Interaction between periodontitis and liver diseases

Abstract

Periodontitis is an oral disease that is highly prevalent worldwide, with a prevalence of 30-50% of the population in developed countries, but only ~10% present with severe forms. It is also estimated that periodontitis results in worldwide productivity losses amounting to ~54 billion USD yearly. In addition to the damage it causes to oral health, periodontitis also affects other types of disease. Numerous studies have confirmed the association between periodontitis and systemic diseases, such as diabetes, respiratory disease, osteoporosis and cardiovascular disease. Increasing evidence also indicated that periodontitis may participate in the progression of liver diseases, such as non-alcoholic fatty liver disease, cirrhosis and hepatocellular carcinoma, as well as affecting liver transplantation. However, to the best of our knowledge, there are currently no reviews elaborating upon the possible links between periodontitis and liver diseases. Therefore, the current review summarizes the human trials and animal experiments that have been conducted to investigate the correlation between periodontitis and liver diseases. Furthermore, in the present review, certain mechanisms that have been postulated to be responsible for the role of periodontitis in liver diseases (such as bacteria, pro-inflammatory mediators and oxidative stress) are considered. The aim of the review is to introduce the hypothesis that periodontitis may be important in the progression of liver disease, thus providing dentists and physicians with an improved understanding of this issue.

Keywords: bacteria; cirrhosis; hepatocellular carcinoma; liver transplantation; non-alcoholic fatty liver disease; periodontitis.

Figure 1.

Periodontitis and liver disease. Periodontitis elevates ALT and GGT levels in patients with NAFLD. LC patients exhibit greater clinical attachment loss while the possible effect of periodontitis on LC has not, to the best of our knowledge, been established. HCC patients with periodontitis are associated with higher JIS scores than those with a healthy periodontal status. LT patients with periodontitis require LT after a shorter period and have a lower MELD score resulting in fewer tooth extractions. NAFLD, LC, HCC, and LT patients have poorer periodontal status than general population. ALT, alanine transaminase; GGT, γ-glutamyl transferase; NAFLD, non-alcoholic fatty liver disease; LC, liver cirrhosis; HCC, hepatocellular carcinoma; JIS, Japan integrated staging; LT, liver transplantation; MELD, Model for End-Stage Liver Disease.

Figure 2.

Role of periodontitis in liver inflammation. During periodontitis, periodontal tissue produces inflammatory cytokines and those inflammatory cytokines, along with other periodontal pathogens (such as periodontal bacteria and their components) translocate to the liver via blood circulation. LPSs released by periodontal bacteria stimulate Kupffer cells to generate cytokines by binding to TLR4 and TLR2, LPSs also stimulate the expression of co-stimulatory molecules CD80/CD86 by binding to TLR4. In addition, LPSs activate T-cells to generate cytokines. Peptidoglycans stimulate macrophages to generate cytokines, by recognizing specific receptors, and activate immune cells by binding to TLR2 receptors. Periodontitis-induced HSP60 stimulates T-cells to generate pro-inflammatory mediators. Periodontitis raises NOX4 and MDA, and lowers glutathione, catalase and selenium levels, which leads to the upregulation of ROS. The periodontal bacteria that translocates to the gut alters the gut microflora and contributes to gut-liver axis malfunction. LPS, lipopolysaccharide; TLR, Toll-like receptor; CD, cluster of differentiation; HSP, heat shock protein; NADPH, nicotinamide adenine dinucleotide phosphate; NOX, NADPH oxidase; MDA, malondialdehyde; ROS, reactive oxygen species; NK-cell, naturel killer cell; IL, interleukin; TNF, tumor necrosis factor; MCP-5, monocyte chemotactic protein 5; MIP, macrophage inflammatory protein; INF, interferon; NO, nitric oxide.