Bay Biosciences provides high quality, clinical grade, matched cryogenically preserved K2EDTA plasma, sera (serum) and peripheral blood mononuclear cells (PBMC), bio-fluid samples from liver fibrosis patients.

The K2EDTA plasma, sera (serum) and PBMC bio-fluid specimens are processed from liver fibrosis patient’s peripheral whole-blood using customized collection and processing protocols.


Liver Fibrosis Overview

Liver fibrosis occurs when the healthy tissue of the liver becomes scarred and therefore cannot work as well. This happens when repetitive or long-lasting injury or inflammation causes excessive amounts of scar tissue to build up in the organ.

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.

Unlike healthy liver cells, scar tissue cells cannot self-repair or otherwise function. As a result of this, fibrosis can reduce overall liver function and impair the organ’s ability to regenerate.

Scar tissue from fibrosis can also block or limit the flow of blood within the liver. This can starve and eventually kill healthy liver cells, creating more scar tissue in the process.

Treatment tends to involve clearing infections, making lifestyle changes, and taking certain medications. This can often reverse the damage of mild to moderate liver fibrosis.

If inflammation continues, possibly because a person has not received treatment, liver fibrosis can develop into more serious liver conditions.


Stages of Liver Fibrosis

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).

But first, a doctor will need to diagnose any underlying chronic liver disease, such as fatty liver disease or hepatitis. This can help identify the underlying causes of inflammation that lead to fibrosis, and better guide the staging and treatment process.

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.

A score of less than 1.3 may be considered low risk, while a Fib4 score of more than 3.25 could mean you’re at a high risk for liver fibrosis.

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 the following:


Signs and Symptoms of Liver Fibrosis

Patients with fibrosis are usually unaware that they have the disease. This is because it rarely causes any obvious symptoms.

However, within the liver, fibrosis can:

  • Reduce overall function, including the purifying of blood, storing of energy, and clearing of infections.
  • Limit the organ’s ability to regenerate.
  • Restrict blood flow within the organ.

People usually start to experience symptoms when fibrosis progresses to cirrhosis. These initial symptoms can vary, but some of the most common indicators of early cirrhosis include:

Following are common signs of more advanced cirrhosis:

  • Ascites, or abdominal bloating from a buildup fluid
  • A tendency to bruise or bleed easily.
  • Darkening of the urine
  • Edema or fluid retention in the lower legs, ankles, or feet
  • Increased sensitivity to medications and their side effects
  • Jaundice which is a yellowing of the skin and eyes
  • Problems with certain cognitive functions, such as memory, concentration, or sleeping. 
  • Very itchy skin


Causes of Liver Fibrosis

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:

The most common cause of liver fibrosis is nonalcoholic fatty liver disease (NAFLD), while the second is alcoholic liver disease due to long-term excesses of drinking alcohol.


Diagnosis of Liver Fibrosis

Your doctor will begin by asking you about your medical history and symptoms. You will also undergo a physical exam.

In order to diagnose liver 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.

Abdominal Ultrasound

This test uses sound waves to produce pictures to evaluate the size and shape of the liver, as well as blood flow through the liver. On ultrasound images, steatotic livers look brighter than normal livers, and cirrhotic livers (advanced fibrosis) look lumpy and shrunken.

CT Scan

Computerized Tomography (CT) Scan of the abdomen and pelvis that combines special x-ray equipment with sophisticated computers to produce multiple images or pictures of the inside of the body. On CT, steatotic livers look darker than normal livers. Cirrhotic livers look lumpy and shrunken.

Liver biopsy

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.

MRI Scan

Magnetic Resonance Imaging (MRI) uses a magnetic field and radio waves to produce detailed pictures of the liver. MRI is the most sensitive imaging test for steatosis, highly accurate even in mild steatosis. When a special technique is used, MRI can calculate the percentage of fat in the liver. More than 5-6% of fat in the liver is considered abnormal.

Transient Elastography

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.

Ultrasound

Ultrasound elastography is a special ultrasound technique to test for liver fibrosis. The movement of the liver caused by ultrasound wave is measured in the middle of the liver, and its stiffness (or elasticity) is calculated. Fibrotic livers are stiffer and moves to a greater degree compared to normal livers.

Nonsurgical Tests

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.


Treatment of Liver Fibrosis

The best way to treat liver fibrosis is to address the root cause. 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.

