Barcelona Clinic Liver Cancer Research Articles

Clinical Significance of Biliary Invasion at Diagnosis in Barcelona Clinic Liver Cancer Stage B-C Hepatocellular Carcinoma: a Nationwide Cohort Analysis in South Korea

Introduction Evidence of biliary invasion as a prognostic factor in patients with hepatocellular carcinoma is unclear. We aimed to verify the significance of clinically diagnosed biliary involvement in patients with Barcelona Clinic Liver Cancer stage B-C (BCLC B-C) hepatocellular carcinoma. Methods The Korean Liver Cancer Study Group randomly extracted data of patients with hepatocellular carcinoma enrolled in the Korean Central Cancer Registry between 2011–2016 from approximately 50 hospitals nationwide. After excluding records without information regarding serum bilirubin level, alpha-fetoprotein level, and Child-Pugh class, a pre-propensity score matching cohort comprising 4077 patients was included. Considering age, sex, body mass index, viral cause, serum bilirubin level, alpha-fetoprotein level, Child-Pugh class, tumor size, multiplicity, portal invasion, and extrahepatic metastasis, patients with and without bile duct invasion at initial imaging diagnosis were matched at a ratio of 1:2 from the pre- propensity score matching cohort to form a matched cohort (propensity score matching cohort). Results The pre-propensity score matching cohort included 4077 patients with BCLC B-C and 165 (4.0%) with biliary invasion at diagnosis. Regarding biliary invasion at diagnosis, one- and two-year overall survival rates were 41.2% and 29.1% (with invasion) and 54% and 40.9% (without invasion), respectively (p<0.0001). Corresponding cancer-specific survival rates at one and two years were 43.4% and 30.7% (with invasion) and 56.6% and 44% (without invasion), respectively (p<0.0001). Although biliary invasion was a significant factor affecting overall and cancer-specific survival rates in a univariate analysis, it was not statistically significant in multivariate analyses for overall (p=0.153) and cancer-specific (p=0.198) survival rates. The propensity score matching cohort included 165 patients with biliary invasion at diagnosis and 330 without biliary invasion. In the propensity score matching cohort, biliary invasion at diagnosis was not a significant factor affecting overall (p=0.603) or cancer-specific (p=0.960) survival rates in the univariate analyses. One- and two-year overall survival were 41.2% and 29.1% (with invasion) and 36.1% and 28.2% (without invasion), respectively. The corresponding cancer-specific survival at one and two years were 43.4% and 30.7% (with invasion) and 39.8% and 31.4% (without invasion), respectively. Multivariate analyses revealed that alpha-fetoprotein levels, Child-Pugh class, tumor singularity, tumor size, portal invasion, lymph node metastases, and distant metastases significantly affected both overall and cancer-specific survival rates. Conclusion Biliary invasion at diagnosis in patients with BCLC B-C does not affect overall or cancer-specific survival rates; however, other prognostic factors associated with biliary invasion could have a greater impact.

Prognostic performance of Hong Kong Liver Cancer with Barcelona Clinic Liver Cancer staging systems in hepatocellular carcinoma

