Cirrhosis of the Liver
What is cirrhosis of the liver?
Cirrhosis is a late-stage liver disease in which healthy liver tissue is replaced with scar tissue and the liver is permanently damaged. Scar tissue keeps your liver from working properly.
Many types of liver diseases and conditions injure healthy liver cells, causing cell death and inflammation. This is followed by cell repair and finally tissue scarring as a result of the repair process.
The scar tissue blocks the flow of blood through the liver and slows the liver’s ability to process nutrients, hormones, drugs and natural toxins (poisons). It also reduces the production of proteins and other substances made by the liver. Cirrhosis eventually keeps the liver from working properly. Late-stage cirrhosis is life-threatening.
How common is cirrhosis?
Scientists estimate that cirrhosis of the liver affects about one in 400 adults in the U.S. It affects about 1 in 200 adults age 45 to 54, the age group most commonly affected by cirrhosis. Cirrhosis causes about 26,000 deaths each year in the U.S. and is the seventh leading cause of death in the U.S. among adults 25 to 64 years of age.
Who gets cirrhosis, who is most at risk?
You are more likely to get cirrhosis of the liver if you:
- Use alcohol for many years.
- Have viral hepatitis.
- Have diabetes.
- Have obesity.
- Inject drugs using shared needles.
- Have a history of liver disease.
- Have unprotected sex.
Is cirrhosis cancer?
No, cirrhosis of the liver isn’t cancer. However, most people who have liver cancer have cirrhosis. If you have cirrhosis, you have an increased risk of liver cancer. If you have hepatitis B or hepatitis C, you have an increased risk of liver cancer because these diseases often lead to cirrhosis. Any cause of liver disease can lead to cirrhosis, which increases your chance of liver cancer. (Even if you have hepatitis B or fatty liver disease without cirrhosis, you are at increased risk of liver cancer.)
Is cirrhosis a hereditary disease?
Cirrhosis itself is not an inherited (passed from parent to child) disease. However, some of the diseases that can cause liver damage that lead to cirrhosis are inherited diseases.
Can cirrhosis be reversed?
Generally no. If you have been told you have cirrhosis, you have a late-stage liver disease and the damage that is already done is permanent. There are many liver diseases and complications of liver diseases that can lead to cirrhosis. If your liver disease or complication is caught early and successfully managed, it may be possible to slow or stop the progression of disease.
Is cirrhosis fatal?
Having a diagnosis of cirrhosis of the liver doesn’t mean you have an immediately fatal condition. However, as cirrhosis continues, more scarring occurs and liver function continues to decline. Eventually, your failing liver may become a life-threatening condition. Yet there’s still hope. You and your medical team will discuss if you are a candidate for a liver transplant. If so, you will begin the process of being placed on a national liver transplant recipient list.
SYMPTOMS AND CAUSES
What are the symptoms of cirrhosis?
The symptoms of cirrhosis depend on the stage of your disease. In the beginning stages, you may not have any symptoms. If you do have symptoms, some are general and could easily be mistaken for symptoms of many other diseases and illnesses.
Early symptoms and signs of cirrhosis include:
- Loss of appetite.
- Feeling weak or tired.
- Unexpected weight loss.
As liver function gets worse, other more commonly recognized symptoms of cirrhosis appear including:
- Easy bruising and bleeding.
- Yellow tint to your skin or the whites of your eyes (jaundice).
- Itchy skin.
- Swelling (edema) in your legs, feet and ankles.
- Fluid buildup in your belly/abdomen (ascites).
- Brownish or orange color to your urine.
- Light-colored stools.
- Confusion, difficulty thinking, memory loss, personality changes.
- Blood in your stool.
- Redness in the palms of your hands.
- Spider-like blood vessels that surround small, red spots on your skin (telangiectasias).
- In men: loss of sex drive, enlarged breasts (gynecomastia), shrunken testicles.
- In women: premature menopause (no longer having your menstrual period).
Is cirrhosis painful?
Yes, cirrhosis can be painful, especially as the disease worsens. Pain is reported by up to 82% of people who have cirrhosis and more than half of these individuals say their pain is long-lasting (chronic).
Most people with liver disease report abdominal pain. Pain in your liver itself can feel like a dull throbbing pain or a stabbing sensation in your right upper abdomen just under your ribs. General abdominal pain and discomfort can also be related to swelling from fluid retention and enlargement of your spleen and liver caused by cirrhosis.
Pain can come both from the diseases that lead to cirrhosis and/or cirrhosis can make the pain from existing diseases worse. For instance, if you have non-alcohol related fatty liver disease and have obesity, you may also have osteoarthritis and cirrhosis makes your bone and joint pain worse. Cirrhosis also causes an inflammatory state in your entire body. Inflammation and your body’s reaction to inflammation can cause general pain.
What causes cirrhosis?
The most common causes of cirrhosis of the liver are:
- Alcohol use disorder (alcohol-related liver disease) caused by long-term [chronic] use of alcohol.
- Chronic viral infections of the liver (hepatitis B and hepatitis C).
- Fatty liver associated with obesity and diabetes, but not alcohol. This condition is called non-alcohol related steatohepatitis.
