HCC-Check: A Novel Diagnostic Tool for Early Detection of Hepatocellular Carcinoma Based on Cytokeratin-1 and Epithelial Membrane Antigen: A Cross-Sectional Study.

Background: Hepatocellular carcinoma is frequently diagnosed in advanced stages, leading to a poorer prognosis. Therefore, early diagnosis and identification of biomarkers may significantly improve outcomes. Methods: This cross-sectional study enrolled 486 participants distributed among 3 groups: F1 to F3 = 184, F4 = 183, and hepatocellular carcinoma = 119. Liver fibrosis staging was performed using FibroScan, while imaging features were used for hepatocellular carcinoma detection. Epithelial membrane antigen and cytokeratin-1 levels in serum were quantified through Western blot and ELISA, respectively. Results: Patients diagnosed with hepatocellular carcinoma exhibited significantly elevated levels of epithelial membrane antigen and cytokeratin-1 compared to non-hepatocellular carcinoma patients, with a highly significant statistical difference (P < .0001). Epithelial membrane antigen demonstrated diagnostic performance with an area under the curve of 0.75, a sensitivity of 69.0%, and a specificity of 68.5%. Cytokeratin-1 for the identification of hepatocellular carcinoma showed a sensitivity of 79.0% and a specificity of 81.4%, resulting in an area under the curve of 0.87. The developed HCC-Check, which incorporates epithelial membrane antigen, cytokeratin-1, albumin, and alpha-fetoprotein, displayed a higher area under the curve of 0.95 to identify hepatocellular carcinoma, with a sensitivity of 89.8% and a specificity of 83.9%. Notably, HCC-Check values exceeding 2.57 substantially increased the likelihood of hepatocellular carcinoma, with an estimated odds ratio of 50.65, indicating a higher susceptibility to hepatocellular carcinoma development than those with lower values. The HCC-Check diagnostic test exhibited high precision in identifying patients with hepatocellular carcinoma, particularly those with small tumor sizes (<5 cm) and a single nodule, as reflected in area under the curve values of 0.92 and 0.85, respectively. HCC-Check was then applied to the validation study to test its accuracy and reproducibility, showing superior area under the curves for identifying different stages of hepatocellular carcinoma. These outcomes underscore the effectiveness of the test in the early detection of hepatocellular carcinoma. Conclusion: The HCC-Check test presents a highly accurate diagnostic method for detecting hepatocellular carcinoma in its early stages.

Prognostic value of S100A4 and Glypican-3 in hepatocellular carcinoma in cirrhotic HCV patients.

AIMS: Both S100A4 and Glypican-3 have been known to be engaged in HCC development and progression. This study aimed to evaluate both S100A4 and GPC3 expression in HCC tissues as a prognostic markers. METHODS: Tissues from 70 patients of HCC in cirrhotic HCV patients were evaluated by immunohistochemistry using antibodies against SA100A4 and GPC3 and compared with tumor-adjacent tissue (controls). All cases were followed for 40 months. RESULTS: GPC3 was more expressed in HCC (79%) than S100A4 (21%). S100A4 was more significantly expressed in cases showing metastasis, microscopic vascular emboli, necrosis, and grade III tumors. There was no relationship between overall survival and both S100A4 and GPC3. The only significant independent predictor for recurrence was decompensation (OR 3.037), while metastasis was significantly predicted by S100A4 expression (OR 9.63) and necrosis (OR 8.33). CONCLUSION: S100A4 might be used as a prognostic marker for HCC, while GPC3 is a reliable marker of HCC diagnosis.

Biomarkers for Hepatocellular Carcinoma: From Origin to Clinical Diagnosis.

