Liver Cirrhosis

Liver cirrhosis ) ( :chronic progressive disease ;means the disease will continue unless you know and discover what is the underlying cause and treat it . it is not a simple disease, it is a very serious disease .

When we could say that the patient has liver cirrhosis ? - If we find some pathological findings from a biopsy or clinical pictures :
Necro-inflammatory reaction. Fibrosis. Loss of the lobular and vascular architecture of liver lobules ; because the lobules is not in the normal architecture then they will not function properly (they are not healthy) ,so the liver will continue to fail. Formation of Regenerating nodules .

Causes of liver cirrhosis

- Liver cirrhosis is the end result of many etiological factors in the liver : 1. Viral hepatitis: B and C ; the commonest all over the world ** viral hepatitis A doesnt lead to liver cirrhosis.

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 2. Alcohol; it is very common in areas where alcohol is essential for life like in Scotland, wales (alcohol is the number one as a cause for liver cirrhosis in these countries) . 3. Biliary diseases: primary or secondary ; liver contains hepatocytes and biliary system , so if there is any diseases in the biliary system this will lead to necrosis, inflammation and cirrhosis in the liver. sometimes this biliary disease happened due to obstruction in the biliary tract , and sometimes it is not due to obstruction but due to difficulty in the flow of the bile and this what we call it (primary biliary cirrhosis) >> there is no underlying cause , it is thought to be autoimmune in origin. While the (secondary biliary cirrhosis) occurs due to strictures(fibrosis) or stones. 4. Autoimmune hepatitis . 5. Vascular causes: CHF, Budd-Chiari syndrome, Veno-occlusive disease. As you know there is inferior vena cava passing behind the liver , and the liver gives the hepatic veins to take blood from the liver into the inferior vena cava . Hepatic veins are the last vessels enter inferior vena cava before it enters the heart, so in heart failure (the heart is not
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pumping blood properly) there will be stagnation of blood behind the liver in the inferior vena cava, so there will be congestion in the hepatic veins and this congestion will be reflected on the liver and it will start to deteriorate due to congestive heart failure. Sometimes this process(stagnation of blood) occur due to occlusion of hepatic veins themselves >> this condition is called (Budd-Chiari syndrome). in another condition there is occlusion in the small vessels of the liver >> this condition is called (Veno-occlusive disease). 6. Drugs and toxins ; we have a lot of drugs which may cause liver cirrhosis such as chemotherapeutic agents used for cancer therapy like(methotrexate , amiodarone) and isoniazide that is used in TB therapy. - Also there is a lot of toxins cause liver cirrhosis , some people use herbal medicines frequently that may contain toxins especially a type of mushroom which is very toxic to the liver. 7. Hereditary and metabolic (GENETIC IN ORIGIN) : A. hemochromatosis ; increase absorption of iron in the intestine that will lead to necrosis of liver with time. B. Wilsons disease ; disturbance in the metabolism and defective
excretion of cupper in the liver that will accumulate in it leading to cirrhosis .

C. 1-antitrypsin deficiency .
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 8. Non alcoholic liver disease (NASH non alcoholic steato hepatitis) ; in which there is fat deposition in the liver leading to liver cirrhosis, deterioration in the liver functions and it might cause hepatocelluar carcinoma.

NASH occurs in what type of people ?

1. In patients who are obese especially who are having central obesity ; patients who have just tummy ) (they are more liable for NASH . 2. Diabetics patients 3. Dyslipidemia

9. Cryptogenic liver cirrhosis ;means we dont know the cause of liver cirrhosis.

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Pathogenesis of the features of liver cirrhosis
- We can divide cirrhotic symptoms according to what caused them into two main categories :

1. Portal hypertension :
Elevation of portal vein pressure to more than 10 mmHg due to anatomic or functional obstruction to blood flow in the portal venous system .
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- portal vein is formed by union between splenic vein and mesenteric vein then it enters into the liver ; so when there is cirrhosis in the liver which causes fibrosis and obstruction of the radicals of the portal vein ) (inside the liver that leads to back pressure and congestion in the portal vein and this will be reflected on the splenic and mesenteric veins .

portal hypertention can be Classified into: (its not important to know them ) : 1. Presinusoidal: portal vein thrombosis 2. Sinusoidal: cirrhosis 3. Postsinusoidal: Budd chiari syndrome, veno-oclussive disease

Consequences : 1. Esophageal varices

2. Splenomegaly and hypersplenism; - Splenomegaly : when the spleen enlarges, it will be aggressive
against all types of blood components. So , instead of removing old blood cells , it will destroy all RBCs , WBCs and platelets whatever their state is . as a result , increment in the destruction of blood components leading to anemia , leucopenia , thrombocytopenia .

