Hepatic Fibrosis

Hepatic fibrosis is a condition where excessive scar tissue builds up in the liver, replacing healthy tissue that normally helps your body function. While early stages can sometimes be reversed, understanding this condition and its causes is crucial for protecting your liver health.

Table of contents

• What Is Hepatic Fibrosis?
• What Causes Hepatic Fibrosis?
• How Fibrosis Develops in the Liver
• Stages of Hepatic Fibrosis
• Symptoms of Hepatic Fibrosis
• How Doctors Diagnose Hepatic Fibrosis
• Complications and Disease Progression
• Treatment and Management
• Can Hepatic Fibrosis Be Reversed?

What Is Hepatic Fibrosis?

Hepatic fibrosis is the buildup of an abnormally large amount of scar tissue in the liver. This occurs when the liver attempts to repair and replace damaged cells^[1]. The term fibrosis refers to excessive connective tissue that accumulates in the liver, representing scarring in response to chronic, repeated liver cell injury^[5].

Unlike healthy liver cells, scar tissue cannot perform any function. A normal, healthy liver is soft and squishy, but as scarring builds up, it becomes hard and bumpy^[8]. This scar tissue can distort the liver’s internal structure and interfere with blood flow to and within the liver, limiting the blood supply that liver cells need to survive^[1].

Hepatic fibrosis is not a specific disorder in itself. Instead, it is the result of other causes of liver damage^[1]. The condition is characterized by abnormal accumulation of extracellular matrix proteins, including collagen, that occurs in most types of chronic liver diseases^[3].

What Causes Hepatic Fibrosis?

Various disorders, medications, and substances can repeatedly or continuously damage the liver and cause fibrosis^[1]. The most common causes in the United States include chronic excessive alcohol use, viral hepatitis C, and metabolic dysfunction-associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH)^[1].

MASH is a condition that characterizes fatty liver not due to excessive alcohol use. This usually occurs in people who have excess body weight, diabetes or prediabetes, and high levels of fats and cholesterol in the blood. This combination of risk factors is often referred to as metabolic syndrome. Over recent years, metabolic syndrome leading to metabolic dysfunction-associated liver disease has become increasingly common in the United States^[1].

Worldwide, viral hepatitis B is a common cause of hepatic fibrosis^[1]. Other causes include certain hereditary metabolic disorders such as alpha-1 antitrypsin deficiency, iron overload (hemochromatosis), and Wilson disease. These disorders affect how foods are absorbed, broken down, and processed in the body^[1].

Autoimmune disorders can also cause fibrosis. In conditions like autoimmune hepatitis, the body attacks its own tissues. In primary biliary cholangitis and primary sclerosing cholangitis, bile ducts become inflamed, scarred, and blocked^[1]. Disorders that affect blood flow to, in, and out of the liver, such as Budd-Chiari syndrome, heart failure, and portal vein thrombosis, can also lead to fibrosis^[1].

Sometimes the cause of fibrosis is not known^[1].

How Fibrosis Develops in the Liver

Fibrosis develops when the liver is repeatedly or continuously damaged^[1]. After a single episode of injury, even if severe (as with acute hepatitis), the liver commonly repairs itself by making new liver cells and attaching them to the web of connective tissue that is left when liver cells die^[1].

However, if injury is repeated or continuous (as occurs in chronic hepatitis), liver cells attempt to repair the damage, but these attempts result in scar tissue formation^[1]. A healthy liver has a repair system to deal with worn out, dead, or damaged cells. This repair system uses collagen, a type of protein, a bit like scaffolding. It supports an area that is being repaired. In a healthy liver, once the repair is complete, the collagen is removed^[8].

If you have hepatitis (inflammation of the liver), your liver is constantly told to keep doing more repairs. The collagen is not removed. Instead, more and more keeps being added, which causes scars^[8]. The activation of special cells called hepatic stellate cells initiates fibrosis. These cells and adjacent cells multiply and become contractile cells termed myofibroblasts. These cells produce excessive amounts of abnormal matrix and other substances^[5].

Scar tissue replaces the liver cells and, unlike liver cells, performs no function. Without enough blood supply, healthy liver cells die, and more scar tissue is formed^[1]. Fibrosis can develop more rapidly when it is caused by a blockage in the bile ducts^[1].

Stages of Hepatic Fibrosis

Healthcare providers use several scales to define the stages of fibrosis. If a liver biopsy is performed, doctors may stage liver fibrosis based on the METAVIR scoring system. This assigns a score based on two factors: inflammation (activity) and damage (fibrosis)^[2].

The activity grades range from A0 to A3:

• A0: no activity
• A1: mild activity
• A2: moderate activity
• A3: severe activity

The fibrosis stages range from F0 to F4:

• F0: no fibrosis
• F1: portal fibrosis without septa
• F2: portal fibrosis with few septa
• F3: numerous septa without cirrhosis
• F4: cirrhosis

A person with the most severe disease form may have an A3, F4 METAVIR score^[2]. Another scoring system is Batts and Ludwig, which grades fibrosis on a scale of grade 1 to grade 4, with grade 4 being the most severe^[2].

While fibrosis staging can help you and a doctor understand the degree to which your liver might be damaged, identifying the underlying cause is more important than focusing on any particular stage^[2].

