Awareness of Side Effects of Corticosteroids among Users and Nonusers in Saudi Arabia.

Background: Corticosteroids are anti-inflammatory medications that are used to reduce inflammation and inhibit the immune system in a variety of disorders, including allergies, asthma, systemic lupus erythematous, eczema, inflammatory bowel disease, and swollen joints or muscles. The goal of this study was to assess the level of awareness and sources of information about the side effects of corticosteroids among the general population in Saudi Arabia. Methods: This observational cross-sectional study was conducted in Saudi Arabia using an electronic questionnaire. A non-probability convenience sampling technique was used. Statistical Package for the Social Sciences (SPSS) was used for data analysis. Results: The study included 755 participants from Saudi Arabia (67.3% females and 32.7% males). Around 26.8% reported using corticosteroids, and 73.9% were aware of the side effects of glucocorticoids. Among steroid users (202 participants), the most common conditions were allergies (36.1%), asthma or chronic obstructive pulmonary disease (COPD) (21.8%), and skin diseases (27.7%). The majority of respondents (57.9%) used steroids for less than 2 weeks, and topical application (52.5%) was the most common form. Only 30.7% received information about side effects at the time of prescription. The most reported side effects were truncal obesity, moon face, skin thinning, bruising, and slower wound healing. Conclusion: This study highlights the importance of promoting awareness and knowledge regarding the side effects of corticosteroids in Saudi Arabia. While overall awareness levels were relatively satisfactory, specific side effects require further attention in educational efforts.

Neutrophil percentage-to-albumin ratio is a new diagnostic marker for spontaneous bacterial peritonitis: a prospective multicenter study.

BACKGROUND: The neutrophil percentage-to-albumin ratio (NPAR) is a novel measure of systemic inflammation and infection. Low albumin levels increase the risk of infection, while high neutrophil counts indicate the presence of infection. Spontaneous bacterial peritonitis (SBP) is a serious infection in cirrhotic ascites, and the potential of NPAR in diagnosing SBP is not yet established. OBJECTIVE: The objective of this study is to determine the diagnostic value of NPAR in identifying SBP. PATIENTS: This prospective multicenter study included 465 patients diagnosed with cirrhotic ascites and SBP according to international guidelines. Demographic, clinical, and laboratory data were collected. The sensitivity and specificity of NPAR values for diagnosing SBP were assessed using the receiver operating characteristic curve. RESULTS: For SBP diagnosis in the total cohort, NPAR of > 17 had a sensitivity of 85.71%, specificity of 66.67%, and 95% CI (42.1-99.6). In culture-positive SBP, the NPAR at a cut-off > 5.2 had a sensitivity of 85.71%, specificity of 83.33%, and 95% CI (0.709 to 0.979), while in culture-negative SBP, the NPAR at a cut-off > 2.1 had a sensitivity of 92.86%, specificity of 33.33% and CI (0.367 to 0.764). The multivariate analysis revealed that albumin (OR = 2.78, [1.11;3.98], INR (OR = 0.198, [0.066;0.596], creatinine (OR = 0.292, [0.1; 0.81], CRP (OR = 3.18, [1.239;4.52] total leukocytic count (TLC) (OR = 1.97, [1.878; 2.07], platelets (OR = 2.09, [0.99; 2.31] and neutrophil (OR = 3.43, [1.04;3.89] were significantly associated with higher prediction rates for culture positive SBP. CONCLUSIONS: NPAR could be a new, affordable, noninvasive test for diagnosing SBP.

Unraveling IL-17 and IL-22 role in occult hepatitis C versus chronic hepatitis C virus infection.

