Association of Sat-a and Alu methylation status with HCV-induced chronic liver disease and hepatocellular carcinoma.

BACKGROUND: The combination of epigenetic and genetic abnormalities contributes together to the development of liver cancer. The methylation status of the repetitive elements (REs) in DNA has been investigated in a variety of human illnesses. However, the methylation patterns of Sat-α and Alu REs in chronic liver disease (CLD) and hepatocellular carcinoma (HCC) caused by hepatitis C virus (HCV) have never been studied before. METHODOLOGY: In this study, 3 groups of participants including 50 patients having HCV-induced CLD, 50 patients having HCV-induced HCC, and 46 healthy subjects were subjected to measurement of Sat-α and Alu methylation using the quantitative MethyLight assay. RESULTS: Sat-α and Alu methylation percentages decreased significantly in both CLD and HCC, compared to control. Also, a significant Sat-α hypomethylation was detected in HCC, compared to CLD. In addition, Sat-α and Alu methylation showed a significant decline as lesion size grew. However, only Sat-α hypomethylation was significantly increased in association with portal vein thrombosis and the MELD score. Sat-α methylation percentage had the highest sensitivity and specificity for diagnosing HCC (100% and 84.4%) followed by α-fetoprotein (80% and 84.4%) and Alu methylation (66% and 61.5%). Furthermore, there was a strong positive correlation between Sat-α and Alu methylation. CONCLUSIONS: Measuring Sat-α and Alu methylation provides us with a new tool for early detecting HCV-induced CLD and hepatocarcinogenesis. Sat-α has the potential to be utilized as an independent predictive parameter for HCC development and progression because of its ability to distinguish between CLD and HCC with their different MELD scores.

Expression of miRNAs-122, -192 and -499 in end stage renal disease associated with acute myocardial infarction.

INTRODUCTION: New diagnostic tools are needed to accurately detect acute myocardial infarction (AMI) in patients with end stage renal disease (ESRD) presenting with ischemic chest pain. We aimed in this study to investigate circulating miR-122, -192 and -499 expression levels in patients with AMI on top of ESRD and evaluate the potential of these miRNAs as blood-based biomarkers for AMI in patients with ESRD. MATERIAL AND METHODS: The study included 80 ESRD patients without AMI, 80 patients with ESRD associated with AMI and 60 healthy subjects. Assessment of microRNAs was done using SYBR Green based real-time PCR. RESULTS: Levels of miR-122 were 28-fold and 20-fold higher in controls than in ESRD patients with or without AMI respectively (p < 0.001), while no differences were detected between the two patient groups (p = 0.9). Levels of miR-192 showed a marked increase in ESRD patients with and without AMI compared to the control group (> 500-fold, > 8000-fold respectively, p ≤ 0.001). Patients who developed AMI had lower expression than ESRD patients without AMI (p < 0.001). Non-significant miR-499 elevation was found in ESRD patients without cardiac disease compared to the control group, while highly significant elevation of miR- 499 was demonstrated in ESRD patients who developed AMI compared to other ESRD patients and the control group (> 100-fold, > 350-fold respectively, p = 0.001). CONCLUSIONS: Altered expression of miR-122 and -192 may contribute in pathogenesis of ESRD. MiR-192 and -499 may serve as potential biomarkers for AMI in ESRD. Further studies are needed to correlate these miRNAs with disease progression and outcome.

A significant upsurge of body mass index in patients with chronic hepatitis C successfully treated with direct-acting antiviral regimens.

BACKGROUND/AIMS: There is less data regarding the changes in body mass index (BMI) after treating hepatitis C virus (HCV) patients with new direct-acting antiviral agents (DAAs). This study aimed to assess the changes in BMI in chronic HCV patients treated with DAAs in Egypt and to explore other factors influencing this change. MATERIALS AND METHODS: The data of chronic HCV patients who received antiviral therapy with new DAAs in one of Egypt's specialized viral hepatitis treatment centers were retrospectively analyzed. In addition to the routine clinical and laboratory workup, changes in body weight during and after treatment were monitored and BMI was calculated. Viral load was measured at 12 weeks post-treatment to assess a sustained virological response. Patients with documented thyroid abnormalities, bariatric surgery, or ensuing special diets were excluded. BMI of >30 was taken as the cutoff for pa¬tients with obesity. RESULTS: The study included 162 patients with a mean age of 48.56±11.49 years, of whom 61.1% were males, 16% were treatment-experienced, 12% were diabetic, and 29% were obese. Treatment duration was 12 weeks in 84% of patients and 24 weeks in 16% of patients. There was a significant increase in BMI post-treatment as compared to pretreatment measures (28.68±5.35 vs 28.18±4.55) (p=0.03). BMI changes were constant regardless of cirrhosis or previous treatment experience. CONCLUSION: Treatment of chronic HCV with DAAs was associated with increased body mass index. Further studies are needed to explore if this effect is secondary to treatment with DAAs or is an improvement in the liver function and lifestyle of treated patients.

