scholarly journals Serum Beclin 1 and autophagy-related protein-5 and the risk of hepatocellular carcinoma among cirrhotic hepatitis C patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ayman El Shayeb ◽  
Akram Deghedy ◽  
Essam Saeed Bedewy ◽  
Sahar Badawy ◽  
Nermeen Abdeen
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Primary Liver Cancer ◽  
Beclin 1 ◽  
Control Group ◽  
List Type ◽  
Related Protein ◽  
Promising Tool ◽  
Group 2 ◽  
Prevention Of Cancer

Abstract Background The most common primary liver cancer in adults is hepatocellular carcinoma (HCC) which is commonly presented with a poor prognosis. Therefore, it is important to explore effective biomarkers and therapeutic targets for HCC patients. Autophagy is involved in the development and prevention of cancer. Mammalian Beclin-1 is needed for an autophagic vesicle in HCC. Autophagy-related protein-5 (ATG5) is an important molecule involved in cell death during autophagy. The objective is to investigate serum ATG 5 and Beclin 1 levels in HCV-induced liver cirrhosis with and without HCC. The study was conducted on 80 individuals classified into 3 groups: Group 1: 30 patients with HCV-induced liver cirrhosis without HCC. Group 2: 30 patients with HCV-induced liver cirrhosis with HCC. Group 3: 20 healthy subjects (control group). Results Serum ATG 5 was significantly lower in HCC than liver cirrhosis patients. Serum Beclin 1 was significantly higher in HCC than liver cirrhosis patients. A cutoff value of < 95.7 and > 5.3 of serum ATG5 and Beclin 1 could be suggested for diagnosis of HCC among patients with HCV-related cirrhosis. Conclusion Serum Beclin 1 and ATG 5 could be used as a novel diagnostic marker for HCC. Moreover, scoring of serum BECLIN 1, ATG 5, and cachexia might be a future promising tool to predict the risk of HCC development.

scholarly journals Neuroprotective Effects of Idebenone on hydrogen peroxide (H2O2)-induced Oxidative Damage in Retinal ganglion cell-5 (RGC-5) Cells

2019 ◽  
Author(s):  
Yuping Wang ◽  
Jing Wang ◽  
Xi Zhang ◽  
Yifan Feng ◽  
Yuanzhi Yuan
Keyword(s):  
Flow Cytometry ◽  
Membrane Potential ◽  
Oxidative Damage ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Beclin 1 ◽  
Control Group ◽  
Related Protein ◽  
H2o2 Treatment ◽  
Cyt C

Abstract Purposes To investigated the neuroprotective effect of Idebenone against H2O2-induced oxidative damage in RGC-5 cells. Methods RGC-5 cells were treated with different concentrations (5, 10, 20μM) of idebenone for 12h prior to addition of 300µM H2O2 for 12 h. The apoptosis of RGC-5 cells were detected by flow cytometry. The changes of mitochondrial membrane potential were detected by JC-1 staining. The autophagy in RGC-5 cells was observed by transmission electron microscopy, and the expression level of autophagy-related protein light chain3, Beclin-1 and mitochondrial membrane potential-related protein Cyt-c in RGC-5 cells were measured by Western blot analysis. Results Flow cytometry showed that the apoptosis rates in control group, H2O2 group and H2O2-treatment with Idebenone pretreatment groups were (6.48±0.55)%, (27.34±0.51)%, (22.88±0.52)%, (15.45±0.81)%, (12.59±0.58)%, respectively(F = 559.7, P <0.0001). After incubation with H2O2, the number of autophagosomes increased significantly, while which was decreased in H2O2-treatment with Idebenone pretreatment groups. After incubation of RGC-5 cells with H2O2, the mitochondrial membrane potential was significantly decreased, while idebenone could prevent the decrease of MMP. Contrast with control group, LC3 II /I, the expression levels of Beclin-1 and Cyt-c in H2O2 group increased significantly(P<0.05); while contrast with H2O2 group, LC3 II/I, the expression of Beclin-1 and Cyt-c in H2O2-treatment with Idebenone pretreatment groups was significantly decreased(P<0.05). Conclusion Idebenone may have protective effects on RGC-5 cells suffering from oxidative damage induced by H2O2 through improving antioxidant capacity, reducing mitochondrial membrane potential decline and the activity of autophagy.

