Evaluation of Circular RNA SMARCA5 as a Novel Biomarker for Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth most prevalent type of cancer in Egypt and the sixth globally. Most patients with HCC are typically diagnosed during the advanced stages of the disease due to the absence of biomarkers for early detection. Consequently, these patients miss the optimal timeframe for receiving therapy. OBJECTIVE: we aimed to assess the circular RNA SMARCA5 level and SMARCA5 mRNA gene expression as a potential biomarker for early detection of HCC. METHODS: The present study utilized a case-control design comprising 159 participants. Participants were selected from both inpatient and outpatient hepatology and gastroenterology clinics at the National Liver Institute Hospital, Menoufia University. They were evenly distributed among three groups: Group I: 53 control subjects, Group II: 53 HCV cirrhotic patients, and Group III: 53 HCC patients. Tumor staging was done using BCLC staging system. Each patient underwent a thorough clinical examination, radiological examination, complete history taking, and serum Alpha-fetoprotein (AFP) assessment and detection of circular RNASMARCA5 and SMARCA5mRNA gene sutilizing quantitative real-time polymerase chain reaction. RESULTS: Statistically substantial differences were observed in the examined groups in terms of AFP, SMARCA5, and CircSMARCA5 (P-value = 0.001, 0.001 & 0.001). CircSMARCA5 and SMARCA5mRNA were markedly down regulated in the HCC group compared to HCV cirrhotic patients and controls. ROC analysis for early HCC diagnosis demonstrated that the CircSMARCA5 area under the curve (AUC) at cut-off point 4.55 yielded a specificity of 83.8% and sensitivity of 91.7%. The AUC for AFP at a cut-off point of 515ng/ml yielded a specificity of 89.2% and a sensitivity of 91.3%. CONCLUSION: CircSMARCA5 has the potential to be a more sensitive predictor of HCC disease compared to AFP.

Prognosis of spontaneous bacterial peritonitis in patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of death from cancer worldwide. Spontaneous bacterial peritonitis (SBP) is associated with poor prognosis. This study aimed to evaluate risk factors, differences in clinical characteristics and prognosis of SBP in patients with HCC in comparison with non-HCC patients. METHODS: This study was conducted on patients with cirrhosis who were admitted to hospital with SBP. The patients were divided into two groups: SBP group with HCC (n = 150) and SBP group without HCC (n = 250). RESULTS: Men and women accounted for 72% and 28% (n = 108 and 42, respectively) of the population in SBP group with HCC with mean age 55.8 ± 13.1 years. They accounted for 68.4% and 31.6% (n = 171 and 79, respectively) in the SBP group without HCC with mean age 56.8 ± 10.5 years. In-hospital mortality was 25.3% in the SBP group with HCC and 18.8% in SBP group without HCC. Gastrointestinal bleeding was the most common cause of death in both groups. No significant difference was observed in patient outcomes between the two studied groups. The deceased patients had significantly higher levels of leukocytes and neutrophils in ascitic fluid as well as a higher frequency of positive culture results than in patients who survived (p < 0.001). However, there was no significant difference in protein level in ascitic fluid or causative organism between patients who survived and those who died (p = 0.63 and 0.19, respectively). CONCLUSIONS: Prognosis of SBP in patients with HCC seemed similar to that in patients without HCC.

Suppressor of Cytokine Signaling-3 Gene Polymorphisms and the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients in Egypt.

BACKGROUND: Hepatocellular carcinoma (HCC) contributes significantly to cancer mortalities worldwide. The association between a specific single nucleotide polymorphism (SNP) located within the SOCS3 gene as well as the likelihood of hepatocellular carcinoma (HCC) progression in individuals with chronic hepatitis C virus (CHC) was found to be significant. We aimed to study SOCS3 gene polymorphisms at rs4969168 and rs4969170and HCC susceptibility in individuals with CHC. METHODS: The current prospective study involved 111 subjects divided in to three groups (HCC, HCV with and with no cirrhosis, and apparently healthy individuals). Tumor staging was done using BCLC staging system. SOCS3 (rs4969168 and rs4969170) gene polymorphisms' analysis was done utilizing real-time polymerase chain reaction (RT-PCR) (via DNA extracted from all subjects). All subjects underwent a complete history, medical examination, and laboratory and radiological data collection. RESULTS: Compared to healthy controls, homozygous AA genotypes and heterozygous GA genotypes were substantially overrepresented in  HCC patients as well as those with CHCaccompanied by cirrhosis.AFP, smoking, glucose level, and AA genotype of rs4969170 might be critical significant parameters for HCC development. CONCLUSION: SOCS3 gene polymorphisms at rs4969168 and rs4969170 are associated with HCC and liver fibrosis progression in the Egyptian population with CHC infection.

