I. What is individualized treatment?
Heredity and variation are two basic characteristics of organisms. Heredity refers to the similarity of the offspring to the parent or the mother, and variation refers to the difference of the offspring from the parent or the mother. Heredity and variation also exist in humans, a biological species that is a carrier of disease. Genetics and variation cover all levels and aspects of human morphology, physiology, histology, and immunology. The various aspects and facets of genetics and variation determine the existence of commonalities and differences in the same disease.
As a physician, it is relatively easy to be familiar with the commonalities of a disease, but it is very difficult to master its differences, which requires not only practical experience with a certain disease, but also theories and methods related to the study of its differences.
Group-based treatment is a treatment that ignores the differences of patients and targets known diseases or known types of diseases; individualized treatment is a treatment that varies from person to person and from condition to condition with full consideration of their differences on the premise of known diseases or known types of diseases. Group-based treatment belongs to science, and the treatments mentioned in medical professional education courses at different levels and in various guidelines currently in vogue basically belong to group-based treatment; individualized treatment belongs to art, and is a specific treatment plan drawn up by experienced doctors or doctors with a rich clinical research background on the basis of grasping the characteristics of individual disease carriers and disease states.
The advanced stage of clinical medicine practice should be the perfect combination of group treatment and individualized treatment.
What is the premise of individualized treatment?
The prerequisite for the implementation of individualized treatment is an accurate and precise assessment of the individual patient’s condition. The specific results of the condition assessment usually need to be described graphically and are difficult to describe in words.
The assessment of the disease requires full consideration of the characteristics of the disease carrier, i.e., the person (e.g., gender, age, genetics, personality, social environment, physiological status, economic status, reproductive needs), the status of the disease itself (e.g., in the case of hepatitis B, viral load, surface antigen titer, E antigen content, viral genotype, pathological grading and staging), drug characteristics (e.g., price, effectiveness, resistance, tolerability, adverse reactions).
How to assess the disease of chronic hepatitis B?
(a) Proper understanding of the stage of the disease
The natural course of chronic hepatitis B virus infection is divided into six stages.
The first stage: the immune tolerance period, the body produces almost ineffective immune response to the virus. It is characterized by “major triple positive”, alanine aminotransferase less than 40 IU/L, viral load greater than 5×107
IU/mL, and the histopathology of the liver shows non-significant inflammation or non-significant fibrosis.
Phase II: Immune activation phase: The body produces an inadequate immune response to the virus. It is characterized by “major triple positive”, alanine aminotransferase greater than or equal to 40 IU/L, viral load fluctuates between (5×107 to 5×102 ) IU/mL [mostly between (5×107
~5×105 ) IU/mL], and the liver histopathology showed a gradual transformation from non-significant inflammation or non-significant fibrosis to significant/severe/progressive inflammation or significant/severe/progressive fibrosis.
Phase III: Immune control phase: The body develops a suboptimal immune response to the virus. It is characterized by “small triplets”, alanine aminotransferase less than 40 IU/L, viral load less than 1.5×103
IU/mL, and the histopathology of the liver shows a gradual transformation from significant/severe/progressive inflammation or significant/severe/progressive fibrosis to non-significant inflammation or non-significant fibrosis.
Stage 4: Immune reactivation phase: The body produces an unstable and sub-sufficient immune response to the virus. It is characterized by “minor triplet”, alanine aminotransferase greater than or equal to 40 IU/L, viral load greater than 1.5×103
IU/mL, and the liver histopathology shows further aggravation or progression based on the inflammatory activity or degree of fibrosis in the immune control phase.
Phase V: Immune clearance phase: The body produces an adequate immune response to the virus. It is characterized by “recovery of triple positive”, alanine aminotransferase less than 40 IU/L, viral load less than 5×102
IU/mL, and the histopathology of the liver shows a gradual transformation from significant/severe/progressive inflammation or significant/severe/progressive fibrosis to non-significant inflammation or non-significant fibrosis.
Stage 6: Immune triple activation phase: The body produces an unstable and adequate immune response to the virus. It is characterized by “resumption of triple positive”, alanine aminotransferase greater than or equal to 40 IU/L, viral load greater than 1.5×103
IU/mL, and the histopathological manifestation of the liver is further aggravated or progressed on the basis of the inflammatory activity or the degree of fibrosis during the immune clearance period.
(B) Proper recognition of disease severity
In the six stages of the natural course of chronic hepatitis B virus infection, the histopathological changes in the liver undergo three dynamic evolutions from “mild to severe”, and there are differences in the “severe” manifestations of each patient: either significant or severe or progressive inflammation, or significant or Severe or progressive fibrosis.
(3) Proper understanding of the meaning of disease assessment
The assessment of disease needs to be “time-sensitive”, i.e., to judge the disease status in terms of the natural course of the disease and the severity of the disease.
The natural trajectory of the disease is not a one-way curve, but a multi-way or multi-directional curve; the severity of the disease is a two-dimensional or multi-dimensional curve.
For the assessment of chronic hepatitis B, familiarity with the natural course of chronic hepatitis B virus infection is a necessary basic condition; more importantly, at least two basic dimensions of function and morphology should be used to determine the severity of the disease.
