Abstract

Background: Non-alcoholic steatohepatitis ((NASH) is the progressive form of (non-alcoholic fatty liver disease) (NAFLD), which can progress to liver cirrhosis and hepatocellular carcinoma. There is no available reliable non-invasive diagnostic tool to diagnose NASH, and still the liver biopsy is the gold standard in diagnosis. In this pilot study, we aimed to evaluate the Nod-like receptor (NLR) signaling pathway related RNA panel in the diagnosis of NASH. Methods: Bioinformatics analysis was done, with retrieval of the HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA panel based on the relation to the NLR-signaling pathway. Hepatitis serum markers, lipid profile, NAFLD score and fibrosis score were assessed in the patients’ sera. Reverse transcriptase real time polymerase chain reaction (RT-PCR) was done to assess the relative expression of the RNA panel among patients who had NAFLD without steatosis, NAFLD with simple steatosis, NASH and healthy controls. Results: We observed up-regulation of Lnc-SPARCL1-1:2 lncRNA that led to upregulation of miR-6881-5P with a subsequent increase in levels of HSPD1, MMP14, and ITGB1 mRNAs. In addition, ROC curve analysis was done, with discriminative cutoff values that aided discrimination between NASH cases and control, and also between NAFLD, simple steatosis and NASH. Conclusion: This pilot study concluded that HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 panel expression has potential in the diagnosis of NASH, and also differentiation between NAFLD, simple steatosis and NASH cases.

Highlights

  • There was a significant difference in total cholesterol, HDLcholesterol, LDL-cholesterol, total triglycerides, albumin-creatinine ratio, ALT, AST, total bilirubin, direct bilirubin, serum albumin, GGT, alfa fetoprotein, fasting blood glucose, glycated hemoglobin (HbA1C) and HOMA-IR between the non-alcoholic fatty liver disease (NAFLD), simple steatosis, Non-alcoholic steatohepatitis (NASH) and healthy control groups (p < 0.01) (Table 1)

  • Non-alcoholic steatohepatitis (NASH), which is a subtype of NAFLD, has a potential progressive course that could result in liver fibrosis, cirrhosis, hepatocellular carcinoma and liver transplantation

  • Pilot preliminary study, there is still nowe reliable non-invasive diagnostic tool. In this pilot preliminary study, we and related to explored a novel RNA panel retrieved from bioinformatics databases explored a novel panel retrieved from bioinformatics databases and related to the the NOD-like receptors (NLRs)-signaling pathway, and evaluated its effectiveness in diagnosis of NASH

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Summary

Introduction

Non-alcoholic steatohepatitis (NASH) is a chronic liver disease marked by the accumulation of fat in the liver (steatosis) and inflammation [1]. NASH, which is the progressive form of non-alcoholic fatty liver disease (NAFLD), is estimated to be present in one third of NAFLD cases. NASH can progress into liver cirrhosis and hepatocellular carcinoma [2]. The progression of NAFLD to NASH is mostly attributed to a combination of genetic and environmental factors. Diabetes mellitus and hypertension are known factors to increase NASH development [3]. NASH manifests with non-specific symptoms such as fatigue and pain in the upper right abdomen, the disease may progress undetected [4]

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