A multicentric and nationwide predictive study role of T cell sub-population in the prevalence and prognosis of cryoglobulinemia among genotype 4 chronic hepatitis C patients.

The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases.

BACKGROUND: Helicobacter pylori (H. pylori) is a significant human pathogen that is responsible for a variety of illnesses, including mucosa-associated lymphoid tissue lymphoma, gastric cancer, peptic ulcers, and gastritis. AIM: To investigate the frequency of H. pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H. pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen. METHODS: H. pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H. pylori infection. The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction. The patients underwent 14 d of triple-therapy treatment. The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation. RESULTS: The intention-to-treat eradication rate was 59.2% (95%CI: 48.2%-70.3%). Rates of H. pylori resistance to clarithromycin, amoxicillin, and metronidazole were 52.8%, 81.9%, and 100%, respectively. Successful eradication of H. pylori was more significantly associated with vacA s1-positive strains [adjusted odds ratio (aOR) = 0.507, 95%CI: 0.175-0.822]. A significant association was found between failed eradication rate and H. pylori strains resistant to clarithromycin (aOR = 0.204, 95%CI: -0.005 to 0.412) and amoxicillin (aOR = 0.223, 95%CI: 0.026-0.537). CONCLUSION: This study's low H. pylori eradication rate following 14-d triple therapy is concerning and worrying. H. pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin, amoxicillin, and clarithromycin in this research is challenging and of great concern.

Hypokalemia as a responsible factor related with the severity of hepatic encephalopathy: a wide multination cross-sectional study.

Several precipitating factors of hepatic encephalopathy have been recognized and studied. Hepatic encephalopathy which is a frequent and grave complication of liver failure, is associated with multiple biochemical changes like high serum ammonia, mercaptan and phenol levels, low albumin levels and derangements in electrolytes. It is characterized by a range of neuronal and psychological aberrations mainly due to the inability of liver to metabolize different neurotoxic chemicals produced in the body. Hypokalemia is one of the most important findings in hepatic encephalopathy and postulated as a precipitating factor of the condition. The authors aimed to know the frequency of hypokalemia and its relation to the severity of hepatic encephalopathy. Methods: After taking approval from the hospital ethical review committee, a total of 5000 patients with hepatic encephalopathy were recruited by consecutive sampling. They were interviewed, examined and investigated for serum potassium levels and other precipitating factors of hepatic encephalopathy. Results: Total of 5000 patients including 3070 (61.4%) males and 1930 (38.6%) females, aging 13 years and above were studied. The frequency of hypokalemia was 78% (3900 patients). Relating the serum potassium level with the severity of hepatic encephalopathy, 1200 (60%) out of 2000 patients with serum potassium below 2.5 mEq/l were in grade 4 (40%) and 800 out of 2000 were in grade 3 encephalopathy. On the other hand, only 700 patients (6.4%) out 1100 with serum potassium above 3.4 mEq/l were in grade 4 encephalopathy. Conclusion: Hypokalemia is a frequent finding in patients with hepatic encephalopathy and found to be directly related to its severity.

Evaluation of Amino Acids Profile as Non-Invasive Biomarkers of Hepatocellular Carcinoma in Egyptians.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most dangerous complication of chronic liver disease. It is a multifactorial complicated disease. Hepatitis C and hepatitis B viruses (HCV and HBV, respectively) represent the main causes of HCC in Egypt. Early diagnosis is very important to aid in early intervention. OBJECTIVES: The goal of this research is to evaluate the metabolic role of different amino acids as non-invasive biomarkers over the course of HCC. METHODS: This study included 302 participants with 97 diagnosed, untreated HCC patients, 81 chronic HCV patients, 56 chronic HBV patients, 18 co-infected patients, and a control group of 50 normal age and gender-matched individuals. All participants provided complete medical histories and underwent complete clinical examinations, abdominal ultrasonography and/or computed tomography, routine laboratory investigations, estimation of serum α-fetoprotein, and determination of amino acid levels using ultra-performance liquid chromatography (UPLC MS/MS). RESULTS: This work revealed a decline in branched chain amino acids (BCAA) and increase in aromatic amino acids (AAA) among infected groups (HCC, HBV, HCV, and co-infected patients) compared to control subjects and a marked change in Fisher's and the BCAAs/tyrosine molar concentration ratios (BTR) between controls and infected groups. CONCLUSION: Different amino acids could be used as non-invasive markers to discriminate and follow chronic hepatitis patients to predict the course of HCC.

