Incidence and risk factors of acute kidney injury in cirrhosis: a systematic review and meta-analysis of 5,202,232 outpatients, inpatients, and ICU-admitted patients.

INTRODUCTION: Acute kidney injury (AKI) is a commonly seen condition in the natural course of cirrhosis. The aim of this study was to evaluate the pooled incidence and risk factors of AKI in different clinical stages and situations in patients with cirrhosis. METHODS: Search was conducted on 13 December 2023 across MEDLINE (PubMed), Embase, and Cochrane databases. Meta-analysis was performed using a generalized linear mixed model. RESULTS: In total, 73 studies with 5,202,232 patients were finally enrolled in the meta-analysis. AKI commonly occurs among hospitalized cirrhotics experiencing any decompensation event (29%) as well as among stable outpatients (28%) throughout a 1-year follow-up period. On admission, patients with infection or sepsis/septic shock had the highest AKI rate (47%), followed by those with hepatic encephalopathy (41%). Furthermore, the severity of liver disease proved to be a substantial driver for AKI development, while patients at intensive care unit had the greatest AKI incidence (61%). CONCLUSIONS: Both hospitalized patients and stable outpatients with cirrhosis exhibited an elevated susceptibility to AKI. Patients at intensive care unit and those with severe liver disease, infection, sepsis/septic shock, hepatic encephalopathy, or acute on chronic liver failure upon admission are at higher risk for AKI. TRIAL REGISTRATION: PROSPERO, registered 09/12/23, CRD42023487736.

High disease burden and healthcare resource usage in patients with acute porphyria-A population-based analysis.

BACKGROUND AND AIMS: Acute porphyria is a chronic recurrent disease with late diagnosis, heterogeneous clinical presentations and potentially devastating complications. The study aimed at providing real-world evidence on the natural course of acute porphyria, patient characteristics, disease burden, and healthcare utilization before diagnosis. METHODS: This observational study used anonymized claims data covering 8 365 867 persons from German statutory health insurance, spanning 6 years (2015-2020). Patients with at least one diagnosis of acute porphyria during the index period (2019-2020) were classified into three groups by attack frequency. These findings were compared with two age- and sex-adjusted reference groups: the general population and fibromyalgia patients. Prevalence over the index period was calculated for all porphyria patients and those with active acute porphyria. RESULTS: We revealed a prevalence of 79.8 per 1 000 000 for acute porphyria, with 12.9 per 1 000 000 being active cases. Acute porphyria patients, particularly with frequent attacks, demonstrated a higher comorbidity burden compared to the general population. Within the year before the recorded diagnosis, patients with acute porphyria required a median of 23.0 physician visits, significantly higher than the general population's 16.0. Additionally, 33.8% were hospitalized at least once during this period, a notably higher proportion than the general population (19.3%). CONCLUSIONS: This study's findings, collected before the introduction of givosiran, as the first approved preventive therapy for acute porphyria in Europe, highlight the need for healthcare strategies and policies tailored to the complex needs of acute porphyria patients. The significant healthcare demands, heightened comorbidity burden, and increased healthcare system utilization emphasize the urgency of developing a comprehensive support infrastructure for these patients. Also, these acute porphyria real-world findings provide additional insights on disease characteristics in Germany.

Portosystemic Hepatic Encephalopathy Scores (PHES) differ between Danish and German healthy populations despite their geographical and cultural similarities.

Minimal hepatic encephalopathy (MHE) is common in liver cirrhosis and is identified by psychometric tests. The portosystemic hepatic encephalopathy score (PHES) is the most widely used and serves as an inter-study comparator. PHES has not been standardised for use in the Danish population, where German normal values have been applied until now based on the notion that the populations are comparable. This study aimed to evaluate if German PHES normal values can be applied in the Danish population and establish Danish normal values if needed. 200 Danish and 217 German healthy persons underwent Number Connection Test A and B (NCT), Line Tracing Test (LTT), Digit Symbol Test (DST), and Serial Dotting Test (SDT), and based on performance, PHES was calculated. German and Danish PHES performance declined with age in all subtests but more rapidly in Danes. Both German and Danish norms were impacted by gender and education, but to a different extent in the single tests of the test battery. Accordingly, there was a need for specific Danish normal values, which are presented here. Applying the new Danish normal values instead of the German in patients with cirrhosis yielded a lower percentage of out-of-norm performances (58% vs. 66%) and, hence, a lower prevalence of MHE. Danes and Germans perform differently on PHES, and therefore, normal German values cannot be used in Danish patients. Danish normal values are presented here and yield a lower number of 'out of norm' performances.

