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Dental considerations in patients with liver disease

Related
2012-Hepatitis C  infection: challenges in dental management and diagnosis of extrahepatic  manifestations
2011-Hepatitis C - Dry Mouth and Treatment
2010-Dental problems delaying the initiation of interferon therapy for  HCV-infected  patients
2007-Dry Mouth (Xerostomia)

2012
Sept 2012
Dental and Orofacial Health and Hepatitis C
Prior to treating HCV it is important that any active dental disease be managed. Non-urgent dental treatment may need to be postponed until HCV treatment has ceased. Unfortunately, dental problems are known to delay the onset of treatment for HCV.
 
Dental treatment during anti-HCV therapy should be undertaken following consultation with medical specialists. Blood tests and further investigations may be appropriate and in some cases in-patient care may be required.
Immunocompromised patients, particularly those with neutropaenia, are at risk of sepsis. If emergency dental treatment is necessary, consultation with medical specialists is recommended. If the patient is anaemic,
coagulopathic or thrombocytopaenic precautions may be needed.
Pre-treatment optimisation and comprehensive post-operative care may be required.
Particular attention must be given to haemostasis....Download PDF Here..


2011

Dental considerations in patients with liver disease

Marta  Cruz-Pamplona1, María Margaix-Muñoz 1, Maria Gracia Sarrión-Pérez 1
1 Degree in Dentistry. Master in Oral Medicine and  Surgery. Faculty of Medicine and
Dentistry. University of Valencia.   Spain.
Correspondence: Av/ Gaspar   Aguilar 81-13 46017  Valencia, Spain
 Phone:   630166697
E-mail:   martacruzp@hotmail.com

Received: 23/06/2010
Accepted:  16/01/2011

Abstract
Introduction: 
Liver diseases are very common, and the main underlying causes are viral infections, alcohol abuse and lipid and 
carbohydrate metabolic disorders. The liver has a broad range of functions in maintaining homeos- tasis and health,  and moreover metabolizes many drug substances. Objective: An update is  provided  on the oral manifestations seen in patients with viral hepatitis, alcoholic and non-alcoholic liver disease, cirrhosis and hepa-tocellular  carcinoma, and on the dental management of such patients. Material and methods: 

A Medline-PubMed search was  conducted of the literature over the last 15 years using the keywords:
“hepatitis”, “alcoholic hepatitis”, “fatty liver”,  “cirrhosis” and “hepatocellular carcinoma”. A total of 28 articles were  reviewed, comprising 20 lite- rature reviews, a clinical guide, three clinical trials and four case series.

Results: Oral   clinical manifestations can be observed  reflecting liver dysfunction, such as bleeding disorders, jaundice, foetor hepaticus, cheilitis, smooth tongue, xerostomia, bruxism and crusted perioral rash. In the case of infection caused by hepatitis C virus (HCV), the most  frequent extrahepatic manifestations mostly affect the oral region in the form  of lichen planus, xerostomia, Sjögren’s  syndrome and sialadenitis. The main complications of the patient with liver disease are risk of contagion (for healthcare personnel and other patients), the risk of bleeding and the risk of toxicity due  to alteration of the
metabolism of  certain drugs.

 Key words: Hepatitis, alcoholic hepatitis, fatty liver, cirrosis, hepatocellular  carcinoma.
Cruz-Pamplona M, Margaix-Muñoz M, Gracia Sarrión-Pérez MG.Dental considerations in patients with liver disease. J Clin Exp Dent. 2011;3(2):e127-34.

 http://www.medicinaoral.com/odo/volumenes/v3i2/jcedv3i2p127.pdf
Article   Number: 50340  http://www.medicinaoral.com/odo/indice.htm
© Medicina   Oral S. L. C.I.F. B 96689336 - eISSN: 1989-5488
eMail:  jced@jced.es 
 
Introduction

Liver diseases  are very common and can be classified as acute (characterized by rapid resolution and complete
restitution of  organ structure and function once the un-derlying cause  has been eliminated) or chronic  (charac-
terized by  persistent damage, with progressively impai-red organ  function secondary to the increase in liver cell
damage). Based on  the extent and origin of the damage, chronic liver  disease ranges from steatosis or fatty  liver
to hepatocellular  carcinoma, and includes hepatitis,  fi-brosis and  cirrhosis. Liver diseases can also be classified
as infectious (hepatitis A, B, C, D and E viruses,  infec-tious  mononucleosis, or secondary syphilis and tubercu-
losis) or non-infectious (substance abuse such as alcohol and drugs, e.g.,  paracetamol, halothane,  ketoconazole,
methyldopa and  methotrexate) (1).

