[Corrigendum] TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Following the publication of the above article, the authors have realized that the first grant number featured in the Funding section of the Declarations on p. 658 appeared incorrectly: The text here should have been written as 'grant nos. 2018J01199, 2018Y0032 and 2016J01441' instead of 'grant nos. 2018J0105, 2018Y0032 and 2016J01441'. The authors regret their oversight in providing this incorrect information in the Funding section of their paper. They thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership of the Journal and to the funding body in question for any inconvenience caused. [the original article was published in Molecular Medicine Reports 22: 651­660, 2020; DOI: 10.3892/mmr.2020.11134].

Clinical cure and liver fibrosis reversal after postoperative antiviral combination therapy in hepatitis B-associated non-cirrhotic hepatocellular carcinoma: A case report.

BACKGROUND: The incidence of hepatocellular carcinoma (HCC) is high in China, and approximately 15%-20% of HCC cases occur in the absence of cirrhosis. Compared with patients with cirrhotic HCC, those with non-cirrhotic HCC have longer postoperative tumor-free survival. However, the overall survival time is not significantly increased, and the risk of postoperative recurrence remains. Strategies to improve the postoperative survival rate in these patients are currently required. CASE SUMMARY: A 47-year-old man with a family history of HCC was found to have hepatitis B virus (HBV) infection 25 years ago. In 2000, he was administered lamivudine for 2 years, and entecavir (ETV 0.5 mg) was administered in 2006. In October 2016, magnetic resonance imaging revealed a tumor in the liver (5.3 cm × 5 cm × 5 cm); no intraoperative hepatic and portal vein and bile duct tumor thrombi were found; and postoperative pathological examination confirmed a grade II HCC with no nodular cirrhosis (G1S3). ETV was continued, and no significant changes were observed on imaging. After receiving pegylated interferon alfa-2b (PEG IFNα-2b) (180 µg) + ETV in February 2019, the HBsAg titer decreased significantly within 12 wk. After receiving hepatitis B vaccine (60 µg) in 12 wk, HBsAg serological conversion was realized at 48 wk. During the treatment, no obvious adverse reactions were observed, except for early alanine aminotransferase flares. The reexamination results of liver pathology were G2S1, and reversal of liver fibrosis was achieved. CONCLUSION: The therapeutic regimen of ETV+ PEG IFNα-2b + hepatitis B vaccine for patients with HBV-associated non-cirrhotic HCC following hepatectomy can achieve an HBV clinical cure and prolong the recurrence-free survival.

TLR4 mediates inflammation and hepatic fibrosis induced by chronic intermittent hypoxia in rats.

Obstructive sleep apnea syndrome (OSAS) is a common and complex disorder that is associated with liver injury. Moreover, previous studies have revealed that chronic intermittent hypoxia (CIH) is associated with the development of non­alcoholic fatty liver disease and hepatic fibrosis. However, the underlying molecular mechanisms remain largely unknown. The present study aimed to investigate whether chronic intermittent hypoxia induced hepatic fibrosis, in addition to determining its underlying mechanisms, in CIH model rats using immunohistochemistry, western blotting and reverse transcription­quantitative PCR. The present results suggested that CIH caused hepatic fibrosis and increased the expression levels of interleukin (IL)­1ß, IL­8, monocyte chemotactic­1, tumor necrosis factor­α, intercellular adhesion molecule­1 and vascular cell adhesion molecule­1 in the liver; these conditions could be reversed by Toll­like receptor 4 (TLR4) short hairpin RNA lentivirus treatment. Moreover, immunohistochemistry and western blotting results indicated that TLR4 and NF­κB expression levels were significantly increased in the CIH and CIH­TLR4 empty vector lentivirus group. However, protein expression levels of TLR4, NF­κB, inhibitor of NF­κB and phosphorylated­mitogen­activated protein kinase (MAPK)­1 in the hypoxia/reoxygenation group were significantly higher compared with the control group (P<0.05), and these results were reversed by the MAPK inhibitor U0126 in vitro. Collectively, the present preliminary results suggested that inflammation and the TLR4/NF­κB/MAPK signaling pathway may be involved in CIH­induced liver fibrosis.

A promising non-invasive index for predicting liver inflammation in chronic hepatitis B patients with alanine aminotransferase ≤2 upper limit of normal.

Inexpensive and simple non-invasive indexes for predicting liver inflammation are urgently required, but have been poorly studied in chronic hepatitis B (CHB) patients with alanine transaminase (ALT) ≤2 times the upper limit of normal (ULN). A total of 356 CHB patients with ALT ≤2 ULN who presented at Huashan Hospital (n=181) and the First Hospital of Quanzhou (n=175) were enrolled and randomly divided into an experimental assessment cohort (n=238) and validation cohort (n=118) at a ratio of 2:1. Histological analysis of liver tissue was performed to determine the pathological stage according to the Scheuer scoring system. For the experimental assessment cohort, univariate and multivariate analysis identified aspartate aminotransferase (AST) and albumin (ALB) as independent predictors of liver necroinflammation [liver necroinflammation grade (G)≥2] in patients with ALT ≤2 ULN. Therefore, a novel index, the AST-to-ALB ratio (ATAR), was proposed, which had a better diagnostic performance [area under receiver operating characteristic curve (AUC)=0.721] than that of ALB (AUC=0.632; P=0.039 vs. ATAR) and AST (AUC=0.682; P=0.082 vs. ATAR). In the validation cohort, the AUC of ATAR (0.728) to identify patients with a G≥2 was slightly greater than that of AST (0.660; P=0.149 vs. ATAR) and ALB (0.672; P=0.282 vs. ATAR). Furthermore, a similar diagnostic superiority was also demonstrated in patients with ALT ≤1 ULN. Thus, ATAR may be a promising non-invasive surrogate marker for liver necroinflammation CHB patients with ALT ≤2 ULN and thereby determine whether anti-viral treatment should be initiated.