Heart rate variability is associated with disease severity and portal hypertension in cirrhosis.

INTRODUCTION: Autonomic nervous system activity in cirrhotic portal hypertension is linked to hyperdynamic circulation. Heart rate variability (HRV) is a validated noninvasive method to assess the sympathovagal balance. To investigate the correlation between HRV parameters and degree of portal hypertension, we studied a cohort of patients with cirrhosis accounting for etiology and treatments. PATIENTS AND METHODS: In this cross-sectional, observational cohort study, 157 outpatients of both sex with nonalcoholic cirrhosis were assessed by upper gastrointestinal endoscopy to search for esophagogastric varices. Twenty-four-hour electrocardiogram Holter monitoring with 3 HRV parameters measurement [SD of the NN intervals, root mean square successive difference of NN intervals, and SD of the averages of NN intervals (SDANN)] according to time-domain analysis were performed in all patients. Sixteen patients with large esophagogastric varices underwent measurements of the HVPG and assessment of HRV parameters at baseline and after 45 days on carvedilol. RESULTS: The liver dysfunction, expressed by Child-Pugh class or MELD score, was directly related to root mean square successive difference of NN intervals and inversely related to SDANN. Presence of ascites was inversely related to SDANN and to SD of the NN intervals. Treatment with carvedilol had an inverse relation with SDANN. Presence and size of esophagogastric varices had an inverse relation to SDANN and SD of the NN intervals. Upon multivariate analysis the associations between SDANN and Child-Pugh class, size of varices and ascites were confirmed. In the subgroup of 16 patients undergoing HVPG measurement, pressure gradient was unrelated to heart rate and HRV parameters. CONCLUSIONS: Time-domain HRV parameters in patients with cirrhosis, confirm the autonomic nervous system alteration, and their correlation to the degree of portal hypertension suggesting a role of the ANS in hepatic decompensation.

RESIST-HCV Criteria to Monitor Progression of Low-Risk Esophageal Varices in Patients With Compensated Cirrhosis After HCV Eradication: The SIMPLE Study: SIMPLE: Scoring Index to Monitor Progression of Low-risk Esophageal varices.

INTRODUCTION: Noninvasive criteria to predict the progression of low-risk esophageal varices (EV) in patients with compensated hepatitis C virus (HCV) cirrhosis after sustained virological response (SVR) by direct-acting antivirals (DAAs) are lacking. Our aim was to assess the diagnostic performance of Rete Sicilia Selezione Terapia-HCV (RESIST-HCV) criteria for EV progression compared with elastography-based criteria (Baveno VI, Expanded Baveno VI, and Baveno VII-HCV criteria). METHODS: All consecutive patients observed at 3 referral centers with compensated HCV cirrhosis with or without F1 EV who achieved sustained virological response by DAAs were classified at last esophagogastroduodenoscopy (EGDS) as RESIST-HCV low risk (i.e., low probability of high-risk varices [HRV]) if platelets were >120 × 10 9 /L and serum albumin >3.6 g/dL or RESIST-HCV high risk (i.e., high probability of HRV) if platelets were <120 × 10 9 /L or serum albumin <3.6 g/dL. The primary outcome was the progression to HRV. The area under the receiver operating characteristic curve and decision curve analysis of noninvasive criteria were calculated. RESULTS: The cohort consisted of 353 patients in Child-Pugh class A (mean age 67.2 years, 53.8% males). During a mean follow-up of 44.2 months, 34 patients (9.6%, 95% CI 6.7%-13.5%) developed HRV. At the last EGDS, 178 patients (50.4%) were RESIST-low risk, and 175 (49.6%) were RESIST-high risk. RESIST-HCV criteria showed the highest area under the receiver operating characteristic curve (0.70, 95% confidence interval 0.65-0.75), correctly sparing the highest number of EGDS (54.3%), with the lowest false-positive rate (45.7%), compared with elastography-based criteria. Decision curve analysis showed that RESIST-HCV had higher clinical utility than elastography-based criteria. DISCUSSION: Biochemical-based RESIST-HCV criteria are useful to easily predict HRV development after HCV eradication by DAAs in patients with compensated cirrhosis and low-risk EV.

Gastrointestinal Bleeding in COVID-19 Patients: A Systematic Review with Meta-Analysis.

The novel coronavirus disease 2019 (COVID-19) has been reported to affect the gastrointestinal system with a variety of symptoms, including bleeding. The prevalence of bleeding in these patients remains unclear. The aim of this meta-analysis is to estimate the rate of gastrointestinal bleeding in COVID-19 patients and its association with mortality. MEDLINE and Embase were searched through December 20, 2020. Studies reporting COVID-19 patients with and without gastrointestinal bleeding were included. Estimated prevalence with 95% confidence intervals (CI) was pooled; heterogeneity was expressed as I 2. Metaregression analysis was performed to assess the impact of confounding covariates. Ten studies met the inclusion criteria and were included in the analysis. A total of 91887 COVID-19 patients were considered, of whom 534 reported gastrointestinal bleeding (0.6%) [409 (76.6%) upper and 121 (22.7%) lower gastrointestinal bleeding (UGIB and LGIB, resp.)]. The overall pooled gastrointestinal bleeding rate was 5% [95% CI 2-8], with high heterogeneity (I 2 99.2%); "small study effect" was observed using the Egger test (p=0.049). After removing two outlier studies, the pooled bleeding rate was 2% [95% CI 0-4], with high heterogeneity (I 2 99.2%), and no "small study effect" (p=0.257). The pooled UGIB rate was 1% (95% CI 0-3, I 2 98.6%, p=0.214), whereas the pooled LGIB rate was 1% (95% CI 0-2, I 2 64.7%, p=0.919). Metaregression analysis showed that overall estimates on gastrointestinal bleeding were affected by studies reporting different sources of bleeding. No significant association between gastrointestinal bleeding and mortality was found. In this meta-analysis of published studies, individuals with COVID-19 were found to be at risk for gastrointestinal bleeding, especially upper gastrointestinal bleeding.