A Meta-Analysis of the Association Between the I148M Variant of Patatin-Like Phospholipase Domain Containing 3 Gene and the Presence of Chronic Hepatitis C

Context:

The objective of the current study was to evaluate the association between the I148M variant of patatin-like phospholipase domain-containing protein 3 (PNPLA3) and the presence of Chronic Hepatitis C (CHC) across different populations.

Evidence Acquisition:

This study was a meta-analysis of all relevant researches published in the literature from year 2000 to 2015. The odds ratios (ORs) of PNPLA3 allele distributions in CHC patients were analyzed and compared with healthy controls. The meta-analysis Revman 5.2 software was applied for investigating heterogeneity among individual studies and for summarizing all the studies. The meta-analysis was carried out according to the Cochrane Reviewers’ Handbook recommendations. A total of 120 clinical trials or reports were retrieved, yet only five trials met the study selection criteria.

Results:

Five hospital-based case-control studies were included in the final analysis. The overall frequency of PNPLA3 gene polymorphisms was 20.4% (205/1005) in CHC and 10.23% (53/518) in controls. The summary odds ratio for the association of gene polymorphisms of PNPLA3 with the risk for CHC was determined as 2.20 (95% CI: 1.56 -3.11) and was statistically significant (P < 0.05).

Conclusions:

The current meta-analysis showed an association between frequency of GG genotype of PNPLA3 and the risk of development of CHC in various populations throughout the world.     

Association of Adiponectin rs1501299 and rs266729 Gene Polymorphisms With Nonalcoholic Fatty Liver Disease

Background

Genetic and environmental factors are important for the development of nonalcoholic fatty liver disease (NAFLD). Adiponectin is a white and brown adipose tissue hormone, and have been found to play essential roles in the regulation of energy homoeostasis. Recent reports have identified a possible role of adiponectin in NAFLD via PPARγ pathway.

Objectives

The present study was designed to find out the impact of adiponectin rs1501299 (276G/T) and rs266729 (-11377C/G) gene polymorphisms in NAFLD.

Patients and Methods

Eighty-three patients with diagnosis of NAFLD, and 93 healthy subjects were included in the study. Tetra ARMS-PCR was designed to detect single nucleotide polymorphisms.

Results

A significant difference was found between NAFLD and control group regarding the rs266729 polymorphism (χ2 = 7.35, P = 0.025). The rs266729 polymorphism increased the risk of NAFLD in codominant (CC vs. CG: OR = 2.18, 95% CI = 1.16 - 4.12, P = 0.016) and dominant (CC vs. CG/GG: OR = 2.31, 95% CI = 1.25 - 4.27; P = 0.008) inheritance tested models. The G allele increased the risk of NAFLD (OR = 1.63, 95% CI = 1.03 - 2.57, P = 0.037) in comparison with C allele. No significant difference was found between the groups concerning adiponectin rs1501299 gene polymorphism (χ2 = 0.70, P = 0.697).

Conclusions

adiponectin rs266729 polymorphism might be a candidate gene, which determines the susceptibility to NAFLD. Larger studies are necessary to confirm these findings in various populations.     

Association of Tumor Necrosis Factor-alpha Polymorphisms and Risk of Coronary Artery Disease in Patients With Non-alcoholic Fatty Liver Disease

Background:

Cardiovascular events account for the main cause of death in patients with non-alcoholic fatty liver disease (NAFLD), and are largely influenced by genetic factors. Although multiple studies showed that tumor necrosis factor-alpha (TNF-α) polymorphisms are risk factors in the progression of NAFLD, few papers on the association of the polymorphisms and the developing coronary artery disease (CAD) in NAFLD patients have been reported.

Objectives:

The present study was designed to evaluate the association of TNF-α polymorphisms at residues -238 and -308, with the risk of developing CAD in Chinese patients with NAFLD.

Patients and Methods:

The TNF-α polymorphisms at residues 238 and 308 were genotyped in B-type ultrasonography proven NAFLD patients with (n = 246), without (n = 247) CAD and healthy controls (n = 304), using polymerase chain reaction (PCR). Serum lipid profiles were determined using biochemical methods. Statistical analyses were performed using SPSS statistical software, version 20.0 for Mac.