BackgroundAccurate staging is necessary for predicting hepatocellular carcinoma (HCC) prognosis and guiding patient management. The Barcelona Clinic Liver Cancer (BCLC) staging system has limitations due to heterogeneity observed among patients in BCLC stages B and C. In contrast, the Hong Kong Liver Cancer (HKLC) staging system offers more aggressive treatment strategies.AimTo compare the prognostic performance of HKLC and BCLC staging systems in Egyptian patients with HCC.MethodsWe conducted a retrospective study at the National Liver Institute, Menoufia University, Egypt, on 1015 HCC patients. Data was collected from patients’ medical records over 10 years (from 2008 to 2018). The BCLC and HKLC stages were identified, and Kaplan-Meier survival analysis was used to compare patients’ overall survival rates within each staging system. Additionally, we evaluated the comparative prognostic performance of the two staging systems.ResultsHepatitis C was identified as the underlying etiology in 799 patients (78.7%), hepatitis B in 12 patients (1.2%), and non-viral causes in 204 patients (20.1%). The survival analysis demonstrated significant differences across the various stages within both the BCLC and HKLC systems. The receiver operating characteristic (ROC) curves indicated a marginally superior performance of the HKLC system in predicting survival at 1, 2, and 3 years compared to the BCLC system. Furthermore, the HKLC staging provided a slightly enhanced prognostic capability, particularly for patients classified under BCLC stages B and C, suggesting a potential survival benefit.ConclusionHKLC classification had a slightly better prognostic performance than BCLC staging system and may offer a survival advantage for certain patients with HCC in BCLC stage B and C HCC cases.

Multidisciplinary approaches to downstaging hepatocellular carcinoma: present and future.

Downstaging of hepatocellular carcinoma (HCC) is typically defined as the reduction in size or number of viable tumors through locoregional therapy (LRT), aiming to meet the established criteria for liver transplantation (LT). According to the Barcelona Clinic Liver Cancer (BCLC) staging system, a subgroup of patients with BCLC-B may benefit most from downstaging therapies. The United Network Organ Sharing downstaging protocol identifies potential candidates for downstaging by setting out 'inclusion criteria' and defining 'successful downstaging.' Additionally, the protocol considers factors related to tumor biology, such as an alphafetoprotein level <500 ng/mL after LRT. Reports indicate that successful downstaging rates following LRT are about 50%, with post- LT recurrence rates comparable to those of patients within the Milan criteria. A comprehensive multicenter US study on 10-year outcomes post-LT after downstaging showed 10-year post-LT survival and recurrence rates of 52.1% and 20.6%, respectively, for patients whose disease was downstaged; this compares to 61.5% and 13.3% for those consistently within the Milan criteria. Recently, the development of effective systemic treatments for HCC, such as immuno-oncologic agents, has provided additional opportunities for downstaging. Numerous clinical trials are exploring a multidisciplinary approach (MDA) combining LRT and systemic therapy. Although concrete evidence of the superiority of MDA for HCC downstaging is lacking, some retrospective studies and phase I and II trials have shown promising results regarding the efficacy and safety of MDA for this purpose. In this review, we will also discuss the future of MDA protocols in downstaging for improved clinical outcomes.

Conversion Therapy to Transplant or Surgical Resection in Patients with Unresectable Hepatocellular Carcinoma Treated with Boosted Dose of Yttrium-90 Radiation Segmentectomy.

