Hepatocellular Carcinoma In Cirrhotic Patients Research Articles

Diagnostic performance of Sonazoid-enhanced CEUS in identifying definitive hepatocellular carcinoma in cirrhotic patients according to KLCA-NCC 2022 and APASL 2017 guidelines

ObjectiveThis study aims to assess the diagnostic performance of Sonazoid-contrast-enhanced ultrasound (CEUS) in identifying definitive HCC within hepatic nodules in cirrhotic patients, comparing the KLCA-NCC 2022 and APASL 2017 diagnostic guidelines.Materials and methodsThis retrospective study analyzed cirrhotic patients who underwent Sonazoid-CEUS for liver lesion evaluation between October 2019 and October 2023. HCC diagnosis was based on the KLCA-NCC 2022 and APASL 2017 guidelines. Inter-reader agreement on CEUS imaging features and the diagnostic accuracy of the guidelines were evaluated. Sensitivity and specificity comparisons were made using McNemar’s test.ResultsAmong 400 patients with 432 lesions, CEUS showed excellent inter-reader consistency in detecting arterial phase hyperenhancement and Kupffer defects. The KLCA-NCC 2022 criteria notably enhanced sensitivity to 96.2%, with specificity and accuracy of 93.8% and 95.8%, respectively. APASL 2017 achieved the highest sensitivity at 97.8%, although specificity dropped to 46.9%, resulting in an accuracy of 90.3%. The KLCA-NCC 2022 guidelines demonstrated significantly higher specificity than APASL 2017 (p < 0.001), while APASL 2017 exhibited the highest sensitivity at 97.8%. Notably, the KLCA-NCC 2022 guidelines also demonstrated an impressive positive predictive value of 98.9%.ConclusionSonazoid-enhanced CEUS, particularly when applied using the KLCA-NCC 2022 guidelines, is an effective diagnostic tool for HCC.Critical relevance statementPerfluorobutane CEUS, particularly in accordance with the KLCA-NCC 2022 guidelines, emerges as a valuable adjunct for diagnosing HCC in cirrhotic patients. It demonstrates superior positive predictive value and specificity compared to APASL 2017, underscoring its potential as an effective diagnostic tool.Key PointsContrast-enhanced (CE)US using Sonazoid with KLCA-NCC 2022 guidelines is highly effective for HCC diagnosis.KLCA-NCC 2022 criteria showed high accuracy, 96.2% sensitivity, and 98.9% PPV.CEUS demonstrated excellent inter-reader consistency in detecting arterial phase hyperenhancement and Kupffer defects.Graphical

Potential value and advances in research on bone mineral density (BMD) measurement in the auxiliary clinical assessment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide and its prognosis is highly heterogeneous, being related not only to underlying chronic liver disease but also to the severity of cancer cachexia. Nutritional factors play a crucial role in influencing the prognosis of HCC. Despite musculoskeletal imbalance being consistently reported as a predictor of perioperative mortality in patients with HCC, this condition is often overlooked in clinical management. Bone mineral density (BMD), which serves as a marker of nutritional status, can be assessed through CT by measuring the pixel density of the vertebral bone. Recent clinical studies have indicated that BMD serves not only as a significant risk factor for development of HCC in cirrhotic patients but also potentially functions as an independent prognostic indicator for post-treatment outcomes in patients with HCC. Preoperative abdominal CT scans provide a convenient and cost-effective method to measure BMD, offering significant assistance in prognostic evaluation of patients with HCC. A thorough grasp of the liver-bone connection, along with the conduct of higher-quality studies and the establishment of standardized methods and cutoff values for BMD measurement, could enhance approaches to manage HCC.

Early warning of hepatocellular carcinoma in cirrhotic patients by three-phase CT-based deep learning radiomics model: a retrospective, multicentre, cohort study

