Ammonia uptake by transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) polymersomes.

Transmembrane pH gradient poly(isoprene)-block-poly(ethylene glycol) (PI-b-PEG) polymersomes were investigated for their potential use in the detoxification of ammonia, a metabolite that is excessively present in patients suffering from urea cycle disorders and advanced liver diseases, and which causes neurotoxic effects (e.g., hepatic encephalopathy). Polymers varying in PI and PEG block length were synthesized via nitroxide-mediated polymerization and screened for their ability to self-assemble into polymersomes in aqueous media. Ammonia sequestration by the polymersomes was investigated in vitro. While most vesicular systems were able to capture ammonia in simulated intestinal fluids, uptake was lost in partially dehydrated medium mimicking conditions in the colon. Polymeric crosslinking of residual olefinic bonds in the PI block increased polymersome stability, partially preserving the ammonia capture capacity in the simulated colon environment. These more stable vesicular systems hold promise for the chronic oral treatment of hyperammonemia.

Management of Thrombocytopenia in Patients with Chronic Liver Disease.

BACKGROUND: Thrombocytopenia is the most common hematologic complication associated with chronic liver disease (CLD) with important clinical implications. While the mechanisms for thrombocytopenia are multifactorial, platelet sequestration in the spleen and decreased thrombopoietin (TPO) production are the main mechanisms in patients with CLD. AIM: This review outlines the current treatment options for thrombocytopenia in patients with CLD, explores their limitations, and proposes a revised treatment algorithm for the management of thrombocytopenia in this patient group. METHODS: A PubMed search of the literature was undertaken with search terms focused on CLD and thrombocytopenia. RESULTS: Until now, the standard-of-care treatment in these patients has been the use of platelet transfusions either prophylactically or periprocedurally to control bleeding. Treatment options, such as splenic artery embolization and splenectomy, are invasive, and their utility is limited by significant complications. The US Food and Drug Administration recently approved 2 s-generation TPO-receptor agonists, avatrombopag and lusutrombopag, as safe and effective therapies for the treatment of thrombocytopenia in patients with CLD scheduled to undergo a procedure. CONCLUSIONS: The addition of avatrombopag and lusutrombopag offers physicians an alternative to platelet transfusions in patients with CLD who have to undergo medical/dental procedures that could potentially put them at an increased risk of bleeding. There are several other drugs in the research pipeline at various stages of development, including a new class of monoclonal antibodies that can bind to and activate TPO-receptor agonists. The outlook for treatment choices for thrombocytopenia in patients with liver disease is promising.

Immunological profile of teeth with inflammatory periapical disease from chronic liver disease patients.

AIM: To evaluate the mRNA expression levels of the cytokines interferon-γ, tumour necrosis factor-α, interleukin (IL)-1ß, IL-10, IL-6, VEGF, and AGT and the chemokine CCL2/MCP-1 in periapical interstitial fluid associated with root canal infections before and after the reduction of the bacterial load using a cleaning procedure. METHODOLOGY: The case group included 11 patients with chronic liver disease, and the control group included 11 healthy patients. Clinical samples were taken from teeth with pulp necrosis. After cleaning and drying the canal, three paper points were introduced into the root canal and passed through the root apex (2 mm) into the periapical tissues for 1 min. The samples were collected immediately after root canal cleaning and 7 days later to characterize those gene expression levels using real-time PCR. The data were subjected to the Shapiro-Wilk and the Wilcoxon tests. RESULTS: In the control group, significantly increased expression of the pro-inflammatory cytokines IFN-γ and TNF-α was observed in teeth with restrained bacterial loads (day 7) (P < 0.05). Similarly, increased TNF-α expression was found on day 7 in the liver group (P < 0.05). No differences were observed in the expression levels of the IL-1ß, IL-10 and, IL-6, MCP-1/CCL-2 and VEGF between the first collection (day 0) and second collection (day 7), over time in either group. CONCLUSION: Chronic liver disease patients exhibited sufficient immunologic ability showing relatively similar expression levels of cytokines, chemokines and angiogenic factors in periapical samples compared with the responses from no-chronic liver disease patients. The outcomes of this study suggest that liver impairment did not compromise the periapical immune response.

