Impact of pre-transplant immune checkpoint inhibitor use on post-transplant outcomes in HCC: A systematic review and individual patient data meta-analysis.

BACKGROUND AND AIM: Treatment with immune checkpoint inhibitors (ICIs) for hepatocellular carcinoma (HCC) prior to liver transplantation (LT) has been reported; however, ICIs may elevate the risk of allograft rejection and impact other clinical outcomes. This study aims to summarize the impact of ICI use on post-LT outcomes. MATERIALS AND METHODS: In this individual patient data meta-analysis, we searched databases to identify HCC cases treated with ICIs before LT, detailing allograft rejection, HCC recurrence, and overall survival. We performed Cox regression analysis to identify risk factors for allograft rejection. RESULTS: Among 91 eligible patients, with a median (interquartile range [IQR]) follow-up of 690.0 (654.5) days, there were 24 (26.4%) allograft rejections, 9 (9.9%) HCC recurrences, and 9 (9.9%) deaths. Age (adjusted hazard ratio [aHR] per 10 years=0.72, 95% confidence interval [CI]=0.53, 0.99, P=0.044) and ICI washout time (aHR per 1 week=0.92, 95% CI=0.86, 0.99, P=0.022) were associated with allograft rejection. The median (IQR) washout period for patients with ≤20% probability of allograft rejection was 94 (196) days. Overall survival did not differ between cases with and without allograft rejection (log-rank test, p=0.2). Individuals with HCC recurrence had fewer median (IQR) ICI cycles than those without recurrence (4.0 [1.8]) vs. 8.0 [9.0]); p=0.025). The proportion of patients within Milan post-ICI was lower for those with recurrence vs. without (16.7% vs. 65.3%, p=0.032) CONCLUSION: Patients have acceptable post-LT outcomes after ICI therapy. Age and ICI washout length relate to the allograft rejection risk, and a 3-month washout may reduce it to that of patients without ICI exposure. Number of ICI cycles and tumor burden may affect recurrence risk. Large prospective studies are necessary to confirm these associations. IMPACT AND IMPLICATIONS: This systematic review and individual patient data meta-analysis of 91 patients with hepatocellular carcinoma and immune checkpoint inhibitors use prior to liver transplantation suggests acceptable overall post-transplant outcomes. Older age and longer immune checkpoint inhibitor washout period have a significant inverse association with the risk of allograft rejection. A 3-month washout may reduce it to that of patients without ICI exposure. Additionally, a higher number of immune checkpoint inhibitor cycles and tumor burden within Milan criteria at the completion of immunotherapy may predict a decreased risk of hepatocellular carcinoma recurrence, but this observation requires further validation in larger prospective studies. CODE FOR INTERNATIONAL PROSPECTIVE REGISTER OF SYSTEMATIC REVIEWS (PROSPERO): CRD42023494951.

MR radiomics to predict microvascular invasion status and biological process in combined hepatocellular carcinoma-cholangiocarcinoma.

OBJECTIVES: To establish an MRI-based radiomics model for predicting the microvascular invasion (MVI) status of cHCC-CCA and to investigate biological processes underlying the radiomics model. METHODS: The study consisted of a retrospective dataset (82 in the training set, 36 in the validation set) and a prospective dataset (25 patients in the test set) from two hospitals. Based on the training set, logistic regression analyses were employed to develop the clinical-imaging model, while radiomic features were extracted to construct a radiomics model. The diagnosis performance was further validated in the validation and test sets. Prognostic aspects of the radiomics model were investigated using the Kaplan-Meier method and log-rank test. Differential gene expression analysis and gene ontology (GO) analysis were conducted to explore biological processes underlying the radiomics model based on RNA sequencing data. RESULTS: One hundred forty-three patients (mean age, 56.4 ± 10.5; 114 men) were enrolled, in which 73 (51.0%) were confirmed as MVI-positive. The radiomics model exhibited good performance in predicting MVI status, with the area under the curve of 0.935, 0.873, and 0.779 in training, validation, and test sets, respectively. Overall survival (OS) was significantly different between the predicted MVI-negative and MVI-positive groups (median OS: 25 vs 18 months, p = 0.008). Radiogenomic analysis revealed associations between the radiomics model and biological processes involved in regulating the immune response. CONCLUSION: A robust MRI-based radiomics model was established for predicting MVI status in cHCC-CCA, in which potential prognostic value and underlying biological processes that regulate immune response were demonstrated. CRITICAL RELEVANCE STATEMENT: MVI is a significant manifestation of tumor invasiveness, and the MR-based radiomics model established in our study will facilitate risk stratification. Furthermore, underlying biological processes demonstrated in the radiomics model will offer valuable insights for guiding immunotherapy strategies. KEY POINTS: MVI is of prognostic significance in cHCC-CCA, but lacks reliable preoperative assessment. The MRI-based radiomics model predicts MVI status effectively in cHCC-CCA. The MRI-based radiomics model demonstrated prognostic value and underlying biological processes. The radiomics model could guide immunotherapy and risk stratification in cHCC-CCA.

