Livers, Volume 6, Issue 2 (April 2026) – 20 articles

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. Full article

Autoimmune hepatitis (AIH) has long been regarded as an organ-specific disorder. However, increasing evidence supports its systemic nature, with extrahepatic manifestations representing key aspects of clinical management. These manifestations can affect musculoskeletal, gastrointestinal, haematologic, and other systems. They also reflect the complex interplay between systemic inflammation, concomitant autoimmune diseases, and drug-related toxicity. A careful evaluation is therefore essential to distinguish between these scenarios, especially for symptoms like fatigue and cytopenias. This narrative review provides a comprehensive, symptom-based overview of extrahepatic clinical and laboratory findings in AIH. By integrating current evidence with practical diagnostic considerations, it aims to offer clinicians a patient-centred and clinically relevant framework for navigating the multifaceted systemic landscape of AIH. Full article

Liver transplantation (LT) is the definitive treatment for patients with end-stage liver disease. Since its inception in the 1960s, transplant medicine has undergone substantial advances in surgical technique, immunosuppression, organ preservation, and organ allocation policies. According to the 2023 WHO census, approximately 47,180 LT procedures occur worldwide each year, with living donors contributing to up to 23% of cases. Additional milestones include the expansion of transplant eligibility to patients with hilar cholangiocarcinoma and advanced colorectal liver metastasis, the incorporation of viscoelastic testing into perioperative blood management algorithms, and the increasing use of mechanical circulatory support for pre-transplant optimization. In parallel, medical training has evolved to meet the complexities associated with these high-risk procedures. Structured fellowship programs now provide focused expertise, and guide investigations to resolve complex clinical dilemmas. Experience accumulated over decades has improved clinicians’ ability to manage the expanding spectrum of comorbidities seen in contemporary transplant candidates. Key perioperative challenges include accurate assessment of fluid status, optimization of intravascular volume, management of vasoplegia, intraoperative renal replacement therapy, treatment of right-ventricular failure, and the mitigation of severe lactic acidosis. As transplant recipients increasingly present at older ages and with multiple comorbidities, perioperative management has become more demanding. One emerging strategy for select high-risk patients involves performing concurrent surgical procedures within a single operative session. This narrative review focuses on the intraoperative management of five variables that proved challenging during the first case of concurrent liver transplantation and off-pump coronary artery bypass surgery in our institution. Full article

Background and goals: The outcomes of patients with primary sclerosing cholangitis (PSC) in central Missouri are unknown. The University of Missouri–Columbia services 600,000 individuals in central Missouri. Our aims were (a) to examine the outcomes of PSC patients receiving care at our academic institution, and (b) to identify the predictors of PSC-related serious adverse events. Methods: A retrospective study of patients with PSC in a non-transplant center. The primary outcome was the development of ≥1 of PSC-related serious adverse event for (1) progression to cirrhosis, or (2) development of cholangiocarcinoma. Results: From 2000 to 2018, 42 patients fulfilled the criteria for the diagnosis of PSC. A total of 55% of the patients were male, and 79% had associated inflammatory bowel disease (IBD). The median follow-up from time of diagnosis of PSC until the last follow-up or death was 5.5 years. A total of 57% of the patients developed ≥ 1 PSC-related adverse event; 36% (8/22) of those who progressed to decompensation underwent liver transplantation. The median time from diagnosis of PSC until progression to decompensation was 6.3 years; the median time from decompensation to transplantation was 10.8 years. A total of 12% of the patients developed ≥ 1 cancer (cholangiocarcinoma = 2; gallbladder cancer = 2; colon cancer = 1; and hepatocellular carcinoma = 1). The overall mortality was 9.5%. The median time from PSC diagnosis until death was 10.2 years. A Cox hazards regression analysis showed only age (HR = 1.16; p = 0.032; 95% CI, 1.01–1.13) and serum bilirubin (HR = 1.42; p = 0.036; 95% CI, 1.03–2.69) at the time of PSC diagnosis were independently associated with PSC-related serious events. Conclusions: Age and bilirubin are important predictors of PSC-related outcomes. Full article

