liver fibrosis



Overview of Liver Fibrosis

What is Liver Fibrosis?

Definition

Liver fibrosis refers to the diffuse overdeposition and abnormal distribution of extracellular matrix (i.e. collagen, glycoproteins and proteoglycans, etc.), which is the liver’s pathologic repair response to chronic injury.

It is a key step in the development of various chronic liver diseases to cirrhosis and an important link that affects the prognosis of chronic liver diseases.

Further development of liver fibrosis can cause structural disorder of liver lobules, nodular regeneration of hepatocytes, formation of pseudolobular structure, i.e., cirrhosis, which can be seen clinically as decompensation of liver function and manifestation of portal hypertension.

Liver fibrosis is histologically reversible.

Staging

Commonly used staging methods for liver fibrosis are Scheuer, METAVIR, and the Ishak scoring system.

The Ishak scoring system classifies the assessment of liver fibrosis into stages 0 to 6, and is currently the most sensitive and commonly used method for assessing changes in liver fibrosis internationally.

The Ishak scoring system stages liver fibrosis as follows:

Stage I: no fiber intervals;

Stage II: 1 fiber interval;

Stage III: 2 to 3 fibrous septa;

Stage IV: 4 fibrous septa;

Stage V: 4 or more fibrous septa + 1~3 clear pseudolobules;

Stage VI: more than 3 or more pseudolobules.

Pathogenesis

There is no report on the prevalence of liver fibrosis in China.

Compared with women of the same age, men are more likely to develop liver fibrosis.

Liver fibrosis occurs more often in people above middle age, and the peak age of onset is 50-60 years old.

Questions you may have

What medications are taken for liver fibrosis?

The main medications used to treat liver fibrosis are antiviral drugs and antifibrotic drugs.

Antiviral therapy drugs include interferon and nucleoside (acid) analogs (entecavir, lamivudine, etc.).

Anti-fibrotic therapeutic drugs include silymarin, polyene phosphatidylcholine, and glycyrrhizic acid-based preparations.

Silymarin has the ability to promote hepatocyte regeneration; polyenophosphatidylcholine can accelerate membrane regeneration and stabilization; glycyrrhetinic acid-based preparations can effectively reduce hepatocyte inflammatory response.

What are the foods to avoid in liver fibrosis?

Liver fibrosis should pay attention to avoiding alcohol, avoiding too greasy and stimulating food, hepatotoxic drugs and so on.

Alcohol should be avoided in daily diet, because alcohol is harmful to the liver, and drinking alcohol will aggravate the patient’s condition. Avoid oily, spicy and stimulating foods, which are not easy to digest and will increase the metabolic burden of the liver.

More intake of food rich in vitamins, high quality protein, supplemental nutrition. You need to pay attention to eating small meals and chewing slowly.

Is liver hardness of 9.7 liver fibrosis?

Liver stiffness of 9.7kPa usually refers to the liver stiffness value of transient elastography, which is considered to be significant liver fibrosis.

Transient elastography is used to determine the degree of liver fibrosis by the degree of rebound of ultrasound waves. It is a non-invasive technique to diagnose liver fibrosis with the advantages of high accuracy and non-invasiveness.

Generally, when bilirubin is normal and ghrelin is less than 5 times the upper limit, liver stiffness value ≥17kPa is considered cirrhosis, and ≥9.4 is considered to consider significant liver fibrosis. However, pathologic examination remains the gold standard for the diagnosis of liver fibrosis.

Etiology

Causes

Chronic liver injury from any cause can lead to liver fibrosis, including viral infections, alcohol, drugs or toxins, autoimmune diseases, metabolic disorders, circulatory disorders, cholestasis, parasitic infections, and malnutrition.

Viral infections

Viral hepatitis B, C, D, and some E, if uncontrolled, may become chronic, causing the virus to continue to attack liver cells, which in the long run can lead to liver fibrosis.

Alcohol

Alcohol can cause liver cell damage. If a large amount of alcohol is consumed over a long period of time, liver fibrosis will occur as the liver is in a constant process of damage repair.

