Natural history of NASH and HCC

Abstract

Widespread unhealthy dietary habits associated with a sedentary lifestyle have made NAFLD the most frequent chronic liver disease worldwide, with a global prevalence of ~25%. Although NAFLD is mainly considered to be a benign disease, it can progress to severe liver fibrosis and hepatocellular carcinoma (HCC), with the latter found in non‐cirrhotic livers in about 40% of cases. Factors favouring the progression of liver disease in NAFLD are only partially understood. Male sex, older age and Caucasian ethnicity have frequently been identified as factors accelerating the progression of fibrosis in NAFLD, although data are not consistent. Host genetic variants appear to be very important, especially in the gene coding for the patatin‐like phospholipase domain‐containing 3 (PNPLA3), and they may also play a role in the development of HCC, independent of activity and the extent of liver damage. However, the most important factors affecting disease progression are found in the metabolic syndrome, that is, obesity, type 2 diabetes and arterial hypertension. This mini‐review will discuss the contribution of these factors to NAFLD‐associated morbidity, emphasizing the importance of preventive measures such as physical activity and weight control in view of the current pandemic of the metabolic syndrome.

Oxidative Stress Management in Chronic Liver Diseases and Hepatocellular Carcinoma

“…Present issues with the management of NAFLD can be summarized as follows: the natural history of the disease is not well defined, high-risk patients cannot be easily identified, and promising treatment protocols for the different stages of the disease are unclear. There have been many studies related to these problems; however, the natural history and the optimal management strategy at different stages, from simple steatosis, steatohepatitis, liver cirrhosis, HCC and beyond, are not clear [4][5][6]. The definition of NAFLD is under reconsideration, because patients with a history of alcohol consumption and those who habitually consume low amounts of alcohol are not definite non-alcoholic patients.…”

Hepatocellular Carcinoma: Updates in Pathogenesis, Detection and Treatment

“…Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease worldwide, and approximately 60% of biopsied NAFLD patients have non-alcoholic steatohepatitis (NASH) [ 3 ]. Importantly, patients with NASH are at high risk of developing HCC even without presenting established cirrhosis [ 6 ]. With widespread HBV vaccination and the advent of direct-acting antiviral drugs for HCV infection, NAFLD and associated conditions such as diabetes and obesity are emerging as major global risk factors for HCC.…”

Hepatocellular carcinoma in patients with non-alcoholic steatohepatitis – epidemiology, risk factors, clinical implications and treatment

“…concern patients with NAFLD/NASH without hepatic cirrhosis. Diagnosing a growing number of HCC cases, reaching even 50%, caused by NAFLD without cirrhosis, and later cancer diagnoses, in comparison to other HCC aetiologies, resulting in delaying the treatment, necessitate the performance of research concerning the rationale behind and the cost efficiency of screening tests in this group of patients [ 24 , 41 - 44 ].…”

“…The proven negative influence of metabolic syndrome, increasing the risk of cancer transition in patients with NASH, paved the way for, initially intuitive, later proven, behaviours, and various therapies potentially helping in cancer prevention. It has been demonstrated that intensive physical exercise decreases the risk of HCC [ 44 , 45 ]. The treatment of diabetes with metformin reduces the risk of cancer by 7% annually.…”