Annals of hepatology最新文献

Chronic hepatitis B virus (HBV) infection remains a major cause of cirrhosis and hepatocellular carcinoma worldwide, with substantial public health implications in Latin America. Despite the availability of an effective vaccine, HBV continues to be underdiagnosed and undertreated across the region, where healthcare access is often limited and heterogeneous. In alignment with the World Health Organization's 2024 strategy for HBV elimination, the Latin American Association for the Study of the Liver (ALEH) presents updated regional guidelines to simplify diagnosis, expand treatment eligibility, and improve vaccination coverage. The recommendations emphasize the use of rapid diagnostic tests and reflex HBV DNA testing to overcome barriers to laboratory access, while promoting non-invasive methods to assess liver disease severity. Expanded treatment criteria include patients with significant fibrosis, elevated HBV DNA levels, co-infections, and other risk factors, ensuring broader access to antiviral therapy with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV). Preventing mother-to-child transmission through universal screening, maternal prophylaxis, and timely neonatal vaccination is prioritized. Additionally, universal HDV testing in HBV-infected patients is recommended. These guidelines highlight the urgent need for decentralization, simplification, and equity in HBV management to achieve elimination goals in Latin America by 2030.

Introduction and objectives: Living donor liver transplantation is a vital option in low- and middle-income countries with limited access to deceased donor organs. In 2017, Fundación Cardioinfantil-La Cardio established Colombia's first adult living donor liver transplantation program. This study describes donor selection, outcomes, and complication proportion over eight years.

Materials and methods: We conducted a retrospective cohort study of all adult donor candidates evaluated between February 2017 and January 2025. Donors underwent a comprehensive four-phase assessment (clinical, laboratory, psychosocial, and imaging). Eligibility criteria included age 18-50, BMI <30 kg/m² or minimal hepatic steatosis, ABO compatibility, residual liver volume >35%, and graft-to-recipient weight ratio >1% (or >0.8% for donors under 35). Graft volume estimates were validated intraoperatively using CT-based volumetry. Postoperative complications were classified using Clavien-Dindo, and bivariate analyses explored predictors of adverse outcomes and hospital stay duration.

Results: Of 137 candidates, 133 were included, and 63 (47.4%) completed donation. Donors had a mean age of 31.4 years, and 51.9% were women. Main exclusion reasons included steatosis >20%, recipient receiving a deceased donor organ, anatomical variants, and low graft volume. Among donors, 81.1% experienced no complications. Minor complications (12.7%) included biliary issues, liver dysfunction, and surgical site infections. No vascular or thrombotic events were reported. Elevated ICU liver enzymes were associated with complications and prolonged hospitalization. A learning curve was evident, with fewer severe complications observed after the 44th procedure.

Conclusions: These findings demonstrate the feasibility and safety of living donor liver transplantation in resource-constrained settings, supporting the development of similar programs in LMICs.

Chronic liver disease (CLD) remains a major global health burden, driven by persistent hepatic injury that triggers inflammation, vascular dysfunction and progressive extracellular matrix (ECM) deposition. These processes disrupt the liver architecture, leading to advanced liver fibrosis or cirrhosis and increasing the risk of severe complications such as portal hypertension, hepatocarcinoma and even death. While fibrosis and cirrhosis were historically regarded as irreversible, accumulating experimental and clinical evidence now support the potential for fibrosis and even cirrhosis regression once the etiological insult is controlled. Nevertheless, fibrosis regression is not universally observed: about 25% of patients with advanced CLD and sustained hepatitis B virus suppression and over one-third of those with metabolic dysfunction-associated steatotic liver disease after bariatric surgery fail to experience fibrosis regression. Notably, fibrosis regression is often partial and slower in advanced CLD or cirrhosis, especially in decompensated stages, highlighting the need for a better understanding of the cellular and molecular mechanisms that either facilitate or restrict hepatic tissue repair. This review summarizes current knowledge on the dynamics of liver fibrosis regression, with a particular emphasis on the liver sinusoidal endothelial cell (LSEC) as a central regulator of the microenvironment. We discuss how LSEC phenotype determines interactions with hepatic stellate cells (HSCs), immune cells, and hepatocytes, thereby shaping the balance between fibrogenesis and resolution. Mechanisms such as endothelial capillarization, macrophage-driven inflammation, HSC activation and hepatocyte regeneration are examined in the context of both disease progression and regression. Special attention is given to vascular alterations, which represent a major limiting factor for recovery in advanced CLD. We also highlight recent experimental advances, including insights from extracellular vesicle-mediated communication, microenvironmental stiffness, transcriptomic studies of LSEC plasticity during regression, and novel biomarkers of fibrosis regression. Understanding the spatiotemporal orchestration of these processes may inform novel therapeutic strategies aimed at restoring vascular and parenchymal homeostasis, ultimately enabling fibrosis reversal, portal pressure reduction, and improved clinical outcomes in patients with advanced CLD.

