Association Between Pre-Transplant Oral Health and Post-Liver Transplant Complications.

Oral disease is linked with systemic inflammation and various systemic conditions, including chronic liver disease. Liver transplantation (LT) candidates often need dental infection focus eradication, and after LT, there is high risk of many inflammation-related complications. We studied whether pre-LT dental status is associated with the occurrence of post-LT complications. This study included 225 adult LT recipients whose teeth were examined and treated before LT, and 40 adult LT recipients who did not have pre-LT dental data available. Data on post-LT complications were collected from the national liver transplant registry and followed up until the end of July 2020. Worse pre-LT dental status was associated with a higher risk of acute rejection post-LT compared to patients with good dental status. Worse dental status was also associated with higher 1-year-post-LT ALT levels and lower albumin levels. In conclusion, poor pre-LT oral health seems to associate with an increased risk of post-LT acute rejection and with elevated ALT levels and decreased albumin levels, suggesting an effect on post-LT liver health. Therefore, prevention and treatment of oral and dental diseases should be promoted early in the course of liver disease.

Persistent oral mucosal lesions preceding diagnosis of Crohn's disease and primary sclerosing cholangitis.

Oral mucosal lesions may persist years before symptoms or diagnosis of inflammatory bowel disease (IBD) and subsequent primary sclerosing cholangitis (PSC). Since a dental practitioner may be the first clinician to suspect IBD with extraintestinal manifestations (EIMs), early referral, and close collaboration with a gastroenterologist are recommended.

Oral Health and Liver Disease: Bidirectional Associations-A Narrative Review.

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.

Generalized infections of putative oral origin in Helsinki University Hospital in 2012 to 2017.

OBJECTIVE: Bacteria entering the bloodstream through oral mucosa cause bacteremia, which can lead to septic or distant infections. The underlying factors and need for dental treatment in patients referred for oral examination because of septic infection were investigated. It was expected that general diseases and poor socioeconomic status of patients would increase the risk of bacteremia. METHOD AND MATERIALS: This descriptive retrospective study included patients (N = 128) referred from medical clinics of the Helsinki University Hospital (HUH), during 2012 to 2017, to the Department of Oral and Maxillofacial Diseases due to bacteremia suspected to be of oral origin. Data were extracted from medical and dental records according to the World Health Organization International Classification of Diseases (ICD-10) for systemic or remote infections. Different groups were formed using modified Skapinakis classification for socioeconomic status (SES), from I (high) to V (low). Underlying medical conditions were retrieved according to McCabe classification: healthy, nonfatal, ultimately fatal, and rapidly fatal diseases. The data were analyzed using the statistical software package SPSS (IBM). RESULTS: Patients were referred most often from the Departments of Infectious Diseases and Internal Medicine. Because of infection, 12 patients needed aortic or mitral valve operations. Many of the patients were intravenous drug users. However, the majority of patients presented McCabe class I, indicating no systemic disease. The main SES was intermediate III. Tooth extraction was the principal mode of treatment. No demographic background variables were identified to explain increase of the risk for bacteremia except that most patients were men with untreated dental problems. CONCLUSIONS: Contrary to the authors' expectation, poor SES and underlying diseases did not seem to link to the outcome. However, untreated dental infections present an evident risk for life-threatening septic complications also in generally healthy individuals.

Triage and urgent dental care for COVID-19 patients in the Hospital District of Helsinki and Uusimaa.

OBJECTIVE: This paper describes and reports the patient-specific characteristics of an urgent dental care clinic for COVID-19 infected, suspected, exposed or quarantined patients from March to December 2020 in the Hospital District of Helsinki and Uusimaa, Finland. MATERIAL AND METHODS: The triage and the treatment protocol were established based on the scientific data. Patient files were evaluated from the hospital district's electronic medical record system. IBM SPSS software was used for statistical analysis. RESULTS: There were 1114 consultations and 257 visits at the clinic. Most of the patients were generally healthy with mean age of 35, had toothache and were suspected to be SARS-CoV-2 positive. Seventeen of the patients received positive tests for COVID-19 infection. The main treatment was tooth extraction, mostly due to caries. Statistically significant differences between COVID-19 infected and other patients occurred in age (45 vs 34 years-of-age, p = .009) and number of teeth (25 vs 28, p = .031). No SARS-CoV-2 infection transmission chains were traced to the clinic. CONCLUSION: During the challenging pandemic time, patients were carefully screened by specialists in clinical dentistry and treated safely and effectively. Patient-specific characteristics revealed no differences between COVID-19 infected and other patients in terms of symptoms or treatment needs.

Salivary Biomarkers and Oral Health in Liver Transplant Recipients, with an Emphasis on Diabetes.

