The Long-Term Effect of Weight Loss on the Prevention of Progression to Cirrhosis among Patients with Obesity and MASH-Related F3 Liver Fibrosis.

This multi-center retrospective study examined the effect of weight loss on the prevention of progression to cirrhosis in a sample exclusively composed of patients with obesity and MASH-related F3 liver fibrosis. Adult patients with obesity and biopsy-confirmed MASH-related F3 liver fibrosis (n = 101) from two liver transplant centers in the US were included in the study. A higher proportion of patients who did not progress to cirrhosis achieved >5% weight loss at follow-up (59% vs. 30%, p = 0.045). In multivariable analysis, patients with >5% weight loss at follow-up had a lower hazard of developing cirrhosis compared to patients with no weight loss or weight gain (HR: 0.29, 95%, CI: 0.08-0.96); whereas, diabetes (HR: 3.24, 95%, CI: 1.21-8.67) and higher LDL levels (HR: 1.02, 95%, CI: 1.01-1.04) were associated with higher hazards of progression to cirrhosis. Weight loss >5% has the potential to prevent disease progression to cirrhosis in patients with obesity and MASH-related F3 liver fibrosis. The realization of this benefit requires weight loss maintenance longer than one year. Larger prospective studies are needed to determine how weight loss impacts other patient-centered outcomes such as mortality, hepatic decompensation, and hepatocellular carcinoma in patients with obesity and MASH-related F3 liver fibrosis.

Predictors of inpatient outcomes of COVID-19 infection in patients with cirrhosis in the early pandemic phase: A nationwide survey.

Background and Aim: Previous studies conducted at single centers have suggested that patients with cirrhosis are at a greater risk for worse outcomes with COVID-19. However, there is limited data on a national level in the United States. We aimed to study hospital-related outcomes and identify the predictors of poor outcomes in patients with cirrhosis and concurrent COVID-19. Methods: We queried 2020 National Inpatient and Readmission databases to identify all hospitalizations due to cirrhosis in adults with a diagnosis of COVID-19. Primary outcomes included inpatient mortality, mechanical ventilation (MV), and intensive care unit (ICU) utilization. Secondary outcomes included mean length of stay (LOS) and mean hospitalization costs. We classified cirrhosis into compensated (CC) and decompensated (DC) groups. Results: We identified 25194 hospitalizations of adult patients due to cirrhosis with a concurrent diagnosis of COVID-19. These patients had higher mortality (19.50% vs 6.19%, P ≤ 0.01), MV (11.7% vs 2.8%, P ≤ 0.01), ICU utilization (17.3% vs 8.1%, P ≤ 0.01), LOS (8.89 days vs 6.16 days, P ≤ 0.01), and total hospitalization costs ($24 817 vs $18 505, P ≤ 0.01) than those without COVID-19. On subgroup analysis, patients in the DC group had higher mortality, LOS, and hospitalization costs compared to those in the CC group. On multivariate analysis, we also found that COVID-19 infection, age, Charlson Comorbidity Index ≥3, acute kidney injury, end-stage renal disease, septic shock, acute respiratory failure, MV, and ICU status were independent predictors for mortality. Conclusion: Our study suggests that COVID-19 infection is an independent predictor of mortality in patients with cirrhosis, with threefold higher mortality and increased resource utilization. Early intervention through immunizations and advanced COVID-19 therapies can help improve these outcomes.

Evidence-based approach to management of hepatic encephalopathy in adults.

Hepatic encephalopathy (HE) is a reversible syndrome of impaired brain function and represents one of the many complications of portal hypertension and decompensated liver disease. Although ammonia is clearly implicated in the pathogenesis of HE, the pathogenesis of HE is multifactorial with numerous mechanisms that results in functional impairment of neuronal cells. The initial management of HE focuses on supportive care and stabilization which includes providing appropriate nutritional support. Thereafter, focus should be on identifying and treating the precipitating factors. There are many therapeutic agents available for the management of HE, most of which are directed towards lowering the gut nitrogen load and thus the serum ammonia level. This review aims to provide an update on the conventional and emerging treatment options for HE.

A Blueprint for Success: Implementation of the Center for Medicare and Medicaid Services Mandated Anesthesiology Oversight for Procedural Sedation in a Large Health System.

In 2009, the Center for Medicare and Medicaid Services (CMS) issued the §482.52 Condition of Participation (CoP) that the director of anesthesia services (DAS) is responsible for all anesthesia administered in the hospital, including moderate and deep procedural sedation provided by nonanesthesiologists. Although this mandate was issued several years ago, many anesthesiology departments remain uncertain as to how best to implement it, who needs to be involved, what resources are needed, and how to leverage this oversight to improve quality of care and patient safety. This article reviews the CMS CoP interpretive guidelines and other regulations as they relate to procedural sedation, outlines the components and benefits of anesthesiology oversight, and describes the tools and structure to implement these guidelines. In addition, we discuss some of the challenges surrounding this implementation. This initiative continues to evolve and expand as needs change and experience develops.

