A 45-year-old male with chronic hepatitis B presented with an advanced hepatocellular carcinoma (HCC) occupying the entire left liver and invading the left portal vein. Despite multiple poor prognostic imaging features, including vascular invasion, corona enhancement, an incomplete capsule, intratumoral necrosis, intratumoral arteries, and irregular tumor borders, the patient elected to undergo a left hepatectomy. Although Barcelona Clinic Liver Cancer (BCLC) staging classified the case as stage C, a resection was successfully performed. Remarkably, 6 years postsurgery, the patient remains recurrence-free. This report highlights a rare, fortunate outcome in a high-risk HCC case and underscores the potential of surgical intervention even in advanced HCC.

This study aimed to compare outcomes between carbon ion radiotherapy (C-ion RT) and transarterial chemoembolization (TACE) in patients with unresectable solitary hepatocellular carcinoma (HCC) >3 cm. Fifty-eight patients who had been treated with C-ion RT (C-ion RT group) and 34 treated with TACE (TACE group) were retrospectively enrolled between January 2016 and December 2021. Propensity score matching was conducted to account for differences between the two groups. The median follow-up duration was 42.1 months for all patients. Propensity score matching successfully balanced the two groups with 29 patients matched to each group. The 3-year overall survival (OS), progression-free survival (PFS) and local control (LC) rates in the C-ion RT vs TACE groups were 75.9% vs 45.4%, 44.8% vs 16.1% and 85.2% vs 23.2%, respectively. The C-ion RT group showed better OS (hazard ratio [HR], 0.578 [95% confidence interval (CI): 0.295-1.132]; P = 0.106), PFS (HR, 0.460 [95% CI: 0.254-0.835]; P = 0.009) and LC (HR, 0.155 [95% CI: 0.062-0.390]; P < 0.001) than the TACE group. Multivariate analysis indicated that C-ion RT was significantly associated with increased PFS (HR, 0.562 [95% CI: 0.341-0.926]; P = 0.024) and LC (HR, 0.282 [95% CI: 0.150-0.528]; P < 0.001). C-ion RT provided better OS, PFS and LC than TACE in patients with solitary HCC >3 cm. This study indicated that C-ion RT is a possible alternative to TACE, which is the standard of care for patients with medium-to-large-sized HCCs.

The diagnosis and prognosis of hepatocellular carcinoma (HCC) present significant challenges in clinical practice. This study aimed to evaluate the clinical utility of tumor abnormal protein (TAP), Prothrombin induced by vitamin K absence-II (PIVKA-II), and alpha-fetoprotein (AFP) in diagnosing HCC as well as to investigate their prognostic significance in patients with HCC undergoing transarterial chemoembolization.

A total of 93 HCC patients were enrolled and 101 healthy individuals served as controls. Fresh venous blood samples were collected, and TAP, PIVKA-II, and AFP levels were measured by chemiluminescence immunoassay.

Significant differences in TAP, PIVKA-II, and AFP levels were found between HCC patients and healthy individuals. The combined assay of TAP, AFP, and PIVKA-II showed better diagnostic performance for HCC. Patients who underwent transarterial chemoembolization and achieved complete response (CR) had lower levels of prechemotherapy serum TAP, AFP, and PIVKA-II. There are significant differences in levels of TAP, AFP, and PIVKA-II between CR and partial response (PR), CR and stable disease (SD), and CR and progressive disease (PD).

Combined detection of TAP, PIVKA-II, and AFP has better diagnostic performance for HCC. Higher levels of prechemotherapy serum TAP, AFP, and PIVKA-II are significantly associated with poor clinical chemoresponse.

This study aimed to evaluate the value of simultaneous multislice diffusion kurtosis imaging (SMS-DKI) for predicting early recurrence (within 2 years) in hepatocellular carcinoma (HCC) and to develop a predictive model.

This prospective study included 67 HCC patients who underwent SMS-DKI on a 3-T MRI between June 2021 and January 2023. Diffusion parameters, including the apparent diffusion coefficient (ADC), SMS-mean kurtosis (SMS-MK), and SMS-mean diffusivity (SMS-MD), along with radiological features, were analyzed. Logistic regression models were used to predict early recurrence, internally validated using 10-fold cross-validation, and assessed using AUC, calibration curves, and decision curve analysis (DCA).

Among 67 patients (58 males; mean age, 53.5 ± 9.9 years), 30 (44.8%) experienced early recurrence. The early recurrence had significantly lower ADC (1.12 vs 1.22 × 10-3 mm2/s) and SMS-MD (1.45 vs 1.70 × 10-3 mm2/s), and higher SMS-MK (0.91 vs 0.75). SMS-MK showed the highest AUC (0.90, 95% CI: 0.80-0.96). Multivariate analysis identified SMS-MK (OR = 3.43 [1.31-8.89]), tumor size (OR = 4.22 [1.58-7.76]), non-smooth tumor margin (OR = 2.68 [1.58-7.96]), and complete capsule (OR = 0.22 [0.02-0.79]) as independent predictors of early recurrence. Based on these four parameters, the final model achieved an AUC of 0.94 (95% CI: 0.88-1.00). Calibration curves and DCA confirmed clinical utility.

SMS-DKI enhances early recurrence prediction in HCC. The predictive model, incorporating SMS-MK, tumor size, and key radiological features, demonstrated good prognostic value.

Question Can SMS-DKI predict HCC early recurrence within 2 years post-surgery? Findings Higher SMS-MK, larger tumor size, non-smooth margins, and incomplete capsule predict HCC early recurrence (model AUC = 0.94). Clinical relevance Integrating preoperative SMS-DKI biomarkers (SMS-MK) with tumor size and capsule status stratifies early HCC recurrence risk, guiding surgical planning and postoperative management.

Direct-acting antivirals (DAAs) are highly effective in treating hepatitis C virus (HCV) infection. The long-term hepatic and extrahepatic outcomes of DAAs in chronic hepatitis C (CHC) patients receiving curative antivirals are elusive.

CHC patients were retrieved from two phase III sofosbuvir-based clinical trials conducted from 2013-2014. Patients who achieved a sustained virological response have been followed prospectively for 5 years since 2016. A propensity score-matched interferon-based historical control with a 1:3 ratio was used for comparison. Quality of life (QoL) was measured by the SF-36, liver fibrosis was measured by electrography, and fibrosis-related markers were followed annually in the prospective cohort.

