• acute-on- chronic liver failure
• antimicrobial resistance
• antimicrobial resistance genes
• decompensated cirrhosis
• enterotype
• gut microbiome
• metagenomic sequencing
• oral microbiome
• resistome
• resistotypes
• salivatype
• sepsis
• virulence factors

• Humans
• Gastrointestinal Microbiome/physiology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/complications
• Male
• Virulence Factors
• Female
• Middle Aged
• Saliva/microbiology
• Aged
• Mouth/microbiology
• Adult
• Drug Resistance, Bacterial

• Bile Acids and Salts
• Cirrhosis
• Diet, Food, and Nutrition
• Fibrosis
• Liver Cirrhosis, Alcoholic
• MASLD
• liver transplantation

• Fondo Nacional de Desarrollo Científico y Tecnológico

• esophageal and gastric varices
• gastrointestinal microbiome
• liver cirrhosis
• non‐absorbable antibiotics
• portal hypertension

• Humans
• Rifaximin/therapeutic use
• Male
• Middle Aged
• Female
• Pilot Projects
• Liver Cirrhosis/complications
• Liver Cirrhosis/microbiology
• Esophageal and Gastric Varices/etiology
• Gastrointestinal Microbiome/drug effects
• Gastrointestinal Hemorrhage/etiology
• Gastrointestinal Hemorrhage/prevention & control
• Aged
• Adult
• Hepatic Encephalopathy/etiology
• Hepatic Encephalopathy/drug therapy
• Treatment Outcome
• Stomach/microbiology

• 2016ZSLC08 Fund of Clinical Research of Zhongshan Hospital, Fudan University
• 19411970200 Innovation Fund of Science and Technology Commission of Shanghai Municipality
• 19YF1406500 Shanghai Sailing Program, Science and Technology Commission of Shanghai Municipality

• hepatic encephalopathy
• immune dysfunction
• microbiome
• oral-gut-liver axis
• dental access
• nutrition
• periodontitis
• infections

• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Oral Health
• Health Status Disparities
• Healthcare Disparities
• Risk Factors

• I01 CX001076 CSRD VA
• I01 CX002472 CSRD VA
• R01 AA029398 NIAAA NIH HHS

• acute rejection
• infection foci
• liver transplantation
• oral disease
• oral health

• Eradicated Hepatitis C
• Frailty
• Minimal Hepatic Encephalopathy
• North American Consortium for Study of End-stage Liver Disease
• Periodontitis

• Male
• Humans
• Female
• Hepatic Encephalopathy/epidemiology
• Hepatic Encephalopathy/etiology
• End Stage Liver Disease/complications
• Frailty/complications
• Frailty/epidemiology
• Prospective Studies
• Cohort Studies
• Outpatients
• Oral Health
• Ascites
• Severity of Illness Index
• Liver Cirrhosis/complications
• Hospitalization

• I01 CX001076 CSRD VA
• R01 AA029398 NIAAA NIH HHS
• P30 DK034989 NIDDK NIH HHS
• I01 CX002472 CSRD VA
• R01 HS025412 AHRQ HHS

• Dysbiosis
• Metabolic syndrome
• Microbiota
• Nonalcoholic fatty liver disease
• Periodontal disease
• Probiotics

• Animals
• Dysbiosis/microbiology
• Fibrosis
• Inflammation/pathology
• Liver/pathology
• Metabolic Syndrome/complications
• Microbiota
• Non-alcoholic Fatty Liver Disease/pathology
• Periodontitis/therapy
• Periodontitis/complications
• Periodontitis/metabolism
• Intestines

• R01 DE025225 NIDCR NIH HHS

• bacteraemia
• peritonitis
• spontaneous

There is a higher incidence rate of upper gastrointestinal cancer in those with liver cirrhosis. The contributing factors include gastric ulcers, congestive gastropathy, zinc deficiency, alcohol drinking, tobacco use and gut microbiota. Most of the de novo malignancies that develop after liver transplantation for cirrhotic patients are upper gastrointestinal cancers. The surgical risk of upper gastrointestinal cancers in cirrhotic patients with advanced liver cirrhosis is higher.

