Rania Elhelaly

De-novo portal vein thrombosis in liver cirrhosis: risk factors and correlation with the Model for End-stage Liver Disease scoring system.

Background and objectivesPortal vein thrombosis (PVT) is a potential lethal complication in late liver cirrhosis. There is a lack of knowledge of the clinical features and risk factors of PVT. We aimed to investigate the clinical and radiological characteristics, and biochemical markers of cirrhotic patients to determine the high-risk individuals for PVT attending our center. Patients and methodsOf 426 cirrhotic patients, only 120 consecutive patients were included. Clinical, biochemical, immunological, Model for End-stage Liver Disease (MELD) score, portal vein patency, and flow velocity were measured in all patients at baseline and every 6 months thereafter. Variables that could predict the development of PVT within 1 year were identified by multiple logistic regression. ResultsOnly 95 patients completed the study; PVT was found in 17 (17.9%) patients. PVT was observed mainly in the portal trunk, superior mesenteric vein, and splenic vein. Univariate analysis showed that diabetes mellitus, lower levels of hemoglobin, platelet counts, and portal vein flow velocity as well as increased MELD scores, platelet indices, portal vein diameter, and splenic thickness were associated with PVT patients than in non-PVT patients (all P<0.01). ConclusionThe incidence of PVT was 17.9%. PVT occurred mainly in the portal vein trunk, superior mesenteric vein, and splenic vein. Diabetes mellitus, lower levels of hemoglobin, platelet count and portal vein flow velocity as well as increased MELD score, platelet indices, portal vein diameter, and splenic thickening were associated with PVT. Splenic thickening, marked reduced of mean portal flow velocity, and diabetes mellitus may be risk factors for PVT.

A novel model using mean platelet volume and neutrophil to lymphocyte ratio as a marker of nonalcoholic steatohepatitis in NAFLD patients: multicentric study.

Background and aim Nonalcoholic fatty liver disease (NAFLD) is a leading cause of progressive and chronic liver injury. Mean platelet volume (MPV) and the neutrophil–lymphocyte ratio (N/L ratio) may be considered cheap and simple markers of inflammation in many disorders. We aimed to investigate the clinical utility of MPV and the N/L ratio to predict fibrosis in NAFLD patients and the presence of nonalcoholic steatohepatitis (NASH). Materials and methods A total of 873 patients with biopsy-proven NAFLD and 150 healthy controls were included. Patients were divided into two groups: non-NASH group (n=753) and NASH group (n=120). Liver biopsy, MPV, lymphocyte, and neutrophil counts were registered; the N/L ratio was calculated. Proinflammatory cytokines (tumor necrosis factor-&agr; and interleukin-6) were measured by an ELISA. Results NASH patients had higher MPV compared with non-NASH patients (10.9±1.8 and 9.5±1.6 fl, respectively, P<0.001). MPV correlated positively with the NAFLD activity score, proinflammatory cytokines, and C-reactive protein (CRP) (P<0.001). Patients with advanced fibrosis (F3–4) had increased MPV (11.3±0.9 fl) compared with patients with early fibrosis (F1–2) (10.2±0.8 fl, P<0.001). NASH patients had an increased N/L ratio compared with non-NASH cases (2.6±1.1 and 1.9±0.7 fl, respectively, P<0.001). The N/L ratio correlated positively with NAFLD activity score, proinflammatory cytokines, and CRP (P<0.001). In addition, patients with advanced fibrosis (F3–4) had an N/L ratio (2.5±1.1) comparable with that of patients with early fibrosis (F1–2) (1.8±0.9) (P<0.001). Conclusion MPV and the N/L ratio were elevated in NASH patients versus non-NASH cases, and in patients with advanced fibrosis (F3–4) versus early fibrosis (F1–2). They can be used as noninvasive novel markers to predict advanced disease.

Ascitic Fluid Calprotectin and Serum Procalcitonin as Accurate Diagnostic Markers for Spontaneous Bacterial Peritonitis

Background/Aims The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a polymorphonuclear leukocytes (PMNs) exceeding 250/μL in ascitic fluid. The aim of the study was to evaluate serum procalcitonin and ascitic fluid calprotectin as accurate diagnostic markers for detecting SBP. Methods Seventy-nine patients with cirrhotic ascites were included. They were divided into a SBP group, including 52 patients, and a non-SBP group of 27 patients. Serum procalcitonin, ascitic calprotectin, and serum and ascitic levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured using an enzyme-linked immunosorbent assay. Results Serum procalcitonin and ascitic calprotectin were significantly higher in SBP patients than in non-SBP patients. Significant increases in both serum and ascitic levels of TNF-α and IL-6 were observed in SBP patients versus non-SBP patients. At a cutoff value of 0.94 ng/mL, serum procalcitonin had 94.3% sensitivity and 91.8% specificity for detecting SBP. In addition, at a cutoff value of 445 ng/mL, ascitic calprotectin had 95.4% sensitivity and 85.2% specificity for detecting SBP. Both were positively correlated with ascitic fluid proteins, PMN count, TNF-α, and IL-6. Conclusions According to our findings, determination of serum procalcitonin levels and ascitic calprotectin appears to provide satisfactory diagnostic markers for the diagnosis of SBP.

