Prevalence Of Hepatocellular Carcinoma Research Articles

Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.

Increased prevalence but decreased survival of nonviral hepatocellular carcinoma compared to viral hepatocellular carcinoma in recent ten years

Due to the comprehensive hepatitis B virus vaccination program in Taiwan since 1986, the development of antiviral therapy for chronic hepatitis B and chronic hepatitis C infection and covered by National health insurance. Besides, the increased prevalence of nonalcoholic fatty liver disease (NAFLD) and currently, approved therapy for NAFLD remain developing. The etiology of liver-related diseases such as cirrhosis and hepatocellular carcinoma required reinterpretation. This study aimed to analyze the incidence and outcome of hepatocellular carcinoma (HCC) due to viral (hepatitis B and hepatitis C) infection compared to that of nonviral etiology. We retrospectively analyzed patients with HCC from January 2011 to December 2020 from the cancer registry at our institution. Viral-related hepatitis was defined as hepatitis B surface antigen positivity or anti-hepatitis C virus (HCV) antibody positivity. A total of 2748 patients with HCC were enrolled, of which 2188 had viral-related HCC and 560 had nonviral-related HCC. In viral HCC group, the median age at diagnosis was significantly lower (65 years versus 71 years, p < 0.001), and the prevalence of early-stage HCC, including stage 0 and stage A Barcelona Clinic Liver Cancer, was significantly higher (52.9% versus 33.6%, p < 0.001). In nonviral HCC group, alcohol use was more common (39.9% versus 30.1%, p < 0.001), the prevalence of type 2 diabetes mellitus (T2DM) was higher (54.5% versus 35.1%, p < 0.001), and obesity was common (25.0% versus 20.5%, p = 0.026). The prevalence of nonviral HCC increased significantly from 19.2 to 19.3% and 23.0% in the last 10 years (p = 0.046). Overall survival was better in the viral HCC group (5.95 years versus 4.00 years, p < 0.001). In the early stage of HCC, overall survival was still better in the viral HCC group (p < 0.001). The prevalence of nonviral HCC has significantly increased in the last ten years. The overall survival was significantly lower in the nonviral HCC, perhaps because the rate of early HCC detection is lower in nonviral HCC and anti-viral therapy. To detect nonviral HCC early, we should evaluate liver fibrosis in high-risk groups (including people with obesity or T2DM with NAFLD/NASH and alcoholic liver disease) and regular follow-up for those with liver fibrosis, regardless of cirrhosis.

Design, Synthesis, and Mechanistic Studies of (R)-3-Amino-5,5-difluorocyclohex-1-ene-1-carboxylic Acid as an Inactivator of Human Ornithine Aminotransferase.

Human ornithine aminotransferase (hOAT), a pyridoxal 5'-phosphate (PLP)-dependent enzyme, has been shown to play an essential role in the metabolic reprogramming and progression of hepatocellular carcinoma (HCC). HCC accounts for approximately 75% of primary liver cancers and is within the top three causes of cancer death worldwide. As a result of treatment limitations, the overall 5-year survival rate for all patients with HCC is under 20%. The prevalence of HCC necessitates continued development of novel and effective treatment methods. In recent years, the therapeutic potential of selective inactivation of hOAT has been demonstrated for the treatment of HCC. Inspired by previous increased selectivity for hOAT by the expansion of the cyclopentene ring scaffold to a cyclohexene, we designed, synthesized, and evaluated a series of novel fluorinated cyclohexene analogues and identified (R)-3-amino-5,5-difluorocyclohex-1-ene-1-carboxylic acid as a time-dependent inhibitor of hOAT. Structural and mechanistic studies have elucidated the mechanism of inactivation of hOAT by 5, resulting in a PLP-inactivator adduct tightly bound to the active site of the enzyme. Intact protein mass spectrometry, 19F NMR spectroscopy, transient state kinetic studies, and X-ray crystallography were used to determine the structure of the final adduct and elucidate the mechanisms of inactivation. Interestingly, despite the highly electrophilic intermediate species conferred by fluorine and structural evidence of solvent accessibility in the hOAT active site, Lys292 and water did not participate in nucleophilic addition during the inactivation mechanism of hOAT by 5. Instead, rapid aromatization to yield the final adduct was favored.

Global prevalence of MAFLD-related hepatocellular carcinoma: A systematic review and meta-analysis.

