0.015) and the Park index (OR: 1.535, 1.091-2.159; p = 0.014) were independently related to the presence of EV. CONCLUSION: ICG-r15 is a practical noninvasive marker with cutoff values of 9.5% for excluding EV and 31.0% for identifying EV in patients with HCC.

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.

Selective serotonin reuptake inhibitors and the risk of hepatocellular carcinoma in hepatitis B virus-infected patients.

BACKGROUND: This study aimed to investigate the association between the use of selective serotonin reuptake inhibitors (SSRIs) and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection. METHODS: We conducted a population-based cohort study by using claims data from the Taiwan National Health Insurance Research Database (NHIRD). The study cohort comprised 1380 newly diagnosed HBV-infected patients with SSRI use who were frequency matched by age, sex, liver cirrhosis, and index year with HBV-infected patients without SSRI use in the comparison cohort. Each patient case was followed from 2000 to 2012 to identify incident HCC cases. Cox proportional hazards regression was performed to evaluate the association between SSRI use and HCC risk. The further sensitivity analysis used case-control study design. A total of 9070 HCC subjects retrieved from NHIRD, and equal non-HCC subjects were analyzed after matching for age and sex. RESULTS: We identified 9 and 24 HCC cases in the study and comparison cohorts during the follow-up period of 7056 and 6845 person-years, respectively. The incidence rate of HCC was 1.28 and 3.51 per 1000 person-years for SSRI and non-SSRI users, respectively. After adjusting for potential confounders, the adjusted hazard ratio (HR) for SSRI use was 0.28 (95% confidence interval [CI], 0.12-0.64; p = 0.0027). For SSRI users with a cumulative defined daily dose (cDDD) of 28-89, 90-364, and ≥365, the adjusted HRs were 0.51, 0.22, and 0.12, respectively, (95% CI, 0.21-1.25, 0.05-0.94, and 0.02-0.90, respectively) compared with non-SSRI users (<28 cDDD). The sensitivity analysis showed that the SSRI presented with a dose-response protective effect for HCC in the multivariate analysis. CONCLUSION: SSRIs use may possibly reduce the risk of HCC in HBV-infected patients in a dose-responsive manner.

Low air temperature increases the risk of oesophageal variceal bleeding: a population and hospital-based case-crossover study in Taiwan.

BACKGROUND & AIMS: Studies concerning seasonal variations and the impact of air temperature on oesophageal variceal bleeding have yielded conflicting results. We aimed to explore the impact of air temperature on the occurrence of variceal bleeding. METHODS: A case-crossover study design was employed, and two cohorts were used, including the NHI-EVB cohort from the National Health Insurance Research Database of Taiwan from 1 January 1999 to 31 December 2010, and the VGH-EVB cohort from the Taipei Veterans General Hospital, from 4 May 2002 to 31 December 2010. A conditional logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In total, 2542 cases from the NHI-EVB cohort and 220 cases from the VGH-EVB cohort were analysed. Our analysis showed that low air temperature (LAT) increased the risk of variceal bleeding regardless of age, sex, decompensated cirrhosis, Child-Pugh classification, aetiology of liver disease and concomitant hepatocellular carcinoma; the lag effect was also observed. The ORs per 5°C decrease in daily mean air temperature were 1.144 (95% CI, 1.060-1.235) for the NHI-EVB cohort and 1.307 (95% CI: 1.031-1.658) for the VGH-EVB cohort. Oesophageal variceal bleeding in patients with small varices, end-stage liver disease score ≧15 or those using non-selective beta blockers was not influenced by air temperature. CONCLUSIONS: Patients have higher risk of oesophageal variceal bleeding at low air temperature regardless of age, sex, aetiology of cirrhosis, Child-Pugh classification, decompensated cirrhosis and concomitant hepatocellular carcinoma and can be protected by use non-selective beta blockers.

Clinical Outcomes and Complications of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasms in the Elderly.

The number of elderly people with superficial gastric neoplasms is increasing, but the clinical outcome of endoscopic submucosal dissection (ESD) for treating elderly people with superficial gastric neoplasms remains unclear. We aimed to compare the efficacy and safety of ESD for patients with early gastric cancer (EGC) and precancerous lesions in elderly (≥75 years of age) and nonelderly (<75 years of age) patients.From October 2005 to December 2014, 83 consecutive patients with EGC and precancerous lesions (86 lesions) who were treated using ESD in our hospital were retrospectively reviewed. There were 44 lesions in 42 elderly patients who were at least 75-years old. The following parameters were compared between the 2 groups: preexisting comorbidities, performance status (PS), lesion inclusion criteria, lesion characteristics, treatment outcomes, surgery time, duration of hospitalization, complications, and intraoperative hemodynamic changes.Elderly patients had significantly higher preexisting comorbidity rates (90.9% vs 59.5%, P = 0.001), expanded lesion criteria rates (43.2% vs 19.0%, P = 0.016), and lower best PS rates (38.6% vs 81.0%, P < 0.001) than nonelderly patients. Lesion characteristics were similar in the 2 groups. The elderly had higher intraoperative hypotension rates (47.7% vs 21.4%, P = 0.011) and oxygen desaturation rates (9.1% vs 0.0%, P = 0.045) than nonelderly patients. In addition, the elderly also had a longer surgery time (107.0 ±â€Š51.4 vs 91.5 ±â€Š66.2 minutes, P = 0.049) and duration of hospitalization (7.5 ±â€Š3.8 vs 5.9 ±â€Š2.0 days, P = 0.016) than nonelderly patients. There were no differences in the prevalence rates of en-bloc resection, complete resection, bleeding, perforation, pneumonia, or intraabdominal free air between the 2 groups.Although elderly patients who underwent ESD for superficial gastric neoplasms had an increasing risk of intraoperative hypotension and oxygen desaturation, all patients were treated appropriately without postoperative sequelae. ESD is a safe and feasible intervention for elderly patients who have more comorbidity, a worse PS and more expanded lesions.