LIVER CARE FOUNDATION , NEW DELHI

About the Liver

The Liver is an organ on the right side of the body weighing about 1.5Kg. It is distinctly the largest and a key organ of a human body, characterized by its muddy red colour. It is strategically the first port of entry from the process of digestion before nutrients leave for the rest of the body. It is the only organ in the human body that can regenerate unless struck by disease.



Essential Functions of the Liver are

Using Food to make chemicals for essential functions of the body
Processing drugs to modified forms that are easily absorbed
Manufacturing essential substances
Storage of nutrients for various processes
Detoxification and excretion of substances that are no longer needed by the body

The liver's key role as a member of the human body


Production of Energy instantly
Making proteins for body building and tissue repair
Storing vitamins, minerals, and sugars for various functions
Regulating fat transport across the body
Regulating Blood clotting activities
Regulating levels of chemicals and drugs in the blood
Regulating hormone balance
Helping in digestion by production of bile
Helping to eliminate excess cholesterol levels
Neutralizing poisonous substances
Metabolism of alcohol
A vital organ in blood formation before birth
Helping to resist infection
Regenerating its own damaged tissue
Resisting infections by helping to remove bacteria from blood
Cleansing Blood by discharging waste products


Anatomy and physiology of the liver related to blood flow and biochemistry

The Liver and Blood Flow

Systemic circulation: Oxygenated blood that has returned from the lungs to the left ventricle of the heart is pumped to all of the tissues of the body.

Pulmonary circulation: After reaching the tissues, blood is returned to the right side of the heart, from where it is pumped to the lungs and then returned to the left side of the heart after taking up oxygen and giving off carbon dioxide.

Portal circulation: Blood from the gut and spleen flow to and through the liver before returning to the right side of the heart. The large vein through which blood is brought to the liver is called the portal vein. After passing through the liver, blood flows into the hepatic vein, which leads into the inferior vena cava to the right side of the heart. The liver also receives some blood directly from the heart via the hepatic artery. In the esophagus, stomach, small intestine and rectum, the portal circulation and veins of the systemic circulation are connected. Under normal conditions, there is little to no back flow from the portal circulation into the systemic circulation.
The Liver and Biochemical Functions
The liver performs many biochemical functions. Blood clotting factors are synthesized in the liver. Albumin, the major protein in the blood, is also synthesized in and secreted from the liver. The modification and/or synthesis of bile components also takes place in the liver. Many of the body's metabolic functions occur primarily in the liver including the metabolism of cholesterol and the conversion of proteins and fats into glucose. The liver is also where most drugs and toxins, including alcohol, are metabolized.

Bilirubin Secretion
The liver is the site of bile formation. Bile contains bile salts, fatty acids, cholesterol, bilirubin and other compounds. The components of bile are synthesized and modified in hepatocytes (the predominant cell type in the liver) and secreted into small bile ducts within the liver itself. These small bile ducts form a branching network of progressively larger ducts that ultimately become the common bile duct that takes bile to the small intestine. Bilirubin is a yellow pigment that derives primarily from old red blood cells. Bilirubin is taken up by hepatocytes from the blood, modified in the hepatocytes to a water soluble form and secreted into the bile.



What is liver disease ?

Liver disease is an acute or chronic damage to the liver, usually caused by infection which can be viral or non-viral, abnormal changes seen through growth of tumors or tumor-like processes, changes or abnormalities in the metabolic process or naturally through a congenital process.

Diseases of the liver can also be categorized by the effect. Hepatitis is inflammation of the liver, cirrhosis involves scarring and progressive cell death, stones develop and form blockages, fatty liver and cancer are modification effects from causes that could be related to genetic defects, lifestyle, environment, or other diseases. All these prevent vital functions of the liver and may cause a build-up of damaging substances to the liver itself that could even be a threat to life. Liver diseases can be acute (usually for a short duration) or chronic (commonly lifelong)






Signs and Symptoms

Liver disease is often discovered during routine testing. Having no symptoms at all is not uncommon.

Acute liver diseases present themselves with symptoms such as high bilirubin-counts (bilirubin is a by-product that is derived from the breakdown of red blood cells), jaundice (yellowing of the skin and eyes), dark yellow/orange coloured urine, or light, clay –coloured stools. A loss of appetite, nausea, vomiting, and diarrhea are not uncommon symptoms either.
Chronic liver disease can present themselves with jaundice (yellowing of the skin and eyes), dark yellow/orange coloured urine, abdominal swelling due to ascites (accumulation of fluid), pruritusunexplained weight loss or gain, (itching), and abdominal pain. Many of these symptoms may not be present until the disease has reached an advanced stage.


Detecting liver disease

Diagnosis of a liver disease considers the patient’s history, symptoms if experienced, a physical examination, laboratory tests, often a radiological study and a biopsy are conducted. A hepatologist would be the expert to make the most reliable diagnosis and recommendations.

