Assessment of disease status in chronic hepatitis B
It is well documented that antiviral is a key measure in the treatment of chronic hepatitis B (CHB), and that sustained effective antiviral therapy can reduce and reverse liver inflammatory activity and fibrosis, and delay and reduce the development of advanced liver disease and its complications. Choosing the right timing of treatment is crucial to ensure the best outcome of antiviral therapy and reduce viral resistance, and adopting an appropriate method of disease status assessment is a prerequisite for determining the timing of treatment.
The initial assessment of CHB should be based on the known natural course of chronic HBV infection and should aim to determine the natural stage of the patient, the severity of the disease, the frequency of monitoring required and the treatment options available.
The initial evaluation should include a comprehensive history, a systematic physical examination, and laboratory and imaging studies as necessary, with a focus on the likely mode and timing of infection, including a family history of hepatitis B, blood product exposure, injection drug abuse, trauma, surgery, occupational exposure, sexual contact, and tattoos.
The exact timing of infection in patients with CHB is often difficult to determine, and most patients do not describe their history of acute hepatitis, and the exact timing of their infection may be unclear. History of hepatitis B treatment, including herbal or herbal medicine and antiviral drugs, is important.
Most patients with CHB have an uneventful physical examination, and the presence of abnormal signs such as jaundice, edema of the lower extremities, hepatic palms, spider nevus, serpentine head sign (varices around the umbilicus), hepatomegaly or atrophy, splenomegaly, and ascites are often indicative of advanced liver disease.
Routine laboratory tests should include routine blood tests, serum biochemistry package (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, direct bilirubin, total bilirubin, albumin, globulin, cholinesterase, etc.), serum protein electrophoresis, serum hepatitis B marker package (HBsAg, anti-HBs, HBeAg, anti-HBe, anti-HBc), serum HBV DNA, etc. serum HBV DNA, etc., to help confirm the diagnosis and determine the natural stage of the disease.
In the immune tolerance phase, normal serum aminotransferases are accompanied by persistently high loads of serum HBV DNA (>10^6 IU/ml); in the immune activation phase, fluctuating serum aminotransferases are accompanied by fluctuating medium loads of serum HBV DNA [(2 ~ 1000) × 10^3 IU/ml]; and in the immune control phase, normal serum aminotransferases are accompanied by fluctuating medium loads of serum HBV DNA [(2 ~ 1000) × 10^3 IU/ml], Normal serum aminotransferases are accompanied by persistent low loads of serum HBV DNA ( <2 × 10^3 IU/ml).
It should be emphasized that normal reference values for serum aminotransferases are controversial and, therefore, absolute values of serum aminotransferases may be more important in interpreting the results than relative values based on local upper limits of normal reference values, which are currently accepted and correlate with the degree of liver damage and progression of liver disease There is a correlation between
Tests related to hepatitis C virus (HCV) and hepatitis D virus (HDV) co-infection also need to be routinely included because they significantly affect the treatment and prognosis of patients with CHB. in routine clinical practice, some other laboratory tests such as lymphocyte subsets, cytokines, HBV genotypes, and drug-resistant associated HBV variants are not appropriate for routine inclusion.
Abdominal ultrasound is important, and the examiner should be aware of signs of advanced liver disease such as abnormal liver morphology, splenomegaly, intrahepatic occupancy, ascites, and altered portal venous flow. The CT and MRI of the abdomen are not routinely performed, but may be chosen if intrahepatic occupations are found in order to further clarify the diagnosis.
The role of liver biopsy as part of the evaluation of the disease status of CHB is controversial. In patients with normal serum transaminases, liver biopsy is particularly important in identifying immune tolerance, immune activation, immune control, and advanced liver disease.
A number of blood indicators and models and imaging methods have been developed to determine the histopathologic status of the liver in CHB with high accuracy for the diagnosis of severe liver fibrosis (pathologic stage ≥S3) and cirrhosis, but limited efficacy for the diagnosis of active hepatitis with non-severe fibrosis or non-cirrhosis. Dynamic observation of blood indicators and models related to the histopathological status of the liver and imaging parameters during treatment may also be useful in the evaluation of efficacy.
