Young Hepatocellular Carcinoma Patients Research Articles

Abstract 822: A retrospective study on the disparities of hepatocellular carcinoma

Abstract Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and the third leading cause of cancer-related deaths worldwide. Studies report that the incidence of, and mortality from HCC vary significantly by age, sex, and race/ethnicity; however, disparities in the expression level of tumor biomarkers, liver functions, lipid profiles, and comorbidities have not been thoroughly investigated among subpopulations of patient with HCC. Methods: A retrospective study was conducted to review 247 serial HCC cases enrolled in the University of Mississippi Medical Center during June 2000 to May 2023. The entire HCC population was stratified into subpopulations by race, gender, age and BMI. Then comparisons were performed between two corresponding subpopulations in the expression level of HCC-related biomarkers including Alpha-FP, liver functions including albumin, ALT, AST, and ALP, plasma lipid profiles including cholesterol, and comorbidity conditions including cirrhosis in benign liver tissues, smoking, alcohol using, and illness with viral hepatitis. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p<0.05. Results: In total 247 HCC cases, males were 178 (72.1%) and females were 69 (27.9%) with a male to female ratio of 2.6:1; black patients were 108 (43.7%), white patients were 127 (51.4%), and others were 4.9%. The mean age was 59.6 years and mean BMI was 27.04. AFP was the only one of detected tumor biomarkers showing disparities: it was significantly higher in patients of male (p=0.026), younger age (p<0.0001), lower BMI (p=0.039), smokers (p=0.0325) and illness with viral hepatitis (p=0.0007). Disparities in liver functions included: 1) AST was significantly higher in Black HCC patients (p=0.027); 2) no statistical difference of liver functions in gender; 3) younger HCC patients had significantly lower level of Albumin (p=0.006), and higher levels of ALT (p=0.014) and AST (p=0.0032); 4) HCC patients with lower BMI also had lower level of Albumin (p=0.015), and higher levels of AST (p=0.0480 and ALP (p=0.0057). There was no statistical difference of plasma lipid profiles between subpopulations, Black HCC patients except that Black HCC patients had significantly higher levels of cholesterol (p=0.0006) and HDL (p=0.048). In comorbidity, Black HCC patients had higher rates of alcohol using and existence of cirrhosis; and male HCC patients had higher rates of smoking, alcohol usage and viral hepatitis. Conclusions: HCC patients are greatly disparate in the expression level of tumor biomarkers, liver functions, plasma lipid profiles and comorbidity conditions between subpopulations stratified by race, gender, age and BMI. These results could provide useful information for clinical management and prognosis of patients with HCC. Citation Format: Xinchun Zhou, Barrett Aldridge, Nazar Rahmanov, Zhirong Liu, Jinghe Mao, Neha Varshney. A retrospective study on the disparities of hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 822.

Fibrolamellar hepatocellular carcinoma: a case report and gene analysis

BackgroundFibrolamellar hepatocellular carcinoma (HCC) (FL-HCC) is rare in Japan. FL-HCC develops in young patients with no history of cirrhosis and tends to manifest lymphatic metastasis with clinical features similar to those of HCC. We present a case of FL-HCC in a young male patient.Case presentationA 14-year-old male patient underwent abdominal computed tomography (CT) to diagnose appendicitis, wherein a hepatic tumor was detected. Dynamic enhanced CT revealed a 35-mm solid tumor, which contrasted at the early phase of dynamic enhanced study of the right hepatic segments, with occlusion of the right portal vein. We performed right hepatectomy for these lesions. The patient experienced a single lymphatic recurrence on the hepatoduodenal ligament 12 months after the initial surgery. We performed lymphadenectomy for the recurrent tumor. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing of the resected specimens (primary tumor, lymphatic metastasis, and normal liver). RNA-seq detected DNAJB1-PRKACA in both primary and metastatic lesions as previously reported. Furthermore, The Cancer Genome Atlas (TCGA) database was used to compare other gene expressions in this case with those of previously reported cases of FL-HCC and HCC in young patients. Principal component analysis of differentially expressed genes in the top 10% revealed that the gene expression in our case was similar to that of previous FL-HCC cases but was a different cluster from that in HCC cases in young patients. Mutational analysis did not detect any somatic mutations associated with carcinogenesis, including previously reported mutations (Kastenhuber et al. in Proc Natl Acad Sci USA 114: 13076–84, 2017).ConclusionWe encountered a case of FL-HCC, a rare hepatic tumor in an adolescent patient, and evaluated the genetic background. Our findings could contribute to the elucidation of the mechanisms underlying carcinogenesis and progression in patients with FL-HCC and thereby contribute to the development of new therapeutic strategies in the future that may improve patient prognosis.

