Etiology Of Hepatocellular Carcinoma Research Articles

Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.

Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group). Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study

BACKGROUND The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest. AIM To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis, tumor features, and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers. METHODS This prospective, diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital. Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer (BCLC) categorization. Demographics, HCC etiology, and HCC features were recorded. Biomarkers and the GALAD score were obtained at baseline. The performance of the GALAD score and biomarkers were prospectively assessed. RESULTS Exactly 115 individuals were diagnosed with HCC. The GALAD score increased with disease severity. Between BCLC-0/A and BCLC-B/C/D, the GALAD score predicted HCC staging with an area under the curve (AUC) of 0.868 (95%CI: 0.80–0.93). For identifying the curative HCC, the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein (AFP) (0.753) and Lens culinaris agglutinin-reactive fraction of AFP-L3 (0.706), and as good as that of Protein induced by vitamin K absence-II (PIVKA-II) (0.897). For detecting aggressive features, the GALAD score gave an AUC of 0.839 (95%CI: 0.75–0.92) and significantly outperformed compared to that of AFP (0.761) and AFP-L3 (0.697), with a trend of superiority to that of PIVKA-II (0.772). The performance to predict 1-year mortality of GALAD score (AUC: 0.711, 95%CI: 0.60–0.82) was better than that of AFP (0.541) and as good as that of PIVKA-II (0.736). The optimal cutoff value of GALAD score was ≥ 6.83, with a specificity of 72.63% for exhibiting substantial reduction in the 1-year mortality. CONCLUSION The GALAD model can diagnose HCC at the curative stage, including the characteristic of advanced disease, more than that by AFP and AFP-L3, but not PIVKA-II. The GALAD score can be used to predict the 1-year mortality of HCC.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Hepatocellular Carcinoma With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in the Absence of Cirrhosis

ABSTRACT This report describes a rare case of hepatocellular carcinoma (HCC) concurrent with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) without traditional risk factors, such as hepatic fibrosis or chronic hepatitis. Initially presenting with hematuria, incidental imaging revealed a liver lesion, later diagnosed as moderately differentiated HCC. Notably, the patient had no history of well-established risk factors of HCC including viral hepatitis or liver cirrhosis. CLL/SLL was unexpectedly discovered in the surgical specimen during the hepatectomy. This case challenges traditional perceptions of HCC etiology, suggesting a potential link between HCC and CLL/SLL even without established risk factors.

Hepatocellular Carcinoma: Current Drug Therapeutic Status, Advances and Challenges.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer, accounting for ~90% of liver neoplasms. It is the second leading cause of cancer-related deaths and the seventh most common cancer worldwide. Although there have been rapid developments in the treatment of HCC over the past decade, the incidence and mortality rates of HCC remain a challenge. With the widespread use of the hepatitis B vaccine and antiviral therapy, the etiology of HCC is shifting more toward metabolic-associated steatohepatitis (MASH). Early-stage HCC can be treated with potentially curative strategies such as surgical resection, liver transplantation, and radiofrequency ablation, improving long-term survival. However, most HCC patients, when diagnosed, are already in the intermediate or advanced stages. Molecular targeted therapy, followed by immune checkpoint inhibitor immunotherapy, has been a revolution in HCC systemic treatment. Systemic treatment of HCC especially for patients with compromised liver function is still a challenge due to a significant resistance to immune checkpoint blockade, tumor heterogeneity, lack of oncogenic addiction, and lack of effective predictive and therapeutic biomarkers.

Hepatitis-C-Related Hepatocellular Carcinoma, Still a Relevant Etiology beyond a Hepatitis C Infection Cure.