Results:

We found a significant association between TNF-α-238 guanine to alanine (GA) polymorphism and carriers of variant allele A between NAFLD patients with and without CAD (P < 0.05). Carriers of the A allele of TNF-α-238 had higher serum triglycerides (TG) and low density lipoprotein (LDL) levels in NAFLD patients with CAD (P = 0.025 and 0.001, respectively) and a higher TG level in NAFLD patients without CAD (P = 0.017), than their non-carrier counterparts.

Conclusions:

In the Chinese Han population that we studied, NAFLD patients who carry the TNF-α-238 GA polymorphism have an increased risk of developing CAD. Mechanisms underlying this potentially important association require further investigation.     

Association Between LYPLAL1 rs12137855 Polymorphism With Ultrasound-Defined Non-Alcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Recent genome-wide association studies (GWAS) identified that gene Lysophospholipase-like 1 (LYPLAL1) rs12137855 associated with non-alcoholic fatty liver disease (NAFLD). No research has been performed regarding the association between LYPLAL1 and NAFLD in China.

Objectives:

The aim of the present study was to investigate the association between the gene LYPLAL1 rs12137855 and NAFLD, and the effect on serum lipid profiles in a Chinese Han population.

Patients and Methods:

LYPLAL1 rs12137855 gene was genotyped in 184 patients with NAFLD and 114 healthy controls using sequencing and polymerase chain reaction analysis (PCR). We tested serum lipid profiles using biochemical methods.

Results:

No significant differences in genotype and allele frequencies of LYPLAL1 rs12137855 was found between the NAFLD group and the controls group (P > 0.05). Subjects with the variant LYPLAL1 rs12137855 CC genotype had a higher mean weight, body mass index (BMI) and low density lipoprotein (LDL).

Conclusions:

Our results showed for the first time that LYPLAL1 gene is not associated with a risk of NAFLD development in the Chinese Han population. The variant carriers of overall subjects significantly increased weight, BMI and LDL.     

Are Women With Polycystic Ovarian Syndrome at a High Risk of Non-Alcoholic Fatty Liver Disease; A Meta-Analysis

Context:

Insulin resistance is a hallmark of metabolic syndrome (MS). It has been proposed that both polycystic ovarian syndrome (PCOS) and nonalcoholic fatty liver disease (NAFLD) are correlated with Insulin resistance. Therefore, PCOS and NAFLD can be attributed with insulin resistance and therefore MS. The aim of this meta-analysis was to determine whether PCOS patients are at a high risk of NAFLD.

Evidence Acquisition:

Google scholar, Scopus, ISI Web of Science, Embase, MEDLINE, and some Iranian databases such as scientific information database (SID), IranMedex, and MagIran were searched to identify relevant studies. We included all papers regardless of their language from January 1985 to June 2013. By using data on prevalence of NAFLD in patients with and without PCOS, odds ratio (OR) with 95% confidence intervals (CIs) were calculated in each study. Chi-squared test was used to assess heterogeneity between studies.

Results:

We finally included seven eligible studies. According to chi-squared test, there was a significant heterogeneity (73.6%) between studies (P = 0.001). NAFLD prevalence was significantly higher in patients with PCOS compared to healthy control, with an overall OR of 3.93 (95% CI: 2.17, 7.11).There was no significant publication bias based on Begg''s and Egger''s tests.

Conclusions:

According to the results of this meta-analysis, there was a high risk of NAFLD in women with PCOS. We suggest evaluating patients with PCOS regarding NAFLD.     

A meta-analysis of antibiotic use for the secondary prevention of cardiovascular diseases

BACKGROUND:

A number of clinical trials have examined whether antibiotics decrease the incidence of adverse events in patients with cardiovascular diseases. However, results have occasionally been conflicting, and a meta-analysis may provide additional clarification.

OBJECTIVE:

To address whether antibiotic use can reduce the risk of future cardiac events among patients with established cardiovascular diseases.

METHODS:

PubMed and the Cochrane Central Register of Controlled Trials were searched using the key words “antibiotic” and “cardiovascular diseases”. Only randomized, placebo-controlled trials of patients with established cardiovascular disease and reporting cardiovascular outcomes were included. A random effects model was used and a fixed model was applied for sensitivity analysis.

