Hepatitis B virus (HBV) infection has shown an intermediate or high endemicity level in low-income countries over the last five decades. In recent years, however, the incidence of acute hepatitis B and the prevalence of hepatitis B surface antigen chronic carriers have decreased in several countries because of the HBV universal vaccination programs started in the nineties. Some countries, however, are still unable to implement these programs, particularly in their hyperendemic rural areas. The diffusion of HBV infection is still wide in several low-income countries where the prevention, management and treatment of HBV infection are a heavy burden for the governments and healthcare authorities. Of note, the information on the HBV epidemiology is scanty in numerous eastern European and Latin-American countries. The studies on molecular epidemiology performed in some countries provide an important contribution for a more comprehensive knowledge of HBV epidemiology, and phylogenetic studies provide information on the impact of recent and older migratory flows.

The liver has a central role in regulating inflammation by its capacity to secrete a number of proteins that control both local and systemic inflammatory responses. Chronic inflammation or an exaggerated inflammatory response can produce detrimental effects on target organs. Chronic hepatitis C virus (HCV) infection causes liver inflammation by complex and not yet well-understood molecular pathways, including direct viral effects and indirect mechanisms involving cytokine pathways, oxidative stress and steatosis induction. An increasing body of evidence recognizes the inflammatory response in chronic hepatitis C as pathogenically linked to the development of both liver-limited injury (fibrosis, cirrhosis and hepatocellular carcinoma) and extrahepatic HCV-related diseases (lymphoproliferative disease, atherosclerosis, cardiovascular and brain disease). Defining the complex mechanisms of HCV-induced inflammation could be crucial to determine the global impact of infection, to estimate progression of the disease, and to explore novel therapeutic approaches to avert HCV-related diseases. This review focuses on HCV-related clinical conditions as a result of chronic liver and systemic inflammatory states.

Hepatitis C virus (HCV) infection is considered a systemic disease because of involvement of other organs and tissues concomitantly with liver disease. Among the extrahepatic manifestations, neuropsychiatric disorders have been reported in up to 50% of chronic HCV infected patients. Both the central and peripheral nervous system may be involved with a wide variety of clinical manifestations. Main HCV-associated neurological conditions include cerebrovascular events, encephalopathy, myelitis, encephalomyelitis, and cognitive impairment, whereas “brain fog”, depression, anxiety, and fatigue are at the top of the list of psychiatric disorders. Moreover, HCV infection is known to cause both motor and sensory peripheral neuropathy in the context of mixed cryoglobulinemia, and has also been recently recognized as an independent risk factor for stroke. These extrahepatic manifestations are independent of severity of the underlying chronic liver disease and hepatic encephalopathy. The brain is a suitable site for HCV replication, where the virus may directly exert neurotoxicity; other mechanisms proposed to explain the pathogenesis of neuropsychiatric disorders in chronic HCV infection include derangement of metabolic pathways of infected cells, alterations in neurotransmitter circuits, autoimmune disorders, and cerebral or systemic inflammation. A pathogenic role for HCV is also suggested by improvement of neurological and psychiatric symptoms in patients achieving a sustained virologic response following interferon treatment; however, further ad hoc trials are needed to fully assess the impact of HCV infection and specific antiviral treatments on associated neuropsychiatric disorders.

Hepatitis C virus (HCV) infection represents a major health issue worldwide due to its burden of chronic liver disease and extrahepatic manifestations including cardiovascular diseases, which are associated with excess mortality. Analysis of published studies supports the view that HCV infection should be considered a risk factor for the development of carotid atherosclerosis, heart failure and stroke. In contrast, findings from studies addressing coronary artery disease and HCV have yielded conflicting results. Therefore, meta-analytic reviews and prospective studies are warranted. The pathogenic mechanisms connecting HCV infection, chronic liver disease, and atherogenesis are not completely understood. However, it has been hypothesized that HCV may promote atherogenesis and its complications through several direct and indirect biological mechanisms involving HCV colonization and replication within arterial walls, liver steatosis and fibrosis, enhanced and imbalanced secretion of inflammatory cytokines, oxidative stress, endotoxemia, mixed cryoglobulinemia, perturbed cellular and humoral immunity, hyperhomocysteinemia, hypo-adiponectinaemia, insulin resistance, type 2 diabetes and other components of the metabolic syndrome. Understanding these complex mechanisms is of fundamental importance for the development of novel therapeutic approaches to prevent and to treat vascular complications in patients with chronic HCV infection. Currently, it seems that HCV clearance by interferon and ribavirin treatment significantly reduces non-liver-related mortality; moreover, interferon-based treatment appears to decrease the risk of ischemic stroke.

The aim of this paper is to review and up to date the prevalence of hepatitis C virus (HCV)-associated non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) and their significance in both accelerating progression of HCV-related liver disease and development of HCV-associated extrahepatic diseases. The reported mean prevalence of HCV-related NAFLD was 55%, whereas NASH was reported in 4%–10% of cases. HCV genotype 3 directly induces fatty liver deposition, namely “viral steatosis” and it is associated with the highest prevalence and degree of severity, whereas, HCV non-3 genotype infection showed lower prevalence of steatosis, which is associated with metabolic factors and insulin resistance. The host’s genetic background predisposes him or her to the development of steatosis. HCV’s impairment of lipid and glucose metabolism causes fatty liver accumulation; this seems to be a viral strategy to optimize its life cycle. Irrespective of insulin resistance, HCV-associated NAFLD, in a degree-dependent manner, contributes towards accelerating the liver fibrosis progression and development of hepatocellular carcinoma by inducing liver inflammation and oxidative stress. Furthermore, NAFLD is associated with the presence of metabolic syndrome, type 2 diabetes, and atherosclerosis. In addition, HCV-related “metabolic steatosis” impairs the response rate to interferon-based treatment, whereas it seems that “viral steatosis” may harm the response rate to new oral direct antiviral agents. In conclusion, a high prevalence of NAFLD occurs in HCV infections, which is, at least in part, induced by the virus, and that NAFLD significantly impacts progression of the liver disease, therapeutic response, and some extrahepatic diseases.