Association between Serum Irisin Levels and Non-Alcoholic Fatty Liver Disease in Health Screen Examinees

<div><p>Irisin is a recently found myokine that aids obesity control and improves glucose homeostasis by acting on white adipose tissue cells and increases total energy consumption. The aim of this study was to evaluate serum irisin levels in patients with non-alcoholic fatty liver disease (NAFLD) and to compare these levels with those of normal controls. Among 595 health screen examinees who had visited our institute between January 2013 to March 2013, 355 patients (84 NAFLD patients and 271 normal controls) were enrolled depending on whether they gave written informed consents and their history of alcohol intake, blood tests, and abdominal ultrasonographic findings. Age; sex; laboratory test parameters; homeostasis model assessment-insulin resistance; and levels of leptin, adiponectin, and irisin were assessed. Serum irisin levels (ng/ml) were significantly higher in the NAFLD group than in normal controls (63.4±32.6 vs. 43.0±29.7, <i>p</i><0.001) and higher in the mild fatty liver group than in the moderate-to-severe fatty liver group (68.3±38.2 vs. 56.6±21.2, <i>p</i><0.001). Additionally, serum irisin levels were not different between the non-obese and obese groups (48.4±34.2 vs. 45.8±22.9, <i>p</i> = 0.492); however, the levels were significantly lowest in normal controls and highest in the mild fatty liver group in the non-obese (44.9±31.7 vs. 73.1±48.5 vs 59.7±18.0, <i>p</i><0.001) and obese groups (35.0±17.0 vs. 62.9±21.2 vs. 54.6±23.3, <i>p</i><0.001). Serum irisin levels were significantly higher in NAFLD patients, which is not consistent with the results of previously published studies. Therefore, more studies are needed to confirm the role of irisin in NAFLD.</p></div

Baseline characteristics of the subjects according to the study group.

<p>Baseline characteristics of the subjects according to the study group.</p

Serum irisin level according to sex.

<p>Serum irisin level according to sex.</p

Baseline characteristics of the subject according to steatosis severity.

<p>Baseline characteristics of the subject according to steatosis severity.</p

Correlations between serum irisin levels and other study parameters.

<p>Correlations between serum irisin levels and other study parameters.</p

Serum irisin level in the control group and NAFLD group.

<p>Serum irisin level in the control group and NAFLD group.</p

Evaluating the efficacy of switching from lamivudine plus adefovir to tenofovir disoproxil fumarate monotherapy in lamivudine-resistant stable hepatitis B patients

<div><p>Background</p><p>The efficacy of switching to tenofovir disoproxil fumarate (TDF) monotherapy from lamivudine (LAM) plus adefovir dipivoxil (ADV) combination therapy (stable switching) in patients with LAM-resistant chronic hepatitis B (CHB) and undetectable hepatitis B virus (HBV) DNA is not clear.</p><p>Methods</p><p>In this non-inferiority trial, patients with LAM-resistant CHB and undetectable serum HBV DNA (<20 IU/mL) for >6 months after initiating LAM+ADV combination therapy were randomized (1:2) either to continue the combination therapy (LAM+ADV group, n = 58) or switched to TDF monotherapy (TDF group, n = 111). They were followed-up with serum biochemistry tests and HBV DNA measurement at 12-week intervals for 96 weeks. The primary endpoint of this study was the proportion of patients with viral reactivation at week 96.</p><p>Results</p><p>Patients with CHB enrolled in this study (n = 169) included 74 patients with compensated liver cirrhosis. In total, 9 patients (4 in the LAM+ADV group and 5 in the TDF group) dropped-out from the study. After a mean follow-up period of 96 weeks, the proportion of HBV reactivation observed was 6.8% (4/58) in the LAM+ADV group and 4.5% (5/111) in the TDF group by using intention-to-treat analysis (difference, -2.3%; 95% CI, -9.84–5.24%). None of the subjects in either group experienced viral reactivation based on per protocol analysis. No serious adverse reactions were observed. In the subgroup analysis for estimated glomerular filtration rate (eGFR) before and after treatment, decreased eGFR was observed only in the TDF group with cirrhosis (85.22 vs. 79.83 mL/min/1.73 m², p = 0.000)</p><p>Conclusions</p><p>Stable switching to TDF monotherapy yielded non-inferior results at 96 weeks compared to the results obtained with LAM+ADV combination therapy in patients with LAM-resistant CHB and undetectable HBV DNA. However, TDF monotherapy in patients with cirrhosis requires close attention with respect to renal function.</p><p>Trial registration</p><p>ClinicalTrials.gov <a href="https://clinicaltrials.gov/ct2/show/NCT01732367" target="_blank">NCT01732367</a></p></div

Comparison between two groups after 96-week follow-up.

<p>Comparison between two groups after 96-week follow-up.</p

LAM-resistance mutation profiles and previous treatment period.

<p>LAM-resistance mutation profiles and previous treatment period.</p

The Autophagy-Related Marker LC3 Can Predict Prognosis in Human Hepatocellular Carcinoma

<div><p>Background</p><p>Defects of autophagy and endoplasmic reticulum (ER) stress are related to many diseases and tumors. However, only a few studies have examined hepatocellular carcinoma (HCC) as related to these processes. Therefore, in this study, we investigated the expression and extent of autophagy and ER stress-related markers in HCC and their influence on clinical characteristics and prognosis for each protein.</p> <p>Methodology</p><p>The expression of autophagy-related markers (LC3 and Beclin-1) and ER stress-related markers (GRP78 and CHOP) was analyzed by immunohistochemistry on tissues from completely resected specimens of 190 HCC patients. Their influence on clinicopathologic features and prognosis were evaluated using the chi-square test and Kaplan-Meier analysis. Correlations of each protein were determined by Spearman's correlation analysis. </p> <p>Principal Findings</p><p>LC3 expression was not correlated with TNM, BCLC stage, or Edmonson-Steiner grading, whereas it was correlated with longer overall survival (OS) (<i>p</i> = 0.039) and tended to be related with longer time to recurrence (TTR) (<i>p</i>=0.068) although it did not show statistical significance. Multivariate analysis indicated that LC3 expression was a significantly independent prognostic factor of OS (HR, 0.42; 95% CI, 0.22-0.80; <i>p</i>-value=0.009) and TTR (HR, 0.54; 95% CI, 0.33–0.90; <i>p</i>=0.017). Expression of LC3 in advanced stages of TNM (III) (<i>p</i>=0.045) and Edmonson-Steiner Grades (III and IV) (<i>p</i>=0.043) was correlated with longer survival, but not in the early stages. A positive correlation was not observed between the expression of autophagy-related markers and ER stress-related markers.</p> <p>Conclusion</p><p>Our results suggest that the expression and extent of LC3 might be a strong prognostic factor of HCC, especially in patients with surgical resection.</p> </div