The global proportion of hepatocellular carcinoma (HCC) attributable to metabolic dysfunction-associated fatty liver disease (MAFLD) is unclear. The MAFLD diagnostic criteria allows objective diagnosis in the presence of steatosis plus defined markers of metabolic dysfunction, irrespective of concurrent liver disease. We aimed to determine the total global prevalence of MAFLD in HCC cohorts (total-MAFLD), including the proportion with MAFLD as their sole liver disease (single-MAFLD), and the proportion of those with concurrent liver disease where MAFLD was a contributary factor (mixed-MAFLD). This systematic review and meta-analysis included studies systematically ascertaining MAFLD in HCC cohorts, defined using international expert panel criteria including ethnicity specific BMI cut-offs. A comparison of clinical and tumour characteristics was performed between single-MAFLD, mixed-MAFLD and non-MAFLD HCC. 22 studies (56,565 individuals with HCC) were included. Total and single-MAFLD HCC prevalence was 48.7% (95% CI; 34.5% - 63.0%) and 12.4% (95% CI; 8.3% - 17.3%), respectively. In HCC due to chronic hepatitis B, C and alcohol-related liver disease, mixed-MAFLD prevalence was 40.0% (95% CI; 30.2% - 50.3%), 54.1% (95% CI; 40.4% - 67.6%) and 64.3% (95% CI; 52.7% - 75.0%), respectively. Mixed-MAFLD HCC had significantly higher likelihood of cirrhosis and lower likelihood of metastatic spread compared to single-MAFLD HCC, and a higher platelet count and lower likelihood of macrovascular invasion compared to non-MAFLD HCC. MAFLD is common as a sole aetiology, but more so and as a co-factor in mixed-aetiology HCC, supporting the use of a positive diagnostic criteria.

The significance of m6A RNA methylation regulators in diagnosis and subtype classification of HBV-related hepatocellular carcinoma.

In recent years, abnormal m6A alteration in hepatocellular carcinoma (HCC) has been a focus on investigating the biological implications. In this study, our objective is to determine whether m6A modification contributes to the progression of HBV-related HCC. To achieve this, we employed a random forest model to screen top 8 characteristic m6A regulators from 19 candidate genes. Subsequently, we developed a nomogram model that utilizes these 8 characteristic m6A regulators to predict the prevalence of HBV-related HCC. According to decision curve analysis, patients may benefit from the nomogram model. The clinical impact curves exhibited a robust predictive capability of the nomogram models. Additionally, consensus molecular subtyping was employed to identify m6A modification patterns and m6A-related gene signature. The quantification of immune cell subsets was accomplished through the implementation of ssGSEA algorithms. PCA algorithms were developed to compute the m6A score for individual tumors. Two distinct m6A modification patterns, namely cluster A and cluster B, exhibited significant correlations with distinct immune infiltration patterns and biological pathways. Notably, patients belonging to cluster B demonstrated higher m6A scores compared to those in cluster A, as determined by the m6A score metric. Furthermore, the expression of IGFBP3 proteins was validated through immunofluorescence, revealing their pronounced lower expression in tumor tissues. In summary, our study underscores the importance of m6A modification in the advancement of HBV-related HCC. This research has the potential to yield novel prognostic biomarkers and therapeutic targets for the identification of HBV-related HCC.

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome.

There is scant literature on hepatocellular carcinoma (HCC) in patients with Budd-Chiari syndrome (BCS). To assess the magnitude, clinical characteristics, feasibility, and outcomes of treatment in BCS-HCC. A total of 904 BCS patients from New Delhi, India and 1140 from Mumbai, India were included. The prevalence and incidence of HCC were determined, and among patients with BCS-HCC, the viability and outcomes of interventional therapy were evaluated. In the New Delhi cohort of 35 BCS-HCC patients, 18 had HCC at index presentation (prevalence 1.99%), and 17 developed HCC over a follow-up of 4601 person-years, [incidence 0.36 (0.22-0.57) per 100 person-years]. BCS-HCC patients were older when compared to patients with BCS alone (P = 0.001) and had a higher proportion of inferior vena cava block, cirrhosis, and long-segment vascular obstruction. The median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up (13029 ng/mL vs 500 ng/mL, P = 0.01). Of the 35 BCS-HCC, 26 (74.3%) underwent radiological interventions for BCS, and 22 (62.8%) patients underwent treatment for HCC [transarterial chemoembolization in 18 (81.8%), oral tyrosine kinase inhibitor in 3 (13.6%), and transarterial radioembolization in 1 (4.5%)]. The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo (P = 0.0001). In contrast to the New Delhi cohort, the Mumbai cohort of BCS-HCC patients were predominantly males, presented with a more advanced HCC [Barcelona Clinic Liver Cancer C and D], and 2 patients underwent liver transplantation. HCC is not uncommon in patients with BCS. Radiological interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

