Search

ABSTRACTIntroduction: The development of direct-acting antiviral (DAA) agents for the treatment of hepatitis C virus (HCV) infection has completely transformed the management of this disease. The advantages of using DAA therapies include high efficacy (sustained virological response (SVR) rate >95%) with minimal side effects, good tolerability, easy drug administration (once daily oral dosing), and short duration of treatment (8–12 weeks). This transformative nature of DAA therapy underpins the goal of the World Health Organization to eliminate HCV infection as a public health threat by 2030.Areas covered: This review seeks to address the current status of DAA therapies, including recent developments, current limitations, and future challenges.Expert opinion: The current DAA regimens, with their high effectiveness and safety profiles, have changed patient perception of HCV infection from a disease that requires complex evaluation and long-term monitoring to a disease that can be cured after one visit to the general practitioner. Despite the remarkably high success rate of DAAs, few patients (4–5%) fail to obtain SVR even after treatment. Five years ahead, the landscape of HCV treatment will undoubtedly continue to evolve, and more pan-genotypic treatment options will be available to all patients.

Nonalcoholic fatty liver disease (NAFLD) has a rising prevalence worldwide. Its potential for evolution towards liver cirrhosis and hepatocellular carcinoma, as well as associations with extrahepatic manifestations, represents a double burden for patients and physicians alike. Recently, there has been increasing evidence of the association between NAFLD and a number of endocrinopathies, such as hypothyroidism, polycystic ovarian syndrome (PCOS), hypopituitarism, growth hormone deficiency (GHD), hypogonadism, and hypercortisolism. Definite correlations are supported by clear evidence so far, but further studies are needed in order to completely clarify the pathogenic mechanisms and, especially, to identify therapeutic implications. In this review, we present the main relationships between NAFLD and endocrinopathies, emphasizing the reciprocal causality, evolutive interconnections, and current clinical scenarios of presentations of which the clinicians should be aware.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the most frequent cause of liver disease worldwide, comprising a plethora of conditions, ranging from steatosis to end-stage liver disease. Cardiovascular disease (CVD) has been associated with NAFLD and CVD-related events represent the main cause of death in patients with NAFLD, surpassing liver-related mortality. This association is not surprising as NAFLD has been considered a part of the metabolic syndrome and has been related to numerous CVD risk factors, namely, insulin resistance, abdominal obesity, dyslipidemia, hyperuricemia, chronic kidney disease, and type 2 diabetes. Moreover, both NAFLD and CVD present similar pathophysiological mechanisms, such as increased visceral adiposity, altered lipid metabolism, increased oxidative stress, and systemic inflammation that could explain their association. Whether NAFLD increases the risk for CVD or these diagnostic entities represent distinct manifestations of the metabolic syndrome has not yet been clarified. This review focuses on the relation between NAFLD and the spectrum of CVD, considering the pathophysiological mechanisms, risk factors, current evidence, and future directions.

Nonalcoholic fatty liver disease has become the main concern of hepatologists around the world and the main research topic for identifying effective and safe therapy. Advances in the treatment of chronic viral hepatitis in recent years have opened the way towards reducing mortality in patients with chronic liver disease. This goal has not yet been reached, as the burden of chronic liver disease remains a future major health problem as the incidence of the nonalcoholic fatty liver disease continues to rise. The proportion of patients with liver cirrhosis and those with hepatocellular carcinoma due to nonalcoholic liver disease on the liver transplant waiting list has increased in the last years. The upward trend in the incidence and prevalence of the disease in recent decades raises concern over a possible global epidemic, especially as the disease is still underestimated and underdiagnosed. Chronic kidney disease presented an increase in incidence and prevalence during the last years, and it has been associated not only with increased morbidity and mortality but also with high costs for the health system. During the last decade, several studies have shown the association between nonalcoholic fatty disease and chronic kidney disease, two major worldwide health problems.

Worldwide, the leading cause of chronic liver disease is represented by nonalcoholic fatty liver disease (NAFLD) which has now become a global epidemic of the 21st century, affecting 1 in 4 adults, and which appears to be associated with the steadily increasing rates of metabolic syndrome and its components (obesity, type 2 diabetes mellitus (T2DM), and dyslipidemia). NAFLD has been reported to be associated with extrahepatic manifestations such as cardiovascular disease, T2DM, chronic kidney disease, extrahepatic malignancies (e.g., colorectal cancer), endocrine diseases (e.g., hypothyroidism, polycystic ovarian syndrome, psoriasis, and osteoporosis), obstructive sleep apnea, and iron overload. The prevalence of NAFLD is very high, affecting 25–30% of the world population and encloses two steps: (1) nonalcoholic fatty liver (NAFL), which includes steatosis only, and (2) nonalcoholic steatohepatitis (NASH) defined by the presence of steatosis and inflammation with hepatocyte ballooning, with or without fibrosis which can progress to liver fibrosis, hepatocellular carcinoma, and liver transplantation. Current data define a more complex relationship between NAFLD and T2DM than was previously believed, underlining a bidirectional and mutual association between the two entities. This review aims to summarize the current literature regarding the incidence of T2DM among patients with NAFLD and also the prevalence of NAFLD in T2DM patients, highlighting the recent key studies. Clinicians should screen, diagnose, and treat T2DM in patients with NAFLD in order to avoid short- and long-term complications.