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.

Oral findings and treatment of patients with face transplants in Helsinki.

OBJECTIVES: Oral health and balanced occlusion are important aspects of a well-functioning face transplant. This study describes the oral and dental status, dental management, and sialoendoscopy of the first 2 patients in Helsinki who underwent face transplantations. STUDY DESIGN: Two patients received near-full face transplantations in 2016 and 2018, respectively. The transplanted tissues included a Le Fort type II maxilla, angle-to-angle mandible, all oral mucosa, ventral tongue tissue, and the muscles of the floor of the mouth. Comprehensive oral examinations and all required dental treatment, including follow-up examinations, were performed for both patients after the transplantations. RESULTS: Both patients rehabilitated well, and their quality of life improved. Stable, functioning dentition and occlusion were achieved for both patients. Hyposalivation and dental caries were issues for both patients. Patient 1 also experienced infections in the jaws. Implants were placed in the transplanted jaws of patient 2 with successful osseointegration. CONCLUSIONS: We report successful tooth-bearing face transplantations in 2 patients. Patient selection, particularly regarding oral health, is crucial in avoiding posttransplantation complications. Moreover, the oral and dental status of the donor should be examined by a dentist before transplantation, and regular follow-up dental examinations should be performed after transplantation.

Periodontitis is associated with incident chronic liver disease-A population-based cohort study.

BACKGROUND & AIMS: Chronic liver disease is a major health concern worldwide and the identification of novel modifiable risk factors may benefit subjects at risk. Few studies have analyzed periodontitis as a risk factor for liver complications. We studied whether periodontitis is associated with incident severe liver disease. METHODS: The study comprised 6165 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Survey (BRIF8901) during 2000-2001, a nationally representative cohort. Follow-up was until 2013 for liver-related admissions, liver cancer and mortality from National Hospital Discharge, Finnish Cancer Registry and Causes of Death Register, Statistics Finland. Mild to moderate periodontitis was defined as ≥1 tooth with periodontal pocket ≥4 mm deep, and advanced periodontitis as ≥5 teeth with such pockets. Multiple confounders were considered. RESULTS: A total of 79 subjects experienced a severe liver event during follow-up. When adjusted for age, sex and number of teeth, hazards ratios by Cox regression regarding incident severe liver disease were, for mild to moderate periodontitis, 2.12 (95% CI 0.98-4.58), and, for advanced periodontitis, 3.69 (95% CI 1.79-7.60). These risk estimates remained stable after additionally adjusting for alcohol use, smoking, metabolic risk, serum gamma-glutamyltransferase, dental-care habits, lifestyle and socioeconomic status. Periodontal disease-associated liver risk was accentuated among subjects with non-alcoholic fatty liver disease or heavy alcohol use at baseline. CONCLUSIONS: Periodontitis was associated with incident liver disease in the general population independently of various confounders. As a preventable disease, periodontal disease might present a modifiable risk factor for chronic liver disease.

Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population.

The metabolic syndrome and alcohol risk use are both associated with a high prevalence of hepatic steatosis, but only a minority develop liver failure or liver cancer. Few general population studies have analyzed metabolic predictors of such severe liver complications. We studied which metabolic factors best predict severe liver complications, stratified by alcohol consumption, in 6732 individuals without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analyzed for liver-related admissions, mortality, and liver cancer. Baseline alcohol use and metabolic factors were analyzed by backward stepwise Cox regression analysis. Eighty-four subjects experienced a severe liver event during follow-up. In the final multivariate model, factors predictive of liver events were age (hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.004-1.04), sex (women: HR, 0.55; 95% CI, 0.34-0.91), alcohol use (HR, 1.002; 95% CI, 1.001-1.002), diabetes (HR, 2.73; 95% CI, 1.55-4.81), low-density lipoprotein (LDL) cholesterol (HR, 0.74; 95% CI, 0.58-0.93), and homeostasis model assessment of insulin resistance (HOMA-IR) (HR, 1.01; 95% CI, 1.004-1.02). Among alcohol risk users (≥210 g/week for men, ≥ 140 g/week for women), diabetes (HR, 6.79; 95% CI, 3.18-14.5) was the only significant predictor. Among nonrisk drinkers, age, alcohol use, smoking, waist circumference, low LDL cholesterol and HOMA-IR were significant independent predictors. The total-to-LDL cholesterol ratio and waist circumference-to-body mass index ratio emerged as additional independent predictors. CONCLUSION: Multiple components of the metabolic syndrome independently affected the risk for severe liver disease. Alcohol was significant even when average alcohol consumption was within the limits currently defining nonalcoholic fatty liver disease. (Hepatology 2018;67:2141-2149).