The extended scope of upper gastrointestinal cancer can include esophageal cancer, gastric cancer and pancreatic cancer. A higher incidence rate of gastric cancer and esophageal cancer in patients with liver cirrhosis has been reported. It is attributable to four possible causes which exist in cirrhotic patients, including a higher prevalence of gastric ulcers and congestive gastropathy, zinc deficiency, alcohol drinking and tobacco use and coexisting gut microbiota. Helicobacter pylori infection enhances the development of gastric cancer. In addition, Helicobacter pylori, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans also contribute to the development of pancreatic cancer in cirrhotic patients. Cirrhotic patients (especially those with alcoholic liver cirrhosis) who undergo liver transplantation have a higher overall risk of developing de novo malignancies. Most de novo malignancies are upper gastrointestinal malignancies. The prognosis is usually poor. Considering the surgical risk of upper gastrointestinal cancer among those with liver cirrhosis, a radical gastrectomy with D1 or D2 lymph node dissection can be undertaken in Child class A patients. D1 lymph node dissection can be performed in Child class B patients. Endoscopic submucosal dissection for gastric cancer or esophageal cancer can be undertaken safely in selected cirrhotic patients. In Child class C patients, a radical gastrectomy is potentially fatal. Pancreatic radical surgery should be avoided in those with liver cirrhosis with Child class B or a MELD score over 15. The current review focuses on the recent reports on some factors in liver cirrhosis that contribute to the development of upper gastrointestinal cancer. Quitting alcohol drinking and tobacco use is important. How to decrease the risk of the development of gastrointestinal cancer in those with liver cirrhosis remains a challenging problem.

• alcohol and tobacco
• gut microbiota
• liver cirrhosis
• upper gastrointestinal cancer
• zinc

• Case-control study
• Liver cirrhosis
• Peri-implant disease
• Risk factors

• Aged
• Case-Control Studies
• Dental Implants
• Humans
• Liver Cirrhosis/complications
• Liver Cirrhosis/epidemiology
• Male
• Middle Aged
• Peri-Implantitis/epidemiology
• Peri-Implantitis/etiology
• Risk Factors

• grants (#402158/2016-4). Conselho Nacional de Desenvolvimento Científico e Tecnológico

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes.

• Diabetes mellitus
• Inflammatory cytokines
• Liver cirrhosis
• Obesity
• Periodontitis

Periodontal disease, a chronic inflammatory disease of the periodontal tissues, is not only a major cause of tooth loss, but it is also known to exacerbate/be associated with various metabolic disorders, such as obesity, diabetes, dyslipidemia, and cardiovascular disease. Recently, growing evidence has suggested that periodontal disease has adverse effects on the pathophysiology of liver disease. In particular, nonalcoholic fatty liver disease, a hepatic manifestation of metabolic syndrome, has been associated with periodontal disease. Nonalcoholic fatty liver disease is characterized by hepatic fat deposition in the absence of a habitual drinking history, viral infections, or autoimmune diseases. A subset of nonalcoholic fatty liver diseases can develop into more severe and progressive forms, namely nonalcoholic steatohepatitis. The latter can lead to cirrhosis and hepatocellular carcinoma, which are end‐stage liver diseases. Extensive research has provided plausible mechanisms to explain how periodontal disease can negatively affect nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, namely via hematogenous or enteral routes. During periodontitis, the liver is under constant exposure to various pathogenic factors that diffuse systemically from the oral cavity, such as bacteria and their by‐products, inflammatory cytokines, and reactive oxygen species, and these can be involved in disease promotion of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Also, gut microbiome dysbiosis induced by enteral translocation of periodontopathic bacteria may impair gut wall barrier function and promote the transfer of hepatotoxins and enterobacteria to the liver through the enterohepatic circulation. Moreover, in a population with metabolic syndrome, the interaction between periodontitis and systemic conditions related to insulin resistance further strengthens the association with nonalcoholic fatty liver disease. However, most of the pathologic links between periodontitis and nonalcoholic fatty liver disease in humans are provided by epidemiologic observational studies, with the causal relationship not yet being established. Several systematic and meta‐analysis studies also show conflicting results. In addition, the effect of periodontal treatment on nonalcoholic fatty liver disease has hardly been studied. Despite these limitations, the global burden of periodontal disease combined with the recent nonalcoholic fatty liver disease epidemic has important clinical and public health implications. Emerging evidence suggests an association between periodontal disease and liver diseases, and thus we propose the term periodontal disease–related nonalcoholic fatty liver disease or periodontal disease–related nonalcoholic steatohepatitis. Continued efforts in this area will pave the way for new diagnostic and therapeutic approaches based on a periodontologic viewpoint to address this life‐threatening liver disease.

