SARS-CoV-2 infection of salivary glands Compromises the production of a secreted antifungal peptide with potential implications for Development of oral candidiasis.

Saliva contains antimicrobial peptides considered integral components of host innate immunity, and crucial for protection against colonizing microbial species. Most notable is histatin-5 which is exclusively produced in salivary glands with uniquely potent antifungal activity against the opportunistic pathogen Candida albicans. Recently, SARS-CoV-2 was shown to replicate in salivary gland acinar cells eliciting local immune cell activation.

Drug-induced Liver Injury Due to Medications for Alcohol Use Disorder: Results From the DILIN Prospective Study.

Objectives: Concerns about drug-induced liver injury (DILI) may deter physicians from prescribing medications for alcohol use disorder (MAUD). We aim to explore DILI due to MAUD in Drug-Induced Liver Injury Network (DILIN) prospective study.

Methods: High-confidence DILI cases (ie, definite, highly likely, or probable) due to MAUD in DILIN prospective study (2004-2024) were included.

Non-cirrhotic portal fibrosis/idiopathic portal hypertension: APASL recommendations for diagnosis and management.

Since the Asian Pacific Association for the Study of the Liver (APASL) published guidelines on non-cirrhotic portal fibrosis/idiopathic portal hypertension in 2007, there has been a surge in new information, especially with the introduction of the term porto-sinusoidal vascular disorder (PSVD). Non-cirrhotic intra-hepatic causes of portal hypertension include disorders with a clearly identifiable etiology, such as schistosomiasis, as well as disorders with an unclear etiology such as non-cirrhotic portal fibrosis (NCPF), also termed idiopathic portal hypertension (IPH). This entity is being increasingly recognized as being associated with systemic disease and drug therapy, especially cancer therapy.

Role of liver biopsy in the management of idiosyncratic DILI.

Drug-induced liver injury (DILI) presents unique challenges in clinical practice. While some types of DILI are mild and resolve quickly after removing the drug, other situations are more complex, with competing aetiologies or underlying liver disease. Guidelines from professional societies agree that the liver biopsy retains a role in understanding and managing DILI in certain situations.

MASLD in people with HIV exhibits higher fibrosis stage despite lower disease activity than in matched controls.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown.

Methods: Overall, 107 liver biopsies from PWH with MASLD (MASLD-PWH) were matched to 107 biopsies from individuals with MASLD and without HIV (MASLD controls) on age at biopsy, race/ethnicity, sex, type 2 diabetes, body mass index (BMI) and alanine aminotransferase (ALT) level.

Liver stiffness progression in biopsy-proven metabolic dysfunction-associated steatotic disease among people with diabetes versus people without diabetes: A prospective multicenter study.

Background And Aims: There are limited data on the progression of liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in people with type 2 diabetes mellitus (T2DM) versus those without T2DM in biopsy-proven metabolic dysfunction-associated steatotic liver disease. We examined LSM progression in participants with T2DM versus those without T2DM in a large, prospective, multicenter cohort study.

Approach And Results: This study included 1231 adult participants (62% female) with biopsy-proven metabolic dysfunction-associated steatotic liver disease who had VCTEs at least 1 year apart.

Clinical characteristics and HLA associations of azithromycin-induced liver injury.

Background: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ.

Methods: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed.

Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT.

Identifying cell types and states remains a time-consuming, error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data.

Taurine-conjugated bile acids and their link to hepatic S1PR2 play a significant role in hepatitis C-related liver disease.

Background: Bile acids mediate gut-liver cross-talk through bile acid receptors. Serum, hepatic, and microbial bile acid metabolism was evaluated in HCV-compensated chronic liver disease.

Methods: Patients underwent liver biopsy; portal and peripheral blood were obtained before (HCVi), and 6 months after sustained virologic response (SVR), splenic blood was obtained only after SVR.

Spatial Deconvolution of Cell Types and Cell States at Scale Utilizing TACIT.

Identifying cell types and states remains a time-consuming and error-prone challenge for spatial biology. While deep learning is increasingly used, it is difficult to generalize due to variability at the level of cells, neighborhoods, and niches in health and disease. To address this, we developed TACIT, an unsupervised algorithm for cell annotation using predefined signatures that operates without training data, using unbiased thresholding to distinguish positive cells from background, focusing on relevant markers to identify ambiguous cells in multiomic assays.

Steatohepatitic hepatocellular Carcinoma:A new approach to classifying morphological subtypes of hepatocellular carcinoma.

Histological subtyping of hepatocellular carcinoma (HCC) is challenging in the presence of histological heterogeneity, where distinctly different morphological patterns are present within the same tumor. Current approaches rely on percent cut-offs. We hypothesized that morphologic intratumor heterogeneity is a non-random biological feature and that incorporating recurrent patterns would improve histological subtyping of HCC.

Increases and decreases in liver stiffness measurement are independently associated with the risk of liver-related events in NAFLD.

Background & Aims: The clinical significance of change in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) in patients with non-alcoholic fatty liver disease (NAFLD) is not well-understood. We prospectively defined rates of progression to and regression from LSM-defined compensated advanced chronic liver disease (cACLD) and their associations with liver-related events (LREs).

Methods: Participants in the NASH Clinical Research Network-led NAFLD Database 2 and 3 studies were included.

Persistent GDNF Expression 45 Months after Putaminal Infusion of AAV2-GDNF in a Patient with Parkinson's Disease.

Objective: Gene therapy by convection-enhanced delivery of type 2 adeno-associated virus-glial cell derived neurotrophic factor (AAV2-GDNF) to the bilateral putamina seeks to increase GDNF gene expression and treat Parkinson's disease (PD).

Methods: A 63-year-old man with advanced PD received AAV2-GDNF in a clinical trial. He died from pneumonia after anterior cervical discectomy and fusion 45 months later.

Inhibition of JAK-STAT pathway corrects salivary gland inflammation and interferon driven immune activation in Sjögren's disease.

Objectives: Inflammatory cytokines that signal through the Janus kinases-signal transducer and activator of transcription (JAK-STAT) pathway, especially interferons (IFNs), are implicated in Sjögren's disease (SjD). Although inhibition of JAKs is effective in other autoimmune diseases, a systematic investigation of IFN-JAK-STAT signalling and the effect of JAK inhibitor (JAKi) therapy in SjD-affected human tissues has not been fully investigated.

Methods: Human minor salivary glands (MSGs) and peripheral blood mononuclear cells (PBMCs) were investigated using bulk or single-cell (sc) RNA sequencing (RNAseq), immunofluorescence (IF) microscopy and flow cytometry.