- hypersplenism : hyper-functioning spleen.

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ASCITES

3. Ascites 4. Hepatic encephalopathy

2. Liver cell dysfunction: - Manifestations:

Fatigue Low grade fever Fetor hepaticus : Destroyed apple like smell , this comes from
the toxins which is not detoxified by the liver.

Loss of muscle mass and subcutaneous fat ; thin patients. Jaundice Coagulopathy ; deficiency in coagulation factors , you know that
all the coagulation factors except factor 8 are synthesized in the liver so when there is a disease in the liver there will be deficiency in these factors which may lead to bleeding .

Low albumin ; albumin is synthesized in the liver and any

deficiency in it will lead to: 1. effect the healing of the tissue 2. abdominal ascites 3. edema of the lower limps

Cardiovascular changes:
Hyperdynamic state due to shunts and vasodilators ; tachycardia Cardiac dysfunction

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 Skin changes: palmar erythema, spider nevi, leuconychia (white

nails)

palmar erythema

spider nevi

leuconychia

Endocrine changes ; estrogen is mainly metabolized by the liver and if it is in excess amount this may lead to : In males: infertility, feminization, decreased potency, testicular atrophy, decreased libido In females: infertility, amenorrhea Metabolic changes: impaired glucose tolerance, hypoglycemia

Bone changes: Osteoporosis and the patient may lose his teeth Pulmonary changes: infections, effusion, pulmonary
Hypertension.

Ascites Hepatic encephalopathy ______________________________________________________________________________

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Investigations in liver cirrhosis

Biopsy: is the gold standard for diagnosis but we rarely take a
biopsy especially if the patient has disturbances in the coagulation system.

Lab abnormalities:
1. Mild to moderate rise in AST and ALT . 2. Bilirubin and alkaline phosphatase may be mildly elevated 3. Low albumin 4. Prolonged PT (prothrombin time): it is the main investigation that reflects the synthetic function of the liver .

Investigations to find the cause of cirrhosis ; if you discover the cause of this cirrhosis and treat it then the process of cirrhosis starts to stop and even to reverse, so it is essential to find the cause . ______________________________________________________________________________

Clinical picture :
Compensated cirrhosis

Decompensated cirrhosis

Cirrhotic patients may develop hepatocellular carcinoma (HCC)

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- Usually most of the conditions of the liver starts with acute hepatitis after that the patient either will be cured or will go into a process called chronic hepatitis , this chronic hepatitis may still as a mild disease or will go into a severe condition which cause liver cirrhosis . - At this stage the patient is still asymptomatic until Decompensated cirrhosis starts ; the signs and features of liver cirrhosis start to appear , and the patient usually deteriorates rapidly at this stage and the condition will be fatal. So , Acute hepatitis >> chronic hepatitis >> compensated liver cirrhosis (asymptomatic) >> decompensated cirrhosis >> death

- In Some types of liver cirrhosis , the patient deteriorates rapidly that within two years he will die. However in other patients may take ten years and that is controlled by several factors like the main underlying cause of liver cirrhosis.

So the main features of Compensated liver cirrhosis :- Usually asymptomatic - Fatigue is the commonest symptom - signs of chronic liver disease may be present: spider nevi, palmar erythema, nail changes, gynecomastia, testicular atrophy, hepatosplenomegaly

the main features of Decompensated cirrhosis :9|Page

Jaundice Bleeding esophageal varices Ascites Hepatic encephalopathy Jaundice

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Esophageal varices :
- Esophageal varices is one of the worst complications that can occur due to liver cirrhosis . it develops due to prevention of blood from going to the systemic circulation resulting in portal hypertension. As a result, the blood is going to find an exit other than liver to pass into the systemic circulation by searching upon the nearby veins(collaterals) , it increases the pressure in collaterals(ansatomotic channels between portal and systemic) . the usual location of those collaterals is present in lower esophagus and occasionally in gastric fundus . a large amount of blood will enter these small blood vessels and this will lead to congestion in these vessels and also may rupture at any time leading to massive severe bleeding.

To sum up : Obstruction in portal circulation >> blood try to find another exit to enter the systemic circulation (in the lower end of esophagus)>> there is no enough blood vessels >> new blood vessels formed >> a lot of congestion and pressure will be on these vessels >> they may at any time rupture >> lead to severe massive bleeding .

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- Treatment of esophageal varices :

1. 2. 3. 4. Resuscitation and blood transfusion as needed Use of somatostatin or octreotide Variceal band ligation (a way to stop bleeding ) Sclerotherapy injection ; using sclerosing agent that will mimic fibrosis in that area. 5. B-blockers 6. TIPS ; a technique that provides an exit for the portal circulation
into the systemic through routs other than collaterals . by this technique we put a stent in the liver between the systemic and portal circulations .