A total of 160 DAA- and 480 interferon-treated patients were enrolled. Twenty-eight patients developed hepatocellular carcinoma (HCC) over a follow-up period of 4424 person-years (annual incidence: 0.6%). The incidence of HCC did not differ significantly between the DAA cohort and interferon-treated patients (P = 0.07). Cox regression analysis revealed that FIB-4 was the only factor independently associated with HCC development (hazard ratio [HR]: 95% confidence interval [CI] 3.59/1.68-7.66, P = 0.001). The incidence of newly developed cardio-cerebrovascular disease was 13.8 per 1000 person-years and 0.9 per 1000 person-years in interferon-treated patients and the DAA cohort, respectively (P < 0.001). Interferon-based patients had a significantly greater incidence of cardio-cerebrovascular disease (HR/CI 3.39/1.28-8.96, P = 0.014). There was a substantial decrease in liver stiffness (Ptrend = 0.08) and M2BPGi (Ptrend = 0.05) and a significant reduction in LOXL2 (Ptrend = 0.02) over 5 years. A significant decrease in QoL was observed in role limitations due to physical health and emotional problems, whereas the other parameters were maintained consistently throughout the 5 years of follow-up.

HCV eradication by DAAs improved liver- and non-liver-related outcomes, constantly promoted liver fibrosis regression, and maintained quality of life after HCV cure.

NCT03042520.

Treatment options for hepatocellular carcinoma (HCC) vary according to known guidelines among liver resection (LR), liver transplantation (LT), radiofrequency ablation (RFA), and transarterial chemoembolization (TACE). This study aimed to compare the outcomes of initial treatment for patients with resectable HCC within Milan criteria (MC) via nationwide data.

Patients with resectable HCC (Child-Pugh class A; platelet count, ≥100,000/µL) within MC from the Korean Liver Cancer Association databank were analyzed, retrospectively. Outcomes according to initial treatment and subgroups according to tumor size and number were analyzed. Overall survival (OS) rates after initial treatment were compared.

A total of 3,241 patients who underwent LR (n = 1,371), LT (n = 12), RFA (n = 679), or TACE (n = 1,179) were included. The 5-year OS rates differed significantly between the groups (P < 0.05), except for LT (LR, 84.9%; LT, 82.5%; RFA, 76.2%; and TACE, 59.9%). For patients with a single tumor of any size, the 5-year OS rates of the LR group were significantly higher than RFA and TACE groups. For patients with multiple tumors, the 5-year OS rates were 78.2%, 100%, 74.3%, and 53.0% for the LR, LT, RFA, and TACE groups, respectively, but without significant difference between LR and RFA (P = 0.86).

For resectable HCC within MC, the LR had the highest OS rate for a single tumor of any size. LR and RFA showed no significant differences in OS rate for multiple tumors. LR has a much more optimistic outlook for HCC within MC.

In cirrhotic livers reliable visualization and exact localization of small hepatocellular carcinoma (HCC) can be challenging without adequate contrast enhancement. To investigate the feasibility, technical success rate, and safety of hepatobiliary phase MRI-guided percutaneous radiofrequency ablation (RFA) of small HCCs invisible on precontrast MRI.

53 patients (17f, 63.6 ± 16.7 years), with small HCC that were not visible in non-contrast MRI underwent MRI guided RFA. Feasibility was assessed by analyzing proper identification of the target tumor, tumor delineation during MRI-guided needle positioning and number of needle adjustments required for accurate placement. Technical success was defined as complete ablation with a safety margin of 5 mm. Safety was assessed from reports of procedure-related complications.

In all 53 cases, target tumors were not visible in non-contrast MRI but in the hepatobiliary phase. In 5 cases, planning imaging showed new tumors, which were either treated in the same session (n = 4) or altered the therapeutic approach (n = 1). Mean tumor diameter was 9.7 ± 1.9 mm and the number of needle adjustments was 5 ± 3. Post-ablation imaging showed a technical success rate of 98 % (51 cases, 55 tumors). No major complications occurred. Follow-up imaging (26.2 ± 22.4 month) showed no local tumor progression or recurrence.

Use of the hepatobiliary phase for MRI-guided ablation of otherwise MR-occult tumors is a feasible approach for an effective and safe treatment of small HCC nodules.

During its 2022 World Congress in New York the International Hepato-Pancreato-Biliary Association (IHPBA) launched the Legacy Initiative, aiming to create sustainable, positive impacts in host countries or regions by addressing critical healthcare challenges in the field of Hepato-Pancreato-Biliary surgery. The 2024 Legacy Initiative focused on hepatocellular carcinoma (HCC) in sub-Saharan Africa (SSA), a region disproportionately burdened by this disease due to a high incidence, limited healthcare infrastructure and resources, lack of screening programs, low awareness, and financial constraints. HCC, the sixth most common malignancy globally, is often diagnosed at advanced stages in SSA, leading to dismal outcomes. The initiative aims to improve management pathways and access to care through a multidisciplinary approach, emphasizing prevention, early diagnosis, curative treatments, potentially life-prolonging treatments, and palliative care. Key strategies include expanding healthcare infrastructure, implementing screening programs, raising awareness, and advocating for policy reforms. The IHPBA has partnered with the African Viral Hepatitis Convention and the African Palliative Care Association to address risk factors for developing HCC, in particular viral hepatitis, a major HCC risk factor. The initiative also highlights the need for capacity building, research, and collaboration with regional and international stakeholders. The 2024 Legacy Initiative aims to drive meaningful change, improve HCC outcomes, and reduce the disease burden in SSA, aligning with the IHPBA's mission to create long-lasting, positive impacts in global HPB healthcare.

To investigate the efficacy of PD-L1 blockade in restoring humoral immune response against HBV.

HBV-persistent C57BL/6J mice were established through hydrodynamic tail vein injection of 10 µg pAAV-HBV1.2 plasmid. Subsequently, mice treated i.p. with anti-PD-L1 and/or anti-CTLA-4 at specified time points, with dosages of 500 µg, 250 µg, and 250 µg, respectively. Additionally, 5 × 105 magnetic bead-purified plasmacytoid dendritic cells (pDCs) were adoptively transferred i.v. into the acute mouse model followed by anti-PD-L1 treatment. Quantitative real-time PCR was employed to assess the expression levels of costimulatory and tolerogenic molecules in two dendritic cell subsets. Serum HBsAg and HBsAb were measured using ELISA. Flow cytometry was utilized to quantify T follicular helper (Tfh) cells, regulatory T cells (Treg), and germinal center (GC) B cells.

