synonymhepatitis B(Hepatitis B) generally refers to chronic hepatitis B
Chronic hepatitis B, often referred to as "hepatitis B", is caused byhepatitis B virus(HBV) infection, persistent infection for more than 6 months, and different degrees ofinflammationNecrosis and/orhepatic fibrosis 。The susceptible population includes those who have not received hepatitis B vaccine, and those who have occupational exposure to the virusbloodOr body fluids, and people with HBV infection in their families.There are about 257 million chronic HBV infected people in the world, and about 887000 people die of HBV infection every year. The prevalence rate of HBsAg in China is 5%~6%, and there are about 70 million chronic HBV infected people, including about 20~30 million chronic hepatitis B patients.
The early symptoms of chronic hepatitis B patients mainly include recurrentweak、dizzy、AnorexiaAs the disease gets worse, it may be manifested asLiver palms、Spider nevus、HepatosplenomegalyEtc.Hepatitis B virus mainly passes through mother and baby, blood, damaged skin and mucosaSexual contact transmission。Both hepatitis B patients and HBV carriers can become the source of infection, but HBV does not pass through the respiratory tract and digestive tract, and rarely passes throughBloodsucking insect(mosquitoes, bedbugs, etc.).
For the treatment of chronic hepatitis B, the primary goal isAntiviral therapyMore comprehensive and individualized treatment methods are adopted, including adequate rest, reasonable diet and nutrition.According to the severity of the disease, the medication scheme of antiviral drugs should be timely adjusted and maintained.Antiviral drugs include nucleosides (acids)Antiviral drugs(e.g.:Ntratabin、TenofovirAnd interferon antiviral drugs (such as:interferon、Pegylated interferonEtc.).
The prevention of hepatitis B mainly depends on vaccination, and antibody detection and supplementary vaccine should be carried out in time for high-risk groups.The prevalence of hepatitis B in China has improved significantly, but the vaccine coverage and prevention work need to be further improved.
TCM disease name
Chronic hepatitis B
alias
hepatitis B
Visiting department
GI Medicine, Hepatology Department, Infection Department
Hepatitis B is caused by hepatitis B virusViral hepatitis, which can be divided into acuteChronic hepatitis BHowever, the former is now rare in clinical practice. People often say that "hepatitis B" usually refers to chronic hepatitis B.
Chronic hepatitis B is caused by infection with hepatitis B virus (HBV), but the onset and progress of the disease are closely related to the virus, infected persons, environment and other factors.
Chronic hepatitis B is caused by infection with hepatitis B virus (HBV), which has strong resistance to heat, low temperature, dry, ultraviolet and general concentrationdisinfectantIt can be tolerated by mother and baby, blood and blood products, damaged skin and mucosaSexual contact transmission。Hepatitis B patients and HBV carriers are the main sources of infection.
Some specific working environment and living habits may increase the risk of HBV infection, including unclean sex, sharing syringes and needles, close contact with blood and body fluids of hepatitis B patients, etc.However, it should be noted that HBV is not transmitted through the respiratory tract and digestive tractBloodsucking insectThe possibility of transmission (mosquitoes, bedbugs, etc.) is also very small.
Blood and body fluid transmission
A small amount of blood or body fluid contaminated with HBV can cause HBV infection after entering the human body.In recent years, China has implemented strict screening for blood donors, and the HBV infection caused by blood transfusion has declined significantly, but the transmission through blood and unsafe injection still plays an important role.
SurgeryHemodialysis、organ transplantSuch medical operations as sharing razors or toothbrushes, foot trimming, tattooing, ear ring piercing, etc. may lead to HBV transmission from damaged skin or mucosa.In addition, semenVaginal dischargeAnd milk contain HBV, so sexual contact can also transmit HBV.
Mother to child transmission
includeintrauterine infection Perinatal transmission and post delivery transmission.Intrauterine infection is mainly caused by the baby's infection through the placenta, and perinatal transmission is mainly caused by the baby's contact with the mother's bloodamniotic fluidOr vaginal secretions, which are transmitted after delivery mainly due to the close contact between mother and baby.