The liver has a  broad range of functions in maintaining homeostasis and  health: it synthesizes most essential
serum proteins  (albumin, transporter proteins, blood coagulation  factors V, VII, IX and X, prothrombin  and
fibrinogen (1),  as well as many hormone and  growth factors),  produces bile and its transporters (bile acids,
cholesterol,  lecithin, phospholipids), intervenes in  the regulation of  nutrients (glucose, glycogen, lipids,  cho-
lesterol, amino  acids), and metabolizes and  conjugates lipophilic  compounds (bilirubin, cations, drugs) to
faci- litate their  excretion in bile or urine.

Liver dysfunction alters the  metabolism of carbohydrates, lipids, proteins, drugs, bilirubin  and hormones (2). Accordingly, liver
di- sease is  characterized by a series of aspects that must be taken into  account in the context of medical and  dental
care  (3).

Since many drug  substances are metabolized in the  liver, it is essential  for the clinician to compile a complete
me- dical history,  evaluating all body systems and the medi-cation used by  the patient. The patient drug  metabolizing
capacity can be  evaluated based on the analysis of enzy-mes such as  alanine aminotransferase (ALT) or aspartate
aminotransferase  (AST), and other liver function tests (2,  4).

In situations of  advanced liver disease, the vitamin K  le-vels can be  significantly lowered, thus giving rise to a  re-
duction in the  production of blood coagulation factors.  In addition, portal  hypertension can scavenge platelets
for- med in the  spleen, thus giving rise to  thrombocytopenia.This in turn can  lead to an excessive bleeding
tendency, which is one of  the main adverse effects seen during  the treatment of  patients with impaired liver function  (4).
 
Dentists are  particularly at risk of hepatitis B and C con- tagion, due to  the transmission routes of these  viruses,
since these  professionals are exposed to the blood and oral secretions  of potentially infected individuals (5)
– particularly in  the case of accidents with sharp or  cutting instruments.

VIRAL  HEPATITIS
Hepatitis of  viral origin comprises a heterogeneous group of  diseases caused by at least 6 different types  of
viruses: A, B,  C, D, E and G (2).

Five million new  cases of viral hepatitis are  documented each year  throughout the world, and a study
published by  Chandler-Gutiérrez et al. (6) estimates the  prevalence in Spain to be  3.7%.
-
Hepatitis  A
Hepatitis A is  caused by the hepatitis A virus (HAV), an RNA  picornavirus (3) endemic in many  developing
countries. Its  estimated prevalence is 1.1% (6). This  vi- rus is  transmitted via the enteral (oral-fecal) route (5),  as
a result of the  ingestion of contaminated water or food (mollusks),  though intrafamilial contagion has also  been
described, as  well as contagion in closed institutions  and secondary to  sexual intercourse.

The disease is  typically mild and self-limiting, and is  cha- racterized by  the sudden onset of nonspecific  symptoms.
There is no  carrier state. In children or young  indivi- duals the  disease tends to be asymptomatic, while  adults
typically  present fever, fatigue, abdominal  discomfort, diarrhea, nausea  and/or jaundice. The patient is able  to
transmit the  infection during the incubation period  (2-6 weeks) and until  the appearance of symptoms. The diagnosis is  based on the signs and symptoms  and on serological  testing for anti-HAV IgM and IgG  anti- bodies (3). Host  response in the form of anti-HAV  anti- bodies affords  lifelong immunity, protecting the  patient against future  HAV infection.

