What are the 4 stages of cirrhosis?

What are the 4 stages of cirrhosis?
September 13, 2015 at 7:54 PM

This post describes all 4 stages of cirrhosis and explains the disorder in detail. At the beginning of the post some main functions of the liver are explained, including their relation to cirrhosis.

Liver is an organ of extreme importance in the body, located in the upper right quadrant of your abdomen. This vital organ weighs about 2.5-3 pounds and is considered to be the largest gland and solid organ in the body. Liver carries out a lot of crucial functions in the body that you can’t live without. Like other vital organs in the body, proper functioning of liver is essential to keep the body systems working in the optimally healthy state.

Here are the main functions of liver that will make you realize its significance in the body:

  • Liver is the chief site of glucose metabolism in the body. It stores excess glucose in the form of “glycogen”. Whenever the body is in the need of glucose, this glycogen breaks down and releases glucose. Thus, liver helps in stabilizing blood glucose level.
  • Like glucose metabolism, liver is also involved in the metabolism of fats and cholesterol in the body. It keeps the level of fats and cholesterol tightly regulated.
  • Liver secretes a specific substance called bile, which is released into the gut and helps in the digestion of fatty foods.
  • It helps remove abnormal blood cells from the circulation by decomposing them. If there is any infectious agent in the blood, liver gets activated and fights against the infectious pathogens.
  • Liver is responsible for the synthesis of blood clotting proteins, which are required for the normal clotting of blood.
  • Liver is supposed to be the main detoxifier of the body where all harmful toxins of the body are detoxified. Being a detoxifier, liver also helps to eliminate the harmful metabolic products of drugs and alcohol from the body.

It would not be wrong to say that function of liver can be summarized in three words; storage, synthesis and detoxification. Now imagine the consequences if the liver fails to function properly.

Obviously, the whole body will suffer and collapse. This is something that happens in “liver cirrhosis”, when liver fails to carry out its functions.

Liver cirrhosis is chronic progressive liver disease in which liver cells start dying and normal liver tissue is replaced by dead non-functioning fibrous tissue. This fibrous tissue, unlike normal healthy liver tissue, cannot compensate the liver functions which in turn, causes marked progressive decline in the liver function. Fibrous or scar tissue compresses the blood vessels supplying theliver and reduces the blood flow. The reduced blood flow causes the death of liver cells which further accelerates the formation of scar or fibrous tissue.

Thus, all these changes end up in a vicious cycle of liver cell death and its replacement by fibrous tissue. As the time passes, these changes in liver become permanent and whole liver tissue is replaced by scar tissue, causing a rapid and progressive deterioration in liver function. As a result, cirrhotic liver becomes unable to handle glucose metabolism, synthesis of blood proteins and detoxification of harmful toxins and drugs.

Stages of liver cirrhosis

Liver cirrhosis is a chronic and progressive disorder that does not happen all of a sudden. It takes months and years for liver to go in to the state of cirrhosis. This disorder develops with time and is divided into 4 stages according to the progression and intensity of the disease (1). As the disease progresses toward late stages, the prognosis becomes poor. No matter the cause of cirrhosis, the stages of liver cirrhosis are more or less same for all. Liver slowly and gradually passes through these stages until the total liver failure develops.

Here is the explanation of the 4 stages of liver cirrhosis:


The first stage of liver cirrhosis is inflammation. Whenever an offending cause or agent irritates the liver, the liver gets activated in response. The threat signals from liver in turn cause activation of immune system of the body. The activation of immune system is followed by movement of immune cells towards liver. When immune cells reach liver through blood circulation, they tend to fight off the cause being responsible for liver irritation. Immune cells release inflammatory mediators that help to eradicate the offending cause. But, in doing so, inflammation occurs and some of the liver cells start dying as a consequence. The changes at the stage of inflammation are totally reversible. But, if the inflammation does not subside and remains persistent for long, the damage to liver starts becoming permanent. Same thing happens in the liver cirrhosis. Inflammation remains persistent in the liver that leads to cirrhosis and liver failure.