Oral Health Status of Kuwaiti Children with a History of Chronic Liver Disease.

OBJECTIVE: To investigate the oral health status and dental manifestations of children with a history of chronic liver disease (CLD) compared to healthy children. SUBJECTS AND METHODS: Twenty children (15 boys and 5 girls) with a history of CLD were compared to 20 healthy controls matched for age and gender. The clinical examination was carried out by the same dentist. Caries prevalence, using the decayed, missing, and filled primary and permanent teeth indices (dmft/DMFT), was recorded. Developmental enamel defects, plaque scores, and gingival overgrowth were also investigated. RESULTS: No statistically significant differences were found in mean dmft scores for children with a history of CLD (4.9 ± 5.4) and for healthy individuals (3.9 ± 4.5). However, the mean DMFT score was significantly higher (p =0.025) in children with CLD (4.2 ± 4.6) compared to controls (1.7 ± 1.6). The mean decayed teeth parameter (DT) was also significantly higher in children with CLD (p =0.004). All patients with CLD exhibited enamel defects compared to only 33% in the control group (p< 0.05). A higher mean plaque index was observed in children with a history of CLD (p< 0.001). Also, a positive correlation for gingival overgrowth was noted in patients with a history of CLD (p< 0.05). Green staining was evident only in the permanent dentition of 1 child with CLD. CONCLUSION: Children with a history of CLD exhibited a high caries prevalence, high plaque scores, and more enamel defects compared to healthy subjects. Gingival overgrowth is less prevalent among pediatric liver transplant patients on tacrolimus therapy.

Oral mucosa lesions and gingival bleeding can indicate the progression of liver disease in children and adolescents aged two to 18 years.

AIM: This study assessed correlations between systemic disturbances of paediatric chronic liver diseases (CLD) and oral symptoms in subjects aged 2-18 years. METHODS: It was carried out during outpatient appointments at the Children's Memorial Health Institute, Warsaw, Poland, from 2010 to 2015 and comprised 52 CLD patients with a mean age of 12.3 ± 4.6. We also recruited 54 generally healthy controls with a mean age of 12.0 ± 3.7 from the Department of Paediatric Dentistry at the Medical University of Warsaw. The study used various measures, including the Child-Pugh score, which assesses CLD prognosis. We also assessed the causes of liver disease and the medication taken by the patients with CLD. RESULTS: A total of 24 patients received a Child-Pugh score of seven or more points, while 28 patients were awarded five or six points. More severe cases of gingivitis and a greater prevalence of oral lesions were evident in patients suffering from liver disease. Oral candidiasis, telangiectasia, bald tongue, cracked strawberry lip, yellowish-brown gum discoloration, petechiae and gingival bleeding all correlated with the severity of liver dysfunction, coagulopathy, protein, bilirubin and creatinine levels and portal hypertension. CONCLUSION: This study found that oral lesions and gingival bleeding may indicate the progression of liver failure.

[Oral diseases structure in patients with diffuse liver lesions before and after transplantation]. / Osobennosti struktury stomatologicheskikh zabolevanii u patsientov s diffuznymi porazheniiami pecheni do i posle transplantatsii.

