Okuda Stage Research Articles

A Clinicopathological Study of Hepatocellular Carcinoma: A Cross Sectional Study

The purpose of the present study was to find out the clinicopathological characteristics of Hepatocellular Carcinoma (HCC) patients. All the clinically suspected patients were recruited as per inclusion and exclusion criteria. The relevant socio-demographic characteristics, clinical findings as well as the physical examination were performed after talking written consent from all the study subjects. The ultrasonography was performed to all the patients. After that, the patients were sent to the department of pathology for histopathological examination. The descriptive cross-sectional study was carried out in the Department of Oncology of National Institute of Cancer Research and Hospital (NICRH), Dhaka, Bangladesh from July 2014 to June 2015 for a period of 12 months. Total sample size was 52 in this study and age distribution of HCC was found from 25 years to 97 years to with the mean age 50.57 ± 12.09 years. Males were predominant (78.0%), male and female ratio was 3.72:1. The common presenting features of HCC were abdominal pain and swelling, fever and jaundice; viral marker was positive in 86.5% of patients (HBsAg-67.3%, Anti HCV-19.2%) with normal tumor marker alpha-fetoprotein (AFP) in 69% of the patients. Okuda staging shows 82.7% patients within stage I and Stage II and performance status, 38.5% patients were unable to carry out normal activity. Sonological findings revealed 69.2% patients had ≤2 cm tumor size, 88.4% had ascites lastly splenomegaly was present among 86.5% respondents.

Safety and Long-Term Survival Outcome in Patients With Unresectable Barcelona Clinic Liver Cancer (BCLC) Stages C and D Advanced Hepatocellular Carcinoma Treated With 40 μm Drug-Eluting Bead Transcatheter Arterial Chemoembolization.

BackgroundTo evaluate the safety, treatment response, and overall survival (OS) following drug-eluting bead transarterial chemoembolization (DEB-TACE) using doxorubicin-loaded 40 μm microspheres in patients with advanced hepatocellular carcinoma (HCC).MethodsThis was a single-center retrospective evaluation of patients with unresectable HCC without extrahepatic spread and Barcelona Clinic Liver Cancer (BCLC) stages C and D disease who underwent DEB-TACE between August 2015 and January 2018. Pre-treatment data included demographics, medical history, cancer staging, tumor size, laboratory results, and prior treatments for HCC. Follow-up data included the date of DEB-TACE treatments or microwave ablation (MWA) procedures, laboratory test results, adverse events, treatment response, and the date and cause of death.ResultsThirty-two patients met the study inclusion criteria. Eighteen patients (56.3%) underwent a single DEB-TACE and 14 patients (43.8%) had two to five DEB-TACE procedures. Five patients (15.6%) had MWA following initial DEB-TACE. Mild postembolization syndrome occurred in six patients (18.8%) during a 30-day period following initial DEB-TACE. Seven patients (21.9%) experienced worsening ascites, pleural fluid, or encephalopathy during the study observation period. Three patients had moderate to severe worsening liver function tests 90 days post-procedure. Seventeen patients (53.1%) had a complete or partial response and nine patients (28.1%) had disease progression. Median OS was 15.0±14.4 months from the time of initial DEB-TACE, with 63% and 33% of patients still alive at 12 and 24 months. Multivariate analyses identified that Okuda Stage (P=0.03) and Cancer of the Liver Italian Programme (CLIP) score (P=0.05) were significantly associated with overall survival after adjusting for other covariates. There were four HCC-related deaths during the 30-day post-procedure period.ConclusionDEB-TACE with small 40 μm doxorubicin-loaded microspheres is a safe and effective treatment for unresectable patients with BCLC stages C and D advanced HCC. Patients with advanced, high-risk unresectable HCC should be considered for DEB-TACE as opposed to supportive or palliative care alone.

