Liver Fibrosis: What Is It, Causes, Symptoms & Treatment

Introduction

Liver fibrosis is a condition in which the liver gets damaged and scarred due to an inflammation that has been present for a long time, because of which the liver does not work properly.
This damage is caused due to various reasons, such as an infection with the hepatitis B or C virus, or when you have a fatty liver disease.
Over time, this can become worse, where the damage becomes irreversible, leading to liver failure^1,2. 

A recent study³ found that about 2 in 100 people may already have serious liver scarring based on blood tests, and 7 in 100 may have fibrosis seen on scans.  

As liver fibrosis can lead to serious liver problems, it is important for you to know about this condition, what causes it, what liver fibrosis symptoms to look for, how it is diagnosed and treated, which we will be discussing in this blog³. 

What is Liver Fibrosis?

The liver is an important organ in our body. It makes bile, which is used to break down fats, removes toxins from the body, makes cholesterol and essential fats, and stores vitamins⁴. 

Constant injury caused by an infection such as hepatitis, fatty liver or as side effects of some medicines, triggers inflammation in the liver. Over time, the liver tries to heal itself by activating special liver cells called hepatic stellate cells. These cells act like scar-forming (fibrous) cells and produce more extracellular proteins like collagen fibres. Slowly, this leads to thickening and scar tissue formation in the injured area, called fibrosis.  

Over time, as the scarring progresses, it can lead to serious liver damage (cirrhosis). This not only affects liver function but also leads to several complications^5,6.  

Now that we know what is liver fibrosis, let us see the stages of liver fibrosis. 

Staging of Liver Fibrosis

Liver fibrosis happens slowly, and doctors will say which liver fibrosis stage a person has based on how much scarring has occurred. This is determined on histopathology (by liver biopsy).  

There are several staging systems used for liver fibrosis such as the Knodell, Ishak and METAVIR systems. According to the commonly used METAVIR system, liver fibrosis has 5 stages, Stage 0 to Stage 4, which are as follows: 

• Stage 0: No fibrosis 
• Stage 1: Portal fibrosis without septa (suggestive of mild fibrosis) 
• Stage 2: Portal fibrosis with few septa (suggestive of moderate fibrosis) 
• Stage 3: Portal fibrosis with numerous septa (suggestive of severe fibrosis) 
• Stage 4: Cirrhosis (suggestive of a serious stage where liver function becomes very poor, and complications start to appear) 

The liver fibrosis stages help doctors decide the right liver fibrosis treatment and check the risk of serious problems like liver failure. The staging can also show if complications are likely to happen^2,6. 

What are the Causes of Liver Fibrosis?

Liver fibrosis mainly occurs due to long-term injury to the liver (hepatotoxic injury). This can be due to the following factors²: 

• Hepatitis B and C viruses: These viruses attack liver cells, triggering constant inflammation and long-term damage, leading to fibrosis^5,7. 
• Alcohol-related liver disease: The liver helps break down alcohol. But when alcohol is taken in excess, it damages liver cells and leads to fibrosis⁸. 
• Non-alcoholic fatty liver disease (NAFLD): Obesity, poor diet, low physical activity and conditions like diabetes cause fat to build up in the liver. This triggers inflammation and liver cell damage, eventually causing fibrosis. This happens because the body does not respond well to insulin, which over time damages liver cells and causes fibrosis⁹. 
• Drug-induced liver injury: Certain medicines like those that suppress the immune system, such as those used after transplants (such as methotrexate, azathioprine, and tacrolimus), may cause liver damage and fibrosis¹⁰. 
• Autoimmune hepatitis: Sometimes, the body’s own immune system creates antibodies that attack liver cells. This leads to liver damage, inflammation, and over time, fibrosis⁸. 
• Inherited conditions in children: Some children are born with rare genetic problems that can lead to fibrosis if not treated early. These include Wilson’s disease, where too much copper builds up in the liver; hereditary hemochromatosis, which causes iron overload; alpha-1 antitrypsin deficiency, where a protective protein is missing; and cystic fibrosis, where thick mucus blocks the bile flow from the liver¹¹. 