PD-L1 blockade markedly enhanced the differentiation of Tfh cells and GC B cells in HBV-persistent C57BL/6J mice, thereby promoting HBV clearance. Additionally, pDCs exhibited an increased capacity to induce immune tolerance, with pDCs isolated from HBV carriers inducing viral persistence. This persistence was effectively counteracted by treatment with anti-PD-L1.

pDCs mediate the dysregulation of the humoral immune response to HBV through PD-L1 in chronic hepatitis B infection, highlighting a promising target for the management of chronic HBV.

Early-stage hepatocellular carcinoma (HCC) represents a critical window for curative treatment. However, treatment selection is complicated by significant heterogeneity in tumor biology, liver function, and patient performance status. This review provides a comprehensive overview of current curative-intent strategies for early-stage HCC, including liver transplantation, surgical resection, and local ablative therapies. We emphasize the importance of integrating tumor-specific characteristics-such as microvascular invasion, size, and anatomical location-with liver reserve metrics, including portal hypertension, Child-Pugh classification, and novel indices like albumin-bilirubin and albumin-indocyanine green evaluation grades. Furthermore, we discuss recent advances in non-thermal ablation techniques (eg, high-intensity focused ultrasound and irreversible electroporation), and technical innovations in radiofrequency ablation and cryoablation that are expanding the therapeutic landscape. By combining macro-level functional assessments with micro-level biological indicators, this review advocates for a personalized, evidence-based framework to optimize long-term outcomes in early HCC. The future of HCC management lies in standardizing individualized therapy.

Terminal branches portal vein embolization (TBPVE) is a novel technical modification. The clinical impact of synchronous TBPVE with transcatheter arterial chemoembolization (TACE) before planned major hepatectomy in hepatitis B virus (HBV) related HCC is still unknown.

From November 2016 to December 2021, the study enrolled 115 patients with HBV-related HCC who were scheduled for major hepatectomy but had insufficient FLR. Patients were grouped according to whether they received TBPVE combined with TACE (the TBPVE group, n = 62) or PVE combined with TACE (the PVE group, n = 53). We compared the outcomes of the procedures and the perioperative and long-term outcomes of patients who subsequently underwent major hepatectomy between the groups.

FLR volume increment and degree of hypertrophy were significantly higher in the TBPVE group than in the PVE group (P≤0.003). FLR proliferation was pronounced remarkably within the first two weeks after TBPVE synchronous with TACE, the kinetic growth rates were 17.4 (12.7-21.9) mL/day and 6.9 (4.1-11.1) mL/day respectively. 54 patients in the TBPVE group and 41 patients in the PVE group finally underwent major hepatectomies. Pringle's maneuver time, intraoperative blood loss, transfusion, and postoperative hospital stays were less in the TBPVE group (P<0.05). Disease-free survival (DFS) rates were better in the TBPVE group than in the PVE group (P=0.042).

TBPVE synchronous with TACE induced safe and rapid FLR hypertrophy with satisfactory efficacy in initially unresectable HBV-related HCC patients improved the planned major hepatectomy resectability rate and has better DFS.

Currently, predictive models that effectively stratify the risk levels for hepatocellular carcinoma (HCC) are insufficient. Our study aimed to assess the 10-year cumulative risk of HCC among patients suffering from chronic hepatitis B (CHB) by employing an artificial neural network (ANN).

This research involved 1717 patients admitted to Beijing Ditan Hospital of Capital Medical University and the People's Liberation Army Fifth Medical Center. The training group included 1309 individuals from Beijing Ditan Hospital of Capital Medical University, whereas the validation group contained 408 individuals from the People's Liberation Army Fifth Medical Center. By performing a univariate analysis, we pinpointed factors that had an independent impact on the development of HCC, which were subsequently employed to create the ANN model. To evaluate the ANN model, we analyzed its predictive accuracy, discriminative performance, and clinical net benefit through measures including the area under the receiver operating characteristic curve (AUC), concordance index (C-index), and calibration curves.

The cumulative incidence rates of HCC over a decade were observed to be 3.59% in the training cohort and 4.41% in the validation cohort. We incorporated nine distinct independent risk factors into the ANN model's development. Notably, in the training group, the area under the receiver operating characteristic (AUROC) curve for the ANN model was reported as 0.929 (95% CI 0.910-0.948), and the C-index was 0.917 (95% CI 0.907-0.927). These results were significantly superior to those of the mREACHE-B(0.700, 95% CI 0.639-0.761), mPAGE-B(0.800, 95% CI 0.757-0.844), HCC-RESCUE(0.787, 95% CI 0.732-0.837), CAMD(0.760, 95% CI 0.708-0.812), REAL-B(0.767, 95% CI 0.719-0.816), and PAGE-B(0.760, 95% CI 0.712-0.808) models (p < 0.001). The ANN model proficiently categorized patients into low-risk and high-risk groups based on their 10-year projections. In the training cohort, the positive predictive value (PPV) for the incidence of liver cancer in low-risk individuals was 92.5% (95% CI 0.921-0.939), whereas the negative predictive value (NPV) stood at 88.2% (95% CI 0.870-0.894). Among high-risk patients, the PPV reached 94.6% (95% CI 0.936-0.956) and the NPV was 90.2% (95% CI 0.897-0.917). These results were also confirmed in the independent validation cohort.

The model utilizing artificial neural networks demonstrates strong performance in personalized predictions and could assist in assessing the likelihood of a 10-year risk of HCC in patients suffering from CHB.

The outcomes of laparoscopic liver resection (LLR) for large (≥ 5 cm) hepatocellular carcinoma (HCC) in elderly (≥ 70 years old) patients have not been deeply investigated so far. The aim of the study was to compare short- and long-term results of LLR vs. open liver resection (OLR) in this setting. Data regarding all patients undergoing liver resection for large HCC were retrospectively collected from referral European and Asian HPB centers. The cases were propensity score matched for age, BMI, center, underlying liver cirrhosis, comorbidities, extent of the resection, tumor size, and numbers. After matching 363 patients with large HCC aged ≥ 70 years old, two cohorts of 90 patients were compared. The laparoscopic group showed a shorter median length of hospital stay (7 vs 9 days, p = 0.01), with a lower rate of R1 resections (4.4% vs 13.3%, p = 0.03). No statistically significant differences were found in the median operative time (p = 0.34), intraoperative blood transfusions (p = 1.00), severe postoperative complications (p = 0.29), postoperative hemorrhage (p = 0.30), post-hepatectomy liver failure (p = 0.47), or in-hospital mortality (p = 0.31). After a median follow-up of 35 months (95% CI 27.6-42.3), there were no statistically significant differences in both overall survival (p = 0.28) and disease-free survival (p = 0.42). LLR was safe and effective in selected cases of large HCC in elderly patients and was proven to shorten median hospital stay and to reduce the R1 rates, without affecting both short- and long-term survival outcomes.