Equal Efficacy and Safety Profile in Elderly Patients with Hepatocellular Carcinoma Receiving Palliative Treatment.

Simple SummaryHepatocellular carcinoma (HCC) is the most common primary liver tumor and a leading cause of cancer-related death worldwide with an increasing incidence, especially in elderly people. However, as elderly patients are often characterized by other comorbidities and frailty, palliative treatment in this subgroup of patients remains challenging for clinicians. In this retrospective study, we found a good tolerability and safety of elderly patients receiving palliative treatment for metastatic HCC, primarily transarterial chemoembolization and systemic treatment. Furthermore, we found no significant difference in terms of overall survival between younger and older patients in this cohort.Palliative treatment of elderly patients with hepatocellular carcinoma (HCC) is often challenging due to comorbidities or frailty, and data about the outcome and overall survival (OS) in these patients are limited. This was a retrospective single centre study. Patients were grouped according to their age as young (<60 years; YP), intermediate (60–70 years; IP) or elderly (>70 years; EP). Administration of chemotherapy or transarterial chemoembolization (TACE) was defined as palliative treatment. Therapy-related adverse events (AE) were assessed via CTCAE 5.0. Out of 656 patients analyzed, n = 359 received palliative treatment: YP: n = 90; IP: n = 127 and EP: n = 142. The median OS (months) in patients receiving TACE (n = 254) was 17 vs. 18 vs. 20 months for YP, IP, and EP, respectively (p = 0.44) and 15 vs. 16 vs. 17 months (p = 0.56), respectively, in patients receiving chemotherapy (n = 105). AEs differed non-significantly between the subgroups. Multivariate analysis revealed impaired liver function and advanced tumor stage as significant factors for impaired OS. In this study, the mOS and rate of AEs were equal between elderly and younger HCC patients receiving palliative treatment. Therefore, we propose regular palliative treatment stratification in spite of the high age of patients.

The Age-Specific Features and Clinical Significance of NRF2 and MAPK10 Expression in HCC Patients

BackgroundNuclear factor (erythroid-derived 2)-like 2 (NRF2) functions decline with age; however, cancer cells can hijack its pathways to ensure survival and aggressiveness. Yet, the role of NRF2 in hepatocellular carcinoma (HCC) is rarely investigated in an age-specific manner. This study investigates the expression of NRF2 and its activator (MAPK10) in different age groups of HCC patients, in addition to the age-specific features of NRF2 and MAPK10 interaction and their clinical significance.MethodsTumor and near-tumor tissue samples of 181 HCC patients were used to complete a protein expression analysis of NRF2 and MAPK10. Patients’ survival and clinical data were collected for clinical analysis. Global databases (TCGA, ICGC) were used to collect MAPK10 genetic mutation and mRNA expression data in patients with HCC, colorectal, stomach, and pancreatic cancers.ResultsOur findings revealed an increase in NRF2 protein expression but only in younger HCC patients, along with a decline in MAPK10 ability to activate NRF2 in older patients. We also found an increased MAPK10 genetic mutation rate and decreased mRNA expression in older patients. Low MAPK10 and NRF2 expression levels were associated with shorter survival and poorer prognosis due to positive correlation with microvascular invasion, tumor thrombus, elevated AFP levels, and larger tumor size.ConclusionNRF2 expression and oxidative stress mechanism in HCC patients are influenced by age. This magnifies the need to consider patients’ age in treatment strategies and guidelines and re-evaluates the application of studies’ age-standardized findings in older patients who are usually excluded from relevant research.

