Multimodal multiphasic preoperative image-based deep-learning predicts HCC outcomes after curative surgery.

Background And Aims: HCC recurrence frequently occurs after curative surgery. Histological microvascular invasion (MVI) predicts recurrence but cannot provide preoperative prognostication, whereas clinical prediction scores have variable performances.

Approach And Results: Recurr-NET, a multimodal multiphasic residual-network random survival forest deep-learning model incorporating preoperative CT and clinical parameters, was developed to predict HCC recurrence.

Dual-tracer PET/CT in the management of hepatocellular carcinoma.

Background & Aims: Combined F-fluorodeoxyglucose (FDG) and C-acetate (dual-tracer) positron-emission tomography/computed tomography (PET/CT) is being increasingly performed for the management of hepatocellular carcinoma (HCC), although its role is not well defined. Therefore, we evaluated its effectiveness in (i) staging, (ii) characterization of indeterminate lesions on conventional imaging, and (iii) detection of HCC in patients with unexplained elevations in serum alpha-fetoprotein (AFP) levels.

Methods: We retrospectively assessed 525 consecutive patients from three tertiary centers between 2014 and 2020.

Sorted-Cell Sequencing on HCC Specimens Reveals EPS8L3 as a Key Player in CD24/CD13/EpCAM-Triple Positive, Stemness-Related HCC Cells.

Background & Aims: Hepatocellular carcinoma (HCC) is a heterogeneous cancer with varying levels of liver tumor initiating or cancer stem cells in the tumors. We aimed to investigate the expression of different liver cancer stem cell (LCSC) markers in human HCCs and identify their regulatory mechanisms in stemness-related cells.

Methods: We used an unbiased, single-marker sorting approach by flow cytometry, fluorescence-activated cell sorting, and transcriptomic analyses on HCC patients' resected specimens.

Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.

The tumor microenvironment of cancers has emerged as a crucial component in regulating cancer stemness and plays a pivotal role in cell-cell communication. However, the specific mechanisms underlying these phenomena remain poorly understood. We performed the single-cell RNA sequencing (scRNA-seq) on nine HBV-associated hepatocellular carcinoma (HCC) patients.

High prevalence of de novo metabolic dysfunction-associated fatty liver disease after liver transplantation and the role of controlled attenuation parameter.

Background & Aims: Although non-alcoholic fatty liver disease (NAFLD) remains an uncommon indication for liver transplantation (LT) in the Chinese, the prevalence of NAFLD is increasing. We aimed to determine the prevalence of de novo steatosis and metabolic dysfunction-associated fatty liver disease (MAFLD) after LT.

Methods: Transient elastography assessment for liver stiffness and controlled attenuation parameter (CAP) were performed after LT in 549 patients at median time of 77 months from LT.

Post-transplant inflammatory cytokine signature adds value for predicting tumor recurrence after liver transplantation for hepatocellular carcinoma.

Background: Cytokines are key regulators of post-transplant inflammation responses which reconstitute post-transplant hepatic and systemic environments to influence the likelihood of tumor relapse. This study investigated the prognostic value of post-transplant cytokines on tumor recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC).

Methods: A retrospective analysis was conducted in prospectively collected 150 adult HCC patients who received liver transplantation from 1997 to 2015.

Association of Multi-Phasic MR-Based Radiomic and Dosimetric Features with Treatment Response in Unresectable Hepatocellular Carcinoma Patients following Novel Sequential TACE-SBRT-Immunotherapy.

This study aims to investigate the association of pre-treatment multi-phasic MR-based radiomics and dosimetric features with treatment response to a novel sequential trans-arterial chemoembolization (TACE) plus stereotactic body radiotherapy (SBRT) plus immunotherapy regimen in unresectable Hepatocellular Carcinoma (HCC) sub-population. Twenty-six patients with unresectable HCC were retrospectively analyzed. Radiomic features were extracted from 42 lesions on arterial phase (AP) and portal-venous phase (PVP) MR images.

Sequential transarterial chemoembolisation and stereotactic body radiotherapy followed by immunotherapy as conversion therapy for patients with locally advanced, unresectable hepatocellular carcinoma (START-FIT): a single-arm, phase 2 trial.

Background: The synergy between locoregional therapies and immune checkpoint inhibitors has not been investigated as conversion therapy for unresectable hepatocellular carcinoma. We aimed to investigate the activity of sequential transarterial chemoembolisation (TACE) and stereotactic body radiotherapy followed by avelumab (an anti-PD-L1 drug) for locally advanced, unresectable hepatocellular carcinoma.

Methods: START-FIT was a single-arm, phase 2 trial in patients with locally advanced hepatocellular carcinoma who were not suitable for curative treatment, conducted in two hospitals in Hong Kong and one in Shenzhen, China.

Sex-specific analysis of microRNA profiles in HBV-associated cirrhosis by small RNA-sequencing.

Liver cirrhosis represents an advanced stage of chronic liver disease and is associated with significant morbidity, mortality, and risk of cancer development. While sex disparity of liver diseases has been observed, understanding at a genetic level awaits more thorough investigation. In this study, we performed a sex-specific analysis of the microRNA (miR) profiles in hepatitis B virus (HBV)-associated cirrhosis by small RNA-sequencing using clinical tissue samples.

Impact of Tumour Biology on Outcomes of Radical Therapy for Hepatocellular Carcinoma Oligo-Recurrence after Liver Transplantation.