Genetic liver diseases encompass a heterogeneous group of conditions that disrupt hepatic development, structure, or function. Advances in high-throughput sequencing have revealed the molecular basis of many disorders previously defined only by clinical or biochemical features, transforming diagnostic and therapeutic approaches. This review proposes a mechanistic framework that distinguishes diseases arising from developmental abnormalities from those caused by functional impairments in hepatocellular or biliary physiology. It outlines how defects in transporters, enzymes, signaling pathways, intracellular trafficking, and mitochondrial function converge to produce diverse hepatic phenotypes. Moreover, translational aspects are discussed such as how the growing integration of genetic testing into clinical practice enables precise diagnosis, informs prognosis and therapy, and refines disease classification. Finally, the review discusses future directions in the field, emphasizing the role of multi-omic approaches, organoid modeling, and data sharing in elucidating unresolved pathogenic mechanisms and advancing precision hepatology. Full article

Background/Objectives: Carbohydrate-restricted diets (CHRs) are increasingly employed in the treatment of obesity. We aimed to investigate the effects of a CHR on hepatic lipid anabolism and its association with changes in the proinflammatory environment and insulin signaling. Methods: Forty-eight C57BL/6J female mice were used in this study. We aimed to analyze the impact of a CHR on the hepatic proinflammatory profile and its relationship with changes in insulin signaling and fatty acid anabolism in obese female mice after two months on a high-fat diet. We also examined the impact of a one-month chow diet after CHR. Blood samples were collected, and the liver was processed during all-time study periods for analyses of biochemical, hormonal, and inflammatory markers, as well as possible changes in leptin and insulin signaling pathways. Results: Compared with chow-fed mice, CHR mice showed increased interleukin (IL)-1β and IL-2 levels, as well as leptin-related signaling in the liver. There was also a decrease in the expression of fatty acid synthase and the phosphorylation of ATP-citrate lyase, which was associated with a reduction in the activation of the insulin receptor, Akt, the mammalian target of rapamycin, cAMP-response element-binding protein, and glycogen synthase kinase 3β. The subsequent reintroduction of a chow diet after CHR resulted in lower hepatic free fatty acid and triglyceride levels than in obese mice without previous CH restriction. Conclusions: This study suggests that CHR inhibits de novo hepatic lipogenesis in obese mice by attenuating insulin signaling in a low-grade proinflammatory state. Full article

Porto-sinusoidal vascular disorder (PSVD) is an umbrella term proposed by the Vascular Liver Disease Interest Group (VALDIG) in 2019. It refers to a group of non-cirrhotic vascular liver diseases that cause portal hypertension. These were previously described as idiopathic non-cirrhotic portal hypertension, hepatoportal sclerosis, nodular regenerative hyperplasia, and incomplete septal fibrosis. PSVD is characterized by injury and remodeling of portal venules and sinusoids. Immune dysregulation, prothrombotic states, infections, medications (e.g., oxaliplatin, thiopurines), toxins (e.g., arsenic), and genetic susceptibility often drive this process. Clinically, PSVD ranges from asymptomatic patients with only abnormal liver tests to severe complications of portal hypertension, such as variceal bleeding, ascites, and portal vein thrombosis. Patients typically have preserved liver synthetic function, helping distinguish PSVD from cirrhosis. Diagnosis is based on VALDIG criteria and requires an adequate liver biopsy that shows no cirrhosis. It also requires specific combinations of clinical signs of portal hypertension and characteristic histological lesions, such as obliterative portal venopathy, nodular regenerative hyperplasia, and incomplete septal fibrosis. Non-invasive tools, including imaging and liver stiffness measurement, are supportive. They often show discordance between marked portal hypertension and low liver stiffness, suggesting a non-cirrhotic cause. Management follows cirrhosis-based portal hypertension guidelines. This includes non-selective beta-blockers, endoscopic variceal ligation, TIPS, anticoagulation in selected patients, and liver transplantation for refractory or end-stage disease. Prognosis is generally better than in cirrhosis, with a 5-year transplant-free survival rate of approximately 85% compared to 60% in matched cirrhotics. However, major gaps remain in the true epidemiology, the natural history of early or subclinical PSVD, validated non-invasive biomarkers, and disease-modifying therapies. Full article