The aim of this study was to assess the efficacy of boosted dose yttrium-90 radioembolization (TARE) as a modality for conversion therapy to transplant or surgical resection in patients with unresectable hepatocellular carcinoma (HCC). In this single-center retrospective study, all patients with a diagnosis of HCC who were treated with boosted dose TARE (>190 Gy) between January 2013 and December 2023 were reviewed. Treatment response and decrease in tumor size were assessed with the RECIST v1.1 and mRECIST criteria. Milan and University of California, San Francisco (UCSF), criteria were used to determine transplant eligibility, and Barcelona Clinic Liver Cancer (BCLC) surgical resection recommendations were used to evaluate tumor resectability. Thirty-eight patients with primary HCC who were treated with boosted dose TARE were retrospectively analyzed. The majority of the patients were Child-Pugh A (n = 35; 92.1%), BCLC C (n = 17; 44.7%), and ECOG performance status 0 (n = 25; 65.8%). The mean sum of the target lesions was 6.0 cm (standard deviation; SD = 4.0). The objective response rate (ORR) was 31.6% by RECIST and 84.2% by mRECIST. The disease control rate (DCR) was 94.7% by both RECIST and mRECIST. Among patients outside of Milan or UCSF, 13/25 (52.0%, Milan) and 9/19 (47.4%, UCSF) patients were successfully converted to within transplant criteria. Of patients who were initially unresectable, conversion was successful in 7/26 (26.9%) patients. This study provides further real-world data demonstrating that boosted-dose TARE is an effective modality for conversion of patients with unresectable HCC to transplant or resection.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Evaluation of different scoring systems for repeating Transarterial Chemoembolization in Egyptian patients with Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) have a diverse range of outcomes due to their high degree of heterogeneity. Therefore, different predictive scoring systems have been created to assist in decision-making regarding retreatment with TACE. We compared the predictive capabilities of different scoring systems, such as ART, ABCR, and SNACOR, for prediction of the outcome of subsequent TACE in HCC patients. In this retrospective study, the three scoring systems were compared for their capability of predicting the outcome of repeating TACE in 149 HCC patients treated at the National Liver Institute, Egypt, between January 2017 and December 2019. We used the likelihood ratio to select the model with the highest predictive capability for overall survival (OS). According to our data, the amount of tumor, the change in Barcelona Clinic Liver Cancer (BCLC) stage following TACE, and the SNACOR score (with a 95% confidence range for HR 1.0305-1.256 and p-value = 0.0106) were the most predictive variables. It was also shown that the ABCR score was a good predictor of survival (90 patients had an ABCR score ≤ 0 with a P- value <0.0001, 56 patients had 0 < ABCR < 4 with a P-value <0.0001, and the ART score was not useful in predicting OS (P-value = 0.18). The SNACOR score is the most predictive score for OS and would be the most helpful scoring system in decision-making regarding retreatment with TACE.

Impact of BMI and Body Composition on First-line Systemic Treatment for Unresectable Hepatocellular Carcinoma.

The effects of body mass index (BMI) and body composition on the outcomes of systemic treatment for unresectable hepatocellular carcinoma (uHCC) remain unclear. In this retrospective study, patients with uHCC treated with lenvatinib (LEN) or atezolizumab+bevacizumab, were classified into high- (≥25 kg/m2) and low- (<25 kg/m2) BMI groups and evaluated for prognosis. Prognostic impact of body composition was also evaluated. Patients with a high BMI had lower skeletal mass index (SMI), subcutaneous adipose tissue index (SATI), and visceral adipose tissue index (VATI) compared to those in the low-BMI cohort. The baseline Child-Pugh scores and Barcelona Clinic Liver Cancer stages were comparable between the two cohorts. The overall survival (OS) was better in the high BMI group compared to the low BMI group (median, 913 vs. 484 days; p=0.008). SMI had a strong influence on OS. Additionally, low BMI, VATI, SATI, and visceral-to-subcutaneous fat ratio (VSR) in the LEN treatment group were associated with shorter progression-free survival (PFS). Following systemic treatment for uHCC, patients with low BMI have a poor prognosis. Among anthropometric factors, low SMI is associated with poor OS. In the LEN treatment group, low VATI may impact PFS negatively.

Tumor burden score and alpha-fetoprotein level predict prognosis of patients with unresectable hepatocellular carcinoma treated with tyrosine kinase inhibitor and anti-PD-1 antibody

BackgroundTyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies in combination provide survival benefits for patients with unresectable hepatocellular carcinoma (uHCC). However, the tool used to determine which patients likely benefit most from this treatment strategy has not been reported. We sought to develop a prognostic scoring system based on tumor burden score (TBS) and alpha-fetoprotein (AFP) to predict the long-term prognosis of uHCC treated with TKIs and anti-PD-1 antibodies. MethodsData on patients with uHCC treated with TKIs and anti-PD-1 antibodies from multiple centers were collected. The prognostic accuracy of TBS, AFP, Barcelona Clinic Liver Cancer (BCLC), and CTA (Combined TBS and AFP) for 2-year progression-free survival (PFS) and overall survival (OS) was evaluated. ResultsOverall, 278 patients with uHCC treated with TKIs and anti-PD-1 antibodies were enrolled, including 48 BCLC-B and 230 BCLC-C HCC patients. CTA (AUC = 0.721 and 0.683) outperformed TBS (AUC = 0.680 and 0.621), AFP (AUC = 0.606 and 0.594), and BCLC staging (AUC = 0.551 and 0.555) in predicting PFS and OS. The 2-year PFS and OS for low CTA (low TBS/low AFP) were 65.7% and 94.4%, respectively, which were significantly higher than 21.6% and 44.9% (p < 0.001 and p = 0.002), respectively, for intermediate CTA (low TBS/high AFP or high TBS/low AFP) and 8.7% and 12.1% (both p < 0.001), respectively, for high CTA (high TBS/high AFP). Multivariable Cox regression analysis indicated that CTA grading was an independent prognostic factor for PFS and OS (referent: low CTA; intermediate CTA, HR 2.87 and 7.17; high CTA, HR 5.52 and 10.31, respectively). ConclusionsCTA grading is an accurate tool for stratifying the prognosis of uHCC treated with TKIs and anti-PD-1 antibodies and may help determine which patients may benefit more from this treatment strategy.

Efficacy of transarterial chemoembolization treatment with 30-60-μm microspheres in patients with hepatocellular carcinoma.

Chemoembolization with small drug-eluting microspheres is widely used in the treatment of hepatocellular carcinoma (HCC). This study aimed to evaluate the efficacy and safety of transarterial chemoembolization with doxorubicin-eluting 30-60-µm microspheres (DEB-TACE) in patients with Barcelona Clinic Liver Cancer (BCLC) stageA andB HCC. In this single-center study, 88patients with HCC (BCLC A/B: 15.9%/84.1%) who underwent 137 DEB-TACE sessions between January 2015 and December 2020 were retrospectively assessed. Response to treatment was assessed 4-8weeks after each DEB-TACE procedure according to mRECIST (Modified Response Evaluation Criteria in Solid Tumors) criteria. Progression-free survival (PFS), time to progression (TTP), overall survival (OS), and adverse events were recorded. In 88patients (84.1% males; median age, 66.0years; range, 22-83), the median follow-up was 17months (range, 2-64). Eight patients (9.1%) had acomplete response, 42 (47.8%) had partial regression, 10 (11.3%) had stable disease, and 28 (31.8%) had progressive disease. There was astatistically significant difference between serum alpha-fetoprotein (AFP) levels before and after DEB-TACE treatment (p < 0.001). The median OS was 17months (95% confidence interval [CI], 10.3-23.7). Cox regression analyses found that preprocedural serum AFP level (400+ vs. < 400; p = 0.024), Child Pugh classification (Bvs. A; p = 0.019), and number of DEB-TACE sessions (1 vs. > 1; p = 0.003) were independent risk factors affecting OS. The median PFS was 8months (95% CI, 5.8-10.2) and TTP was 6months (1-14months). Chemoembolization with 30-60-µm microspheres is an effective and safe treatment for HCC. The number of DEB-TACE sessions is also one of the factors affecting OS.

Assessment of Albumin-Incorporating Scores at Hepatocellular Carcinoma Diagnosis Using Machine Learning Techniques: An Evaluation of Prognostic Relevance.

