Cannabinoids are a group of compounds acting primarily via CB1 and CB2 receptors. The expression of cannabinoid receptors in normal liver is low or absent. However, many reports have proven up-regulation of the expression of CB1 and CB2 receptors in hepatic myofibroblasts and vascular endothelial cells, as well as increased concentration of endocannabinoids in liver in the course of chronic progressive liver diseases. It has been shown that CB1 receptor signalling exerts profibrogenic and proinflammatory effects in liver tissue, primarily due to the stimulation of hepatic stellate cells, whereas the activation of CB2 receptors inhibits or even reverses liver fibrogenesis. Similarly, CB1 receptor stimulation contributes to progression of liver steatosis. In end-stage liver disease, the endocannabinoid system has been shown to contribute to hepatic encephalopathy and vascular effects, such as portal hypertension, splanchnic vasodilatation, relative peripheral hypotension and probably cirrhotic cardiomyopathy. So far, available evidence is based on cellular cultures or animal models. Clinical data on the effects of cannabinoids in chronic liver diseases are limited. However, recent studies have shown the contribution of cannabis smoking to the progression of liver fibrosis and steatosis. Moreover, controlling CB1 or CB2 signalling appears to be an attractive target in managing liver diseases.

Hepatitis C virus (HCV) infection affects 180 million people worldwide with the predominant prevalence being infection with genotype 1, followed by genotypes 2 and 3. Standard anti-HCV therapy currently aims to enhance natural immune responses to the virus, whereas new therapeutic concepts directly target HCV RNA and viral enzymes or influence host-virus interactions. Novel treatment options now in development are focused on inhibitors of HCVspecific enzymes, NS3 protease and NS5B polymerase. These agents acting in concert represent the concept of specifically targeted antiviral therapy for HCV (STAT-C). STAT-C is an attractive strategy in which the main goal is to increase the effectiveness of antiviral responses across all genotypes, with shorter treatment duration and better tolerability. However, the emergence of resistant mutations that limit the use of these compounds in monotherapy complicates the regimens. Thus, a predictable scenario for HCV treatment in the future will be combinations of drugs with distinct mechanisms of action. For now, it seems that interferon will remain a fundamental component of any new anti-HCV therapeutic regimens in the near future; therefore, there is pressure to develop forms of interferon that are more effective, less toxic, and more convenient than pegylated interferon.

In coming years, we can expect that triple therapy becomes a standard medication, and treatment without interferon and/or ribavirin becomes a new studied therapeutic scenario.

These findings indicate that there is an increased susceptibility of PBMC to apoptosis, which can be attributed to the constant contact of leucocytes with the inflamed liver tissue, or from direct HCV influence.