The diagnosis of hepatocellular carcinoma (HCC) often experiences latency, ultimately leading to unfavorable patient outcomes due to delayed therapeutic interventions. Our study is designed to develop and validate a model that employs triple-phase computerized tomography (CT)-based deep learning radiomics and clinical variables for early warning of HCC in patients with cirrhosis. We studied 1858 patients with cirrhosis primarily from the PreCar cohort (NCT03588442) between June 2018 and January 2020at 11 centres, and collected triple-phase CT images and laboratory results 3-12 months prior to HCC diagnosis or non-HCC final follow-up. Using radiomics and deep learning techniques, early warning model was developed in the discovery cohort (n=924), and then validated in an internal validation cohort (n=231), and an external validation cohort from 10 external centres (n=703). We developed a hybrid model, named ALARM model, which integrates deep learning radiomics with clinical variables, enabling early warning of the majority of HCC cases. The ALARM model effectively predicted short-term HCC development in cirrhotic patients with area under the curve (AUC) of 0.929 (95% confidence interval 0.918-0.941) in the discovery cohort, 0.902 (0.818-0.987) in the internal validation cohort, and 0.918 (0.898-0.961) in the external validation cohort. By applying optimal thresholds of 0.21 and 0.65, the high-risk (n=221, 11.9%) and medium-risk (n=433, 23.3%) groups, which covered 94.4% (84/89) of the patients who developed HCC, had significantly higher rates of HCC occurrence compared to the low-risk group (n=1204, 64.8%) (24.3% vs 6.4% vs 0.42%, P<0.001). Furthermore, ALARM also demonstrated consistent performance in subgroup analysis. The novel ALARM model, based on deep learning radiomics with clinical variables, provides reliable estimates of short-term HCC development for cirrhotic patients, and may have the potential to improve the precision in clinical decision-making and early initiation of HCC treatments. This work was supported by National Key Research and Development Program of China (2022YFC2303600, 2022YFC2304800), and the National Natural Science Foundation of China (82170610), Guangdong Basic and Applied Basic Research Foundation (2023A1515011211).

Role of Α-L-Fucosidase as a Diagnostic Marker versus Α-Fetoprotein in HCC Post Viral Cirrhotic Patients

Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third cause of cancer-related mortality world- wide. The incidence of HCC is on the increase, and it is a major threat to our modern life. Epidemiological studies have indicated that HCC are related to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Aim of the Work To evaluate the role of AFU as a diagnostic marker versus AFP in HCC post viral cirrhotic Egyptian patients. Patients and Methods This study had been carried out on 90 subjects, age range 21-75 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals from January 2022 to June 2022. Results We found that serum levels of AFU were highest in patients of group A with HCC (129.867 ± 32.997 μl U/ml) compared to those with liver cirrhosis (33.433± 14.818 μl U/ml) with P value &amp;lt; 0.001 and the control groups (3.177 ± 1.199 μl U/ml) with P value &amp;lt; 0.001. Similarly alpha fetoprotein its serum levels were much higher in the HCC group (4688.223±11490.009 ng/ml) compared to the cirrhotic patients (4.407±3.107 ng/ml) with P value 0.02 Also, compared to healthy individuals (2.623±1.566 ng/ml) with p value 1.00. We found that there is No significant statistical correlation between serum AFP and AFU in our studied HCC and cirrhotic patients (R 0.332, P 0.073 for HCC and R 0.222, P 0.238 for cirrhotic). Regarding the negative correlation between serum AFU level and AFP level in order to predict the diagnostic value, sensitivity and specificity of both of them in term of tumor size, our study show that for AFU when the best cut off value was &amp;gt;52μl U/ml the sensitivity was 100% and specificity was 90% while for AFP when the best cut off value was &amp;gt; 10.5 ng/ml the sensitivity was 96.67% and specificity 96.67%. AFU is a promising serum tumor marker for HCC diagnosis and can be combined with AFP. Conclusion We concluded from this study that: Serum AFP was highly significant increase in HCC patients compared to cirrhotic and healthy controls, this is in agreement with many several reports that consider AFP in high serum levels as diagnostic for HCC combined with triphasic CT abdomen or dynamic MRI. Serum AFU levels were significantly higher in patients with HCC and mildly elevated in patients with liver cirrhosis compared to the control group. So it can be used as a tumor marker for HCC diagnosis. No correlation between AFU and laboratory data and child score. AFU was not influenced by clinical condition of the liver itself but with HCC. Around 40% of HCC patients have normal or low AFP level so AFU may be useful as a diagnostic marker in those patients. Serum AFP is the standard tumor marker used in clinical practice for diagnosis and surveillance of HCC in cirrhotic patients in spite of normal and low AFP HCC patients that may reach 40%. Sensitivity and specificity of AFU was nearly similar to sensitivity and specificity of AFP. Combined use of AFU with AFP or possibly other markers will improve the diagnostic field and can help in early detection of HCC in surveillance programms.