Background and Objectives: This study investigated the correlation of the liver-to-spleen (L/S) Hounsfield unit ratio on abdominal CT with liver function and diabetic indicators before and after laparoscopic sleeve gastrectomy (LSG), comparing patients with and without diabetes mellitus (DM and non-DM groups). Methods: Patients undergoing LSG were categorized into DM and non-DM groups. Metabolic parameters and abdominal CT scans were assessed preoperatively and one year postoperatively. Correlations among these variables were analyzed, and intergroup comparisons were performed. Results: Preoperative body weight and postoperative weight loss were comparable between the DM and non-DM groups. Before surgery, the DM group showed significantly higher levels of fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), aspartate transaminase (AST), alanine transaminase (ALT), and γ-glutamyl transpeptidase (γ-GTP). After LSG, both groups exhibited significant reductions in FPG, HbA1c, AST, ALT, and γ-GTP, along with a significant increase in the L/S ratio. The reduction in γ-GTP was more pronounced in the DM group. In the DM group, changes in glycemic markers (FPG and HbA1c) were significantly correlated with changes in liver enzymes and with the change in L/S ratio. Conclusions: LSG reduced body weight and fat mass and improved glucose metabolism and liver function in patients with obesity, regardless of their diabetes status. Improvements in liver enzymes and/or the L/S ratio were more marked in diabetic patients and might be closely linked to better glycemic control following surgery. Full article

The liver produces the majority of plasma proteins, maintaining the metabolic homeostasis. The dysregulation of liver protein synthesis underlies many systemic conditions. Therefore, there is a great potential in therapies that inhibit the hepatic protein production. This is the mechanism of action of antisense oligonucleotides (ASOs) and small interfering RNA (siRNA). These therapeutics have undergone rapid development and are revolutionizing the pharmacological landscape of many liver-related diseases (e.g., inclisiran in familial hypercholesterolemia). Furthermore, gene-editing technologies that allow a direct correction of impaired genes in the liver are currently being evaluated. They hold a promise for future advances in treatment, especially of monogenic disorders such as hereditary transthyretin amyloidosis or alpha-1 antitrypsin deficiency. In this review, we describe the most relevant systemic diseases caused by dysfunction of protein synthesis in liver cells, in which significant therapeutic progress has been made over the last decades. Moreover, we present currently available drugs and their mechanisms of action, including six siRNA agents and five ASOs that have been approved to date. Finally, we discuss emerging strategies, focusing on novel RNA-based therapeutics that are the subjects of ongoing clinical trials. Full article

Background: Intrahepatic cholangiocarcinoma (ICC) is an uncommon but increasingly recognized primary liver malignancy with a poor prognosis. Although surgical resection offers the only realistic opportunity for cure, recurrence is common and the optimal integration of surgery with systemic and liver-directed therapies continues to evolve. Summary: This review summarizes contemporary evidence on the diagnosis and multidisciplinary management of ICC with particular emphasis on surgical, systemic, locoregional, and transplant-based strategies. Cross-sectional imaging plays a central role in staging and assessing resectability including evaluation of vascular invasion and the future liver remnant. Upfront resection is appropriate for selected patients with resectable disease and preserved liver function, with margin-negative resection and lymphadenectomy remaining key oncologic goals. Systemic therapy continues to evolve with cytotoxic chemotherapy forming the backbone of treatment for advanced disease and immunotherapy and targeted agents demonstrating promise in biomarker-defined subgroups. Locoregional modalities such as hepatic arterial infusion therapy and radioembolization may provide disease control in liver-dominant ICC and are increasingly used within a multidisciplinary framework. Liver transplantation remains investigational but may offer favorable outcomes in highly selected early-stage disease. Full article