The risk of  nosocomial contagion among healthcare  per- sonnel is quite  low (3). Vaccines are available that  offer
immunity against  HAV (Havrix®, Vaqta®) for  people at risk (i.e.,  subjects traveling to endemic areas,  drug
abusers,  patients with chronic liver disease and  subjects with  occupational risk factors) (2, 3). 
-
Hepatitis  B
The hepatitis B  virus (HBV) is an encapsulated DNA  virus that  replicates within the hepatocyte (3).  Hepatitis
B is a worldwide  health problem, with an estimated  400 million carriers  of the virus (5). It has been calculated
that 1.53% of  all patients reporting to the dental  clinic  are HBV carriers  (6). The transmission  routes comprise sexual contact, intra- venous drug use  and blood transfusions. In Asia  perinatal transmission is  common (3). An important
consideration among dental  professionals is the risk of percutaneous transmission  through punctures or cuts with
instruments infected from  HBV-positive patients, or  absorption  through the  mucosal surfaces (eyes, oral cavity).
Trans- mission through  saliva can occur as a result of  absorp- tion from  mucosal surfaces (2). Some studies have
re- ported the  presence of HBsAg in saliva and  crevicular fluid of  HBV-positive patients. Dental  professionals,
particularly  those dedicated to oral surgery (7), have a three- to  four-fold greater risk of HBV infection than the general 
population (3), though vaccines and barrier methods have  contributed to lessen the risk (2, 7). Fo- llowing  inoculation, the seroconversion risk is 30% (8).
 
The incubation  period lasts 2-6 months. Over 50% of all infections  are subclinical and are not associated with jaundice. In 
 this context, since the disease may prove asymptomatic,   many people are unaware that they have suffered the  infection in the past (5). Approximately 90% of all  HBV-infected adults show complete healing, but 5-10%  develop chronic hepatitis with complications in the form of   cirrhosis and hepatocellular carcinoma (3, 4), resulting  in  5000-6000 deaths a year due to liver fa- ilure   (4).

The disease is  diagnosed by quantifying the levels of HBV DNA, HBsAg  and the antigen / antibody ratio. Vaccines have 
been developed that induce an effective immune response  against the virus in most patients. If a non-immunized  individual becomes exposed to HBV, immunoglobulin can be administered to afford protec-tion after exposure. The current management protocols include HBV  immunization as part of the pediatric vac-cination program  (3)

Hepatitis C

Hepatitis C  virus (HCV) infection is the main cause of chronic liver disease (9, 10) and of liver-related morbi-dity and   mortality worldwide (9). It has been estimated that 8000 to 10,000 deaths a year are attributable to HCV (4), and the latter represents the main indication for li- ver  transplantation in Europe and the United States (9).The estimated global prevalence of the disease is 2.2%, representing  approximately 130 million infected indivi-duals in the  world (10). Great geographical variability is observed (9),  possibly as a result of immunogenetic factors. The lowest prevalences are found in the Uni- ted Kingdom and   Scandinavia, and the highest in Egypt (11).
HCV is an RNA  virus mainly transmitted via the paren- teral route from  infected blood (3, 9, 12). The sources of contagion 
include blood transfusion (although the risk has been minimized since donor blood tests and controls are made (12)), 
percutaneous exposure through contami- nated instruments, and occupational exposure to blood (9). The  individuals at greatest risk are hemophiliacs,patients on dialysis and parenteral drug abusers.

Other transmission  routes are sexual contact and perinatal and idiopathic contagion (3). The prevalence of the infection among dental professionals is similar to that found in the general population, though epidemiological studies suggest that 
dentists constitute a risk group for HCV in- fection   (12).
Following  inoculation, the estimated seroconversion risk is 1.8%  (8). The incubation period is long (up to three months),  and 85% of all patients with HCV in- fection develop chronic hepatitis. In those cases where symptoms are observed, these tend to be mild, and most subjects remain   relatively asymptomatic during the first two decades  after infection with the virus (4).
The morbidity   associated to HCV infection is due not only to the consequences of chronic liver disease but also to the   extrahepatic manifestations (11). The best documented  condition associated to hepatitis C is cryo- glubulinemia, a   multisystemic disorder often characte- rized by purpura, weakness and joint pain, and which may precede the development of B-cell non-Hodgkin lymphoma or   membrane proliferative glomerulonephri- tis (12).

Other related disorders are porphyria cutanea tarda, lichen planus, sialadenitis, thyroid gland dys-function,  diabetes mellitus and peripheral neuropathy (11). Over 74%  of all HCV-infected patients ultimately develop extrahepatic manifestations in the course of the infection  (10).

