Liver fibrosis What we need to know

Liver fibrosis is the result of the regenerative (restorative) process after liver damage. After prolonged inflammation or other injury, collagen and other connective tissue proteins are overproduced at the site of the injury, leading to the formation of a scar (fibrous) structure. Excess connective tissue disrupts tissue blood supply, impairs liver cell function, and further exacerbates the injury.

Causes of liver fibrosis

The main cause of fibrosis is chronic cellular damage, especially if there is an inflammatory component.

1. B or C viral hepatitis
2. Chronic alcohol consumption
3. Non-alcoholic liver diseases (NAFLDs) due to obesity and/or diabetes
4. autoimmune diseases,
5. Blockage of the bile duct
6. certain medications
7. Hereditary metabolic disorders

If the underlying cause of the fibrosis is reversible/curable, its severity may decrease. The degree of fibrosis is important here, that is, the severity of the damage.

Pathophysiology of liver fibrosis

The process of fibrosis begins in perivascular stellate cells. These cells begin to proliferate with excess synthesis of collagen and other structural glycoproteins, followed by the aggregation of damaged hepatocytes, macrophages (Kupffer cells), platelets, and leukocytes. The release of inflammatory mediators (platelet and connective tissue growth factors) begins. Thus, activation of stellate cells leads to excessive synthesis of cellular matrix and progression of fibrosis.

Myofibroblasts participate in the formation of connective tissue fibrous threads, which increases the resistance of the portal vein and the descending veins of the liver, and ultimately - portal hypertension (increased pressure in the portal vein of the liver). Thus, fibrosis contributes to liver cell ischemia and cell dysfunction.

Symptoms of liver fibrosis

Liver fibrosis is not characterized by symptoms. The presence of symptoms is related to the disease causing it. As fibrosis progresses, advanced cirrhosis and portal hypertension also cause symptoms such as:

Jaundice

Varicose bleeding from the esophagus

ascites

Portosystemic encephalopathy.

Cirrhosis can lead to potentially fatal liver failure.

Diagnosis of liver fibrosis

Based on clinical history, laboratory tests, biopsy data, and imaging studies. Algorithmic tests for assessing the risk of fibrosis are also actively used.

Liver fibrosis is suspected if a person has chronic liver diseases:

• Chronic viral hepatitis C
• Chronic hepatitis B
• Alcoholic liver disease
• Metabolic dysfunction – diabetes, metabolic syndrome and other disorders of carbohydrate metabolism
• or if the indicators of liver function tests are outside the normal range

In these cases, testing is done to detect fibrosis and, if fibrosis is present, to determine its severity (stage). Knowing the stage of fibrosis can guide medical decisions, as well as predicting chronic liver disease.

Noninvasive laboratory tests are the standard for diagnosing liver fibrosis, along with imaging and biopsy methods.

Fibromax test

(FibroMax) is a study developed by the company BioPredictive, which combines 5 different non-invasive tests: FibroTest, ActiTest, SteatoTest, NashTest and AshTest.

The Fibromax test is based on an algorithm for evaluating liver damage, which combines the data of serum biochemical markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, total bilirubin, GGT, ALT, AST, basal blood glucose, cholesterol, triglycerides) with the patient's age, sex, weight and with height

Accordingly:

• Fibrotest measures the degree of fibrosis (METAVIR scale F0-F4)
• act-test measures necrotic-inflammatory activity in patients with chronic hepatitis B and C (METAVIR scale grade A0-A3)
• Steatotest evaluates liver steatosis or the degree of fatness, which is often the basis of ALT and GGT increase (METAVIR scale grade S0-S3)
• NASH-test Assesses the degree of non-alcoholic steato-hepatitis in patients with obesity and dyslipidemia (3 degrees of the Kleiner classification scale)
• ASH-test measures the degree of alcoholic liver damage (H0-H3 degree)

Fibro-test It was initially developed for patients with chronic hepatitis C, but later it was tested for the assessment of hepatitis B, D, HIV co-infections, alcoholic liver damage and non-alcoholic steatohepatitis. Fibrotest – evaluates the degree of liver fibrosis, according to the indicators of 6 serum markers:

• alpha-2-macroglobulin
• Haptoglobin
• Apolipoprotein A1
• Gamma-glutamyl-transpeptidase (GGT)
• Total bilirubin
• Alanine amino transferase (ALT)

act-test It is the only validated laboratory test for necrotizing-inflammatory activity and is used in patients with chronic hepatitis B and C. Includes the following serum markers:

• alpha-2-macroglobulin
• Haptoglobin
• Apolipoprotein A1
• Gamma-glutamyl-transpeptidase (GGT)
• Total bilirubin
• Alanine amino transferase (ALT)

