Hepatology最新文献

Malnutrition, sarcopenia (low muscle mass), and physical frailty have gained increasing recognition in candidates for liver transplant (LT) as these conditions can impact postoperative functional capacity. Multidimensional prehabilitation programs have been proposed as a safe intervention in adults awaiting LT but the nutritional pillar of prehabilitation has been understudied. This review summarizes the nutritional recommendations for prehabilitation for individuals with cirrhosis awaiting LT. Three major aspects of nutritional prehabilitation are discussed: (1) Assess: Evaluate nutritional status and assess for malnutrition, sarcopenia, and frailty to guide the nutritional prehabilitation intervention intensity, increasing across universal, targeted, and specialist levels; (2) Intervene: Prescribe a nutritional prehabilitation intervention to meet established nutrition guidelines in cirrhosis with a targeted focus on improving nutritional status and muscle health; (3) Reassess: Follow-up based on the required intensity of nutritional care with as needed intervention adjustment. Topics covered in the review include nutritional care levels for prehabilitation, energy prescriptions across body mass index strata, detailed considerations around protein intake (amount, distribution, and quality), carbohydrate and fat intake, other nutritional considerations, and the potential role of dietary supplements and nutraceuticals. Future research is warranted to more accurately evaluate energy needs, evaluate emerging dietary supplementation strategies, and establish the role of nutraceuticals alongside food-based interventions. While the general principles of nutritional prehabilitation are ready for immediate application, future large-scale randomized controlled trials in this space will help to quantify the benefit that can be gained by transitioning the LT approach from passive "transplant waitlist time" to active "transplant preparation time."

Steatohepatitis with diverse etiologies is the most common histological manifestation in patients with liver disease. However, there are currently no specific histopathological features pathognomonic for metabolic dysfunction-associated steatotic liver disease, alcohol-associated liver disease, or metabolic dysfunction-associated steatotic liver disease with increased alcohol intake. Digitizing traditional pathology slides has created an emerging field of digital pathology, allowing for easier access, storage, sharing, and analysis of whole-slide images. Artificial intelligence (AI) algorithms have been developed for whole-slide images to enhance the accuracy and speed of the histological interpretation of steatohepatitis and are currently employed in biomarker development. Spatial biology is a novel field that enables investigators to map gene and protein expression within a specific region of interest on liver histological sections, examine disease heterogeneity within tissues, and understand the relationship between molecular changes and distinct tissue morphology. Here, we review the utility of digital pathology (using linear and nonlinear microscopy) augmented with AI analysis to improve the accuracy of histological interpretation. We will also discuss the spatial omics landscape with special emphasis on the strengths and limitations of established spatial transcriptomics and proteomics technologies and their application in steatohepatitis. We then highlight the power of multimodal integration of digital pathology augmented by machine learning (ML)algorithms with spatial biology. The review concludes with a discussion of the current gaps in knowledge, the limitations and premises of these tools and technologies, and the areas of future research.

Background and aims: Bulevirtide (BLV) is a novel and the only approved treatment option for patients with chronic hepatitis D (CHD). BLV alleviates liver inflammation early during treatment when only minor HDV RNA changes are observed. We hypothesized that BLV treatment may influence immune cells in patients with CHD and performed a high-resolution analysis of natural killer (NK) cells before and during BLV therapy.

Approach and results: BLV-treated patients with CHD (n=20) from a single-center cohort were longitudinally analyzed for clinical, molecular, and virological parameters. Peripheral blood mononuclear cells were studied at baseline, and therapy weeks 3 and 48 by spectral flow cytometry. Healthy donors, patients with chronic hepatitis C after direct-acting antiviral treatment, and patients with chronic hepatitis B were used as controls. Overall, NK cell frequencies remained stable during BLV treatment. However, biochemical responders showed distinct NK cell immunophenotypic features before and during therapy. TIGIT expression increased on CD56 dim and CD56 bright NK cells during the course of BLV treatment and inversely correlated with ALT levels in CHD but not patients with CHC or CHB. High frequencies of TIGIT - CD57 + CD56 dim NK cells at baseline and low levels during therapy were indicative of a biochemical response.

Conclusions: We here suggest that lacking the expression of the immune checkpoint inhibitor TIGIT on NK cell subtypes may be a hallmark of liver inflammation in HDV infection. BLV therapy is associated with a reappearance of TIGIT on these cells, which may be one mechanism of why liver enzymes rapidly improve during therapy.