Profile of patients with hepatocellular carcinoma: An experience from a tertiary care center in India

BackgroundThe prevalence of hepatocellular carcinoma (HCC) is increasing worldwide and it is now the third most common cause of cancer-related death. HCC is becoming a major health burden with steadily increasing incidence globally.MethodsThis is an observational study over a 3-year period in a tertiary care center in India. Three hundred and thirty-nine patients diagnosed to have HCC were included in this study. Patients’ clinical, etiological, radiological and cytohistological data and therapy offered were recorded and analyzed.ResultsCirrhosis of the liver was seen in 73.2% of the patients. 16.8% of patients were asymptomatic at the time of presentation. Ascites (57.2%) and jaundice (22.4%) were the most common signs of hepatic decompensation. The most common etiology of HCC was cryptogenic/non-alcoholic fatty liver disease (NAFLD) in 51% of the patients, while hepatitis B and C were seen in 17.4% and 5.8% of the patients, respectively. Advanced and end-stage disease with Barcelona Clinic Liver Cancer (BCLC) stages C and D were seen in 62.4% of patients. 56.6% had Albumin-bilirubin (ALBI) score of 2, while 62.8% had Okuda stage II disease. High alpha-fetoprotein (AFP) levels (>400 ng/mL) were seen in 48.9% of patients. Macrovascular invasion and metastases were seen in 45.9% and 22.2% of the patients, respectively. 17.6% of patients had evidence of tumor thrombus. 14.5% of biopsy specimens showed associated steatosis/steatohepatitis along with confirmation of HCC. Only 26.6% of the cirrhotic HCC patients were diagnosed during surveillance.ConclusionsHCC due to unknown cause/NAFLD appears to be overtaking hepatitis B as the commonest cause for HCC. Despite the advances in diagnostic methods and surveillance, most cases of HCC tend to be diagnosed at advanced stages.

A novel model based on interleukin 6 and insulin-like growth factor II for detection of hepatocellular carcinoma associated with hepatitis C virus

BackgroundThe coexistence of cirrhosis complicates the early detection of hepatocellular carcinoma (HCC). Thus, novel biomarkers for HCC early detection are needed urgently. Traditionally, HCC detection is carried out by evaluating alpha-fetoprotein (AFP) levels combined with imaging techniques. This work aimed to assess interleukin (IL-6) and insulin-like growth factor 2 (IGF 2) as possible HCC markers in comparison to AFP in patients with and without HCC. ResultsROC analysis showed that IGF2 had the highest area under the curve (AUC) for discriminating HCC from liver cirrhosis (0.86), followed by IL6 (0.82), AFP (0.72), and platelet count (0.6). A four-marker model was developed and discriminated HCC from liver cirrhosis with an AUC of 0.97. The best cut-off was 1.28, at which sensitivity and specificity were 90% and 85%, respectively. For small tumor (< 2 cm), the model had an AUC of 0.95 compared to AFP (0.72). Also, the model achieved perfect performance with AUC of 0.93, 0.94, and 0.95 for BCLC (0-A), CLIP (0-1), and Okuda (stage I), respectively, compared to AFP (AUC of 0.71, 0.69, and 0.67, respectively). ConclusionsThe four markers may serve as a diagnostic model for HCC early stages and help overcome AFP poor sensitivity.

An Inflammation-Index Signature Predicts Prognosis of Patients with Intrahepatic Cholangiocarcinoma After Curative Resection.