A nomogram to predict prognosis after surgery for young patients with hepatocellular carcinoma.

BackgroundOnly few studies have been evaluated the clinical characteristics and prognosis of hepatocellular carcinoma (HCC) in young patients. The purpose of this study is to identify prognostic factors and develop an efficient and practical nomogram to predict cancer-specific survival (CSS) in young patients with HCC.MethodsFour hundred and forty-one young patients with HCC who had undergone surgery from 2004–2015 were selected from the Surveillance, Epidemiology, and End Results (SEER) database. The competing risk model, Lasso and Cox regression were used to screen prognostic factors for CSS, and a prognostic nomogram was established using these factors. Thirty-nine young patients with HCC from the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Science were used to validate our model. To further evaluate the predictive performance of our model, the concordance index was calculated and the calibration curves were drawn. The clinical usefulness was evaluated by decision curve analysis (DCA). Finally, all patients were grouped by our nomogram. The survival of different risk groups was analyzed using the Kaplan-Meier method, and the differences among survival curves were compared by the log-rank test.ResultsThe median survival times of the SEER training group and the external National Cancer Center validation group were 41 and 52 months, respectively. Histological grade, tumor size, Alpha-fetoprotein (AFP), T stage, and M stage were selected as independent factors for CSS, and a prognostic nomogram was established. The concordance indices of the training and external validation groups were 0.76 (95% CI, 0.72 to 0.80) and 0.92 (SE=0.085), respectively. The calibration plots showed good agreement. DCA revealed that our nomogram resulted in a better clinical net benefit than the AJCC 7th edition and Barcelona Clinic Liver Cancer staging systems. Patients were divided into two risk groups according to the cut-off value of 125 of the total points from our nomogram. Kaplan-Meier plots for CSS were performed using the log-rank test, the P-value of which was <0.001.ConclusionsThe practical nomogram resulted in a more-accurate prognostic prediction for young HCC patients after curative liver resection.

A nomogram predicting the prognosis of young adult patients diagnosed with hepatocellular carcinoma: A population-based analysis

BackgroundFew studies have reported the clinical characteristics and outcomes of young adult patients diagnosed with hepatocellular carcinoma (HCC). This study aimed to formulate a nomogram to predict the prognosis of young adult HCC patients.MethodsYoung adult patients diagnosed with HCC from 2004 to 2015 were screened from the Surveillance, Epidemiology, and End Results (SEER) database. Based on the multivariate analysis results, a nomogram was constructed. The concordance index (c-index) and calibration were used to assess the predictive performance of the nomogram. The clinical benefit was measured by using decision curve analysis (DCA).ResultsThe mean follow-up time of the patients was 25.0±34.0 months. Gender, race, AFP level, Edmondson–Steiner classification, treatment and TNM stage were selected as independent prognostic factors and integrated into the nomogram. The c-indexes of the two sets were 0.786 and 0.775, respectively. The calibration curves showed good agreement between the nomogram-predicted probability and the actual observations. Furthermore, the DCA indicated that the nomogram had positive net benefits compared with the conventional staging system.ConclusionsThe nomogram could accurately predict the prognosis of young adult HCC patients.

