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Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus. Although it is considered a benign disease, NAFLD can progress to non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation, especially in the Western World. Although cirrhosis constitutes the main risk factor for HCC development, in patients with NAFLD, HCC can arise in the absence of cirrhosis, indicating specific carcinogenic molecular pathways. Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population, NAFLD-HCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes. In this current review, we summarize the latest literature on the epidemiology, other than liver cirrhosis-pathogenesis, risk factors and prognosis of NAFLD-HCC patients. Finally, we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury worldwide. Bile acids and their receptors are profoundly implicated in the pathogenesis of NAFLD and its progression to nonalcoholic steatohepatitis and cirrhosis.We conducted extensive literature search using PubMed database, and we summarized the relevant literature. We provided an overview of the fibroblast growth factor 19 (FGF-19)-farnesoid X receptor (FXR) axis and summarized the latest findings derived from animal and human studies concerning the impact of FGF-19 on NAFLD.FGF-19, a nutritionally regulated endocrine post-prandial hormone, governs bile acid metabolism, lipid oxidation, lipogenesis, and energy homeostasis. As no approved medication for NAFLD exists, FGF-19 seems to be a propitious therapeutic opportunity for NAFLD, since its administration was associated with ameliorated results in hepatic steatosis, liver inflammation and fibrosis. Furthermore, promising results have been derived from clinical trials concerning the beneficial efficacy of FGF-19 on histological findings and laboratory parameters of NAFLD. However, we should bear in mind the pleiotropic effects of FGF-19 on various metabolically active tissues along with its potential tumorigenic reservoir. Further clinical research is required to determine the clinical application of FGF-19-based therapies on NAFLD.

Excessive alcohol intake is an established risk factor for chronic liver disease. At the same time, moderate alcohol intake appears to reduce cardiovascular morbidity. Accordingly, recommendations for alcohol intake in patients with nonalcoholic fatty liver disease (NAFLD), who are at increased risk for liver-related and cardiovascular events, are a point of debate. Some studies have shown beneficial effects of alcohol on cardiovascular and overall mortality in this specific subset of patients. Nonetheless, even light alcohol intake appears to aggravate liver disease and increase the risk of hepatocellular cancer. Therefore, patients with nonalcoholic steatohepatitis or advanced fibrosis should be advised against consuming alcohol. On the other hand, only light alcohol consumption (

Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long-term oral antiviral therapy, but its pathogenesis in the setting of long-standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell-free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg-negative CHB patients with (HCC cases, n = 37) or without HCC development during the first 5 years of oral antiviral therapy (controls, n = 74). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNase P coding DNA, copies of mitochondrial DNA and levels of 5-methyl-2'-deoxycytidine as an indicator of DNA methylation was performed. HCC cases compared with controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, p = .042) and RNase P coding DNA (68 vs 15 genomic equivalent, p < .001). In contrast, median cfDNA concentration, Alu115 levels, Alu247/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNase P coding DNA offered good prediction of subsequent HCC development (c-statistic: 0.80, p < .001). In conclusion, serum levels of RNase P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg-negative CHB patients.

Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.

Affecting one fourth of the global population, non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disorder. It encompasses the simple liver fat accumulation to more progressive steatosis, inflammation, and fibrosis characterized as non-alcoholic steatohepatitis (NASH) and in some cases cirrhosis and hepatocellular carcinoma. NAFLD regularly coexists with metabolic disorders, such as obesity and mostly type 2 diabetes mellitus (T2DM). A relatively new class of antidiabetic drugs, the sodium glucose co-transporter 2 (SGLT2) inhibitors exert their action by increasing the urinary glucose and calorie excretion leading to ameliorated plasma glucose levels and lower bodyweight. Recently, several animal studies and human clinical trial have emphasized the possible beneficial impact of SGLT2 inhibitors on NAFLD and its progression to NASH. In this present review, we summarize the current literature regarding the efficacy of the aforementioned category of drugs on anthropometric, laboratory, and histological features of patients with NAFLD. Conclusively, as SGLT2 inhibitors seem to be an appealing therapeutic opportunity for NAFLD management, we identify the open issues and questions to be addressed in order to clarify the impact in choosing antidiabetic medication to treat NAFLD patients associated with T2DM.