BackgroundThe prognosis of patients with intrahepatic cholangiocarcinoma (ICC) after resection is at great variance. We aimed to establish a novel prognostic nomogram in facilitating the risk stratification for these patients.MethodsA total of 82 high-dimensional radiological and pathological data were analyzed by LASSO-penalized Cox regression analyses and the panels with the best predictive performance were selected. Specific nomograms were established based on the selected panels and were validated in both primary (n=292) and validation cohorts (n=107). The area under the receiver operating characteristic curve (AUC) and the concordance index (C-index) were used to compare the predictive ability of nomograms and other staging systems.ResultsThe modified Glasgow Prognostic Score (mGPS) was identified as the prognostic factor for both overall survival (OS) and progression-free survival (PFS). The nomograms built on the prognostic factors showed powerful efficacy in survival prediction, with C-indexes of 0.800 (95% CI 0.767–0.833) and 0.752 (95% CI 0.718–0.786) for OS and PFS in the primary cohort, 0.659 (95% CI 0.586–0.732) and 0.638 (95% CI 0.571–0.705) for OS and PFS in the validation cohort, respectively. Compared with tumor-node-metastasis stage, Barcelona Clinic Liver Cancer staging score, Cancer of the Liver Italian Program score, and Okuda staging system, the nomograms had significantly higher values of AUC and C-indexes in survival prediction in the primary and validation cohorts.ConclusionCompared with currently used staging systems, the nomograms showed significantly higher efficacy in predicting survival of ICC patients after resection. The nomograms provide new versions of personalized management for these patients.

Hepatic Arterial Infusion Chemotherapy with Modified FOLFOX as an Alternative Treatment Option in Advanced Hepatocellular Carcinoma Patients with Failed or Unsuitability for Transarterial Chemoembolization

This study aimed to assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with modified FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as an alternative treatment option in advanced hepatocellular carcinoma (HCC) patients with failed or unsuitability for transarterial chemoembolization (TACE). MATERIALS ANDMETHODS: From September 2018 to January 2020, 87 advanced HCC patients who progressed on TACE or were not eligible for TACE received HAIC treatment with modified FOLFOX. The primary endpoint was overall survival (OS) and secondary endpoints included progression-free survival (PFS), tumor response assessed by Response Evaluation Criteria in Solid Tumors 1.1, and adverse events graded according to CTCAE 5.0. Based on prognostic factors determined by multivariate analysis, a nomogram was developed to predict patient survival. The median OS and PFS were 9.0 months (95%CI 7.6-10.4) and 3.7 months (95%CI 3.1-4.3), respectively. The objective response rate was 13.8%, with a disease control rate of 48.3%. Grade 3 adverse events were observed, such as infection (9.2%), thrombocytopenia (5.7%), hyperbilirubinemia (3.4%), abdominal pain (2.3%) and alanine aminotransferase increase (2.3%). Albumin, AST, and extrahepatic metastasis were incorporated to construct a new nomogram that could stratify patients into three prognostic subgroups, including low-, intermediate-, and high-risk groups, with significant differences in 9-month OS rates (71%, 42% and 6%, respectively; p< 0.001). The nomogram was better than the Okuda, AJCC, and CLIP staging systems for OS prediction. These findings support the feasibility of HAIC with modified FOLFOX as an alternative treatment strategy for advanced HCC when TACEis ineffective or unsuitable.

HCC-Mark: a simple non-invasive model based on routine parameters for predicting hepatitis C virus related hepatocellular carcinoma

ABSTRACT Background Early detection of hepatocellular carcinoma (HCC) is crucial in providing more effective therapies. As routine laboratory variables are readily accessible, this study aimed to develop a simple non-invasive model for predicting hepatocellular cancer. Methods Two groups of patients were recruited: an estimation group (n = 300) and a validation group (n = 625). Each comprised two categories: hepatocellular cancer and liver cirrhosis. Logistic regression analyses and receiver operating characteristic (ROC) curves were used to develop and validate the HCC-Mark model comprising AFP, high-sensitivity C-reactive protein, albumin and platelet count. This model was tested in cancer patients classified by the Barcelona Clinic Liver Cancer (BCLC), Cancer of Liver Italian Program (CLIP) and Okuda systems, and was compared with other non-invasive models for predicting hepatocellular cancer. Results HCC-Mark produced a ROC AUC of 0.89 (95% CI 0.85–0.90) for discriminating hepatocellular carcinoma from liver cirrhosis in the estimation group and 0.90 (0.86–0.90) in the validation group (both p < 0.0001). This AUC exceeded all other models, that had AUCs from 0.41 to 0.81. AUCs of HCC-Mark for discriminating patients with a single focal lesion, absent macrovascular invasion, tumour size <2 cm, BCLC (0-A), CLIP (0–1) and Okuda (stage Ι) from cirrhotic patients were 0.88 (0.85–0.90), 0.87 (0.85–0.89), 0.89 (0.85–0.93), 0.87 (0.84–0.89), 0.85 (0.82–0.87) and 0.86 (0.83–0.89), respectively (all p < 0.0001). Conclusion HCC-Mark is an accurate and validated model for the detection of hepatocellular cancer and certain of its clinical features.

