Introduction

Non-alcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver disease, ranging from simple steatosis to steatohepatitis, advanced fibrosis and liver cirrhosis, with histological features of alcohol induced liver disease. Despite the high morbidity and mortality burden of NAFLD, no definite treatment is established yet. Lifestyle modifications are one of the most valued measures for NAFLD amelioration. A lot of dietary regimens have been recommended with pro-ved weight loss, inflammation reduction, along with improved cardiovascular and metabolic markers. Many regimens have been suggested for NAFLD patients: caloric restriction, low carbohydrate high fat diet, or intermittent fasting diets (IF). Notably, in IF people are allowed to eat for a restricted time and abstain food and caloric fluids for another time. Remarkably, IF is capable of reversal of insulin resistance, leading to marvelous achievements in most resistant cases. Accordingly, IF is one of the most promising regimens suggested for improving the unhealthy NAFLD parameters. Being an Islamic pillar, Ramadan fasting (RF) might also be considered as a form of dry intermittent fasting. Despite the reported deleterious impacts of fasting on liver cirrhosis, fruitfully IF had been suggested to improve NAFLD patients.

Aims & Methods

Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients.
Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases).

Results

Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01).

Conclusion

Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

References

Badran H, Elsabaawy M, Sakr A, Eltahawy M, Elsayed M, Elsabaawy DM, Abdelkreem M. Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients. Clin Exp Hepatol. 2022 Jun;8(2):118-124. doi: 10.5114/ceh.2022.115056. Epub 2022 May 30. PMID: 36092752; PMCID: PMC9442655.

Pubmed:
https://pubmed.ncbi.nlm.nih.gov/36092752/

Disclosure

No conflict of interest.

Introduction

Long-term maintenance treatment efficacy, safety and tolerability in eosinophilic esophagitis (EoE) is still partially understood. The aim of this study was to evaluate long-term outcomes of maintenance treatment for EoE with various drugs and dose regimens in real-world observational studies and randomized controlled trials (RCTs).

Aims & Methods

Systematic search was performed on Pubmed-MEDLINE, Embase and Cochrane Central Register of Controlled Trials from inception to October 2023. Studies reporting histologic success of maintenance therapy for EoE patients > 48 weeks, following 8-12 weeks of induction therapy with the same drug were included. Primary outcome was pooled histologic success (defined as < 15 eosinophils/HPF) at the end of follow-up for both study designs. Risk Difference (RD) or Odds Ratio (ORs) for histological success of maintenance therapy versus placebo (PBO) (for RCTs) and versus induction (for both study designs), pooled drug-related adverse events (AEs), endoscopic and clinical success rates were assessed as secondary outcomes. Random effects model metanalyses were performed. A-priori sub-group analyses were performed to address substantial inter-study heterogeneity (measured with I² statistic).

Results

From 3,916 full articles, 23 articles matched inclusion criteria (17 observational studies and 6 RCTs), 7 with pediatric patients only. Overall, 1,923 patients (M 70.1%; mean age 29.8±12.6 years). Mean follow-up time was 78.4 weeks. Budesonide (either oro-dispersible or viscous suspension) was administered in 7 studies (including 2 RCTs), PPI in 6 studies (all observational, 4 pediatric), Fluticasone in 5 studies (including 1 RCT with 4 cohorts), Dupilumab in 2 RCTs and Cendakimab in 1 RTC. Pooled rate of long-term histologic success for RCTs was 83% (95% CI, 77%-89%; I² 73.1%), while for observational studies attested at 53% (95% CI, 42%-65%; I² 93.5%) at a median follow-up of 97.8 weeks. Maintenance therapy in RCTs showed a RD of -0.71 (95% CI; -0.92-0.50; p<0.01; I² 88.9%) versus PBO, while a RD of -0.06 (95% CI; -0.11-0.01; p<0.016; I² 23.1%) compared with induction. Observational studies showed a non-significant (p=0.38) Odds Ratio (OR) of 1.37 (95% CI, 0.66-2.85; I² 81.3%) of losing histologic success during therapy de-escalation. Pooled clinical success among RCTs attested at 61% (95% CI, 51%-75%; I² 71.3%), comparable with observational studies (60% [95% CI, 42%-77%; I² 97.3%]). Biological therapy (either Dupilumab or Cendakimab at various regimens) ranked first for pooled histologic success rate among RCTs with 79% (95% CI; 71%-87%; I² 54.9%). In observational studies, PPI with histologic success of 64% (95% CI, 50%-78%; I² 88.7%) and clinical success of 79% (95% CI; 66%-93%; I² 85.2%) ranked first. Pooled rate of AEs among RCTs attested at 34% (95% CI; 22%-45%; I² 93.2%), with a pooled candidiasis infection rate of 6% (95% CI; 2%-10%; I² 61.9%), comparable with pooled AEs among observational studies (5% [95% CI, 2%-7%; I² 66.7%]). Pooled therapy discontinuation rate was 0.14 (95% CI, 0.073-0.210, I² 94.49%) in real-world data.

