2. What is the liver?
• The liver is a large organ, and occupies the upper
right quadrant of the abdomen.
• It develops as an outgrowth of the gut
• Veins returning from the gut come together to form
the portal vein.
• Hepatic veins join the vena cava.
• The liver will retain normal function until 85%
• Often enjoyed with fava beans and a nice chianti.
3. Function of the Liver
Metabolism / Detoxification
• Metabolizes products of digestion
• Glucose regulation
• Vitamin storage
• Metabolizes drugs
• Some of the common drugs used in Dentistry
• Breaks down bilirubin
Synthesis and Secretion
• Components of clotting factors
• Cholesterol, triglyceride synthesis
• Bile production
• Other proteins and hormones
Storage and Filtration of Blood
• Acts as a blood reservoir
• Contains phagocytic cells
• Part of the reticuloendothelial system.
4. Liver Function Tests (LFTs)
AST (aspartate aminotransferase) (11 – 47 IU/L)
• AST is an enzyme found throughout the body, but predominantly in
heart and liver cells.
• Most useful in detecting liver damage due to hepatitis, drugs toxic to the
liver, cirrhosis, and alcoholism.
• Often ordered in conjunction with ALT.
ALT (alanine aminotransferase) (7 – 56 IU/L)
• An enzyme found mostly in the cells of the liver and kidney. When the
liver is damaged, ALT is released into the blood stream. ALT is a useful
test for detecting liver damage.
• Most useful in detecting damage due to hepatitis and drugs or other
substances toxic to the liver.
• Often ordered in conjunction with AST.
• The AST/ALT ratio is usually increased in alcoholic hepatitis, cirrhosis, and
in the first day or two of acute hepatitis or injury from bile duct
ALP (alkaline phosphatase) (30 – 120 IU/L)
• Found in bone and in the cells of bile ducts. ALP can indicate blockage of
one or more bile ducts, liver cancer, hepatitis, cirrhosis, or when
hepatotoxic drugs are taken.
5. Liver Function Tests (LFTs)
Total Bilirubin (0.2 – 1.2 mg/dL)
• A breakdown product of hemoglobin (orange-yellow
pigmented). Unconjugated (non-water soluble) bilirubin is
processed in the liver.
• High unconjugated bilirubin means either hemoglobin is being
broken down too fast, or the liver can’t process it fast enough.
• High conjugated bilirubin indicates that bilirubin is backing up
in the liver.
Albumin (3.5 – 5.3 g/dL)
• A protein made by the liver. Low levels indicate liver disease or
Prothrombin Time (PT) (10 – 14 seconds)
• The prothrombin time (PT) test measures how long it takes for
a clot to form in a sample of blood.
• Evaluates the overall ability to produce a clot in a reasonable
amount of time.
Platelet Count (150,000 – 450,000 mm3)
• Thrombocytopenia is a decrease in the number of circulating
platelets. Platelets are not part of the coagulation cascade, but
are essential for the initiation of hemostasis.
• A yellowing of the skin and eyes from excessive bilirubin in the blood. Also causes itching.
• The diseased liver either cannot processes bilirubin fast enough, or it is backing up from an
obstruction to the flow of bile.
• Increased resistance to portal blood flow.
• Leads to the formation of collateral veins that bypass the liver. Enlarged vessels are prone
to rupturing causing massive bleeding and often death.
• The accumulation of excess fluid in the peritoneal cavity.
• Disturbances in consciousness: subtle to marked confusion and stupor, to deep coma and
• Elevated levels of ammonia – brain edema, impaired neural function. Reversible if the
underlying hepatic condition can be corrected.
• Spleen to enlarges due to increased pressure from the spleen into portal blood vessels.
White blood cell count can decrease, platelet count can decrease.
Manifestations of Liver
8. Blood abnormalities
• Leukopenia and thrombocytopenia due to splenomegaly.
• Clotting abnormalities – decreased ability to synthesize clotting factors.
Light Stools/Dark Urine
• Bilirubin gives stool its characteristic color. In patients with hepatitis or cirrhosis, little
bilirubin makes it into the gut, and stool is light in color.
• Dark brown but clear urine is a sign of excess bilirubin in the urine. Light stool and dark
urine are generally concurrent with jaundice.
• Hypoalbuminemia causes reduced blood osmolarity. Fluid to escapes into the tissues.
• Abdominal pain, discomfort, or “feeling full” due to hepatomegaly or hepatocellular
Manifestations of Liver
Excessive use of toxic substances
• Secondary syphilis
• Hepatitis A
• Hepatitis B
• Hepatitis C
• Hepatitis D, E
• Acute non A-E
11. Hepatitis A Virus
• HAV immunoglobulin M (IgM) test
(preferred confirmatory test for acute
• Serum antibodies IgM usually can be
detected 5–10 days before symptom
onset, and the level remains elevated
for 4–6 months.