Hepatocellular Carcinoma in Cirrhotic Patients with Hepatitis-C Virus Positive Patients

Objective: To assess the frequency of Hepatocellular carcinoma in cirrhotic patients with hepatitis-C virus positive patients. Methodology: This study descriptive Cross-Sectional Study was conducted at Gastroenterology department, Isra University Hospital, Hyderabad, Pakistan, during Six months after the approval of synopsis from February 22, 2020 to August 21, 2020. Patients aged 25 to 60 years old, diagnosed as the cases of cirrhosis for more than five years, caused by hepatitis C of either gender, were included. Patients were evaluated clinically, biochemically, and serologically at baseline. CT scan of liver was done to assess hepatocellular carcinoma. A specially designed Proforma was utilized to gather the information, which was then input and analyzed employing SPSS version 23. Results: The participant's mean age is 42.3 years, with a standard deviation of 7.5 years, and an average body mass index (BMI) reached 16.9+3.6kg/m2. Additionally, the mean duration of cirrhosis is reported as 12.5 years. Majority of the patients were males 74.6%. Among all study participants with liver cirrhosis for over 5 years, 8.30% of patients had developed hepatocellular carcinoma. The HCC occurrence rate was statistically significant, with 1.9% of individuals aged 25-40 years and 6.4% of those over 40 years having hepatocellular carcinoma (p=0.008). However, gender, BMI categories, diabetes mellitus and hypertension did not show a significant association (p-&gt;0.05). Conclusion: In conclusion, hepatocellular carcinoma appeared relatively prevalent among patients having cirrhosis with hepatitis-C virus. Advanced age emerged as a significantly predominant factor contributing to hepatocellular carcinoma.

Effect of malnutrition on cirrhotic patients with hepatocellular carcinoma: A nationwide study.

e16250 Background: Liver cancer is the sixth most common cancer and the third leading cause of cancer mortality worldwide. There are two main types of primary liver cancers; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma. HCC accounts for around 80% of primary liver cancer cases. Generally, HCC develops in genetically susceptible individuals with risk factors, especially in the presence of cirrhosis. Cirrhosis is a systemic disease, and malnutrition is a key feature as well as an important complication which can be associated with worse outcomes. In this study, we aim to characterize the potential effects of malnutrition on HCC patients with underlying cirrhosis. Methods: The United States Nationwide Inpatient Sample (NIS) was used to extract hospitalization data of patients admitted between 2016 to 2018. Using ICD10 revision codes, we identified adults with the diagnosis of cirrhosis who have HCC with concomitant malnutrition, including sarcopenia. The control group included cirrhotic HCC patients without malnutrition. The primary outcome was the in-hospital mortality. Secondary outcomes included encephalopathy, ascites, variceal bleed, hepatorenal syndrome (HRS) and length of stay (LOS). Multivariate logistic regression was used to adjust for relevant variables. Results: We identified 423,158 patients admitted with cirrhosis. 20,582 had HCC, and of those, 2560 patients had the diagnosis of malnutrition. In this group of patients, the mean age was 59.85 years. 30% were females and 62% were Caucasians. When adjusted to other relevant variables, malnutrition was associated with increased in-hospital mortality (OR 1.40; P-value 0.000). It was also associated with an increased chance of developing encephalopathy (OR 1.42; P-value 0.000), ascites (OR 1.62; P-value 0.000), and HRS (OR 1.33; P-value 0.000). Moreover, it was associated with increased LOS (OR 1.99; P-value 0.001). Other factors associated with increased in-hospital mortality in cirrhotic HCC patients are described in the table. Conclusions: Malnutrition is a common complication in patients with cirrhosis. If identified, it can be treated efficiently. In this study, cirrhotic HCC patients with malnutrition had an increased chance of mortality. Further, they were at increased risk for cirrhosis decompensation and other in-hospital complications, which in turn can lead to increased LOS and therefore increased financial burden. We recommend that clinicians pay attention to patients with malnutrition and to treat them in order to prevent these complications. [Table: see text]

The clinical value of the hepatic venous pressure gradient in patients undergoing hepatic resection for hepatocellular carcinoma with or without liver cirrhosis.

The role of hepatic venous pressure gradient (HVPG) measurement in risk stratification before liver resection is an ongoing area of debate. This study examines the impact of preoperative HVPG levels on overall survival (OS)/time to recurrence (TTR) and postoperative complications after hepatic resection of hepatocellular carcinoma (HCC). Thirty-eight HCC patients undergoing HVPG measurement before liver resection at Cambridge University Hospitals NHS Foundation Trust between January 2014 and April 2022 were retrospectively analysed. Statistical analysis comprised univariable/multivariable Cox/logistic regression to identify risk factors of reduced OS/TTR or 90-day post-resection complications and Kaplan-Meier estimator, log-rank, chi-squared, Fisher's exact, and Mann-Whitney U test, or Student's t-test for survival/subgroup analysis. The median HPVG was 6 (range: 0-14) mmHg. The HVPG was an independent risk factor for poorer TTR in the overall cohort (cut-off: ≥7.5 mmHg (17.18/43.81 months; P = 0.009)). In the subgroup analysis of cirrhotic patients (N = 29 (76%)), HVPG was additionally an independent risk factor for lower OS (cut-off: ≥8.5 mmHg [44.39/76.84 months; P = 0.012]). The HVPG had no impact on OS/TTR in non-cirrhotic patients (N = 9 (24%)), nor was it associated with postoperative complications in any cohort. In conclusion, preoperative HVPG levels are useful predictors for TTR and OS in cirrhotic HCC patients undergoing hepatic resection.