Fructooligosaccharides reverses hepatic vascular dysfunction and dysbiosis in rats with liver cirrhosis and portal hypertension.

BACKGROUND: Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome. METHODS: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations. RESULTS: Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that Negativicutes, Selenomonadales and Lactobacillus salivarius reduced in the fructooligosaccharides-treated group. CONCLUSION: In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress.

Remifentanil represses oxidative stress to relieve hepatic ischemia/reperfusion injury via regulating BACH1/PRDX1 axis.

BACKGROUND: Hepatic ischemia-reperfusion injury (HIRI) is a major cause of liver dysfunction after clinical liver surgery, which seriously affects the prognosis of patients. Remifentanil (RE) has been verified to attenuate HIRI. However, its therapeutic mechanism is still unclear. This study aimed to explore the protective mechanism of RE against HIRI. METHODS: A mouse HIRI model and an in vitro model of hypoxia/reoxygenation (H/R)-stimulated AML12 hepatocytes were established. Liver histopathological changes were evaluated by hematoxylin and eosin (HE) staining. Oxidative stress damage was assessed by malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) levels. Liver function was determined by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH). and adenosine triphosphate (ATP) levels. Cell counting kit-8 (CCK-8) assessed cell viability. Apoptosis was measured by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) and flow cytometry. The levels of inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA) kits. The differentially expressed genes were evaluated by mRNA microarray analysis. Western blotting and real-time quantitative polymerase chain reaction (RT-qPCR) were conducted to detect molecule expression. The binding of BTB and CNC homology 1 (BACH1) to peroxiredoxin 1 (PRDX1) was validated by chromatin immunoprecipitation (ChIP) and dual luciferase reporter assay. RESULTS: RE treatment improved liver function, and repressed oxidative stress damage and apoptosis in HIRI mice. Nine differentially expressed genes in the liver tissues of HIRI mice were selected by microarray analysis, among which BACH1 was down-regulated and PRDX1 was up-regulated after RE treatment. In addition, BACH1 directly bound to the promoter region of PRDX1 to inhibit its transcription and expression, which led to oxidative stress injury. BACH1 overexpression or PRDX1 silencing could counteract the beneficial effects of RE against HIRI. CONCLUSION: RE suppressed oxidative stress injury and inflammation via inactivation of the BACH1/PRDX1 axis, thereby ameliorating HIRI. Our findings enrich the understanding of the protective mechanisms of RE against HIRI, and provide novel evidence for its clinical application.

Detection of minimal hepatic encephalopathy in patients with cirrhosis based on the Stroop-CN model (NCRCID-CHESS 2106): a prospective multicenter study.

Minimal hepatic encephalopathy (MHE) has a substantial impact on the clinical outcomes and quality of life (QOL) of patients with cirrhosis. However, timely diagnosis and intervention are challenging due to sophisticated diagnostic methods. In this study, 673 healthy controls and 905 patients with cirrhosis were screened, and 660 healthy controls and 757 patients with cirrhosis, divided into the test (292 patients) and validation (465 patients) cohort, were analyzed after screening. A diagnostic model of the Stroop test (Stroop-CN) was constructed by multivariate linear regression based on the results of healthy controls. The prevalence of MHE and the comparison results with psychometric hepatic encephalopathy score through the Stroop-CN model were stable in the test and validation cohorts. Moreover, the prevalence of MHE remained significantly higher in patients with worse disease conditions marked as high Child-Pugh grades and the Model for End-stage Liver Disease and Sodium (MELD-Na) scores in the test and validation cohort. The EuroQol 5-D questionnaire revealed that patients with MHE had a worse QOL than those without MHE both in the test and validation cohort. In conclusion, an easy and practical Stroop-CN model for MHE diagnosis based on the EncephalApp is established. It is found that a considerable number of Chinese patients with cirrhosis experience MHE, which significantly impacts their QOL.

Pharmacokinetics and safety of GST-HG171, a novel 3CL protease inhibitor, in Chinese subjects with impaired and normal liver function.