In the past decades, global changes, including hepatitis B vaccination, hepatitis B and C antiviral therapies, and the increasing prevalence of steatotic liver disease, have influenced the landscape of liver cancer etiologies. We performed a retrospective study focused on the etiological factors of de novo hepatocellular carcinoma (HCC) diagnoses in an academic center between 2019 and 2022. Among 352 consecutive patients with HCC, alcohol-related liver disease was the predominant etiology (33.3%), followed by hepatitis C (HCV) infection (30.7%). Significant associations were found between HCC etiology and patient demographics, BCLC stage at diagnosis, and cirrhosis prevalence. Whereas accessibility to antiviral therapy is granted, HCV infection remains as one of the main HCC etiologies. MASLD-related HCC, although growing globally, is not as relevant in our area. Strong public policies need to be implemented to prevent alcohol consumption, the main etiology of liver disease and liver cancer.

Disease Etiology Impact on Outcomes of Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab: A Real-World, Multicenter Study

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab (A + B) is equally effective in viral and nonviral patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We retrospectively analyzed 885 HCC patients treated with the first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% nonviral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multivariate models to explore potential differences on overall survival (OS), time-to-progression (TTP), disease control rates (DCRs) based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to the second-line treatments and outcomes were also reported and compared between etiologies. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Overall, no statistically significant differences were found in median OS (mOS: viral 15.9 months; nonviral 16.3 months), TTP (mTTP: viral 8.3 months; nonviral 7.2 months), and DCRs (viral 78.1%; nonviral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and nonviral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e., NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of the second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and nonviral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.

Abstract CT211: Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B

Abstract Background: Chronic hepatitis B is an etiology of HCC. Clinical trials using immune checkpoint inhibitors (ICIs) as HCC treatment typically exclude patients with chronic active hepatitis B (serum hepatitis B virus [HBV] viral load &amp;gt; 2000 IU/mL) or require the HBV viral load to be below a certain level using anti-HBV medications. In the phase 3 HIMALAYA study, the STRIDE regimen was superior to sorafenib and durvalumab was noninferior to sorafenib in overall survival benefits. This study explored the safety of concurrent administration of STRIDE or durvalumab with anti-HBV mediations for patients with chronic, active hepatitis B infection. Methods: We enrolled patients with advanced HCC, Child-Pugh A liver function reserve, and chronic active hepatitis B not under anti-HBV treatment. Initially, only patients naïve to ICIs were eligible, and patients received durvalumab 1500mg iv every 4 weeks until disease progression, occurrence of unacceptable toxicities, or the maximum treatment duration of 2 years. After the positive results of the HIMALAYA study, we added tremelimumab 300mg iv on D1 following the STRIDE regimen and allowed enrollment of patients who had received prior programmed cell death-1 blockade therapy. Patients initiated entecavir as HBV treatment within 7 days of starting ICI therapy. The plan was to enroll 30 patients, with the primary outcome of HBV reactivation (a ≥2 log increase in serum HBV DNA compared to the baseline level). Results: The study is still ongoing and as of 31 Aug 2023, 19 patients were enrolled. Two patients were female, and the median age was 65.5 years. Ten patients received durvalumab alone, and 9 received the STRIDE regimen. The ALBI grade was 1 and 2 in 3 (16%) and 16 (84%) patients, respectively. Macrovascular invasion and extrahepatic spread were present in 11 (58%) and 11 (58%) patients, respectively; 12 (63%) patients had alpha-fetoprotein level ≥ 400 ng/mL. Eleven (58%) patients had received prior systemic therapy for HCC, such as sorafenib (n = 9), lenvatinib (n = 5), and regorafenib (n = 4). The mean±standard deviation baseline HBV viral load was 1.18±0.44 mIU/mL. With the median follow-up on 6.1 months, no patients experienced HBV reactivation or HBV-associated hepatitis. Hepatitis flare (ALT increase to ≥3 times the baseline level) was noted in 4 (21%) patients, but none were considered HBV-associated. The best objective tumor response was complete and partial response in 0 and 5 (26.3%) patients, respectively, and the disease control rate was 63.2%. Conclusion: In the preliminary results, simultaneous initiation of immunotherapy and anti-HBV medications in patients with HCC and chronic active hepatitis B did not increase HBV reactivation rate. This study was supported by AstraZeneca (NCT04294498). Citation Format: Yu-Yun Shao, Ching-Tso Chen, Tsung-Che Wu, Tsung-Hao Liu, Chien-Huai Chuang, Ann-Lii Cheng, Chih-Hung Hsu. Safety of prompt initiation of durvalumab or STRIDE (single tremelimumab regular interval durvalumab) regimen as hepatocellular carcinoma (HCC) treatment for patients with chronic active hepatitis B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT211.