Red Blood Cell Distribution Width as a Diagnostic Marker of Hepatocellular Carcinoma in Cirrhotic Patients

Background and Aim Although α-fetoprotein (AFP) is the main marker used for the diagnosis of hepatocellular carcinoma(HCC), its sensitivity and specificity as a screening tool have been questionable. Red blood cell distribution width (RDW) has been involved as a prognostic tool for many diseases and cancers including liver diseases. Still, its role in the diagnosis of HCC needs to be identified. This study aimed to evaluate the clinical importance of RDW as a novel marker in the diagnosis of HCC in Egyptian cirrhotic patients. Patients and Methods This cross-sectional study was carried out on 162 cirrhotic patients who attended Tropical medicine department clinics and inpatient wards at the Faculty of Medicine, Tanta University. Then they were divided into 2 groups of 81 patients each depending on their diagnosis with or without HCC (group I and group II respectively). Complete blood picture (CBC) that included red cell distribution width- coefficient of variation (RDW-CV) and AFP were obtained from all patients. Results There was a statistically significant elevation in RDW-CV in the HCC group as its mean± SD was 15.2.± 1.86 in HCC group versus 13.8 ± 1.99 in non HCC group (P&lt;0.001). In addition, AFP was significantly elevated in group I than in group II (P&lt;0.001). RDW-CV at a cut–off &gt;14% had a 66.76%sensitivity and 61.73%specificity while AFP at a cut-off value&gt;20 ng/ml had a 60.49%sensitivity and 79.01%specificity in the diagnosis of HCC. The combination of RDW-CV and AFP increased the sensitivity and specificity for the diagnosis of HCC(72.84% and 87.65% respectively) than each marker alone. Conclusions RDW may be considered a novel and cheap biomarker for the diagnosis of HCC either alone or in combination with AFP as it is readily available in CBC and does not need sophisticated techniques.

The Weight of Risk: Exploring the Link Between Obesity and Liver Cancer

Obesity is a chronic, preventable condition, and has a significant public health concern. Its implications extend beyond metabolic syndrome, casting a shadow over the development and prognosis of various cancers, with a particularly strong tie to hepatocellular carcinoma (HCC) among all cancer types. Non-Alcoholic Fatty Liver Disease (NAFLD) is now a leading cause of liver cancer, along with the treatment of hepatitis B and C. Liver cancer is the fourth most common cause of cancer related deaths worldwide, with obesity, exacerbating the risk especially two times higher in Body Mass Index (BMI) above 30 and four times higher in BMI above 35. Visceral adiposity, measured by waist circumference, is considered more important risk factor than general adiposity. Several mechanisms have been proposed to explain the pathophysiology of how obesity can trigger HCC, but the precise mechanisms that control the progression from steatosis to steatohepatitis and tumor initiation remain unclear. Hepatocellular cancer may occur in patients with NAFLD without cirrhosis. The diagnosis of HCC in NAFLD can be challenging due to an increase in poor-quality ultrasound in obese individuals, which necessitates a more accurate and cost-effective surveillance strategy for early detection. The delay in diagnosis, older age, and the presence of relevant comorbidities limit the possibility of therapeutic intervention. Weight management through lifestyle changes and surgical interventions like bariatric surgery offers promise in mitigating both metabolic syndrome and the risk of HCC. Diagnosis hinges on advanced imaging techniques like multiphase Magnetic Resonance Imaging or Computed Tomography scan using specific criteria. Treatment modalities for HCC are multifaceted, depends upon tumor characteristics, metastasis, cirrhosis, and overall liver function. However, despite advancements, there remains a pressing need for more efficacious interventions to combat obesity and curb the trajectory of HCC, given its persistently high mortality rate. Surveillance protocols for HCC in cirrhotic patients entail regular abdominal ultrasounds with or without Alpha Fetoprotein testing at six-month intervals. However, there is a need for cost effective surveillance strategies for HCC in non-cirrhotic NAFLD.