GST-HG171 is a potent, broad-spectrum, orally bioavailable small-molecule 3C-like (3CL) protease inhibitor that was recently approved for treating mild to moderate coronavirus disease 2019 patients in China. Since cytochrome P450 (CYP) enzymes, primarily CYP3A, are the main metabolic enzymes of GST-HG171, hepatic impairment may affect its pharmacokinetic (PK) profile. Aiming to guide clinical dosing for patients with hepatic impairment, this study, using a non-randomized, open-label, single-dose design, assessed the impact of hepatic impairment on the PK, safety, and tolerability of GST-HG171. Patients with mild and moderate hepatic impairment along with healthy subjects were enrolled (n = 8 each), receiving a single oral dose of 150 mg GST-HG171, with concurrent administration of 100 mg ritonavir to sustain CYP3A inhibition before and after GST-HG171 administration (-12, 0, 12, and 24 hours). Compared to subjects with normal hepatic function, the geometric least-squares mean ratios (90% confidence intervals) for GST-HG171's maximum plasma concentration (Cmax), area under the concentration-time curve up to the last quantifiable time (AUC0-t), and area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC0-∞) in subjects with mild hepatic impairment were 1.14 (0.99, 1.31), 1.07 (0.88, 1.30), and 1.07 (0.88, 1.29), respectively. For moderate hepatic impairment, the ratios were 0.87 (0.70, 1.07), 0.82 (0.61, 1.10), and 0.82 (0.61, 1.10), respectively. Hepatic impairment did not significantly alter GST-HG171's peak time (Tmax) and elimination half-life (T1/2). GST-HG171 exhibited good safety and tolerability in the study. Taken together, mild to moderate hepatic impairment minimally impacted GST-HG171 exposure, suggesting no need to adjust GST-HG171 dosage for patients with mild to moderate hepatic impairment in the clinic.Clinical TrialsRegistered at ClinicalTrials.gov (NCT06106113).

A Close Clinical Workup of a Spontaneous Idiopathic Hepatic Rupture.

Atraumatic spontaneous liver rupture is a very rare occurrence. Most case reports and case series focus on patients during pregnancy, conditions associated with malignancy, hepatomegaly/hepatic pathology, benign masses/lesions, or infectious etiologies. This case report presents a unique circumstance where none of the above-mentioned etiologies were evident at the initial presentation or during the clinical workup. The patient presented with some non-specific symptoms of biliary colic without a conclusive diagnosis before the hepatic rupture. Given the high morbidity and mortality associated with spontaneous liver rupture, we believe this case allows for a closer look at the pre-rupture presentation and eventual sequelae not mentioned elsewhere in the literature.

Exploring the lutein therapeutic potential in steatotic liver disease: mechanistic insights and future directions.

The global prevalence of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is increasing, now affecting 25%-30% of the population worldwide. MASLD, characterized by hepatic steatosis, results from an imbalance in lipid metabolism, leading to oxidative stress, lipoperoxidation, and inflammation. The activation of autophagy, particularly lipophagy, alleviates hepatic steatosis by regulating intracellular lipid levels. Lutein, a carotenoid with antioxidant and anti-inflammatory properties, protects against liver damage, and individuals who consume high amounts of lutein have a lower risk of developing MASLD. Evidence suggests that lutein could modulate autophagy-related signaling pathways, such as the transcription factor EB (TFEB). TFEB plays a crucial role in regulating lipid homeostasis by linking autophagy to energy metabolism at the transcriptional level, making TFEB a potential target against MASLD. STARD3, a transmembrane protein that binds and transports cholesterol and sphingosine from lysosomes to the endoplasmic reticulum and mitochondria, has been shown to transport and bind lutein with high affinity. This protein may play a crucial role in the uptake and transport of lutein in the liver, contributing to the decrease in hepatic steatosis and the regulation of oxidative stress and inflammation. This review summarizes current knowledge on the role of lutein in lipophagy, the pathways it is involved in, its relationship with STARD3, and its potential as a pharmacological strategy to treat hepatic steatosis.

Prognostic Value of Alpha-Fetoprotein in Unresectable Hepatocellular Carcinoma Treated with Hepatic Artery Infusion Chemotherapy Combined with Lenvatinib and Camrelizumab.

Purpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab. Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a >20% decrease in AFP within 4 weeks, and AFP response as a >75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated. Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p<0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p<0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333-6.585, p=0.008, and HR 6.182, 95% CI 1.780-21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107-4.318, p=0.024, and HR 3.078, 95% CI 1.407-6.730, p=0.005), serving as significant prognostic values. Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.

Associations between systemic inflammation indicators and nonalcoholic fatty liver disease: evidence from a prospective study.