Anything that damages the liver can lead to cirrhosis. Other causes include:
- Inherited diseases:
- Alpha-1 antitrypsin deficiency (build-up of an abnormal protein in the liver)
- Hemochromatosis (excess iron stored in the liver).
- Wilson disease (excess copper stored in the liver).
- Cystic fibrosis (sticky, thick mucus builds up in the liver).
- Glycogen storage diseases (liver can’t store or break down glycogen, a form of sugar).
- Alagille syndrome (born with fewer than normal number of bile ducts; affects bile flow and causes jaundice).
- Autoimmune hepatitis (your body’s own immune system attacks healthy liver tissue causing damage).
- Diseases that damage or block bile ducts in the liver (tubes that carry bile from the liver to other parts of digestive system; bile helps digest fats):
- Primary biliary cholangitis (bile ducts become injured, then inflamed, then permanently damaged).
- Primary sclerosing cholangitis (inflammation of the bile ducts leads to scarring and narrowing of the ducts and buildup of bile in the liver).
- Blocked bile duct (can cause infections, backup of products in the liver).
- Biliary atresia (infants are born with poorly formed or blocked bile ducts, causing damage, scarring, loss of liver tissue and cirrhosis).
- Chronic heart failure (causes fluid to back up in your liver, swelling in other areas of your body and other symptoms).
- Rare diseases, such as amyloidosis, in which abnormal deposits in the liver of an abnormal protein called amyloid disrupts normal liver function.
Changes from liver diseases that lead to cirrhosis are gradual. Liver cells are injured and if injury – from whatever cause – continues, liver cells start to die. Over time, scar tissue replaces the damaged liver cells and the liver can’t function properly.
What are the complications of cirrhosis?
There are many complications of cirrhosis of the liver. Because cirrhosis develops over many years, some of these complications may be your first noticeable signs and symptoms of the disease.
Portal hypertension: This is the most common serious complication. Portal hypertension is an increase in the pressure in your portal vein (the large blood vessel that carries blood from the digestive organs to the liver). This increase in pressure is caused by a blockage of blood flow through your liver as a result of cirrhosis. When blood flow through veins is partially blocked, veins in your esophagus, stomach or intestines can become enlarged (a condition called varices). As the pressure in these veins builds, the veins can bleed or even burst, causing severe internal bleeding.
Additional complications of portal hypertension include:
- Swelling (edema) in your legs, ankles or feet.
- Buildup of fluids in your abdomen (called ascites).
- Swelling/enlargement of your spleen (splenomegaly).
- Formation and dilation (expansion) of blood vessels in the lungs (hepatopulmonary syndrome), leading to low levels of oxygen in the blood and body and shortness of breath.
- Failure of kidney function as a result of having portal hypertension as a complication of cirrhosis (hepatorenal syndrome). This is a type of kidney failure.
- Confusion, difficulty thinking, changes in your behavior, even coma. This occur when toxins from your intestines aren’t removed by your damaged liver and circulate in the bloodstream and buildup in your brain (a condition called hepatic encephalopathy).
Hypersplenism: Hypersplenism is an overactive spleen. This condition causes quick and premature destruction of blood cells.
Infections: Cirrhosis increases your risk of getting and fighting serious infections, such as bacterial peritonitis (infection of the tissue that lines the inner wall of your abdomen).
Malnutrition: Your liver processes nutrients. A damaged liver makes this more difficult and leads to weight loss and general weakness.
Liver cancer: Most people who develop liver cancer have cirrhosis of the liver.
Liver failure: Many diseases and conditions cause liver failure including cirrhosis of the liver. As its name implies, liver failure occurs when your liver isn’t working well enough to perform its many functions.
DIAGNOSIS AND TESTS
How is cirrhosis of the liver diagnosed?
Your healthcare provider will first ask about your medical history and over-the-counter and prescription drug use. They will also ask about any supplements or herbal products you may take. Your provider may suspect you have cirrhosis if you have a long history of alcohol use, injectable drug use or have had hepatitis B or C and have the symptoms listed in this article.
To diagnosis cirrhosis, your provider will perform a physical exam and may order one or more of the following tests:
- Physical exam: Your doctor will examine you, looking for the signs and symptoms of cirrhosis including: the red, spider-like blood vessels on your skin; yellowing of your skin or whites of your eyes; bruises on your skin; redness on your palms; swelling, tenderness or pain in your abdomen; enlarged firmer-feeling, bumpy texture to the lower edge of your liver (the part of your liver below the rib cage that can be felt).
- Blood tests: If your doctor suspects cirrhosis, your blood will be checked for signs of liver disease. Signs of liver damage include:
- Lower than normal levels of albumin and blood clotting factors (lower levels means your liver has lost its ability to make these proteins).
- Raised levels of liver enzymes (suggests inflammation).
- Higher level of iron (may indicate hemochromatosis).
- Presence of autoantibodies (may indicate autoimmune hepatitis or primary biliary cirrhosis).
- Raised bilirubin level (suggests liver isn’t working properly to remove bilirubin from the blood).
- High white blood cell count (indicates an infection).
- High creatinine level (a sign of kidney disease that suggests late-stage cirrhosis).
- Lower levels of sodium (is an indicator of cirrhosis).
- Raised level of alpha-fetoprotein (indicates presence of liver cancer).