RESULTS:

A total of 393 papers published between January 1, 1994, and April 31, 2006, were initially identified. Thirteen trials (12,491 patients in the treatment group and 12,518 patients in the control group) were retained and included in the present meta-analysis. The pooled RR for the composite event end point, including death, myocardial infarction admission and unplanned revascularization procedures, was 0.96 (95% CI 0.90 to 1.04). No associations were seen for the individual outcomes of mortality (RR 1.07, 95% CI 0.96 to 1.19) or myocardial infarction/unstable angina (RR 0.96, 95% CI 0.85 to 1.07). Subgroup analyses based on patient populations (stable or unstable), type of antibiotics, or restricted to those with immunoglobulin G Chlamydia pneumoniae antibodies were also negative for a beneficial treatment effect. Similar results were found using a fixed effects model.

CONCLUSIONS:

The meta-analysis did not provide evidence of an association between antibiotic use and the secondary prevention of cardiac events. Further research in this area does not appear to be promising.     

Impact of the IL-10 Promoter Gene Polymorphisms in the Severity of Chronic Hepatitis B Infection

Background:

Interleukin-10 (IL-10) is an important anti-inflammatory cytokine. The polymorphisms of its promoter gene have been considered to be related with the chronicity of hepatitis B infection.

Objectives:

The aim of this study was to evaluate the polymorphisms at different positions in the IL-10 promoter gene in patients with chronic hepatitis B.

Patients and Methods:

Totally, 166 patients with chronic hepatitis B infection were enrolled. Genotypes at different positions (i.e. -819, - 592, and - 1082) in the IL-10 gene promoter were determined.

Results:

The C/A genotype at position -592, C/T genotype at position -819, and GCC/ATA haplotype of the IL-10 gene promoter were significantly more common in the patients with cirrhosis. The genotypes were significantly different between the hepatitis B e antigen (HBeAg)-negative and HBeAg-positive patients at position -592 (C/A and C/C), position -819 (C/C and C/T), and position -1082 (A/A and G/A).

Conclusions:

Some IL-10 promoter gene polymorphisms predisposed the infected hepatitis B virus cases to cirrhosis in our study population.     

Efficacy of Hepatoprotective Agents With or Without Antiviral Drugs on Liver Function and Fibrosis in Patients With Hepatitis B: A Meta-Analysis

Context:

To systematically evaluate the effects of hepatoprotective agents, when delivered either alone or in combination with other antiviral or non-antiviral drugs in patients with hepatitis B and hepatic fibrosis.

Objectives:

The current randomized controlled clinical trials aimed to evaluate the efficacy of combinations of antiviral and non-antiviral hepatoprotective agents on indexes of liver function and liver fibrosis in patients with hepatitis B.

Data Sources:

Published literatures in Chinese and English on hepatoprotective treatment strategies for chronic hepatitis B and liver fibrosis were searched in three databases and randomized controlled clinical trials were selected.

Study Selection:

Data were extracted according to a variety of inclusion and exclusion criteria. Meta-analysis was employed to analyze the data.

Results:

A total of 22 randomized controlled trials encompassing 1,714 cases were considered in the meta-analysis. The obtained results indicated that the combination of antiviral drug and hepatoprotective agent was better than antiviral drug alone to improve liver function. Similarly, regarding liver fibrosis, using two different hepatoprotective agents was better than using one agent. The normalization rates of Aminotransferase (ALT) and total Bilirubin (TBil) were improved 25.7% by two hepatoprotective agents compared to the single agent. Acetylcysteine was superior to ursodeoxycholic acid or silibinin to reduce ALT. Ursodeoxycholic acid was superior to acetylcysteine or silibinin to reduce TBIL.

Conclusions:

Hepatoprotective agents combined with antiviral drugs can significantly improve liver function and liver fibrosis parameters in patients with hepatitis B.     

Probiotics as a Novel Treatment for Non-Alcoholic Fatty Liver Disease; A Systematic Review on the Current Evidences

Context

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease, with 5-10% of liver having extra fat. Increase in its prevalence in all age groups is linked with obesity and Type II diabetes. The treatment of NAFLD remains controversial. A growing body of evidence suggests a relation between overgrowth of gut microbiota with NAFLD and non-alcoholic steatohepatitis (NASH). The objective of this review is to provide an overview on experimental and clinical studies assessing all positive and negative effects of probiotics.

Evidence Acquisition

We made a critical appraisal on various types of documents published from 1999 to March 2012 in journals, electronic books, seminars, and symposium contexts including Medline, PubMed, and Cochrane Central Register of Controlled Trials databases. We used the key words: “non-alcoholic fatty liver disease, probiotics, non-alcoholic steatohepatitis, liver disease, and fatty liver”.

