Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta‐analysis

Background

Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta‐analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV‐infected patients would be helpful.

Methods

Chronic HBV infection was defined as the persistence of HBsAg for more than 6 months. To gather sufficient data for this meta‐analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study.

Results

This meta‐analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10^–6, odds ratio (OR) = 2.85], dominant (p = 4.35 × 10^‐6, OR = 1.84), co‐dominant (p = 6.18 × 10^‐8; OR = 3.74) and allelic (p = 9.79 × 10^‐9; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co‐dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models.

Conclusions

Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen.     

Characterization of benthic microhabitat: An experimental system for aquatic insects

An experimental system used to determine microhabitat current velocity and microhabitat selection by aquatic insects is described. The experimental system includes a microvelocity probe and a hydraulically calibrated artificial substrate. A thermistor velocity probe detects flow velocities to 0.5 m s^–1 near the surface of substrates at locations inhabited by aquatic insects. The artificial substrate was designed to provide two major habitat types, highly turbulent vortex areas and regions with unidirectional, near laminar flow. Substrate calibration and microhabitat characteristics of the substrates are demonstrated. Experimental studies of Simulium sp. location on substrates indicated that while simuliid larvae are characteristic of lotic, erosional habitats, actual microhabitats selected are governed by substantially lower flow velocity.     

Gender differences in healthy ranges for serum alanine aminotransferase levels in adolescence

Background & Aims

There is a worldwide epidemic of obesity among adolescents who subsequently are at increased risk for the development of non alcoholic fatty liver disease (NAFLD). The serum alanine aminotransferase (ALT) is the most frequently used test for screening these individuals, but no age and gender-specific upper limits of normal (ULN) based on healthy population data in children are available. The objective of the present study was to define ULN for ALT in healthy children in order to use this as a tool for case finding.

Methods

A total of 975 school children (aged 7–18 years) were included in the study cohort. Highly significant correlations (all p<0.001) were noted between ALT values and measures of BMI, systolic and diastolic blood pressure, insulin levels, HOMA-IR, total cholesterol and triglyceride concentrations. In order to define the population with no risk factors, we excluded subjects having abnormal values for factors that correlated with ALT. This population comprised 186 boys and 185 girls.

Results

In boys, median serum ALT levels were 16 IU/L and 9, 11, 18, and 30 IU/L for the 5th, 25th, 75th, and 95th percentiles. In girls, median serum ALT was 13, and 7, 9, 16, and 21 IU/L for the 5th, 25th, 75th, and 95th percentiles, respectively. The ULNs for ALT were 30 IU/L and 21 IU/L for boys and girls respectively. We found a linear relationship between age and ALT in females (p<0.001) but not in males. By multiple logistic regression, independent predictors of an elevated ALT included the BMI, waist hip ratio and levels of serum total cholesterol. In females, age was an additional inverse predictor.

Conclusions

In children and adolescents, these normal limits for ALT should be applied. Those with persistent elevations should be investigated further.     

Evaluation of miR-122 level in the plasma of chronically HCV infected patients

MicroRNAs (miRNAs) are small non-coding RNA molecules, which have an important function in regulating RNA stability and gene expression. They also can circulate in a cell-free form in the blood thatmakes them potential disease markers. The liver contains various classes of miRNAs in which miR-122 accounts for about 70% of all miRNAs and it has been proved that its level increases in case of liver damage. Here, we investigated plasma levels of miR-122 as a useful disease parameter in patients with chronic hepatitis C (CHC) infection. Thirty five hemophilia and thalassemia patients with CHC were studied. The total RNA was extracted from plasma samples, and miR-122 levels were measured by qPCR and then compared with the specific liver markers. The plasma levels of alanine transaminase (ALT) and aspartate transaminase(AST) were correlated with plasma miR-122 level in CHC patients, and the level of circulating miR-122 in healthy individual groups were rarely lower than those of patients with CHC. In our study, miR-122 levels correlated well with markers of liver inflammatory activity. Plasma miR-122 can be assumed to be another marker in liver similar to the currently used specific markers such as ALT and AST for evaluation of liver damage in hepatitis C virus (HCV) infected patients. Moreover, the correlation between miR-122 and ALT was shown to be higher than between miR-122 and AST.     

Prevalence and determinants of diabetes mellitus among Iranian patients with chronic liver disease

BACKGROUND: Alterations in carbohydrate metabolism are frequently observed in cirrhosis. We conducted this study to define the prevalence of diabetes mellitus (DM) and impaired glucose tolerance (IGT) in Iranian patients with chronic liver disease (CLD), and explore the factors associated with DM in these patients. METHODS: One hundred and eighty-five patients with CLD were enrolled into the study. Fasting plasma glucose and two-hour plasma glucose were measured in patients' sera. DM and IGT were diagnosed according to the latest American Diabetes Association criteria. RESULTS: The subjects included 42 inactive HBV carriers with a mean age of 42.2 +/- 12.0 years, 102 patients with HBV or HCV chronic hepatitis with a mean age of 41.2 +/- 10.9 years, and 41 cirrhotic patients with a mean age of 52.1 +/- 11.4 years. DM and IGT were diagnosed in 40 (21.6%) and 21 (11.4%) patients, respectively. Univariate analysis showed that age (P = 0.000), CLD status (P = 0.000), history of hypertension (P = 0.007), family history of DM (P = 0.000), and body mass index (BMI) (P = 0.009) were associated with DM. Using Multivariate analysis, age (OR = 4.7, 95%CI: 1.8-12.2), family history of DM (OR = 6.6, 95%CI: 2.6-17.6), chronic hepatitis (OR = 11.6, 95%CI: 2.9-45.4), and cirrhosis (OR = 6.5, 95%CI: 2.4-17.4) remained as the factors independently associated with DM. When patients with cirrhosis and chronic hepatitis were analyzed separately, higher Child-Pugh's score in cirrhotic patients (OR = 9.6, 95%CI: 1.0-88.4) and older age (OR = 7.2, 95%CI: 1.0-49.1), higher fibrosis score (OR = 59.5, 95%CI: 2.9-1211.3/ OR = 11.9, 95%CI: 1.0-132.2), and higher BMI (OR = 30.3, 95%CI: 3.0-306.7) in patients with chronic hepatitis were found to be associated with higher prevalence of DM. CONCLUSIONS: Our findings indicate that patients with cirrhosis and chronic hepatitis are at the increased risk of DM occurrence. Older age, severe liver disease, and obesity were associated with DM in these patients.     

A New Combination: Anti Glypican-3 scFv and Diphtheria Toxin with the Best Flexible Linker

The Protein Journal - Along with all cancer treatments, including chemotherapy, radiotherapy, and surgery, targeting therapy is a new treatment manner. Immunotoxins are new recombinant structures...