In addition, other blood work will include a complete blood count to look for signs of infection and anemia caused by internal bleeding and a viral hepatitis test to check for hepatitis B or C.
- Imaging tests: Imaging test show the size, shape and texture of the liver. These tests can also determine the amount of scarring, the amount of fat you have in your liver and fluid in your abdomen. Imaging tests of your liver that could be ordered include computerized tomography (CT) scan, abdominal ultrasound and magnetic resonance imaging (MRI). A special ultrasound, called a transient elastography, measures the fat content and amount of stiffness in your liver. Two different types of endoscopies might be ordered: an endoscopic retrograde cholangiopancreatography to detect bile duct problems, and/or upper endoscopy to detect enlarged veins (varices) or bleeding in your esophagus, stomach or intestines.
- Biopsy: A sample of liver tissue (biopsy) is removed from your liver and examined under the microscope. A liver biopsy can confirm a diagnosis of cirrhosis, determine other causes or extent of liver damage or enlargement or diagnosis liver cancer.
Are there stages of cirrhosis?
If you have been diagnosed with cirrhosis of the liver, you are already beyond the early stages of liver disease. Having cirrhosis means your liver has scar tissue in it because it has been damaged.
Liver specialists and researchers have developed many different scoring systems to predict outcome and to guide treatment for chronic liver disease. Some specific liver diseases also have their own scoring systems. However, not every liver disease has a scoring system and there’s no scoring system if you happen to have more than one liver disease at the same time.
For these reasons, perhaps it’s easier to talk about cirrhosis according to a classification system you are more likely to hear from your healthcare provider. He or she may refer to you having either compensated cirrhosis or decompensated cirrhosis.
Compensated cirrhosis means you have cirrhosis but you don’t yet have noticeable symptoms (you are asymptomatic). Your lab work and imaging findings may not be abnormal. A liver biopsy may be the only way to confirm a diagnosis of cirrhosis. Median survival in patients with compensated cirrhosis is approximately nine to 12 years. (Median is the middle point in set of numbers, so an equal number of individuals survived less than 9 to 12 years as the number of individuals who survived over this time range.)
Decompensated cirrhosis means your cirrhosis has worsened to the point that you have noticeable symptoms. Your healthcare provider recognizes your condition based on your history, physical and lab findings. You have at least one complication, which includes jaundice, ascites, hepatic encephalopathy, hepatorenal syndrome, variceal bleeding or liver cancer. You are usually admitted to the hospital for care. Median survival in patients with decompensated cirrhosis is approximately two years.
MANAGEMENT AND TREATMENT
Is there a cure for cirrhosis of the liver?
No, there is no cure for cirrhosis. The damage already done to your liver is permanent. However, depending on the underlying cause of your cirrhosis, there may be actions you can take to keep your cirrhosis from getting worse. These actions include:
- Stop drinking alcohol.
- Treat chronic hepatitis (if you have it).
- Avoid medications that stress the liver.
- Eat a healthy, well-balanced, low-fat diet, such as the Mediterranean diet.
Follow other tips listed under the Prevention section in this article.
What are the goals of cirrhosis treatment?
The goals of treatment for cirrhosis of the liver are to:
- Slow further damage to your liver.
- Prevent and treat symptoms.
- Prevent and treat complications.
How is cirrhosis of the liver treated?
Treatment depends on what’s causing your cirrhosis and how much damage exists.
Although there is no cure for cirrhosis, treatments can delay or stop its progress and reduce complications.
Treatments for the causes of cirrhosis are as follows:
- Alcohol-related liver disease: If you’ve developed cirrhosis from alcohol use, talk with your provider about how to stop drinking alcohol. If you need help, ask your healthcare provider for recommendations for alcohol addiction treatment programs.
- Hepatitis B or C: Several approved antiviral medications are available to treat hepatitis types B and C.
- Non-alcohol related fatty liver disease: Management of non-alcohol related fatty liver disease includes losing weight, following a healthy diet, getting physical exercise and following your provider’s instructions for managing your diabetes.
- Inherited liver diseases: Treatment depends on the specific inherited disease. Treatments are aimed at treating symptoms and managing complications. Treatment of alpha-1 antitrypsin deficiency may include medicine to reduce swelling in your abdomen and legs, antibiotics to treat infections and other medicines for complications. For hemochromatosis, treatment is to remove blood to reduce the level of iron in your blood. For Wilson disease, treatment is medicines to remove copper from your body and zinc to prevent absorption of cooper. For cystic fibrosis, medications are prescribed to improve lung function, methods to clear mucous and treatment of complications. Treatment for glycogen storage diseases that involve the liver is to keep glucose at the right level.
- Autoimmune hepatitis: Treatment includes medications to suppress your immune system.
- Diseases that damage or block bile ducts in the liver: Treatments include medications such as ursodiol (Actigall®) or surgery to open narrowed or blocked bile ducts.
- Heart failure: Treatment depends on the cause and stage of your heart failure. Medications include drugs to treat high blood pressure, reduce cholesterol, remove excess fluids (edema) from your body and improve heart pumping function. Other treatments include implantation of devices to help pump blood or monitor heart rhythm, surgeries to unblock arteries or replace or repair heart valves and transplant surgery to replace your heart.