Patients with liver diseases often have questions about their various results while trying to understand their importance. Our attempt is to explain some of the commonly prescribed tests for liver diseases that could be abnormal in individual patients. Please do bear in mind that abnormalities of these tests do not mean a diagnosis of a specific disease. Only a qualified physician who is aware of the entire case is able to give the best diagnosis.



What laboratory tests are used to detect a problem with the liver?

Three types of tests are often used to detect liver disease; these tests measure the levels of specific enzymes, bilirubin, or protein present as part of assessing the liver function. A test sample is usually a blood sample. This sample is extracted from the body using a syringe.

Enzymes: are proteins that help cells do their work. When cells are injured, enzymes tend to leak into the blood stream to produce higher-than-normal levels. All liver enzymes are measured by the amounts in the serum (blood), which is why they may be referred to as Serum ALT, AST, ALP. Three common enzymes used to detect liver diseases are:


Alanine aminotransferase (ALT) – an enzyme found mainly in liver cells. Raised ALT levels can be due to damage or death of a liver cell causing its leakage in the blood stream. All forms of hepatitis cause damage to liver cells where a raised ALT level can lead the physician to suspect a liver disease. Its severity, however, will be subject to other tests as part of confirmation.
Aspartate aminotransferase (AST) – another enzyme found in the liver and a few other places, particularly the heart and other muscles. It is less specific for liver disease alone as a raised AST could also be one early indication for a heart attack. Usually where the liver is inflamed, raised ALT and AST levels are in the ratio of 1:1. However, in specific diseases such as alcoholic hepatitis or liver shock, AST levels could be higher than blood ALT levels.
Alkaline phosphatase (ALP) – an enzyme related to the bile ducts; often increased when they are blocked. Alkaline phosphatase is also produced by the kidneys, intestine, placenta and bone. Increased levels of ALP in the presence of normal or moderately elevated AST and ALT are suggestive of an obstruction in the bile duct or a bile duct disease such as primary biliary cirrhosis or primary sclerosing cholangitis. ALP elevated can also be an indication of a bone disorder as it is also produced in bones.
Gamma-glutamyltranspeptidase (GGT) - another enzyme produced in the bile ducts which may be elevated in the blood alongside ALP in patients with bile duct diseases. GGT is an extremely sensitive test. There are also chances of increased GGT due to drugs and alcohol, particularly in heavy drinkers with no liver damage or inflammation.


Bilirubin is a waste product made from destruction of old red blood cells. It is a yellow compound that causes the jaundice and dark yellow coloured urine when present in increased amounts. Bilirubin is removed from the blood by the liver that chemically modifies it by a process called conjugation and secretes as bile. Tests for bilirubin are
Total bilirubin measures all the bilirubin in the blood (direct + indirect)
Conjugated or direct bilirubin - measures a form produced in the liver
Un-conjugated or indirect bilirubin- measures an indirect form of bilirubin that was not converted to the conjugated form in the liver.

A Variation in the ratios of direct and indirect bilirubin may be an indication for a liver disease that could be due to
increased production
decreased uptake by the liver
decreased conjugation
decreased secretion from the liver
due to blockage in the bile duct

Protein tests
Albumin - tell how well the liver is synthesizing this protein. Low albumin levels are suggestive of poor liver function. Chronic liver diseases that are compensated may show normal albumin levels. Decreased levels of albumin are common in cirrhosis or where significant liver damage is present. Low levels of albumin can also be indications for other diseases such as malnutrition and certain kidney disorders.

Serum Protein electrophoresis is a test where the major proteins in the serum are separated in an electric field to determine concentrations. The four major types of serum proteins are albumin, alpha-globulins, beta-globulins and gamma-globulins. Serum protein electrophoresis is a useful test for patients with liver diseases as it can give the physician several diagnostic possibilities. For instance: in cirrhosis the albumin can be decreased but the gamma-globulin level may be elevated. High gamma-globulin levels may also be found in types of autoimmune hepatitis whereas a low alpha-globulin level could suggest a metabolic disease such as alpha-1-antitrypsis deficiency.
Prothrombin time (PT)- Factors needed for blood clotting are made in the liver. In cases where the liver function is abnormal, the synthesis and secretion of these factors into the blood is lowered. The PT is a test where clotting time becomes prolonged if factors made by the liver are found to be low in the blood. In compensated chronic liver diseases, clotting factors are not low until the liver reaches the stage of cirrhosis or significant damage. An elevated PT can also be seen in acute liver diseases where there may be severe liver damage which becomes normal once the patient recovers. PT time can also be prolonged in cases of vitamin K deficiency and from drugs such as warfarin (which is used as an anti-coagulant) and in other non-liver diseases.
Platelet count- These are the smallest units of blood cells that are involved in clotting. In certain individuals with a liver disease, the spleen becomes enlarged as the blood flow to the liver is impaired. Platelet counts fall following development of cirrhosis, however, platelet counts could be abnormal in disorders other than liver diseases.


