Correlation Between Vascular Endothelial Growth Factor and Long-Term Occurrence of HCV-Related Hepatocellular Carcinoma After Treatment with Direct-Acting Antivirals.

We aimed to evaluate the correlation between vascular endothelial growth factor (VEGF) and long-term occurrence of hepatocellular carcinoma after HCV treatment with direct-acting antivirals (DAAs) and the HCC stage. Two groups with HCV-related liver cirrhosis and HCC were included: group 1, HCC following DAAs; group 2, HCC did not receive DAAs. The serum level of VEGF and HCC staging was evaluated. The duration between DAAs and HCC was 21.81 ± 11.66 months. Portal vein thrombosis (PVT) was observed more in group 1 (31%). VEGF was relatively elevated in group 1 compared to group 2. HCC patients after DAAs, showed elevated VEGF with frequent PVT.

Regulatory B Cells and Their Cytokine Profile in HCV-Related Hepatocellular Carcinoma: Association with Regulatory T Cells and Disease Progression.

Although regulatory B cells (Bregs) have been proven to play a suppressive role in autoimmune diseases, infections and different tumors, little is known regarding hepatocellular carcinoma (HCC), especially in hepatitis C-related settings. Herein, we analyzed the frequency of circulating Bregs, serum levels of IL-10, IL-35 and B-cell activating factor (BAFF) and investigated their association with regulatory T cells (Tregs) and disease progression in HCV-related HCC. For comparative purposes, four groups were enrolled; chronic HCV (CHC group, n = 35), HCV-related liver cirrhosis (HCV-LC group, n = 35), HCV-related HCC (HCV-HCC group, n = 60) and an apparently healthy control (Control-group, n = 20). HCC diagnosis and staging were in concordance with the Barcelona Clinic Liver Cancer (BCLC) staging system. Analysis of the percentage of Breg cells and peripheral lymphocyte subsets (Treg) was performed by flow cytometry. Serum cytokine levels of IL-10, IL-35 and B-cell activating factor (BAFF) were measured by ELISA. The frequency of Bregs was significantly higher in the HCV-HCC group compared to the other groups and controls. A significant increase was noted in late-HCC versus those in the early stages. The frequency of Bregs was positively correlated with Tregs, serum IL-10, IL-35 and BAFF. In conclusion, Peripheral Bregs were positively correlated with the frequency of Tregs, IL-10, IL-35 and BAFF, and may be associated with HCV-related HCC progression.

Impact of interleukin IL-6 rs-1474347 and IL-10 rs-1800896 genetic polymorphisms on the susceptibility of HCV-infected Egyptian patients to hepatocellular carcinoma.

Hepatitis C virus (HCV) is considered leading cause of cirrhosis and hepatocellular carcinoma (HCC). We aimed to examine the association of IL-6 and IL-10 single-nucleotide polymorphisms with the progression of chronic HCV (CHC) infection to cirrhosis and HCC. For comparative purposes, four groups were enrolled; chronic HCV group (CHC, n = 22), HCV-related liver cirrhosis group (HCV-LC, n = 22), HCV-related HCC group (HCV-HCC, n = 54), and an apparently healthy control group (controls, n = 48). HCC diagnosis and staging were in concordance to Barcelona Clinic Liver Cancer (BCLC) staging system. IL-6 rs-1474347 and IL-10 rs-1800896 genotyping was performed by allelic (VIC- and FAM-labeled) discrimination method using assay-on-demand TaqMan real-time PCR assays. For IL-6 rs1474347, the AA genotype was more frequent in CHC, HCV-LC, and HCV-HCC compared to controls. Also, the IL-6 rs1474347 AC genotype was favorable for the progression of HCV chronic infection to cirrhosis and HCC. On the other hand, the IL-10 rs1800896 TT genotype was found to be prominent in the HCC group. Additionally, the IL-10 rs180096 TT genotype was favorable for the progression of chronic HCV infection to cirrhosis and HCC. Furthermore, higher levels of AFP were observed in HCC patients with IL-6 rs1474347 AA genotype and HCC patients with IL-10 rs1800896 CC and TT genotypes. Screening for IL-6 rs 1474347 AC genotype and IL-10 rs180096 TT genotype as well as the determination of AFP level showed to be good markers for examining the susceptibility of HCV Egyptian patients to develop cirrhosis and HCC.

Serum Alpha-fetoprotein Levels and Response to Direct Antiviral Therapy in Patients with Chronic Hepatitis C: Real-world Results from 1716 Patients in Egypt.

