Cirrhotic Group Research Articles

Serum MiRNA-122 as a Diagnostic Marker in HCV Related Liver Cirrhosis

Background and study aim: MicroRNAs were evaluated as biomarkers for liver injury in various liver diseases. This study aimed to evaluate the serum miRNA-122 as a potential biomarker for diagnosis and monitoring different stages of disease in chronic hepatitis C patients. Patients and Methods: A case-control study included 45 subjects, divided into three groups: control group, compensated, and decompensated cirrhotic patients groups. All participants were subjected to full history taking, clinical assessment, routine lab investigations, hepatitis B surface antigen, HCV antibodies, HCV-RNA using PCR, and determination of serum expression of miRNA-122 using real-time PCR. Results: The miRNA-122 expression levels among the two groups with liver disease were significantly higher than the control group. Among cirrhotic patients, the expression levels were significantly higher in the compensated subjects compared to the decompensated group. The miRNA-122 levels decreased with the progression of liver disease (from Child-Pugh class A to C) but without significant difference. Patients with ascites had a significantly lower expression of miR-122 compared to those without ascites. Patients with gastrointestinal bleeding and hepatic encephalopathy had statistically insignificant lower expression of miRNA 122 compared to subjects without these complications. As regards all patients groups there were significant positive correlations between miRNA-122 expression and (AST, ALT, albumin, and viral load) and a significant negative correlation as regard INR. Conclusion: Serum miRNA-122 expression levels decreased with the progression of liver disease and at a cut-off value ≤ 2.74 fold change could predict the occurrence of hepatic decompensation. So Serum miRNA-122 seems to be a useful new diagnostic marker in hepatitis C patients with different stages of the disease.

Genetic Polymorphism of Epidermal Growth Factor Gene as a Predictor of Hepatocellular Carcinoma in Hepatitis C Cirrhotic Patients.

Background:In Egypt, the incidence of hepatocellular carcinoma (HCC) is approximately 4.7% of chronic liver disease patients due to (HCV) infection. Epidermal growth factor (EGF) plays an important role in hepatocyte regeneration. A functional polymorphism in EGF 61A>G was identified; itwas associated with higher risk of HCC. Objectives:to investigate the correlation between the epidermal growth factor (EGF) polymorphism and the risk of hepatocellular carcinoma (HCC) in hepatitis C viral (HCV) cirrhotic patients as well as its relation to EGF protein expression in HCC tissue. Patients and methods:this casecontrol study was conducted on 75 HCV cirrhotic patients including 50 HCC patients (25 withresectable HCC and 25 with advanced unresectable HCC) and 25 healthy persons were included. EGF genotype was detected by restriction fragment length polymorphism. EGF expression in HCC tissue biopsiesfrom patientswhounderwent surgical resection was done by immunohistochemical examination. Results:The GG genotype was associated with significant increased risk of HCC compared to AA genotypes (P=0.031) in cirrhotic group. The G allele had a highly significant risk of HCC compared to allele Ain recessive model GG vs. AG+AA (P=0.036) rather than in the dominant model GG +AG vs. AA (P=0.66). There was significant increased expression of EGF in tumour tissues in patients with GG genotype compared to AG genotype and AA genotype p= 0.019. Conclusion: EGF gene polymorphism (GG genotype) had a significant risk of HCC development in cirrhotic patients. This is confirmed by increased EGF expression in liver tumor tissue from HCC patients.

Minimal Hepatic Encephalopathy: Effect of H. pylori infection and small intestinal bacterial overgrowth treatment on clinical outcomes

The effect Helicobacter pylori (Hp) infection and small intestinal bacterial over growth (SIBO) in minimal hepatic encephalopathy (MHE) is not well understood. The aim of the study was to determine the effect of eradication of Hp infection and SIBO treatment on MHE in patients with cirrhosis. Patients with cirrhosis were enrolled and MHE was determined by psychometric tests and critical flicker frequency analysis. Hp infection and SIBO were assessed by urea breath and Hydrogen breath tests respectively in patients with cirrhosis and in healthy volunteers. Patients with Hp infection and SIBO were given appropriate treatment. At six weeks follow-up, presence of Hp infection, SIBO and MHE status was reassessed. Ninety patients with cirrhosis and equal number of healthy controls were included. 55 (61.1%) patients in the cirrhotic group were diagnosed to have underlying MHE. Among cirrhotic group, Hp infection was present in 28 with MHE (50.9%) vs. in 15 without MHE (42.8%) (p = 0.45). Similarly, SIBO was present in 17 (30.9%) vs. 11 (31.4%) (p = 0.95) in patients with and without MHE respectively. In comparison with healthy controls, patients with cirrhosis were more frequently harboring Hp and SIBO (47.7% vs. 17.7% (p < 0.001) and 31.1% vs. 4.4% (p < 0.001) respectively. On follow-up, all patients showed evidence of eradication of Hp and SIBO infection. Treatment of SIBO significantly improved the state of MHE in cirrhotics, however eradication of Hp infection did not improve MHE significantly. Additionally, patients with low Model for End-Stage Liver Disease (MELD) score and belonging to Child class B had significantly better improvement in MHE. A large number of patients with cirrhosis had either active Hp infection or SIBO with or without MHE, compared to healthy controls. Treatment of SIBO significantly improved MHE in patients with cirrhosis, whereas eradication of Hp did not affect the outcome of MHE in these patients.