Clinical Significance of Serum Midkine Level as a Biomarker in Diagnosis of Hepatocellular Carcinoma

Background Early diagnosis of hepatocellular carcinoma enhances its effective management. Aim Evaluation of Midkine as a biomarker for diagnosis of hepatocellular carcinoma. Methods: 90 subjects devided into three groups, Group I included 40 HCV patients with liver cirrhosis, Group II included 40 HCV cirrhotic patients with hepatocellular carcinoma and Group III included 10 healthy subjects as a control group. Demographic, laboratory and imaging data were collected. All cirrhotic cases were evaluated by Child-Pugh and MELD scores while BCLC score and Okuda staging were applied for hepatocellular carcinoma cases. Serum Midkine was measured by ELISA technique. Results HCC group had significant elevation in Midkine level compared when to Cirrhotic and Control groups (3.5±2.5 ng/ml versus 1±0.7 ng/ml and 0.1±0.1 ng/ml) (p = 0.000). No significant correlations were found between Midkine and age, sex, site or size of focal lesion, Child classification, MELD score, Okuda staging or BCLC score. ROC analysis showed that the best cut-off value for Midkine was 1.33ng/ml and for AFP was 41.3ng/ml. Area Under the Curve was higher in Midkine than AFP (0.921 and 0.79 respectively) with higher specificity of AFP than Midkine (97.5% and 82.5% respectively) and higher sensitivity of Midkine than AFP (87.5 and 62.5% respectively). By combination of serum AFP and Midkine, AUC was 0.94 with specificity 97.5 % and sensitivity 87.5% Conclusion Midkine may be a sensitive biomarker for diagnosis of hepatocellular carcinoma and combination between alpha-fetoprotein and Midkine increases the accuracy in diagnosis.

Evaluation of Golgi Protein-73 as a Tumor Marker in Patients with Hepatocellular Carcinoma

Background and study aim: Hepatocellular carcinoma (HCC) is the most common type of primary liver tumors. In Egypt, it is the second most common cancer in men, and the sixth most frequent cancer in women. Prognosis of HCC depends on tumor stage, with curative therapies effective only in early stage; thus, new and appropriate HCC markers are highly required. The aim was to evaluate serum diagnostic value Golgi Protein 73 in Egyptian HCC patients. Patients and Methods: This study included 30 HCC patients, 30 cirrhotic patients and 20 healthy controls. For all groups clinical data and imaging results were studied; serum alpha-fetoprotein and Golgi Protein 73 were identified. Evaluation of the tumor characteristics including size, number and location. Okuda, CLIP and Tokyo staging methods used in tumor staging. Results: GP73 was significantly higher in HCC patients compared to cirrhotic patients and controls. Its sensitivity and specificity in HCC diagnosis were 95% and 83.3%, respectively, at cut-off 5.8%. There is a positive correlation between GP73 and Okuda score and ClIP score and no correlations with number and size of the tumor, child's classification, MELD, uMELD and Tokyo stages. Conclusion: GP73 could be a useful diagnostic marker for detection and screening of HCC.

Can Hematological Inflammatory Parameters Predict Mortality in Hepatocellular Carcinoma?