• Elevated liver enzymes
• Elevated bilirubin levels
• Food, water borne; heat labile
• Fecal – oral contamination; contagious
• Usually self limited, lasting days to
• 99% spontaneous recovery, no
12. Hepatitis B Virus
• Blood, semen, saliva, vaginal secretions
• Highly contagious; sexually transmitted
• 90 – 95% self limited over 6 months
• Chronic infection: >6 months
• DNA virus: incorporates into host with
• Hepatitis B surface antigen (HBsAg)
• Indicates currently infectious, with acute or
• Hepatitis B surface antibody (HBsAb)
• Indicates recovery or successful
• Hepatitis B core antibody (HBcAb)
• Indicates previous or ongoing infection
• IgM antibody to HBc antigen (IgM anti-HBc)
• Indicates acute infection, acquired in the
last 6 months
13. Hepatitis C Virus
• Enzyme immunoassay to detect antibodies
to multiple HCV antigens
• Hepatitis C RNA virus by polymerase chain
reaction (PCR) detects quantity of the virus
itself in the blood (quantification of the
• Blood borne, not in food or water; not
highly sexually transmitted
• Not highly contagious
• 20% self clearing; 80% chronicity
• RNA virus: does not incorporate into
• Can cause HCC; #1 cause of transplant
• 2 – 20 weeks
• Virus becomes detectable in blood
• Serum aminotransferase, bilirubin levels
• Antibody not detected
Pre-Icteric (Prodromal) Phase
• Onset of nonspecific symptoms
• Lasts 3 – 10 days
• Virus specific antibody detectable
• Viral titers at highest point
• Serum aminotransferase levels increase
• 1 – 3 weeks
• Jaundice appears
• Fatigue, nausea worsen
• Hepatic tenderness
• Aminotransferase levels are 10x normal limit.
• Levels of virus begin to decrease
Post-Icteric (Recovery) Phase
• Resolution of jaundice
• Usually 6-8 weeks after exposure
• Symptoms diminish
• LFTs usually return to normal
• Chronic infection
• Fulminant hepatic failure
• Relapsing or cholestatic hepatitis
• Extrahepatic syndromes
Fulminant Hepatic Failure
• Acute liver failure
• Evidence of hepatic encephalopathy
• Prolongation of PT
• Worsening of jaundice
• Decrease in liver size
15. Alcoholic Liver Disease (ALD)
• US: 50-70% consume alcohol
• Only 5% have more than 2 drinks/day; 11-15g
• Maximum recommended daily intake:
• women: 22-30g alcohol/day
• men: 33-45g alcohol/day
• Three types of ALD:
• Hepatic steatosis (fatty liver disease)
• Alcoholic hepatitis
16. Alcoholic Liver Disease (ALD)
Alcoholic fatty liver disease
• Hepatic steatosis
• Micro-vesicular lipid droplets in
hepatocytes, become macro-
• Large, soft, yellow, greasy liver
• Non-fibrous initially
• Severe liver dysfuncion unusual
• Reversible with abstinence
17. Alcoholic Liver Disease (ALD)
• Hepatocyte swelling and necrosis
• Neutrophilic reaction
• Non-specific symptoms
• Appears acutely after drinking
• 10-20% risk of death
• May resolve, or may progress to
18. Alcoholic Liver Disease (ALD)
• Usually develops slowly
• Progression from large, tan, fatty to shrunken, brown, non-fatty
• Fibrous septa form around nodules of hepatocytes
• Eventual ischemic necrosis and fibrous obliteration of nodules
• Tough, pale scar tissue
• Similar appearance to other forms of cirrhosis
19. Non-Alcoholic Fatty Liver Disease
• NAFLD includes simple hepatic
steatosis; steatosis w/ minor,
• Develops in patients who are not
• Causes liver damage that is
from alcoholic hepatitis
• Risk factors: obesity,
dyslipidemia, glucose intolerance
• Pathogenesis poorly understood
but seems to be linked to insulin
• Most patients are asymptomatic
• Elevations in aminotransferase
• Biopsy is required to confirm the
• Treatment includes elimination
of causes and risk factors
• Hepatocellular carcinoma accounts for the vast majority of liver cancers.
Globally, HCC is the 3rd most frequent cause of cancer death.