Impact of prothrombin and factor V Leiden mutations on the progression of fibrosis in patients with chronic hepatitis C.

BACKGROUND: The role of thrombotic factors in the pathogenesis and progression of liver fibrosis remains obscure. We aimed to study the relationship between prothrombin G20210A (PT20210) and factor V Leiden (FVL) mutations and the progression of fibrosis and liver function in chronic HCV patients. METHODS: The study included 100 subjects, 88 patients with HCV-related cirrhosis (compensated: 38, decompensated: 50), and 12 controls. Patients with other viral hepatitis or coinfection, inherited metabolic disease, autoimmune hepatitis, hepatic or extrahepatic malignancy, in addition to patients with causes of hypoalbuminemia, elevated bilirubin or prolonged INR not related to cirrhosis were excluded from the study. Relevant clinical data were collected and basic laboratory tests were performed. Liver fibrosis was assessed using APRI and FIB-4 scores. FVL and PT20210 mutations were analyzed. RESULTS: FVL and PT20210 mutations were significantly higher in decompensated vs. compensated patients (32% vs. 5.3%, P = 0.001; 20% vs. 5.3%, 0.043, respectively) and absent in controls. Both mutations significantly correlated to the duration of infection, platelet count and fibrosis scores. PT20210 mutation significantly correlated to serum albumin and INR. Both mutations significantly predicted fibrosis scores, especially PT20210 (AUROC: 0.833 for APRI and 0.895 for FIB-4). CONCLUSIONS: Both mutations are significantly correlated to fibrosis progression and liver profile and could be considered as markers predicting the need for early and different intervention.

Association between thrombocytopenia and the severity of Covid-19 infection among hospitalized Egyptian patients.

Background: COVID-19, which is caused by the corona virus 2 that causes severe acute respiratory syndrome, causes a respiratory and systemic illness that in 10-15% of patients escalates to a severe form of pneumonia. Thrombocytopenia is frequent in patients with COVID-19. We aimed to evaluate the association between thrombocytopenia and the severity of COVID-19 infection in hospitalized patients. Methods: A cross-sectional study was done on 800 Egyptian patients with confirmed covid-19 infection. They were divided into Group I (Mild): 200 symptomatic patients meeting the case definition for COVID-19 without radiological evidence of pneumonia or hypoxia. Group II (Moderate): 200 patients with clinical signs of non-severe pneumonia and radiological evidence of pneumonia. Group III (Severe): 200 patients with clinical signs of pneumonia plus: respiratory or lung dysfunction. Group IV: 200 critically ill patient in ICU: Acute respiratory distress syndrome (ARDS).Results: there was a highly statistically significant difference between the studied groups regarding thrombocytopenia (p < 0.001). Thrombocytopenia was statistically higher in severe and critically ill patients. In addition, a statistically significant difference found in outcome among the studied groups (p < 0.05) {critically ill (40%), severe (17.5%)}. The most common cause of death was respiratory failure, which occurred in 28 severe patients (80%) and 65 critically ill patients (81.25%), followed by hemorrhage due to thrombocytopenia, which occurred in 7 severe patients (20%) and 15 critically ill patients, respectively (18.75%). Conclusion: The Platelet count is a straightforward, inexpensive, as well as easily available laboratory parameter that is frequently linked to severe covid-19 infection and a significant death risk.

The association between micro-RNA gene polymorphisms and the development of hepatocellular carcinoma in Egyptian patients.

