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Hepatitis B with positive HBsAg, HBeAg, and anti-HBc

OVERVIEW

What is Hepatitis B "Da San Yang"?

Hepatitis B "Da San Yang" is a colloquial term referring to a positive result for three markers in the hepatitis B virus "two-and-a-half" test: hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antibody (HBcAb). This indicates active viral replication and high infectivity in chronic hepatitis B patients. However, "Da San Yang" does not necessarily mean the presence of hepatitis[1].

The primary goal of antiviral treatment for "Da San Yang" is to persistently suppress hepatitis B virus replication, slow disease progression, and minimize the risk of developing cirrhosis, liver cancer, or other complications, thereby maintaining a good quality of life for patients.

What is the "Two-and-a-Half" Hepatitis B Test?

The "two-and-a-half" hepatitis B test refers to the five-item hepatitis B serology panel. Since the hepatitis B core antigen (HBcAg) is difficult to detect clinically, the following five items are typically tested, known as the "two-and-a-half" test[2]:

  1. Hepatitis B surface antigen (HBsAg)
  2. Hepatitis B surface antibody (anti-HBs or HBsAb)
  3. Hepatitis B e antigen (HBeAg)
  4. Hepatitis B e antibody (anti-HBe or HBeAb)
  5. Hepatitis B core antibody (anti-HBc or HBcAb)

"Da San Yang" refers to positive results for items 1, 3, and 5, while "Xiao San Yang" refers to positive results for items 1, 4, and 5.

Is "Da San Yang" More Severe Than "Xiao San Yang"?

In terms of infectivity, "Da San Yang" is more severe than "Xiao San Yang." However, regarding liver damage, whether "Da San Yang" is more severe depends on other indicators.

  1. Infectivity: A positive HBeAg indicates active viral replication and high infectivity, so "Da San Yang" is more contagious than "Xiao San Yang"[3].

  2. Liver damage: Generally, higher levels of hepatitis B virus DNA correlate with greater liver damage, often reflected in liver function tests (e.g., alanine aminotransferase, serum bilirubin) and clinical symptoms (e.g., dizziness, fatigue, loss of appetite). However, "Da San Yang" patients may not always have higher HBV DNA levels than "Xiao San Yang" patients, so their liver damage may not necessarily be more severe[4].

SYMPTOMS

What are the symptoms of Hepatitis B "Big Three Yang" patients?

Whether Hepatitis B "Big Three Yang" causes symptoms depends on whether there is liver inflammation or fibrosis.

  1. No obvious liver inflammation or fibrosis: The patient is in the immune tolerance phase, liver function tests are normal, and there are generally no obvious clinical symptoms[1].

  2. Liver inflammation or fibrosis: The patient is in a chronic hepatitis state, which is classified into mild, moderate, and severe based on the condition[4].

    • Mild chronic hepatitis: Liver function tests show 1 or 2 abnormal indicators. Symptoms may include recurrent fatigue, weakness, aversion to greasy foods, discomfort or tenderness in the upper right abdomen, while some patients may have no symptoms.
    • Moderate chronic hepatitis: Falls between mild and severe.
    • Severe chronic hepatitis: Symptoms are obvious or persistent, liver function test indicators remain abnormal, and symptoms include fatigue, weakness, bloating, diarrhea, loss of appetite, aversion to greasy foods; dull complexion, spider angiomas (spider-like capillary dilation on the face, neck, upper chest, etc.), and palmar erythema (reddening of the palms, especially the thenar and hypothenar eminences and fingertips).

Why does Hepatitis B "Big Three Yang" lead to cirrhosis?

The essence of cirrhosis can be understood as the self-repair of damaged liver cells, forming "scars" on the liver. The hepatitis B virus in "Big Three Yang" patients causes liver cell damage. During repeated damage and repair, connective tissue in the liver continuously proliferates, which may eventually lead to cirrhosis[4].

Can Hepatitis B "Big Three Yang" develop into liver cancer?

Possibly. Hepatitis B virus infection is the leading cause of liver cancer in China, which may be related to repeated liver cell damage and proliferation, activation of cancer genes, and other factors[4].

Doctors often refer to the "hepatitis-cirrhosis-liver cancer" progression, meaning that without proper treatment or with inadequate treatment, chronic hepatitis may progress to cirrhosis and liver cancer.

However, with correct treatment and regular liver function tests and imaging examinations, the risk of Hepatitis B "Big Three Yang" worsening or progressing to liver cancer can be significantly reduced.

CAUSES

What is the cause of Hepatitis B "Big Three Yang"?

Hepatitis B "Big Three Yang" is a disease state in chronic hepatitis B patients, and the cause is naturally infection with the hepatitis B virus.