Liver clear cell foci and viral infection are associated with non-cirrhotic, non-fibrolamellar hepatocellular carcinoma in young patients from South America

We previously described a divergent clinical and molecular presentation of hepatocellular carcinoma (HCC) in Peru. The present study aimed to further characterize the tissue features associated with this singular nosological form of HCC in order to gain insight into the natural history of the disease. We performed an exploratory analysis of the histology of both tumor and non-tumor liver (NTL) tissues from 50 Peruvian HCC patients, and compared with that of 75 individuals with non-HCC liver tumor or benign liver lesions as a baseline for NTL features. We complemented this approach with a transcriptome analysis in a subset of NTL tissue samples and also performed an ultra-sensitive hepatitis B virus (HBV) detection in liver tissues of the patients. Overall, results highlighted the low rate of liver parenchymal alterations in a young patient cohort (median age: 40 years old), despite a strong prevalence of underlying HBV infection (c. 67%). Withal, liver clear cell foci of cellular alteration were genuinely associated with HCC and appended to some changes in immune and G protein-coupled receptor gene expression ontologies. Our findings confirm the occurrence of a particular setting of HCC in South America, a region where the pathophysiology of liver cancer remains largely unexplored.

Perioperative Outcomes of Laparoscopic Minor Hepatectomy for Hepatocellular Carcinoma in the Elderly.

This study aims to evaluate the safety and feasibility of laparoscopic minor hepatectomy (LMH) in elderly patients with hepatocellular carcinoma (HCC). A total of 40 consecutive elderly (≥ 70years) patients were compared with 94 young patients (< 70years). The 40 patients were also compared with 85 consecutive elderly patients who underwent open minor hepatectomies (OMH). After 1:1 propensity-score matching (PSM), 32 LMHs were compared with 32 OMHs in elderly patients. Comparison between the baseline characteristics of elderly and young HCC patients showed that elderly patients were significantly more likely to have comorbidities, ASA score > 2, non-hepatitis B, previous liver resection and larger tumor size. Comparison between perioperative outcomes demonstrated that elderly patients were significantly more likely to have a longer operation time, increased blood loss, increased need for blood transfusion, longer Pringles duration and longer postoperative stay. Comparison between LMH and OMH in elderly patients demonstrated no significant difference in baseline characteristics except the LMH cohort were significantly more likely to have > 1 comorbidity, higher platelet count and lower median AFP level. Comparison between outcomes before and after PSM demonstrated that LMH was associated with longer operation time, increased blood loss, longer Pringles duration but decreased postoperative pulmonary complications and shorter postoperative stay compared to OMH. LMH is safe and feasible in elderly patients with HCC. However, LMH in elderly patients is associated with poorer perioperative outcomes compared to LMH in young patients. Comparison between LMH and OMH in elderly patients demonstrated advantages in terms of decreased pulmonary complications and shorter length of stay at the expense of increased operation time and blood loss.

Short- and Long-term Outcomes between Young and Older HCC Patients Exceeding The Milan Criteria after Hepatectomy

Aim. The objective of this study was to evaluate short- and long-term survival after surgical treatment between young and older hepatocellular carcinoma (HCC) patients beyond the Milan criteria.Material and methods. One hundred fifty-seven HCC patients (≤ 55 years old) were categorized into group A, and one hundred fifty-eight HCC patients (> 55 years old) were categorized into group B. Postoperative complications and overall survival were retrospectively analyzed.Results. Older HCC patients had a higher rate of delayed extubation after surgery and suffered more complications after surgery, especially major complications. Intraoperative blood transfusion, liver fibrosis/cirrhosis and delayed extubation were risk factors related to postoperative complications. Microvascular invasion (MVI), tumor diameter, postoperative alpha-fetoprotein and the presence of satellites were independent risk factors for long-term survival. Young patients had more advanced tumors. Overall survival rates at 1, 3 and 5-years were 78.1%, 45.1% and 27.4% for young patients, respectively, and 86.5%, 57.5% and 42.4% for older patients, respectively (p = 0.007).Conclusion. The category A group had poorer tumor characteristics and worse prognoses than the category B group.

Clinical characteristics and survival outcomes of super-elderly hepatocellular carcinoma patients not indicated for surgical resection.