48 Analyzing Changing Trends in Hepatocellular Carcinoma

OBJECTIVES/GOALS: To quantify changing trends in hepatocellular carcinoma (HCC) etiologies, mainly hepatitis C related HCC (HCV-HCC), nonalcoholic fatty liver disease related HCC (NAFLD-HCC), and alcoholic liver disease related HCC (ALD-HCC), at a single center as well as compared to large national databases. METHODS/STUDY POPULATION: This is a retrospective longitudinal study using a single-center database of patients presenting with HCC from January 1995 to September 2023. Etiologies were confirmed through patient history, clinical exam, and viral serologies. Trends in rate of etiology were analyzed using linear regression. Further investigation will include survival analysis. To improve generalizability, the single-center data were supplemented with national cross-sectional data from the NHANES database on liver disease prevalence from March 1999 to August 2023. Data were provided through questionnaire, clinical exam, and viral serologies. Trends in rates will be analyzed using linear regression. RESULTS/ANTICIPATED RESULTS: Among the single center cohort, NAFLD-HCC increased at an average rate of 1.3% per year (95% Confidence Interval (CI) = 1.1% to 1.4%) and HCV-HCC decreased at an average rate of -0.56% per year (95% CI = -0.83% to -0.29%). Projecting the linear models for the past ten years forward, HCV-HCC is predicted to take up a lower proportion than NASH-HCC by 2026 and lower proportion than ALD-HCC by 2028. Future results will include analysis of the changing proportions of etiologies for liver transplant and survival analysis for HCC by etiology from the single center cohort. Additionally, national trends in HCC etiologies will be provided from the NHANES database. The trends from liver transplant etiology and NHANES are expected to parallel the preliminary results. DISCUSSION/SIGNIFICANCE: As the prevalence of NAFLD increases in the general population, more cases of NAFLD-HCC will be seen in the future. Understanding the changing trends can guide surveillance recommendations, shape treatment algorithms, and frame research priorities.

Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide.

Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. The etiology and epidemiology of HCC have recently changed worldwide. Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019. In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. NASH-related HCC has characteristics that differ from those of virus-associated HCC. Compared with other etiologies, patients with NASHassociated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

Hepatitis B virus-related hepatocellular carcinoma has superior overall survival compared with other etiologies.

Whether the etiology of chronic liver disease (CLD) impacts the overall survival (OS) of patients with hepatocellular carcinoma (HCC) remains unclear. We aim to clarify this issue. Between 2011 and 2020, 3941 patients who were newly diagnosed with HCC at our institution were enrolled in this study. In patients with multiple CLD etiologies, etiology was classified using the following hierarchy: hepatitis C virus (HCV) > hepatitis B virus (HBV) > alcohol-related > all negative. All negative was defined as negative for HCV, HBV, and alcohol use disorder. Among 3941 patients, 1407 patients were classified with HCV-related HCC, 1677 patients had HBV-related HCC, 145 patients had alcohol-related HCC, and 712 patients had all-negative HCC. Using the all-negative group as the reference group, multivariate analysis showed that HBV is an independent predictor of mortality (hazard ratio: 0.856; 95% confidence interval: 0.745-0.983; p = 0.027). Patients with HBV-related HCC had superior OS compared with patients with other CLD etiologies (p<0.001). Subgroup analyses were performed, for Barcelona Clinic Liver Cancer (BCLC) stages 0-A (p<0.001); serum alpha-fetoprotein (AFP) levels≧20 ng/ml (p<0.001); AFP levels < 20 ng/ml (p<0.001); age > 65 years (p<0.001); and the use of curative treatments (p = 0.002). No significant difference in OS between HBV and other etiologies was observed among patients aged ≤ 65 years (p = 0.304); with BCLC stages B-D (p = 0.973); or who underwent non-curative treatments (p = 0.1). Patients with HBV-related HCC had superior OS than patients with other HCC etiologies.