Solitary hepatocellular carcinoma measuring ≤3 cm represents approximately 30% of hepatocellular carcinoma cases, yet treatment guidelines lack robust evidence. This study compares oncologic outcomes after ablation, liver resection, and liver transplantation for solitary, small hepatocellular carcinoma.

We systematically searched databases up to 7 February 2022, for studies including adults with solitary hepatocellular carcinoma ≤3 cm treated by any ablation, liver resection, or liver transplantation. We excluded non-hepatocellular carcinoma cancers, recurrent/metastatic diseases, and alternative therapies. A frequentist network meta-analysis assessed 5-year overall survival and recurrence-free survival using only adjusted effect estimates while accounting for bias risk.

We identified 80 studies (4 randomized controlled trials, 72 retrospectives, and 4 prospective cohorts) with 28,211 patients. In the network meta-analysis for 5-year overall survival (26 studies), liver transplantation was associated with the lowest mortality hazard (hazard ratio, 0.47; 95% confidence interval, 0.31-0.73, referenced to liver resection), followed by liver resection (reference), whereas ablation had the greatest mortality hazard (hazard ratio, 1.32; 95% confidence interval, 1.16-1.49, referenced to liver resection). For 5-year recurrence-free survival (19 studies), liver transplantation had the best outcome (hazard ratio, 0.36; 95% confidence interval, 0.20-0.63, referenced to liver transplantation), followed by liver resection (reference), with ablation showing the least favorable outcome (hazard ratio, 1.67; 95% confidence interval, 1.45-1.93, referenced to liver resection).

This network meta-analysis provides the evidence for comparing treatment modality outcomes for solitary, small (≤3 cm) hepatocellular carcinoma. LT emerges as the superior choice for achieving a better 5-year OS, followed by liver resection, then ablation. When feasible to preserve liver function, liver resection can be prioritized. Ablation with close surveillance should be reserved for individuals unfit for surgery.

Hepatitis B virus (HBV) RNA is an important serum biomarker of hepatic covalently closed circular DNA (cccDNA) transcriptional activity; however, its clinical characteristics remain unclear. This study evaluated the clinical utility of HBV RNA levels in patients with chronic hepatitis B (CHB).

We studied 87 CHB patients with serum HBV DNA levels ≥ 5.0 log IU/mL who initiated entecavir (ETV) treatment between 2000 and 2018. Serum HBV RNA levels were measured at three-time points: before ETV treatment, at 12 weeks, and at 48 weeks after starting ETV treatment. Clinical markers associated with the antiviral effects of ETV treatment were analyzed.

Serum HBV RNA levels decreased in both HBeAg-positive and -negative patients during the observation period. In HBeAg-positive patients, multivariable analysis showed that lower HBV RNA levels at 48 weeks of ETV treatment were independently associated with HBeAg seroconversion. Additionally, lower baseline HBV RNA levels significantly predicted virologic response in those patients. In contrast, among HBeAg-negative patients, lower HBV core-related antigen (HBcrAg) levels and the FIB-4 index were independently associated with virologic response. In HBeAg-positive patients, those with higher baseline HBV RNA levels showed a more significant reduction in hepatitis B surface antigen levels.

Serum HBV RNA levels predicted HBeAg seroconversion and early HBV DNA reduction in HBeAg-positive patients, while HBcrAg was significantly associated with virologic response in HBeAg-negative patients. These findings highlight the different predictive roles of HBV RNA and HBcrAg based on HBeAg status, which may provide individualized treatment strategies.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment. The guidelines aim to advance clinical practice, knowledge, and research on MAFLD, particularly in special groups. The guidelines are designed to advance clinical practice, to provide evidence-based recommendations to assist healthcare stakeholders in decision-making and to improve patient care and disease awareness. The guidelines take into account the burden of clinical management for the healthcare sector.

The CT/MRI Liver Imaging Reporting and Data System (LI-RADS) demonstrates high specificity with relatively limited sensitivity for diagnosing hepatocellular carcinoma (HCC) in high-risk patients. This study aimed to explore the possibility of improving sensitivity by combining CT/MRI LI-RADS v2018 with second-line contrast-enhanced ultrasound (CEUS) LI-RADS v2017 using sulfur hexafluoride (SHF) or perfluorobutane (PFB).

This retrospective analysis of prospectively collected multicenter data included high-risk patients with treatment-naive hepatic observations. The reference standard was pathological confirmation or a composite reference standard (only for benign lesions). Each participant underwent concurrent CT/MRI, SHF-enhanced US, and PFB-enhanced US examinations. The diagnostic performances for HCC of CT/MRI LI-RADS alone and three combination strategies (combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or a modified algorithm incorporating the Kupffer-phase findings for PFB [modified PFB]) were evaluated. For the three combination strategies, apart from the CT/MRI LR-5 criteria, HCC was diagnosed if CT/MRI LR-3 or LR-4 observations met the LR-5 criteria using LI-RADS SHF, LI-RADS PFB, or modified PFB.

In total, 281 participants (237 males; mean age, 55 ± 11 years) with 306 observations (227 HCCs, 40 non-HCC malignancies, and 39 benign lesions) were included. Using LI-RADS SHF, LI-RADS PFB, and modified PFB, 20, 23, and 31 CT/MRI LR-3/4 observations, respectively, were reclassified as LR-5, and all were pathologically confirmed as HCCs. Compared to CT/MRI LI-RADS alone (74%, 95% confidence interval [CI]: 68%-79%), the three combination strategies combining CT/MRI LI-RADS with either LI-RADS SHF, LI-RADS PFB, or modified PFB increased sensitivity (83% [95% CI: 77%-87%], 84% [95% CI: 79%-89%], 88% [95% CI: 83%-92%], respectively; all P < 0.001), while maintaining the specificity at 92% (95% CI: 84%-97%).

The combination of CT/MRI LI-RADS with second-line CEUS using SHF or PFB improved the sensitivity of HCC diagnosis without compromising specificity.