scholarly journals A Comparative Study of the Diagnostic and Prognostic Value of Squamous Cell Carcinoma Antigen and Alfa-foeto Protien in Hepatocellular Carcinoma Before and After Therapeutic Intervention

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
S Abdelhamid ◽  
T M Alsakty ◽  
H H Radwan ◽  
M E Abouelmaaty ◽  
A S Allam ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Squamous Cell Carcinoma ◽  
Liver Cirrhosis ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Prognostic Value ◽  
Control Group ◽  
Squamous Cell Carcinoma Antigen ◽  
Group I ◽  
Group Ii

Abstract Background hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and it is one of the major causes of death, because of its high frequency and poor prognosis. Hepatocellular carcinoma is now a common malignancy in Egypt which usually develops on top of liver cirrhosis secondary to viral infection, as hepatitis C viruses increased the risk of HCC in the Egyptian patients. Aim of the Work was to verify the possibility of using the plasma squamous cell carcinoma antigen level as a tumor marker for hepatocellular carcinoma and to evaluate its prognostic value in management of HCC. Patients and Methods the study included 60 subjects divided into three groups: group I was 30 patients with hepatocellular carcinomas, group II was 15 patients with liver cirrhosis and group III was 15 normal subjects serving as a control group. Follow up of the patients who had HCC and undergone either RFA or TACE will be done after 1 month by measuring serum level of alfa feto protein & SCCA. Results the plasma SCCA level was significantly higher in group I patients (with HCC), than in the group II patients (cirrhosis) and control group. SCCA showed direct significant correlation with the most of laboratory data specially AST, INR, number and size of lesion and its values were decreased after intervention. Conclusion plasma SCCA is a sensitive and specific serum marker for the diagnosis and prognosis of HCC and combination of AFP and SCCA in screening and diagnosis of HCC yielded a better sensitivity in diagnosis of HCC.

Evaluation of Serum voltage gated calcium channel α2δ1 as a novel Marker for diagnosis of Hepatocellular Carcinoma in Cirrhotic Egyptian Patient

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Essam Mohammed Bayoumi ◽  
Ahmed El Saady Mohamed ◽  
Ahmed El Metwally Ahmed ◽  
Al Saied Al Saied Al Refaey
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Calcium Channel ◽  
Liver Tumors ◽  
Control Group ◽  
Voltage Gated ◽  
Group A ◽  
Cirrhotic Patients ◽  
Voltage Gated Calcium Channel ◽  
Group B

Abstract Background Hepatocellular carcinoma (HCC) is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery – either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the diagnosis and treatment of this highly lethal cancer. Objectives Evaluation of Serum voltage gated calcium channel α2δ1 as a novel Marker for diagnosis of Hepatocellular Carcinoma in Cirrhotic Egyptian Patients. Patients and Methods This study had been carried out on 90 subjects, age range 21-73 year selected from Internal medicine and Hepatology outpatient clinics and inpatient wards at Ain shams university hospitals. Subjects were divided as follow: Group A(Case): 40 patients with liver cirrhosis without Hepatocellular carcinoma and group B (Control): 40 patients with liver cirrhosis and Hepatocellular carcinoma and group C: 10 normal population for detecting normal value of the marker with exclusion criteria including age &lt; 18 years old and Patients diagnosed with malignancy other than HCC. Results The study subjects are classified into three groups: Group A cirrhotic patients without HCC, Group B cirrhotic patients with HCC and Group C normal individual subjects. Conclusion Serum voltage gated calcium channel levels were significantly higher in patients with HCC and mildly elevated in patients with liver cirrhosis compared to the control group. Thus it can be used as a tumor marker for HCC.

scholarly journals Role of bile acids in the prediction of hepatocellular carcinoma in HCV-induced liver cirrhosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashraf Khalil ◽  
Azza Elsheashaey ◽  
Eman Abdelsameea ◽  
Manar Obada ◽  
F. F. Mohamed Bayomy ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Bile Acids ◽  
Organic Molecules ◽  
Roc Curves ◽  
Chronic Liver ◽  
Control Group ◽  
Serum Bile Acid ◽  
And Control