Different  enzyme-linked immunosorbent assay (ELISA) and recombinant  immunoblot assay (RIBA) techniques have been 
developed for the diagnosis of HCV infection, though the diagnostic gold standard remains detection of the viral  genome using real time polymerase chain reaction  (RT-PCR) technology (3, 12).
No effective  vaccine against HCV has yet been deve- loped, and  spontaneous resolution is unusual (12). The existing
therapy  comprises combination treatment with interferon and   ribavirin, which offers a sustained res- ponse rate of   30-40% (3).
CHRONIC  HEPATITIS
Chronic  hepatitis is a diffuse inflammatory disorder of the liver with a  duration of over 6 months in which the underlying
cause  can be infectious (mainly hepatitis C virus and, to a  lesser extent, hepatitis B and D viruses), pharmacological   or immunological.
The disease can   develop in the absence of symptoms or with nonspecific  manifestations such as fatigue, nausea or abdominal   pain. The course is normally slow and pro- gressive, and  symptoms typically do not manifest until years after the 
initial causal event (e.g., infection). Some patients develop  the disorder without significant liver damage, while  others rapidly progress towards cirrhosis and possible  hepatocarcinoma. Chronic hepatitis due to HCV infection  is  the principal cause of cirrhosis and he- patocellular   carcinoma (3).

ALCOHOLIC LIVER  DISEASE
Alcoholic liver  disease is one of the 10 most common causes of death  in the industrialized world, and is res- ponsible for 3% 
of all fatalities. The epidemiological data indicate a  threshold of 80 g of alcohol in males and 20 g in females,  consumed on a daily basis during 10-12 years, in order   to cause the corresponding liver damage.
Ten grams of  pure ethanol are equivalent to a glass of wine or a beer, while a glass of whiskey doubles that amount. Factors 
such as chronic hepatitis C infection, obesity and genetic factors can accelerate the develop
ment of alcoholic  liver disease even with smaller doses of  alcohol. Alcoholism is  characterized by physical dependency that includes great tolerance of large amounts of alcohol in blood, a strong urge to drink, difficulty controlling consumption (13),  progressive abandonment of usual daily life activities, and persistence of the habit despite its consequences.  Alcoholism in turn leads to malnutri-tion, anemias, diminished immune function and impor- tant drug interactions.
The clinical  spectrum of alcoholic liver disease ranges from simple liver  steatosis (fatty liver) with alcoholic (toxic)
hepatitis  to more severe steatohepatitis or cirrho- sis.
 
Simple  steatosis is the most common presentation, is found in 90%  of all heavy drinkers, and proves rever- sible upon 
abandoning the habit. Alcoholic hepatitis is observed in over  35% of all heavy drinkers and tends to be a precursor
of cirrhosis. The condition ranges from asymptomatic  forms to liver failure and life-threatening situations, and  is usually accompanied by febricula, jaundice,  leukocytosis and liver enzyme elevations.

NON-ALCOHOLIC  FATTY LIVER
Non-alcoholic  fatty liver is defined as the accumulation of fat (mainly  triglycerides) in the liver, representing over 5% of the 
weight of the organ (5), in the absence of alcohol  consumption in excess of 10 g a day (15).The observed liver damage ranges greatly from simple steatosis (accumulation of fat in the liver) to steatohepatitis (fat  accumulation with added inflammation), advan- ced fibrosis and cirrhosis (16).
This disorder is  mainly associated to obesity, diabetes, hyperlipidemia  and insulin resistance. There is a strong correlation 
between insulin resistance and excessive triglyceride  accumulation within the liver cells (15). However, 16.4%
of  all patients with non-alcoholic fatty liver present none of these predisposing factors (17) The condition is potentially reversible after eliminating or minimizing the  aforementioned causal factors (14). No clear  treatments have been established to date for non-alcoholic  fatty liver, though interventions such as bariatric surgery  (in the case of obese individuals) and
oral  antidiabetic  drugs (glitazones) in patients with type 2 diabetes have  shown encouraging results (15).