Characteristics and survival of advanced untreated hepatocellular carcinoma of non-viral etiology.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) is an aggressive tumor and presents late. The underlying etiology of HCC is changing rapidly. HCC in Sri Lanka is unique due to its predominant non-viral etiology (nvHCC) but lacks survival data. METHOD: Data was collected from patients who presented with HCC from 2011 to 2018. There were 560/568 (98.6%) nvHCC. The patients who were not candidates for tumor-specific treatment (149/560 [26.7%]) were selected. Population characteristics, demographic data, tumor characteristics, survival and factors affecting survival were analyzed. RESULTS: The median age was 64 years (range 30-88) and 86% (n = 129) were males. As many as 124 (83%) were cirrhotic. The overall performance score was 80%. Nearly 21/124 tumors were detected in cirrhotic screening. Tumors were single nodular in 32 (21%), up to three nodules in 28 (18%), more than three nodules in 33 (22%) and diffusely infiltrating in 56 (37%). The major venous invasions were present in 78 (52.3%). Extra-hepatic tumor spread was seen in 19 (12.7%) (lungs 13 [72.2%], bones 2 [11.1%]). The median survival of patients receiving palliative care was three months (1-43 months). Tumor size and cirrhotic status were significant predictors in univariate analysis. CONCLUSION: A quarter of nvHCCs were not amenable to treatment at presentation as they had dismal survival. CLINICAL TRIAL REGISTRY NUMBER: P/126/09/2021.

Should Hypervascular Incidentalomas Detected on Per-Interventional Cone Beam Computed Tomography during Intra-Arterial Therapies for Hepatocellular Carcinoma Impact the Treatment Plan in Patients Waiting for Liver Transplantation?

BACKGROUND: Current guidelines do not indicate any comprehensive management of hepatic hypervascular incidentalomas (HVIs) discovered in hepatocellular carcinoma (HCC) patients during intra-arterial therapies (IATs). This study aims to evaluate the prognostic value of HVIs detected on per-interventional cone beam computed tomography (CBCT) during IAT for HCC in patients waiting for liver transplantation (LT). MATERIAL AND METHODS: In this retrospective single-institutional study, all liver-transplanted HCC patients between January 2014 and December 2018 who received transarterial chemoembolization (TACE) or radioembolization (TARE) before LT were included. The number of ≥10 mm HCCs diagnosed on contrast-enhanced pre-interventional imaging (PII) was compared with that detected on per-interventional CBCT with a nonparametric Wilcoxon test. The correlation between the presence of an HVI and histopathological criteria associated with poor prognosis (HPP) on liver explants was investigated using the chi-square test. Tumor recurrence (TR) and TR-related mortality were investigated using the chi-square test. Recurrence-free survival (RFS), TR-related survival (TRRS), and overall survival (OS) were assessed according to the presence of HVI using Kaplan-Meier analysis. RESULTS: Among 63 included patients (average age: 59 ± 7 years, H/F = 50/13), 36 presented HVIs on per-interventional CBCT. The overall nodule detection rate of per-interventional CBCT was superior to that of PII (median at 3 [Q1:2, Q3:5] vs. 2 [Q1:1, Q3:3], respectively, p < 0.001). No significant correlation was shown between the presence of HVI and HPP (p = 0.34), TR (p = 0.095), and TR-related mortality (0.22). Kaplan-Meier analysis did not show a significant impact of the presence of HVI on RFS (p = 0.07), TRRS (0.48), or OS (p = 0.14). CONCLUSIONS: These results may indicate that the treatment plan during IAT should not be impacted or modified in response to HVI detection.