Machine Learning-Based Assessment of Survival and Risk Factors in Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma for Optimized Patient Management.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, with an incidence that is exponentially increasing. Hepatocellular carcinoma (HCC) is the most frequent primary tumor. There is an increasing relationship between these entities due to the potential risk of developing NAFLD-related HCC and the prevalence of NAFLD. There is limited evidence regarding prognostic factors at the diagnosis of HCC. This study compares the prognosis of HCC in patients with NAFLD against other etiologies. It also evaluates the prognostic factors at the diagnosis of these patients. For this purpose, a multicenter retrospective study was conducted involving a total of 191 patients. Out of the total, 29 presented NAFLD-related HCC. The extreme gradient boosting (XGB) method was employed to develop the reference predictive model. Patients with NAFLD-related HCC showed a worse prognosis compared to other potential etiologies of HCC. Among the variables with the worst prognosis, alcohol consumption in NAFLD patients had the greatest weight within the developed predictive model. In comparison with other studied methods, XGB obtained the highest values for the analyzed metrics. In conclusion, patients with NAFLD-related HCC and alcohol consumption, obesity, cirrhosis, and clinically significant portal hypertension (CSPH) exhibited a worse prognosis than other patients. XGB developed a highly efficient predictive model for the assessment of these patients.

Changing Etiological Spectrum of Hepatocellular Carcinoma in India—A Systematic Review and Meta-analysis

BackgroundRecent studies from both India and outside India have shown a change in the etiological profile of hepatocellular carcinoma (HCC). We aimed to analyze the etiological spectrum and changing trends of HCC etiology in India using a systematic review of current literature and meta-analysis. MethodsElectronic databases of Pubmed/Medline, Scopus, and Embase were searched from inception to July 2023 for studies reporting the data on the etiology of HCC from India. The pooled proportions with 95% confidence interval were calculated using summative statistics. ResultsA total of 60 studies (n = 12327) were included in the final analysis. The pooled proportions of HCC cases with at least one positive and negative viral marker were 56.0 (49.5 – 62.6) and 43.1% (36.5 – 49.8), respectively. The pooled proportion of HCC cases with positive hepatitis B virus (HBV) markers was 41.0 (35.8 – 46.1), while those with positive markers for hepatitis C virus (HCV) were 20.3 (17.0 – 23.6). The pooled proportion of cases with HCC with significant alcohol intake was 19.0% (15.6 – 22.4), and those related to non-alcoholic fatty liver disease (NAFLD) were 16.9% (12.1 – 21.7). Around 7.9% (5.8 – 10.0) of the cases had HCC with multiple etiologies. Subgroup analysis showed a significant variation with the location of the study based on zone. Meta-regression analysis based on publication year (1990-2023) showed a significant reduction in the proportion of cases with HBV and an increase in cases with NAFLD. In contrast, the proportion of cases with HCV and alcohol did not change significantly. ConclusionViral hepatitis is the most common etiology of HCC in India, predominantly HBV. The proportions of cases with HCC related to NAFLD are increasing, and those related to HBV are declining.

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology

The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic. Notably, the incidence of non-cirrhotic HCC increased by 61% in the time frame between 2009 and 2020. Interestingly 39% of non-cirrhotic HCC cases had cryptogenic origins. Cryptogenic non-cirrhotic HCC exhibited similarities with non-cirrhotic NAFLD HCC, but displayed advanced tumor stages, lower surgical rates, and a more frequent presence of symptoms, which substantiated in poor survival rates. Advanced cryptogenic non-cirrhotic HCC stages exhibited elevated serum interleukin-6 levels compared to non-cirrhotic HCC with defined etiologies. Comparative analysis encompassing cryptogenic and NAFLD non-cirrhotic HCC cohorts and controls unveiled comparable circulating immune biomarker profiles and PNPLA3 polymorphisms. To conclude, the primary etiology of non-cirrhotic HCC in our cohort has not defined risk factors. This cryptogenic variant exhibits distinct traits, such as advanced tumors and increased symptoms, and most resemble burned-out NAFLD. Understanding this HCC variant is crucial for improving screening and management strategies.