BACKGROUND: Cytokines play a crucial role in regulating the function of the immune system by controlling the production, differentiation, and activity of immune cells. Occult hepatitis C virus (OHCV) infection can lead to liver damage, including cirrhosis and hepatocellular carcinoma. This study investigates the immunopathogenic impact of the cytokines IL-17 and IL-22 in OHCV infection compared to chronic hepatitis C (CHC) infection. METHODS: We studied three groups of patients: 35 with OHCV, 100 untreated patients with CHC, and 30 healthy control subjects. All subjects underwent physical examination and biochemical testing. We used the sandwich enzyme-linked immunosorbent assay method to measure serum IL-17 and IL-22 levels in all groups. RESULTS: Compared to the occult and control groups, the CHC group had significantly higher serum IL-17 levels (p < 0.001). The occult group also had higher serum IL-17 levels compared to the control group (p < 0.0001). There were no significant differences in IL-22 levels across the research groups. In the OHCV group, individuals with moderate inflammation (A2-A3) had significantly higher serum IL-17 levels than those with minimal inflammation (A0-A1), while in the CHC group, this difference was not statistically significant (p = 0.601). Neither the occult nor the CHC groups showed a correlation between serum IL-22 and inflammatory activity. There was no significant correlation between the levels of IL-17 or IL-22 and the stage of fibrosis/cirrhosis in either group. ROC curves were calculated for serum IL-17 and IL-22 levels and occult HCV infection, with cut-off values set at ≤ 32.1 pg/ml and < 14.3 pg/ml for IL-17 and IL-22, respectively. The AUROC (95%CI) was significantly higher for IL-17 than IL-22 (0.829 (0.732-0.902) vs. 0.504 (0.393-0.614), p < 0.001), suggesting that IL-17 has a stronger correlation with infection risk than IL-22. CONCLUSION: This study suggests that IL-17 may be involved in the immunopathogenesis of OHCV infection, especially in patients with moderate inflammation.

A risk score to predict 30-day hospital readmission rate in cirrhotic patients with spontaneous bacterial peritonitis.

BACKGROUND AND AIM: There is lack of 30-day hospital readmission prediction score in patients with liver cirrhosis and SBP. The aim of this study is to recognize factors capable of predicting 30-day readmission and to develop a readmission risk score in patients with SBP. METHODS: This study prospectively examined the 30-day hospital readmission for patients previously discharged with a diagnosis of SBP. Based on index hospitalization variables, a multivariable logistic regression model was implemented to recognize predictors of patient hospital readmission within 30 days. Consequently, Mousa readmission risk score was established to predict 30-day hospital readmission. RESULTS: Of 475 patients hospitalized with SBP, 400 patients were included in this study. The 30-day readmission rate was 26.5%, with 16.03% of patients readmitted with SBP. Age ≥ 60, MELD > 15, serum bilirubin > 1.5 mg/dL, creatinine > 1.2 mg/dL, INR > 1.4, albumin < 2.5 g/dL, platelets count ≤ 74 (103/dL) were found to be independent predictors of 30-day readmission. Incorporating these predictors, Mousa readmission score was established to predict 30-day patient readmissions. ROC curve analysis demonstrated that at a cutoff value ≥ 4, Mousa score had optimum discriminative power for predicting the readmission in SBP with sensitivity 90.6% and specificity 92.9%. However, at cutoff value ≥ 6 the sensitivity and specificity were 77.4% and 99.7%, respectively, while a cutoff value ≥ 2 had sensitivity of 99.1% and specificity of 31.6%. CONCLUSIONS: The 30-day readmission rate of SBP was 25.6%. With the suggested simple risk assessment Mousa score, patients at high risk for early readmission can be easily identified so as to possibly prevent poorer outcomes.

International multicenter validation of GES score for HCC risk stratification in chronic hepatitis C patients.

We have recently demonstrated the ability of a simple predictive model (GES) score to determine the risk of hepatocellular carcinoma (HCC) after using direct-acting antivirals. However, our results were restricted to Egyptian patients with hepatitis C virus (HCV) genotype 4. Therefore, we studied a large, independent cohort of multiethnic populations through our international collaborative activity. Depending on their GES scores, patients are stratified into low risk (≤ 6/12.5), intermediate risk (> 6-7.5/12.5), and high risk (> 7.5/12.5) for HCC. A total of 12,038 patients with chronic HCV were analyzed in this study, of whom 11,202 were recruited from 54 centers in France, Japan, India, the U.S., and Spain, and the remaining 836 were selected from the Gilead-sponsored randomized controlled trial conducted across the U.S., Europe, Canada, and Australia. Descriptive statistics and log-rank tests. The performance of the GES score was evaluated using Harrell's C-index (HCI). The GES score proved successful at stratifying all patients into 3 risk groups, namely low-risk, intermediate-risk, and high-risk. It also displayed significant predictive value for HCC development in all participants (p < .0001), with HCI ranging from 0.55 to 0.76 among all cohorts after adjusting for HCV genotypes and patient ethnicities. The GES score can be used to stratify HCV patients into 3 categories of risk for HCC, namely low-risk, intermediate-risk, and high-risk, irrespective of their ethnicities or HCV genotypes. This international multicenter validation may allow the use of GES score in individualized HCC risk-based surveillance programs.

