Baveno VI criteria as a prognostic factor for clinical complications in patients with compensated cirrhosis

BackgroundCombination of liver stiffness measurement and platelets count is a tool to safely rule out varices needing treatment (VNT) in patients with compensated advanced chronic liver disease (cACLD). Aims: to evaluate 4-year liver-related complications and survival in low-risk patients according to Baveno VI criteria.Methodswe conducted a monocentric retrospective analysis of prospectively collected data of all consecutive patients, with cirrhosis (LSM≥12.5 kPa) and without previous complication, evaluated between 2012 and 2015. Liver-related complications and survival were compared between 2 groups of patients: favourable (LSM< 20 kPa and platelet count>150.000/mm3) and unfavourable Baveno VI status patients (LSM ≥ 20 kPa or platelet count ≤150.000/mm3).Results455 patients with cACLD were analysed. Two hundred patients had favourable Baveno VI criteria, 3.6% with VNT. The 4-year probability of being free of acute decompensation was higher in low-risk patients (94.4 ± 1.8% vs. 85.7%±2.6%, p = 0.018). Unfavourable Baveno status was independently associated with acute decompensation. The probability of being free of HCC was significantly higher in low-risk patients (94.2 ± 1.8% vs. 87.6 ± 2.4%, p = 0.048). Liver-related mortality was not different between the 2 groups (p = 0.56).ConclusionThe Baveno VI criteria could predict clinical outcome in cACLD.     

Prognosis Comparison Between Chronic Hepatitis B Patients Receiving a Finite Course of Tenofovir and Entecavir Treatment: A Nationwide Cohort Study in Taiwan

PurposeEntecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both recommended as first-line treatments for patients with chronic hepatitis B virus (CHB) infection according to international HBV treatment guidelines. However, recent studies reported conflicting results regarding the preferred antiviral in the prevention of hepatocellular carcinoma (HCC). This cohort study aimed to investigate this issue by using Taiwan's National Health Insurance Research Database, wherein a “finite” but not life-long treatment policy was applied.MethodsFrom January 2008 to December 2013, a total of 12,388 consecutive adult patients with CHB who received a finite course of TDF treatment (n = 1250) or ETV treatment (n = 11,138) were analyzed through screening for study eligibility followed by the 1:4 propensity score matching method.FindingsIn the entire cohort, the annual incidence and survival between the ETV and TDF groups were not significantly different regarding HCC occurrence (2.05 vs 2.74 per 100 patient-years [PY]; P = 0.055; hazard ratio [HR], 0.975; log-rank, P = 0.966), cirrhosis-related complications (1.9 vs 2.4 per 100 PY; P = 0.149; HR, 0.869; log-rank, P = 0.388), or all-cause mortality (2.16 vs 1.6 per 100 PY; P = 0.119; HR, 0.831; log-rank, P = 0.342), respectively. Propensity score matching analyses yielded similar results regarding HCC occurrence, cirrhosis-related complications, and all-cause mortality. In addition, these findings were consistently reproduced in the subgroups of patients with chronic hepatitis and cirrhosis that developed before antiviral treatment.ImplicationsETV and TDF did not significantly differ in prevention of HCC occurrence or reduction of cirrhosis-related complications and all-cause mortality in patients with CHB receiving a finite period of treatment.     

Progression of retinopathy with glucagon-like peptide-1 receptor agonists with cardiovascular benefits in type 2 diabetes – A systematic review and meta-analysis

AimsThe effect of Glucagon-like peptide 1 receptor agonists (GLP1 RA) on diabetic retinopathy (DR) remains controversial. Previous reviews combined data from randomized clinical trials (RCTs) with or without cardiovascular (CV) benefits and did not address confounders, therefore may have generated misleading results. The study aimed to examine the effect of GLP1RA on DR in type 2 diabetes (T2DM) in RCTs with or without CV benefits and distinguish the effect by major confounders.MethodsWe conducted electronic searches of multiple databases and a manual search using references lists. We included 13 RCTs examining the effect of GLP1 RA on health outcomes/adverse events including DR or DR complications in T2DM. We performed a random-effects model meta-analysis.ResultsGLP1RA was associated with an elevated risk of rapidly worsening DR in four major RCTs with CV benefits in T2DM (OR 1.23, 95 % CI 1.05–1.44). The association between GLP1 RA and DR was significant in subgroups of RCTs with length over 52 weeks (1.2, 1.00–1.43), using placebo as a comparator (1.22, 1.05–1.42). In subgroups with patients who had T2DM ≥10 years (1.19, 0.99–1.42) or with subjects enrolled from multiple countries (1.2, 0.99–1.46), the association appeared to be evident but did not reach statistical significance.ConclusionsGLP1 RA including liraglutide, semaglutide, and dulaglutide are associated with an increased risk of rapidly worsening DR in RCTs with CV benefits. Further data from clinical studies with longer follow-up purposefully designed for DR risk assessment, particularly including patients of established DR are warranted.     

Performance of risk prediction models for post-operative mortality in patients undergoing liver resection

BackgroundLiver resection is commonly performed for hepatic tumors, however preoperative risk stratification remains challenging. We evaluated the performance of contemporary prediction models for short-term mortality after liver resection in patients with and without cirrhosis.MethodsThis retrospective cohort study examined National Surgical Quality Improvement Program data. We included patients who underwent liver resections from 2014 to 2019. VOCAL-Penn, MELD, MELD-Na, ALBI, and Mayo risk scores were evaluated in terms of model discrimination and calibration for 30-day post-operative mortality.ResultsA total 15,198 patients underwent liver resection, of whom 249 (1.6%) experienced 30-day post-operative mortality. The VOCAL-Penn score had the highest discrimination (area under the ROC curve [AUC] 0.74) compared to all other models. The VOCAL-Penn score similarly outperformed other models in patients with (AUC 0.70) and without (AUC 0.74) cirrhosis.ConclusionThe VOCAL-Penn score demonstrated superior predictive performance for 30-day post-operative mortality after liver resection as compared to existing clinical standards.     

Plectin ensures intestinal epithelial integrity and protects colon against colitis

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; Ple^ΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the Ple^ΔIEC colon.