Circulating miRNA’s biomarkers for early detection of hepatocellular carcinoma in Egyptian patients based on machine learning algorithms

Liver cancer, which ranks sixth globally and third in cancer-related deaths, is caused by chronic liver disorders and a variety of risk factors. Despite therapeutic improvements, the prognosis for Hepatocellular Carcinoma (HCC) remains poor, with a 5-year survival rate for advanced cases of less than 12%. Although there is a noticeable decrease in the frequency of cases, liver cancer remains a significant worldwide health concern, with estimates surpassing one million cases by 2025. The prevalence of HCC has increased in Egypt, and it includes several neoplasms with distinctive messenger RNA (mRNA) and microRNA (miRNA) expression profiles. In HCC patients, certain miRNAs, such as miRNA-483-5P and miRNA-21, are upregulated, whereas miRNA-155 is elevated in HCV-infected people, encouraging hepatocyte proliferation. Short noncoding RNAs called miRNAs in circulation have the potential as HCC diagnostic and prognostic markers. This paper proposed a model for examining circulating miRNAs as diagnostic and predictive markers for HCC in Egyptian patients and their clinical and pathological characteristics. The proposed HCC detection model consists of three main phases: data preprocessing phase, feature selection based on the proposed Binary African Vulture Optimization Algorithm (BAVO) phase, and finally, classification as well as cross-validation phase. The first phase namely the data preprocessing phase tackle the main problems associated with the adopted datasets. In the feature selection based on the proposed BAVO algorithm phase, a new binary version of the BAVO swarm-based algorithm is introduced to select the relevant markers for HCC. Finally, in the last phase, namely the classification and cross-validation phase, the support vector machine and k-folds cross-validation method are utilized. The proposed model is evaluated on three studies on Egyptians who had HCC. A comparison between the proposed model and traditional statistical studies is reported to demonstrate the superiority of using the machine learning model for evaluating circulating miRNAs as diagnostic markers of HCC. The specificity and sensitivity for differentiation of HCC cases in comparison with the statistical-based method for the first study were 98% against 88% and 99% versus 92%, respectively. The second study revealed the sensitivity and specificity were 97.78% against 90% and 98.89% versus 92.5%, respectively. The third study reported 83.2% against 88.8% and 95.80% versus 92.4%, respectively. Additionally, the results show that circulating miRNA-483-5p, 21, and 155 may be potential new prognostic and early diagnostic biomarkers for HCC.

First-line therapies in a Latino-rich cohort of US patients (pts) with hepatocellular carcinoma (HCC) and Child Pugh B (CPB) cirrhosis.

453 Background: There are limited prospective clinical trials in patients with both HCC and CPB cirrhosis. As the prevalence of HCC and cirrhosis has been rising among Latinos in South Texas, it is crucial to examine the liver dysfunction within this demographic to understand the contributing factors to treatment patterns. Therefore, we conducted a retrospective analysis of 36 patients with both HCC and Child Pugh B (CPB) cirrhosis. Methods: A dataset of 65 patients with HCC and cirrhosis from 2009 – 2019 was used to identify 36 patients with CPB treated at a Latino-Rich NCI-designated Cancer Center. We further segmented patients of Child Pugh Class B by ALBI grades (1-3) to explore variations in demographics, liver dysfunction, and first-line therapies. Results: Median age overall of the cohort is 59 (50-71). Ethnicity: Latino White (83%), Non-Latino White (14%), Black (3%). Etiology: HCV (78 %) EtOH (50%), NASH (19%), and HBV (3%). ALBI Grade: I (6%), II (50%), III (44%). First line treatment in CPB: Sorafenib (86%), Nivolumab (8%), Lenvatinib (6%). Sorafenib was used across all ALBI grades, while Lenvatinib and Nivolumab were given only in ALBI II (Table). Conclusions: Sorafenib was more often given to patients with CPB cirrhosis, in the first line setting; however, more patients were treated with nivolumab or lenvatinib with ALBI II. Further investigation of survival based on ALBI levels and the trajectory of liver function over time in response to different treatment approaches is underway in a larger cohort who has received newer immunotherapy-based regimens. With more agents approved for HCC, prospective clinical trials are needed in CPB and HCC. [Table: see text]

Prevalence and prediction of hepatocellular carcinoma in alcohol-associated liver disease: a retrospective study of 136 571 patients with chronic liver diseases

Background and aimsTo explore the incidence of alcohol-related hepatocellular carcinoma (HCC), evaluate possible synergisms between alcohol and well-known risk factors associated with HCC and establish a nomogram to predict alcohol-associated...