[Multiparametric MRI in hepatocellular carcinoma, part 2 : Diffusion-weighted imaging in the primary diagnostics and treatment monitoring]. / Multiparametrische MRT-Bildgebung beim hepatozellulären Karzinom, Teil 2 : Diffusionsbildgebung in der Primärdiagnostik und Therapieverlaufskontrolle.

In addition to morphology and tissue perfusion, diffusion-weighted imaging (DWI) is the third pillar of multiparametric diagnostics in oncology. Due to the strong correlation between the apparent diffusion coefficient (ADC) and cell count in hepatocellular carcinoma (HCC), it can be used as a surrogate marker for tumor cell quantity. Therefore, ADC effectively reflects the effects of cytoreductive treatment, such as transarterial chemoembolization (TACE) and systemic chemotherapy and becomes an important clinical marker for treatment response. The DWI should remain an integral part of a magnetic resonance imaging (MRI) protocol in primary HCC diagnostics and treatment monitoring but is of secondary clinical importance compared to contrast-enhanced MRI perfusion sequences and the use of liver-specific contrast agents. For the future, standardization of DWI sequences for better comparability of various study protocols would be desirable.

Accuracy of contrast-enhanced CT in liver neoplasms in children under 2 years age.

BACKGROUND: Multiple differentials exist for pediatric liver tumors under 2 years. Accurate imaging diagnosis may obviate the need for tissue sampling in most cases. OBJECTIVE: To evaluate the imaging features and diagnostic accuracy of computed tomography (CT) in liver tumors in children under 2 years. METHODS: Eighty-eight children under 2 years with treatment naive liver neoplasms and baseline contrast-enhanced CT were included in this institutional review board approved retrospective study. Two blinded onco-radiologists assessed these tumors in consensus. Findings assessed included enhancement pattern, lobulated appearance, cystic change, calcifications, central scar-like appearance, and metastases. The radiologists classified the lesion as hepatoblastoma, infantile hemangioma, mesenchymal hamartoma, rhabdoid tumor, or indeterminate, first based purely on imaging and then after alpha-fetoprotein (AFP) correlation. Multivariate analysis and methods of comparing means and frequencies were used for statistical analysis wherever applicable. Diagnostic accuracy, sensitivity, and positive predictive values were analyzed. RESULTS: The mean age of the sample was 11.4 months (95% CI, 10.9-11.8) with 50/88 (57%) boys. The study included 72 hepatoblastomas, 6 hemangiomas, 4 mesenchymal hamartomas, and 6 rhabdoid tumors. Presence of calcifications, multilobular pattern of arterial enhancement, lobulated morphology, and central scar-like appearance was significantly associated with hepatoblastomas (P-value < 0.05). Fourteen out of eighty-eight lesions were called indeterminate based on imaging alone; six lesions remained indeterminate after AFP correlation. Pure radiology-based diagnostic accuracy was 81.8% (95% CI, 72.2-89.2%), which increased to 92.1% (95% CI, 84.3-96.7%) (P-value > 0.05) after AFP correlation, with one hepatoblastoma misdiagnosed as a rhabdoid tumor. If indeterminate lesions were excluded for biopsy, the accuracy would be 98.8% (95% CI, 93.4-99.9%). CONCLUSION: CT had high accuracy for diagnosing liver neoplasms in the under 2-year age population after AFP correlation. Certain imaging features were significantly associated with the diagnosis of hepatoblastoma. A policy of biopsying only indeterminate lesions after CT and AFP correlation would avoid sampling in the majority of patients.