Results

Probiotics, as biological factors, control the gut microbiota and result in its progression. It is in this sense that they are suggestive of a new and a natural way of promoting liver function. Correspondingly, limited evidence suggests that probiotics could be considered as a new way of treatment for NAFLD.

Conclusions

Various experimental studies and clinical trials revealed promising effects of probiotics in improving NAFLD; however given the limited experience in this field, generalization of probiotics as treatment of NAFLD needs substantiation through more trials with a larger sample sizes and with longer-term follow up.     

Nonalcoholic Fatty Liver Disease/Non-Alcoholic Steatohepatitis in Childhood: Endocrine-Metabolic “Mal-Programming”

Context:

Nonalcoholic Fatty Liver Disease (NAFLD) is the major chronic liver disease in the pediatric population. NAFLD includes a broad spectrum of abnormalities (inflammation, fibrosis and cirrhosis), ranging from accumulation of fat (also known as steatosis) towards non-alcoholic steatohepatitis (NASH). The development of NAFLD in children is significantly increased.

Evidence Acquisition:

A literature search of electronic databases was undertaken for the major studies published from 1998 to today. The databases searched were: PubMed, EMBASE, Orphanet, Midline and Cochrane Library. We used the key words: "non-alcoholic fatty liver disease, children, non-alcoholic steatohepatitis and fatty liver".

Results:

NAFLD/NASH is probably promoted by “multiple parallel hits”: environmental and genetic factors, systemic immunological disorders (oxidative stress, persistent-low grade of inflammation) as well as obesity and metabolic alterations (insulin resistance and metabolic syndrome). However its exact cause still underdiagnosed and unknown.

Conclusions:

Pediatric NAFLD/NASH is emerging problem. Longitudinal follow-up studies, unfortunately still insufficient, are needed to better understand the natural history and outcome of NAFLD in children. This review focuses on the current knowledge regarding the epidemiology, pathogenesis, environmental, genetic and metabolic factors of disease. The review also highlights the importance of studying the underlying mechanisms of pediatric NAFLD and the need for complete and personalized approach in the management of NAFLD/NASH.     

Genetic Variants in the SAMM50 Gene Create Susceptibility to Nonalcoholic Fatty Liver Disease in a Chinese Han Population

Background:

Genome-wide association studies have shown that rs738491, rs2143571, and rs3761472 in the sorting and assembly machinery component 50 homolog (SAMM50) gene are significantly associated with susceptibility to nonalcoholic fatty liver disease (NAFLD).

Objectives:

The present study evaluated the association between the three genetic variants in the SAMM50 gene and susceptibility to NAFLD in a Chinese Han population.

Patients and Methods:

Genotypes for 3 single nucleotide polymorphisms (SNPs), viz rs738491, rs2143571, and rs3761472, in the SAMM50 gene were determined using an improved multiplex ligation detection reaction technique in 340 B-type ultrasonography-diagnosed NAFLD patients and 452 healthy controls. Meanwhile, serum lipid profiles and liver enzymes were estimated using standard clinical laboratory methods. The SNP-SNP interactions were analyzed by performing multifactor dimensionality reduction (MDR) and generalized multifactor dimensionality reduction (GMDR).

Results:

The genotype and allele frequencies of the SAMM50 polymorphisms between the NAFLD group and the control group were significantly different (all Ps < 0.05). In the multivariate analysis adjusted for gender, age, and body mass index, the carriers of the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele had significantly increased susceptibility to NAFLD (OR, 1.507; 95% CI, 1.035 to 2.195; P = 0.032; OR, 1.761; 95% CI, 1.232 to 2.517; P = 0.002; OR, 1.483; 95% CI, 1.039 to 2.115; P = 0.030, respectively). Moreover, the rs738491 T allele carriers had significantly higher levels of alanine aminotransferase (ALT) (P = 0.017) than did the noncarriers. However, differences in the levels of serum triglyceride (TG) and aspartate aminotransferase (AST) were not statistically significant (P = 0.123; P = 0.107). The Rs2143571 A allele and the rs3761472 G allele were both deeply associated with increased levels of serum TG, ALT, and AST (all Ps < 0.05). Furthermore, the MDR and GMDR showed that a synergistic relationship might exist between rs738491, rs2143571, and rs3761472 in the SAMM50 gene and the pathophysiology and genetics of NAFLD.

