Preventive and Therapeutic Effect of Ganoderma (Lingzhi) on Liver Injury

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries that is predicted to become also the most frequent indication for liver transplantation by 2030. Over the last decade, it has been shown that the clinical burden of NAFLD is not only confined to liver-related morbidity and mortality, but there is now growing evidence that NAFLD is a multisystem disease, affecting extra-hepatic organs and regulatory pathways. For example, NAFLD increases risk of type 2 diabetes mellitus (T2DM), cardiovascular (CVD) and cardiac diseases, and chronic kidney disease (CKD). Although the primary liver pathology in NAFLD affects hepatic structure and function to cause morbidity and mortality from cirrhosis, liver failure and hepatocellular carcinoma, the majority of deaths among NAFLD patients are attributable to CVD. This narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease. The review discusses the factors involved in the progression of liver disease in NAFLD and the factors linking NAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD. The review will not discuss NAFLD treatments as these are discussed elsewhere in this issue of the Journal. For this review, PubMed was searched for articles using the keywords "non-alcoholic fatty liver disease" or "fatty liver" combined with "diabetes", "cardiovascular (or cardiac) disease", "cardiovascular mortality" or "chronic kidney disease" between 1990 and 2014. Articles published in languages other than English were excluded.

Chemotherapeutics are the most effective treatment for metastatic tumours. However, the ability of cancer cells to become simultaneously resistant to different drugs--a trait known as multidrug resistance--remains a significant impediment to successful chemotherapy. Three decades of multidrug-resistance research have identified a myriad of ways in which cancer cells can elude chemotherapy, and it has become apparent that resistance exists against every effective drug, even our newest agents. Therefore, the ability to predict and circumvent drug resistance is likely to improve chemotherapy.

Lifestyle intervention can be useful across all the spectrum of NAFLD patients. Losing weight decreases cardiovascular / diabetes risk and also regresses liver disease. Weight reductions of ≥ 10% are required for inducing near universal NASH resolution or fibrosis improvement by at least one stage. However, modest weight losses (>5%) also produce important benefits on NAS and its components. In addition, to improve the success of this intervention we need to explore, beyond total calories and type of weight loss diet, the role of micro and macronutrients, evidence-based benefits of physical activity and exercise and finally supporting these modifications through established behaviour change models and techniques. The Mediterranean diet can reduce liver fat even without weight loss and is the most recommended dietary pattern in NAFLD. The Mediterranean diet is characterized by reduced carbohydrates intake, especially sugars and refined carbohydrates (40% of the calories vs. 50-60% in a typical low fat diet), and increased monounsaturated and omega-3 fatty acids intake (40% of the calories as fat vs. up-to 30% in a typical low fat diet). Both TV sitting (a reliable marker of overall sedentary behaviour) and physical activity are associated with cardio-metabolic health, NAFLD and overall mortality. A 'triple hit behavioural phenotype' of 1) sedentary behaviour, 2) low physical activity, and 3) poor diet have been defined. Clinical evidence strongly supports the role of lifestyle modification as a primary therapy for the management of NAFLD and NASH, and this should be accompanied by the implementation of strategies to avoid relapse and weight regain.