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Inflammatory and hematological parameters such as neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) provided useful information especially in the diagnosis, treatment, and follow-up of malignancies. In this study, we planned to demonstrate the efficacy of NLR and PLR levels in the evaluation of the prognosis of patients with HCC in our clinic. This study was planned as a prospective observational cohort study. The study included 105 patients with HCC on the base of cirrhosis. Our study group was classified according to Barcelona Clinic Liver Cancer (BCLC), Okuda staging system, and Milan criteria at the time of admission. The mean age of all cases was 60.6 ± 12.4years, and 77 (73.3%) of the patients were male. The mean life expectancy of all patients was 7.7 ± 4.3months. During 1-year follow-up, 61 (58.1%) HCC patients died. The mean survival of the patients who died was 4.6 ± 3.0months. In our study, patients with NLR > 2.7, patients with PLR > 100.29, BCLC advanced stage, and Okuda advanced stage, and patients who did not meet the Milan criteria had shorter survival duration. NLR > 2.7, BCLC advanced stage, and Child C were determined as independent risk factors affecting mortality. There was a strong correlation between NLR-PLR levels and mortality. PLR and NLR levels can be used in conjunction with other staging systems to regulate, monitor, and predict the survival of HCC patients.

Study of Toll-like Receptor 3 Gene Polymorphism as a Novel Risk Factor for HCV-related Hepatocellular Carcinoma in Egypt.

Hepatocellular carcinoma (HCC) is a highly aggressive cancer with few treatment options. Toll-like receptor 3 (TLR3) plays a key role in innate immunity and may affect the development of cancers. This study aimed to investigate the association between TLR3 gene polymorphism and HCV-related hepatocellular carcinoma in Egypt. This work was conducted on 70 individuals; fifty HCV cirrhotic patients were included in two groups; with HCC (30 patients) and without HCC (20 patients) compared with a group of 20 apparently healthy controls. All of the studied individuals underwent clinical-laboratory evaluation. TLR3 gene single-nucleotide polymorphism (SNP) (+1234C/T) was tested by polymerase chain reaction- restriction fragment length polymorphism. This study reported that the prevalence of TLR3 +1234TT genotype was significantly increased in cirrhotic patients with HCC than without HCC, while it was not detected at all among the controls. When analyzing the TLR3 SNP +1234C/T with different clinical parameters in HCC patients, there was a significant association between+1234C/T SNP; namely TT genotype and each of the hepatic focal lesions᾽ number, size and the patients᾽ higher Okuda and BCLC stages. No association could be detected between TLR3 SNP and the age, sex, Child-Pugh grades, MELD score or AFP of the studied HCC cases. TLR3 gene SN P +1234C/T could be a novel risk factor for the HCV-related HCC among the Egyptian population.

Development and Validation of a Nomogram-Based Prognostic Evaluation Model for Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of liver cancer with extremely poor prognosis. This study aimed to identify the prognostic factors and develop an exclusive and efficient nomogram to predict cancer-specific survival (CSS) for SHC. The data on patients diagnosed with SHC from January 1973 to December 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were included as the training cohort. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analyses were used to identify the prognostic risk factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to compare the clinical benefits of the prognostic evaluation model (PEM) with that of the American Joint Committee on Cancer (AJCC) staging system. The results were validated with an external validation cohort. In total, 116 patients with SHC were included in the training cohort. Multivariate Cox analysis revealed M stage (distant metastasis), primary tumor surgery, and chemotherapy to be associated with CSS, and along with tumor size, an integrated PEM was constructed. A calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The C-index value of the nomogram for predicting CSS and AJCC was 0.853 and 0.649, respectively. In the validation cohort, the C-index value of the PEM discrimination was better than that of the Barcelona Clinic Liver Cancer (BCLC) staging system, CLIP score, and Okuda staging system, and no statistical difference was observed with eighth edition of the AJCC staging system and Izumi staging system. The proposed four-factor nomogram of PEM could accurately predict the prognosis of SHC and could be used in clinical practice.