Polyethylene glycol versus lactulose in the treatment of hepatic encephalopathy: a systematic review and meta-analysis.

BACKGROUND: Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators. METHODS: We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE. RESULTS: Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG. CONCLUSION: PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial.

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of 91 days, overall survival (OS) was assessed by using a Kaplan-Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent-to-treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380-393 2018 AASLD.

The role of gastric and duodenal agents in laryngeal injury: an experimental canine model.

BACKGROUND AND AIMS: The specific agents responsible for producing laryngeal signs and symptoms are currently unknown. We systematically evaluated the damaging role of gastric (acid and pepsin) and duodenal (bile acids and trypsin) ingredients individually and in combination on different laryngeal structures in an experimental canine model. METHODS: A total of 42 beagles were studied (wt 9-15 kg each). After pentathol anesthesia all dogs underwent laryngoscopy. Injury (punch biopsy) was caused to the right vocal cord, medial arytenoid wall, and posterior cricoid wall on day 1. Pepsin (0.5 mg/ml), conjugated bile acid (CBA) (ursodeoxycholic acid, 300 micromolar), unconjugated bile acids (UBA) (cholic, 300 micromolar), trypsin (0.5 mg/ml) at pH 1-2, 4-5, and 6-7 were applied bilaterally to laryngeal sites three times per week for a total of 9-12 applications. Changes in laryngeal sites were scored visually. All dogs were sacrificed 1 day post last application. Laryngeal tissue was harvested and sent for blinded pathological examination. Histologic and visual scores were compared to each other and to control- and sham-treated dogs. RESULTS: Pepsin alone (8.5 +/- 1.66) or combined with CBA (16.63 +/- 1.66) at pH 1-2 resulted in significant (p < 0.001) severe histological inflammation much greater than with other agents. Duodenal ingredients caused no or minimal degree of histological damage at all pH values. Visual scores above subtle erythema were significantly (p < 0.001) higher in the animals exposed to pepsin followed by CBA alone or in combination with pepsin at pH 1-2. There was a significant (p < 0.01) correlation between histology and visual scores (rho = 0.47; 95% CI = 0.30-0.60) for all sites combined. Of the three laryngeal sites, vocal cords were the most sensitive to injury by applied solutions. CONCLUSIONS: (i) In acidic refluxate, pepsin and CBAs are the most injurious agents affecting laryngeal tissue. (ii) Duodenal agents do not play a significant role in causing laryngeal injury. (iii) Aggressive acid suppression should eliminate the injurious potential of any gastroduodenal refluxate.

Twenty-four hour ambulatory simultaneous impedance and pH monitoring: a multicenter report of normal values from 60 healthy volunteers.

OBJECTIVES: Impedance monitoring is a new diagnostic method for gastroesophageal reflux disease (GERD) where multiple impedance electrode pairs are placed on a standard pH catheter. It detects reflux of a liquid and/or gas bolus into the esophagus, as well as its distribution, composition, and clearing. The aim of this collaborative study is to define normal values for 24-h ambulatory simultaneous impedance and pH monitoring (24-h Imp-pH), and compare bolus parameters by impedance monitoring to changes in [H(+)] measured by pH monitoring. METHODS: Sixty normal volunteers without GER symptoms underwent 24-h Imp-pH with impedance measured at six sites (centered at 3, 5, 7, 9, 15, and 17 cm above lower esophageal sphincter) and pH 5 cm above the LES. Reflux detected by impedance was characterized by the pH probe as either acid, weakly acidic, nonacid, or superimposed acid reflux. Proximal reflux was defined as reflux that reached the impedance site 15 cm above the LES. RESULTS: Reflux frequency was common upright (median-27, 25th and 75th quartile-16, 42), but rare recumbent (median-1; 0, 4). A median of 34% (14%, 49%) of upright reflux reached the proximal esophagus. There was a similar number of mixed composition (liquid + gas; 49%) and liquid-only reflux (51%). Acid reflux was two-fold more common than weakly acidic reflux (p < 0.001). Superimposed acid reflux and nonacid reflux were rare. Acid neutralization to pH 4 took twice as long as volume clearance measured by impedance. CONCLUSIONS: Combining impedance and pH monitoring improves the detection and characterization of GER. This study characterizes the frequency, duration, and extent of reflux in health and provides normal values for 24-h Imp-pH for future comparison with GERD patients.