Hepatocellular carcinoma (HCC) presents high mortality rates worldwide, with limited evidence on prognostic factors at diagnosis. This study evaluates the utility of common scores incorporating albumin as predictors of mortality at HCC diagnosis using Machine Learning techniques. They are also compared to other scores and variables commonly used. A retrospective cohort study was conducted with 191 patients from Virgen de la Luz Hospital of Cuenca and University Hospital of Guadalajara. Demographic, analytical, and tumor-specific variables were included. Various Machine Learning algorithms were implemented, with eXtreme Gradient Boosting (XGB) as the reference method. In the predictive model developed, the Barcelona Clinic Liver Cancer score was the best predictor of mortality, closely followed by the Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores. Albumin levels alone also showed high relevance. Other scores, such as C-Reactive Protein/albumin and Child-Pugh performed less effectively. XGB proved to be the most accurate method across the metrics analyzed, outperforming other ML algorithms. In conclusion, the Barcelona Clinic Liver Cancer, Platelet-Albumin-Bilirubin and Albumin-Bilirubin scores are highly reliable for assessing survival at HCC diagnosis. The XGB-developed model proved to be the most reliable for this purpose compared to the other proposed methods.

Improved survival outcome of curative liver resection for Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma in the era of tyrosine kinase inhibitors.

This study was undertaken to evaluate the outcome of curative liver resection, (LR) of Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma (BCLC-C HCC) after tyrosine kinase inhibitors (TKIs) became approved as a treatment option for recurrent lesions. Sixty-seven patients with BCLC-C HCC who underwent curative LR were enrolled in this study. The patients were classified into two groups according to whether LR was performed before (n=24) or after (n=43) TKI approval ("beforeTKI" and "afterTKI" group, respectively). There was no difference in the median disease-free survival time after LR between the beforeTKI and afterTKI groups (5.6 and 7.1months, respectively; p=0.435). However, the median survival time after LR was longer in the afterTKI than beforeTKI group (42.7 and 14.9months, respectively; p=0.022). Univariate and multivariate analyses showed that the date of LR was the only independent factor affecting postresection survival. When the patients were limited to those with recurrence, there were no differences in the recurrence pattern or progression of HCC at the time of recurrence between the two groups. The only difference in the treatment distribution was the administration of TKIs (14 of 34 patients in afterTKI group and only 1 of 19 patients in beforeTKI group, p<0.001). These data suggest that TKI therapy for recurrent BCLC-C HCC is associated with improved overall survival. Thus, LR could be a promising option for BCLC-C HCC in the current era of TKI therapy.

Outcomes and safety of atezolizumab plus bevacizumab in the treatment of hepatocellular carcinoma: treatment prognosis and comparison with tyrosine kinase inhibitors in a French multicenter matched real-life study.

The combination of atezolizumab plus bevacizumab (Atz/Bev) has radically changed the treatment strategy for advanced hepatocellular carcinoma (HCC) but raises questions. Our objectives were to determine survival outcomes and safety in a real-life multicenter French cohort, to investigate the on-treatment prognostic value of the bioinflammatory RECA score, and to perform a matched comparison with patients who previously received tyrosine kinase inhibitors (TKIs). A retrospective analysis of 109 consecutive patients enrolled from September 2020 to January 2023 and a post matched comparison with a TKI cohort (n = 79) by the propensity score matching method. The Atz/Bev population was mainly nonviral disease patients (69%) with Child-Pugh grade A (90%), performance status 0/1 (90%), and Barcelona Clinic Liver Cancer stage B (38%) or stage C (62%) classification. After a median follow-up of 6.5 months (3.6-11.7), overall survival (OS) was 13.0 (5.1-28.7) months. OS was independently associated with metastasis, increased alkaline phosphatase, and serum bilirubin levels. Treatment-related adverse events were reported in 78% of patients, mostly grade 1 or 2. The RECA score clearly revealed two different prognosis groups after three cycles. No difference in OS was observed after matching between sequential treatment with TKIs and Atz/Bev. This real-life study highlights the importance of liver function when using Atz/Bev combination and the necessity of identifying predictive markers of response to HCC therapies. Our findings suggest a change in practices, with a marked proportion of intermediate stages, and support the on-treatment prognostic value of an inflammatory score.

