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.

Sarcopenia-related gut microbial changes are associated with the risk of complications in people with cirrhosis.

Background & Aims: Sarcopenia and gut dysbiosis are common in individuals with cirrhosis. However, the association between sarcopenia and microbial alterations, and the subsequent impact on cirrhotic outcomes are poorly understood. This study aimed to identify muscle-dependent microbial changes and related risks of cirrhotic complications. Methods: From September 2018 to December 2020, 89 individuals with cirrhosis and 16 healthy volunteers were prospectively enrolled. Muscle and nutritional status, serum amino acids, and fecal microbiota were analyzed. The association between microbial signatures of sarcopenia and cirrhotic complications was investigated. Results: A decline in muscle mass and strength were associated with gut microbial alterations in individuals with cirrhosis. The greatest microbial dissimilarity was observed between those with sarcopenia (both decline in muscle mass and strength) and those with normal-muscle status (p = 0.035). Individuals with sarcopenia had lower serum levels of alanine, valine, leucine, isoleucine, proline, tryptophan and ornithine. Besides, gut microbial functions associated with amino acid biosynthesis were significantly reduced in individuals with sarcopenia and cirrhosis. Depletion of Dialister, Ruminococcus 2, and Anaerostipes were associated with cirrhotic sarcopenia, and significantly correlated with the serum levels of amino acids. Individuals with coexistent depletion of Ruminococcus 2 and Anaerostipes developed more infectious (44.4% vs. 3.0%) and non-infectious (74.1% vs. 3.0%) complications, and more hospitalizations (54 vs. 3) than those with cirrhosis with good microbial signatures (all p <0.001). In contrast, fecal enrichment of Ruminococcus 2 and Anaerostipes independently decreased the risk of 1-year complications. Conclusions: Sarcopenia-related fecal microbial alterations are associated with cirrhotic complications. These findings may facilitate measures to improve the outcomes of individuals with cirrhosis and sarcopenia by modifying gut microbiota. Impact and implications: The composition and biosynthetic functions of gut microbiota are significantly changed in individuals with sarcopenic cirrhosis. Those with a sarcopenia-related poor microbial signature, in which Ruminococcus 2 and Anaerostipes were both depleted, had significantly more infectious and non-infectious complications, as well as more hospitalizations. These findings highlight the therapeutic potential of modifying the gut microbiota of individuals with sarcopenic cirrhosis to improve their clinical outcomes.

The risk of variceal bleeding during endoscopic retrograde cholangiopancreatography.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely performed procedure. However, the risk of variceal bleeding during ERCP has rarely been assessed. This study aims to evaluate the risk of variceal bleeding in patients with esophageal varices (EV) undergoing ERCP. METHODS: From October 2010 to November 2017, the study retrospectively enrolled 75 cirrhotic patients who received elective ERCP. The patient's risk of gastrointestinal (GI) and variceal bleeding and other procedure-related adverse events within 30 days of ERCP were evaluated. RESULTS: Among the 75 patients, 45 patients (60.0%) had EV. Most of the patients were males (65.3%), and there were high rates of viral hepatitis B-related cirrhosis (36.0%), Child-Pugh B (49.3%), and an indication of choledocholithiasis (40.0%). Thirty-three of 45 (73.3%) patients had high-risk EV, and nine (20.0%) patients had concomitant gastric varices. There was no esophageal variceal bleeding; however, one patient had gastric variceal bleeding after ERCP. Nonvariceal significant GI bleeding occurred in three patients with EV and one without EV ( p = 0.529). Post-ERCP pancreatitis occurred in three patients with EV and five without EV ( p = 0.169). No perforation or procedure-associated mortality was noted. CONCLUSION: The risk of esophageal variceal bleeding within 30 days of ERCP is neglectable, except for a patient who suffered from gastric variceal bleeding. Other complications, such as nonvariceal bleeding and pancreatitis, are also no higher in patients with EV. Therefore, ERCP is generally a safe procedure for a patient with high-risk esophageal varices.

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.

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.