To investigate the association between air pollution and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

We enrolled 1298 CHB patients treated with nucleotide/nucleoside analogues and analysed the incidence and risk factors for HCC. Daily estimates of air pollutants were estimated since the previous year from the enrolment date.

The annual incidence of HCC was 2.1/100 person-years after a follow-up period of over 4840.5 person-years. Factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 3.00/1.55-5.81; p = 0.001), male sex (2.98/1.51-5.90; p = 0.02), body mass index (1.11/1.04-1.18; p = 0.002) and age (1.06/1.04-1.09; p < 0.001). Among patients with cirrhosis, the factors associated with HCC development were male sex (HR/95% CI: 2.10/1.00-4.25; p = 0.04) and NO2 (per one-unit increment, parts per billion; 1.07/1.01-1.13; p = 0.01). Moreover, patients with the highest quartile of annual NO2 exposure had more than a three-fold risk of HCC than those with the lowest quartile of annual exposure (HR/95% CI: 3.26/1.34-7.93; p = 0.01). Among patients without cirrhosis, the strongest factors associated with HCC development were male sex (HR/95% CI: 5.86/1.79-19.23; p = 0.004), age (1.12/1.07-1.17; p < 0.001) and platelet count (0.99/0.98-1.00; p = 0.04).

Air pollution influences HCC development in CHB patients who receive nucleotide/nucleoside analogue therapy. Long-term NO2 exposure might accelerate HCC development in CHB patients with cirrhosis receiving nucleotide/nucleoside analogue treatment.

Despite the expanding indications for laparoscopic liver resection (LLR), its role in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains unclear. The aim of the current study is to compare the short- and long-term outcomes following LLR and open liver resection (OLR) for HCC with PVTT.

All HCC patients with PVTT registered for surgery between April 2015 and May 2022 were enrolled. Patients were divided into LLR and OLR groups, and postoperative recovery and oncological outcomes were analyzed.

Twenty-eight patients in the LLR group and one hundred seventeen patients in the OLR group were included for comparison. The blood loss was less and the postoperative hospital stay was shorter in LLR group compared to OLR group both before and after propensity score matching. The median recurrence-free survival (RFS) time did not significantly differ between the two groups (8.0 months [95% CI 3.1-13.0] vs. 7.5 months [95% CI 6.0-9.1]; P = 0.845). In stratified analysis, both the recurrence pattern and the median RFS time were comparable between the LLR group and the OLR group in type I PVTT (7.23 [95% CI 0.35-14.12] vs. 7.17 months [95% CI 3.49-10.85]; P = 0.794) and type II PVTT (8.96 [95% CI 0-19.56] vs. 7.60 months [95% CI 5.98-9.22], P = 0.651), respectively. The multivariate regression analysis showed that the tumor size ≥ 10 cm, AFP > 200 ng/ml, and HBV-DNA > 1000 copies/ml were independent risk factors for RFS.

LLR for HCC patients with type I/II PVTT could be safely performed with superior short-term recovery and similar long-term survival compared to OLR. Larger tumor size, higher AFP, and elevated HBV-DNA levels contribute to worse RFS.

Chronic liver disease (CLD) in children poses significant challenges, necessitating timely management to mitigate morbidity and mortality. Liver transplantation (LT) has emerged as a transformative intervention, offering improved long-term survival for paediatric patients with CLD. This review explores the evolving landscape of liver transplantation, focusing on indications and timing considerations. The aetiology of CLD is diverse, encompassing intrahepatic, extrahepatic cholestatic conditions, metabolic diseases, malignancy, and drug-induced liver injury. LT is indicated when children exhibit signs of hepatic decompensation, necessitating a comprehensive evaluation to assess transplant suitability. Indications for LT include biliary atresia, inborn errors of metabolism, hepatocellular carcinoma, and emerging indications such as mitochondrial hepatopathies and acute on chronic liver failure. The timing of transplantation is critical, emphasizing the need for early recognition of decompensation signs to optimise outcomes. Advancements in LT techniques and immunosuppressive therapies have enhanced patient and graft survival rates. Various transplant modalities, including reduced-size LT and living-related LT, offer tailored solutions to address the unique needs of paediatric patients. While LT represents a cornerstone in the management of paediatric CLD, careful patient selection, multidisciplinary collaboration, and ongoing refinements in transplant protocols are imperative for optimizing outcomes and addressing the evolving landscape of paediatric liver disease management.

Currently, only tumors classified as LR-5 are considered definitive hepatocellular carcinoma (HCC), and no further pathologic confirmation is required to initiate therapy. Previous studies have shown that the sensitivity of LR-5 is modest, and lesions enhanced by gadoxetic acid (Gd-EOB-DTPA) may exhibit lower sensitivity than those enhanced by Gd-DTPA.

To identify malignant ancillary features (AFs) that can independently and significantly predict HCC in Liver Imaging Reporting and Data System version 2018, and to develop modified LR-5 criteria to improve diagnostic performance on Gd-EOB-DTPA - enhanced magnetic resonance imaging.

Imaging data from patients with HCC risk factors who underwent abdominal Gd-EOB-DTPA - enhanced magnetic resonance imaging were collected. Univariate and multivariate logistic regression analyses were performed to determine AFs that could independently and significantly predict HCC. The modified LR-5 criteria involved reclassifying LR-4/LR-3 lesions based on major features combined with independently significant AFs for HCC, or by substituting threshold growth with significant AFs. McNemar's test was used to compare the diagnostic performance of the modified LR-5 criteria.

A total of 244 lesions from 216 patients were included. Transitional phase hypointensity, mild - moderate T2 hyperintensity, and fat in mass (more than adjacent liver) were identified as significant independent predictors of HCC. Using the modified LR-5 criteria (e.g., LR-5-M1: LR-4 + transitional phase hypointensity; LR-5-M4: LR-5 by transitional phase hypointensity instead of threshold growth; LR-5-M5: LR-5 by mild - moderate T2 hyperintensity instead of threshold growth; LR-5-M8: LR-3/LR-4 + any two features of transitional phase hypointensity/mild - moderate T2 hyperintensity/fat in mass), sensitivities were significantly increased (88.5%-89.1%) compared to the standard LR-5 (60.6%; all P values < 0.05), while specificities (84.8%-89.9%) remained largely unchanged (93.7%; all P values > 0.05). The LR-5-M8 criterion achieved the highest sensitivity.