Assessment of Hepatocellular Carcinoma Patients Infected with Covid-19 Infection during the Pandemic

Hepatocellular carcinoma (HCC) patients are more susceptible to decompensation if they get Coronavirus disease 2019 (COVID-19) infection that leads to significant reduction in HCC related health services, reduction in surveillance activities and progression of HCC. On the other hand, symptoms of covid-19 infection are usually severe in HCC patients. Assessment of severity of covid-19 infection in HCC patients. And assessment of clinical course and outcome of HCC patients when they get infected by Covid-19. This is a retrospective case control study including 100 HCC patients (50 of them were infected by covid-19 while the other 50 were not infected). All patients were Egyptians presented to HCC clinic in national hepatology &amp; tropical research institute (NHTMRI) from 1/2022 to 1/2023 assessed for covid-19 infection (by typical CT chest, covid swab and covid symptoms) and assessed for HCC staging (by Barcelona clinic liver cancer BCLC), clinical course over six months (by Child Pugh score) and mortality rates. Most of Covid-19 infected HCC patients had severe covid symptoms and progressive HCC course with mortality 72%, while low percentage of covid-19 HCC infected group were mild with stationary course. On the other hand, high percentage of non-infected HCC group have stationary HCC course with low mortality 24%. COVID-19 infection seems to have a significant effect on clinical course and outcome of HCC. Also, HCC patients are vulnerable to have more severe COVID-19 symptoms.

Deep learning-based 3D quantitative total tumor burden predicts early recurrence of BCLC A and B HCC after resection.

This study aimed to evaluate the potential of deep learning (DL)-assisted automated three-dimensional quantitative tumor burden at MRI to predict postoperative early recurrence (ER) of hepatocellular carcinoma (HCC). This was a single-center retrospective study enrolling patients who underwent resection for BCLC A and B HCC and preoperative contrast-enhanced MRI. Quantitative total tumor volume (cm3) and total tumor burden (TTB, %) were obtained using a DL automated segmentation tool. Radiologists' visual assessment was used to ensure the quality control of automated segmentation. The prognostic value of clinicopathological variables and tumor burden-related parameters for ER was determined by Cox regression analyses. A total of 592 patients were included, with 525 and 67 patients assigned to BCLC A and B, respectively (2-year ER rate: 30.0% vs. 45.3%; hazard ratio (HR) = 1.8; p = 0.007). TTB was the most important predictor of ER (HR = 2.2; p < 0.001). Using 6.84% as the threshold of TTB, two ER risk strata were obtained in overall (p < 0.001), BCLC A (p < 0.001), and BCLC B (p = 0.027) patients, respectively. The BCLC B low-TTB patients had a similar risk for ER to BCLC A patients and thus were reassigned to a BCLC An stage; whilst the BCLC B high-TTB patients remained in a BCLC Bn stage. The 2-year ER rate was 30.5% for BCLC An patients vs. 58.1% for BCLC Bn patients (HR = 2.8; p < 0.001). TTB determined by DL-based automated segmentation at MRI was a predictive biomarker for postoperative ER and facilitated refined subcategorization of patients within BCLC stages A and B. Total tumor burden derived by deep learning-based automated segmentation at MRI may serve as an imaging biomarker for predicting early recurrence, thereby improving subclassification of Barcelona Clinic Liver Cancer A and B hepatocellular carcinoma patients after hepatectomy. Total tumor burden (TTB) is important for Barcelona Clinic Liver Cancer (BCLC) staging, but is heterogenous. TTB derived by deep learning-based automated segmentation was predictive of postoperative early recurrence. Incorporating TTB into the BCLC algorithm resulted in successful subcategorization of BCLC A and B patients.

Comparison between patient characteristics, aetiology and outcomes in patients with and without cirrhosis with hepatocellular carcinoma diagnosed in a regional centre

IntroductionHepatocellular carcinoma (HCC) is increasing in incidence across the UK. Most patients have underlying cirrhosis, but a significant minority do not. Progression and outcomes of HCC in patients without cirrhosis...