Another reason for fibrosis is cholestatic liver injury, which happens when bile cannot flow properly. This can result from conditions that affect or block the bile ducts. Examples include Primary Biliary Cholangitis (PBC), where the immune system attacks the small bile ducts inside the liver; Primary Sclerosing Cholangitis (PSC), which leads to inflammation and scarring of bile ducts inside and outside the liver; and Biliary Atresia, a condition present at birth where bile ducts are blocked or missing. When bile starts to build up in the liver, it damages the liver cells and causes inflammation. Special cells near the bile ducts (called portal fibroblasts) then form scars on the liver^2,5. 

Symptoms of Liver Fibrosis

Liver fibrosis symptoms are mostly absent or mild and usually appear when the scarring progresses.  

The common symptoms seen include: 

• Feeling tired 
• Not able to eat properly 
• Nausea 
• Loss of weight 
• Pain in the abdomen 
• Yellowing of skin and eyes (signs of jaundice) 
• Dark-coloured urine, pale stools, and itching (signs of obstruction to bile flow)^12,13 

Liver fibrosis, when in the early stage, can improve if the cause of injury is removed. But if the injury continues for many months or years, the fibrosis becomes irreversible and leads to a severe condition called liver cirrhosis, which can result in several complications. 

Complications of Liver Fibrosis

The complications of liver fibrosis occur either due to direct damage to liver cells or increased pressure in the portal vein (a large blood vessel that carries blood to the liver), a condition known as portal hypertension. These include^10,24: 

• Excess fluid in the belly (ascites) 
• Bleeding from veins inside the food pipe (variceal bleeding) 
• Toxin buildup in brain (hepatic encephalopathy) 
• Kidney failure linked to liver disease (hepatorenal syndrome) 
• Lung issues (hepatopulmonary syndrome) 
• Liver cancer 
• Poor clotting (coagulopathy) 

When these complications arise, symptoms such as easy bruising and bleeding, swelling of legs and abdomen, confusion, forgetfulness, mood changes, and sleep disturbances, and breathing difficulty can occur, which need immediate medical attention. 

Diagnosis of Liver Fibrosis

Liver fibrosis is usually checked in people who have long-term liver problems like hepatitis B or C, non-alcoholic fatty liver disease (NAFLD), or other liver conditions such as autoimmune or bile duct diseases. Doctors may use the following methods to diagnose liver fibrosis¹⁴: 

1. Blood tests: There are new blood scoring tests now commonly used by doctors because they are simple, avoid biopsy in many cases, and help detect liver fibrosis early. More people are also searching about these tests to know what they mean. These include special scores like: 

• FIB-4 Index: This is a score calculated based on blood test results of platelets, AST, ALT, and age. The test is used to detect likelihood of fibrosis in individuals with viral hepatitis or those with NAFLD. A high score indicates greater possibility of advanced fibrosis, wherein further testing or liver biopsy is needed¹⁵. 
• NFS (NAFLD Fibrosis Score): This score helps to find out if fatty liver disease has scarring or not by calculating a score based on BMI and blood sugar levels in addition to factors used for FIB-4 scoring¹⁶. 
• MAF-5 Score: The Metabolic Dysfunction-Associated Fibrosis 5 (MAF-5) score helps to predict the fibrosis risk in those with metabolic diseases like obesity and diabetes. The score uses waist size, BMI, sugar status, AST, and platelets to show if you are at low, medium, or high risk and also correlates with the chance of death¹⁷. 
• ELF test: The Enhanced Liver Fibrosis (ELF) score is calculated using three blood markers: TIMP-1, PIIINP, and hyaluronic acid. It helps check for advanced liver scarring (fibrosis) in people with fatty liver disease caused by obesity or diabetes and is considered to be diagnostically accurate^17,18. 
• FibroTest: It is a blood test panel where the score is calculated based on levels of alpha2-macroglobulin, apolipoprotein A1, haptoglobin, total bilirubin, and GGT, adjusted for age and gender. The score ranges from 0 to 1, and a value above 0.58 suggests severe fibrosis, helping to check liver damage in people with long-term liver diseases²⁰. 
• FibroMeter: It is a panel of blood tests that checks how much scarring (fibrosis) is there in the liver. It is used for different liver problems like hepatitis, alcohol-related liver disease, or fatty liver, and helps find the stage of fibrosis without needing a biopsy²¹. 