• 78% of HCC cases caused by chronic HBV and HCV infections
• Three types of gross morphology
1. Unifocal large mass
2. Multifocal and widely distributed nodules
3. Diffusely infiltrative, permeating widely
• Strong propensity for invasion of vascular structures
• If venous invasion is identified during transplant, recurrence of HCC is likely
• Clinical manifestations often masked by underlying cirrhosis or chronic
• Causes death by:
• Wasting syndrome (cachexia)
• Esophageal or gastric variceal bleeding
• Liver failure with hepatic coma
21. Cirrhosis of the Liver
• Irreversible damage to liver
• Fibrosis with areas of nodular regeneration
• Primary causes:
• Alcoholic liver disease
• Chronic infection with hepatitis B virus and hepatitis C virus
• Less common causes:
• Primary biliary cirrhosis, hemochromatosis, Budd–Chiari syndrome, Wilson’s disease and alpha 1- antitrypsin deficiency
• Medication such as amiodarone and methotrexate can also cause cirrhosis
• In just under 1/3 of cases, cause is unknown – referred to as cryptogenic cirrhosis
• Decompensation – Infection, alcohol consumption, imbalance of urea and electrolytes, GI bleeds or progression of
the underlying disorder – can cause mortality rates without liver transplantation can be as high as 85% within 5 years
• Classification: Child-Turcotte-Pugh Classification of Cirrhosis is helpful in determining prognosis of disease
Factor Units 1 2 3
Serum bilirubin mol/L
Serum albumin g/L
Ascites None Easily
None Minimal Advanced
Child-Turcotte-Pugh Classification of Cirrhosis
Risk (grade) is based on the total number of points:
Low (A): 5–6; Moderate (B): 7–9; High (C): 10–15
Major Clinical Manifestations of Cirrhosis
• Hepatic encephalopathy
• Esophageal, gastric varicies
• Portal hypertension
• Blood abnormalities
• Nutritional supplements
• Low protein diet if encephalopathy
• Vegetables as main protein source
• Lactulose to clear bowels, and reduce absorption of
• Low salt diet if there is ascites
• Avoid alcohol, NSAIDs, sedatives, opiates
• Prognosis is relatively poor, with a 5-year survival
rate of approximately 50%
Cirrhosis of the Liver
24. Dental Management of Liver
• Oral candidiasis – Immunotherapy
• Angular cheilitis – Immunotherapy
• Atrophic glossitis – Anemia
• Petechiae – Thrombocytopenia
• Lichen planus – HCV
• Oral metastases of HCC primarily manifest
as hemorrhagic expanding masses located
in the premolar and ramus region of the
Oral Manifestations of Liver Disease
25. Protection for the Practitioner
• Difficult or impossible to identify
carriers of HBV, HCV, HDV. Most
carriers are unaware that they
have had hepatitis
• Standard precautions
• HBV vaccination
• Post exposure prophylaxis
Dental Management of Liver
26. Dental Management of Liver
• Aspirin, ibuprofen, and other NSAIDs – use caution
• Acetaminophen – use caution
• Narcotics – increase dose interval, short term
• Morphine – safe
• Lidocaine, mepivicaine – limit to 300 mg max dosage
• Prilocaine – limit to 400 mg max dosage
• Articaine – safe (metabolized in plasma)
• Benzodiazepines – reduce dosage, increase intervals
• Beta-lactam (penicillins, ampicillin, cephalexin,
cefazolin, ceftriaxone) – safe (renal excretion)
• Metronidazole – interaction w/ alcohol
• Clindamycin, aminoglycosides – use caution
• Tetracyclines – reduced dosage, increase intervals
27. Dental Management of Liver
• PT/INR, Platelet count requirements for surgery:
• Maximum INR 3.5
• Minimum platelets 50,000
• 2 units fresh frozen plasma (FFP) + 6 pack platelets
28. Dental Management of Liver
• Comprehensive dental evaluation
• Extraction of infected, non-restorable, or
periodontally hopeless teeth.
• Oral hygiene instruction
• No elective dental tx for 3 months following
• Routine Ab prophylaxis is not recommended
• Recall program after 3 months
• Prophylactic care
1. Little, J. W. (2013). Dental management of the medically compromised
patient. St. Louis, Mo: Elsevier/Mosby.
2. http://labtestsonline.org/ (2001 - 2013 by American Association for
3. http://www.merckmanuals.com/professional/index.html (2004-2012
Merck Sharp & Dohme Corp)
4. Robbins & Cotran (2010). Pathologic Basis of Disease, 8th Edition.
5. Patton, L. (2012). The ADA Practical Guide to Patients with Medical
The liver is a large organ, weighing about 2 kg, and occupies the upper right quadrant of the abdomen under the diaphragm.It develops as an outgrowth of the gut and thus receives the same blood supply as the gut.Veins returning from the gut come together to form the portal vein. The portal vein enters the liver, bringing the products of digestion for processing. The hepatic veins leave the liver to enter the inferior vena cava.The liver has the ability to regenerate, and will retain normal function until 85% damaged. Thus liver disease may not be clinically evident until it has reached an advanced stage.
