RARE-seq: an inflection point in cfRNA liquid biopsy.

Historically, the clinical application of cell-free RNA (cfRNA) liquid biopsies has been limited by background noise. In a recent study, Nesselbush et al. developed a method for denoising cfRNA analysis, resulting in RARE-seq, a versatile liquid biopsy platform that enables transcriptomic profiling, and cancer detection and monitoring, unlocking the potential of this exciting analyte.

Therapeutic targeting of mismatch repair-deficient cancers.

DNA mismatch repair (MMR) is one of many evolutionarily conserved processes that act as guardians of genomic integrity. MMR proteins recognize errors that occur during DNA replication and initiate countermeasures to rectify those mistakes. MMR deficiency (MMRd) therefore leads to a dramatic accumulation of mutations.

The Rising Global Burden of MASLD and Other Metabolic Diseases (2000-2021).

Background: Metabolic diseases are a public health threat to diverse populations worldwide. This study aims to update the epidemiological trends of metabolic diseases across regions and sociodemographic stratifications using the Global Burden of Diseases Study 2021.

Methods: This study focused on metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) along with obesity, hypertension, and dyslipidemia.

Latin American association for the study of the liver (ALEH) guidance on preoperative care in liver transplantation: referral criteria, patient assessment, and waiting list management.

Liver transplantation (LT) is the standard of care therapy for patients with decompensated cirrhosis, early-stage hepatocellular carcinoma, acute liver failure, and other expanding indications. Latin America is a highly heterogeneous region characterized by an uneven distribution of socio-economic conditions and irregular access to health resources, and consequently LT activity varies across the region. This current guidance on preoperative care in LT represents a collaborative effort to assess and standardize preoperative evaluation of liver transplant candidates in Latin America.

Pharmacological Strategies for the Management of Severe Alcohol-associated Hepatitis: A Systematic Review and Meta-analysis.

Background & Aims: Alcohol-associated hepatitis (AH) is a severe form of alcohol-associated liver disease, with a short-term mortality of up to 50% within 3 months. The aim of this systematic review was to determine the optimal pharmacological treatment for severe AH that results in better survival outcomes.

Methods: MEDLINE, EMBASE, and CENTRAL were searched through February 16, 2025, for randomized controlled trials (RCTs) of medical therapy for adults with severe AH.

Clinical utility of phosphatidylethanol to detect underreported alcohol use and enhance steatotic liver disease subclassification.

Background & Aims: The 2023 subclassification of steatotic liver disease (SLD) relies on self-reported alcohol use, which lacks diagnostic precision in routine clinical practice. Phosphatidylethanol (PEth) is a quantitative, objective alcohol biomarker with high sensitivity and specificity. In this study, we aimed to estimate the prevalence of underreported alcohol use, identify its independent predictors, and enhance SLD subclassification using PEth in a large, population-based cohort of individuals with overweight/obesity and SLD from the US.

Safety and Tolerability of Injectable Extended-Release Naltrexone for the Management of Alcohol Use Disorder in Advanced Alcohol-Associated Liver Disease.

Background: Pharmacologic treatment of alcohol use disorder (AUD) in patients with advanced alcohol-associated liver disease (ALD) remains underutilised due to concerns regarding hepatotoxicity. Injectable extended-release naltrexone (XR-NTX) may offer a safer alternative by avoiding first-pass hepatic metabolism, but data on its safety and effectiveness in patients with advanced ALD are limited.

Aim: To describe the clinical experience with XR-NTX in individuals with advanced ALD, evaluating its safety, tolerability and impact on liver function and alcohol use.

Cisplatin and temozolomide combinatorial treatment triggers hypermutability and immune surveillance in experimental cancer models.

Hypermutation induced by mismatch repair (MMR) inactivation leads to immune surveillance in colorectal cancer (CRC) and in several other malignancies. We investigated the impact of a rationally designed chemotherapy combination on the generation of hypermutation and immunogenicity in otherwise immune-refractory CRC and breast cancer mouse models. Combinatorial treatment with cisplatin (CDDP) and temozolomide (TMZ) induces an adaptive downregulation of MMR, resulting in chemotherapy-dependent hypermutability and increase in predicted neoantigens.

Induction of a mismatch repair deficient genotype by tailored chemical mutagenesis in experimental models of cancer.

