Decreased Incidence of Hepatocellular Carcinoma after Directly Acting Antiviral Therapy in Patients with Hepatitis C-Related Advanced Fibrosis and Cirrhosis.

BACKGROUND AND AIM: Existing data are controversial regarding the incidence of hepatitis C (HCV)-related hepatocellular carcinoma (HCC) following directly acting antiviral (DAA) therapy. This prospective study aimed to assess incidence, and risk factorss of HCC following DAA therapy in patients with HCV-related advanced fibrosis (F3) and cirrhosis (F4). METHODS: Incidence of HCC was calculated in 1,630 patients with HCV-related F3 and F4 treated with DAA prospectively followed for up to 43 months in a single tertiary referral center and compared to historical controls. Risk factors of incident HCC were also determined. RESULTS: The crude outcome rate was 2.15/100 person-years, significantly lower than a similar historical cohort (5.57/100 person-years). Risk of developing HCC was higher with the presence of cirrhosis (F4 vs F3, AHR 3.59) and treatment failure (vs achieving SVR, AHR 3.37). Presence of decompensated cirrhosis, platelet count <100×103/mL, and high AFP were independent risk factors of developing HCC. CONCLUSION: Incidence of HCC was significantly lower in patients with HCV-related advanced fibrosis and cirrhosis treated with DAAs than in a historical cohort of untreated patients. Decompensated cirrhosis, baseline AFP ≥10 ng/mL, diabetes, and nonresponse to DAA were independent risk factors of incident HCC.

Clinical Impact of Circulated miR-1291 in Plasma of Patients with Liver Cirrhosis (LC) and Hepatocellular Carcinoma (HCC): Implication on Glypican-3 Expression.

PURPOSE: Liver cirrhosis (LC) is considered to be the end stage of chronic hepatopathies which may lead to hepatocellular carcinoma (HCC). Glypican-3 is one of the most promising serum markers for HCC. Abnormal expression of miRNAs may participate in cancer development and progression. In this study, we aimed to evaluate the relation between the expression of miR-1291 and GPC3 production as a non-invasive tool to differentiate patients with LC and HCC. METHODS: HCV patients (100) were divided into two groups; HCC (I) and LC (II). Fifty hepatitis-free subjects served as the control group (III). Expression of serum GPC3 was performed by enzyme-linked immunosorbent assay, and expression of circulating miR-1291 was performed by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Serum levels of GPC3 were significantly elevated in patients with HCC compared with the LC group. Both groups have increased GPC3 levels in relation to healthy controls. Serum GPC3 levels with a cutoff value of 619.5 pg/ml had a 50% sensitivity and 89.3% specificity while alpha-fetoprotein (AFP) with a cutoff value of 8.5 ng/ml had a higher sensitivity (87.5%) and specificity (100%) in the detection of HCC. The primary use of both markers improved the specificity to 100%. miR-1291 was significantly upregulated in HCC and LC patients compared with control subjects. CONCLUSIONS: Our findings might indicate that miR-1291 exert oncogenic effects in hepatic carcinogenesis through positive regulation of GPC3 expression. We propose that GPC3 overexpression and its associated oncogenic effects are linked to the upregulation of miR-1291 in HCV patients.

Effect of magnesium sulphate on bi-spectral index (BIS) values during general anesthesia in children.

BACKGROUND: Magnesium was reported to reduce both the anesthetic requirements and the period needed to reach a bi-spectral index value of 60 when used intra-operatively (Br J Anaesth 83:302-20, 1999; Anesth Analg 20:1273-5, 1988; Br J Anaesth 89:594-8, 2002; Anesth Analg 87:206-10, 1998; Br J Anaesth 89:594-8, 2002; Br J Anaesth 94:438-41, 2005) and to minimize the emergence agitation (Anaesthesia 61:1058-63, 2006). Previous studies examined the influence of magnesium on the anesthetic requirements while the bi-spectral Index values were kept within a constant range. We evaluated the effect of intraoperative magnesium on the bi-spectral index values during pediatric anesthesia while we kept other anesthetic variables unchanged. METHODS: Eighty pediatric patients with ASA physical status I, age 2-8 years and scheduled for minor infra-umbilical elective procedures included in a prospective randomized controlled study. We randomly divided patients into two groups. Group I (40 patients); received a bolus dose 50 mg/kg of magnesium sulphate followed by an infusion at rate of 15 mg/kg/h throughout the procedure. Group II (40 patients); received the same amount in the form of ringer acetate for blinding. We compared between the groups regarding: 1) BIS values. 2) Hemodynamic parameters. 3) Arterial oxygen saturation 4) End-tidal CO2 5) Respiratory rate and 6) Tidal volume. RESULTS: Magnesium group (Group I) showed significantly lower BIS values and shorter time to achieve BIS values below 60. Respiratory parameters (tidal volume and respiratory rate) were significantly lower in the magnesium group. Otherwise, no significant differences between the study group and the control group were detected. DISCUSSION: Our study has the advantage of evaluating the direct effect of magnesium sulphate on the Bi-spectral index scale with keeping other intraoperative factors almost constant (as the type of operations, induction and maintenance techniques, end-tidal anesthetic concentration, analgesia and mode of ventilation) for accurate assessment. CONCLUSION: Magnesium produced significantly lower BIS values, less time to reach BIS values below 60, lower tidal volume and lower respiratory rate during pediatric general anesthesia. TRIAL REGISTRATION: Pan African Clinical Trial Registry, www.pactr.org , PACTR201312000666231 . Registered at 6 October 2013.