What types of imaging are used to detect the severity of a liver disease ?

Imaging is important for making an accurate diagnosis on various biliary tract diseases and for diagnosing focal liver lesions such as tumours. In diagnosing diffuse hepatic diseases such as cirrhosis or hepatitis, it is limited.
Transabdominal Ultrasound- is traditionally performed across the abdomen. Preparation for an ultrasound may require a period of fasting. It is the least expensive, safest and fairly sensitive for imaging the biliary system especially the gall-bladder. Often it is selected as the procedure of choice for screening biliary tract abnormalities and making a difference between a intrahepatic (that which occurs within liver cells and can be managed medically) and extrahepatic (that which occurs within a duct and can be managed surgically) causes of jaundice as well as detecting liver masses. The kidney, pancreas and blood vessels can also be seen on such ultrasounds. Usually presence of intestinal gas or obesity can obscure visibility.

Transabdominal ultrasound can detect focused liver lesions (> 1 cm in diameter) more accurately than diffuse diseases (eg, fatty liver, cirrhosis). Generally, cysts are echo-free; solid lesions (eg, tumors, abscesses) which are echogenic (can reflect high-frequency sound waves that allows imaging by ultrasound techniques).

Carcinoma (cancers) also appear as nonspecific solid mass. Ultrasound has been used to screen for hepatocellular carcinoma in patients at high risk (those with chronic hepatitis B). This ability to localize focal lesions can permits ultrasound-guided aspiration and biopsy.
Doppler ultrasound is a noninvasive method that assesses direction of blood flow and patency (extent of any obstruction) of key blood vessels around the liver. These are the portal vein and hepatic artery.70% of the blood and nutrients are supplied to the liver is through the portal vein and 30% through the hepatic artery. Doppler ultrasound can reveal evidence of portal hypertension with collateral flow, assess the patency (obstruction) of liver shunts (eg, surgical portocaval, percutaneous transhepatic), and reveal hepatic artery thrombosis after a liver transplantation. It also can detect any unusual vascular structures. Most patients with cirrhosis are recommended a Doppler ultrasound.
Computerized Tomography (CT) is commonly used to identify hepatic masses, particularly small metastases. It has an accuracy of about 80%. A CT with an intravenous (IV) contrast is accurate for diagnosing carvenous (deep-set) hemangiomas of the liver as well as distinguishing them from other abdominal masses. Unlike an ultrasound, neither obesity nor intestinal gas can cloud a CT image. CT can detect fatty liver and increased hepatic density possibly associated with iron overload. However, a CT is less helpful than ultrasound in diagnosing biliary obstruction.
Magnetic Resonance Imaging (MRI) consists of imaging blood vessels (without using a contrast dye) and hepatic tissues. It is an expensive technique where its indications are still evolving. MRI is superior to CT and ultrasound for diagnosing diffuse liver diseases such as fatty liver and hemochromatosis and for clarifying some focal defects such as hemangiomas. MRI can reveal blood flow and complements doppler ultrasound and CT angiography in diagnosing any vascular abnormalities and in performing vascular mapping before a liver transplantation.
Magnetic Resonance Cholangiopancreatography (MRCP). MRCP is more sensitive than CT or ultrasound in diagnosing common bile duct abnormalities, particularly stones. Its images are comparable to those from an ERCP and percutaneous transhepatic cholangiography, which are more invasive. MRCP is a useful screening tool where biliary obstruction is suspected and a usual step before proceeding to therapeutic ERCP.

Endoscopic Retrograde Cholangiopancreatography (ERCP) combines endoscopy through the second portion of the duodenum with contrast imaging of the biliary and pancreatic ducts. An endoscope is placed in the descending duodenum, then where the Papilla of Vater is cannulated (a procedure involving adding a tube so that fluids are drained to maximize the effect of the procedure) Meanwhile the pancreatic and biliary ducts are injected with contrast. ERCP is the procedure of choice when bile duct stones are suspected but have not been found on less invasive tests. The test is especially valuable for diagnosing correctable biliary tract lesions causing persistent jaundice (eg, stone, stricture, sphincter of Oddi dysfunction). Besides providing excellent images of the biliary tract and pancreas, ERCP reveals some of the upper GI tract. This procedure allows biopsies and other interventional procedures to be performed such as biliary stone extraction.