Considering the dramatic increase in average life expectancy during the 20th century throughout the world, the management of elderly patients with cancer has become a global issue. We herein investigated the clinical characteristics and outcomes of super-elderly hepatocellular carcinoma (HCC) patients over 80 years old not indicated for surgical resection. We retrospectively evaluated 206 newly diagnosed HCC patients. The patients were divided into two groups according to their age at inclusion; a super-elderly group (n = 37, ≥80 years) and a younger group (n = 169, <80 years). We compared the clinical characteristics, overall survival (OS) and disease-specific survival (DSS) rates among the two groups. Both univariate and multivariate analyses were performed to identify the factors associated with the OS and DSS. The proportion of women was higher in the super-elderly group than in the younger group (P = 0.017). There were no significant differences in the OS (P = 0.171) or DSS (P = 0.176) between the two groups. The multivariate analysis revealed that only the Cancer Liver Italian Program score (hazard ratio [HR], 2.972; P < 0.0001; HR, 3.694; P < 0.0001) was independently associated with the OS and DSS. Age was not found to be associated with the OS or DSS according to either the univariate or multivariate analysis. There were no significant differences in the OS and DSS rates among the super-elderly HCC patients and younger HCC patients not indicated for surgical resection. An advanced age itself does not restrict the therapeutic approach, even in super-elderly HCC patients not indicated for surgical resection.

Forfeited hepatogenesis program and increased embryonic stem cell traits in young hepatocellular carcinoma (HCC) comparing to elderly HCC

BackgroundHepatocellular carcinoma (HCC) in young subjects is rare but more devastating. We hypothesize that genes and etiological pathways are unique to young HCC (yHCC; ≤40 years old at diagnosis) patients. We therefore compared the gene expression profiles between yHCCs and HCCs from elderly patients.ResultsAll 44 young HCCs (≤40 years old at the diagnosis; 23 cases in the training set while another 21 in the validation cohort) were positive for serum hepatitis B surface antigen (HBsAg), but negative for antibodies to hepatitis C virus (anti-HCV). All 48 elderly (>40 years old; 38 in the training set while another 10 in the validation cohort) HCC patients enrolled were also serum HBsAg positive and anti-HCV negative. Comparative genomics analysis was further performed for elucidating enriched or suppressed biological activities in different HCC subtypes.The yHCC group showed more macroscopic venous invasions (60.9% vs. 10.5%, p < 0.001), fewer associated cirrhosis (17.4% vs. 63.2%, p < 0.001), and distinct profiles of expressed genes, especially those related to DNA replication and repair. yHCCs possessed increased embryonic stem cell (ESC) traits and were more dedifferentiated. A 309-gene signature was obtained from two training cohorts and validated in another independent data set. The ILF3 ESC gene, which was previously reported in poorly differentiated breast cancers and bladder carcinomas, was also present in yHCCs. Genes associated with HCC suppression, including AR and ADRA1A, were less abundant in yHCCs. ESC genes were also more enriched in advanced HCCs from elderly patients.ConclusionThis study revealed the molecular makeup of yHCC and the link between ESC traits and HCC subtypes. Findings in elderly tumors, therefore, cannot be simply extrapolated to young patients, and yHCC should be treated differently.

Clinical characteristics, treatment patterns and survival outcome of hepatocellular carcinoma patients aged 70 years or older: a single-center retrospective study from China

The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. Clinical data of 164 "elderly" (≥70years old) and 531 "younger" (<70years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. Compared with younger patients, the elderly patients had a higher proportion of females (32.9% vs. 18.1%, p<0.001), less hepatitis B virus (HBV) infection (40.9% vs. 76.6%, p<0.001), more hepatitis C virus (HCV) infection (23.8% vs. 5.6%, p<0.001), less liver cirrhosis (68.3% vs. 76.8%, p=0.03) and massive tumors (12.8% vs. 21.8%, p=0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6% vs. 29.6%, p<0.001) and more supportive care (48.8% vs. 37.9%, p=0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p=0.75). Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.