Industrial poisons or drugs

Prolonged or repeated exposure to arsenic-containing insecticides, carbon tetrachloride, yellow phosphorus, chloroform, etc., or long-term use of drugs with hepatotoxicity such as bisacodyl, isoniazid, octocrylene, tetracycline, methotrexate, methyldopa, etc., can also lead to liver fibrosis.

Autoimmune disease

Autoimmune liver disease or various rheumatic immune diseases involving the liver can cause liver fibrosis.

Metabolic disorders

Diseases such as hemochromatosis and hepatomegaly (Wilson’s disease) can cause certain metabolites to be unable to be removed in a timely manner and deposited in the liver causing damage to the liver cells, which can lead to liver fibrosis in the long run.

Obstruction of hepatic venous return

Chronic congestive heart failure and chronic constrictive pericarditis can cause long-term stagnation and hypoxia in the liver, resulting in hepatocellular necrosis and fibrosis.

Biliary stasis

The high concentration of bilirubin in the case of extrahepatic bile duct obstruction or intrahepatic biliary stasis has a damaging effect on liver cells, and repeated intrahepatic bile duct inflammation and infection and other stimuli can induce hepatic fibrosis.

Parasitic infection

After infection with Schistosoma haematobium, the eggs of the worm stimulate the proliferation of connective tissue in the confluent area, which becomes schistosomiasis hepatic fibrosis.

Malnutrition

Malnutrition, especially protein malnutrition, is also a cause of liver fibrosis.

Pathogenesis

Liver fibrosis is an abnormal proliferation of fibrous connective tissue in the liver, mostly as a consequence of persistent liver injury.

Just as scarring occurs when the skin is injured, liver fibrosis occurs when the normal liver tissue is replaced by “scarring” as a result of sustained liver injury.

Liver fibrosis is an inevitable stage in the progression from chronic liver disease or other factors that cause liver damage to cirrhosis. The gold standard for the diagnosis of liver fibrosis is a liver biopsy.

Symptoms

Symptoms of liver fibrosis are closely related to the degree of fibrosis. Generally speaking, early stage of liver fibrosis can be asymptomatic, and some of them appear a series of symptoms after the burden of liver increases.

Systemic Symptoms

Easy fatigue.

Digestive tract symptoms

Hidden pain in the right upper abdomen.

Loss of appetite and aversion to oil.

Some may also experience nausea, vomiting, abdominal distension, constipation or diarrhea, acid reflux and belching.

Skin symptoms

Some may develop spider nevi. Spider nevi are spider-like dilations of capillaries.

In severe cases, liver palms may appear, which are mainly characterized by flaky congestion of the skin on the palms of the hands at the greater and lesser pectineus muscles, with discoloration on pressure.

There are purple spots or scattered bleeding spots on the skin and mucous membranes.

Oral as well as ear, nose and throat symptoms

Some may also experience bleeding gums and nosebleeds.

Female-specific symptoms

Increased menstrual flow.

Where to see a doctor

Department of Medicine

Gastroenterology

If you experience symptoms such as vague pain in the upper right abdomen, abdominal distension, loss of appetite, fatigue, yellowing of the skin and sclera, or if your routine physical examination reveals signs of hepatic fibrosis, we recommend that you consult a doctor promptly.

Preparation

Consultation: Registration, Preparation of Information, Frequently Asked Questions

Tips for seeking medical treatment

Before seeking medical treatment, try to record the symptoms you have experienced and their duration for the doctor’s reference.

Preparation List

Symptom list

Pay particular attention to the time of onset of symptoms, special manifestations, etc.

What is the discomfort?

Any abdominal pain or discomfort in the abdomen?

Is there any fatigue?

Is there any bloating and what conditions relieve it?

What is your recent appetite?

Medical History Checklist

Any previous liver or gallbladder disease, such as diseases of the hepatobiliary system, diabetes, dyslipidemia, etc.?

Do you drink alcohol? How much do you drink per day? How long have you been drinking?

Any history of drug allergy, etc.?

Have you ever taken any medication?