BACKGROUND & AIMS: Direct Antiretroviral Agents (DAAs), sofosbuvir-based therapies, have opened a new era in the treatment of chronic HCV infection. The aim of the study was to investigate the potential use of baseline and in serial serum, AFP levels as a predictor for response to DAAs in patients with Chronic Hepatitis C. METHODS: This multicenter observational study was carried out on 1716 chronic hepatitis C virusinfected patients who received direct anti-viral drugs for 12 weeks. The primary end point was sustained virological response at 12 weeks after the end of treatment determined by quantitative PCR for HCV RNA. Serum AFP was quantitatively assessed at baseline then after 12week after stoppage of treatment (SVR12). RESULTS: SVR12 rate was 97.8%. Elevated serum AFP was significantly higher in non -SVR group p value (<0.001). There was a significantly marked decrease in AFP after treatment in comparison to pretreatment values. The multivariate logistic regression analysis on the resulting significant variable from the univariate analysis revealed that only AFP was significantly related to the response to direct antiviral therapy in patients with chronic hepatitis C with p <0.001, OR 1.10 (95% CI 1.07:1.12). Other sociodemographic (e.g. Age, gender, BMI, ..) or laboratory factors (Hb, ANC, WBCs, …) did not show any significant association with the patients' response to treatment. CONCLUSIONS: Serum AFP levels were a predictor for response in patients with chronic HCV with the administration of direct antiviral drugs.

Role of vitamin D deficiency as a risk factor for infections in cirrhotic patients.

BACKGROUND: Vitamin D plays a role in innate and acquired immunity. The risk for bacterial infections is increased in cirrhotic patients due to low levels of vitamin D. This study aimed to determine serum 25-(OH) vitamin D levels among cirrhotic patients in the presence and absence of infections and correlate this level with liver disease severity. METHODS: This cross-sectional analytic study recruited 87 hospitalised cirrhotic patients who were divided into the following groups: group with evidence of infection (45 cases) and group without infection (42 cases). Urine analysis, ascetic fluid study and chest X-rays were performed to find the site of infection. Serum 25-(OH) vitamin D was also measured. RESULTS: Vitamin D levels were lower in the cirrhotic with infection group than in the cirrhotic without infection group (17.3 ± 2.5 vs. 41.1 ± 3.1, respectively) (P-value < 0.001). Approximately 71.4% cirrhotic patients without infection had sufficient vitamin D levels, while 60% of cirrhotic patients with infection had insufficient vitamin D levels, and 28.9% had vitamin D deficiency (P-value < 0.001). Spontaneous bacterial peritonitis was the most common infection (62.2%). The cutoff point of vitamin D levels for cirrhotic patients with infection was 21 ng/mL. CONCLUSION: Vitamin D deficiency was found to be an independent predictor of infection in cirrhotic patients suggesting that vitamin D supplementation may be useful in these patients. No significant correlations were found between the vitamin D level and the Child-Pugh class and MELD score among the infected group and non-infected group.

Noninvasive biomarkers as surrogate predictors of clinical and endoscopic remission after infliximab induction in patients with refractory ulcerative colitis.

BACKGROUND/AIMS: Treatment of refractory ulcerative colitis (UC) is a clinical challenge, and after biological therapy, monitoring clinical and endoscopic responses is fundamental. We aimed to investigate and compare the predictive power of different noninvasive parameters for clinical remission and mucosal healing after infliximab induction therapy in refractory UC patients. PATIENTS AND METHODS: Serum and fecal biomarkers, including hemoglobin, white blood cells, erythrocyte sedimentation rate, C-reactive protein (CRP), and fecal calprotectin (FC), and colonoscopy were assessed in 44 patients with refractory UC before and after (week 12) infliximab induction. Clinical and endoscopic responses were measured by clinical Mayo score and endoscopic Mayo subscore, respectively. RESULTS: After infliximab induction, 54.5% and 65.9% had clinical remission and mucosal healing, respectively. Post-induction CRP and FC were significantly lower in clinical responders versus nonresponders (P = 0.01 and 0.001, respectively) and in patients with mucosal healing than without (P < 0.001). Among all the parameters tested, FC had the best predictive value of clinical remission [Area under the curve (AUC = 0.826)] and mucosal healing (AUC = 0.949). Post-induction FC had 87.5% sensitivity and 89% specificity (cut-off <100 µg/g) for predicting clinical remission and 89.7% sensitivity and 93.3% specificity (cut-off <58 µg/g) for predicting mucosal healing. CONCLUSIONS: Post-infliximab induction FC can be used as a surrogate marker for predicting clinical remission and mucosal healing in refractory UC patients.