Background: Although inflammation has been linked to nonalcoholic fatty liver disease (NAFLD), most studies have focused only on a single indicator, leading to inconsistent results. Therefore, a large prospective study that includes a variety of well-documented single and composite indicators of inflammation is needed. This study aimed to thoroughly investigate the potential associations between different systemic inflammatory indicators and NAFLD in the UK Biobank cohort. Methods: After excluding ineligible participants, 378,139 individuals were included in the study. Associations between systemic inflammatory indicators and hepatic steatosis were assessed using multivariate logistic regression. The relationships between systemic inflammatory indicators and nonalcoholic fatty liver disease were analysed using Cox proportional hazards models, and nonlinear associations were investigated using restricted cubic splines. Results: According to the cross-sectional analysis, systemic inflammatory indicators significantly correlated with hepatic steatosis. Over a median follow-up of 13.9 years, 4,145 individuals developed NAFLD. After sufficient adjustment for confounding factors, CRP levels were found to be nonlinearly positively associated with NAFLD risk (P<0.001), representing the strongest correlation among the tested relationships; lymphocyte count and the LMR showed an L-shaped correlation; monocyte count and neutrophil count showed a linear positive correlation (all P< 0.001); and the NLR, PLR, and SII showed a U-shaped correlation (all P<0.001). Conclusions: Multiple systemic inflammatory indicators are strongly associated with the development of NAFLD, and aggressive systemic inflammation management may have a favourable impact on reducing the burden of NAFLD; further randomized controlled studies are needed.

Laparoscopic cholecystectomy for a gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct using indocyanine green fluorescence imaging: A case report.

INTRODUCTION: Gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct is a rare variation. It is frequently associated with bile duct injury during laparoscopic cholecystectomy. We present a case of a gallbladder with this variation safely treated with laparoscopic cholecystectomy using indocyanine green (ICG) fluorescence imaging. PRESENTATION OF CASE: A 57-year-old man had right upper quadrant pain and showed a gallbladder stone on a preoperative computed tomography. Bile duct anomaly was not detected before operation. However, a short cystic duct draining to the accessory right anterior hepatic duct intraoperatively was found using ICG fluorescence imaging. To confirm the exact anatomy, we firstly detached the gallbladder from the liver with a "fundus first technique" and visualized the whole course of the short cystic duct and the accessory right anterior with ICG fluorescence imaging. Laparoscopic cholecystectomy was completed safely. No bile leakage was detected on ICG fluorescence imaging. The patient had no postoperative complication. DISCUSSION: Accessory right hepatic duct is one of the rare variations of bile duct. It can be related to bile duct injury during laparoscopic cholecystectomy. Although it can be injured easily because of its smaller size, we can identify the short cystic duct from it with the aid of ICG fluorescence imaging without injuring the accessory right anterior hepatic duct. CONCLUSION: Laparoscopic cholecystectomy for gallbladder with a short cystic duct draining to the accessory right anterior hepatic duct can be safely performed by identifying biliary anatomy with ICG fluorescence imaging.

Phase 1 pharmacokinetic and safety study of soticlestat in participants with mild or moderate hepatic impairment or normal hepatic function.

This phase 1, open-label, three-arm study (NCT05098054) compared the pharmacokinetics and safety of soticlestat (TAK-935) in participants with hepatic impairment. Participants aged ≥18 to <75 years had moderate (Child-Pugh B) or mild (Child-Pugh A) hepatic impairment or normal hepatic function (matched to hepatic-impaired participants by sex, age, and body mass index). Soticlestat was administered as a single oral 300 mg dose. Pharmacokinetic parameters of soticlestat and its metabolites TAK-935-G (M3) and M-I were assessed and compared by group. The incidence of treatment-emergent adverse events (TEAEs) and other safety parameters were also monitored. The pharmacokinetic analyses comprised 35 participants. Participants with moderate hepatic impairment had lower proportions of bound and higher proportions of unbound soticlestat than participants with mild hepatic impairment and normal hepatic function. Total plasma soticlestat pharmacokinetic parameters (maximum observed concentration [Cmax], area under the concentration-time curve from time 0 to time of last quantifiable concentration [AUClast], and AUC from time 0 to infinity [AUC∞]) were approximately 115%, 216%, and 199% higher with moderate and approximately 45%, 35%, and 30% higher with mild hepatic impairment, respectively, than healthy matched participants. Moderate hepatic impairment decreased the liver's ability to metabolize soticlestat to M-I; glucuronidation to M3 was also affected. Mild hepatic impairment resulted in a lower total plasma M-I exposure, but glucuronidation was unaffected. TEAEs were similar across study arms, mild, and no new safety findings were observed. A soticlestat dose reduction is required for individuals with moderate but not mild hepatic impairment.