At this initial stage of liver, the liver function does not decline because only a few liver cells die and rest of the healthy liver tissue compensate for it. Thus, symptoms of cirrhosis do not appear this stage and most of the patients remain asymptomatic. However, if the inflammation is detected and treated at this stage, the prognosis is very good and all damage that has occurred to liver can be reversed.


The second stage in the course of liver cirrhosis is scarring or fibrosis of liver. If the inflammation of liver persists for a longer time and remains untreated, then it initiates the formation of dead scar tissue in liver. There are specialized cells in the liver parenchyma (normal liver tissue) named as stellate cell. These are the culprit cells mainly involved in causing fibrosis. Prolonged inflammation of liver parenchyma activates these stellate cells. Once activated, these cells secrete a growth factor known as Transforming Growth Factor Beta1 (TGF-β1), which starts depositing collagen fibers in the liver parenchyma and replaces normal liver tissue with non functioning scar or fibrous tissue.

This scar tissue reduces blood flow and causes further compromise in liver structure and function. Furthermore, these stellate cells secrete “tissue inhibitors of metalloproteinases (TMP)”, the enzymes that strengthen the fibrous tissue by preventing its breakdown. Fibrosis is a permanent change and nothing can be done once a scar or fibrous tissue is formed.

The person may remain asymptomatic at this stage because fibrosis is not widespread and rest of the healthy liver parenchyma tries to compensate the loss of function caused by fibrosis. As a result, there is just a mild decline in liver functions and the patient remains symptom free. However, mild symptoms like nausea and loss of appetite may appear at this stage. If the diagnosis is made at this stage, the prognosis is good because early treatment can be done to prevent the further progression of fibrosis.


If the fibrosis remains neglected and is not treated in time, it progresses to the stage of cirrhosis. The hallmark of this stage is the formation of bridging fibrous septa and nodules. In this stage of cirrhosis, the fibrosis worsens and becomes widespread. There is formation of band like fibrous tissue that runs throughout the liver parenchyma, causing distortion of its structure. As the fibrous tissue goes on replacing the normal tissue, the blood supply is compromised which further triggers the inflammation and fibrosis of liver. Marked fibrosis of liver causes a rapid decline in its functions.

 In order to overcome this loss, the rest of liver tissue becomes enlarged and nodular. Hence the overall structure of liver at this stage shows a picture like fibrous band like septa running through liver parenchyma with the enlarged liver nodules entrapped within them. In addition to this, the fibrous tissue compresses the portal vein passing through liver. The blood in portal vein now has to flow against high resistance which then leads to portal hypertension. Portal hypertension is another hallmark of liver cirrhosis that further deteriorates the liver structure and function.

Due to rapid decline in liver functions, the symptoms begin to appear at this stage. These symptoms include fatigue, weakness, loss of appetite, skin itching, abdominal distention and skin bruising. However, the prognosis of this stage is not good because marked permanent liver damage occurs. The purpose of treatment at this stage is to relieve symptoms and halt the further progression of cirrhosis.


Liver failure is the most advanced stage that follows liver cirrhosis. It is the end stage liver disease at which liver completely fails to carry out its functions. At this stage, the fibrosis becomes so extensive that it replaces almost all healthy tissue with a scar tissue. Liver failure is supposed to be a life threatening and fatal condition. Liver damage is so widespread at this stage that no treatment can reverse it. When liver goes into failure, the symptoms become more prominent and the patient may present with symptoms like jaundice, swelling of legs, abdominal distention, skin bruising, poor memory function and state of confusion. Liver failure may ultimately lead to coma and death.

As liver damage is extensive and permanent at this stage, no treatment can restore the liver function. Only symptomatic and supportive treatment is done to relieve the symptoms. The only treatment that can be done at this stage is liver transplant. Otherwise, the prognosis is extremely poor and patient dies ultimately.

