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.

De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?

Background and Purpose: The advanced glycation end products (AGEs) have been implicated in different diseases' pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis. Methods: Only 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period. Results: HCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P <0.001), and AGEs levels (P <0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development. Conclusion: This work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.

Study of Uromodulin Gene Polymorphism in Egyptian Patients with End-Stage Renal Disease.

Uromodulin (UMOD) gene polymorphism has been linked with end-stage renal disease. In this research, we studied the prevalence of UMOD rs42993393 T>C in Egyptian hemodialysis (HD) patients and the blood level of UMOD in those patients. The study was a case-control study and included 100 patients on regular HD and 100 healthy control subjects. The blood samples from the studied groups were subjected to the determination of UMOD blood level and molecular study of UMOD rs42993393 T>C genotype by polymerase chain reaction with restriction fragment length polymorphism. The serum UMOD level was significantly low in patients (38.6 7.6 ng/mL) compared to control subjects (221.3 ± 54.2, P = 0.0001). On the other hand, the UMOD rs42993393T>C was significantly increased in TC in patients (28%, odds ratio 1.3-1.0-2.0) compared to controls (22%, P = 0.03), and there was a significant increase in CC in patients (10%) compared to control subjects (3%; P = 0.0001). The T allele was significantly increased in controls compared to patients with a significant increase in C allele in patients compared to controls (P = 0.01). The present study highlights the prevalence of UMOD gene polymorphism at rs42993393T>C. There was a significant prevalence of C allele and C genotypes in HD patients. This finding may indicate that this allele may be a predisposing genotype for renal failure in susceptible patients. On the other hand, the significant reduction of serum UMOD in patients with end-stage renal disease may be attributed to the reduced functioning renal mass.

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.

Ramadan fasting and liver diseases: A review with practice advices and recommendations.

Ramadan fasting is obligatory for Muslim healthy adults. However, there are many exemptions from fasting; including patients, whose diseases will be aggravated by fasting. Muslim patients with different liver diseases are frequently seen in the clinics discussing their intent to fast this month with their treating physicians. To answer our patients' inquiries about the expected benefits and/or risks of fasting and delivering them the best care, we carried out this review and we draw advices and recommendations based on the available evidence. A web-based search, combining multiple keywords representing different liver diseases with Ramadan fasting had been carried out. To answer the research question: Do adult Muslim patients with different liver diseases who fast the month of Ramadan have had a deleterious effect on their health in comparison to those who did not fast? Relevant publications were retrieved. No randomized controlled trials were focusing on Ramadan fasting and liver diseases in the filtered databases, eg Cochrane library. Consequently, non-filtered databases, eg PubMed, Google Scholar and Egyptian Knowledge Bank searched and full-text high-quality research articles were carefully analysed to draw recommendations. Other relevant publications with low quality of evidence like case studies and short communications were also reviewed to address practice advices. Although Ramadan fasting was found beneficial for patients with NAFLD, it was found deleterious to patients with Child B and C cirrhosis and patients with peptic ulcer. Patients with chronic hepatitis, Child A cirrhosis and those with non-complicated liver transplant can fast with prefasting assessment and strict follow up.

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.

Recurrence of spontaneous bacterial peritonitis in cirrhosis: novel predictors.

BACKGROUND AND AIMS: Recurrence of spontaneous bacterial peritonitis (SBP) is still a matter of debate. We conducted this study to evaluate the probable factors that predict the recurrence of SBP in patients who recovered from the first episode of SBP and the long-term outcomes of SBP recurrence. METHODS: One hundred twenty-four patients diagnosed with liver cirrhosis, SBP and did not receive secondary prophylaxis either with norfloxacin or other antibiotics were included in this prospective cohort pilot study. Clinical, biochemical and ascitic fluid analysis parameters were evaluated. Ascitic fluid interferon-γ-induced protein (IP-10), calprotectin, interleukin-6 and tumor necrosis factor-α were measured by ELISA. RESULTS: Of these, 76 patients survived with an in-hospital mortality rate of 38.7%. The survivors were classified into two groups according to recurrence and nonrecurrence of SBP and survival time, clinical parameters and cause of death were investigated. Thirty-one participants had one or more attacks of SBP, with a recurrence rate of 40.8% within one-year follow-up. Before discharge, multivariate analysis showed that ascitic IP-10 (≥1220 pg/ml), ascitic calprotectin (≥550 ng/ml), serum albumin (≤2.5 g/dl), nonuse of prophylactic ß-blockers and use of proton-pump inhibitors (PPIs) were the independent variables in predicting recurrent SBP. Sepsis-related organ failure was the most common etiology of mortality in the recurrent SBP group within 3 and 6 months. CONCLUSION: Increased ascitic calprotectin and IP-10, hypoalbuminemia, nonuse of prophylactic ß-blockers and use of PPI were independently associated with increased SBP recurrence rate. Sepsis-related organ failure was the most common etiology of mortality.

