INTRODUCTION: Periodontal disease is associated with nonalcoholic fatty liver disease (NAFLD). We evaluated periodontal treatment efficacy in patients with NAFLD and periodontal disease. METHODS: This multicenter, 2-arm, randomized study recruited adult patients with NAFLD and periodontitis, alanine aminotransferase levels ≥40 U/L, and equivalent steatosis grade ≥1. Forty eligible patients (18 men and 22 women) were randomly assigned to 2 groups (scaling and root planning [SRP; n = 20] and tooth brushing [n = 20] groups) stratified by age and sex. The primary and secondary endpoints were changes in alanine aminotransferase levels and serum Porphyromonas gingivalis IgG antibody titers from baseline to 12 weeks, respectively. Efficacy analysis was performed using an intention-to-treat approach (t test). This trial was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000022079). RESULTS: We observed a significantly higher decrease in absolute alanine aminotransferase levels and P. gingivalis IgG antibody titers in the SRP group than in the tooth brushing group (−12 vs 1 U/L; mean difference [δ], −12; 95% confidence interval [CI], −20 to −5; P = 0.002). The decrease in P. gingivalis IgG antibody titer was significantly higher in the SRP group than in the tooth brushing group (FDC381, −1.6 [2.5]; δ, −1.6; 95% CI, −2.7 to −0.4; P = 0.0092; SU63, −1.7 [2.0]; δ, −1.7; 95% CI, −2.7 to −0.7). No life-threatening events or treatment-related deaths occurred. DISCUSSION: Periodontal treatment induced significant short-term and mid-term reductions in liver enzyme levels and antibody titers. Further research is warranted to clearly define SRP efficacy and tolerability in patients with NAFLD and periodontitis.

Background: We report the first protocol for a multicenter, randomized comparison study to compare the efficacies of periodontal scaling and root-planing treatment against that of tooth-brushing treatment for nonalcoholic fatty liver disease (NAFLD) (PERION: PERIOdontal treatment for NAFLD). Nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD, which can progress to cirrhosis and hepatocellular carcinoma. Increased endotoxemia is associated with the progression of NAFLD. Periodontal bacteria possess endotoxins; Porphyromonas gingivalis is well-known as a major pathogenic bacterium in periodontitis, and serum antibody levels for P. gingivalis are high in patients with periodontitis. Several reports have indicated that P. gingivalis is related to NAFLD. This study aims to investigate the effect of periodontal treatment for liver damage, P. gingivalis infection, and endotoxemia on patients with NAFLD. Methods: We will include adult patients (20–85 years old) with NAFLD, alanine aminotransferase (ALT) ≥ 40 IU/L, and equivalent steatosis grade ≥ 1 (target sample size, n = 40 patients; planned number of patients with outcome data, n = 32). Participants will be randomly assigned to one of two groups: a scaling and root-planing group or tooth-brushing as the usual group. The primary outcome will be the change in ALT levels from baseline to 12 weeks; the key secondary outcome will be the change in the serum immunoglobulin G (IgG) antibody titer for P. gingivalis at 12 weeks. Discussion: This study should determine whether periodontal treatment decreases liver damage, P. gingivalis infection, and endotoxemia in patients with NAFLD. Trial registration: University Hospital Medical Information Network (UMIN) Clinical Trials Registry, ID: UMIN000022079.

Background and Objectives: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing worldwide, alongside the epidemic of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Materials and Methods: Forty-one patients with MASH and nineteen with MASH-HCC participated in the study, completing survey questionnaires, undergoing periodontal examinations, and providing samples of saliva, mouth-rinsed water, feces, and peripheral blood. The oral and fecal microbiome profiles were analyzed by 16S ribosomal RNA sequencing. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The genus Fusobacterium had a significantly higher occupancy rate (p = 0.002) in the intestinal microflora of the MASH-HCC group compared to the MASH group. However, Butyricicoccus (p = 0.022) and Roseburia (p < 0.05) had significantly lower occupancy rates. The Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusions: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

A relationship between periodontitis and liver function has been suggested. Indeed, patients with severe periodontal disease have been found to be more prone to liver dysfunction. The periodontal inflammatory surface area (PISA) has been shown to be a useful indicator of periodontal and systemic diseases. However, little information is available regarding whether the PISA is associated with liver function markers, such as gamma-glutamyltransferase (GGT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). This study aimed to clarify relationship between liver function markers, AST, ALT, and GGT, and PISA level in a cross-sectional study. The subjects were recruited between 2018 and 2021 at the Medical and Dental Collaboration Center of Kanagawa Dental College Hospital. A periodontal clinical examination was performed, and the PISA was calculated. Peripheral blood samples were collected, and serum levels of liver function markers were measured. The levels of liver function markers were examined in different values of PISA. Participants with high PISA scores were more likely to have increased GGT levels while AST and ALT were not changed with PISA. Increased GGT was found in 10.8% and 29.4% (p = 0.0056), increased AST in 48.2% and 52.9% (p = 0.62), and increased ALT in 35.2% and 47.0% (p = 0.20) among <300 mm² and ≧300 mm² PISA groups, respectively. It was found that males with a PISA of 300 mm² or higher had an elevated level of serum GGT. In conclusion, elevated GGT was found in the high PISA group, particularly in males, while AST and ALT did not differ by PISA.

Intake of fiber, as well as protein, and lipid preloading help to control postprandial glycemic elevation in people with type 2 diabetes and in healthy individuals. However, there are few studies on the awareness of meal sequence and nutrient intake status that consider oral conditions. This cross-sectional study aimed to determine the effects of meal sequences on nutrient intake status and whether these relationships were related to the number of teeth present. The subjects were recruited from the Medical and Dental Collaboration Center of Kanagawa Dental University Hospital between 2018 and 2021. Medical and dental examinations were performed, and a questionnaire was used to determine whether the diet consisted of vegetables, meat or fish, and carbohydrates in that order. Nutrient intake status was assessed using the brief-type self-administered diet history questionnaire. Data were collected from 238 participants. The group with awareness of meal sequence ingested increased nutrients such as n-3 fatty acids, total dietary fiber, calcium, and vitamin C. Saturated fatty acid intake increased in those with fewer teeth, while it was not significantly related to meal sequence. In conclusion, our results showed that meal sequence was associated with nutrient intake status. In addition, the intake of saturated fatty acids increased when many teeth were lost, regardless of meal sequence.

The incidence of non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC) is increasing annually as the metabolic syndrome factors increase. This study aimed to analyze the involvement of periodontopathic bacteria in NASH-related HCC (NASH-HCC). Questionnaire investigation, periodontal examination, medical examination, and specimen collection (saliva, mouth-rinsed water, and peripheral blood) were performed in 40 patients with NASH and in 20 patients with NASH-HCC. Immunoglobulin (Ig) G antibody titers against Porphyromonas gingivalis (p = 0.031) and Fusobacterium nucleatum (p = 0.003) were significantly higher in the NASH-HCC group than in the NASH group. P. gingivalis and F. nucleatum ratios were higher in the NASH-HCC group than in the NASH group; however, only F. nucleatum ratio was significant (p = 0.009). The Shannon index of salivary bacterial flora was significantly lower in the NASH-HCC group than in the NASH group (p < 0.001). The NASH-HCC group had a significantly lower salivary IgA concentration (p = 0.007) and a slower salivary IgA flow rate (p = 0.003). In all participants, the salivary IgA flow rate and the F. nucleatum ratio showed a significant negative correlation (p = 0.02). Oral P. gingivalis and F. nucleatum were possibly associated with NASH-HCC pathogenesis, and salivary IgA levels were correlated with F. nucleatum.