Mismatch repair deficient (MMRd) tumors harbor thousands of somatic mutations enriched for insertion-deletion (indels) conferring high sensitivity to immunotherapy. We sought to reproduce this phenotype using mutagenic agents to engineer an MMRd genotype in immunoresistant cells. The combination of temozolomide (TMZ) and cisplatin led to a rapid accumulation of a high mutational load enriched for indels in murine cell lines resulting from the epigenetic loss of Msh2.

Disproportionately rising mortality rates of alcohol-associated acute Pancreatitis: Analysis from centers for Disease Control and prevention database (2011-2020).

Background/objective: Acute pancreatitis leads to over 300,000 emergency department visits annually. Assessing its current epidemiology is crucial for developing effective preventive strategies.

Methods: The CDC WONDER database was utilized to obtain deaths and age-adjusted mortality rates of acute pancreatitis from 2011 to 2020, categorized by sex, type (alcohol- and non-alcohol-associated acute pancreatitis), race/ethnicity, and region.

Noninvasive pathway for stratifying fibrosis in suspected metabolic dysfunction and alcohol-associated liver disease (MetALD).

Background: Metabolic dysfunction and alcohol-associated liver disease (MetALD) may increase liver fibrosis progression, but data on screening are scarce. We aimed to assess the performance of noninvasive tests (NITs) for detecting significant fibrosis in individuals with suspected MetALD.

Methods: This is a cross-sectional study of prospectively enrolled adults identified as overweight or obese.

High inherited risk predicts age-associated increases in fibrosis in patients with MASLD.

Background & Aims: Limited data have prevented routine genetic testing from being integrated into clinical practice in metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to quantify the effect of genetic variants on changes in fibrosis severity per decade in patients with MASLD.

Methods: This cross-sectional study included prospectively recruited adults with MASLD aged 18-70 who underwent magnetic resonance elastography (MRE) and genotyping for PNPLA3, TM6SF2, MBOAT7, GCKR, and HSD17B13.

An Expert Consensus Delphi Panel in Metabolic Dysfunction- and Alcohol-associated Liver Disease: Opportunities and Challenges in Clinical Practice.

Background & Aims: Metabolic dysfunction- and alcohol-associated liver disease (MetALD) is a recently defined entity for individuals with liver steatosis, metabolic dysfunction, and increased alcohol intake. However, the current definition of MetALD poses multiple challenges in clinical practice and research. In this Delphi consensus, we provide practical recommendations for the clinical assessment and management of MetALD to address current clinical challenges in MetALD.

Nonoperative Management of Mismatch Repair-Deficient Tumors.

Background: Among patients with mismatch repair-deficient (dMMR), locally advanced rectal cancer, neoadjuvant checkpoint blockade eliminated the need for surgery in a high proportion of patients. Whether this approach can be extended to all early-stage dMMR solid tumors, regardless of tumor site, is unknown.

Methods: We conducted a phase 2 study in which patients with stage I, II, or III dMMR solid tumors that were amenable to curative-intent surgery were treated with neoadjuvant dostarlimab, a programmed cell death 1 (PD-1) blocking agent, for 6 months.

Alcohol-Attributable Cancer: Update From the Global Burden of Disease 2021 Study.

Background And Aims: Alcohol is a major risk factor for cancer development. Our study aimed to provide the updated global, regional and national burden of alcohol-attributable cancer.

Approach And Results: We analysed the Global Burden of Disease Study 2021 to determine the death and age-standardised death rate (ASDR) from alcohol-attributable cancer and the change of these measures between 2000 and 2021 (reflected as annual percent change [APC]), classified by region, nation and country's developmental status, which is based on the sociodemographic index (SDI).

Pentoxifylline use in alcohol-associated hepatitis with acute kidney injury does not improve survival: a global study.

Background: Severe alcohol-associated hepatitis (sAH) is a life-threatening condition with high mortality, where corticosteroid use is the only treatment that has shown short-term benefits. Pentoxifylline, an anti-tumour necrosis factor-alpha agent, has been proposed for its potential to improve outcomes, especially in patients with acute kidney injury (AKI). We aimed to evaluate the impact of pentoxifylline on mortality in patients with sAH and AKI in a well-characterised global cohort.

The role of recurrent somatic mutations that alter conserved mA motifs in human cancer.

N-methyladenosine (mA) is the most abundant internal RNA modification in eukaryotes and plays a key role in cellular growth and development. Global changes in cellular methylated RNA and mA-mediated transcript regulation significantly impact oncogenesis. Here, we investigate how recurrent synonymous and non-synonymous somatic mutations abolishing individual canonical methylated mA motifs affect transcript levels and survival of patients with cancer.