The incidence of hepatocellular carcinoma (HCC) and HCC-related deaths has increased over the last few decades. There are several risk factors of HCC such as viral hepatitis (B, C), cirrhosis, tobacco and alcohol use, aflatoxin-contaminated food, pesticides, diabetes, obesity, nonalcoholic fatty liver disease (NAFLD), and metabolic and genetic diseases. Diagnosis of HCC is based on different methods such as imaging ultrasonography (US), multiphasic enhanced computed tomography (CT), magnetic resonance imaging (MRI), and several diagnostic biomarkers. In this review, we examine the epidemiology of HCC worldwide and in Egypt as well as risk factors associated with the development of HCC and, finally, provide the updated diagnostic biomarkers for the diagnosis of HCC, particularly in the early stages of HCC. Several biomarkers are considered to diagnose HCC, including downregulated or upregulated protein markers secreted during HCC development, circulating nucleic acids or cells, metabolites, and the promising, recently identified biomarkers based on quantitative proteomics through the isobaric tags for relative and absolute quantitation (iTRAQ). In addition, a diagnostic model used to improve the sensitivity of combined biomarkers for the diagnosis of early HCC is discussed.

Assessing the readability of online information about jones fracture.

BACKGROUND: Hand in hand with technological advancements, treatment modalities continue to grow. With the turn of the century, the internet has become the number one source of information for almost every topic. Thus, many patients look toward the internet as their primary source of information to learn about their respective medical conditions. The American Medical Association and National Institute of Health strongly recommend that online medical information be written at the 6th to 8th-grade level to aid comprehension by patients of all literacy backgrounds. AIM: To assess the readability of online information regarding Jones fracture. Our hypothesis is that the reading level of medical information published on websites far exceeds the recommended reading level of 6th-8th grade as proposed by the American Medical Associate and National Institute of Health. The result of this study can help us formulate improved recommendations for publishing more comprehensible material and, thus, eventually improve patient compliance and clinical outcomes. METHODS: The exact phrase "Jones fracture" was queried on the three most common search engines, Google, Yahoo!, and Bing, on December 28, 2022. As of December 2022, Google held 84%, Bing held 9%, and Yahoo! held 2% of the worldwide search engine market share. Web pages uniform resource locator from the first three pages of search results were recorded from each search engine. These web pages were classified according to academic, physician-sponsored, governmental and non-government organizations (NGO), commercial, and unspecified as per formally defined categories. Websites associated with an educational institution or medical organization were classified as academic. Websites with products for sale, corporate sponsorship, or advertisements were classified as commercial. Governmental websites or NGOs comprised those that received government subsidies or grants. Webpages that were independently owned by physicians or physician groups were respectively classed as physician sponsored. The remainder of websites that did not fall under the above categories were classified as unspecified. RESULTS: A total of 93 websites were analyzed for reading assessment. A whopping 44% of websites were commercial, followed by 22% of physician-sponsored websites. Third place belonged to non-government organization websites holding a 15% share. The academic website held a meager 9% portion, while unspecified sites were 3%. The table illustrates mean readability scores, along with average cumulative grade level. The average grade level was 10.95 ± 2.28 for all websites, with a range of 6.18 to 18.90. Since P values were more than 0.05, there was not a significant statistical difference between the first page results and the results of all pages. Thus, we can rationalize that readability scores are consistent throughout all pages of a website. CONCLUSION: Hand in hand with technological advancements, treatment modalities continue to grow. With the turn of the century, the internet has become the number one source of information for almost every topic. Thus, many patients look towards the internet as the primary source of information to learn about their respective medical conditions. Our study demonstrates that current online medical information regarding Jones fracture is written at an extraordinarily high-grade level, with an average grade level of all websites at 10.95, nearly an 10th-grade educational level. The American Medical Association and National Institute of Health strongly recommend that online medical information should be written at the 6th to 8th-grade level to aid comprehension by patients of all literacy backgrounds. On the contrary, most of the medical information evaluated was at an 10th-grade level, which far exceeds recommendations by AMA and NIH. This is particularly relevant because readability scores are directly proportional to the level of comprehension attained by readers, thus directly impacting patient outcomes. In conclusion, we suggest and encourage that all online reading materials should be re-written at the 6th to 8th-grade level in a public service effort to increase compliance with treatment goals and raise awareness of preventive measures.

Efficacy of combined Sofosbuvir and Daclatasvir in the treatment of COVID-19 patients with pneumonia: a multicenter Egyptian study.