Mild - moderate T2 hyperintensity, transitional phase hypointensity, and fat in mass are independent and significant predictors of HCC malignant AFs. The modified LR-5 criteria can improve sensitivity without significantly reducing specificity.

Noncontrast-abbreviated magnetic resonance imaging (NC-AMRI) is emerging as a promising alternative to ultrasound (US) for surveillance of hepatocellular carcinoma (HCC) in at-risk patients. We aimed to assess the effectiveness of NC-AMRI in a real-world surveillance population, and to evaluate the appropriateness of NC-AMRI in selected patients with inadequate prior US.

This retrospective study included Child-Pugh class A or B adults with chronic hepatitis B or cirrhosis from any cause who underwent NC-AMRI between December 2018 and August 2022. Early- and very early-stage detection, receipt of curative treatment, and false referral were evaluated. Subgroup analysis was performed for patients with inadequate prior US examinations. Descriptive statistics were used.

Among the 1853 patients (mean age, 58.8 years; 1045 males), 68 HCCs developed in 61 (61/1853, 3.3%, 95% confidence interval: 2.5-4.2) patients. The proportions of early- and very early-stage detection were 95.1% (58/61, 72.2-100.0) and 70.5% (43/61, 51.0-95.0); receipt of curative treatment, 67.2% (41/61, 48.2-91.2); and proportion of false referral, 12.9% (9/70, 5.9-24.4). Among the 375 patients with inadequate prior US, the proportions of early- and very early-stage detection were 94.7% (18/19, 56.2-100.0) and 57.9% (11/19, 28.9-100.0); receipt of curative treatment, 52.6% (10/19, 25.2-96.8); and proportion of false referrals, 17.4% (4/23, 4.7-44.5).

NC-AMRI may be an effective HCC surveillance modality given the results related to early- and very early-stage detection, receipt of curative treatment, and false referral. NC-AMRI can be an alternative HCC surveillance strategy, especially for patients with inadequate prior US examinations.

Question There is insufficient evidence to support the use of noncontrast-abbreviated MRI as an effective surveillance tool in large real-life populations under surveillance. Findings Using noncontrast-abbreviated MRI, most patients who developed HCCs during surveillance were diagnosed at an early stage, with an acceptable false referral rate of 12.9%. Clinical relevance Noncontrast-abbreviated MRI is an effective HCC surveillance modality, especially for patients with inadequate prior ultrasound examinations.

Immune checkpoint inhibitors (ICIs) have revolutionized hepatocellular carcinoma (HCC) treatment, while immune-related adverse events (IRAEs) pose significant challenges. We report a 60-year-old male with unresectable HCC who developed Guillain-Barré syndrome (GBS), a rare but severe neurologic complication, after three cycles of sintilimab plus bevacizumab biosimilar and conventional transarterial chemoembolization (c-TACE). The patient presented with progressive ascending weakness, reaching symmetric quadriparesis with proximal muscle strength of 2/5 in upper limbs and 1/5 in lower limbs. Following sintilimab discontinuation, treatment with intravenous immunoglobulin (2 g/kg) and oral prednisone (30 mg/day) achieved complete neurological recovery within one month. Given the patient's favorable initial tumor response and strong request, immunotherapy was cautiously reinstated using tislelizumab after thorough clinical evaluation. Following four cycles of treatment, significant tumor response enabled successful conversion surgery with major pathological response (necrosis rate >70%). With 26-month survival and no evidence of recurrence, this case demonstrates the potential feasibility of ICI rechallenge with an alternative PD-1 inhibitor following sintilimab-induced GBS. Our experience suggests that ICI-related neurological adverse events may be drug-specific rather than class-specific, potentially providing valuable treatment options for patients showing favorable tumor response despite experiencing severe IRAEs, though larger studies are needed for validation.

This study aimed to develop a multiregional radiomics-based model using multisequence MRI to predict microvascular invasion in hepatocellular carcinoma.

We enrolled 141 patients with hepatocellular carcinoma, including 61 with microvascular invasion, who were diagnosed between March 2017 and July 2022. Clinical data were compared using the Wilcoxon rank-sum test or χ2 test. Patients were randomly divided into training (n=112, 80%) and test (n=29, 20%) data sets. Four MRI sequences-including T2-weighted imaging, T2-weighted imaging with fat suppression, arterial phase-contrast enhancement, and portal venous phase contrast enhancement-were used to build the radiomics model. The tumor volumes of interest were manually delineated, and the expand-5 mm and expand-10 mm volumes of interest were automatically generated. A total of 1409 radiomic features were extracted from each volume of interest. Feature selection was performed using the least absolute shrinkage and selection operator and Spearman correlation analysis. Three logistic regression models (Tumor, Tumor-Expand5, and Tumor-Expand10) were established based on the radiomic features. Model performance was assessed using receiver operating characteristic analysis and Delong's test.

Maximum tumor diameter, hepatitis B virus DNA, and aspartate aminotransferase levels were significantly different between the groups. The Tumor-Expand5mm model exhibited the best performance among the 3 models, with areas under the curve of 0.90 and 0.84 in the training and test data sets.

The Tumor-Expand5 model based on multisequence MRI shows great potential for predicting microvascular invasion in patients with hepatocellular carcinoma, and may further contribute to personal clinical decision-making.

Despite advances in surgical treatment, high recurrence after surgery remains a challenge for patients with hepatocellular carcinoma (HCC). This study aimed to investigate the association between compliance to regular follow-up and long-term oncological outcomes among patients undergoing curative resection for HCC.

This multicenter study included patients who underwent curative resection for early-stage HCC between January 2012 and December 2021 at 12 liver surgery centers. Patients were stratified into a regular follow-up group (follow-up every 2-3 months for the first 2 years and every 3-6 months thereafter) and an irregular/no follow-up group. Overall survival (OS), time to recurrence (TTR), and post-recurrence survival (PRS) were compared between the two groups.

Among 1544 patients, 786 (50.9 %) underwent regular follow-up during postoperative follow-up. The regular follow-up group had better OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) than the irregular/no follow-up group, although TTR was comparable (median: 61.4 vs. 66.2 months, P = 0.161). Furthermore, patients in the regular follow-up group had a lower incidence of tumor beyond the Milan criteria at recurrence (41.6 % vs. 50.4 %, P = 0.013) and were more likely to receive curative treatments for recurrence (56.1 % vs. 49.3 %, P = 0.061). On multivariate analysis, compliance to regular follow-up was an independent factor associated with better OS [hazard ratio (HR) = 0.777, 95 % confidence interval (CI): 0.663-0.910, P = 0.002] and PRS (HR = 0.523, 95 % CI: 0.428-0.638, P < 0.001).