Association Between the ACE (I/D) Gene Polymorphism and Hepatocellular Carcinoma Risk in Egyptian HCV Patients

Background: Hepatocellular carcinoma is one of the most fatal malignancies worldwide and is related to many risk factors. Chronic HCV is associated with a 20–30-fold increased risk for HCC. Angiotensin-converting enzyme (ACE) is overexpressed in many cancers and plays a major role in angiogenesis and carcinogenesis. Aim: We aimed to elucidate the effect of the ACE I/D gene polymorphism in patients with HCV-related liver cirrhosis and HCC, and its relationship to clinical parameters. Patients and Methods: The study included 180 participants, cirrhotic (n=60), HCC (n=60) and control healthy subjects (n=60). Liver and renal function tests, alpha-fetoprotein, HCV antibodies and triphasic CT were assessed. ACE Gene polymorphism was assessed by Nested PCR. Results: We observed higher frequencies of DD (36.7%) and DI (51.7%) genotypes, along with the D allele (62.5%), in HCC patients compared to those of cirrhotic cases (10%, 40% and 30%, respectively) and control subjects (6.7%, 38.3%, and 25.8%, respectively). DD and DI genotypes increased the risk and predicted the occurrence of HCC by OR 25.932 and OR 6.354, respectively. The D allele conveys significant risk for HCC compared to control and cirrhotic groups with OR 4.785 and OR 3.889, respectively. Both DD genotype and D allele are significantly correlated with larger tumor size and metastasis. Conclusion: The ACE I/D polymorphism (DD genotype and D allele) is significantly associated with HCC risk in HCV patients and is correlated with increased tumor growth and advanced stage.

P0520EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS ON SECONDARY ACUTE KIDNEY INJURY IN RATS WITH LIVER CIRRHOSIS

Abstract Background and Aims Acute kidney injury( AKI) is one of the most common complications of decompensated cirrhosis, and it primarily presents as a sharp decrease in glomerular filtration rate, rapid increase in serum creatinine( SCr) and urea nitrogen. And the search for specific and safe treatment has been a research hot spot in recent years. In this article, the effect of human umbilical cord mesenchymal stem cells on carbon tetrachloride (CCl4)-induced liver fibrosis (HF) in rats with acute kidney injury and the possible mechanism are investigated. Method Human umbilical cord blood mesenchymal stem cells were sub-cultured by adherent method, and the cells were identified by morphological observation, cell phenotypic analysis and multi-directional differentiation potential analysis methods. WASTA rats were randomly divided into control group, cirrhosis model group and treatment group, with 10 rats in each group. Model group and treatment group were injected with CCl4-olive oil (1:1) solution 3 mL·kg -1, and the control group was given the same amount of olive oil for intervention, twice a week for 8 weeks. Rats in treatment group were administrated wth Human umbilical cord mesenchymal stem cells (2 × 109 /L) via the tail vein at the 5th week after injection of CCl4-olive oil solution, but the other rats were injected with 0.9% normal saline, once a week for 6 weeks. After the intervention, Serum, kidneys and 24 hours urine of rats in each group were collected, which were applied for a detection of serum creatinine and urea nitrogen, malondialdehyde (MDA), NO content and superoxide dismutase (SOD), as well as renal pathological examination. Results 1.In vitro, umbilical cord blood mesenchymal stem cells was passaged to the third generation, and the morphology was uniform and spiraled. Phenotypic analysis showed that the positive rates of stem cell markers CD29, CD44 and CD105 were all greater than 95%, the positive rate of HLA-DR (graft-versus-host disease-associated factor) less than 10%, and the positive rate of CD34 and CD45 lower than 20% (Figure 1). 2. Compared with the cirrhotic model group, MDA content of serum and kidney in model group significantly decreased under the effect of mesenchymal stem cell (p &amp;lt;0.01) (Table 1). 3. The normal group had normal liver tissue structure, ordered liver cells, no hepatic edema, and no lesions. In the model group, large-area lesions, including edema of liver cells, rupture of cell membranes, and infiltration of inflammatory cells, had appeared. Compared with the model group, Hepatocellular necrosis, edema, and inflammatory cell infiltration were significantly improved after transplanting Human umbilical cord mesenchymal stem cells (Figure 2). 4.In the model group, the rat renal tubules disappeared and the lumen was disordered. After injection of Human umbilical cord mesenchymal stem cells, renal tubular and renal interstitial damage is improved and the thickening of glomerular basement membrane is reduced (Figure 3). Conclusion In CCl4-induced liver cirrhosis model rats, human umbilical cord mesenchymal stem cells can protect the kidney by reducing free radicals and cellular lipid peroxidation in vivo.