Cesarean section does not reduce the risk of mother to child transmission.In recent years, the application of hepatitis B vaccine combined with hepatitis B immunoglobulin has significantly reduced the mother to child transmission of hepatitis B, but there are still 5%~10% of newborns delivered by hepatitis B surface antigen (HBsAg) positive pregnant women who have immune failure.Once infected, more than 90% of newborns will develop into chronic HBV infection.
symptom
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Patients with chronic hepatitis B have mild symptoms in the early stage, which can cause fatigue, dizziness, loss of appetite and other symptoms repeatedly. With the aggravation of the disease, liver palmsSpider nevus、HepatosplenomegalyAnd other symptoms.When the disease is serious to decompensated cirrhosis or hepatocellular carcinoma, the corresponding symptoms of serious damage to liver function will also appear.
Typical symptoms
Chronic hepatitis B is defined as acute hepatitis B with a course of more than half a year, or hepatitis B symptoms, signs and liver function abnormalities occur again after the acute attack of the original hepatitis B.According to the severity of the disease, it can be divided into three degrees: mild, moderate and severe.
Mild hepatitis B
The patient's condition is mild and atypical, and symptoms such as fatigue, dizziness, anorexia, greasy anorexia, yellow urine, discomfort or slight tenderness in the liver area, and poor sleep may occur repeatedly.
The symptoms and signs of some patients are not obvious. If liver function test is performed, only one or two indicators are slightly abnormal. See the introduction of "Visit" for details.
Moderate hepatitis B
Symptoms range in severity from mild to severe.
Severe hepatitis B
There are obvious or persistent hepatitis symptoms, such as fatigue, lack of appetite, abdominal distension, yellow urine, loose stool, etc. The more specific symptoms are as follows:
Liver disease face: dark and lusterless, dark, rough and dry skin, even "bronze";
Liver palm: the palms of the hands are big and small, and the thenar is in sheet congestion, or red spots and patches appear, which turn white when pressed;
Spider nevus: a newly emerging "nevus" with a red dot in the center and capillaries arranged radially around it, which looks like a spider. The nevus disappears after pressing the central point;
Splenomegaly: The patient may feel the left costal distension or have no feeling at all, which is generally found by the doctor during examination.
The corresponding laboratory examination can show repeated or continuous increase of transaminase, decrease of albumin, and obvious increase of gamma globulin. See the introduction of "Visit" for details.
Accompanying symptoms
Some patients with chronic hepatitis B may be accompanied by mild fever.
Medical treatment
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Chronic hepatitis B is a chronic disease. If it is not controlled in time in the early stage, the disease will gradually progress, and may progress tocirrhosisorliver cancerTherefore, it is necessary to see a doctor in time and check regularly.
Visiting department
The common departments for patients with chronic hepatitis B areGI Medicine、Hepatology DepartmentAnd Department of Infectious Diseases.
Indication for medical treatment
If the course of disease is more than half a year or the date of onset is uncertain, the patient has fatigue, anorexia, greasy, liver discomfort and other symptoms, and has chest telangiectasia, or has spider like red nevus and other signs, they all need medical treatment.
It should be noted that the main reason for the occurrence of liver palms and spider nevi is that the inactivation of liver on estrogen (a female hormone) is weakened after the liver is damaged due to disease, and excessive estrogen makes the terminal branches of blood vessels dilate, which is manifested asLiver palmsorSpider nevus。However, spider nevus may also be caused by other reasons, which does not necessarily mean the occurrence of liver disease.
With the above manifestations, history of blood transfusion and unclean injection, close contact with chronic hepatitis B virus (HBV) infected persons, family members with HBV infected persons or mothers with positive HBsAg, etc., the possibility of hepatitis B should be considered and early treatment should be given.
Diagnostic process
When patients have symptoms such as fatigue, dizziness, loss of appetite, anorexia, yellow urine, and liver discomfort, they should first consider seeking the help of a physician from the Department of Gastroenterology or the Department of Hepatology.The doctor will inquire about the patient's medical history, make a simple physical examination, and observe whether there are liver palms, spider moles and other conditions.Then the doctor will recommend that the patient receive B ultrasound, liver function test and etiology test to judge the degree of liver function damage and whether there is cirrhosis.
Relevant inspection
Medical history and physical examination
Detailed medical history and physical examination are the diagnosishepatitisThe patients and their families need to be prepared to answer the following questions of the doctor before going to the hospital.