Metabolism / DetoxificationMetabolizes products of digestionGlucose regulationBlood glucose is transformed in the liver to glycogen and stored. When the concentration of blood glucose is low, the glycogen in the liver is reconverted into glucose and released to the body through the blood stream.Vitamin storageThe liver stores vitamin A, which is essential for the maintenance of mucous membranes. In addition, vitamins D, B12, K, iron in the form of ferritin, and copper are stored.Metabolizes drugsSome of the common drugs used in Dentistry are NSAIDs, acetaminophen, narcotic analgesics, local anesthetics, benzodiazepines, and many antibiotics.The liver also metabolizes many other drugs, including ethanol.Breaks down bilirubinSynthesis and SecretionMakes components of clotting factors, fibrinogen, prothrombin, accelerator globulins, and others.Cholesterol synthesis, Lipogenesis – triglyceride synthesisBile is produced by the liver cells from cholesterol and bilirubinOther proteins and hormonesAlbumin, amino acids, angiotensinogen, thrombopoetin, insulin-like growth factor 1Storage and Filtration of BloodThe liver acts as a blood reservoir and can store from 500 to 1000 ml of blood within the sinusoids. The liver contains phagocytic cells, which protrude into the blood sinusoids to filter bacteria from the blood. Thus, like the spleen and lymphoid tissues, the liver is part of the reticuloendothelial system.
The standard battery of tests that are most helpful in assessing liver disease includes determinations of bilirubin, albumin, prothrombin time, and the serum enzymes ALT, AST, and alkaline phosphatase. Interpretation of these results in concert with careful history taking and a physical examination may suggest a specific type of liver injury, allowing a directed evaluation, risk assessment for surgical procedures, and estimation of prognosis.AST (aspartate aminotransferase)AST is an enzyme found throughout the body, but predominantly in heart and liver cells. In healthy individuals, levels of AST in the blood are low. When liver or muscle cells are injured, they release AST into the blood. This makes AST a useful test for detecting liver damage.Most useful in detecting liver damage due to hepatitis, drugs toxic to the liver, cirrhosis, and alcoholism. AST, however, it is not specific for the liver and may be increased in conditions affecting other parts of the body.Often ordered in conjunction with ALT.ALT (alanine aminotransferase)ALT is an enzyme found mostly in the cells of the liver and kidney; much smaller amounts of it are also found in the heart and muscles. In healthy individuals, ALT levels in the blood are low. When the liver is damaged, ALT is released into the blood stream, usually before more obvious symptoms of liver damage occur, such as jaundice. This makes ALT a useful test for detecting early liver damage.Most useful in detecting damage due to hepatitis and drugs or other substances toxic to the liver. ALT, however, is not entirely specific for the liver, and mild to moderately increased levels may also be seen in conditions affecting other parts of the body.Often ordered in conjunction with AST.AST/ALT RatioIn most types of liver disease, the ALT level is higher than AST, and the AST/ALT ratio will be low. There are a few exceptions. The AST/ALT ratio is usually increased in alcoholic hepatitis, cirrhosis, and in the first day or two of acute hepatitis or injury from bile duct obstruction.ALP (alkaline phosphatase)An enzyme found in its highest concentrations in bone and in the cells of bile ducts. A sharp spike in ALP can indicate blockage of one or more bile ducts. Smaller increases in ALP indicate liver cancer, hepatitis, cirrhosis, or when hepatotoxic drugs are taken.
BilirubinA breakdown product of hemoglobin (orange-yellow pigmented). Unconjugated (non-water soluble) bilirubin is processed in the liver to form conjugated (water-soluble) bilirubin that can pass into the intestine for elimination. When a high level of unconjugated bilirubin is detected, that means either hemoglobin is being broken down too fast, or the liver can’t process it fast enough due to disease. When a high level of conjugated bilirubin is detected, it can indicate that bilirubin is backing up in the liver due to acute hepatitis, or a blocked bile duct.AlbuminA protein made by the liver. Low levels of albumin can indicate liver disease. It can also indicate nephrotic syndrome if it is lost through the urine.Prothrombin Time (PT)The prothrombin time (PT) test measures how long it takes for a clot to form in a sample of blood. The clotting process involves a series of sequential chemical reactions called the coagulation cascade, in which clotting factors are activated one after another and result in the formation of a clot. The PT test evaluates the overall ability to produce a clot in a reasonable amount of time and, if any of the factors in the extrinsic or common pathways are deficient or dysfunctional, the PT will be prolonged.Vitamin K dependent clotting factors (II, VII, IX, and X) are synthesized in the liver and their production is inhibited with advanced liver disease leading to a prolonged PT.Platelet CountCongestive splenomegaly, a consequence of portal hypertension, can lead to a decrease in the number of circulating platelets (thrombocytopenia). Platelets are not part of the coagulation cascade, but are essential for the initiation of hemostasis.
The enormous functional reserve of the liver masks the clinical impact of mild liver damage, but with progression of diffuse disease or disruption of bile flow, the consequences of deranged liver function may become life-threatening.