Conclusion

This is the first meta-analysis on efficacy and safety of long-term maintenance treatment (median 78 weeks) for EoE. All treatments showed good efficacy in maintaining long-term histological remission without clear disadvantage in de-escalating therapy during maintenance in real-word data. Biological therapies resulted the most effective in RCTs, while PPIs in observational studies. Low adverse events rates and low therapy discontinuation rates confirm long-term treatment is well tolerated.

References

1. Nistel M, Andrews R, Furuta GT, Atkins D. Elimination Diet or Swallowed Topical Steroid Treatment of Pediatric Eosinophilic Esophagitis: Five-Year Outcomes. J Allergy Clin Immunol Pract. 2023 Aug;11(8):2516-2523.e2. doi: 10.1016/j.jaip.2023.05.036. Epub 2023 May 30. PMID: 37263351; PMCID: PMC10525024.

Disclosure

ES has served as speaker for Abbvie, Agave, AGPharma, Alfasigma, Aurora Pharma, CaDiGroup, Celltrion, Dr Falk, EG Stada Group, Fenix Pharma, Fresenius Kabi, Galapa-gos, Janssen, JB Pharmaceuticals, Innovamedica/Adacyte, Malesci, Mayoly Biohealth, Omega Pharma, Pfizer, Reckitt Benckiser, Sandoz, SILA, Sofar, Takeda, Tillots, Uni-farco; has served as consultant for Abbvie, Agave, Alfasigma, Biogen, Bristol-Myers Squibb, Celltrion, Diadema Farmaceutici, Dr. Falk, Fenix Pharma, Fresenius Kabi, Janssen, JB Pharmaceuticals, Merck & Co, Nestlè, Reckitt Benckiser, Regeneron, Sanofi, SILA, Sofar, Synformulas GmbH, Takeda, Unifarco; he received research support from Pfizer, Reckitt Benckiser, SILA, Sofar, Unifarco, Zeta Farmaceutici.
Danese has served as a speaker, consultant and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Fer-ring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor.

Introduction

Hepatic encephalopathy (HE) is a group of neuropsychiatric disorders caused by liver dysfunction or portosystemic shunting, and it is a common complication in the progression of liver cirrhosis. Pathophysiologically, there is an imbalance between the hepatic production and clearance of ammonia, leading to an increase in serum ammonium levels, which can lead to neurological dysfunction, intracranial hypertension, cerebral oedema and ultimately death (1). There are multiple triggering factors; one of the most well-known is upper gastrointestinal bleeding (UGIB) (2). Therefore, we suggest that the coexistence of UGIB and HE is associated with an increased risk of in-hospital mortality and prolonged hospital stay. This study aims to analyse the risk factors for HE during an episode of UGIB and its impact on the patient's prognosis.

Aims & Methods

Retrospective analysis of a prospective registry of patients with UGIB treated at the Hospital Universitario Virgen de las Nieves (2013-2022). Statistical analysis was performed using R v4.3.2. Categorical variables were compared using the Chi-square or Fisher's exact test. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated using the Woolf-Haldane formula for significant variables. Continuous variables were assessed using the Shapiro-Wilk test for normality, and Levene's test was used to check for homogeneity of variances. The t-test for independent samples, with or without Welch's correction, and the Mann-Whitney U test were used for hypothesis testing. Multivariate analysis is performed to identify independent risk factors for variables with statistically significant differences, calculating Odds Ratios (OR) and their 95% confidence intervals (95%CI).

Results

A total of 343 patients with liver cirrhosis and UGIB were analysed, of whom 260 were male and 83 were female, with an overall mean age of 61.51 ± 12.38, developing HE in a total of 66 patients.
After comparing the cirrhotic population that developed HE with those that did not, we observed a series of variables that correlated significantly, as shown in Table 1. Subsequently, after performing multivariate analysis, we noticed that only four variables had a significant independent relationship: bilirubin with an OR (95% CI) of 1.07 (1-1.16) with p0.064; albumin with an OR (95%CI) of 0.41 (0.23-0.7) with p0.0017; ascites with an OR (95%CI) of 1.65(1.01-2.71) with p0.04; and urea on admission with an OR (95% CI) of 1.01 (1-1.102) with p0.0005.

Conclusion

We conclude that patients with cirrhosis admitted for UGIB and who develop HE have higher mortality rates during admission without an apparent increase in hospital stay. Our study indicates that bilirubin, albumin, ascites, and urea are the most accurate predictors of HE development. These findings aligns with Rattanasupar et al. (2), concluding that the Child-Pugh score, which also considers the abovementioned variables, best predicts hepatic encephalopathy after UGIB. Further research is necessary to explore additional risk factors that aid in predicting and modelling the disease based on our findings.

References

1. Elsaid MI, Rustgi VK. Epidemiology of Hepatic Encephalopathy. Clinics in Liver Disease. 2020 May;24(2):157–74.
2. Rattanasupar A, Tiawijit N, Rachatapantanakorn B. Predictive factor for hepatic encephalopathy in cirrhotic patients who presented with acute variceal bleeding. J Med Assoc Thai. 2014 Jun;97(6):567–73.