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.

Homocysteine: a new diagnostic marker in spontaneous bacterial peritonitis.

BACKGROUND AND AIMS: The diagnosis of spontaneous bacterial peritonitis (SBP) depends primarily on a polymorphonuclear leukocyte cell count more than 250/mm. This method is invasive, and not diagnostic in all variants of SBP; we aimed to assess serum homocysteine as a precise indicative marker for the diagnosis of all variants of SBP. PATIENTS AND METHODS: A total 323 consecutive ascitic patients were registered in this prospective work. Serum and ascitic fluid of homocysteine were evaluated utilizing an enzyme-linked immunosorbent assay. RESULTS: Participants were classified into a non-SBP group, including 262 participants and 61 patients with SBP. Serum and ascitic homocysteine were considerably elevated in the SBP group than in the non-SBP group (17.94±7.57 vs. 11.75±5.68 µmol/l; P<0.001 and 14.70±5.45 vs. 9.75±4.55 µmol/l; P<0.001). At a cutoff value of 17.79 µmol/l, serum homocysteine had 89.3% specificity and 95.1% sensitivity for distinguishing SBP (area under the curve: 0.932) and, at a cutoff value of 16.1 µmol/l, ascitic homocysteine had 84.4% specificity and 92.7% sensitivity for distinguishing SBP (area under the curve: 0.901). Both were positively correlated with the polymorphonuclear count, C-reactive protein, Child-Pugh score, and Model For End-Stage Liver Disease score as well as negatively correlated with the protein content in the ascitic fluid and estimated glomerular filtration rate. After SBP therapy, there was a marked reduction in serum and ascitic homocysteine levels. CONCLUSION: This study demonstrates that serum and ascitic homocysteine are considerably higher in SBP participants versus non-SBP patients. Serum homocysteine may provide a reliable and noninvasive diagnostic marker for all variants of SBP.

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.

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

BACKGROUND AND AIM: 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. METHODS: In this prospective study, 398 consecutive patients with ascites were included. Serum and ascitic fluid levels of IGF-1 and CRP were measured using an enzyme-linked immunosorbent assay. RESULTS: Patients were divided into group 1, due to benign ascites (n = 324), and group 2, due to malignant ascites (n = 74). Serum and ascitic IGF-1 were significantly increased in malignant ascites than benign ascites group [305 ± 65.7 ng/mL vs 95 ± 53.8 ng/mL; P < 0.001 and 288 ± 54.7 ng/mL vs 83.2 ± 36.7 ng/mL; P < 0.001], respectively. Serum and ascitic CRP were significantly higher in malignant ascites than benign ascites patients [12.8 ± 6.3 mg/mL vs 6.1 ± 4.9 mg/mL; P < 0.001 and 5.1 ± 2.2 mg/mL vs 1.6 ± 1.3 mg/mL; P < 0.001], respectively. At a cutoff value of 309.4 ng/mL and 7.8 mg/mL, serum IGF-1 and CRP had (95.1%, 81%) sensitivity and (88.6%, 75.5%) specificity for detecting malignant ascites [area under the curve: 0.932, 0.845], respectively. At a cutoff value of 291.6 ng/mL and 2.6 mg/mL, ascitic IGF-1 and CRP had (94.6%, 84%) sensitivity and (83.2%, 80.3%) specificity for detecting malignant ascites (area under the curve: 0.911, 0.893) correspondingly. CONCLUSION: Elevated serum and ascitic fluid IGF-1 and CRP levels were associated with malignant ascites.