• NAFLD
• NASH
• gut microbial dysbiosis
• metabolic syndrome
• obesity
• periodontal disease
• periodontopathic bacteria
• systemic inflammation

• DMFT index
• dental calculus
• liver transplantation
• oral hygiene
• panoramic radiography

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.

• liver disease
• oral infections
• periodontitis
• saliva
• salivary biomarkers
• teeth

• cirrhosis
• disease course
• mortality
• oral diseases
• oral health

• A.P. Møller og Hustru Chastine Mc‐Kinney Møllers Fond til almene Formaal
• Aarhus Universitetshospital
• Novo Nordisk UK Research Foundation

Oro-dental diseases are prevalent in chronic liver failure (CLF) patients. The aim of this study was to evaluate the quality of life associated with oral health in candidates for liver transplant surgery.

The demographic information of 105 end-stage liver cirrhotic patients was collected. All patients were ordered a panoramic view for pretransplant dental evaluation. The DMFT (decayed-missing-filled tooth) index was calculated for dental examination. The model for end-stage liver disease (MELD) was used for the severity of liver disease. The OHIP-14 (Oral Health Impact Profile) questionnaire and GOHAI (Geriatric Oral Health Assessment Index) questionnaire were applied to evaluate the impact of oral disease on the quality of life.

A total of 79 patients thoroughly completed the questionnaires; 79.7% were male, 32.9% were over 50, and 25.3% were less than 30 years old. Further, 12.7% smoked, 2.5% were illiterate, 64.6% had not finished school, and 10.1% had university degrees. Almost half of the cirrhotic patients were suffering from the disease for more than 3 years. Most complaints reported by the patients as “very often” were becoming self-conscious (13.9%) and being uncomfortable when eating any foods (13.9%) followed by feeling tense (12.8%). There was no significant difference between gender, smoking, age, and MELD score based on quality of life (OHIP and GOHAI) (P > 0.05). The level of education (P = 0.020), duration of disease (P = 0.017), and DMFT index (P = 0.039) had a significant impact on oral health-related quality of life in CLF patients. An inverse relationship was seen between the DMFT index and the quality of life.

Oral health has a high impact on the quality of life of cirrhotic patients. The psychological dimension of oral health is the most debilitating factor affecting the quality of life. This shows the importance of professional oral care, oral health, and self-care education in this group of patients.

Non-alcoholic steatohepatitis (NASH) is a severe state of non-alcoholic fatty liver disease (NAFLD), which is pathologically characterised by steatosis, hepatocyte ballooning, and lobular inflammation. Host–microbial interaction has gained attention as one of the risk factors for NASH. Recently, cnm-gene positive Streptococcus mutans expressing cell surface collagen-binding protein, Cnm (cnm-positive S. mutans), was shown to aggravate NASH in model mice. Here, we assessed the detection rate of cnm-positive S. mutans in oral samples from patients with NASH among NAFLD.

This single hospital cohort study included 41 patients with NAFLD. NASH was diagnosed histologically or by clinical score. The prevalence of cnm-positive S. mutans, oral hygiene and blood tests, including liver enzymes, adipocytokines and inflammatory and fibrosis markers, were assessed in biopsy-proven or clinically suspected NASH among NAFLD.

Prevalence of cnm-positive S. mutans was significantly higher in patients with NASH than patients without NASH (OR 3.8; 95% CI 1.02 to 15.5). The cnm-positive S. mutans was related to decreased numbers of naturally remaining teeth and increased type IV collagen 7S level (median (IQR) 10.0 (5.0–17.5) vs 20.0 (5.0–25.0), p=0.06; 5.1 (4.0–7.9) vs 4.4 (3.7–5.3), p=0.13, respectively).

Prevalence of cnm-positive S. mutans in the oral cavity could be related to fibrosis of NASH among NAFLD.