Quantitative assessment of hepatic and splenic blood flow status in patients with hypersplenism of different degrees based on multi-slice spiral CT whole-liver perfusion imaging

Objective: To investigate the differences and changes of blood flow status of splenic volume, common hepatic artery, splenic arteriovenous, inner diameter of portal vein and hepatic in patients with hypersplenism of different degrees using multi-slice spiral CT whole-liver perfusion model. Methods: 42 cases with hypersplenism of chronic hepatitis B with cirrhosis and 15 cases without hepatosplenic disease were collected as controls. All patients underwent multi-slice spiral CT whole-liver perfusion imaging. (1) The differences of spleen volume, common hepatic artery, splenic arteriovenous, and portal vein diameter between different degrees of hypersplenism and the control group were measured and compared. (2) The correlation between spleen volume and the inner diameter of each related vessels were analyzed and compared. (3) The values of perfusion parameters related to the five lobes of the liver in Couinaud segments based on hepatic artery perfusion (HAP), portal venous perfusion (PVP), total hepatic perfusion (TLP) and hepatic artery perfusion index (HPI) were measured and compared. One-way ANOVA was used to analyze the measurement data. The correlation between the spleen volume and the inner diameter of each blood vessel was analyzed by Pearson's correlation analysis. Results: (1) spleen volume and the inner diameter of splenic artery, splenic vein and portal vein in the cirrhotic hypersplenism group were significantly larger than control group, and the difference was statistically significant (F = 37.108, 17.484, 23.124, 13.636, P < 0.05). (2) spleen volume and the inner diameter of splenic artery, vein and portal vein in the moderate and severe hypersplenism groups were significantly larger than the mild hypersplenism group, and the difference was statistically significant (F = 25.418, 13.293, 15.136, 7.093, P < 0.05), but there was no statistically significant difference between the moderate and severe hypersplenism groups (P > 0.05). (3) The inner diameter of splenic vein, portal vein, and splenic artery was positively correlated with spleen volume (r = 0.680, 0.548, and 0.726). (4) PVP and TLP of the whole liver in hypersplenism group were lower than control group (P < 0.05), and the differences were statistically significant (P < 0.05). HPI in the right posterior lobe of the liver in the moderate and severe hypersplenism group was higher than mild hypersplenism group (F = 3.555, 4.570, P < 0.05), and there was no significant difference in the HAP in the whole liver among the groups (P > 0.05), but the HAP in the whole liver in the severe hypersplenism group was lower than control, mild and moderate hypersplenism group. Conclusion: The inner diameter of the splenic arteriovenous in patients with hypersplenism of different degrees has widened to varying degrees, and is consistent with the increase in spleen volume, particularly in moderate and severe cases. Portal venous perfusion and total liver perfusion in patients with hypersplenism of different degrees have declined and the hepatic arterial perfusion in patients with severe hypersplenism is significantly reduced.

Association between miR-196a2 polymorphism and the development of hepatocellular carcinoma in the Egyptian population

BackgroundHepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide. Circulating microRNAs (miRNAs) are endogenous, small (17–25 nucleotides) non-coding RNAs that are overexpressed in many human cancers including HCC. Single-nucleotide polymorphisms (SNPs) of miRNAs play an important role in the pathogenesis of HCC. In our study, we aimed to evaluate the role of miR-196a2 rs11614913 polymorphism in the development of HCC. A total of 200 subjects, including 80 HCC patients, 60 patients with liver cirrhosis, and 60 healthy controls were selected. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine miR-196a2 rs11614913 polymorphism.ResultsThe genotype distribution of the TC and CC, TC + CC genotypes, and the C allele were significantly higher in HCC patients than control and cirrhotic groups (P = 0.02, P = 0.005, and P = 0.003, respectively). Compared with the wild-type TT genotype, both the variant TC, CC, TC + CC genotypes were associated with an elevated risk of HCC (OR = 2.77, 95% CI = 1.27–6.04), (OR = 4.94, 95% CI = 1.74–14.07), (OR = 3.24, 95% CI = 1.55–6.78) respectively. Moreover, the C allele was correlated with an increased risk of HCC (OR = 2.30, 95% CI = 1.40–3.76) compared to the wide-type T allele. Also, there is no significant correlation between the different miR-196a2 genotypes and either the clinico-pathologic features of HCC or its aggressiveness.ConclusionOur results suggest that the miR-196a2 rs11614913 polymorphism is associated with an increased risk of HCC in the Egyptian population.