Could serotonin be a potential marker for hepatocellular carcinoma? A prospective single-center observational study.

Background Hepatocellular carcinoma (HCC) is the third most common cause of cancer mortality among men worldwide. Serotonin is a biogenic amine, which may be involved in the tumorigenesis of HCC. Aim We aimed to determine whether serotonin is a dependable marker for the diagnosis of HCC in cirrhotic patients in comparison with &agr;-fetoprotein protein (AFP) and prothrombin induced by vitamin K absence-II (PIVKA-II). Patients and methods Serum serotonin, AFP, and PIVKA-II were measured in 262 patients with chronic hepatitis C (CHC): 82 cirrhotic patients with HCC (group I), 80 cirrhotic patients without HCC (group II), and 100 CHC-infected patients without cirrhosis (group III); in addition, 60 healthy controls were studied (group IV). Results AFP showed significant statistical differences among the groups studied (P<0.001). PIVKA-II and serotonin levels showed no statistically significant differences between the patients with CHC group and the healthy controls (P1=0.614 and P1=0.13, respectively), whereas their levels were statistically higher in cirrhotic patients than patients with CHC (all P values <0.001) and in the cirrhotic patients with HCC group than the cirrhotic patients without HCC (P<0.001). A significant positive correlation was found between serum serotonin and AFP (rho=0.794; P<0.001) and serum serotonin and PIVKA-II (rho=0.889; P<0.001) among the patient groups. The receiver operator characteristic curve showed a higher area under the curve for serotonin than AFP and PIVKA-II (0.942, 0.824, and 0.921, respectively). Conclusion Serotonin may be used together with PIVKA-II to screen for HCC in cirrhotic patients with CHC.

Diagnostic utility of interferon gamma-induced protein 10 kDa in spontaneous bacterial peritonitis: single-center study.

Background and aims Spontaneous bacterial peritonitis (SBP) is an important cause of mortality and morbidity in cirrhotic patients with ascites. The diagnosis of SBP is mainly made on the basis of a polymorphonuclear leukocyte cell count exceeding 250/&mgr;l in ascitic fluid. However, this procedure is subjective. We aimed to evaluate serum and ascitic fluid interferon-&ggr;-induced protein (IP-10) as accurate diagnostic markers for detecting SBP. Methods A total of 425 consecutive patients with ascites were included. Serum and ascitic fluid of IP-10, tumor necrosis factor-&agr; (TNF-&agr;), and interleukin-6 (IL-6) were measured using an enzyme-linked immunosorbent assay. Results Patients were divided into an SBP group, including 61 patients, and a non-SBP group, including 364 patients. Serum and ascitic IP-10 were significantly higher in SBP patients than in patients without SBP (1855±825 vs. 955±510 pg/ml; P<0.001 and 2160±994 vs. 1110±623 pg/ml; P<0.001), respectively. There was a significant increase in both serum and ascitic levels of TNF-&agr; and IL-6 in SBP patients than in patients without SBP. At a cut-off value of 1915 pg/ml, serum IP-10 had 91% sensitivity and 89% specificity for detecting SBP (area under the curve: 0.912). Also, at a cut-off value of 2355 pg/ml, ascitic IP-10 had 92.5% sensitivity and 87% specificity for detecting SBP (area under the curve: 0.943). Both were correlated with ascitic fluid proteins, polymorphonuclear count, TNF-&agr;, and IL-6. Conclusion Serum and ascitic IP-10, TNF-&agr;, and IL-6 are significantly increased in SBP patients versus patients without SBP. Serum level of IP-10 is more specific and sensitive, such as ascites. Thus, it seems to represent a satisfactory diagnostic marker for the diagnosis of SBP.

The role of antioxidants and zinc in minimal hepatic encephalopathy: a randomized trial.

Background: Minimal hepatic encephalopathy (MHE) has a far-reaching impact on quality and function ability in daily life and may progress to overt hepatic encephalopathy. There is a synergistic effect between systemic oxidative stress and ammonia that is implicated in the pathogenesis of hepatic encephalopathy. The aim of this study is to investigate the effectiveness of oral supplementation of antioxidants and zinc gluconate on MHE versus lactulose. Methods: Our study included 58 patients with cirrhosis diagnosed as having MHE by neuropsychometric tests, including number connection test part A (NCT-A), digit symbol test (DST) and block design tests (BDTs). Patients were randomized to receive 175 mg zinc gluconate, 50,000 IU vitamin A, 500 mg vitamin C and 100 mg vitamin E once daily plus lactulose, dose 30–60 ml/day for 3 months [group A (n = 31)] or initiated and maintained on lactulose dose 30–60 ml/day for 3 months [group B (n = 27)]. Neuropsychometric tests and laboratory investigations were repeated after 3 months of therapy. Results: Compared with the baseline neuropsychometric tests, a significant improvement was reported in patients with MHE after 3 months of antioxidant and zinc therapy (group A) versus patients with lactulose therapy (group B) (NCT-A, p <0.001; DST, p = 0.006; BDT, p < 0.001). Antioxidant and zinc supplementation significantly decreased arterial ammonia level, alanine aminotransferase (ALT), aspartate aminotransferase (AST) (p < 0.001) and improved Child–Pugh score in MHE after 3 months of therapy (p= 0.024). Conclusion: Antioxidant and zinc supplementation can improve MHE in patients with liver cirrhosis.