- Medications that may be contributing to cirrhosis: Your provider will review all of your medications to determine if any are causing problems for your liver and if so, stop the drug, lower the dosage or change to a different drug if possible.
How are the complications of cirrhosis treated?
Portal hypertension: Portal hypertension is mainly the result of chronic end-stage liver disease. Treatment consists of treating its many complications. Treatments of portal hypertension include:
- Giving beta blockers or nitrates to lower blood pressure in your veins.
- Cutting off blood flow through the varices to stop or reduce further bleeding with procedure using tiny elastic bands (band ligation) or with sclerotherapy.
- Redirecting blood from the portal vein to reduce pressure in the portal vein and to control variceal bleeding. This is achieved using either one of two techniques – distal splenorenal shunt or transjugular intrahepatic portosystemic shunt.
- Prescribing lactulose to absorb toxins in the blood that result from hepatic encephalopathy, which cause symptoms including confusion and other mental changes.
- Draining excess fluid in your abdomen (ascites) in a procedure called paracentesis or taking a diuretic medication to decrease extra fluids (edema) in your legs and other areas of your body.
Bacterial peritonitis: Antibiotics and infusion of a protein (albumin) will be prescribed. Typically patients are admitted to the hospital for treatment and monitoring. Following a diagnosis of bacterial peritonitis, an oral antibiotic will be prescribed for daily use to prevent recurrence of infection.
Liver cancer: Treatment depends on the stage of your cancer and other factors. One or more treatments may be tried. Options include surgery to remove part of your liver or your whole liver (to be replaced with a new liver as part of a liver transplantation) and nonsurgical tumor-destroying methods including ablation, chemotherapy, targeted therapy (drugs zero in on cancer genes or tissue), immunotherapy and radiation bead therapy (inject bead that give off radiation into the blood vessels that feed the tumor).
Kidney failure: Treatment may include medication, dialysis and kidney transplant, depending on the cause and extent of failure.
Liver failure: Treatment depends on if you have acute or chronic failure. For chronic liver failure, diet and lifestyle changes include stopping alcohol and medications that harm the liver; eating less red meat, cheese and eggs; losing weight; managing high blood pressure and diabetes and cutting down on salt.
Acute treatments for liver failure include intravenous fluids to maintain blood pressure, laxatives to help flush toxins from the body and blood glucose monitoring.
If you have either acute or chronic liver failure, your liver specialist may recommend a liver transplant. Liver transplants can come from a living or deceased donor. Only a portion of the donor liver needs to be transplanted. The liver is the only human organ capable of growing back.
Many tests are required of both you (the liver transplant recipient) and the person donating a portion of their liver or the cadaver liver (liver from a deceased person). If your doctors determine that you need a liver transplant, you will be placed on a national liver transplant waiting list, which lists patients by blood type, body size and severity of end-stage liver disease.
How can I prevent cirrhosis of the liver?
Food and drink issues:
- Use alcohol only in moderation. If you do drink alcohol, limit how much you drink and how often. If you drink more than two drinks a day if you are a man or more than one if you are a woman, you are increasing your risk. A drink is a glass of wine or a 12-ounce can of beer or a 1.5 ounce serving of hard liquor. If you have liver disease, you shouldn’t drink alcohol at all.
- Eat a well-balanced, low-fat diet, such as the Mediterranean diet. A well-balanced healthy diet consists of fruits, vegetables, lean proteins and whole grains.
- Don’t eat raw seafood, especially oysters and clams. These foods can contain a bacteria that can cause serious illness.
- Cut back on the amount of salt in your diet. Use other seasonings to flavor your foods.
Healthy body habits:
- Maintain a weight that’s healthy for you. Excess body fat can damage your liver. Ask your healthcare provider for a weight loss plan if you are overweight.
- Exercise regularly.
- See your healthcare provider regularly for check-ups. Follow medical recommendations to manage obesity, diabetes, hypertension (high blood pressure) and cholesterol (high bad cholesterol [LDL] and/or low good cholesterol [HDL]) and high triglycerides.
- Quit smoking if you smoke.
Healthy liver practices:
- Avoid high-risk behaviors that can lead to infection with hepatitis B or C, such as sharing needles for illegal drug use or having unprotected sex.
- Get vaccinated against hepatitis B. If you already have hepatitis, ask your provider if drug treatment is appropriate for you.
- Get your annual flu shot and ask if a pneumonia vaccine makes sense for you (people with cirrhosis are more likely to get infections).
- Avoid nonsteroidal anti-inflammatory drugs (such as ibuprofen [Advil®, Motrin®] indomethacin [Indocin®] celecoxib [Celebrex®] and aspirin) and high doses of acetaminophen (Tylenol®). Acetaminophen can be taken safely at a dose up to 2,000 mg daily. These drugs can cause or worsen liver function.
- Take all medications and keep all appointments as recommended by your healthcare provider.
Pathology of Hepatobiliary System
Morphologic Patterns of Hepatic Injury:
• Degeneration and intracellular accumulation
• Necrosis and apoptosis
Degeneration and Intracellular Accumulation:
• Ballooning degeneration: Swollen oedematous hepatocytes with irregularly clumped
cytoplasm and large clear space, result from toxic damage and immunologic insult.
