Background: Direct-acting antivirals (DAAs) achieve high sustained virologic response (SVR) in hepatitis C virus (HCV) patients with cirrhosis, yet the risk of hepatic decompensation or hepatocellular carcinoma (HCC) persists. Fibrosis-4 (FIB-4), a pre-treatment index that predicts advanced fibrosis, is linked to HCC risk post SVR. We compared post-SVR outcomes and care engagement, and determined the optimal pre-treatment FIB-4 index to predict the risk of HCC or decompensation in HCV patients with cirrhosis treated at the Department of Corrections (DOC) and non-DOC clinics. Methods: HCV patients with cirrhosis treated with DAAs since 2014 in the HCV Treatment Registry were included. Cirrhosis was defined by elastography, imaging, or clinical criteria. Patients with prior decompensation or HCC were excluded. Outcomes (HCC, decompensation) were collected from records. The FIB-4 index was compared between DOC and non-DOC groups. Results: Among 2104 cirrhotic patients (mean age 54; 76% male), 53% were treated in DOC via telemedicine and 47% in non-DOC clinics. HCC developed in 4.8% and decompensation in 8.1%. DOC patients had lower FIB-4 scores and SVR, partly from higher loss to follow-up (9% vs. 1%). Of 1581 with follow-up, surveillance was more common in non-DOC, which also had higher HCC and decompensation. A higher baseline FIB-4 index independently predicted HCC and decompensation (cutoffs: 3.24, 3.7; AUROC 0.79, 0.75, respectively). Conclusions: Despite SVR, cirrhotic patients—especially with a high FIB-4 index—remain at risk for HCC and decompensation. Outcomes differ by care setting, highlighting the need for continued AASLD-recommended surveillance post-SVR.

Antitubercular drug-induced liver injury (ATDILI) poses a significant obstacle to successful tuberculosis treatment, including for tuberculous lymphadenitis. Its global incidence varies considerably, typically ranging from 2% to 30%, influenced by factors like patient demographics, co-morbidities, and geographical context. Despite some findings suggesting potentially lower rates in tuberculous lymphadenitis, the inherent hepatotoxic nature of standard anti-TB drugs means the risk remains clinically relevant. Key risk factors for ATDILI encompass older age, female gender, pre-existing liver conditions, HIV co-infection, malnutrition, alcoholism, and genetic polymorphisms, particularly in N-acetyltransferase 2 which affects isoniazid metabolism. The mechanisms of injury are drug-specific: isoniazid primarily causes hepatocellular damage via oxidative stress from toxic metabolites, while rifampicin induces cholestasis and endoplasmic reticulum stress, and pyrazinamide is linked to mitochondrial dysfunction. Management involves prompt withdrawal of antitubercular therapy when liver enzyme thresholds are exceeded, followed by careful reintroduction. Challenges are amplified in resource-limited settings due to higher prevalence of risk factors and limited access to consistent monitoring and sophisticated diagnostics. Promising advancements include safer regimens like the 3-month once-weekly isoniazid-rifapentine (3HP) for latent TB, which significantly reduces hepatotoxicity. The development of shorter active TB regimens and novel anti-TB drugs with improved safety profiles further aims to enhance treatment adherence and reduce ATDILI incidence, ultimately improving patient outcomes globally.

Background and Aim: Adjuvant therapy after curative intent treatment for hepatocellular carcinoma (HCC) is a significant unmet need. The IMbrave050 study demonstrated improved recurrence-free survival (RFS) in patients with high-risk HCC receiving adjuvant atezolizumab and bevacizumab post-curative treatment compared to active surveillance. However, the IMbrave050 cohort was predominantly Asian, largely underwent surgical resection, and had chronic liver disease (CLD) mainly due to hepatitis B features that differ markedly from the Australian setting, where microwave ablation (MWA) is more common and hepatitis B-related CLD is less prevalent. Given these differences, this study aimed to explore the performance of the IMbrave050 risk criteria in an Australian population of patients with early-stage HCC undergoing curative treatment to determine if the criteria identified patients with a high risk of recurrence who may benefit from adjuvant treatment. Method: We performed a retrospective 5-year study of 50 patients with early-stage HCC undergoing MWA with curative intent or liver resection. Patients were stratified into high- and low-risk groups using the IMbrave050 criteria. The primary outcomes were RFS and overall survival (OS) in the high- and low-risk cohorts. Results: For patients who underwent liver resection, the 1-year RFS was 77.8% and 100% in high- and low-risk patients respectively (p = NS). In those who underwent MWA, the 1-year RFS was 89.5% in the high-risk cohort and 73.3% in the low-risk cohort (p = NS). OS at 1-year was 100% in all cohorts (p = NS). Conclusions: In this Western cohort receiving predominantly ablation as curative therapy the current high-risk criteria do not reliably distinguish between those with increased risk of early recurrence and those without. Criteria defining high-risk may need to be refined to better identify patients who may benefit from adjuvant therapy in this setting.