The role of living donor liver transplantation in treating intrahepatic cholangiocarcinoma.

Introduction: Intrahepatic cholangiocarcinoma (iCC) is the liver's second most common neoplasm. Until now, surgery is the only curative option, but only 35% of the cases are considered resectable at the diagnosis, with a post-resection survival of around 30%. Advancements in surgical techniques and perioperative care related to liver transplantation (LT) have facilitated the expansion of indications for hepatic neoplasms. Method: This study is a comprehensive review of the global experience in living donor LT (LDLT) for treating iCC and describes our first case of LDLT for an unresectable iCC. Results: While exploring LT for intrahepatic cholangiocarcinoma dates to the 1990s, the initial outcomes were discouraging, marked by poor survival and high recurrence rates. Nevertheless, contemporary perspectives underscore a reinvigorated emphasis on extending the frontiers of LT indications within the context of the "oncologic era." The insights gleaned from examining explants, wherein incidental iCC was categorized as hepatocellular carcinoma in the preoperative period, have demonstrated comparable survival rates to small hepatocellular carcinoma. These findings substantiate the potential viability of LT as a curative alternative for iCC. Another investigated scenario pertains to "unresectable tumors with favorable biological behavior," LT presents a theoretical advantage by providing free margins without the concern of a small future liver remnant. The constraint of organ shortage persists, particularly in nations with low donation rates. LDLT emerges as a viable and secure alternative for treating iCC. Conclusion: LDLT is an excellent option for augmenting the graft pool, particularly in carefully selected patients.

Robotic management of huge hepatic angiomyolipoma: A case report and literature review.

Hepatic angiomyolipoma (HAML) is a rare, benign mesenchymal liver tumor encountered in Asia, primarily in females, and can be found within the right hepatic lobe, but also in other areas of the liver. Immunohistochemically, HAMLs are characteristically positive for human melanoma black-45 antigen (HMB-45) and can histochemically vary in the composition of angiomatous, lipomatous, and myomatous tissue, together with the presence of epithelioid cells. In this case report, we discuss a previously healthy patient presenting with bloating and previously documented concern of liver lesions, found to have HAML confirmed by surgical pathology. Surgery was decided, as HAMLs greater than 10 cm are at risk of rupture. This is one of the first documented cases of HAML resected through robot-assisted bisegmentectomy and cholecystectomy, and therefore, intraoperative images have been included to assist in the planning of future robotic cases.

Recipient blood group does not affect hepatocellular carcinoma recurrence after living donor liver transplantation in Korea.

PURPOSE: This study assessed whether or not the ABO blood type affects the incidence of HCC recurrence after living donor liver transplantation (LDLT). METHODS: This retrospective observational study included 856 patients with hepatocellular carcinoma (HCC) who underwent LDLT between January 2006 and December 2016 at the Asan Medical Center. RESULTS: This study included 324 patients (37.9%) with blood type A, 215 (25.1%) with blood type B, 210 (24.5%) with blood type O, and 107 (12.5%) with blood type AB. ABO-incompatible LT was performed in 136 (15.9%) patients. The independent risk factors for the disease-free survival (DFS) were maximal tumor diameter, microvascular invasion, and Milan criteria. The only independent risk factor for the overall survival (OS) was microvascular invasion. The ABO blood group did not affect the DFS (P = 0.978) or OS (P = 0.261). The DFS according to the ABO blood group did not differ significantly between the ABO-compatible (p = 0.701) and ABO-incompatible LDLT recipients (p = 0.147). The DFS according to the ABO blood group did not differ significantly between patients within the Milan criteria (p = 0.934) and beyond the Milan criteria (p = 0.525). The DFS did not differ significantly between recipients with and without type A blood (p = 0.941). CONCLUSIONS: This study demonstrated that the ABO blood group system had no prognostic impact on the oncological outcomes of patients undergoing LT for HCC.

Surgical margin status outcome of intraoperative indocyanine green fluorescence-guided laparoscopic hepatectomy in liver malignancy: a systematic review and meta-analysis.

