What Is Involved in Chronic Hepatitis Treatment?

Chronic hepatitis is a collective term for a group of diseases. The clinical characteristics, treatment methods, and prognostic outcomes may be different due to different causes, but they also share common characteristics: liver function fluctuates repeatedly and persists; Necrosis and fibrous connective tissue hyperplasia, showing chronic fibrosis. (3) The final stages of disease development are cirrhosis. Both need liver protection and antifibrotic treatment.

Wang Xiaomei	(Chief physician)	Liver Disease Center of Beijing Ditan Hospital
Xing Huichun	(Chief physician)	Liver Disease Center of Beijing Ditan Hospital
Cheng Danying	(Attending physician)	Liver Disease Center of Beijing Ditan Hospital

Chronic hepatitis refers to liver necrosis and inflammation caused by different causes, which last at least 6 months, such as infection with hepatitis virus (HBV, HCV), long-term drinking, taking hepatotoxic drugs, etc. Corresponding symptoms, signs, and abnormal liver biochemical examination may be clinically observed, or there may be no obvious clinical symptoms, but only necrosis and inflammation of liver tissue. The course of the disease is fluctuating or continuous, and some patients may progress to cirrhosis without proper treatment.

Western Medicine Name: Chronic hepatitis
Disease site: liver

The main symptoms: Early symptoms are mild, with nausea, bloating, jaundice, etc.
Main cause: Hepatitis virus infection, long-term drinking, taking hepatotoxic drugs, etc.

Introduction to chronic hepatitis diseases

Causes and classification of chronic hepatitis

According to the cause, chronic hepatitis can be classified as follows:

chronic hepatitis B (chronic hepatitis B,

chronic hepatitis C (CHC)

autoimmune hepatitis (AIH)

Alcoholic liver disease (ALD)

Drug-induced liver injury: also known as drug-induced liver injury (DILI)

According to the severity of the disease, chronic hepatitis can be divided into mild, moderate, severe and chronic severe hepatitis

Chronic hepatitis pathophysiology

The common feature of chronic hepatitis is that different degrees of liver tissue necrosis and inflammatory response, followed by liver fibrosis, can eventually develop into cirrhosis. At present, the assessment of chronic liver damage is still mainly based on liver biopsy, which is commonly referred to as liver puncture. The pathological changes of chronic hepatitis are divided into grades of necrosis (G) and stages of fibrosis (S). Grade of inflammation activity (Grade, G) is grade 4 (G1 ~ 4). G1 is mild activity, G2 mild activity, G3 moderate activity, G4 severe activity. G1-2 is mild liver inflammation activity, G3- 4 indicates severe liver necrosis; the stage of fibrosis (Stage, S) is 4 (S1 ~ 4). Stage S1: fibrosis of the hepatic lobules in the manifold area, and the lesions are lighter; stage S4 is cirrhosis, and the lesions are more severe. ^[1]

Pathogenesis of chronic hepatitis

The pathogenesis of various types of chronic hepatitis is different, as outlined below:

1) Chronic hepatitis B (CHB): It is generally believed that HBV does not directly damage liver cells, but causes damage and destruction of liver cells through the host immune response and response, leading to corresponding clinical manifestations. Due to the different immune responses of the host, including genetic and metabolic differences among individuals, the clinical manifestations and counters caused by HBV infection are also different. The immune tolerance period is basically no immune response, high viral load in the blood, but basically no liver damage. Immune activator is the emergence of partial immune response. Liver injury leads to active hepatitis. The viral load is reduced, but the immune response is not complete, so the virus cannot be eliminated. If the immune response reaches a dynamic balance with viral replication, it is manifested by reduced hepatitis activity and decreased viral load. If mutations in the pre-C region and basic core promoter (BCP) of the viral gene occur, HBeAg-negative chronic hepatitis B appears and HBVDNA is positive.

2) Chronic hepatitis C (CHC): The pathogenesis of hepatitis C is very complex. The interaction of the virus and the human immune system determines the occurrence, development and outcome of the disease.

3) Autoimmune hepatitis (AIH): The basic pathogenesis is that the body's tolerance to self-antigens is broken, which stimulates the immune response to self-antigens, and immune cells attack their corresponding target antigens, causing cell apoptosis and necrosis. And inflammation.