Correlation of Soluble Programmed Death Ligand-1 (sPD-L1) with Alpha-Fetoprotein Levels as a Predictor of Prognosis in Hepatocellular Carcinoma Patients

Background: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and one of the leading causes of cancer death worldwide. Chronic hepatitis B virus infection is the most common etiology of HCC. Programmed death ligand-1 (PD-L1) is a protein that is overexpressed on the surface of tumor cells, which can be detected in serum (sPD-L1). Elevated sPD-L1 concentrations in the plasma of cancer patients are associated with poor prognosis in HCC patients, as indicated by increased AFP levels. There have been no previous studies examining the correlation of sPD-L1 levels with AFP in HCC patients. The aim of the study was to determine the correlation of sPD-L1 and AFP as predictors of prognosis in HCC patients.&#x0D; Methods: The research is an observational study with a cross-sectional design to see the correlation of sPD-L 1 with serum alpha-fetoprotein levels in HCC patients at Dr. Mohammad Hoesin General Hospital Palembang starts from April to July 2023. Measurement of sPD-L1 levels and serum AFP levels is carried out using ELISA examination.&#x0D; Results: Of the 28 subjects studied, HCC patients were more commonly found in men (89.29%) aged 18-60 years (75%). sPD-L1 and AFP values were found to be increased in the advanced stages of HCC. The sPD-L1 value is directly proportional to the serum AFP value.&#x0D; Conclusion: There is a strong positive correlation between sPD-L1 levels and serum AFP levels caused by hepatitis B in HCC patients, so the higher the sPD-L1, the higher the serum AFP levels.

Aetiology of hepatocellular carcinoma and response to immunotherapy: is the problem inherent in the classification of non-viral disease?

Aetiology of hepatocellular carcinoma and response to immunotherapy: is the problem inherent in the classification of non-viral disease?

Organ-specific response with first-line atezolizumab-bevacizumab versus lenvatinib for patients with advanced hepatocellular carcinoma.

467 Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the second leading cause of cancer-related death worldwide. Immune checkpoint inhibitor (ICI)-based treatments have become the mainstay of first-line treatment for unresectable HCC, but there has been a concern that intrahepatic HCC lesions may be less responsive to ICI monotherapy. Methods: This retrospective study included 386 patients with Child-Pugh A unresectable HCC who were treated with first-line atezolizumab-bevacizumab (n = 217) or lenvatinib (n = 169). The organ-specific response was separately evaluated according to the site of the lesions: liver, lung, lymph node (LN), and intra-abdomen based on a radiological evaluation adopted from RECIST v 1.1. Up to 2 lesions were chosen as target lesions in each organ for the organ-specific response evaluation. Results: The median age was 60 years. The majority of study patients were male in both groups (83.4% and 85.8% in the atezolizumab-bevacizumab and lenvatinib groups, respectively). The etiology of HCC was similar between the two groups: hepatitis B virus infection was the most common etiology in both groups (73.3% and 65.7% in the atezolizumab-bevacizumab and lenvatinib groups, respectively), while 21.2% and 29.0% of patients had non-viral HCC, respectively. Extrahepatic spread was identified in 76.0% and 74.6% of patients in the atezolizumab-bevacizumab and lenvatinib groups, respectively: lung, LN, and intra-abdominal metastases were present in 39.6% vs. 39.1%, 30.0% vs. 33.1% and 16.6% vs. 15.4% of patients, respectively. The proportion of patients achieving a ≥ 30% reduction in the tumor burden for each organ category was higher overall in the atezolizumab-bevacizumab group than in the lenvatinib group: 20.2% vs. 11.8%, 23.0% vs. 12.2%, 27.9% vs. 17.9%, and 33.3% vs. 15.0% for intrahepatic, lung, LN and intra-abdominal lesions, respectively. The corresponding values for the subgroup with a viral etiology were 17.3% vs. 8.1%, 18.8% vs. 13.3%, 28.9% vs. 3.6% and 36.0% vs. 12.5%, respectively. Among patients with a non-viral etiology, atezolizumab-bevacizumab was not clearly associated with a better organ-specific response for the LN and intra-abdominal lesions: 20.0% vs. 54.5% and 20.0% vs. 25.0%, respectively, for a ≥ 30% reduction in the tumor burden. Conclusions: Compared to lenvatinib, atezolizumab-bevacizumab was associated with a favorable organ-specific response regardless of the site of the tumor lesions. Unlike anti-PD-1 monotherapy, atezolizumab-bevacizumab had a comparable organ-specific response between intrahepatic and extrahepatic lesions, especially for those with viral etiology HCCs.