BACKGROUND: Hepatectomy stands as a curative management for liver cancer. The critical factor for minimizing recurrence rate and enhancing overall survival of liver malignancy is to attain a negative margin hepatic resection. Recently, Indocyanine green (ICG) fluorescence imaging has been proven implemental in aiding laparoscopic liver resection, enabling real-time tumor identification and precise liver segmentation. The purpose of this study is to conduct a systematic review and meta-analysis to ascertain whether ICG-guided laparoscopic hepatectomy yields a higher incidence of complete tumor eradication (R0) resections. METHODS: The search encompassed databases such as PubMed, Cochrane Library database, Scopus, ScienceDirect, and Ovid in April 2024, in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies involving patients with malignant liver lesions who underwent ICG-guided laparoscopic hepatectomy and reported R0 resection outcomes were eligible for inclusion in this review. RESULTS: In a total of seven studies, involving 598 patients, were included in the meta-analysis. The ICG demonstrated a significantly elevated R0 resection rate compared to the non-ICG group [98.6% (359/364) vs. 93.1% (339/364), odds ratio (OR) = 3.76, 95% confidence intervals (CI) 1.45-9.51, P = 0.005]. Notably, no heterogeneity was observed (I2 = 0%, P = 0.5). However, the subtype analysis focusing on hepatocellular carcinoma [98.2% (165/168) vs. 93.6% (161/172), OR = 3.34, 95% CI 0.94-11.91, P = 0.06) and the evaluation of margin distance (4.96 ± 2.41 vs. 2.79 ± 1.92 millimeters, weighted mean difference = 1.26, 95% CI -1.8-4.32, P = 0.42) revealed no apparent differences. Additionally, the incidence of overall postoperative complications was comparable between both groups, 27.6% (66/239) in the ICG group and 25.4% (75/295) in the non-ICG group (OR = 0.96, 95% CI 0.53-1.76, P = 0.9). No disparities were identified in operative time, intraoperative blood loss, postoperative blood transfusion, and length of hospital stay after the surgery. CONCLUSIONS: The implementation of ICG-guided laparoscopic hepatectomy can be undertaken with confidence, as it does not compromise either intraoperative or postoperative events. Furthermore, the ICG-guided approach is beneficial to achieving a complete eradication of the tumor during hepatic resection. TRIAL REGISTRATION: PROSPERO registration number CRD42023446440.

Analysis of Factors Predicting the Real-World Efficacy of Atezolizumab and Bevacizumab in Patients with Advanced Hepatocellular Carcinoma.

Background/Aims: Atezolizumab and bevacizumab have shown promising results for the treatment of advanced hepatocellular carcinoma (HCC) in clinical trials. In this study, the real-world efficacy and safety of atezolizumab and bevacizumab in treating advanced HCC were evaluated. Methods: In this retrospective study of patients at a Korean tertiary cancer center, 111 patients with Barcelona Clinic Liver Cancer stage B or C HCC received atezolizumab and bevacizumab as first-line therapy from May 2022 to June 2023. We assessed the progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and adverse events. Results: Patients with Barcelona Clinic Liver Cancer stage C HCC and Child-Pugh class A liver function were included in the study. The median PFS was 6.5 months, with an ORR of 27% and a DCR of 63%. Several factors, including the albumin-bilirubin grade, age, C-reactive protein and α-fetoprotein in immunotherapy score, macrovascular invasion, lung metastases, and combined radiotherapy, were found to significantly influence PFS (p<0.05). Patients with peritoneal seeding showed an higher ORR. The safety profile was consistent with that observed in clinical trials. Conclusions: Atezolizumab and bevacizumab demonstrated real-world efficacy in the treatment of advanced HCC, with ORRs and DCRs aligning with those observed in clinical trials. Variations in PFS and ORR based on specific risk factors highlight the potential of atezolizumab and bevacizumab in precision medicine for advanced HCC.

Molecular targets and mechanisms of different aberrant alternative splicing in metastatic liver cancer.