CIRRHOSIS
Liver cirrhosis   is very common in our setting, with well defined  morphopathological characteristics that lead to destruction
of  the liver parenchyma. The disease is accompanied by a  series of extrahepatic manifestations in other body  organs and system (18). Liver cirrhosis is irreversible,   and is characterized by the formation of fibrous scarring  in the liver, with the formation of rege-neration nodules  that increase resistance to blood flow through the organ. The resulting deficient liver perfu-
sion damages  vital structures in the organ and adversely affects its   physiological functions (19). The main cau-ses of liver   cirrhosis are hepatitis B and C infection and alcohol abuse. Other potential causes are non-alcoholic steatohepatitis,  genetic alterations and autoimmune di-sorders  (3).
The main complications of cirrhosis are portal hyperten- sion, hepatocellular carcinoma and organ function loss. Cirrhosis in 
itself constitutes a risk factor for the develo- pment of  hepatocellular carcinoma (16). The treatment  options comprise suppression of the cau- sal stimulus,  antiviral therapy and liver transplantation in the end stages of cirrhotic disease (3).

HEPATOCELLULAR  CARCINOMA
Hepatocellular carcinoma is the fifth most frequent can-cer worldwide  (16). As such, it constitutes an important public health 
problem, and is one of the most common and  life-threatening malignancies in the world – with a survival rate  after two years of only about 2% (3). It has been  estimated that HBV and HCV are responsible for over 80% of  all hepatocarcinomas. The other cau- ses are  alcoholic and non-alcoholic steatohepatitis. Most patients with  hepatocellular carcinoma have a history of
cirrhosis, which  in itself constitutes a preneoplastic con- dition (12,   16). Liver cirrhosis  has a prolonged natural course, and pro- duces symptoms  only in the advanced stages of the di-sease, when no  healing treatment options are available.
The main  treatment for hepatocellular carcinoma is sur- gery (in those cases where the tumor proves resectable),
though  unfortunately many cases are non-operable due to the proximity  of vital structures, the presence of me-
tastases, or   other comorbidities (3).
 
Objectives
The present  study offers a literature review of the oral manifestations  that can be found in patients with viral hepatitis, 
alcoholic and non-alcoholic liver disease, cirr- hosis and  hepatocellular carcinoma, and the dental ma-nagement of  patients with these liver disorders.

 Material and  Methods
A literature  search was made of the articles indexed in the PubMed – Medline database, using the following MeSH validated 
key words: hepatitis, alcoholic hepati- tis, fatty  liver, cirrhosis and hepatocellular carcinoma. The search was  limited to articles in English or Spanish published over the last 15 years. A total of 28 articles were reviewed,  comprising 20 literature reviews, a clini- cal guide,  three  clinical trials and four case series.

 Results
1. ORAL CLINICAL  MANIFESTATIONS
The oral cavity  can reflect liver dysfunction in the form of mucosal   membrane jaundice, bleeding disorders, pe-techiae,
  increased vulnerability to bruising, gingivitis, gingival  bleeding (even in response to minimum trau-ma) (3, 19), foetor hepaticus (a characteristic odor of advanced liver  disease), cheilitis, smooth and atrophic tongue,  xerostomia, bruxism and crusted perioral rash (1).

In these  patients, chronic periodontal disease is a common   finding. Patients with  alcoholic hepatitis can present glossitis,
angle cheilitis  and gingivitis, particularly in combination with nutritional  deficiencies (3, 20). Some patients who consume large amounts of alcohol for prolonged periods of time can  develop sialadenosis. As commented by Frie- dlander (20),  this is believed to be the result of ethanol- induced  peripheral autonomic neuropathy giving rise to alterations in salivary metabolism and secretion.

Patients with  advanced cirrhosis tend to present defi-cient oral  hygiene, particularly in those cases where the liver
impairment  is associated to alcohol abuse. Bagán et al. (18)  reported worsened dental conditions in patients
with liver cirrhosis, in coincidence with other authors such as Novacek  et al. (21), who considered that due to the severity
and  characteristics of cirrhosis, patients tend to neglect care  of the oral cavity (18).
In a recent  study, Grossmann et al (9). found many patients with HCV  infection to present poor dental health – a situation
that  contributes to worsen their quality of life.
Extrahepatic  manifestations have been reported in 74% of all  HCV-infected individuals (19), and some of these conditions 
predominantly or exclusively affect the oral region (10).
The  main disorders associated with HCV infection are  xerostomia, Sjögren’s syndrome (SS), sia-ladenitis and  particularly lichen planus (LP) (9). Xerostomia  increases patient vulnerability to caries and oral soft tissue  disorders (9) which, in combination with deficient  hygiene, in turn facilitate the development of candidiasis. It has not yet  been demonstrated whether HCV infection causes disease  similar to primary Sjögren’s syndrome or whether it is  directly responsible for development of Sjögren’s  syndrome in certain types of patients. Howe-ver, it is notorious that some subjects can present a triple association of  HCV infection, Sjögren’s syndrome and sialadenitis or salivary gland lymphoma (10).