Percutaneous transhepatic cholangiography (PTC): PTC involves puncture of the liver with a needle under fluoroscopic or ultrasound guidance to cannulate (a procedure involving adding a tube so that fluids are drained to maximize the effect of the procedure) the peripheral intrahepatic bile duct system which is just above the common hepatic duct where contrast material is injected. PTC is highly diagnostic for biliary disease and can be therapeutic such as during decompression of the biliary system. However, ERCP is generally preferred because PTC causes complications such as sepsis, bleeding, bile leaks).
What invasive diagnostic procedures are used to confirm the severity of a liver disease?
Liver biopsy can provide a tissue of the liver, which is then mounted on a slide and studied for changes due to disease. A small core of tissue is obtained that is representative even with focal lesions. Ultrasound- or CT-guided biopsies definitely improve the yield. A biopsy is valuable in detecting tuberculosis (TB) or other infiltrations and help to clarifying the underlying cause of the liver inflammation such as ischemic injury, rejection after liver transplantation, biliary tract disease, or viral hepatitis. Serial biopsies are commonly performed over years, may be necessary for monitoring disease progression.
Gross examination and histopathology are often definitive. Cytology, frozen section, and culture are useful processes in selected cases. Metal content can be measured in the biopsy specimen: copper in suspected Wilson's disease and iron in hemochromatosis.
Limitations of liver biopsy include a sampling error and occasional errors or uncertainty in cases of cholestasis.
Indications for Liver Biopsy

Unexplained liver enzyme abnormalities

Alcoholic liver disease or nonalcoholic steatosis (diagnose and stage)

Chronic hepatitis (diagnose and stage)

Suspected rejection after liver transplantation that cannot be diagnosed by less invasive methods

Hepatosplenomegaly of unknown cause

Unexplained intrahepatic cholestasis

Suspected malignancy (focal lesions)

Unexplained systemic illness–eg, fever of unknown origin, inflammatory or granulomatous diseases (culture is performed with biopsy)

Endoscopy
An endoscope as used in the field of gastroenterology is a thin flexible tube which uses a lens or miniature camera to view various areas of the gastrointestinal tract. When the procedure is performed to examine certain organs such as the bile ducts or pancreas, the organs are not viewed directly, but rather indirectly through the injection of x-ray dye into the bile duct.
The performance of an exam using an endoscope is referred by the general term endoscopy. Diagnosis through biopsies or other means and therapeutic procedures can be done with these instruments.
Extracorporeal shock-wave lithotripsy (ESWL)
This is a technique that uses high-pressure waves similar to sound waves that can be "focused" on a very small area, thereby fracturing small solid objects such as gallstones, kidney stones, etc. The small fragments can pass more easily and harmlessly into the intestine or can be dissolved with medications.

The Hepatic Venous Pressure Gradient (HVPG)
The HVPG represents the gradient between portal vein and intra-abdominal vena cava pressure. HVPG measurement is done after an overnight fast, under conscious sedation and monitoring for vital signs (This includes heart rate, arterial blood pressures, digital oxygen saturation, and ECG).

Under local anesthesia, central vein (for pressure monitoring) is punctured using the Seldinger technique. There are four steps to the Seldinger technique

Venepuncture is performed with a introducer needle or trocar (a sharp hollow needle)

A soft tipped guide wire is passed through the needle and the needle removed

A cannula or dilator is passed over the guide wire

Cannula or dilator is removed and catheter is passed over wire using fluoroscopy to establish its position- The guidewire is then removed

The Seldinger technique has been refined to help reduce complications such as infection, haemorrhage and accidental perforation during intervention into a vein. The advantage of this procedure is a possibility of a biopsy alongside measurement of the pressure in the portal vein. Use of doppler ultrasound helps to minimize complications such as leakage, hematoma, and rarely, reaction in the vein, rupture of venous trocar, or arteriovenous puncture causing a fistula. The key measurement of a HVPG procedure are the Free Hepatic Venous Pressure and the Wedge Hepatic Venous Pressure. The difference between the two measurements will provide the pressure gradient in the liver to ascertain severity of portal hypertension.


Grading of pressure

Persons with normal portal pressure measure between 1-5mmHg.

Persons with portal pressure above 5mmHg are graded as subclinical portal hypertension.

Persons with portal pressure equal and over 10mmHg are assessed to be clinically significant portal hypertension.

Persons with a portal pressure over 12mmHg are at risk for a varaceal rupture.

What are some common liver disease symptoms?
When diagnosing liver disease, the physician looks at the patient's symptoms and conducts a physical examination. In addition, the physician may request a liver biopsy, liver function tests, an ultrasound, or a CT scan (computerized tomography scan).
Some common liver disease symptoms include the following, each of which are described briefly below:

jaundice

cholestasis

liver enlargement

portal hypertension

ascites

liver encephalopathy

liver failure


What is jaundice?
Jaundice is a yellow discoloration of the skin and eye whites due to abnormally high levels of bilirubin (bile pigment) in the bloodstream. Urine is usually dark because of the bilirubin excreted through the kidneys. High levels of bilirubin may be attributed to inflammation or other abnormalities of the liver cells or blockage of the bile ducts. Sometimes jaundice is caused by the breakdown of a large number of red blood cells, which can occur in newborns. Jaundice is usually the first sign, and sometimes the only sign, of liver disease.