Basic information: including the patient's age, occupation, whether he has paid blood donation history, whether he has surgery or blood transfusion history, whether he smokes, whether he takes drugs, whether he drinks, whether he has multiple sexual partners, etc.
Time of onset: doctors need to know whether the patient is in the epidemic period of a certain disease at the time of onset to help make a clear diagnosis.
Imaging examination
Abdominal B-ultrasound
This is the most commonly used method for liver examination. It can help to interpret the size and shape of the liver and spleen, the important blood vessels in the liver, and whether there is a space occupying lesion in the liver. It is useful for identifying the causes of liver diseases, such asObstructive jaundice、Fatty liverAnd space occupying lesions in the liver, which has a high diagnostic value for cirrhosis.
CT and MRI
It is more sensitive to differentiate the nature of space occupying lesions.
Instantaneous elastography
Transient elastography (TE) can accurately identify mild liver fibrosis, progressive liver fibrosis or early cirrhosis, which is simple and repeatable.This examination is usually carried out under normal bilirubin, and it needs to be combined with patientsAlanine aminotransferaseThe diagnostic accuracy of liver fibrosis can be improved by using ALT level and other serological indicators.
Etiological examination
HBV surface antigen and antibody (HBsAg and anti HBs)
HBsAg can be positive two weeks after HBV infection, and the positive reaction indicates that there is HBV infection at present;
Anti HBs positive indicates that the body is immune to HBV, and a small number of patients still do not produceAnti HBs；
Both HBsAg and anti HBs are positive at the same time, which may occur in the mutant infection, and the anti HBs produced by the original HBV cannot clear the mutantHBsAg。
HBV e antigen and antibody (HBeAg and anti HBe)
The existence of HBeAg indicates that HBV replication is active and has strong infectivity;
The disappearance of HBeAg and the production of anti HBe are called "serological conversion". At this time, HBV is mostly in a low replication state, and the infectivity is reduced.
HBV core antigen and antibody (HBcAg and anti HBc)
Positive HBcAg indicates that HBV is in replication status and infectious;
High levels of anti HBc IgG often coexist with HBsAg, reflecting current infection;
Low levels of anti HBc IgG often coexist with anti HBs, indicating past infection.
HBV DNA
This indicator has different results according to different detection methods in different hospitals. It can be detected as a direct sign of virus replication and infectivity.
laboratory examination
Routine blood test and routine urine test
When liver function is abnormalred blood cell、white blood cell、plateletThe levels of red blood cells, white blood cells and platelets may change. When the disease progresses to cirrhosis with hypersplenism, the "three shortages" phenomenon of red blood cells, white blood cells and platelets may appear;Routine urine examination is helpful in the differential diagnosis of jaundice.
Blood biochemical examination
Liver function test
Alanine aminotransferase (ALT) is released into the blood when hepatocytes are injured, which is the most commonly used indicator to reflect the function of hepatocytes in clinical practice.chronic hepatitisandcirrhosisALT was slightly to moderately elevated or repeatedly abnormal.
The increase of aspartate aminotransferase (AST) reflects the serious injury of hepatocytes.
Chronic hepatitis above moderatecirrhosisThere may be a decrease in serum albumin, an increase in gamma globulin, and a decrease or even inversion of the white/globular (A/G) ratio.
Serum bilirubin may also be elevated in the presence of chronic icteric hepatitis or active cirrhosis.
other
When hepatocytes are severely damaged,blood sugar、Blood cholesterol(a kind of blood lipid index) can be significantly reduced.
Alpha fetoprotein (AFP)
AFP is a routine method for screening and early diagnosis of hepatocellular carcinoma.The abnormal increase of AFP indicates a suspicious hepatocellular carcinoma, but it will also increase in some benign diseases, such as hepatitis activity, or when liver diseases enter the recovery period and hepatocyte repair,AFPThere may also be different levels of increase, so the doctor will arrange several tests to dynamically observe the AFP level.
Histopathological examination of liver
The liver puncture under the guidance of B ultrasound and some tissues were taken for pathological examination. This is a traumatic examination, which is of great value for clear diagnosis, measurement of hepatitis activity, fibrosis and evaluation of curative effect.
Liver injury: there is a history of using liver injury drugs. After stopping the drug, the liver function can recover to normal, and HBV markers are negative.