BACKGROUND: Limited experimental and clinical evidence suggests a potential role for sofosbuvir/daclatasvir in treating COVID19. We aim to evaluate the efficacy of generic sofosbuvir/daclatasvir in treating COVID-19 patients with pneumonia. RESEARCH DESIGN AND METHODS: This multicenter prospective study involved 174 patients with COVID-19. Patients were randomized into two groups. Group A (96 patients) received sofosbuvir (400 mg)/daclatasvir (60 mg) for 14 days in combination with conventional therapy. Group B (78 patients) received conventional therapy alone. Clinical, laboratory, and radiological data were collected at baseline, after 7, 14, and 28 days of therapy. Primary endpoint was rate of clinical/virological cure. RESULTS: A lower mortality rate was observed in group (A) (14% vs 21%, P = 0.07). After 1 month of therapy, no differences were found in rates of ICU admission, oxygen therapy, or ventilation. Additionally, a statistically significant shorter duration of hospital stay (9% vs 12%, P < 0.01) and a faster achievement of PCR negativity at day 14 (84% versus 47%, P < 0.01) were noticed in group (A). CONCLUSION: Adding sofosbuvir/daclatasvir to conventional therapy of COVID-19 is promising. Their use is associated with shorter hospital stay, faster PCR negativity and may be reduced mortality.

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

BACKGROUND: The 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. RESULTS: ROC 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). CONCLUSIONS: The four markers may serve as a diagnostic model for HCC early stages and help overcome AFP poor sensitivity.

High blood glucose levels are associated with fibrosis/cirrhosis progression in chronic hepatitis C.

Chronic hepatitis C (CHC) leads eventually to liver fibrosis, advanced hepatic disease and related deaths. Therefore, it is very important to assess clinical risk factors associated with rapid CHC and hepatic fibrosis progression. Former studies reported diabetes mellitus synergistic interactions with other host factors to fibrosis progression. Here, we aimed to evaluate the association between elevated blood glucose levels and CHC progression according to METAVIR system in patients chronically infected with HCV-genotype 4 and to evaluate the correlation between elevated glucose levels and liver- and viral-related biochemical parameters. A total of 160 patients with CHC (80 with liver fibrosis and 80 with cirrhosis) and 40 healthy volunteers, negative for HCV, were included. Our results revealed that cirrhotic patients had high (P = .0001) fasting (169.1 ± 50.2 mg/dL), postprandial (208 (123-320) mg/dL), and random (176.8 ± 51 mg/dL) glucose levels compared to patients with liver fibrosis (105.0 ± 32, 120 (105-135), and 113.5 ± 35 mg/dL, respectively). Mean serum fasting, postprandial and random glucose levels were significantly (P = .0001) increased with an increase in fibrosis stages, F1< F2< F3< F4. Blood glucose levels were also significantly (P < .05) correlated with liver disease related biological parameters and HCV-Ab titer. In conclusion, our results highlighted the fibrogenic impact of elevated glucose levels on CHC patients.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Development of a novel glycated protein-based fibrosis prediction score for determination of significant liver fibrosis in HCV-infected patients, a preliminary study.

The current study aimed to investigate the diagnostic value of glycated albumin (GA), glycated hemoglobin (HbA1c), and a number of routine biomarkers as noninvasive indicators of liver fibrosis in patients with chronic hepatitis C (CHC). One hundred patients with CHC were subjected to full medical history and examination, in addition to ultrasound-guided liver biopsy and histopathological examination for assessment of liver fibrosis stage. GA and HbA1c values, GA/HbA1c ratio, liver function tests, complete blood count, and alpha fetoprotein (AFP) were determined. A novel noninvasive index, dubbed Fibrosis Prediction Score (FPS), was selected for predicting significant liver fibrosis based on total bilirubin, glycated albumin, platelet count, age, and AFP. A validation study for FPS was applied on archival data which include 66 diabetics' patients. The FPS had area under the curve (AUC) of 0.92 for classification of patients with significant fibrosis with 81% sensitivity and 95% specificity. The AUCs of FPS in predicting advanced fibrosis and cirrhosis were 0.86 and 0.82, respectively. Comparison of AST-to-platelet ratio index (APRI) and FIB-4 with FPS indicated increased sensitivity and specificity of FPS over APRI and FIB4 in both significant and advanced fibrosis. FPS has a good sensitivity and specificity for prediction of significant and advanced liver fibrosis in patients with CHC.

