Towards genetic prediction of non-alcoholic fatty liver disease trajectories: PNPLA3 and beyond

Non-alcoholic fatty liver disease (NAFLD) is on the verge of becoming the leading cause of liver disease. NAFLD develops at the interface between environmental factors and inherited predisposition. Genome-wide association studies, followed by exome-wide analyses, led to identification of genetic risk variants (e.g. PNPLA3, TM6SF2, SERPINA1) and key pathways involved in fatty liver disease pathobiology. Functional studies improved our understanding of these genetic factors and the molecular mechanisms underlying the trajectories from fat accumulation to fibrosis, cirrhosis and cancer over time.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research

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Basel, 4 March 2020 - Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Device Designation to the Elecsys ® GALAD score.* This algorithmic score combines gender and age with the biomarker results of the Elecsys AFP, AFP-L3 and PIVKA-II and is intended to aid diagnosis of early stage hepatocellular carcinoma (HCC). Dr. Amit Singal, Medical Director of the Liver Tumor Program   and Clinical Chief of Pathology at UT Southwestern Medical Center in Dallas, USA, stated, " HCC is the fourth leading cause of cancer-related death worldwide, wit...
Source: Roche Investor Update - Category: Pharmaceuticals Source Type: news
Conclusion: NAFLD may be associated with increased liver metastasis, and for NAFLD-related advanced liver fibrosis and cirrhosis may be associated with reduced synchronous liver metastasis in CRC patients. However, the correlation between simple steatosis and steatohepatitis remains to be further determined. Certain factors such as NAFLD, lymph node metastasis, elevated levels of preoperative CEA and CA19-9 are suggesting a high risk of synCRLM.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Based on these results, 8.1% of Mexican general population without a history of liver disease is at high risk of having advanced liver fibrosis and complications and death derived from cardiovascular disease and cirrhosis. Most of them showed normal ALT serum levels. PMID: 32063504 [PubMed - as supplied by publisher]
Source: Annals of Hepatology - Category: Gastroenterology Tags: Ann Hepatol Source Type: research
ConclusionA substantial further reduction in cases of HCC requires a wider application of universal HBV vaccination and effective treatment of HBV- and HCV-related chronic hepatitis and cirrhosis, more effective campaigns to favor correct dietary habits and reduce alcohol consumption and the intensification of studies on HCC pathogenesis for future optimized prevention strategies.
Source: Infection - Category: Infectious Diseases Source Type: research
Nonalcoholic fatty liver disease (NAFLD) is a leading etiology for chronic liver disease with immense public health impact, affecting over 25% of the U.S. and global population, of whom up to one in four may have non-alcoholic steatohepatitis (NASH). NASH is associated with significant morbidity and mortality due to complications of liver cirrhosis, hepatic decompensation, and hepatocellular carcinoma (HCC). Recent data confirm that HCC represents the 5th most common cancer and 2nd leading cause of cancer-related death worldwide, and NAFLD has been identified as a rapidly emerging risk factor for this malignancy.
Source: Gastroenterology - Category: Gastroenterology Authors: Source Type: research
Abstract Metabolic disorders are increasingly leading to non-alcoholic fatty liver disease, subsequent steatohepatitis, cirrhosis and hepatocellular carcinoma. Fibroblast growth factors and their receptors play an important role in maintaining metabolic homeostasis also in the liver and disorders in signaling have been identified to contribute to those pathophysiologic conditions leading to hepatic lipid accumulation and chronic inflammation. While specific and well tolerated inhibitors of fibroblast growth factor receptor activity are currently developed for (non-liver) cancer therapy, treatment of non-alcoholic ...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Liver diseases, including liver cancer, cirrhosis, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH), impose a heavy disease burden worldwide [1,2]. Liver cancer and cirrhosis may derive from any chronic liver disease, such as hepatitis B/C virus (HBV/HCV) infections, alcoholic liver disease, NAFLD, haemochromatosis, and autoimmune hepatitis [3]. Over the last four decades, the prevalence of overweight has increased over fourfold in children, and there has been a great relative increase in obesity prevalence with no signs of slowing [4].
Source: Digestive and Liver Disease - Category: Gastroenterology Authors: Tags: Correspondence Source Type: research
ra Grieco The biological clock controls at the molecular level several aspects of mammalian physiology, by regulating daily oscillations of crucial biological processes such as nutrient metabolism in the liver. Disruption of the circadian clock circuitry has recently been identified as an independent risk factor for cancer and classified as a potential group 2A carcinogen to humans. Hepatocellular carcinoma (HCC) is the prevailing histological type of primary liver cancer, one of the most important causes of cancer-related death worldwide. HCC onset and progression is related to B and C viral hepatitis, alcoholic an...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
Conclusions: The constantly increasing prevalence of NAFLD in the general population can contribute to a growing role of NAFLD/NASH in HCC epidemiology. Moreover, some particular challenges specific for patients with liver steatosis may impede proper HCC diagnosis, treatment and follow-up. PMID: 31631714 [PubMed - as supplied by publisher]
Source: Current Medical Research and Opinion - Category: Research Tags: Curr Med Res Opin Source Type: research
idinis Liver cancer is one of the leading causes of death worldwide due to late diagnosis and scarcity of treatment options. The major risk factor for liver cancer is cirrhosis with the underlying causes of cirrhosis being viral infection (hepatitis B or C), metabolic deregulation (Non-alcoholic fatty liver disease (NAFLD) in the presence of obesity and diabetes), alcohol or cholestatic disorders. Lysophosphatidic acid (LPA) is a bioactive phospholipid with numerous effects, most of them compatible with the hallmarks of cancer (proliferation, migration, invasion, survival, evasion of apoptosis, deregulated metabolism, ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
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