Compliance to regular follow-up improved OS and PRS after curative resection for HCC, highlighting the importance of postoperative regular follow-up for early detection of recurrence and timely intervention.

Hepatocellular carcinoma (HCC) is often diagnosed using gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI). Standardized reporting according to the Liver Imaging Reporting and Data System (LI-RADS) can improve Gd-MRI interpretation but is rather complex and time-consuming. These limitations could potentially be alleviated using recent deep learning-based segmentation and classification methods such as nnU-Net. The study aims to create and evaluate an automatic segmentation model for HCC risk assessment, according to LI-RADS v2018 using nnU-Net.

For this single-center retrospective study, 602 patients at risk for HCC were included, who had dynamic EOB-MRI examinations between 05/2005 and 09/2022, containing ≥ LR-3 lesion(s). Manual lesion segmentations in semantic segmentation masks as LR-3, LR-4, LR-5 or LR-M served as ground truth. A set of U-Net models with 14 input channels was trained using the nnU-Net framework for automatic segmentation. Lesion detection, LI-RADS classification, and instance segmentation metrics were calculated by post-processing the semantic segmentation outputs of the final model ensemble. For the external evaluation, a modified version of the LiverHccSeg dataset was used.

The final training/internal test/external test cohorts included 383/219/16 patients. In the three cohorts, LI-RADS lesions (≥ LR-3 and LR-M) ≥ 10 mm were detected with sensitivities of 0.41-0.85/0.40-0.90/0.83 (LR-5: 0.85/0.90/0.83) and positive predictive values of 0.70-0.94/0.67-0.88/0.90 (LR-5: 0.94/0.88/0.90). F1 scores for LI-RADS classification of detected lesions ranged between 0.48-0.69/0.47-0.74/0.84 (LR-5: 0.69/0.74/0.84). Median per lesion Sørensen-Dice coefficients were between 0.61-0.74/0.52-0.77/0.84 (LR-5: 0.74/0.77/0.84).

Deep learning-based HCC risk assessment according to LI-RADS can be implemented as automatically generated tumor risk maps using out-of-the-box image segmentation tools with high detection performance for LR-5 lesions. Before translation into clinical practice, further improvements in automatic LI-RADS classification, for example through large multi-center studies, would be desirable.

Hepatocellular carcinoma remains a significant cause of mortality worldwide, particularly among patients with liver cirrhosis. In most cases, surveillance in cirrhotic patients is neglected, leading to a diagnosis when the neoplasm is at an advanced stage. Within this context, Zhou et al carried out a network meta-analysis to demonstrate the effectiveness of hepatic arterial infusion chemotherapy, concluding that it is a superior approach compared to sorafenib and transarterial chemoembolization in the treatment of advanced hepatocellular carcinoma. Unfortunately, the meta-analysis in question lacks methodological rigor, preventing the authors from making more definitive assertions. Additionally, we understand that transarterial chemoembolization, when properly indicated, is a highly effective therapeutic option, and that sorafenib, given the results of new therapies based on immune checkpoint inhibitors, is no longer the recommended drug for the treatment of these patients. Therefore, we believe the use of hepatic arterial infusion chemotherapy is increasingly limited and lacks strong scientific support.

The aim of this study was to investigate the effect of a surgical treatment algorithm recently proposed by the American Association for the Study of Liver Diseases (AASLD) on survival outcomes in patients with early-stage hepatocellular carcinoma (HCC) and identify effective alternative treatment modalities when liver transplantation (LT) is not available.

We studied the clinical data of 1,442 patients who were diagnosed with early-stage HCC (a single lesion measuring 2-5 cm in size or 2 to 3 lesions measuring ≤3 cm in size) between 2013 and 2018 and classified as Child-Turcotte-Pugh (CTP) A or B. Analyses were separately performed for individuals recommended for resection (single lesion, CTP A and no clinically significant portal hypertension) and those recommended for LT (single lesion with impaired liver function such as CTP B or clinically significant portal hypertension or multiple lesions).

Of 791 patients recommended for surgical resection, 85.8% underwent resection. The 5-year survival rate was higher for patients who underwent surgical resection than for those who received other treatments (89.4% vs 72.3%). Among 651 patients recommended for LT, only 3.4% underwent the procedure. The most common alternative treatment modalities were transarterial therapy (39.3%) followed by resection (28.9%) and ablation (27.8%). The overall survival rate associated with transarterial therapy was lower than that for resection and ablation, whereas that of the latter two treatments were comparable.

The survival outcomes of treatment strategies that most closely aligned with the algorithm proposed by the AASLD were superior to those of alternative treatment approaches. However, LT in patients with early-stage HCC can be challenging. When LT is not feasible, resection and ablation can be considered first-line alternative options.

To report final results of a prospective study of stereotactic body radiation therapy (SBRT) in patients with previously untreated solitary primary hepatocellular carcinoma (HCC).

This prospective, single-arm, multicenter phase 2 trial recruited patients with HCC who were unsuitable for, or refused, surgery and radiofrequency ablation, with 3-year overall survival rates as the primary endpoint and survival outcomes and adverse events as secondary endpoints. The prescribed SBRT dose was 40 Gy in 5 fractions. The final data were analyzed in November 2022.

Between 2014 and 2018, 36 patients (median age, 73.5 years) were registered; enrollment was closed before full recruitment due to slow accrual. Overall, 34 patients were analyzed for efficacy evaluation after excluding 2 patients. The median tumor size was 2.3 cm. The median follow-up times for all patients and for survivors were 49 and 56 months, respectively. The 3-year overall survival rate was 82% (95% confidence interval, 65%-92%). The 3-year local control rate was 93% (95% confidence interval, 76%-98%). Grade 3 or higher SBRT-related nonlaboratory toxicities were observed in 4 patients (11%). No grade 5 adverse events were observed.

Final results of this phase 2 trial suggest the efficacy and safety of SBRT for newly diagnosed early-stage HCC that is unfit for other local therapies. Although this study was underpowered by the small number of registrations, the excellent results indicate that SBRT may be an alternative option for the management of early-stage HCC.