What is cholestasis?
Cholestasis is reduced or stopped bile flow. Bile flow may be blocked inside or outside the liver. Symptoms may include:

jaundice

dark urine

pale stool

bone loss

easy bleeding

itching

small, spider-like blood vessels visible in the skin

enlarged spleen

fluid in the abdominal cavity

chills

pain from the biliary tract or pancrea

enlarged gallbladder

Some causes of cholestasis include:

hepatitis

primary biliary cirrhosis

drug effects

hormonal changes during pregnancy

a stone in the bile duct

bile duct narrowing

bile duct cancer

pancreatic cancer

inflammation of the pancreas

What is liver enlargement?
Liver enlargement is usually an indicator of liver disease, although there are usually no symptoms associated with a slightly enlarged liver (hepatomegaly). Symptoms of a grossly enlarged liver include abdominal discomfort or "feeling full."

What is portal hypertension?
The portal vein carries about 1500 ml/min of blood from the small and large bowel, spleen, and stomach to the liver at a pressure of about 5 mmHg. Any obstruction or increased resistance to flow or due to pathological increases in portal blood flow could lead to portal hypertension with portal pressures over 12 mm Hg. Although the differential diagnosis is extensive, alcoholic and viral cirrhosis are the leading causes of portal hypertension in Western countries, whereas liver disease due to schistosomiasis is the main cause in other areas of the world (caused by a parasitic worm). Portal vein thrombosis is the commonest cause in children. In India and Japan non-cirrhotic portal fibrosis is a known cause of portal hypertension seen in lower-social groups and low hygiene.

Portal hypertension is abnormal high blood pressure in the portal vein, which supplies the liver with blood from the intestine. Portal hypertension may be due to increased blood pressure in the portal blood vessels or resistance to blood flow through the liver. Portal hypertension can lead to the growth of collateral vessels that connect to the general circulation, bypassing the liver. When this occurs, substances that are normally removed by the liver pass into the general circulation. Symptoms of portal hypertension may include:

a distended abdominal cavity (ascites)

bleeding of the varicose veins at the lower end of the esophagus and in the stomach lining


What is gastric bleeding?
Increases in portal pressure disturb the portal systemic circulation. These factors are partly responsible for the important complications of chronic liver disease, including variceal bleeding, hepatic encephalopathy, ascites, hepatorenal syndrome, recurrent infection, and abnormalities in coagulation. Variceal or gastric bleeding is the most serious complication and is an important cause of death in patients with cirrhotic liver disease.

Patients with varices have a 30% lifetime risk of gastric bleeding, and a third of those who bleed will die. Patients who have bled once from oesophageal varices have a 70% chance of bleeding again and about a third of further bleeding episodes are fatal.

What is ascites?
Ascites is fluid build-up in the abdominal cavity, caused by fluid leaks from the surface of the liver and intestine. Ascites due to liver disease usually accompanies other liver disease characteristics such as portal hypertension. Symptoms of ascites may include a distended abdominal cavity, which causes discomfort and shortness of breath. Causes of ascites may include:

liver cirrhosis (especially cirrhosis caused by alcoholism)

alcoholic hepatitis

chronic hepatitis

obstruction of the hepatic vein

Ascites can also be caused by non-liver disorders.


What is Cirrhosis?
Cirrhosis is characterized anatomically by widespread nodules in the liver combined with fibrosis. The fibrosis and nodule formation causes distortion of the normal liver architecture which interferes with blood flow through the liver. Cirrhosis can also lead to an inability of the liver to perform its biochemical functions.

The journey of what goes wrong in Cirrhosis

Cirrhosis results from damage to liver cells from toxins, inflammation, metabolic derangements and other causes. In cryptogenic liver disease, the cause is unknown.


Damaged and dead liver cells are replaced by fibrous tissue leads to fibrosis (scarring). Liver cells begin to regenerate in an abnormal pattern primarily forming nodules that are surrounded by fibrous tissue
.

Grossly abnormal liver architecture leads to decreased blood flow to and through the liver. There is decreased blood flow to the liver and blood back up in the portal vein and portal circulation leads to some of the serious complications of cirrhosis. Blood can back up in the spleen causing it to enlarge and sequester blood cells.


Most often, the platelet count falls because of splenic sequestration (withholding of the blood) leading to abnormal bleeding. If the pressure in the portal circulation increases because of cirrhosis and blood withheld, blood can flow backwards from the portal circulation to the systemic circulation where they are connected. This can lead to varicose veins in the stomach and esophagus (gastric and esophageal varices) and rectum (hemorrhoids). Gastric and esophageal varices can rupture, bleed massively and even cause death.