Abstract Background Bile acids are essential organic molecules synthesized from cholesterol in the liver and regarded as indicators of hepatobiliary impairment; however, their role in the pathogenesis of hepatocellular carcinoma (HCC) is still unclear. The study aimed to examine the feasibility of bile acids in distinguishing HCC from post hepatitis C virus liver cirrhosis. A UPLC/MS was used to measure 14 bile acids in patients with noncirrhotic HCV disease (n = 50), cirrhotic HCV disease (n = 50), hepatocellular carcinoma (n = 50), and control group (n = 50). Results The progression of liver cirrhosis to HCC was associated with a significant increase in serum bile acids compared to the normal or the noncirrhotic HCV disease (p < 0.05). The fold changes in bile acids concentrations showed a trend that HCC > cirrhotic HCV disease > noncirrhotic HCV disease. Four conjugated acids GCA, GCDCA, GUDCA, and TCDCA steadily increased across the different groups. ROC curves analysis revealed that these bile acids discriminated noncirrhotic liver patients from HCC (AUC 0.850–0.963), with a weaker potential to distinguish chronic liver cirrhosis from HCC (AUC 0.414–0.638). Conclusion The level of serum bile acid was associated primarily with liver cirrhosis, with little value in predicting the progress of chronic liver cirrhotic disease into hepatocellular carcinoma.

scholarly journals Accuracy of Serum Golgi Protein 73 and Alpha Fetoprotein (AFP) to Diagnose Hepatocellular Carcinoma

2021 ◽  
Vol 8 (9) ◽  
pp. 468-473
Author(s):  
Karina Dwi Swastika ◽  
Gontar Alamsyah Siregar ◽  
Dharma Lindarto
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Cross Sectional Study ◽  
Alpha Fetoprotein ◽  
Control Group ◽  
Healthy Population ◽  
Sectional Study ◽  
Cross Sectional ◽  
Golgi Protein ◽  
Common Malignancy

Background: Hepatocellular Carcinoma (HCC) is one of the most common malignancy in the liver. Modalities of diagnostic are often an obstacle in HCC surveillance. Alpha fetoprotein (AFP) is one of protein that often used in the diagnostic of HCC in chronic liver disease. Golgi protein 73 (GP73), is one of the candidate biomarkers in early diagnostic of HCC and found in biliary epithelial cells but rarely expressed by normal hepatocytes. Expression of GP73 was reported to be increased in a large number of malignancies. Aims of this study to evaluate differences in Golgi protein 73 serum (sGP73) and AFP in diagnosing hepatocellular carcinoma in patients with liver cirrhosis. Materials and Methods: This cross-sectional study was conducted at Haji Adam Malik Hospital in 2020. Serum level of GP73 and others biomarker was detected using enzyme-like immunosorbent assay. Results: From 90 subjects, Liver cirrhosis and HCC group had significantly higher AFP than the control group. AFP was superior in determining HCC to GP73. At a cut off value of > 394.5.00 ng/mL, AFP yielded a sensitivity of 83.3% and specificity of 67%, for discriminating liver cirrhosis and HCC (AUC 0.84), while GP73 with cut off value of > 82.5 ng/mL, sensitivity of 70% and specificity of 57% (AUC 0.74). Conclusion:GP73 was significantly higher in HCC patients in comparison to non-HCC patients and healthy population. Compared with alpha fetoprotein, GP73 was superior in discriminating HCC in healthy population but inferior in group of liver cirrhosis. Keywords: Golgi Protein 73, Alpha Fetoprotein, Hepatocellular carcinoma.

scholarly journals Assessment of Plasma Vitronectin as Diagnostic and Prognostic Marker of Hepatocellular Carcinoma in Patients with Hepatitis C Virus Cirrhosis

2022 ◽  
Vol 13 (1) ◽  
pp. 9-19
Author(s):  
Salem Youssef Mohamed ◽  
Ahmed Elsayed Esmaiel ◽  
Marwa Abo Shabana ◽  
Nevin Fouad Ibrahim
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hepatitis C Virus ◽  
Hepatitis C ◽  
Serum Level ◽  
Primary Liver Cancer ◽  
Liver Function Tests ◽  
Control Group ◽  
Focal Lesion ◽  
University Hospitals ◽  
Hepatitis C Infection

