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

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 < 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.

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Cerebral Hemodynamics and Cognitive Function in Cirrhotic Patients with Hepatic Encephalopathy

Gastroenterology Research and Practice ◽

10.1155/2016/8485032 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 7

Author(s):

Yuqing Zhou ◽

Qian Dong ◽

Rong Zhang ◽

Shunfeng Zhou ◽

Linqiang Li ◽

...

Keyword(s):

Cognitive Function ◽

Treated Group ◽

Cerebral Hemodynamics ◽

Control Group ◽

Group 4 ◽

Group A ◽

Cirrhotic Patients ◽

Group 3 ◽

Group 2 ◽

Group B

Aims.To investigate cerebral hemodynamics in cirrhotic patients with HE and to observe effects of treatment in cerebral hemodynamics and correlations among ammonia, cerebral hemodynamics, and cognitive function.Methods. There were four groups: healthy controls (group 1), cirrhosis without HE (group 2), cirrhosis with MHE (group 3), and cirrhosis with OHE (group 4). Ammonia and cerebral hemodynamics (by TCD) were assessed. Patients in group 3 were subsequently randomized to two subgroups: the control (group A) and the treated (group B, treated with lactulose for two months), and they were retested for ammonia and TCD after treatment. Results. Ammonia,Vm,Vd, PI, and RI were statistically different before treatment, and ammonia, PI, and RI levels paralleled the severity of HE (P<0.05). In group B,Vdincreased and ammonia, PI, and RI declined following treatment (P<0.05), while there were no differences in group A (P>0.05). Correlations were found between ammonia andVd, PI, RI, NCT-A, and DST and also found betweenVd, PI, RI, and NCT-A and DST (P<0.05).Conclusions. This study revealed that cerebral hemodynamics were related to the severity of HE and cerebral autoregulation was impaired. There were tight correlations among ammonia, cerebral hemodynamics, and cognitive function, and, following treatment, cerebral hemodynamics improved.

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The Serum NT-proBNP in Patients with Cirrhosis: Relationship to Cardiac Dysfunction and Liver Function

Infection International ◽

10.1515/ii-2017-0038 ◽

2013 ◽

Vol 2 (1) ◽

pp. 36-42

Author(s):

Hua Mao ◽

Deng-feng Jiang ◽

Li-yun Huang

Keyword(s):

Liver Cirrhosis ◽

Liver Function ◽

Cardiac Dysfunction ◽

Control Group ◽

Clinical Implications ◽

Healthy Controls ◽

Cirrhotic Cardiomyopathy ◽

Group A ◽

Cirrhotic Patients ◽

Left And Right

Abstract Objective To detect the values of NT-proBNP and evaluate its relationship with liver function, cardiac structure, and cardiac function which was evaluated by echocardiography in patients with liver cirrhosis. Methods A total of 50 liver cirrhotic patients and 11 healthy controls were studied by two dimensional Doppler echocardiography. Liver cirrhotic patients were divided into group A, B and C according to the Child-Pugh score. Cardiac dimensions and left and right ventricular functions were also evaluated. At the same time, the serum NTproBNP of liver cirrhotic patients and healthy controls were detected, respectively. Results By Comparison between two groups, we found that the values of LVd, LAs, LVPW, AAO, A Wave, RVOTs, PV and NT-proBNP in liver cirrhosis group were higher than those in control group, whereas the value of E/A decreased. As for the value of LAs and serum NT-proBNP, A and B group were all lower than C group. With LAs > 35 mm, the number of cases in liver cirrhosis group was higher than that in control group. So did that With E/A < 1. Conclusions The cardiac dysfunction confirmed the existence of cirrhotic cardiomyopathy. More clinical implications were found in liver cirrhotic patients with increased values of serum NT-proBNP.

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Comparing the Effectiveness of Carvedilol and Propranolol to Prevent Reoccurrence of Esophageal Variceal Bleeding in Patients with Liver Cirrhosis.