Primary biliary cholangitis (PBC) is an autoimmune-mediated disease characterized by chronic, non-suppurative, small-duct lymphocytic cholangitis. The prognosis largely depends on early disease recognition and treatment. Suboptimal response to first-line therapy (ursodeoxycholic acid) is associated with risk for disease progression. Reliable biomarkers are also required to enhance risk stratification. The traditional gold standard for assessing fibrosis is liver biopsy, but it is invasive and unsuitable for serial evaluations. Hence, trends are towards non-invasive surrogate biomarkers (blood-based and imaging biomarkers respectively) which have a much better safety profile. Blood-based biomarkers include: (i) Fibrosis-4 [Fib-4], (ii) Aspartate Aminotransferase to Platelet Ratio Index [APRI], (iii) Enhanced Liver Fibrosis score [ELF], and (iv) total bile acid to platelet ratio [TPR]. They show much potential but are not particularly sensitive tests. Ultrasound-based imaging biomarkers are increasingly being utilized for liver stiffness measurement (LSM), with vibration-controlled transient elastography (VCTE) emerging as the preferred technique. However, despite its growing popularity, VCTE is limited by technical issues. Hence, currently, none of the non-invasive tests fulfill the prerequisites to be the new gold standard as defined by the FDA. Nonetheless, there may be value to combining LSM with various serum biomarkers such as Fib-4, APRI, as aforementioned. The hope is to create nomograms for predicting liver-related events and decision tree algorithms. Newer studies are investigating microbiota in the gut-liver axis, biomolecules such as nanovesicles/nanofibers, and metabolic reprogramming as it pertains to e.g., proteomics and lipidomics. These approaches hold much promise, and if validated, could significantly change the management of PBC. Full article

Background/Aims: Sepsis as an acute cause of liver dysfunction is associated with high mortality. Routine infection/inflammation markers—C-reactive-protein (CRP), procalcitonin (PCT), and leukocyte count (LeuC)—are frequently used for risk stratification in septic patients. This study aimed to evaluate these markers as predictors of short-term and 12-month mortality in septic patients with distinct liver dysfunction phenotypes. Methods: This single-center retrospective pilot analysis involved adults with sepsis and varying degrees of liver dysfunction—acute liver failure (ALF), acute-on-chronic liver failure (ACLF), or acute-on-cirrhosis (ACOC)—treated in intermediate or intensive care units between 2016 and 2017. At sepsis onset, patients were categorized into ACOC, ACLF, and ALF groups. Only patients with recorded CRP, PCT, and LeuC measurements 24 h before, on the day of, and 24/48 h after sepsis onset were included in the analysis. Associations with in-hospital and 12-month mortality were analyzed using Firth bias-reduced logistic regression, ROC analysis, and internal validation by bootstrapping and cross-validation. Results: 49 patients were included (ACOC n = 21; ACLF n = 20; ALF n = 8). In-hospital and 12-month mortality rates were 34.7% and 61.2%, respectively, with the highest long-term mortality observed in the ACOC group (76.2%). In the ACOC group, PCT 24 h before sepsis onset independently predicted in-hospital mortality (OR ~5 per PCT doubling; AUC 0.94), with an optimal rule-in cut-off of 1.0 ng/mL (specificity 1.00, PPV 1.00). PCT was not predictive in ACLF/ALF, and CRP/LeuC offered limited prognostic value. Conclusions: In this hypothesis-generating analysis, PCT 24 h before sepsis onset shows a phenotype-specific association with early mortality in ACOC. Larger, prospective multicenter studies are needed to validate PCT-guided risk stratification. Full article