Impact of Hispanic ethnicity on immunotherapy outcomes in hepatocellular carcinoma: Insights from the National Cancer Database.

438 Background: Hepatocellular carcinoma (HCC) is the fastest-growing cancer in the US with more age-adjusted incident cases in Hispanics compared to non-Hispanics. Immunotherapies are considered integral part of treatment for most unresectable HCC. Recent multinational phase III trials suggest the benefit of immunotherapies may differ based on geographic region and underlying etiology of HCC. We hypothesized that Hispanic ethnicity might influence responses to immunotherapy in HCC. Methods: We analyzed the National Cancer Database (NCDB) to assess the impact of immunotherapy on overall survival (OS) in Hispanic patients with HCC. The database was queried for liver cancer from 2004 to 2020. Kaplan Meier method was used to assess OS and a log-rank test was used to compare survival distribution between Hispanic and non-Hispanic groups. Cox regression analysis was performed to estimate the adjusted effect of ethnicity on OS based on immunotherapy status. NCDB is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoCÕs NCDB are the source of the de-identified data used herein. Results: A total of 225079 patients were identified of whom 2036 patients (0.9%) received immunotherapy as first-line treatment. Patients with non-Hispanic ethnicity, male sex, who received treatment at academic/research institutions, and were insured were more likely to receive immunotherapy. In the entire cohort, there was no difference (p=0.94) in survival between those who did not receive immunotherapy (median OS,11.63 months; IQR: 2.79, 34.83) vs. those who did (median OS, 10.68 months, IQR: 5.19, 23.29[DA2]). There were more Hispanics in the cohort who did not receive immunotherapy (12.28% vs. 10.61%). In the adjusted Cox analysis, Hispanics had a reduced risk of death than non-Hispanics among patients who did not receive immunotherapy (HR: 0.873, 95%CI, 0.858-0.889; p&lt;0.001). Among patients with immunotherapy, there was no OS difference between ethnicities (HR 0.904, 95% CI, 0.755-1.082; p 0.271). Conclusions: Hispanics were less likely to receive immunotherapy than non-Hispanics. Although Hispanics had a better OS than non-Hispanics among patients without immunotherapy, the differences no longer persist among patients who received immunotherapy. These findings suggest that Hispanic ethnicity may influence responses to immunotherapy. As compared to non-Hispanic whites, Hispanics with HCC have significantly more nonalcoholic fatty liver disease and alcohol-related liver disease as contributing factors. A better understanding of the impact of immunotherapies on alcoholic and nonalcoholic liver disease-related HCC is needed.

Comparison of the treatment effect between lenvatinib and atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in pathologically diagnosed metabolic dysfunction–associated steatotic liver disease.