• Foamy degeneration: Diffuse foamy swollen hepatocytes due to retained billiary
• Steatosis: Accumulation of fat droplets within hepatocytes, occur in alcoholic liver
disease and pregnancy.
• Haemochromatosis and Wilson’s disease: Accumulation of iron and copper in
Necrosis and Apoptosis:
• Ischaemic coagulation necrosis: Hepatocytes are poorly stained and “mummified”
and often have lysed nuclei.
• Councilman bodies: Isolated hepatocytes become round to form shrunken, pycnotic
nuclei and intensely eosinophilic fragmented nuclei in the process of apoptosis.
• Lytic necrosis: Hepatocytes become swollen osmotically and ruptured.
• Centrilobular necrosis: Necrosis of hepatocytes immediately around the terminal
hepatic veins in case of ischaemic injury and a number of drugs and toxic reactions.
• Mid-zonal and peri-portal necrosis: Rarely occur in eclampsia.
• Focal necrosis: Limited to scattered cells within hepatic lobules.
• Bridging necrosis: Necrosis of contiguous hepatocytes spanning adjacent lobules in
portal-to-portal, portal to central, central-to-central fashion occurs in severe
• Sub-massive necrosis: Necrosis of entire lobule.
• Massie necrosis: Necrosis of entire liver.
• Macroscopic abscess: Occur in disseminated candidal or bacterial infections.
Influx of acute or chronic inflammatory cells into the liver is termed hepatitis. Inflammatory
cells may be limited to the sites of entry (portal tracts) or spill over into the parenchyma.
Regeneration is signified by thickening of the hepatocyte cords and some disorganization of
the parenchymal structures.
Fibrous tissue is formed in response to inflammation or direct toxic insult to the liver. In
initial stage fibrosis develop around portal tracts or the central veins or within the spaces of
Disse. With continuing fibrosis, liver is subdivided into nodules of regenerating hepatocytes
surrounded by scar tissue, termed cirrhosis.
Cirrhosis of Liver:
Cirrhosis is a condition in which liver is subdivided into nodules of regenerating hepatocytes
surrounded by scar tissue.
Cirrhosis is characterised by three features:
1. Bridging fibrous septa in the form of delicate bands or broad scars replacing multiple
2. Disruption of architecture of the entire liver.
3. Parenchymal nodules created by regeneration of encircled hepatocytes.
• The parenchymal injury and consequent fibrosis are diffuse.
• Nodularity is requisite for diagnosis of cirrhosis.
• The fibrosis is irreversible.
• Vascular architecture is reorganised y the parenchymal damage and scarring.
Classification of Cirrhosis of Liver:
• Alcoholic liver diseases (60-70%)
• Viral hepatitis (10%)
• Billiary disease (5-10%)
• Primary Haemochromatosis (5%)
• Wilson’s diseases (rare)
• Alpha1-anti-trypsin deficiency (rare)
• Cryptogenic cirrhosis (10-15%)
• Macronodular cirrhosis
• Micronodular cirrhosis
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• Mixed type cirrhosis
Infrequent types of cirrhosis:
• Cirrhosis in infant and children with galactosaemia and tyrosinosis
• Cirrhosis in liver destruction by diffuse infiltrating cancer.
• Drug-induced cirrhosis
• Cirrhosis in syphilis
Macronodular cirrhosis: Nodule 3 mm or more.
Micronodular cirrhosis: Nodule less than 3 mm.
Unless otherwise specified, the term ‘viral hepatitis’ is reserved for infection of the liver by a
small group of viruses having a particular affinity for the liver such as Hepatitis viruses A, B,
C, D and E.
Other systemic viral infection may involve the liver such as Epstein-Barr virus, cytomegalo
virus and yellow fever virus.
Hepatitis A Virus (HAV):
• Causes infectious hepatitis
• Infectious hepatitis is a benign, self-limited disease.
• Incubation period: 2 to 6 weeks.
• HAV does not cause chronic hepatitis or carrier state, rare causes fulminant hepatitis.
• Fatality rate: 0.1%
Hepatitis B Virus (HBV):
• Causes ‘serum hepatitis’
• HBV can produces:
1. Acute hepatitis
2. Non-progressive chronic hepatitis
3. Progressive chronic hepatitis ending in cirrhosis
4. Fulminant hepatitis with massive liver necrosis.
5. An asymptomatic carrier state with or without progressive diseases.
6. Backdrop for hepatitis D virus (HDV).
• HBV plays an important role in the development of hepatocellular carcinoma.
• Incubation period: 4 to 26 weeks.
Serum markers: HBsAg, HBeAg, Anti-HBe, Anti-HBc and Anti-HBs.
• Presence of HBsAg in serum for 6 months or longer after initial detection is known as
• The presence of HBsAg alone does not necessarily indicate replication of complete
virons. Patients may be asymptomatic and without liver damage.
• Chronic replication of HBV is characterised by presence of circulating HBsAg,
HBeAg, and HBV DNA, usually with anti-HBc, occasionally with anti-HBs.
Hepatitis C (HCV):
• HCV has high rate of progression to chronic liver disease and eventual cirrhosis.
• Incubation period: 2 to 26 weeks.