Although  bacteria are the main cause of sialadenitis, vi- ruses such as  HCV have been implicated as causes of sialadenitis 
associated to xerostomia (19). Epidemiological  evidence suggests that lichen planus may be  significantly associated to HCV infection, though the existing   data are controversial (22). This association appears to be  dependent upon the geographical setting, being more   common in Mediterranean countries and in Japan (22).  Bagán et al. (23) found the prevalence of
HCV infection  to  be greater in patients with oral lichen planus (OLP)  than in the control group. Although further studies are 
needed, recent data suggest that patients are most likely  first infected with HCV and posteriorly de- velop lichen  planus (24) – though the way in which this

2. DENTAL MANAGEMENT
Liver disease has important implications for patients receiving dental treatment (3). The most frequent pro-blems associated with liver disease in clinical practice refer to the risk of viral contagion on the part of the den-tal professionals and rest of patients (cross-infection),the risk of bleeding in patients with serious liver disease,and alterations in the metabolism of certain drug subs-tances (1) – which increases the risk of toxicity. HCV has been detected on different surfaces within the dental clinic after treating patients with hepatitis C, and the virus moreover is able to remain stable at room tem-perature for over 5 days (12). Strict sterilization mea-sures are therefore required, since deficient sterilizationcan expose both the dentist and other patients to hepa-titis infection (5). The universal protective measures areapplicable in order to prevent cross-infection, i.e., theuse of barrier methods, with correct sterilization and di-sinfection measures (1). It has been demonstrated thatconventional sterilization techniques eliminate specificproteins and nucleic acids (HBV DNA and HCV RNA)from dental instruments previously infected with HBVand HCV.
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Although there are no data confirming theirefficacy in lessening the risk of contagion, the measuresre commended in the case of accidental perforation of the skin with instruments or needles comprise careful was-hing of the wound (without rubbing, as this may inocula-te the virus into deeper tissues) for several minutes withsoap and water, or using a disinfectant of established efficacy against the virus (iodine solutions or chlorine formulations). In turn, pressure should be applied benea-th the level of the wound in order to induce bleeding and thus help evacuate any possible infectious material.If exposure through some mucosal membrane has oc-curred, abundant irrigation with tap water, sterile saline solution or sterile water is advised, for several minutes. The rationale behind these measures is to reduce the number of viral units to below the threshold count nee-ded to cause infection (i.e., the infectious dose). In this sense, dilution with water may lower the viral count to below this threshold (8). Whenever possible, the hepa-titis antigen status of the patient should be determined.In the event of parenteral exposure to hepatitis virus-positive antigens, the dentist should receive treatment with anti-hepatitis B immunoglobulin (5). Table 1 offers a schematic description of the steps to be followed. The compilation of a detailed clinical history is essen-tial before dental treatment in order to identify patientsposing possible risks (5), together with a thorough oralexploration. Interconsultation with the patient physicianor specialist is advisable in order to establish a safe andadequate treatment plan adapted to the medical condi-tion of the patient (3), considering the degree of liver functional impairment involved (1).

