Molecular Adsorbent Recirculating System in Acute Liver Failure.

Acetaminophen (APAP) overdose is the most common cause of acute liver failure (ALF) in the United States. Liver transplantation (LT) is potentially lifesaving for patients with ALF, but its feasibility in clinical practice is limited. Liver assist devices, such as the Molecular Adsorbent Recirculating System (MARS), are used in some centers as a "bridge" to liver transplantation or as a means of liver recovery, but their role in the treatment of ALF is not well-defined. We present the case of a 44-year-old man with APAP-associated ALF who experienced hepatic recovery after treatment with MARS.

Maternal, obstetrical, and neonatal outcomes in celiac disease.

OBJECTIVES: Some studies have suggested a link between celiac disease (CD) and adverse maternal, obstetrical, and neonatal outcomes. Using a large database, we evaluated the effect of CD on pregnancy outcomes. METHODS: We conducted a retrospective cohort study using the National Inpatient Sample (NIS) of all deliveries from 2015 to 2019 in the United States. Using ICD-10 codes, we identified pregnant patients who had CD and those who did not. A multivariate logistic regression was used to generate odds ratios (ORs) with 95% confidence intervals (CIs) for maternal, obstetrical, and neonatal outcomes. RESULTS: Of 12,039,222 deliveries between 2015 and 2019, there were 10,555 births in women with CD. Pregnant women with CD were more likely to be white and older compared to those without CD. Pregnant women with CD were significantly more likely to carry a diagnosis of gestational hypertension (OR 1.26; 95% CI 1.04-1.52), preeclampsia (1.28; 1.08-1.53), and severe preeclampsia (1.62; 1.25-2.09). They were less likely to have a full-term uncomplicated delivery (OR 0.11; 95% CI, 0.05-0.20), while being more likely to require device-assisted delivery (1.25; 1.04-1.50) and sustain 3rd or 4th degree vaginal lacerations (1.56; 1.21-2.02). Babies of pregnant women with CD were more likely to be small for gestational age (SGA) (OR 1.29; 95% CI 1.03-1.61). CONCLUSIONS: CD in pregnancy appears to be associated with increased adverse maternal, obstetrical, and neonatal outcomes. Clinicians should discuss these increased risks with CD patients who are planning to conceive.

Increased prevalence of gout in patients with inflammatory bowel disease: A population-based study.

Background and Aim: Arthritis is a recognized extra-intestinal manifestation of inflammatory bowel disease (IBD). Studies show altered uric acid metabolism in IBD. This study aims to investigate the association between IBD and gout. Methods: We used a multi-center database (Explorys Inc.) consisting of data from several US healthcare systems. We identified adults diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between 1999 and 2022. In this cohort, we identified patients diagnosed with gout. We collected demographic data and identified patients diagnosed with IBD-associated arthritis and those who had intestinal resection. Risk factors associated with gout were collected. Multivariate analysis was used. Results: Out of the 69 260 780 patients in the database, we identified 209 020 patients with UC (0.30%) of whom 9130 had gout (4.3%). Additionally, 249 480 had CD (0.36%) of whom 14 000 had gout (5.61%). Males were more prevalent in the UC and gout group than in the CD and gout group (58% vs 51%). After adjustment, CD was significantly associated with gout (odds ratio [OR] 1.68, confidence interval [CI]: 1.60-1.75). UC was also significantly associated with gout (OR 1.38, CI: 1.31-1.44). In subgroup analysis with intestinal resection, CD patients who had intestinal resection had higher association with gout versus those without surgery (OR 2.34, CI: 2.25-2.43). Similar increase was observed in the UC group with intestinal resection (OR 1.53, CI: 1.49-1.56). Conclusion: IBD is strongly associated with gout, with higher correlation observed with CD. Intestinal resection is associated with an increase in the risk of gout. Patients with IBD who present with new-onset arthritis should be investigated for gout.

The epidemiology of non-alcoholic steatohepatitis (NASH) in the United States between 2010-2020: a population-based study.