Background: hepatitis C is an inflammatory liver disease caused by the hepatitis C infection (HCV), and without treatment, almost 50% will progress to liver cirrhosis. Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and the fourth leading cause of cancer-related mortality. Aim of the study: the objective of this study was to evaluate the serum level of vitronectin (VTN) compared to AFP and determine their role as diagnostic and prognostic markers of HCV-related liver diseases. Subject and Methods: this study involved 52 HCV patients from which 26 patients were cirrhotic, and 26 patients had HCC (on top of hepatitis C virus-related cirrhosis) plus 10 healthy people as a control group. It was carried out in Gastroenterology and Hepatology Unit, Internal Medicine Department, Zagazig University Hospitals, Egypt. All individuals in this study were subjected to physical examination, full history taking, liver function tests, assessment of serum levels of Vitronectin (VTN) and alpha-fetoprotein (AFP) before and after the intervention within three months. Results: serum level of vitronectin increased significantly in cirrhosis patients and HCC patients than controls (p = 0.0041), (p < 0.001), respectively, and in HCC than cirrhosis patients (p < 0.001). Significant positive correlations were observed between levels of serum VTN and AFP in all HCV patients as well as cirrhotic patients (p < 0.001, p = 0.011, respectively). On the contrary, VTN and AFP didn’t show a significant correlation in HCC patients’ group. Moreover, the median serum level of VTN decreased significantly after treatment in patients with HCC (p < 0.001). At cut-off 38.5 ng/mL for AFP it shows sensitivity 80.8%, specificity 76.9% to differentiate HCC from cirrhosis cases. While VTN shows 84.6% sensitivity, 96.2% specificity at cut-off 26.5 μg/mL. Regarding clinicopathological characteristics and VTN levels, half of patients were stage B, 63.9% had tumor size >3 cm, 84.6% had more than one focal lesion. Conclusions: these results may allow one to speculate a potential role of Vitronectin in diagnosis and prognosis of HCC on top of cirrhosis related to HCV infection in addition to AFP and US and CT.

scholarly journals COL1A1 Gene Expression in Hepatitis B Virus (HBV) Related Hepatocellular Carcinoma (HCC) Egyptian's Patients

2021 ◽  
Vol 11 (1) ◽  
pp. 108-114
Author(s):  
Amal A. Mohamed ◽  
Yousry Esam-Eldin Abo-Amer ◽  
Amyan Aalkhalegy ◽  
Lamiaa Abdelfattah Fathalla ◽  
Mostafa Bedair Elmaghraby ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Healthy Volunteers ◽  
Complete Blood Count ◽  
Venous Blood ◽  
The Other ◽  
Col1a1 Gene ◽  
Group 2

Introduction: Collagens are the most abundant proteins in the human body, accounting for one-third of total proteins. Over the last few years, accumulated evidence have indicated that some collagens are differentially expressed in cancer. The aim of the study was to assess COL1A1 gene expression as a novel marker for the progression of hepatitis B cirrhosis into hepatocellular carcinoma. Methods: This cohort study included 348 subjects and was conducted between May 2018 and June 2019. Subjects were divided into 4 groups: group1 included HBV positive hepatocellular carcinoma patients “HCC” (n= 87), group II included HBV positive patients with liver cirrhosis “LC” (n = 87), group III included chronic hepatitis B patients with neither HCC nor cirrhosis “ C-HBV” (n = 87) and group IV consisted of healthy volunteers as controls (n = 87). Fasting venous blood samples (10 ml) were collected from each participant in this study and were used for assessment of aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin, albumin and alfa-fetoprotein (AFP). Another portion of blood was collected in 2 vacutainer tubes containing EDTA, one for Complete blood count and the other for gene expression of COL1A1. Results: The gene expression of collagen was 6.9 ± 8.8 in group 1 (HBV positive hepatocellular carcinoma patients) and this was a significant increase in comparison with the other groups. In group 2 (HBV positive patients with liver cirrhosis), the gene expression (collagen) was 3.7±1.5 and it was significantly increased when compared with group 4 (healthy volunteers). Conclusion: COL1A1 gene expression can be used as an indicator of the progression of hepatitis B cirrhosis into hepatocellular carcinoma.

scholarly journals Molecular Mechanisms Driving Progression of Liver Cirrhosis towards Hepatocellular Carcinoma in Chronic Hepatitis B and C Infections: A Review

2019 ◽  
Vol 20 (6) ◽  
pp. 1358 ◽  
Author(s):  
Tatsuo Kanda ◽  
Taichiro Goto ◽  
Yosuke Hirotsu ◽  
Mitsuhiko Moriyama ◽  
Masao Omata
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Hepatitis B ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Primary Liver Cancer ◽  
Immune Checkpoints ◽  
Major Type ◽  
Advanced Stages ◽  
Almost All