Single nucleotide polymorphisms (SNPs) in patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes were reported to be strongly associated with non-alcoholic fatty liver disease (NAFLD) pathogenicity among different populations. We investigated whether these SNPs are associated with prognostic factors and genetic biomarkers of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) in the Sri Lankan context.

We conducted an exploratory study to evaluate the prevalence of five SNPs (PNPLA3 rs738409, PNPLA3 rs2281135, PNPLA3 rs2294918, TM6SF2 rs58542926 and MBOAT7 rs641738) as genetic risk factors for NASH-HCC pathogenicity. We genotyped 48 NASH-HCC patient samples collected at a clinical setting using a minisequencing method. Impact of each SNP with tumor prognostic factors such as nodularity, tumor size and AFP (alpha-feto protein) level was analyzed using chi square test. We also analyzed the expression of micro RNA-122 (miR-122) in serum and leukocyte telomere length via quantitative real-time PCR. Associations between each SNP with micro RNA-122 (miR-122) expression level and leukocyte telomere length of NASH-HCC patients were analyzed using one-way analysis of variance (ANOVA) test and independent t test. Relationships among tested SNPs and some well-established HCC risk factors such as age, BMI, gender, diabetes status and the cirrhotic stage were also analyzed using chi square test, independent t-test and One-way ANOVA test.

Our analyses demonstrated significant associations between PNPLA3 rs2281135 variant and tumor nodularity. Also, PNPLA3 rs2281135 and PNPLA3 rs2294918 variants were significantly associated with miR-122 expression levels of NASH-HCC patients. Further, age and body mass index (BMI) were significantly associated with PNPLA3 rs2281135 variant in our study cohort.

We found that in the Sri Lankan NASH-related HCC cohort, some PNPLA3 variants (rs2281135 and rs2294918) correlate with tumor nodularity, higher miR-122 expression, and distinct demographic features such as age and BMI. Our work highlights the role of specific SNPs in tumor aggressiveness, contributing to the precision screening for HCC in NASH patients.

Transcatheter arterial chemoembolization (TACE) has been combined with immune checkpoint inhibitor (ICI)-based systemic therapies for unresectable hepatocellular carcinoma (uHCC) with promising efficacy. However, whether the addition of TACE to the combination of ICI and tyrosine kinase inhibitor (TKI) (ICI+TKI+TACE) is superior to ICI+TKI combination therapy is still not clear. Thus, this study compares the efficacy of ICI+TKI+TACE triple therapy and ICI+TKI doublet therapy in patients with uHCC.

uHCC patients treated with either ICI+TKI+TACE triple therapy or ICI+TKI doublet therapy were retrospectively recruited between January 2016 and December 2021 at Eastern Hepatobiliary Surgery Hospital. The patients from ICI+TKI+TACE group and ICI+TKI group were further subjected to propensity score matching (PSM). The primary outcome was progression-free survival (PFS). The secondary outcomes were overall survival (OS) and objective response rate (ORR). Post-progression survival (PPS) as well as treatment-related adverse events (TRAEs) were also assessed.

A total of 120 patients were matched. The median PFS was 8.4 months in ICI+TKI+TACE triple therapy group versus 6.6 months in ICI+TKI doublet therapy group (HR 0.72, 95%CI 0.48-1.08; p=0.115). Similar results were obtained in term of OS (26.9 versus 24.2 months, HR 0.88, 95% CI 0.51-1.52; p=0.670). The ORR in the triple therapy group was comparable with that in the doublet therapy group (16.6% versus 21.6%, p=0.487). Further subgroup analysis for PFS illustrated that patients without previous locoregional treatment (preLRT) (10.5 versus 3.7 months, HR 0.35 [0.16-0.76]; p=0.009), without previous treatment (10.5 versus 3.5 months, HR 0.34 [0.14-0.81]; p=0.015) or treated with lenvatinib (14.8 versus 6.9 months, HR 0.52 [0.31-0.87]; p=0.013) can significantly benefit from triple therapy compared with doublet therapy. A remarkable interaction between treatment and preLRT (p=0.049) or TKIs-combined (p=0.005) was also detected in term of PFS. Post progression treatment significantly improved PPS in both groups. The incidence of TRAEs was comparable between two groups.

The addition of TACE to ICI+TKI combination therapy did not result in a substantial improvement in efficacy and prognosis of patients. However, in selected uHCC patients (without preLRT or treated with lenvatinib as combination), ICI+TKI+TACE triple therapy may remarkably improve PFS.

While the value of Des-γ-carboxy prothrombin in hepatocellular carcinoma diagnosis has been widely acknowledged, whether or how Des-γ-carboxy prothrombin could be used in recurrence evaluation remains largely unexplored.

We performed a multicenter retrospective analysis including an Exploration Cohort (1074 patients, 5133 Des-γ-carboxy prothrombin measurements) and a Validation Cohort (263 patients, 612 Des-γ-carboxy prothrombin measurements) to investigate whether Des-γ-carboxy prothrombin could evaluate patients' prognosis. We introduced the Des-γ-carboxy prothrombin dynamic rate as a normalized quantitative measurement of Des-γ-carboxy prothrombin dynamic change. Des-γ-carboxy prothrombin dynamic rates were further applied in a high-risk liver cirrhosis patient cohort (PreCar Cohort, 542 liver cirrhosis patients, 2023 Des-γ-carboxy prothrombin measurements).

Here, we show a post-operative decrease of Des-γ-carboxy prothrombin in the Exploration Cohort, making the Des-γ-carboxy prothrombin threshold in diagnosis unsuitable for prognosis, while Des-γ-carboxy prothrombin dynamic rates significantly associate with recurrence risk. Categorizing patients based on Des-γ-carboxy prothrombin dynamic rates and final concentrations shows that patients negative for both exhibit the best median recurrence-free survival and patients positive for both show the worst median recurrence-free survival. Patients with consistently positive status have a significantly lower median recurrence-free survival compared to those whose status reverted to negative. These findings are validated in the Validation Cohort. Furthermore, the Des-γ-carboxy prothrombin dynamic rates in the PreCar Cohort can identify an additional 28% of cirrhosis patients progressing to hepatocellular carcinoma.

These results expand on the clinical utilization of the hepatocellular carcinoma diagnosis biomarker, Des-γ-carboxy prothrombin, by proposing a quantification measurement of Des-γ-carboxy prothrombin dynamics to monitor hepatocellular carcinoma recurrence. This measurement is not limited in prognosis but can also improve the sensitivity of early hepatocellular carcinoma screening.