Metastasis remains a major challenge in the successful management of malignant diseases. The liver is a major site of metastatic disease and a leading cause of death from gastrointestinal malignancies such as colon, stomach, and pancreatic cancers, as well as melanoma, breast cancer, and sarcoma. As an important factor that influences the development of metastatic liver cancer, alternative splicing drives the diversity of RNA transcripts and protein subtypes, which may provide potential to broaden the target space. In particular, the dysfunction of splicing factors and abnormal expression of splicing variants are associated with the occurrence, progression, aggressiveness, and drug resistance of cancers caused by the selective splicing of specific genes. This review is the first to provide a detailed summary of the normal splicing process and alterations that occur during metastatic liver cancer. It will cover the role of alternative splicing in the mechanisms of metastatic liver cancer by examining splicing factor changes, abnormal splicing, and the contribution of hypoxia to these changes during metastasis.

Re-assessing the diagnostic value of the enhancing "capsule" in hepatocellular carcinoma imaging.

Background/Aims: The enhancing "capsule" (EC) in hepatocellular carcinoma (HCC) diagnosis has received varying degrees of recognition across major guidelines. This study aimed to assess the diagnostic utility of EC in HCC detection. Methods: We retrospectively analyzed patients who underwent pre-surgical computed tomography (CT) and hepatobiliary agent-enhanced magnetic resonance imaging (HBA-MRI) between January 2016 and December 2019. A single hepatic tumor was confirmed based on the pathology of each patient. Three radiologists independently reviewed the images according to the Liver Imaging Reporting and Data System (LIRADS) v2018 criteria and reached a consensus. Interobserver agreement for EC before reaching a consensus was quantified using Fleiss κ statistics. The impact of EC on the LI-RADS classification was assessed by comparing the positive predictive values for HCC detection in the presence and absence of EC. Results: In total, 237 patients (median age, 60 years; 184 men) with 237 observations were included. The interobserver agreement for EC detection was notably low for CT (κ=0.169) and HBA-MRI (κ=0.138). The presence of EC did not significantly alter the positive predictive value for HCC detection in LI-RADS category 5 observations on CT (94.1% [80/85] vs. 94.6% [88/93], P=0.886) or HBA-MRI (95.7% [88/92] vs. 90.6% [77/85], P=0.178). Conclusions: The diagnostic value of EC in HCC diagnosis remains questionable, given its poor interobserver agreement and negligible impact on positive predictive values for HCC detection. This study challenges the emphasis on EC in certain diagnostic guidelines and suggests the need to re-evaluate its role in HCC imaging.

Three-dimensional treatment-planning-based prediction of seed migration to chest after 125I seed brachytherapy for hepatic malignancy.

PURPOSE: To develop and validate risk models incorporating clinical and/or imaging parameters based on three-dimensional treatment-planning systems (3D-TPS) to predict the occurrence of 125I seed migration and the number of migrated seeds <2/≥2 to the chest after brachytherapy for patients with malignant hepatic tumors. METHODS AND MATERIALS: A total of 480 patients diagnosed with malignant liver tumors receiving 125I seed brachytherapy from July 2010 to May 2020 were retrospectively enrolled. Variables included 3D-TPS-based CT parameters, that is, the distance from the seed to the inferior vena cava (DSI), the distance from the seed to the second hepatic portal (DSP) and the angle from the seed to the second hepatic portal (ASP), and patients' clinical characteristics, that is, the number of seed implantation procedures (NSP), the maximum number of implanted seeds one time (MAX) and laboratory parameters within 1 week before treatment. Two sets of logistic regression models incorporating clinical and/or imaging variables were developed to predict the occurrence of seed migration and the number of migrated seeds <2/≥2. Model performance was assessed by ROC analysis and decision curve analysis. RESULTS: Compared with the clinical models, the combined model showed a higher discriminative ability for both the prediction of migration occurrence and number of migrated seeds ≥ 2/<2 to the chest (AUC, 0.879 vs. 0.668, p < 0.05; 0.895 vs. 0.701, p < 0.05). The decision curve analysis results indicated higher net benefits of combined models than clinical models. Variables, including DSI, NSP and pretreatment lymphocyte-to-neutrophil ratio, acted as the most important predictors in combined models. CONCLUSIONS: The proposed combined models based on 3D-TPS improved discriminative abilities for predicting 125I seed migration and number of migrated seeds <2/≥2 to the chest after hepatic brachytherapy, being promising to aid clinical decision-making.