Binge drinking and the risk of liver events: A population-based cohort study.

BACKGROUND & AIMS: Binge drinking or heavy episodic drinking is increasingly prevalent, but the health effects are incompletely understood. We investigated whether binge drinking increases the risk for liver disease above and beyond the risk due to average alcohol consumption. METHODS: 6366 subjects without baseline liver disease who participated in the Finnish population-based Health 2000 Study (2000-2001), a nationally representative cohort. Follow-up data from national registers until 2013 were analysed for liver-related admissions, mortality and liver cancer. Binge drinking (≥5 drinks per occasion, standard drink 12 g ethanol) was categorised as weekly, monthly, or as less often or none. Multiple confounders were considered. RESULTS: Eighty-four subjects developed decompensated liver disease. Binge drinking frequency showed a direct association with liver-disease risk after adjustment for average daily alcohol intake and age. After adjustment, the hazard ratios (HRs) for weekly and monthly binge drinking were 3.45 (P=.001) and 2.26 (P=.007) and were higher after excluding regular heavy drinkers. The HR for weekly binging was 6.82 (P=.02) in women; 2.34 (P=.03) in men; and 4.29 (P=.001) in subjects with the metabolic syndrome. Weekly binge drinking and the metabolic syndrome produced supra-additive increases in the risk of decompensated liver disease. Weekly, and to a lesser extent monthly, binging retained significance in sequential multivariate models that additionally adjusted for beverage preference and lifestyle, metabolic, and socioeconomic factors. CONCLUSIONS: Binge drinking is associated with an increased risk for liver disease independently of average alcohol intake and confounders. The rising prevalence of binge drinking and the metabolic syndrome is particularly concerning.

Oral surgery in liver transplant candidates: a retrospective study on delayed bleeding and other complications.

OBJECTIVE: Untreated dental infections pose a threat for immunocompromised liver transplant (LT) recipients. Therefore, pretransplant dental evaluations are recommended. However, risk of bleeding should be considered among patients with end-stage liver disease, and prophylactic blood transfusions may be used to prevent bleeding. We performed a retrospective study of the incidence of and risk factors for oral surgery-related bleeding in candidates for LT and hypothesized that complications may occur despite preoperative and perioperative hemostatic actions. STUDY DESIGN: One hundred thirty-four patients who had tooth extractions performed by oral and maxillofacial surgeons before LT were studied. The primary endpoint was bleeding between 24 hours and 2 weeks after extraction. Bleeding risk was analyzed by preoperative platelet (PLT) count and international normalized ratio (INR). Invasiveness of procedures, severity of liver disease, PLT, INR, prophylactic transfusions of PLT, fresh frozen plasma, and tranexamic acid (TA) were included in univariate and multivariate logistic regression analyses to further assess risk. RESULTS: Twelve patients exhibited minor bleeding; four despite PLT >100 × 10(9)/L and INR <1.5. Increased bleeding associated with INR and prophylactic transfusions by univariate analysis; by multivariate analyses, prophylactic TA (odds ratio [OR] = 8.0; 95% confidence interval [CI] 1.7-37.0), and PLT (OR = 8.3; 95% CI 1.1-62.7) remained significant. CONCLUSIONS: Most extractions were safe, but prophylactic transfusions did not ensure adequate hemostasis. Local hemostatic measures and close follow-up are warranted.

Association between dental infections and the clinical course of chronic liver disease.

AIM: Dental infections are implicated in several systemic diseases due to bacteremia and pro-inflammatory effects, but their possible role in liver disease is unclear. METHODS: We retrospectively analyzed the clinical course of liver disease in relation to dental health among 116 patients with liver cirrhosis who underwent dental examination before liver transplantation. RESULTS: The need for multiple tooth extractions, a surrogate marker of dental infections, was associated with reduced time from diagnosis of liver disease to the need for liver transplantation (P = 0.02). The association was independent of age, sex, liver disease etiology and Model for End-Stage Liver Disease (MELD) score (P = 0.04). Among 38 patients with accurate laboratory follow-up data, the number of tooth extractions correlated with the change in MELD score during the year preceding dental examination (r = 0.43, P = 0.03). Spontaneous bacterial peritonitis caused by Streptococcus viridans occurred only among patients with multiple dental infections. CONCLUSION: Dental infections may influence the clinical course of liver disease, but prospective studies are needed.

Oral mucosal health in liver transplant recipients and controls.