The relationship between hepatocellular carcinoma and Resolvin D1

Aims: Liver cancer is the second most common cause of cancer death, and hepatocellular carcinoma (HCC) is the most common hepatic primary tumor. Hepatocellular carcinoma develops based on inflammation in the cirrhotic liver. The aim of our study was to determine the relationship between the decrease in Resolvin D1, the lipid mediator involved in the resolution, and hepatocarcinogenesis. Methods: Thirty patients with HCC, thirty patients with cirrhosis, and thirty healthy subjects followed in our clinic between March 2018 and June 2019 were included in the study. Routine laboratory test results of the patients were recorded from the institutional database. Resolvin D1 and other parameters of the study groups were compared. Results: The Resolvin D1 levels were found to be significantly different from each other group, with the ranking as follows: the HCC group (1.71 ± 1.46 ng/ml)&lt; the cirrhotic group (3.63 ± 2.92 ng/ml)&lt; the healthy control group (6.24 ± 3.18 ng/ml). Moreover, Resolvin D1 levels were negatively correlated with ?-fetoprotein (AFP) level and tumor stage. Conclusion: Reduced lipid mediators that aid in the resolution process cause an increase in pro-inflammatory cytokines involved in the development of hepatocellular carcinoma. A decrease in Resolvin D1 may serve as a biomarker contributing to the diagnosis of progression to HCC in cirrhotic patients by triggering chronic inflammation and hepatocarcinogenesis.

Hepatic venous pressure gradient in hepatic resection for hepatocellular carcinoma

Liver transplantation is considered the gold standard for curative treatment of hepatocellular carcinoma (HCC) in patients with cirrhosis, but limited organ availability and high costs necessitate alternative options. Hepatic resection (HR) is preferred for select patients, providing tumor removal and prognostic information. However, HR has been associated with life-threatening complications, especially in the presence of clinically significant portal hypertension (CSPH). Current guidelines recommend HR only for patients with well-preserved liver function, normal bilirubin levels, good performance status, and no CSPH. However, advancements in surgical techniques and portal hypertension management are challenging these guidelines, potentially allowing the consideration of hepatic resection for HCC in cirrhotic patients with CSPH. Indeed, minimally invasive approaches improve safety and outcomes for selected CSPH patients and accurate assessment of CSPH allows risk stratification according to liver function, tumor location, and extent of resection. Thus, despite the negative impact of CSPH on HR outcomes, careful patient selection and minimally invasive techniques expand the potential for HR in CSPH patients. This comprehensive review examines the evidence on HR in HCC treatment for cirrhotic patients with CSPH, highlighting challenges in surgical decision-making, the importance of direct measurement of hepatic venous pressure gradient, and exploring the benefits and risks associated with HR. Moreover, it underscores the need for refined prediction models and algorithms to optimize patient selection and enhance surgical outcomes.

The impact of liver fibrosis on the progression of hepatocellular carcinoma via a hypoxia-immune-integrated prognostic model

The impact of liver fibrosis on the deterioration of hepatocellular carcinoma (HCC) remains controversial. We hope to explore this issue through establishing a fibrosis-hypoxia-glycolysis-immune related prognostic model. Liver fibrosis-related genes from Molecular Signatures Database were used to evaluate the degree of fibrosis in HCC patients from the TCGA database. The patients were divided into two groups using the fibrosis-related expression matrix based on the algorithm uniform manifold approximation and projection (UMAP) and evaluated for fibrosis by UMAP cluster and gene enrichment analysis. Prognostic model was constructed by differential analysis, LASSO, and multivariate regression analysis. Immune-infiltration analysis was performed by CIBERSORT. Quantitative PCR and immunohistochemistry were performed to measure the gene expression levels in HCC patients from our hospital. In 365 HCC patients from the TCGA database, 111 HCC patients with high fibrosis score have a worse prognosis than those with low fibrosis based on 129 genes related to liver fibrosis, which may be caused by the interaction between fibrosis, angiogenesis, hypoxia, glycolysis, inflammatory response, and high immune infiltration. We constructed a Fibrosis-Hypoxia-Glycolysis-Immune Prognostic Model (FHGISig), which could significantly predict disease progression in HCC patients. Furthermore, we revealed a close correlation between FHGISig and immune cell infiltration level as well as immune checkpoints. Finally, PCR results found TFF3 mRNA was significantly lower in cirrhotic HCC patients compared with non-cirrhotic ones. Liver fibrosis is a poor-prognostic factor for HCC, and our FHGISig could significantly predict disease progression, which could also be a potential predictive marker for immunotherapy in HCC patients.