Purpose of the study was to identify dental risk factors for complications at the stage of rehabilitation adaptation in patients with diffuse liver lesions. The study included 52 patients with diffuse liver lesions aged 25-55 years, who were divided between two groups of 26 persons with different dental status, depending on the main disease stage of treatment. RESEARCH METHODS: Clinical, x-ray, morphological, analytical, statistical. RESULTS: It has been reliably established that low level of oral hygiene, high intensity and prevalence of caries and its complications (foci of odontogenic infection), inflammatory periodontal diseases joined with severe teeth hyperesthesia, dominate in patients before liver transplantation, which confirms low level of sanitation on stages of preparation for surgical treatment. Chronic odontogenic infection in periodontal tissues with phenomena of epithelial cells dystrophy, candidiasis of the oral mucosa, foci of odontogenic infection, low level of oral hygine, tendency to precancerous diseases development are the risk factors for complications arise on the stage of rehabilitation adaptation in patients with diffuse liver lesions. CONCLUSION: The revealed relationship between diffuse liver lesions and dental status of patients, at the stages of preparation and after liver transplantation indicates, that a low level of oral cavity sanitation, the presence of odontogenic infection and periodontal disease worsen the course of the main disease, increase the risk of transplant rejection and require the creation of a dental rehabilitation system for this category of patients.

Oral Surgical Treatment of Patients With Chronic Liver Disease: Assessments of Bleeding and Its Relationship With Thrombocytopenia and Blood Coagulation Parameters.

PURPOSE: Cirrhotic patients awaiting liver transplantation require eradication of infectious oral foci to prevent septic episodes after transplantation; however, cirrhosis can hinder hemostasis and can result in severe bleeding. The present study assessed the bleeding risk factors connected with the clinical history of these patients and the characteristics of the extractions. MATERIALS AND METHODS: We retrospectively analyzed 1183 extractions in 318 patients, including 47 with severe end-stage liver disease who were outside of our intention-to-treat bracket (ie, platelet count [PLT] >40 × 103/µL and international normalized ratio [INR] <2.5). Follow-up examinations included inspection of the oral cavity on the first, third, and seventh days, with reparatory surgery in the case of severe bleeding. Continuous variables were compared using the Mann-Whitney U and Kruskal-Wallis tests, and categorical variables were compared using Fisher's exact test. Binary logistic regression analysis was also performed. RESULTS: Within the intention-to-treat bracket, 1 of the 271 patients (0.4%) required surgical repair. The bleeding rate for an INR of 2.5 or more was significantly greater than that for a PLT of 40 × 103/µL or less (4 of 10 [40%] versus 2 of 34 [6%]; P = .02]. All 3 patients with both an INR of 2.5 or more and a PLT of 40 × 103/µL or less exhibited severe bleeding. No significant association between the occurrence of bleeding with either liver disease etiology or the number of molars extracted was found. No patient required hospitalization. CONCLUSIONS: Patients with a PLT greater than 40 × 103/µL and an INR of less than 2.5 can be considered relatively low-risk patients. However, an INR of 2.5 or more and, to a minor degree, a PLT of 40 × 103/µL or less represent significant risk factors.

Oral and dental health in children with chronic liver disease in the Turkey Northeast.

BACKGROUND: It is important to be aware of oral and dental problems in the early period in children with chronic liver disease (CLD) to prevent late complications. Therefore, we aimed to analyze the oral and dental health status in children with CLD. METHODS: The three groups of children (3-18 years old); Group 1 (disease group, n = 31) patients with CLD, Group 2 (disease control group, n = 17) patients with chronic renal failure, and Group 3 healthy children (control group, n = 35). Examination of oral and dental structures were made, and then salivary parameters were analyzed. Antegonial index were calculated from panoramic X-rays. RESULTS: Enamel hypoplasia was found in 54.8%, 41.1%, and 31.4% of the children in the Groups 1, 2, and 3, respectively (P1-3 < 0.05). High salivary buffer capacity was found in 45.2% and 70.6% of the patients in Groups 1 and 2, respectively, and 45.7% of the children in healthy group, (P1-2 and P2-3 < 0.05). Factors associated with enamel hypoplasia in patients with CLD were male gender (64.7% vs. 21.4%, P < 0.05) and the presence of malnutrition (41.1% vs. 7.1%, P < 0.05). CONCLUSION: Pediatric hepatologists must be aware of the dental problems in children with CLD. Enamel hypoplasia is common in children with CLD, and it may predispose to dental caries.

Peginterferon and ribavirin for treatment of recurrent hepatitis C disease in HCV-HIV coinfected liver transplant recipients.