JAUNDICEJaundice is a yellowing of the skin and eyes from excessive bilirubin in the blood. Excess unconjugated bilirubin suggests decreased hepatic uptake, or decreased hepatic processing. Excess conjugated bilirubin can come from dysfunctional hepatocytes, slowing of bile flow from the liver, or obstruction of extrahepatic bile flow.The excess bilirubin in the skin causes pruritis (itching).PORTAL HYPERTENSIONPortal hypertension is an increased resistance to portal blood flow entering the liver, leaving the liver, or within the liver. Some causes of this restricted blood flow are cirrhosis (the major cause), right sided heart failure, fatty liver, and splenomegaly.Portal hypertension leads to the formation of collateral veins that bypass the liver, so many of the toxins normally processed by the liver now go directly into the blood stream. Some of these collateral vessels form at the base of the esophagus (esophageal varices), or in the stomach (gastric varices). These enlarged vessels are prone to rupturing causing massive bleeding and often death.ASCITESAscites is the accumulation of excess fluid in the peritoneal cavity due to high pressure in blood vessels of the liver, and low levels of albumin (hypoalbuminemia). Clinically detectable when at least 500ml of fluid has collected.HEPATIC ENCEPHALOPATHYA spectrum of disturbances in consciousness, ranging from subtle behavioral abnormalities, to marked confusion and stupor, to deep coma and death. This can happen in hours or days in someone with acute liver failure, or more slowly in someone with chronic disease.Associated with elevated levels of ammonia in the blood and CNS, promoting brain edema and impaired neural function. This is reversible if the underlying hepatic condition can be corrected.SPLENOMEGALYPortal hypertension often causes the spleen to enlarge because the pressure interferes with blood flow from the spleen into the portal blood vessels. The white blood cell count can decrease (increasing the risk of infections), and the platelet count can decrease (increasing the risk of bleeding).
Blood abnormalitiesLeukopenia and thrombocytopenia often accompany splenomegaly in advanced portal hypertension. As previously mentioned this can lead to increased infection and increased bleeding.Clotting abnormalities due to malabsorption of vitamin K, leading to the liver’s decreased ability to synthesize a number of clotting factors.Light Stools/Dark UrineBilirubin is normally excreted along with bile into the gut where it is broken down by bacteria, giving stool its characteristic color. In patients with hepatitis or cirrhosis, bilirubin cannot be moved through the liver or bile ducts quickly enough and it instead builds up in the blood stream. Little bilirubin makes it into the gut, and stool is light in color.Dark brown but clear urine is a sign of a liver disorder such as acute viral hepatitis or cirrhosis, which causes excess bilirubin in the urine. Light stool and dark urine are generally concurrent with jaundice.Peripheral edemaAlbumin, a circulating protein synthesized in the liver, becomes deficient (hypoalbuminemia) causing reduced blood osmolarity. This in turn causes fluid to escape into the tissues and migrate to the lower extremities with gravity.Abdominal PainHepatomegaly, or an enlarged liver, is usually asymptomatic; but a grossly enlarged liver can cause abdominal pain, discomfort, or a feeling of fullness.Abdominal pain can also be a symptom of hepatocellular carcinoma.
The liver is vulnerable to a wide variety of metabolic, toxic, microbial, circulatory, and neoplastic insults. The major primary diseases of the liver are viral hepatitis, alcoholic liverdisease, nonalcoholic fatty liver disease (NAFLD), and hepatocellular carcinoma (HCC). Incidence and mortality rates for hepatocellular carcinoma are rising rapidly in the United States because of the increased prevalence of cirrhosis associated with HCV infection in younger patients resulting in up to 4% of patients with cirrhosis developing cancer each year.
Hepatitis means “inflammation of the liver”, and can result from infections or other causes. Non-infectious hepatitis can be the result of toxicity from drugs or alcoholInfectious hepatitis can be caused by various bacteria and viruses. Viral Hepatitis is a collective term that includes several viruses. There are 5 viruses known to cause acute viral hepatitis, but the three main ones responsible are hepatitis A, B and C. There are other hepatitis viruses though - Hep D,Hep E, and non A-E. Approximately 15,000 people die each year in the U.S. from cirrhosis caused by viral hepatitisHep A and Hep E are known as infectious hepatitis because they are highly contagious, occur in outbreaks, and cause self-limited hepatitis only.Hep B, C and D are known as serum hepatitis. They are introduced by parenteral routes, they’re less contagious, and rarely cause outbreaks. They can lead to acute or chronic hepatitis, cirrhosis, and hepatocellular carcinoma.