Impact of treating chronic hepatitis C infection with direct-acting antivirals on the risk of hepatocellular carcinoma: The debate continues - A mini-review.

Hepatitis C virus clearance is expected in more than 95% of patients treated with direct-acting antivirals (DAAs). However, an extensive debate about the impact of DAAs on the development of hepatocellular carcinoma (HCC) is currently ongoing. This review aimed to explore currently available evidence about the relationship between DAAs and HCC development. The American studies and some European studies clearly showed no relation, while the Japanese and Egyptian studies and the other European studies showed an increased risk of developing HCC after DAA exposure. These conflicting results may be due to geographical and ethnic variations and differences in the design and inclusion criteria among the studies. After reviewing the data from these different studies, it seems that some patients are at increased risk of developing HCC after DAA exposure. Identifying those at increased risk is very important for the management of HCC in light of the potentially major consequences of HCC for the patients' quality of life and the subsequent major burden imposed on healthcare resources.

Real-world results of direct-acting antivirals use for the treatment of chronic hepatitis C in old patients.

BACKGROUND AND AIM: Old people with chronic hepatitis C (HCV) were considered a difficult-to-treat category with more frequent adverse events until recently. Interferon-free direct-acting antivirals (DAAs) improved treatment adherence and quality of life of old patients. In this study, we aimed at reporting the real-world efficacy and safety of DAAs, in addition to predictors of sustained virological response (SVR) in old chronic HCV population. METHODS: This is a prospective observational intention-to-treat analysis that included old chronic hepatitis C genotype-4 patients (> 65 years) treated in a single specialized viral hepatitis treatment center in Egypt. Treatment regimens were allocated according to national guidelines for treatment of hepatitis C. Primary outcome was undetectable HCV-RNA at 12-week post-treatment by PCR. Secondary outcomes were identification of predictors of SVR and assessment of safety related issues. RESULTS: Our study included 864 patients (64% females) with mean age of 67.7 ± 2.8 years. Overall SVR rate was 98.9% while SVR rates for sofosbuvir/daclatasvir/ribavirin, paritaprevir/ombitasvir/ritonavir/ribavirin, sofosbuvir/daclatasvir, sofosbuvir/ledipasvir/ribavirin, sofosbuvir/simeprevir/daclatasvir/ribavirin, sofosbuvir/simeprevir, interferon/sofosbuvir/ribavirin and sofosbuvir/ribavirin were 100%, 100%, 100%, 100%, 100%, 99.3%, 98% and 94.2%, respectively. DAAs were well tolerated. None of the patients discontinued the treatment due to adverse effects. Higher albumin, higher platelet count, lower bilirubin and lower stage of fibrosis were among predictors of favourable response. CONCLUSION: Different DAAs regimens were safe and effective in old Egyptian patients with chronic HCV.

Spontaneous Viral Load Decline and Subsequent Clearance of Chronic Hepatitis C Virus in Postpartum Women Correlates With Favorable Interleukin-28B Gene Allele.

BACKGROUND: Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women. METHODS: Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-months apart. Associations between viral load and demographic, obstetrical, HCV risk factors, and interleukin-28B gene (IL28B) polymorphism (rs12979860) were assessed. RESULTS: Of 2514 women, 97 (3.9%) had anti-HCV antibodies, 54 (2.1%) were viremic and of those, 52 (2.1%) agreed to IL28B testing. From pregnancy until 12 months postpartum, IL28B-CC allele women had a significant viral decline (P = .009). After adjusting, the IL28B-CC allele had a near significant difference compared to the CT allele (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.75,1.00; P = .05), but not the TT allele (OR, 0.91; 95% CI, 0.61,1.38; P = .64). All 14/52 (26.9%) women who subsequently cleared were among the 15 with undetectable viremia at 12 months, making that time point a strong predictor of subsequent clearance (sensitivity = 100%, specificity = 97.4%, positive predictive value = 93.3%, negative predictive value = 100%). CONCLUSIONS: IL28B-CC genotype and 12-month postpartum undetectable viremia were the best predictors for viral decline and subsequent clearance. These 2 predictors should influence clinical decision making.

Prevalence of human papilloma virus (HPV) and its genotypes in cervical specimens of Egyptian women by linear array HPV genotyping test.