Conclusions:

We first demonstrated that the rs738491 T allele, rs2143571 A allele, and rs3761472 G allele in the SAMM50 gene created susceptibility to NAFLD in a Chinese Han population. The combination of the three SNPs in the SAMM50 gene may have synergism to predict the predisposition to NAFLD.     

Relationship between Neck Circumference and Non-Alcoholic Fatty Liver Disease in Childhood Obesity

Objective:

The aim of this study was to establish the association between anthropometric parameters and non-alcoholic fatty liver disease (NAFLD) and to determine the most reliable measurement as a parameter in predicting NAFLD.

Methods:

Two-hundred fifty-three obese children of ages 10 to 18 years were enrolled in this study. Anthropometric data and metabolic parameters such as fasting blood glucose, insulin and lipid levels, were measured. Liver function tests were assessed. NAFLD was determined by ultrasound.

Results:

Most metabolic parameters and anthropometric indices were significantly higher in children with NAFLD. A univariate logistic regression analysis was performed, taking NAFLD status as the dependent variable and anthropometric parameters as the independent variables. NAFLD was affected significantly by the anthropometric values. The multiple logistic regression analysis showed that neck circumference (NC) was the only parameter which determined the risk in both genders. Each 1 cm increase in the NC increased the risk of NAFLD 1.544-fold (p<0.001, 95% confidence interval (CI): 1.357-2.214) in the boys and 1.733-fold (p=0.001, 95% CI: 1.185-2.012) in the girls. Receiver operating characteristic analysis was performed to compare the reliability of anthropometric measurements. NC was observed to be a better indicator.

Conclusion:

Measurement of the NC was shown to be associated with NAFLD in children. We suggest the use of NC as a novel, simple, practical, and reliable anthropometric index in predicting children at risk for NAFLD.     

NAFLD Prevalence in a Young Cadaveric Organ Donor Population

Background:

Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients’ survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases.

Objectives:

In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years.

Materials and Methods:

All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score).

Results:

Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis.

Conclusions:

Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.     

Antibiotic prophylaxis in transarterial therapy of hepatocellular carcinoma: a meta-analysis

BACKGROUND:

The use of prophylactic antibiotics against postprocedure infection in patients undergoing transarterial therapy for hepatocellular carcinoma is controversial.

AIM:

To compare the effects of prophylactic antibiotic treatment and no prophylactic antibiotic treatment on infectious complications following transarterial procedures.

METHODS:

Clinical trials fulfilling predefined selection criteria were identified by searching several bibliographic databases; a meta-analysis was performed where appropriate.

RESULTS:

Four trials of inadequate quality consisting of 210 patients were included in the analysis. Only one case of possible postprocedure infection in each group was reported. The rate of patients developing fever (RR 0.91 [95% CI 0.61 to 1.35]), changes in peripheral white blood cell count or serum C-reactive protein levels, and the mean length of hospital stay (mean difference 0.20 [95% CI 0.75 to 1.14]) showed no significant intergroup differences between antibiotic and no antibiotic treatment. Furthermore, the results of the present study indicated that the incidence of bacteremia, septicemia, sepsis or hepatic abscess after transarterial therapy was rare.

CONCLUSION:

Antibiotic prophylaxis in patients undergoing transarterial therapy for hepatocellular carcinoma may not be routinely necessary. However, a more judicious use of antibiotics is recommended for patients who are at an increased risk of infection. Nevertheless, prospective trials on a larger scale are clearly needed.     

Inter-observer and Intra-observer Agreement in Pathological Evaluation of Non-alcoholic Fatty Liver Disease Suspected Liver Biopsies

Background:

Histopathologic assessment of liver tissue is an essential step in management and follow-up of non-alcoholic fatty liver disease (NAFLD) while inter- and intra-observer variations limit the accuracy of these assessments.

Objectives:

The aim of this study was to assess the inter- and intra-observer reproducibility of histopathologic assessment of liver biopsies based on NAFLD activity score (NAS) scoring system.

Materials and Methods:

The anonymous liver biopsy samples of 100 consecutive NAFLD suspected adults were randomly assigned to four pathologists. Then, the samples were randomly reassigned to the pathologists for the second time in a way that each sample would be evaluated by two different pathologists. Biopsies were revisited by their first evaluator after two months. The results were reported based on NAS scoring system.