Other blood tests used to check for liver fibrosis are some indirect tests which investigate the liver enzymes, platelets, and bilirubin which shows how the liver is working, though it doesn’t directly show the fibrosis. But direct tests are also there which check for substances made or broken-down during scarring like collagen, laminin, and TGF beta. These tests are often combined to get an idea on the level of liver damage and fibrosis²³. 

2. Imaging tests: They are non-invasive methods used to detect liver fibrosis and determine its stage. Besides the traditional methods like ultrasound, CT and MRI, newer imaging modalities are also used, including: 

• FibroScan or Vibration controlled transient elastography (VCTE): A special type of ultrasound that uses high-frequency sound waves to find out the amount of fibrosis in the liver^22,23. 
• Acoustic radio force image (ARFI): It uses regular ultrasound with added pressure to measure liver scarring more accurately, even in people with obesity or fluid build-up. 
• 2D shear wave elastography: It gives a detailed real-time picture of liver scarring with high accuracy, but more expensive and needs trained people to do it. 
• Real time elastography (Hi-RTE): In this, the evaluation of fibrosis is obtained after compressing manually. 
• Magnetic Resonance Elastography (MRE) – This is a special MRI scan that checks how stiff the liver is by sending gentle mechanical waves through it. It helps show how much liver damage is present and where it is, making it easier to understand and diagnose liver disease²⁴. 

3. Liver biopsy: Liver biopsy is the most accurate test to find out how much liver damage (fibrosis) is present and what is causing it. But since it is invasive and may cause pain or bleeding, doctors don’t always use it, especially when safer tests are available. 

To get a correct diagnosis, doctors may combine blood tests with scans to get a clear idea about the extent of liver fibrosis¹⁰. 

Treatment Options for Liver Fibrosis

Liver fibrosis treatment focuses on removing the underlying cause of liver damage.
When the cause is removed, it lowers inflammation and stops scar-forming cells from becoming active. This may slow down or improve liver scarring over time. The treatment options are: 

• Antiviral medicines: These are used to treat infections like hepatitis B or hepatitis C (infections caused by viruses that affect the liver). Medicines like faldaprevir, ribavirin, and peginterferon alfa-2a may help to reduce liver inflammation in viral hepatitis. 
• Biologic treatment: Drugs like simtuzumab have been shown to decrease the progression of fibrosis. Other drug trials are on way. 
• Iron or copper removal therapy/chelation therapy: In some inherited conditions like hereditary haemochromatosis (where the body stores too much iron) or Wilson’s disease (where the body stores too much copper), medicines or procedures are used to remove the excess iron or copper. This can reduce damage and help the liver recover. 
• Cholangitis medications: Medicines like ursodeoxycholic acid can be used to improve bile flow and prevent further liver damage. 
• Natural and supportive treatments: These include vitamin D, omega-3 fatty acids and probiotics, which may help reduce inflammation and support liver healing in some cases^2,25. 

If your condition occurs as a side effect of a medication you are taking, your doctor will stop/change the offending medicine to prevent further liver injury. In addition, there are certain lifestyle changes you can follow to help prevent turning fatty liver into fibrosis. These include^1,2: 

• Lose weight and aim for a BMI between 18.5 and 24.9.  
• Eat a balanced diet high in fruits, nuts, vegetables, protein, and carbs but low in salt, sugar, and unhealthy fats.  
• Be physically active by walking or cycling at least 150 minutes a week. 
• Avoid alcohol to prevent injury and help improve liver health and metabolism.  

When to See a Doctor

If you have risk factors for liver fibrosis or are experiencing liver fibrosis symptoms mentioned above, you should see your doctor. 

Immediate medical attention is required if you have been diagnosed with cirrhosis and there is:  

• Stools in black or tar-like colour 
• Worsening of yellowish appearance of skin and white of eyes  
• Blood in vomit 
• Fever and Confusion 

These show that your condition may be worsening, and you need to address this as early as possible. 

Conclusion

Liver fibrosis is a slow but ongoing injury that can become serious and lead to complications. If treated early, the damage can be reversed. By finding it early, removing the cause, making healthy lifestyle changes, and doing regular check-ups, we can manage it well and stop it from progressing into more severe liver problems. 

Frequently Asked Questions (FAQs)

References

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