Specific liver volume parameters in cirrhotic patients with peribiliary cysts

The presence of peribiliary cysts and morphological changes in the volumes of lobes in the livers of patients with cirrhosis are both related to the alteration of portal flow. Our study explored the relationship between these two features in patients with cirrhosis. We retrospectively selected 150 computed tomography (CT) images of cirrhotic livers and 105 CT images of healthy livers. The cirrhotic livers were further classified according to the presence of peribiliary cysts (peribiliary cysts group) or the absence of peribiliary cysts (control cirrhotic group). The characteristic features of liver cirrhosis, including modified caudate-right lobe ratio (mCR ratio), splenomegaly, ascites, and collateral shunts, were reviewed. Liver volume calculations included the sum of the left hepatic volume (LHV) and right hepatic volume (RHV; LHV + RHV) and the ratio of LHV to RHV (LHV/RHV). The two groups did not differ in the presence of splenomegaly, ascites, or collateral shunts. The control cirrhotic group exhibited a significantly higher mCR ratio and LHV/RHV ratio than the peribiliary cysts group did (p < 0.001). The healthy liver group exhibited a significantly higher LHV + RHV value than either the peribiliary cysts group or the control cirrhotic group did (p < 0.001). The peribiliary cysts group and the control cirrhotic group did not differ significantly for LHV + RHV (p > 0.05). The control cirrhotic group exhibited a significantly higher mCR ratio and LHV/RHV ratio than the peribiliary cysts group did, but the two groups were similar for most measurements. Peribiliary cysts might result in reduction of portal flow, causing cirrhotic liver with peribiliary cysts with left-sided dominance not to demonstrate the typical morphological appearance of the common cirrhotic liver.

Can hypothyroidism be a protective factor for hepatocellular carcinoma in cirrhosis?

Despite many studies, the molecular mechanisms of hepatocellular carcinoma (HCC) development remain unclear. Thyroid hormone (TH) levels may vary in many chronic diseases including cirrhosis. The aim of this study was to evaluate TH status in patients with cirrhosis and HCC and to investigate the relationship between THs and HCC development.Five hundred seventy-seven patients with cirrhosis who applied to Demiroğlu Bilim University, Faculty of Medicine, Gastroenterology Department between 2004 and 2019 were included the study. Three hundred sixty-seven patients who applied to Internal Medicine Unit for general health check-up were included in the study as healthy control group. Demographic, laboratory, and imaging findings of study groups were retrospectively reviewed and recorded from hospital information system.In the cirrhosis group, 252 patients had HCC (43.67%), and 325 patients had non-HCC cirrhosis (56.33%). Free thyroxine (FT4) levels were higher in the control group than in the cirrhotic group but there was no significant difference (P = .501). Thyroid-stimulating hormone (TSH) and FT4 levels were similar between groups, while free triiodothyronine (FT3) levels were significantly different between HCC group, non-HCC cirrhosis group, and control group (P = .299 for TSH, P = .263 for FT4, P < .001 for FT3). FT3 levels were significantly higher in HCC group than non-HCC cirrhosis group, but significantly lower than control group (P < .05).Our study confirmed the presence of hypothyroidism in cirrhosis patients and clearly demonstrated a strong relationship between FT3 levels and HCC development.

Association between Bone Morphogenic Protein-7 (BMP-7) Polymorphism (rs162316) and Chronic Liver Diseases among Egyptian Patients

The bone morphogenic protein-7 (BMP-7) gene is a member of the transforming growth factor-β (TGF-β) superfamily. BMP-7 is believed to act as a regulator of endogenous control of hepatocytes proliferation and liver homeostasis in adult hepatocytes. The present study aimed to assess the association of single nucleotide polymorphism (SNP), rs162316 (G>A), in BMP-7 gene with the progression of HCV or HBV- chronic liver cirrhosis to hepatocellular carcinoma (HCC). The tetra-primer amplification-refractory mutation system (ARMS-PCR) method was used for rs162316 genotyping. In this study, 150 subjects were divided into 50 healthy controls, 50 HCV or HBV-cirrhotic patients with HCC and 50 HCV or HBV-cirrhotic patients and HCC-free. Results of rs162316 genotyping revealed an association of SNP with 1.14 (0.64-2.03) and 1.43(0.79-2.58) alleles A frequencies (OR, CI 95%) in HCC patients compared to cirrhotic and healthy control groups respectively. For the specific studied SNP of BMP7 gene rs162316, the A allele (AG genotype) and was significantly associated with HCC progression. However, AG genotype of rs162316 may be considered as a predictor for HCC in Egyptian cirrhosis patients.