INTRODUCTION: The development and progression of hepatocellular carcinoma (HCC) is a multistage process involving the deregulation of genes that are crucial to cellular processes. Multiple risk factors are correlated with HCC. MicroRNA is differentially expressed in the development of different types of malignancies, including hepatic malignancy. Single nucleotide polymorphisms (SNPs) are the most common sequence variation in the human genome. SNPs in miRNAs may affect transcription, processing, or target recognition and result in malignant disease. The aim of the study was to determine the association between microRNA gene polymorphisms and the development of HCC in Egyptian patients. MATERIAL AND METHODS: This study included 200 individuals who were matched in age and sex. Tumour staging was done using the BCLC staging system. Quantification and genotyping of microRNA were performed. RESULTS: Among the 200 patients, 2 groups were described: group I included 90 HCC patients with a male majority (72.2%), and group II comprised 110 controls. Three microRNA SNPs were assayed in both patients and controls. There was a significant association between rs10061133 miR-499b and the risk of HCC. The genotypes GG or G allele were significantly associated with an increased risk of HCC (GG: OR = 2.91, 95% CI: 1.23-4.22, p = 0.013; G allele: OR = 1.79, 95% CI: 1.12-2.15, p = 0.026) compared with the genotype of AA or AG or A allele. CONCLUSIONS: There is an association between the miRNA SNPs and the susceptibility to HCC, to explore some roles and mechanisms of SNPs within miRNAs in the occurrence and development of HCC.

A cross-sectional study of gastrointestinal manifestations in COVID-19 Egyptian patients.

BACKGROUND: The latest novel corona virus disease (COVID-19) pandemic shows a significant health concern. We aimed to study the prevalence of gastrointestinal symptoms among COVID-19 Egyptian patients. METHODS: A cross-sectional study was carried out on 860 patients with COVID-19 infection classified according to Ministry of Health Program (MOHP) into three groups (280 patients with mild infection, 258 patients with moderate disease and 322 patients with severe disease). All patients were subjected to medical history, clinical examination, laboratory investigations, high-resolution computed tomography chest (HRCT chest) and other investigations when needed in some patients e.g., upper gastro-intestinal (GI) endoscopy, abdomino-pelvic ultrasound and ECHO. RESULTS: Gastro-intestinal symptoms were present in 27.2% of the studied patients. The most common reported GIT symptoms were vomiting, diarrhea, abdominal/gastric pain, followed by nausea. GIT symptoms presence was significantly higher in severe cases in comparison to mild or moderate cases. C-reactive protein (CRP), serum ferritin, Aspartate aminotransferase (AST), bilirubin, and creatinine were significantly associated with the presence of GI symptoms. CONCLUSIONS: GI symptoms are prevalent among COVID-19 patients, the most common were vomiting and diarrhea and were associated with COVID-19 severity.

The Putative Role of Natural Killer Cells in Patients with Hepatitis C Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Natural Killer (NK) cells have crucial roles in immune responses against malignant transformation including hepatocellular carcinoma (HCC). The NKG2D receptor has a critical role in the NK recognition of target cells. AIM: We assessed NKG2D receptor expression as a diagnostic biomarker for HCC detection and progression in Egyptian patients with hepatitis C virus (HCV)-related HCC. METHODS: We classified 81 patients into three groups: chronic hepatitis (21), cirrhotic (30) and HCC (30) patients, with 36 individuals enrolled to the control group. We analyzed NK levels in peripheral blood and NKG2D receptor expression in NK cells using flow cytometry. RESULTS: We observed a significant decrease in NKG2D (CD314) expression on circulating NK cells and frequency of NK cells expressing NKG2D (CD314) in HCC patients. Also, in patients, larger foci lesions significantly correlated with decreased NK cell numbers. Multiple foci numbers and patients with a Child score C significantly correlated with decreased circulating NK cells expressing NKG2D and decreased NKG2D expression. CONCLUSION: The percentage of NK cells in peripheral blood and NKG2D receptor expression could function as potential biomarkers for HCC detection and progression.

Red cell distribution width as a predictor of outcome in hospitalized cirrhotic patients.