De novo Portal Vein Thrombosis in Non-Cirrhotic Non-Alcoholic Fatty Liver Disease: A 9-Year Prospective Cohort Study.

Background and Aims: Approximately 30-40% of portal vein thrombosis (PVT) remains of unknown origin. The association between non-alcoholic fatty liver disease (NAFLD) and PVT is a matter of debate. This study aimed to investigate the association between PVT and NAFLD. Methods: We included 94 out of 105 consecutive NAFLD patients in this prospective cohort study in addition to 94 from the healthy control group. We evaluated biochemical, clinical, immunological, and histopathological parameters; waist circumference (WC); leptin; adiponectin; and leptin/adiponectin ratio (LAR) for all participants at baseline and every 3 years thereafter. We described the characteristics of participants at baseline and showed individual WC, LAR, and PVT characteristics. Potential parameters to predict PVT development within 9 years were determined. Results: PVT developed in eight (8.5%) patients, mainly in the portal trunk. Univariate analysis showed three PVT-associated factors: diabetes mellitus (P = 0.013), WC (P < 0.001), and LAR (P = 0.002). After adjusting multiple confounding variables, the multivariate model showed that the only significant variables were WC and LAR. By applying the receiver operating characteristic curve, WC had 98.8% specificity, 87.5% sensitivity, and 0.894 area under the curve (AUC) for prediction of PVT (P < 0.001) at cutoff values of > 105 cm. In comparison, LAR had 60.5% specificity, 87.5% sensitivity, and 0.805 AUC for PVT prediction (P < 0.001) at cutoff values of >7.5. Conclusions: This study suggests that increased central obesity and LAR were independently associated with PVT development in non-cirrhotic NAFLD patients, and they should be considered risk factors that may participate in PVT multifactorial pathogenesis.

Advanced Glycation End Products as a Predictor of Diabetes Mellitus in Chronic Hepatitis C-Related Cirrhosis.

Background and Aims: Advanced glycation end products (AGEs) were found to be involved in the pathogenesis of various disorders. Chronic hepatitis C virus infection is the major cause of liver cirrhosis development and glucose metabolism alteration. We aimed to explore the association of AGEs with the development of diabetes mellitus (DM) in patients with cirrhosis in this study. Methods: Only 144 of the 165 non-diabetic patients with cirrhosis were consecutively included in this prospective cohort pilot study, in addition to 72 healthy control subjects. Clinical data and biochemical parameters including basal insulin secretion and insulin sensitivity indices together with AGEs were evaluated in all participants at baseline and every 1 year thereafter for 2 years. Multivariable Cox regression analysis was used to determine the parameters that could predict the development of DM within this period. Results: DM developed in 14 (10%) patients only. Univariate Cox regression analysis showed that AGEs (P = 0.004), Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) (P = 0.018), HOMA-ß (P = 0.015), and age (P = 0.012) were associated with DM. After adjusting multiple confounders, the multivariable Cox regression model showed that AGEs, HOMA-IR, and age were the strongest variables associated with DM (all P < 0.05). Using the receiver operating characteristic curve, AGEs at a cutoff value of more than 82.4 ng/ml had 99.23% specificity, 100% sensitivity, and 0.992 area under the curve (AUC) (all P < 0.001) for DM prediction. Conclusion: Our study suggests that AGEs are related to increased incidence of DM, especially in patients with cirrhosis, which is very promising in lowering the risk of DM in these patients.

Helicobacter pylori as an Initiating Factor of Complications in Patients With Cirrhosis: A Single-Center Observational Study.