Background: Gadoxetic acid-enhanced MRI is essential for detecting and characterizing focal liver lesions. However, transient severe motion artifacts in the arterial phase can degrade image quality. Gadoxetic acid dilution has been proposed to mitigate these artifacts, but its impact on multiple arterial phase acquisition remains unclear. Objective: To evaluate the effect of gadoxetic acid dilution on image quality across multiple arterial phases in liver MRI, incorporating a phase-by-phase analysis. Methods: This retrospective study included 81 patients (52 men, 29 women; mean age 70.1 years) who underwent serial gadoxetic acid-enhanced MRI with undiluted and diluted contrast (1:1 saline dilution). MRI was performed on 1.5 T and 3.0 T scanners with a standardized injection rate of 1.0 mL/s. Two radiologists independently rated anatomic conspicuity, respiratory motion artifacts, and overall image quality using a Likert scale (1 to 5 with higher scores indicating better quality). A phase-by-phase analysis was conducted after a three-month washout period. Wilcoxon signed-rank tests were used for statistical comparisons, and inter-rater agreement was assessed with quadratic kappa coefficients. Results: Inter-observer agreement was substantial (ƙ = 0.602–0.702). Phase-by-phase analysis revealed significant improvement in image quality for the first three arterial phases (p = 0.003, 0.005, 0.050). Although the diluted method showed higher scores, the differences were not statistically significant in anatomic conspicuity (3.73 vs. 3.59, p = 0.110), respiratory artifacts (3.54 vs. 3.41, p = 0.291), and overall image quality (3.67 vs. 3.51, p = 0.083). Conclusions: Gadoxetic acid dilution improves image quality in early arterial phases of liver MRI, suggesting its potential to reduce motion artifacts. Full article

Primary Biliary Cholangitis (PBC) is a chronic, immune-mediated cholestatic liver disease characterized by progressive intrahepatic bile duct destruction, leading to pruritus, fatigue, cirrhosis, and eventually hepatocellular carcinoma. Early diagnosis has improved with the development of sensitive serologic assays (e.g., antimitochondrial antibodies, antinuclear antibodies) and the introduction of newer biomarkers. Risk stratification has become standardized with the help of GLOBE and UK-PBC scores, alongside non-invasive tools such as vibration-controlled transient elastography, enabling earlier intervention. Ursodeoxycholic acid (UDCA) is the first-line therapy; however, 30–40% of patients show an incomplete response, increasing their risk of liver failure and mortality. Second-line therapies have emerged which provide viable treatment avenues for those who do not respond to UDCA or are unable to tolerate it. However, in certain situations, such as decompensated cirrhosis, carcinoma, or refractory pruritus, liver transplantation constitutes the only curative therapy. While PBC has excellent post-liver transplant (post-LT) outcomes, patients with PBC face higher waitlist mortality as they tend to have lower MELD scores. Management post-LT includes the use of UDCA, immunosuppressants, and surveillance for recurrent PBC. Our review highlights the recent advances in medical management and transplant risk stratification of patients at risk of decompensation, as well as the perioperative transplant period outcomes and long-term post-transplant management strategies in patients with PBC. Full article

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. Full article

The liver plays a fundamental role in maintaining homeostasis thanks to the numerous functions performed by this organ. Non-inherited metabolic liver diseases, inherited metabolic liver diseases, and liver cancers are pathological conditions affecting liver function and that can lead to its failure. To date, for end-stage liver diseases—where the remaining hepatic tissue is no longer capable of regenerating sufficiently rapidly—or for metabolic diseases involving the liver, liver transplantation remains the standard and ideal therapeutic approach. However, this is limited by donor availability, surgical costs, and the tangible risk of autoimmune rejection, which may occur at varying intervals post-surgery. Furthermore, for the duration of their lives, transplant recipients must undergo systemic immunosuppressive treatment to prevent rejection; this is associated with high costs and severe side effects, including infections and secondary malignancies. In this review, we discuss these pathologies and how recent cell-based therapies and/or gene therapy approaches have emerged as promising alternatives that can provide either temporary restoration of hepatic function or long-term benefits, potentially reducing the global burden of liver disorders. Full article

Transmembrane 6 superfamily 2 (TM6SF2) was first described as a key regulator of hepatic lipid metabolism and lipoprotein secretion. Today, TM6SF2 is recognized to influence broader mechanisms in liver physiology and pathology. The protein has been linked to influence protein stability, very-low density lipoprotein (VLDL) assembly and secretion, hepatic lipid accumulation and development of Chronic liver disease (CLD). Furthermore, the TM6SF2 E167K variant has attracted scientific interest as it is associated with an increased risk of MASLD and other progressive liver diseases. This review provides an overview of the current knowledge of TM6SF2 and the E167K variant on hepatic lipid metabolism, VLDL mechanisms, protein interactions, CLD and antitumor immunity. Full article