BACKGROUND: A systemic inflammatory response syndrome (SIRS) is linked to red cell distribution width (RCDW), which produces pro-inflammatory signals that act directly on hematopoietic stem cells in the bone marrow. This stimulation may cause alterations in the membrane of red blood cells (RBCs), as assessed by RCDW, which have been linked to increased morbidity and death in a number of systemic disorders. AIM: This study aims to evaluate RCDW as a predictor of outcome in hospitalized cirrhotic patients. METHODS: This prospective cross-sectional study was conducted on 1000 patients. The outcome was assessed by days of hospitalization; mortality in hospitalized patients or during short-term follow-up (3 months) and rehospitalization during follow-up of 6 months. RESULTS: Male represented 69.6%. Mean age was 57.67 ± 13.07 years old. Baseline co-morbidities were recorded as the presence of diabetes mellitus (200 patients) and hypertension (400 patients). Hepatitis C virus was the commonest etiology of the diseased liver (90%). Child-Pugh classes A, B and C of studied patients represented (21.2%, 38.8% and 40%). The survived patients during follow-up represented 63.3%. Area under the curve for RCDW was 0.923 (95% CI, 0.904-0.943), 0.910 for C-reactive protein (95% CI, 0.890-0.930), 0.904 for Hb (95% CI, 0.883-0.925) and 0.903 for platelets (95% CI, 0.882-0.924). RCDW cutoff point at 21.35 for predicting survival had sensitivity 93%, specificity 91%, accuracy 92%, positive predictive value 85 and negative predictive value 96. Regression analysis revealed a significant positive association between both RCDW and white blood cells with mortality. CONCLUSION: RCDW could provide useful information for predicting the length of hospitalization and survival in hospitalized cirrhotic patients.

Variceal recurrence 4 years post endoscopic band ligation in hepatitis C patients who achieved sustained virological response with oral direct-acting antiviral therapy.

Oral Direct-acting antivirals (DAAs) are safe, highly effective altering disease burden and prognosis in hepatitis C patients. Sustained virologic response (SVR) is achieved nowadays in more than 90% of the treated patients and related to the improvements in functions of the liver, fibrosis plus survival. Furthermore, portal hypertension is thought to be improved with achievement of virological response, parallel to the improvements in hepatic inflammation and fibrosis. We aimed to assess the recurrence rate of oesophageal varices by long-term follow-up in patients treated with different DAAs regimens who had achieved SVR. We studied 176 Child A cirrhotic HCV patients who achieved SVR after DAAs treatment and had a history of endoscopic oesophageal varices obliteration and were on maximum tolerated propranolol dose. They were subjected to follow-up upper gastrointestinal endoscopy repeated every 6 months for 4 years. Fifty-two patients (29.5%) had recurrence of oesophageal varices observed during the 4-years follow-up upper GIT endoscopy. On multivariate analysis, platelet count was the only significant variable, P-value = .007*. HbA1C, HOMA IR, BMI 1 and BMI 2 showed non-significant differences between the studied groups. By ROC analysis, we identified baseline platelet count of 96 000/µL with 100% sensitivity (95% confidence interval [CI] [91%-100%]) and 74% specificity (95% CI [65%-81%]). Spearman correlation showed a positive correlation between AFP, age, AST, Bilirubin, creatinine, INR. Patients who achieved SVR post DAAs showed a significant decrease in oesophageal varices recurrence post endoscopic obliteration. Baseline platelet count was found to be a strong independent predictor for oesophageal varices recurrence.

Direct acting antivirals are associated with more liver stiffness regression than pegylated interferon therapy in chronic hepatitis C patients.

OBJECTIVES: Extent of post-treatment fibrosis change in patients with different stages of fibrosis not fully known. We aimed to study changes in liver fibrosis in chronic hepatitis C patients who were treated with pegylated interferon/ribavirin (PEG/RBV) or direct acting antivirals (DAAs). METHODS: Retrospective evaluation of results of transient elastography (TE) was done before and 1 year after end of treatment for patients treated with PEG/RBV (n = 268) and DAAs (n = 245). RESULTS: The average age was 45.54 ± 10.64 years; mainly males. All patients in the DAAs group achieved sustained virological response (SVR), unlike 56.3% of the patients in the PEG/RBV group. F3-F4 fibrosis was predominant in the PEG/RBV nonresponder patients (51.3%) and DAAs responders (57.1%). TE decreased 1 year after end of treatment (p = 0.001) in the viral responders of the PEG/RBV group (7.44 ± 4.02 vs. 10.24 ± 7.29 kPa) and DAAs group (12.12 ± 9.21 vs. 16.81 ± 12.84 kPa) respectively. The delta TE change in the DAAs responders was higher than the PEG/RBV responders (p = 0.001) and PEG/RBV nonresponders (p = 0.001). The percentage of patients with liver fibrosis regression was higher in DAAs responders (52.5%) than in PEG/RBV responders (23.3%). CONCLUSION: Treatment with DAAs is associated with fibrosis improvement more than treatment with PEG/RBV in chronic hepatitis C patients.