• bacterial infection
• infectious disease
• nonalcoholic steatohepatitis

• cirrhosis
• periodontal disease
• periodontitis

• Anti-Bacterial Agents
• Antibiotic Prophylaxis
• Female
• Humans
• Liver Transplantation
• Male
• Middle Aged
• Retrospective Studies
• Tooth Extraction/adverse effects

• bacterial translocation
• chronic liver disease
• mortality
• oral infection
• periodontal disease

• Dysbiosis
• Fecal Microbial Transplant
• Hepatic Encephalopathy
• Oral
• Outcomes

• dysbiosis
• inflammatory mediators
• liver cirrhosis
• oral microbiota
• pancreatic cancer
• probiotics
• risk

• cognition
• hepatic encephalopathy
• inflammation
• microbiota
• quality of life

• Adult
• Aged
• Dysbiosis/epidemiology
• Female
• Gingivitis/epidemiology
• Gingivitis/therapy
• Humans
• Liver Cirrhosis/epidemiology
• Male
• Middle Aged
• Oral Health
• Periodontics

• I01 CX001076 CSRD VA
• R01 DE025037 NIDCR NIH HHS
• R21 TR002024 NCATS NIH HHS
• R21 TR002024 NCATS NIH HHS

Cirrhosis is an increasing cause of morbidity and mortality. Recent studies are trying to clarify the role of microbiome in clinical exacerbation of patients with decompensated cirrhosis. Nowadays, it is accepted that patients with cirrhosis have altered salivary and enteric microbiome, characterized by the presence of dysbiosis. This altered microbiome along with small bowel bacterial overgrowth, through translocation across the gut, is associated with the development of decompensating complications. Studies have analyzed the correlation of certain bacterial families with the development of hepatic encephalopathy in cirrhotics. In general, stool and saliva dysbiosis with reduction of autochthonous bacteria in patients with cirrhosis incites changes in bacterial defenses and higher risk for bacterial infections, such as spontaneous bacterial peritonitis, and sepsis. Gut microbiome has even been associated with oncogenic pathways and under circumstances might promote the development of hepatocarcinogenesis. Lately, the existence of the oral-gut-liver axis has been related with the development of decompensating events. This link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that allows direct translocation of bacteria from the oral cavity to the systemic circulation. Overall, the contribution of the microbiome to pathogenesis becomes more pronounced with progressive disease and therefore may represent an important therapeutic target in the management of cirrhosis.

• Microbiome
• Dysbiosis
• Oral-gut-liver axis
• Hepatic encephalopathy
• Decompensated cirrhosis
• Liver carcinoma

• Disease Progression
• Dysbiosis/microbiology
• Dysbiosis/physiopathology
• Gastrointestinal Microbiome/physiology
• Hepatic Encephalopathy/microbiology
• Hepatic Encephalopathy/physiopathology
• Humans
• Intestines/microbiology
• Liver/microbiology
• Liver/physiopathology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/physiopathology
• Peritonitis/epidemiology
• Peritonitis/immunology
• Peritonitis/microbiology
• Prevalence
• Sepsis/epidemiology
• Sepsis/immunology
• Sepsis/microbiology

• polymerase chain reaction
• 16s ribosomal rna gene
• ascites
• spontaneous bacterial peritonitis
• bacterial translocation

• Ascitic Fluid/microbiology
• Bacteria/genetics
• DNA, Bacterial/genetics
• DNA, Ribosomal/genetics
• Female
• Genome, Bacterial/genetics
• Humans
• Liver Cirrhosis/microbiology
• Male
• Polymerase Chain Reaction/methods
• RNA, Ribosomal, 16S/genetics

Liver cirrhosis is a severe disease with major impact on the overall health of the patient including poor oral health. Lately, there has been increasing focus on oral diseases as cirrhosis-related complications due to the potential impact on systemic health and ultimately mortality. Periodontitis is one of the most common oral diseases in cirrhosis patients. However, no studies have investigated the composition of the subgingival microbiome in patients suffering from periodontitis and liver cirrhosis. We analysed the subgingival microbiome in 21 patients with periodontitis and cirrhosis using long-reads Illumina sequencing. The subgingival microbiota was dominated by bacteria belonging to the Firmicutes phylum and to a lesser extend the Actinobacteria and Bacteroidetes phyla. Bacteria usually considered periodontal pathogens, like Porhyromonas ginigivalis, Tannerella forsythia, Treponema denticola, generally showed low abundancy. Comparing the microbiota in our patients with that of periodontitis patients and healthy controls of three other studies revealed that the periodontitis-associated subgingival microbiota in cirrhosis patients is composed of a unique microbiota of bacteria not normally associated with periodontitis. We hypothesise that periodontitis in cirrhosis patients is a consequence of dysbiosis due to a compromised immune system that renders commensal bacteria pathogenic.