What are the causes of liver cirrhosis?

Here are described the major causes of liver cirrhosis:


In western countries, alcoholism is one of the leading causes of liver cirrhosis (2). Those who are chronic alcohol abusers are more likely to get liver cirrhosis. However, not all people who drink alcohol will end up having liver cirrhosis. Only 20-30 percent of chronic alcoholics suffer from liver cirrhosis and this depends on the duration and daily amount of consumption.

Liver is the main organ that helps detoxify the toxic alcohol products. But when alcohol abuse is too much, liver becomes unable to handle the detoxification of alcohol. As a result, toxic alcohol product called acetaldehyde is produced which irritates the liver and causes inflammation. Toxic liver products induce those enzymes in liver that are involved in the synthesis of fats. This in turn increases the production of fat molecules in the liver that are deposited inside liver cell. These deposited fats in liver get oxidized and start causing the inflammation of liver. If the condition remains uncontrolled, it slowly progresses to cirrhosis. Since excess fat deposit is the main reason causing cirrhosis in alcoholism, this type of cirrhosis due alcohol abuse termed as fatty liver disease.

Chronic hepatitis C

Hepatitis C is another leading and common cause of liver cirrhosis (3). When hepatitis C virus infects liver, it invades into the cells and starts causing their inflammation. If hepatitis C is treated in is early and acute stage, the prognosis is good and damage to liver will be minimal. But some of the patients retain virus in their liver and develop chronic hepatitis C.

Chronic hepatitis C is something that needs to be managed in time. Otherwise, it will eventually lead to liver cirrhosis. About 20-30 percent of patient with chronic hepatitis end up having liver cirrhosis. In patients having chronic hepatitis C, the virus remains activated in liver for years and causes slow degeneration of liver cells followed by formation of fibrous tissue that leads to cirrhosis.

Chronic hepatitis B

Like chronic hepatitis C infection, some people having hepatitis B may develop chronic hepatitis B infection. However, the chances of liver cirrhosis with chronic hepatitis B are less as compared to chronic hepatitis C. If hepatitis B virus persists for prolonged time in liver, for years and years; it causes inflammation and death of liver cells. The dead liver cells are then replaced by scar tissue that triggers the process of cirrhosis.

Non-alcoholic steatohepatitis (NASH)

Non alcoholic steatohepatitis occurs in obese people or people having diabetes or metabolic syndrome (4). The mechanism of liver cirrhosis is same as in alcoholic liver cirrhosis. But, the cause of cirrhosis here is not alcohol. Therefore, the term non alcoholic steatohepatitis is used for this condition. In NASH, fat metabolism by liver gets disturbed and there is accumulation of fat particles in liver cells that causes inflammation, cell damage and ultimately cirrhosis of liver.

Primary biliary cirrhosis

Liver secretes bile which helps in improving digestion. Liver contains bile ducts through which bile flows out of liver. These bile ductules join to form a common hepatic duct which drains bile from liver into the common bile duct. In order to maintain the liver health, this bile keeps flowing out of liver all the time. Whenever, there is stasis of bile in liver, it causes inflammation and damage to liver cells.

Primary biliary cirrhosis is an autoimmune disorder is which body’s own immune system starts attacking the biliary system. Progression of this disease causes damage and narrowing of bile ducts and common bile duct. As a result, bile cannot flow out of the liver and starts accumulating in liver. This bile stasis in liver irritates the liver cells and triggers the viscous cycle of inflammation, fibrosis and cirrhosis.

Primary sclerosing cholangitis

Primary sclerosing cholangitis is another autoimmune disorder that affects bile ducts in the liver and common bile duct. This condition is associated with other autoimmune disorders like Crohn’s disease and ulcerative colitis. This immune mediated destruction of bile ducts causes their constriction and narrowing that blocks the bile flow out of liver. The bile accumulation in liver then gradually ends up in liver inflammation and fibrosis.