Prevalence of HCC among Living Donor Liver Transplant Recipients and Effect on Outcome Georgian Experience

: Liver transplantation (LT) may be the best curative treatment that offers a chance of cure for the tumor and the underlying cirrhosis by complete extirpation of both. Hepatocellular Carcinoma (HCC) is a formidable global health challenge, representing one of the most prevalent primary liver malignancies with increasing incidence rates worldwide. It sets the stage for a comprehensive exploration of how LDLT has redefined the paradigms of treatment for HCC and contributed to enhanced patient outcomes. To answer the question of this paper we used cross sectional study design among 84 Living Donor Liver Transplant Recipients. After collecting data analyzing patient’s medical cards we have found that out of 84 recipients 12 (11%) had a Hepatocellular Carcinoma, out of this 8 (6.7%) recipients dead and 4 (3.3%) is alive. We may have challenges such as: Diagnostic Challenges, Treatment Options, and Selection Criteria for LDLT in HCC. The relationship between HCC and LDLT is a dynamic and evolving field. LDLT has significantly expanded the therapeutic options for selected HCC patients, offering hope for improved outcomes. However, the intricate interplay between patient selection, surgical techniques, and post-transplant care underscores the importance of a multidisciplinary approach to HCC management. Ongoing research and advances in both HCC treatment and LDLT continue to shape the landscape of this complex disease and transplantation strategy.&#x0D;