Hepatobiliary phase imaging in cirrhotic patients using compressed sensing and controlled aliasing in parallel imaging results in higher acceleration.

We aimed to compare the image quality and focal lesion detection ability of hepatobiliary phase (HBP) images obtained using compressed sensing (CS) and controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) in patients with liver cirrhosis. We retrospectively included 244 gadoxetic acid-enhanced liver MRI from 244 patients with cirrhosis obtained by two HBP images using CS and CAIPIRINHA from July 2020 to December 2020. The optimized resolution and scan time for CS-HBP and CAIPIRINHA-HBP were 0.9 × 0.9 × 1.5 mm3 and 15s and 1.3 × 1.3 × 3 mm3 and 16s, respectively. We compared the image quality between the two sets of images in 244 patients and focal lesion (n = 294) analyses for 112 patients. CS-HBP showed comparable overall image quality (3.7 ± 0.9 vs. 3.6 ± 0.8, p = 0.680), superior liver edge sharpness (3.9 ± 0.6 vs. 3.6 ± 0.5, p < 0.001), and fewer respiratory motion artifacts (4.0 ± 0.7 vs. 3.8 ± 0.5, p < 0.001), but higher non-respiratory artifacts (3.4 ± 0.7 vs. 3.6 ± 0.6, p < 0.001) and subjective image noise (3.5 ± 0.8 vs. 3.6 ± 0.7, p = 0.014) than CAIPIRINHA-HBP. CS-HBP showed a higher signal-to-noise ratio in the liver than CAIPIRINHA-HBP (20.9 ± 9.0 vs. 18.9 ± 7.1, p = 0.008). The pooled sensitivity, specificity, and AUC were 90.0%, 77.5%, and 0.84 for CS-HBP and 73.5%, 82.4%, and 0.78 for CAIPIRINHA-HBP, respectively. CS-HBP showed better focal lesion detection ability, comparable overall image quality, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and noise compared to CAIPIRINHA-HBP. Thus, CS-HBP could be recommended for liver MRI in patients with cirrhosis to improve diagnostic performance. Thin-slice CS-HBP may be useful for detecting sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A while maintaining comparable subjective image quality. • Compared with controlled aliasing in parallel imaging results in higher acceleration, compressed sensing hepatobiliary phase yielded thinner slices and shorter scan time at a higher accelerating factor. • Compressed sensing hepatobiliary phase showed comparable overall image quality, superior liver edge sharpness, and fewer respiratory motion artifacts, but higher non-respiratory artifacts and subjective image noise than controlled aliasing in parallel imaging results in higher acceleration-hepatobiliary phase. • Compressed sensing hepatobiliary phase can detect sub-centimeter hepatocellular carcinoma in cirrhotic patients with Child-Pugh classification A.

Fuzheng Huayu capsules reducing development of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B based on the ratio of neutrophils/lymphocytes

Objective: To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC). Methods: 916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ(2) test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results: There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ(2) = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ(2) = 4.519, P = 0.029; 13.2% vs. 26.2%, χ(2) = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group (P = 0.38). Conclusion: Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

Study for the Significance of Osteopontin vs Alpha Feto Protein as a Diagnostic Marker for Hepatocellular Carcinoma in Cirrhotic Patients with HCV

Abstract Background Outcome of hepatocellular carcinoma (HCC) depends mainly on its early diagnosis. The performance of traditional biomarkers is not satisfactory. Alpha-fetoprotein (AFP) is the most widely used serum biomarker for hepatocellular carcinoma (HCC), despite its limitations. Several studies have reported that osteopontin (OPN) is a promising marker for the diagnosis of hepatocellular carcinoma (HCC); however, some studies emerged with conflicting results, Aim of the Work To evaluate the clinical significance of the plasma osteopontin (OPN) versus alpha-fetoprotein (AFP) in the diagnosis of HCC in cirrhotic patients Patients and Methods This study was Case-Control study, was conducted at internal Medicine and Gastroenterology outpatient clinics and ward in Ain Shams University Hospitals on Patients divided into 3 groups: (Group 1): 50 patients with previously diagnosed HCC on top of chronic HCV induced cirrhosis, (Group II): 15 chronic HCV patients with cirrhosis, (Group III):15 healthy controls during a period of Six months Results There was high statistically significant difference between the studied groups as regard OPN and AFP, Conclusion Plasma OPN level was elevated in the HCV-related HCC patients by comparison to the chronic HCV patients with cirrhosis and healthy controls. OPN is a promising tumor marker that could be added to the current standard tests for the diagnosis of HCC in patients with liver cirrhosis, due to Chronic HCV infection, in order to detect the disease at an early stage and, hence, improve the prognosis and survival rates of these patients

