ALT poorly predicts Nonalcoholic Fatty Liver Disease (NAFLD) and liver fibrosis as determined by vibration-controlled transient elastography in adult National Health and Nutrition Examination Survey 2017-2018.

BACKGROUND: Non-alcoholic fatty liver disease is a growing problem in the United States, contributing to a range of liver disease as well as cardiovascular disease. ALT is the most widely used liver chemistry for NAFLD evaluation. We hypothesized that the normal range many laboratories use was too high, missing many patients with clinically important steatosis and/or fibrosis. METHODS: This study utilized 2017-2018 NHANES data including 9254 participants. We compared four different upper limits of normal for ALT with specific measurements of steatosis and liver stiffness as determined by liver elastography with FibroScan®. Liver stiffness was further characterized as showing any fibrosis or advanced fibrosis. After exclusions, our final pool was 4184 for liver stiffness measurement and 4183 for steatosis grade as measured by Controlled Attenuation Parameter (CAP). Using these variables, we performed logistic regression between ALT and CAP, and ALT and fibrosis/advanced fibrosis, and did a Receiver Operating Characteristic curve. RESULTS: Based on three of the most widely used cut off values for ALT, we found that ALT does not reliably rule out NAFLD in over 50% of cases. It also missed 45.9-64.2% of patients with liver fibrosis. CONCLUSIONS: Our study revealed that ALT is an inaccurate marker for NAFLD as measured by FibroScan® with CAP greater than or equal to 300 dB/m. Accuracy improved specific risk factors were considered. These data also showed that ALT was a poor marker for liver fibrosis. We conclude that there is no single ALT level that accurately predicts hepatic steatosis or fibrosis.

Past, Present, and Future Therapies for Alcohol-associated Hepatitis.

PURPOSE: Alcohol-associated hepatitis (AH) is a unique presentation of cholestatic steatohepatitis with liver dysfunction and malaise preceded by heavy alcohol intake. Although AH exists on a spectrum, in its most severe form, 28-day mortality approaches 50%. Clinical trials of therapeutic interventions over the last 50 years have yielded few durable therapies, none of which convey benefit beyond the short term. METHODS: A qualitative systematic review was performed via searches of PubMed, the International Clinical Trials Registry Platform, and ClinicalTrials.gov for therapeutic interventions for AH. FINDINGS: Prior to 2005, clinical trial results for AH were identified within PubMed. From 2005 to the present, trials were well catalogued within online registries and included information regarding trial status (eg, complete, terminated, actively enrolling). Most clinical trials for AH have used existing medications broadly targeting pathogenic themes of AH (eg, inflammation, cell death) in an off-label manner. The trend of initially promising pilot studies answered by larger trials showing lack of efficacy or safety signals have ended the hopes of many new therapeutics. The emergence of theragnostics to identify patients who may benefit from existing therapies and trials of agents with novel mechanisms of action, including epigenetic modifications and hyaluronic acid signaling targeted to AH pathogenesis, are currently under investigation. IMPLICATIONS: This review of AH treatments details the historical interventions and clinical trials that have led to the current treatment algorithm and active studies shaping the therapeutic pipeline for AH.

Theragnostic Efficacy of K18 Response in Alcohol Use Disorder with Clinically Significant Fibrosis Using Gut-Liver Axis.

(1) Background: Fibrosis in early-stage alcohol-associated liver disease (ALD) is commonly under-diagnosed in routine clinical practice. This study characterized the liver-injury and cell death response in alcohol use disorder (AUD) patients with ALD who also exhibited fibrosis and assessed the efficacy of standard of care (SOC) treatment in the improvement in liver injury. (2) Methods: Forty-eight heavy-drinking AUD patients aged 21−65 yrs. without clinical manifestations of liver injury were grouped by Fibrosis-4 (FIB-4) score, as negative (Gr.1 < 1.45, n = 21) or positive (Gr.2 ≥ 1.45, n = 27). Patients received 2-weeks (2 w) inpatient SOC. Data on demographics, drinking patterns, liver-injury, immune markers, and liver cell death (K18s) markers were analyzed at baseline (BL) and after 2 w SOC. (3) Results: Lifetime drinking (LTDH, yrs.) and acute heavy drinking (Heavy Drinking Days Past 90 Days [HDD90]) markers were significantly higher in Gr.2 vs. Gr.1. BL ALT, AST, AST:ALT and K18M65 were considerably higher in Gr.2. Dysregulated gut dysfunction and elevated immune activity were evident in Gr.2 characterized by TNF-α, IL-8 and LPS levels. After SOC, Gr.2 showed improvement in AST, ALT, AST/ALT ratio; and in the K18M65, K18M30 and K18M65/M30 ratio vs. Gr.1. The true positivity of BL IL-8 response to predict the improvement in K18M65 to normal levels among Gr.2 patients against those who did not have improvement after 2 w SOC was very high (AUROC = 0.830, p = 0.042). (4) Conclusions: Gut dysfunction, elevated cytokine response and necrotic liver cell death were elevated in AUD patients with early-stage ALD. K18 showed promise as a predictive theragnostic factor to differentiate among the AUD patients with early-stage ALD and baseline fibrosis who had improvement in liver injury against those who did not, by the levels of baseline IL-8.

Malnutrition and Alcohol-Associated Hepatitis.

Malnutrition is common in alcohol-associated hepatitis (AH); almost all patients with severe AH have some component of malnutrition. The classic phenotype of malnutrition in AH is sarcopenia, but this has become more difficult to discern clinically as patients have become more obese. Patients with AH are often drinking 10 to 15 standard drinks per day. This substantial alcohol consumption becomes a major source of calories, but these are considered "empty" calories that contain little nutritional value. Malnutrition is associated with liver complications, such as hepatic encephalopathy, and worse liver outcomes. Nutrition support can improve nutrition status and reduce complications.

Gastric Electrical Stimulators Causing Erosion Through the Colonic Wall.

Gastroparesis is a chronic motor disorder of the stomach characterized by the demonstration of delayed gastric emptying without obstruction and a grouping of symptoms including nausea, vomiting, early satiety, postprandial fullness, bloating and abdominal pain. When conservative medical management is not effective, gastric electrical stimulation is an effective alternative. Gastric electrical stimulation, in general, has had a low complication rate as of yet, with the most common being infection of the implanted device. We present a complication in which the gastric electrical stimulator electrodes eroded through the colonic wall.