Checklist

Test results for the past six months, which you can bring with you to the doctor’s office

Liver Function, Blood Lipid

Coagulation function

Virology

Immunologic antibody test

Abdominal ultrasound, abdominal CT, abdominal MRI, liver transient elastography

Liver puncture, pathology report

Medication List

Medications used in the last 3 months, if available in boxes or packages, bring them with you to the doctor’s office

Hepatotoxic drugs: isoniazid, tetracycline, methotrexate, methyldopa

Industrial poisons and pesticides: arsenic-containing pesticides, carbon tetrachloride, yellow phosphorus, chloroform

Diagnosis

Disease Diagnosis

History of illness

History of viral hepatitis and biliary tract disease in self and or family members, alcoholism, drugs such as isoniazid, prolonged or repeated exposure to toxic substances, etc.

Clinical manifestations

Fatigue and weakness, loss of appetite, anorexia, even nausea and vomiting, abdominal distension, constipation or diarrhea, acid reflux, belching, and in severe cases, vague pain in the liver area and bleeding gums.

Laboratory Tests

Liver function tests

By testing alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, serum albumin, and bilirubin levels, as well as monitoring liver function, you can find out if the liver is in normal working order.

Coagulation Function

The liver is the site of synthesis of many types of prothrombin, so monitoring coagulation function can determine whether the liver is working properly.

Pathogenetic Tests

Pathogenetic tests help determine whether viral hepatitis is present. It can provide options for follow-up treatment.

Fibrosis test

An increase in preclinical collagen type III peptide (PIIIP) values, prolyl hydroxylase (PHO), monoamine oxidase (MAO), serum laminin (LM), and hyaluronic acid, collagen, and laminin suggests the presence of fibrosis in the liver.

However, the specificity of this test is low and it is rarely used in the diagnosis of liver fibrosis.

Immunologic tests

Positive antinuclear antibodies, antimitochondrial antibodies, anti-smooth muscle antibodies, and anti-hepatic lipoprotein membrane antibodies suggest autoimmune liver disease.

Serum copper blue protein test

Significant in ruling out hepatomegaly (Wilson’s disease).

Imaging

Ultrasonography

B-mode and color Doppler ultrasonography can detect some structural changes in the liver, which is of diagnostic value for liver fibrosis.

However, it is limited to the diagnosis of liver fibrosis, cirrhosis and liver occupying lesions.

CT examination

It can find the changes of liver proportion, density and so on, which is helpful for the differential diagnosis of liver fibrosis and hepatocellular carcinoma.

Transient elastography

Evaluating the degree of liver fibrosis by measuring the elasticity of the liver is one of the main tests for diagnosing liver fibrosis in recent years.

Instantaneous elastography is a non-invasive technique for diagnosing liver fibrosis, which has the advantages of high accuracy and non-invasiveness.

Pathologic examination

Pathological examination is the “gold standard” for the diagnosis of liver fibrosis, and puncture biopsy is very important for the confirmation of liver fibrosis.

However, there are drawbacks: firstly, it is an invasive test, which may cause complications; secondly, liver fibrosis may be unevenly distributed, and the sampling may not reach the fibrotic areas, which may lead to misdiagnosis.

Refresh

Differential Diagnosis

Cirrhosis

Similarity: symptoms such as fatigue, loss of appetite, anorexia, nausea and vomiting, abdominal distension, constipation or diarrhea, acid reflux, belching, vague pain in the liver area and bleeding gums may occur.

Differences: Cirrhosis is the end stage after the progression of liver fibrosis, and more complications will occur, such as gastrointestinal bleeding caused by portal hypertension, and personality changes and confusion caused by hepatic encephalopathy. It needs to be differentiated by imaging and pathologic examination.

Treatment

The treatment of liver fibrosis mainly includes alcohol cessation, antiviral therapy and other treatments targeting the cause of the disease, as well as antifibrotic therapy targeting liver fibrosis.

General treatment

Diet

The diet for liver fibrosis should be light, with plenty of fresh vegetables and fruits. Avoid overeating and eat small, frequent meals.

Weight control

Reasonable weight control for abdominal obese people will help liver fibrosis recovery, so they should exercise regularly to avoid obesity, but the exercise should be gradual and not too strenuous.

Avoid taking health products and non-medical drugs

Drugs and health supplements generally need to be metabolized by the liver, so overdosed health supplements or unnecessary drugs will increase the burden on the liver and should be avoided by liver fibrosis patients.

Alcohol cessation

Alcohol metabolism is also in the liver, liver fibrosis should avoid drinking alcohol to increase the burden on the liver.