Retreatment of chronic hepatitis C virus genotype-4 patients after non-structural protein 5A inhibitors' failure: efficacy and safety of different regimens.

Nonstructural protein 5A (NS5A) is an important regimen for the treatment of chronic hepatitis C virus (HCV) genotype-4 infected patients. Retreatments for NS5A virologic failure are limited. The aim of this study is to provide real-life data regarding the effectiveness and safety of retreatment with different regimens after NS5A regimen virologic failure in GT4 patients. A total of 524 HCV patients (mean age 48 ± 11 years, 71% males), with virologic failure to sofosbuvir+daclatasvir, n = 450 and sofosbuvir/ledipasvir, n = 74 were included in this study. Patients were retreated with sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin, n = 278 and sofosbuvir + simeprevir + daclatasvir + ribavirin, n = 246. Response was evaluated 12 weeks after the end of treatment (SVR12). Overall, SVR12 was 95.2% [95% confidence interval (CI) 93.3%-97.1%]. In sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir + simeprevir + daclatasvir + ribavirin, SVR12s were 94.9% (95% CI 92.5%-97.4%) and 95.5% (95% CI 92.8%-98%), respectively. In liver cirrhosis patients, SVR12s were 96.4% (95% CI 90.7%-100%) and 98% (95% CI 94.9%-100%), respectively. Relapse in the sofosbuvir + ombitasvir/paritaprevir/ritonavir + ribavirin was n = 14 patients, and n = 11 patients in sofosbuvir + simeprevir + daclatasvir + ribavirin. Three patients developed hepatic encephalopathy, haematemesis, lower limb oedema, and one patient died in the SOF + OBV/PTV/RTV + RIB. In the sofosbuvir + simeprevir + daclatasvir + ribavirin, three patients developed hepatocellular carcinoma and one patient died. No treatment discontinuation due to anaemia. Salvage treatment for NS5A-treatment failure is effective and well tolerated in genotype-4 patients, in both noncirrhotic and compensated cirrhotic groups.

Diagnostic Performance of Serum Asialo α1-Acid Glycoprotein Levels to Predict Liver Cirrhosis.

Background/AimsTo date, studies on various noninvasive techniques have been suggested to evaluate the degree of liver fibrosis. We aimed to investigate the diagnostic performance of serum asialo α1-acid glycoprotein (AsAGP) in the diagnosis of liver cirrhosis compared with chronic hepatitis for clinically useful result.MethodsWe conducted a case-control study of 96 patients with chronic liver disease. Chronic hepatitis was defined as the presence of chronic liver disease on ultrasonography, with a liver stiffness of less than 5.0 kPa as shown on magnetic resonance elastography (MRE). Liver cirrhosis was defined as liver stiffness of more than 5.0 kPa on MRE. The serum AsAGP concentration was compared between the two groups.ResultsSerum AsAGP levels were significantly higher in patients with cirrhosis than in those with chronic hepatitis (1.83 μg/mL vs 1.42 μg/mL, p<0.001). Additionally, when comparing patients in each cirrhotic group (Child-Pugh grades A, B, and C) to those with chronic hepatitis, AsAGP levels were significantly higher in all the cirrhotic groups (p<0.05, p<0.01, p<0.001, respectively). The sensitivity and specificity of AsAGP for detecting cirrhosis were 79.2% and 64.6%, respectively, and the area under the curve value was 0.733. The best diagnostic cutoff to predict cirrhosis was 1.4 μg/mL. AsAGP and bilirubin were found to be independent risk factors for the prediction of cirrhosis in the logistic regression analysis.ConclusionsSerum AsAGP showed an acceptable diagnostic performance in predicting liver cirrhosis.