Results:

Inter-observer agreement of the pathology scores based on NAS scoring system was acceptable for steatosis, lobular inflammation, and fibrosis, but not for hepatocyte ballooning. The intra-observer agreement was acceptable in all scales, with lowest intra-class correlation observed for lobular inflammation.

Conclusions:

NAS scoring system has good overall inter- and intra-observer agreement, but more attention should be given to defining the hepatocyte ballooning and lobular inflammation, and training the pathologists to improve the accuracy of pathology reports.     

Hepatitis C virus-infected patients are ‘spared’ from the metabolic syndrome but not from insulin resistance. A comparative study of nonalcoholic fatty liver disease and hepatitis C virus-related steatosis

BACKGROUND:

Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C feature steatosis and insulin resistance (IR), conditions associated with the metabolic syndrome (MS).

OBJECTIVES:

To assess the prevalence of MS and determinants of IR in patients with NAFLD and chronic hepatitis C.

METHODS:

Ninety-three consecutive patients with NAFLD, 97 with chronic hepatitis C virus (HCV) genotypes 1 and 2, and 182 ‘healthy’ controls without steatosis were enrolled in the present study. The prevalence of MS was assessed by modified Adult Treatment Panel III criteria and IR by the homeostasis model assessment of insulin resistance (HOMA-IR). IR was defined as the 75th percentile of the HOMA-IR of control subjects.

RESULTS:

While the prevalence of IR was similar in NAFLD and HCV-infected subjects (70.0% and 78.7%, respectively), the prevalence of MS was significantly higher in NAFLD patients than in HCV-infected patients (27.9% versus 4.1%) and in controls (5.6%). With multivariate analysis, IR was predicted by body mass index (OR 1.263; 95% CI 1.078 to 1.480) and triglyceridemia (OR 1.011; 95% CI 1.002 to 1.020) in NAFLD and by sex (OR for female sex 0.297; 95% CI 0.094 to 0.940) and fibrosis stage (OR 2.751; 95% CI 1.417 to 5.340) in chronic hepatitis C.

CONCLUSIONS:

IR is independently associated with body mass index and triglyceridemia in NAFLD, sex and fibrosis in chronic HCV infection, and has a higher prevalence in NAFLD and chronic hepatitis C than in controls. However, the frequency of MS in HCV-infected patients, similar to that of controls, is significantly lower than that seen in NAFLD patients. The current diagnostic criteria of MS are more likely to ‘capture’ patients with NAFLD than with chronic hepatitis C, although both groups are insulin resistant.     

Knee-length graduated compression stockings for thromboprophylaxis in air travellers: A meta-analysis

OBJECTIVE:

To systematically review the randomized controlled trials that have evaluated the efficacy of knee-length (KL) compression stockings for thromboprophylaxis in air travellers.

METHOD:

After an electronic database search, the randomized controlled trials that studied passengers on long-haul flights were selected and analyzed to generate summative data.

RESULTS:

Nine trials studying participants using KL stockings were analyzed. Forty-six of 1261 participants randomly assigned to the control group developed deep vein thrombosis (DVT), compared with two of 1237 participants (0.16%) in the KL stockings group. The weighted risk difference was −0.034, which indicated that the absolute difference was 3.4% in the incidence of DVT, in favour of KL stockings. The number needed to treat with KL stockings to avoid one case of DVT was 29.4. However, there was significant heterogeneity among trials. The RR for DVT was 0.08 in high-risk participants and 0.14 in low- to medium-risk participants.

CONCLUSION:

KL stockings are effective for thromboprophylaxis in air travellers at low, medium and high risk of DVT. The use of KL stockings should form an important part of air traveller education on lowering the burden of DVT. The results of the present meta-analysis can be used to advise travellers on their risk of DVT and preventive strategies.     

A meta-analysis of glucose-insulin-potassium therapy for treatment of acute myocardial infarction

BACKGROUND:

Glucose-insulin-potassium (GIK) therapy has been proposed to provide metabolic support to ischemic myocardium. A meta-analysis that included 1932 patients performed 10 years previously demonstrated that GIK therapy may have an important role in reducing mortality after acute myocardial infarction (AMI). Since then, many larger randomized trials investigating the role of GIK in the setting of AMI have been published; hence, the present study repeats the previous meta-analysis performed by the current authors to include these trials.