Metabolic dysfunction-associated steatotic liver disease has become the most common cause of hepatocellular carcinoma in Sweden: A nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Epidemiology, pathophysiology and clinical aspects of Hepatocellular Carcinoma in MAFLD patients.

Hepatocellular carcinoma (HCC) is undergoing a transformative shift, with metabolic-associated fatty liver disease (MAFLD) emerging as a dominant etiology. Diagnostic criteria for MAFLD involve hepatic steatosis and metabolic dysregulation. Globally, MAFLD prevalence stands at 38.77%, significantly linked to the escalating rates of obesity. Epidemiological data indicate a dynamic shift in the major etiologies of hepatocellular carcinoma (HCC), transitioning from viral to metabolic liver diseases. Besides the degree of liver fibrosis, several modifiable lifestyle risk factors, such as type 2 diabetes, obesity, alcohol use, smoking, and HBV, HCV infection contribute to the pathogenesis of HCC. Moreover gut microbiota and genetic variants maycontribute to HCCdevelopment.The pathophysiological link between MAFLD and HCC involves metabolic dysregulation, impairing glucose and lipid metabolism, inflammation and oxidative stress. Silent presentation poses challenges in early MAFLD-HCC diagnosis. Imaging, biopsy, and AI-assisted techniques aid diagnosis, while HCC surveillance in non-cirrhotic MAFLD patients remains debated.ITA.LI.CA. group proposes a survival-based algorithm for treatmentbased on Barcelona clinic liver cancer (BCLC) algorithm. Liver resection, transplantation, ablation, and locoregional therapies are applied based on the disease stage. Systemic treatments is promising, with initial immunotherapy results indicating a less favorable response in MAFLD-related HCC.Adopting lifestyle interventions and chemopreventive measures with medications, including aspirin, metformin, and statins, constitute promising approaches for the primary prevention of HCC.Prognosis is influenced by multiple factors, with MAFLD-HCC associated with prolonged survival. Emerging diagnostic biomarkers and epigenomic markers, show promising results for early HCC detection in the MAFLD population.

Hepatic arterial infusion chemotherapy combined with lenvatinib and PD-1 inhibitor for treating unresectable hepatocellular carcinoma

Aims/Background The combination of lenvatinib and programmed cell death protein 1 (PD-1) inhibitor has demonstrated significant efficacy in treating unresectable hepatocellular carcinoma. Our study aimed to evaluate the safety and efficacy of triple therapy that includes hepatic arterial infusion chemotherapy, lenvatinib and PD-1 inhibitor for treating unresectable hepatocellular carcinoma. Methods Patients with a primary diagnosis of advanced hepatocellular carcinoma between June 2020 and August 2023 were included in this study. Initially, 53 patients with hepatocellular carcinoma were enrolled. Then, 13 patients were excluded based on the inclusion criteria, resulting in 40 patients included for analysis. Among them, 31 patients received triple therapy, including 16 Barcelona Clinic Liver Cancer C stage, 12 Barcelona Clinic Liver Cancer-B, and 3 Barcelona Clinic Liver Cancer-A hepatocellular carcinoma patients. The primary endpoint was the objective response rate, while the secondary endpoints included the conversion resection rate, pathological complete response rate, pathological partial response rate, and treatment-related adverse events. Results The objective response rate was 80.65% at a median follow-up of 24.5 months (range: 12.6–55.8 months). Of the 14 patients (45.2%) who underwent conversion therapy and were eligible for surgery, 7 patients underwent liver resection and the remaining 7 patients underwent liver transplantation. The median interval between the start of triple therapy and surgery was 117 days, ranging from 25 to 215 days. The pathological complete response was observed in six patients (19.4%) and the pathological partial response rate in eight patients (25.8%). All adverse events occurred in 77.4% of the patients. Conclusion In patients with unresectable hepatocellular carcinoma, the combination of hepatic arterial infusion chemotherapy, lenvatinib, and PD-1 inhibitor exhibits favourable efficacy and well tolerability, achieving a desirable pathological complete response rate while maintaining manageable drug toxicity.