4) Chronic Alcoholic Liver Disease (ALD): The occurrence and development of ALD are related to at least the following mechanisms: Oxidative stress: a large number of reactive oxygen species (ROS) produced during the metabolism of ethanol, toxic reactions of oxygen free radicals, causing the body to occur Oxidative stress is one of the key mechanisms for the development of alcoholic liver disease. Toxic effects of acetaldehyde: acetaldehyde is an intermediate product of ethanol metabolism and is one of the main factors causing chronic progressive liver damage. Endotoxin: Intestinal endotoxin production and absorption are increased in patients with ALD, and the liver is insufficient to clear endotoxins, resulting in intestinal endotoxemia, which aggravates liver inflammation damage through a variety of mechanisms. Toxicity of ethanol: During the metabolism of ethanol, a large amount of NAD + is consumed, which causes a series of biochemical metabolic disorders, induces hypoglycemia, causes lactic acidosis, causes fatty acid accumulation and leads to fatty liver; ethanol also interferes with protein and nucleic acid metabolism. In addition, long-term intake of ethanol can also directly or indirectly cause malnutrition. In short, ALD caused by excessive drinking is the result of sequential or superimposed mechanisms. These mechanisms are causal, induce, and promote each other, forming a vicious circle.

5) DILI for drug-induced liver disease: hepatotoxicity of drugs can be divided into predictable and non-predictable hepatotoxicity; the former liver toxicity is related to the dosage of the drug and has a dose-effect relationship, which can be replicated in animal experiments; the latter It is related to the specificity of the body, there is no obvious dose-response relationship, it is difficult to predict and it is not easy to replicate in animal experiments. The vast majority of clinical DILI is the latter type. The pathogenesis of DILI is the drug itself or its toxic metabolites, which directly affect liver cells or cause lesions through immune mechanisms. The immune mechanism is that a drug acts as a hapten to form a new antigen in the body. T antigens and B cells are stimulated to respond by antigen-presenting cells, leading to immune damage, mainly immune responses. ^[2-4]

Clinical manifestations of chronic hepatitis

Chronic hepatitis is mild and moderate: the typical early symptoms of typical chronic hepatitis are mild and lack specificity, fluctuating intermittently, and even without symptoms for many years. The most common are fatigue and stomach upset, which can be easily overlooked and mistaken for gastric disease. Patients with occult cirrhosis are often seen clinically. Before the onset of cirrhosis, they did not feel obvious discomfort or routine. The physical examination gradually progressed to cirrhosis without knowing it; occasionally, patients developed nausea, abdominal distension, jaundice, and dark urine, but the severity of chronic hepatitis could not be judged based on the symptoms.

Severe chronic hepatitis and chronic severe hepatitis: When the patient's urine color deepens progressively, the skin sclera yellow stains progressively deepen, and the decline in fatigue and appetite is more and more obvious, which indicates that the condition is worsening, and the occurrence of chronic severe hepatitis is particularly important. The manifestations of liver failure can be manifested as high fatigue, high abdominal distension, high jaundice, and high appetite loss, hypoproteinemia, ascites, pleural effusion, abdominal infection, decreased coagulation function, upper gastrointestinal bleeding, hepatic encephalopathy, etc. Mortality is high and requires active treatment. ^[5]

Chronic hepatitis complications

Complications of chronic hepatitis, such as chronic cholecystitis, hepatic diabetes, and hepatitis B-related nephropathy, are more common, which can control the stability of liver disease and help stabilize the complications. On the basis of chronic hepatitis, when there are incentives such as patients being overworked, drinking a lot of alcohol, or overlapping infection with other hepatitis viruses, the condition can suddenly worsen and develop into chronic severe hepatitis. In addition, if chronic hepatitis progresses, it can progress to cirrhosis. Chronic severe hepatitis and cirrhosis are both developed from chronic hepatitis. The condition is serious and even life-threatening, but it is not a complication in the strict sense of chronic hepatitis.

Diagnosis of chronic hepatitis

Chronic hepatitis auxiliary examination

Chronic hepatitis needs to be checked as follows:

(1) Liver function: including serum ALT, AST, total bilirubin, direct bilirubin, indirect bilirubin, albumin, globulin, cholinesterase, alkaline phosphatase, transpeptidase, etc. degree of damage.

(2) Prothrombin time (PT) and PTA: PT is an important indicator of the function of liver coagulation factor synthesis. PTA is a commonly used expression of PT measurement value, which is of great value in judging disease progression and prognosis. Sexual decline to below 40% is one of the important diagnostic criteria for liver failure, and <20% indicates a poor prognosis. There are also those who use the International Normalized Ratio (INR) to indicate this indicator. An increase in the INR value has the same meaning as a decrease in the PTA value.