Is Hepatitis B "Big Three Yang" contagious?

Yes, Hepatitis B "Big Three Yang" is highly contagious and can be transmitted through mother-to-child transmission (e.g., intrauterine infection, delivery through the birth canal, breastfeeding), blood (e.g., transfusion of hepatitis B virus-contaminated blood), and sexual contact (e.g., unprotected sex with a hepatitis B virus carrier)[4,5].

How do patients with Hepatitis B "Big Three Yang" transmit the virus?

  1. Mother-to-child vertical transmission. In China, hepatitis B virus is primarily transmitted from mother to child, mostly during the perinatal period, particularly from 24 weeks of pregnancy to one week after birth, through the blood and bodily fluids of hepatitis B-positive mothers. This includes intrauterine infection (possibly due to contact with amniotic fluid during placental separation), delivery through the birth canal (possibly due to the infant's broken skin or mucous membranes coming into contact with the mother's blood, amniotic fluid, or vaginal secretions), and breastfeeding (possibly due to the mother's cracked and bleeding nipples transmitting the virus to the baby)[4].

  2. Blood transmission: For example, transfusion of contaminated blood, sharing unclean needles, endoscopes, and other medical devices.

  3. Sexual contact transmission: Engaging in unprotected sex (i.e., without using condoms) with a Hepatitis B "Big Three Yang" patient, having multiple sexual partners, or being a man who has sex with men increases the likelihood of hepatitis B virus infection[5].

It should be noted that so-called "close lifestyle contact transmission" may be a special form of blood transmission where healthy individuals' broken skin or mucous membranes come into contact with the patient's wounds, leading to infection.

Daily study, work, and life interactions generally do not transmit the hepatitis B virus. For example, hugging, shaking hands, sharing toilets, or eating at the same restaurant—where there is no blood exposure—do not lead to hepatitis B virus infection[5].

DIAGNOSIS

What tests do patients with hepatitis B "big three positive" usually need?

They need the hepatitis B two-and-a-half test and may also require hepatitis B virus DNA quantification, liver function tests, liver ultrasound, etc.

After testing positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), and hepatitis B core antibody (anti-HBc or HBcAb) through the "two-and-a-half" test, further tests such as HBV-DNA quantification, liver function tests, liver B-ultrasound, and biopsy may be needed to determine the severity of liver damage and guide treatment.

Why do hepatitis B "big three positive" patients need HBV-DNA quantification after the two-and-a-half test?

HBV-DNA quantification measures the level of free virus in the blood, with a detection limit typically around 10–20 U/mL[6].

The level of free virus in the blood reflects viral replication activity—higher levels indicate more active replication and greater infectivity. Additionally, HBV-DNA quantification helps guide antiviral therapy and evaluate treatment efficacy[5].

However, the severity of liver damage cannot be determined by viral replication alone, so besides the two-and-a-half test and HBV-DNA quantification, "big three positive" patients should also undergo regular liver function tests and liver B-ultrasound.

What tests are needed if cirrhosis is suspected in hepatitis B "big three positive" patients?

  1. Imaging tests: Cirrhosis shows distinct features on X-rays, abdominal B-ultrasound, and CT scans (e.g., "chrysanthemum-like" changes in barium meal X-rays for esophageal varices; uneven liver surface, liver shrinkage, splenomegaly, ascites on B-ultrasound; widened portal vein, ascites on CT). B-ultrasound and CT are commonly used clinically[4].

Thus, if cirrhosis is suspected, liver B-ultrasound or CT is usually performed, though neither is the "gold standard" for diagnosis.

  1. Biopsy: A definitive diagnosis of cirrhosis may require a liver biopsy—a needle puncture through the skin to extract liver tissue for microscopic examination. This helps determine the degree of liver fibrosis[7].

  2. Blood tests: Such as type III procollagen amino-terminal peptide (PⅢP) and protein electrophoresis to assess liver function[4].

How is a liver biopsy performed for hepatitis B "big three positive" patients?

Modern liver biopsies typically use rapid needle aspiration, a safe method with minimal liver damage and bleeding.

The procedure involves: The patient empties their bladder and lies supine with their right hand under a pillow. The doctor locates the puncture site via ultrasound, sterilizes and anesthetizes the area. The patient inhales, holds their breath at the end of exhalation, and the doctor swiftly inserts a disposable biopsy needle. An assistant performs suction to obtain the sample, which is immediately withdrawn. The puncture site is pressed with sterile gauze for 5–10 minutes and secured with adhesive tape[4].

Post-procedure, patients are advised to lie on their right side for 2 hours, then supine for another hour. They should monitor for bleeding, keep the puncture site dry and clean, and avoid lifting objects heavier than 6.8–9.1 kg for a week[7].