Introduction and objectives: Livers from donation after circulatory death (DCD) are less frequently utilized than those from donation after brain death (DBD). Normothermic machine perfusion (NMP) offers the opportunity to assess high-risk grafts before transplantation; however, the predictive value for each respective donor type remains unclear. The aim of this meta-analysis was to compare outcomes between DBD and DCD livers subjected to NMP.

Patients and methods: Studies on clinical liver NMPs published in four databases up to March 2025 were reviewed. A random-effects meta-analysis using Cohen's D and log odds ratios to calculate effect sizes (ES) was conducted.

Results: Sixteen studies were included, encompassing 568 livers (297 DBD, 271 DCD) subjected to NMP. Following the viability assessment, the utilization rate was 91% for DBD and 74% for DCD livers (ES: 0.59, p=0.10), despite exposure to worse donor risk factors in DBD grafts such as higher age (ES: 0.36, p=0.006), and longer CIT (ES: 0.33, p=0.015). Stringency in viability assessment, such as the inclusion of cholangiocyte criteria and lactate clearance within 2 hours, resulted in 20-22% lower DCD utilization rates, compared to DBD. Post-transplantation, DBD and DCD grafts had 3.6% and 12% non-anastomotic strictures (ES: -0.69, p=0.053), and 95% and 90% one-year death-censored graft survival (ES: 0.56, p=0.41).

Conclusions: Presumed high-risk DBD and DCD grafts achieve excellent transplant results after viability assessment during NMP. Stringency of viability criteria correlated with lower DCD utilization rates. More research is needed to elucidate evidence-based assessment criteria that correlate directly to transplant outcomes.

Introduction and objectives: Coronary artery disease (CAD) is common in liver transplant (LT) recipients, but post-LT rates compared to the general population are unknown in Sweden.

Materials and methods: We identified all LT recipients in the Swedish National Patient Registry (1987-2020). Each patient was matched with up to 10 population controls for age, sex, municipality, and transplantation year. International Classification of Diseases (ICD) codes defined liver disease aetiology and cardiovascular risk factors. New CAD events were a composite of myocardial infarction, coronary revascularisation, angina, or CAD-related death. Cox regression compared CAD risk in LT recipients and controls across subgroups.

Results: We identified 2925 LT recipients and 27,589 controls. Mean age was 54 years; 63 % were men. Cardiovascular risk factors were more common in LT recipients. During a median follow-up of 8.0 years, LT recipients had over twice the CAD risk compared with controls (adjusted hazard ratio [aHR]=2.02; 95 % confidence interval [CI]=1.80-2.30). Among LT recipients, chronic kidney disease (CKD) (aHR=2.64; 95 %CI=1.94-3.60) and previous CAD (aHR=7.85; 95 %CI=6.10-10.11) predicted incident CAD. In controls, several factors-including previous CAD, hypertension, diabetes, hypercholesterolemia, CKD, and lung disease-were predictive.

Conclusions: The CAD rate was twofold higher in LT recipients than controls. In recipients, only CKD and prior CAD predicted post-transplant CAD, whereas traditional risk factors predicted CAD in controls.

Introduction and objectives: Cirrhosis is a major global public health concern. In South America, previous studies have identified alcohol-related liver disease (ALD) and chronic hepatitis C as the leading causes. This study describes and characterizes a contemporary South American cohort of patients with cirrhosis, focusing on current spectrum of etiologies, demographic aspects, and the frequency of complications.