In recent years, frailty has been increasingly recognized among researchers of distinct medical specialties worldwide. Frailty comprises a complex of multisystemic physiological decline, reduced physiologic reserve, and vulnerability to stressors. Frail people tend to have a shorter lifespan and greater disability, morbidity and mortality. In the field of hepatology, frailty is identified in nearly 50% of patients who have cirrhosis of any cause. The most predominant cause of chronic liver disease is nonalcoholic fatty liver disease (NAFLD), considered as the hepatic manifestation of the metabolic syndrome (MetS). Although it is viewed as a benign disease, it may progress to nonalcoholic steatohepatitis (NASH), characterized by the additional emergence of inflammation and hepatocyte ballooning, with or without fibrosis. During the progression of NAFLD to NASH and liver cirrhosis, NAFLD patients present sarcopenia along with lower skeletal muscle strength and function. Moreover, aging and the increased prevalence of comorbidities further exacerbate their physical performance. The aforementioned features are strongly associated with the frailty phenotype, implying that the latter could be associated with both MetS and NAFLD. Although it is a relatively new topic of research interest, in this review we aim to provide a synopsis of the current literature dealing with the interplay between frailty and MetS, and to shed more light on the association between NAFLD and frailty. Finally, we discuss the potential pathophysiological mechanisms linking the distinct features of MetS and NAFLD with aspects of the frailty phenotype.

The pathogenetic mechanisms involved in the progression of non-alcoholic fatty liver disease (NAFLD) have not been completely elucidated, while the significance of circulating cell-free DNA (cf-DNA) species has been rarely evaluated in NAFLD. Herein, we assessed the serum levels of cf-DNA species in NAFLD patients and investigated their potential associations with patients’ characteristics and severity of liver disease. Forty-nine adult patients with NAFLD of any stage were included in this cohort study. Cf-DNA was isolated from patients’ sera and the levels of several distinct cf-DNA species including total cf-DNA, gene-coding cf-DNA, Alu repeat sequences, mitochondrial DNA copies and 5-methyl-2′-deoxycytidine were determined. Cirrhotic compared to non-cirrhotic patients had significantly lower serum levels of cf-DNA and RNAse P coding DNA as well as higher expression of 5-methyl-2′-deoxycytidine. After adjustment for the significant clinico-epidemiological factors, lower serum levels of cf-DNA or RNAse P were independently associated with the presence of cirrhosis. Serum levels of total and gene-coding DNA are associated with the presence of cirrhosis in NAFLD patients regardless of clinical or epidemiological parameters and may therefore be used as a screening tool for NAFLD progression.

Non-alcoholic fatty liver disease (NAFLD) is the predominant cause of chronic liver disease worldwide. NAFLD progresses in some cases to non-alcoholic steatohepatitis (NASH), which is characterized, in addition to liver fat deposition, by hepatocyte ballooning, inflammation and liver fibrosis, and in some cases may lead to hepatocellular carcinoma. NAFLD prevalence increases along with the rising incidence of type 2 diabetes mellitus (T2DM). Currently, lifestyle interventions and weight loss are used as the major therapeutic strategy in the vast majority of patients with NAFLD. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used in the management of T2DM and do not have major side effects like hypoglycemia. In patients with NAFLD, the GLP-1 receptor production is down-regulated. Recently, several animal and human studies have emphasized the role of GLP-1RAs in ameliorating liver fat accumulation, alleviating the inflammatory environment and preventing NAFLD progression to NASH. In this review, we summarize the updated literature data on the beneficial effects of GLP-1RAs in NAFLD/NASH. Finally, as GLP-1RAs seem to be an attractive therapeutic option for T2DM patients with concomitant NAFLD, we discuss whether GLP-1RAs should represent the first line pharmacotherapy for these patients.