Matrix Metalloproteinase-11 Gene Polymorphisms as a Risk for Hepatocellular Carcinoma Development in Egyptian Patients.

BACKGROUND: Chronic hepatitis C (CHC) virus infection is one of major risk factors of hepatocellular carcinoma (HCC) in Egypt, which is a major cause of cancer mortalityin the world. Matrix metalloproteinase-11 (MMP-11) has an important role in tumor migration and metastasis. Therefore, this study aimed to determine relation between MMP-11 gene polymorphisms and risk of HCC development among Egyptian cirrhotic patients. SUBJECTS AND METHODS: Two hundred and sixty patients were included, 140 of them with HCC on top of CHC and 120 patients with post CHC liver cirrhosis (LC) as well as 140 subjects were enrolled in the study as healthy controls. Two single nucleotide polymorphisms (SNPs) rs738791 and rs738792 for MMP-11 gene were done using real-time PCR. RESULTS: Combination of CT and TT allele of rs738791 genotypes was more significantly frequent in HCC compared to LC patients and controls, however, a higher frequency of T allele was found in HCC patients compared to LC and controls. In spite of lake of significant difference between patient groups regarding the rs738792 genotypes, the CC genotype was considered a risk of developing portal vein thrombosis, and was associated with advanced tumor stage, increased tumor size, higher Cancer of the Liver Italian Program [CLIP] score, more advanced Barcelona stage [D] and with child Pugh class [C]. CONCLUSION: Genetic variations in MMP-11 may be implicated in post HCV-HCC development and might be dependable biomarkers for HCC progression.

DNA Methyltransferases as Potential Biomarkers for HCV Related Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern in many countries including Egypt. The alteration in DNA methylation that was observed in HCC patients suggests a possible role of DNA methyltransferases (DNMTs) in the disease pathogenesis in addition to potential role as a disease biomarker. AIM: To study the change in DNMTs expression in chronic HCV infected patients as potential non- invasive biomarker for diagnosis of hepatocellular carcinoma. METHODS: 26 patients with HCC, 45 patients with liver cirrhosis, 20 chronic HCV patients and 20 apparently healthy individuals as a control group were enrolled in this study. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed for all study participants. RESULTS: A significant difference in DNMTs expression was observed among the studied groups. Receiver operating characteristics (ROC) curve analysis revealed that with a cutoff value of 3.16 for DNMT 3A expression, sensitivity and specificity were 80.8 and 95.6% respectively and area under curve (AUC) was 0.958, p < 0.001 for discriminating hepatocellular carcinoma among post hepatitis C cirrhotic patients. Besides DNMT 3B relative expression cutoff value of 3.10 showed 84.6% sensitivity and 77.8% specificity and AUC was 0.888, p < 0.001. On the other hand, cutoff value 0.65 for DNMT1 relative expression showed 92.3% sensitivity and 44.4% specificity and AUC was 0.72, p= 0.002. DNMT1, DNMT 3A and DNMT 3B have significant positive correlation with the level of AFP (p-value = 0.003, 0.004 and 0.008 respectively). The relative expression of DNMT3B was significantly correlated to focal lesion size (p-value = 0.015). High DNMTs expression was significantly associated with the presence of multiple focal lesions but not with the Child Pugh grade (p> 0.05). CONCLUSION: The mRNA levels of DNMTs could be a potential biomarker for early detection of HCC development.
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Sudomotor Changes in Hepatitis C Virus Infection with or without Diabetes Mellitus: A Pilot Study in Egyptian Patients.

Hepatitis C virus (HCV) infection can affect the neurological system, and neuropathy is one of these manifestations. Hepatitis C virus infection is associated with diabetes mellitus (DM) type II, and diabetic patients are at higher risk of acquiring HCV infection. Sweat function has been proposed to assess early autonomic neuropathy. This study aimed to evaluate small fiber neuropathy in asymptomatic HCV-related cirrhotic patients with or without DM through sweat function assessment by Sudoscan test. Three groups were involved: 47 healthy controls, 48 HCV-related cirrhotic patients without DM (group 1), and 49 HCV-related cirrhotic patients with DM type II (group 2). All participants were subjected to liver panel tests, renal function tests, cell blood counts, HbA1c, and abdominal ultrasound. Sweat function was assessed in all patients and controls by measuring hand and feet electrochemical skin conductance (ESC, microSiemens [µS]) using Sudoscan. Peripheral neuropathy was detected in none of the controls, 39% of group 1 patients, and 62% of group 2 patients (P < 0.0001). The mean feet ESC (FESC) was 88.3 ± 6.8 µS in controls, 67.2 ± 19.2 µS in group 1, and 57.9 ± 19.4 µS in group 2 (P < 0.0001). A significant correlation was observed between FESC and bilirubin, albumin, creatinine, international normalized ratio, transaminases, and splenic size. Electrochemical skin conductance measurement is a valuable, noninvasive method for early detection of small fiber neuropathy in asymptomatic HCV-related cirrhosis, with or without DM.