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

INTRODUCTION AND OBJECTIVES: The 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 METHODS: This 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. RESULTS: The 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. CONCLUSION: This model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.

Circulating levels of collagen III and MMP-1 in patients with chronic hepatitis C co-infected with hepatitis B virus.

BACKGROUND: There is controversial data in the literature about the characteristics and features of dual hepatitis B and hepatitis C infection. This work is concerned with estimating the extent to which HBV could influence circulating levels of hepatitis C viral nonstructural-4 (HCV-NS4) in addition to some direct fibrosis markers in chronic hepatitis C. METHODS: Thirty-eight HCV mono-infected and 87 HCV/HBV co-infected patients constituted this study. Western-blot and ELISA were used for identifying HCV-NS4, hepatitis B surface antigen (HBsAg), collagen III and matrixmetalloproteinase-1 (MMP-1) in patients' sera. RESULTS: Hepatitis B surface antigen (HBsAg) provided area under curve (AUC) of 0.97 for identifying HBV-patients with 89% sensitivity and 94% specificity, while HCV-NS4 antigen provided an AUC of 0.95 for identifying HCV-patients with 89% sensitivity and absolute specificity (100%). In general, patients with significant fibrosis (F2-F4) showed significantly higher concentration of collagen III (P = 0.009) and lower concentrations of MMP-1 (P = 0.007) when compared to patients with minimal fibrosis (F1). However, HCV/HBV co-infected patients with F1 and F2-F4 did not show any significant difference (P > 0.05) from HCV mono-infected patients with respect to HCV-NS4, collagen III and MMP-1. These results indicate that HBV does not influence the rate of HCV-NS4 synthesis and the deposition of extracellular matrix in HCV/HBV co-infected patients and subsequently does not affect the progression rates of hepatic fibrosis. CONCLUSION: HCV/HBV co-infected and HCV- mono-infected patients had similar clinical characteristics and there is no effect of HBV co-infection on the progression rates of liver fibrosis in chronic hepatitis C patients.

Simplified HCC-ART score for highly sensitive detection of small-sized and early-stage hepatocellular carcinoma in the widely used Okuda, CLIP, and BCLC staging systems.

BACKGROUND: Small-sized HCC can be effectively cured by surgery with good clinical outcomes. A highly sensitive HCC α-fetoprotein routine test (HCC-ART) for HCC diagnosis as well as a simplied form of the HCC-ART were reported in the British Journal of Cancer. Here, we verified and studied the applicability of the HCC-ART to the detection of early-stage HCC. METHODS: 341 cirrhotic patients and 318 HCC patients were included in this study. For each, the HCC-ART score was calculated, and then the sensitivity, specificity, and results of an ROC curve analysis were compared between the HCC-ART and AFP when these biomarkers were used to detect small-sized HCC. RESULTS: Different HCC-ART cutoffs were set for the detection of different tumor sizes. The HCC-ART (AUC = 0.871, 70% sensitivity, 97% specificity) and the simplified HCC-ART (AUC = 0.934, 82% sensitivity, 100% specificity) were found to have high predictive power when attempting to separate cirrhotic patients from those with small-sized HCC. The simplified HCC-ART score was superior to AFP for determining stages according to the early Okuda (0.950 AUC, 84% sensitivity, 99% specificity), CLIP (0.945 AUC, 84% sensitivity, 99% specificity), and BCLC (1.000 AUC, 100% sensitivity, 99% specificity) staging systems. The simplified HCC-ART score was more strongly correlated than AFP and other staging systems with HCC tumor size (P < 0.0001; r = 0.8). CONCLUSION: The HCC-ART is superior to AFP for diagnosing early-stage HCC. Due to its advantages of minimal variability and a wide continuous scale for assessing HCC severity, the simplified HCC-ART has the potential to be more widely used than the original HCC-ART.

Impact of Hepatitis C Virus/Schistosoma mansoni Coinfection on the Circulating Levels of HCV-NS4 Protein and Extracellular-Matrix Deposition in Patients with Different Hepatic Fibrosis Stages.