Evaluation of washout using subtraction MRI for the diagnosis of hepatocellular carcinoma in cirrhotic patients with spontaneously T1-hyperintense nodules

PurposeThe purpose of this study was to assess the value of subtraction imaging on post-arterial phase images (i.e., portal venous, delayed/transitional and hepatobiliary phases) for the non-invasive diagnosis of hepatocellular carcinoma (HCC) in spontaneously hyperintense nodules on T1-weighted imaging in patients with cirrhosis. Materials and methodsForty-five patients with a total 55 hepatic nodules that were spontaneously hyperintense on T1-weighted images were initially retrieved. All patients underwent MRI examination of the liver using extracellular agent. Each nodule was assessed for sensitivity and specificity using LI-RADS (Liver Imaging Reporting and Data System) during two reading sessions performed first without then with subtraction images on post-arterial phase images. The final standard of reference was defined by a step-by-step algorithm previously published combining histology, typical imaging, alfa fetoprotein and follow-up. ResultsForty-six nodules (26 HCC) in 39 patients with cirrhosis were analyzed. Using LI-RADS, the sensitivity and specificity for the diagnosis of HCC were 64% (95% CI: 41–83) and 67% (95% CI: 41–87) without subtraction; and 73% (95% CI: 50–89) (P > 0.999) and 33% (95% CI: 13–59) (P = 0.553) on subtraction imaging using extracellular contrast agent. Fifty-five percent (22/40) of nodules displayed a washout without subtraction and 70% (28/40) did so on subtraction imaging obtained with extracellular contrast agent. Twenty nodules out of 40 (50%) were classified LI-RADS 5 without subtraction, and 28 out of 40 nodules (70%) with subtraction. ConclusionThe results of this study suggest that the use of subtraction imaging on post-arterial phase images (i.e., PVP, DP/TP and HBP) is not relevant for the non-invasive diagnosis of HCC for spontaneously hyperintense nodules on T1-weighted images in patients with liver cirrhosis.

Interleukin-6: A New Marker of Advanced-Sarcopenic HCC Cirrhotic Patients.

Hepatocellular carcinoma (HCC) is the major cause of liver-related death worldwide. Interleukin 6 (IL-6) promotes the growth of the HCC microenvironment. The correlation between Child-Pugh (CP) and HCC stage and between HCC stage and sarcopenia is still not clear. Our aim was to investigate whether IL-6 is correlated with HCC stage and could represent a diagnostic marker for sarcopenia. Ninety-three HCC cirrhotic patients in different stages, according to BCLC-2022 (stages A, B, and C), were enrolled. Anthropometric and biochemical parameters, comprehensive of IL-6, were collected. The skeletal muscle index (SMI) was measured using dedicated software on computer tomography (CT) images. IL-6 level was higher in advanced (BCLC C) compared to the early-intermediate (BCLC A-B) stages (21.4 vs. 7.7 pg/mL, p < 0.005). On multivariate analysis, IL-6 levels were statistically dependent on the degree of liver disease severity (CP score) and HCC stages (p = 0.001 and p = 0.044, respectively). Sarcopenic patients presented lower BMI (24.7 ± 5.3 vs. 28.5 ± 7.0), higher PMN/lymphocyte ratio (2.9 ± 2.4 vs. 2.3 ± 1.2) and increased values of log (IL-6) (1.3 ± 0.6 vs. 1.1 ± 0.3). Univariate logistic regression between sarcopenia and log (IL-6) showed a significant odds ratio (OR 14.88, p = 0.044) with an AUC of 0.72. IL-6 appears to be an effective biomarker for the diagnosis of advanced cirrhotic HCC. In addition, IL-6 could be considered a marker of cirrhotic HCC-related sarcopenia, suggesting further investigation with BIA- or CT-dedicated software.