INTRODUCTION AND OBJECTIVES: Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD) that can progress to liver cirrhosis, liver failure and hepatocellular carcinoma. It is the second leading cause of liver transplant in the US. We aim to investigate the prevalence, demographics and risk factors NASH patients in the US. PATIENTS AND METHODS: We used a large database (Explorys IBM) that aggregates electronic health records from 26 nationwide healthcare systems. We identified adults with NASH between 2010-2020. Demographics including age, gender and race were collected. NASH risk factors including Diabetes Millets (DM), Hyperlipidemia (HLD), Hypertension (HTN) and Obesity were also collected. Cochran-Armitage test was used to assess the statistical significance of year-by-year trend. Univariable and multivariable logistic regression were used to estimate the odds ratio (OR) of risk factors. RESULTS: NASH annual prevalence rate increased from 1.51% in 2010 to 2.79% in 2020 (p < 0.0001). The proportion of patients with NASH by gender was 54.1% female vs 45.9% male (OR 1.04 [0.91-1.11]). Caucasian had higher odds of NASH than non-Caucasian (OR 1.42 [1.31-1.54]). NASH is strongly associated with DM and obesity (OR 18.61 [17.35-19.94]) and (OR 20.97 [17.87-23.21]), respectively. Other components of metabolic syndrome were associated with NASH to a lesser degree; HTN (OR 3.24 [3.20-3.28]) and HLD (OR 4.93 [4.85-4.01]). CONCLUSION: The prevalence of NASH has significantly increased in the US in the last decade. This is likely related to the increased prevalence of risk factors as well as increased awareness of the disease.

Activated Protein Phosphatase 2A Disrupts Nutrient Sensing Balance Between Mechanistic Target of Rapamycin Complex 1 and Adenosine Monophosphate-Activated Protein Kinase, Causing Sarcopenia in Alcohol-Associated Liver Disease.

BACKGROUND AND AIMS: Despite the high clinical significance of sarcopenia in alcohol-associated cirrhosis, there are currently no effective therapies because the underlying mechanisms are poorly understood. We determined the mechanisms of ethanol-induced impaired phosphorylation of mechanistic target of rapamycin complex 1 (mTORC1) and adenosine monophosphate-activated protein kinase (AMPK) with consequent dysregulated skeletal muscle protein homeostasis (balance between protein synthesis and breakdown). APPROACH AND RESULTS: Differentiated murine myotubes, gastrocnemius muscle from mice with loss and gain of function of regulatory genes following ethanol treatment, and skeletal muscle from patients with alcohol-associated cirrhosis were used. Ethanol increases skeletal muscle autophagy by dephosphorylating mTORC1, circumventing the classical kinase regulation by protein kinase B (Akt). Concurrently and paradoxically, ethanol exposure results in dephosphorylation and inhibition of AMPK, an activator of autophagy and inhibitor of mTORC1 signaling. However, AMPK remains inactive with ethanol exposure despite lower cellular and tissue adenosine triphosphate, indicating a "pseudofed" state. We identified protein phosphatase (PP) 2A as a key mediator of ethanol-induced signaling and functional perturbations using loss and gain of function studies. Ethanol impairs binding of endogenous inhibitor of PP2A to PP2A, resulting in methylation and targeting of PP2A to cause dephosphorylation of mTORC1 and AMPK. Activity of phosphoinositide 3-kinase-γ (PI3Kγ), a negative regulator of PP2A, was decreased in response to ethanol. Ethanol-induced molecular and phenotypic perturbations in wild-type mice were observed in PI3Kγ-/- mice even at baseline. Importantly, overexpressing kinase-active PI3Kγ but not the kinase-dead mutant reversed ethanol-induced molecular perturbations. CONCLUSIONS: Our study describes the mechanistic underpinnings for ethanol-mediated dysregulation of protein homeostasis by PP2A that leads to sarcopenia with a potential for therapeutic approaches by targeting the PI3Kγ-PP2A axis.