Table 1

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Exploration of the oral cavity should assess any signs alerting to the exis-tence of systemic disease. The patient should receive an explanation of the risks associated with treatment, and informed consent is to be obtained.In patients with acute-phase viral hepatitis, only emer-gency treatment should be considered. In subjects with chronic hepatitis it is important to determine the pos-sible existence of associated disorders (autoimmuneprocesses, diabetes, etc.) in order to prevent their direct complications and problems derived from specific me-dication use (corticosteroids and/or immune suppres-sors). Evaluation is also required of the possible medical conditions associated to HCV contagion, fundamentally blood transmitted infections (HIV, HBV).It also must be taken into account that liver disease is often associated with a decrease in plasma coagulation factor concentrations (2, 3). In a patient with liver di-sease, the surgical risk is related to the severity of the disease, the type of surgery planned, and the presence of comorbidities. Surgery is contraindicated in patients with certain conditions such as acute hepatitis, acute li-ver failure or alcoholic hepatitis (25). If invasive mea-sures are required, prior coagulation and hemostasistests are required: complete blood count, bleeding time,prothrombin time / international normalized ratio (INR),thrombin time, thromboplastin time and liver bioche-mistry (GOT, GPT and GGT) (1, 26). Table 2 reports the normal coagulation test values. In the event altered test values are detected, the hematologist or liver spe-cialist should be consulted (3), with the postponement of elective treatment. Any emergency treatments should be provided in the hospital setting.
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In the event of surgery, trauma should be minimized (3) in order to optimize hemostasis, with a careful surgical technique,applying pressure to control bleeding and using hemos-tatic agents (2). Based on the laboratory test findings and the treatment to be carried out, local hemostatic agents may be advisable (oxidized and regenerated cellulose),as well as antifibrinolytic agents (tranexamic acid), fresh plasma, platelets and vitamin K (1, 26). Antibiotic pro-phylaxis is suggested, since liver dysfunction is associa-ted to diminished immune competence (2).Liver disease may result in alterations in the metabolism of certain drugs. The physician treating the patient the-refore should be consulted in order to establish which drugs are used, their doses and possible interactions(3). The administration of certain analgesics, antibioticsand local anesthetics is generally well tolerated by pa-tients with mild to moderate liver dysfunction, though modifications may prove necessary in individuals with advanced stage liver disease (2). In this context, drugs metabolized in the liver may have to be used with cau-tion or their doses reduced (1, 26) (Table 3), and certain substances such as erythromycin, metronidazole or te-tracyclines must be avoided entirely (3). Most of the an-tibiotics prescribed for oral and maxillofacial infections can be used in patients with chronic liver disease, and in general the beta-lactams can be administered. Amino-glycosides can increase the risk of liver toxicity in pa-tients with liver disease, and so should be avoided. Themetabolism of clindamycin in turn is prolonged in suchpatients, and different studies suggest that it contribu-tes to liver degeneration (27).
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Nonsteroidal antiinflam-matory drugs (NSAIDs) should be used with caution oravoided, due to the risk of gastrointestinal bleeding andgastritis usually associated to liver disease. Prophylaxiscan be provided in the form of antacids or histamine re-ceptor antagonists (2, 3). Acetaminophen (paracetamol)is to be avoided in patients with serious liver disease (4),and aspirin and NSAIDs are not indicated in patientswith altered hemostasis (4). Authors such as Douglas etal. (27) describe acetaminophen as a safe alternative toaspirin or NSAIDs that can be administered at doses ofup to 4 g/day during two weeks without adverse liver effects, warning patients to avoid alcohol consumption while receiving treatment with the drug. In patients using benzodiazepines, the dose should be lowered, withprolongation of the interval between doses. Local anes-thetics are generally safe provided the total dosage doesnot exceed 7 mg/kg, combined with epinephrine (27).Table 4 shows the drugs that are contraindicated and those that can be used with caution. Although some of these substances are metabolized in the liver, the doses at which they are used in dental practice are considered to be acceptable – unless the patient suffers very severe liver dysfunction.

Table 4 shows the drugs that are contraindicated and those that can be used with caution.
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Patients with  alcoholic cirrhosis show increased toleran-ce of  anesthetics, sedatives and hypnotic agents; as a re-
sult, the  anesthesia doses should be increased. The safety and efficacy of  many drug substances are influenced by concomitant  alcohol consumption. Concern is greatest regarding the  effects of combining alcohol and central nervous system  depressors, and the complex effects of alcohol upon the  capacity of the liver to metabolize drug substances  (20).  Paracetamol combined with alcohol can prove   particularly dangerous, since the metabolism of both substances   involves the same enzyme (isoenzyme CYP2E1 of the  P-450 cytochrome system) (28), and care is required  not to prescribe alcohol-containing rin- ses among  patients recovering from alcohol abuse (1). Lastly,  preventive oral hygiene measures are indicated
to lessen the   need for dental surgical treatments (12).

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