Alcoholic liver disease: Have a long history of heavy drinking, and HBV markers are negative.
Autoimmune hepatitisIt mainly includes primary biliary cirrhosis and autoimmune liver disease. The diagnosis mainly depends on blood sampling to detect autoantibodies.
Fatty liver or acute fatty liver during pregnancy: Fatty liver mostly occurs in obese people, or secondary to hepatitis, which is easy to be diagnosed by B-ultrasound.Fatty liver during pregnancy usually starts with acute abdominal pain, or may be complicated with pancreatitis, reduced liver volume, and severe hypoglycemia and hypoproteinemia.
Wilson disease: an inherited disorder of copper metabolism, which can affect the liver and is characterized by severe liver damage such as cirrhosis,Serum copperandCeruloplasminThe yellow brown pigment ring with a width of 1-3 mm can be seen at the edge of the cornea of the patient.
treatment
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Hepatitis B is a viral hepatitis caused by the hepatitis B virus. It can be divided into acute and chronic hepatitis B according to the speed of disease development, but the former is now rare in clinical practice. People often say that "hepatitis B" usually refers to chronic hepatitis B.
Chronic hepatitis B needs to adopt a comprehensive and individualized treatment plan according to the specific situation of the patient, including adequate rest and reasonable diet and nutrition, regulating the psychological state, avoiding drinking and taking drugs that damage the liver, using appropriate drugs to improve and restore liver function, regulating body immunity, antiviral and anti hepatic fibrosis treatment.
General treatment
Patients with chronic hepatitis B should pay attention to rest, eat reasonably, establish a correct concept of disease, and establish confidence in cure.Those with obvious symptoms or serious illness should stay in bed.
Patients should abstain from alcohol and eat food with high protein, high vitamin and easy digestion, but it is not necessary to overemphasize high nutrition to avoid fatty liver.
Patients with severe hepatitis complicated with hepatic encephalopathy should also be given a low protein diet in strict accordance with the doctor's advice.
medication
Antiviral therapy
according toserumAfter comprehensively evaluating the risk of disease progression of the patient, the doctor will decide whether to give antiviral treatment and what kind of antiviral program to give, based on the HBV DNA level, blood alanine aminotransferase (ALT) and the severity of liver disease, combined with the patient's age, family history, accompanying diseases and other factors.
Nucleoside (acid) analogs (NAs)
These drugs are oral drugs, which play a therapeutic role by inhibiting virus replication. The course of treatment depends on the patient's condition.
HBeAgPositive chronic hepatitis B patients continue to use drugs for more than one year after HBeAg serum conversion;
Patients with HBeAg negative chronic hepatitis B should take medicine for at least 2 years;
Patients with cirrhosis need long-term medication.
When applying antiviral therapy with nucleoside (acid) analogues, we should pay close attention to the problem of drug resistance. Once drug resistance occurs, it may cause a sharp rebound of the disease, and a few may appear decompensation of liver function, acute liver failure, or even death. Therefore, we should choose drugs with "high drug resistance barrier", that is, drugs that are not easy to produce drug resistance.Therefore, the level of HBV DNA should be closely monitored during treatment, and once drug resistance is found, relevant detection and rescue treatment should be given as soon as possible.
At present, such drugs approved for marketing in China mainly includeLamivudine、Entecaway、Telbivudine、Adefovir dipivoxil、Tenofovir dipivoxilAnd propofol tenofovir. It is suggested that the newly treated patients should give priority to entecavir, tenofovir dipivoxil or propofol tenofovir to reduce the possibility of drug resistance.
The side effects of nucleoside (acid) analogues are also different. Doctors and patients need to pay attention to the following points:
A few of entecavir may suffer from lactic acid poisoning, nausea, vomiting and other discomfort. If discomfort occurs, it is necessary to consider the possibility of this adverse reaction according to the medication situation and arrange relevant blood tests;
Long term use of tenofovir dipivoxil and adefovir dipivoxil should be alert to renal insufficiency and low phosphorus osteopathy, and the renal function should be continuously and regularly tested;
Tepivudine happenedMyositisIn the case of rhabdomyolysis, attention should be paid to the development of severe muscle soreness after medication.