• Persistent infection and chronic hepatitis are the hallmark of HCV infection.
• Repeated bout of hepatic damage is the characteristic features of HCV infection.
• Cirrhosis can be present at the time of diagnosis or may develop during a period of 5
to 10 days.
Hepatitis D Virus (HDV):
• HDV causes infection when it is encapsulated with HBsAg.
• Simultaneous infection with HBV and HDV result in hepatitis ranging from mild to
Hepatitis E Virus (HEV):
• Hepatitis is self-limited.
• It is not associated with chronic liver diseases.
• Incubation period: 6 weeks.
Clinicopathologic Syndromes of Viral Hepatitis:
1) Carrier Sate: Without clinically apparent diseases or with chronic hepatitis.
2) Asymptomatic infection: Serologic evidence only.
3) Acute hepatitis: anicteric or icteric
4) Chronic hepatitis: without progression to cirrhosis or with progression to
5) Fulminant hepatitis: Submassive to massive hepatic necrosis.
• The liver biopsy is more or less normal.
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• Viable isolated hepatocytes or clusters of cells have ground glass, finely granular
eosinophilic cytoplasm, laden with HBsAg. Hepatocytes may have sanded nuclei
imparted by abundant HBeAg.
Acute Viral Hepatitis:
• Morphological changes in acute hepatitis are virtually the same regardless of the
causative agent and can be mimicked by drug reaction.
• Grossly the liver is slightly enlarged.
• Major histological findings are:
– Ballooning degeneration
– Fatty change
– Hyperplasia and hypertrophy of Kupffer cells
– Infiltration of portal tract by a mixture of inflammatory cells.
– Periportal spill over of inflammatory cells.
Chronic Viral Hepatitis:
Chronic hepatitis is defined as symptomatic, biochemical or serological evidence of
continuing or relapsing hepatic disease for more than 6 months, with histologically
documented inflammation and necrosis.
1) Chronic persistent hepatitis: Inflammation is confined to portal tracts.
2) Chronic active hepatitis: Portal tract inflammation spills over into parenchyma and
surrounds regions of necrotic hepatocytes.
3) Chronic lobular hepatitis: Persistent inflammation is confined to the lobule.
Association of hepatitis virus with chronic hepatitis:
• HAV: Extremely rare
• HBV: Develops in more than 90% of neonates and 5% of infected adults, of which
one-fourth progress to cirrhosis.
• HCV: Develops in more than 50% of infected patients, of whom half progress to
• HDV: Rare
• HEV: Does not produce chronic hepatitis
Chronic hepatitis with HBV and apparently with HCV contributes significantly to the
development of primary hepatocellular carcinoma.
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Morphology in chronic viral hepatitis:
• In mildest form: An inflammatory infiltrate is limited to portal tracts, consisting of
lymphocytes, macrophages, occasional plasma cells, neutrophils or eosinophils. Liver
architecture is preserved.
• In progressive disease: Piece meal necrosis or bridging necrosis may occur.
It is a chronic hepatitis of unknown aetiology, which has clinical and histological features
virtually indistinguishable from chronic viral hepatitis.
• When hepatic insufficiency progress from onset of symptoms to hepatic
encephalopathy within two to three weeks it is termed as fulminant hepatitis.
• Histologically necrosis may wipe out entire lobules or destroy central and midzonal
regions sparing Periportal region of lobules.
Alcoholic Liver Disease:
Chronic alcohol consumption has a variety of adverse effects, of these three are important:
• Hepatic Steatosis
• Alcoholic hepatitis
Haemochromatosis is characterised by the excessive accumulation of body iron, most of
which is deposited in the parenchymal organ, such as the liver and pancreas.
• Hereditary Haemochromatosis or primary Haemochromatosis
• Secondary Haemochromatosis
Fully developed cases exhibits:
• Micronodular cirrhosis
• Diabetes mellitus
• Skin pigmentation
• Deposition of haemosiderin in the liver, pancreas, myocardium, pituitary gland and
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• Pancreatic fibrosis
Wilson’s disease is an Autosomal disorder marked by the accumulation of copper in many
tissues and organs, principally the liver, brain and eye.
During metabolism in liver copper is incorporated into _ 2-globulin to form ceruloplasmin
and secreted into plasma. The gene for Wilson’s disease is on chromosome 13 and encodes a
transmembrane copper transporting ATPase located on the hepatocytes canalicular
membrane. Majority of the patients are compound heterozygous containing different
mutations of the Wilson’s disease gene on each. Defective bile excretion leads to copper
accumulation causes toxic liver injury.
Hepatic Changes are:
• Fatty changes
• Acute hepatitis
• Chronic hepatitis
• Massive hepatic necrosis
• Solitary or multiple, well demarcated but poorly encapsulated hyperplastic
hepatocellular nodule may develop in the non-cirrhotic liver.
• Nodule ranges up to many centimetres in diameter.
• Two type:
o Focal nodular hyperplasia and nodular regenerative hyperplasia
o Nodular regenerative hyperplasia may affect the entire liver with round
spherical nodule in the absence of fibrosis.
• Arise from hepatocytes or bile duct epithelial cells.
• Liver cell adenomas are pale, yellow-tan and usually bile stained nodules.