Performance of LI-RADS category 5 vs combined categories 4 and 5: a systemic review and meta-analysis.

OBJECTIVE: Computed tomography (CT)/magnetic resonance imaging (MRI) Liver Imaging Reporting and Data System (LI-RADS, LR) category 5 has high specificity and modest sensitivity for diagnosis of hepatocellular carcinoma (HCC). The purpose of this study was to compare the diagnostic performance of LR-5 vs combined LR-4 and LR-5 (LR-4/5) for HCC diagnosis. METHODS: MEDLINE and EMBASE databases through January 03, 2023 were searched for studies reporting the performance of LR-5 and combined LR-4/5 for HCC diagnosis, using CT/MRI LI-RADS version 2014, 2017, or 2018. A bivariate random-effects model was used to calculate the pooled per-observation diagnostic performance. Subgroup analysis was performed based on imaging modalities and type of MRI contrast material. RESULTS: Sixty-nine studies (15,108 observations, 9928 (65.7%) HCCs) were included. Compared to LR-5, combined LR-4/5 showed significantly higher pooled sensitivity (83.0% (95% CI [80.3-85.8%]) vs 65.7% (95% CI [62.4-69.1%]); p < 0.001), lower pooled specificity (75.0% (95% CI [70.5-79.6%]) vs 91.7% (95% CI [90.2-93.1%]); p < 0.001), lower pooled positive likelihood ratio (3.60 (95% CI [3.06-4.23]) vs 6.18 (95% CI [5.35-7.14]); p < 0.001), and lower pooled negative likelihood ratio (0.22 (95% CI [0.19-0.25]) vs 0.38 (95% CI [0.35-0.41]) vs; p < 0.001). Similar results were seen in all subgroups. CONCLUSIONS: Our meta-analysis showed that combining LR-4 and LR-5 would increase sensitivity but decrease specificity, positive likelihood ratio, and negative likelihood ratio. These findings may inform management guidelines and individualized management. CLINICAL RELEVANCE STATEMENT: This meta-analysis estimated the magnitude of changes in the sensitivity and specificity of imaging criteria when LI-RADS categories 4 and 5 were combined; these findings can inform management guidelines and individualized management. KEY POINTS: There is no single worldwide reporting system for liver imaging, partly due to regional needs. Combining LI-RADS categories 4 and 5 increased sensitivity and decreased specificity and positive and negative likelihood ratios. Changes in the sensitivity and specificity of imaging criteria can inform management guidelines and individualized management.

Liver cancer in China: the analysis of mortality and burden of disease trends from 2008 to 2021.

