The latter may explain the synthetic and metabolic dysfunction and the impaired transport of solutes from the sinusoid to hepatocytes in advanced fibrosis and cirrhosis. ECM directly influences the function of surrounding cells through interaction with cell surface receptors, including integrins and nonintegrin matrix receptors (such as discoidin domain receptor 2). It can also indirectly affect cell function via release of soluble cytokines, which in turn are controlled by local metallopro-teinases (for details, see reviews at http://dispatch.mail-list.com/archives/hbv_research, or http://janis7hepc.com/learning_about_liver_fibrosis.htm#Predicting).