Talin-1 Gene Expression as a Tumor Marker in Hepatocellular Carcinoma Patients: A Pilot Study

Background &amp; Aims: Hepatocellular Carcinoma (HCC) is the most common primary liver tumor. It is the second most common cancer in men and the sixth in women in Egypt. One of the proteins participating in the trans-endothelial migration is Talin-1. It also has a role in the formation and metastasis of different types of cancer. This study aimed to evaluate the diagnostic impact of Talin-1 gene expression in HCC Egyptian patients. Methods: Our study included forty HCC patients, thirty liver cirrhosis patients without HCC and thirty healthy subjects. For all groups, clinical and biochemical parameters were investigated. Tumor characteristics were assessed and tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. In addition, Serum Alpha-Fetoprotein (AFP) levels were assayed using Enzyme Immunoassay (EIA) and Talin-1 gene expression was assessed in the Peripheral Blood Mononuclear Cells (PBMCs) via quantitative real-time Polymerase Chain Reaction (PCR). Results: Talin-1 gene expression was significantly upregulated in HCC patients in comparison to cirrhotic and control subjects. The Receiver Operating Characteristic (ROC) analysis indicated that Talin-1 gene expression surpasses serum levels of AFP in the diagnosis of HCC. In particular, the cut off value of 9.5 (2-∆∆Ct) recorded an AUC of 85.7% with a sensitivity of 93.3% and specificity of 80%. Conclusion: Our data confirmed an évident diagnostic role of Talin-1 gene expression for HCC detection.

May Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level Predict Mortality in Patients with Hepatocellular Carcinoma (HCC)?

Hepatocellular carcinoma (HCC) ranks fifth among the common cancers worldwide. Hepatocarcinogenesis is a multiple-phases process, which involves changes in cellular genomes including high cell proliferation.In this study, we aimed to evaluate the relationship of NGAL level at the time of diagnosis with mortality in patients diagnosed with HCC. A total of 35 patients who developed HCC on the ground of HBV(+) and 30 healthy subjects were included in the study. Barcelona Clinic Liver Cancer (BCLC), Okuda staging system, and Milan criteria were used for staging of the patients with HCC. The mean age of all patients was 59.54 ± 11.57 years. Seventeen (48.6%) HCC patients died during 1-year follow-up. Survival of the patients who met the Milan criteria was longer (log-rank (Mantel-Cox) test, χ2 = 5.353, p = 0.021). Kaplan-Meier curve was drawn for NGAL cut-off value, mortality was found to be higher in patients with a NGAL level higher than 217.50 (log-rank (Mantel-Cox) test, χ2 = 15.540, p < 0.001). In this study, we found that high levels of NGAL at the time of diagnosis were associated with poor prognosis in HCC patients.

A combination of α-fetoprotein, midkine, thioredoxin and a metabolite for predicting hepatocellular carcinoma

Introduction and objectivesThe heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection. Patients/materials and methodsThis study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography–mass spectrometry (GC–MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC. ResultsThe model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0–1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups. ConclusionThis model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.