Background and Aim: The relationship between liver cirrhosis and Helicobacter pylori (H. pylori) is a debatable matter. The aim of this study is to evaluate the possible association between H. pylori infection and liver cirrhosis. Methods: A single-center prospective cohort pilot study of 558 patients with cirrhosis was followed up for 1 year. Serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), vascular endothelial growth factor (VEGF) levels and Fecal H. pylori antigen were evaluated by enzyme-linked immunosorbent assay (ELISA). All patients with positive H. pylori were treated and then followed up for 3 months. Participants with eradicated H. pylori were followed up for one further year. Results: H. pylori-positive patients (48.4%) were associated with increased levels of serum CRP, TNF-α, IL-6, NO, and VEGF, as well as increased incidence of varices, portal hypertensive gastropathy, gastric antral vascular ectasia, hepatocellular carcinoma (HCC), spontaneous bacterial peritonitis, hepatic encephalopathy, portal vein thrombosis (PVT), and hepatorenal syndrome (all P < 0.05). Multivariate analysis models revealed that the presence of H. pylori was an independent risk variable for the development of portal vein thrombosis and hepatocellular carcinoma (P = 0.043, P = 0.037) respectively. After treatment of H. pylori infection, there was a significant reduction in all measured biochemical parameters and reported cirrhotic complications (all P < 0.05). Conclusion: Incidence of PVT and HCC development increased with H. pylori infection through increased inflammatory markers and vascular mediators. Moreover, its eradication may reduce the incidence of these complications.

Endothelin-1/Nitric Oxide Ratio as a Predictive Factor of Response to Therapy With Terlipressin and Albumin in Patients With Type-1 Hepatorenal Syndrome.

BACKGROUND AND PURPOSE: Predictors of response to type-1 hepatorenal syndrome (HRS) therapy are urgently needed. This study's purpose is to evaluate the proposed predictors in these patients. METHODS: Forty-two type-1 HRS patients with cirrhosis were treated with albumin and terlipressin. Clinical, biochemical, and demographic parameters taken at the onset of therapy and changes in endothelin-1/nitric oxide (ET-1/NO) ratio during therapy were analyzed to check their predictive value. RESULTS: Response to treatment (serum creatinine level <1.5 mg/dL at the end of therapy) was shown in 20 patients (48%). Independent predictive variables of response to therapy were early reduction of ET-1/NO ratio ≥0.15 at day 3 of therapy and serum bilirubin baseline <8 mg/dL (area under the receiver operating characteristic curve, 0.751; P < 0.001; specificity, 55%; sensitivity, 85%). Response rates in patients with serum bilirubin level <8 and ≥8 mg/dL were 63% and 20%, respectively (P = 0.008). The corresponding values in patients with an early reduction of ET-1/NO ratio ≥0.15 and <0.15 on day 3 were 85% and 13.6%, respectively (P < 0.001). CONCLUSIONS: Early reduction of ET-1/NO ratio and lower serum bilirubin baseline can predict response to type-1 HRS therapy with albumin and terlipressin. Alternative therapy should be investigated for nonresponder type-1 HRS patients.

Incidence of HCC in chronic hepatitis C patients with advanced hepatic fibrosis who achieved SVR following DAAs: A prospective study.

Liver cirrhosis is an important risk factor for hepatocellular carcinoma. The reported annual incidence of HCC is about 3%-8% in CHC cirrhotic patients. Based on the Cochrane systematic review, there was no clear evidence, on the long-term clinical effects of DAAs in patients achieving SVR, as regard liver cirrhosis-related HCC incidence. The aim of the study was to determine the incidence of HCC in chronic hepatitis C patients genotype IV with liver cirrhosis and advanced liver fibrosis after achieving SVR following DAA treatment in a prospective large cohort of HCV patients with long follow-up. This was a prospective observational cohort study including 2372 CHC patients with advanced liver fibrosis or cirrhosis receiving DAA therapy in outpatient clinics at the Egyptian Liver Research Institute and Hospital since January 2015. Liver fibrosis was assessed using transient elastography. Abdominal ultrasonography and AFP measurement were done at baseline and follow-up visits every 6 months, in addition to triphasic abdominal MSCT when needed. Patients were followed up after achieving SVR12 for at least 12 months. HCC developed in 109 cases during the follow-up period (mean 23.60 ± 8.25 months). Overall HCC incidence was 2.338/100 PY, 95% CI = 1.942-2.814. In patients with cirrhosis, the incidence of HCC was 2.917/100 PY, 95% CI = 2.407-3.535, while in patients with advanced liver fibrosis the incidence of HCC was 0.664/100 PY, 95% CI = 0.333-1.326. In conclusion, the incidence of HCC was reduced in chronic hepatitis C genotype 4 patients with liver cirrhosis (F4) and advanced hepatic fibrosis (F3) who achieved SVR following DAA therapy.

Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt.

BACKGROUND AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP. PATIENTS AND METHODS: Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants. RESULTS: The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135). CONCLUSION: The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.

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

BACKGROUND AND AIM: 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. METHODS: A cohort multicenter pilot study of 369 adults without NAFLD at baseline was followed up for 2 years. Serum leptin, insulin, tumor necrosis factor-α, adiponectin, and interleukin-6 were measured using an enzyme-linked immunosorbent assay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR) and leptin/adiponectin ratio (LAR) were calculated. Fecal H. pylori antigen was measured by ELISA. A total of 127 participants with H. pylori positive were treated and then followed up for 3 months. RESULTS: Helicobacter pylori-positive patients (46.3%) were associated with an increase in IR, proinflammatory cytokines, C-reactive protein (CRP), LAR, NAFLD-liver fat score (NAFLD-LFS), and hepatic steatosis index (HSI) (all P < 0.01). Multivariate analysis of NAFLD according to HSI and NAFLD-LFS reported that presence of H. pylori, LAR, CRP, IL-6, smoking, and age (all P < 0.01) were independent risk factors for the presence of NAFLD. Multiple models adjusted for potential mediators or confounders such as metabolic, inflammatory, and biochemical factors were constructed. After therapy of H. pylori infection, there was a significant reduction in lipogenic profile, IR, leptin, LAR, CRP, proinflammatory cytokines, HSI, and NAFLD-LFS, as well as, increasing HDL. CONCLUSION: Helicobacter pylori infection was related to an increased risk of NAFLD development, through increased markers of IR, inflammatory mediators, and lipid metabolism. Moreover, its eradication can recover these NAFLD risk factors.

Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot.

BACKGROUND/AIMS: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS: Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study. BMI, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll-like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-α, and cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6 months of rifaximin therapy (1100 mg/day). RESULTS: Patients were randomized into two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of rifaximin therapy, patients with NASH showed a significant reduction in homeostatic model assessment, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, endotoxin, toll-like receptor-4, IL-6, tumor necrosis factor-α, CK-18, and NAFLD-liver fat score (all P<0.05), but no changes in the lipid profile; moreover, there was a mild nonstatistically significant reduction of BMI. However, in the placebo group, there was no significant difference in these variables at baseline and after therapy. CONCLUSION: Rifaximin therapy appears to be effective and safe in modifying NASH through reduction of serum endotoxin and improvement of insulin resistance, proinflammatory cytokines, CK-18, and NAFLD-liver fat score.

New predictive factors of poor response to therapy in autoimmune hepatitis: role of mean platelet volume.

BACKGROUND AND OBJECTIVES: The response to immunosuppressive therapy in autoimmune hepatitis (AIH) is a matter of debate. The aim of this work is to identify the histological, biochemical, and clinical predictive factors of incomplete response/treatment failure to the standard treatment (prednisone with or without azathioprine) in a well-characterized series of AIH Egyptian patients. PATIENTS AND METHODS: Of 49 AIH patients, only 36 patients completed this retrospective cohort study. The immunological, biochemical, histopathological, and clinical characteristics of patients were evaluated at diagnosis and during follow-up. RESULTS: Patients were classified into two groups; group A showed a complete response to therapy (n=22; 61%) and group B showed partial response/treatment failure (n=14; 39%). In a multivariate analysis, we observed that age at diagnosis up to 22 years [odds ratio (OR): 23.22; confidence interval (CI): 3.978-135.549; P<0.001], serum albumin up to 3.2 g/dl (OR: 5.36; CI: 1.237-23.209; P=0.025), mean platelet volume (MPV) of at least 10.75 fl (OR: 16.5; CI: 3.093-88.037; P<0.001), and presence of cirrhosis at diagnosis (OR: 8.44; CI: 1.682-42.392; P=0.001) were independent variables that can predict partial response/treatment failure. MPV correlated positively with stages of fibrosis/cirrhosis and grades of activity in liver biopsy at diagnosis and correlated inversely with serum albumin and age at presentation. During therapy, group B showed a fluctuation in MPV levels, however, group A showed a progressive decline until the end point. CONCLUSION: Our study confirmed that younger age, hypoalbuminemia, increased MPV, and cirrhosis at diagnosis were all independent predictors of incomplete response/treatment failure in AIH patients. MPV may reflect the response to therapy.