Interleukin-27 levels and its Polymorphism in Hepatocellular carcinoma associated with Hepatitis C

The prevalence of Hepatocellular carcinoma (HCC) in Egypt represents about 11% of the gastrointestinal tract malignancies. The development of HCC usually is preceded by chronic infections with Hepatitis C virus (HCV). Interleukin-27 (IL27) is implicated in the antiviral immunity. Little is known about the use of IL27 as a biomarker for the development of HCC associated with HCV. Moreover, the role of IL-27 rs153109 gene polymorphism in the development of HCC associated with HCV has not been well studied yet. A case control study included three groups; Group I, 60 healthy control patients, Group II, 60 patients with cirrhosis associated with HCV infection, and Group III, included 60 patients with HCC associated with HCV. ELISA technique was used to measure serum IL27, while restriction fragment length polymorphism (RFLP) was used to detect single-nucleotide polymorphisms (SNP). Results showed that the serum levels of IL27 is significantly higher in both cirrhotic and HCC groups. G allele is significantly associated with HCC and cirrhotic cases, compared with the healthy control group. Current results encourage the use of IL 27 as a diagnostic marker for both cirrhotic and HCC diseases. The aims of current work were to study the serum levels of IL27 in HCV positive hepatic patients, to evaluate its role as a biomarker for early detection of HCC, and to find any association of rs153109 with the hepatic diseases.

Serum microRNA let-7a-1/let-7d/let-7f and miRNA 143/145 Gene Expression Profiles as Potential Biomarkers in HCV Induced Hepatocellular Carcinoma.

Background:Egypt has the highest prevalence of hepatitis C virus (HCV) worldwide. Which make liver cirrhosis and hepatocellular carcinoma (HCC) major health concerns in Egypt. Circulating microRNAs (miRNAs) have been investigated as biomarkers for malignancies. We investigated miRNA gene expression of Lethal-7 (let-7) cluster: let7-a-1, let-7d-1, let-7f-1 and miRNA (miR)143/145 cluster in sera of HCC patients and chronic HCV patients. Methods:The study included 40 post HCV-Hepatocellular carcinoma patients, 40 chronic HCV patients divided into 2 subgroups, 20 cirrhotic patients and 20 non-cirrhotic patients, and 40 apparently healthy subjects as a control group. Gene expression analysis for studied miRNAs was done using quantitative SYBR Green reverse-transcription Real-Time polymerase chain reaction (PCR). Results:We found that Let-7a-1 gene expression was significantly downregulated in the serum of HCV-HCC patients than in HCV non HCC cirrhotic group and was significantly upregulated in the serum of liver cirrhosis patients than HCV non-cirrhotic group. miR-143 and miR-145 expressions were significantly downregulated in the serum of HCC patients than in control group and miR-143 was significantly downregulated in the serum of non-cirrhotic HCV patients than in control group. Conclusion:The downregulation of serum let-7-a1, miR-143, and miR-145 gene expression may exhibit significant influence on the development of HCC in chronic HCV Egyptian patients and can be used as biomarkers for HCC diagnosis.

Assessment of renal artery resistive index as a predictor of esophageal varices and its bleeding risk in post-hepatitic cirrhosis

Background Bleeding from rupture esophageal varices (EV) is a major and life-threatening complication of liver cirrhosis (LC). Early detection of EV and prediction of its bleeding risk is important. Objective To assess and evaluate the resistive index (RI) of the renal artery (RA) by Doppler in various stages of portal hypertensive manifestations of LC, and their values for detection of EV and its bleeding. Patients and methods The study included 90 patients, comprising 75 patients with confirmed diagnosis of LC, classified into the following groups: group 1 included 25 patients with EV and having history of variceal bleeding episodes, group 2 included 25 patients with EV and having no variceal bleeding episodes history, and group 3 included 25 patients without EV; in addition, 15 noncirrhotic controls were included as group 4. All patients were subjected to history taking, clinical examination, laboratory investigations, calculation of some important noninvasive indices (CHILD, FIB 4, and APRI) in cirrhotic groups, abdominal ultrasonography, renal Doppler, and upper gastrointestinal endoscopy. Results RA RI served as a predictor of the presence as well as bleeding risk of EV. LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 90% and a specificity of 76% to predict EV. Moreover, LT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 92% and a specificity of 40% to predict EV bleeding. RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 80% and a specificity of 76% to predict EV. In addition, RT RA RI revealed that a cutoff value of 0.70 has a sensitivity of 88% and a specificity of 52% to predict EV bleeding. Conclusion RI of the RA may help in predictions of EV and its bleeding risk. LRA RI was more sensitive for prediction of EV bleeding.