METHOD AND RESULTS:

A systematic MEDLINE search for all randomized, placebo-controlled studies of GIK therapy in the setting of AMI was conducted and a meta-analysis of the mortality data was performed. A total of 16 randomized trials from 1966 to 2008 were identified, with 28,374 patients included in the current meta-analysis. There was a total of 1367 deaths (9.6%) in the GIK group, with 1351 deaths (9.6%) in the control group. Meta-analysis did not reveal any benefit from GIK treatment (OR 1.0; 95% CI 0.9 to 1.1; P=0.9). Subgroup analysis of patients given high-dose GIK and in patients in whom reperfusion was not obtained did not demonstrate a benefit from GIK therapy.

CONCLUSION:

A meta-analysis of 16 randomized trials that spanned 40 years and involved more than 28,000 patients did not reveal any mortality benefit for ST segment elevation AMI using GIK therapy when data from the modern thrombolysis/primary percutaneous coronary intervention era were included.     

Prevalence and Factors Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Korean Population

Background/Aims

Nonalcoholic fatty liver disease (NAFLD) is an emerging problem in Asia, but little is known about the disease in the nonobese population. The aims of this study were to investigate the prevalence of NAFLD and the factors associated with it in a nonobese Korean population and to compare the clinical characteristics of nonobese and obese subjects with NAFLD.

Methods

This cross-sectional study used data from 2,058 subjects who participated in a medical checkup program.

Results

The prevalence of NAFLD was 12.4% (213/1,711) in the nonobese population. A higher body mass index (BMI), higher homeostasis model assessment of insulin resistance (HOMA-IR) values, higher alanine aminotransferase (ALT) levels, triglyceride concentrations 150 mg/dL, and hyperuricemia were independently associated with the presence of NAFLD in the nonobese subjects. Compared with the obese subjects with NAFLD, the nonobese subjects with NAFLD were composed of a higher proportion of females and had lower BMIs, smaller waist circumferences, lower HOMA-IR values, and fewer metabolic irregularities.

Conclusions

Higher BMIs, HOMA-IR values, ALT levels, hypertriglyceridemia, and hyperuricemia were associated with NAFLD in the nonobese subjects. Clinicians should be particularly aware of the possibility of NAFLD in nonobese Asian people.     

The utility of Xenon-133 liver scan in the diagnosis and management of nonalcoholic fatty liver disease

BACKGROUND:

Nonalcoholic fatty liver disease (NAFLD) is an important and common condition affecting approximately 20% of the general population. Given the limitation of radiological investigations, diagnosis often requires a liver biopsy.

OBJECTIVE:

To compare Xenon-133 (Xe-133) liver scanning with ultrasonography in the diagnosis of NAFLD.

METHODS:

From January 2003 to February 2007, 258 consecutive patients with suspected NAFLD underwent Xe-133 liver scanning at Royal Victoria Hospital (Montreal, Quebec). Of these, 43 patients underwent ultrasonography and liver biopsy for the evaluation of NAFLD. Patients with other liver diseases and significant alcohol consumption were excluded. Two nuclear medicine physicians assessed liver Xe-133 uptake and measured the grade of steatosis using a standardized protocol. The degree of steatosis was determined from biopsy specimens assessed by two hepatopathologists.

RESULTS:

NAFLD was identified by liver biopsy in 35 of 43 patients (81.4%). Xe-133 scan demonstrated 94.3% sensitivity (95% CI 81.4% to 98.4%) and 87.5% specificity (95% CI 52.9% to 99.4%) for the presence of NAFLD. The positive and negative predictive values for detection of steatosis by Xe-133 scan were 97.1% (95% CI 85.1% to 99.8%) and 77.8% (95% CI 45.3% to 93.7%), respectively. The positive and negative likelihood ratios were 7.54 (95% CI 1.20 to 47.26) and 0.07 (95% CI 0.02 to 0.26), respectively. Two patients with NAFLD (5.7%) who had a negative Xe-133 scan result had histologically mild steatosis (<10%). The grade of steatosis on liver biopsy was highly correlated with the results of the Xe-133 scan (r=0.87; P<0.001). The sensitivity and specificity of ultrasound in diagnosing steatosis were 62.9% and 75%, respectively.

CONCLUSION:

Xe-133 liver scan proved to be a safe, reliable, non-invasive method for diagnosing and quantifying hepatic steatosis, and was superior to ultrasound.