scholarly journals Association of Adiponutrin/Patatin Like Phospholipase 3 (PNPLA3) I148M Gene Variant with Chronic Hepatitis C in Egyptian Children

Author(s):  
Mahmoud Mohamed Motawae ◽  
Mohiee El-Deen Abd El-Aziz Awad ◽  
Hanaa Ahmed Elaraby ◽  
Manal Abd El-Wahed Eid ◽  
Hanan Hamed Soliman ◽  
...  

Background: Chronic hepatitis C (CHC) represents a leading cause of liver-related mortality worldwide. The patatin-like phospholipase domain-containing 3 gene (PNPLA3/adiponutrin) rs738409 (I148M) single-nucleotide polymorphism (SNP) has been reported to be linked with the severity and progression of liver fat content and liver fibrosis in CHC among different racial groups. Such reports are lacking in CHC Egyptian children. Aim of Study: To evaluate the possible association of PNPLA3-I148M gene variant with the severity of liver fat content and liver fibrosis in Egyptian children with CHC. Patients and Methods: Fifty normal-weighted children (mean age 10.62±2.59 years) with CHC were subjected to genotyping of PNPLA3-I148M gene variant using the real time PCR TaqMan assay. FibroScan examination for assessment of both liver fibrosis by Fibroscan liver stiffness (LMS) and liver steatosis by the controlled attenuation parameter (CAP) scores and histological examination of liver biopsies for assessment of liver steatosis, and METAVIER scoring for necroinflammatory activity grades and liver fibrosis stages were done for all patients as well as appropriate laboratory investigations. APRI and FIB-4 indices as well as insulin resistance using HOMA-IR were also calculated. Results: 34 cases (68%) had CC genotype (wild CC genotype) ,9 cases (18%) had CG genotype (heterozygous for the risk G allele) and 7 cases (14%) had GG genotype (homozygous for the risk G allele). Significant higher values of LSM and CAP steatosis scores were found in patients with CG and GG genotypes compared to those with CC genotype. CG gene variant and GG gene variant were significant positive predictive factors for histopathological liver steatosis and fibrosis stages and inflammatory activity grades among the studied patients. Significant higher values of many laboratory variables (AST, fasting blood glucose, fasting serum insulin, and HOMA-IR) but lower platelets count was found in patients with G allele (CG+ GG) compared to patients without G allele (CC). In addition, significant positive correlations between PNPLA3-I148M gene variant and indicators of hepatic steatosis and fibrosis and many laboratory parameters (AST, APRI, FIB4, FBS, fasting serum insulin, and HOMA-IR) but a significant negative correlation between PNPLA3-I148M gene variant and platelet cell count were found among the studied patients. Conclusion: Data of this study suggested that polymorphisms in the PNPLA3 I148M gene variant could contribute to the severity of hepatic steatosis and fibrosis of the studied Egyptian children with CHC.

Author(s):  
Arjun N. A. Jayaswal ◽  
Christina Levick ◽  
Jane Collier ◽  
Elizabeth M. Tunnicliffe ◽  
Matthew D. Kelly ◽  
...  

Abstract Purpose Direct-acting antiviral therapies (DAAs) for treatment of chronic hepatitis C virus (HCV) have excellent rates of viral eradication, but their effect on regression of liver fibrosis is unclear. The primary aim was to use magnetic resonance imaging (MRI) and spectroscopy (MRS) to evaluate changes in liver fibrosis, liver fat and liver iron content (LIC) in patients with chronic HCV following treatment with DAAs. Methods In this prospective study, 15 patients with chronic HCV due to start treatment with DAAs and with transient elastography (TE) > 8 kPa were recruited consecutively. Patients underwent MRI and MRS at baseline (before treatment), and at 24 weeks and 48 weeks after the end of treatment (EoT) for the measurement of liver cT1 (fibroinflammation), liver fat and T2* (LIC). Results All patients achieved a sustained virological response. Liver cT1 showed significant decreases from baseline to 24 weeks post EoT (876 vs 806 ms, p = 0.002, n = 15), baseline to 48 weeks post EoT (876 vs 788 ms, p = 0.0002, n = 13) and 24 weeks post EoT to 48 weeks post EoT (806 vs 788 ms, p = 0.016, n = 13). Between baseline and 48 weeks EoT significant reduction in liver fat (5.17% vs 2.65%, p = 0.027) and an increase in reported LIC (0.913 vs 0.950 mg/g, p = 0.021) was observed. Conclusion Liver cT1 decreases in patients with chronic HCV undergoing successful DAA treatment. The relatively fast reduction in cT1 suggests a reduction in inflammation rather than regression of fibrosis.