Do we need to screen for de-novo diabetes mellitus in chronic hepatitis C patients after a sustained virological response?

BACKGROUND AND AIM: There are millions of chronic hepatitis C (CHC) virus-infected patients who have been treated with a combination therapy (interferon and ribavirin) and have achieved a virological response (SVR) worldwide. The aim of this study is to evaluate the risk factors for de-novo diabetes mellitus in CHC patients treated with combination therapy (interferon and ribavirin) and have achieved an SVR. PATIENTS AND METHODS: A total of 214 nondiabetic CHC patients with SVR and baseline homeostasis model assessment (HOMA) less than or equal to 2 were divided into group A, which included 108 patients with a BMI less than 25, and group B, which included 106 patients with a BMI of at least 25 and less than 30. HOMA insulin resistance (IR) and BMI were measured at the baseline, at achievement of an SVR, and 1 year after achievement of an SVR. Leptin levels were assessed at baseline and 1 year after achievement of an SVR in patients with increased BMI. RESULTS: One year after SVR, 36 (33.33%) patients from group A developed increasing BMI with no significant changes in HOMA versus that at SVR (P=0.53), but showed a significant reduction versus baseline HOMA (P=0.02). In group B, 68 (64.1%) patients showed increased BMI of at least 25, with a significant increase in HOMA versus that at SVR (P=0.02), and with no significant reduction versus baseline HOMA (P=0.44). In group B, serum leptin showed a significant reduction 12 months after achievement of an SVR versus baseline in patients with increased BMI. Six patients from group B with increased BMI after 1 year developed de-novo IR and type two diabetes mellitus. CONCLUSION: In nondiabetic CHC patients with SVR and baseline BMI of at least 25, the post-SVR increase in BMI predisposed to an increase in HOMA-IR and could be considered a predisposing factor for diabetes mellitus.

A Novel Combination of C-Reactive Protein and Vascular Endothelial Growth Factor in Differential Diagnosis of Ascites.

BACKGROUND AND AIMS: Ascites with unknown cause remains a diagnostic challenge, which needs novel noninvasive biomarkers for the precise diagnosis. We aimed to evaluate the ascitic fluid and serum C-reactive protein (CRP) and vascular endothelial growth factor (VEGF) as diagnostic markers in the differential diagnosis of malignant and benign ascites. METHODS: In this prospective work, 315 consecutive patients with ascites were studied. Ascitic fluid and serum levels of CRP and VEGF were evaluated by using an enzyme-linked immunosorbent assay. RESULTS: Patients were divided into a benign ascites group (group 1) (n = 256) and a malignant ascites group (group 2) (n = 59). Ascitic and serum CRP were significantly elevated in malignant ascites than benign ascites group [5.08 (3.62-6.58) vs. 1.82 (0.64-3.86) ng/ml; P < 0.001 and 12.7 (8.55-17.05) vs. 5.94 (2.57-10.64) ng/ml; P < 0.001], respectively. Ascitic and serum VEGF were significantly increased in malignant ascites than benign ascites patients [0.68 (0.39-0.96) vs. 0.41 (0.25-0.83) ng/ml; P < 0.001 and 0.74 (0.41-1.08) vs. 0.54 (0.23-0.86) ng/ml; P < 0.001], respectively. At a cutoff value of 7.3 and 0.63 ng/ml, serum CRP and VEGF had specificity (77.3 and 89.5 %) and sensitivity (83.1 and 94.9 %) for detecting malignant ascites [area under the curve (AUC) 0.821, 0.921], respectively. At a cutoff value of 2.5 and 0.57 ng/ml, ascitic CRP and VEGF had specificity (81.6 and 85.5 %) and sensitivity (84.7 and 91.5 %) for detecting malignant ascites (AUC 0.842, 0.894), respectively. CONCLUSION: Elevated ascitic fluid and serum CRP and VEGF values were related to the malignant ascites.

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.

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-α 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.