A Comparative Analysis of Hepatocellular Carcinoma after Hepatic Resection in Young versus Elderly Patients

PurposeThe aim of this study was to investigate the clinical outcomes after surgical treatment of hepatocellular carcinoma (HCC) in the elderly patients compared with younger patients. MethodsClinicopathological data and treatment outcomes in 61 elderly (≥70 years old) and 90 younger (≤40 years old) patients with HCC who underwent curative liver resection between 2000 and 2010 were retrospectively collected and compared using various parameters. ResultsThe older HCC group was more likely to have hepatitis C virus and non-B non-C hepatitis virus infection, higher values of indocyanine green retention at 15 min (ICGR)15, more preoperative comorbidities, and more postoperative complications. There were no significant differences in intraoperative parameters and pathologic features. The recurrence rate, overall survival and disease-free survival rates were similar amongst the two groups. The only independent prognostic factor of overall survival was postoperative complications. ConclusionOur findings suggest that age by itself does not have an adverse effect on operative outcomes, including long-term prognosis. For young and elderly HCC patients, hepatic resection is a safe and effective treatment.

Younger Hepatocellular Carcinoma Patients Have Better Prognosis After Percutaneous Radiofrequency Ablation Therapy

To evaluate the impact of age on the prognosis of patients with hepatocellular carcinoma (HCC) undergoing percutaneous radiofrequency ablation (RFA). Whether age plays an important role in the outcomes of HCC after RFA remains controversial. Two hundred fifty-eight consecutive treatment naive HCC patients who underwent RFA were enrolled. Patients aged ≤ 65 years (n = 100) were defined as the younger group and those aged > 65 years (n = 158) were the elderly group. Their clinicopathologic features and prognosis were compared. Younger patients had a higher male-to-female ratio, higher prevalence of hepatitis B virus, and smaller tumor size than elder patients. After median follow-up of 28.5 ± 18.7 months, 45 patients died. The cumulative 5-year survival rates were 81.3% and 65.4% in younger and elder HCC patients, respectively (P = 0.008). Multivariate analysis disclosed that age > 65 years, serum albumin level ≤ 3.7 g/dL, prothrombin time international normalized ratio > 1.1, α-fetoprotein (AFP) > 20 ng/mL, and no antiviral therapy after RFA were independent risk factors associated with poor overall survival. Besides, there were 163 patients with tumor recurrence after RFA. Multivariate analysis showed that age > 65 years, platelet count ≤ 10/mm, AFP > 20 ng/mL, multinodularity, and tumor size > 2 cm were the independent risk factors predicting recurrence. Both liver functional reserve (serum albumin level, prothrombin time international normalized ratio, platelet count, and antiviral therapy) and tumor factors (tumor size, number, and AFP level) were crucial in determining post-RFA prognosis in HCC patients. Moreover, younger HCC patients have better overall survival and lower recurrence rate after RFA compared with elder patients.

Clinicopathological Features and Outcomes of Young Patients with Hepatocellular Carcinoma after Hepatectomy

There are few reports about hepatectomy for young patients with hepatocellular carcinoma (HCC), and the significance of resection for young patients remains unknown. The present study aimed to investigate retrospectively the clinicopathological features and outcomes after hepatectomy of young HCC patients. Among 610 patients who underwent curative hepatectomy for HCC between January 1987 and December 2007, 13 patients younger than 40 years of age were defined as the young group. Because none of the young group had hepatitis C virus antibodies (HCVAb), 246 patients aged above 40 years without HCVAb were defined as the older group. The clinicopathological findings and outcomes after hepatectomy were compared between the two groups. In the young group, 7 patients had hepatitis B surface antigen and 3 other patients had hepatitis B core antibodies. The young group had better liver function but more advanced HCC, with a large tumor size and a high incidence of portal vein invasion compared with the older group. Major hepatectomy was more frequently chosen in the young group than in the older group. There was no significant difference in the incidences of postoperative complications. The overall survival tended to be better in the young group than in the older group (p=0.057). Hepatitis B virus-related HCC was common in the younger group of patients reported here. Although the young patients had advanced HCC, there were no significant differences in the complication rate and the overall survival rate of the young and older groups. Aggressive hepatic resection for young patients would contribute to improved survival and should be recommended.