10.53350/pjmhs211582491 ◽

2021 ◽

Vol 15 (8) ◽

pp. 2491-2493

Author(s):

Liaqat Khurshid ◽

Asadullah Khan ◽

Salim Hassan ◽

Adil Naseer Khan

Keyword(s):

Liver Cirrhosis ◽

Arterial Pressure ◽

Portal Vein ◽

Variceal Bleeding ◽

Esophageal Variceal ◽

Esophageal Variceal Bleeding ◽

Portal Vein Flow ◽

Group A ◽

Cirrhotic Patients ◽

Group B

Objective: To compare the efficacy of carvedilol and propranolol to prevent reoccurrence of esophageal variceal bleeding in patients with liver cirrhosis. Study Design: Place and Duration: Department of Gastroenterology and Hepatology, Ayub Teaching Hospital, Abbottabad, Pakistan for six months duration from 15th November 2020 to 15th May 2021. Methods: Total one hundred and forty patients of ages between 18-65 years were presented in this study. Patients detailed demographics age, sex, body mass index and Child-Turcotte-Pugh (CTP) class were recorded after taking written informed consent. Patients were equally (n=70) divided into two groups. Group A had 70 patients and received carvedilol while group B had 70 patients and received propranolol for 6 months. Reoccurrence ofesophageal variceal bleeding in cirrhotic patients among both groups were observed at 2nd, 4th and 6th months and patients pulse rate, arterial pressure and portal vein flow were recorded at these time points. Complete data was analyzed by SPSS 26.0 version. Results: Mean age of the patients in group A was 40.38 ± 5.87 years with mean BMI 28.09 ± 7.33 kg/m2 and in group B mean age was 39.43 ± 12.69 years with mean BMI 27.53 ± 8.84 kg/m2. In group A 45 (64.3%) patients were males and 25 (35.7%) were female patients while in group B 50 (71.43%) were male patients and 20 (28.7%) patients were females. We found that there was no statistically significant difference observed among both groups regarding these demographic variables. Reoccurrence of bleeding observed in group A was significantly lower (among 20 (28.6%) cases) as compared to group B (among 36 (51.43%) cases). Pulse rate, mean arterial pressure and portal vein flow was found lower in the carvedilol group as compared to propanol group with p value < 0.05 upon follow up at2,4 and 6 months. Conclusion: We found in this study that the drug carvedilol was more effective and safe to prevent reoccurrence of esophageal variceal bleeding in cirrhotic patients as compared to propanol. Keywords: Cirrhotic patients, Carvedilol, Propanol, Portal vein flow, Mean arterial pressure

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Systemic Oxidative Stress Markers in Cirrhotic Patients with Hepatic Encephalopathy: Possible Connections with Systemic Ammoniemia

Medicina ◽

10.3390/medicina56040196 ◽

2020 ◽

Vol 56 (4) ◽

pp. 196 ◽

Cited By ~ 1

Author(s):

Cătălin Sfarti ◽

Alin Ciobica ◽

Ioana-Miruna Balmus ◽

Ovidiu-Dumitru Ilie ◽

Anca Trifan ◽

...

Keyword(s):

Oxidative Stress ◽

Hepatic Encephalopathy ◽

Control Group ◽

Oxidative Stress Markers ◽

Stress Markers ◽

Systemic Oxidative Stress ◽

Group A ◽

Cirrhotic Patients ◽

Group B ◽

Control Study

Background and objectives: Oxidative stress shows evidence of dysregulation in cirrhotic patients with hepatic encephalopathy (HE), although there are still controversies regarding the connections between oxidative stress and ammonia in these patients. The aim of this study was to evaluate the oxidative stress implication in overt HE pathogenesis of cirrhotic patients. Materials and Methods: We performed a prospective case-control study, which included 40 patients divided into two groups: group A consisted of 20 cirrhotic patients with HE and increased systemic ammoniemia, and group B consisted of 20 cirrhotic patients with HE and normal systemic ammoniemia. The control group consisted of 21 healthy subjects matched by age and sex. The activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), malondialdehyde (MDA) levels (lipid peroxidation marker), and ammoniemia were evaluated. Results: We found a significant decrease in SOD and GPx activity and also a significant increase of MDA levels in cirrhotic patients with HE as compared to the healthy age-matched control group (1.35 ± 0.08 vs. 0.90 ± 0.08 U/mL, p = 0.002; 0.093 ± 0.06 vs. 0.006 ± 0.008 U/mL, p = 0.001; and 35.94 ± 1.37 vs. 68.90 ± 5.68 nmols/mL, p = 0.0001, respectively). Additionally, we found significant correlations between the main oxidative stress markers and the levels of systemic ammonia (r = 0.452, p = 0.005). Patients from group A had a significant increase of MDA as compared with those from group B (76.93 ± 5.48 vs. 50.06 ± 5.60 nmols/mL, p = 0.019). Also, there was a compensatory increase in the activity of both antioxidant enzymes (SOD and GPx) in patients with increased systemic ammoniemia (group A), as compared to HE patients from group B. Conclusions: Our results demonstrated a significant decrease in antioxidants enzymes activities (SOD and GPx), as well as a significant increase in MDA concentrations, adding new data regarding the influence of oxidative stress in HE pathogenesis in cirrhotic patients.