Interferons
It includes ordinary interferon - α (INF - α) and polyethylene glycol interferon - α (Peg IFN - α), which are injection drugs. For patients with antiviral indications, Peg IFN - α can be given priority to relatively young people (including adolescents), those who hope to have children in recent years, those who expect to complete treatment in a short time, and those who receive antiviral treatment for the first time.
Peg IFN - α only needs to be administered once a week, which is a long-term preparation and has better antiviral effect than ordinary INF - α.PegIFN - α commonly used in China mainly includes pegylated interferon α - 2a and pegylated interferon α - 2b, both of which are injected once a week for one year.
Contraindications to interferon therapy are as follows:
Serum bilirubin ≥ 2 times the upper limit of normal value;
Decompensated cirrhosis;
Have autoimmune disease;
There are important organ diseases (serious heart and kidney diseases, diabetes, hyperthyroidism or hypothyroidism, and psychoneurological abnormalities, etc.);
Pregnancy in progress or planned in the short term.
The common adverse reactions of interferon alpha are mainly influenza like syndrome, which are shown as follows:
Most of them have fever, chills, headache, muscle aches and weakness, etc;
A few people may have nausea and vomiting symptoms.
Taking antipyretic and analgesic drugs while injecting interferon, and other adverse reactions, such as bone marrow suppression (decreased blood cell level), neuropsychiatric symptoms, etc.
Anti fibrosis treatment
At present, anti fibrosis drugs are mainly antiviral drugs, and other proprietary Chinese medicines, such asanluohuaxian capsule 、fufang biejia ruangan tablet , Huoxue Huayu Capsule, etc. also has a certain effect.
surgical treatment
Chronic hepatitis B generally does not require surgical treatment.However, when the disease develops to end-stage cirrhosis and liver failure, it can be consideredLiver transplantation。During liver transplantation, surgeons will remove the damaged liver and replace it with a healthy one.Most of the transplanted livers came from deceased donors, but a few came from living donors who donated part of their livers.
For patients receiving liver transplantation due to HBV infection, lifelong use of antiviral drugs is required to prevent hepatitis B recurrence.
TCM treatment
Chinese herbal medicine plays a certain role in protecting the liver, reducing enzymes, reducing jaundice and combating liver fibrosis, but it is necessary to see a doctor in a regular hospital. You should not listen to folk prescriptions and go to an irregular hospital for TCM treatment.
Other treatments
For chronic hepatitis B patients with multiple complications caused by liver failure, a variety of support treatments and artificial liver support systems need to be given, which is of certain value for advanced severe hepatitis and liver failure, and can buy time to regenerate hepatocytes or prepare for liver transplantation.
Frontier treatment
In recent years, a variety of new drugs have entered the clinical trial stage, mainly including antiviral drugs directly acting on HBV, immunomodulatory drugs such as immune activators, therapeutic vaccines, etc., but they are still in preclinical, clinical trial phase I and phase II.
prognosis
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Hepatitis B is caused by hepatitis B virusViral hepatitisAccording to the development speed of the disease, it can be divided into acute hepatitis and chronic hepatitis B. However, the former is now rare in clinical practice. People often say "hepatitis B" usually refers to chronic hepatitis B.
The prognosis of mild chronic hepatitis is generally good;The prognosis of patients with severe chronic hepatitis is poor. About 80% of patients develop cirrhosis within five years, and some may become hepatocellular carcinoma.
With the prolongation of the course of disease, chronic hepatitis B will lead to intrahepatic complications such as cirrhosis and even liver cancer.The liver function of patients with chronic severe hepatitis is severely damaged, which may lead to infectionUpper gastrointestinal bleeding、hepatic encephalopathyandHepatorenal syndromeAnd other serious extrahepatic complications.
Intrahepatic complications
It mainly includes fatty liver, cirrhosis and hepatocellular carcinoma.HBV is closely related to hepatocellular carcinoma. The annual incidence of hepatocellular carcinoma in patients with HBV infection without cirrhosis is 0.5%~1.0%, and that in patients with cirrhosis is as high as 3%~6%.The prevention methods are timely medical treatment, standardized treatment and regular follow-up.
Extrahepatic complications
hepatic encephalopathy
Hepatic encephalopathy is a complication of chronic severe hepatitis and cirrhosis.It can show different degrees of mental and neurological symptoms.
Patients should maintain a low protein diet;Keep the stool unobstructed;Lactulose oral or enema, etc.