Histologically composed of normal hepatocytes or have some variation in cell and
• Bile duct adenomas are firm, pale and usually single discrete nodule. They are almost
never bile stained. They are composed of uniformly sized epithelium lined channels
or ducts separated by a scant to abundant connective tissue stroma and sharply
demarcated from the surrounding liver.
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• Malignant tumour usually of young childhood.
• Exhibits two anatomic type: epithelial type and mixed epithelial and mesenchymal
• Epithelial type composed of small polygonal fetal cells, even smaller embryonal cells
forming acini, tubular or papillary structures.
• Mixed type contains foci of mesenchymal differentiation, may contains primitive
mesenchyme, osteoid, cartilage or striated muscle.
Primary Carcinoma of Liver:
• Hepatocellular Carcinoma (HCC) or Hepatoma (90%)
• HCC is strongly associated with HBV infection.
• HCC is also associated with chronic infection with HCV and alcohol consumption.
• Cholangiocarcinomas are associated with previous exposure to Thorotrast and billiary
invasion by liver fluke Opisthorchis sinensis.
• Repeated cycle of cell death and regeneration in HBV and HCV infection accumulate
mutation and eventually transform some hepatocytes.
• In HBV associated liver cancer, the viral DNA is integrated into host genome leading
• HBV DNA integration induces genome instability.
• Aflatoxin, produced by food spoilage moulds, are most potent environmental factors
implicating in hepatocellular carcinogenesis. Aflatoxins are activated in hepatocytes,
their products interlude into DNA to form mutagenic adduct with guanosine. It may
cause G to T transversion at 249 codon of P53 tumour suppressor gene.
• It appears that HBV infection, Aflatoxin exposure and genetic variation act
synergistically in some world regions to increase risk for HCC.
• It would appear that stimulation of hepatocellular division in the midst of ongoing
necrosis and inflammation theme common to HCC cases not associated with HBV
infection such as alcoholic cirrhosis, HCV infection and primary Haemochromatosis.
• HCC may be unifocal, multifocalor diffusely infiltratie
• HCC are usually paler than the surrounding liver substances. Some times it takes a
green hue when composed of well-differentiated hepatocytes of secretory bile.
Cholangiocarcinomas are rarely bile staining.
• HCC composed well-differentiated to highly anaplastic undifferentiated cells.
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• Cholangiocarcinoma composed of anaplastic cuboidal to low columnar cells.
• Metastatic involvement of the liver is far more common than primary neoplasm
• Common organs are breast, lungs and colon.
Cholelithiasis (Gall Stone):
• Affect 10 to 20% of adult populations in developed countries.
• Majorities of gall stones are asymptomatic
• Gall stones are mainly two types:
o Cholesterol stone (80%)
o Pigment stone (20%)
• Risk factors of cholelithiasis:
o Cholesterol stone:
_ Demography: Northern Europe, North and South Africa, native
Americans, Mexican Americans.
_ Advance age
_ Female sex hormone
• Female gender
• Oral contraceptive
_ Rapid weight reduction
_ Gall bladder stasis
_ Inborn disease of bile acid metabolism
_ Hyperlipidaemia syndrome
o Pigment stone:
_ Demography: Asian more than Western; Rural more than urban.
_ Chronic haemolytic syndrome
_ Billiary infection
• Cholesterol stone: When cholesterol becomes supersaturated, it cannot remain
dispersed and nucleate into solid cholesterol monohydrate crystals.
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• Pigment stone: Calcium salt of un-conjugated bilirubin is participated in the
formation of pigment stones. Billiary tract infection induces de-conjugation of
excreted bilirubin glucoronides to formation of pigment stone.
Pure Cholesterol Stone:
• Pale yellow, round to ovoid, finely granular, hard external surface.
• Transection reveals a glistening radiating crystalline palisade.
• Single or multiple
• Surface of multiple stone may be faceted.
• Usually Radioluscent; 10-20% are radio-opaque.
Black pigment stone:
• Found in sterile gall bladder bile.
• Composed of unconjugated bilirubin, calcium carbonate, calcium phosphate and
• Usually speculated and moulded.
Brown Pigment Stone:
• Found in infected intrahepatic or extrahepatic ducts.
• Contains pure calcium salt of unconjugated bilirubin, mucin, cholesterol and calcium
salt of palpitate and stearate.
• Are laminated and soft.
50-75% pigment stones are radio-opaque.
• Acute Cholecystitis
o Acute calculus cholecystitis
o Acute acalculus cholecystitis
• Chronic Cholecystitis
Acute Calculus Cholecystitis:
• Is an acute inflammation of gall bladder precipitated 90% of the tome by obstruction
of the neck or cystic duct.
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• Results from chemical irritation and inflammation of the obstructed gall bladder.
Mucosal phospholipases hydrolyses luminal lecithin to lysolecithin. Mucous layer is
disrupted. Exposed mucosal epithelium is come in contact with detergent action of
bile salts. Gall bladder motility develops; resulting distension and increase
intraluminal pressure reduces the blood flow of mucosa.
• The gall bladder is usually enlarged and tense. The surface shows green-black
discolouration. Serosa may cover by fibrin or suppurative coagulated exudate. The
gall bladder may fill with pure pus (empyema). The wall is thickened and
oedematous. The wall may be necrosed (gangrenous cholecystitis).