Predictors of Liver Disease Outcomes in People with Hemophilia and HCV Infection

Introduction: Hemophilia is an X-linked bleeding disorder among whom the majority have chronic hepatitis C (HCV) from past factor infusion. With among the longest duration HCV infection, now 30+ years from their first factor infusion, better predictors of HCV outcomes are needed now that liver-based gene therapy is FDA-approved. While antiviral therapy clears HCV viral load and reduces end-stage liver disease (ESLD), it may not reverse fibrosis/ cirrhosis or prevent hepatocellular carcinoma (HCC). We, therefore, studied the natural history of HCV in a well-characterized cohort of men with hemophilia and HCV to determine HCV prevalence and cumulative incidence of ESLD, HCC, and mortality. Methods: This was a retrospective cohort study of 121 men with HCV and hemophilia cared for at the Hemophilia Center of Western PA, whose medical outpatient charts were reviewed under University of Pittsburgh IRB exempt determination, #21100086. HCV outcomes, including ESLD, HCC, platelet count (PLT)&amp;lt;100,000 (100K) u/L, and mortality were analyzed by age, ethnicity, HIV status, hemophilia type, inhibitor status, and antiviral therapy. Liver biopsies available on 32 patients were assessed for steatosis, Knodell, Ishak and Metavir scores. Fisher's exact test was used to compare outcomes by discrete variables. Kaplan Meier time to event analyses log-rank test was used to determine time-to-event outcomes for HCC and mortality, and logistic regression was used to determine variables predictive of HCV outcomes. Results: The mean duration of HCV infection in 121 subjects was 54 years (range: 36-80 yr). Of these, 48 (39.6%) had received antiviral therapy (IFN-based or DAA-based): of those untreated, most died prior to its availability. A total of 31(25.6%) were HIV+, 24 (19.8%) had ESLD, and 7 (5.8%) had HCC. Among the 34 (25.9%) who died, ESLD was the cause in 11 (32.3%), HCC in 6 (20.6%), bleeding in 9 (26.5%), sepsis in 3 (8.8%), and AIDS, Parkinson disease, intravenous drug use, and suicide in 1(2.9%) each. The overall prevalence of ESLD was 0.365 per 100 person-years (py); PLT&amp;lt;100K, 0.173 per 100py; HCC, 0.106 per 100 py; and HCV-associated mortality, 0.335 per 100py. Significant risk factors for ESLD included PLT&amp;lt;100K/uL, OR=6.159, p=0.014; HIV infection, OR=3.883, p=0.001; and age&amp;gt;50, OR=2.460, p=0.023. No antiviral-treated subject developed ESLD, p=0.001. The presence of ESLD was the most significant predictor of HCC, OR=11.476, p=0.003. An elevated Knodell score was a significant predictor of HCC, OR =2.450, p=0.044, while an elevated Ishak score was a significant predictor of ESLD, OR 1.930, p=0.030. Neither Metavir nor steatosis scores were predictive of ESLD or HCC, and no score was predictive of HCV mortality. Kaplan Meier time-to-event survival analysis for all-cause mortality, 95% confidence interval (dotted lines) based on ESLD, HIV, treatment status, HCC, and age is shown in Figure 1a-1e. The overall mean ± SE (standard error) survival from initial HCV infection was 8890 ± 240 days. Comparing ESLD with non-ESLD, mean survival was 5321 ± 649 vs. 9773 ± 152 days, p=0.001 (Fig. 1a); for HIV+ vs. HIV-, 7032 ± 676 vs. 9530 ± 178 days, p=0.001 (Fig. 1b); for antiviral-treated vs. untreated, 10210 ± 19 vs. 8094 ± 365 days, p=0.001 (Fig. 1c); for HCC vs. non-HCC, 8433 ± 614 vs. 8918 ± 251 days, p=0.027 (Fig. 1d); and for age &amp;gt; 50 vs. ≤ 50 yr , 9588 ± 173 vs. 8052 ± 460 days, p=0.001 (Fig. 1e). The cumulative incidence (CI) of ESLD was 16.86% overall. Comparing HIV+ vs. HIV-, ESLD-CI was 41.44% vs. 7.36%, p= 0.001; in antiviral-treated vs. untreated, 0% vs. 27.08%, p=0.001; in age &amp;gt; 50 vs. ≤ 50 yr, 13.10% vs. 14.03%, p&amp;lt;0.001; and in PLT&amp;lt;100K/uL vs. PLT≥100K/uL, 48.15% vs. 1.61%, p&amp;lt;0.001. The HCC-CI was 2.88% overall, including in HIV+ vs. HIV-, 0% vs. 3.71%, p= 0.27; in antiviral untreated vs. treated, 2.00% vs. 3.85%, p=0.760; in age &amp;gt; 50 vs. age ≤ 50, 5.63% vs. 0% , p=0.040; and in PLT&amp;lt;100K/uL vs. PLT ≥ 100K/uL, 33.3% vs.1.61%, p=0.001. HCC-CI was similar between those with vs. without ESLD, 6.67% vs 2.04%, p=0.27. Conclusion: ESLD in people with hemophilia and HCV is associated with increased risk of mortality, HCC, and PLT&amp;lt;100K. The risk for ESLD is increased in those with HIV and antiviral untreated. HCV remains an important cause of major morbidity and mortality in this cohort of people with hemophilia and HCV, despite antiviral therapy. This suggests ESLD, HCC, HIV, PLT&amp;lt;50K/uL, and antiviral Rx assessment before hemophilia liver-based gene therapy.

Prevalence of Hepatocellular Carcinoma in Hepatitis B Population within Southeast Asia: A Systematic Review and Meta-Analysis of 39,050 Participants.

Hepatocellular carcinoma (HCC) is a significant complication of hepatitis B and still poses a global public health concern. This systematic review and meta-analysis provide adequate details on the prevalence of HCC in the HBV population within Southeast Asian countries. Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, a thorough search for literature discussing the prevalence of HCC in the HBV population within southeast Asia was performed. Eligible studies were subjected to a meta-analysis utilising a DerSimonian and Laird approach and a random effect model. A protocol was registered with PROSPERO (CRD42023423953). Our study meticulously recovered 41 articles from seven countries in Southeast Asia, namely Cambodia, Indonesia, Malaysia, the Philippines, Singapore, Thailand, and Vietnam. A total of 39,050 HBV patients and 7479 HCC cases in southeast Asia were analysed. The pooled prevalence of HCC in HBV cases within southeast Asia was 45.8% (95% CI, 34.3-57.8%, I2 = 99.51%, p < 0.001). Singapore (62.5%, CI: 42.4-79.1) had the highest pooled prevalence of HCC in the HBV population compared to Vietnam, with the lowest estimate (22.4%, CI: 9.9-44.9). There was a drop in the pooled prevalence of HCC in HBV from 2016 until now (37.6%, CI: 19.2-60.5). The findings of this review reveal a high pooled prevalence of HCC in the HBV population and therefore stir the need for routine screening, management, and surveillance.