Autoimmune hepatitis

Like in other autoimmune disorders, the mechanism of liver cirrhosis is same in autoimmune hepatitis. Autoimmune hepatitis is less common than other causes of liver cirrhosis like chronic viral infection and alcohol abuse. The condition is more likely to occur in women who are predisposed to other autoimmune disorders. In autoimmune hepatitis, body’s immune system produces antibodies against liver. These antibodies start attacking healthy liver tissue and cause damage to it. Long term autoimmune destruction culminates in fibrosis and cirrhosis. Steroids and immune suppressant drugs can improve the survival. But, some patients present with fulminant liver failure that has worst prognosis and can only be treated through liver transplant.


Hematochromatosis is a genetic disorder in which body absorbs excess amount of iron and as a result there is iron overload in the body. This excess iron starts depositing in liver, skin, pancreas, heart muscles and joints. When iron deposits in liver, it induces inflammation of liver. If not treated in time, iron keeps on accumulating in liver tissue and stimulates fibrosis.

Wilson’s disease

Wilson disease is a rare cause of liver cirrhosis (5). Like hemochromatosis, in Wilson’s disease there is excess of copper in the body. Something goes wrong with the protein that regulates copper levels in the body. As a consequence, copper overload takes place. This copper deposits in liver and gradually causes cirrhosis. Besides liver, copper also gets deposited in brain and eyes, causing damage to them.

Glycogen storage diseases

Glycogen storage disease is another rare cause of liver cirrhosis. It is a genetic disorder in which enzyme involved in glucose metabolism gets mutated. As a result, excess glycogen begins to deposit in the liver and causes liver cirrhosis. Since it is a genetic disease, it causes liver damage at very young age and symptoms of liver cirrhosis appear early.

Hepatotoxic drugs

There are certain drugs like immune suppressants and chemotherapy drugs that can increase the risk of liver cirrhosis. The chances of liver cirrhosis with these drugs in rare. But, prolonged use of these drugs may cause liver cirrhosis.

Alpha 1-antitrypsin deficiency

Alpha 1-antirtypsin is an inhibitor of protease, enzyme that tends to damage lungs and liver structure. Deficiency if alpha 1-antitrypsin leads to damage of lung and liver. Hence, chances of liver cirrhosis are high in patient with genetic deficiency of alpha 1-antitrypsin.

Cardiac cirrhosis

Cardiac cirrhosis is defined as liver cirrhosis caused by right sided heart failure. Although it a rare cause of liver cirrhosis, yet it can happen in patients with long standing heart failure. In right sided heart failure, the blood pools back in inferior vana cava. This causes stasis of venous blood in liver that causes progressive deterioration of liver structure and its function, ultimately leading to liver cirrhosis.

How does liver cirrhosis present?

Signs and symptoms of liver cirrhosis mostly do not appear in the initial stages of disease. But, as the disease progresses to stage of complete cirrhosis and failure, the symptoms become prominent. Symptoms that appear early are non specific and do not indicate towards liver cirrhosis. These symptoms start to become more specific in the advanced stages of disease and raise the suspicion of liver cirrhosis. Here are the characteristic signs and symptoms of liver cirrhosis:

Non specific symptoms include:

  • Fatigue
  • Weakness
  • Muscle cramps
  • Loss of appetite (6)
  • Weight loss
  • Feeling of being unwell and tired all the time

Specific symptoms that are suggestive of liver cirrhosis include:

  • Jaundice – yellow discoloration of eyes and skin.
  • Skin itching or pruritis – this happen due to blockage of bile release. Bile salts present in bile are absorbed in blood and cause intense itching.
  • Skin bruising – due to defective synthesis of blood clotting proteins.
  • Clay colored stools
  • Darkening of urine
  • Whitening of nail – due to reduced synthesis of albumin protein by cirrhotic liver
  • Loss of hair
  • Palmar erythema – a condition in which redness of palms occurs. The reason for this is increased estrogen concentration in the body because cirrhotic liver become unable to excrete excess estrogen from the body.
  • Spider nevi – these are spider shaped vascular lesion seen in the areas of trunk and face.  Excess estrogen in patients of liver cirrhosis causes spider shaped dilation of superficial blood vessels.
  • Hepatomegaly – enlarged liver size that can be palpated. However, in advanced stages of cirrhosis, hepatomegaly may not be present because whole of the liver is replaced by fibrous tissue which causes shrinkage of liver.
  • Finger clubbing – a condition in which there is loss of angle between nail and nail bed.
  • Gynaecomastia – characterized by increase in breast size in male. The reason for gynaecomastia in liver cirrhosis is increased estrogen level in the body which stimulates the breast growth and enlargement.
  • Loss of libido, impotence and infertility.
  • Testicular atrophy in male. More common in cirrhosis caused by hemochromatosis and alcohol abuse.
  • Shortness of breath and extreme fatigue
  • Ascites – collection of fluid in the abdomen characterized by abdominal distention, swelling and discomfort. The cause of ascites is portal hypertension. Portal vein carries deoxygenated blood from whole gastrointestinal system and passes through liver. But, when fibrosis of liver occurs, it compresses the portal vein and makes the blood flow through it difficult. The high resistance to portal blood flow leads to portal hypertension. When blood becomes difficult, the blood instead of going to heart starts to back up in portal vein. The water content of the blood start oozing out in the abdomen, causing ascites. Another possible cause of ascites in liver cirrhosis is defective synthesis of those blood proteins that hold the water or fluid inside the blood vessels. Once these proteins get absent, the fluid starts oozing out of blood vessel and causes ascites.
  • Swelling or edema of legs – the principal of leg swelling is same as that of ascites. Loss of blood protein reduces osmotic pressure inside blood vessels and causes fluid collection in dependant parts of body like legs.
  • Enlarged spleen may also be palpated due to portal hypertension and back up of blood in spleen.
  • Esophageal varices – when portal hypertension occurs, the blood in portal vein tries to bypass liver by passing through shunting or collateral blood vessels. Esophageal varices are the shunting blood vessel present within stomach and esophagus. In portal hypertension, blood flows through these low pressure shunt vessels and by passes the liver. But, the persistent pressure in these vessels can burst them that lead to vomiting of blood.
  • Caput medusa – dilation of superficial veins around the umbilicus. Again portal hypertension is the main culprit of caput medusa. Due to portal hypertension, the blood is shunted through collateral vessels in umbilical region, causing the superficial dilation of these vessels.
  • Passing black tarry stools – like esophageal varices, there are collateral vessels in intestine too through which blood flows in case of portal hypertension. Persistent dilation of these collateral vessels can make them burst. The leaked blood then passes into stool and make them appear black and tarry.
  • Hepatic encephalopathy – this happens in liver failure when liver fails to excrete toxic ammonia from the body, causing its accumulation in the body. The ammonia reaches brain and harmfully affects its functioning. Symptoms of hepatic encephalopathy include confusion, sudden change in personality, depression, poor memory function, difficulty in concentration, increased forgetfulness and flapping tremors of hand.

How is liver cirrhosis diagnosed?

Following steps help in the diagnosis of liver cirrhosis:

History and examination of patient

First patient is asked about his symptoms and then careful physical examination is carried out. Clues about alcohol abuse, drug abuse or hepatitis can be obtained through history taking. On physical examination, doctor may find enlarged palpate liver in patient of cirrhosis, jaundice, abdominal distention and spider nevi on skin.