Hepatitis A virus (HAV): HAV is the most common cause of acute viral hepatitis and is particularly common among children and young adults. In some countries, > 75% of adults have been exposed. HAV spreads primarily by fecal-oral contact and thus may occur in areas of poor hygiene. Waterborne and food-borne epidemics occur, especially in underdeveloped countries. Sporadic cases are also common, usually as a result of person-to-person contact. Fecal shedding of the virus occurs before symptoms develop and usually ceases a few days after symptoms begin; that means infectivity often has already ceased when hepatitis becomes clinically evident. HAV has no known chronic carrier state and does not cause chronic hepatitis or cirrhosis.
HBV is the most thoroughly characterized and complex hepatitis virus, and is the 2nd most common cause of acute viral hepatitis. It is transmitted parenterally, typically by contaminated blood, and transmission through needles shared by drug users. The virus may be spread through contact with other body fluids, and can be sexually transmitted, but it’s far less contagious than HAV.Chronic HBV carriers provide a worldwide reservoir of infection, and vertical transmission from mother to infant is common unless the neonate is treated with hepatitis B immunoglobulin and is vaccinated immediately after delivery.
HCV has 6 major subtypes with varying genotypes. It is most commonly transmitted through blood, primarily when drug users share needles, but it is possible to transmit through tattoos or body piercing. Sexual transmission and vertical transmission from mother to infant are possible, but rare.Up to 20% of patients with alcoholic liver disease have HCV although the reason for this association is unclear. In these patients, HCV and alcohol act synergistically to worsen liver inflammation and fibrosis.
The incubation period ranges from 2 to 20 weeks, as determined largely on the basis of the viral agent and exposure dose. During this phase, virus becomes detectable in blood, but serum aminotransferase and bilirubin levels are normal, and antibody is not detected.During the pre-icteric phase, the patient experiences symptoms like fatigue, nausea, poor appetite, and vague UR quadrant pain. It usually lasts 3-10 days, but may last longer, and even constitute the entire illness in subclinical cases.Icteric Phase – icteric is the medical term for jaundice. The onset of jaundice, and production of dark urine marks the icteric phase of hepatitis. Jaundice may be coupled with pruritis, and light colored stool. In severe cases, there will be hepatomegaly, and splenomegaly with associated hepatic and abdominal pain.The recovery or post-icteric phase begins about 6-8 weeks after initial exposure. Symptoms diminish, and LFTs usually return to normal.COMPLICATIONS– The infection can become chronic if it lasts greater than 6 months. This happens in about 2-7% of adults with HBV, and 50-85% with HCV.FULMINANT HEPATITIS – Acute liver failure or fulminant hepatitis occurs in 1% to 2% of patients with symptomatic acute hepatitis. This is most common with hepatitis B and hepatitis D and least common with hepatitis C. The disease is called fulminant if there is evidence of hepatic encephalopathy.
Another type of liver disease is Alcoholic Liver Disease or (ALD). This is the leading cause of liver disease in most western countries. One source that I read estimated that 50% of US adults drink alcohol, but another source said 70%. I think it’s safe to say that the majority of adults in the US consume alcohol. The maximum recommended daily intake of alcohol is 2 drinks for women, and 3 drinks for men.There are three types of ALD, but they aren’t a clear progression as you will see.
Alcoholic liver disease starts out as a fatty liver with microscopic lipid droplets accumulating in the hepatocytes. This can actually happen with as little as 8 oz of alcohol, or a six pack of beer. Daily intake of this amount generates significant risk for severe hepatic injury, and daily intake of 12 beers or 16 oz of alcohol over 10-20 years is strongly associated with severe injury. So I figure I’ve got about 4 or 5 years left (laughter, applause etc…)Alcoholic fatty liver disease is generally not associated with permanent liver damage, and is reversible if you stop drinking. But with continued heavy drinking, the fatty liver can gradually progress to cirrhosis, or it can be hit with alcoholic hepatitis.
Alcoholic hepatitis usually appears acutely after an episode of binge drinking. It can range from minimally symptomatic to fulminant hepatic failure. Hepatocytes are ballooned from accumulation of fat, water, and proteins, and some become necrotic. Most patients with moderate disease present with fatigue, anorexia, fever, jaundice, right upper quadrant pain, and tenderhepatomegaly.The outlook is unpredictable – each bout of alcoholic hepatitis carries about a 10-20% risk of death. With repeated bouts, cirrhosis appears in about one third of patients within a few years. With proper nutrition and abstinence from alcohol, the hepatitis may slowly clear. Unfortunately, in some patients it progresses to cirrhosis even after they stop drinking.
The manifestations of alcoholic cirrhosisare similar to those of other forms of cirrhosis. The liver becomes brown and shrunken as fibrous septa divide the hepatocytes into little islands or nodules. Over time the fibrosis overtakes the liver, causing ischemic necrosis and fibrous obliteration of the hepatocyte nodules. Symptoms range from those of alcoholic hepatitis to those of fulminant hepatic failure. Alcoholic cirrhosis is non-reversible, and hepatocellular carcinoma develops in 10-15% of patients with alcoholic cirrhosis.