• Cirrhosis
• Inflammation status
• Nutritional status
• Oral health
• Periodontitis

• Adult
• Aged
• Cross-Sectional Studies
• Dental Care/statistics & numerical data
• Dental Plaque/epidemiology
• Female
• Humans
• Liver Cirrhosis/complications
• Logistic Models
• Male
• Middle Aged
• Nutritional Status
• Periodontal Attachment Loss/epidemiology
• Periodontal Index
• Periodontitis/epidemiology
• Periodontitis/etiology
• Prevalence
• Smoking/adverse effects
• Toothbrushing/statistics & numerical data

• Aarhus Universitetshospital
• Aase og Ejnar Danielsens Fond
• A.P. Møller Foundation
• Central Denmark Region Foundation for Health Research
• Novo Nordisk Foundation

• Dysbiosis/microbiology
• Gastrointestinal Microbiome
• Humans
• Inflammation/microbiology
• Liver/microbiology
• Liver Cirrhosis/microbiology
• Liver Cirrhosis/physiopathology
• Microbiota
• Mouth Mucosa/microbiology

• I01 CX001076 CSRD VA
• R01 DE025037 NIDCR NIH HHS

• Animals
• Bacterial Infections/complications
• Bacterial Infections/diagnosis
• Dental Care
• End Stage Liver Disease/complications
• End Stage Liver Disease/diagnosis
• Humans
• Inflammation
• Liver Cirrhosis/complications
• Liver Cirrhosis/diagnosis
• Mice
• Models, Theoretical
• Periodontitis/complications
• Periodontitis/diagnosis
• Risk Factors

• All-cause mortality
• cirrhosis
• mortality
• oral health
• periodontitis

• Brain-derived neurotrophic factor
• Memory deficit
• Molar loss
• Powder diet

Periapical radiolucency is the radiographic sign of inflammatory bone lesions around the apex of the tooth. We determined the prevalence and predictors of periapical radiolucency in patients with cirrhosis and the association with systemic inflammation status and cirrhosis-related complications.

A total of 110 cirrhosis patients were consecutively enrolled. Periapical radiolucency was defined as the presence of radiolucency or widening of the periapical periodontal ligament space to more than twice the normal width. Predictors of periapical radiolucency and the association with systemic inflammation markers and cirrhosis-related complications were explored by univariable and multivariable logistic regression analyses.

Periapical radiolucency was present in one or more teeth in 46% of the patients. Strong predictors were gross caries (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.43–6.79) and severe periodontitis (OR 3.98, 95% CI 1.04–15.20). Also old age (OR 1.10, 95% CI 1.01–1.19) and smoking (OR 3.24, 95% CI 1.02–17.62) were predictors. However, cirrhosis etiology (alcoholic vs nonalcoholic) or severity (Model of End-Stage Liver Disease score) were not predictors. The patients with periapical radiolucency had higher C-reactive protein (15.8 mg/L vs 8.1 mg/L, P=0.02) and lower albumin contents (25 g/L vs 28 g/L, P=0.04) than those without. Furthermore, the patients with periapical radiolucency had a higher prevalence of cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or variceal bleeding (46% vs 27%, P=0.05).

Periapical radiolucency is often present as an element of poor oral health status and likely has an adverse clinical significance, which should motivate diagnostic and clinical attention to the findings.

• C-reactive protein
• MELD score
• apical periodontitis
• cirrhosis
• inflammation status
• periapical radiolucency

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.

• bacteria
• cirrhosis
• hepatocellular carcinoma
• liver transplantation
• non-alcoholic fatty liver disease
• periodontitis

• Bleeding
• Cirrhosis
• Cirrosis
• Drugs
• Fármacos
• Infecciones
• Infections
• Management
• Manejo
• Odontology
• Odontología
• Sangrado

• Liver cirrhosis
• oral health
• periodontal disease
• periodontitis
• systematic review