Hypertension in the portal circulation, along with other hormonal, metabolic and kidney abnormalities in cirrhosis, can also lead to fluid accumulation the abdomen (ascites) and the peripheral tissue (peripheral edema).


Decreased bilirubin secretion from hepatocytes in cirrhosis leads to the back up of bilirubin in the blood. This leads to jaundice, the yellow discoloration of the skin and eyes. As the water-soluble form of bilirubin also backs up in the blood, bilirubin can also spill into the urine giving it a bright yellow to dark brown color.


Abnormal biochemical function of the liver in cirrhosis can lead to several complications. The serum albumin concentration falls which can lead to aggravation of ascites and edema. The metabolism of drugs can change requiring dose adjustments.


In men, breast enlargement (gynecomastia) sometimes occurs because metabolism of estrogen in the liver is decreased.


Decreased production of blood clotting factors can lead to bleeding complications.


Derangements in the metabolism of triglycerides, cholesterol and sugar can occur.


In earlier stages, cirrhosis frequently can cause insulin resistance and diabetes mellitus.


In later stages or in severe liver failure, blood glucose may be low because it cannot be synthesized from fats or proteins.


Cirrhosis, especially in advanced cases, can cause profound abnormalities in the brain. In cirrhosis, some blood leaving the gut bypasses the liver as blood flow through the liver is decreased.


Metabolism of components absorbed in the gut can also be decreased as liver cell function deteriorates.
Both of these derangements can lead to hepatic encephalopathy as toxic metabolites, normally removed from the blood by the liver, can reach the brain.


In its early stages, subtle mental changes such as poor concentration or the inability to construct simple objects occurs.
In severe cases, hepatic encephalopathy can lead to stupor, coma, brain swelling and death.


Cirrhosis can lead to immune system dysfunction causing an increased risk of infection. Ascites fluid in the abdomen often becomes infected with bacteria normally present in the gut (spontaneous bacterial peritonitis).


Cirrhosis can also lead to kidney dysfunction and failure.


End-stage cirrhosis, can trigger kidney dysfunction called hepatorenal syndrome can occur. This is fatal unless a liver transplant takes place.


Clinical Symptoms and Diagnosis of Cirrhosis

Cirrhosis is usually an easy diagnosis to make when any or all of the above abnormalities and complications are present. This is especially true when the underlying liver disease can be identified. The underlying liver disease is identified in most patients, however, sometimes it will not be discovered despite recommending specific diagnostic tests. Such cases are called "cryptogenic" cirrhosis.

Some patients with cirrhosis, especially early in the course of the disease, will have no overt clinical signs or symptoms. Some may have only subtle physical changes such as


Red palms or red spots that blanch on their upper body (spider angiomata)

Hypertrophy of the parotid glands

Gynecomastia or fibrosis of tendons in the palms.
Some patients may only have subtle abnormalities on blood tests, and in some cases, all blood tests may be normal.

Radiological and nuclear medicine tests may give clues as to the presence of cirrhosis

The diagnosis of cirrhosis can often be made by an ultrasound

The diagnosis of the liver architecture can only be made by a biopsy.


Treatment
Cirrhosis of the liver is irreversible but treatment of the underlying liver disease may slow or stop the progression. Such treatment depends upon the underlying etiology. In cryptogenic cirrhosis, since the cause is unknown, supportive therapy directed at alleviating symptoms due to progression and its complications is the only answer.


Bleeding esophageal varices can be treated with endoscopic sclerotherapy or rubber band ligation.

Ascites and edema are often responsive to a low sodium diet and such a diet must be emphasized in patients with these symptoms. More advanced ascites and edema can respond to diuretic therapy.

A low protein diet and agents such as lactulose may help hepatic encephalopathy.
Infections such as spontaneous bacterial peritonitis must be rapidly treated with appropriate antibiotics.

Drugs metabolized in the liver must be given with caution.

Coagulation disorders will sometimes respond to vitamin K.

Liver transplantation is highly effective for the treatment of end-stage cirrhosis. Transplantation is usually needed when complications such as encephalopathy, ascites or bleeding varices are uncontrollable or when biochemical function is severely depressed.



What is liver encephalopathy?
Liver encephalopathy is the deterioration of brain function due to toxic substances building up in the blood, which are normally removed by the liver. Liver encephalopathy is also called portal-systemic encephalopathy, hepatic encephalopathy, or hepatic coma. Symptoms may include:

impaired consciousness

changes in logical thinking, personality, and behavior

mood changes

impaired judgement

drowsiness

confusion

sluggish speech and movement

disorientation

loss of consciousness

coma


What is liver failure?
Liver failure is severe deterioration of liver function. Liver failure occurs when a large portion of the liver is damaged due to any type of liver disorder. Symptoms may include:

jaundice

tendency to bruise or bleed easily

ascites

impaired brain function

general failing health

fatigue

weakness

nausea

loss of appetite


Supportive Treatments in management of characteristics of Liver Disease

Sclerotherapy
In sclerotherapy a sclerosant solution (ethanolamine oleate or sodium tetradecyl sulphate) is injected into the bleeding varix or the overlying submucosa. Injection into the varix obliterates the lumen by thrombosis whereas injection into the submucosa produces inflammation followed by fibrosis. The first injection controls bleeding in 80% of cases. If bleeding recurs, the injection is repeated. Complications are related to toxicity of the sclerosant and include transient fever, dysphagia and chest pain, ulceration, stricture, and (rarely) perforation.