Achievement of a sustained virologic response (SVR) with antiviral therapy significantly improves graft survival in hepatitis C virus (HCV) monoinfected liver transplant (LT) patients. Risks and benefits of HCV therapy in HCV-human immunodeficiency virus (HIV) coinfected LT recipients are not well established. Among 89 HCV-HIV LT recipients in the HIVTR cohort, 39 (23% Black, 79% genotype 1, 83% fibrosis stage ≤ 1) were treated with peginterferon-a2a or a2b plus ribavirin for a median 363 days (14-1373). On intent-to-treat basis, 22% (95% CI: 10-39) and 14% (95% CI: 5-30) achieved an end-of-treatment response (EOTR) and SVR, respectively. By per-protocol analysis (completed 48 weeks of therapy ± dose reductions), 42% and 26% had EOTR and SVR, respectively. Severe adverse events occurred in 85%, with 26% hospitalized with infections and 13% developing acute rejection. Early discontinuations and dose reductions occurred in 38% and 82%, respectively, despite use of growth factors in 85%. Eighteen of 39 treated patients (46%) subsequently died/had graft loss, with 10 (26%) attributed to recurrent HCV. In conclusion, SVR rates are low and tolerability is poor in HCV-HIV coinfected transplant recipients treated with peginterferon and ribavirin. These results highlight the critical need for better tolerated and more efficacious HCV therapies for HCV-HIV coinfected transplant recipients.

Bleeding rate during oral surgery of oral anticoagulant therapy patients with associated systemic pathologic entities: a prospective study of more than 500 extractions.

PURPOSE: Oral anticoagulant therapy (OAT) patients have international normalized ratio (INR) safety windows for oral surgery, the lower limit of which is determined by the thromboembolic risk, with the upper limit typically 3.0. We sought to assess whether these limits will also be true with comorbidities that favor bleeding, such as diabetes, liver disease, and chronic renal failure. MATERIALS AND METHODS: The study was designed for 500 consecutive extractions. Patients with an INR greater than 3.0 were switched to heparin and used as controls. The primary outcome was the incidence of bleeding with the need for reoperation, in connection with 3 principal predictors: the INR, reasons for OAT, and comorbidity type. Continuous variables were analyzed using the Mann-Whitney U test and categorical variables using χ2 or Fisher's exact test. Statistical significance was set at P < .05. The reliability of the INR as a bleeding predictor was assessed using receiver operating characteristic (ROC) curves. RESULTS: Extractions in patients receiving OAT without comorbidities had a success rate of 99.7% against severe bleeding. Despite equivalent INR values, patients with comorbidities had a significantly lower rate (81.3%, P < .001). For these patients, the ROC curve procedure indicated lower INR upper limits, 2.8 for mechanical heart prosthesis subjects and 2.3 for all others. Among the comorbidities, diabetes was associated with the greatest frequency of bleeding (31%) compared with liver disease (15%) and kidney failure (11%). CONCLUSIONS: Patients with comorbidities should be advised to bring their INR within narrower safety windows (upper limit of 2.5 to 2.8 for mechanical prosthesis and 2.0 to 2.3 otherwise) or be switched to heparin. Alternatively, we propose applying to the socket, a platelet-rich growth factor preparation to foster hemostasis.

Nucleic acid-binding polymers as anti-inflammatory agents.

Dead and dying cells release nucleic acids. These extracellular RNAs and DNAs can be taken up by inflammatory cells and activate multiple nucleic acid-sensing toll-like receptors (TLR3, 7, 8, and 9). The inappropriate activation of these TLRs can engender a variety of inflammatory and autoimmune diseases. The redundancy of the TLR family encouraged us to seek materials that can neutralize the proinflammatory effects of any nucleic acid regardless of its sequence, structure or chemistry. Herein we demonstrate that certain nucleic acid-binding polymers can inhibit activation of all nucleic acid-sensing TLRs irrespective of whether they recognize ssRNA, dsRNA or hypomethylated DNA. Furthermore, systemic administration of such polymers can prevent fatal liver injury engendered by proinflammatory nucleic acids in an acute toxic shock model in mice. Therefore these polymers represent a novel class of anti-inflammatory agent that can act as molecular scavengers to neutralize the proinflammatory effects of various nucleic acids.