BACKGROUND: The association of human papillomavirus (HPV) with cervical cancer is well established. AIM: To investigate HPV genotype distribution and co-infection occurrence in cervical specimens from a group of Egyptian women. METHODS: A group of 152 women with and without cervical lesions were studied. All women had cervical cytology and HPV testing. They were classified according to cytology into those with normal cytology, with squamous intraepithelial lesions (SIL) and invasive squamous cell carcinoma (SCC). Cervical samples were analyzed to identify the presence of HPV by PCR, and all positive HPV-DNA samples underwent viral genotype analysis by means of LINEAR ARRAY HPV Genotyping assay. RESULTS: A total of 26 HPV types with a prevalence of 40.8 % were detected. This prevalence was distributed as follows: 17.7 % among cytologically normal females, 56.5, 3.2, and 22.6 % among those with LSIL, HSIL and invasive SCC respectively. Low-risk HPV types were detected in 81.8 % of the cytologically-normal women, in 5.7 % of those in LSIL women, and in 14.3 % of infections with invasive SCC, while no low-risk types were detected in HSIL. High-risk HPV types were detected in 18.2 % of infections in the cytologically normal women, 14.3 % of infections in LSIL, and in 21.4 % of invasive lesions. The probable and possible carcinogenic HPV were not detected as single infections. Mixed infection was present in 80 % of women with LSIL, in 100 % of those with HSIL, and in 64.3 % of those with invasive SCC. This difference was statistically significant. HPV 16, 18 and 31 were the most prevalent HR HPV types, constituting 41.9, 29.03 and 12.9 % respectively, and HPV 6, 62 and CP6108 were the most prevalent LR HPV types constituting 11.3, 9.7 and 9.7 % respectively. CONCLUSION: These data expand the knowledge concerning HPV prevalence and type distribution in Egypt which may help to create a national HPV prevention program. HPV testing using the LINEAR ARRAY HPV Genotyping assay is a useful tool when combined with cytology in the diagnosis of mixed and non-conventional HPV viral types.

Hepatitis C Virus (HCV) Vertical Transmission in 12-Month-Old Infants Born to HCV-Infected Women and Assessment of Maternal Risk Factors.

Background. Hepatitis C virus (HCV) is an underappreciated cause of pediatric liver disease, most frequently acquired by vertical transmission (VT). Current guidelines that include the option of screening infants for HCV RNA at 1-2 months are based on data prior to current real-time polymerase chain reaction (PCR)-based testing. Previous studies have demonstrated VT rates of 4%-15% and an association with high maternal viral load. We evaluated HCV RNA in infants with HCV VT and assessed maternal risk factors in a prospective cohort in Cairo, Egypt. Methods. Pregnant women were screened for HCV from December 2012 to March 2014. For those with HCV viremia, their infants were tested at 12 months for HCV RNA using real-time PCR. Maternal risk factors assessed for HCV VT association included HCV RNA levels, mode of delivery, and maternal IL28B genotype. Results. Of 2514 women screened, a total of 54 women were viremic (2.1%) and delivered 56 infants. Of those, 51 infants of 49 women were tested at 12 months of age. Only 7 infants were viremic, with an HCV VT rate of 14.3% (7 of 49). Median HCV RNA in the infants was 2100 IU/mL. None of the maternal risk factors analyzed were associated with transmission. Conclusions. In Egypt where HCV is highly endemic, we observed an overall 12-month HCV VT rate of 14.3%. Further studies should focus on better identification of pregnant women more likely to vertically transmit HCV and earlier testing of infants to identify those likely to develop chronicity.

Reliability of risk-based screening for hepatitis C virus infection among pregnant women in Egypt.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) only recommends risk-based HCV screening for pregnant women in the United States. This study sought to determine the reliability of risk-based versus universal HCV screening for pregnant women in Egypt, a country with the world's highest HCV prevalence that also relies on risk-based screening, and to identify additional characteristics that could increase the reliability of risk-based screening. METHODS: Pregnant women attending the Cairo University antenatal clinic were tested for anti-HCV antibodies and RNA, and demographic characteristics and risk factors for infection were assessed. RESULTS: All 1250 pregnant women approached agreed to participate (100%) with a mean age of 27.4 ± 5.5 years (range:16-45). HCV antibodies and RNA were positive in 52 (4.2%) and 30 (2.4%) women respectively. After adjustment, only age (OR:1.08, 95%CI:1.002-1.16, p < 0.01), history of prior pregnancies (OR:1.20, 95%CI:1.01-1.43, p < 0.04), and working in the healthcare sector (OR:8.68, 95%CI:1.72-43.62, p < 0.01), remained significantly associated with chronic HCV infection. CONCLUSIONS: Universal antenatal HCV screening was widely accepted (100%) and traditional risk-based screening alone would have missed 3 (10%) chronically infected women, thereby supporting universal screening of pregnant women whenever possible. Otherwise, risk-based screening should be modified to include history of prior pregnancy and healthcare employment.