Hepatitis C virus (HCV)/Schistosoma mansoni coinfection is common in Egypt and other developing countries. This study aimed to investigate the influence of HCV/S. mansoni coinfection on the concentration of HCV-nonstructural protein-4 (NS4) in addition to collagen III and matrix metalloproteinase-1 (MMP-1) in different hepatic fibrosis stages. We found that coinfected patients (N = 186) showed significantly (P < 0.05, Mann-Whitney U test) higher concentrations of HCV-NS4, collagen III, and collagen III/MMP-1 ratio (CMR) than those with HCV monoinfection (N = 104) in different fibrosis stages. Conversely, coinfected patients showed significantly lower concentrations of MMP-1 when compared with HCV monoinfection. The elevated levels of CMR in case of HCV monoinfection yielded an estimated odds ratio of 1.8 and 2.6 for developing significant fibrosis (F2-F4) and cirrhosis (F4), respectively. HCV/S. mansoni coinfection increased the risk for developing F2-F4 and F4 several fold yielding an estimated odds ratio of 11.1 and 5.2, respectively. This means that coinfected patients have a 6-fold and 2-fold increased risk of developing F2-F4 and F4, respectively, over HCV-monoinfected patients. Thus, elevated levels of HCV-NS4 and CMR in HCV/S. mansoni coinfection suggest increased susceptibility of coinfected patients, compared with those with HCV monoinfection, for accelerating hepatic fibrosis progression.

GPC-HCC model: a combination of glybican-3 with other routine parameters improves the diagnostic efficacy in hepatocellular carcinoma.

Conflicting results for circulating glypican-3 (GPC3) were reported in hepatocellular carcinoma (HCC) diagnosis. We aimed to improve the diagnostic power of GPC3 by developing a GPC-HCC model for diagnosing HCC. GPC3 was tested for HCC (138), liver cirrhosis (56), and fibrosis (62) patients by ELISA. Data from patient groups were retrospectively analyzed. A novel score, GPC-HCC, based on combination of GPC3 and routine laboratory tests, was developed for HCC diagnosis. The GPC-HCC model values produced a significant 1.7-fold increase in liver cirrhosis and 3.2-fold increase in HCC, in comparison with liver fibrosis. In contrast to GPC3 and alpha fetoprotein (AFP), the GPC-HCC model showed high HCC diagnostic power with area under the curve (AUC) of 0.939, sensitivity 93 %, specificity 93 %, positive predictive value 89 %, negative predictive value 95 %, and efficiency 93 %. GPC-HCC AUC in HCC with single tumor, absent vascular invasion, and tumor size ≤3 cm were 0.93, 0.92, and 0.92, respectively, compared with 0.63, 0.63, and 0.64, respectively, for GPC3 and 0.69, 0.70, 0.55, respectively, for AFP. In conclusion, owing to these promising findings, the combination of GPC3 with other laboratory simple routine tests (GPC-HCC model) could improve the diagnostic power of GPC3 in HCC screening and follow up of cirrhotic patients.

Interferon-gamma is associated with hepatic dysfunction in fibrosis, cirrhosis, and hepatocellular carcinoma.

The relation between interferon-gamma (IFN-γ) levels and the severity of liver diseases through fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) has not been fully clarified. Thus, we aimed to characterize IFN-γ levels in liver-diseased patients. IFN-γ levels were determined by Western-blot and ELISA in sera from 30 healthy individuals, 53 patients with non-significant fibrosis (F0-F1), 47 with moderate/severe fibrosis (F2-F3), 44 cirrhotic patients (F4), and 50 with HCC. Enhanced levels of IFN-γ were associated with the progression of liver disease. The differences were statistically significant (P < 0.0001) when patients with F2-F3, F4, or HCC were compared with F0-F1 or healthy controls. The increase in IFN-γ was associated with HCC (OR = 0.98, 95% CI 0.97-0.99, P = 0.002). There was no statistically significant association between IFN-γ levels and HCV-RNA (IU/ml) (r = 0.1, P = 0.43) or HCV-NS4 (µg/mL) (r = 0.1, P = 0.17). There was significant (P < 0.0001) association between IFN-γ levels and the fibrosis stages and activity, albumin, platelet count, total bilirubin, and international normalized ratio (INR). In conclusion, elevated concentrations of IFN-γ represent a characteristic feature of liver disease severity regardless of underlying disease. Significant correlations with indices of hepatic dysfunction suggest that enhanced IFN-γ levels represent a consequence of liver dysfunction rather than of inflammatory disease.

