Clinical Significance of Evaluation of Monocytic Receptors in Patients with Hepatitis C Virus Infection.

Monocytes in hepatitis C virus (HCV) infection play a critical role in chronic liver inflammation and fibrosis. We studied circulating monocytes and monocyte receptors in patients with HCV infection who were naive to treatment and those who received direct acting antiviral therapy and achieved sustained virological response. CD64+ CCR2+ (M1-like) and CD206+ CD163+ CX3CR1+ (M2-like) monocyte numbers and receptor expression were evaluated by flow cytometry. Higher expression of the monocyte chemokine receptor CCR2 predicted the severity of liver fibrosis, independent of successful treatment and viral clearance (R2 = 0.235, p = 0.002), whereas monocyte CX3CR1 expression was lower in both treated and untreated patients compared with controls (p = 0.011). The expression of the scavenger receptor CD163 was lower in patients with successful treatment (p = 0.005), supporting its role as a marker of treatment response. CD64+ CCR2+ (M1-like) and CD206+ CD163+ CX3CR1+ (M2-like) monocyte numbers were not altered with fibrosis progression or treatment response. Our findings reflect the diverse functions of monocytes in liver inflammation, fibrosis, and therapy. However, HCV clearance did not lead to complete monocyte reconstitution. Targeting monocytes and their chemokine receptors bears therapeutic potential to reduce liver fibrosis and improve disease outcome.

Schistosoma mansoni infection and the occurrence, characteristics, and survival of patients with hepatocellular carcinoma: an observational study over a decade.

Schistosoma mansoni infection (SMI) is suspected to be directly and indirectly involved in hepato-carcinogenesis. This study evaluated the association of a previous SMI with hepatocellular carcinoma (HCC) development, patients, tumor characteristics, treatment outcomes, and survival. This observational study included patients with HCC with and without previous SMI who presented to the multidisciplinary HCC clinic, Kasr-Alainy hospital (November 2009 to December 2019). It also included 313 patients with liver cirrhosis without HCC. Clinical and laboratory features of the patients (complete blood count, liver/renal functions , alpha-fetoprotein, and hepatitis B/C status), tumor characteristics (Triphasic CT and/or dynamic MRI), liver stiffness (transient elastography), HCC treatment outcome, and overall survival were studied. This study included 1446 patients with HCC; 688(47.6%) composed group-1, defined by patients having a history of SMI, and 758(52.4%) were in group-2 and without history of SMI. Male sex, smoking, diabetes mellitus, splenomegaly, deteriorated performance status, synthetic liver functions, and platelet count were significantly higher in group-1. The groups did not differ with regard to liver stiffness, tumor characteristics, or the occurrence of post-HCC treatment hepatic decompensation or recurrence. HCC treatment response was better in group-2. Group-1 showed lower sustained virological response to hepatitis C direct-acting antivirals (DAAs) compared with group-2 (60% versus 84.3%, respectively, P = 0.027). Prior SMI was associated with HCC (adjusted odds ratio = 1.589, 95% confidence interval = 1.187-2.127), and it was concluded that it increases the risk of HCC. In addition, it significantly affects the performance status, laboratory characteristics, response to DAAs, and overall survival.

Circulating microRNAs (miR-21, miR-223, miR-885-5p) along the clinical spectrum of HCV-related chronic liver disease in Egyptian patients.

BACKGROUND AND STUDY AIMS: MicroRNAs (miRNAs), small single stranded RNAs, function in the post-transcriptional regulation of gene expression and incorporated in pathogenesis of HCV related chronic liver disease. This study was designed to evaluate the significance of serum miR-21, miR-223, and miR-885-5p as biomarkers in various clinicopathological stages of HCV related chronic liver disease. PATIENTS AND METHODS: Serum miR-21, miR-223, and miR-885-5p were quantified by quantitative RT PCR in 60 patients with HCV-related liver disease (presumably genotype 4), in addition to 25 healthy controls. HCV patients were classified into: chronic non-cirrhotic HCV (n = 15), HCV related liver cirrhosis (n = 15), and hepatocellular carcinoma (HCC) (n = 30). RESULTS: Serum levels of miR-885-5p in cirrhotic patients ± HCC (n = 45) were significantly higher than the non-cirrhotic patients (n = 15); p = 0.007 and healthy control; p = 0.001. However, no such significance was detected between HCC and non-HCC HCV patients; p = 0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis; AUC 0.85, 87% sensitivity and 80% specificity. On the other hand, HCC patients had significantly higher serum miR-2 1evels than non-HCC patients (non-cirrhotic and cirrhotic groups, n = 30); p = 0.048 and the control group; p = 0.002. ROC could differentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specificity. Both serum bilirubin and albumin showed significant weak correlation with miRNA-885-5p (r = 0.42, p = 0.001) and (r = -0.27, p = 0.04), respectively but no such correlation was observed with serum miRNA-21. In contrast, miRNA-223 showed no significant difference across the studied groups. CONCLUSION: Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

Disease progression from chronic hepatitis C to cirrhosis and hepatocellular carcinoma is associated with increasing DNA promoter methylation.

BACKGROUND: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. MATERIALS AND METHODS: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. RESULTS: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%) , respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. CONCLUSIONS: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.