Clinical utility of serum chromogranin A as a marker of hepatocellular carcinoma in chronic hepatitis patients

<br><b>Background</b><br>Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third most common cause of cancer deaths accounting for about 745 000 deaths per year globally. HCC is often diagnosed at an advanced stage where effective therapies are lacking.<br><b>Aim</b><br>Is to investigate the role of serum chromogranin A (CgA) as a marker for detection of HCC in patients with HCC complicating chronic hepatitis and correlate its serum levels with alpha fetoprotein (AFP).<br>This study was conducted on 90 HCC patients (group I), 30 patients with hepatic cirrhosis (group II), and 30 age-matched and sex-matched healthy-controls (group III). Group I was further subdivided into group Ia (30 patients) with HCC complicating chronic hepatitis B, and group Ib (60 patients) with HCC complicating chronic hepatitis C. All participants included in the study were subjected to full history taking and clinical examination, laboratory investigations, including complete blood count, liver-function tests, renal-function tests, and viral markers. Serum AFP and serum CgA levels were also determined.<br><b>Results</b><br>Our results revealed that there was a highly significant elevation (<i>P</i> < 0.01) in the median serum CgA in hepatitis-B virus -related HCC (200 ng/ml) and hepatitis-C virus-related HCC (190 ng/ml) when compared with the control group (30 ng/ml) and when compared with cirrhotic group (60 ng/ml) with no significant difference between the median serum CgA in hepatitis-B virus -related HCC and hepatitis-C virus-related HCC (<i>P</i> > 0.05). A highly significant positive correlation between chromogranin and AFP (<i>P</i> < 0.01) was found in HCC patients. On the other hand, no significant correlations were found between chromogranin and complete blood count, kidney functions, and liver-function tests in patient groups. Diagnostic reliability testing revealed that for CgA, the best cutoff for discriminating HCC patients was 100 ng/ml at which the sensitivity was 77.78%, the specificity 93.3% with positive predictive value 94.59% and negative predictive value 73.68%. Regarding the combination between CgA and AFP, it showed a sensitivity of 97.78% and a specificity of 86.67%.<br><b>Conclusion</b><br>Serum CgA is a promising sensitive and specific tumor marker for identification of HCC. Addition of serum CgA to the current standard tests will improve the sensitivity and accuracy of diagnosis of HCC patients and thus could allow them to benefit from earlier treatment.<br>

P1603 Changes of cardiac function in cirrhotic patients after liver transplantation

Abstract Funding Acknowledgements This study was supported by the grant of CJ healthcare 2016 research fund. Background Liver cirrhosis (LC) has been known to affect cardiovascular performance. Limited study have evaluated the alteration of myocardial function in patients with LC after liver transplantation (LT). Purpose The aim of study was to evaluate changes of cardiac function in patients with cirrhosis following LT using conventional and speckle-tracking echocardiography and late gadolinium enhancement (LGE) of cardiac magnetic resonance (MR). Methods Thirty-five patients with cirrhosis (mean age, 57.1 ± 9.0; male, 75%) who were listed for LT were prospectively enrolled. Patients underwent conventional, speckle-tracking echocardiography, and cardiac MR imaging with LGE. Echocardiography and cardiac MR were performed at pre and 1 year after LT. Cirrhotic patients were compared with normal control (n = 20, mean age, 65.0 ± 14.8; men, 11(55%)) and echocardiographic and cardiac MR data were compared pre and post LT. Results Conventional and speckle-tracking echocardiography and Cardiac MR imaging demonstrated hyperdynamic left ventricular (LV) function in patients with cirrhosis (LV ejection fraction (EF) with cardiac MR 67.8 ± 7.0% in LC vs. 63.4 ± 6.4% in control, P = 0.028; global longitudinal strain (GLS) -24.3 ± 2.6% in LC vs. -18.6 ± 2.2% in control, P &amp;lt; 0.001). There were no LGE in patients with cirrhosis and no significant differences in LV size, LV wall thickness, LV mass index, and diastolic function between cirrhotic patients and control group (all P &amp;gt; 0.1). Corrected QT interval (QTc) in electrocardiogram was prolonged in LC patients (P &amp;lt; 0.001). One-year after LT, LV end-diastolic diameter and LV end-diastolic volume significantly decreased (P = 0.016 and 0.022, respectively). Although LVEF showed no significant changes 1 year post-LT (P = 0.362), LV-GLS (from -24.7 ± 1.8% to -20.8 ± 3.4%, P &amp;lt; 0.001) significantly decreased. QTc interval also decreased 1 year after LT (from 470.4 ± 29.6msec to 428.2 ± 31.6msec, P = 0.001). Conclusions The present study demonstrated that cirrhotic patients showed hyperdynamic circulation and prolonged QTc interval compared with normal controls. After 1 year LT, LV size reduced and augmented LV function was normalized. Given that no LGE in cardiac MR and normalized GLS and QTc after LT, cardiac dysfunction in LC patients could be reversed by LT.

A Novel Noninvasive Method for Predicting Liver Fibrosis by Quantifying the Estrangement of Indocyanine Green Retention Rate and Tc-99m-diethylenetriamine-penta-acetic Acid-galactosyl Human Serum Albumin Scintigraphy.