Increased infection risk postliver transplant without pretransplant dental treatment.

OBJECTIVE: Infections cause considerable morbidity after liver transplantation (LT). Acute liver failure is a rapidly progressing life-threatening condition where pretransplant dental evaluation is not always possible. We investigated how missing pretransplant dental treatment in acute or subacute liver failure correlates with post-transplant infectious complications. SUBJECTS AND METHODS: Medical and dental data came from hospital records and infection data from the Finnish LT registry. The follow-up was until February 2011. Of 51 patients (LT during 2000-2006), 16 had and 35 did not have dental treatment pretransplant. RESULTS: Univariate Cox regression analysis demonstrated a 2.46-fold (95% CI 1.06-5.69) infection risk among the patients omitted from dental treatment. After adjustment for either pretransplant factors alone or both pre- and post-transplant factors, the corresponding infection risk increased, respectively, to 8.17-fold (95% CI 2.19-30.6) and 8.54-fold (95% CI 1.82-40.1). This increased risk involved a variety of bacterial, viral, and fungal infections of various sources both < 6 and > 6 months after transplantation. CONCLUSION: High risk of infections was noticed in acute liver failure patients without pretransplant dental treatment, but a more severe medical condition might have influenced the results. We encourage eradication of dental infection foci whenever clinical condition allows.

Special care dentistry: part 3. Dental management of patients with medical conditions causing acquired bleeding disorders.

UNLABELLED: The second paper in this three part series discussed the dental management of patients with drug-related acquired bleeding disorders. This paper will discuss and outline the dental management of patients with acquired bleeding disorders that can result from medical conditions. Again, these may be associated with vascular defects, platelet defects or coagulation defects. In an age when people are living longer, and medical interventions are continually becoming more advanced, clinicians will need to be aware of systemic disorders and treatments that may cause complications in the dental setting. CLINICAL RELEVANCE: Being able to recognize which medical conditions, including their management, may cause bleeding problems at an early stage will lead to good patient management, particularly in planning and delivering treatment involving any invasive dental procedures that can cause bleeding. Whilst most patients can be successfully treated in general dental practice, the clinician may need to make a decision on whether or not to refer a patient to specialist services for all dental treatment, or to share care between primary care and specialist services.

Patient with Chronic Liver Disease Was Referred for Evaluation of Oral Infection and Facial Swelling and Needs Multiple Dental Extractions.

When a patient with chronic liver disease due to a hepatitis C virus infection presents with a dental emergency, it is important to identify whether the patient is under good medical management, if severe liver dysfunction exists, or if the patient is with active hepatitis. If records are not available, contacting the patient's physician to obtain the necessary information is prudent. If the source of infection is odontogenic, extraction should not be delayed. Patients with stable chronic liver disease can safely undergo dental extractions with some modifications to the dental treatment plan.

Pruritus in Chronic Liver Disease.

Pruritus can be associated with chronic liver disease, particularly cholestatic liver disease. Although the pathophysiology is uncertain, there are a few proposed mechanisms and much is still being discovered. Workup involves an assessment to rule out a dermatologic, neurologic, psychogenic, or other underlying systemic disorder. First-line therapy is cholestyramine, which is generally well tolerated and effective. In those who fail cholestyramine, alternative drugs including rifampicin and µ-opioid receptor antagonists can be considered. If medical therapy is ineffective and pruritus is significant, alternative experimental therapies such as albumin dialysis, photopheresis, plasmapheresis, and biliary diversion can be considered.

Hemorrhagic complications in individuals with liver disease submitted to minor oral surgery.

