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PNPLA3 rs738409 and TM6SF2 rs58542926 variants increase the risk of hepatocellular carcinoma in alcoholic cirrhosis
BACKGROUND:
PNPLA3 rs738409 polymorphism is associated with fatty liver disease, alcoholic or non-alcoholic (NAFLD) and hepatocellular carcinoma (HCC). TM6SF2 rs58542926 is clearly associated with NAFLD, but it is not clearly associated with HCC. The relationship between TM6SF2 rs58542926 and HCC and the potential synergistic effect of TM6SF2 and PNPLA3 variants in modifying the risk of HCC are not known.
AIM:
This study assessed the interaction between PNPLA3 rs738409 and TM6SF2 rs58542926 variants in the conditioning of HCC development.
METHODS:
A total of 511 cirrhotic patients (44% alcohol-related, 56% viral, 57.5% liver transplanted) were retrospectively investigated for HCC occurrence. PNPLA3 rs734809 and TM6SF2 rs58542926 were genotyped using restriction fragment length polymorphism and real-time allelic discrimination polymerase chain reaction methods.
RESULTS:
Patients with HCC were more likely to be PNPLA3 rs734809 G/G homozygotes (41/150 vs. 60/361, p=0.009) or TM6SF2 rs58542926 C/T-T/T (27/150 vs. 41/361, p=0.044). The presence of either PNPLA3 G/G or TM6SF2*/T identified high-risk genotypes for HCC, which were strongly associated with HCC (64/150 vs. 93/361, p=0.0002). This association was evident in alcohol-related (p=0.0007) but not in viral cirrhosis.
CONCLUSION:
TM6SF2 C/T or T/T in conjunction with PNPLA3 G/G variants may be potential genetic risk factors for developing HCC in alcohol-related cirrhosis
Circulating standard CD44 isoform in patients with liver disease: Relationship with other soluble adhesion molecules and evaluation of diagnostic usefulness
A comparison of four serum markers of fibrosis in the diagnosis of cirrhosis
C-terminal peptide of procollagen I, N-terminal peptide of procollagen III, collagen IV and serum prolyl hydroxylase were measured in 100 patients with cirrhosis and 71 patients with noncirrhotic chronic liver disease. Patients with cirrhosis had significantly higher mean values of prolyl hydroxylase, collagen IV, N-terminal peptide of procollagen III and C-terminal peptide of procollagen I as compared to noncirrhotic patients. This difference was maintained for collagen products even after stratification for alcohol intake, although all markers of fibrosis were higher in alcoholics. Stepwise logistic regression analysis showed that collagen IV, and N-terminal peptide of procollagen III were independently associated with cirrhosis. Receiver-operating characteristic (ROC) curves showed that collagen IV and N-terminal peptide of procollagen III perform more efficiently than C-terminal peptide of procollagen I and prolyl hydroxylase in identifying cirrhosis
GENE POLYMORPHISM AT THE INTERLEUKIN 6 -174 G > C LOCUS AFFECTS THE OUTCOME OF CHRONIC HEPATITIS B
Association of serum lipoprotein(a) levels and apolipoprotein(a) size polymorphism with target-organ damage in arterial hypertension
Objective.-To investigate the association between lipoprotein(a) [Lp(a)] and other plasma lipids and apolipoproteins and target-organ damage (TOD) in patients with arteria[ hypertension. Design.-Cross-sectional study of a case series. Setting.-University medical center. Participants.-Lipoprotein(a) and apolipoproteins were analyzed in 277 untreated patients with mild to moderate essential hypertension and in 102 healthy controls. Apolipoprotein(a) [apo(a)] phenotypes were additionally analyzed in an independent sample set of 106 hypertensive and 105 control subjects. Main Outcome Measures.-Staging of TOD obtained according to World Health Organization guidelines by clinical evaluation, and laboratory tests including measurments of creatinine clearance, proteinuria, ophthalmoscopy, electrocardiography, echocardiography, and ultrasound examination of major arteries; levels of lipids, apolipoproteins, Lp(a), fibrinogen, and apo(a) phenotypes. Results.-Blood pressure, duration of hypertension, and levels of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, Lp(a), and fibrinogen were significantly related to the presence and severity of TOD in univariate analysis. Stepwise multivariate analysis showed Lp(a) levels (P<.001) to be the best discriminator of the presence of TOD, followed by systolic blood pressure (P<.001), duration of hypertension (P=.01), and low-density lipoprotein cholesterol (P=.04). The Lp(a) levels were related to TOD independent of the level of blood pressure. We confirmed this association between Lp(a) concentrations and severity of TOD in a second independent sample set and observed a significantly higher frequency of low-molecular-weight apo(a) isoforms with increasing severity of TOD (P=.02). Conclusions.-Lipoprotein(a) and apo(a) phenotype are sensitive indicators of the severity of TOD in patients with essential hypertension, and their evaluation might permit identification of hypertensive subjects liable to the development of organ damage. The higher frequency of low-molecular-weight apo(a) isoforms in patients with TOD demonstrates a genetically determined risk for the development of TOD in hypertensive patients
Efficacy of serum procalcitonin in evaluating severity of community-acquired pneumonia in childhood.