Indocyanine green (ICG) clearance test is one of the most popular dynamic methods for evaluating preoperative liver function to avoid posthepatectomy liver failure (PHLF). Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin scintigraphy (GSA) also facilitates the direct estimation of functional hepatocytes and can estimate the ICG retention rate (R15); however, in some cases, there is a discrepancy between results of a preoperative examination of ICG-R15 and the estimated ICG-R15 obtained by 99mTc-GSA (GSA-R15). This study evaluated the gap between ICG-R15 and GSA-R15 (ΔICG) for predicting background liver fibrosis in patients who underwent hepatectomy. Sixty-four consecutive patients who underwent hepatectomy and preoperative ICG-R15 and GSA-R15 examinations from 2016 to 2019 were retrospectively evaluated. The gap between GSA-R15 and ICG-R15 was defined as ΔICG and the factors predicting liver fibrosis were investigated. In the pathologically-proven cirrhotic group, platelet counts were significantly lower and ΔICG values were significantly larger than those in the non-/early-cirrhotic group. A multivariate analysis identified a higher total bilirubin level, a higher AST level, and a larger ΔICG level as significant predictive factors for liver cirrhosis. Larger ΔICG was found to be an independent preoperative predictor of liver fibrosis and may positively contribute to decision-making before hepatectomy to avoid PHLF.

Prevalence of Vitamin-D deficiency is related to severity of liver damage in Hepatitis-C patients.

Objective:Serum Vitamin-D plays pivotal role in inflammatory and infectious diseases; among them liver infections are more distinct. This study was aimed to determine Vitamin-D status in HCV-infected patients and healthy controls in Faisalabad, Pakistan.Methods:We performed randomized cross-sectional study of 74 individuals from 20th August, 2017 to 20th February 2018 at The University of Faisalabad and Dar us Shifa Clinic, Faisalabad. Fifty-one patients were hepatitis C RNA-PCR positive (22 compensated cirrhotic and 29 decompensated cirrhotic patients). In addition, 23 subjects without liver disease were recruited as healthy control. HCV RNA–PCR was performed by ARTUS ® HCV QS-RGQ V1. Vitamin-D levels were measured by chemiluminescence. SPSS version 20 was used for statistical analysis.Results:The mean level of Vitamin-D was significantly lower in HCV patients in compensated and decompensated cirrhotic patients (26.85 ng/mL & 20.65 ng/mL respectively) as compared to healthy controls (30.41 ng/mL). This study showed sub optimal level of Vitamin-D in 76.5% of HCV patients. Vitamin-D insufficiency (21-29 ng/mL) as prevalent among healthy individuals (47.8%) as well as in HCV patients (39.2%) (P < 0.001). In addition, Vitamin-D levels showed inverse relationship with more severe conditions of liver disease as 55.2% of decompensated cirrhosis patients were sufferer of Vitamin-D deficiency as compared to 13.6% deficiency of Vitamin-D in compensated cirrhotic group (P <0.0001).Conclusion:Suboptimal levels of Vitamin-D (deficiency or insufficiency) are prevalent in patients having hepatitis C infection as compared to healthy controls. Deficiency of Vitamin-D was directly associated with severity of disease.

Circulatory miRNA-484, 524, 615 and 628 expression profiling in HCV mediated HCC among Egyptian patients; implications for diagnosis and staging of hepatic cirrhosis and fibrosis

Circulatory microRNAs have recently emerged as non-invasive and effective biomarkers for diagnosis of various diseases. Currently there is no reliable biomarker for diagnosis, prognosis or even staging of fibrotic and cirrhotic complications arising from HCV infection. This study aimed at investigating plasma miR-484, miR-524, miR-615-5p and miR-628-3p expression signatures in Egyptian patients with HCV mediated cirrhosis, fibrosis and HCC. Plasma miRNAs expressions in 168 samples [(40 healthy controls, 47 with HCV liver fibrosis, 40 with HCV-cirrhosis and 41 with HCV-hepatocellular carcinoma (HCC)] were quantified using RT-PCR. The studied miRNAs were differentially expressed among all participating groups. Plasma miR-484 levels exhibited significant downregulation in advanced fibrosis as compared to mild fibrosis and HCC. Moreover, miR-484 showed significant upregulation in HCC versus cirrhosis. Both miR-524-5p and miR-615-5p were upregulated in cirrhotic group as compared to controls. Differential expression between HCC and controls was noticeable in miR-524-5p. Receiver operator characteristic curve analysis revealed promising diagnostic performance for miR-484 in discriminating late fibrosis from both mild fibrosis and HCC and also for miR-524 in distinguishing between cirrhosis and fibrosis. In conclusion, investigated miRNAs could serve as potential and sensitive biomarkers for staging, prognosis and early diagnosis of various HCV mediated hepatic disease progression.