7. Surgical shunt operations ; we dont prefer it because it is very

dangerous .

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Ascites
Definition :
- It is an accumulation of fluid in the peritoneal cavity of the abdomen distending it forwards.

Etiology:
1. 2. 3. 4. sinusoidal hypertension sodium retention Hypoalbuminemia Lymphatic exudation

Treatment:
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1. 2. 3. 4. 5. 6. 7. 8.

Sodium restriction and bed rest Spironolactone Loop diuretics Albumin infusion Large volume paracentesis; removal of fluids from the abdomen TIPS Peritoneovenous shunts Liver transplantation(best treatment)

Hepatorenal syndrome (HRS):

it is the development of renal failure despite normality of structure. fatal condition that requires a patient to be cirrhotic and ascetic . Kidneys are histologically normal . Carries very poor prognosis .

Hepatic encephalopathy (HE):

-It is the worst complication of liver cirrhosis. -it is a neuropsychiatric syndrome in patients with advanced liver disease due to toxins.
Normally , ammonia is absorbed from intestine where there are bacteria acting on ingested proteins to produce it before absorbed . then , it accumulates in the circulation in large amounts. When goes to the liver , it(ammonia) is converted into urea which is easy to be cleared by the kidneys

- The main toxic we are talking about it here in this syndrome is ammonia. - Ammonia accumulates in the circulation of cirrhotic patients that goes to the brain making this syndrome; means when there is a disease in the liver , the ammonia will not be cleared so it will accumulate and effect the function of the brain.

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1. Deterioration in level of consciousness

2. Behavioral and psychiatric changes 3. Lack of concentration 4. Sleep disturbances 5. Flapping tremors

Precipitating factors for HE : Factors that increase the incidence of HE

1. 2. 3. 4. 5. 6. 7. 8. Gastrointestinal bleeding Infection Narcotics and sedative drugs Surgery Constipation Hypokalemia High protein diet Biliary diseases

Treatment :
- Identify and treat underlying cause. - Lactulose therapy: the main treatment ; lactulose could kill the bacteria that produce ammonia by lowering the ph in the intestine. - Antibiotics: Neomycin, metronidazole, rifaximin - Drugs that metabolize ammonia: To hippuric acid: sodium benzoate To glutamine: L-aspartate, L-ornithine (LOLA) - Extracorporeal albumin dialysis.

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Hematological disturbances in liver cirrhosis

i. Anemia: 1. 2. 3. 4. Bleeding Folate deficiency Hemolytic anemia Hypersplenism

ii. Leucopenia due to hypersplenism iii. Thrombocytopenia due to cirrhosis and hypersplenism iv. Defective coagulation with prolonged prothrombin time and INR

Screening for Hepatocellular carcinoma (HCC) :

- Cirrhotic patients are at increased risk for HCC especially:
Hepatitis B and C Alcoholic cirrhosis Genetic hemochromatosis Primary biliary cirrhosis

How we can detect HCC? 1. serum alpha-fetoprotein (AFP) testing ; usually the level of AFP is increased in cirrhotic patients. 2. ultrasonography ______________________________________________________________________________
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Liver transplantation :
- For patients with advanced decompensated liver cirrhosis. - Either from living donor(take half of the liver) or from cadaver(dead donor) . - 5-year-survival after transplantation is 80%

Significance of liver cirrhosis to dentists:

Risk to patients with cirrhosis: - Increased incidence of infection
- Decreased wound healing - Increased bleeding - May precipitate hepatic encephalopathy - Defective teeth and caries So you should deal correctly with those patients.

Risk to dentist: - Increased risk of infection with HBV (hepatitis B virus) or HCV
if the patient is having any of them. So always try to protect yourself by wearing gloves , sterilize all the instruments after use .

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Past years questions about this lecture ^_^

1) if a patient with liver cirrhosis come to your dental clinic , what is the best test that should done before any dental treatment ? a. PT (INR) b. ALT . AST c. Biopsy 2) All of the following are risk factors for liver cirrhosis expect : a. Hepatitis B b. Hepatitis A c. Hepatitis C d. Hemachromatosis 3) Which of the following is not a complication of liver cirrhosis ? a. Esophageal varices b. Ascitis c. Hepatorenal syndrome d. Caries 4) Which of the following is not a treatment for esophageal varices? a. blood transfusion b. Sclerotherapy injection c. Variceal band ligation d. Loop diuretics

May protection from GOD be upon all of you .. excuse us if there is any mistake ..
Done by : Rasha Al-Shboul & Rawan shatnawi

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