What is the significance of liver biopsy in diagnosing hepatitis B "big three positive"?

Not all "big three positive" patients require a biopsy. It is generally recommended for:

  1. Long-term "big three positive" carriers with HBeAg positivity, normal liver function, and no obvious hepatitis symptoms (e.g., fatigue, nausea, loss of appetite) but suspected cirrhosis. A biopsy helps assess fibrosis and guide timely treatment, potentially reversing cirrhosis.
  2. Patients showing significant treatment response, where biopsy helps determine the optimal time to stop medication[7].

Additionally, if other liver conditions (e.g., fatty liver) are suspected, biopsy aids in diagnosis, treatment selection, and prognosis evaluation. Patients should cooperate with their doctors.

TREATMENT

What are the treatment options for Hepatitis B "Big Three Yang"?

The primary treatment for Hepatitis B "Big Three Yang" is antiviral therapy. Commonly used medications include interferons (such as pegylated interferon α and standard interferon α, with side effects like headaches, myalgia, and fatigue, mainly occurring in the early stages; long-term use may lead to hair loss and depression) and nucleoside analogs (such as entecavir and tenofovir, which have fewer side effects but may cause elevated serum creatinine levels, myalgia, and fatigue)[5].

These two types of drugs differ significantly in treatment duration, indications, and contraindications, and the course of treatment generally exceeds one year. The use of antiviral drugs should strictly follow the doctor's prescribed regimen.

Can Hepatitis B "Big Three Yang" be cured?

Hepatitis B "Big Three Yang" cannot yet be completely cured, meaning current medical technology cannot entirely eliminate the virus.

The goal of treatment is not to completely eradicate the virus but to persistently suppress hepatitis B virus replication, delay disease progression, and minimize the risk of developing severe consequences like cirrhosis or liver cancer, allowing patients to lead a normal life[5].

Under what circumstances does Hepatitis B "Big Three Yang" require antiviral treatment?

Simply put, patients with active hepatitis B virus replication and abnormal liver function should undergo antiviral treatment. Therefore, not all "Big Three Yang" patients require antiviral therapy. The following conditions necessitate antiviral treatment:

  1. Positive hepatitis B virus DNA;
  2. Repeated elevation of alanine aminotransferase (ALT), exceeding twice the upper limit of normal, excluding other liver diseases like fatty liver;
  3. Family history of liver cancer or cirrhosis, and the patient is over 30 years old;
  4. Imaging or liver biopsy indicating cirrhosis[5].

Patients should never self-treat based on their own understanding and must seek comprehensive evaluation at a reputable hospital to have a doctor develop a suitable treatment plan.

What does the transition from Hepatitis B "Big Three Yang" to "Small Three Yang" signify?

For acute hepatitis B, the transition from "Big Three Yang" to "Small Three Yang" indicates reduced virus replication, improvement in the condition, better response to treatment, and a potential for recovery in the near term.

For chronic hepatitis B, it signifies reduced virus replication and lower viral load, decreasing infectivity, but it is not a sign of potential cure.

Is liver-protective medication useful for Hepatitis B "Big Three Yang" patients?

Liver-protective medications address symptoms rather than the root cause. They mainly help reduce liver inflammation and damage and may be used for patients with significant liver inflammation or markedly elevated ALT levels (exceeding 300 U/L), but multiple combinations are not recommended[5].

Many liver-protective drugs can temporarily lower transaminase levels or improve lab results but do not have antiviral effects against hepatitis B and do not fundamentally benefit the liver.

Now, more doctors recognize the limitations of liver-protective drugs, and their use has decreased compared to the past.

If Hepatitis B "Big Three Yang" persists, can folk remedies or herbal medicines be tried?

Under no circumstances should patients resort to so-called miraculous folk remedies or herbal medicines advertised in legends. Treatment should be sought at reputable hospitals.

Some folk remedies or herbal medicines not only fail to "protect the liver" but may also harm it due to drug abuse, their properties, or ingredients, worsening the condition.

Which department should Hepatitis B "Big Three Yang" patients visit for treatment?

Infectious Diseases, Infectious Disease, or Hepatology departments.

Patients are generally advised to visit the Infectious Diseases or Infectious Disease departments. If these departments are unavailable, they may opt for the Hepatology department.

DIET & LIFESTYLE

What should patients with hepatitis B "big three positives" pay attention to in their diet?

It is generally believed that hepatitis B patients, including those with "big three positives," should follow the principle of "three highs and one moderate," namely high protein, high carbohydrates, high vitamins, and moderate fat[4].