Medication

Antiviral drugs and antifibrotic drugs can be used for treatment as prescribed by the doctor, and the dosage should not be adjusted or discontinued on one’s own.

Antiviral therapy

Antiviral therapy has the potential to reverse liver fibrosis.

Therapeutic drugs include interferon (regular interferon, long-acting interferon) and nucleoside (acid) analogs (entecavir, tenofovir disoproxil, adefovir, telbivudine, lamivudine, etc.).

Anti-fibrotic therapy

There are no clinically effective drugs to reverse fibrosis, so there is no such thing as a specific drug. However, the following hepatoprotective drugs can, to a certain extent, anti-fibrosis and improve the effect of liver function.

Silymarin

Silymarin is an effective bioactive ingredient extracted from silymarin, a plant of the Asteraceae family. Pharmacological studies have shown that silymarin has antioxidant activity, thus preventing further damage to liver cells.

It has a certain degree of ability to promote liver cell regeneration. Therefore it can be used in the treatment of liver fibrosis.

Polyene phosphatidylcholine

Pharmacological studies have shown that polyenophosphatidylcholine can accelerate membrane regeneration and stabilization, inhibit lipid peroxidation, and thus inhibit collagen synthesis, which is commonly known as anti-fibrosis.

Polyenophosphatidylcholine also aids in the improvement of toxic liver injury, as well as relieving loss of appetite and right upper abdominal pressure.

Glycyrrhizic acid-based preparations

This kind of drug has certain anti-inflammatory effect, can effectively reduce the inflammatory reaction of hepatocytes, improve fibrosis and other effects.

Representative drugs include magnesium isoglycyrrhizinate and so on.

Chinese medicine treatment

Chinese medicine treatment for liver fibrosis requires evidence-based treatment. It is necessary to go to the regular Chinese medicine hospital for evidence-based treatment.

Prognosis

Cure

Mild hepatic fibrosis is reversible, generally after active and regular treatment, the progression of fibrosis can be terminated in time, which can be cured and avoid the occurrence of cirrhosis.

Harmfulness

Liver fibrosis itself is not harmful, but if it is not treated actively and progresses to cirrhosis or even liver cancer, the consequences will be more serious.

Daily life

Daily life

In daily life, liver fibrosis requires active treatment of the primary disease, simple medication, moderate exercise, dietary regulation and psychological adjustment.

Active treatment of primary diseases

Various factors lead to liver damage, in the active inflammation period, we should pay attention to liver protection and anti-inflammatory treatment, and hospitalization if necessary. Don’t take it lightly just because the symptoms are mild or no symptoms, and control the inflammation in the shortest possible time to avoid aggravation of liver fibrosis.

Keep medication simple

Blindly abusing too many general drugs will increase the burden on the liver, which is not conducive to liver recovery. Drugs that are harmful to the liver, such as isoniazid, should be used with caution or avoided.

Moderate exercise

During the period of disease stabilization, you can do some easy work or appropriate activities, and carry out beneficial physical exercise, such as walking, doing health exercises, playing tai chi, practicing qigong, etc. The amount of activity should be enough to not feel fatigue. The amount of activity should not feel fatigue.

Dietary regulation

Consume more diets rich in vitamins and high quality protein to supplement nutrition and strengthen resistance. Pay attention to eating small meals and chewing slowly.

Mental regulation

The liver has a very close relationship with mental emotions. Poor mood, depression, anger and excitement can affect liver function and accelerate the development of lesions. Maintaining a cheerful mood, cheering up the spirit and eliminating the burden of thoughts are beneficial to the improvement of the condition.

Follow-up

Follow the doctor’s instructions for regular follow-up. If symptoms do not subside or even worsen during treatment, or if new symptoms appear, it is necessary to go to the hospital in time.

Prevention

Prevent infection: Avoid unnecessary blood transfusions, injections, ear piercings, tattoos, sharing toothbrushes or razors with others, and avoiding contact with instruments that may be contaminated with blood.

Maintain good mood.

Pay attention to dietary hygiene.

Exercise moderately.

Quit smoking and drinking.

Eat a healthy diet and avoid excessively oily and stimulating food.

Do not abuse drugs.