RECK gene polymorphism in patients with hepatocellular carcinoma

BackgroundLiver cancer is the sixth most common cancer and the third cause of cancer related deaths. In Egypt, hepatocellular carcinoma (HCC) has become the second most prevalent cancer among men. Gene and protein expression profiling will allow better screening of different stages of HCC as well as establishment of criteria for targeted therapies. The reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a novel transformation suppressor gene against activated oncogenes. Downregulation of RECK is documented in a wide range of malignant neoplasms and correlates with poor prognosis and tumor metastasis. The aim of this work was to study the association between RECK gene polymorphism and the development of hepatocellular carcinoma in patients with liver cirrhosis. MethodsThis study was conducted on 115 individuals; 47 patients with HCC, 48 patients with cirrhosis without HCC, and 20 healthy volunteers as controls. For all groups, clinical data and image findings were studied as well as laboratory investigations mainly alpha fetoprotein assay by enzyme immunoassay (ELISA) and RECK gene rs10814325 using PCR-RFLP analysis. Tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. ResultsHCC is more prevalent (55.3%) in mutant RECK genotypes (T/C and C/C) than the wild RECK genotype T/T (44.7%). In Child A class, the wild T/T group was significantly higher than the mutant T/C group (p = 0.04). The mean value of MELD score in the mutant genotype T/C was significantly higher than that of the wild type T/T and the mutant type C/C (p = 0.03). In Okuda stage 1, a significant difference was found between the wild T/T and the mutant C/C groups, also between the mutant T/C and the mutant C/C groups. RECK gene polymorphism analysis using ROC curve in HCC patients and healthy controls yields low sensitivity result (55.3%), high specificity (95%), and an AUC of 0.752. RECK gene polymorphism analysis using ROC curve in HCC and cirrhosis patients yields a low sensitivity (55.3%), moderate specificity (77.1%), and an AUC of 0.664. ConclusionsRECK gene rs10814325 is associated with higher HCC susceptibility.

IL-28B rs12979860 polymorphism affect the course of chronic hepatitis and the development of HCC in Egyptian patients with hepatitis C type 4

ABSTRACTBackground: A single nucleotide polymorphism (SNP) in the interleukin 28B (IL28B) gene may alter the trajectory of hepatitis C virus (HCV) chronic infection. Several studies have sought to determine a link between IL28B rs12979860 SNP and the development of HCV-related hepatocellular carcinoma (HCC), but with variable results, and consensus is awaited. We hypothesised that IL28B rs12979860 SNP is linked to HCC in patients with HCV type 4.Methods: IL28B genotyping of 300 patients with HCV-related fibrosis (n = 100), cirrhosis (n = 100) and HCC (n = 100) was carried out and the results were analysed to determine the association between the IL28B genotype and clinical outcome.Results: In IL28B TT genotype carriers, the proportions of moderate/severe fibrosis, advanced cirrhosis (Child B-C) and HCC (50%, 84% and 60.2%, respectively) were higher (p < 0.05) than in CC/CT (4.3%, 46% and 23%, respectively). IL-28B SNP was linked significantly (p < 0.05) with cirrhosis progression and HCC advanced stages. Moreover, HCC advanced Child, Okuda and CLIP stages were associated with T allele carriage (73.9%, 82.6% and 78.3% vs. 44.2%, 50.6% and 46.8% in CC/CT). The percentage of large tumour size (> 3cm) increased (p = 0.028) in TT genotype carriers (81.8% vs.52.6% in CC/CT).Conclusion: IL-28B rs12979860 TT genotype is more prevalent in patients with advanced fibrosis, cirrhosis and HCC stages. Thus, it seems to be associated with poor outcomes in chronic HCV patients and to augment the risk of developing HCC.

A nomogram integrating hepatic reserve and tumor characteristics for hepatocellular carcinoma following curative liver resection

BackgroundBecause of the mutual influence of liver dysfunction and malignancy, overall survival (OS) is a composite clinical endpoint in hepatocellular carcinoma (HCC). We developed a nomogram integrating albumin–bilirubin (ALBI) grade, a new index of hepatic reserve, and tumor characteristics of HCC for predicting OS following curative liver resection. MethodsThe nomogram was built to estimate the probabilities of 1, 3, and 5-y OS based on training cohort of 709 HCC, which was validated in an international independent dataset. The prognostic value of the nomogram was determined by concordance index (C-index), time-dependent receiver operating characteristics (tdROC), and decision curves, comparing with ALBI grade alone, the Cancer of the Liver Italian Program (CLIP), the Barcelona Clinic Liver Cancer (BCLC), and Okuda staging systems. ResultsIndependent factors derived from multivariable Cox analysis of the training cohort to predict OS were tumor grade, microvascular invasion, tumor size and ALBI grade which were assembled into nomogram. The calibration curves for probability of OS showed optimal agreement between nomogram-prediction and actual observation, which was tested in validation cohort. The C-index, tdROC and decision curves showed the nomogram was superior to CLIP, ALBI grade, BCLC and Okuda. The patients could also be stratified into low, intermediate risk, and high risk of the mortality by the normogram in both development and validation cohorts. ConclusionsThe nomogram integrating hepatic reserve and tumor characteristics provided a highly accurate estimation of OS in patients with HCC after curative liver resection, contributing to assess patient prognosis.