(3) Hepatic virological indicators: five items of hepatitis B, antibodies to hepatitis C, and understanding of hepatitis virus infection.

(4) Tumor markers: such as alpha-fetoprotein AFP, CA199, AFU, etc., for early detection of liver cancer.

(5) Imaging: including abdominal liver, gallbladder and spleen color Doppler ultrasound, to understand whether the liver has chronic damage and early screening for liver cancer. If necessary, perform abdominal enhanced CT or nuclear magnetic resonance to understand the degree of chronic liver damage.

(6) Fibroscan of liver: It is a non-invasive test that can be used to evaluate the degree of liver fibrosis in patients with chronic hepatitis. Assessing the degree of liver fibrosis in patients with chronic hepatitis is important in determining treatment options.

(7) Liver tissue biopsy: It is still the gold standard for assessing the degree of liver damage in patients, including two aspects of inflammation grading and fibrosis stage.

Differential diagnosis of chronic hepatitis

Chronic hepatitis needs to be distinguished from chronic gastritis and chronic cholecystitis. Based on the above tests, it is not difficult to identify chronic hepatitis.

1) Chronic gastritis: bloating and upset stomach. The liver function was normal, and there was no chronic damage to the liver in color Doppler ultrasound. No sign of hepatitis virus infection.

2) Chronic cholecystitis: manifested as discomfort in the liver area, anorexia and greasy, etc. Color Doppler ultrasound showed changes in chronic cholecystitis and normal liver imaging. Laboratory tests of liver function are usually normal, without signs of hepatitis virus infection; jaundice occurs when gallstone obstruction occurs, serum bilirubin rises, bile duct enzymes alkaline phosphatase (AKP, ALP), and transpeptidase (r-GT, GGT) increased. Often co-existing with chronic hepatitis, it is a secondary manifestation of chronic hepatitis, covering chronic hepatitis, attention should be paid to identification.

Treatment of chronic hepatitis disease

The treatment of chronic hepatitis includes multiple aspects, liver protection, anti-fibrosis, antiviral removal of etiology, prevention of liver cancer, etc. Among them, it is the most important principle in the treatment of chronic hepatitis to address different etiology and remove the etiology. Carriers of chronic hepatitis B virus require regular physical check-ups and usually do not require treatment.

Liver protection treatment: There are many types of drugs, including glycyrrhizic acid preparations, silymarin preparations, and Schisandra preparations.

Suitable for all patients with chronic hepatitis.

Anti-fibrosis treatment: mostly oral preparations of proprietary Chinese medicines, but also suitable for all patients with chronic hepatitis

Interferon injection antiviral therapy: including ordinary interferon (2a, 2b and 1b) and pegylated interferon (2a and 2b), suitable for patients with chronic hepatitis B and chronic hepatitis C, the course of treatment is at least 1 year. Interferon combined with ribavirin is the standard treatment for chronic hepatitis C, and its efficacy depends on the HCV genotyping and how fast it responds to treatment. Those with hepatitis C virus lower than the detection line within 4 weeks of treatment (commonly known as negative conversion) are said to have rapid response (RVR). This group has the best effect on interferon treatment, with a cure rate of 87%.

Oral nucleoside analog antiviral therapy: This class of drugs is only suitable for the treatment of hepatitis B, including chronic hepatitis B and hepatitis B cirrhosis. There are four drugs in mainland China: lamivudine (LAM), adefovir dipivoxil (ADV), telbivudine (LdT), entecavir (ETV); internationally There is also a fifth drug: tenofovir disoproxil fumarate (TDF), which is used to treat patients who are resistant to these four drugs. The advantages of nucleoside analogues are good antiviral efficacy, small side effects, and convenient administration. One tablet per day is widely used in clinical practice, prolongs the survival period of patients with liver cirrhosis and significantly improves the quality of life of patients with liver cirrhosis. . The disadvantage is that it needs to be taken for a long time and there is a risk of drug resistance. As a special drug for treating chronic hepatitis B, it must be applied under the guidance of a doctor, and the hepatitis B virus quantification needs to be regularly reviewed. If you stop taking the medicine at will, it will promote the occurrence of hepatitis B virus resistance, lead to aggravation of the disease, and even cause death.

Immunosuppressive agent: When autoimmune hepatitis is repeated in liver function that is difficult to control with liver-protective drugs, liver puncture indicates obvious intrahepatic inflammatory activity, you need to use glucocorticoids, or use another immunosuppressive agent, thiazole Purines can promote recovery.

