Inflammatory status in human hepatic cirrhosis

Abstract

This review focuses on new findings about the inflammatory status involved in the development of human liver cirrhosis induced by the two main causes, hepatitis C virus (HCV) infection and chronic alcohol abuse, avoiding results obtained from animal models. When liver is faced to a persistent and/or intense local damage the maintained inflammatory response gives rise to a progressive replacement of normal hepatic tissue by non-functional fibrotic scar. The imbalance between tissue regeneration and fibrosis will determine the outcome toward health recovery or hepatic cirrhosis. In all cases progression toward liver cirrhosis is caused by a dysregulation of mechanisms that govern the balance between activation/homeostasis of the immune system. Detecting differences between the inflammatory status in HCV-induced vs alcohol-induced cirrhosis could be useful to identify specific targets for preventive and therapeutic intervention in each case. Thus, although survival of patients with alcoholic cirrhosis seems to be similar to that of patients with HCV-related cirrhosis (HCV-C), there are important differences in the altered cellular and molecular mechanisms implicated in the progression toward human liver cirrhosis. The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. On the contrary, the inflammatory status of alcohol-induced cirrhosis is determined by the combined effect of direct hepatotoxicity of ethanol metabolites and increases of the intestinal permeability, allowing bacteria and bacterial products translocation, into the portal circulation, mesenteric lymph nodes and peritoneal cavity. This phenomenon generates a stronger pro-inflammatory response compared with HCV-related cirrhosis. Hence, therapeutic intervention in HCV-related cirrhosis must be mainly focused to counteract HCV-immune system evasion, while in the case of alcohol-induced cirrhosis it must try to break the inflammatory loop established at the gut-mesenteric lymph nodes-peritoneal-systemic axis.

Role of apoptotic hepatocytes in HCV dissemination: regulation by acetaldehyde

“…AB also may induce inflammation by programming liver macrophages (Kupffer cells) toward a proinflammatory phenotype. This, in turn, would promote the uptake of virus by hepatocytes (16) and finally contribute to cirrhosis/HCC development (32). The regulation of a cytokine profile of dendritic cells phagocytosed HCV ϩ AB was reported before (59).…”

Impact of Cirrhosis on Resource Use and Inpatient Complications in Patients Undergoing Total Knee and Hip Arthroplasty

“…Alcohol-related cirrhosis causes a stronger inflammatory response resulting in problems controlling the immune system, compared to viral-related cirrhosis[26]. Among patients who were hospitalized due to complications of cirrhosis, alcohol-related cirrhosis was the predominant cause[27].…”

Physiological potential of cytokines and liver damages

“…[53] Consequently, The predominant features of HCV-C are more related with those that allow viral evasion of the immune defenses, especially although not exclusively, inhibition of interferons secretion, natural killer cells activation and T cell-mediated cytotoxicity. [54] Several researchers have suggested that an adequate T-helper 1 (Th1) response [i.e. high interferon (IFN)-γ secretion by peripheral blood mononuclear cells] may be associated with a protective antiviral immune response, [55] while insufficient systemic Th1 cytokine secretion may be associated with increased viral load and disease progression.…”