Band ligation
Band ligation is achieved by a banding device attached to the tip of the endoscope. The varix is aspirated into the banding chamber, and a trip wire dislodges a rubber band carried on the banding chamber, ligating the entrapped varix. One to three bands are applied to each varix, resulting in thrombosis. Band ligation eradicates oesophageal varices with fewer treatment sessions and complications than sclerotherapy.




Balloon tube tamponade
The balloon tube tamponade may be life saving in patients with active variceal bleeding if emergency sclerotherapy or banding is unavailable or not technically possible because visibility is obscured. In patients with active bleeding, an endotracheal tube is inserted to protect the airway before attempting to place the oesophageal balloon tube.

A Minnesota balloon tube has four entry points

1for gastric aspiration

2 to inflate the gastric and oesophageal balloons

1 above the oesophageal balloon for suction of secretions to prevent aspiration.


The tube is inserted through the mouth, and correct positioning in the stomach is checked by auscultation while injecting air through the gastric lumen. The gastric balloon is then inflated with 200 ml of air. Once fully inflated, the gastric balloon is pulled up against the oesophagogastric junction, compressing the submucosal varices. The tension is maintained by strapping a split tennis ball to the tube at the patient's mouth.
An oesophageal balloon is rarely required. Complications could be


gastric and oesophageal ulceration

pneumonia

oesophageal perforation.


Continued bleeding during balloon tamponade indicates an incorrectly positioned tube or bleeding from another source. After resuscitation, and within 12 hours, the tube is removed and endoscopic treatment repeated.





Transjugular intrahepatic portosystemic shunt (TIPS)
Transjugular intrahepatic portosystemic shunt is the best procedure for patients whose bleeding is not controlled by endoscopy. It is effective only in portal hypertension of hepatic origin (caused by fibrosis of the liver for example). The procedure is performed via the internal jugular vein under local anaesthesia with sedation. The hepatic vein is cannulated and a tract created through the liver from the hepatic to the portal vein, with a needle under ultrasonographic and fluoroscopic guidance. The tract is dilated and an expandable metal stent inserted to create an intrahepatic portosystemic shunt. The success rate is excellent. Haemodynamic effects are similar to those found with surgical shunts, with a lower procedural morbidity and mortality. The process lasts one to three hours, but you should expect to stay in the hospital overnight after the procedure.

Transjugular intrahepatic portosystemic shunting is an effective salvage procedure for stopping acute variceal haemorrhage, controlling bleeding from gastric varices, and congestive gastropathy after failure of medical and endoscopic treatment.


What Tests Are Required Before the TIPS?
Before receiving either of these procedures, the following tests may be performed to determine the extent and severity of your condition:

Evaluation of your medical history

A physical examination

Blood tests

Angiogram (an X-ray test that takes pictures of the blood flow within a particular artery)

Ultrasound

Endoscopy

Before either the TIPS procedure, your doctor may ask you to have other preoperative tests, which may include an electrocardiogram (EKG) (a test that records the electrical activity of your heart), chest X-ray, or additional blood tests. If your doctor thinks you will need additional blood products they will be ordered at this time.



How Successful Is the TIPS Procedure?
The TIPS procedure controls bleeding immediately in more than 90% of patients. However, in about 20% of patients, the shunt may narrow, causing varices to re-bleed at a later time.

What Complications Are Associated With TIPS?
Shunt narrowing or occlusion (blockage) can occur within the first year after the procedure. Follow-up ultrasound examinations are performed frequently after the TIPS procedure to detect these complications. The signs of occlusion include increased ascites (accumulation of fluid in the abdomen) and re-bleeding. This condition can be treated by a radiologist who re-expands the shunt with a balloon or repeats the procedure to place a new stent.
Encephalopathy, or abnormal functioning of the brain, can occur with severe liver disease. Hepatic encephalopathy can become worse when blood flow to the liver is reduced by TIPS, which may result in toxic substances reaching the brain without being metabolized first by the liver. This condition can be treated with medications, diet, or by occluding the shunt (making the shunt inaccessible).