Non-Alcoholic Fatty Liver Disease (NAFLD) is actually a group of conditions that all have in common the presence of a fatty liver. It has become the most common cause of chronic liver disease in the United States, and in its various forms, probably affects more than 30% of the population. The different conditions are: simple Hepatic Steatosis; Steatosis w/ Minor Non-specific Inflammation; Non-alcoholic Steatohepatitis. Of these, the only condition with symptoms is NASH in which there is hepatocyte injury that may progress to cirrhosis in 10% to 20% of cases. NAFLD is the most common cause of cryptogenic cirrhosis (cirrhosis of unknown origin).NAFLD is strongly associated with obesity, and other components of Metabolic Syndrome which is probably why it’s so prevalent in the United States. It’s estimated that more than 70% of obese individuals have some form of NAFLD.
Malignant neoplasms of the liver that arise from parenchymal cells are called hepatocellular carcinomas (HCC). HCCs are associated with cirrhosis in 80% of cases, and so patients will already be experiencing symptoms associated with cirrhosis.The presence of hepatocellular carcinoma may be unsuspected, until there is deterioration in the condition of a previously stablepatient with liver cirrhosis. Weakness and weight loss are associated symptoms, and there can be a sudden appearance of ascites, which may be bloody, suggesting portal or hepatic vein thrombosis by a tumor, or bleeding from a necrotic tumor. Physical examination may show tender enlargement of the liver with occasionally a palpable mass.Incidence and mortality rates for hepatocellular carcinoma are rising rapidly in the United States, and HCC is the ninth leading cause of cancer deaths in the U.S.Surgical resection of solitary hepatocellular carcinomas may result in cure if liver function is preserved. Treatment of underlying chronic viral hepatitis may lower postsurgical recurrence rates.
CirrhosisThe term cirrhosis implies liver damage that is irreversible. Microscopically the liver will be fibrosed with areas of nodular regeneration. The primary causes of cirrhosis are alcoholic liver disease, and chronic infection with Hep B or Hep C. In about a 1/3 of cases the cause of cirrhosis is not found – this is referred to as cryptogenic cirrhosis – but it is thought that NAFLD may be the major cause for these.Major Clinical Manifestations of CirrhosisHepatic encephalopathyAscitesEsophageal, gastric variciesPortal hypertensionJaundiceSplenomegalyBlood abnormalitiesThe Child-Turcotte-Pugh classification is a tool for determining prognosis of the disease. For example, patients with 5-6 points have a 100% 1 yr survival rate, and 85% for 2 yrs. On the other hand patients with 10-15 points only have a 45% 1 yr survival rate, and 35% for 2 yrs.
ManagementCirrhosis can be managed assuming cessation of injurious drugs and treatment of underlying conditions. But certain conditions may lead to cirrhosis becoming decompensated (meaning complications of impaired liver function arise due to some other underlying problem). Examples include infection, alcohol consumption, imbalance of urea and electrolytes, GI bleeds or progression of the underlying disorder.Nutritional supplements are required and the diet should be low in protein if there is encephalopathy and low in salt if there is ascites. Lactulose syrup can be ingested in order to move things quickly through the bowels, and reduce absorption of protein. It also lowers colonic pH, decreasing fecal ammonia production.Clearly alcohol should be avoided, but so should NSAIDs, sedatives and opiates. Interferon-α has been shown to improve liver biochemistry and may slow the development of hepatocellular cancer in cirrhosis induced by hepatitis C virus.The overall prognosis is relatively poor, with a 5-year survival rate of approximately 50%.
Bleeding tendencies are a major problem in advanced liver disease. This is partly due to a deficiency of coagulation factors, especially the prothrombin group (factors 2, 7, 9, and 10), because these all rely on vitamin K as a precursor for production. Vitamin K is absorbed from the large intestine and stored in the liver, where it is converted into an enzymatic cofactor for the carboxylation of prothrombin complex proteins. Widespread hepatocellular destruction, as seen in cirrhosis, decreases the liver’s storage and its ability to convert vitamin K, leading to deficiencies of the prothrombin-dependent coagulation factors. In addition to these deficiencies, thrombocytopenia may be caused by splenomegaly secondary to portal hypertension and to bone marrow depression. Accelerated fibrinolysis also is seen.The combination of hemorrhagic tendencies and severe portal hypertension (which causes thrombocytopenia as a consequence of sequestration of platelets in the spleen) sets the stage for episodes of gastrointestinal bleeding, or ruptured esophageal varices. Most patients with advanced cirrhosis die of complications of hepatic coma, often precipitated by massive hemorrhage from esophageal varices or concurrent infection.