II. Follow-up evaluation
A single evaluation cannot accurately determine the natural stage and severity of disease in patients with chronic HBV infection; therefore, follow-up evaluation is necessary to reasonably determine the treatment options to be adopted. CHB is a chronic disease with a potential risk of cirrhosis, hepatocellular carcinoma, and liver failure, and should be monitored over time or even throughout life.
The frequency of follow-up assessment should be based on the age-specific and temporal characteristics of CHB disease activity and progression; chronic HBV-infected patients before adolescence tend to exhibit a persistent immune tolerance and rarely experience hepatitis activity; chronic HBV-infected patients in adolescence begin to exhibit immune activation and may experience atypical hepatitis activity; chronic HBV-infected patients after adolescence tend to exhibit a persistent immune activation and often experience typical hepatitis activity. After puberty, chronic HBV-infected patients tend to show a continuous state of immune activation and often have typical hepatitis activity.
The age of cirrhosis in patients with CHB is usually above 40 years, and clinical evidence suggests that reversal of liver histopathologic grading and staging can be achieved with antiviral therapy that maintains a sustained adequate virologic response. Most patients with chronic HBV infection transition from immune activation to immune control, and for patients in immune control, a 3-month monitoring cycle for serum transaminases and HBV DNA can detect most disease activity.
Patients who have developed cirrhosis and may have spontaneous liver failure and primary hepatocellular carcinoma should be monitored at a 3-month interval if they are not on antiviral therapy. In patients under 35 years of age, routine serum biochemistry and HBV DNA testing is usually sufficient to determine disease activity, monitor disease progression, and determine the timing of treatment; in patients over 35 years of age, routine blood work and serum protein electrophoresis should be included in addition to the routine serum biochemistry package and HBV DNA.
In patients with signs of cirrhosis, abdominal ultrasound and serum methemoglobin every 3-6 months may help detect hepatocellular carcinoma. Patients with serum HBV DNA below the limit of detection have an annual disappearance rate of HBsAg of 0.5% to 1.4% and are likely to develop anti-HBs, and should be checked for serum hepatitis B markers from time to time.
Assessment of special populations
The purpose is to determine whether pregnancy is tolerated and whether antiviral therapy is necessary before and after pregnancy. patients with hepatic disease that is decompensated or has a tendency to decompensate should avoid pregnancy. the periodicity and content of follow-up evaluation during pregnancy are the same as for non-pregnant patients, but the physiological changes in serum biochemical parameters during mid- and late pregnancy should be taken into account.
To avoid reproductive, genetic and developmental toxicity of drugs, patients with planned pregnancy should avoid interferon-alpha and nucleoside (acid) antivirals if their disease status permits. Patients with unintended pregnancy during interferon-alpha, entecavir and adefovir therapy should terminate the pregnancy.
It should be emphasized that although there is clinical evidence that the use of lamivudine and telbivudine in patients with intermediate and late pregnancy can reduce mother-to-child transmission, the use of antiviral therapy for all chronic HBV-infected patients for the sole purpose of reducing mother-to-child transmission is not recommended. Although clinical evidence suggests that the use of lamivudine and telbivudine in mid- and late-stage pregnant patients may reduce mother-to-child transmission, caution should be exercised in the use of antiviral therapy for all chronic HBV-infected populations solely to reduce mother-to-child transmission.
The dose and duration of immunosuppressive drugs should be individualized according to the patient’s liver disease status.
Patients in the immune tolerance phase should be exempted from antiviral therapy, but must be closely followed up; patients with cirrhosis, hepatic decompensation, and those in the immune activation and control phases should be treated with nucleoside (acid) antiviral drugs at least 1-2 weeks before the start of immunosuppressive drug therapy. The follow-up period should be determined based on the patient’s disease status and the characteristics of the immunosuppressive drugs.