What is the Distal splenorenal shunt (DSRS) Procedure?
The DSRS is a surgical procedure during which the vein from the spleen (called the splenic vein) is detached from the portal vein and attached to the left kidney (renal) vein. This surgery selectively reduces the pressure in the varices and controls the bleeding. It is usually performed only in patients with good liver function. General anesthesia is given before the surgery, which lasts about four hours. You should expect to stay in the hospital from seven to 10 days.

How Successful Is the DSRS Surgery?
DSRS controls bleeding in more than 90% of patients, with the highest risk of any re-bleeding occurring in the first month. The DSRS procedure provides good long-term control of bleeding.

What Complications Are Associated With DSRS Surgery?
Ascites, an accumulation of fluid in the abdomen, can occur. This can be treated with diuretics and restricted sodium intake.

Follow-Up Care Following TIPS or DSRS Procedures
DSRS controls bleeding in more than 90% of patients, with the highest risk of any re-bleeding occurring in the first month. The DSRS procedure provides good long-term control of bleeding.

Ten days after hospital discharge, meet with your surgeon or hepatologist (liver specialist) to evaluate your progress. Lab work will be done at this time.

Six weeks after the TIPS procedure (and again three months after the procedure), have an ultrasound so your doctor can check that the shunt is functioning properly. You will have an angiogram (an x-ray of blood vessels) only if the ultrasound indicates that there is a problem. You will also have lab work done at these times.

Six weeks after the DSRS procedure (and again three months after the procedure), meet with the surgeon to evaluate your progress. Lab work will be done at this time.

Six months after either the TIPS or DSRS procedure, have an ultrasound to make sure the shunt is working properly. Also, visit the surgeon or hepatologist.

Twelve months after either procedure, have another ultrasound of the shunt. Also, you may have an angiogram so that your doctor can check the pressure within your veins across the shunt.

If the shunt is working well, every six months after the first year of follow-up appointments, have an ultrasound, lab work, and visit with your doctor.

More frequent follow-up visits may be necessary, depending on your condition.

Attend all follow-up appointments as scheduled to ensure that the shunt is functioning properly. Be sure to follow the dietary recommendations that your healthcare providers give you.


Long term management
After the acute variceal haemorrhage has been controlled, treatment should be initiated to prevent rebleeding, which occurs in most patients.

Repeated endoscopic treatment
Repeated endoscopic treatment eradicates oesophageal varices in most patients, and provided that follow up is adequate serious recurrent variceal bleeding is uncommon. Because the underlying portal hypertension persists, patients remain at risk of developing recurrent varices and therefore require lifelong regular surveillance endoscopy.

Long term drug treatment
The use of beta blockers after variceal bleeding has been shown to reduce portal blood pressures and lower the risk of further variceal bleeding. Patients would be recommended beta blockers unless they have contraindications. Best results are obtained when portal blood pressure is reduced by more than 20% of baseline or to below 12 mm Hg.



Surgical management of varices

Surgical procedures
Patients with good liver function in whom endoscopic management fails or who live far from centres where endoscopic sclerotherapy services are available are candidates for surgical shunt procedures. A successful portosystemic shunt prevents recurrent variceal bleeding but is a major operation that may cause further impairment of liver function.

Partial portacaval shunts with 8 mm interposition grafts are equally effective to other shunts in preventing rebleeding and have a low rate of encephalopathy. Oesophageal transection and gastric devascularisation are now rarely performed but have a role in patients with portaland splenic vein thrombosis who are unsuitable for shunt procedures

and continue to have serious variceal bleeding despite endoscopic and drug treatment. Liver transplantation is the treatment of choice in advanced liver disease. Hepatic decompensation is the ultimate decompressive shunt for portal hypertension and also restores liver function. Transplantation treats other complications of portal hypertension and has one year and five year survival rates of 80% and 60% respectively.

Prophylactic management
Most patients with portal hypertension never bleed, and it is difficult to predict who will. Attempts at identifying patients at high risk of variceal haemorrhage by measuring the size or appearance of varices have been largely unsuccessful. Beta blockers have been shown to reduce the risk of bleeding, and all patients with varices should take them unless contraindicated.

Hypertensive portal gastropathy
Gastric varices and portal hypertensive gastropathy
Gastric varices are the source of bleeding in 5.10% of patients with variceal haemorrhage. Higher rates are reported in patients with left sided portal hypertension due to thrombosis of the splenic vein. Endoscopic control of gastric varices is difficult unless they are located on the proximal lesser curve in continuation with oesophageal varices. Endoscopic administration of cyanoacrylate monomer (superglue) is useful for gastric varices. The transjugular intrahepatic portosystemic shunt is increasingly used to control bleeding in this group. Bleeding from portal hypertensive gastropathy accounts for 2.3% of bleeding episodes in cirrhosis. When bleeding occurs its diffuse nature precludes the use of endoscopic treatment. Optimal management is with a combination of terlipressin and beta blockers.




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