Transcriptional Control: A Directional Sign at the Crossroads of Adult Hepatic Progenitor Cells' Fates.

Hepatic progenitor cells (HPCs) have a bidirectional potential to differentiate into hepatocytes and bile duct epithelial cells and constitute a second barrier to liver regeneration in the adult liver. They are usually located in the Hering duct in the portal vein region where various cells, extracellular matrix, cytokines, and communication signals together constitute the niche of HPCs in homeostasis to maintain cellular plasticity. In various types of liver injury, different cellular signaling streams crosstalk with each other and point to the inducible transcription factor set, including FoxA1/2/3, YB-1, Foxl1, Sox9, HNF4α, HNF1α, and HNF1ß. These transcription factors exert different functions by binding to specific target genes, and their products often interact with each other, with diverse cascades of regulation in different molecular events that are essential for homeostatic regulation, self-renewal, proliferation, and selective differentiation of HPCs. Furthermore, the tumor predisposition of adult HPCs is found to be significantly increased under transcriptional factor dysregulation in transcriptional analysis, and the altered initial commitment of the differentiation pathway of HPCs may be one of the sources of intrahepatic tumors. Related transcription factors such as HNF4α and HNF1 are expected to be future targets for tumor treatment.

High dietary Fructose Drives Metabolic Dysfunction-Associated Steatotic Liver Disease via Activating ubiquitin-specific peptidase 2/11ß-hydroxysteroid dehydrogenase type 1 Pathway in Mice.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common cause of chronic liver-related morbidity and mortality. Though high fructose intake is acknowledged as a metabolic hazard, its role in the etiology of MASLD requires further clarification. Here, we demonstrated that high dietary fructose drives MASLD development and promotes MASLD progression in mice, and identified Usp2 as a fructose-responsive gene in the liver. Elevated USP2 levels were detected in the hepatocytes of MASLD mice; a similar increase was observed following fructose exposure in primary hepatocytes and mouse AML12 cells. Notably, hepatocytes overexpressing USP2 presented with exaggerated lipid accumulation and metabolic inflammation when exposed to fructose. Conversely, USP2 knockdown mitigated these fructose-induced changes. Furthermore, USP2 was found to activate the C/EBPα/11ß-HSD1 signaling, which further impacted the equilibrium of cortisol and cortisone in the circulation of mice. Collectively, our findings revealed the role of dietary fructose in MASLD pathogenesis and identified the USP2-mediated C/EBPα/ 11ß-HSD1 signaling as a potential target for the management of MASLD.

Liver metastasis from hepatoid adenocarcinoma of the stomach: a case report and literature review.

Hepatoid adenocarcinoma of the stomach (HAS) represents a rare malignant neoplasm sharing morphological and immunophenotypic similarities with hepatocellular carcinoma (HCC). Pathological morphology serves as the cornerstone for diagnosis, often accompanied by elevated alpha-fetoprotein (AFP) levels, nonspecific clinical symptoms, and imaging features reminiscent of gastric adenocarcinoma (GA). Liver metastases from HAS can mimic the enhancement patterns of HCC, posing challenges in differentiation from high-risk HCC cases. Conversely, HAS typically exhibits poorer prognostic outcomes compared to HCC and GA. This report presents a case of HAS with liver metastasis alongside a comprehensive literature review covering its pathology, molecular mechanisms, clinical presentations, and treatment modalities. Special focus is given to imaging characteristics and the utilization of radiomics for early-stage detection. The integration of imaging findings with laboratory results aids in HAS diagnosis, while radiomics provides novel insights for precise discrimination. In conclusion, the identification of distinct imaging markers distinguishing HAS from HCC and GA shows promise in facilitating optimal treatment strategies and improving patient outcomes.

Value of intralesional and perilesional radiomics for predicting the bioactivity of hepatic alveolar echinococcosis.