An update review of smart nanotherapeutics and liver cancer: opportunities and challenges.

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, typically diagnosed in advanced stages. Chemotherapy is necessary for treating advanced liver cancer; however, several challenges affect its effectiveness. These challenges include low specificity, high dosage requirements, high systemic toxicity and severe side effects, which significantly limit the efficacy of chemotherapy. These limitations can hinder the treatment of HCC. This review focuses on the prevalence of HCC, different types of liver cancer and the staging of the disease, along with available treatment methods. Additionally, explores recent and relevant studies on smart drug- and gene-delivery systems specifically designed for HCC. These systems include targeted endogenous and exogenous stimuli-responsive platforms.

Clinical characteristics of hepatocellular carcinoma in patients with cirrhosis: a comparative cohort study.

The epidemiology of cirrhosis has changed over the last two decades. We aimed to assess whether the epidemiology and clinical presentation of hepatocellular carcinoma (HCC) occurring in cirrhosis has changed. The patients were recruited from the Cirrhosis Registry. This database included patients with cirrhosis who had attended the outpatient' liver clinic at the Centre Hospitalier Jolimont in La Louvière, Belgium, since January 1995. We extracted data on two cohorts of patients with cirrhosis collected over an identical time period and followed up for the same duration. Cohort 1 included 504 patients enrolled from 1995 to 2005; among them, 89 patients developed HCC during the defined follow-up period (group 1). Cohort 2 included 566 patients enrolled from 2006 to 2016, among whom 73 patients developed HCC during the defined follow-up period (group 2). When patients with HCC in both groups were compared, no differences were found in the age at HCC diagnosis, the test that alerted on the presence of HCC, the extension, and the stage of the lesion at diagnosis. In the group 1, hepatitis C virus-related HCC occurred in 53% of the cases compared with 18% in the group 2 (P<0.001). Alcohol-related HCC occurred in 27% in the group 1 compared with 60% in the group 2 (P<0.001). The prevalence of metabolic dysfunction-associated steatotic liver disease-related HCC accounted for 10% in all groups. The general epidemiology of HCC has not changed; however the etiology of underlying cirrhosis has changed.

Screening of Cirrhotic Compensated Hepatitis C Virus Infected Patients Who Received Oral Direct Acting Antiviral Drugs for Hepatocellular Carcinoma and Other Malignancies

Abstract Background HCV is now recognized as a major factor in the development of severe liver damage as chronic infection is associated with the development of hepatic steatosis, cirrhosis and hepatocellular carcinoma. Aim of the Work screening of our patients for the incidence of hepatocellular carcinoma and other malignancies during or after end of treatment with orally direct acting antiviral drugs to prove or disprove this allegation. Patients and Methods This retrospective observational study was performed at Maadi Military Hospital during the period from July 2015 to July 2016 including 290 naive compensated cirrhotic hepatitis C virus infected patients with no prior history of hepatocellular carcinoma or any other malignancy and divided into 5 groups: Group (A) patients treated with combined sofosbuvir and ribavirin for 24 weeks. Group (B) patients treated with combined sofosbuvir and daclatasvir and low dose ribavirin for 12 weeks. Group(C) patients treated with combined sofosbuvir and ledipasvir with weight based ribavirin for 12 weeks. Group (D) patients with chronic renal failure on regular hemodialysis treated with combined ompitasvir+paritaprevir+ritonavir and low dose ribavirin for 12 weeks. Group (E) patients with the same criteria were taken from the waiting list of treatment and studied as the control group and were subjected to the same investigations and follow up. Results Highly significant increase in HCC prevalence in A group (23.3%) during follow up period. Significant increase in HCC prevalence in B group (8%) during follow up period. Non-significant difference in HCC prevalence in C group; during follow up period. In group D; non-significant difference in HCC prevalence during treatment and follow up periods. There was no detected occurrence of HCC or any other malignancies during the course of the study in group E. Conclusion Increased HCV detection combined with the availability of simple, well-tolerated treatment regimens can potentially reduce the need for liver transplantation and reduce HCV-related mortality. No evidence of an increased risk of de novo HCC by patients treated with interferon free SOF-based regimens. However, cirrhosis was strongly associated with the short-term development of HCC after HCV eradication. Treatment of HCV in patients with CKD is highly effective, with SVR12 rates similar to those seen in patients without CKD. The role of SVR by DAAs on the incidence or recurrence of hepatocellular carcinoma (HCC) is still a matter of debate, although it is known that SVR does not eliminate the risk of HCC.