493 Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading etiologies of HCC. Recent evidence indicates that MASLD might affect the response to immune checkpoint inhibitors and multi-receptor tyrosine kinase inhibitors in the treatment for unresectable hepatocellular carcinoma (HCC), yet real-world data with accurate pathological diagnosis of MASLD has not been confirmed. Methods: Patients with unresectable HCC who had been pathologically diagnosed with MASLD by liver biopsy and/or hepatectomy and later received treatment with lenvatinib (LEN) or atezolizumab plus bevacizumab (ATZ/Bev) as first-line systemic treatment for HCC were included. Outcomes of treatment with LEN or ATZ/Bev were compared. Results: A total of 48 patients who received LEN (n=26) and ATZ/Bev (n=22) were included. The mean time from pathological diagnosis to the initiation of treatment was not different (LEN 1,542 days, ATZ/Bev 1,260 days; p=0.48). The degree of steatosis, inflammation, ballooning hepatocytes and fibrosis did not differ between LEN and ATZ/Bev. At the initiation of treatment, BCLC stage, albumin–bilirubin grade, and Child–Pugh grade did not differ between LEN and ATZ/Bev. The overall response rate and disease control rate evaluated with modified RECIST criteria were not different between LEN and ATZ/Bev (26.1% and 77.2% for LEN, and 22.7% and 70.8% for ATZ/Bev). Median progression-free survival (PFS) was not different between LEN and ATZ/Bev (266 days vs 287 days, p=0.278). Median overall survival (OS) of LEN tended to be longer than that of ATZ/Bev (1364 days vs 663 days, p=0.081). The potential advantage of LEN in OS was statistically significant in the patients with Child-Pugh score = 5 (P=0.0443). A total of 17 patients received both LEN and ATZ/Bev treatment and order of the treatment did not associate with PFS and OS. Conclusions: Outcomes of LEN and ATZ/Bev treatment for advanced HCC were not different in pathologically confirmed MASLD. Longer OS of LEN than ATZ/Bev was observed in the patients with relatively better liver function, suggesting that LEN might be a suitable first-line treatment for HCC with compensated liver function in the patients with pathologically confirmed MASLD.

Understanding the efficacy of frontline therapies for hepatocellular carcinoma through etiologic stratification.

491 Background: Despite significant advancements in recent years, hepatocellular carcinoma (HCC) treatment options remain limited for patients who progress on locoregional therapy. Given increasing interest in personalized cancer care for HCC, analysis was done to understand whether the etiology of HCC influenced the efficacy of four common first-line FDA approved systemic therapy regimens. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database from 1/1/2003 to 8/1/2021 with 3519 HCC patients who have received either atezolizumab-bevacizumab (AB), nivolumab, sorafenib, or lenvatinib as a first-line systemic therapy. Information on demographics (age, gender, sex race, ethnicity, ECOG, SES Index), cancer stage, and treatment type was collected. In addition, comorbidities of hepatitis B, hepatitis C, alcohol use, diabetes, and obesity were collected as surrogates for disease etiology: viral hepatic disease, alcohol induced hepatic dysfunction or non-alcoholic fatty liver disease (NAFLD). Patients with missing data in any of the population stratifying variables were excluded. Overall survival (OS), Progression-free-survival (PFS) and time to treatment discontinuation (TTTD) were analyzed for each systemic therapy stratified by etiology as endpoints. Kaplan-Meier (KM) univariate analysis was performed along with the log-rank test for the primary outcome. Multivariate analysis (MVA) was conducted on all three endpoints via cox proportional hazard model to adjust for possible covariates in the patient population. Results: After exclusion criteria, 548 patients with complete data were included (AB N=124, Sorafenib N=324, Lenvatinib N=61, Nivolumab N=39) with variable etiologic presence (hepatitis B N=14, hepatitis C N=50, alcohol use N=41, diabetes N=50, Obesity N=44). When comparing patients across all recorded systemic therapies stratified by the etiologic variables, there was no statistically significant difference in OS, PFS, or TTTD. When stratified by presence of Hepatitis B, patients treated with atezolizumab-bevacizumab trended towards improved outcomes but did not reach statistical significance (P = 0.064). Other treatments showed mixed results in relation to specific etiologies, but no clear trend in efficacy emerged. Conclusions: This early retrospective study suggests that systemic therapy for HCC is not significantly impacted by factors associated with the etiology of disease, such as hepatitis C, alcohol use, and obesity. However, small population sizes and potential nonrandom covariate missingness in this study may obscure effects. Future studies are needed to further elucidate this trend along with subpopulation effects of other systemic therapies.