BACKGROUND: Liver cancer is one of the most common cancers in China. To understand the basic death situation and disease burden change trend, we analyze the death information of liver cancer among Chinese residents from 2008 to 2021. METHODS: Data was collected from the Cause-of-Death Surveillance dataset of the National Cause-of-Death Surveillance System from 2008 to 2021. Excel 2016 was used for data entry and to calculate the Crude Mortality Rate (CMR), Age-Standardized Mortality Rate (ASMR), Potential Years of Life Lost (PYLL), and Potential Years of Life Lost Rate (PYLLR). SPSS 25.0 was used to statistically analyze CMR, ASMR, PYLL, and other indicators. Annual percent change (APC) and average APC(AAPC) was used for trend analysis and tested by t tests. Joinpoint 4.9.1.0 was used to calculate APC and AAPC. Age-Period-Cohort model was used to assess the effects of age, period, and birth cohort on liver cancer mortality. RESULTS: From 2008 to 2021, 491,701 liver cancer deaths were reported in the National Disease Surveillance Points System. The ASMR of liver cancer in Chinese residents decreased from 27.58/100,000 in 2008 to 17.95/100,000 in 2021 at an average annual rate of 3.40% (t = -5.10, P < 0.001). The mortality rate was higher in males than in females (all P < 0.001) and higher in rural areas than in urban areas (all P < 0.001). The mortality rate of liver cancer varied significantly among eastern, central, and western China (all P < 0.001). The PYLLR of liver cancer in Chinese residents decreased from 2.89‰ in 2008 to 2.06‰ in 2021 at an average annual rate of 2.40% (t = -5.10, P < 0.001). Males had a lower PYLLR than females, decreasing at average annual rates of 2.20% (t = -5.40, P < 0.001) and 2.90% (t = -8.40, P < 0.001), respectively. Urban areas had a lower PYLLR than rural areas, decreasing at average annual rate of 3.30% (t = -4.00, P < 0.001) and 2.50% (t = -11.60, P < 0.001), respectively. Eastern, central, and western China decreased at average annual rates of 3.40%, 2.30%, and 2.10%, respectively (t = -7.80, -3.60, -7.10, P < 0.001 for all). The risk of China liver cancer mortality increased with age, decreased with birth cohort. CONCLUSIONS: The mortality and disease burdens of liver cancer in China decreased yearly and were higher in males and in people living in rural areas, with significant differences among those living in eastern, central, and western China.

von Meyenburg complexes are more frequently associated with cholangiocarcinoma.

AIM: There is some evidence that von Meyenburg complexes (VMCs) can progress to cholangiocarcinoma (CC). This study aimed to evaluate the prevalence of VMCs in CC cases. METHODS: All hepatic resections and explants with intra-hepatic CC (I-CC) and hilar-CC (H-CC) from 1985 to 2020 were studied. Hepatic resections (n=68) for benign lesions or metastatic colonic carcinoma and 15 cases with cirrhosis without any cancer were used as controls. RESULTS: A total of 118 cases of CC (88 I-CC, 30 H-CC) were identified. Of these, 61 (52%) patients had no known background liver disease, and 20 (17%) had cirrhosis. Associated liver disorders included metabolic dysfunction-associated steatohepatitis (23), chronic viral hepatitis B or C (13), biliary disease (primary or secondary sclerosing cholangitis) (8), polycystic kidney disease (6), cryptogenic cirrhosis (5) and others miscellaneous disorders (7). VMCs were present in 34 (39%) of 88 I-CC cases and 7 (23%) of 30 H-CC cases. VMCs were present within the tumour (20 cases), outside the cancer (21 cases) or at both locations (10 cases). VMCs with dysplasia/carcinoma in situ were seen in 19 of 41 (46%) cases with CC and VMCs. In addition, bile duct adenomas were identified in 6 (5%) of CC. 7% of controls showed the presence of VMCs compared with 35% of CC cases (p<0.05). CONCLUSIONS: VMCs are seen far more frequently in patients with CC than in the control group. The findings support the hypothesis that VMCs could represent a precursor of CC or a marker for a higher risk of developing CC.

Early detection of HCC in patients with cirrhosis using AI; a Systematic Review.

Introduction: Hepatocellular carcinoma constitutes for approximately 75% of primary cancers of liver. Around 80- 90% of patients with HCC have cirrhosis at the time of diagnosis. Use of AI has recently gained significance in the field of hepatology, especially for the detection of HCC, owing to its increasing incidence and specific radiological features which have been established for its diagnostic criteria. Objectives: A systematic review was performed to evaluate the current literature for early diagnosis of hepatocellular carcinoma in cirrhotic patients. METHODS: Systematic review was conducted using PRISMA guidelines and the relevant studies were narrated in detail with assessment of quality for each paper. RESULTS: This systematic review displays the significance of AI in early detection and prognosis of HCC with the pressing need for further exploration in this field. CONCLUSIONS: AI can have a significant role in early diagnosis of HCC in cirrhotic patients.

Assessment of birth cohort screening of chronic hepatitis C in colorectal cancer screening patients in British Columbia.

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.