Liver fibrosis occurs when the healthy tissue of your liver becomes scarred and therefore cannot work as well. Fibrosis is the first stage of liver scarring. Later, if more of the liver becomes scarred, it’s known as liver cirrhosis.
Scarring of the liver occurs on a spectrum, with different degrees. Some of them may be treatable and reversible. However, medications and lifestyle changes can help to keep fibrosis from getting worse.
There are several different scales of liver fibrosis staging, where a doctor determines the degree of liver damage. This may be achieved with a variety of methods, such as blood work, imaging tests, and a tissue biopsy that may be further examined under a microscope (histology).
While fibrosis staging can help you and a doctor understand the degree to which your liver might be damaged, it’s important to note that the identifying the underlying cause is more important than focusing on any particular stage.
If a liver biopsy and histology is performed, a doctor may stage liver fibrosis based on the METAVIR scoring system.
This assigns a “score” based on two factors: inflammation (activity) and damage (fibrosis). A lower score may indicate less inflammation and damage, while a higher score could mean more.
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
Therefore, a person with the most severe disease form may have an A3, F4 METAVIR score.
Another scoring system based in histology is Batts and Ludwig, which grades fibrosis on a scale of grade 1 to grade 4, with grade 4 being the most severe.
The International Association of the Study of the Liver (IASL) also has a histological scoring system with four categories that include:
- Minimal chronic hepatitis
- Mild chronic hepatitis
- Moderate chronic hepatitis
- Severe chronic hepatitis
Fibrosis staging may also be based on other tests outside of a liver biopsy and histology. For example, a doctor may confirm liver fibrosis with a blood test that measures fibrosis 4 (Fib4) in the blood.
Additionally, fibrosis staging may be confirmed with the help of imaging tests. These look at the size and shape of you liver, as well as for excess fat, lumps, or shrinkage. Possible imaging study techniques include:
- abdominal ultrasound
- computed tomography (CT) scan of your abdomen
- magnetic resonance imaging (MRI) scan
- elastography, which is combined with either an ultrasound or MRI scan
Doctors don’t often diagnose liver fibrosis in its mild to moderate stages. This is because liver fibrosis doesn’t usually cause symptoms until more of the liver is damaged.
When a person does progress in their liver disease, they may experience symptoms that include:
- appetite loss
- difficulty thinking clearly
- fluid buildup in the legs or stomach
- jaundice (where the skin and eyes appear yellow)
- unexplained weight loss
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Liver fibrosis occurs after a person experiences injury or inflammation in the liver. The liver’s cells stimulate wound healing. During this wound healing, excess proteins such as collagen and glycoproteins build up in the liver.
Eventually, after many instances of repair, the liver cells (known as hepatocytes) can no longer repair themselves. The excess proteins form scar tissue or fibrosis.
Several types of liver diseases exist that can cause fibrosis. These include:
- autoimmune hepatitis
- biliary obstruction
- iron overload
- nonalcoholic fatty liver disease, which includes nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH)
- viral hepatitis B and C
- alcoholic liver disease
Treatment options for liver fibrosis usually depend upon the underlying cause of the fibrosis. A doctor will treat the underlying illness, if possible, to reduce the effects of liver disease.
For example, if a person drinks alcohol excessively, a doctor may recommend a treatment program to help them stop drinking. If a person has NAFLD, a doctor may recommend making dietary changes to lose weight and taking medications to promote better blood sugar control.
Exercising and losing weight may also help to reduce the disease’s progression.
Treatments for specific causes of liver fibrosis include:
- chronic liver disease: ACE inhibitors, such as benazepril, Lisinopril, and ramipril
- hepatitis C virus: direct action antivirals such as Epclusa, Harvoni, Mayvret, etc.
- nonalcoholic steatohepatitis: PPAR-alpha agonist
- autoimmune hepatitis: immunosuppressive therapy
- alcohol liver disease: abstinence from alcohol
A doctor may also recommend antifibrotics that may possibly help reduce the likelihood of permanent liver scarring (cirrhosis). Depending on the drug, antifibrotics are classified as:
- anti-inflammatories: examples include belapectin, cenicriviroc, and liraglutide
- hepatocyte apoptosis inhibitors: these include emricasan, pentoxifylline, and selonsertib
- oxidative stress inhibitors: possibilities include methyl ferulic acid and losartan
- hepatic stellate cell (HSC) inhibitors: these drugs target various cytokines that
may activate HSCsand contribute to fibrosis
Still, there are limitations to antifibrotic treatment. While some of the above medications are used for other purposes, such as high blood pressure and vascular diseases, not all are yet approved for the treatment of liver fibrosis. Animal studies show promise, but human clinical trials are limited.
If a person’s liver fibrosis advances to where their liver is very scarred and doesn’t work, a person’s only definitive treatment is often to receive a liver transplant. However, the waiting list is long for these transplant types and not every person is a surgical candidate.
Traditionally, doctors considered taking a liver biopsy the “gold standard” of testing for liver fibrosis. This is a surgical procedure where a doctor would take a tissue sample. A specialist known as a pathologist will examine the tissue for the presence of scarring or fibrosis.
Another option is an imaging test known as transient elastography. This is a test that measures how stiff the liver is. When a person has liver fibrosis, the scarred cells make the liver stiffer.
This test uses low-frequency sound waves to measure how stiff liver tissue is. However, it’s possible to have false positives where the liver tissue may appear stiff, but a biopsy doesn’t show liver scarring.
However, doctors have been able to use other tests that don’t require surgery to determine the likelihood a person may have liver fibrosis.
Examples include serum hyaluronate, matrix metalloproteinase-1 (MMP), and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1).
Doctors may also use tests that require calculations, such as an aminotransferase-to-platelet ratio (APRI) or a blood test called FibroSURE that measures six different markers of liver function and puts them into an algorithm before assigning a score.
However, a doctor can’t usually determine the stage of liver fibrosis based on these tests.
Ideally, a doctor will diagnose a person with liver fibrosis at an earlier stage when the condition is more treatable. However, because the condition doesn’t usually cause symptoms in earlier stages, doctors don’t usually diagnose the condition earlier.
The most significant complication of liver fibrosis can be liver cirrhosis, or severe scarring that makes the liver so damaged a person will become sick. Usually, this takes a long time to occur, such as over the course of one or two decades.
A person needs their liver to survive because the liver is responsible for filtering harmful substances in the blood and performing many other tasks that are important to the body.
Ultimately, if a person’s fibrosis progresses to cirrhosis and liver failure, they can have complications such as:
- ascites (severe buildup of fluid in the abdomen)
- hepatic encephalopathy (buildup of waste products that causes confusion)
- hepatorenal syndrome
- portal hypertension
- variceal bleeding
Each of these conditions can be deadly to a person with liver disease.
Liver cirrhosis is
Because liver fibrosis doesn’t always cause symptoms, this is hard to do. Sometimes doctors have to consider a person’s risk factors, such as being overweight or a heavy drinker, in diagnosing fibrosis and recommending treatments.