Objectives: To investigate the value of intralesional and perilesional radiomics based on computed tomography (CT) in predicting the bioactivity of hepatic alveolar echinococcosis (HAE). Materials and methods: In this retrospective study, 131 patients who underwent surgical resection and diagnosed HAE in pathology were included (bioactive, n=69; bioinactive, n=62). All patients were randomly assigned to the training cohort (n=78) and validation cohort (n=53) in a 6:4 ratio. The gross lesion volume (GLV), perilesional volume (PLV), and gross combined perilesional volume (GPLV) radiomics features were extracted on CT images of portal vein phase. Feature selection was performed by intra-class correlation coefficient (ICC), univariate analysis, and least absolute shrinkage and selection operator (LASSO). Radiomics models were established by support vector machine (SVM). The Radscore of the best radiomics model and clinical independent predictors were combined to establish a clinical radiomics nomogram. Receiver operating characteristic curve (ROC) and decision curves were used to evaluate the predictive performance of the nomogram model. Results: In the training cohort, the area under the ROC curve (AUC) of the GLV, PLV, and GPLV radiomic models was 0.774, 0.729, and 0.868, respectively. GPLV radiomic models performed best among the three models in training and validation cohort. Calcification type and fibrinogen were clinical independent predictors (p<0.05). The AUC of the nomogram-model-based clinical and GPLV radiomic signatures was 0.914 in the training cohort and 0.833 in the validation cohort. The decision curve analysis showed that the nomogram had greater benefits compared with the single radiomics model or clinical model. Conclusion: The nomogram model based on clinical and GPLV radiomic signatures shows the best performance in prediction of the bioactivity of HAE. Radiomics including perilesional tissue can significantly improve the prediction efficacy of HAE bioactivity.

Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for ≥ 5 cm hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth globally in cancer incidence and third in mortality rates. Unfortunately, over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations, poor physical condition, and limited organ availability upon diagnosis. Clinical guidelines endorse transarterial chemoembolization (TACE) as the frontline treatment for intermediate to advanced-stage HCC. Cryoablation (CRA) is an emerging local ablative therapy increasingly used in HCC management. Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects, potentially improving long-term survival rates. However, the superiority of combined TACE + CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation. AIM: To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of ≥ 5 cm. METHODS: PubMed, EMBASE, Cochrane Library, CNKI, Wanfang, and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022. Meta-analysis was performed using RevMan 5.3 software. RESULTS: After screening according to the inclusion and exclusion criteria, 6 articles were included, including 2 randomized controlled trials and 4 nonrandomized controlled trials, with a total of 575 patients included in the meta-analysis. The results showed that the objective response rate [odds ratio (OR) = 2.56, 95% confidence interval (CI):1.66-3.96, P < 0.0001), disease control rate (OR = 3.03, 95%CI: 1.88-4.89, P < 0.00001), 1-year survival rate (OR = 3.79, 95%CI: 2.50-5.76, P < 0.00001), 2-year survival rate (OR = 2.34, 95%CI: 1.43-3.85, P = 0.0008), and 3-year survival rate (OR = 3.34, 95%CI: 1.61-6.94, P = 0.001) were all superior to those of the control group; the postoperative decrease in alpha-fetoprotein value (OR = 295.53, 95%CI: 250.22-340.85, P < 0.0001), the postoperative increase in CD4 value (OR = 10.59, 95%CI: 8.78-12.40, P < 0.00001), and the postoperative decrease in CD8 value (OR = 6.47, 95%CI: 4.44-8.50, P < 0.00001) were also significantly higher than those in the TACE-alone treatment group. CONCLUSION: Compared with TACE-alone treatment, TACE + CRA combined treatment not only improves the immune function of HCC patients with a diameter of ≥ 5 cm, but also enhances the therapeutic efficacy and long-term survival rate, without increasing the risk of complications. Therefore, TACE + CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of ≥ 5 cm.

Primary Hepatic Neuroendocrine Carcinoma: A Rare Entity.

Neuroendocrine tumors are typically low-malignancy growths arising from neuroectodermal cells of neural crest origin. Neuroendocrine carcinoma, on the other hand, represents a high-malignancy form of these tumors. While rare in the liver, they often indicate metastasis when present. We present a unique case of incidentally discovered primary hepatic neuroendocrine carcinoma. Initially, the patient's management was based on misleading radiological findings. However, histopathology confirmed the diagnosis, with subsequent imaging ruling out an extrahepatic source. Despite this, the patient opted against surgical intervention, resulting in a fatal outcome. This case underscores the critical importance of prompt diagnosis and intervention to avert adverse outcomes.