Patients and methods: This was a multicenter, retrospective cohort study conducted across 11 centers in 6 South American countries. Patients included were adults (>18 years) with confirmed cirrhosis, and a minimum of two follow-up visits.

Results: A total of 1780 patients (50.7 % male, median age 61 years) were evaluated. Metabolic dysfunction-associated steatotic liver disease (MASLD) was the leading cause of cirrhosis (34.1 %), followed by viral etiology (19.8 %), autoimmune liver disease (18 %), and ALD alone (16 %). Comorbidities were highly prevalent, with self-reported alcohol intake in 37.8 %, hypertension in 36.2 %, and diabetes in 33.7 %. Nearly two-thirds of patients (63.5 %) developed at least one complication, with ascites being the most common (43.5 %). Only 28.1 % of the cohort underwent pre-transplant evaluation.

Conclusions: In this contemporary South American cohort, MASLD has emerged as the leading cause of cirrhosis, and autoimmune disease affected nearly one-fifth of individuals with cirrhosis. The high burden of complications, with nearly two-thirds of patients developing at least one, and the low rate of pre-transplant evaluation suggest a significant unmet need for timely diagnosis and advanced care in the region.

Chronic hepatitis C virus (HCV) infection remains a major global public health challenge. Despite the availability of highly effective therapies capable of curing the vast majority of patients, millions remain undiagnosed and often present for medical care at advanced stages of disease. This delay not only increases mortality and the burden of cirrhosis and hepatocellular carcinoma but also affects quality of life, productivity, and healthcare system costs. In this context, screening emerges as a cornerstone for achieving HCV elimination. It enables the identification of hidden cases, early treatment initiation, prevention of complications, and reduction of community transmission. At the population level, prioritizing individuals with the highest likelihood of transmitting infection produces a multiplier effect, while both universal and risk-based strategies have consistently proven cost-effective, generating medium-term savings. In Latin America, the epidemiological landscape is heterogeneous. While overall prevalence in the general population is relatively low, high endemicity persists in vulnerable groups such as people who inject drugs, incarcerated individuals, and patients undergoing hemodialysis. Major barriers include fragmented health systems, lack of clinical registries, stigma, and restricted access to diagnosis and therapy. Yet, the region also holds clear opportunities: simplified diagnostic pathways using rapid testing and reflex algorithms, micro-elimination in key populations, pooled procurement of antivirals through the Pan American Health Organization, and the integration of digital health and telemedicine. In conclusion, HCV screening constitutes both a public health necessity and an ethical obligation. Its organized and sustainable implementation is essential to translate therapeutic efficacy into collective benefit and to accelerate progress toward the elimination of hepatitis C.

The gut and the liver are the main organs in the regulation and distribution of zinc. Therefore, gut and liver disease impact zinc functions in other organs. Many of the phenomenological observations made in the past century concerning the role of zinc in growth and development and the role of zinc deficiency in many diseases are now better understood on the basis of zinc's remarkable catalytic, structural, and regulatory functions in over 3200 human proteins and its functions as an ionic messenger similar to calcium in intra- and extracellular communication, regulation of metabolism, and gene expression. Zinc has key roles in carbohydrate and lipid metabolism, nitrogen balance, pH control, and the synthesis and degradation of proteins. Its classification as a trace element distracts from its global significance in the proliferation and differentiation of all cells. Zinc is at least as important as iron, if not even more so. Its intricate cellular regulation by 24 membrane zinc transporters, a dozen metallothioneins and other zinc homeostatic proteins supports this tenet. This review will summarize the role of zinc in the integrity of the intestinal barrier, in maintaining a healthy gut, and, through the gut-liver axis, a healthy liver. Zinc is critical for a proper immune response to support and control inflammation, in fighting off insults and repairing tissues, but also in avoiding chronic inflammation. About 75% of patients with decompensated liver cirrhosis are zinc deficient. Zinc deficiency, a prooxidant and proinflammatory condition, needs clinical attention in liver disease, should include attention to gut health, and involve pharmacological treatment with supplemental zinc. Monotherapy with zinc alone, however, is not the answer. Along with zinc, additional therapeutics are required to restore intestinal and hepatic functions.