Abstract 3336: A novel clinical and biomarker model accurately predicts hepatocellular carcinoma (HCC) across racial groups

Abstract Purpose: HCC incidence, which is highest in Asians and Pacific Islanders (API), followed by Black/African Americans (AA), Hispanics (H), and non-Hispanic Whites (W), is rising at an alarming rate in the United States. Most HCC is diagnosed at an advanced incurable stage, emphasizing the need for accurate biomarkers for early diagnosis. The predictive accuracy in available biomarkers such as alpha-fetoprotein (AFP) is sub-optimal, and these have not been systematically assessed across ethnic and racial subgroups. Here, we report on the performance characteristics of a model derived from an ethnically diverse population including API, distinct from the mainland USA. This model includes biologically relevant proteins, as well as clinical characteristics and seeks to capture the molecular changes underlying hepatocarcinogenesis. Experimental Procedures: We combined human genomic studies using The Cancer Genome Atlas (TCGA) and mechanistic insight from animal models to identify biologically relevant proteins. A proteomic analysis of 7,000 proteins (SomaScan) utilizing serum samples (55 uL/each) from 520 individuals with cirrhosis, 158 of whom had HCC by imaging criteria. Patients were recruited from three participating centers with significant cohorts of ethnic minorities (27% AA, 3% H, 2.3% API, 63%W patients, 3.8% other). We combined serum biomarkers with clinical and demographic risk factors to develop a risk prediction model. Results: Using multivariate logistic regression analysis, we developed a model that incorporated race and ethnicity in predicting the likelihood of HCC in cirrhotic patients. This functional model included 4 clinical variables (age, serum AFP and Bilirubin levels, HBV infection or not) and 3 serum protein biomarkers (AKR1B10, COL15A1, and INHBB), resulting in an area under the receiver operating characteristics curve (AUC) of 0.86 and sensitivity of 57% at 91% specificity. Focusing on the TGF-β superfamily signaling, clustering analysis identified several proteomic signatures that performed well in distinguishing HCC patients from cirrhosis. Our model outperformed both AFP alone and the Doylestown model by clinically relevant margins: at 90% specificity, the sensitivity of our model was 20% higher than AFP alone and 33% higher than the Doylestown model in the derivation samples. Conclusions and Next Steps: This study successfully demonstrates the performance of our biologically functional model combining 4 serum biomarkers with 3 clinical parameters to predict HCC across cirrhotic patients from a racially and ethnically diverse population, which outperformed the Doylestown model or AFP alone. The next steps will be large-scale validations of this biomarker panel in cirrhotic patients across all racial and ethnic subgroups in Phase II/III studies. Citation Format: Xiyan Xiang, Anil K. Vegesna, Richard L. Amdur, Kirti Shetty, Herbert Yu, Linda L. Wong, Sharon S. Fox, Michael G. Ryan, Nyasha Chambwe, Sanjaya K. Satapathy, James M. Crawford, Gregory M. Grimaldi, Vikas Kundra, Lopa Mishra. A novel clinical and biomarker model accurately predicts hepatocellular carcinoma (HCC) across racial groups [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3336.

Single-cell RNA-seq Revealed that Altered Tumor Infiltrating Lymphocytes in Cirrhotic Liver Indicate Development of Hepatocellular Carcinoma.

Cirrhosis is the precursor lesion for most hepatocellular carcinoma (HCC) cases. However, no biomarker effectively predicted HCC initiation before diagnosis by imaging. We aimed to investigate the hallmarks of immune microenvironments in healthy, cirrhotic livers and HCC tumor tissues and to identify immune biomarkers of cirrhosis-HCC transition. Expression matrices of single-cell RNA sequencing studies were downloaded and integrated with Seurat package vignettes. Clustering was performed to analyze the immune cell compositions of different sample types. The cirrhotic liver and HCC tumors had distinct immune microenvironments, but the immune landscape of cirrhotic livers was not markedly modified compared with healthy livers. Two subsets of B cells and three subsets of T cells were identified in the samples. Among the T cells, naïve T cells were more prominent in the cirrhotic and healthy liver samples than in the HCC samples. In contrast, the neutrophil count was lower in cirrhotic livers. Two macrophage clusters were identified, one that actively interacted with T cells and B cells and was enriched in cirrhotic blood compared with HCC blood samples. Decreased naïve T cell infiltration and increased neutrophil infiltration in the liver may indicate the development of HCC in cirrhotic patients. Alterations in blood-resident immune cells may also be a sign of HCC development in cirrhotic patients. The dynamics of the immune cell subsets may serve as novel biomarkers to predict the transition from cirrhosis to HCC.

Direct Acting Anti-Viral Therapy, and Potential Increase in the Incidence of Hepato-Cellular Carcinoma in Cirrhotic Patients With Hepatitis C Virus

Direct Acting Anti-Viral Therapy, and Potential Increase in the Incidence of Hepato-Cellular Carcinoma in Cirrhotic Patients With Hepatitis C Virus