This comment discusses a recent review by Wu and colleagues on multimodal artificial intelligence in gastroenterology and hepatology. The review outlined advancements in endoscopic, radiomics, pathologic, and multi-omics technologies. Additionally, it highlights persistent barriers, such as data heterogeneity, “black box” opacity, reimbursement uncertainty, and third-party data security risks. The comment also discusses current payment models for autonomous algorithms and emphasizes the importance of robust governance frameworks. Beyond summarizing recent progress, this commentary proposes a pragmatic, five-point roadmap to facilitate the safe and fair deployment of multimodal artificial intelligence in digestive disease care in the future, including standardization, explainability, federated governance, equitable reimbursement, and sustainability metrics. By implementing these action items, stakeholders can transform promising algorithms into clinically validated, workflow-compatible, and economically viable tools.

Background/Objectives: The donor liver shortage has created an urgent need to utilize higher-risk grafts for transplantation. Normothermic machine perfusion enables ex vivo graft assessment prior to transplantation, offering a route to expand access safely. However, proposed performance metrics often fail to differentiate dysfunctional grafts from functional grafts. Organs showing borderline results require careful deliberation as clinicians seek to balance recipient safety with waiting list access. The crucial question remains: are we discarding organs appropriately? Methods: To address this question, we describe a novel “secondary perfusion” model. We suggest that organs declined for transplantation after normothermic perfusion be subjected to an additional trial of cold ischemia and warm reanimation, mimicking reperfusion. Results: We present a protocol description and proof-of-concept case study using a marginal donor liver, showing how secondary perfusion enabled confirmation of predicted dysfunction. Conclusions: We share a protocol for modeling the performance of discarded organs in a recipient. We aim for this proof of concept to enable further investigation of existing viability criteria and better inform clinical decision-making.

Background: Surgical resection (SR) and liver transplantation (LT) are the main curative options for non-hepatocellular carcinoma (non-HCC) liver malignancies, including colorectal liver metastases (CRLMs), intrahepatic cholangiocarcinoma (iCCA), hilar cholangiocarcinoma (hCCA), and neuroendocrine tumor liver metastases (NETLMs). Resection aims for negative margins and adequate hepatic reserve, while LT offers treatment for unresectable disease but is limited by donor scarcity, immunosuppression, and ethical constraints. Methods: A targeted literature search (2005–2025) was conducted using PubMed and Google Scholar with predefined MeSH terms combining “liver resection,” “hepatectomy,” and “liver transplantation” across non-HCC malignancies. Relevant studies, reviews, and guidelines were included. Results: For CRLMs, SR remains standard with 5-year overall survival (OS) up to 58%, while LT offers 60–83% in highly selected unresectable cases. In iCCA, resection achieves median survival around 40 months, and LT yields OS up to 69% in very early or neoadjuvant-controlled disease. For hCCA, the Mayo protocol combining neoadjuvant therapy with LT provides 5-year OS of 65–80%. In NETLMs, LT achieves 63–97% OS under strict criteria. Conclusions: SR remains first-line for resectable non-HCC malignancies, while LT provides superior outcomes in unresectable yet biologically favorable disease, emphasizing careful selection and organ allocation.

Background/Objectives: Patients with isolated adult-onset growth hormone (GH) deficiency may present with hepatic steatosis and metabolic dysfunction. The effect of replacement therapy on metabolic phenotype has not been exhaustively studied yet. Methods: Patients with isolated adult-onset GH deficiency (GHD) were enrolled and prescribed GH-replacement therapy. DEXA scans for assessing body composition, anthropometric and biochemical parameters were evaluated at baseline and after 12 months of therapy. A fatty liver index, hepatic steatosis index and Fibrosis 4-test were calculated at baseline and after 12 months of therapy. Results and Conclusions: In our cohort, GH replacement therapy in adults with isolated adult-onset GHD is associated with weight loss and reduction of BMI (p < 0.001), amelioration in body composition with reduction in fat mass and trunk fat (respectively, p = 0.023 and p = 0.02), amelioration in lipid profile (significant reduction of total and LDL cholesterol and increase in HDL cholesterol) and reduction in fatty liver index (p = 0.021). Further long-term, randomized studies with bigger cohorts and advanced diagnostics are needed to confirm these results of our exploratory study.