Insulin-Like Growth Factor-1 and Vascular Endothelial Growth Factor in Malignant and Benign Biliary Obstructions.

Background: Despite the presence of various diagnostic tools, the differential diagnosis between malignant and benign biliary obstructions is so difficult. This study aimed to evaluate the role of serum and biliary insulin‐like growth factor‐1 (IGF‐1) and vascular endothelial growth factor (VEGF) in this differential diagnosis. Materials and Methods: Patients (n = 109, 61 men and 48 women) with diagnosis of benign (n = 62) or malignant (n = 47) biliary obstruction were included. Serum and biliary IGF‐1 and VEGF markers were analyzed by the chemiluminescent immunometric method. Results: Mean age was 62.7 ± 8.1 years for the malignant group and 58.5 ± 15.4 years for the benign group (P = 0.092). Choledocholithiasis (79%), cancer head of the pancreas (53.2%) and cholangiocarcinoma (38.3%) were the most common etiologies. No statistical difference was detected regarding serum IGF‐1 and VEGF levels between 2 groups. At a cutoff value of 308.55 and 0.5 ng/mL, biliary IGF‐1 and VEGF had (91.4% and 90.3%) sensitivity and (89.5% and 84.9%) specificity differential diagnosis between malignant and benign biliary obstructions (area under the curve: 0.943, 0.915), respectively. Conclusions: Biliary levels of IGF‐1 and VEGF significantly increase in malignant than benign obstructive lesions. Measurement of these markers in the bile of these patients may aid in the detection of biliary tumors.

C‐reactive protein and insulin‐like growth factor‐1 in differential diagnosis of ascites

Insulin‐like growth factor‐1 (IGF‐1) and C‐reactive protein (CRP) are produced mainly by the liver; the output of these markers in response to inflammatory processes may be affected in patients with hepatic dysfunction. This may explain the differences in IGF‐1 and CRP values in patients with non‐portal and portal hypertension ascites. We aimed to evaluate serum and ascitic fluid IGF‐1 and CRP as diagnostic markers in the differential diagnosis of benign and malignant ascites.

Helicobacter pylori and non-alcoholic fatty liver disease: A new enigma?

The relationship between Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. We achieved this prospective work to study whether H. pylori infection is a risk factor for NAFLD.

Elevated serum α-fetoprotein levels in patients with chronic hepatitis C virus genotype 4: not the end of the story.

Background and aim Elevated serum &agr;-fetoprotein (AFP) is not uncommonly seen among patients with chronic hepatitis C. This study aimed to identify clinical characteristics, histological characteristics, and biochemical markers associated with increased serum AFP levels in hepatitis C virus genotype 4-infected patients with no evidence of hepatocellular carcinoma and to determine the effect of lifestyle modification on these parameters. Methods The study included 447 chronic hepatitis C patients with no evidence of hepatocellular carcinoma and 100 healthy controls. They underwent liver biopsies, homeostasis model assessment-insulin resistance (HOMA-IR), measurement of serum insulin, leptin, adiponectin, tumor necrosis factor-&agr;, and interleukin-6 levels by an enzyme-linked immunosorbent assay, and assessment of AFP levels. Eighty patients with HOMA-IR greater than 3 received prospective longitudinal lifestyle intervention. Results In a multivariate analysis, platelet count less than 140×103/cm, a mean platelet volume of at least 9.5 fl, a neutrophil–lymphocyte ratio (NLR) of at least 2, an aspartate transaminase level of at least 55 IU/l, a &ggr;-glutamyl transpeptidase level of at least 40 IU/l, an albumin level of up to 3.8 g/dl, HOMA-IR greater than 3, a leptin level of at least 10 pg/ml, an iron level of at least 165 &mgr;g/dl, a ferritin level of at level 175 ng/ml, and hepatic fibrosis F3–F4 were found to be independently associated with elevated AFP levels. The lifestyle intervention significantly improved BMI, platelet indices, NLR, &ggr;-glutamyl transpeptidase, leptin, leptin/adiponectin ratio, tumor necrosis factor-&agr;, interleukin-6, HOMA-IR, and AFP levels. Conclusion Elevated insulin resistance, leptin, serum iron, ferritin, mean platelet volume, NLR, and advanced fibrosis, as well as decreased platelet count and serum albumin, are independently associated with an elevated AFP level. Lifestyle modification can improve (reduce) insulin resistance, leptin, leptin/adiponectin ratio, platelet count and their indices, NLR, and AFP level.