Toxicity profile, palliative care and hospice utilization of geriatric patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in the veteran health administration.

e24022 Background: Over the last decade, the incidence of Hepatocellular carcinoma (HCC) has increased in the geriatric population. Atezolizumab plus Bevacizumab (A+B) has become an established systemic therapy for patients with HCC. Even with the aging population and elevated prevalence of HCC amongst Veterans, limited studies have explored the safety of A+B in geriatric patients. This study aims to investigate the toxicity profile of A+B in the geriatric population as well as Palliative Care and Hospice utilization within the Veteran Health Administration (VHA). Methods: Data were extracted from the electronic medical records (EMR) for adults (deceased and living) with ICD9 and ICD10 HCC codes that received 1st line systemic therapy with A+B within the VHA between December 1, 2019, and March 1, 2023. Descriptive statistics were used to summarize baseline characteristics, toxicity profile and Palliative Care and Hospice enrollment between 3 populations aged &lt; 65, 65-69, and &gt; 70 years. A significant p-value of ≤0.05 was used. Results: In total, 332 patients were included in the study; 206 were deceased. Approximately 70% of patients were &gt; 65 years. The majority in each age group were non-Hispanic white males, ECOG ≥1, CPS class A and BCLC score of C. Veterans &gt; 70, significantly had less cirrhosis caused by viral hepatitis(p &lt; 0.0001) and no prior local therapy (p = 0.002). There was no significant difference in either median A+B doses, cessation of therapy due to toxicities or median reported toxicities of any grade, as reported in Table 1. Most common toxicities in all age groups were fatigue, decreased appetite, proteinuria and transaminitis. There was a significant difference in Hospice enrollment in deceased patients (p = 0.027), with Veterans &gt; 70 years more likely to enroll in Hospice. Conclusions: This is the first known study that reports geriatric advanced HCC patients with A+Z toxicities in VHA patients. This study demonstrates that A+Z can be used safely in geriatric patients. Further quality improvements projects need to be implemented to improve number and timing Hospice utilization.[Table: see text]

Characterization of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement on gadoxetic acid-enhanced MRI via contrast-enhanced ultrasound using perfluorobutane.

Hepatobiliary phase (HBP) hypointense nodules without arterial phase hyperenhancement (APHE) on gadoxetic acid-enhanced MRI (GA-MRI) may be nonmalignant cirrhosis-associated nodules or hepatocellular carcinomas (HCCs). We aimed to characterize HBP hypointense nodules without APHE on GA-MRI by performing contrast-enhanced ultrasound using perfluorobutane (PFB-CEUS). In this prospective, single-center study, participants at high-risk of HCC having HBP hypointense nodules without APHE at GA-MRI were enrolled. All participants underwent PFB-CEUS; if APHE and late, mild washout or washout in the Kupffer phase were present, the diagnosis of HCC was established according to the v2022 Korean guidelines. The reference standard consisted of histopathology or imaging. The sensitivity, specificity, and positive/negative predictive values of PFB-CEUS for detecting HCC were calculated. Associations between clinical/imaging features and the diagnosis of HCC were evaluated with logistic regression analyses. In total, 67 participants (age, 67.0years ± 8.4; 56 men) with 67 HBP hypointense nodules without APHE (median size, 1.5cm [range, 1.0-3.0cm]) were included. The prevalence of HCC was 11.9% (8/67). The sensitivity, specificity, and positive and negative predictive values of PFB-CEUS for detecting HCC were 12.5%(1/8), 96.6%(57/59), 33.3%(1/3) and 89.1%(57/64), respectively. Mild-moderate T2 hyperintensity on GA-MRI (odds ratio, 5.756; P = 0.042) and washout in the Kupffer phase on PFB-CEUS (odds ratio, 5.828; P = 0.048) were independently associated with HCC. Among HBP hypointense nodules without APHE, PFB-CEUS was specific for detecting HCC, which had a low prevalence. Mild-moderate T2 hyperintensity on GA-MRI and washout in the Kupffer phase on PFB-CEUS may be useful to detect HCC in those nodules.