Background: The National Surgical Quality Improvement Program (NSQIP) database provides one of the largest repositories of surgical outcome data—guiding local, national, and international quality improvement and research. We aim to describe a model to estimate Clavien–Dindo complication (CDC) rates from NSQIP data to enable comprehensive outcome measurement, allowing an NSQIP-based surrogate measure for longer-term outcomes. Methods: This is a validation study of a model to estimate CDCs from NSQIP data for pancreaticoduodenectomy (PD) and hepatic resection (HR). The primary objective of this study is to evaluate whether our method to estimate CDCs ≥ 3 outcomes from NSQIP data results in similar serious complication rates to large benchmark studies on outcomes following PD and HR. Secondary outcomes evaluate whether specific NSQIP outcomes provide adequate information to estimate CDC grades I-V following PD and HR. Results: We evaluated 20,575 patients undergoing PD, with 71.3% having pancreatic ductal adenocarcinoma. Comparing CDCs ≥ 3 complications for NSQIP and benchmark PD patients, we estimated a 23.2% rate with our model, which was significantly lower than the reported 27.6% in the benchmark study (p < 0.001). Additionally, the benchmark reported higher complication rates for every CDC grade compared to our estimates using NSQIP PD patients (p < 0.001). Further, we evaluated 29,809 patients within NSQIP undergoing HR, where most patients with a diagnosis listed had colorectal cancer metastases (30.8%). Compared to the benchmark HR study (n = 2159), the NSQIP patients were less likely to have hepatic resection for malignancy (57.7% vs. 84.0%; p < 0.001). Comparing CDCs ≥ 3 complications following HR demonstrated that rates were clinically similar (13.0% vs. 15.8%) but statistically different between the benchmark study and NSQIP data (p < 0.001). Additionally, the NSQIP patients had lower rates of estimated complications for nearly all CDC grades (p < 0.001). Conclusions: This is the first reported method to estimate aggregate morbidity from NSQIP data. Results demonstrate that despite differences in this and comparator cohorts, this model may underestimate CDC grade 1–2 complications but provide similar rates of CDCs ≥ 3 complications compared to benchmark studies. Future studies to validate or modify this estimation method are warranted and may allow extrapolation of short-term NSQIP measures to oncologic, quality of life, and long-term outcomes.

Ascites and renal dysfunction are among the most frequent and severe complications of decompensated advanced chronic liver disease (dACLD), often representing two interrelated manifestations of a shared pathophysiological continuum. Recurrent ascites and refractory ascites pose significant therapeutic challenges and are frequently associated with kidney impairment, particularly hepatorenal syndrome. Recent advances have reshaped the understanding of the underlying mechanisms, moving beyond the classical paradigm of peripheral arterial vasodilation to encompass systemic inflammation, gut dysbiosis, and cirrhosis-associated immune dysfunction (CAID). These insights have prompted a shift from uniform treatment protocols toward personalized, multidisciplinary strategies. Therapeutic innovations such as long-term albumin infusion, a transjugular intrahepatic portosystemic shunt, and the Alfapump® system offer promising options, though each requires careful patient selection. Emerging approaches—including fecal microbiota transplantation and peritoneal dialysis—further expand the therapeutic landscape. Ultimately, early risk stratification, the integration of non-invasive tools, and individualized care models are essential to improving outcomes in this high-risk population. This review synthesizes current evidence and highlights future directions for the tailored management of dACLD patients with ascites and renal dysfunction.

Herbal and dietary supplements (HDS) are used by over half of American adults and represent a multi-billion-dollar industry. More recently, they have gained popularity, in part due to promotion on multiple social media platforms. However, the Food and Drug Administration (FDA) does not regulate these products rigorously, and up to 20% of acute liver injuries are attributed to HDS. The true incidence of HDS hepatotoxicity is unknown but thought to be underreported. According to the World Health Organization (WHO), HDS-induced liver injuries are now the fifth most common cause of liver disease–associated death. The most common type of supplements associated with liver injury are bodybuilding and weight loss supplements. This study represents a comprehensive literature review of HDS-induced liver injury with a focus on the two most common culprits: bodybuilding supplements and weight loss supplements. Future strategies recommended to mitigate hepatotoxicity include strengthening regulatory oversight through mandatory product listing, enhancing post-market surveillance with standardized reporting and registries, improving product quality via ingredient verification and contaminant testing and, possibly, implementing standardized risk labeling.