Levels of Schistosoma mansoni Circulating Antigen in Chronic Hepatitis C Patients with Different Stages of Liver Fibrosis.

The goal of this study was to determine the levels of S. mansoni antigen in different liver fibrosis stages with chronic hepatitis C (CHC) Egyptian patients. A total of 174 CHC patients showing HCV-NS4 antigen and HCV- RNA in their sera were included. S. mansoni antigen was detected in serum using Western blot and ELISA. The levels of interferon-γ (IFN- γ) were determined using ELISA. The 50 kDa S. mansoni antigen discriminated patients infected with S. mansoni from healthy individuals with 0.93 area under curve (AUC), 92% sensitivity, and 97% specificity. The level of S. mansoni antigen (µg/ml) was significantly (P < 0.0001) increased with the progression of liver fibrosis stages (26.9 ± 17.5 in F1, 42.1 ± 25.2 in F2, 49.8 ± 30.3 in F3 and 62.2 ± 26.3 µg/mL in F4 liver cirrhosis), 26.9 ± 17.59 in significant fibrosis (F2-F4); 51.2 ± 27.9 in advanced fibrosis (F3-F4). A significant correlation (r = 0.506; P < 0.0001) was shown between the levels of the S. mansoni antigen and the HCV-NS4 antigen. In conclusion, the presence of S. mansoni antigen in different liver fibrosis stages of CHC patients confirming that concomitant schistosome infection aggravates liver disease.

An Easy and Useful Noninvasive Score Based on α-1-acid Glycoprotein and C-Reactive Protein for Diagnosis of Patients with Hepatocellular Carcinoma Associated with Hepatitis C Virus Infection.

This study aimed to evaluate the diagnostic value of α-1-acid glycoprotein (AGP) and C-reactive protein (CRP) and develop a predictive score to improve the diagnosis of hepatocellular carcinoma (HCC). AGP and CRP were measured in serum of 53 HCC patients and 20 liver cirrhosis (LC) patients, in addition to 15 healthy individuals. Area under receiver-operating characteristic curves (AUCs) was used to create a predictive score comprising AGP, CRP, alpha fetoprotein, and albumin. The diagnostic performances of score was determined and compared with AFP alone for the diagnosis of HCC. The combination of AGP, albumin, CRP, and AFP had AUC 0.92 and sensitivity 85% which was higher than AFP alone. The odds ratio of having HCC was 8.4 for AGP, 5.8 for CRP, 12.5 for AFP and 6.5 for albumin. Our score predicted HCC with an OR of 50.6 for HCC. The AUC of score in HCC with single tumor, absent vascular invasion and CLIP score (0-1) were 0.9, 0.9, 0.82, respectively, compared with 0.71, 0.71, 0.68, respectively, for AFP. In conclusion, a non-invasive and simple score based on AGP, CRP, AFP, and albumin could improve the accuracy of HCC diagnosis.

A simple diagnostic index comprising epithelial membrane antigen and fibronectin for hepatocellular carcinoma.

UNLABELLED: Background and rationale for the study. Continuing search for suitable tumor-markers is of clinical value in managing patients with various malignancies. These markers may be presented as intracellular substances in tissues or may be released into the circulation and appear in serum. Therefore, this work is concerned with identification and quantitative determination of epithelial membrane antigen (EMA) and fibronectin and estimating their performances as surrogate markers for identifying hepatocellular carcinoma (HCC). RESULTS: A total of 627 individuals constituted this study [fibrosis (F1-F3) = 217; cirrhosis = 191; HCC = 219]. Western-blot was used for identifying EMA and fibronectin in sera. As a result, a single immunoreactive band was shown at 130-kDa and 90-kDa corresponding to EMA and fibronectin, respectively. They were quantified using ELISA providing values in HCC higher than fibrosis or cirrhosis with a significant difference (P < 0.0001). For identifying HCC, EMA showed 0.82 area under receiver-operating characteristic curve (AUC) with sensitivity = 70% and specificity = 78% while fibronectin yielded AUC = 0.70 with sensitivity = 67% and specificity = 82%. FEBA-Test comprising fibronectin and EMA together with total-bilirubin and AFP was constructed yielding AUC = 0.92 for identifying HCC from cirrhosis with sensitivity = 89% and specificity = 85%. FEBA-Test was then tested for differentiating HCC from fibrosis showing AUC = 0.97 with sensitivity = 90% and specificity = 89%. FEBA-Test enabled the correct identification of HCC patients with CLIP 0-1 and size ≤ 3 cm with AUC = 0.80 and AUC = 0.84, respectively, indicating its ability in identifying early HCC. CONCLUSIONS: A four-marker index may improve the early detection of HCC with a high degree of accuracy.