• Histological findings are oedema, leucocytic infiltration, vascular congestion, frank
abscess formation or gangrenous necrosis.
Acute Acalculus Cholecystitis:
• Results from direct ischaemic compromise as cystic artery is an end artery.
• Predisposing factors:
o Post-operative state
o Severe trauma
o Severe burn
o Multisystem organ failure
o Prolonged intravenous hypralimentation
o Postpartum state
• Contributory factors:
o Dehydration and multiple blood transfusions.
o Gall bladder stasis
o Accumulation of billiary slugs and viscous bile
o Inflammation and oedema of wall
o Bacterial contamination and generation of lysolecithin
• Morphology: There is no specific difference between acute calculus and acalculus
• Chronic cholecystitis may be a sequel to repeated bouts of mild-to-moderate acute
• About 90% are associated with cholelithiasis
• E. coli and Enterococci can be cultured from bile in about one-third of cases.
• Gall bladder may be contracted, normal or enlarged in size.
• Serosa is usually smooth and glistening or dull by subserosal fibrosis.
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• On sectioning, the wall is thickened, opaque, grey-white and less flexible than normal.
• The lumen contains fairly clear, green-yellow, mucoid bile and usually stones.
• The mucosa may normal, thin or atrophied.
• In mildest case, only scattered lymphocytes, plasma cells and macrophages are found
in mucosa and subserosal fibrous tissue.
• In more severe cases, there is marked subepithelial and subserosal fibrosis
accompanied by mononuclear cells infiltration.
• Inflammatory proliferation of the mucosa and fusion of the mucosal folds may give
rise to buried crypts of epithelium within the gall bladder wall. Out pouching of the
mucosal epithelium through the wall may be present which is known as Rokitansky-
• Rare features:
o Porcelain gall bladder – extensive dystrophic calcification within gall bladder
o Xanthomatous cholecystitis – Shrunken, nodular necrosis and haemorrhage.
o Hydrops gall bladder – Atrophic, chronically obstructed gall bladder
containing only clear secretion.
Carcinoma of the Gall Bladder:
• 60-90% are associated with cholelithiasis
• Exhibit two patterns: Infiltrating and fungating
• Most common sites: Fundus and necks.
• Most common histologic type: Adenocarcinoma
• About 5% are squamous cell carcinoma.
• Minority are carcinoid and mesenchymal tumours.
Diseases of exrahepatic bile ducts:
• Billiary atresia
• Ascending cholengitis
• Choledocal cyst
• Carcinoma of exrahepatic duct
OUTLOOK / PROGNOSIS
What can I expect if I have cirrhosis?
Damage already done to your liver is permanent. But your liver is a large organ. If part of your liver is still working, you might be able to slow the progression of disease, depending on its cause. For instance, if your cirrhosis is caused by alcohol use, talk to your provider about how to stop drinking. If you have obesity or diabetes, you will need to lose weight and manage your blood sugar so you can lower the damage caused by fatty liver disease.
You and your healthcare provider or team will work together to determine what’s causing your cirrhosis and what complications may have resulted from your cirrhosis and treat them accordingly.
What’s the life expectancy for people with cirrhosis?
Life expectancy depends on several factors including the cause and severity of your cirrhosis, your response to treatments, the presence of cirrhosis complications, your age and any other existing general health problems. Ask your liver specialist about your life expectancy since every person is unique, with unique overall health issues and specific liver health issues.
If your cirrhosis is advanced, liver transplantation may be an option. You and your doctors will discuss if this is an option for you.
What’s a Child-Turcotte-Pugh score and MELD score?
A Child-Turcotte-Pugh (CTP) score, also known simply as the Child-Pugh score, is a clinical score that tells your doctors how severe your liver disease is and forecasts your expected survival rate. The scoring system provides a score on the presence of five clinical measures (the lab values of bilirubin, serum albumin and prothrombin time; presence of ascites and hepatic encephalopathy) and the degree of severity of each of these measures.
The Model for End-stage Liver Disease (MELD) score is a score that is used to rank the urgency for a liver transplant. The worse your liver function is, the higher your MELD score and the higher your position is on the transplant list. The Pediatric End-stage Liver Disease (PELD) score is similar to MELD but is a scoring system for children under the age of 12.
Cirrhosis of the liver is a late-stage result of liver disease and its complications. Cirrhosis causes your liver to not function properly. Your liver plays a vital role in many of the processes and functions that keep you alive.
Although scarring from liver disease causes permanent damage, it’s still possible to live a long life. Depending on the underlying cause, it’s possible to slow or stop cirrhosis from worsening. Many of the causes and complications that lead to cirrhosis are treatable or manageable. If you drink alcohol, stop. If you have non-alcohol related fatty liver disease, lose weight and manage your metabolic risk factors. If you have diabetes, make sure you are following your healthcare provider’s management recommendations. Take all medications for all your medical conditions as directed by your healthcare team. Get vaccinated for hepatitis A and B.
If you have end-stage cirrhosis, don’t lose hope. You and your healthcare team will work together to closely manage your condition and put you on a wait list for a donor liver.