Immunosuppressive drugs and other medications may predispose patients to oral diseases. Data on oral mucosal health in recipients of liver transplantation (LT) are limited. We, therefore, recruited 84 LT recipients (64 with chronic liver disease and 20 with acute liver failure) for clinical oral examinations in a cross-sectional, case-control study. Their oral health had been clinically examined before transplantation. The prevalence of oral mucosal lesions (OMLs) was assessed in groups with different etiologies of liver disease and in groups with different immunosuppressive medications, and these groups were compared to controls selected from a nationwide survey in Finland (n = 252). Risk factors for OMLs were evaluated with logistic regression. OMLs were more frequent in LT recipients versus controls (43% versus 15%, P < 0.001), and the use of steroids raised the prevalence to 53%. Drug-induced gingival overgrowth was the single most common type of lesion, and its prevalence was significantly higher for patients using cyclosporine A (CSA; 29%) versus patients using tacrolimus (TAC; 5%, P = 0.007); the prevalence was even higher with the simultaneous use of calcium channel blockers and CSA (47%) or TAC (8%, P = 0.002). Lesions with malignant potential such as drug-induced lichenoid reactions, oral lichen planus-like lesions, leukoplakias, and ulcers occurred in 13% of the patients with chronic liver disease and in 6% of the controls. Every third patient with chronic liver disease had reduced salivary flow, and more than half of all patients were positive for Candida; this risk was higher with steroids. In conclusion, the high frequency of OMLs among LT recipients can be explained not only by immunosuppressive drugs but also by other medications. Because dry mouth affects oral health and OMLs may have the potential for malignant transformation, annual oral examinations are indicated.

Self-reported oral symptoms and signs in liver transplant recipients and a control population.

Recipients of liver transplantation (LT) receive lifelong immunosuppression, which causes side effects. We investigated self-reported oral symptoms and associated risk factors with the following hypothesis: symptoms and signs would differ between LT recipients of different etiology groups and also between LT recipients and a control population. Eighty-four LT recipients (64 with chronic liver disease and 20 with acute liver disease) were recruited for clinical oral and salivary examinations (median follow-up = 5.7 years). A structured questionnaire was used to record subjective oral symptoms. Matched controls (n = 252) came from the National Finnish Health 2000 survey. The prevalence of symptoms was compared between the groups, and the risk factors for oral symptoms were analyzed. Xerostomia was prevalent in 48.4% of the chronic LT recipients and in 42.1% of the acute LT recipients. This subjective feeling of dry mouth was only partly linked to objectively measured hyposalivation. The chronic transplant recipients had significantly lower unstimulated salivary flow rates than the acute transplant recipients (0.34 ± 0.31 versus 0.61 ± 0.49 mL/minute, P = 0.005). Among the chronic transplant recipients, hyposalivation with unstimulated salivary flow was associated with fewer teeth (17.7 ± 8.2 versus 21.9 ± 8.4, P = 0.047) and more dentures (33.3% versus 12.2%, P = not significant). The chronic patients reported significantly more dysphagia than their controls (23.4% versus 11.5%, P = 0.02). Increases in the number of medications increased the symptoms in all groups. In conclusion, dysphagia was significantly more prevalent among the chronic LT recipients versus the controls. The number of medications was a risk factor for dry mouth-related symptoms for both the LT recipients and the controls. The chronic transplant recipients presented with lower salivary flow rates than the acute transplant recipients. Hyposalivation correlated with generally worse oral health among the chronic transplant recipients. These differences between the chronic and acute LT recipients may have been due to differences in their medical conditions due to the different etiologies.

Effect of the aetiology and severity of liver disease on oral health and dental treatment prior to transplantation.

Elimination of dental infection foci has been recommended before liver transplantation (LT) because lifelong immunosuppression may predispose to infection spread. Association between pre-LT oral health and the aetiology and severity of chronic liver disease (CLD) was investigated retrospectively. A total of 212 adult patients (median age 51.1) who had received LT during 2000-2006 in Finland were included. Their oral health had been pre-operatively examined. Patients were divided into seven different CLD groups. Common indications for LT were primary sclerosing cholangitis (PSC 25.5%), alcohol cirrhosis (ALCI 17.5%) and primary biliary cirrhosis (PBC 14.6%). Patients were also categorized by the Model for End stage Liver Disease (MELD) scoring system. Medical, dental and panoramic jaw x-ray data were analysed between groups. PBC patients had the lowest number of teeth with significant difference to PSC patients (19.7 vs. 25.6, P < 0.005, anova, t-test). ALCI patients had the highest number of tooth extractions with significant difference in comparison to PSC patients (5.6 vs. 2.5, P < 0.005). Lower MELD score resulted in fewer tooth extractions but after adjusting for several confounding factors, age was the most important factor associated with extractions (P < 0.005). The aetiology of CLD associated with the oral health status and there was a tendency towards worse dental health with higher MELD scores.