Steato-test It evaluates the degree of steatosis in patients with high metabolic risk: in excessive alcohol users, in chronic carriers of hepatitis B and C. The steatotest assesses the risk of cardiovascular disease associated with steatosis. Moicavs Sratis Semdeg markerebs:

• alpha-2-macroglobulin
• Haptoglobin
• Apolipoprotein A1
• Gamma-glutamyl-transpeptidase (GGT)
• Total bilirubin
• Alanine amino transferase (ALT)

NASH-test Represents the possibility of predicting non-alcoholic liver damage. The combination of the NASH-test and the fibro test provides information to assess the patient's metabolic risk based on the values ​​of 10 serum markers:

• Gamma-glutamyltransferase (GGT)
• Total bilirubin
• alpha-2-macroglobulin
• Apolipoprotein A1
• Haptoglobin
• alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Total cholesterol
• Triglycerides
• fasting glucose

ASH-test It is used to diagnose acute alcoholic steatohepatitis. An alternative diagnostic method of liver biopsy in patients with alcoholic liver disease is the analysis of 5 serum markers:

• alanine aminotransferase (ALT)
• Aspartate aminotransferase (AST)
• Alkaline phosphatase (ALP)
• Gamma-glutamyltransferase (GGT)
• Bilirubin

The combination of these tests provides an assessment of the degree of liver fibrosis within one study:

• Fatty liver (steatotest)
• In case of non-alcoholic steatohepatitis (NASH-test)
• in alcoholic steatohepatitis (ASH-test)

The study is an alternative to liver biopsy and its clinical value has been proven by studies.

Preparation of the patient: Research is carried out without fail!

Material for examination: Venous blood

Interpretation of results:

In accordance with the indicators of serum markers, indicators of necrotic-inflammatory activity of liver fibrosis, steatosis, non-alcoholic steatohepatitis and alcoholic steatohepatitis are generated.

Fibrotest

F0 - Absence of fibrosis

F1 - Portal (portal vein) fibrosis

F2 - Progressive fibrosis with rare septal-like ("bridges") formations

F3 - Fibrosis with multiple septum-like ("bridges") formation

F4 - Cirrhosis

Actitest

Degrees of necrotic-inflammatory activity:

A0 - Absence of necrotic-inflammatory activity

A1 - minimal necrotic-inflammatory activity

A2 - moderate necrotic-inflammatory activity

A3 - Severe necrotic-inflammatory activity

Steato-test

S0 - absence of steatosis

S1 – Minimal steatosis/fatty (<5% of liver cells)

S2 - Moderate steatosis/fatness (6-32% of liver cells)

S3 - Severe steatosis/fatness (33-100% of liver cells)

Nash-test

N0 - Absence of non-alcoholic steatohepatitis

N1 - Borderline condition of non-alcoholic steatohepatitis

N2 - Presence of non-alcoholic steatohepatitis

Ash-test

H0 - Absence of alcoholic steatohepatitis

H1 – Minimal alcoholic steatohepatitis

H2 - Moderate alcoholic steatohepatitis

H3 - Severe alcoholic steatohepatitis

When is the FIBROMAX study not conducted?

Test Fibromax is not recommended for patients who are prescribed:

• Acute hepatitis (characterized by a dramatic increase in ALT)
• Acute hemolysis (the level of haptoglobin decreases)
• Acute inflammatory conditions (alpha-2-macroglobulin increases)
• Extrahepatic cholestasis (bile duct obstruction)

In patients with acute hemolysis, i.e. Gilbert's syndrome, it is necessary to consult a specialist to interpret the results.

Test Fibromax is not used in patients with liver transplantation.

Important information!

• Self-healing, acute liver injuries (eg, acute viral hepatitis A), even when severe, do not cause fibrosis!
• The most common causes of liver fibrosis are hepatitis B and C, metabolic steatohepatitis, and alcoholic liver damage.
• Fibrosis does not cause symptoms. Symptoms are characteristic of fibrosis-causing diseases, or cirrhosis - the progression of fibrosis.
• Liver biopsy, although imperfect, is the gold standard for diagnostics, although it is increasingly being replaced by non-invasive alternative tests.
• It is necessary to treat the cause of fibrosis

Treatment of liver fibrosis

Treatment of liver fibrosis and reversal of fibrosis is a very slow and sometimes impossible process, depending on the stage of the disease and the degree of damage.

Antifibrotic drugs, herbal and chemical drugs, adequate diet and healthy lifestyle allow to delay the development of fibrosis complication - cirrhosis.

"Synevo" offers laboratory tests for diagnosing and monitoring liver fibrosis:

The time for issuing research results is not absolute, it can change taking into account various factors

! If the information you are interested in is not enough, please contact us on the hotline - 0322800111, or write to us on our Facebook page, or info@synevo.ge

n.manjaparashvili@synevo.ge