Radiofrequency ablation therapy for hepatocellular carcinoma in elderly patients

With the aging of society, the number of elderly patients with hepatocellular carcinoma (HCC) has been increasing in Japan. The Government of Japan defines elderly as being over 65 and has divided the elderly into two stages: the first elderly stage (< 75 years old) and the second elderly stage (> or = 75). We investigated the efficacy and safety of radiofrequency ablation therapy (RFA) in patients in the second elderly stage in comparison with other HCC patients, retrospectively. Two hundred six patients with HCC, who were within the Milan criteria, with low-grade performance status (0 or 1) and a Child-Pugh classification of A or B were enrolled. All were treated with RFA from January 2000 to December 2008 as an initial therapy and were divided into elderly HCC group (e-HCC group; > or = 75, n = 63) and non e-HCC group (< 75, n = 143), and their clinical data and survival rates were compared. Age and the level of protein induced by vitamin K absence or antagonist (PIVKA-II) were higher in the e-HCC group as compared with the non e-HCC group (78.3 +/- 3.2 vs 64.2 +/- 7.5 years, 676.3 +/- 2643.7 vs 142.4 +/- 442.2 mAU/mL: P < 0.01, respectively). There were no significant differences for Child-Pugh class, tumor node metastasis stage, and Japan Integrated Stage score and in survival rates after 3, and 5 years between the groups (e-HCC group: 82.5% and 49.7%, respectively; non e-HCC group: 78.3% and 57.5%, respectively). There were no severe complications in the e-HCC group. Elderly HCC patients, who have good performance status, should be treated in the same manner and with the same strategy as young HCC patients.

Correlation of preoperative neutrophil-to-lymphocyte ratio to prognosis of young patients with hepatocellular carcinoma

As an index of inflammation, neutrophil-to-lymphocyte ratio (NLR) is regarded as one of prognostic factors of hepatocellular carcinoma (HCC). This study was to evaluate the correlation of preoperative NLR to the prognosis of young HCC patients after radical resection. Clinical data of 91 HCC patients with age of younger than 35 years who underwent radical resection from 2000 to 2005 were analyzed. According to preoperative NLR, the patients were divided into the low NLR group (NLR<or=2) and the high NLR group (NLR>2). The overall and disease-free survival rates of the two groups were compared. The 1-and 3-year overall survival rates were 92.9% and 85.6% in the low NLR group, 89.8% and 57.1% in the high NLR group; the 1-and 3-year disease-free survival rates were 85.3% and 80.0% in the low NLR group, 69.1% and 43.5% in the high NLR group. The difference between the two groups was significant (P<0.05). Cox multivariate analysis showed that preoperative NLR and tumor size were independent prognostic factors of disease-free survival and overall survival for young HCC patients after radical resection. Preoperative NLR>2 was a negative prognostic factor of disease-free and overall survival for young HCC patients after radical resection.

Hepatitis B Virus Double Mutations is There any Role in Pathogenesis of Hepatocellular Carcinoma in Young Patients

Background: The incidence of hepatocellular carcinoma (HCC) below age 40 years old in our institution were relatively high compared with other institutions in Asia. Hepatitis B virus (HBV) basal core promoter (BCP) double mutations correspond with increasing age. The aim of this study was to know if there was any role of HBV double mutations in young HCC patients. Method: A descriptive study was performed on HBV related HCC patients in Cipto Mangunkusumo Hospital in May 2006-November 2008. Patient were recruited consecutively and divided in to two groups, below 40 and above 40 years old. The genotypes were examined by polymerase chain reaction (PCR) method. The alpha feto protein (AFP) values were diagnosed based on ELISA method. The BCP A1762T/G1764A double mutations were examined by direct sequencing. Results: There were 49 HBV related HCC samples consist of 14 (28.5%) samples with age below 40 years old and 35 (71.5%) samples with age above 40 years old. We only found two genotype, genotype B was dominant in patients with HBV related HCC compare to genotype C, 43 (88%) and 6 (12%) respectively. The increasing of AFP level above 400 ng/mL was only found in about half of the samples, 7 (50%) 40 years old. Double mutations of A1762T/G1764A in BCP occurred in 5 (36%) 40 years old. Conclusion: The incidence of HBV related HCC in young patients were relatively high. The proportion of patients with AFP level < 400 ng/mL in patients below 40 years old were higher compared to patients above 40 years. Keywords : hepatocellular carcinoma, BCP double mutation, HBV genotype