Upper gastrointestinal bleeding
Upper gastrointestinal bleeding is one of the common complications of chronic severe hepatitis and cirrhosis, which can be manifested as hematemesis or hematochezia.The reason is that the liver function is severely damaged, and the coagulation function is impaired. At the same time, cirrhosis of the liver leads to portal hypertension, extensive erosion of the esophageal and gastric mucosa, ulcers or varices.
Patients should avoid eating rough and hard food and taking antipyretic and analgesic drugs on an empty stomach to reduce the chance of damage to digestive tract mucosaRanitidine、CimetidineTo prevent bleeding, and proton pump inhibitors can be used for patients with peptic ulcer, such asomeprazoleEtc;Patients should also pay attention to proper supplementation of vitamin K and C.
Hepatorenal syndrome
Hepatorenal syndrome is a complication of chronic severe hepatitis, which is often the end stage manifestation of severe liver disease, often accompanied by severe infection, bleeding and other incentives.The main manifestations are oliguria or anuria, and electrolyte imbalance.
Patients should try not to take drugs that may lead to serious kidney damage, and avoid various factors that cause blood volume reduction.
prevention
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Control the source of infection
Patients with acute hepatitis B should be treated in isolation.Chronic hepatitis B patients and hepatitis B virus carriers shall not donate blood.Those infected with the disease cannot work in catering industry or childcare institutions.
Cut off transmission routes
Develop good personal hygiene habits and wash hands with soap and flowing water after contacting patients;Strictly implement the disinfection system;It is recommended to use disposable injection equipment, and HBsAg detection should be carried out for blood products to prevent iatrogenic transmission.
Protect vulnerable groups
Hepatitis B vaccination is the most effective way to prevent HBV infection.Susceptible persons can be vaccinated. The target of vaccination is mainly newborns. At the same time, high-risk groups such as those who have close contact with HBV infected persons, medical workers, homosexuals, and those who are engaged in childcare education, food processing, catering services, etc. should be vaccinated with hepatitis B vaccine, and their antibodies should be reviewed regularly.
Daily health care
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Those whose liver function (serum transaminase) is normal for more than 3 months can gradually engage in light work, and then gradually increase the workload until the original work is restored.
The immune function of chronic hepatitis B patients is low, and they are easily infected by various viruses, bacteria and other pathogenic factors, which will make the disease that has been static or tends to recover reactivate and worsen.Patients should be more careful about food, drink, daily living, personal hygiene, etc., should exercise properly, and should increase or decrease clothing according to the change of weather and temperature at any time to preventcoldAnd various infections.
Patients with chronic hepatitis B should eat high quality protein foods, pay attention to high fiber, high vitamin foods, selenium supplements, and low-fat, appropriate sugar diet.Avoid alcohol and eat less spicy and fried food;Avoid sweet food;It is forbidden to supplement blindly to avoid damaging the liver or increasing the burden on the liver.
Patients with chronic hepatitis B can have regular reexamination of liver function, hepatitis B, alpha fetoprotein and B-ultrasound.
Research progress
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In June 2022,Fujian Guangsheng Zhonglin Biotechnology Co., LtdgetThe First Hospital of Jilin UniversityThe review comments on the Phase I clinical trial and research of the global innovative drug GST-HG121 for hepatitis B treatment issued by the Ethics Committee indicate that the Phase I clinical trial scheme has been reviewed and confirmed, and is approved to enter the substantive development phase.GST-HG121 is a new class of anti hepatitis B virus drugs with a new target. It belongs to the first in class global leading project. It is a new type of small molecule hepatitis B surface antigen (HBsAg) inhibitor. By destabilizing and degrading HBV mRNA, it can block the expression of hepatitis B virus related antigen, which can rapidly reduce HBsAgHBeAg also has inhibitory effects to varying degrees, and has therapeutic benefits on multiple virological indicators. In the animal pharmacodynamics experiment, the effect of inhibiting HBsAg is obvious, and the preclinical toxicological study shows that it has good safety.The decline of HBsAg surface antigen and the realization of immune recovery are considered to be the key to challenge the clinical cure of hepatitis B.GST-HG121 is one of the important components of the "Peak Plan" for clinical treatment of hepatitis B in Guangshengtang.