Role of resistin, IL-6 and NH2-terminal portion proBNP in the pathogenesis of cardiac disease in type 2 diabetes mellitus.

INTRODUCTION: Epidemiological and genetic studies have recorded the association between proinflammatory cytokines and the development of insulin resistance, diabetes, and cardiovascular disease. The role of interleukin 6 (IL-6), NH2-terminal portion pro-brain natriuretic peptide (NT-proBNP) and resistin in the pathogenesis of heart disease in type 2 diabetes mellitus (T2DM) is still a matter of controversy. The current study aimed to evaluate the role of these biomarkers in the development of left ventricular systolic dysfunction and the ability to use them as non-invasive test in the prediction of left ventricular hypertrophy and systolic dysfunction in T2DM. RESEARCH DESIGN AND METHODS: 150 participants were included in this case-control study. Patients were divided into two subgroups according to echocardiographic findings: group 1a included 46 patients with type 2 diabetes mellitus and echocardiographic evidence of abnormal systolic function; group 1b included 54 patients with type 2 diabetes mellitus and with normal echocardiogenic study; and group 2 included 50 apparently healthy controls. Routine laboratory investigations such as complete blood count, liver and renal function tests, and lipid profile, serum IL-6, NT-proBNP, and resistin were measured in all participants. Conventional echocardiography was done with special concern on the assessment of left ventricular systolic function (ejection fraction). RESULTS: There was a significant increase in the level of resistin, NT-proBNP and IL-6 in group 1a patients compared with group 1b and in healthy controls. Echocardiographic parameters showed a significant increase in left ventricular mass index, left ventricle posterior wall thickness, interventricular septum thickness, and left ventricle mass in group 1a compared with group 1b and the control group. The increased left ventricular mass index was associated with higher levels of IL-6, NT-proBNP and resistin. CONCLUSIONS: Proinflammatory cytokines had a clear relation with left ventricular systolic dysfunction and hypertrophy and can be used as early non-invasive markers for detection of left ventricular remodeling and systolic dysfunction in patients with T2DM.

Total tumor volume as a prognostic value for survival following liver resection in patients with hepatocellular carcinoma. Retrospective cohort study.

BACKGROUND: Total tumor volume (TTV) can provide a simplified parameter in describing the tumor burden by incorporating the size and number of tumor nodules into one continuous variable. The aim of the study was to evaluate the prognostic value of TTV in resection of hepatocellular carcinoma (HCC). METHODS: Patients who underwent liver resection for HCC between 2012 and 2017 were retrospectively analyzed. Patients were divided into a group with TTV ≤65.5 cm³ (which nearly equal to a single tumor with a diameter of 5 cm), and another group with TTV > 65.5 cm³. RESULTS: Two hundred and four patients were included in this study (108 patients had TTV ≤ 65.5cm3, and 96 patients had TTV > 65.5 cm³). Ninety patients (44.1%) were within Milan and 114 patients (55.9%) were beyond Milan criteria. Eighteen patients (15.8%) of beyond Milan criteria had TTV ≤ 65.5 cm³, with a median survival of 32 months which is comparable to a median survival of patients with TTV< 65.5 cm³ (38 months, P = 0.38). TTV-based Cancer of Liver Italian Program (CLIP) score gained the highest value of likelihood ratio 114.7 and the highest Concordance-index 0.73 among other prognostic scoring and staging systems. In multivariate analysis, independent risk factors for diminished survival were serum AFP level >400 ng/ml, TTV >65.5 cm³, microvascular invasion, postoperative decompensation (all P values < 0.05). CONCLUSION: TTV is a feasible prognostic measure to describe the tumor burden in patients with HCC. TTV-CLIP score may provide good prognostic value for resection of HCC than other staging systems.