Is the prognosis of young patients with hepatocellular carcinoma poorer than the prognosis of older patients? A comparative analysis of clinical characteristics, prognostic features, and survival outcome

Hepatocellular carcinoma (HCC) is uncommon in young adults. This study examined the clinical characteristics and survival outcome of young HCC patients compared with those in older patients. Data were prospectively collected from 638 patients diagnosed with HCC over a 9-year period. Patients aged < or =40 years at diagnosis of HCC were defined as young HCC patients. Their clinical characteristics and survival was compared with those aged >40 years. The prevalence of young HCC was 8.6% (55/638). Young HCC patients had a significantly higher rate of hepatitis B-related disease (HBsAg positivity: 85.5% vs. 59.7%, P = 0.003), better Child-Pugh status (Child-Pugh class A: 69.1% vs. 43.9%, P = 0.002), and lower rates of cirrhosis (12.7% vs. 34.3%, P = 0.001) compared with the older group. They had more advanced disease at diagnosis, with higher alpha-fetoprotein levels (>12 000 microg/l: 45.4% vs. 30.5%, P = 0.026), a higher incidence of portal vein involvement (63.6% vs. 40%, P = 0.003), and a more advanced TNM stage (TNM IV: 83.6% vs. 66.4%, P = 0.018). More young patients were eligible for surgical resection (18.2% vs. 8.2%, P = 0.014). The overall survival between the two groups was similar, but when the patients were stratified for stage of disease, the median survival of young patients with early disease was superior to that of older patients (51.2 vs. 11.6 months, P = 0.025). HCC in young adults occurs mainly in hepatitis B carriers and is often diagnosed at an advanced stage. Their survival outcome is not different from that of older patients because the advanced disease at presentation offsets the advantages of better liver function and a higher resection rate. However, there is a distinct survival advantage for young patients diagnosed with early disease. These results support the importance of extending HCC surveillance to young hepatitis B carriers.

Do young hepatocellular carcinoma patients with relatively good liver function have poorer outcomes than elderly patients?

The risk of hepatocellular carcinoma (HCC) is known to be age dependent; the influence of age on prognosis is, however, controversial. The aim of this study was to compare the tumor characteristics and survival rates of young and old HCC patients, with respect to tumor stage. We reviewed the clinical data and survival times of 71 young HCC patients from 1987 to 2003 and compared these with those of their older counterparts (n = 239). Patients were categorized into three age groups: group A, age <30 years (n = 71); group B, age >/=30 to <61 years (n = 168); and group C, age >/=61 years (n = 81). Kaplan-Meier methods and Cox proportional hazards regression were used to analyze survival. The overall survival time of group A was shorter than groups B or C (P = 0.0071). Survival was not different in the three groups in subgroup analysis according to several tumor staging systems (e.g. Japan Integrated Staging score, Cancer of the Liver Italian Program scoring system and Barcelona Clinic Liver Cancer staging classification). The multivariate hazard ratio of group B was 0.840 (95% confidence interval [CI] 0.490-1.440) and that of group C was 0.770 (95% CI 0.410-1.446) in reference to group A. Young HCC patients showed a poorer prognosis than older HCC patients because they have a more advanced tumor stage at diagnosis. However, age was not an independent prognostic factor when stages were matched. Therefore, we suggest that periodic surveillance in young chronic hepatitis B virus carriers would improve outcomes.