Biliary strictures after liver transplantation: Role of interleukin 28B genotypes in cyclosporine treated
AbstractIntroduction: The role of Interleukin 28B (IL-28B) genetic polymorphisms in influencing the occurrence of biliary complications after liver transplantation has never been evaluated. This study aimed to investigate whether IL-28B rs12979860C/T polymorphisms associate with the occurrence of biliary complications after liver transplantation and if these complications may influence survival. Methods: One hundred seventy one recipients (133 males) who underwent liver transplantation were recruited. To confirm the mechanical etiology of cholestasis, endoscopic cholangio pancreatography, percutaneous and/or trans-Kehr cholangiography or cholangio magnetic resonance were performed. Two main clinical pictures were identified: biliary strictures and biliary leakage. Immunosuppressive therapy was based on cyclosporine (N = 54) or tacrolimus (N = 117), in association with steroids during the first month after operation. IL-28B rs12979860C/T genotypes were detected by means of polymerase chain reaction. Results: Forty patients (23.4%) presented anastomotic strictures, 7 (4.1%) non-anastomotic strictures, 10 (5.8%) leakage, 8 (4.7%) leakage plus anastomotic strictures. IL-28B rs12979860C/C genotype in association with cyclosporin was found to be an independent predictor of anastomotic strictures occurrence (p = 0.008). A significant difference in 5 years survival was observed between patients with viral etiology of liver disease experiencing either anastomotic or non-anastomotic strictures (16/23) and the remaining patients (104/112, p = 0.001). Conclusions: In recipients carrying rs12979860 IL-28B C/C genotype the use of cyclosporine seems to contribute to enhance the probability of developing biliary complications which in hepatitis B and C positives appear to reduce patient survival. If confirmed in larger studies the use of cyclosporine in these patients could be revised
Endotoxin priming and liver damage by experimental duodenal obstruction in the rat
To verify whether endotoxin (LPS) might act as a priming cofactor of liver injury caused by obstructing the duodenum, four groups of male Wistar rats were studied. The first two groups comprised rats in which a closed duodenal loop (CDL) was created: CDL, n = 6 and CDL + LPS, n = 7; the next two groups comprised sham-operated animals: Sham n = 6 and Sham + LPS, n = 6. LPS, 400 mu g/kg bodyweight, was administered i.p, to the rats belonging to groups CDL + LPS and Sham + LPS, 24 h before laparotomy. Twenty-four hours after laparotomy the animals were killed. Damage to bile ducts, extent and grading of coagulative and lytic spotty necrosis in liver tissue were evaluated morphologically. Coagulative necrosis was severe in four of seven rats of the group CDL + LPS, mild in six of six rats of group CDL, and absent in four of six and five of six rats of groups Sham and Sham + LPS (chi(2) 32.8, P = 0.0001). The animals of group CDL + LPS had more frequently diffuse lytic spotty necrosis than the animals in the three other groups (chi(2) 9.57 P < 0.01). The results of our study indicate that, in rodents subjected to a closed duodenal loop, priming with LPS exacerbates liver injury due to cholate stasis
Morbidity and mortality after transjugular intrahepatic portosystemic shunt placement in patients with cirrhosis
Transjugular intrahepatic portosystemic shunt (TIPS) is adopted to treat refractory complications of portal hypertension, such as variceal bleeding and ascites. This study aimed to assess predictors of hepatic encephalopathy (HE) development and cumulative transplant-free survival after TIPS placement in patients with cirrhosis complicated by refractory ascites and major gastroesophageal bleeding
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