Blood tests

Following blood tests are carried out to evaluate liver cirrhosis:

  • Full blood count or FBC – may show low hemoglobin or platelet count.
  • Liver function tests or LFTs – LFTs include assessment of level of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), bilirubin, gamma-glutamyltransferase (gamma-GT), bilirubin and albumin. All of these are raised in liver cirrhosis except albumin which is markedly low. AST and ALT are raised in cirrhosis due to hepatitis while GGT is more likely to rise in alcoholic cirrhosis.
  • Coagulation profile – coagulation defects are seen because liver fails to synthesize clotting factors.
  • Prothrombin time – prothrombin time is increased due to reduced synthesis of clotting factors.
  • Viral markers or serology to detect hepatitis B and C virus
  • Antibodies testing to exclude the autoimmune causes of liver cirrhosis
  • Fasting glucose levels to detect metabolic syndrome as a cause of cirrhosis
  • Ferritin and transferring saturation to detect hemochromatosis.
  • Alpha 1 antitrypsin evaluation.
  • Ceruloplasmin and urinary copper levels to exclude Wilson’s disease.

Imaging studies

Imaging studies like ultrasound, MRI and CT are next step in the diagnosis of liver cirrhosis. Imaging studies may show findings like enlarged liver and spleen size, nodules formation liver, portal hypertension and fluid collection in the abdomen.


Endoscopy may be carried out to rule out the risk of esophageal varices. Presence of these varices indicates the advance stage of cirrhosis.

Liver biopsy

The most accurate test for diagnosis of liver cirrhosis is liver biopsy. But, most of the time, biopsy is not taken and diagnosis is made on lab tests and imaging studies.

How is liver cirrhosis treated?

Prognosis is excellent if liver cirrhosis is diagnosed and treated in its early stages. However, advanced stages are associated with so many complications like portal hypertension, ascites and hepatic encephalopathy that make the prognosis poor. Following treatment are adopted for dealing with liver cirrhosis.

Identify the cause and treat it

First step in the treatment of liver cirrhosis is to identify the cause of liver cirrhosis and then improvise the treatment according to it. For example, in case of cirrhosis due to viral hepatitis, interferons are given to resolve infection and prevent cirrhosis. While, in case of autoimmune cirrhosis, corticosteroids are the mainstay of therapy for treatment. In hemochromatosis and Wilson’s disease, chelation therapy is done to remove excess iron and copper from body.

Improve diet and nutrition

Improving diet can help prevent progression of cirrhosis. Zinc deficiency can occur in these patients, so multivitamin supplements should be added to diet.

Stop consuming alcohol

In case of cirrhosis due to alcoholism, stopping alcohol can prevent further progression of disease.

Reduce risk of bleeding

Vitamin K supplements and platelets can be given to reduce the risk of bleeding. In advanced stage disease, when clotting factor synthesis in decreased, clotting factors can be given to avoid complications.

Treat ascites

Ascites can be controlled by restricting salt consumption and by using diuretic drugs that excrete extra water from the body. Another complication associated with ascites is bacterial peritonitis that can be treated by giving antibiotics.

Treat portal hypertension

Portal hypertension is controlled by using antihypertensive drugs. These drugs control portal hypertension somehow. Incidence of esophageal varices can be reduced by repeated endoscopy at intervals. If varices are present, their band ligation or sclerotherapy can be done to reduce the risk of rupture. If still portal hypertension remains uncontrolled, transjugular intrahepatic portosystemic stent shunt (TIPPS) can be done. In this technique, a stent is placed in portal vein to keep the blood flowing through it.

Prevent hepatic encephalopathy

This can be prevented by using lactulose which acts as a laxative and helps increasing ammonia excretion from the body.

Liver transplant

Liver transplant is considered as the last option when everything else fails to control the symptoms of liver cirrhosis. Liver transplant is the only treatment option for liver failure or end stage liver disease. Survival rate with liver transplantation is quite high.

Share this article
Written by: Michal Vilímovský (EN)
Education: Physician
Article resources: See numbered references within the article.
Image resources: Dollarphotoclub.com
Published: September 13, 2015 at 7:54 PM
Next scheduled update: September 13, 2017 at 7:54 PM
Our site uses cookies to provide services, personalize ads and analyze traffic. By using this site you agree. More info