Prediction of microvascular invasion in hepatocellular carcinoma patients with MRI radiomics based on susceptibility weighted imaging and T2-weighted imaging.

The accurate identification of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC) is of great clinical importance. To develop a radiomics nomogram based on susceptibility-weighted imaging (SWI) and T2-weighted imaging (T2WI) for predicting MVI in early-stage (Barcelona Clinic Liver Cancer stages 0 and A) HCC patients. A prospective cohort of 189 participants with HCC was included for model training and testing, and an additional 34 participants were enrolled for external validation. ITK-SNAP was used to manually segment the tumour, and PyRadiomics was used to extract radiomic features from the SWI and T2W images. Variance filtering, student's t test, least absolute shrinkage and selection operator regression and random forest (RF) were applied to select meaningful features. Four machine learning classifiers, including K-nearest neighbour, RF, logistic regression and support vector machine-based models, were established. Independent clinical and radiological risk factors were also determined to establish a clinical model. The best radiomics and clinical models were further evaluated in the validation set. In addition, a nomogram was constructed from the radiomic model and independent clinical factors. Diagnostic efficacy was evaluated by receiver operating characteristic curve analysis with fivefold cross-validation. AFP levels greater than 400ng/mL [odds ratio (OR) 2.50; 95% confidence interval (CI) 1.239-5.047], tumour diameter greater than 5cm (OR 2.39; 95% CI 1.178-4.839), and absence of pseudocapsule (OR 2.053; 95% CI 1.007-4.202) were found to be independent risk factors for MVI. The areas under the curve (AUCs) of the best radiomic model were 1.000 and 0.882 in the training and testing cohorts, respectively, while those of the clinical model were 0.688 and 0.6691. In the validation set, the radiomic model achieved better diagnostic performance (AUC = 0.888) than the clinical model (AUC = 0.602). The combination of clinical factors and the radiomic model yielded a nomogram with the best diagnostic performance (AUC = 0.948). SWI and T2WI-derived radiomic features are valuable for noninvasively and accurately identifying MVI in early-stage HCC. Furthermore, the integration of radiomics and clinical factors yielded a predictive nomogram with satisfactory diagnostic performance and potential clinical benefits.

Phase Angle but Not Psoas Muscle Predicts Nutritional Risk and Prognosis in Males with Hepatocellular Carcinoma

Despite those with hepatocellular carcinoma (HCC) being at increased risk of malnutrition, there is a notable absence of practical approaches for nutritional assessment in clinical practice. We investigated the usefulness of phase angle (PhA) and Total Psoas Area Index (TPAI) for indicating nutritional risk and HCC prognosis. Weight, height, body mass index (BMI), adductor pollicis muscle thickness (APMT), and handgrip strength (HGS) were assessed. The Nutritional Risk Index (NRI) was calculated. Body composition was assessed using bioimpedance spectroscopy and magnetic resonance imaging. The Child-Turcotte-Pugh (CTP) score and Barcelona-Clinic Liver Cancer (BCLC) classification determined the prognosis. Fifty-one males with HCC were enrolled (CTP C = 11.8%). PhA showed a moderate positive correlation with APMT (r = 0.450; p < 0.001) and HGS (r = 0.418; p = 0.002) and a weak positive correlation with TPAI (r = 0.332; p = 0.021). PhA had a strong positive correlation with NRI (r = 0.614; p < 0.001). Mean PhA values were significantly different according to disease severity (CTP C p = 0.001, and BCLC D p = 0.053). TPAI had no significant correlation with HGS, CTP, or BCLC. PhA was a superior approach for predicting nutritional risk and prognosis in HCC than TPAI. Lower PhA is associated with disease progression, lower muscle mass and function, greater severity of nutritional risk, and increased mortality in HCC.