Successfully treating the cause of early to moderate liver fibrosis may reverse most, if not all, of the damage that the fibrosis has caused.

Nearly every chronic liver condition eventually results in fibrosis, as each condition causes lasting inflammation in the liver. This inflammation can lead to the formation of scar tissue, which is fibrous.

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:

  • Alcohol Liver Disease: abstinence from alcohol
  • Autoimmune Hepatitis: Immunosuppressive therap
  • Chronic Liver Disease: ACE inhibitors, such as benazepril, Lisinopril, and ramipril
  • Hepatitis C Virus: Direct action antivirals such as Epclusa, Harvoni, Mayvret, etc.
  • Non-Alcoholic Steatohepatitis: PPAR-alpha agonist

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 the following:

  • Anti-inflammatories: Examples include belapectin, cenicriviroc, and liraglutide
  • hepatic stellate cell (HSC) inhibitors: these drugs target various cytokines that may activate HSCs and contribute to fibrosis
  • Hepatocyte Apoptosis Inhibitors: these include emricasan, pentoxifylline, and selonsertib
  • Oxidative stress inhibitors: possibilities include methyl ferulic acid and losartan

If a patient’s liver fibrosis advances to where their liver is very scarred and is not working properly, the patients only definitive treatment is often to receive a liver transplant.


Complications of Liver Fibrosis

The most significant complication of liver fibrosis can be cirrhosis of the liver, or severe scarring that makes the liver so damaged that the patient will become sick. Usually, this takes a long time to occur, such as over the course of one or two decades.

An individual 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.

Eventually, if the patient’s fibrosis progresses to cirrhosis and liver failure, they can have the following complications:

  • Ascites (severe buildup of fluid in the abdomen)
  • Hepatic encephalopathy (buildup of waste products that causes confusion)
  • Hepatorenal syndrome
  • Portal hypertension
  • Variceal bleeding


Prognosis of Liver Fibrosis

Liver cirrhosis is one of the leading causes of death worldwide. Therefore, it’s important that the patient be diagnosed and treated for liver fibrosis as early as possible before it progresses to liver cirrhosis.

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.

Bay Biosciences is a global leader in providing researchers with high quality, clinical grade, fully characterized human tissue samples, bio-specimens, and human bio-fluid collections.

Samples available include cancer (tumor) tissue, cancer serum, cancer plasma, cancer, peripheral blood mononuclear cells (PBMC). and human tissue samples from most other therapeutic areas and diseases.

Bay Biosciences maintains and manages its own biorepository, the human tissue bank (biobank) consisting of thousands of diseased samples (specimens) and from normal healthy donors available in all formats and types.

Our biobank procures and stores fully consented, deidentified and institutional review boards (IRB) approved human tissue samples and matched controls.

All our human tissue collections, human specimens and human bio-fluids are provided with detailed, samples associated patient’s clinical data.

This critical patient’s clinical data includes information relating to their past and current disease, treatment history, lifestyle choices, biomarkers, and genetic information.

Patient’s data is extremely valuable for researchers and is used to help identify new effective treatments (drug discovery & development) in oncology, and other therapeutic areas and diseases.

Bay Biosciences banks wide variety of human tissue samples and biological samples, including cryogenically preserved at – 80°C.

Including fresh frozen tissue samples, tumor tissue samples, formalin-fixed paraffin-embedded (FFPE), tissue slides, with matching human bio-fluids, whole blood and blood-derived products such as serum, plasma and PBMC.

Bay Biosciences is a global leader in collecting and providing human tissue samples according to the specified requirements and customized, tailor-made collection protocols.

Please contact us anytime to discuss your special research projects and customized human tissue sample requirements.

Bay Biosciences provides human tissue samples (human specimens) from diseased and normal healthy donors which includes:

We can also procure most human bio-specimens, special collections and requests for human samples that are difficult to find. All our human tissue samples are procured through IRB-approved clinical protocols and procedures.

In addition to the standard processing protocols, Bay Biosciences can also provide human plasma, serum, and PBMC bio-fluid samples using custom processing protocols; you buy donor-specific collections in higher volumes and specified sample aliquots from us.

Bay Biosciences also provides human samples from normal healthy donors; volunteers, for controls and clinical research, contact us Now.

  • 日本のお客様は、ベイバイオサイエンスジャパンBay Biosciences Japanまたはhttp://baybiosciences-jp.com/contact/までご連絡ください。