  1. Consume more protein-rich foods to ensure adequate protein intake. The recommended daily intake is 1.5–2.0 g per kilogram of body weight, with a focus on high-quality protein sources such as milk, fish, and lean pork.
  2. Carbohydrates (e.g., sweet potatoes, steamed buns, rice) should generally be consumed in amounts of 300–400 g per day (equivalent to 1.2–1.6 fast-food box servings of rice) to ensure sufficient caloric intake.
  3. Eat more fruits and vegetables rich in vitamins, typically a handful per day, such as apples or oranges.
  4. Fat intake should be around 50–60 g per day (equivalent to 5–6 household ceramic spoonfuls), preferably from vegetable oils.

Additionally, patients with hepatitis B "big three positives" should observe dietary restrictions: avoid alcohol and refrain from long-term consumption of high-calorie, high-sugar foods (e.g., sugary drinks, fried foods) to prevent adding burden to the liver[4].

Can hepatitis B "big three positives" be transmitted through shared meals?

Generally not, as the hepatitis B virus is not transmitted via the respiratory or digestive tracts[5].

While the saliva of hepatitis B "big three positives" patients may contain the virus, transmission through shared utensils is theoretically possible only when the viral load is high, the strain is highly virulent, and the exposed individual has a weakened immune system or oral mucosal damage. This is essentially a special form of bloodborne transmission.

However, there is no clear evidence of hepatitis B transmission via this route in real-world settings. Therefore, if feasible, patients may use separate utensils, though it is not mandatory.

Why should patients with hepatitis B "big three positives" avoid alcohol?

Alcohol metabolism occurs in the liver, and drinking may further burden an already compromised liver. Additionally, alcohol can damage liver cells, exacerbating hepatitis.

Thus, patients with hepatitis B "big three positives" should abstain from alcohol[4].

Can patients with hepatitis B "big three positives" get pregnant?

Yes. Currently, it is believed that patients with long-term stable conditions and normal liver function can conceive. Those undergoing antiviral therapy should consult their doctors to weigh the pros and cons.

However, patients must be aware that pregnancy increases the liver's workload and raises the likelihood of the child contracting hepatitis B. Regular prenatal checkups are essential to monitor liver function and prevent fetal infection. If the maternal hepatitis B virus DNA level exceeds 2 × 105 IU/mL during pregnancy, antiviral therapy is recommended starting at 24–28 weeks after thorough discussion with the patient to improve the success rate of mother-to-child transmission prevention. Antiviral therapy does not affect breastfeeding[5]. Newborns should receive immediate standardized prophylaxis (e.g., hepatitis B immunoglobulin injection).

PREVENTION

How to prevent Hepatitis B with the "Big Three Yang"?

Getting vaccinated against hepatitis B can prevent infection with the hepatitis B virus. Only those who develop effective antibodies after vaccination (confirmed by a positive serum hepatitis B surface antibody test, i.e., anti-HBs positive) will have protective effects[5].

Why is it still possible to get infected with hepatitis B after vaccination?

Due to factors such as the dosage, number of vaccine doses, or personal reasons (e.g., receiving only 1 or 2 doses out of the required 3-dose regimen), some individuals may not develop sufficient antibodies or any antibodies at all after vaccination, leaving them susceptible to hepatitis B infection.

Does the hepatitis B vaccine require regular booster shots?

For babies under three years old, unvaccinated individuals under 15, and high-risk groups (such as family members of hepatitis B surface antigen-positive patients, healthcare workers, prisoners, etc.), hepatitis B vaccination should be administered as early as possible. Pregnant women who have never been infected with hepatitis B can also receive the vaccine.

The hepatitis B vaccine requires a full course of 3 doses. After the first dose, the second dose is given at 1 month, and the third dose at 6 months. If no antibodies are produced after vaccination, the vaccine dosage or frequency may be increased under medical supervision to enhance immunity.

It is generally believed that successful vaccination resulting in antibody production (hepatitis B surface antibody positive, i.e., anti-HBs positive) provides effective protection for about 30 years. If needed, revaccination can be administered under medical guidance[5].

How should people in close contact with hepatitis B "Big Three Yang" patients protect themselves?

Since hepatitis B "Big Three Yang" is primarily transmitted through blood and bodily fluids, patients should carefully handle their blood (e.g., menstrual blood and sanitary pads) and other secretions to avoid contaminating the surrounding environment. They are also prohibited from donating blood[5].

Those around them should avoid contact with contaminated items, such as the patient's toothbrush or razor, and wash their hands promptly with soap or running water after contact. Regularly disinfect items used by the patient (e.g., tableware, teacups) by boiling them in water for 20 minutes[8].

Note that casual contact such as hugging or handshaking generally does not transmit hepatitis B[5].