Author(s):  
Mohamed S. Zaghlol, Mohamed T. Al-Sayed Ahmed Qasem Mohamed,

Patients with chronic hepatitis have impaired glucose metabolism with hyperinsulinemia and insulin resistance, this hyperinsulinemia has been shown to be due to decreased insulin catabolism rather than increased pancreatic insulin secretion.We aim to evaluate insulin resistance in non diabetic patients with chronic hepatitis C virus infection. our study was a case-control study conducted in Tropical Medicine and Gastroenterology Department AL-Azhar University Hospital. 60 patients and 30 healthy controls were included in the study. The patients were classified into two groups:Group A: 30 patients with chronic hepatitis C infection were selected with positive HCV RNA in serum for at least 6 months; Patients were not receiving anti-viral therapy at the time of sampling They showed no evidence of cirrhosis. Group B: 30 patients with HCV related liver cirrhosis. They were divided according to Child Pugh score; twenty patients with HCV related compensated liver cirrhosis (Child A) Ten patients with HCV related decompensated liver cirrhosis (Child B and C). Group C: The control group: included 30 healthy individuals.  All patients and control were subjected to the following: Liver function tests: Alanine transaminase (ALT), Aspartate transaminase (AST), total and direct bilirubin, total protein, serum albumin. Prothrombin time (PT) & international normalization ratio (INR). Renal function tests: Blood urea nitrogen (BUN), Na, K. Complete blood count. Alpha fetoprotein (αFP).  Overnight fasting and two hours postprandial blood glucose level. Fasting serum insulin of each individual.  Insulin resistance was  determined via the Homeostasis  Model assessment (HOMA-IR) Statistical analysis of data will be done by using SPSS(statistical program for social science version22,produced by IBM SPSS Inc.,Chicago,USA). Results: We found that out of 30 CHC and 30 LC (20 compensated LC, 10 de compensated LC) 8 (26.7%); 8 (40%) patients and 5(50%) respectively had HOMA-IR levels greater than 2.5, which is consistent with IR diagnosis. Decompensated cirrhotic patients showed higher frequency of IR compared  to CHC, and compensated cirrhotic patients. Coclusion: In chronic hepatitis C patients, HOMA-IR, fasting serum insulin and fasting blood glucose were significantly higher than healthy controls.


2015 ◽  
Vol 53 (05) ◽  
Author(s):  
K Kozbial ◽  
S Beinhardt ◽  
C Freissmuth ◽  
A Stättermayer ◽  
R Stern ◽  
...  

2001 ◽  
Vol 34 ◽  
pp. 163-164 ◽  
Author(s):  
V.D. Ratziu ◽  
M. Munteanu ◽  
L. Bonyhay ◽  
F. Charlotte ◽  
P. Opolon ◽  
...  

2006 ◽  
Vol 291 (2) ◽  
pp. E282-E290 ◽  
Author(s):  
Riikka Lautamäki ◽  
Ronald Borra ◽  
Patricia Iozzo ◽  
Markku Komu ◽  
Terho Lehtimäki ◽  
...  

Nonalcoholic fatty liver (NAFL) is a common comorbidity in patients with type 2 diabetes and links to the risk of coronary syndromes. The aim was to determine the manifestations of metabolic syndrome in different organs in patients with liver steatosis. We studied 55 type 2 diabetic patients with coronary artery disease using positron emission tomography. Myocardial perfusion was measured with [15O]H2O and myocardial and skeletal muscle glucose uptake with 2-deoxy-2-[18F]fluoro-d-glucose during hyperinsulinemic euglycemia. Liver fat content was determined by magnetic resonance proton spectroscopy. Patients were divided on the basis of their median (8%) into two groups with low (4.6 ± 2.0%) and high (17.4 ± 8.0%) liver fat content. The groups were well matched for age, BMI, and fasting plasma glucose. In addition to insulin resistance at the whole body level ( P = 0.012) and muscle ( P = 0.002), the high liver fat group had lower insulin-stimulated myocardial glucose uptake ( P = 0.040) and glucose extraction rate ( P = 0.0006) compared with the low liver fat group. In multiple regression analysis, liver fat content was the most significant explanatory variable for myocardial insulin resistance. In addition, the high liver fat group had increased concentrations of high sensitivity C-reactive protein, soluble forms of E-selectin, vascular adhesion protein-1, and intercellular adhesion molecule-1 ( P < 0.05) and lower coronary flow reserve ( P = 0.02) compared with the low liver fat group. In conclusion, in patients with type 2 diabetes and coronary artery disease, liver fat content is a novel independent indicator of myocardial insulin resistance and reduced coronary functional capacity. Further studies will reveal the effect of hepatic fat reduction on myocardial metabolism and coronary function.


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