Prevent the occurrence of tumors: Chronic hepatitis has a long history, and the incidence of liver cancer increases. Trace element selenium supplementation can help to strengthen the ability to fight cancer. In addition, injection of thymosin can improve the immune function, which is also conducive to the ability to prevent tumors.

Remove the cause: prohibit alcohol, stop taking drugs that damage the liver: especially important for patients with alcoholic liver disease and drug-induced liver disease. It is also important for chronic hepatitis caused by other causes.

Prognosis of chronic hepatitis disease

The prognosis of chronic hepatitis varies widely, depending on its etiology, the progression of the disease, the state of the disease at the time of diagnosis, and whether the treatment is timely and reasonable. Chronic hepatitis B and chronic hepatitis C can be controlled by antiviral therapy, and virus replication can be controlled, which can control disease progression. Abstaining from alcohol is very important for the development of alcoholic liver disease. After abstaining from alcohol, active treatment of liver disease can lead to improvement. Even with active drinking, the condition will continue to progress and develop into cirrhosis and even liver cancer. Autoimmune hepatitis is prone to fluctuations and recurrences, and the long-term prognosis is poor. The prognosis of drug-induced liver disease is good.

Chronic hepatitis diet attention

Chronic hepatitis diet has no special requirements, pay attention to balanced nutrition, eat more fresh vegetables and fruits, eat less fried foods, ban smoking and alcohol, maintain normal weight, ensure sleep time, pay attention to work and rest, and feel peaceful. Medicines rich in multi-vitamin and mineral ingredients, propolis, spirulina, fresh royal jelly, cordyceps, etc. are also helpful for improving liver nutrition and immune function.

Prevention of chronic hepatitis disease

(A) prevention of chronic hepatitis vaccine

Hepatitis B can be prevented by injecting hepatitis B vaccine to produce hepatitis B surface antibodies. The higher the level of hepatitis B surface antibodies, the stronger the protection of the human body. Before getting hepatitis B vaccine, you need to check your liver function and hepatitis B. Hepatitis B virus is usually not transmitted through the respiratory tract and digestive tract, so daily study, work or life contact, such as working in the same office (including shared office supplies and other office supplies), shaking hands, hugging, living in the same dormitory, dining in the same restaurant, and sharing toilets Exposure to blood is generally not transmitted by hepatitis B virus. There is currently no effective vaccine for hepatitis C prevention.

(2) Strict selection of blood donors

Strictly implement the "People's Republic of China's Blood Donation Law" and promote unpaid blood donation. By detecting serum HBsAg, anti-HCV, alanine aminotransferase (ALT), strict screening of blood donors, reducing blood-borne transmission

(Three) prevention of transdermal and mucosal transmission

Promote safe injections. Medical instruments such as dental instruments and endoscopes should be strictly disinfected. Medical personnel should wear gloves when touching patients' blood and body fluids. Provide psychological counseling and safety education to intravenous drug users to persuade them to quit. Shavers and dental appliances are not shared. Hairdressing appliances, punctures, tattoos, and beauty appliances should be strictly disinfected.

(IV) Prevention of sexual transmission

People with a history of sexual disorder should be checked regularly to strengthen management. It is recommended that HBV and HCV-infected people use the condom during sexual intercourse during the virus replication-positive period. Youth should be properly sexually educated.

(5) Prevention of mother-to-child transmission

For pregnant women who are HBVDNA positive, they should go to a special medical institution to implement maternal and infant block, and the success rate is> 95%. For pregnant women who are HCV RNA positive, avoid amniocentesis, minimize delivery time, ensure the integrity of the placenta, and reduce the number of newborns. Chronic exposure to maternal blood.

Chronic hepatitis expert opinion

The treatment of chronic hepatitis requires doctors to comprehensively evaluate the degree of liver damage, the etiology, the risk of possible recurrence, the probability of cirrhosis, the expected efficacy, the cost of medical treatment, the characteristics and toxic and side effects of various drugs, and the degree of awareness of the disease and Compliance, and national health insurance policies, etc., to develop a practical treatment plan for patients. Patients should not listen to false advertisements blindly and arbitrarily. It is recommended that patients go to a regular specialist hospital for treatment. During the treatment, they should not stop the medicine at will, or change the treatment plan on their own, so as not to worsen the condition and endanger health. Patients are advised to consult with a specialist in a regular medical institution before planning a change in treatment plan, and obtain appropriate guidance before making a decision to ensure the safety of medication.