Prognostic value of pretreatment PET/CT lean body mass-corrected parameters in patients with hepatocellular carcinoma.

This study was designed to investigate whether pretreatment fluorine-18-fluorodeoxyglucose (F-FDG) PET/computed tomography (CT) lean body mass-corrected parameters could predict the overall survival (OS) better than the established predictors in patients with hepatocellular carcinoma (HCC). We retrospectively analyzed 61 patients with HCC with pretreatment F-FDG-PET/CT. Besides obtaining clinical factors, we measured both lean body mass-corrected and body weight-corrected PET/CT parameters, including metabolic tumor volume, maximal standardized uptake value of the tumor, total lesion glycolysis, tumor-to-normal liver uptake ratio, and so on. The prognostic value of those factors for OS was assessed by statistical software. In the univariate analysis, PET/CT parameters, ascites, serum α-fetoprotein, alkaline phosphatase, aspartate transaminase (AST), tumor number, tumor size of the maximal one, vascular invasion, TNM stage, Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) staging, and Okuda staging were significant predictors of OS. In multivariate and Kaplan-Meier analyses, lean body mass-corrected maximum standardized uptake value (lbmSUVmax) more than 3.35 g/ml, AST more than 42.00 U/l, and BCLC staging B-C were significant independent predictors of poor OS. When BCLC staging variable was stratified by four categories instead of two in the multivariate analysis, it was not the statistically significant independent predictor anymore, but lbmSUVmax and AST still were. Pretreatment F-FDG-PET/CT lean body mass-corrected parameters can predict the OS in patients with HCC. Moreover, lbmSUVmax and AST, as the independent predictors of OS, could supplement the prognostic value of the BCLC staging system.

Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy.

In this study, we aimed to compare and validate the prognostic abilities of preoperative systemic immune cells in hepatocellular carcinoma (HCC) after curative hepatectomy. We developed two nomograms to predict the postoperative recurrence‐free survival (RFS) and overall survival (OS) after comparisons of the systemic immune cell prognostic scores. The two nomograms were constructed based on 305 patients who underwent curative hepatectomy for HCC. The predictive accuracy and discriminative ability of the nomograms were compared with six commonly used staging systems for HCC. The results were validated using bootstrap resampling and an internal validation cohort of 142 patients and an external validation cohort of 169 patients. Necroinflammatory activity in peritumoral liver tissues in the primary cohort was evaluated by hematoxylin and eosin (H&E) staining. Neutrophil, monocyte, and lymphocyte ratio (NMLR) had a higher area under the receiver operating characteristic curves (AUROC) value at both RFS (AUC = 0.603) and OS (AUC = 0.726) compared to that of other systemic immune cell prognostic scores. The independent predictors of RFS or OS, including α‐fetoprotein (AFP), tumor size, tumor number, microvascular invasion, and NMLR, were incorporated into the two nomograms. In the primary cohort, the C‐indexes of the RFS and OS nomograms were 0.705 and 0.797, respectively. The ROC analyses showed that the two nomograms had larger AUC values (0.664 for RFS and 0.821 for OS) than those of the American Joint Commission on Cancer seventh edition, Barcelona Clinic Liver Cancer, Cancer of the Liver Italian Program, Japan Integrated Staging Score, Okuda stage, and the Vauthey's system. These results were verified by internal and external validations. The nomogram‐predicted probability of RFS was associated with peritumoral necroinflammatory activity scores (r = 0.304, P < 0.001). The proposed nomograms had accurate prognostic prediction in patients with HCC after curative hepatectomy.