Oral candidiasis – Can be caused by immunotherapy following liver transplant to prevent rejection of the organAngular cheilitis – Also associated with candidiasis from immunotherapy.Atrophic glossitis – Caused by anemia from malabsorption of vitamin B12, and iron.Petechiae – Little red dots usually seen on the palate, caused by thrombocytopeniaLichen planus – This is associated with Hep C infection, although I wasn’t able to find a pathogenesis.Oral metastases of HCC primarily manifest as hemorrhagic expanding masses located in the premolar and ramus region of the mandible
Many cases of hepatitis B and hepatitis C are mild, subclinical, and have no associated jaundice. These cases are essentially asymptomatic and go undetected. This means that many patients may be carriers of HBV or HCV and not even know it. For that reason we, as practitioners, need to assume that all of our patients could potentially have hepatitis, or be carriers of the virus. The most important thing to consider in the management of any patient is your own health and safety.Dentists need to follow standard precautions and wear their protective gear including gown, mask, eye protection, and gloves. There is a vaccine for the Hepatitis B virus, and OSHA requires that employers offer HBV vaccinations to employees who are occupationally exposed.Proper post-exposure protocol is important also. It is estimated that the risk of contracting HBV from a sharps injury is nearly 30%. If a vaccinated person has a needlestick, he/she needs to be tested for adequate antibody levels and if needed, be given immunoglobulin and a booster. Non-vaccinated people would receive the HB immunoglobulin. No post-exposure protocol exists yet for HCV, but the individual should be followed for 6 months for HC antibodies and liver enzyme activity.
Generally, for short periods of time, normal therapeutic doses of drugs can be used except when liver function is severely compromised. If necessary, alternative drugs not metabolized in the liver can be selected or doses and intervals adjusted. Extreme caution should be used in prescribing medications that are metabolized in the liver for patients with severe liver disease.NSAIDs increase the risk of GI bleeding and interfere with fluid balance, and are best avoided. Some texts advise to avoid acetaminophen, but others say it is relatively safe if limited to <4 g/day for acute pain management. It seems logical to limit acetaminophen to those patients with only mild liver impairment.Codeine, hydrocodone, and oxycodone, meperidineare conjugated in the liver and should beused at increased dose intervals and forshort-term use only.Limit the maximum dosage of lidocaine and mepivicaine to 300 mg.Limit Prilocaine to 400 mg max dosageSeptocaine may be a better choice since it is metabolized in the plasmaBenzodiazepines need reduced dosages and increased intervalsBeta-lactam antibiotics (penicillins, ampicillin, cephalexin, cefazolin, ceftriaxone) are safe because they are excreted by the kidneys (although as you can see in the figure, ampicillin is listed as a drug metabolized by the liver). It seems there is controversy regarding the use of some medications with liver disease.Metronidazole has a severe interaction with alcohol and should be avoided if there is any chance that the pt is drinking. It is also metabolized in the liver.Clindamycin, aminoglycosides, tetracyclines are all metabolized in the liver so use caution, reduce dosages, and increase intervals.
Before surgical procedures, patients with liver disease must have a careful evaluation of their capacity for hemostasis, and testing should include at minimum a platelet count, and PT/INR tests. Platelet count should be above 50,000 and INR below 2.0–3.5 for surgical procedures depending on the extentof surgery.Nonsurgical dental procedures may be safely performed in the higher INR ranges (below 4.0) and lower platelet counts. If laboratory values are not within an acceptable range, consultation with the physician. The patient may need platelet transfusions to correct the thrombocytopenia and/or fresh frozen plasma (FFP) to correct the factor-related coagulopathy. We generally give 2 units of FFP which will increase levels of all the clotting factors by 4-6%, and a 6 pack of platelets (60,000).Vitamin K injections the week prior to dental surgery may also be helpful. Intraoperative hemostatic agents, such as collagen matrix or absorbable gelatin sponge, should be used in extraction sites when hemostasis is impaired.
Liver TransplantPre-transplantComprehensive dental evaluationExtraction of infected, non-restorable, or periodontally hopeless teeth.Oral hygiene instructionPost-transplantNo elective dental tx for 3 months following surgeryRoutine Ab prophylaxis is not recommendedRecall program after 3 monthsProphylactic care
A few final things to consider:We already talked about a lot of this stuff, but I wanted to point out a thing or two.When it comes to local anesthetic, we talked about the dosage of anesthetic, but there is something else to consider. Portal hypertension can lead to congestive heart failure over time, so we need to be careful not to give too much epinephrine.You can give up to 0.2 mg of epi to a healthy person, but with congestive heart failure, we need to limit epinephrine to 0.04 mg. That is significant, because it works out to about 2.3 carpules of anesthetic containing 1:100,000 epi.And finally, we need to monitor blood pressure since it may be significantly high with portal hypertension.