Background. Somatostatin and its synthetic analog octreotide are suppressive hormones that have been used in the treatment of variceal bleeding or bleeding from portal hypertensive gastropathy. They are also used in the treatment of some cancers, including hepatocellular carcinoma (HCC). Experimental evidence reported that they have potentially useful effects on liver inflammation and fibrosis, acting on Kupffer cells (KCs) and hepatic stellate cells (HSCs). However, clinical data is missing. Therefore, the effect of somatostatin and octreotide was studied on several fibrosis mediators in patients with compensated cirrhosis. Patients and Methods. Fifty-eight patients with HCV-related compensated cirrhosis treated with either somatostatin or octreotide for bleeding from portal gastropathy were compared with twenty-nine healthy controls matched for age and sex. Serum levels of three metalloproteases (MMP1, MMP2 and MMP9) and their inhibitors, TIMP1 and TIMP2, were measured. Additional fibrosis and inflammation mediators—such as nitric oxide (NO), TNFα, soluble ICAM-1, and the CC chemokines RANTES (CCL5) and MIP1a (CCL3)—were also measured. Results. Serum levels of MMP1, MMP2, MMP9 and TIMP1 were significantly decreased in cirrhosis (p < 0.01). TIMP2 levels were increased (p < 0.01). RANTES levels were also significantly decreased (p < 0.01), but NO, TNFα, MIP1a and sICAM-1 were significantly increased (p < 0.01). Administration of somatostatin had no effect on MMP2 or MMP9 but significantly decreased all other mediators. Octreotide had similar but milder effects, but it had no effects on MIP1a and sICAM-1 were demonstrated. Conclusions. Somatostatin and octreotide modulate factors implicated in the progression of fibrosis in the short term. Whether they could be used in the long term as treatment for liver diseases with progressive fibrosis or in cases with intense inflammatory reactions, such as alcoholic hepatitis, requires further investigation. Full article

Background/Objectives: Systemic levels of the adipokine adiponectin are elevated in chronic liver disease including primary sclerosing cholangitis (PSC). Inflammatory bowel disease (IBD) and PSC are closely associated diseases, but in IBD serum adiponectin levels are near normal. Urinary and fecal biomarkers have been suggested to be superior to the corresponding serum protein for disease diagnosis, but urinary and fecal adiponectin have not been analyzed in PSC. The aim of this study was to evaluate the adiponectin in human serum, urine, and feces as a potential diagnostic tool for PSC. Methods: Serum and urine samples were collected from 74 IBD patients, 40 PSC patients (35 patients with PSC and IBD (16 patients for urine) and 5 patients with PSC without underlying IBD), and 17 controls. Feces samples from 53 IBD patients and 11 PSC patients (8 of them with PSC-IBD) were available for this study. Adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Results: Urinary and serum adiponectin levels in IBD patients and controls were comparable. Urinary, fecal and serum adiponectin in patients with ulcerative colitis and Crohn’s disease were similar and did not change, even with higher fecal calprotectin, a marker of intestinal inflammation in IBD. The three IBD patients with a high Gastrointestinal Symptom Rating Scale score as a marker for clinical activity had highly elevated urinary adiponectin. Systemic adiponectin levels were significantly elevated in the PSC-IBD cohort relative to the IBD-only group, suggesting its potential utility in clinical screening. Urinary and fecal adiponectin levels were similar between the cohorts. In PSC/PSC-IBD, serum adiponectin did not increase with higher fibrosis scores. Serum, urine, and fecal adiponectin were not correlated in both patient cohorts, except for a negative association of fecal and urine adiponectin in PSC. Conclusions: This exploratory study revealed preliminary findings suggesting an association between urinary adiponectin and severe gastrointestinal symptoms in IBD. In PSC-IBD, serum adiponectin is higher compared to IBD patients and continuous measurement may be used for PSC-IBD screening. Full article

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. Full article