Endoscopic variceal ligation versus propranolol for the primary prevention of oesophageal variceal bleeding in patients with hepatocellular carcinoma: an open-label, two-centre, randomised controlled trial

Objective
This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC).

Design
Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3–4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression.

Results
Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray’s test, p=0.009) than its counterpart, with no mortality difference (Gray’s test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p

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Marzo 2024

Non-linear association of baseline viral load with on-treatment hepatocellular carcinoma risk in chronic hepatitis B

Objective
The association between baseline pretreatment serum HBV DNA levels and on-treatment hepatocellular carcinoma (HCC) risk remains controversial in patients with chronic hepatitis B (CHB). We aimed to investigate the association between baseline HBV viral load and on-treatment HCC risk in CHB patients without cirrhosis.

Design
Using a multicentre historical cohort study including 4693 hepatitis B e antigen (HBeAg)-negative and HBeAg-positive, adult CHB patients without cirrhosis who initiated antiviral treatment, HCC risk was estimated by baseline HBV viral load as a categorical variable.

Results
During a median of 7.6 years of antiviral treatment, 193 patients developed HCC (0.53 per 100 person- years). Baseline HBV DNA level was independently associated with on-treatment HCC risk in a non-linear, parabolic pattern. Patients with moderate baseline viral loads (5.00–7.99 log10 IU/mL) exhibited the highest HCC risk (HR, 2.60; p

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Marzo 2024

Camrelizumab in combination with chemotherapy versus concurrent chemoradiotherapy for the conversion of locally advanced unresectable oesophageal squamous carcinoma: protocol for a two-arm, open-label phase II trial

Introduction
Oesophageal cancer (OC) has higher morbidity and mortality rate than most other malignancies. The standard treatment for unresectable locally advanced oesophageal squamous cell carcinoma (OSCC) is concurrent chemoradiotherapy, with tumour regression observed in a proportion of patients after treatment, but prognostic improvement remains limited. Immunotherapy in combination with chemotherapy (CT) has been shown to be efficacious as the first-line treatment of advanced OC and neoadjuvant therapy. Therefore, we conducted a prospective, two-arm, randomised, unblinded phase II study to explore the efficacy of camrelizumab in combination with CT versus chemoradiotherapy for the conversion of unresectable advanced OSCC.

Methods and analysis
All participants meeting the inclusion criteria will be enrolled after signing an informed consent form. Patients with clinically cT4b or spread to at least one group of lymph nodes with possible invasion of surrounding organs and unresectable locally advanced squamous carcinoma of the thoracic segment of the oesophagus will be included in the study. Patients with suspected distant metastases on the preoperative examination will be excluded from this study. Patients eligible for enrolment will be grouped by centre randomisation according to the study plan. Patients will undergo radical surgery after completion of two cycles of chemotherapy (CT) combined with camrelizumab induction therapy or concurrent chemoradiotherapy if assessed to be operable. Patients evaluated as inoperable will be scheduled for a multidisciplinary consultation to determine the next treatment option. The primary endpoint is the R0 resection rate in patients undergoing surgery after treatment. Secondary endpoints are the rate of major pathological remission, pathological complete response rate, overall survival, progression-free survival and adverse events for all patients.

Ethics and dissemination
Ethical approval was obtained from the ethics committees of Fujian Medical University Union Hospital (No. 2022YF039-02). The findings will be disseminated in peer-reviewed publications.

Trial registration number
NCT05821452.

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Febbraio 2024

TGF-β1 Induced SOX18 Elevation Promotes Hepatocellular Carcinoma Progression and Metastasis through Transcriptionally Upregulating PD-L1 and CXCL12

Hepatocellular carcinoma (HCC) is characterized by an immune-suppressive microenvironment, which contributes to tumor progression, metastasis and immunotherapy resistance. Identification of HCC-intrinsic factors regulating immunosuppressive microenvironment is urgently needed. Here, we aimed to elucidate the role of SYR-Related High-Mobility Group Box 18 (SOX18) in inducing immunosuppression and to validate novel combination strategies for SOX18-mediated HCC progression and metastasis.

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Febbraio 2024