Almost all patients with hepatocellular carcinoma (HCC), a major type of primary liver cancer, also have liver cirrhosis, the severity of which hampers effective treatment for HCC despite recent progress in the efficacy of anticancer drugs for advanced stages of HCC. Here, we review recent knowledge concerning the molecular mechanisms of liver cirrhosis and its progression to HCC from genetic and epigenomic points of view. Because ~70% of patients with HCC have hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection, we focused on HBV- and HCV-associated HCC. The literature suggests that genetic and epigenetic factors, such as microRNAs, play a role in liver cirrhosis and its progression to HCC, and that HBV- and HCV-encoded proteins appear to be involved in hepatocarcinogenesis. Further studies are needed to elucidate the mechanisms, including immune checkpoints and molecular targets of kinase inhibitors, associated with liver cirrhosis and its progression to HCC.

scholarly journals NOTCH3 rs1043996 Polymorphism Is Associated with the Occurrence of Alcoholic Liver Cirrhosis Independently of PNPLA3 and TM6SF2 Polymorphisms

2021 ◽  
Vol 10 (19) ◽  
pp. 4621
Author(s):  
Ana Bainrauch ◽  
Dino Šisl ◽  
Antonio Markotić ◽  
Ana Ostojić ◽  
Slavko Gašparov ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Transplantation ◽  
Logistic Regression ◽  
Liver Cirrhosis ◽  
Logistic Regression Model ◽  
Control Group ◽  
Alcoholic Liver Cirrhosis ◽  
Common Indication ◽  
Model Adjustment ◽  
Cirrhotic Patients

Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms PNPLA3 rs738409, EGF rs4444903, TM6SF2 rs58542926, MTHFR rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms (NOTCH1 rs3124591, NOTCH3 rs1043996 and rs1044116, NOTCH4 rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients’ susceptibility to ALC was significantly associated with PNPLA3 rs738409, TM6SF2 rs58542926, and NOTCH3 rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the PNPLA3 GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with PNPLA3 rs738409 and EGF rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors.

Increased levels of typically fetal bile acid species in patients with hepatocellular carcinoma

2001 ◽  
Vol 100 (5) ◽  
pp. 499-508 ◽  
Author(s):  
Mohamad Y. EL-MIR ◽  
Maria D. BADIA ◽  
Nazaret LUENGO ◽  
Maria J. MONTE ◽  
Jose J. G. MARIN
Keyword(s):  
Hepatocellular Carcinoma ◽  
Liver Cirrhosis ◽  
Liver Metastasis ◽  
Viral Hepatitis ◽  
Chronic Viral Hepatitis ◽  
Control Group ◽  
Serum Alpha Fetoprotein ◽  
Liver Neoplasia ◽  
Urine And Serum ◽  
Serum And Urine

The aim of this work was to investigate the reappearance during liver neoplasia of bile acids (BAs) species, which are unusual in healthy adults, but common in fetuses. Serum and urine samples were collected from patients with hepatocellular carcinoma (HCC; n = 27), and for comparative purposes, with liver cirrhosis (n = 49), liver metastasis (n = 19), chronic viral hepatitis (n = 11) and healthy volunteer (control group; n = 26) groups. BAs were identified and measured by GC–MS. Hypercholanaemia was found in all groups of patients. In HCC, this was characterized by a marked increase in the chenodeoxycholate/cholate ratio in both serum and urine. Although increased levels of BAs, with hydroxylations at unusual positions, and oxo-BAs were found in HCC, these were not significantly different from those observed in other groups. However, BAs with a flat structure, i.e. Δ4-unsaturated- and 5α- or allo-BAs, which were almost absent in healthy subjects, were markedly increased in the serum and urine of HCC patients. They were also detected, although in much lower amounts, in liver metastasis and liver cirrhosis, but not in viral hepatitis. Flat-BAs were better detected in urine than in serum. Urinary Δ4-unsaturated-BA output was significantly lower in patients with small tumours (< 3 cm) compared with those with higher size tumours. No correlation between flat-BA output into urine and serum alpha-fetoprotein or total BAs was found. These results suggest that Δ4- and/or allo-BAs are particularly elevated in patients with HCC, which may be a potentially useful complementary, rather than alternative, marker for early detection of liver neoplasia.

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