HCC-DETECT: a combination of nuclear, cytoplasmic, and oncofetal proteins as biomarkers for hepatocellular carcinoma.

Currently, the search for suitable hepatocellular carcinoma (HCC) biomarkers is very intensive. Besides, efficacy and cost/effectiveness of screening and surveillance of cirrhotics for the diagnosis of HCC is still debated. So, the present study is concerned with the evaluation of cytokeratin-1 (CK-1) and nuclear matrix protein-52 (NMP-52) for identifying HCC. Two-hundred and eighty individuals categorized into three groups [liver fibrosis (F1-F3), cirrhosis (F4), and HCC] constituted this study. Western blot was used for identifying CK-1 and NMP-52 in serum samples. As a result, a single immunoreactive band was shown at 67 and 52 kDa corresponding to CK-1 and NMP-52, respectively. Both CK-1 and NMP-52 bands were cut and electroeluted separately. These markers were quantified in sera using ELISA. Patients with HCC were associated with higher concentrations of CK-1 and NMP-52 than those without HCC with a significant difference (P < 0.0001). CK-1 showed an area under receiver-operating characteristic curve (AUC) of 0.83 with 75 % sensitivity and 82 % specificity while NMP-52 yielded 0.72 AUC with 62 % sensitivity and 70 % specificity for identifying HCC. HCC-DETECT comprising CK-1 and NMP-52 together with AFP was then constructed yielding 0.90 AUC for identifying HCC with 80 % sensitivity and 92 % specificity. HCC-DETECT was then tested for separating HCC from F1-F3 showing 0.94 AUC with 80 % sensitivity and 93 % specificity. In conclusion, CK-1 in conjunction with NMP-52 and AFP could have a potential role for improving the detection of HCC with a high degree of accuracy.

Fibro-check: a combination of direct and indirect markers for liver fibrosis staging in chronic hepatitis C patients.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: The assessment of liver fibrosis provides useful information not only for diagnosis but also for therapeutic decision. This study was concerned with determining the levels of collagen III and its degrading enzyme matrix metalloproteinase-1 (MMP-1) as direct and complementary markers for liver fibrosis staging. RESULTS: A total of 269 chronic hepatitis C patients constituted this study. Western blotting was used for identifying collagen III and MMP-1 in serum samples. As a result, collagen III and MMP-1 were identified, respectively, at 70 and 245 kDa using their respective mono-specific antibodies. These two markers were quantified in sera of patients using ELISA. Next, Fibro-check was constructed combining collagen III and MMP-1 together with other indirect markers which reflect alteration in hepatic functions that proved useful to stage liver fibrosis. Fibro-check produced area under the receiver-operating characteristic curve (AUC) 0.91 and 0.83 for significant (F2-F4) and cirrhosis (F4), respectively. Additionally, we estimated the performance of Fibro-check in comparison with aspartate to platelet ratio index (APRI) and fibrosis index. Fibro-check seems to be more efficient than both of them. Fibro-check was then applied to the validation study to test its accuracy and reproducibility showing AUCs 0.90 for F2-F4 and 0.86 for F4. CONCLUSIONS: Fibro-check combining 'direct' and 'indirect' markers using a mathematical formula may improve the staging of liver fibrosis with a high degree of accuracy and seems more efficient than APRI and Fibrosis index in this group of Egyptian patients.