It is uncertain whether tumour biology affects radical treatment for post-transplant hepatocellular carcinoma (HCC) oligo-recurrence, i.e. recurrence limited in numbers and locations amendable to radical therapy.

Magnetic resonance elastography and proton density fat fraction predict adverse outcomes in hepatocellular carcinoma.

Background: Magnetic resonance (MR) elastography and proton density fat fraction (PDFF) are emerging techniques for non-invasive assessment of liver stiffness and steatosis, respectively. We investigated the role of MR metrics in pre-treatment prognostication of hepatocellular carcinoma (HCC).

Methods: Patients with newly diagnosed HCC were prospectively recruited.

Stanniocalcin 1 is a serum biomarker and potential therapeutic target for HBV-associated liver fibrosis.

Stanniocalcin 1 (STC1), a secreted protein, is upregulated in human cancers including hepatocellular carcinoma (HCC). While most HCCs develop from chronic liver disease, which involves progressive parenchymal injury and fibrosis, the role of STC1 in this preneoplastic stage remains poorly understood. In this study we investigated the clinical relevance and functional significance of secreted STC1 in liver fibrosis.

Combined Stereotactic Body Radiotherapy and Immunotherapy Versus Transarterial Chemoembolization in Locally Advanced Hepatocellular Carcinoma: A Propensity Score Matching Analysis.

Immunotherapy has achieved modest clinical activity in HCC patients. Propensity score matching analysis was conducted to compare the efficacy and safety of combined stereotactic SBRT-IO versus TACE in patients with locally advanced HCC in a tertiary center of Hong Kong. Patients with locally advanced HCC who were medically inoperable for, refractory to, or refused to curative surgical interventions were eligible.

Single-cell RNA sequencing shows the immunosuppressive landscape and tumor heterogeneity of HBV-associated hepatocellular carcinoma.

Interaction between tumor cells and immune cells in the tumor microenvironment is important in cancer development. Immune cells interact with the tumor cells to shape this process. Here, we use single-cell RNA sequencing analysis to delineate the immune landscape and tumor heterogeneity in a cohort of patients with HBV-associated human hepatocellular carcinoma (HCC).

Prospective Study of Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma on Waitlist for Liver Transplant.

Background And Aims: There are no prospective data on stereotactic body radiation therapy (SBRT) as a bridge to liver transplantation for HCC. This study aimed to evaluate the efficacy and safety of SBRT as bridging therapy, with comparison with transarterial chemoembolization (TACE) and high-intensity focused ultrasound (HIFU).

Approach And Results: Patients were prospectively enrolled for SBRT under a standardized protocol from July 2015 and compared with a retrospective cohort of patients who underwent TACE or HIFU from 2010.

Prognostic value and reversibility of liver stiffness in patients undergoing tricuspid annuloplasty.

Background: Liver stiffness (LS) assessed by transient elastography is associated with adverse events in patients with heart failure. However, the predictive value of LS for adverse outcome is uncertain in patients undergoing tricuspid annuloplasty (TA). This study sought to evaluate the prognostic value and reversibility of LS in patients undergoing TA during left-sided valve surgery.

Analysis of Survival Benefits of Living Versus Deceased Donor Liver Transplant in High Model for End-Stage Liver Disease and Hepatorenal Syndrome.

Background And Aims: Previous recommendations suggested living donor liver transplantation (LDLT) should not be considered for patients with Model for End-Stage Liver Disease (MELD) > 25 and hepatorenal syndrome (HRS).

Approach And Results: Patients who were listed with MELD > 25 from 2008 to 2017 were analyzed with intention-to-treat (ITT) basis retrospectively. Patients who had a potential live donor were analyzed as ITT-LDLT, whereas those who had none belonged to ITT-deceased donor liver transplantation (DDLT) group.

RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma.

Background & Aims: Mutational profiling of patient tumors has suggested that hepatocellular carcinoma (HCC) development is mainly driven by loss-of-function mutations in tumor suppressor genes. p90 ribosomal S6 kinase 2 (RSK2) functions as a direct downstream kinase of ERK1/2 and elevated RSK2 expression has been reported to support oncogenic functions in some cancers. We investigated if RSK2 was also dysregulated by inactivating mutations in cancers including HCC.

Extended liver surgery for gallbladder cancer revisited: Is there a role for hepatopancreatoduodenectomy?

Gallbladder cancer (GBCA) is a rare and fatal disease and the majority of patients presents with advanced stage. Surgical resection associated with lymphadenectomy is the only chance for cure. For patients in stages III and IV, extended resection is the only treatment to achieve R0 margins.

An international multicenter study of protocols for liver transplantation during a pandemic: A case for quadripartite equipoise.

Background & Aims: The outbreak of COVID-19 has vastly increased the operational burden on healthcare systems worldwide. For patients with end-stage liver failure, liver transplantation is the only option. However, the strain on intensive care facilities caused by the pandemic is a major concern.

Hepatitis B Virus-Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma.

Background And Aims: Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear.

Approach And Results: We adopted a targeted sequencing strategy to survey HBV integrations in human HBV-associated HCCs (n = 95).

Model for End-Stage Liver Disease With Additional Criteria to Predict Short-Term Mortality in Severe Flares of Chronic Hepatitis B.

Background And Aims: The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB.

Approach And Results: Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.