Implications of pre-transplant sarcopenia and frailty in patients with non-alcoholic steatohepatitis and alcoholic liver disease.

Frailty manifesting as sarcopenia is an independent risk factor for mortality in cirrhosis, and often presents in low model for end-stage liver disease (MELD) patients. Its etiology is multifactorial, but key physiologic changes culminate in altered energy utilization in the fasting state, preferentially utilizing muscle amino acids for gluconeogenesis thereby promoting sarcopenia. Hyperammonemia alters the circulating amino acid profile, diminishing pro-muscle branched-chain amino acids like leucine.

Hepatitis C-positive liver transplantation: outcomes and current practice.

Purpose Of Review: The coincidence of the opioid epidemic and the approval of direct-acting antivirals for the treatment of hepatitis C virus (HCV) has resulted in an imbalance in HCV viraemic donors relative to HCV viraemic patients awaiting liver transplantation. Although ethical concerns exist about knowingly infecting patients with HCV in the absence of prospective, protocolized studies, transplantation of HCV-positive liver allografts into HCV-negative recipients has increased exponentially in recent years. For this reason, we sought to review outcomes, cost-effectiveness and ethical concerns associated with this practice.

Training of hepatology providers improves the screening and resultant interventions for alcohol use disorder.

Alcohol use disorder (AUD) screening is important but focused training with using AUDIT-10 with counselling/mental health (MH) referral may be needed. We aimed to compare the effect of training on AUD screening/intervention in hepatology clinics in pre vs post-training phases of a quality-improvement initiative. Pre-training encounters were evaluated for inquiry into AUD, AUDIT-10 and MH referrals.

Treating HCV in a Captive Audience: Eradication Efforts in the Prison Microenvironment.

Testing for and treating Hepatitis C (HCV) patients in the prison setting is effective in the short term to reducing the overall burden of HCV in the prison microenvironment, with growing evidence that such efforts could yield substantial overall benefits in the effort to eradicate HCV in society. However, rates of reinfection are as yet unknown.

Pharmacokinetic and Chemical Synthesis Optimization of a Potent d-Peptide HIV Entry Inhibitor Suitable for Extended-Release Delivery.

Peptides often suffer from short in vivo half-lives due to proteolysis and renal clearance that limit their therapeutic potential in many indications, necessitating pharmacokinetic (PK) enhancement. d-Peptides, composed of mirror-image d-amino acids, overcome proteolytic degradation but are still vulnerable to renal filtration due to their small size. If renal filtration could be slowed, d-peptides would be promising therapeutic agents for infrequent dosing, such as in extended-release depots.

Accurate Identification of Fatty Liver Disease in Data Warehouse Utilizing Natural Language Processing.

Introduction: Natural language processing is a powerful technique of machine learning capable of maximizing data extraction from complex electronic medical records.

Methods: We utilized this technique to develop algorithms capable of "reading" full-text radiology reports to accurately identify the presence of fatty liver disease. Abdominal ultrasound, computerized tomography, and magnetic resonance imaging reports were retrieved from the Veterans Affairs Corporate Data Warehouse from a random national sample of 652 patients.

Protease-resistant peptide design-empowering nature's fragile warriors against HIV.

Peptides have great potential as therapeutic agents, but their use is often limited by susceptibility to proteolysis and their resulting in vivo fragility. In this review, we focus on peptidomimetic approaches to produce protease-resistant peptides with the potential for greatly improved clinical utility. We focus on the use of mirror-image (D-peptide) and ß-peptides as two leading approaches with distinct design principles and challenges.

Design of a modular tetrameric scaffold for the synthesis of membrane-localized D-peptide inhibitors of HIV-1 entry.

The highly conserved HIV-1 gp41 "pocket" region is a promising target for inhibiting viral entry. PIE12-trimer is a protease-resistant trimeric d-peptide inhibitor that binds to this pocket and potently blocks HIV entry. PIE12-trimer also possesses a reserve of binding energy that provides it with a strong genetic barrier to resistance ("resistance capacitor").

Design of a potent D-peptide HIV-1 entry inhibitor with a strong barrier to resistance.

The HIV gp41 N-trimer pocket region is an ideal viral target because it is extracellular, highly conserved, and essential for viral entry. Here, we report on the design of a pocket-specific D-peptide, PIE12-trimer, that is extraordinarily elusive to resistance and characterize its inhibitory and structural properties. D-peptides (peptides composed of D-amino acids) are promising therapeutic agents due to their insensitivity to protease degradation.