IV. What are the goals of treatment for chronic hepatitis B?
To reduce the inflammatory necrosis of hepatocytes and liver fibrosis, to delay and stop the progression of the disease, to reduce and prevent the occurrence of liver failure, cirrhosis, liver cancer and their complications, thus improving the quality of life and prolonging survival.
V. What are the drugs used to treat chronic hepatitis B?
The drugs widely used in clinical practice for the treatment of chronic hepatitis B can be divided into four categories: anti-inflammatory and hepatoprotective drugs, direct antiviral drugs, interferon drugs and thymidine drugs.
The anti-inflammatory and hepatoprotective drugs are mainly from herbal medicines, including cucurbitacin, silymarin, pentosidine, oleanolic acid, glycyrrhizin, bitter ginseng, etc. Most of the proprietary Chinese medicines for the treatment of chronic hepatitis B contain herbal medicines that can extract several ingredients of the above drugs; chemically synthesized drugs include polyenyl phosphatidylcholine, adenosylmethionine, etc.
The direct antiviral class are all chemically synthesized drugs, including lamivudine, adefovir, entecavir, telbivudine, tenofovir, etc., all belong to the nucleoside (acid) class. Their antiviral efficacy in descending order is entecavir, telbivudine, tenofovir, lamivudine, adefovir; viral resistance barrier in descending order is tenofovir, adefovir, entecavir, telbivudine, lamivudine; reproductive toxicity in descending order is tenofovir, telbivudine, lamivudine, adefovir, entecavir.
The interferon class includes regular interferon and pegylated interferon, which are biosynthetic drugs. For the treatment of chronic hepatitis C, the efficacy of pegylated interferon is significantly higher than that of regular interferon; for the treatment of chronic hepatitis B, the effects of regular interferon and pegylated interferon are comparable. The main adverse effects of interferon analogs are fever, leukopenia/thrombocytopenia and depressive disorders.
Thymidine analogs include thymidine extracted from calf thymus and chemically synthesized thymidine, the former being a multicomponent and the latter a single component. Thymopeptide drugs all have the effect of stabilizing or regulating the immunity of the patient’s body, which helps to stabilize the disease; their adverse effects are not significant.
Sixth, which drugs have better effect in treating chronic hepatitis B?
At present, the treatment of chronic hepatitis B has shifted from liver protection therapy to antiviral therapy. In other words, the mainstream drugs for the treatment of chronic hepatitis B are nucleoside (acid) analogues. The main reason for this is that clinical trials and clinical practice have demonstrated that nucleoside analogs are more effective and more definitive in reducing hepatocyte inflammation and necrosis and liver fibrosis, and in delaying and stopping disease progression.
The essence of hepatoprotective therapy is to suppress liver inflammation, and its focus is mainly on directly controlling the immune response to clear the virus that causes liver damage. The essence of antiviral therapy is to suppress the virus, and its focus is mainly on indirectly controlling the immune response that leads to liver damage by inhibiting viral replication or multiplication; however, the immune response that leads to liver damage may be enhanced during the early stage of antiviral therapy when viral load decreases.
Interferon therapy not only inhibits viral replication or multiplication, but also promotes an immune response that clears the virus. The purpose of treatment with interferon is to facilitate the patient’s transition from the immune activation phase to the immune control phase or from the immune reactivation phase to the immune clearance phase. Although interferon is also involved in the pathogenesis of chronic hepatitis B, interferon is not a dominant factor in the clearance of the virus in patients with chronic hepatitis B; therefore, only a minority of patients in the immune activation or immune reactivation phase can achieve stabilization or delayed disease progression with interferon therapy.
Thymidine therapy can stabilize or modulate the immune response of patients to clear the virus that causes liver damage, and has some efficacy in stabilizing the disease. The specific mechanism of thymidine therapy has not been elucidated, and classifying thymidine as an immune enhancer is an inaccurate understanding.
A large number of clinical practices and studies point out that liver protection therapy, antiviral therapy and interferon therapy all have the effect of delaying disease progression, preventing cirrhosis and preventing liver failure to some extent. However, each treatment method, each treatment plan and each treatment drug can only solve part of the problems of some patients.
Seven, how to individualize the treatment of chronic hepatitis B?
The six stages of the natural course of chronic hepatitis B virus infection require drug therapy, except for the first stage – the immune tolerance period – which does not require treatment. However, the intervention strategy to be adopted needs to be designed according to the patient’s needs, the needs of the disease, and the characteristics of the medication. For example, during the immune activation phase, if there is no significant/severe/progressive inflammation or significant/severe/progressive fibrosis, liver protection therapy may be considered; if there is significant/severe/progressive inflammation or significant/severe/progressive fibrosis, liver protection or antiviral or interferon therapy may be used depending on the specific needs of the patient (e.g., fertility requirements).
It is important to emphasize that regardless of the treatment strategy, including no treatment at all, and regardless of the efficacy, it is first important to have regular check-ups and follow-ups as recommended by the physician. Only checkups and follow-ups give the doctor the opportunity to “review the situation” and “change the situation” and, of course, to provide the patient with “long-term treatment” or “long-term treatment”. This will, of course, create the conditions for the patient’s “long-term treatment” or “long-lasting treatment”.