Symptoms of Hepatic Fibrosis

Fibrosis itself causes no symptoms^[1]. Many patients with fatty liver disease and liver fibrosis do not realize they have liver disease because the symptoms are often vague, like mild fatigue or abdominal discomfort^[9].

As liver disease progresses over time, patients may begin to experience appetite and weight loss, weakness, nausea, yellowing of skin and eyes (jaundice), fluid buildup and swelling in legs and abdomen, and confusion and trouble concentrating^[9].

Severe scarring can result in cirrhosis, which can cause symptoms^[1]. Blood pressure in the vein that carries blood from the intestine to the liver increases, a condition called portal hypertension^[1].

How Doctors Diagnose Hepatic Fibrosis

Doctors can often diagnose fibrosis and estimate its severity based on results of blood and imaging tests, but sometimes liver biopsy is required^[1]. Your doctor will begin by asking you about your medical history and symptoms. You will also undergo a physical exam^[9].

In order to diagnose fibrosis, your doctor may order blood tests to evaluate liver function, including tests to assess the level of the liver enzymes ALT and AST, which can be high when the liver is fatty^[9].

Your doctor may also order imaging tests of the liver such as:

• Abdominal ultrasound, which uses sound waves to produce pictures to evaluate the size and shape of the liver, as well as blood flow through the liver^[9]
• Computed tomography (CT) that combines special x-ray equipment with sophisticated computers to produce multiple images of the inside of the body^[9]
• Magnetic resonance imaging (MRI), which uses a magnetic field and radio waves to produce detailed pictures of the liver. MRI is the most sensitive imaging test, highly accurate even in mild cases^[9]
• Ultrasound elastography, a special ultrasound technique to test for liver fibrosis. The stiffness of the liver is calculated. Fibrotic livers are stiffer compared to normal livers^[9]
• MR elastography (MRE), a special MRI technique to test for liver fibrosis^[9]

If a doctor believes that someone has liver fibrosis, they may carefully collect a small tissue sample, or biopsy, from the liver using a large needle. A pathologist, a doctor who specializes in finding the root cause of disease, will then examine the sample under a microscope to assess the extent and type of damage^[11].

Complications and Disease Progression

If inflammation continues, possibly because a person has not received treatment, liver fibrosis can develop into more serious liver conditions^[11]. After months or years of repeated or continual damage, fibrosis becomes widespread and permanent. The scar tissue can form bands throughout the liver, destroying the liver’s internal structure and impairing the liver’s ability to regenerate itself and to function. Such severe scarring is called cirrhosis^[1].

Advanced liver fibrosis results in cirrhosis, liver failure, and portal hypertension, and often requires liver transplantation^[3]. Without treatment, liver fibrosis may lead to cirrhosis of the liver, liver failure, and liver cancer^[9].

As healthy liver tissue is lost, the liver also loses its ability to function. Cirrhosis produces hepatocellular dysfunction and increased resistance to blood flow within the liver, which result in hepatic insufficiency and portal hypertension, respectively^[3].

Treatment and Management

Treatment involves correcting the underlying condition when possible^[1]. Treatment for liver fibrosis depends on the underlying cause and is typically aimed at preventing, slowing, or reversing the progression of liver fibrosis^[9].

The first step in treatment is to address the underlying cause of liver disease, which may include weight loss, healthier eating habits, and exercise^[17]. Adopting a healthy lifestyle helps your liver work as efficiently as possible and lowers your risk for liver disease. Recommendations for a healthy lifestyle may include maintaining a healthy weight, eating a healthy diet, exercising regularly, and avoiding alcohol, which makes your liver work harder^[18].

Options include lifestyle changes, medication, and cholesterol and diabetes management^[9]. If the condition has progressed to more advanced stages, medication such as antiviral and immunosuppressive drugs may be prescribed. In advanced cases, a liver transplant may be necessary^[17].

Many treatments for liver fibrosis have been investigated in clinical trials, including dietary supplementation (such as vitamin C), biological treatment (such as simtuzumab), drugs (such as pegbelfermin and natural herbs), genetic regulation (such as non-coding RNAs), and transplantation of stem cells (such as hematopoietic stem cells). However, none of these treatments has been approved by Food and Drug Administration^[10].

Consistent medical management of liver disease and fibrosis is vital for preventing irreversible liver damage. If you have liver disease or other medical conditions, it is important to follow care instructions and follow up with your doctor whenever you need help^[18].

Can Hepatic Fibrosis Be Reversed?

Fibrosis can sometimes be reversed if the cause is identified promptly and corrected^[1]. It is possible to stop fibrosis from getting worse. If this is done early enough, then your liver will be able to carry on working normally. It might even be able to completely repair the damage^[8].

Reversibility of advanced liver fibrosis in patients has been recently documented, which has stimulated researchers to develop antifibrotic drugs^[3]. In its initial stages, hepatic fibrosis can regress if the cause is reversible (for example, with viral clearance)^[5].

However, after months or years of repeated or continual damage, fibrosis becomes widespread and permanent^[1]. The reverse of liver fibrosis is slow and frequently impossible for advanced fibrosis or cirrhosis. To avoid the life-threatening stage of liver fibrosis, anti-fibrotic treatments, especially combined behavior prevention, biological treatment, drugs or herb medicines, and dietary regulation are needed^[10].

If fibrosis continues to get worse, it can lead to serious, permanent damage (cirrhosis)^[8]. Treatment can often reverse the damage of mild to moderate liver fibrosis^[11].

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