Should we undertake surveillance for HCC in patients with MAFLD?

Over the last decade, metabolic-associated fatty liver disease (MAFLD) has become an important public health issue worldwide. In many countries, MAFLD has become the most common cause of chronic liver disease. On the contrary, hepatocellular carcinoma (HCC) mortality is rising. Liver tumors have become the third cause of cancer mortality worldwide. HCC is the most frequent liver tumor. While the burden of HCC related to viral hepatitis is declining, the prevalence of MAFLD-related HCC is rising rapidly. Classical screening criteria for HCC consider cirrhotic, advanced fibrosis, and viral hepatitis patients. Metabolic syndrome with liver involvement or MAFLD is associated with a higher risk of HCC development, even in the absence of cirrhosis. The question about the cost effectiveness of surveillance for HCC in MAFLD is yet not fully answered. There are no guidelines that address the question of when to start or how to define the population who can benefit of surveillance for HCC in MAFLD patients. This review aims to revise the evidence of HCC development in MAFLD. It hopes to be a step closer to defining screening criteria for HCC in MAFLD.

Hepatocellular Carcinoma Recurrence and Mortality Rate Post Liver Transplantation: Meta-Analysis and Systematic Review of Real-World Evidence.

Simple SummaryThis is a systematic and meta-analysis study that looked at the hepatocellular carcinoma recurrence rate and its risk factors after liver transplantation. The recurrence rate, overall survival rate, and mortality rates in HCC patients post-liver transplantation remain relatively high. Significant regional differences exist in the prevalence of the recurrence, overall survival, and mortality rates. These findings will be of valuable guidance both for clinicians considering patients for an LT, and for providing tailored post-transplant HCC recurrence counselling to different populations with different risk levels. Background: liver transplantation (LT) is the best curative option for eligible patients with hepatocellular carcinoma (HCC), however recurrence remains a major concern. This meta-analysis aimed to investigate the prevalence and risk factors of HCC recurrence. Methods: studies were selected using PubMed, Epistemonikas, and Google Scholar databases published from inception to 15 May 2022 and a meta-analysis of the proportions was conducted. Observational studies reporting the prevalence of recurrent HCC after an LT were included, with the analysis being stratified by an adherence to the Milan criteria (MC), geographical region, AFP levels, and donor type. Results: out of 4081 articles, 125 were included in the study. The prevalence of recurrent HCC was 17% (CI: 15–19). Patients beyond the MC were more likely to recur than patients within the MC. Asian populations had the greatest prevalence of HCC recurrence (21%; CI: 18–24), whereas North American populations had the lowest recurrence (10%; CI: 7–12). The mortality rate after HCC recurrence was 9%; CI: 8–11. North American populations had the greatest prevalence of mortality with 11% (CI: 5–17). Conclusions: the recurrence, overall survival, and mortality rates among patients with HCC post-LT remains high, with substantial differences between regions.

Improved survival of viral hepatocellular carcinoma but not non-viral hepatocellular carcinoma from 2000 to 2020: A multi-centre cohort study of 6007 patients from high-volume academic centres in Japan.

While surveillance improves the early detection of hepatocellular carcinoma (HCC), it is unclear whether this has improved prognosis in clinical practice. To investigate the characteristics and prognoses of patients with viral versus non-viral HCC over the previous two decades in Japan, while HCC surveillance has been active. This multi-centre study enrolled 6007 patients initially diagnosed with HCC between 2000 and 2020 at seven high-volume academic centres. Patients were categorised based on dates of diagnosis: 2000-2006, 2007-2013 and 2014-2020. HCC characteristics and post-diagnosis survival rates were compared between periods in patients with viral and non-viral HCC. The percentage of patients with non-viral HCC increased during the study period. The maximal tumour size and percentage of patients with multinodular HCC decreased significantly over time in the viral HCC group but remained unchanged in the non-viral HCC group. Liver function at diagnosis improved over time in both groups, but to a greater extent in the viral HCC group. Survival rates increased significantly with time in the viral HCC group, but not in the non-viral HCC group. The prevalence of non-viral HCC is increasing. Although the survival of patients with viral HCC improved significantly over the past two decades, there was no improvement in patients with non-viral HCC. This was presumably due mainly to lower surveillance among patients with non-viral HCC and failure to diagnose early-stage HCC.