Individuals with chronic liver disease (CLD) have an increased risk of bleeding from thrombocytopenia and changes in hemostasis. The aim of this study was to evaluate the frequency of and the factors associated with the occurrence of bleeding in CLD patients who underwent dental surgical procedures. This was a retrospective study whose data were collected in a hospital dentistry service between 2010 and 2016. The patients were referred from the gastroenterology and liver transplantation services of a university hospital for dental treatment. The study followed the STROBE guidelines. Among the 71 surgical procedures performed, there were 17 (24%) perioperative and postoperative bleeding episodes, 14 of which were in pretransplant patients and 11 received blood transfusion before dental surgery. Individuals with a previous history of bleeding (PR = 2.67, CI = 1.07-6.67, P  = 0.035) and those with a platelet count before surgery 50 × 10 9 /l or less (PR = 7.48, CI = 1.70-32.86, P  = 0.008) had a higher prevalence of perioperative and postoperative bleeding episodes than their peers without a previous history of bleeding, and those with platelet count greater than 50 × 10 9 /l. The approach to individuals with CLD is complex and represents a challenge to the clinician. A careful anamnesis combined with laboratory screening of coagulation disorders appears to be useful to identify individuals at a major risk of bleeding. Studies identifying the predisposing factors of bleeding in CLD patients support well tolerated protocols for oral surgery in this group.

Cholestyramine resin for erythropoietic protoporphyria with severe hepatic disease: a case report.

Erythropoietic protoporphyria (EPP) is a rare disorder of heme biosynthesis caused by mutations in the gene encoding the enzyme ferrochelatase. In EPP, deficient ferrochelatase activity leads to the excessive production and biliary excretion of protoporphyrin (PP). The major clinical features of EPP are photosensitivity and hepatobiliary disease that may progress to severe liver disease, that are caused by the toxicity of PP. EPP-related liver disease has been treated medically or surgically including liver transplantation. We described a 20-year-old male with severe liver disease who was diagnosed with EPP based on clinical and laboratory findings. He was treated with cholestyramine resin. Six months after the treatment, he was doing well without any abdominal pain or photosensitivity.

Transarterial embolization with n-butyl cyanoacrylate for the treatment of abdominal wall hemorrhage.

PURPOSE: We aimed to evaluate the effectiveness and safety of n-butyl cyanoacrylate (n-BCA) in the context of the transarterial embolization (TAE) of abdominal wall hemorrhage in an urgent scenario. METHODS: A retrospective study of cases admitted from January 2008 to December 2017 in the emergency unit of our institution revealed 11 patients with abdominal wall hemorrhage who underwent digital subtraction angiography and TAE with n-BCA. We analyzed the sex, age, hemorrhagic risk factors, etiology, embolized vessel, technical success (no rebleeding in the embolized area), clinical success (hemoglobin level control and hemodynamic stability after the procedure), complications inherent to the procedure, and clinical outcome (mortality in 30 days). RESULTS: The mean age was 63.4 years (52-83 years), with a predominance of the female sex (64%). The majority (91%) of patients presented hemorrhagic risk factors (chronic hepatopathy and anticoagulation drug usage). Spontaneous hemorrhage was present in 18% of patients, and the other 82% had an iatrogenic etiology. Technical success was achieved in 100% of the patients, which required the embolization of inferior epigastric artery in 10 patients (91%), circumflex iliac artery in 2 (18%), and superior epigastric artery in 1 (9%). Five patients were hemodynamically unstable, and despite achieving technical success, 4 (36%) died in less than 30 days due to decompensation of their clinical comorbidities caused by the acute phase. There were no complications inherent to the procedures. CONCLUSION: The present study concludes that TAE with n-BCA is a safe and effective treatment for abdominal wall hemorrhage in an urgent scenario, with high rates of technical and clinical success.

Medical disorders and orthodontics.

The orthodontic treatment of patients with medical disorders is becoming an increasing aspect of modern day practice. This article will draw attention to some of the difficulties faced when orthodontic treatment is provided and will make recommendations on how to avoid potential problems.