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

Journal of Clinical Medicine ◽

10.3390/jcm10194621 ◽

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.

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Reduction therapy of ALT levels and prevention of HCC development in patients with HCV-associated cirrhosis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.1529 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 1529-1529

Author(s):

Y. Rino ◽

N. Yukawa ◽

T. Yamada ◽

T. Imada ◽

S. Morinaga ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Hepatitis C ◽

First Year ◽

Factors Affecting ◽

Group A ◽

Second Year ◽

Group B ◽

Observation Period

1529 Background: Approximately 30 million people worldwide are estimated to have liver cirrhosis (LC) associated with hepatitis C virus (HCV). In addition, patients with HCV-associated liver cirrhosis (HCV-LC) have a high risk of developing hepatocellular carcinoma (HCC). Namely, 60–80% of the patients may develop HCC in 10 years. So, preventing these patients from developing HCC is an urgent problem to be solved. To find a way to prevent the development of hepatocellular carcinoma (HCC) from hepatitis C-virus associated liver cirrhosis (HCV-LC), an analysis of the HCV-LC patients who had reduction therapy of ALT levels was performed. Patients and Methods: Seventy-four consecutive HCV-LC patients of Child Stage A were followed for > 10 years for the development of HCC. They were divided into two groups: In group A, the reduction therapy for ALT levels is aggressively performed and in group B, the reduction therapy was not performed aggressively. Results: Initial ALT was higher in group A than in group B, but there was no significance. After reduction therapy, ALT level was significantly high in group A in the first year. However, there were no significant differences between ALT levels in groups A and B of after the second year. In total, 39 patients out of 74 (52.7%) developed HCC within 13 years from the beginning of the study and 35 patients did not developed HCC in the same observation period. The incidence of HCC development in group B [65.7% (23/35)] was significantly higher than in group A [41.0% (16/39)] (p=0.039). The median HCC developing time in group A (12.8 years) was significantly longer than in group B (3.8 years) (p=0.0013). Multivariate analysis demonstrated that reduction therapy and ALT levels were the significant factors affecting HCC development. The incidence of HCC development in group B was 5.8 times higher than in group A. The high and unclassified ALT groups were 4.6 times and 2.2 times higher than in the low ALT group. Conclusion: The chances of surviving for more than 10 years without developing HCC in the HCV-LC patients of Child Stage A were far more favorable in group A than in group B. These results suggest that aggressive reduction therapy for ALT levels in HCV-LC patients could significantly prevent HCC development. No significant financial relationships to disclose.

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Annexin A5 as a marker for hepatocellular carcinoma in cirrhotic hepatitis C virus patients

Egyptian Liver Journal ◽

10.1186/s43066-021-00101-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Waleed Mohamed Serag ◽

Basem Eysa Elsayed

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cirrhosis ◽

Hepatitis C Virus ◽

Longitudinal Study ◽

Hepatitis C ◽

Serum Levels ◽

Control Group ◽

Annexin A5 ◽

Medicine Research ◽

Cirrhotic Patients

Abstract Background The tumorigenesis and development in a variety of cancers is reportedly encouraged via Annexin A5. The levels of Annexin A5 were tested in patients with or without HCC who were affected by liver cirrhosis. The objective of our study was to detect Annexin A5 levels in such patients in order to assess their function as an HCC marker. The longitudinal study comprised 91 cirrhotic HCV patients with and without HCC, and 20 healthy volunteers in the control group approved by the National Hepatology and Tropical Medicine Research Institute (NHTMRI) between March 2017 and August 2018.The serum levels Annexin A5 were found in all groups with ELISA. ANOVA, Mann-Whitney, and χ2 tests had been applied. Results High scales of Annexin A5 (3.89 + 0.85) were recorded for cirrhosis with HCC, either than cirrhotic patients without HCC (3.06 ± 0.88) (P = 0.041), and either than the control group (0.54 ± 0.11) (P < 0.001). Conclusion In HCV cirrhotic patients with and without HCC, AnxA5 can be used as HCC marker.

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