• Asian Pacific Journal of Cancer Prevention
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• 제17권5호
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• pp.2539-2543
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• 2016

Background: In the Barcelona Clinic Liver Cancer (BCLC) system, only sorafenib is suggested for HCC patients having performance status (PS) 1 or 2 even if they have treatable lesions. In the current study, we aimed to explore the outcome of using aggressive treatment for HCC patients with PS 1 and 2. Materials and Methods: Five hundred and twenty four patients with HCC were enrolled in this study and divided into 2 groups: 404 PS 1 and 120 PS 2. Of the included 524 patients, 136 recceived non-aggressive supportive treatment and sorafenib, while 388 patients were offered aggressive treatment in the form of surgical resection, transplantation, percutaneous ablation, trans-arterial chemoembolization and/or chemoperfusion. All the patients were followed up for a period of 2 years to determine their survival. Results: Most HCC patients were CHILD A and B grades (89.4% versus 85.0%, for PS1 and PS2, respectively). Patients with PS1 were significantly younger. Out of the enrolled 524 patients, 388 were offered aggressive treatment, 253 (65.2%) having their lesions fully ablated, 94 (24.2%) undergoing partial ablation and 41 patients with no ablation (10.6%). The median survival of the patients with PS 1 who were offered aggressive treatment was 20 months versus 9 months only for those who were offered supportive treatment and sorafenib (p<0.001). Regarding HCC patients with PS 2, the median survivals were similarly 19.7 months versus 8.7 months only (p<0.001). Conclusions: Aggressive treatment of HCC patients with PS 1 and 2 significantly improves their survival. Revising the BCLC guidelines regarding such patients is recommended.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7825-7829
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• 2015

Background: Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum B2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. Materials and Methods: In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. B2M levels were measured in serum with a fully-automated IMX system. Results: The mean serum B2M level of Group (1) was $4.25{\pm}1.48{\mu}g/ml$., Group (2) was $7.48{\pm}3.04$, Group (3) was $6.62{\pm}2.49$ and Group (4) was $1.62{\pm}0.63$. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis ($7.48{\pm}3.04$) and HCC groups ($6.62{\pm}2.49$) than the HCV group ($4.25{\pm}1.48$) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB andWBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%.The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Conclusions: Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.3915-3920
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• 2014

Background: Hepatocellular carcinoma (HCC) is a dismal tumor with a high incidence, prevalence and poor prognosis and survival. Management of HCC necessitates multidisciplinary clinics due to the wide heterogeneity in its presentation, different therapeutic options, variable biologic behavior and background presence of chronic liver disease. We studied the different prognostic factors that affected survival of our patients to improve future HCC management and patient survival. Materials and Methods: This study is performed in a specialized multidisciplinary clinic for HCC in Kasr El Eini Hospital, Cairo University, Egypt. We retrospectively analyzed the different patient and tumor characteristics and the primary mode of management applied to our patients. Further analysis was performed using univariate and multivariate statistics. Results: During the period February 2009 till February 2013, 290 HCC patients presented to our multidisciplinary clinic. They were predominantly males and the mean age was $56.5{\pm}7.7years$. All cases developed HCC on top of cirrhosis that was mainly due to HCV (71%). Most of our patients were Child-Pugh A (50%) or B (36.9%) and commonly presented with small single lesions. Transarterial chemoembolization was the most common line of treatment used (32.4%). The overall survival was 79.9% at 6 months, 54.5% at 1 year and 22.4% at 2 years. Serum bilirubin, site of the tumor and type of treatment were the significant independent prognostic factors for survival. Conclusions: Our main prognostic variables are the bilirubin level, the bilobar hepatic affection and the application of specific treatment (either curative or palliative). Multidisciplinary clinics enhance better HCC management.

• Journal of Ginseng Research
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• 제35권1호
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• pp.69-79
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• 2011

Hepatocellular carcinoma (HCC) is the fi fth most common malignancy in the world and complicates liver cirrhosis related to hepatitis C virus (HCV) in many cases. We evaluated the therapeutic effect of Korean red ginseng extract (KGE) in patients with chronic liver diseases. Thirty male and female patients with HCC and another thirty with liver cirrhosis were included. Each category was divided into two groups; the first was used as control group, and received medical therapy only and the second group received the medical therapy supplemented with KGE capsules. The treated group with HCC received three KGE capsules/day (900 mg) while the treated group with HCV received two KGE capsules/day (600 mg) for 11 weeks along with their medical therapy. All patients were subjected to clinical examination and laboratory investigations, including liver function tests (at baseline, after 6 weeks of treatment and at the end of the study) and abdominal ultrasonography. Patients showing focal hepatic lesions were subjected to triphasic spiral abdominal computerized tomography and alpha-fetoprotein (AFP). HCV RNA was determined quantitatively by Roche for patients in the HCV group. Results showed that the medical therapy alone failed to normalize the liver enzymes or decrease the virus concentration. KGE administration induced a significant improvement in liver function tests, decreased the tumor marker (AFP) levels, and decreased the viral titers in HCV patients. Thus, KGE demonstrated powerful therapeutic effects against HCV and liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.1281-1287
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• 2015

Background: Early detection of hepatocellular carcinoma using serological markers with better sensitivity and specificity than alpha fetoprotein (AFP) is needed. Aims: The aim of this study was to evaluate the diagnostic value of serum sICAM-1, ${\beta}$-catenin, IL-8, proteasome and sTNFR-II in early detection of HCC. Materials and Methods: Serum levels of IL-8, sICAM-1, sTNFR-II, proteasome and ${\beta}$-catenin were measured by ELISA assay in 479 serum samples from 192 patients with HCC, 96 patients with liver cirrhosis (LC), 96 patients with chronic hepatitis C (CHC) and 95 healthy controls. Results: Serum levels of proteasome, sICAM-1, ${\beta}$-catenin and ${\alpha}FP$ were significantly elevated in HCC group compared to other groups (P-value<0.001), where serum level of IL-8 was significantly elevated in the LC and HCC groups compared to CHC and control groups (P-value <0.001), while no significant difference was noticed in patients with HCC and LC (P-value=0.09). Serum level of sTNFR-II was significantly elevated in patients with LC compared to HCC, CHC and control groups (P-value <0.001); also it was significantly higher in HCC compared to CHC and control groups (P-value <0.001). ROC curve analysis of the studied markers between HCC and other groups revealed that the serum level of proteasome had sensitivity of 75.9% and specificity of 73.4% at a cut-off value of $0.32{\mu}g/ml$ with AUC 0.803 sICAM-1 at cut off value of 778ng/ml, the sensitivity was 75.8% and the specificity was 71.8% with AUC 0.776. ${\beta}$-catenin had sensitivity and specificity of 70% and 68.6% respectively at a cut off value of 8.75ng/ml with an AUC of 0.729. sTNFR-II showed sensitivity of 86.3% and specificity of 51.8% at a cut off value of 6239.5pg/ml with an AUC of 0.722. IL-8 had sensitivity of 70.4% and specificity of 52.3% at a cut off value of 51.5pg/ml with AUC 0.631. Conclusions: Our data supported the role of proteasome, sICAM-1, sTNFR-II and ${\beta}$-catenin in early detection of HCC. Also, using this panel of serological markers in combination with ${\alpha}FP$ may offer improved diagnostic performance over ${\alpha}FP$ alone in the early detection of HCC.

• Asian Pacific Journal of Cancer Prevention
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• 제14권11호
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.